 Obesity: Metabolic Dysfunctions

Obesity: Metabolic and Clinical Consequences

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What is Obesity?

Obesity is defined as a physical condition in which an individual has a body mass index (BMI) ≥30kg/m2. The BMI is a measure of the relationship between an individuals weight and height. The BMI is calculated by dividing a persons weight in kilograms by the square of their height in meters. The medical utility for determining a persons BMI is that this measure describes the body weight relative to height and it thus, strongly correlates with the total body fat content in adults. It is important to note that in certain individuals, such as body builders who have large muscle mass, a high BMI does not correlate with high fat content. Given that most Americans measure their weight in pounds and their height in inches the following Table can be used to approximate ones weight from their BMI and their height in inches or their BMI from their approximate weight and their height in inches.

Weight (lb)
70 132 139 146 153 160 167 174 181 188 195 202 207 243 278

Obesity is approaching epidemic proportions in the US and many other industrialized countries. In the US the prevalence of obesity now exceeds 30% of the population and represents the highest rate of obesity worldwide. Since 1980 the prevalence of obesity in adults in the US has increased 2-fold. However, much more disturbing is the fact that in this same time period the rate of childhood and adolescent obesity increased 3-fold. The Table below associates a given BMI range with the risk for cardiovascular disease and atherosclerosis.

18.5 or less underweight N/A N/A
18.5 - 24.9 normal N/A N/A
25.0 - 29.9 overweight increased risk high risk
30.0 - 34.9 obese high risk very high risk
35.0 - 39.9 obese very high risk very high risk
40 or greater extremely obese extremely high risk extremely high risk

Obesity is associated with several serious and life threatening complications resulting in significant increases in morbidity and mortality relative to lean individuals. These complications include insulin resistance (IR), type 2 diabetes, non-alcoholic fatty liver disease (NAFLD), atherosclerosis, degenerative disorders such as dementia, and also in many instances cancers. The combination of abdominal obesity, hyperlipidemia, IR, pro-inflammatory status, and hypertension is clinically referred to as the Metabolic Syndrome. Many of these conditions are discussed in this page and elsewhere in this site.

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Obesity and Development of the Metabolic Syndrome

A little more than 20 years ago Dr. Gerald M. Reaven put forth the concept that the insulin resistance syndrome was the root cause of glucose intolerance, elevated LDL along with reduced HDL, and hypertension. This clinical concept has evolved into what is now referred to as the metabolic syndrome. The metabolic syndrome, MetS (also once referred to as Syndrome X), is a disorder that defines a combination of metabolic and cardiovascular risk determinants. These risk factors include insulin resistance, hyperinsulinemia, central adiposity (obesity associated with excess fat deposits around the waist), dyslipidemia, glucose intolerance, hypertension, pro-inflammatory status, and microalbuminemia. The hallmark feature of MetS is indeed insulin resistance. Several other clinical abnormalities have recently been associated with MetS including non-alcoholic fatty liver disease (NAFLD), atherosclerosis, oxidative stress, and polycystic ovary syndrome (PCOS). Although obesity, ectopic fat accumulation, and an inflammatory status are central to the pathology of MetS, not all obese individuals develop MetS and not all individuals with MetS are obese. These observations indicate that MetS has a multi-factorial etiology that involves a series of complex interactions between a particular individuals dietary habits, hormonal status, and genetic background. Increasing evidence indicates that the risk of MetS can be developmentally induced. Epidemiological studies in humans and animal models of MetS demonstrate an association between poor nutrition during fetal development and an increased risk of adult cardiovascular disease.

Given the complexities of the factors contributing to the metabolic syndrome numerous health groups in various countries have defined the disorder with slightly different criteria. Some health organizations believe that insulin resistance is the signal most important predictor for future development of type 2 diabetes and cardiovascular disease that the disorder is defined as the insulin resistance syndrome. In addition, there are significant differences in ethnic predisposition to the effects of the dysfunctions of the metabolic syndrome that some criteria must be assessed with this in mind. Of particular note is the use of waist circumference as an indicator of obesity. The following Table lists the criteria set forth by the American Heart Association and the National Heart, Lung and Blood Institute as defining the metabolic syndrome.

Defining Criteria Parameters of Criteria
elevated fasting blood glucose ≥ 100 mg/dL (≥ 5.6mmol/L)
elevated waist circumference ≥ 102 cm (≥ 40 inches) in men
≥ 88cm (≥ 35 inches) in women
elevated triglycerides ≥ 150mg/dL (≥ 1.7mmol/L)
reduced HDL cholesterol (HDLc) < 40mg/dL (< 1.03mmol/L) in men
< 50mg/dL (< 1.3mmol/L) in women
elevated blood pressure ≥ 130mm Hg systolic
≥ 85mm Hg diastolic

Although MetS is not exclusively associated with type 2 diabetes and the associated insulin resistance, the increasing prevalence of obesity and associated development of type 2 diabetes places insulin resistance as a major contributor to the syndrome. The metabolic syndrome is defined as a clustering of atherosclerotic cardiovascular disease risk factors that include visceral adiposity (obesity), insulin resistance, low levels of HDLs and a systemic proinflammatory state. There are key components to the metabolic syndrome which include in addition to insulin resistance (the hallmark feature of the syndrome), hypertension, dyslipidemia, chronic inflammation, impaired fibrinolysis, procoagulation and most telling central obesity.

The role of adipose tissue (fat) stems from the fact that the organ is active at secretion of cytokines, termed adipocytokines. These include tumor necrosis factor-α (TNFα), interleukin-6 (IL-6), leptin, adiponectin and resistin. Leptin has received particular attention of late due to its role in obesity in addition to the fact that recent data indicates that plasma leptin levels are found to be predictive of the potential for cardiovascular pathology.

Many clinicians and researchers believe that insulin resistance underlies the cardiovascular pathologies of the metabolic syndrome. One primary reason for this is the role of insulin in fat homeostasis. As indicated above, the major role of insulin is to induce the storage of fuel. This can be as fat (triacylglycerides, TGs) in adipose tissue or as carbohydrate in the form of glycogen in liver and skeletal muscle. The effect of insulin resistance at the level of fat homeostasis is an increase in circulating TGs, referred to as dyslipidemia. Due to insulin resistance there is an increase in the delivery of peripheral fatty acids to the liver which in turn drives hepatic TG synthesis. These TGs are then packaged into lipoprotein particles termed VLDLs (very low density lipoproteins) which are returned to the circulation.

An additional role of insulin resistance in the overall cardiac pathology associated with the metabolic syndrome relates to the normal role of insulin in platelet function. In platelets, insulin action leads to an increase in endothelial nitric oxide synthase (eNOS) activity that is due to its phosphorylation by AMPK. Activation of NO production in platelets leads to a decrease in thrombin-induced aggregation, thereby, limiting the pro-coagulant effects of platelet activation. This response of platelets to insulin function clearly indicates why disruption in insulin action is a major contributing factor in the development of the metabolic syndrome.

Taken together, the insulin resistance and its associated negative effects on metabolism, the increased levels of circulating TGs, the reduced levels of HDLs and hypertension, all contribute to the progression of atherosclerosis. With associated coagulation and fibrinolysis pathologies, the cardiovascular events of the metabolic syndrome can be devastating.

Although, as indicated above, there are many examples of individuals who are obese but do not manifest MetS there is still a very strong correlation between obesity and increased risk for development of MetS. In addition, the incidence of MetS increases with the severity of obesity. It has been observed that over 50% of obese adolescents go on to develop MetS. Also, given the high correlation between MetS and insulin resistance it is not at all surprising that there is a strong link between obesity and MetS. Insulin resistance (identified as type 2 diabetes) is 5 to 6 times more common in individuals with a body mass index (BMI) >30kg/m2 than in individuals of normal weight.

Although the precise mechanism(s) by which obesity leads to the development of MetS is not fully understood, there are many overlapping pathways of metabolism that are disrupted in obesity that can be identified as important in the progression to MetS. Not the least of which is the role that obesity, in particular visceral obesity, plays in the progression to insulin resistance. Recall that as mentioned above, insulin resistance is the hallmark manifestation of MetS.

Since many of these pathologies can be reversed with proper diet and exercise, it is in a persons best interest to take responsibility for the role their life style choices play in the development of the metabolic syndrome.

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Genetic Factors in Metabolic Syndrome

Numerous epidemiological studies have implicated developmental origins in the progression to the metabolic syndrome. There appears to be a clear correlation between poor nutritional status of the mother during fetal development and the potential for increased risk for MetS to her child in later life. These correlations have also been observed in animal studies where prenatal diets in mothers impacts their offspring. Overfeeding during of the mother during fetal development as well as excessive nutritional intake by the mother during the pre-weaning period of postnatal development results in increased obesity, adipocyte hypertrophy, reduced activity, insulin resistance, elevated blood pressure, endothelial cell dysfunction, and altered cardiovascular and renal function in offspring. When mothers are obese and fed high-fat diets during fetal development their adult offspring exhibit impaired glucose tolerance, hyperinsulinemia, dyslipidemia, hypertension, resistance to the anorexic actions of the leptin on the hypothalamus, and develop NAFLD. Additional evidence indicates that manipulation of fetal protein access leads to modified pancreatic islet cell expansion resulting in reduced pancreatic β-cell mass and persistent deficits in glucose homeostasis.

There is now a clear link between maternal dietary status and future development of MetS in adult offspring. Likewise, because the risks of metabolic syndrome in the general population, due to identified inherited polymorphisms is relatively small, the huge increase in the numbers of individuals with the disorder is most likely due to epigenetic changes that occur during early fetal development. The role of epigenetics in transgenerational disease manifestation has been outlined in several studies on the outcomes of children born to parents who experienced famine while pregnant. These children are far more likely to develop diabetes, obesity, and cardiovascular disease than children from parents of similar backgrounds who were not nutritionally deprived. Of striking significance is that the second generation children (grandchildren of the starved mothers) were more likely to be born with low birth weight regardless of the nutritional status of their mothers. The potential for diet and nutrition to effect epigenetic changes in offspring on multiple generations has been conclusively demonstrated in animal models. In mice, the lack of adequate fetal nutrition results in a reduction in the methylation status of the promoter regions of several transcriptional regulators. Hypomethylation of genes is most often associated with increased transcriptional activation. One transcriptional regulator of key metabolic significance whose promoter has been found to be hypomethylated in offspring of nutritionally deprived mothers is PPARα. PPARα is highly expressed in the liver, skeletal muscle, heart, and kidney. Its function in the liver is to induce hepatic peroxisomal fatty acid oxidation during periods of fasting. Expression of PPARα is also seen in macrophage foam cells and vascular endothelium. Its role in these cells is thought to be the activation of anti-inflammatory and anti-atherogenic effects. For a detailed discussion of the PPAR family of transcriptional regulators visit the PPAR page.

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Hypothalamic Control of Appetite

Hypothalamic circuits in the control of appetite

Neuropeptide Y, NPY

Protein Tyrosine Tyrosine, PYY

PYY produced by and is secreted from intestinal enteroendocrine L-cells of the ileum and colon. Additional gut hormones that are secreted along with PYY include GLP-1 and oxyntomodulin (OXM). Both of these latter gut hormones are discussed above. Secreted forms of PYY include PYY1-36 and PYY3-36 with PYY3-36 being generated via the actions of dipetidylpeptidase IV (DPP-4 or DPP-IV). DPP-4 is the same enzyme that inactivates GLP-1. Within the gastrointestinal tract the highest detectable levels PYY are found in the rectum with low levels found in the duodenum and jejunum. Within the central nervous system (CNS) PYY is detectable in the hypothalamus, medulla, pons, and spinal cord.

Oxyntomodulin, OXM

Cholecystokinin, CCK

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Obesity and Cardiovascular Disease

Obesity is directly correlated to increased morbidity resulting primarily from hypertension and cardiovascular disease. However, since obesity is highly correlated to the development of type 2 diabetes, the pathophysiological complications associated with diabetes also contributes to obesity related mortality. Obesity is the result of excess accumulation of body fat including both cutaneous and visceral adipose tissue. As adipose tissue enlarges due to excess triglyceride accumulation physiological changes occur that result in increased inflammatory responses in the tissue. In addition to increased pro-inflammatory events in adipose tissue in response to excess lipid accumulation, so too do these same disruption occur in the liver. One consequence of the enhanced inflammatory status of the liver and adipose tissue in obesity is an associated insulin resistance (IR). For more information on the effects of obesity-induced IR in the liver see the section below and also see the discussion of IR in the Insulin Functions page.

Insulin resistance induced by obesity is a major factor in the development of cardiovascular disease in obese individuals. Within the vasculature insulin exerts vasodilator action as a result of increased nitric oxide (NO) production. This function of insulin is an important component of the ability of the hormone to enhance glucose uptake by skeletal muscle. The insulin-mediated signaling pathway that triggers production of NO in vascular endothelium involves the same signaling proteins (PI3K, PKD, and AKT/PKB) that are components of metabolic regulatory pathways induced by insulin. Inactivation of endothelial cell NO production, as occurs due to IR, results in endothelial dysfunction and promotes the development of atherosclerosis.

Atherosclerosis is in essence a pro-inflammatory condition where there is enhanced leukocyte infiltration into the vascular endothelium and an associated increase in secretion of pro-inflammatory cytokines which sets up a feed-forward process that builds upon itself. One of the principal pro-inflammatory cytokines whose expression is increased in obesity, and plays a critical role in the development of atherosclerosis, is tumor necrosis factor-α (TNF-α). Expanding adipose tissue secrete ever increasing amounts of TNF-α as well as other proatherogenic factors such as plasminogen activator inhibitor type 1 (PAI-1). Increased circulating TNF-α results in enhanced adhesion of leukocytes to the endothelium. Adherent monocytes infiltrate the endothelial layer of the vasculature where they phagocytose the excess lipoprotein particles in the vasculature and become foam cells. Foam cell secretion of cytokines activates the underlying smooth muscle cells (SMCs) to proliferate and migrate. As SMCs proliferate they increase production of extracellular matrix which leads to decreased fluidity ("hardening") of the vasculature. The increased levels of PAI-1 inhibit the ability of plasminogen to be converted to plasmin which is required to dissolve fibrin clots that will be generated as a result of the local inflammatory processes. As the disease progresses atherosclerotic plaque formation occurs and expands. Plaques can become large enough to result in vessel occlusion or to the release of a fibrous clot which can travel to the heart of lungs leading to fatal embolisms.

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Non-Alcoholic Fatty Liver disease: NAFLD

Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease in the Western world. NAFLD is characterized by fatty infiltration of the liver in the absence of alcohol consumption. For information on the role of alcohol consumption and the formation of the fatty liver syndrome visit the Ethanol Metabolism page. The mildest forms of NAFLD consists of simple steatosis (abnormal retention of lipids inside cells) and can progress to non-alcoholic steatohepatitis (NASH) which represents a deleterious hepatic inflammatory disorder characterized by advanced liver fibrosis and cirrhosis which ultimately can result in hepatocellular carcinoma and death. In the clinical environment NAFLD is believed to account for as much as 90% of all cases of elevated liver function test enzymes in patients who do not manifest with identifiable causes of hepatic disease (e.g. viral hepatitis).

The abnormal deposition of fat in the liver in NAFLD comprises a complex pathophysiology. However, what is known about the process is that there is increased visceral adiposity plus insulin resistance with increased free fatty acids (FFAs) being released from adipose tissue. As there is a large increase in visceral adipose tissue in obese individuals this contribution of adipose tissue derived FFAs is significant to the development of NAFLD. These conditions set the stage for the onset and perpetuation of the steatosis in the liver. Additional pathophysiology includes an enhanced state of hepatic oxidative stress and lipid peroxidation, decreased antioxidant defenses, early mitochondrial dysfunction, and iron accumulation. Associated with these abnormal hepatic processes are an imbalance in the secretion of adipokines and a chronic pro-inflammatory status. In addition, gut-derived microbial adducts participate in the propagation of the hepatic dysfunction (see section below on role of gut bacteria in obesity).

One of the most significant contributing factors to the development of NAFLD is insulin resistance in the liver. For more information on the causes of insulin resistance visit the Insulin Functions page. Insulin resistance (IR) in the liver is associated with increased hepatic glucose output since the insulin-suppressing effects on gluconeogenesis are impaired. The increased hepatic glucose output exacerbates the hyperglycemia that is present in obesity and contributes to the IR in the periphery ultimately resulting in progression to type 2 diabetes. Peripheral IR at the level of adipose tissue and skeletal muscle results in increased circulating FFAs which make their way to the liver. In addition, the hepatic IR results in increased hepatic fatty acid synthesis which then, in conjunction with the circulating FFAs, serves as the precursors for increased triglyceride accumulation in the liver.

Hepatic IR is induced by the excess accumulation of FFAs. Within the hepatocyte metabolites of the FFA re-esterification process, including long-chain acyl-CoAs and diacylglycerol (DAG), accumulate. Excess FFAs also participate in the relocation of several protein kinase C (PKC) isoforms, from the cytosol to the membrane compartment. These PKC isoforms include PKC-β2, PKC-δ, and PKC-theta (PKC-θ). DAG is a potent activator of these PKC isoforms and the membrane-associated PKC will phosphorylate the intracellular portion of the insulin receptor on serine residues which results in impairment of insulin receptor interaction with downstream signaling proteins including insulin receptor substrate 1 (IRS1) and IRS2. Loss of IRS1 and IRS2 interaction with the receptor prevents interaction with phosphatidylinositol 3-kinase (PI3K) and its' subsequent activation. For more information on insulin receptor signaling pathways visit the Insulin Functions page. In addition to serine phosphorylation of the insulin receptor, various PKCs have been shown to phosphorylate IRS1 and IRS2 further impairing the ability of these insulin receptor substrates to associate with the insulin receptor.

The FFA-induced down-regulation of insulin signaling pathways results in activation of several kinases involved in stress responses. These kinases include Jun N-terminal kinase (JNK), inhibitor of nuclear factor kappa B kinase beta (IKKβ), and suppressors of cytokine signaling-3 (SOCS-3). Like PKC, JNK activity is also regulated by FFAs and is an important regulator of IR. The target of JNK action is the Ser307 of IRS-1 and this phosphorylation plays an important role in the progression to hepatic IR. Activation of IKKβ (which is required for the activation of nuclear factor kappa B, NFκB) may have the most pronounced effect on inflammatory responses in the lever. NFκB is the most important transcription factor activating the expression of numerous pro-inflammatory cytokine genes such as interleukin-1 (IL-1), IL-6, and TNF-α each of which have been shown to be involved in promoting IR. NFκB-dependent inflammatory mediators produced in hepatocytes act to reduce insulin sensitivity and to promote liver injury.

The loss of insulin-mediated repression of hepatic gluconeogenesis (leading to increased hepatic glucose output) is due to the inability of the transcription factor, forkhead box-containing protein O subfamily-1 (FOXO1), from being taken up by the nucleus. FOXO1 regulates the expression of the catalytic subunit of glucose-6-phosphatase (G6PC) and phosphoenolpyruvate carboxykinase (PEPCK). The activation of these gluconeogensis genes by FOXO1 requires an association with peroxisome proliferator-activated receptor-gamma co-activator 1 alpha (PGC-1α) and possibly also with CAAAT/enhancer-binding protein-alpha (C/EBPα). Normally the expression of C/EBPα is down-regulated by insulin via induction of the inhibitory isoform of liver-enriched transcriptional inhibitory protein.

Altered lipogenesis that occurs in the presence of hepatic and peripheral IR also contribute to the development of NAFLD. The primary regulators of hepatic lipogenesis include sterol regulated element-binding protein-1c (SREBP-1c), carbohydrate response element-binding protein (ChREBP), and peroxisome proliferator-activated receptor-gamma (PPARγ). As indicated above, hepatic IR results in increased expression of SOCS-3 which in turn results in a significant upregulation of SREBP-1c expression. The increased SREBP-1c levels activates acetyl-CoA carboxylase-2 (ACC2) which is the isoform of ACC that produces malonyl-CoA at the mitochondrial membrane. The increase in malonyl-CoA at the mitochondrial membrane causes an inhibition of carnitine palmitoyl transferase-1 (CPT-1) which transports fatty acids into the mitochondria for oxidation. Thus, inhibited CPT-1 results in decreased oxidation of fatty acids further increasing the pool of FFAs in the hepatocyte. Increased activity of SREBP-1c results in increased expression of PPARγ due to the production of an activating ligand for this transcription factor. Genes regulated by PPARγ that are involved in lipid metabolism or glucose homeostasis include lipoprotein lipase (LPL), acyl-CoA synthase (ACS), acetyl-CoA acetyltransferase (ACAT), several phospholipase A (PLA) genes, PEPCK, and glycerol-3-phosphate dehydrogenase (GPDH). The increased hepatic glucose production results in activation of ChREBP and a consequent activation of its target genes that includes ACC, fatty acid synthase (FAS) and liver-type pyruvate kinase (L-PK). The activation of these genes leads to increased de novo synthesis of fatty acids. L-PK activation results in diversion of some of the excess glucose into pyruvate and ultimately to acetyl-CoA via pyruvate dehydrogenase, and this acetyl-CoA is in excess of the ability of liver mitochondria to oxidize in the TCA cycle thus increasing the substrate pool for fatty acid synthesis. In addition, ChREBP regulates the expression of glycerol 3-phosphate acyltransferase (GPAT). GPAT is the enzyme that esterifies glycerol-3-phospate generating lysophosphatidic acid which is the first step in the synthesis of triacylglycerols (TAGs).

Whereas the development of hepatic IR is the first dysfunction contributing to the progression to NAFLD, the contribution of impaired fatty acid and complex lipid metabolism stems form the oxidative stress that is induced. Under the conditions of excess fat accumulation there is an increase in the production of reactive oxygen species (ROS) in the liver. The increased ROS production is due to a combination of mitochondrial and peroxisomal lipid oxidation. In addition mechanisms involving cytochrome P450, nicotinamide adenine dinucleotide oxidase, cyclooxygenase, and lipoxygenase participate in increased ROS production and reduced hepatic antioxidant synthesis. One mechanism resulting in reduced hepatic antioxidant production is a defect in mitochondrial uptake of glutathione (GSH). Increased hepatocyte lipid content leads to increased lipid peroxidation reactions that can result in gross morphological alterations in mitochondria and an associated impairment of electron transport. These changes result in increased TNFα expression which leads to enhanced lipid peroxidation which then exacerbates the mitochondrial dysfunction. In addition to increased TNFα production, lipid peroxidation induces the expression of other pro-inflammatory cytokines such as IL-8 and transforming growth factor-β (TGF-β). IL-8 is a chemoattractant that promotes neutrophil infiltration into the liver and TGF-β is known to promote hepatic fibrosis via induction of collagen production.

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Mitochondrial Dysfunction in Obesity and Type 2 Diabetes

Well established data demonstrate that mitochondrial dysfunction, particularly as it relates to the processes of oxidative phosphorylation (oxphos), is contributory to the development of encephalomyopathy, mitochondrial myopathy, and several age-related disorders that include neurodegenerative diseases, the metabolic syndrome, and diabetes. Indeed, with respect to diabetes, several mitochondrial diseases manifest with diabetic complications such as mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) and maternally inherited diabetes and deafness (MIDD).

Normal biogenesis of mitochondria is triggered in response to changes in the ATP/ADP ratio and to activation of AMPK which in turn results in increased expression of PPARγ co-activator 1α (PGC-1α) and nuclear respiratory factor-1 (NRF1). PGC-1α is a master transcriptional co-activator of numerous genes involved in mitochondrial biogenesis. NRF1 is a transcription factor that regulates the expression of mitochondrial transcription factor A (TFAM, for transcription factor A, mitochondrial; also designated mtTFA) which is a nuclear transcription factor essential replication, maintenance, and transcription of mitochondrial DNA. NRF1 also controls the expression of nuclear genes required for mitochondrial respiration and heme biosynthesis. Evidence has shown that both PGC-1α and NRF1 expression levels are lower in diabetic patients as as in non-diabetic subjects from families with type 2 diabetes. The expression of NRF1 is highest in skeletal muscle which is also the tissue that accounts for the largest percentage of glucose disposal in the body and, therefore, is the tissue that is most responsible for the hyperglycemia resulting from impaired insulin signaling.

Mitochondrial dysfunction results in increased production of ROS which activates stress responses leading to increased activity of MAPK and JNK. Both of these serine/threonine kinases phosphorylate IRS1 and IRS2 resulting in decreased signaling downstream of the insulin receptor. Inhibited IRS1 and IRS2 activity results in decreased activation of PI3K. PI3K activation is involved in the translocation of GLUT4 to the plasma membrane resulting in increased glucose uptake. Therefore, inhibition of PI3K results in reduced glucose uptake in skeletal muscle and adipose tissue. Mitochondrial dysfunction results in a reduction in the level of enzymes involved in β-oxidation leading to increases in intramyocellular lipid content. Indeed, skeletal muscle metabolism of lipids has been shown to be impaired in type 2 diabetics. An increased delivery of fatty acids to skeletal muscle, as well as diminished mitochondrial oxidation, results in increased intracellular content of fatty acid metabolites such as diacylglycerol (DAG), fatty acyl-CoAs, and ceramides. These metabolites of fatty acids are all known to induce the activity of protein kinase C isoforms (PKCβ and PKCδ) that phosphorylate IRS1 and IRS2 on serine residues resulting in impaired insulin signaling downstream of the insulin receptor.

Because skeletal muscle consumes the largest amount of serum glucose, mitochondrial dysfunction in this tissue will have the greatest impact on glucose disposal. However, adipose tissue also plays an important role in glucose homeostasis and mitochondrial dysfunction in this tissue has been shown to result in impaired glucose homeostasis resulting in diabetes. For example, when animals are treated with inhibitors of mitochondrial oxidation insulin-stimulated glucose uptake in adipose tissue is significantly impaired. Adipose tissue secretes a number of proteins classified as adipokines. Adiponectin is an adipokine that promotes insulin-sensitivity in insulin-responsive tissues, such as skeletal muscle. When plasma levels of adiponectin are measured in obese or type 2 diabetic subjects it is found to be significantly lower than in age and sex matched control subjects that are of normal weight or that do not have diabetes. In animal studies, the enhancement of adipocyte mitochondrial biogenesis results in increased adiponectin release from adipose tissue. Conversely, expression of adiponectin expression is decreased in adipocytes with mitochondrial dysfunction.

Given that impaired mitochondrial function is clearly associated with obesity and type 2 diabetes, it is not surprising that there is great interest in the use of pharmacology to augment mitochondrial function in the treatment of these disorders. Of significance is the fact that the thiazolidinedione (TZD) class of drugs used to treat the hyperglycemia of type 2 diabetes (see the next section) activate PPARγ which in turn increases the level of activity of PGC-1α. Although the TZDs were first marketed due to their ability to improve insulin sensitivity, they have since been shown to increase mitochondrial functions both in vitro and in vivo. Antioxidants have also been shown to enhance mitochondrial function by reducing the production of ROS. Resveratrol (found in grape skins and red wine) is a potent antioxidant whose activity is, in part, due to its ability to activate the deacetylase SIRT1 (see below). Activated SIRT1 deacetylates PGC-1α resulting in increased transcriptional activity and thus, enhanced mitochondrial biogenesis.

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Role of Gut Bacteria in Obesity

In trying to understand the epidemic of obesity much of the research has focused on two critical areas. The first is research driven by the notion that the biological and physiological interrelationships of the organ systems, primarily liver, adipose tissue, and skeletal muscle, are tightly connected and any disruption in the metabolic profile of one organ can exert a negative impact on the others. An additional avenue of more recent research is the use of modern genetic tools to scan the human genome for polymorphisms that are associated with increased risks for obesity and diabetes. However, very recently a new area of study has begun to focus on the role of the bacterial complement (microbiota) of the gut and the role these microorganisms play in altering dietary and metabolic processes.

The idea that gut bacteria can influence overall metabolism was discovered in studies using germ free mice. Mice raised in a germ free environment are resistant to diet-induced obesity. The primary mechanisms underlying this resistance are decreased absorption of glucose, decreased generation of short-chain fatty acids in the gut, reductions in hepatic lipogenesis, and alterations in adipose tissue metabolism that favors reduced triglyceride accumulation and increased fatty acid oxidation. A number of striking observations have been made in the use of animal models for studying the interaction between gut bacteria and diet-induced obesity and the development of insulin resistance and type 2 diabetes. When the guts of mice reared in a germ-free environment are colonized with bacteria from mice raised in a non-sterile environment the germ free mice amass a 60% increase in body weight and this weight gain is associated with insulin resistance. Another important observation was made when comparing the source of the bacteria to be used for gut colonization. If bacteria are used from obese mice (the ob/ob genotype) the recipient mice have a significantly greater increase in body fat mass than in recipients that were colonized with bacteria from lean mice.

The mechanism of the weight gain in these study mice was due to increased digestion of polysaccharides resulting in higher absorption and delivery of sugars to the liver. The increased carbohydrate delivery to the liver results in increased lipogenesis. When the transcriptional profiles of the livers were analyzed it was found that germ-free mice colonized with bacteria from ob/ob mice had increased levels of expression of ChREBP and SREBP-1c, both of which drive increased fatty acid synthesis via activation of the expression of ACC and FAS. Although the re-colonized mice had increased fat deposition in the liver via the described transcriptional changes, the increase in adipose tissue mass was determined to be due to increases in the activity of lipoprotein lipase (LPL). LPL is present on the surface of vascular endothelial cells and has a central role in lipoprotein metabolism.

During periods of fasting, the expression of a protein called fasting-induced adipose factor (FIAF) is stimulated by PPARα in liver and by PPARγ in white adipose tissue. FIAF is encoded by the ANGPTL4 gene (angiopoietin-like 4). FIAF inhibits adipose tissue LPL activity by acting extracellularly as an unfolding molecular chaperone. The N-terminal coiled-coil domain of FIAF transiently binds to LPL and this interaction converts LPL from a catalytically active dimer to an inactive monomer. In the re-colonized germ-free mice the level of FIAF expression was significantly reduced allowing for increased uptake of fatty acids from circulating lipoproteins and a concomitant increase in adipose tissue triglyceride storage. These changes in lipid profiles in the liver and adipose tissue of obese bacteria re-colonized rodents was correlated to changes in the composition of gut microbiota such that there was a 50% reduction in the abundance of Bacteriodetes and a proportional increase in Firmicutes.

The intestinal epithelium is the largest immunologically active organ system in the human body. This tissue provides defense of the host from invading pathogens. However, given that the microorganisms of the gut are essential for the metabolism of xenobiotic compounds, production of vitamins, degradation of non-digestible polysaccharides (involving fermentation of resistant starches and oligosaccharides), and absorption of nutrients, there is a fine interplay between the gut immune system surveillance and maintenance of the gut microbiota. The human gut contains a wide variety of microorganisms of which bacteria constitute the largest fraction. The average human gut contains some 1014 bacteria of which anaerobic bacteria constitutes the largest proportion. There are anywhere from 500 to 1000 different species of bacteria in the gut population divided into three bacterial phyla: Bacteroidetes (gram-negative), Actinobacteria (gram-positive), and Firmicutes (gram-positive). The Firmicutes consist of over 200 genera which includes Bacillus, Clostridium, Lactobacillus, and Mycoplasma.

Bacteria of the Bacteroidetes phylum constitute up to 30% of the total gut flora. These bacteria are important in the digestion of otherwise non-digestible polysaccharides into monosaccharides and short-chain fatty acids (SCFA) and also may be involved in the synthesis of vitamin K. The bacterial digestion of polysaccharides into SCFA involves a process called saccharolytic fermentation. The primary SCFAs are acetic acid, propionic acid, and butyric acid. SCFAs affect the growth and proliferation of intestinal epithelial cells through a signal transduction process that involves binding to a G-protein coupled receptor identified as GPR41. Following absorption, propionic acid aids the liver in the production of ATP by being converted to propionyl-CoA and then propionyl-CoA is converted to succinyl-CoA followed by oxidation in the TCA cycle. Butryate is used for energy production by intestinal epithelial cells and also has anti-inflammatory properties in the gut. Of significance to the relationship between gut microbiota and obesity, studies have shown that obese individuals had lower levels of Bacteroidetes and more Firmicutes than lean control subjects. When obese patients are placed on either a carbohydrate restricted low calorie diet or a fat restricted diet their ratios of Bacteroidetes to Firmicutes approached those of lean control subjects after several months.

Given that obesity, insulin resistance, and type 2 diabetes are all associated with low-grade systemic inflammation of unclear etiology, it has been proposed that one mechanism leading to this state involves inflammatory modulation by gut bacteria. High-fat diet-induced obesity has been shown to be correlated with the increased expression of several pro-inflammatory cytokines including IL-1, IL-6, MCP-1, and TNF-α. In particular, TNF-α is known to cause insulin resistance, as described above in the NAFLD section (also see Insulin Functions page). Bacterial lipopolysaccharide (LPS) evokes an inflammatory response triggering the secretion of many of these same pro-inflammatory cytokines. LPS is continuously produced by gut bacteria through the lysis of dead and dying gram-negative bacteria. LPS binds to a complex of CD14 and the toll-like receptor 4 (TLR4) on cells of the innate immune system resulting in the secretion of these cytokines. LPS is also transported from the gut to peripheral tissues via interaction with chylomicrons. Since the rate of chylomicron synthesis is elevated in response to a high-fat and/or high-carbohydrate diet, there will be more LPS uptake in obese individuals due to the elevated intake of lipids and carbohydrates. The fat-induced increase in LPS uptake is referred to as metabolic endotoxemia. The role of a high-fat diet in triggering metabolic endotoxemia can be mimicked in the absence of dietary fat by direct infusion of LPS. When these experiments are carried out in mice fed a fat-restricted diet, LPS infusion resulted in fasting hyperglycemia, obesity, steatosis, infiltration of macrophages into adipose tissue, insulin resistance and hyepinsulinemia, the same conditions found in high-fat diet fed mice.

Gut bacteria have also been shown to play a role in the secretion of gastrointestinal hormones that function in digestion and appetite control. One very important gut hormone is glucagon-like peptide-1 (GLP-1). GLP-1 is called an incretin which is a term referring to a substance that promotes pancreatic insulin secretion in response to food intake. For detailed information on GLP-1 see the Gut-Brain Interactions page. The role of GLP-1 in the regulation of digestion, insulin secretion, and appetite is precisely the reason it is a current pharmaceutical target in the treatment of hyperglycemia and type 2 diabetes. GLP-1 is secreted from specialized enteroendocrine cells (L-cells) of the ileum and colon and the composition of the diet affects the release of this hormone. High fat and glucose content stimulate GLP-1 release but proteins do not appear to be involved in its secretion. When animals are fed a high fiber diet composed of non-digestible oligofructose, which can be fermented by gut bacteria, there is an increase in GLP-1 release. Oligofructose is called a prebiotic which is any substance that is non-digestible by humans but can be fermented by gut bacteria thereby promoting their growth and activity. In addition, feeding animals oligofructose results in increased L-cell proliferation in the proximal colon and this contributes to a higher level of GLP-1 release. When rats are fed a high-fat diet which also includes oligofructose there is an improvement in the diabetes induced by the high-fat diet alone. In humans, the consumption of oligofructose protects against weight gain, reduces fat accumulation, reduces serum triglyceride accumulation, and promotes satiety. These effects are presumably due, in part, to changes in the composition of gut microbiota as is seen in experimental animals.

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Is There a Viral Link to Obesity?

A potential link between obesity and viral infection was initially suggested from studies that demonstrated increased body weight, increased glucose uptake, and decreased leptin secretion in animals infected with adenovirus-36 (Ad-36). Subsequently other viruses such as canine distemper, rous-associated virus 7, scrapie, Borna disease virus, SMAM-1, as well as other adenoviruses were correlated to increasing obesity in animal models. Ad-36 is a virus that primarily infects humans and studies have shown that 30% of obese individuals (compared to only 11% of lean subjects) have circulating antibodies to Ad-36. The precise mechanism by which Ad-36 infection might lead to obesity is unknown. Unlike in animal studies where canine distemper virus and Borna disease virus particles were found in the hypothalamus of obese animals, Ad-36 particles are not found in the hypothalamus of obese human subjects positive for Ad-36 antibodies. However, Ad-36 viral particles have been found in adipocytes and Ad-36 infection increases adipocyte differentiation from pre-adipocytes. It is also possible that adenoviral infection leads to increased inflammatory responses in adipose tissue, and possibly also the liver, that in turn leads to the metabolic disruptions seen to be typical of the pro-inflammatory state associated with, and resulting in, obesity.

Although the current evidence is suggestive of a link between viral infection and obesity the data are not conclusive nor of large enough numbers to clearly demonstrate a causal association to obesity. As more epidemiological data is collected viral infection may indeed be added to the list of known factors in the multifactorial model of the causes of obesity.

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Last modified: May 26, 2017


Thomas Jefferson Knowledge Institute

Franklin Pierce

Served from 1853 to 1857

Franklin PierceCongress passed a bill to give financial aid to the indigent mentally ill. President Pierce, after examining the bill, vetoed it. Why? "The question presented, therefore, clearly is upon the constitutionality and propriety of the Federal Government assuming to enter into a novel and vast field of legislation, namely, that of providing for the care and support of all those among the people of the United States who by any form of calamity become fit objects of public philanthropy." Such legislation clearly exceeded the limits set by the constitution.

Pierce recounted that the States ratified a constitution containing the amendment "The powers not delegated to the United States by the Constitution nor prohibited by it to the States are reserved to the States respectively or to the people." Therefore care of the poor and the sick was the purview of the states, not the federal government. Pierce's argument against federal extra-constitutional legislation is a long read, carefully constructed, and quite compelling.


Biomedical Research

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Effect of qidan granule and tetrandrine on the information transmission channel of TGF-?1-smads for silicosis fibrosis

The study is aimed to investigate the effect of Qidan Granule and tetrandrine on the signal transduction pathway of TGF-β1 (Transforming Growth Factor-β1) for silicosis fibrosison in Wistar rats developed by dust injection. Silicon nodules are mainly of grade III-IV without any treatment, while those in Qidan Granule and tetrandrine groups were of grade II. Pulmonary coefficient and content of hydroxyproline in both Qidan groups and tetrandrine ones are lower, so are the expressions of TGFβ1 and Smad3 in bronchoalveolar lavage fluid and pulmonary tissue. Furthermore, expressions of Smad7 in treating groups are higher than those in the model group. Meanwhile, kidney injuries can be found in all rats of both tetrandrine groups, while not in those of other groups. It is clear that Both Qidan Granule and tetrandrine can inhibit expression of both Smad3 and TGF-β1 and promoting expression of Smad7. Qidan granules and Tetrandrine could inhibit remarkably silicotic fibrosis in rats. However, Qidan Granule is much safer without renal toxicity.

Author(s): Zhang H, Xu S, Wu Q, Wang W, Xin H


Why the name Black Swan?

Early Europeans once thought that all swans were white.

In fact, a common saying if you believed someone was telling you an untruth was "I'll believe that when I see a feather from a black swan!"  Then in 1697 Dutch explorers discovered Black Swans in Western Australia. This discovery proved sometimes things are not always as we believe them to be. So the Black Swan became a symbol of a moment in time that challenges common beliefs and turns prior thinking upside-down.

How certain are you about your retirement beliefs?  If you were to "Test Drive" your future retirement what new information might you uncover?   If you had a future financial concern in your retirement plan, when would you and your spouse want to know about it?    Sooner of later?

Current day definition of a 'Black Swan' event:

An event or occurrence that deviates beyond what is normally expected of a situation and that would be extremely difficult to predict. This term was popularized by Nassim Nicholas Taleb, a finance professor and former Wall Street trader. His book, a New York Times Best Seller is "The Black Swan" - The Impact of the HIGHLY IMPROBABLE.

A current example of this reference is the newspaper article below using "black swan" to describe what happened to 19 Arizona firefighters in July, 2013.

Investopedia explains 'Black Swan'
Black swan events are typically random and unexpected. For example, the previously successful hedge fund Long Term Capital Management (LTCM) was driven into the ground as a result of the ripple effect caused by the Russian government's debt default. The Russian government's default represents a black swan event because none of LTCM's computer models could have predicted this event and its subsequent effects.

The black swan theory or theory of black swan events is a metaphor that describes an event that is a surprise (to the observer), has a major impact, and after the fact is often inappropriately rationalized with the benefit of hindsight.  The event can either be positive or negative relative to your position.

The theory was developed by Nassim Nicholas Taleb to explain:
The disproportionate role of high-impact, hard-to-predict, and rare events that are beyond the realm of normal expectations in history, science, finance and technology.  The non-computability of the probability of the consequential rare events using scientific methods (owing to the very nature of small probabilities)

of the rare event in historical affairs.

Specifically, Taleb asserts in the New York Times: What we call here a Black Swan (and capitalize it) is an event with the following three attributes.

Second, it carries an extreme impact.

Black swan events were introduced by Nassim Nicholas Taleb in his 2004 book Fooled By Randomness, which concerned financial events. His 2007 book (revised and completed in 2010), The Black Swan extended the metaphor to events outside of financial markets. Taleb regards almost all major scientific discoveries, historical events, and artistic accomplishments as "black swans"—undirected and unpredicted. He gives the rise of the Internet, the personal computer, World War I, and the September 11 attacks as examples of black swan events.

After the first recorded instance of the event, it is rationalized by hindsight, as if it could have been expected; that is, the relevant data was available but unaccounted for in risk mitigation programs. The same is true for the personal perception by individuals.

An example Taleb uses to explain his theory is the events of 11 September 2001. 9/11 was a shock to all common observers. Its ramifications continue to be felt in many ways: increased levels of security; "preventive" strikes or wars by Western governments. The coordinated, successful attack on the World Trade Center and The Pentagon using commercial airliners was virtually unthinkable at the time. However, with the benefit of hindsight, it has come to be seen as a predictable incident in the context of the changes in terrorist tactics.

Coping with black swan events

The main idea in Taleb's book is not to attempt to predict black swan events, but to build robustness against negative ones that occur and be able to exploit positive ones. Taleb contends that banks and trading firms are very vulnerable to hazardous black swan events and are exposed to losses beyond those predicted by their defective models. On the subject of business in particular, Taleb is highly critical of the widespread use of the normal distribution model as the basis for calculating financial or other risk. In the second edition of The Black Swan, Taleb provides "Ten Principles for a Black-Swan-Robust Society".


Microsoft & Novell Networks

Dedicated Novell, Microsoft & SuSE Linux support - Essex

Microsoft are by far and away the market leading provider of business level network operating systems and related packages. Worldwide, more small to medium-sized business networks are run on the Windows 2008/2012 Server platforms than all other brands put together. Advantages include a huge range of popular networking and desktop products, along with availability of technical expertise. Disadvantages include being prone to malicious attack. For example, the vast majority of viruses are written specifically to attack Microsoft products.

Novell Netware was the first widely used PC networking platform back in the early 1980's. Netware has since evolved and now, along with many other Novell products such as GroupWise and BorderManager, it is often found at the core of many larger well-known corporations IT systems. However Novell's range of products is also available for smaller companies. Advantages include a second-to-none security and reliability record. The main disadvantage being a general misconception that Novell are from the past and in decline, which fortunately is not the case.


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NYFF Review: With ‘Flight,’ the Festival Caps a Spiritual 50th Year

NYFF Review: With 'Flight,' the Festival Caps a Spiritual 50th Year

The New York Film Festival has chosen to acknowledge the landmark moment of its 50th year with paragons of the medium, none more pronounced than its closing-night selection. Robert Zemeckis hasn’t made a live-action feature since 2000’s “Cast Away,” which makes it appropriate that his return to the form, “Flight,” also involves a plane crash and grand themes of regret and reconciliation centered around a dedicated lead performance. Now he has made another Hollywood spectacle, this one far sturdier.

“Flight” soars above “Cast Away” with a more fully realized calibration of suspense, entertainment value and emotional payoff. Slickly paced and carried by mature performances, “Flight” embodies one of the finer strains of Hollywood filmmaking in recent years. In a larger sense, it figures into a portrait of global cinema that has felt especially complete at this year’s NYFF.

Beyond its impressive special effects (a touchstone of Zemeckis’ career), “Flight” foregrounds movie stars in firm control of their material, particularly its leading man: Denzel Washington delivers one of his most astute roles in years as Captain Whip Whitaker, the alcoholic pilot of a doomed plane who manages to land it in a spectacular feat before dealing with the investigation into his culpability. Zemeckis’ tight direction jives nicely with John Gatis’ long-admired screenplay, resulting in a stylishly engaging character study with bold stabs at big ideas.

The last five words of the previous sentence could equally apply to Ang Lee’s “Life of Pi,” which opened the 50th edition of the New York Film Festival. “Flight” closes it with another overtly spiritual movie about men in search of meaning behind the cruelties afflicted upon them. Both “Life of Pi” and “Flight” directly invoke religion, a distinguishing aspect that may testify to their commercial viability as well as the foolhardy ingredients of the classic redemption story.

But where “Life of Pi” celebrates the possibilities of faith in a higher authority, “Flight” sublimates its dogma into a shrewd narrative about surviving addiction and coming to grips with the imperfections of human behavior. As a studio product, “Flight” broadly emphasizes concepts with noticeable currency in contemporary culture and visible throughout this year’s program.

In the span of less than a month, NYFF has unveiled a wide variety of international cinema, but nearly all of it has been haunted by death. The specter of colonialism hangs over the Portuguese films “Tabu” and “The Last Time I Saw Macao,” where characters both real and imaginary face untimely deaths. The French-Algerian war casts a shadow on the young revolutionaries of Olivier Assayas’ “Something in the Air,” while the Civil War imbues each scene in Steven Spielberg’s “Lincoln” with a grim atmosphere. Leos Carax’s “Holy Motors” includes more than one solemn death scene as well as an abstract form of wonder for the fragility of life, while “Leviathan” assumes the perspective of dead fish.

Despite such dour connective tissue, each finds a source of catharsis in the power of movies to explore this timeless inevitability. In a world still recovering from global financial collapse, crippled by ferociously partisan ideologies and murky predictions about our future prospects, the pervasively dour temperament makes sense. Even the expensive studio movies acknowledge as much while striking a tentatively positive note.

In “Flight,” Whip deals with his role in an incident that killed six people and constantly tries to bury his guilt. “Whose god would do this?” asks Washington’s character as he spends most of the running time trying to evade responsibility for his actions. These include the lines of coke he does before his ill-fated flight and the homemade mimosa he cooks up during it. In between those moments, he navigates choppy weather with ease, establishing the no-nonsense piloting skills that enable him to land the damaged aircraft in a field through a near-miraculous moment of acrobatic versatility.

Using mainly close-ups and a somersaulting camera, Zemeckis constructs as tense a crash sequence as the big screen has ever displayed. Frontloaded with the power of this brilliantly suspenseful moment, “Flight” speeds into a prolonged story of its fallout: While hiding from the public eye, Whip deals with inquiries into his private life while forming a relationship with alienated junkie he meets at the Atlanta hospital where he recovers from the crash. Their ensuing drama has a tacked-on quality that never fully syncs with the rest of the material, although it’s among several ingredients used to expand on Whip’s alcohol problems and the perilous hubris involved in his ongoing attempts to disguise them.

As the institutional interest in his life heats up, Whip gets increasingly candid with the muted lawyer (Don Cheadle) tasked with keeping him out of jail; John Goodman surfaces in a couple of scenes as a hilarious fixer able to keep Whip comfortably shrouded from media scrutiny. Gatis’ sharp screenplay nimbly juggles these various characters by foregrounding Whip’s undulating problems with addiction. Zemeckis moves the proceedings along by relying on calculated music cues ranging from the Rolling Stones to the Red Hot Chili Peppers (as well as recurring use of Traffic’s “Feelin’ Alright,” the de facto theme song) in addition to Washington’s evident commitment to the material.

The movie is notably not about the crash but rather the transformative power of a single cataclysmic event. For obvious reasons, “Flight” has post-9/11 demons in its DNA, but reflects the temperament of the current era to make peace with darkness and soldier forward to a better tomorrow. That’s an undeniably cheeky takeaway rendered in somewhat distractingly obvious terms with an overly familiar tell-all monologue in its concluding moments. But there’s nevertheless a welcome form of comfort that can be derived from its blatant sentimentalism. Viewed in the context of the festival, “Flight” epitomizes a dogged willingness to convey hope for the future while acknowledging the possibility of more dark days ahead. It’s a good way to go out.

Criticwire grade: B+

HOW WILL IT PLAY? Paramount opens “Flight” on November 2, right in the heat of Oscar season, where it’s a definitive candidate for several major prizes — particularly for Washington’s performance and Gatis’ screenplay. It should satisfy audiences in search of top-caliber studio fare during the fall season and perform decently during its initial weeks of release.


The Eastland Disaster

The Eastland disaster was one of the deadliest maritime disasters in American history. And in this particular case, safety regulations actually made things worse.

A History of Pizza Live at C2E2

Pizza-like foods go way, way back in history, long before we associated the delicious dish with Italy. How did pizza's pedigree develop, and how did it get to its second home in the U.S.?

Katharine Dexter McCormick: The Money Behind the Pill

Henry Gerber and Chicago's Society for Human Rights

In the 1920s, the Society for Human Rights was founded in Chicago with the intent to decriminalize homosexuality. The society's founder was inspired by Germany's homosexual emancipation movement.

Christmas Tree Ship

It's a Christmas episode, a shipwreck and a ghost story rolled into one! It's the story of the the Rouse Simmons, which sank in Lake Michigan while hauling a load of Christmas trees to Chicago.

The Iroquois Theater Fire

Maria Tallchief

Frances Glessner Lee and Tiny Forensics

Many forensic investigation standards of today have roots in the work of a Chicago heiress who was more interested in crime scenes than high society. Her most notable contribution to the field came in the form of tiny homicide dioramas. Read the show notes here.

Jane Addams, Pt. 2

Jane Addams was a leader and advocate, especially for the working poor - but her work really boiled down to a better quality of life for everyone. Part two covers her life beyond Hull House, controversial war stance, Nobel Prize and legacy.

Jane Addams, Pt. 1

Jane Addams was one of the foremost women in America's Progressive Era. She co founded the social settlement Hull House, spoke and wrote on social issues, and had a hand in the founding of many social organizations, including the NAACP and ACLU.


The 31-year-old man who fell to his death on a South Island mountain face has been named as Gergo Verhas, a Hungarian who lived in Auckland.

Mr Verhas was climbing on Mt Rolleston with two women companions when he fell about 7.30am yesterday.

Despite an immediate emergency response from the Canterbury Westpac Rescue Helicopter, he was unable to be saved.

Mr Verhas was an experienced climber and a member of the New Zealand Alpine Club.

Chief executive Sam Newton described what happened yesterday.

"In a team of three climbers, Gergo had ascended the Central Direct Route on the Otira Face of Mount Rolleston on Sunday. After spending the night near the summit, the party was descending via the standard descent route, early on Monday morning," he said.

"During that descent, Gergo slipped on loose scree, slid across a small patch of snow and came to a halt in a loose rocky area 50m below.

"His passing is a tragic loss to his friends and family. Our thoughts are with them."

Mr Newton said Mr Verhas was "an active and popular" member of the Auckland branch of the club had completed instruction courses in rock climbing and snowcraft.

"Gergo had enjoyed numerous climbs of significant mountains in New Zealand.

"In the last six months, Gergo had summited Mount Taranaki, all 12 peaks of Mount Ruapehu, Mount Earnslaw, Mount Temple and Mount Sefton - an impressive list.

"Prior to coming to New Zealand Gergo had completed the Haute Route Pyrénéenne, an incredible 800km trek in Europe.

"It is saddening that someone who was enjoying the mountains so much, has had such a tragic accident.

"Gergo will be fondly remembered by the Auckland Section of NZAC and the wider climbing community."


“You are what you eat”

Suppose a consumer who is allergic to dairy products is shopping for a non-dairy yogurt.  After browsing through a variety of brands, she sees the product “O’Soy," with a product label claim identifying the product as “organic soy yogurt.” Is it safe for the food allergic consumer to rely on this information, purchase and then consume this product?

            This is a serious question faced by many food allergic consumers today and the answer is not as simple as one would presume.  The “O’Soy” brand name appears to indicate this is a soy based yogurt.  In addition to the brand name itself, a prominent product label claim in large bold font on the front label, identifies the product as "Organic Soy Yogurt." A recent research study has suggested that food consumers are influenced by and base their purchase decisions  on the name of the food product (Irmak, Vallen, & Rosen Robinson, 2011).  Additionally, prior research has substantiated the notion that food allergic consumers utilize package information and product claims to evaluate if a product contains an allergenic substance (Voordouw et al., 2012).

            If the above food allergic consumer assesses allergen risk in a similar fashion, this is but one example of how a food allergic consumer may unknowingly consume an allergenic substance, since an inspection of the back label of the “O’Soy” yogurt states that the product does in fact "contains milk."  This potential mistake, relying on the package information found on the front of the yogurt container's label, could be life threatening to a food allergic consumer allergic to dairy products.   Further investigation revealed an online disclosure, found on the "O'Soy" website that states  "O’Soy is lactose free and that those who are only lactose intolerant, and not allergic to milk, can safely enjoy O’Soy" (Stony Field Farm, 2011).   In 2014, Stonyfield Farms modified the ingredients and cultures used in O'Soy yogurt in order to eliminate dairy in the yogurt.

            As the previous example illustrates, more understanding and research is needed on this issue, since confusing and often conflicting product ingredient information appears on food product labeling. Domestically and internationally, food allergies have become exceedingly prevalent in children, adolescents and adults (American Academy of Allergy, 2011). Both the United States and various European governments recognize the importance of clear and complete ingredient communications of known allergens to allergic consumers and have instituted various labeling and allergen disclosure laws such as the United States’ Food Allergen Labeling and Consumer Protection Act (FALCPA) and legislation improvements like those found in the EU's Food Information for Consumers Regulation (Agency, 2014; Services, 2006).

            Regardless of legislative mandates, manufacturers should institute clear labeling if the product(s) place consumers at risk for harm. Yet, despite the ethical benefits and legislative mandates designed to assist the food allergic consumer, food allergy labeling still remains unclear and there is no clear consensus on the best manner to convey allergen information to the food allergic stakeholder, and as noted in the prior example, there have been examples of conflicting (incongruent) allergen information communicated to the allergic consumer via the product information and packaging material.

            This domain of food allergic consumers, current labeling issues and their decision making processes is an under-researched and newly emerging issue that needs to be addressed so as to provide a safer and more consumer friendly food shopping experience for allergic consumers and stakeholders of food allergic individuals.
Do you agree?  Have you had any experiences similar to the example shared above?  What are your thoughts to improve the labeling on food?

*This blog is based on a doctoral dissertation by Roger Wortman entitled ‘Impact of Product Label Claims.' His committee consists of Dr. Suri Weisfeld-Spolter (chair), Dr. John Stanton (reader), Dr. Cindy Ruppel (methodologist) and Dr. Herb Brotspies (4th member).

Image Source: Speech Buddies, Inc., 2017

Sara Weisfeld-Spolter, Ph.D., Associate Professor of Marketing, H. Wayne Huizenga College of Business and Entrepreneurship, Nova Southeastern University. Dr. Weisfeld-Spolter can be reached at sw887@nova.edu

Study Shows 10 Ways Humor Lifts Social Content

As social content explodes beyond the attention capacity of us all, it’s no surprise that entertaining content has taken center stage. Humor, in particular, accounts for a vast majority of social videos reaching over 50,000 views. But many brands are still cautious about using comic devices to attract their target audiences.

Fearing a tarnished image to serious business, offended audiences, or simply a joke gone flat, many opt for inspirational content as an alternative to rousing emotions. But a large scale study (http://bit.ly/1dg5yex) of commercials parked on YouTube found a pattern of tasteful comic devices that works well in generating views and engagement.

The following is a countdown of ten types of humor that align well with three theories of humor. In general, we tend to laugh when we:

  1. See something out of sorts (incongruence)
  2. Enjoy others’ misfortunes (disparagement)
  3. Release ourselves from inhibitions or childlike innocence (arousal-safety)

 #10 Awkwardness

Why we laugh at awkward moments has much to do with the pleasure derived from seeing others fail or suffer misfortune. Rooted in the Theory of Superiority, this disparaging form of humor leads to a feeling of sudden glory when we displace our own histories of embarrassing moments onto others. Among the types of humor that capitalize on awkwardness are remorseful regrets, uncomfortable settings, exercising humility and revealed secrets.

One way to enjoy others’ misfortunes is through the depiction of embarrassing situations where victims are left speechless. By displacing own recollection of these embarrassments onto others, we are in effect saying: “I am glad this did not happen to me.” Arguably, this laughter increases the more a victim is caught off guard or left with an unsolvable quandary.

 #9 Sentimental Humor

Sentimental Humor taps into our emotions through an arousal-safety mechanism. For example, in the first stage or arousal-safety, emotions are aroused with sentimentality, empathy or some form of negative anxiety. As the story-line develops, we then see this heightened arousal state as safe, cute or inconsequential. This shift from high arousal to relief is what creates laughter.

A way to imagine this type of humor is to consider how we laugh. Comic wit, for example, is normally expressed as “Ah Hah.” Laughter from disparaging humor (e.g., putdowns) is normally expressed as “Ha, Ha.” Sentimental humor would be expressed as “Ahhh.” This could happen when we witness someone escaping danger as well as when we experience a child doing something cute.

Among the types of humor that capitalize on this arousal-safety mechanism are those involving false alarms, melodrama or child innocence. Another successful way to get laughter from sentimental humor is through the relief of fear and anxiety.

 #8 Malicious Joy

Malicious joy, or schadenfreude, refers to the pleasure we derive from seeing others fail or suffer misfortune. Also rooted in the Theory of Superiority, this feeling of sudden glory can occur when we witness bungled behaviors, unanticipated spoilers, unfortunate happenstances, deserved repercussions or the acts of cretins.

Many videos of this type are based on characters that are prone to accidents or saying the wrong thing. Another successful way to get laughter from malicious joy is through the portrayal of spoilers. This cause of laughter taps more into our emotional senses where a feeling of superiority is felt over those whose peace or excitement is snatched away.

 #7 Social Order Deviancy

The most engaging form of humor in viral videos involves social order deviance or those behaviors that challenge society rules and expectations.  Many of us love watching others unleash their innate desire to break the law, enter forbidden territory or simply act out our inhibitions. Most of the viral videos featuring this form of humor involve society irreverence, taboos, offensive behaviors or unleashed mania.

Several viral YouTube videos are based on high society satires, rule breaking and undermining authority. Common to all is the release of tension we experience by unloading on someone’s statutes. Witness how this works when we outwit the censorship imposed by honorable judges, pious clergymen or smug professors.

 #6 Unruliness

Unruliness refers to outrageous behavior. Consider how Snicker’s Mr. T, Nike’s Clay Matthews, and Reebock’s “Terry Tate Office Linebacker” videos reached millions of views as these icons disrupt peaceful settings.

The Relief Theory contends that laughter is created when we release tension or nervous energy such as when we unleash our suppressed desires. Consequently, we love watching others act out uncontrollably or violate some social order. In effect, we are likely enjoying the observation of others acting out our own inhibitions through hysteria, impulsive outbursts, displaced irritation or exercising improprieties.

A popular technique for entertaining audiences with humor is to show people unleashing their anxiety through uncontrollable screaming and yelling. Another common way to release suppressed desires is to display scenes of wishful naughtiness.

 #5 Irony

Irony much like that of any perceptual discord, is characterized by a contrast, between expectations and reality. It makes us laugh by showing the opposite or undesired intentions of someone’s actions. Mentally, we are saying to ourselves: “…I did not see that coming…”

An unusual pairing of well-known characters or scenes, for example, make us laugh at the imagined conflict. Other examples of visual irony include the casting of humans as animals or cyborgs as humans. We often laugh over situational irony in which actions have an effect that is contrary to what was expected. This often happens in the case of a coincidental backlash, where the odds of such an unexpected scene spoiler are infinitely low.

 #4 Surprise Twist

Surprise twist causes us to laugh as we witness or experience a change in course. Stemming from the Theory of Incongruity, this concept entertains us through a distracting segue. Mentally, we are asking ourselves: “…Where did this come from?”

This surprise twist can be realized in the form of visual anomalies (e.g., sudden appearances, changes or revelations) or conceptual incongruities (e.g., storyline twists or unexpected responses). In each case, we detect a mismatch with what we expect to occur next. Research suggests that we laugh when our minds anticipate a certain outcome, only to be tricked at the end with a wrong or uneventful answer.

 #3 Perceptual Discords

Perceptual Discords come in at number three on the list.  Like exaggeration, discords represent a form of comic wit. But instead of showing extremes, they show us something out of touch. Stemming from the Theory of Incongruity, this concept entertains us by contrasting what we see with what is routinely expected.  Mentally, we are asking ourselves: “Did I see that correctly?”

This perceptual discord can be realized in the form of visual anomalies like impersonations, eccentric behaviors or bizarre substitutions. In each case, we detect a mismatch with common perceptions. Some of the top viral videos show unconventional routines or unusual settings surrounding the highlighted activity. In other cases, the viral videos make us laugh when we imagine a human depiction of abstract concepts or literal interpretation of idioms.

 #2 Putdown Mockery

Mockery comes in at number 2 on our list. This technique capitalizes on our emotional reaction to watching others experience a well-deserved putdown. Stemming from the Theory of Superiority, we often experience sudden glory when dethroning others or elevating ourselves at the expense of others’ peculiarities. Of the viral videos featuring putdowns, most include mocked peculiarities, lofty conquests, society satires or stereotyping.

One technique used in putdowns taps into our desire to dethrone the self-righteous, the popular, the pretentious and the hyper-masculine.  Some of the top viral videos show scenes of humbled haughtiness featuring those we despise or compete against.

 #1: Exaggeration

Hyperbole, is the number one attention getter among all humor techniques used in viral YouTube videos. Dating back centuries as a comic device, it suggests that laughter results from seeing things out of sorts.

So have we left anything out? What type of humor do you feel most comfortable using for your audience?

James Barry, D.B.A., is an Associate Professor of Marketing in the Huizenga College of Business and Entrepreneurship, Nova Southeastern University. He develops, teaches and consults on a variety of social media marketing subjects. He can be reached at jimbarry@huizenga.nova.edu

Types of Electronic Word-of-Mouth (eWOM)

Electronic Word-of-Mouth (eWOM) is a rapidly growing, quickly evolving and increasingly important extension of traditional face-to-face word-of-mouth (WOM) in the marketing and consumer environment, and most recently, a very important outcome of activity on social media. Indeed, social media have greatly changed the way in which firms and their constituents are able to communicate electronically, extending the possibilities of eWOM from the traditional one-to-many and one-to-one marketing communications, to the new many-to-many and many-to-one communications.

Social network sites in their essence are built on eWOM in various forms and guises.  While much literature has addressed some of the different types of eWOM and their differences, there has not been a consolidated conceptualization of such differences. We suggest a concise typology of eWOM communications based on the level of user interactivity and participation, and thus locate these forms in a 2 (communication: collective, individual) x 2 (C2C interactivity: low, high) framework below. Four distinct categories of eWOM emerge from our framework: many-to-one, one-to-many, many-to-many, and one-to-one.

Many-to-one eWOM (e.g., the number of votes) represents the trend or explicit preference of a crowd. One-to-many text-based eWOM (e.g., product reviews) is descriptive and requires the audience to use more cognitive effort to read the reviews.  Many-to-many eWOM (e.g., online discussion groups) is a high involvement activity in which consumers continuously participate in the communication process. Finally, dyad-based one-to-one eWOM (e.g., instant messaging) is mostly private and non-transparent communications. The typology of eWOM presented in our figure not only depicts how different eWOM types are generated but also reflects how these different types are processed by users.

What are your thoughts on our suggested framework of eWOM types?

Do you think they are equal in their degrees of persuasiveness on the users of these eWOM?

Which eWOM category do you use most?

Suri Weisfeld-Spolter, Ph.D., is Associate Professor of Marketing and Chair of Doctoral Programs in the H. Wayne Huizenga School of Business and Entrepreneurship, Nova Southeastern University. She can be reached at sw887@nova.edu

Image Positioning - Differentiate to Communicate Value

American society is intrigued by image. Consider this related word - imagine. Disney is all about the customer experience and emotionally and magically transports guests to another time or place. Image is often associated with entertainment, fashion, and technology markets. Corporate image is the reputation of an organization viewed by its various stakeholders – investors, employees, customers, business partners, communities, etc. All companies have a singular corporate personality that differentiates them from their rivals. The communication challenge is to manage and enhance the firm's identity over time.

A perceived image is based on two components: 1) what the company does and says, and 2) what the customers/market say about the organization - this is more important. Companies must manage a strong IMC (integrated marketing communications) program consisting of advertising, selling, sales promotion, online, social media, and public relations activities. Customer-generated content such as Facebook posts, tweets, blogs, and online communities can dramatically impact organizational performance.

Perhaps your company is not a global giant – does image research make sense for you? Consider these queries as you revisit your marketing communications strategy. How important is image in your value proposition? Should it be even more important? Does your image clearly resonate with your target market? How can you get your customers and the market to share more positive messages about your company? What is your main point of differentiation from your competitors? Should coolness be a major or minor part of your IMC strategy? How can you best tell your business story to communicate value?

Art Weinstein, Ph.D., is Chair and Professor of Marketing at Nova Southeastern University and author of Superior Customer Value – Strategies for Winning and Retaining Customers. He may be reached at art@nova.edu or 954-262-5097; visit his website www.artweinstein.com Read More


Lord of the Flies

Lord of the Flies

The power of literature is that it highlights significant social issues within society.

Argue point of view/position of the essay, outline points.

One of the many different uses or powers of literature is that it can put you in someone else’s shoes, it allows the reader to see and acknowledge issues that are otherwise confronting or uncomfortable. Literature, for hundreds of years has been used as a tool to persuade you to think a certain way, to see things from a different point of view and even to bring to light issues within society itself. The most written about are bullying, violence and forced maturity.

In William Goldings Lord of the Flies these issues are all discussed frequently, as you read the book you begin to notice that almost every character has been developed to represent similar social issues. Ralph is an example of forced maturity. He takes on the position as leader despite being so young, and tries his best to keep the boys safe while also trying to find an escape off the island. This forces him to be the mature grown up of the group, to be smart about every decision; Jack is an example of youth violence, he thrives on desolation and violence and entirely comes out of his shell when he realises that there are no consequences for his actions while separated from civilization. Piggy is a clear example of bullying in todays society, he is the most blatantly written and talked about character of the book, he was bullied in England because of his weight and despite being so far away from his old life he seems unable to shed the obedient nature that had been beaten into him for so many years.

Ralph/Forced Maturity/Quote from book
Forced maturity in today’s society is a serious problem among teens and young children. From a very young age we are taught that if we want to make it in the world, we have to look a certain way, if we want to be taken seriously, we have to act a certain way, and if we decide we want to do a certain job,...

Similar Essays


1.该OJ由于交换空间受限，暂不不支持万能头文件：bits/stdc++.h！！！ 2.该OJ如果是长整型的话，C的输入输出请使用%lld！！！

Problem 1004. -- 【2012四川省热身赛】Problem B. How Many Roads?

1004: 【2012四川省热身赛】Problem B. How Many Roads?

Time Limit: 1 Sec  Memory Limit: 32 MB
Submit: 3  Solved: 0
[Submit][Status][Web Board]

As a director of cities transportation construction, Elfness is given a mission to connect n cities by
a lot of roads. Of course, the more roads to be built, the more convenient it would be. But if there
are two roads cross each other, traffic accidents may happen. So it means on Elfness’s ACM(All
Cities’ Map), there are no cross roads. And now, Elfness wants to know how many roads can be
built at most(Attention: a road won’t have to be a segment, it can be a straight line or a ray)?

The first line of input is a single number T(T < 1000),means the number of test cases.Then T
cases followed, each case contains only one line with a single number n(0 < n ≤ 108),the number
of cities.

For each test case,you should output one line. First, output “Case #t: ”, t means the number
of the test case which is from 1 to T. Then, output an integer indicates the maximal number of
roads can be built.

Sample Input

Sample Output

Case #1: 0
Case #2: 1
Case #3: 3

[Submit][Status][Web Board]


Knife Tattoo Symbolism

The Symbolic Knife

Knife Tattoos often signify a lost love, and the knife conveys a cold, steely pain encountered with having been cut by the brutality of a lovers neglect or betrayal. In this scenario, we could also say a tattooed knife could symbolize a "cutting away" from a bad relationship - slicing through the trauma & difficulties caused by a lover and becoming liberated from the drama of a dysfunctional relationship.

In Buddhist symbology the knife often represents cutting the ties of materialism.

In the suit of swords in the Tarot. This suit represents challenges, usually wrought from mental nuances like doubt, fear, worry. We see a constant struggle to slice through confusion. The knife in these cards symbolizes the double-edged nature of the mind.


Why does Sinusitis re-occur.

Chloe JohnsonHealth Tip

Sinusitis health tip.

Why does Sinusitis frequently reoccur?

Sinusitis is better divided into one off or occasional episodes (acute sinusitis) or a constant grumbling disease (chronic sinusitis).

Chronic sinusitis always involves more than just the sinuses, so we call it chronic rhinosinusitis (it is often associated with asthma too).

There are some people who suffer something in between the two – a propensity to regular attacks called recurrent acute sinusitis.

Acute Sinusitis

Acute sinusitis leads to cold-like symptoms associated with more severe aspects including facial pain, fever (high temperature), and copious discoloured nasal discharge.

Treatment is as per a cold (as above) but antibiotics may have an additional role, especially if the patient is more unwell than a typical cold and has a temperature.

Recurrent Acute Sinusitis

If you are prone to recurrent cold-like illnesses and are more affected than most, it may be that you have some form of predisposition.

It may be structural (a deviated nasal septum causing partial nasal or sinus blockage that is easily compromised.

It may also be that you have allergy or chronic sinusitis (often associated with asthma) underlying the problems.

In such cases, medical or surgical treatments may have a role – as in Chronic Rhinosinusitis (next).

Chronic Rhinosinusitis

Chronic rhinosinusitis is when symptoms become constant.

It is often less severe, with no fever, and much less pain.

A poor sense of smell, nasal blockage, pressure, and a runny nose may be constant features.

In these cases, medical and sometimes surgical treatments can be helpful, but there is no outright ‘cure’.

I usually recommend nasal corticosteroid sprays and daily saline (salt water) nasal washes.

Neilmed sinusrinse (available ‘over the counter’) is the best way I have found to deliver saline washes.

Antibiotics usually only give a transient relief that can lead to a misconception that they are helpful.

In the longer term they only lead to more complicated antibiotic resistant infections.

In severe cases (usually acute sinusitis) with a persistent high fever antibiotics ARE required however.

Decongestants are harmful if used more than occasionally – avoid them except perhaps for a special occasion or flight.

Antihistamines are mainly useful for mild allergy only.

“Sinus” Pain

People with facial pain often think, or are told that they have sinusitis.

Acute sinusitis can be painful, but is easily recognised by the fever, nasal symptoms, and resolution within a week or two.

Very few patients with constant facial pain for more than a week or two have sinus troubles.

Common causes in these patients are either dental, related to the jaw, stress or tension headaches, migraines or neuralgia.

Many of these processes can cause some limited nasal symptoms (congestion, clear mucous), but this is NOT sinusitis.

If there is uncertainty, examination in an ENT clinic of the inside of the nose (and sinuses) can be helpful.

To find out more about our ENT consultants >>click here<<

Alternatively you can call our friendly and helpful team on 01245 474070 or e-mail enquiries@baddowhospital.co.uk.


ROME, Sept. 10— Janet Evans was trying to explain how it felt to win her 21st consecutive 800-meter freestyle race, but the Chinese kept interrupting.

Evans was in the interview room at the Foro Italico, basking in the afterglow of the first and, in all probability, only, gold medal for an American woman in the swimming world championships. From her seat, she could lean over and see the electronic scoreboard as the first leg of the 400-meter medley relay came to an end.

"What's the world record in the 100-meter backstroke?" she asked the reporters in the room. "Because I think some Chinese girl just broke it."

The girl was He Cihong, and her time of 1:00.16 on the lead leg was indeed a world record: 15 hundredths of a second faster than Hungarian Krisztina Egerszegi's three-year mark.

Evans resumed answering questions, but not for long. The numbers on the scoreboard were simply too low; the Chinese lead too overwhelming. And as Le Jingyi churned toward the finish on the anchor freestyle leg, a hush came over the room as Evans, Hayley Lewis, the silver medalist of Australia, and the surprise bronze medalist, Brooke Bennett of the United States, stared at the scoreboard, waiting for the clock to stop moving.

It stopped at 4:01.67, giving the Chinese women their fourth world record and ninth gold medal of these championships, and bringing the total number of world marks set here to eight. Flashing That Grin

Evans looked back at the reporters and flashed the lopsided grin that charmed many a Nielsen family at the 1988 Summer Olympics. No one needed to ask about the Chinese.

"I think probably a lot of teams have had a hard time," Evans said. "It started with those two great times they had in the 100 free, and people began thinking, 'How can we keep up with that.' Myself included in the 400 free."

Evans, the defending world champion in the 400, finished a stunning fifth on Wednesday in that race, won by the previously unheralded Chinese swimmer, Yang Aihua. But tonight she was back on more familiar territory: back on the highest step of the medals stand.

The gold medal was her third individual gold in a world championship and her second straight in the 800 free, a race she has not lost since the Pan- Pacific Championships in 1987. But while Evans led from the 300-meter mark to the finish, her remarkable streak nearly came to an end. Lewis, the Olympic silver medalist behind Evans in 1992, made up nearly a second in the last 100 meters, and, in the end, Evans's right hand touched the wall just 9-100ths of a second before Lewis's left hand.

Evans finished in 8:29.85, well off her world record of 8:16.22, but that was hardly her primary concern.

"I'm really happy about this one, mostly because my confidence was down a little bit," she said. "This shows me I can really brace myself and be tough when the chips are down." Following an Idol

As for Bennett, a 14-year-old from Tampa who decided to become a distance swimmer after watching Evans win three Olympic golds in Seoul, she made it clear she could be a major factor in Atlanta in two years, improving on her personal best by more than five seconds.

The Chinese gold-medal team in the 800-meter freestyle was composed of He Cihong, Dai Guohong, Liu Limin and Le Jingyi, who all have won gold medals in individual events here. And though they lost some time between legs with slow starts, they still managed to beat the Americans' world record of 4:02.54, set at the 1992 Summer Olympics, by .87 seconds.

More impressive was the margin of victory: nearly five seconds over the Americans, who took the silver in 4:06.53. The Russians were third in 4:06.70. Through 13 events, the Chinese women have won nine golds, five silvers and a bronze. They also have kept their cool in the face of repeated allegations of performance-enhancing drug use.

"You all know China has a population of one billion," said Liu, who swam the butterfly leg tonight. "So it is no surprise some world champions come out." SPLASHES

GARY HALL, the 19-year-old American competing for the first time internationally, won his second individual silver, finishing behind Aleksandr Popov, the Russian Olympic champion, in the 50 free. Popov's time of 22.17 was the fourth fastest in history; Hall, who swam the anchor on the Americans' victorious 400-meter relay team, finished in 22.44. JEFF ROUSE, the American world-record holder in the 100 backstroke, had to settle for silver after MARTIN LOPEZ-ZUBERO of Spain caught him in the second 50 and won the gold in 55.17 seconds. DENNIS PANKRATOV of Russia won the 200 butterfly in 1:56.94.

Photo: Janet Evans won the United States' first world championship gold medal with an 800-meter freestyle victory. (Reuters)


Weather Forecast

Letter: Sailer is best candidate for House

Brita Sailer knows firsthand the importance of education. She educated herself, then her children, then spent time in schools teaching about recycling and the environment, and finally moved to defending in the legislature the right of everyone to have a quality education.

She understands that education is perhaps the best way (other than coming from a rich family) for individuals to improve their living conditions, that with education come innovations necessary for a strong economy, and that without it, people are more easily manipulated by those with money and power. Well-educated citizens are vital for the survival of a successful democracy, and public education is the one area where everyone should have equal opportunities. It shouldn't matter if you live in the Cities or a rural area; a high-quality, free K-12 education must be available to everyone, and Brita Sailer will fight for that right.

Education doesn't end with K-12 however. Students with moderate or lower family financial support must be able to find low-cost funding to attend technical schools and colleges. Brains aren't given to children on the basis of their parents' income. What a waste for our country if only rich people's children could afford higher education. Brita will work hard to provide the funding that keeps tuition costs down, student loan interest low and ensures that programs like Pell grants, work-study, and Stafford loans remain available for Minnesota students.

As a teacher with personal experience working with Brita in the past, I value many aspects of her personality, such as intelligence, creative problem-solving skills, empathy for others, hard work ethic, honesty, etc., but for me the two most important elements she will bring to the Minnesota Legislature are these: Brita sincerely listens. She tries to get others' views and insights while collecting all available factual information on an issue. Secondly, she is very capable of making decisions beneficial to our area and to the state as a whole without just being a rubber stamp for a national political party.

Brita can be trusted to work hard for all of us, no matter our political party, income, gender, race, or age. She is the best candidate overall, but when it comes to the issue of protecting quality education for every Minnesota child, Brita Sailer is the undisputed favorite.

Linda Uscola


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