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Ethanol is a small two carbon alcohol that, due to its small size and alcoholic hydroxyl group is soluble in both aqueous and lipid environments. This allows ethanol to freely pass from bodily fluids into cells. Since the portal circulation from the small intestines passes first through the liver, the bulk of ingested alcohol is metabolized in the liver. The process of ethanol oxidation involves at least three distinct enzymatic pathways.
The most significant pathway, responsible for the bulk of ethanol metabolism, is that initiated by alcohol dehydrogenase, ADH. As outlined below, humans express several ADH genes with the class I members being responsible for hepatic ethanol metabolism. The ADH enzymes are NAD+-requiring and they are expressed at high concentrations in hepatocytes. Animal cells (primarily hepatocytes) contain cytosolic ADH which oxidizes ethanol to acetaldehyde. Acetaldehyde then enters the mitochondria where it is oxidized to acetate by mitochondrial aldehyde dehydrogenase (ALDH). A cytosolic ALDH exists but is responsible for only a minor amount of acetaldehyde oxidation.
The second major pathway for ethanol metabolism is the microsomal ethanol oxidizing system (MEOS) which involves the cytochrome P450 enzyme CYP2E1 and requires NADPH instead of NAD+ as for ADH. The MEOS pathway is induced in individuals who chronically consume alcohol.
The third pathway involves a non-oxidative pathway catalyzed by fatty acid ethyl ester (FAEE) synthase. This latter pathway results in the formation of fatty acid ethyl esters and takes place primarily in the liver and pancreas, both of which are highly susceptible to the toxic effects of alcohol.
Oxidation of ethanol can also occur in peroxisomes via the activity of catalase. However, this oxidation pathway requires the presence of a hydrogen peroxide (H2O2) generating system and as such plays no major role in alcohol metabolism under normal physiological conditions.
Acetate from EtOH Metabolism and Fatty Liver
Under normal conditions the levels of acetate in human serum is < 0.2mM. Therefore, the roles of acetate metabolism in mammals under normal physiological conditions remain to be established. Normal physiological sources of acetate include bacterial fermentation in the colon which increases significantly when consuming a high fiber diet. This intestinal acetate enters the portal circulation and is taken up by the liver where it is converted to acetyl-CoA. Intracellular generation of acetate is the consequence of the ubiquitously expressed cytosolic enzyme acetyl-CoA hydrolase. The acetate can then be salvaged by reactivation to acetyl-CoA.
In the nervous system, the neurotransmitter acetylcholine (ACh) is degraded to acetate by acetylcholinesterase. In order to replenish the pool of ACh the acetate must be reactivated to acetyl-CoA so that it can participate in the choline acetyltransferase catalyzed reaction.
Acetate is also generated within the nucleus of all cells via the action of histone deacetylases (HDAC). As with the other sources of acetate, this nuclear acetate must be reactivated before it can be oxidized or reused.
Under conditions of prolonged starvation and in type 1 diabetes, the endogenous pathways of acetate production are the main sources for serum acetate. Following the consumption of ethanol, acetate levels can be elevated by as much as 20–fold.
Acetate, from whatever source, is converted to acetyl-CoA by ATP-dependent acetyl-CoA synthetases (AceCS: encoded by acyl-CoA synthetase short-chain family member genes: ACSS) by the following reaction:
ATP + acetate + CoA ↔ AMP + PPi + acetyl-CoA
Humans express cytosolic and mitochondrial acetyl-CoA synthetases, encoded by the ACSS2 and ACSS1 genes, respectively. Expression of ACSS2 is under the control of SREBP-1c which is itself transcriptionally regulated by PGC-1α. Interestingly, mammalian AceCS are regulated by reversible acetylation catalyzed by the sirtuins, SIRT1 and SIRT3, and the activity of PGC-1α is also regulated by SIRT1 activity. Cytosolic ACSS2 is a target of cytoplasmic SIRT1 whereas, mitochondrial ACSS1 is a target of mitochondrial SIRT3.
The primary causes of fatty liver syndrome (hepatic steatosis), induced by excess alcohol consumption are the altered NADH/NAD+ levels that in turn inhibits gluconeogenesis, inhibits fatty acid oxidation and inhibits the activity of the TCA cycle (see below for details). Each of these inhibited pathways results in the diversion of acetyl-CoA into de novo fatty acid synthesis. Ethanol has also been shown to activate SREBP-1c which results in the transcriptional activation of numerous genes involved in lipogenesis. However, given that large amounts of acetate are generated via ethanol metabolism in the liver, this can be a significant contributor to the overall pool of acetyl-CoA utilized as the precursor for fatty acid and cholesterol biosynthesis.
Enzymes of Ethanol Metabolism
In humans there are multiple isoforms of ADH encoded for by seven different ADH genes. All seven ADH genes reside within a 365kbp region on chromosome 4q23. All human ADH genes are members of a large family of enzymes known as the medium-chain dehydrogenase/reductase (MDR) superfamily. Within the human genome there are at least 25 members of the MDR family of genes. Functional ADH exists as either a homo- or a heterodimer and the active enzymes are divided into five distinct classes denoted I–V. It should be pointed out that humans evolved to express multiple ADH genes and isoforms, not for metabolism of ethanol, but to metabolize naturally occurring alcohols found in foods as well as those produced by intestinal bacteria. As an example, one form of ADH (encoded by the ADH7 gene) is responsible for the metabolism of not only ethanol but also retinol to retinaldehyde which is the form of vitamin A necessary for vision.
Table of Mammalian Alcohol Dehydrogenases
|Gene/*Allele ID||Gene Class||Protein Name||KM(mM) for Ethanol||Primary Tissue|
(also identified as ADHX)
The hepatic forms of ADH are derived from the protein subunits encoded by the class I genes: ADH1A (also known as ADH1), ADH1B (also known as ADH2), and ADH1C (also known as ADH3). The α, β, and γ subunits encoded by these three genes, respectively, can form homo- and heterodimers as indicated above. These ADH isoforms account for the vast majority of ethanol oxidation in the liver. As the concentration of ethanol increases in the liver the π-ADH isoform, encoded by the ADH4 gene, contributes significantly to overall hepatic ethanol oxidation. The ADH5 gene is ubiquitously expressed and the encoded protein functions in the oxidation of long-chain primary alcohols and as a formaldehyde dehydrogenase. The ADH5 encoded protein exhibits little, if any, ethanol oxidizing activity as can be seen by the extremely high Km indicated in the Table. The ADH6 encoded enzyme has not been characterized so little is known regarding its substrate(s) and activity. As indicated above the ADH7 encoded enzyme oxidizes both ethanol and retinol.
As a consequence of single nucleotide polymorphisms (SNPs) in several of the ADH genes there are isoforms derived from the same gene that exhibit different kinetic characteristics. As shown in the Table above there are three known polymorphisms in the ADH1B gene and two in the ADH1C gene. The ADH1B*1 allele, encoding the β1 subunit, is referred to as the reference ADH1 allele. This particular allele encodes Arg(R) at positions 48 and 370. The ADH1B*2 allele encodes the β2 subunit that has His(H) at position 48. The ADH1B*3 allele encodes the β3 subunit that has Cys(C) at position 370. Both the ADH1B*2 and ADH1B*3 encoded subunits harbor amino acid substitutions that affect the binding of the NAD+ cofactor. The consequence of these alleles is that the ADH enzyme has a much higher turnover rate because the NADH is more readily released at the completion of the reaction. The ADH1B*2 allele is common in person of Asian descent while the ADH1B*3 allele is common in people of African descent. The activity of the ADH1B*2 protein is on the order of 40 times greater than the ADH1B*1 protein. Individuals who express the ADH1B*2 allele are, therefore, much less likely (deemed protective) to abuse alcohol since they rapidly produce large quantities of acetaldehyde resulting in rapid onset of severe side effects such as tachycardia, nausea, flushing, and vomiting.
There are two known alleles in the ADH1C gene. The ADH1C*1 allele encodes the γ1 subunit which contains Arg(R) at position 272 and Ile(I) at position 350. The ADH1C*2 allele encodes the γ2 subunit that has Gln(Q) at position 272 and Val(V) at position 350. In almost all cases the dimers formed from the subunits encoded by these two ADH1C alleles are homodimeric (e.g. γ1γ1). A third ADH1C allele encodes a Thr(T) at position 352 (identified as the ADH1C*Thr352 allele) that has been found in Native American populations but the protein has yet to be fully characterized.
There are two primary aldehyde dehydrogenase (ALDH) genes in humans that encode enzymes that are responsible for the oxidation of the acetaldehyde generated during the oxidation of ethanol. These genes are identified as ALDH1A1 and ALDH2 and they encode the ALDH1 and ALDH2 enzymes, respectively. The ALDH1A1 gene is located on chromosome 9q21.13 and is composed of 13 exons that encode a 501 amino acid protein. The ALDH2 gene is found on chromosome 12q24.12 and is composed of 13 exons that generate two alternatively spliced mRNAs that encode proteins of 517 amino acids (isoform 1) and 470 amino acids (isoform 2). The ALDH1 protein is a cytosolic enzyme while the ALDH2 proteins reside in the mitochondria.
The bulk of acetaldehyde oxidation occurs in the mitochondria via ALDH2. However, some oxidation will occur in the cytosol via ALDH1 as a means to help control overall levels of acetaldehyde. This latter fact is most apparent in individuals with ALDH2 alleles that exhibit low to no acetaldehyde oxidizing capacity. Several ALDH2 polymorphisms are known to exist in various populations. Indeed, the most highly studied gene variations in alcohol-metabolizing enzymes are those in the ALDH2 gene. The ALDH2*2 allele harbors a Lys(K) residue at position 487 instead of the normal Glu(D) residue. This allele encodes a nearly inactive ALDH2 enzyme.
Of particular biochemical and physiological significance is the fact that the ALDH2*2 allele acts in a near dominant manner such that even heterozygotes have almost no detectable ALDH2 activity. The ALDH2*2 allele is prevalent in people of Chinese, Japanese, and Korean descent but is essentially absent from persons of African or European descent. This particular ALDH2 allele is responsible for the ease with which many Orientals become intoxicated by alcohol consumption and this fact is due to the reduced rate of ethanol metabolism. In addition, because the levels of acetaldehyde in the blood of these individuals rises rapidly following alcohol consumption it leads to the highly adverse reactions to this compound that includes severe flushing, nausea, and tachycardia. Due to the negative effects of the ALDH2*2 allele, even heterozygous individuals are strongly protected against alcohol dependence (discussed below).
Microsomal Ethanol Oxidation System: MEOS
The original model of alcohol metabolism in humans involved ADH as the sole physiologically significant pathway of oxidation. However, under conditions of chronic alcohol ingestion, the pathway of ethanol oxidation via solely ADH and ALDH could not account for all of the increased metabolism. Original studies in rodents demonstrated that the alcohol-induced increase in metabolism was associated with hepatic smooth endoplasmic reticulum (SER; also referred to as microsomal membranes). Although catalase is associated with peroxisomes and microsomal membranes it was clearly shown not to be responsible for the observed microsomal ethanol oxidation. This ethanol-induced metabolic system is therefore, referred to as the microsomal ethanol oxidation system (MEOS). The MEOS was shown to contain a cytochrome P450 activity responsible for ethanol oxidation and that this activity was distinct from ADH and catalase. The ethanol-induced cytochrome P450 present in the MEOS was purified and designated as CYP2E1.
The CYP2E1 gene is located on chromosome 10q26.3 and is composed of 9 exons that encode a 493 amino acid precursor protein. Expression of the CYP2E1 gene is restricted to the liver. Induction of CYP2E1 mRNA and enzyme activity ranges from 4- to 10-fold following ethanol consumption. The cytochrome P450 activity of the MEOS is not solely due to CYP2E1 as it has been shown that in human liver microsomes CYP1A2 and CYP3A4 also contribute to ethanol oxidation in this subcellular compartment. However, it should be noted that CYP2E1-dependent ethanol oxidation activity is at least twice that of either of the other two enzymes. Therefore, CYP2E1 represents the major MEOS activity. Combined, the activities of CYP1A2 and CYP3A4 are comparable to that of CYP2E1, thus it is important to appreciate that these two enzymes can indeed contribute significantly to microsomal ethanol oxidation and thus, are likely to also contribute to the pathophysiology associated with hepatic ethanol oxidation.
Given that the MEOS pathway for ethanol metabolism is induced in chronic alcoholics, the enhanced ethanol metabolism likely contributes to alcoholics’ metabolic tolerance for ethanol which in turn promotes further alcohol consumption. The activity of CYP2E1 is also essential in the metabolism of several xenobiotics, particularly those found in cigarette smoke (e.g. benzene and nitrosamines). Therefore, the increased level of expression of this enzyme in alcoholics can have a significant impact on the production of toxic metabolites and this is thought to contribute to ethanol-induced liver injury (discussed below). Of particular clinical significance is that increased levels of CYP2E1 result in accelerated metabolism of several medications. CYP2E1 activity results in the conversion of the non-aspirin pain reliever, acetaminophen (also known as paracetamol), into toxic metabolites that can result in severe liver damage. Additionally, the metabolism of medications by CYP2E1 can lead to tolerance and ineffective dosages. Medications that are metabolized by CYP2E1 include the hypertension drug propranolol, the anticoagulant warfarin, and the sedative diazepam.
Metabolism of ethanol by CYP2E1 also results in a significant increase in free radical and acetaldehyde production which, in turn, diminish reduced glutathione (GSH) and other defense systems against oxidative stress leading to further hepatocyte damage. Increased activity of CYP2E1 results in accelerated production of lipid hydroperoxides (designated LOOH in the Figure above) and is a significant contributor to the development of nonalcoholic fatty liver disease, NAFLD and nonalcoholic steatohepatitis, NASH. Both NAFLD and NASH are commonly associated with obesity, type 2 diabetes, and hyperlipidemia. Along with increased CYP2E1 activity there is an induction of microsomal enzymes involved in lipoprotein production, resulting in hyperlipemia which contributes to the development of NAFLD and NASH (discussed in more detail below).
The function of CYP2E1 is not solely for the metabolism of ethanol and xenobiotics. The enzyme also plays a role in normal physiological processes. CYP2E1 is involved in fatty acid oxidation as well as the diversion of ketones into the gluconeogenesis pathway. With respect to ketone utilization, CYP2E1 is responsible for metabolism of acetone which is a product of the ketogenesis pathway. CYP2E1 is involved in the conversion of acetone to acetol which is then converted to methylglyoxal, both of which can participate in gluconeogenesis. Methylglyoxal is converted to lactate via the actions of glyoxalase I (GLO1) and glyoxalase II (GLO2). With respect to fatty acid metabolism, CYP2E1 catalyzes the microsomal (ω-1)- and (ω-2)-hydroxylation of saturated fatty acids and the epoxidation of unsaturated fatty acids.
CYP2E1 and Acetaminophen Toxicity
Acetaminophen [N-acetyl-p-aminophenol (APAP), also commonly called paracetamol, is a widely used over-the-counter medication for its analgesic and antipyretic properties in many formulations in both adults and children. The maximum recommended therapeutic dose of acetaminophen/paracetamol is 4 gm/day in adults and 50–75 mg/kg/day in children. Consumption of a single dose greater than 7 gm in an adult and 150 mg/kg in a child is considered potentially toxic to the liver and kidneys. The toxicity of acetaminophen (paracetamol) is due to its metabolism to the highly active metabolite, N-acetyl-p-benzoquinone imine (NAPQI). Indeed, acetaminophen overdose is one of the most common drug-related toxicities.
The metabolism of acetaminophen occurs primarily in the liver and, to a lesser extent, the kidneys and intestines. Following the administration of a therapeutic dose, essentially all of the acetaminophen is converted to pharmacologically inactive glucuronide and sulfate conjugates. At normal therapeutic dosing only a minor fraction of acetaminophen is oxidized to the reactive metabolite NAPQI. The glucuronidation of acetaminophen is catalyzed by at least four different UDP-glucuronyltransferase (UGT) enzymes, UGT1A1, UGT1A6, UGT1A9, and UGT2B15. The UGT1A6 and UGT1A9 enzymes are the predominant acetaminophen glucuronidating enzymes. The sulfation of acetaminophen is catalyzed by a number of different sulfotransferase enzyme family members including SULT1A1, SULT1A3, SULT1A4, SULT1E1, and SULT2A1. The sulfotransferases use the activated form of sulfate, 3′-phosphoadenosine-5′-phosphosulfate, (PAPS) in the process of attaching sulfate to their substrate. Following glucuronidation or sulfation the modified acetaminophen is transported out of hepatocytes into the blood or the bile canaliculi via ATP-binding cassette (ABC) family transporters. The transporters encoded by the ABCC3 and ABCC4 gene transport the modified acetaminophen into the blood while those encoded by the ABCC2 and ABCG2 gene transport the compounds into the bile.
NAPQI is highly reactive and is primarily responsible for acetaminophen-induced hepatotoxicity. Metabolism of acetaminophen to NAPQI is carried out by various CYP enzymes including CYP1A2, CYP2A6, CYP2D6, CYP2E1, and CYP3A4. Of particular significance to ethanol metabolism and acetaminophen toxicity is the role of CYP2E1 in the generation of NAPQI. Of all the CYP enzymes converting acetaminophen to NAPQI, CYP2E1 is the most significant. As indicated above, the chronic consumption of ethanol results in the induction of the CYP2E1 gene and this can result in severe toxicity to acetaminophen due to enhanced conversion to NAPQI. The normal route for the detoxification of NAPQI is through its binding to the sulfhydryl group of glutathione (GSH). This detoxification reaction is catalyzed by at least three members of the glutathione S-transferase (GST) family of enzymes, specifically GSTM1, GSTP1, and GSTT1, where GSTP1 is the major contributor to NAPQI conjugation to GSH. Following glutathione conjugation NAPQI is ultimately excreted in the urine as cysteine and mercapturic acid conjugates. Although most of the NAPQI is formed in the liver, the kidney also metabolizes acetaminophen to the toxic metabolite and releases the cysteine conjugate into the bile as well as the blood for further elimination in urine.
At doses of acetaminophen that exceed 4 gm/day the normal sulfation pathway becomes saturated, whereas glucuronidation and oxidation to NAPQI increase. This situation is demonstrably exacerbated in the context of ethanol consumption and the induction of CYP2E1. The glucuronidation pathway can also become saturated leading to even more acetaminophen oxidation to NAPQI, especially during ethanol consumption and metabolism. In the context of excessive NAPQI production there is an eventual depletion of GSH stores. Under these conditions NAPQI will form adducts with proteins through the sulfhydryl side chains of cysteines. In this protein adduct pathway NAPQI primarily targets mitochondrial proteins and ion channels, leading to the loss of energy production, disturbances in ionic balance, and ultimately cell death.
In conditions of acetaminophen toxicity the administration of N-acetylcysteine (NAC) has been shown to replenish GSH stores, to scavenge reactive oxygen species (ROS) in the mitochondria, and to enhance the metabolism of acetaminophen via the sulfation pathway. If NAC is administered within 8–10 hr after an acute overdose, there is a reduced risk for hepatotoxicity and protection from renal failure.
Ethanol Metabolism and Alcoholism
There are several different alleles of both ADH and ALDH genes, such as indicated in the Table above for the ADH1B and ADH1C genes. Several of these alleles have been correlated with either an increased or decreased propensity toward alcohol abuse or dependence. Of clinical significance is the fact that these associations between ADH and ALDH alleles and alcoholism are the strongest and most widely reproduced associations of any gene with this disorder.
Variations in the rate of alcohol absorption, distribution, and elimination contribute significantly to clinical conditions observed after chronic alcohol consumption. These variations have been attributed to both genetic and environmental factors, gender, drinking pattern, fasting or fed states, and chronic alcohol consumption.
Class I ADH and ALDH2 play a central role in alcohol metabolism. Variations in the genes encoding ADH and ALDH produce enzymes that vary in activity. This genetic variability has been associated with an individuals susceptibility to developing alcoholism and alcohol-related tissue damage. The ADH enzymes are responsible for the metabolism of various substances, including ethanol. The activity of these enzymes varies across different organs. When ethanol is present, the metabolism of the other substances that ADH acts on may be inhibited, which may contribute to ethanol-induced tissue damage. As shown in the Table above, polymorphisms exist in the ADH1B and ADH1C genes, and the different enzymes that result from these polymorphisms are associated with varying levels of activity. The ADH1B alleles occur at different frequencies in different populations. For example, the ADH1B*1 form is found predominantly in Caucasian and Black populations, whereas ADH1B*2 frequency is higher in Chinese and Japanese populations and in 25 percent of people with Jewish ancestry. ADH1C*1 and ADH1C*2 appear with roughly equal frequency in Caucasian populations. People of Jewish descent carrying the ADH1B*2 allele show only marginally higher alcohol elimination rates compared with people with ADH1B*1. Also, African Americans, and Native Americans with the ADH1B*3 allele metabolize alcohol at a faster rate than those with ADH1B*1.
Although several ALDH isozymes have been identified, only the cytosolic ALDH1 and the mitochondrial ALDH2 metabolize acetaldehyde. There is one significant genetic polymorphism of the ALDH2 gene, resulting in allelic variants ALDH2*1 and ALDH2*2, which is virtually inactive. ALDH2*2 is present in about 50 percent of the Taiwanese, Chinese, and Japanese populations and shows virtually no acetaldehyde metabolizing activity in vitro. ALDH2*2 heterozygous, and particularly homozygotes show increased acetaldehyde levels after alcohol consumption and therefore experience significant negative physiological responses to alcohol.
Because polymorphisms of ADH and ALDH2 play an important role in determining peak blood acetaldehyde levels and voluntary ethanol consumption, they also influence vulnerability to alcohol dependence. A fast ADH or a slow ALDH are expected to elevate acetaldehyde levels and thus reduce alcohol drinking. ADH and ALDH isozyme activity also influences the prevalence of alcohol-induced tissue damage. Alcoholic cirrhosis is reduced more than 70 percent in populations carrying the ALDH2*2 allele. A positive correlation exists between genetic polymorphisms for low-activity ADH and ALDH and esophageal and head and neck cancers. Moderate drinkers who are homozygous for the slow-oxidizing ADH1C*2 allele, and therefore who are expected to drink at higher levels than those with the ADH1C*1 allele, have been shown to have a substantially decreased risk of heart attack.
Although several CYP2E1 polymorphisms have been identified, only a few studies have been done to determine the effect on alcohol metabolism and tissue damage. In one study, the presence of the rare c2 allele was associated with higher alcohol metabolism in Japanese alcoholics but this effect was only seen at high blood alcohol concentrations. Individuals with the CYP2E1 RsaI polymorphism were shown to be more likely than others to be abstain from alcohol consumption over their lifetimes.
Acute Effects of Ethanol Metabolism
The primary acute effects of ethanol consumption are the result of the altered NADH/NAD+ ratio that is the consequence of both the ADH and ALDH catalyzed reaction. Acute effects resulting from ethanol metabolism are also due to the fact that acetaldehyde forms adducts with proteins, nucleic acids and other compounds resulting in impaired activity of the affected compounds. Additional acute consequences of ethanol metabolism include oxygen deficits (i.e., hypoxia) in the liver and the formation of highly reactive oxygen-containing molecules (i.e., reactive oxygen species, ROS) that can damage other cell components.
As indicated above, both the ADH and ALDH catalyzed oxidation reactions lead to the concomitant reduction of NAD+ to NADH. The majority of the aberrant metabolic effects of ethanol intoxication stem from the actions of ADH and ALDH and the resultant cellular imbalance in the NADH/NAD+ ratio. The NADH produced in the cytosol by ADH must be reduced back to NAD+ via either the malate-aspartate shuttle or the glycerol-phosphate shuttle. Thus, the ability of an individual to metabolize ethanol is dependent upon the capacity of hepatocytes to carry out either of these two shuttles, which in turn is affected by the rate of the TCA cycle in the mitochondria.
The rate of flux through the TCA cycle is itself being negatively affected by the NADH produced by the ADH and ALDH reactions. The reduction in NAD+ impairs the flux of glucose through glycolysis at the glyceraldehyde-3-phosphate dehydrogenase reaction, thereby limiting energy production. Additionally, there is an increased rate of hepatic lactate production due to the effect of increased NADH on direction of the hepatic lactate dehydrogenase (LDH) reaction. This reversal of the LDH reaction in hepatocytes diverts pyruvate from gluconeogenesis leading to a reduction in the capacity of the liver to deliver glucose to the blood.
In addition to the effects on biochemical reactions just discussed, the NADH/NAD+ ratio, and as a consequence the redox state of the cell, is also dramatically altered as a result of ethanol metabolism. Alterations in cellular redox state are known to affect the level of expression of certain genes. To appreciate this fact one can look to research done on calorie-restriction diets. Research on reduced food intake (caloric restriction) has shown that NAD+ levels may act as a sensor that regulates the activity of certain genes. Activation of those genes, in turn, has been shown to be related to extended lifespans in a wide variety of organisms. In addition, the NAD+-regulated gene networks have been shown to reduce the incidence of age-related diseases, such as diabetes, cancer, immune deficiencies, and cardiovascular disorders. Therefore, alterations in the NADH/NAD+ ratio (in particular reductions in NAD+) resulting from ethanol metabolism may result is negatively altered expression of gene networks that promote healthy cells.
Ultimately, the NADH produced by ADH and ALDH is oxidized in the mitochondria via the pathway of oxidative phosphorylation which requires an input of oxygen. To have enough oxygen available to accept the electrons from NADH, hepatocytes must take up more oxygen than normal from the blood. Indeed, studies have shown that ethanol metabolism does result in increased uptake of oxygen by hepatocytes. Hepatocytes that reside close to the artery supplying oxygen-rich blood to the liver will tend to take up more than their normal share of oxygen. This results in limitations to the amount of oxygen left in the blood to adequately supply other liver regions. Experimental evidence shows that alcohol consumption does indeed result in significant hypoxia in perivenous hepatocytes (hepatocytes that are located close to the vein where the cleansed blood exits the liver). The perivenous hepatocytes also are the first ones to show evidence of damage from chronic alcohol consumption, indicating the potential harmful consequences of hypoxia induced by ethanol metabolism.
In addition to directly increasing oxygen consumption by hepatocytes, ethanol metabolism indirectly increases Kupffer cell oxygen use. Kupffer cells are specialized immune cells resident within the liver. When Kupffer cells become activated in response to ethanol consumption, they release various stimulatory molecules such as prostaglandin E2 (PGE2). The release of PGE2 results in increased metabolic activity of hepatocytes leading to even more oxygen consumption. As a result, alcohol-induced Kupffer cell activation also contributes to the onset of hypoxia.
The acetaldehyde produced by the ADH reaction, as well as the ROS produced via CYP2E1 oxidation, both can interact with proteins and other biomolecules in the cell to form both stable and unstable adducts. Acetaldehyde preferably interacts with certain amino acids in proteins but not all amino acids are equally susceptible to adduct formation with acetaldehyde. Lysine, cysteine, and aromatic amino acids are commonly altered via acetaldehyde interaction. In addition, certain proteins are particularly susceptible to forming adducts with acetaldehyde. These include proteins found in red blood cell membranes, lipoproteins, hemoglobin, albumin, collagen, tubulin, and several cytochromes including CYP2E1. Adduct formation with hemoglobin can result in reduced oxygen-binding capacity. Albumin is a major protein of the blood and among its functions is to transport fatty acids from adipose tissue. Therefore, altered albumin function could impair tissue access to energy from fatty acid oxidation. Tubulin is involved in the formation of microtubules which are necessary for intracellular transport and cell division. Collagen is the most abundant protein in the body forming a significant portion of the connective tissue.
Acetaldehyde–lysine adducts can indirectly contribute to liver damage because the body recognizes them as “foreign” resulting in an immune response and antibody production. The presence of such antibodies has been demonstrated following chronic alcohol consumption. The production of these antibodies leads to immune system-mediated destruction of hepatocytes containing these adducts. This process is known as immune-mediated hepatotoxicity or antibody-dependent cell-mediated cytotoxicity (ADCC). Adducts formed by the interaction of acetaldehyde with erythrocyte membranes may be associated with ethanol-induced macrocytosis, a condition characterized by unusually large numbers of enlarged erythrocytes in the blood. Indeed, macrocytosis is a marker for alcohol abuse. Acetaldehyde can also form adducts with biogenic amines such as the neurotransmitters serotonin and dopamine. These adducts may have pharmacological effects on the nervous system.
As discussed above, ethanol metabolism by CYP2E1 and NADH oxidation by the electron transport chain generate ROS that lead to lipid peroxidation. Ethanol-induced lipid peroxidation is associated with the formation of malondialdehyde (MDA) and 4-hydroxy-2-nonenal (HNE), both of which can form adducts with proteins. Acetaldehyde and MDA together can react with proteins to generate a stable MDA–acetaldehyde–protein adduct (MAA). Like the acetaldehyde-amino acid adducts, peroxylipid-acetaldehyde adducts can induce immune responses resulting in antibody formation. Importantly, MAA adducts can induce inflammatory processes in stellate and endothelial cells of the liver. Thus, there is a close link between the production of MDA and HNE, and the formation of MAA adducts and subsequent development of liver disease.
The metabolism of ethanol via the CYP2E1 pathway results in increased ROS production, including superoxide, hydrogen peroxide (H2O2), and hydroxyl radicals. ROS production is associated with cancer development, atherosclerosis, diabetes, inflammation, aging, and other harmful processes. The cell regulates ROS levels via numerous defense systems involving a variety of different antioxidant compounds (e.g. glutathione, GSH). Under normal conditions, a balance between ROS production and antioxidant removal exists in cells but this balance can be disturbed. During ethanol oxidation ROS production increases dramatically due to induction of CYP2E1 and by activation of Kupffer cells in the liver. Both acute and chronic alcohol consumption can increase ROS production and lead to oxidative stress.
Chronic Effects of Ethanol Metabolism
In addition to the negative effects of the altered NADH/NAD+ ratio on hepatic gluconeogenesis, fatty acid oxidation is also reduced as this process requires NAD+ as a cofactor. Concomitant with reduced fatty acid oxidation is enhanced fatty acid synthesis and increased triglyceride production by the liver. In the mitochondria, the production of acetate from acetaldehyde leads to increased levels of acetyl-CoA. Since the increased generation of NADH also reduces the activity of the TCA cycle, the acetyl-CoA is diverted to fatty acid synthesis. The reduction in cytosolic NAD+ leads to reduced activity of glycerol-3-phosphate dehydrogenase (in the glycerol 3-phosphate to DHAP direction) resulting in increased levels of glycerol 3-phosphate which is the backbone for the synthesis of the triglycerides. Both of these two events lead to fatty acid deposition in the liver leading to fatty liver syndrome and excessive levels of lipids in the blood, referred to as hyperlipidemia.
Because ethanol metabolism by ADH and ALDH occurs essentially only in the liver, any of the adverse effects described above that are associated with ethanol metabolism by these enzymes, and the associated ROS production, primarily affect that organ. In contrast, CYP2E1 is found in many tissues in addition to the liver, including the brain, heart, lungs, neutrophils, and macrophages. Accordingly, metabolic consequences of CYP2E1-mediated ethanol oxidation will affect numerous tissues. The harmful effects associated with CYP2E1-mediated ethanol metabolism are primarily related to the production of ROS, mainly superoxide and hydroxyl radicals. In the liver, the oxidative stress resulting from CYP2E1-mediated ethanol metabolism plays an important role in alcohol-related development of liver cancer.
Chronic ethanol consumption and alcohol metabolism also negatively affects several other metabolic pathways, thereby contributing to the spectrum of metabolic disorders frequently found in alcoholics. These disorders include fatty liver syndromes such as NAFLD and NASH, hyperlipidemia, lactic acidosis, ketoacidosis, and hyperuricemia. The first stage of liver damage following chronic alcohol consumption is the appearance of fatty liver, which is followed by inflammation, apoptosis, fibrosis, and finally cirrhosis.
Chronic alcohol consumption has also been shown to significantly enhance the risk of developing cancers of the esophagus and oral cavity as well as playing a major role in the development of liver cancer. As indicated above metabolism of ethanol results in increased production of acetaldehyde and ROS. Acetaldehyde adducts are known to promote cancer development. In addition, the induction of CYP2E1 results in increased ROS production and all of the associated cellular disruptions associated with these reactive substances including cancer.
Alcoholic Ketoacidosis: AKA
Alcoholic ketoacidosis (AKA) represents a pathology that is often associated with prolonged and excessive ethanol consumption. Alcoholic ketoacidosis (also referred to as alcoholic ketosis or alcoholic acidosis) manifests with nausea, intractable vomiting, and abdominal pain. These symptoms overlap with manifestations of crises in individuals who are addicted to ethanol (alcohol dependence) and as such AKA is often not diagnosed nor treated and managed properly in the hospital setting. Forensic studies have led to the suggestion that the untreated metabolic disturbance attendant with AKA may be associated with sudden death in patients with severe alcoholism.
Alcoholic ketoacidosis was originally characterized in patients who presented with nausea, severe vomiting, and abdominal pain whose history includes prolonged heavy alcohol misuse. The severe symptoms occurred following a bout of particularly excessive ethanol intake. Due to the onset of symptoms, these patients will have discontinued ethanol consumption and as such when blood work is done in the hospital setting the results will show no ethanol. In contrast to the symptoms of diabetic ketoacidosis (DKA), AKA patients usually present in an alert and lucid state despite the severity of the acidosis and the marked ketonemia.
In addition to the absence of blood alcohol, AKA patients will have a normal or a reduced blood glucose level, and a variably severe metabolic acidosis with an increased anion gap. The metabolic acidosis results from the accumulation of plasma lactate and the ketone bodies, β-hydroxybutyrate and acetoacetate. Often patients with AKA are found to have extremely elevated concentrations of plasma free fatty acids, levels that are much higher than those associated with DKA. Endocrine abnormalities are also often found in AKA patients including markedly elevated levels of cortisol and growth hormone and relatively low plasma insulin levels. The symptoms of AKA normally resolve quickly if intravenous glucose and large amounts of intravenous saline are administered.
As describes earlier, the metabolism of ethanol in the cytosol and in the mitochondria results in significant elevations of NADH in both compartments. Elevated mitochondrial NADH is thought to be pivotal in the development of the ketoacidosis and lactic acidosis seen in AKA patients. The acetate produced in the mitochondria, through the action of aldehyde dehydrogenase, can be converted to acetyl-CoA via mitochondrial acetyl-CoA synthetase or the acetate can pass to the cytosol where it is converted to acetyl-CoA via cytosolic acetyl-CoA synthetase. In the cytosol, as described above, the acetyl-CoA contributes to fatty acid synthesis and fatty infiltration in hepatocytes. In the mitochondria the acetyl-CoA is diverted into the ketone synthesis pathway producing acetoacetate which, due to the elevated NADH levels, is preferentially converted to β-hydroxybutyrate.
The metabolic disturbances that result from the altered NADH/NAD+ ratio is further exacerbated in chronic alcohol consumers since they are prone to having depleted protein and carbohydrate stores due to defective dietary habits. Whereas alcohol consumption does provide a form of caloric intake, other sources are chronically reduced, resulting in starvation and depleted hepatic glycogen stores. As indicated above the elevated NADH resulting from the metabolism of ethanol results in the impairment of hepatic gluconeogenesis from lactate, alanine (and other amino acids), and glycerol. In addition, the severe vomiting that can be induced by alcohol or that result from the complications associated with excessive ethanol ingestion lead to dehydration and decreased extracellular fluid volume, resulting in hypotension triggering a sympathetic nervous system response.
Combined with the hormonal responses to hypoglycemia and starvation chronic ethanol intake leads to reduced insulin production and increased catecholamine, cortisol, glucagon, and growth hormone release. The effects of these hormonal disturbances include increased fatty acid release from adipose tissue triglycerides. The free fatty acids contribute to the hyperlipidemia resulting from increased fatty acid and VLDL synthesis by the liver as a consequence of the increased acetyl-CoA. In addition, the free fatty acids can be oxidized in the liver contributing to the potential for increased ketogenesis.
The greatest threats to patients with AKA are the marked reduction in extracellular fluid volume (resulting in shock), hypokalemia, hypoglycemia, and acidosis. The recommended intervention is to institute rapid isotonic saline infusion along with glucose, and if necessary potassium. The use of saline infusion alone, although resulting in reductions in serum lactate, actually leads to increased serum β-hydroxybutyrate and a worsening of the metabolic acidosis. In contrast, the addition of glucose results in progressively increased pH, reductions in lactate, β-hydroxybutyrate, plasma free fatty acid, growth hormone, and cortisol levels, and an increased insulin level. In addition to saline and glucose infusion, chronic alcohol abusers should receive intravenous B vitamins.

domain: biology


has been built by markets assistant Dale Jones, who bought it as a half-finished project.
Their Doctor Who-themed day saw a creative cake, light-up Daleks, a 6ft Cyberman, a replica Tardis
and K9 the dog.
Whittaker said: "Being a part of this, you do appreciate what a big deal the Tardis
is to so many people."
But her joy was shortlived as a series of explosions shook the Tardis
and it lurched violently around.
Had I entered the Tardis
time machine in 1967, setting down in Wales last week, the Westminster dinosaurs had disappeared, Carwyn Jones and Alun Davies AM have these measures agreed by the Labour Assembly group.
The clip, also posted on Twitter by the official Doctor Who account, showed a cloaked Whittaker approaching the Tardis
in a leafy forest and opened her hand to reveal a key.
comes complete with sound effects, a full control panel and electric lighting.
Their theory states that a TARDIS
is a space-time geometry 'bubble' that travels faster than the speed of light.
Adapt the rules to what you are comfortable with, and never drink before flying a TARDIS
From Saturday, February 20, until Sunday, March 6, the Doctor Who Experience's Filming Locations Tour programme brings this exclusive access to the most important filming location of all - the Tardis
4 WHO KNEW THEIR WAY AROUND THE TARDIS
?Frazer Hines is the longestserving companion.
M2 EQUITYBITES-September 3, 2015-Publicis Healthcare Communications Group Acquires Tardis


text:
This is my Snowflake Sweater, designed by me and "star" of my Disaster post from April. The blocking board is the one I purchased from Webbs. Note - the dark patches are damp spots from me steaming the sweater.
That's the back view and here's one of the left front. (Yes, it's a v-neck and I haven't knitted up the boarder yet.)
Here's a close up of the snowflake design.

domain: design


text:
The original gangsta, Perez Hilton, gets the jump on this new video from 50 Cent featuring Brevi called “Be My B***h.” This will be featured on 50 Cent’s newest album, Street King Immortal, and this one is a sensual video filled with beautiful women who can’t keep their hands off of each other.
Despite the fact this video drops on Perez Hilton’s website, of all places, this is a pretty dope record. Maybe Curtis Jackson can find the magic again we once had in spades in the middle of the last decade. Maybe not. Hit the jump to check the video for “Be My B***h,” and be on the look out for Street King Immortal on November 13th.
MORE ON HIP-HOP WIRED!

domain: artistic


The Black Lives Matter murals around Carrboro highlight and advocate for values that are important to Carrboro. They express our community’s acknowledgment of and opposition to systemic and institutional racism.
The Town of Carrboro completed a Black Lives Matter mural on Dec. 18, 2020, at Communityworx, 125 W. Main St. The mural faces West Main Street at the intersection of Jones Ferry Road.
The Carrboro Town Council selected artist Tyrone Small and a young artist team, as well as the mural rendering, at its Nov. 17, 20202, meeting. The Council supported recommendations from the Arts Committee in the selection process.
"The BLM mural done by myself and the students was a testament to what we can all do as a people if we can just put our differences aside and come together to create something beautiful and lasting forever," Mr. Small said.
Mr. Small led the student artist team of Ash Granda-Bondurant, Carina Rockart, Theo Preston and Cyani Jacobs. The team was selected from a pool of 17 applicants, who were asked to submit work samples and mural proposals.
The Town of Carrboro installed a Black Lives Matter mural on Friday, Jan. 15, 2021, at the Carrboro Century Center, 100 N. Greensboro St.
Erbriyon Barrett, who was selected through a competitive application process, painted the mural on the building’s side facing E. Main Street. Mr. Barrett noted "a lot of positive energy" expressed by passersby during his work.
The Century Center is home to the Carrboro Recreation, Parks and Cultural Resources Department, the Carrboro Cybrary, and the Carrboro Police Department. The mural was approved by the Town Council on Oct. 27, 2020.


J. Phys. IV France
Volume 10, Numéro PR2, February 2000Proceedings of the Twelfth European Conference on Chemical Vapour Deposition
|Page(s)||Pr2-49 - Pr2-54|
J. Phys. IV France 10 (2000) Pr2-49-Pr2-54
Moderate temperature CVD of Ti-B-C-N on cemented carbide tools : Properties and metal-cutting testsH. Holzschuh
R&D, Walter AG, Derendinger Str. 53, 72072 Tübingen, Germany
Moderate Temperature CVD (substrate temperature : 850°C) was used to deposit wear resistant coatings in the Ti-B-C-N system onto cemented carbides. The effects of various process parameters on composition, microstructure, hardness and wear resistance were investigated. X-ray diffraction studies of the coatings revealed an isomorphous mixture of cubic TiBCN. It was found that the C:N ratio in the coatings could be maintained constant by varying the precursor content in the gas phase. In addition the coating microstructure changed from columnar to fine grained when small amounts of B were introduced. Raising the B-content of the coatings increased the hardness from 2500 to 4300 HV. The decarburization effect (building of eta-phases) at the cemented carbide surface was also enhanced by higher B levels. Since the diffusion of the B is responsible for this decarburization effects, coatings of TiN or TiCN could act as diffusion barrier. Milling tests showed good abrasion wear resistance with coatings having low B content. Turning experiments were performed with monolayer and double layer coatings of TiBCN and TiCN/TiBCN. The dominant wear mechanism was crater wear.
© EDP Sciences 2000


text:
World's Best Cat Mom Card
This variant is currently sold out
WORLD'S BEST CAT MOM
Medium: Card based on my original ink drawing.
Size: A2 4.25 x 5.5 inches each
Paper: Radiant White Card Stock
Edition: Limited edition cards, hand signed, numbered, and dated on the back.
Envelopes: 1 envelope included. Option to choose pink or white envelope!
*Card is packaged in a cellophane sleeve and shipped in a sturdy bend proof mailer.


text:
No Blackouts: Weathering the Perfect Storm
By Mark Viguet, Associated Electric Cooperative
In mid-February, the midsection of America from the Canadian border to the Gulf of Mexico endured one of the worst winter storms on record. For power generation companies like Associated Electric Cooperative, a system that supplies electricity to six transmission and 51 distribution cooperatives with 2.1 million member-consumers in rural Missouri, Iowa and Oklahoma, it was the perfect storm.
Record-setting prolonged subzero temperatures, heavy snow and ice brought all-time high customer electricity usage, limits on natural gas supply that drove prices to historic highs and many operational challenges to keep the lights on. So, how did Associated weather the storm? In a word: balance.
Balanced Generation Strategy Resulted in Reliability
While much of the focus in that storm’s aftermath has been on utility systems that imposed rolling blackouts, Associated’s system of cooperatives in Missouri, Oklahoma and Iowa avoided putting members in the dark. The key: Associated relies on a balanced generation mix, with proven and reliable coal and natural gas generating plants as a valuable foundation for reliability.
Despite significant outside pressure in recent years to move to other options, these fossil-fuel generating stations were the major factor in keeping the lights on for the 2.1 million people who count on Associated. Hydropower allocated by the federal Southwestern Power Administration also was a reliable energy source. Wind generation in Associated’s mix played a small role during the storm.
Cooperative Network, Fossil Fuel Generation Key to Reliability
All facets of the Associated cooperative network – power generation, transmission and distribution – performed exceptionally well through a record hourly peak significantly greater than the pre-storm all-time peak set in 2018, doing so with no rolling blackouts. (See chart below).
Well-maintained and winter-ready coal and natural gas plants, weatherized to withstand negative 20-degree temperatures, were prepared to generate power as electricity demand quickly escalated while temperatures dropped. More than 10,000 miles of high-voltage transmission lines operated by Associated’s transmission cooperatives, independent of regional transmission organizations, delivered power reliably. Distribution cooperatives served member-owners to the end of the lines at their homes and businesses with their usual determination and kept them informed with effective member communications.
Performance of Coal, Natural Gas Generation Meets Member Needs
During two critical peak energy demand days (February 15-16), coal plants operated close to full capacity, producing more than one-third of the generation needed by Associated’s members. (See all-time peak charts on this page). Natural gas served about one-fourth of the demand. Associated’s contracted imported power purchases (1,474 MW) and hydropower (478 MW) made meaningful contributions.
Associated’s 1,240 MW of wind energy from eight wind farms produced little to no energy. During the all-time peak of 5,549 MW set February 15, as energy demands were close to exceeding generation capacity, those 1,240 MW of wind produced only 3 percent of the energy generated. On February 16, wind dropped to nearly zero. Member-owned solar installations across the system weren’t generating much, if any, electricity at all during these peaks due to time of day combined with snow and ice cover.
Foundation Built on Coal Generation Ensured Fuel Availability, Lower Power Cost
What made Associated different than so many other utilities impacted by the extreme weather? Baseload coal generation – the foundation of Associated’s reliability and affordability – remained online throughout the event. The regions around Associated’s footprint and the utilities serving them came into the storm shorthanded, having replaced 24/7/365 capacity with resources like wind and solar that are inherently intermittent. They are particularly unreliable during extreme weather like the 2021 winter storm. When natural gas fuel supply, in high demand for home heating as well as power generation, was compromised or extremely expensive, Associated’s coal generating plants could rely on a two-month supply of coal previously delivered on site at a fixed price.
Consequences of Energy Transition: How Did the Industry Get Here?
Government policies that forced the early retirement of many coal plants have significantly decreased the reliability of the generation and transmission system designed to serve residential, commercial and industrial consumers throughout the Midwest. Retirement by other utilities of these coal plants resulted in reliance on natural gas power plants and renewable wind and solar farms.
Natural gas power plants rely on a network of gathering systems, processing plants, compression facilities and pipelines, compromised during the severe weather, to deliver fuel as needed to the gas-fired plants, while coal plants maintain a dependable two-month supply of fuel on site. As noted, wind, solar and other intermittent sources may not be producing energy at significant levels, or at all, during extreme weather events.
The responsibility for the retirement of reliable and affordable generating resources is a policy direction pushing the United States too quickly to rely on technologies designed to provide green energy, but unable to serve as reliable power supplies in extreme weather. This same policy direction also means more price volatility for end-users during extreme weather, when the market price of natural gas spikes during periods of high demand, sending the cost of generation fueled by natural gas skyrocketing.
Consumer-centric Priorities: Reliability, Affordability, Responsibility
Reliable sources of generation are necessary to meet the priorities of most consumers. Advocates for only and all renewable generation by near-term specific future dates are unrealistic, do not rely on engineering expertise and compromise reliability and affordability for the sake of an agenda that irresponsibly puts homes and businesses and the people in them at risk. Patience is needed because the technology does not exist today to replace all fossil fuel plants, high-voltage transmission systems were not designed for a rapid influx of intermittent generation like wind and solar, and ample time is needed to meet arbitrary deadlines put in place despite these challenges.
As this winter storm and the challenges it brought to utilities in the Midwest clearly demonstrate, an unreliable and costly future awaits the nation by relying on power generation sources that rarely will perform when people need electricity the most. Reliability and affordability should be top priorities. Ensuring reliable electricity requires generation that can be depended upon during all weather conditions.
The historic 2021 winter storm and Associated’s reliable performance throughout its duration serve as an important reminder and lesson that demonstrate the value of a balanced electric generation strategy, for consumers and the nation.
Mark Viguet is managing director at Associated Electric Cooperative, Inc.

domain: news


text:
James Antle, RealClearPolicyAbout That Gay Marriage...
When President Barack Obama discovered the missing link in his evolution on gay marriage, he cited his personal experience with same-sex couples. Obama told ABC about "members of my own staff who are in incredibly committed monogamous relationships, same-sex relationships, who are raising kids together." He also mentioned gays serving in the military, now openly since he succeeded in repealing "Don't Ask, Don't Tell."
James Antle, RealClearPolicy
Tue, 29 May 2012 06:01:33 GMT


David started working with Accurate on May 5, 2014—Cinco de Mayo—which, he says, makes it easy for him to remember his work anniversary.
He’s a “data person,” he says. It’s work he loves, and, looking ahead, it’s work he says he’s happy to continue doing. While he’s less directly involved these days, he still supervises a team of data professionals at Accurate, which, he says, he equally enjoys.
“I was kind of pleasantly delighted that I can actually do that as well and actually enjoy that as much as working as a lone contributor.”
But, while working with data has always been the type of work David loves, he didn’t know much, if anything, about background screening when he first came to Accurate. He had been working for a television provider when his department was eliminated. Fortunately, a former colleague told him about opportunities at Accurate, which, even then, was expanding and growing.
It’s been “a big, big journey,” David says, from being “the kind of person who could work in a closet with nobody around to touching base with a team of almost 20 people regularly.”
Growth Has Been the Biggest Change
Looking back, David says that Accurate’s growth has been the biggest change he’s noted during his tenure with the company. It’s growth that has put Accurate’s name on the map—and on the tongues of customers and prospects.
“We’ve gone from being this unknown small company to where we’re in every conversation, and everybody knows who Accurate is in the industry,” he says. “That’s the biggest change.”
When thinking about what’s changed the most, David says he also thinks about what hasn’t—the culture. “From Dave Dickerson, at the top, and everyone on down, it still feels like a small company. I can send an email or talk to anyone—I don’t feel there’s this arbitrary wall in between different levels or even different departments that you might find at a big company.”
So many people have been with Accurate for years, David says. “We kind of have that sense of this is our company. This is not just where we work.” He acknowledges being actively protective of the culture at Accurate.
“When I’m interviewing either for my team or if I’m asked to help out for someone else’s team, I’m looking for somebody to fit into that mold of who we want to work with and who will be a good fit with our company. We have a protective kind of instinct. We don’t want someone to mess it up.”
Accurate’s culture is built on four core values pillars that unify the company with a common purpose, define where they’re headed, indicate what they’ll do to get there, what they believe in, and how they will behave with each other and their customers. They are:
- Take ownership: be accountable for your actions, your team, and the company.
- Be open: be open to new ideas.
- Stay curious: stay curious even as you move forward.
- Work as one: work together to create the best customer and workplace experience.
The one that resonates the most with David is “stay curious.” “Being a data person, I always question things,” he says. And, he adds, “a lot of time you can’t keep doing things the way you did in the past because things have changed.”
A Focus on Team
David is committed to building a strong team—something that has been challenging for many during the pandemic. Fortunately, though, he’s worked remotely for a long time, so that wasn’t new to him. It was to some of his team members. Now, though, he says, “nobody is full-time back in the office.” He says he hasn’t even personally met about a third of his team members.
Efficiency, he says, has been a byproduct of the ability to work from home. Accurate, he says, “seemed to adapt as quickly or quicker than most companies to working remotely during the pandemic.”
As a team leader, David recognizes the importance of communication and getting to know his team members. He’s used the DiSC assessment as one way to help him get to know them and them to know each other better, including helping to understand their communication preferences.
He has regular calls with his team members not just to cover work-related issues but also to get to know each other better—maybe talking about sports or fast food interests. With team members located in different geographic areas, they’ve discovered that regional food interests vary. These discussions have been a good way to build camaraderie while working remotely—always focused on supporting the Accurate culture.
“I think you really have to know your team,” David says. “One size doesn’t fit all.” One culture, though, does.


text:
Best moments of Sheldon Lee Cooper from "The Big Bang Theory"
- published: 06 Nov 2016
- views: 12452652
This is a compilation of the funniest moments of Sheldon Cooper from The Big Bang Theory. This is just a fan made video.I do not own any rights.All rights belong to the creators of the show,Chuck Lorre and Bill Prady. Follow our Facebook page :- https://www.facebook.com/TheBigGameTheory24/ My instagram :- https://www.instagram.com/the_illuminati_98/?hl=en Thanks for watching :)...

domain: entertainment


text:
This summer has been too long, too hot,too humid and too draining. In Australia the current season has been very fierce with weeks of hot and humid days as well as many fierce fires and storms.No doubt many others, like me, are wishing for an Autumn that might bring cooler days and gentle,refreshing rain and fear that climate change has greatly impacted Natures ability to heal and recover.
Pondering about this much desired change of season, reminded me of these little sprites that were made last year ; tiny beings who indicate that each season has its specific character and tasks necessary for nature to create and replenish.
My muse is nature and when instinctively we synchronise it is such a feeling of wonder and awe. After I finished this piece I took a walk in the garden.
Delighted and surprised to find that almost by magic these had appeared.
An unexpected discovery as it is not the usual season. Perhaps a they are a tiny miracle, or rather an indicator of climate change?
Whatever the reason their delicate beauty masks their ability to thrive, survive and multiply. Mushrooms are powerhouses we do not yet fully understand. Nature is our greatest teacher who asks us to carefully observe,respect,cherish and to protect all that she has so lovingly created and shared..
Reality has taken on a fuzziness, and settling to creating again has taken time. If anything it is not so much a matter of what and how but rather total sensory, physical and emotional overload. Travelling kept presenting so much to absorb and to process that the experience seems to have completely numbed. Just imagine standing in the garden, pictured above, at Hever Castle in England where four thousand rose bushes were in full bloom. That alone presented a sensory extravaganza of epic proportions.
However the first “wow” factor came at the beginning of this trip at the end of May, seeing the green initiatives in Singapore.
Along many roadsides there were cool, shady tunnels of overarching trees. Major roads had large pots planted with trees and shrubs placed in gaps of the laneways. Creepers wrapped around concrete pylons under the overpasses creating small green oases.The Big Wheel emerged from a recreated rain forest that twined around it’s base. It was encouraging to see that attention to detail, to nature, and the environment incorporated as an essential in urban planning.
Many new buildings were innovative in design as well as incorporating live walls of plants, garden terraces on each level and roof top gardens.
Dotted around the city were signs encouraging awareness of the value of green, as well as these characters below who frolicked in the parks and promoted “Love Green”.
Although Singapore has a wonderful Botanic garden housing a legendary orchid collection my main desire was to visit Gardens at the Bay. This project is set up as a dynamic working and teaching resource . There are excellent displays, information, films and models to encourage awareness of climate change in order to encourage and initiate more sustainable practices and lifestyles. Two huge glass domes protect micro climates. One dome area houses a cloud or mist environment. The second dome various gardens to show the different climates and vegetation from all around the planet.
The entire garden itself is a working example of sustainability and interrelationships. Planted in the grounds are several large Super Trees, which are 250 m tall metal trees that harvest and store sunlight and water. At night the trees create a solar powered light display . I wondered if these trees may be the trees of future generations .
Soon after we left Singapore, the city was severely affected by a thick smog from fires lit to burn off large tracts of forests felled in Indonesia. Not even love green could lessen the impact.
Later in the trip., in July this year we came across a “super Flower” planted on the banks of the Danube in Vienna. Seeing this interesting artwork ,a recycled plane propeller, made me wonder again if something like this would become the replacement of wildflowers .
Growing alarm was being raised about the loss of wildflowers and insects in Britain. This situation was felt to be the result of councils spraying and mowing parks, footpaths, and roadside verges as well as modern mono-agricultural practices. The fragility of previously abundant and hardy , seeding and pollen producing plants is linked to the demise of bees and butterflies, a situation that threatens the very existence of all life forms on the planet . We really do need to love green much more.
When the idea for a winter scape comes to mind for our area, creating a snow scene seemed somewhat alien. However winter does bring snow, frost and ice down south in the higher mountain ranges and also in Antarctica, part of which is Australian Territory. Because this piece was a commission for a recipient fascinated by snow and penguins the idea of trying to create a scape representing Antarctica seemed feasible at first, even easy.
As it has turned out this has been one of the most difficult projects so far attempted. White and lots of it is flat, dull, uninspiring. The challenge to encapsulate the essence of a continent covered in snow and permafrost, barren to all appearances yet vast, wild and home to millions of sea creatures was both exhilarating and daunting. Such an extreme and beautiful place had to be reduced to a very small scale with the added restraint of using warm, wool felt to portray this freezing climate. It seemed a crazy and impossible notion.
Using pure white just did not work, nor did some of my original ideas. Instead of a flat base this piece required sculpting from very hard industrial felt that resulted in bleeding fingers. For some time nothing worked and it was poked away .
The breakthrough came when my friend Mia bought some of her wonderful splotchy felt that she hand dyes to craft. Splotchy felt is perfect to use for water. As I placed a piece down to make the sea it seemed that it could create a cold effect when used in the scene. This lovely felt was the missing link and helped to give the illusion of shadows and crevices, as well as to introduce the blue tones connected with the continent.
Even so the scene was still dull and lifeless, requiring the glisten that snow has as the light dances over it. This came through using a shimmery organza to make an ice sheet with sparing application of silver glitter.
Iconic Emperor Penguins were used to represent the species that use this incredible area to raise their young. As the Emperor penguin is found over the entire continent it seemed the right creature to place in this setting and to also indicate that even in such a harsh environment life can exist.
This environment is fragile and threatened. The ice cap is melting because air and sea temperatures are rising. As a consequence so will sea levels. This will have a far ranging impact on other continents as well as the potential for many species to face extinction.
Antarctica is a place that has attracted and fascinated scientists for many years with considerable research being undertaken. Let us hope this is not in vain and the warning signals will be heeded and, more importantly, that significant action is taken immediately on a global scale.


text:
Guard Airmen Celebrate African Americans in the Arts
U.S. Air Force Maj. Ariel Green, council chair, diversity and inclusion, Air National Guard, National Guard Bureau, speaks about the impact of art in the African American and military communities during a Black History Month event at the Air National Guard Readiness Center on Joint Base Andrews, Maryland, Feb. 22, 2024. Video by Tech. Sgt. Sarah M. McClanahan.
Featured Video Archive

domain: library


text:
“You don't ever have to apologize to me, Dexter. Not for who you are, or anything you do.” – Brian Moser, “Born Free”
“Heya, Dexter,” Brian says, and then raises a hand and waves at me one finger at a time, one-two-three-four-five. A ridiculous gesture. “How are you holding up?” He props his feet up on a stool and tips his head back so I can see the thin white line of an improbable scar. Huh.
You’re dead would be cliché. “You’re dead,” I say anyway. Brian grins at me, a little too wide.
“That’s the thing about us,” Brian says. “We don’t behave like good little boys.” He’s playing with my box of slides. I don’t know where he got it. “Look, Dexter, I know it’s not personal.”
I don’t say anything. I glance down and Deb’s on the floor, eyes wide and glazed over with fear and the knowledge of her own death. Brian clicks through my slides, closes the box, and stands up, fluid and natural like he was never dead.
“I forgive you,” he says.
“I don’t need your forgiveness.”
“As long as you believe that,” Brian says, almost coy. He glances down at Deb. “She wasn’t so bad,” he says. “We were going to get married. I think it would have been a lovely wedding.”
“Please, Dex,” Deb says. “Please.”
“Ah well,” Brian sighs. “All good things must come to an end.” He reaches out and taps my face shield down. “Are you ready?”
I wake up because someone is walking around in my apartment, and it takes me a couple seconds to recognize that it’s Debra. I check the clock. 2 AM, or just before. I roll out of bed and walk out to see her drinking a beer with the fridge hanging open. She jumps when her peripheral vision catches me.
“Fuck – Dex, say something before you sneak up on me, all right?”
“You okay?” I ask, more by rote than anything. I know the answer. I can see it just by looking at her. I wouldn’t be a very good predator if I didn’t recognize fear. Debra scoffs.
“Yeah, of course I’m okay. Just couldn’t sleep.”
There’s silence for a moment, and then Deb slams the door closed. “I’m not going to let that fucker ruin my life,” she hisses. “I’m not. He’s dead, the sick fuck, and I’m…”
I don’t say anything. I don’t need to. Deb’s voice drops and she shifts a little. She’s wearing ankle socks; that I notice this detail strikes me as absurd. “I should’ve known, right? Fuck, I should’ve known. The instant he started…”
“It’s not your fault, Deb,” I say, because it really isn’t.
She scoffs. “Yeah,” she says. “Yeah. Thanks, Dex. I think I’ll try to go back to sleep now.”
She won’t fall asleep. She’s too wired, too tense. I just nod. “Okay.” Deb doesn’t go. After a couple seconds she turns back.
“Can you stay up with me and watch cheesy horror movies on TV?” This isn’t Deb, I have to think, even though I know she’s been there this whole time. This is what he did to her.
I nod again. “Okay.”
She falls asleep on my shoulder halfway through the first movie, to the tune of monsters growling like lawn mowers. I should feel honored. Mostly I just feel uncomfortable.
Brian is painting on my coffee table. I’m pretty sure he’s using his own blood. It takes him a second to notice me, and then he looks up and blinks. “Oh, Dexter. Come around again?”
“Why are you here?”
“Because you want me to be.” Brian goes back to painting. It looks like he’s drawing Deb. “You know , this isn’t really a good time.”
“You aren’t real,” I say, and Brian snickers.
“You say that like it matters.” He looks up, examines his fingers, and wipes them off on his pants. “You know what I think?”
“I don’t want to know what you think.”
“I’m sorry,” Brian goes on, without waiting for me. “I’m sorry that you chose this over me.” He gestures at Deb, painted in blood, on the table. “She’ll never love all of you, Dex. Not like me. I love everything you are, and she? Can only love parts of the whole.” He prowls a little closer and touches my face. His fingertips are still a little wet.
“I love you, Dexter. And I’ll love you forever. Death doesn’t mean much to people like us, huh?”
“Biney-” I say the name without thinking about it. I remember the way he held my hand, chin to knees, pants soaking up blood.
“Harry took you away from me, little brother,” he whispers. “I was just going to bring you back. I’m sorry it took me so long to find you. But now I have.”
Deb goes back to work the first day they let her. She hasn’t been sleeping and looks like crap but I think she needs the work. I get that. I haven’t stopped. (Haven’t killed, either.)
She almost stabs a guy in the stomach with a fork when he comes up behind her while she’s making coffee, though, so maybe she’s not all that okay. I get that too. I wonder, a little, what she dreams about. Wedding rings and white cake and a groom with a knife instead of a wedding ring.
I notice the way she’s watching strangers, almost obsessively. I work it out after a little while. She didn’t see through Rudy. Now she’s trying to guess; is that one a killer? Is that one? This one? (She never looks at me.)
The fallout is still all over the papers. People keep trying to interview Debra. Deb gets pissed off but she’s a little scared too, but it’s Angel, not me, who tells them to leave her alone and get lost.
Debra keeps telling me I’m such a good brother – staying up with her, letting her sleep on my couch. I keep thinking about what I’d be doing now if I hadn’t chosen family over blood. I wonder how it would end. What he would have been like. I really don’t know anything about him.
My blood brother. My brother in blood.
Deb keeps her head high and soldiers on. I keep my head down and do the same. Everyone else buzzes like insects.
I keep dreaming.
“Dexter. Are you ready?”
I blink. The kill room is small but big enough. The plastic flutters slightly in a minor breeze, so there’s something bigger outside, but that no longer exists. There’s a table, and a knife, and Brian with his hand on my shoulder and smiling at me, eyes bright.
There’s a girl on the table, making small, muffled, unhappy noises. She’s probably around thirty-five, pretty but non-descript. “What did she do?” I ask. Brian leans in and rests his forehead against mine.
“Nothing,” he says, nearly gleeful. “We do this because we can.” I have memories, suddenly, of a hundred rooms just like this, a hundred people, sometimes killers, sometimes not. It doesn’t matter. Whoever we like, whoever catches our eye. We are the hunters.
“I forgot,” I say, and pause. Brian gives me a little nudge.
“This one’s all yours, Dex,” He says, all affection. “I’ll just watch.”
I know this is right, this is good, this is what’s supposed to happen. And I’m not thinking about anything – about Harry or Deb or the Code or anything at all. My head is so, so clear.
It’s Deb on the table, I realize, and she says “Please, Dex,” just before I open her throat.
“There he is,” Brian says. “There’s my brother.”
“I don’t want Deb dead,” I say, looking down at her corpse with more dispassion than is strictly realistic. Brian tilts his head to the side.
“What about me, then?” He says, and tilts his head back. The stitches holding his throat closed are dark black and obvious, messy. “You couldn’t let me live, but you didn’t want me gone either. You can’t have both, Dexter. You can’t be a killer and a hero.”
“I’m not a hero,” I object. Brian shakes his head at me and smiles a bit.
“I’m just looking out for your happiness, little brother,” he says. “Someone’s got to.”
“You know what’s funny,” Deb says, a little slurred. “I thought he was…I thought he was too sweet. For me.”
“Huh,” I say. She’s been working out all day and hasn’t taken a shower yet. She smells a little ripe, but I don’t think mentioning it would be a good idea right now. Deb snickers like she’s trying to convince herself it really is funny.
“You know,” she goes on. “A real nice guy. The kind I never seem to end up with.”
If anyone should have known, I don’t say, I should have. We were kin. We were more than that. “Never say never,” I say, hoping it sounds less cliché than it…sounds. “Don’t beat yourself up over it.”
(I haven’t killed in fifteen days. There’s something wrong with me.)
“Ha,” Deb says, and doesn’t expand on that cryptic little interjection. “Least I’ve got you,” she says, after a couple seconds. “My hero.” She grins at me like she’s kidding. She is. Mostly. Or maybe she does feel safe around me, which is a weird thought, given …things.
“And I’m not going anywhere,” I assure her, with the most natural smile I can summon. She snorts.
“Wasn’t worried,” she says. “Not about you, anyway.” She glances away, and then says, “It’s stupid. The other day I was like – ‘I wonder if he really liked me.’ How stupid is that? He wasn’t even…” She shakes her head. “God, I’m a stupid fuck. I’m going to go for a run.”
“It’s the middle of the night.”
“On the treadmill, jackass,” she says, and pushes to her feet to flee in a hurry. Deb isn’t much better at the emotional stuff than I am, not really. I might even be better at pretending.
Brian is going through my blood slides again. “This is really very nice,” he says. “Well organized. Aesthetically pleasing.”
“Thanks,” I say. Brian pulls one out, examines it, and puts it back carefully.
“Did I get one?” He asks, sounding legitimately curious.
“Why not?” He looks like he’s sulking now, and this is just ridiculous. I stare at him, and he does that funny thing again where he tips his head to the side and I’m not sure if he did that in real life, maybe, maybe not. “Was I not special enough?”
“No,” I say, almost plaintively. “Those are – those are the ones for the Code. You were different.”
“Why’d you kill me, then? If it wasn’t about your precious Code.” His green eyes gleam at me, and he props his feet up on my coffee table. There’s no blood on it this time. Debra’s sleeping on the couch, and he glances at her when I do. “Is that why?”
“I didn’t want you to kill her. Deb matters. And I was – setting you free.”
“I was already free.” Brian looks like he pities me. “I’ve always been free. Just because you built your own cage doesn’t mean it’s not there, Dexter.”
“I wish you’d leave me alone,” I say.
“Do you?” Brian asks. “Do you really?”
I think Deb is going a little crazy. She’s not talking to me, though. And I think if someone suggested therapy to her she’d probably punch them in the face. I don’t really know what to do with her. This is what they call being too close to a case.
I haven’t killed in thirty-eight days. I’ve been counting. Thirty-eight days.
That’s how long it’s been since my brother died.
I’ve been dreaming every single night.
“Come on, Dex,” Brian says, and spreads out his arms, grinning. “How do I look?” He’s wearing a three piece suit with a lab coat. And a scarf. I’m wearing my kill shirt and a face shield.
“You look good,” I say. Brian smiles and reaches out, ruffles my hair. It feels kind of nice.
“Thanks, little brother. I’m so glad you could be here today.”
“What’s today?” I ask.
“My wedding,” he says, and the door opens. We’re standing in one of my kill rooms, but there’s a priest between us. It’s Deb walking down the aisle, wearing her uniform. Her fingernails are painted like the prostitute’s fake hand. She’s grinning like I’ve never seen before.
“One big happy family,” Brian says to me, and I realize the floor is coated in a thin layer of blood. “Symmetry,” Brian explains casually. “I wanted everything to be perfect for our special day.”
“Are you going to kill her?” I ask.
“No,” he says, and then thinks about it. “Probably not. We’ll be just like any other couple. Go on double dates with you and Rita. Take turns hosting Thanksgiving. Whatever.” Brian smiles. “Is that what you want? Is that really what you want?”
Apparently the ceremony’s been going on without us, because the priest says, “You may kiss the bride.” Brian pulls a knife out of his lap coat and sticks it through the clergyman’s throat before kissing Debra, who doesn’t seem particularly bothered.
“I don’t like priests,” Brian says, once he surfaces, holding Deb loosely around the waist. She’s looking at me without any of the wariness she has in real life.
“I killed one once,” I say. Brian nods, a little.
“Yes,” he says, “I know.”
He’s looking at me. Smiling, just a little.
“Miss me, little brother?”
He never left.


text:
Yesterday we met up again with some customers and partners from our community to play golf.
This time we went to the beautiful Otelfingen golf course in the canton of Zurich. It was a lot of fun to swing the golf clubs together with some of you and to exchange ideas at the aperitif afterwards.
Thank you very much for the great day and we are looking forward to the next time!
Brewing Beer and Securities Trading?
On International Beer Day, George Macdonald, CEO MACD tells us about his hobby of brewing beer and explains the similarities with securities trading.
It's Pride Month again! At MACD, we set an example against discrimination, which is why our company logo on the website once again shines in rainbow colors, symbolic of greater tolerance and diversity.
AGENDA: MACD CONFERENCE 2023
With just three weeks to go until the MACD Conference 2023 in Zurich, you can look forward to interesting presentations and discussions on current topics in the world of finance, including crypto trading.
As a specialist for electronic trading, MACD has been successfully developing products and services for financial institutions for more than 20 years.
The company is market leader in trading connectivity in Switzerland. More than 60 banks and stock exchanges across Europe trust in the comprehensive range of services in software development, project management, consulting, hosting and support.

domain: finance


text:
by H. Mayor
The name Rainer Zietlow first hit the headlines in 2005, when he drove to the top of the Chilean volcano Ojos del Salado on board a Volkswagen Touareg. At 20.000 feet (approximately 6.100 meters), this feat made it to the Guinness book of Records as the highest elevation reached by a stock vehicle. But this adventurer didn’t stop there; since then he has built up a career plagued with new records and impossible challenges. The last one took place only a few days ago: a journey from Dakar to Moscow in just 3 days, 4 hours and 54 minutes… and without speeding!
Accompanied as usual by Russian blogger Peter Bakanov and journalist Georgy Gloube; Zietlow has accomplished a new record, to cover a distance of almost 8.000 kilometres in just three days and on board a Volkswagen Amarok. The journey took place between the 22nd and 25th of April and took them across ten different countries and through such diverse places as the Sahel desert, the great European motorways and the sinuous roads of Eastern Europe. Furthermore, the feat was accomplished at an average speed of 103 km/h and without any technical fault (this is a key point). As usual he also raised a generous amount of cash for good causes.
easternmost point in Russia (Magadán) to the westernmost point in Europe (Lisbon). The journey extended for 15.200 kilometres and it was concluded in 6 days, 9 hours and 38 minutes. A great achievement, even more so taking into account the initial forecast of 8 days.
The challenges that this driving adventurer sets himself are in no way easy. They require a perfect combination of planning, rhythm and technical and mechanical efficiency. But above all else the frame of mind to carry to completion stages that are at times very complex; easier to do no doubt for a driving lover. A the top of his achievements are the 22.000 kilometres of his Melbourne – St. Petersburg journey in 17 days in 2012, the 23.000 of the Panamerican Highway completed in just 11 days during 2011 or the two way expedition between Cape Agulhas and North Cape (18.000 kilometres from Norway and South Africa) in 2004 and 2005.

domain: geography


The new Nokia phones focus on being more durable and affordable. With their C-range series, they promise all-day battery life.
The flagship of the series, C21 Plus features a 6.5-inch display and a battery of up to 5,050 mAh in size, which Nokia says can last three days. The phone is IP52 rated for water and dust resistance, with an additional metal casing for extra protection from heavy drops. The C21 also has a 6.5-inch display, with an octa-core processor of 2 or 3GB of RAM. The phone has an 8-megapixel rear camera and a 3,000-mAh battery.
The cheapest of the series, according to Cnet, the C2 2nd edition, is designed to be an upgrade for users who are still stuck with feature phones. It has a small 5.7-inch display, 5-megapixel rear camera, and a battery that lasts all day, and Nokia calls it a “small wristband Nordic”.
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Sonoma Coast State Park is a scenic, coastal park extending 27 km in Sonoma County, Northern California. It’s located about 75 km north of San Francisco. The Park is made up of several disconnected sections of hike-able coastline prairie and beaches, all accessible via the famous California Route 1 along the Pacific Ocean coast. Not only is it a spectacular location for hiking, picnicking, surfing, diving, and other outdoor activities, it also offers the opportunity to see all sorts of wildlife. Here you can spot bald eagles year-round, catch whales migrating from October to May, witness harbour seals giving birth and feeding their pups every Spring and Summer, and find migrating hawks that can only be observed in this part of the world from late August to early December.
Different parts of the park are ideal for different activities. Some of our favourites (organised from North to South) are set out below:
- Goat Rock – for watching seals (please stay at least 50 ft / 15 m back), whales, and several large colonies of seabirds. Also great for paddleboarding and kayaking at the mouth of the Russian River when conditions allow.
- Shell Beach – for tide pooling and beachcombing.
- Duncan’s Landing – for wildflower blooms in Spring, make sure to watch out for dangerous and unpredictable surf.
- Portuguese and Schoolhouse Beach – for rock and surf fishing.
- Salmon Creek Beach – for beach hangouts, surfing, and its protected habitat that supports the western snowy plover.
- Bodega Head – for crabbing and whale watching. It’s considered one of the best locations on the coast to watch seasonally migrating grey whales.
- Kortum Trail – hiking, bird watching, climbing/bouldering, and running your hands on the smooth face of ‘Mammoth Rocks’ (or ‘Sunset Boulders’). These are rock faces that have been polished by mammoths rubbing their backs after mud baths!
Average rating: 5.0 (very good)
Average cost: free!
Best time to visit: the Park can be visited year-round, however in Summer it can be very foggy. Sunrises and sunsets are spectacular from any of the various lookouts throughout the Park – it’s also the best time to see wildlife.
How to get there: to get to the Park you need your own vehicle. The entire Park is accessible from Highway 1, starting on the northern end from the town of Jenner (and ending on the southern end at the town of Bodega Bay). If you’re coming from inland, you can access it via Highway 116 by turning left (South) when it meets Highway 1. For detailed information about accessibility, trails, parking lots, and campgrounds see here.
Typical activities: bird watching, bouldering, camping, hiking, kayaking, stand-up paddleboarding, surfing, tide pooling, and whale watching. Swimming is not advised due to the extremely dangerous rip currents and unpredictable surf.
Number of reports: 1
Last update: 2021
WILDLIFE IN Sonoma Coast
According to reports submitted to WildSide the most popular species that can be seen here are:
Bald eagle – 0% OF Wildside users (0/1) REPORTED SIGHTINGS
Bald eagles have had a difficult time since the end of the second world war and the growth in the use of DDT to control insect populations. In 1972 DDT was banned for most uses in the United States. By that time there were fewer than 30 pairs in California. Nowadays, thanks to captive breeding and the ban on DDT, their numbers are recovering.
In 2001 a pair of eagles made a nest at Lake Sonoma and have been raising chicks every year since. They have been spreading throughout the area and can be seen at Laguna de Santa Rosa, near the Occidental Road Bridge, and at Jenner, the mouth of the Russian River. There’s a great guide to the bald eagles of Sonoma here, which suggests that the best time to see them is between sunrise and mid-morning at the overlooks by Highway 1. They are mostly seen foraging near lakes, rivers, and at the coast, favouring areas with tall trees for nest-building and as perches for hunting from. For further information about the Jenner bald eagles, there is even a handy Facebook page!
harbour seal – 100% OF Wildside users (1/1) REPORTED SIGHTINGS
The Sonoma Coast is an important breeding ground for the harbour or common seal. Goat Rock State Beach is home to the largest concentration of harbour seals along the Coast. The Russian River estuary is a good spot to observe these shy mammals. This guide recommends stopping at the Highway 1 overlook in Jenner (which is also recommended for bald eagle spotting), then walking along the beach or kayaking in the estuary. When the tide is out, seals are visible resting on the shoreline or on exposed offshore rocks. At sea, they can be glimpsed snatching a breath before diving to hunt for fish.
Photo credit: WildSide team member Sara Camnasio


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According to yet more “sources in the know” the iPhone 5 launch is just a few weeks away. At least, that’s what the New York Times is claiming. Apple may be delaying its usual September music event, replacing it with one at the beginning of October.
“We’re just weeks away from the announcement of the new Apple iPhone 5, according to an Apple employee who asked not to be named because he was not allowed to speak publicly for the company.”
So far we know, or can at least assume, a good deal about the next generation device. From Case-Mate’s leaks yesterday we can bet confidently on a wider, thinner handset with an aluminum back. We’re almost certain it will have the same A5 processor as the iPad 2, which it will need to power the 4″ Retina display dominating the front face.
9to5Mac, in addition to the NYT post, is reporting that production of the new device has hit a few problems and could be slightly delayed. This delay is also likely to cause stock shortages all the way through to the beginning of next year. Saying that, it’s hardly surprising. Especially when you consider how long it took Apple to get the iPad 2 shipping times down from 4 weeks to 24 hours. It may be bad news, but the site does throw in a little tasty rumor to whet your appetite:
“The iPhone 5 itself is a sight to behold, we’ve been told. It is impossibly light, yet much firmer than Samsung Galaxy phones which are backed in plastic. The camera rivals point and shoot cameras and will be a major marketing point for this device.”
The Apple dedicated blog also claims with some certainty that there will be two different iPhone models launched side-by-side. The cheaper option is purportedly the same form factor as the iPhone 4, and could be priced to compete with lower end Android devices. (It may even be available on a pre-paid plan.)
Bear in mind that these are rumors, however reputable the sources may be, they may not be 100% accurate. The only thing I’m betting on is the leaked cases from Case-Mate. All the rest, we’ll just have to wait on.


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Accomplishing electrical wiring by oneself may be tough. This can be especially so when you lack the information plus the working experience in electrical stuff. The factor is you can't do a trial and error system when dealing with electrical wiring. Issues could charge you a fortune or perhaps your daily life. Which is why ahead of setting up any do-it-yourself electrical repair, you will need to question some electrical wiring inquiries simply to make certain you understand what you are undertaking. Something about electrical wiring is always that wires are often coloration coded. Hence, it is actually essentially easier to understand which of them go along with which. Down below would be the most popular electrical wiring inquiries whose solutions generally entail colours to help you you recognize just about every certain wire. - Series And Parallel Circuit Diagram
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How do You Wire a Change?
One among probably the most common electrical wiring inquiries is regarding how to wire a swap. Whilst making use of switches in your house is sort of uncomplicated, wiring a person might not be that easy for everybody. An ON-OFF switch is really quite simple to wire. There are actually different kinds of switches, but for this example, let's say you might be putting in a single-pole toggle switch, an exceptionally common switch (and also the most basic).
You will discover 3 colors of wires in a very typical single-pole toggle switch: black, white, and green. Splice the black wire in two and link them over the terminal screws - a single on prime and the other within the bottom screw with the switch. The white wire serves like a resource of uninterrupted energy which is ordinarily linked to some gentle coloured terminal screw (e.g., silver). Join the eco-friendly wire to your ground screw of one's change.
These methods would frequently be ample to create a standard switch operate and not using a challenge. However, when you will not be self-confident that you can complete the activity effectively and securely you far better permit the professionals do it instead. Soon after all, there is certainly a motive why this task is among the most typical electrical wiring thoughts asked by many people.
How can You Wire a Ceiling Fan?
For many purpose, how you can wire a ceiling fan is likewise one among by far the most frequent electrical wiring concerns. To simplify this endeavor, you should utilize one switch for a single ceiling fan. To wire the lover, it can be merely a make a difference of connecting the black wire of your ceiling fan to the black wire in the swap. When there is a light-weight, the blue wire must be linked on the black wire with the swap as well.
How do You Replace a Breaker and just how Would you Increase a Sub Panel?
Whilst lots of try to try and do these responsibilities them selves, the majority of people are encouraged to rent an electrician in its place. It can be more complicated and as a consequence hazardous for many persons to try to replace a breaker or increase a panel. To give you an plan about these prevalent electrical wiring queries, you'd have to perform with a scorching electrical panel. For those who will not even understand what what this means is, you might be just not equipped to try and do the job by yourself. Even if you must invest extra by using the services of a professional electrician, it's much safer and much more reasonable to do this as a substitute. - How To Wire Recessed Lighting Fantastic Lovely Recessed How To Wire For Recessed Lighting Lovely Recessed Ceiling Lights Wiring Diagram Gallery Electrical Light Wiring Diagram #8613
You will discover good reasons why these are one of the most frequently questioned electrical wiring queries. 1, numerous think it can be straightforward to do, and two, they are the common electrical duties in the home. But then you definately mustn't place your security at risk inside your intention to economize. The stakes could even be much bigger for those who attempt to save cash and do an electrical wiring job with out ample know-how or expertise.
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In the mid-1990s a new strain of talk show emerged, led by the American shows Ricki Lake and Jerry Springer. This type of show is guest-based, rather than being an audience participation debate on pertinent social issues, as for example the long-running shows Donahue and, in the United Kingdom, Kilroy. The topics or themes of the show center not around questions of wider public concern but “everyday life dilemmas,” and the guests, who do most of the talking, are ordinary members of the public, usually with a bone to pick with each other. The show’s discourse routinely revolves around confrontations between ex-lovers, family members, friends who have fallen out, neighbors who are in dispute, and so on. In this sense, such shows create what could be called confrontation as a spectacle, in which guests are encouraged to air publicly disputes that ordinarily would be confined to the private sphere of everyday life.