Published on

Published in: Technology, Business
  • Be the first to comment

  • Be the first to like this

No Downloads
Total views
On SlideShare
From Embeds
Number of Embeds
Embeds 0
No embeds

No notes for slide

  1. 1. REVIEWS The who, how and where of antigen presentation to B cells Facundo D. Batista and Naomi E. Harwood Abstract | A functional immune system depends on the appropriate activation of lymphocytes following antigen encounter. In this Review, we summarize studies that have used high-resolution imaging approaches to visualize antigen presentation to B cells in secondary lymphoid organs. These studies illustrate that encounters of B cells with antigen in these organs can be facilitated by diffusion of the antigen or by the presentation of antigen by macrophages, dendritic cells and follicular dendritic cells. We describe cell-surface molecules that might be important in mediating antigen presentation to B cells and also highlight the key role of B cells themselves in antigen transport. Data obtained from the studies discussed here highlight the predominance, importance and variety of the cell-mediated processes that are involved in presenting antigen to B cells in vivo. Total internal reflection The immune system is highly dynamic and diverse, which and present antigen in association with MHC class II fluorescence microscopy enables it to effectively protect an individual from numer- molecules, thereby recruiting specific CD4 + T-cell A microscopy method that ous potentially pathogenic encounters. Early studies that help and stimulating B-cell proliferation and dif- allows for the identification combined techniques such as electron microscopy and ferentiation15,16 (BOX 2). Although the precise factors of fluorescence within immunofluorescence yielded valuable information on that determine the fate of activated B cells currently 100–200 nm of the interface between cells and their the static location and organization of the cells of the remain unclear, B cells can differentiate along two substrate (for example, lipid immune system, and inferred their dynamic properties distinct pathways. On the one hand, B cells can dif- bilayers or glass coverslips), (for a historical perspective and references to original ferentiate to form extrafollicular plasmablasts that thereby providing a high lateral articles see REFS 1–3). However, it is necessary to consider are essential for rapid antibody production and early and axial resolution at the cell–substrate interface and the development of immune responses in terms of both protective immune responses. On the other hand, the ability to observe intracellular and intercellular interactions in the appro- activated B cells can enter germinal centres, where they nanoscale movement of priate environment and in real time4–8. Indeed, the recent can differentiate into plasma cells, which can secrete signalling molecules during development of high-resolution imaging techniques, high-affinity antibody following affinity maturation, cellular activation. including confocal microscopy, total internal reflection or memory B cells, which confer long-lasting protection fluorescence microscopy and intravital multiphoton micro- from secondary challenge with antigen17,18. scopy, has provided insights into the spatio-temporal In this Review, we discuss recent insights into the dynamics of the molecular and cellular events that sites at which B cells encounter antigen in vivo, as well underlie immune responses to pathogenic infection. One as the mechanisms by which these interactions occur example of such an insight is the molecular description (for excellent reviews that include comprehensive Lymphocyte Interaction of the immunological synapse, a structure that is com- descriptions of antigen presentation to T cells in vivo, Laboratory, Cancer Research monly associated with lymphocyte activation following see REFS 2,19–21 ). It is now clear that B cells can UK London Research the recognition of a specific antigen9–12 (BOX 1). encounter and respond to antigen through many dif- Institute, Lincoln’s Inn Fields Laboratories, 44 Lincoln’s Inn B-cell activation is initiated following engagement ferent mechanisms depending on the nature and size Fields, London WC2A 3PX, UK. of the B-cell receptor (BCR) by a specific antigen. of the antigen itself, as well as on the cellular context Correspondence to F.D.B. B cells can recognize and respond to both soluble and location in which antigen presentation occurs. e‑mail: facundo.batista@ and membrane-associated antigen, although recent This provides great versatility in terms of initiating doi:10.1038/nri2454 insights suggest that membrane-associated antigens responses that are appropriate to the particular antigen Published online are more important for B-cell activation in vivo 13,14. and are therefore the most effective for the protection 12 December 2008 Following antigenic stimulation, B cells can process of the host. nATuRE REvIEws | Immunology vOluME 9 | jAnuARy 2009 | 15 © 2009 Macmillan Publishers Limited. All rights reserved
  2. 2. REVIEWS Intravital multiphoton Sites of antigen encounter slOs are extremely well connected to the blood and microscopy As cells of the immune system can respond to a huge lymphatic systems, allowing them to continually sample A microscopy method that range of potential pathogenic challenges throughout the and concentrate antigens that are circulating through- combines the advanced whole body, these responses must be tightly coordinated out the body. The importance of slOs in organizing optical techniques of laser-scanning confocal to confer effective protection. Owing to this great anti- and coordinating immune responses is evident from microscopy with genic diversity, the event of antigen encounter with an the severe impairment in the activation of naive lym- long-wavelength multiphoton antigen-specific lymphocyte that can mount a rapid and phocytes in alymphoplastic (aly/aly) mice and asplenic fluorescence excitation to appropriate response would seem unlikely. To maximize (homebox 11-deficient) mice23. Accordingly, any mean- capture high-resolution, the probability of such an interaction, these events occur ingful investigation into the spatio-temporal dynamics three-dimensional images of living cells and/or tissues that in defined sites, such as the lymph nodes and spleen, and the mechanisms by which lymphocytes encounter have been labelled with which are collectively known as secondary lymphoid antigen in vivo must be considered within such highly fluorophores. It provides a organs (slOs). These sites possess a highly organized organized environments. greater tissue imaging depth microarchitecture that is necessary for the compartmen- (up to 350 µm depending on the tissue) and less talization of numerous cellular interactions and there- Lymph nodes. It is now widely understood that photobleaching and fore provide the optimal environment for the initiation beneath the protective outer collagenous capsule, a phototoxicity than of immune responses, including the determination of lymph node is divided into three discrete (but non- conventional imaging cell fate22. Furthermore, within 24 hours lymphocytes rigid) regions that are defined by the expression of methods. that have been unsuccessful in their search for antigen specific chemokines3,24 (FIG. 1a). Directly beneath the Germinal centre recirculate throughout the body and between slOs to subcapsular sinus is a macrophage-rich sheet that sur- A highly specialized and dramatically increase the probability of encountering rounds the B-cell zone, which is also termed the cor- dynamic microenvironment cognate antigen3. tex. B cells in this region are organized into aggregates, that gives rise to secondary B-cell follicles during an immune response. It is the main site of B-cell maturation, Box 1 | The immunological synapse during which memory B cells and plasma cells that produce Lymphocyte activation is initiated following the recognition of specific antigen by clonotypic immunoreceptors, such high-affinity antibody are as the B‑cell receptor (BCR) and the T‑cell receptor (TCR). The recognition of specific antigen on a spatially constrained generated. surface is associated with membrane reorganization that results in the formation of an immunological synapse9–12. The structure of the mature immunological synapse is characterized by the spatial segregation of immunoreceptors into Plasma cell a central supramolecular activation cluster (cSMAC) from the surrounding peripheral SMAC (pSMAC), which contains integrins, A non-dividing, terminally such as lymphocyte function‑associated antigen 1 (LFA1) (see the figure). The early molecular events that underlie the formation differentiated, antibody- of the immunological synapse have been revealed by high‑resolution imaging techniques and are highly coordinated and tightly secreting cell of the B-cell regulated. Following the recognition of specific antigen and before the formation of the immunological synapse, B cells rapidly lineage. spread over the antigen‑containing surface in a manner that is dependent on intracellular signalling and cytoskeletal Memory B cell rearrangements120. During B‑cell spreading, antigen–BCR microclusters are continually assembled at the periphery of the An antigen-experienced B cell contact area between the cells14. As similar microclusters are crucial for sustained signalling in T cells121–123, we have proposed that expresses high-affinity that these microclusters form functional signalling units that are common to both types of lymphocyte14. antibodies and quickly A comprehensive genetic dissection of the requirements for B‑cell spreading identified an important role for the sequential differentiates into a plasma recruitment of the kinases LYN and spleen tyrosine kinase (SYK) to antigen–BCR microclusters in the initiation of cell during antigen-recall BCR‑induced signalling124. Furthermore, this study visualized the formation of microsignalosomes through the recruitment of responses. signalling molecules and adaptors to the antigen–BCR microclusters and showed the importance of cooperation between VAV and phospholipase Cγ2 in mediating the spreading response. The role of LYN and SYK in the initiation of BCR signalling Alymphoplastic (aly/aly) has been further supported through mice B-cell contact area with APC Antigen–BCR microcluster: side view fluorescence resonance energy transfer Mice that are characterized (APC not shown) CR APC (FRET)‑based assays125. B‑cell spreading by the absence of lymph FcR nodes and Peyer’s patches. facilitates the propagation of signalling Alymphoplasia is caused by a Antigen through microclusters by allowing the BCR spontaneous mutation in the C3 Antibody to engage more antigen, which promotes gene that encodes nuclear- fragment further localized signalling and cytoskeleton factor-κB-inducing kinase. rearrangements120. The spreading response BCR Mature immunological synapse: is followed by a prolonged contraction top view Microsignalosome phase, which results in the accumulation B cell of antigen–BCR microclusters in the cSMAC of the mature immunological Immunological synapse: side view synapse. The cSMAC functions as a site for APC internalization of antigen12,120, before it is processed and presented in association pSMAC cSMAC with MHC class II molecules; presentation Integrin receptor of antigen–MHC molecules mediates the B-cell contact area recruitment of the CD4+ T‑cell help that is necessary for full B‑cell activation15,16. APC, antigen‑presenting cell; C3, complement component 3; CR, complement receptor; cSMAC pSMAC B cell FcR, Fc receptor. Nature Reviews | Immunology 16 | jAnuARy 2009 | vOluME 9 © 2009 Macmillan Publishers Limited. All rights reserved
  3. 3. REVIEWS T-cell-dependent antigen known as follicles, and are the largest population of The medulla, which is the innermost area of the A protein antigen that needs to IgMmedIgDhiCD21medCD23hi B cells in the body. Follicles lymph node, contains both B and T cells that are organ- be recognized by T helper cells are also rich in radiation-resistant follicular dendritic ized into medullary cords and is also rich in DCs and (in the context of MHC cells (FDCs) that express high levels of the adhesion macrophages. molecules) and requires cooperation between these molecules vascular cell-adhesion molecule 1 (vCAM1) lymph nodes are strategically positioned at branches antigen-specific T cells and and intercellular adhesion molecule 1 (ICAM1), as well throughout the lymphatic system to enable extensive B cells for a specific antibody as complement and Fc receptors25–28. FDCs are thought antigenic sampling of lymphatic fluid4. lymphatic fluid, response to be generated. to be of mesenchymal origin and thus form a popu- which contains various chemokines and antigens that lation of cells that is distinct from classic DCs 29. The have been collected from the body, enters the lymph Affinity maturation A process whereby the precise mechanism of FDC development is not yet node through the afferent lymph vessel and is subse- mutation of antibody fully understood, but is known to require the expres- quently filtered by the lymph node as it flows towards variable-region genes followed sion of various chemokine receptors and the presence the efferent lymph vessel. lymphatic fluid is prevented by selection for higher-affinity of B cells17,30. Following exposure to antigen, follicles from freely diffusing into the interior when it enters variants in the germinal centre leads to an increase in average may also contain specialized structures, known as the lymph node by the subcapsular sinus; instead, it antibody affinity for an antigen germinal centres, which consist of rapidly proliferat- travels to the medulla through structures known as as an immune response ing B cells within a network of FDCs. The formation trabecular sinuses. In addition, components of lym- progresses. The selection is of germinal centres is important during the develop- phatic fluid that have a molecular weight of below thought to be a competitive ment of humoral immune responses to T-cell-dependent ~70 kDa (equivalent to a dynamic radius of ~5.5 nm) process in which B cells compete with free antibody antigens, as they serve as sites for affinity maturation and the are allowed to move towards the HEv through the intri- to capture decreasing amounts generation of long-lasting memory B cells. cate meshwork of fibroblastic reticular cell (FRC)-lined of antigen. The T-cell zone, or paracortex, which is adjacent to collagenous conduits that are associated with DCs32,33 the follicles, contains high endothelial venules (HEvs) (FIG. 1b). Accordingly, early observations indicated that µ mt−/− mice A strain of mutant mice that and numerous antigen-presenting cells. The HEvs are the paracortex did not contain unprocessed antigen, carry a stop codon in the first specialized capillaries that continually supply the lymph although some antigen could be detected in DCs34. The membrane exon of the µ-chain node with and drain it of lymphocytes from and to the lymphatic fluid that exits the lymph node is enriched constant region. They lack periphery. Furthermore, HEvs in the paracortex can often with lymphocytes35 and therefore provides a means for IgM+ B cells, and B-cell mediate the recruitment of cells other than lymphocytes, these cells to return to the circulation24. development is arrested before the differentiation stage at such as antigen-presenting cells that have accumulated which IgD can be expressed. antigen in the periphery. The paracortex also contains Spleen. The organization of the lymphoid tissue of the a network of collagenous conduit fibres that allow the spleen is similar to that of the lymph node, with B-cell passage of low-molecular-mass components of lymphatic follicles and T-cell zones that contain networks of retic- fluid, including chemokines, from the subcapsular sinus ular cells (also known as the periarteriolar lymphoid to HEvs (reviewed in REF. 31). sheath) and a similar conduit system36 in the splenic Box 2 | B cells mediate antigen presentation to antigen-specific T cells B cells can have a role in initiating T‑cell responses by functioning as antigen‑presenting cells (APCs). When compared with dendritic cells, B cells are relatively poor APCs, and therefore the importance of B cells in antigen presentation to T cells has been controversial. However, their presentation potential can be enhanced following specific recognition of antigen126. Furthermore, it has been recently shown that reconstitution of chimeric µ mt–/– mice with B cells that lack MHC class II molecules results in impairment of T‑cell responses following antigen stimulation127, which suggests that presentation of antigen by B cells does contribute to T‑cell activation. Tracking and intravital microscopy of antigen‑specific lymphocytes in lymph nodes (see the figure) showed that around 24 hours following antigen encounter, B cells (green) migrated towards the B‑cell–T‑cell boundary at the edge of the follicles70 in a CC‑chemokine receptor‑7‑dependent manner48. When they reached this boundary, B cells were found to engage antigen‑specific T cells (red) for up to 1 hour. A similar migration pattern to the B‑cell–T‑cell boundary was observed in response to stimulation with particulate antigen or immune complexes following their accumulation at the subcapsular sinus (SCS)64,67. B‑cell–T‑cell conjugates are suprisingly motile and migrate through the lymph node at the same rate as unconjugated B cells. The importance of these long‑lived B‑cell–T‑cell Follicle conjugates in the generation of sustained immunity has recently been highlighted through the investigation SCS of mice that are deficient in SLAM‑associated protein (SAP)128. Although the CD4+ T cells from SAP‑deficient mice exhibit typical dendritic‑cell‑mediated activation, they cannot interact with cognate B cells, resulting in severely impaired formation and function of germinal centres. Thus, it seems that although the number of naive antigen‑specific B cells in vivo is T-cell probably low, this mechanism of antigen presentation zone to T cells by B cells contributes to the initiation of T‑cell responses in vivo. Follicle Nature Reviews | Immunology nATuRE REvIEws | Immunology vOluME 9 | jAnuARy 2009 | 17 © 2009 Macmillan Publishers Limited. All rights reserved
  4. 4. REVIEWS a Lymph node Spleen Afferent lymph Red pulp Trabecular sinus Paracortex White Subcapsular pulp sinus Follicle HEV Marginal zone Medulla Marginal Efferent sinus lymph PALS Blood Central Conduit network arteriole Conduit network Follicle Arteriole branch b Conduit network c SCS Follicle T-cell zone Collagen bundles FRC Associated DC Follicle Figure 1 | The organization of secondary lymphoid organs. a | A schematic representation of secondary lymphoid organs (SLOs). The lymph node is organized into three discrete (but non-rigid) regions: the medulla, the paracortex (also known as the T-cell zone) and the follicles (also known as the B-cell zone). Antigen-laden lymphatic fluid flows from the afferent lymph vessel Nature Reviews | Immunology into the subcapsular sinus and through the trabecular sinuses to the medulla, where it exits through the efferent lymph vessel. Lymphatic fluid also flows through the conduit network in the paracortex, allowing passage of low-molecular-mass components, including chemokines and antigen, from the subcapsular sinus to high endothelial venules (HEVs). HEVs in the paracortex also allow for the entry and exit of lymphocytes to and from the lymph node. The white pulp of the spleen consists of the paracortex (also known as the periarteriolar lymphoid sheath; PALS), B-cell follicles, a central arteriole and the marginal zone. Blood arrives at the spleen at the marginal sinus through branches of the central arteriole and from there it flows to the red pulp through the marginal zone or to the white pulp through the conduit network. b | The conduit network in the lymph node is composed of a collagen core and is lined with fibroblastic reticular cells (FRCs). Dendritic cells (DCs) are often associated with FRCs and can extend short protrusions into the conduits, possibly to sample the lymphatic fluid that is transported through this network. c | A snapshot of a video generated using multiphoton microscopy on the popliteal lymph node. The distribution of seminaphtho-rhodafluor (SNARF)-labelled B cells (red) within the follicles (delineated by a dashed line) beneath the subcapsular sinus (SCS; solid line) and of carboxyfluorescein diacetate succinimidyl ester (CFSE)-labelled T cells (green) in the paracortex is shown in the absence of antigen. Scale bar represents 100 µm. white pulp37 (FIG. 1a). The spleen also contains red pulp, These marginal-zone B cells form a population of cells which is richly supplied with blood and contains various that is distinct from follicular B cells, a large propor- antigen-presenting cells, lymphocytes and plasma cells38. tion of which are polyreactive clones. Marginal-zone The outer limit of the white pulp is separated from the B cells have an IgMhiIgDlowCD21hiCD23low phenotype red pulp by a region known as the marginal zone 39. and are thought to participate in the development of This area has extensive vasculature, and blood that early immune responses to both T-cell-dependent and enters the spleen through follicular arteriole branches T-cell-independent antigens42. In contrast to lymph nodes, in the marginal sinus reaches the marginal zone before the spleen is not supplied with afferent lymphatic fluid T-cell-independent antigen its permeation through the red pulp40. The marginal (although it does contain efferent lymphatics); instead, An antigen that directly zone also contains numerous macrophages and DCs, it is specialized in mounting immune responses to activates B cells. and a sizable population of non-recirculating B cells41. blood-borne antigens43. 18 | jAnuARy 2009 | vOluME 9 © 2009 Macmillan Publishers Limited. All rights reserved
  5. 5. REVIEWS Lymphocyte behaviour in ‘resting’ SLOs diffusion of antigen into the lymphoid tissue; how- To establish the sites and mechanisms of antigen encoun- ever, these encounters are usually mediated through ter with lymphocytes in vivo, it is important to understand macrophages, DCs and FDCs (FIG. 2). the localization and dynamics of these cells in the resting lymphoid organs. Although information on cell dynam- Encountering of soluble antigen. Antigen can be rap- ics in the past was inferred from studies using static idly supplied to the lymph node through the afferent approaches1–3, initial groundbreaking studies that directly lymph vessels. Indeed, antigen arrival at the subcapsu- visualized the spatio-temporal dynamics of lymphocytes lar sinus can be detected within minutes of subcutane- in vivo were possible because of advances in the field of ous administration51. As most B cells are mainly located multiphoton microscopy (reviewed in REFS 5,19). This in the follicles, lymph-borne antigens must gain access method allows for the investigation of cellular behaviour to follicular B cells in a manner that is independent in real time and to a depth in living tissue that is prohib- of the conduit system, which is present predominantly in ited by techniques such as confocal microscopy 5. The ear- the paracortex. liest multiphoton microscopy investigations were carried Interestingly, several electron microscopy stud- out on explanted or isolated lymph nodes44–46, and many ies have identified pores of ~0.1–1 µm diameter in the of the original observations have since been confirmed in regions of the subcapsular sinus that are adjacent to lymph nodes in vivo following minimal surgical disrup- the lymph-node parenchyma52–54. These pores might tion. However, high-resolution imaging of lymphocyte allow small soluble antigen, such as low-molecular-mass behaviour in splenic tissue is hampered by the technical toxins, that enter the lymph node through the afferent challenges that are associated with the isolation of this lymph vessel to directly pass into the follicle and gain vital and deeply embedded organ6. access to B cells55 (FIG. 2a). Indeed, using immunohisto- The first surprising observation from these multi- chemistry of frozen lymph-node sections, it was shown photon microscopy studies was the highly motile nature that this rapid diffusion of antigen was independent of of lymphocytes within the resting lymph node45–48. B and DCs and did not require migration of B cells from their T cells that were highly polarized in shape were found follicular location. These observations are consistent to move within their restricted cellular zones (FIG. 1c) with a previous study, which showed that immuniza- but along apparently random trajectories, with average tion of mice with soluble antigen initially resulted in a velocities of around 6 µm (for B cells) and 12 µm (for T substantial decrease in the motility of antigen-specific cells) per minute. Closer inspection of this movement fol- B cells in the follicle48. Furthermore, in the 24 hours lowing the visualization of the conduit network provided following immunization these B cells were shown to evidence for an order to this process. using an elegant present antigen in association with MHC class II mol- system involving chimeric mice that express green fluo- ecules on their surface (BOX 2) and to migrate towards rescent protein, Bajénoff et al.49 could visualize the FDCs the boundary between the follicle and the paracortex. and FRCs in the lymph node before the introduction of a Therefore, small low-molecular-mass antigens may gain population of labelled lymphocytes. This study showed access to cells in the follicles without requiring cell- that the T cells in the paracortex are in close association mediated presentation, through direct diffusion from with FRCs, which allows the T cells to be guided along pores in the subcapsular sinus. However the existence a defined network. As B cells enter the lymph node of these pores remains controversial, as they may simply through HEvs in the paracortex, it was also suggested be sites generated by cells that have recently migrated that these cells could migrate along FRCs in this area through the sinus wall. Furthermore, there is a discrep- before migrating in a chemokine-directed manner to the ancy between the dimensions of the observed pores follicles, where a similar network composed of FDCs can and the radius of the antigens that have been excluded be used to orchestrate their movement. such rapid move- from accessing the follicle by diffusion. In view of this, it ment across these networks suggests that lymphocytes in seems reasonable to postulate the existence of an alter- the lymph node are continually scanning their environ- native means of mediating the movement of smaller ment and are ready to respond to antigen as soon as it antigens into the follicles, perhaps in a manner that is is encountered. Interestingly, similar investigations have reminiscent of diffusion from the conduit system, as offered insight into the behaviour of CD11c+ DCs in the observed in the paracortex. paracortex 50. In contrast to lymphocytes, and as expected given their potential role in structural support of the con- Macrophage-mediated presentation. Although diffu- duit network, these DCs were found to be sessile, show- sion of antigen from the subcapsular sinus provides one ing movement at a velocity of less than 2 µm per minute. mechanism for exposing follicular B cells to small soluble However, this restriction in motility did not prevent the antigens, the access of larger particulate antigens to B cells rapid movement of their dendritic processes, indicating in the follicle is limited. It was therefore suggested that that these DCs retain the capacity to sample and respond specialized cells, possibly located in the subcapsular sinus, to environmental signals. might transport large antigens to the B-cell follicles53,56–58. Early microscopy studies revealed a population of macro- Presentation of antigen to B cells phages that reside directly beneath the subcapsular B cells can promptly detect and mount responses sinus52,53 and can extend their processes through it to gain to antigen after immunization. In the case of small soluble access to afferent lymphatic fluid53,56,58. As these macro- antigens, responses can be mounted following a simple phages have been shown to bind a soluble recombinant nATuRE REvIEws | Immunology vOluME 9 | jAnuARy 2009 | 19 © 2009 Macmillan Publishers Limited. All rights reserved
  6. 6. REVIEWS a Afferent lymph vessel Antigen C3 fragment Antibody Subcapsular sinus Immune MAC1 complex DC-SIGN FcR SCS macrophage BCR Small soluble antigen CR Antigen-specific Follicular B cell dendritic cell Primary follicle b c SCS Antigen-specific Paracortex B cell HEV Recently migrated DC FRC Resident DC Antigen-specific B cells Antigen non-specific B cells T cell Antigen Figure 2 | B-cell encounters with specific antigen in the lymph node. a | B cells in follicles have been found to encounter small soluble antigens from the lymphatic fluid as they diffuse from the subcapsular sinus (SCS) to the follicles55. Large antigens, immune complexes and viruses can be presented to follicular B cells at the macrophage- rich SCS64,67,68. In addition, follicular B cells may recognize antigen that is presented on the surface of follicular dendritic Nature Reviews | Immunology cells (FDCs). b | Snapshot of a video that was generated using multiphoton intravital microscopy on the popliteal lymph node. The solid line identifies the position of the SCS. A magnified view of antigen–B-cell conjugates is shown, in which conjugates appear yellow as a result of the merge of the red antigen-specific B cells and green antigen (P. Barral and F. B., unpublished observations). c | Schematic view of the paracortex to illustrate where antigen-specific B cells encounter antigen at this site. B cells entering the lymph node can encounter unprocessed antigen on the surface of resident or recently migrated DCs, in close proximity to the high-endothelial venules (HEVs)73,77–79. The conduit system, which is lined with FRCs and DCs, transports low-molecular-mass components of the lymphatic fluid through the lymph node; B cells and T cells have been shown to migrate in association with the FRC network49. BCR, B-cell receptor; C3, complement component 3; CR, complement receptor; DC-SIGN, DC-specific ICAM3-grabbing non-integrin; FcR, Fc receptor; ICAM3, intercellular adhesion molecule 3; MAC1, macrophage receptor 1. Metallophilic macrophage protein that contains domains of the mannose receptor, intact antigen on their cell surface 56,58. Indeed, these A macrophage that is located it has been suggested that they may capture and concen- macrophages have been shown to capture and retain at the border of the white pulp trate antigen in a similar way to metallophilic macrophages antigen for up to 72 hours following the initial antigen and the marginal zone of the that reside in the splenic marginal zone59–61. exposure62. However, whether this involves the simple spleen. These macrophages express high levels of CD169 The macrophages in the subcapsular sinus are a dis- retention of antigen on the macrophage surface or anti- but lack expression of the tinct population to those in the medulla and have lim- gen internalization into non-degradative intracellular mannose receptor. ited phagocytic activity, which enables them to present compartments before it is recycled to the cell surface 20 | jAnuARy 2009 | vOluME 9 © 2009 Macmillan Publishers Limited. All rights reserved
  7. 7. REVIEWS Table 1 | Cell-surface molecules that are implicated in presenting antigen to B cells Presenting cell Receptor Antigen presented Presentation strategy Macrophage MAC1 Complement-coated antigen Remains on the cell surface FcγRIIB IgG-coated antigen Internalized in neutral endosomes and recycled? DC-SIGN Carbohydrate-containing antigen Internalized in neutral endosomes and recycled? DC FcγRIIB IgG-coated antigen Internalized in neutral endosomes and recycled? DC-SIGN Carbohydrate-containing antigen Internalized in neutral endosomes and recycled? FDC CR1 and CR2 Complement-coated antigen Remains on the cell surface FcγRIIB IgG-coated antigen Internalized in neutral endosomes and recycled? Marginal-zone CR1 and CR2 Complement-coated antigen Remains on the cell surface B cell Follicular B cell CR1 and CR2 Complement-coated antigen Remains on the cell surface FcγRIIB IgG-coated antigen Internalized in neutral endosomes and recycled? CR, complement receptor; DC, dendritic cell; DC-SIGN, DC-specific ICAM3-grabbing non-integrin; FcγRIIB, low-affinity Fc receptor for IgG; FDC, follicular DC; ICAM3, intercellular adhesion molecule 3; MAC1, macrophage receptor 1. is not clear. In addition, macrophages are known to this virus68. Furthermore, as the retention of antigen was express a wide range of cell-surface receptors that not impaired following the depletion of C3, complement- could participate in the presentation of unprocessed independent mechanisms might also contribute to the antigen, including complement receptors, pattern- maintenance of antigen on the macrophage surface68. recognition receptors and/or carbohydrate-binding The accumulated antigen is subsequently presented scavenger receptors63 (TABLE 1). Indeed, macrophage in its intact form by macrophages for recognition by receptor 1 (MAC1; also known as αMβ2 integrin neighbouring follicular B cells. Accordingly, following and CD11b–CD18 dimer), which is a receptor for administration of antigen, it was shown that antigen- complement component 3 (C3) that is expressed by specific B cells in the follicle exhibited reduced migration macrophages, has been suggested to contribute to the over time and made stable contacts with macrophages retention of antigen on the cell surface64. Alternatively, in the subcapsular sinus64,67,68. As ICAM1 and vCAM1 the inhibitory low-affinity receptor for IgG (FcγRIIB) are expressed in the subcapsular sinus68, it is expected might mediate the internalization and recycling of IgG- that they may facilitate B-cell adhesion in this region and containing immune complexes to the macrophage cell thereby lower the threshold of antigen that is required surface, as has been shown in DCs65. Finally, the C-type for B-cell activation13,69. Together, these studies provide lectin DC-specific ICAM3-grabbing non-integrin the first clear demonstration of a role for macrophages (DC-sIGn; also known as CD209) could participate in the initiation of follicular B-cell responses. The macro- in the retention of glycosylated antigens, which is con- phage–B-cell interactions at the subcapsular sinus allow sistent with the observation that mice deficient in the antigen-specific B cells to acquire and internalize antigen mouse homologue of DC-sIGn, sIGnR1, fail to mount through their BCR before their migration to the B-cell– humoral immune responses following infection with T-cell boundary 67, where they may receive specific T-cell Streptococcus pneumoniae66. help48,70 (BOX 2). Interestingly, it has recently been noted A crucial and newly described role for subcapsular- that the response of B cells and CD4+ T cells to large viral sinus macrophages in the presentation of antigen to particles is deterministically linked to their antigen spe- follicular B cells has been recently established by three cificities71, suggesting that antigen uptake by the B cell independent studies64,67,68. These studies identified that, may not involve internalization of whole viral pathogens soon after antigen administration, subcapsular-sinus at the subcapsular sinus. macrophages are responsible for the rapid accumula- tion of various larger antigens, such as those found in DC-mediated presentation. B cells enter the lymph node immune complexes (with antibody and/or complement through the HEvs, so the paracortex would seem the ideal fragments), particulates, bacteria and viruses (FIG. 2a,b). site for the immediate presentation of antigen to these These macrophages might favour the retention of anti- cells. Furthermore, this region contains both resident DCs gen on their surface through their expression of sul- in close association with FRCs and recently migrated phated glycoproteins, such as CD169, and the lack of DCs that have collected antigen from peripheral tis- expression of the mannose receptor, which is usually sues. DCs are widely considered to be the most efficient Clodronate-loaded liposome associated with phagocytosis of opsonized antigen68. professional antigen-presenting cells and therefore are A liposome that contains the Depletion of macrophages, including those in the sub- particularly important for the presentation of peptides drug dichloromethylene capsular sinus and the medulla, through treatment with in a complex with MHC molecules to naive T cells72–74. diphosphonate. These clodronate-loaded liposomes rendered mice unable to However, B cells recognize antigen in its unprocessed liposomes are ingested by macrophages, resulting in capture and retain vesicular stomatitis virus at the sub- native state, and consequently presentation to B cells cell death. capsular sinus, resulting in systemic dissemination of would necessitate a mechanism whereby DC-accumulated nATuRE REvIEws | Immunology vOluME 9 | jAnuARy 2009 | 21 © 2009 Macmillan Publishers Limited. All rights reserved
  8. 8. REVIEWS antigen is either stably displayed on the cell surface or is FDC-mediated presentation. Classically, FDCs have resistant to intracellular degradation65,75 (TABLE 1). Indeed, been considered to be the cells that are mainly respon- it has been shown that FcγRIIB can mediate the intern- sible for antigen presentation to B cells in slOs. Early alization of antigen-containing immune complexes into autoradiography analysis combined with high-resolution non-degradative intracellular compartments65, and it electron microscopy showed that extracellular antigen in has also been suggested that DC-sIGn might allow the a plasma-membrane-associated form is retained in the accumulation of intact antigen in neutral endosomes in follicles for prolonged periods after immunization51,84. DCs. Concomitant with this hypothesis, sIGnR1 has subsequently, it was established that FDCs in the fol- been implicated in the internalization of HIv-1 into a licles are responsible for mediating the retention of anti- non-lysosomal compartment of DCs and the subsequent gen in the form of immune complexes26,85,86. In addition delivery of intact HIv-1 virions to slOs76. to their role in antigen retention and presentation, it is A population of DCs in the paracortex that can known that FDCs function as potent accessory cells dur- present intact antigen to B cells has been identified77–79. ing B-cell activation, possibly through mechanisms that A detailed characterization of this DC population by involve the secretion of chemokines and/or the expres- intravital multiphoton microscopy showed that these sion of FcγRIIB87. cells are mainly located around HEvs so that migrat- The distinctive phenotype of FDCs supports the ing B cells can survey their antigenic contents79 (FIG. 2c). retention of immune complexes in the follicles through Following the administration of antigen-loaded DCs two different mechanisms (TABLE 1). The first mechanism to mice, recently migrated antigen-specific B cells depends on the complement system85,88,89. FDCs express show decreased motility and an increase in their resi- high levels of complement receptor 1 (CR1) and CR2 dency time on DCs. Interestingly, these DCs retained (also known as CD35 and CD21, respectively), which the capacity to stimulate B cells following treatment bind to various fragments of C3. Chimeric mice that lack with pronase (a mixture of proteinases) to remove cell- expression of CR1 and CR2 in the radioresistant stromal- surface-exposed antigen, suggesting that DCs can inter- cell compartment (including FDCs) cannot deposit nalize and then recycle intact antigen to their cell surface. antigen on the surface of FDCs90,91, and FDCs from mice The DC-mediated presentation of antigen to B cells that are unable to produce CR2 ligands cannot present in the paracortex is the ideal environment in which to antigen to B cells92. receive the necessary T-cell help for their maximal acti- The second mechanism of antigen deposition involves vation79. In support of this, DCs, B cells and T cells have the retention of immune complexes that contain IgG fol- been shown to colocalize in this region of the lymph lowing their binding to Fc receptors, such as FcγRIIB, node50. This DC-mediated activation of B cells may that are expressed on the surface of FDCs in germinal give rise to extrafollicular plasma cells that mount early centres28,93. Consistent with this, FcγRIIB-deficient mice antibody responses to antigen. Alternatively, following show severely reduced trapping of immune complexes in activation by CD4+ T cells, B cells might migrate to the the lymph node and spleen, and FcγRIIB-deficient mice follicle and mediate germinal-centre formation. It will that were reconstituted with wild-type, antigen-specific also prove valuable to characterize the in vivo dynamics lymphocytes exhibit severely impaired recall responses of a population of mannose-receptor-binding DCs that to immune complexes28. accumulate soluble antigen in the follicles and present it Deposition of antigen on the surface of FDCs through Endosome to follicular B cells80. either or both of these mechanisms would therefore be A vacuolar compartment Technical constraints have limited the application expected to increase the initiation of immune responses. where large molecules are transported after being of intravital multiphoton microscopy in the study of Indeed, preformed immune complexes58,94 and antigen engulfed by endocytosis. The lymphocyte dynamics in the spleen. However, as the con- coated with C3d fragments95 are both associated with the endosome can then mature duit system in the white pulp36 and the core organization stimulation of B-cell activation, potentially as a result of and fuse with lysosomes, which of B- and T-cell zones in the spleen are similar to those increased deposition of antigen on the surface of FDCs96. contain degrading enzymes. in the lymph node, the mechanisms of antigen presen- Furthermore, following their binding to antigen, natural Endosomal and phagosomal pathways are interconnected. tation to B cells might be similar in both tissues. The IgM antibodies that are produced mainly by peritoneal splenic marginal-zone B-cell population has been shown B-1 cells97 induce the formation of immune complexes B-1 cell to rapidly produce antibody in response to blood-borne and accelerate the deposition of antigen on the surface An IgMhiIgDlowMAC1+ antigen, and therefore these cells have an important role of FDCs27. Mice with a targeted deletion in the carboxy- B220lowCD23– cell that is dominant in the peritoneal and in the initiation of early immune responses81. However, terminal tail of IgM fail to express serum IgM and show pleural cavities. B-1-precursor the participation of marginal-zone B cells at later stages delayed humoral immune responses, suggesting a role cells develop in the fetal liver of the immune response has been less well character- for FDCs in the initiation of immune responses98,99. and omentum, and in adult ized. static in vitro imaging approaches have been used Despite the ability of FDCs to present unprocessed mice the size of the B-1-cell to study DC-mediated antigen presentation to splenic antigen, the importance of this pathway for the activation population is kept constant owing to the self-renewing marginal-zone B cells82 and have shown that this activa- of naive B cells during the initiation of primary immune capacity of these cells. B-1 tion leads to the rapid generation of plasma cells that responses, as well as its underlying mechanism, have yet cells recognize self produce IgM independently of T-cell help, allowing for to be firmly established. Interestingly, it has been postu- components, as well as the rapid and enhanced formation of antigen-containing lated that FDCs may be particularly important for the common bacterial antigens, and they secrete antibodies immune complexes. Intriguingly, a population of B cells presentation of microbial antigens, in response to which that tend to have low affinity with similar characteristics to marginal-zone B cells has pre-existing natural IgM antibodies could facilitate the and broad specificity. been detected in human lymph nodes83. rapid formation of immune complexes, thereby resulting 22 | jAnuARy 2009 | vOluME 9 © 2009 Macmillan Publishers Limited. All rights reserved
  9. 9. REVIEWS in microbial-antigen presentation by Fc receptors on the to antigen retention, FDCs might have another role surface of FDCs100. However, it is known that FDCs in during affinity maturation109. However, these studies primary follicles do not express high levels of FcγRIIB28 did not exclude the possibility that competition among and therefore this receptor cannot have an important B cells for antigen could have a role in the selection of role in antigen retention and presentation during the high-affinity B-cell clones in the germinal centre. In initiation of immune responses. view of this, it would prove extremely informative to FDCs can also act as antigen ‘depots’ in the slOs characterize the spatio-temporal dynamics of cells that such that they can present antigen even after the initial retain antigen within immune complexes, which would ‘wave’ of antigen has passed26–28,101. This is important establish the precise role of deposits of antigen on FDCs for the development of an effective and long-lasting during the process of affinity maturation. immune response, as the initial encounter of antigen with naive B cells in the slOs is likely to be of low How does antigen gain access to FDCs? As a consequence affinity. under these conditions, activated B cells then of the role of FDCs in mediating antigen presentation to enter germinal centres, where they undergo affinity B cells, much effort has been invested in addressing the maturation17. This process allows the selection of B-cell apparent anomaly of how antigen in the form of immune clones with higher affinity for antigen during a T-cell- complexes can gain rapid access to FDCs, which are con- dependent antibody response and starts a few days after fined to the B-cell follicles. As the subcapsular sinus and the initiation of the response. the conduit system restrict the diffusion of large antigens The classic model that described the mechanism of from the lymphatic fluid, a cell-mediated mechanism antigen presentation to B cells in germinal centres was must operate to transport antigen to FDCs. based on several biochemical and histological observa- In the spleen, marginal-zone B cells have been impli- tions. In this model, the germinal centre was divided cated in this process59,110 (FIG. 3a). The location of B cells into two functionally distinct zones17. The dark zone in the marginal zone makes them ideally positioned was thought to contain centroblasts and to be the site to sample and mount rapid responses to blood-borne of rapid B-cell proliferation, whereas the FDC-rich light antigen. Indeed, displacement of these B cells by treat- zone functioned as the site for the selection of B-cell ment with endotoxins, such as lipopolysaccharide, was clones that express BCRs of the highest affinity follow- accompanied by impaired accumulation of immune ing somatic hypermutation. Recently, three independent complexes on the surface of FDCs in the follicles59,111,112. studies examining the spatio-temporal dynamics of Moreover, it has been shown that the accumulation of B cells have questioned the original model and the abso- IgM-containing immune complexes on FDCs was abro- lute ‘division of labour’ between the two zones of the gated in the absence of functional marginal-zone B cells. germinal centre102–104. Interestingly, each of these studies This suggests that marginal-zone B cells facilitate the showed that 6 days after antigen administration B cells adjuvant activity of IgM113. moved rapidly within the germinal centre, which indi- Marginal-zone B cells express complement receptors cated they did not make prolonged contacts with antigen (TABLE 1), and these may be important for their function presented on the surface of FDCs. It was therefore sug- in transporting antigen to FDCs. Indeed, early investi- gested that the mode of antigen recognition by B cells gations using cobra venom factor and antibodies against occurring during the later stages of an immune response C3 showed that the transport of immune complexes may operate differently to that observed during early from the marginal zone to the FDCs depends on com- antigen encounters. Indeed, these studies showed that ponents of the complement system85,89,114. In the absence germinal-centre B cells adopted an unusual morphology of CR2 expression by marginal-zone B cells, immune with many extended processes102–104. These processes complexes were associated predominantly with macro- may be responsible for mediating antigen internaliza- phages in the marginal zone, as the B cells failed to tion as the B cells migrate along the surface of the FDCs. transport antigen to the FDCs115. The mechanism by under antigen-limiting conditions, B cells expressing which marginal-zone B cells transport antigen from the Somatic hypermutation BCRs with higher affinity can accumulate more antigen marginal zone to the follicles was revealed by a recent (SHM). A unique mutation and consequently compete more effectively to recruit study involving the treatment of chimeric mice with the mechanism that is targeted specific T-cell help for their development, with only sphingosine 1-phosphate receptor 1 (s1PR1) antagonist to the variable regions of the highest affinity clones being selected for survival FTy720 (REF. 116). Marginal-zone B cells were found to rearranged immunoglobulin gene segments. Combined with in the germinal centre102,105. However, it is important to continually shuttle to and from the follicles in a process selection for B cells that note that CD4+ T cells reside exclusively within the light that depended on the expression of CXC-chemokine produce high-affinity antibody, zone, so the complete absence of functional segregation receptor 5 (CXCR5) and s1PR1, respectively. As mar- SHM leads to affinity in the germinal centre is unlikely. ginal-zone B cells can bind immune complexes through maturation of B cells in Antigen presentation by FDCs through binding of CR1 and CR2, this shuttling process could be the way germinal centres. immune complexes to FcRs or complement receptors may in which antigen is effectively delivered from the blood Cobra venom factor be important for the development of high-affinity antibody to FDCs. Interestingly, it has been postulated that the The complement-activating and long-lasting memory responses106. surprisingly, how- actual transfer of immune complexes from marginal- glycoprotein component of ever, the process of affinity maturation and the survival zone B cells to FDCs occurs through proteolysis of CR2 cobra venom, which is functionally analogous to the of memory B cells, although impaired, can occur in the on the surface of the marginal-zone B cells117. However, mammalian complement absence of detectable antigen deposition on FDCs107,108. it is not known whether marginal-zone B cells can pass factor C3b. This observation led to the hypothesis that in addition free antigen directly to follicular B cells. nATuRE REvIEws | Immunology vOluME 9 | jAnuARy 2009 | 23 © 2009 Macmillan Publishers Limited. All rights reserved
  10. 10. REVIEWS similarly, it has been suggested that follicular B cells Conclusions and perspectives themselves function as antigen transporters in the lymph Overall, it is clear that B cells can respond rapidly to nodes and spleen89,118 (FIG. 3b). This activity does not antigenic stimulation through several mechanisms, and depend on antigen-specific recognition and therefore they also have a unique strategic role in the transport is mediated by receptors other than the BCR (TABLE 1). of antigen to FDCs in the germinal centre. This wide It has been proposed that antigen can be acquired by variety in potential antigen-presentation mechanisms is other follicular B cells in the absence of antigen-specific promoted by functional specialization within slOs and B cells64,67, and this may depend on the expression of provides invaluable flexibility in mounting appropriate complement receptors on the B-cell surface64. As FDCs immune responses to antigens. As such, the mechanism express higher levels of complement receptors than that is used to present a specific antigen can be effec- follicular B cells, it would be expected that they could tively tailored both to the antigen itself and to the way compete effectively with B cells for antigen binding 27. the antigen is delivered to the B cell. The predominance It remains to be determined whether other receptors of of cell-based strategies for the presentation of antigen to the innate immune system have a role in the transport B cells allows for extensive regulation and coordination of antigen by B cells within slOs. CD23+ mature B cells of the resulting immune responses. have in fact been shown to mediate the transport of In spite of significant recent progress in character- IgE-containing immune complexes into the follicle in a izing the sites and dynamics of antigen presentation BCR-independent manner 119. Although such a situation to B cells in vivo, some issues remain to be addressed. is unlikely to occur in physiological conditions, it does These include a definitive molecular description of the indicate that alternative receptors might be involved in mechanisms of antigen presentation to B cells, includ- antigen transport. ing the retention and internalization strategies that are a Splenic marginal-zone B cells transport antigen to FDCs b Follicular B cells in the lymph node transport antigen to FDCs S1Phi Immune Marginal zone Subcapsular sinus CXCL13low complex SCS macrophage C3 fragment CR Antigen FcR non-specific DC-SIGN BCR Marginal-zone B cell Follicular B cell ? ? Follicular dendritic cell S1Plow CXCL13hi Primary follicle Primary follicle Figure 3 | B cells mediate antigen transport to follicular dendritic cells using complement receptors. a | Marginal-zone B cells in the spleen can bind to immune complexes that contain antigen and are coated in complement fragments, using complement receptors (CR) in a manner that is independent of B-cell receptor (BCR) specificity. These Nature Reviews | Immunology marginal-zone B cells can shuttle to the follicular region, which is rich in CXC-chemokine ligand 13 (CXCL13), in a CXC- chemokine-receptor-5-dependent manner116. Follicular dendritic cells (FDCs) in the follicle, which express high levels of CR, can then compete for binding to antigen that is presented by marginal-zone B cells. The marginal-zone B cells then migrate back to the marginal zone, where there are high levels of sphingosine 1-phosphate (S1P), and this depends on their expression of the receptors for S1P1 and S1P3. b | Follicular B cells in the lymph node can bind to particulate antigen on the surface of subcapsular sinus (SCS) macrophages. This binding does not depend on the specificity of the BCR and is mediated by CRs. It has been suggested that these follicular B cells can then mediate the transport of antigen to FDCs, which express higher levels of CRs64,67. C3, complement component 3; DC-SIGN, DC-specific ICAM3-grabbing non-integrin; FcR, Fc receptor; ICAM3, intercellular adhesion molecule 3. 24 | jAnuARy 2009 | vOluME 9 © 2009 Macmillan Publishers Limited. All rights reserved


Artillery: Israel Replaces 155mm Guns With Smart Rockets

February 13, 2012:  Israel has decided to replace its four decade old M109 155mm self-propelled armored artillery vehicles with guided rockets. This comes a year after deciding that the M109s could not be refurbished and upgraded anymore and would have to be replaced. At first, other artillery systems were examined. But then it was remembered that two years ago Israel had accepted that the U.S. use of GPS guidance in rockets, while more expensive, was more effective than the cheaper (but less accurate) Israeli developed rocket guidance system and even cheaper unguided artillery shells. So now the M109s are being replaced with guided rockets.

This radical shift in artillery weapons has been coming since the 2006 war with Hezbollah, when the Israelis found that they did little damage to Hezbollah bunkers, even though over 120,000 unguided 155mm shells were fired (mostly by M109 guns) at them. Meanwhile, they noted that the U.S. 227mm MLRS rockets with GPS guidance was excellent at taking out similar targets in Iraq and Afghanistan. So Israel equipped its 160mm Accular rockets with GPS. These 110 kg (242 pound) rockets have a range of 40 kilometers and enable one bunker to be destroyed with one rocket.

Israel always recognized the superiority of GPS in some situations. For example, Israel developed LORA (Long Range Artillery Rocket) which is similar to the U.S. ATACMS. Each LORA missile weighs 1.23 tons and carries a half ton warhead. With a range of 300 kilometers, GPS guidance is used to land the warhead within 10 meters (31 feet) of the aim point. These missiles are expensive. The similar U.S. ATACMS, which is fired from a MLRS container that normally carries six of the standard MLRS rockets, cost a million dollars each. It's often a lot cheaper if you can use smart bombs (which cost less than $50,000). But if you don't have aircraft up there, or control of the air is contested, you can get a LORA missile on a target within ten minutes of the order being given.

Israel expects to replace a lot of artillery shells, air delivered missiles, and bombs with its GPS guided rockets and take out more targets with far fewer rockets and artillery shells.

Article Archive


The coordinate plane

We use coordinates to describe where something is. In geometry, coordinates say where points are on a grid we call the "coordinate plane".

Coordinate plane

We first explored the coordinate plane in the 5th grade. But that was only dealing with positive coordinate. Now, however, we know all about negative numbers so why not have negative coordinates as well! Common Core Standards: 6.NS.C.6, 6.NS.C.6b, 6.NS.C.6c, 6.NS.C.8


- this week

Gender: F Meaning of Minerva: "of the mind, intellect" Origin of Minerva: Latin

Minerva Pott is a character in Dickens's novel . In Harry Potter, Minerva McGonagall is a Witch and Deputy Headmistress of Hogswarts, and in the Artemis Fowl books, Minerva Paradizo is equally intellectual. There's also a series of kids' mystery books centering around a Minerva Clark.

Minerva was a Top 500 name through the early 1920s, dropping off the list in 1973/ It's well liked on Nameberry though--currently at Number 297. Nickname Minnie fits right in with the other currently stylish vintage nickname names. Curiously, though, actress Minnie Driver was not born Minerva--but Amelia.

Famous People Named Minerva

Minerva Urecal, American actress
Minerva Teichert, American painter
Minerva Josephine Chapman, American painter
Minerva Cuevas, Mexican conceptual artist
Minerva Parker Nichols, American architect
Minerva Pious, American actress
Minerva Mendez, American actress

Pop Culture References for the name Minerva

Minerva, Roman goddess of wisdom
Minerva "Min" Green, main character in "Why We Broke Up" by Daniel Handler
Minerva McGonagall, character in the Harry Potter series
Minerva Clark, main character in the book series by Karen Karbo
Minerva Louise, chicken from the children's book series by Janet Stoeke
Minerva, ugly stepsister in Rodgers and Hammerstein's "Cinderella"
Minerva Mink, character in animated series "Animaniacs"
Minerva "Mini" McGuinness, character on TV's "Skins"
Owl of Minerva, symbol used by the Illuminati

Merva, Myna, Minnie, Min, Minivera

Minerva's International Variations

Minerve, Minette (French) Minetta (Spanish)


The Playroom: Where Things Almost Happen

The Playroom is one of those films that you hope has that dramatic edge to carry toward a wider release, but disappointingly believes too much in itself and fizzles quickly into the eye glazing over dream state that sometimes accompanies a non-ballyhooed indie February release.

The uncomplicated story hovers around the four Cantwell children coping with yet another night entertaining themselves in the playroom while their parents Martin (John Hawkes) and Donna (Molly Parker) have an “adult party” downstairs with their neighbors. Over the course of an hour and a half nothing happens until the end when something almost happens but then it doesn’t.  I suppose the plot was subtle, quiet, elusive, something, something, something artsy words. I was rolling my eyes two minutes in and I couldn’t stop until I was thanking the final credits.

I really checked out twenty minutes in when the inciting incident was supposed to happen, and then didn’t. Rather, a contrived family dinner scene occurred that played out like the first night of rehearsal of a senior thesis play, with each actor waiting to deliver their line and laugh-tracking at each poorly timed grossly un-funny joke meant to break up the non-existent tension. Other than some blatant foreshadowing occurring, where each child speaks about “where they would go on an adventure” (Setting up the stories that each child tells the others to entertain themselves while their parents frolic downstairs) nothing of consequence happened in the “pivotal” scene that was supposed to set the mood for act two. A strong story happened before the events shown in this film, and a strong story probably happened sometime after. The filmmakers decided to show us a story that almost happened, as if we were watching a bunch actors milling around a soundstage waiting for another scene to be set up. Just as the scene is well lit and sound is rolling, the film cuts away and leaves us guessing, “What could have happened?”

A majority of the story flipped back and forth from the oldest child Maggie’s (Olivia Harris) perspective from existing upstairs as a parent figure for her siblings, and downstairs a therapist for her parents. Each time she went upstairs a chunk of intended dialogue occurred, stories between the siblings, and each time she went downstairs the story did not progress to anything substantial. Instead, we were once again treated to a scene in which Donna blatantly flirts with their neighbor Clark (Jonathan Brooks) and Martin slowly gets less and less oblivious to it. It’s blasphemy to criticize the plot point choices of a writer more successful than myself, but perhaps another trained screenwriter could have taken the events of the entire film and condensed them into an act one, leaving the rest of the film to show the aftermath in dramatic rising and falling action.

Individually the performances of the actors in the film were above respectable, but their chemistry with each other was sub-par at its best. The semi-palpable dissention between Hawkes and Parker as they dealt with the lingering aura of Dolly’s obvious yet somehow “surprising” affair carried the film. The relationships between the cookie-cutter stock characters of the Cantwell children were paint-by-numbers, although the acting effort was definitely there. Perhaps the direction could have been better, but frankly there wasn’t much dramatic action for the young actors to work with.

I have a strong suspicion the film may have been drawn from some autobiographical source, as The Playroom fiddled with the machinery of a large family dynamic, and was coincidentally produced by one. Of the Dyer siblings, Julia directed, Stephen produced, and Gretchen wrote. Sadly screenwriter Gretchen Dyer passed away in 2009 before she could really take flight, because she probably could have had a promising career as a novelist. Her screenplay dealt a lot with inner tension and the caustic family dynamic of a disconnected family growing up in the 1970’s. If I were reading a novel or watching a stage play, I might have enjoyed the poignant yet understated family drama. However, as a film it had very little impact due to its lack of payoff and slow nature. The inner writer slash editor slash director in me kept shouting “Faster!” “Cut that!” “Cut that!” “Faster!” “Step on her line!” “Somebody do something… anything!”

The Playroom is in very few theaters this weekend for a reason. Several indie film aficionados will strongly disagree with me, and perhaps I watched the film under the wrong circumstances. Maybe the lighting was bad. Or I was hungry. I’m searching for more excuses, but as the credits rolled I couldn’t help thinking how much I needed to pack more dramatic action into my own screenplays if I ever hope to produce a film as frustrating as this one.


Homefront: The Revolution

| |
Release Date: May 17, 2016

Homefront 2 Wiki Guide

Edit Page    Last Edit: 10 days 3 hours ago
17 May 2016 Xbox One, PS4, PC
Developer Publisher
Crytek Studios UK
Deep Silver
Official Sites
Official Site

Homefront: The Revolution in development by Crytek UK (the TimeSplitters developers, not the Ryse or Crysis developers) is taking the series in a decidedly different gameplay direction. In The Revolution, Crytek UK promises an open-world romp through Philadelphia, where the Korean People’s Army has been oppressing the citizens of Philadelphia for four years, and you as an average-Joe member of the American resistance decides to fight back.

The game was announced at the begining of June 2014 leading up to E3 2014.

Homefront: The Revolution is a free-roam first person shooter where you must lead the Resistance movement in guerrilla warfare against a superior military force. A sprawling city responds to your actions - you and your Resistance Cell can inspire a rebellion on the streets and turn Occupation into Revolution, as oppressed civilians take up the fight.

in Co-Op you and three other players can form your own Resistance Cell and become renowned as Heroes of the Revolution.

Her once-proud citizens live in a police state, forced to collaborate just to survive, their dreams of freedom long since extinguished.But in the badlands of the Red Zone, in the bombed out streets and abandoned subways, a Resistance is forming. A guerrilla force, determined to fight for their freedoms despite overwhelming odds and ignite the second American Revolution.

EditHomefront: The Revolution Sections


Partner Series
What Is an Herbivore?
Herbivores eat only plants, but can be very picky.
Credit: stock.xchng

Herbivorous animals are vegetarians. They only eat plants.

Herbivores can be very picky eaters. Scientists group these creatures by the parts of plants the herbivore eats.

Frugivores only eat fruit. Folivorous birds feed on leaves. Nectivorous bats suck on nectar. Granivorous insects munch on seeds whereas polynivorous ones prefer pollen.

When the weather changes, however, herbivores often have to alter their diets to feed on whatever plant food is in season.

The teeth of herbivores have adapted to chew the tough fibers of plants. Their big molars grind up seeds and twigs. Special stomach chambers in some herbivores, such as cows and moose, are called rumen. The rumen contains microorganisms that break down the cellulose in grass so that the animal can collect as much energy as possible from the food.


Academic journal article Magistra

Ancrene Wisse: A Modern Lay Person's Guide to a Medieval Religious Text

Academic journal article Magistra

Article excerpt

This paper is, in part, an account of a personal journey; I approached the study of Ancrene Wisse from a training in modern literature and philosophy via study of feminist critical study. How was a late twentieth century feminist agnostic to deal with a thirteenth century text written initially for the guidance of three sisters who were leading a religious life in solitude? How could I give a modern lay person's reading of a medieval religious text?

In order to formulate an approach to a coherent reading, I had first to clarify the terms that would be used. The two major problems encountered, those of definition and anachronism, were, I realized, interlinked. Terms I was dealing with, such as "spirituality" and "lay," had to be understood in the historical context in which they (or their Middle English/Latin equivalent) were used, while other terms, most notably "misogyny," were anachronistic and as such had no historical context.

While it may not always be possible to follow the exhortation of John Bossy that "a historian writing about an earlier period should not use a key word, such as religio, except in the sense it had in the period about which he is writing,"(1) it is often useful to look at the way key terms were used in the period in question. Jacques Le Goff points out that "Every idea is embodied in words, and every word reflects some reality. The history of words is history itself."(2)

An investigation of terms used can provide an insight into the text being read. What is meant by "text," is, of course, also problematic especially when, as with Ancrene Wisse, the original version is no longer extant and the versions that do exist exhibit variations. It is a modern prejudice that the "original" version, or that which most closely conveys the author's intentions, is the "best" in some quasi-moral sense. Bella Millett, herself in the final stages of preparing an edition of Ancrene Wisse, is not attempting to produce a "reconstructed definitive authorial version," but rather to come to terms with mouvance, that is, the "textual instability or fluidity." She points out that:

Editors have been preoccupied with the loss of "une authenticité perdue" the hypothetical perfection of the completed work as it left the author's hands, rather than coming to terms with the "une authorité generalisée" of medieval vernacular works which might be revised and rewritten indefinitely, both by their original authors and by others.(3)

The variability and complexity of Ancrene Wisse needs to be kept in mind in any reading of it. Readers also needs to be clear about the sort of category in which they are placing it in any reading. Categories tend to be supplied by the departmentalized structure of academic studies, a structure which can be at best unhelpful and at worst damaging. There has recently been a move towards cross-disciplinary study, but in the case of reading a medieval work such as Ancrene Wisse, the desire to compartmentalize, or put things in boxes and label them so they can be more easily handled, remains. What sort of thing is Ancrene Wisse? Into what sort of box can it be put? Is it to be studied as literature or as history? Is it misogynistic? Is it mystical?

Ancrene Wisse has traditionally been studied by English students as an example of early Middle English prose, as literature that is, but now many historians turn to it for evidence of anchoritic lifestyles in the Middle Ages. In his 1997 study of the current state of Ancrene Wisse group studies, Roger Dahood points out that the study of Ancrene Wisse and its associated works is on the rise among historians and literary critics with particular interests in the roles of women in late twelfth and early thirteenth century English society.(4) But what would it mean to study Ancrene Wisse as literature?

When this author was first studying literature at university in the late 1970s, literature departments were still under the influence of New Criticism. …

Author Advanced search


Belgian Nuclear Society

Dear BNS-member, Dear Visitor,

At the end of last year, France was hosting and presiding the 21st session of the Conference of the parties to the United Nations Framework Convention on Climate Change (COP21/CMP11). Within this crucial conference, a new international agreement, pledged by more than 180 countries, was achieved, with the aim of keeping the increase in global temperatures well below 2°C.

Climate change remains thus a “hot” and societal topic. Energy politics is a key element in this frame.

In order to keep up with the pledge of COP21, the scientific community must support every technology which limits the carbon footprint and allows energy efficiency for a sustainable energy future available to everyone. It is therefore important for a scientific society such as the BNS to play a role in the debate around energy, as nuclear energy remains a key player all over the world and can in our opinion provide safe, clean and reliable energy.

The BNS is delighted to have one of the most recognized experts in the field of climate change: Prof. Em. André Berger will enlighten us on this topic during the Evening Lecture of April.

We sincerely hope to meet you on the occasion of this Evening Lecture!

BNS Corporate Members 2015_Banner1

Roger Schène, Chairman of the Belgian Nuclear Society

The Fukushima accident and its multiple consequences created a significant and renewed interest among the population to better understand nuclear sciences and applications, their associated risks and their potential future developments. Our mission at the BNS is to try to give you access to a set of information as complete and as diversified as possible about various aspects of peaceful applications of Nuclear Energy.

We are willing to provide detailed relevant scientific information for nuclear specialists from Belgium industries, universities and research centers but also to the public including schools, teachers, researchers which have their own question marks about nuclear applications and nuclear sciences in general. As you know, nuclear sciences are very broad and include already many applications as well as many ongoing developments full of hope for many medical domains. Nuclear sciences include obviously but are not limited to design, construction and operation of nuclear plants.

The Belgian Nuclear Society has an important role to play today: from expressing thoughts to writing papers and organizing lectures and conferences. Our monthly Evening Lectures contribute to create a dialogue between experts and the public. This allows for having a direct contact with some of our best nuclear Belgian experts and raising the questions you might have. You will find more information on the upcoming Evening Lectures in the Activities section of our website.

Thank you for your visit and do not hesitate to contact us should you have any questions related to nuclear sciences.


•Plan, execute and evaluate events •Manage and utilize resources effectively •Strengthen teamwork and employ/ utilize everyone’s unique capacities •Continuously educate members on a variety of skills

Welcome to Sigma Alpha Delta's Alumni Database. Explore the lives of our illustrious alumni. Find out who they are, where they came from, where they're going, and how Sigma Alpha Delta played a role in their personal and professional development.

To get started, start typing a name in the search box below. You can also select a year, letter, or period to browse all biographies for that period or letter. Biographies are sorted by last name.


Pell, ‘a celebrity who knows nothing about RI needs’

My take on the news

LET’S STOP VOTING FOR A FAMILY NAME: Clay Pell, the 31-year old grandson of the Rhode Island’s late U.S. Senator Claiborne Pell, has indicated that he may seek the Democratic gubernatorial nomination in 2014. Pell is probably a very nice young man. Further, he may have many admirable qualities that would serve him well in political office. However, his primary asset is his name; and names should not trump merit!

Pell is nothing more than a celebrity because of his name, his marriage to Olympic skating star Michelle Kwan, and because his political name got him an Obama appointment to a third-tier position in the U.S. Education Department. He is also a Coast Guard Reserve officer.

Pell is one of thousands of very good Coast Guard Reserve officers; so that’s no qualifying experience to become governor. More important, young Pell is no Gina Raimondo. He’s no Allan Fung. He’s no Angel Taveras. And, he’s no Kenneth Block. He’s only a famous name, a celebrity who knows nothing about Rhode Island’s needs. He’s not someone who deserves consideration to be our next governor, so let’s stop talking about it.

It’s high time we stopped voting for candidates simply because of their family names. We’ve had enough Kennedys, Bushes, and other political dynasties. In the state founded on principles of individual merit, selection of our leaders should be made purely on just that - merit.

TAVERAS AND DAVEY LOPES SWIMMING POOL: Providence Mayor Angel Taveras has hit a snag among those voters most likely to support him in his likely gubernatorial bid in 2014. It’s the minority community that has been served for decades by the Davey Lopes swimming pool in south central Providence. His decision to close the pool and divert the money to other recreational programs for children has elicited widespread objections from the minority community. Even though offers have poured in to help finance the pool’s continued operations, to include an offer from the Republican Party of Rhode Island, Taveras steadfastly refuses to reverse his decision and has opened bids from companies vying to fill the pool with concrete.

With a likely primary election pitting him against General Treasurer Gina Raimondo, who has more than $2 million in her campaign chest, Taveras will need the complete support of the minority community in Providence and elsewhere in the state. Though Raimondo is too professional to use the pool closing as a campaign issue, political action committees that support her will not hesitate to excoriate Taveras for his stubbornness on the issue. Additionally, his opponents will emphasize statistics on the abnormally high number of black children who drown, primarily because they never learned to swim since they grew up with no pool available as youngsters.

Perhaps it’s time for Taveras to admit that he is wrong and show that he can be conciliatory, an attribute that can very valuable to a successful governor.

NOW FOR THE REST OF THE STORY: First, the Rhode Island Ethics Commission ruled, against all common sense, that the state director of administration, Richard Licht, one of Governor Chafee’s closest confidants and a key advisor, is not in “a senior policy-making, discretionary or confidential position” and, thus, is eligible to skirt the Code of Ethic’s revolving door requirement and be immediately appointed a superior court judge if selected. As discussed last week, that inane ruling smacks of politics and favoritism and reduces the Code of Ethics to mere rubbish.

“Now for the rest of the story,” as Paul Harvey used to say. It has now been revealed that a law passed in 1974 that was clearly meant to benefit only one person, deceased former governor Frank Licht - Richard Licht’s uncle - will also apply to Richard if he retires from the superior court bench. The law, which has become known as the “Frank Licht” rule, says that anyone who served as a legislator, a state officer and a judge is eligible to receive in retirement 75 percent of his active pay. But wait; there’s more! How does the law affect Richard Licht? Without being appointed to a judgeship, he is eligible for a $49,122 annual pension. Retiring from the judicial bench, however, boosts his retirement pay to $128,691 per year.  What a story it is!

Fortunately, practically all senior lawmakers and potential gubernatorial candidates have indicated their objection to the law and have promised to work to repeal it.

WHEN ENOUGH IS ENOUGH: When voters in the 18,000 population Central Coventry Fire District rejected the district’s proposed $6.6 million budget last February, they were saying “enough is enough.” They voted down a subsequent proposed budget of $6.3 million the very next month. Finally, Monday night – after months of court arguments, a union contract rejection, and talks about liquidating the fire district - they voted to accept a proposed $5.3 million budget that is much smaller than what is needed to fund the district if it is not to be liquidated. The voters were, in essence, saying once again that enough is enough; either live within a budget that is affordable to taxpayers or liquidate. It looks like liquidation is on the horizon.

Finally, at least in Coventry, taxpayers are showing enough concern and courage to reject tax and spend politicians and their union backers. It’s about time! Now, if only the rest of Rhode Island’s taxpayers will be as courageous as those in Coventry and vote such politicians out of office in 2014.

EXETER RECALL ELECTION: It is unfortunate that voters have to resort to forcing a recall election in order to protect constitutional rights. The U.S. Constitution’s Second Amendment is clear and the Supreme Court has agreed. Americans have the right to own and bear arms. Certainly, government can place reasonable restrictions on this right - such as requiring background checks and waiting periods. Government cannot, however, arbitrarily restrict gun ownership and the right to carry firearms once a citizen has overcome the reasonable hurdles. Yet, that is exactly what happens when the attorney general’s office is involved in issuing concealed carry permits.

State law rightfully requires that local police chiefs or other local issuing officials “shall” issue such permits so long as a background check is negative. The same law, however, says that the attorney general’s office “may” issue a permit - even when a background check is negative. This constitutes an arbitrary exercise of unconstitutional power by the attorney general’s office that is frequently used or abused.

Our General Assembly needs to strengthen the law and make sure all permits issued by local police chiefs and other local officials are entered into a statewide database so that police can immediately determine whether a permit is valid, and the law needs to require a waiting period with a new national criminal background check before a permit holder can purchase another gun. Additionally, the new law needs to read that the Attorney General’s office, just like local officials, “shall” issue permits to those who have passed the background check. Were this the case already, Exeter residents would not have had to resort to a recall election to protect their constitutional rights.

OBAMA ADMINISTRATION ADMITS FAILURE: The Obama administration’s Health and Human Services Department finally admitted failure Sunday when it posted a blog apologizing to the American people for its ineptitude in failing to create a functional website for Americans to sign up for health insurance under the Affordable Care Act (Obamacare).  After three weeks of claiming the website was experiences “glitches” but was performing effectively overall, the administration has finally admitted that after spending millions of dollars and devoting countless man-years of effort, the government just couldn’t create a functional website. The administration is now calling in private experts to help it get the program on track.

The question every American should be asking is this: If the government isn’t even capable of registering Americans for health insurance, how in the world will it be able to administer such a colossal, expensive program as Obamacare?

QUOTE OF THE WEEK: I was in Arlington, Virginia last weekend for the Army Ten Miler road race that starts at the Pentagon, crosses the Potomac, goes by DC monuments and government buildings, then crosses the Potomac again and ends back to the Pentagon. There were many memorable signs being held by onlookers along the running route. The best: “Keep going! You’re working a lot harder than Congress!”

Please log in or register to add your comment


In it was discovered that adding blocks to the testing profile causes errors, even though they are removed in the setUp().
If blocks are added and then removed again, it should not affect the following tests.

The failing test is testBlockRehash.
It fails on first line:

Drupal\Component\Plugin\Exception\PluginException: The plugin (test_html_id) did not specify an instance class. in Drupal\Component\Plugin\Factory\DefaultFactory::getPluginClass() (line 62 of /var/www/drupal8/core/lib/Drupal/Component/Plugin/Factory/DefaultFactory.php).

blocks-in-testing.patch2.58 KBRunePhilosof

tim.plunkett’s picture

I'm not sure this is a bug, since those lines are being deleted.

RunePhilosof’s picture

I know that those lines are deleted now, so I should actually renew this patch and add them again.
This bug was discovered because of those seemingly unnecessary lines.

Drupal 8.0.6 was released on April 6 and is the final bugfix release for the Drupal 8.0.x series. Drupal 8.0.x will not receive any further development aside from security fixes. Drupal 8.1.0-rc1 is now available and sites should prepare to update to 8.1.0.

Bug reports should be targeted against the 8.1.x-dev branch from now on, and new development or disruptive changes should be targeted against the 8.2.x-dev branch. For more information see the Drupal 8 minor version schedule and the Allowed changes during the Drupal 8 release cycle.


I got strace working. It is only opening the default.d directory, local.d directory (both empty) and my default.ini and local.ini files. I'm ignoring futon now since it doesn't agree with the actual behavior. It is easy to tell what db directory is being used so I'm just playing with that one setting. I tried deleting the default config line and it made no difference. I looked at the process with ps and it is a very long complicated erlang line that starts beam. So I don't think I'll try that trick. It may be a bug, but I'm not confident I could put together a decent report. The 'how to repeat" section would be pretty big. Also I guess it could be a problem with build-couch. I've got an old install of build-couchdb that works, so I'll use that now. I guess the next thing to try would be to build from source instead of using build-couchdb, but I've never had any luck doing that before.


Why Brent crude prices advanced, benefiting international oil producers

Why Brent crude prices advanced, benefiting international oil producersBrent crude is regarded as the international oil benchmark

Brent crude is viewed as the benchmark crude for international oil prices. So movements in Brent oil prices are a major driver in the valuation of international oil producers. Higher oil prices also incentivize producers to spend more money on drilling, which results in increased revenues for oilfield service companies (that is, companies that provide services such as drilling, fracking, and well servicing). Consequently, Brent crude prices are an important indicator to watch for investors who own international energy stocks.

Brent crude finished up last week

Last week, Brent crude prices finished up, closing at $108.81 per barrel compared to $107.72 per barrel the Friday before, as U.S. inventories had a much larger than expected draw (see Must-know: Oil prices rise to new highs on supportive inventory report). Since mid February, when Brent touched nearly $119 per barrel, prices fell dramatically to touch below $98 per barrel in mid April. Since then, Brent had been roughly range-bound in the $100-to-$105-per-barrel area. In recent weeks, oil prices moved higher due to unrest in the Middle East and draws in U.S. inventory levels.

Divergence from U.S. benchmark crude

Note that Brent crude doesn’t properly reflect the price that producers within the United States receive. For domestic producers, WTI (West Texas Intermediate) is a more appropriate benchmark (read about last week’s movement in WTI prices here), mainly due to a recent surge in domestic crude production, which has struggled to find sufficient transportation and outlets to bring WTI prices in line with Brent prices. For more on the price difference between the two benchmarks, please see Spread between WTI and Brent vanishes, lower relative U.S. oil prices. Note, though, that recently, the spread has narrowed significantly, and if it continues to narrow, the two benchmarks may soon trade in line again. Also, Brent represents a certain grade of crude, and differences in the qualities of oil can affect the price that producers receive. Nevertheless, most market participants view Brent as the international oil benchmark, and price movements in Brent affect international energy stocks such as Exxon Mobil (XOM), Chevron Corp. (CVX), ConocoPhillips (COP), and Anadarko Petroleum Corp. (APC).

Higher oil prices can drive higher energy stock valuations

As we’ve seen, higher crude prices generally have a positive effect on stocks in the energy sector. The graph below shows Brent crude oil price movements compared to XLE and XOM on a percentage change basis from January 2007 onward. You can see that crude oil, the XLE ETF, and XOM have largely moved in the same direction over the past several years. Why Brent crude prices advanced, benefiting international oil producers

The price increase this past week was a short-term positive for the sector

As demonstrated in the graph above, crude oil prices are a major driver in the valuation of many energy investments. Oil prices affect the revenues of oil producers, and consequently affect the amount of money oil producers are incentivized to spend on oilfield services. So the upward movement in prices this past week was a short-term positive for the sector. Investors with energy holdings in names with international exposure such as XOM, CVX, COP, and APC as well as the XLE (Energy Select Sector SPDR) ETF may find it prudent to track the movements of benchmarks such as Brent crude.

The Realist Discussions

Become a Market Realist member today to enjoy full access


Public Release:

New research ensures car LCDs work in extreme cold, heat

Novel liquid crystal formulations usable from minus 40 degrees Fahrenheit to 212 degrees Fahrenheit

University of Central Florida

One of UCF's most prolific inventors has solved a stubborn problem: How to keep the electronic displays in your car working, whether you're driving in the frigid depths of winter or under the broiling desert sun.

LCD screens are everywhere -- our smartphones, televisions, laptops and more. Increasingly, they're now popping up in automobiles, where it's now common to find liquid crystal displays showing speed, distance, fuel consumption and other information, as well as GPS mapping, rearview cameras and audio systems.

But current technology has an Achilles heel: The displays grow blurry and sluggish in extreme temperatures.

"Liquid crystals exist only in a certain temperature range. In order to work in extreme environments, we need to widen that temperature range," said researcher Shin-Tson Wu of the University of Central Florida.

That's what Wu and his team have done in his lab in UCF's College of Optics & Photonics.

As reported recently in the scholarly journal Optical Materials Express, Wu and his collaborators formulated several new liquid crystal mixtures that don't have the temperature limitations of those now in use. The liquid crystals should maintain their speed and viscosity in temperatures as high as 212 degrees Fahrenheit and as low as minus 40 degrees Fahrenheit.

Wu, who holds UCF's highest faculty honor as a Pegasus Professor, is no stranger to new discoveries with practical uses in the real world. He previously played a key role in developing LCDs for smartphones and other devices that are readable in sunlight.

Through his work with advanced LCDs, adaptive optics, laser- beam steering, biophotonics and new materials, Wu has registered about 84 patents. In 2014, he was one of the first inductees to the Florida Inventors Hall of Fame.

Wu worked with a team of doctoral students from his research group -- Fenglin Peng, Yuge "Esther" Huang and Fangwang "Grace" Gou -- as well as collaborators from Xi'an Modern Chemistry Research Institute in Xi'an, China, and DIC Corp. in Japan.

"Our team is always trying to find new recipes for materials," Huang said.


Short description

The QUEST 4000m remotely operated vehicle (ROV) is a full sized, so called "workclass" deepwater ROV, originially designed to serve industrial needs for offshore production and intervention tasks. At Marum, QUEST is continuously adapted to the needs of deepsea research, utilizing its high electrical power and large payload capacity to provide a versatile platform for state-of-the-art deepwater science at water depths down to 4000 m. Today, it has proven it's value during over 30 expeditions since 2003. By December 2015, QUEST completed over 360 scientifc dives between 280 and 4014 m depth.

QUEST was originally developed as a commercial robotic vehicle by Schilling Robotics, Davis, USA, primarily for heavy duty offshore industrial applications in the deep ocean. In contrast to the commercial model, the Bremen QUEST has been adapted at Marum for a number of scientific applications.

Since it's initial deployment during expedition "M58-3" in June 2003, QUEST is routinely operated worldwide aboard research vessels between 2 to 5 times per year. Expeditions include work for several national german DFG and BMBF funded programs, internal MARUM research projects, the EU supported programmes ACES, HERMES, ESONET, the US NOAA's Ring of Fire expedition programme, and others.

Please follow below links to gain a more detailed insight into QUEST's capabilities, requirements, related media and work examples.

Detailed system information

(detailed technical specification, dimensions, cameras and sensors)
more ...

User Guide

(scientific capabilities, payload specifications, data products)
more ...

Operational Requirements

(operational modes, personnel requirements, mobilization, logistics)
more ...

(exhibitions and TV programs, websites, media gallery)
more ...

(past and future dates and expeditions, dive numbers)
more ...

(Manipulation, Simulation, Courses)
more ...

Dr. Volker Ratmeyer

+49  421 218 - 65604

+49  421 218 - 9865604


Botanical Garden
Orto Botanico
Putto Fountain

The Botanical Gardens of Florence were founded on December 1st, 1545, when Grand Duke Cosimo dei Medici purchased the land from the Dominican sisters. The orchard that was known with the name of "Giardino dei Semplici", because of the fact that it was used to cultivate and raise medicinal plants, is the third oldest botanical garden after those of Padua and Pisa.

The original layout was designed by Niccolò called "il Tribolo" who had already planned several other grand ducal gardens, like the one of the Medici villa in Castello. Initially the gardens were directed by the botanist Luca Ghini, who had already followed, two years earlier, the Botanical Gardens of Pisa by order of the Grand Duke. The garden was improved and embellished with the 18th century collections thanks to the commitment of Cosimo III dei Medici who assigned its direction to the Florentine Botanical Society, under the direction of the famous botanist Pier Antonio Micheli. Its direction was transferred in 1783 to the "Accademia dei Georgofili" and was referred to as "Agricultural experimental garden", then renamed into "Giardino dei Semplici" in 1847 and finally into "Botanical Garden of the Upper Education Institute" in 1880.

The Gardens currently take up an area of 2.39 hectars, divided into smaller and larger avenues. The structure also has its own greenhouses and hot houses for the cultivation of special plants. The vegetable patrimony is formed by over 5,000 examples with several very old trees, some of which, such as the Taxus baccata, planted by Micheli himself round 1720, a very large cork oak planted in 1805 and never stripped, several examples of Coniferae like the Araucaria, Torreya, Sequoia and a beautiful example of Metasequoia glytostroboides, a species originally known as fossil and rediscovered in China only in 1941.

The most important collections are those comprising Cicadidae, Tillandsia, Orchids and ferns. Extremely interesting, because of its dimensions and number, is the collection of azaleas that always draws the attention of a large number of visitors during the flowering period. Even the sections dedicated to medicinal plants, cactuses and carnivorous plants are also very interesting from the didactic point of view.

The large greenhouse
Time by time an exhibition
In the garden a statue of Esculapio
Vandopsis lissochiloides
Nice pot
Pachystachys lutea
Aristolochia machrophylla
Pachystachys coccinea
Citrus aurantium bergamia (Bergamotto)
Aristolochia elegans
Pavonia multiflora
Inside the greenhouse
A very old cork oak
Pears? No, lemons...
A world of rare plants
Drosera binata
Climbing roses
Carnivorous plants
Dionaea muscipula