cssi/SciSciGPT-SciSciNet huggingface dataset:
Hot and Cold TRP Ion Channels

Tasting menthol evokes a cool sensation. In his Perspective, Clapham discusses new work published elsewhere that identifies a TRP ion channel, which is opened by both cold temperature and menthol. The channel is expressed in neurons of the trigeminal and dorsal root ganglia that receive sensations from regions such as the mouth and in the skin.
Successful reduction of a high defibrillation threshold by a combined implantation of a subcutaneous array and azygos vein lead

A 72-year-old man with nonischemic cardiomyopathy was referred because his implantable cardioverter defibrillator had failed to terminate spontaneous ventricular fibrillation (VF). Defibrillation threshold (DFT) testing confirmed that 830-V shocks failed to defibrillate VF despite optimization of the biphasic waveform and reversal of shock polarity. The placement of a new right ventricular lead and the addition of a subcutaneous array failed to defibrillate VF at 830 V. The combination of a subcutaneous array and azygos vein coil successfully defibrillated VF. The mechanism for successful DFT reduction was likely greater current supplied to the posterior basal left ventricle by the azygos vein lead.
Prostate Cancer Chemoprevention by Green Tea: In Vitro and in Vivo Inhibition of Testosterone-mediated Induction of Ornithine Decarboxylase

Recently, we have shown that ornithine decarboxylase (ODC), a rate-controlling enzyme in the polyamine biosynthetic pathway, is overexpressed in prostate cancer (PCA) and prostatic fluid in humans (R. R. Mohan et al., Clin. Cancer Res., 5: 143-147, 1999). ODC is also characterized as an androgen-responsive gene, and the androgenic stimulation regulates the development and growth of both normal and tumorigenic prostate cells. Thus, chemopreventive approaches aimed toward the modulation of ODC could be effective against PCA. Green tea polyphenols (GTPs) possess strong chemopreventive properties against a variety of animal tumor models and in some human epidemiological studies. At least two epidemiological studies have suggested that people who consume tea regularly may have a decreased risk of PCA. In this study, we investigated the effect of GTPs against testosterone-mediated induction of ODC in human prostate carcinoma cells, LNCaP as an in vitro model, and in Cpb:WU rats and C57BL/6 mice as in vivo models. Treatment of LNCaP cells with testosterone resulted in induction of ODC activity in a dose-dependent manner. Pretreatment of the cells with GTPs resulted in a significant inhibition of testosterone-caused induction of ODC activity in a dose-dependent manner. Similar effects of GTPs were observed in anchorage-independent growth assay of LNCaP cells where pretreatment of the cells with GTP was found to result in dose-dependent inhibition of colony formation. Testosterone treatment of the cells resulted in a significant increase in the level of ODC mRNA, and this increase was almost completely abolished by prior treatment of the cells with GTPs. The administration of testosterone (10 mg/kg body weight, i.p.) to sham-operated and castrated Cpb:WU rats resulted in 2- and 38-fold increases in ODC activity, respectively, in the ventral prostate. Oral feeding of 0.2% GTPs in drinking water for 7 days before testosterone administration resulted in 20 and 54% decreases in testosterone-caused induction of ODC activity in sham-operated and castrated rats, respectively. Similar results were obtained with C57BL/6 mice, where testosterone treatment at similar dosage resulted in a 2-fold increase in ODC activity in the ventral prostate and prior oral feeding with 0.2% GTPs resulted in 40% inhibition in this induction.
Thirty-day mortality in ED patients with new onset atrial fibrillation and actively treated cancer.

Abstract Objectives Studies suggest that inflammatory, autonomic, and coagulation alterations associated with cancer may increase incident atrial fibrillation (AF). New-onset AF is associated with increased mortality in other nonneoplastic disease processes. We investigated the association of active cancer with 30-day mortality in emergency department (ED) patients with new-onset AF. Methods We conducted an analysis within an observational cohort study at a tertiary care hospital that included ED patients with new-onset AF. The exposure variable was presence of active cancer. We defined active cancer as the patient received chemotherapy, radiotherapy, or recent cancer-related surgery within 90 days of the ED visit. The primary outcome was 30-day mortality. Logistic regression was used to analyze the association between cancer status and 30-day mortality adjusting for patient age and sex. Results During the 5.5-year study period, 420 patients with new-onset AF were included in our cohort, including 37 (8.8%) with active cancer. Patients with active cancer had no clinically relevant differences in their hemodynamic stability. Among the 37 patients with active cancer, 9 (24%) died within 30 days. Of the 383 patients without active cancer, 11 (3%) died within 30 days. After adjusting for age and sex, active cancer was an independent predictor of 30-day mortality, with an adjusted odds ratio of 10.8 (95% confidence interval, 3.8-31.1). Conclusions Among ED patients with new-onset AF, active cancer appears to be associated with 11-fold increased odds of 30-day mortality; new-onset AF may represent progressive organ dysfunction leading to an increased risk of short-term mortality in patients with cancer.
Understanding The Negative Graduate Student Perceptions Of Required Statistics And Research Methods Courses: Implications For Programs And Faculty

The authors of this study endeavor to explore the negative opinions and perceptions of graduate students in business and social science programs, regarding their required statistics and research methods courses. The general sense of instructors of such courses is that students dread and resent having to take courses dealing with statistics and social research because they are both intellectually demanding and require students to call on mathematics skills. Students also seem to put a low value on such courses in terms of application to their own careers. Clearly, the above-mentioned perceptions derive from intuitive knowledge and anecdotal statements by students. The authors of this study devised a research design to test the validity of the perceptions of negative attitudes among students in their graduate programs and to gain some understanding of the basis of the negativity.
Regulation of Spinach Chloroplast Acetyl-CoA Carboxylase

We have investigated several factors which influence acetyl-CoA carboxylase (ACCase) activity in lysed spinach chloroplasts. (1) When assayed after rapid lysis of light-incubated chloroplasts, ACCase activity was 2-fold higher than activity from dark-incubated chloroplasts. Within 5 min after lysis, activity from dark-incubated chloroplasts increased, suggesting a transient inactivation or inhibition of ACCase in the dark. (2) When lysed chloroplast suspensions were incubated with 30 to 100 microM acetyl-CoA before starting assays, activity was 4-fold higher than if suspensions were not preincubated with acetyl-CoA. CoA, malonyl-CoA, propionyl-CoA, and butyryl-CoA also activated ACCase. Full acetyl-CoA activation required MgATP and was essentially complete after 8 min. ACCase activity decreased upon removal of acetyl-CoA by gel filtration and was partially restored by readdition of acetyl-CoA. Thus, ACCase activation by acetyl-CoA was reversible. (3) Dithiothreitol and thioredoxin stimulated ACCase activity, but only in preparations where ACCase activity was low. (4) ACCase was assayed in concentrations of ATP, ADP, NADPH, NADP+, Mg2+, and CO2/HCO-3, which are estimated to occur in the stroma of chloroplasts under illumination or darkness. ACCase activity from lysed chloroplast suspensions was 10-fold higher when illuminated conditions were used. However, this activity was still 5-fold to 10-fold lower than the rates required to sustain known in vivo rates of fatty acid synthesis and in vitro rates achieved under optimum assay conditions with saturating substrates.
Neurotrophin-3 targets the translational initiation machinery in oligodendrocytes.

Neurotrophin-3 (NT-3) regulates oligodendrocyte (OLG) differentiation by mechanisms that remain poorly understood. Exposure of OLGs to NT-3 induces a significant increase in the levels of myelin basic protein (MBP). However, we found that this stimulation occurs in the absence of measurable effects on MBP gene promoter activation or mRNA expression, suggesting that NT-3 upregulates MBP protein expression by a posttranscriptional mechanism. Furthermore, NT-3 also causes an increase in the levels of myelin-associated glycoprotein (MAG) and myelin OLG glycoprotein (MOG), raising the possibility of a more general effect on myelin protein synthesis. Surprisingly, 35S-methionine incorporation into total OLG proteins demonstrated a 50% increase in labeling following only a brief, 15-min treatment with NT-3. Such a remarkably fast response is unlikely due to transcriptional activation, reinforcing the possibility that NT-3 may play a crucial role in regulating protein expression by a posttranscriptional mechanism. In support of this idea, we found that NT-3 stimulates the phosphorylation of essential regulators of the initiation machinery, eukaryotic initiation factor 4E (eIF4E), and its inhibitory binding partner 4E binding protein 1 (4EBP1), two crucial players in controlling cap-dependent protein synthesis. This stimulation involves the activation of pathways mediated by ERK1/2 and PI3K/mTOR, implicating these two kinase systems as modulators of protein synthesis in developing OLGs. Altogether, these observations show for the first time that NT-3 has the capacity of targeting the translational machinery and suggest a potential stimulatory effect of this neurotrophin on myelination by direct action on protein translation in the OLGs. © 2009 Wiley-Liss, Inc.
Digitalis Delirium A Report on Three Cases

The use and suitability of the term digitalis delirium are briefly discussed. Attention is drawn to the paucity of detailed reports on this important manifestation of digitalis poisoning. Three cases of digitalis delirium resulting from toxicity with 3 different preparations—gitalin, digoxin, and digitoxin—are presented. The first case demonstrates how the signs of early intoxication in a single patient may vary with different preparations and indeed with the same glycoside on separate occasions. The second case provides an alarming example of delirium which, although provoked by a short-acting glycoside, nevertheless lasted longer than 2 weeks. The third illustrates how easily the diagnosis of digitalis intoxication can go unrecognized when superimposed on a complex clinical picture. The clinical features of these cases are discussed in the light of previous reports.
microManaging Mitochondrial Translation

Regulation of gene expression in mammalian mitochondria by microRNAs is reported by Zhang et al. During muscle cell differentiation, localization of a miRNA is increased within mitochondria, where it interacts with Ago2 to selectively activate translation of mtDNA-encoded mRNAs. The findings represent a new mitochondrial regulatory pathway and a potentially powerful means to purposefully manipulate mtDNA expression.
Preliminary results of concomitant radiotherapy and chemotherapy in advanced cervical carcinoma.

Ten patients with advanced and previously untreated squamous cell carcinoma of the cervix were treated with a synchronous course of radiotherapy (RT) and chemotherapy (CT). RT consisted of 3600 to 4500 cGy external pelvic treatments on a 6-MeV linear accelerator followed by two intracavitary applications administering a total of 4000 mg hr of radium equivalent cesium. CT consisted of a course of mitomycin C (10 mg/m 2 iv bolus) and 5-fluorouracil (5FU; 1000 mg/m 2 /24 hr for 96 hr) during the second week of external RT and another course of cis -platinum (CDDP; 75 mg/m 2 , 1–6 hr infusion) and 5FU (1000 mg/m 2 /24 hr for 96 hr) during the first intracavitary cesium application. Toxicity was acceptable and complete clinical response was obtained in all patients at the end of the regimen. Nine patients are alive (eight without disease) 6 to 37 months following initiation of treatment (median 20 months). One patient has developed lumbar spine bone metastases and another died of local and pulmonary disease at 28 months. This combination of 5FU/mitomycin C/CDDP and RT appears to be a practical, well-tolerated, and highly effective regimen for advanced cervical carcinoma.
Metal Solubility in Phosphogypsum-Amended Sediment under Controlled pH and Redox Conditions

The storage of phosphogypsum (PG, CaSO 4 xH 2 O) has occupied vast areas of land that remain abandoned and subject to leaching and erosion by wind and water. The major constraints for PG use in the environment are the presence of several heavy metals and its radioactivity. Mississippi River alluvial sediment amended with PG (1%) was equilibrated under controlled redox (-250, -100, 0, 150, 300, and 500 mV) and pH (5.0 and 7.0) conditions to evaluate the feasibility of using PG to reduce aqueous concentrations of potentially toxic heavy metals and as a nutrients source. Phosphogypsum is an effective nutrient source since it increased water soluble Ca, Mg, K, and P concentrations (essential plant nutrients). At the same time, PG significantly reduced soluble Al at pH 7.0 (normal pH value of anaerobic wetland sediments), thereby reducing Al toxicity to plants growing in the sediment. Phosphogypsum addition resulted in a large increase in sulfide levels in reduced sediment suspensions. As a result, at low redox potential values, the solubility of spiked heavy metals (Cd and Ni at rates of 1000 mg kg -1 ) and natural trace elements was substantially reduced by precipitation as insoluble sulfides. Low sediment pH (pH 5.0) resulted in the highest release of all the studied metals [Ca, Mg, P, K, Fe, Mn, Cd, and Ni] into the sediment solution, likely due to H + , Fe 2+ , Mn 2+ , and Al 3+ displacing these metals from the exchange complex. This study, therefore, indicates that PG application to Louisiana Mississippi River alluvial sediments is useful for alleviating Al toxicity (neutral pH), increasing nutrient availability under watterlogged conditions, and reducing aqueous concentrations of toxic heavy metals to trace levels under anoxic conditions by precipitating these toxic elements as insoluble sulfides. If PG or PG-products are placed in neutral to alkaline sediments/soils and/or reducing environments, metals release at toxic levels should be of little concern to the wetland environment.
Physiological relationships between hypothalamus and cerebral cortex

Abstract 1. 1. After small bilateral hypothalamic lesions which produced affective behavior changes, the ECG was usually of fast normal type. In some animals, affect-evoking stimuli produced alerting patterns with subsequent rhythmic slow waves, followed again by fast activity. 2. 2. After lesions which were primarily restricted to the posterior hypothalamus, but which involved upper midbrain, the animals developed catalepsy, there were rhythmic bursts of high voltage slow waves, and alerting was difficult. After several days recovery, alerting was readily possible. 3. 3. After massive bilateral hypothalamic destruction, the dominant frequencies shifted to the slow bands, and strong stimuli (often noxious) were required to produce alert ECGs. With less extensive destruction, the pattern was identical during the early days, but as normal behavior and temperature control returned, the ECG returned toward preoperative levels; alerting was more and more easily produced. 4. 4. After massive unilateral lesions there was a change to slow frequencies in ipsilateral cortex, but with stimulation the cortical pattern tended to become bilaterally symmetrical as alerting occurred. When the remaining half of the hypothalamus was destroyed, greater symmetry appeared; the effects resembled those following one-stage destruction. 5. 5. It may be concluded that destruction of the hypothalamus produced a cortical potential pattern of the sleep type, which could, however, be blocked and changed to the alert type by stimuli of sufficient intensity. This supports the hypothesis that the hypothalamus normally exerts an alerting effect upon the cortex, which is involved in maintaining resting wakefulness. This is but one component, however, because strong alerting stimuli can break through the sleep of cats lacking a hypothalamus, indicating that accessory components may still serve to support wakefulness in the absence of the hypothalamo-cortical facilitatory mechanisms.
Rates of size increase and of phyletic evolution

THE RATE of phyletic evolution (evolution of the non-branching, non-cladogenetic type) is highly correlated inversely with the overall population size of genera and species. Factors which can materially decrease overall population size include increases in one or more of the following: number of biogeographic entities; number of communities; degree of climatic differentiation; and degree of marine regression on the continents (smaller populations of shallow water, marine organisms with regression). When all of these factors act in one direction rates of phyletic evolution are high or low; when they interfere with each other rates are intermediate1,2.
Morphological transformation in esophageal submucosa by bone marrow cells: esophageal implantation under external esophageal perfusion.

Accumulating clinical and experimental studies indicate that Barrett's esophagus might arise through multipotential stem cells under the stress of gastroesophageal reflux. Previously, we have prese...
A Specific Domain of Giα Required for the Transactivation of Giα by Tubulin Is Implicated in the Organization of Cellular Microtubules

Abstract Gsα, Giα1, and Gqα subunits bind tubulin with high affinity, whereas transducin (Gtα) does not. The interaction between tubulin and Gα, which also involves the direct transfer of GTP from tubulin to Gα (transactivation), is not yet fully understood. This study, using chimeras of Giα and Gtα, showed that the Giα (215–295) segment converted Gtα to bind to tubulin and this chimera (chimera 1) could be transactivated by tubulin. Insertion of Gtα (237–270) into chimera 1 to form chimera 2 resulted in a protein that, like Gtα, did not bind tubulin. Thus, it was thought that the Giα (237–270) domain was essential to modulate the binding of Giα1 to tubulin. Surprisingly, when domain (237–270) of Giα was replaced by Gtα (237–270) to form chimera 3, the chimera bound to tubulin with a similar affinity (K D ≅120 nm) as wild-type Giα1. However, even though chimera 3 displayed normal GTP binding, it was not transactivated by GTP-tubulin. Furthermore, when these chimeras were expressed in COS-1 cells, cellular processes in cells overexpressing Giα1 or chimera 1 were more abundant and longer than those in native cells. Gα was seen throughout the length of the process. Morphology of cells expressing chimera 2 was identical to controls. Consistent with the role of Chimera 3 as a “dominant negative” Gα, cells transfected with chimera 3 had only few truncated processes. This study demonstrates that although Giα (237–270) is not obligatory for the binding of Giα to tubulin, it is crucial for the transactivation of Gα by tubulin. These results also suggest that the transactivation of Gα by tubulin may play an important role in modulating microtubule organization and cell morphology.
Spatial Patterns of Tree Growth Anomalies in the Pacific Northwest

Regional patterns of ring width anomalies in Washington, Oregon, and Idaho, USA forests are examined using eigenvector (principal component) techniques. The first two eigenvectors, accounting for nearly 50% of the total variance, represent large-scale spatial patterns. Eigenvector I represents a pattern in which growth anomalies are positively correlated among all sites, and Eigen- vector II one in which growth anomalies are negatively correlated between sites located on opposite sides of the Cascade Mountain crest. These patterns most likely result from two types of tree growth responses to climate variations that extend uniformly across the study area. Common responses to spring-summer rainfall probably cause the positive, region-wide correlations identified by Eigenvector I, and opposite east-west re- sponses to summer temperature and winter precipitation may account for the negative correlations identified by Eigenvector II. No evidence supports the idea that the tree growth eigenvectors directly reflect two distinctive patterns of climate anomalies. The spatial patterns of these tree growth anomalies have remained essentially constant during the past 300 (possibly 400) yr.
Influence of recipient atrial contraction on left ventricular filling dynamics of the transplanted heart assessed by Doppler echocardiography

Recipient atrial remnants retain electrical and mechanical activity after orthotopic cardiac transplantation. This study investigated the influence of recipient atrial contraction timing on Doppler ultrasound mitral flow velocity curves, isovolumic relaxation time, peak early mitral flow velocity (M1), mitral valve pressure half-time and peak mitral flow velocity due to atrial systole (M2). Clearly identifiable recipient atrial electrical activity (P waves) was present in 7 of 10 patients studied early postoperatively 2 to 6 months (mean 2.5) (early group) and in 20 of 24 patients seen 1 to 11 years (mean 3) after transplantation (late group). Median age and gender distribution were similar in both groups. For analysis of its influence on isovolumic relaxation time, pressure half-time and M1, recipient atrial contraction was classified by its position in the cardiac cycle as early systole, late systole or diastole. For analysis of M2, it was classified as early diastole, late diastole or systole. Compared with its occurrence in diastole, recipient atrial contraction in late systole was associated with a shorter isovolumic relaxation time, shorter pressure half-time and higher M1. In early systole it was associated with a longer pressure half-time and lower M1 than in diastole; isovolumic relaxation time was unchanged. Recipient atrial contraction in early diastole resulted in a lower M2 than in systole, whereas simultaneous contraction of recipient and donor atria in late diastole resulted in an increase in M2. These results indicate that the timing of recipient atrial contraction and relaxation significantly influences left ventricular filling dynamics.
Editors’ Introduction to the Thematic Issue: Bringing Interactive Simulations into the Political Science Classroom

Over the last 20 years the nature of undergraduate education has changed dramatically, at least in part in response to shifting student demographics. At the same time, college and university profes...
Electron—proton distance changes during solvation of electrons in 3-methylhexane and other organic glasses by matrix ENDOR and second moment EPR lineshape analyses

Abstract Matrix proton ENDOR signals have been measured for stabilized electrons produced by irradiation at 4 K and at 77 K in 3-methylhexane glass. The matrix proton ENDOR linewidths are smaller when irradiation is carried out at 77 K. This difference is analyzed to show a 0.15 A change in the average electron—proton distance as the electron produced at 4 K is solvated by warming to 77 K. Similar distance changes have been deduced from a second moment EPR lineshape analysis for electrons in several organic glasses for which the proton hyperfine interaction is mainly dipolar.
A finite surface element model for two concentric nearly circular rings in partial contact

Abstract A numerical model is derived for the plane-stress elastic deformation of two concentric hollow cylinders with acircular contact surfaces. Given the detailed undeformed section geometry, the model computes the circumferential distributions of interfacial pressure and gap, and the distortion of the two free surfaces. The interface is partitioned into axial strip elements with radial displacement nodes at their boundaries and a piecewise linear pressure distribution from node to node. Influence coefficients linearly relating nodal displacements to nodal pressures are computed using a finite Fourier series expansion of the pressure distribution in conjuction with exact expressions for the deformation of a sinusoidally loaded thick ring. The iterative solution of the nonlinear system of node equations entails computing the currently nonzero nodal pressures by matrix inversion and then updating the contact/gap configuration. The model is demonstrated for a 400 node, multiple-contact interface between a machined shaft and sleeve with measured acircularity profiles.
Calcific Uremic Arteriolopathy (Calciphylaxis)

A 61-year-old man who had had diabetes mellitus for 25 years and renal failure requiring peritoneal dialysis for 7 years initially presented with a gangrenous left foot and underwent a partial amputation. During that admission, the patient received low-dose warfarin prophylaxis. Four months later, he presented with a presumed penile infection. The infection did not resolve with antibiotic treatment, and the tip of his penis formed an eschar. He returned 1 month later with complaints of tenderness and a violet rash on the lateral aspect of both thighs. Skin biopsy findings were consistent with a diagnosis of calcific uremic arteriolopathy (CUA). Histopathologic studies showed thrombi within arterioles (white arrows) and intimal calcification (black arrow). Retrospective evaluation of specimens obtained from the original foot surgery also revealed evidence of CUA. The penile lesion was not biopsied but was likely related to the same disease process. Acral (fingers, toes, tongue, penis) distribution of lesions has been described in patients with CUA. Dermatologic findings may resemble vasculitis and atherosclerotic peripheral vascular disease. The defining feature of CUA is calcification of the medial layer of small vessels. Although calcification is usually chronic, unknown triggers lead to acute thrombogenic microangiopathy and infarction of subcutaneous adipose tissue. Lesions begin as localized tender, broad violaceous nodular plaques. Necrosis and eschar formation may develop within days. Risk factors for CUA include elevated phosphorus levels, increased body mass index, and hypoalbuminemia. Warfarin therapy has also been implicated as a cause of CUA, and animal studies have helped to define the pathophysiology. Matrix Gla protein (MGP) has been shown to inhibit vascular calcification. In mice, disruption of MGP leads to diffuse calcification of vessels and rapid death. Warfain-induced γ-carboxylation inhibits activation of MGP and predisposes patients to vascular calcification. Therapy consists of lowering serum phosphorus, calcium, and parathyroid hormone levels. Local wound management including debridement and antibiotics may be necessary. In some cases, hyperbaric oxygen therapy helps heal wounds.
COMPREHENSIVE, THEORETICALLY BASED, CORRELATING EQUATIONS FOR FREE CONVECTION FROM ISOTHERMAL SPHERES

Abstract Correlating equations are developed for the local and mean Nusselt number for free convection from an isothermal sphere as a function of the Rayleigh and Prandtl numbers. These expressions are based primarily on theoretical solutions for limiting cases, and hence are presumed to be more reliable than purely empirical correlations. The predictions of the proposed expressions are, however, validated by comparisons with prior experimental data. The expressions for the mean Nusselt number are shown to be applicable for all Ra and Pr. The expressions for the local Nusselt number are limited in applicability to the laminar boundary layer regime. The same equations are applicable to mass transfer and to combined heat and mass transfer in terms of the Sherwood, Schmidt and appropriately modified Rayleigh numbers.
The methionine sulfoximine syndrome in the cat.

SUMMARY Methionine sulfoximine, the toxic principle of the agenized protein diet, produces in the cat a complex syndrome characterized by behavioral and convulsive changes. In a series of 50 cats, the following features were most consistently observed: 1 Sniffing movements, involving the upper lip, nose and lower eyelid, and accompanied by profuse salivation and impairment of consciousness. 2 Episodic behavioral changes consisting of head-turning, sniffing, and crouching movements strongly suggesting apprehension, orientation and fear. 3 Running fits at the onset of which the animal may appear fearful or hysterical. 4 Generalized tonic-clonic convulsions. A detailed description of the syndrome is given and the influence of external stimuli and such factors as dosage of toxic agent, age, nutritional status of experimental animal, upon the character, frequency, rapidity of onset, and duration of the various behavioral and convulsive phenomena are discussed. The significance of the sulfoximine syndrome, as regards its biochemical and behavioral similarities to certain types of human epilepsy and its value as an experimental tool i n the investigation of the patho-physiology of seizures are discussed. REUME La methionine sulfoximine, principe toxique du regime de proteine agenisee, produit chez le chat un syndfrome complexe characterise par des changements du comportement et des convulsions. Les caracteristiques suivants ont ete constamment observees sur une serie de 50 chats: 1 Mouvements de reniflument comprenant la levre superieure, le nez et la paupiere inferieure, accompagnes de salivation profuse et d'abaissement de la conscience. 2 Des changements episodiques du comportement consistant en tournement de la těte, reniflement et mouvements de rampement donnant fortement l'impression de crainte, d'orientation et d'apprehension. 3 Acces de course folle au debut desquels l'animal peut sembler tres craintif ou hysterique. 4 Convulsions toniques-cloniques generalisees. L'auteur donne une description detaillee du syndrome et decrit l'influence de stimuli externes et celle de facteurs tels que le dosage d'un agent toxique, de l'age et de l'etat de nutrition de l'animal d'experience, sur le caractere, la frequence et la rapidite du debut de la crise, la duree du changement du comportment et des phenomenes convgulsifs. La significatin du syndrome de la sulfoximine fait l'objet d'une discussion en ce qui concerne les similitudes biochimiques et celles du comportement a l'endroit de certains types d'epilepsie humaine ainsi que sa valeur en tant qu'instrument d'experience dans des recherches sur la pathophysiologie des crises.
Analysis of stress in the metatarsals

Shear and normal stresses throughout the second, third, fourth and fifth metatarsals under various loading conditions were determined mathematically using standard techniques from the theory of mechanics of solids. Anatomical data was obtained by CAT scanning the foot of a 20-year-old man at 5 mm increments. For each segment, the horizontal and vertical co-ordinates of points were determined along the outer and inner surfaces of the bone cross sections. Using this data, the stress was calculated throughout each cross-section for a load applied at the metatarsal head in the frontal plane at every 15° interval between the horizontal and the vertical directions. Maximum tensile stress occurred in the second metatarsal in the cross-sections 3.0 cm and 4.0 cm from the proximal end, and were the result of a vertical load. The maximum tensile stress in the third metatarsal occurred in the cross section 3.5 cm from the proximal end, as a result of a horizontal load applied on the lateral side. A similar loading produced the maximum tensile stress in the fourth metatarsal, at a distance of 3.0 cm from the proximal end. The maximum tensile stress in the fifth metatarsal occurred 3.5 cm from the proximal end, as a result of a load applied on the lateral side in a direction slightly inclined to the horizontal. The findings of this study closely relate to the incidence and location of metatarsal stress fractures.
Nursing Home Reform and the Politics of Long-Term Care

Nursing home care has been described as the most troubled and troublesome segment of the American health care system. Despite the annual expenditure of billions of dollars, extensive regulation, and the emergence of an increasingly sophisticated and concentrated industry, significant problems persist. Inadequate quality of care continues to be a serious and pervasive problem. Discrimination against patients whose care is paid for by Medicaid and Medicare, as well as against those with "heavy care" or extensive needs, is rampant. Costs have escalated at a phenomenal rate and continue to represent a substantial fiscal burden, causing one state Medicaid director to refer to nursing home payments as "the black hole of state budgets." These circumstances are neither new nor surprising. They are, in fact, the result of rather startling failures in the public sector that are rooted in the special nature of the politics of long-term care. This article discusses the history of public policy toward nursing homes and the politics of long-term care, emphasizing problems in assuring acceptable quality of care. It also addresses the possibilities for reform during the next two years, particularly in light of new patient advocate and nursing home reform coalitions that promise to change the face of long-term care politics.
Probability matching behavior, association, and rational choice

In two-event noncontingent probability learning experiments with individual human beings (systems at the organism level), probability matching behavior (the widely reported experimental finding that the prediction probability of subjects tends to match the outcome probability of events) has been regarded as anomalous by economists and decision theorists since in sight of the goal of maximizing the number of correct predictions, the maximize expected value strategy—always predict the more frequent event—dominates it as a strategy. In part one of this paper, a flexible explanation based upon the stipulation that subjects assume that there is positive association between the prediction and the outcome is proposed and grounded in the theory of reflexive predictions. Given this stipulation, probability matching is the dominant rational strategy. Numerous experiments which utilize a blocked sampling without replacement procedure introduce dependence between the remaining trials in a block and the past outcomes in violation of noncontingency. In part two of this paper, an exact solution to the amount of dependence introduced by sampling without replacement is given. Formulae are derived for the expected payoff and expected response proportions for an equivalence class of value maximizing decision rules. Two conclusions follow. First, precise limits are placed on the applicability of explanations which rely on the assumption that subjects can detect patterns in the outcomes. Second, experiments with relatively large block sizes are approximately equivalent to the analogous noncontingent experiment at least for the middle to high range of outcome probability.
Targeting Cardiac Fibroblasts to Treat Fibrosis of the Heart: Focus on HDACs

Cardiac fibrosis is implicated in numerous physiologic and pathologic conditions, including scar formation, heart failure and cardiac arrhythmias. However the specific cells and signaling pathways mediating this process are poorly understood. Lysine acetylation of nucleosomal histone tails is an important mechanism for the regulation of gene expression. Additionally, proteomic studies have revealed that thousands of proteins in all cellular compartments are subject to reversible lysine acetylation, and thus it is becoming clear that this post-translational modification will rival phosphorylation in terms of biological import. Acetyl groups are conjugated to lysine by histone acetyltransferases (HATs) and removed from lysine by histone deacetylases (HDACs). Recent studies have shown that pharmacologic agents that alter lysine acetylation by targeting HDACs have the remarkable ability to block pathological fibrosis. Here, we review the current understanding of cardiac fibroblasts and the fibrogenic process with respect to the roles of lysine acetylation in the control of disease-related cardiac fibrosis. Potential for small molecule HDAC inhibitors as anti-fibrotic therapeutics that target cardiac fibroblasts is highlighted. This article is part of a Special Issue entitled "Myocyte-Fibroblast Signalling in Myocardium."
Carcinoid tumors of the lung and family history of cancer

Family history of cancer has been described among patients with lung neoplasms. Carcinoid tumors, originally thought to be slow growing and nonmetastatic, have not historically been included in these studies. In some instances these tumors have demonstrated aggressive metastatic potential. A medical record review of 86 patients with histopathologically confirmed carcinoid tumors of the lung, treated at the University of Texas M.D. Anderson Cancer Center between 1959 and 1994, was conducted to describe family history of cancer. Family history of cancer was recorded in 74 (86%) of the medical records and 32 (43%) reported first-degree relatives with cancer. Five-year survival for patients with affected relatives was 45% and 73% for patients without affected relatives (p = .23). Among 67 patients without metastatic disease at diagnosis, the risk of distant metastasis by 5 years was 40% among patients with a positive family history of cancer compared to 6% of the patients without affected relatives (p = .03), (rate ratio 5.01). These results suggest that genetic susceptibility may affect the metastatic potential of some carcinoid tumors.
Time-resolved diffraction profiles and atomic dynamics in short-pulse laser-induced structural transformations: Molecular dynamics study

The diffraction profiles and density correlation functions are calculated for transient atomic configurations generated in molecular dynamics simulations of a $20\phantom{\rule{0.3em}{0ex}}\mathrm{nm}$ Au film irradiated with $200\phantom{\rule{0.3em}{0ex}}\mathrm{fs}$ laser pulses of different intensity. The results of the calculations provide an opportunity to directly relate the detailed information on the atomic-level structural rearrangements available from the simulations to the diffraction spectra measured in time-resolved x-ray and electron diffraction experiments. Three processes are found to be responsible for the evolution of the diffraction profiles. During the first several picoseconds after the laser excitation, the decrease of the intensity of the diffraction peaks is largely due to the increasing amplitude of thermal atomic vibrations and can be well described by the Debye-Waller factor. The effect of thermoelastic deformation of the film prior to melting is reflected in shifts and splittings of the diffraction peaks, providing an opportunity for experimental probing of the ultrafast deformations. Finally, the onset of the melting process results in complete disappearance of the crystalline diffraction peaks. The homogeneous nucleation of a large number of liquid regions throughout the film is found to be more effective in reducing long-range correlations in atomic positions and diminishing the diffraction peaks as compared to the heterogeneous melting by melting front propagation. For the same fraction of atoms retaining the local crystalline environment, the diffraction peaks are more pronounced in heterogeneous melting. A detailed analysis of the real space correlations in atomic positions is also performed and the atomic-level picture behind the experimentally observed fast disappearance of the correlation peak corresponding to the second nearest neighbors in the fcc lattice during the laser heating and melting processes is revealed.
Transient conductive, radiative heat transfer coupled with moisture transport in attic insulations

A transient, one-dimensional thermal model that incorporates combined conduction, radiation heat transfer, and moisture transport for residential attic insulations has been developed. The governing equations are the energy equation, the radiative transport equation for volumetric radiation within the insulation batt, and the species equations for bound H2O and vapor H2O. A simultaneous solution procedure with a Eulerian control volume-based finite difference method was used to solve the energy equation and the species equations. The method of discrete ordinates was used in solving the radiative transport equation. For H2O transport, both diffusion of vapor H2O and bound H2O and moisture adsorption/desorption within the insulation binder are included in the model. The experimental data measured at an occupied North Mississippi residence for R19STD (standard R19 fiberglass insulation batt without a foil radiant barrier) were used to validate the model which predicted heat fluxes for summer, spring, winter, and fall seasonal conditions. These predictions were compared with the measured heat flux data and the predictions from the dry model (without the moisture transport). Various profiles such as temperature-time histories, relative humidity time histories, spatial H2O concentrations, spatial temperatures, and spatial heat fluxes are presented to explain the overall heat transfer behavior. 18 refs.
Biosynthesis and axonal transport of proteins and identified peptide hormones in the X-organ sinus gland neurosecretory system

In vitro biosynthesis of neurosecretory peptides specific to the X-organ sinus gland (XOSG) of the land crabCardisoma carnifex was studied. The neurosecretory somata comprising the X-organ were selectively exposed to saline containing3H-leucine, glucose and antibiotics for 5 h (pulse) followed by 19–24 h of superfusion with nutrient media (chase). Analysis of extracts of somata and terminal regions by high voltage paper electrophoresis demonstrated the uptake and incorporation of3H-leucine into protein by X-organ somata and its axonal transport to terminal regions. Tritiated-leucine incorporation was reduced 90% by 50 μg/ml puromycin, indicating ribosome-mediated synthesis. Axonal transport was blocked by ligation of the axons; this did not affect the rate of3H-leucine incorporation by the somata. Radiolabelled peptide hormones were identified by comigration of radiolabel with RPLC and/or SDS-PAGE determined regions of bioactivity and by comparison of RPLC elution patterns with those of sinus gland peptides purified and analyzed for amino acid composition by Newcomb (1983a). Erythrophore concentrating hormone (ECH) and at least two 6,000 Dalton peptides having crustacean hyperglycemic hormone activity (CHH) were identified among peptides biosynthetically radiolabelled. Comparison of XOSG systems receiving 5 h of incubation with those receiving a pulse-chase (5 h∶19 h) regime demonstrates the existence of polypeptide precursors to the XOSG peptide hormones.
Finite Deformation of Slender Beams

The present investigation considers the problem of finite deformation of slender, elastic beams with constant cross-section. The pertinent non-linear equations characterizing the deformation of the beam are derived using a variational principle which also yields the associated natural and imposed boundary conditions. The mathematical model of the beam accounts for the (coupled) flexure, torsion, and extension (contraction) of the beam but it neglects deformations due to shear. Two example problems are presented, each considering the deformation of a cantilever beam subjected to oblique (unsymmetrical) loading. Example 1 treats the case of an end loaded beam, whereas Example 2 treats the same beam subjected to a uniformly distributed load. In both examples results are compared to the equivalent cases treated within the framework of (conventional) linear theory.
Energy dependence of quasiparticle damping at a metal surface

We evaluate the energy dependence of the imaginary part of the electron self-energy Im\ensuremath{\Sigma} in the vicinity of a metal surface modeled with jellium via numerical calculations based on the GW approximation. When the electron is inside the surface, conventional quadratic scaling, Im\ensuremath{\Sigma}\ensuremath{\simeq}(E-${\mathrm{E}}_{\mathrm{F}}$${)}^{2}$ for E\ensuremath{\rightarrow}${\mathrm{E}}_{\mathrm{F}}$, holds for electron positions all the way to the jellium edge and for energies at least up to the vacuum level E-${\mathrm{E}}_{\mathrm{F}}$\ensuremath{\simeq}4 eV. However, when the electron is in the vacuum outside the surface, large departures from quadratic scaling are obtained for most energies for which it holds in the bulk. These departures grow as the electron-surface separation increases. This effect is traced to the suppression of one-electron decay channels near the Fermi level.
Inside the Matrix: Integrating the Paradigms of Intergovernmental and Network Management

Abstract The basic research concepts of intergovernmental and network management are examined with regard to blending the two into a unified theory of collaborative management. A substantial literature in both fields has emerged and is ripe for conceptually enhancing interorganizational management in the public sector. The collaborative management concepts forwarded emanate from the authors' comprehensive study of collaborative public management in 237 cities. The major concerns that are found to be ready for knowledge unification include: (1) multiple network complexity and the emergence of governance through policy networks, (2) strategic behavior and its implementation through networks, (3) the role of government institutions in network governance, and (4) the use of myriad policy instruments and multiorganizational activity. Each of these research arenas are representative of the kind of knowledge base that can be blended and extended to help public managers understand how to operate in the vertical/h...
Inhibition of WNT Signaling by G Protein-Coupled Receptor (GPCR) Kinase 2 (GRK2)

Activation of Wnt signaling pathways causes release and stabilization of the transcription regulator β-catenin from a destruction complex composed of axin and the adenomatous polyposis coli (APC) protein (canonical signaling pathway). Assembly of this complex is facilitated by a protein-protein interaction between APC and a regulator of G protein signaling (RGS) domain in axin. Because G protein-coupled receptor kinase 2 (GRK2) has a RGS domain that is closely related to the RGS domain in axin, we determined whether GRK2 regulated canonical signaling. We found that GRK2 inhibited Wnt1-induced activation of a reporter construct as well as reduced Wnt3a-dependent stabilization and nuclear translocation of β-catenin. GRK2 enzymatic activity was required for this negative regulatory effect, and depletion of endogenous GRK2 using small interfering RNA enhanced canonical signaling. GRK2-dependent inhibition of canonical signaling is relevant to osteoblast (OB) biology because overexpression of GRK2 attenuated Wnt/β-catenin signaling in calvarial OBs. Coimmunoprecipitation studies found that: 1) GRK2 bound APC; 2) The GRK2-APC interaction was promoted by GRK2 enzymatic activity; and 3) Deletion of the RGS domain in GRK2 prevented both the GRK2-APC interaction and GRK2-dependent inhibition of canonical signaling. These data suggest that: 1) GRK2 negatively regulates Wnt signaling; 2) GRK2-dependent inhibition of canonical signaling requires a protein-protein interaction between the RGS domain in GRK2 and APC; and 3) Enzymatic activity promotes the GRK2-APC interaction and is required for the negative regulatory effect on canonical signaling. We speculate that inhibiting GRK2 activity in bone-forming OBs might be a useful therapeutic strategy for increasing bone mass.