cssi/SciSciGPT-SciSciNet huggingface dataset:
Akt1 signaling in dopamine-dependent behaviors (LB116)

Background: One biochemical change acquired following induction of depression-like behavior and exposure to drugs of abuse is decreased phosphorylation of the Akt1 serine-threonine kinase. Methods: To examine the relevance of intact Akt signaling, we used Akt1-mutant mice as genetic model. By combining biochemical, pharmacological, genetic and behavioral approaches, we examined if altered Akt signal transduction affects behavioral responses in experimental paradigms related to mesolimbic/nigrostriatal dopamine function. Results: Loss-of-function Akt1-mutant mice exhibited a phenotype of increased susceptibility in the learned helplessness paradigm. In this experimental model for acquired behavioral depression, the exposure to inescapable electric foot shocks (IES) disrupts the subject’s escape to subsequent noxious stimuli. While no significant differences were observed between sham-treated control mice depending on genotypes, IES-treated Akt1-mutant mice showed increased latencies of crossing and a highe...
Adriana Craciun. British Women Writers and the French Revolution: Citizens of the World

The subject of cosmopolitanism had its heyday in the heated discussions of multiculturalism in the 1990s. This political trope is now going through a welcome revitalization, and Adriana Craciun's B...
URBAN ENTREPRENEURSHIP AND THE PROMISE OF FOR-PROFIT PHILANTHROPY

The entrepreneurial spirit is universal. Challenges to raising capital vary from region to region, however, making a comparative analysis of entrepreneurship a potentially fruitful inquiry. The fo­ cus of the conference, of course, is on urban entrepreneurship, which I understand to mean start-up businesses in economically dis­ advantaged urban areas. Entrepreneurs seeking investment for projects in urban areas face unusual barriers in raising capital. The chief problem, I think, is that many urban projects, even profitable ones, are slow-growth projects; traditional venture capital seeks out investments in new technologies that promise to disrupt existing product markets, thereby generating the outsized returns that sup­ port the venture capital business model. Traditional solutions to the urban-entrepreneurship challenge include community networks, investments from nonprofits, and investment tax credits, but, as I explain, each of these solutions suffers from significant limitations. A promising alternative is emerging, however: for-profit philan­ thropy-altruistic investments guided by the discipline and account­ ability of for-profit venture investing.! While no panacea, for-profit philanthropy may supplement the other efforts necessary to make urban environments more conducive to entrepreneurship.
The aldo-keto reductase superfamily. cDNAs and deduced amino acid sequences of human aldehyde and aldose reductases.

Aldehyde reductase [EC 1.1.1.2] and aldose reductase [EC 1.1.1.21] are monomeric NADPH-dependent oxidoreductases having wide substrate specificities for carbonyl compounds. These enzymes are implicated in the development of diabetic complications by catalyzing the reduction of glucose to sorbitol. Enzyme inhibition as a direct pharmacokinetic approach to the prevention of diabetic complications resulting from the hyperglycemia of diabetes has not been effective because of nonspecificity of the inhibitors and some appreciable side effects. To understand the structural and evolutionary relationship of these enzymes, we cloned and sequenced cDNAs coding for aldose and aldehyde reductases from human liver and placental cDNA libraries. Human placental aldose reductase (open reading frame of 316 amino acids) has a 65% identity (identical plus conservative substitutions) to human liver and placental aldehyde reductase (open reading frame of 325 amino acids). The two sequences have significant identity to 2,5-diketogluconic acid reductase from corynebacterium, frog ρ-crystallin, and bovine lung prostaglandin F synthase (reductase). Southern hybridization analysis of human genomic DNA indicates a multigene system for aldose reductase, suggesting the existence of additional proteins. Thus, the aldo-keto reductase superfamily of proteins may have a more significant and hitherto not fully appreciated role in general cellular metabolism.
Are there radiologically identifiable prodromal changes in Thoroughbred racehorses with parasagittal fractures of the proximal phalanx

Summary Reasons for performing study Fractures of the proximal phalanx are generally considered to result from monotonic supraphysiological loads, but radiological observations from clinical cases suggest there may be a stress-related aetiology. Objectives To determine whether there are radiologically identifiable prodromal changes in Thoroughbred racehorses with confirmed parasagittal fractures of the proximal phalanx. Study design Retrospective cross-sectional study. Methods Case records and radiographs of Thoroughbred racehorses with parasagittal fractures of the proximal phalanx were analysed. Thickness of the subchondral bone plate was measured in fractured and contralateral limbs, and additional radiological features consistent with prodromal fracture pathology documented. Results The subchondral bone plate was significantly thicker in affected than in contralateral limbs. Evidence of additional prodromal fracture pathology was observed in 15/110 (14%) limbs with parasagittal fractures, and in 4% of contralateral limbs. Conclusions The results of this study are not consistent with monotonic loading as a cause of fracture in at least a proportion of cases, but suggest a stress-related aetiology. Increased thickness of the subchondral bone plate may reflect (failed) adaptive changes that precede fracture. Potential relevance Better understanding of the aetiology of fractures of the proximal phalanx may help develop strategies to reduce the risk of fracture. The Summary is available in Chinese – see Supporting information.
Chemical Phosphorylation of Deoxyribonucleosides and Thermolytic DNA Oligonucleotides

The phosphorylating reagent bis[S-(4,4′-dimethoxytrityl)-2-mercaptoethyl]-N,N-diisopropylphosphoramidite is prepared in three steps from commercial methyl thioglycolate and diisopropylphosphoramidous dichloride. The phosphorylating reagent has been used successfully in the solid-phase synthesis of deoxyribonucleoside 5′-/3′-phosphate or -thiophosphate monoesters and oligonucleotide 5′-phosphate/-thiophosphate monoesters. Bis[S-(4,4′-dimethoxytrityl)-2-mercaptoethyl]-N,N-diisopropylphosphoramidite has also been employed in the construction of a thermolytic dinucleotide prodrug model to evaluate the ability of the reagent to produce thermosentive oligonucleotide prodrugs under mild temperature conditions (∼25°C) for potential therapeutic applications. Keywords: bis[S-(4,4′-dimethoxytrityl)-2-mercaptoethyl]-N,N-diisopropylphosphoramidite; phosphorylation; thermolytic oligonucleotide prodrugs; solid-phase oligonucleotide synthesis
Unified theory of reversible diffusion-limited electrode reactions with adsorption under potentiostatic conditions

Summary It is shown that equations arising in the theoretical treatment of diffusion-limited reversible electrode reactions with adsorption of reactants under potentiostatic conditions are the same as those arising in the simpler cases of diffusion-limited adsorption without reaction in a broad class of cases. Thus, previously published treatments of the latter case for linear, Langmuir, and Frumkin adsorption at stationary planar and spherical and expanding planar electrodes can be transposed readily to the former case. Simple limiting approximations which can be applied with any adsorption isotherm are also given.
A quadratically convergent algorithm for convex-set constrained signal recovery

This paper addresses the problem of recovering a signal that is constrained to lie in a convex set, from linear measurements. The current standard is the alternating projections paradigm (POCS), which has only first-order convergence in general. We present a quadratically convergent iterative algorithm (Newton algorithm) for signal recovery from linear measurements and convex-set constraints. A new result on the existence and construction of the derivative of the projection operator onto a convex set is obtained, which is used in the Newton algorithm. An interesting feature of the new algorithm is that each iteration requires the solution of a simpler subspace-constrained reconstruction problem. A computation- and memory-efficient version of the algorithm is also obtained by using the conjugate-gradient algorithm within each Newton iteration to avoid matrix inversion and storage. From a computational point of view, the computation per iteration of this algorithm is similar to the computation per iteration of the standard alternating projections algorithm. The faster rate of convergence (compared to alternating projections) enables us to obtain a high-resolution reconstruction with fewer computations. The algorithm is thus well suited for large-scale problems that typically arise in image recovery applications. The algorithm is demonstrated in several applications.
Pathological correlates of pituitary adenomas presenting with apoplexy

Pituitary adenomas presenting de novo with apoplectic symptoms are uncommon. Several series on pituitary adenomas with apoplexy have been reported but have emphasized clinical aspects, incidence, or radiographic appearance by computed tomography (CT) scan. We reviewed our 13 years' experience, focusing on pathological appearance. We identified 15 patients with pituitary adenomas whose first presentation to our institution was with apoplexy. By combining histological and intraoperative findings with more sensitive magnetic resonance imaging (MRI) scans, we were able to attribute 5 of 15 cases to bland infarction, five cases to hemorrhagic infarction, four cases to pure clot, and one to a remote hemorrhagic infarction leaving extensive residual fibrosis and hemosiderin. Despite extensive tumor necrosis, reticulin staining still allowed identification of specimens as adenomas. Immunohistochemical staining was informative in 13 of 15 cases and endocrine-inactive, weak gonadotroph and null cell adenomas predominated. Cases with the greatest interval between symptom onset and surgery showed peripheral rim enhancement by MRI. Pathologically, this corresponded to granulation tissue, T cell lymphocytic infiltration, and atrophic pituicytes at the edge of the infarction or hemorrhage. Occasionally this reaction overshadowed the necrotic adenoma and contributed to diagnostic confusion. Our finding of lymphocytic inflammation in pituitary adenomas that have undergone an apoplectic event may suggest at least a modest immune-mediated response to damaged anterior pituitary tissue.
Genro Rule in China and Japan: A Comparative Perspective

For a time in both Japan (roughly 1890–1915) and much more briefly in China (about 1987–1992), major political decisions were made by cohesive groups of retired elders of the founding generation. Necessary if not sufficient conditions for rule by elders include a closed system, with the elite not held responsible to a wider public; and a constitutional or practical vagueness about the locus of final political authority. The more general pattern in such systems is personal dictatorship, with rule by elders as an alternative when cultural or political conditions stand in the way of one-man rule. This essay explores the pattern, conditions, and characteristics of rule by elders in China and Japan as genro rule serves as an alternative to one-man rule in generational transitions in political regimes with a relatively cohesive ruling group and a weak institutional structure.
Comprehensive review of genetic association studies and meta-analyses on miRNA polymorphisms and cancer risk.

Background MicroRNAs (miRNAs) are small RNA molecules that regulate the expression of corresponding messenger RNAs (mRNAs). Variations in the level of expression of distinct miRNAs have been observed in the genesis, progression and prognosis of multiple human malignancies. The present study was aimed to investigate the association between four highly studied miRNA polymorphisms (mir-146a rs2910164, mir-196a2 rs11614913, mir-149 rs2292832 and mir-499 rs3746444) and cancer risk by using a two-sided meta-analytic approach. Methods An updated meta-analysis based on 53 independent case-control studies consisting of 27573 cancer cases and 34791 controls was performed. Odds ratio (OR) and 95% confidence interval (95% CI) were used to investigate the strength of the association. Results Overall, the pooled analysis showed that mir-196a2 rs11614913 was associated with a decreased cancer risk (OR = 0.846, P = 0.004, TT vs. CC) while other miRNA SNPs showed no association with overall cancer risk. Subgroup analyses based on type of cancer and ethnicity were also performed, and results indicated that there was a strong association between miR-146a rs2910164 and overall cancer risk in Caucasian population under recessive model (OR = 1.274, 95%CI = 1.096–1.481, P = 0.002). Stratified analysis by cancer type also associated mir-196a2 rs11614913 with lung and colorectal cancer at allelic and genotypic level. Conclusions The present meta-analysis suggests an important role of mir-196a2 rs11614913 polymorphism with overall cancer risk especially in Asian population. Further studies with large sample size are needed to evaluate and confirm this association.
The Role of the LH Subdomain in the Function of the Cip/Kip Cyclin-Dependent Kinase Regulators

The Cip/Kip protein family, which includes p27, p21, and p57, modulates the activity of cyclin-dependent kinases (Cdks). A domain within these proteins, termed the kinase inhibitory domain (KID), is necessary and sufficient for Cdk inhibition. The KID consists of a cyclin-binding subdomain (termed D1) and a Cdk-binding subdomain (termed D2) joined by a 22-residue linker subdomain (termed LH). Before binding the Cdks, D1 and D2 are largely unstructured and the LH subdomain exhibits nascent helical characteristics. Curiously, although the sequence of the linker subdomain is not highly conserved within the family, its nascent helical structure is conserved. In this study, we explored the role of this structural conservation in interactions with cyclin-dependent kinase 2 (Cdk2) and cyclin A. We constructed chimeric p27-KID molecules in which the p27 LH subdomain was replaced with the corresponding segments of either p21 or p57. The chimeric molecules bind and inhibit Cdk2 in a manner similar to wild-type p27-KID. However, the extent of enthalpy/entropy compensation associated with these interactions was dramatically different, indicating different extents of LH subdomain folding upon binding. Our results indicate that the different LH subdomains, despite their sequence and thermodynamic differences, play similar roles in binding and inhibiting Cdk2/cyclin A.
Brain and Behavioral Modifications That Accompany the Onset of Motherhood

Objective. To discuss the brain and behavioral modifications that accompany the onset of motherhood. Design. Following a consideration of the evolutionary significance of the emergence of nurturing and caring responses in mammals, a thorough analysis of neurobiological modifications thought to maintain maternal responses in both rodent models and humans is presented. Results. The dramatic neurobiological changes accompanying the onset of parental responses provide a unique model for investigating the dynamic nature of the brain in response to changing demands. Conclusions. As conveyed throughout this tutorial, the maternal brain is a striking example of the adaptation necessary for various aspects of mammalian survival.
Polymer implants for drug delivery in the brain

Abstract The delivery of drugs to the brain represents a complex and important area. In this paper we review our research in four areas: (1) development of experimental techniques to “paint” controlled release polymers on brain microvessels to release proteins, (2) controlled release of dopamine from polymer matrix systems for the potential treatment of Parkinson's disease, (3) controlled release of bethanechol from biodegradable polymeric microspheres for potential treatment of Alzheimer's disease, (4) controlled release ofnitrosoureas from biodegradable polymer discs for potential treatment of brain cancer.
Statistically Enhanced Self-Attraction of Random Patterns

In this work we develop a theory of interaction of randomly patterned surfaces as a generic prototype model of protein-protein interactions. The theory predicts that pairs of randomly superimposed identical (homodimeric) random patterns have always twice as large magnitude of the energy fluctuations with respect to their mutual orientation, as compared with pairs of different (heterodimeric) random patterns. The amplitude of the energy fluctuations is proportional to the square of the average pattern density, to the square of the amplitude of the potential and its characteristic length, and scales linearly with the area of surfaces. The greater dispersion of interaction energies in the ensemble of homodimers implies that strongly attractive complexes of random surfaces are much more likely to be homodimers, rather than heterodimers. Our findings suggest a plausible physical reason for the anomalously high fraction of homodimers observed in real protein interaction networks.
The Historical Development of GaAs FET Digital IC Technology

Only ten years have passed since the first GaAs field-effect transistor (FET) digital IC was reported showing the potential for gigabit data rates for microwave systems. During this short time, GaAs FET digital IC technology has matured to produce a 4K static RAM with 3-ns access time. This rapid progress of the technology is due in part of the synergistic research on FET's for microwave device applications, progress in materials growth, lithography, and processing techniques necessary to made uniform and reproducible devices and the support and leadership of the military services. The events that lead to the present, state of the art for GaAs digital IC technology are discussed in chronological order starting with Shockley's theory for the field effect transistor and concluding with performance projections for the technology. Discussions with individuals involved in the technology and review of the published literature have been taken into account in an attempt to outline the contributions that have been made to the technology.
Cationic liposome-mediated gene transfer during acute pancreatitis: tissue specificity, duration, and effects of acute inflammation☆☆☆

Abstract Production of inflammatory cytokines in the pancreas, lung, and liver is believed to play a major role in the development of severe pancreatitis. This tissue-specific production could lend itself to directed anticytokine gene therapy if an appropriate delivery system could be developed. This study was undertaken to examine a novel approach for the delivery of protein-based therapies to the tissues involved during acute pancreatitis. Healthy mice received an intraperitoneal injection of cationic liposomes and a DNA plasmid containing the chloramphenicol acetyltransferase (CAT) reporter gene. Animals were killed at 12 hours and 1, 2, 3, 7, and 14 days with serum, pancreas, lung, and liver harvested. Acute pancreatitis was induced (cerulein, 50 μg/kg/hr intraperitoneally ×4) in additional mice before or after CAT transfection. The presence of pancreatitis was established in all animals by histologic scoring of pancreata and by serum amylase and lipase levels. CAT transfection efficiency was determined by quantitative CAT enzyme activity within tissue homogenates. Animals that received the liposome were successfully transfected with the CAT gene into the pancreas, lungs, and liver. Maximal transfection in each tissue occurred at 12 hours with decreasing CAT activity over the ensuing 14 days. No healthy animals receiving the CAT gene developed elevations in amylase, lipase, or any histologic parameter of pancreatitis. Transfection efficiency in the pancreas was markedly increased by preexisting or delayed induction of pancreatitis, whereas transfection of the lung and liver was increased to a lesser extent. Gene transfection into the pancreas, liver, and lungs is possible using a cationic liposome delivery system that does not induce pancreatitis or pancreatic inflammation. Pancreatic expression of the gene product is equal to or greater than that of the organs of the reticuloendothelial system and continues at very high efficiency rates during acute pancreatitis.
Mitochondrial chemiluminescence elicited by acetaldehyde.

Acetaldehyde-dependent chemiluminescence has been found to be a sensitive technique for the study of superoxide and hydrogen peroxide formation in beef heart mitochondria. The system responds to ATP and antimycin A with increased emission intensities and to ADP and rotenone with decreased intensities, indicating that the chemiluminescence reflects the energy status of the mitochondrion. These effects are based on the ability of acetaldehyde to react with superoxide and hydrogen peroxide to form metastable intermediates which decay spontaneously with the emission of light. Additionally, these intermediates can react with cyanide to give alternative products which can also decay with the emission of light, the cyanide-evokable chemiluminescence. The interaction of acetaldehyde with mitochondria is complex because acetaldehyde can serve as a hydrogen source for NADH and as an inhibitor (at high concentration) of electron transport, and appears to be a reducing agent for a heat-stable site that autoxidatively generates HOOH from O2−·. Inasmuch as acetaldehyde is a metabolite of ethanol, this broad spectrum of reactivity may play a role in the hepatic and cardiac toxicity that is associated with alcoholism. The heat-stable site that generates HOOH from O2−· has been studied further and appears to contain vicinal dithiol which is primarily responsible for the cyanide-evokable chemiluminescence.
The effect of cold adaptation on food-motivated behavior

In order to investigate the relationship between physiological adaptation to the cold and behavioral responses for food while in the cold, groups of rats were exposed to either −10°C or 21°C ambient temperatures. Exposures to the −10°C temperature produced a physiological adaptation to the cold as indicated by a progressively smaller reduction in body temperature over days following cold exposure. After 16 days of 50-min temperature exposures, behavioral testing started. Subjects were placed in −10°C environment and their barpress rates for food reinforcement were recorded. Results showed that the rats previously adapted to the cold responded more for food than rats not previously adapted to the cold. The physiological and behavioral effects of cold adaptation were not maintained after a 10-day retention period.
Spherical wave interaction with cylindrical holes in large limestone specimens

On a mesure dans du calcaire seche la fermeture de cavites cylindriques soumises a des trajectoires de deformation identiques par onde spherique divergente ou compression quasistatique. L'onde spherique est produite par une charge explosive et le chargement quasi-statique par une machine de compression triaxiale. Les fermetures maximales dans l'axe de chargement (crown-invert) sont presque egales, a part que l'on enregistre un rebond important dans l'essai dynamique et negligeable dans l'essai statique. La fermeture dans la direction perpendiculaire a l'axe de chargement (springline) est six fois plus grande pour le cas statique que pour le cas dynamique. Des coupes post-mortem de l'echantillon montrent dans les deux cas des «bandes de cisaillement» hyperboliques se propageant dans la roche adjacente a la cavite perpendiculairement a l'axe de chargement
Bone morphogenetic protein receptor 1A signaling is dispensable for hematopoietic development but essential for vessel and atrioventricular endocardial cushion formation

Bone morphogenetic protein 4 (BMP4) is crucial for the formation of FLK1-expressing (FLK1 + ) mesodermal cells. To further define the requirement for BMP signaling in the differentiation of blood, endothelial and smooth muscle cells from FLK1 + mesoderm, we inactivated Alk3 ( Bmpr1a ) in FLK1 + cells by crossing Alk3 floxed/floxed and Flk1 +/Cre Alk3 +/floxed mice. Alk3 conditional knockout (CKO) mice died between E10.5 and E11.5. Unexpectedly, Alk3 CKO embryos did not show any hematopoietic defects. However, Alk3 CKO embryos displayed multiple abnormalities in vascular development, including vessel remodeling and maturation, which contributed to severe abdominal hemorrhage. Alk3 CKO embryos also displayed defects in atrioventricular canal (AVC) endocardial cushion formation in the heart. Collectively, our studies indicate a crucial role for ALK3 in vessel remodeling, vessel integrity and endocardial cushion formation during the development of the circulation system.
Efficacy of preoperative combined 18-fluorodeoxyglucose positron emission tomography and computed tomography for assessing primary rectal cancer response to neoadjuvant therapy.

Efficacy of F-18 fluorodeoxyglucose positron emission tomography combined with computed tomography (FDG-PET/CT) for determining neoadjuvant therapy response in rectal cancer is not well established. We sought to evaluate serial FDG-PET/CT for assessing tumor down-staging, percentage residual tumor, and complete response or microscopic disease with rectal cancer neoadjuvant therapy. Patients with rectal cancer undergoing neoadjuvant therapy, definitive surgical resection, and FDG-PET/CT before and 4–6 weeks after neoadjuvant treatment were included. Tumors were evaluated pretreatment and on final pathology for size and stage. FDG-PET/CT parameters assessed were visual response score (VRS), standardized uptake value (SUV), PET-derived tumor volume (PETvol), CT-derived tumor volume (CTvol), and total lesion glycolysis (δTLG). Twenty-one rectal cancer patients over 3 years underwent neoadjuvant treatment, serial FDG-PET/CT, and resection. Complete response or microscopic disease (n = 7, 33%) was associated with higher ΔCTvol (AUC = 0.82, p = 0.004) and ΔSUV (AUC = 0.79, p = 0.01). Tumor down-staging (n = 14, 67%) was associated with greater ΔPETvol (AUC = 0.82, p < 0.001) and ΔSUV (AUC = 0.82, p < 0.001). Pathologic lymph node disease (n = 7, 33%) correlated with ΔCTvol (AUC = 0.75, p = 0.03) and ΔPETvol (AUC = 0.70, p = 0.08). FDG-PET/CT parameters were best for assessing tumor down-staging and percentage of residual tumor after neoadjuvant treatment of rectal cancer and can potentially assist in treatment planning.
Acute and chronic exposure of mouse cerebral microvessel endothelial cells to increased concentrations of glucose and galactose: effect on myo-inositol metabolism, PGE2 synthesis, and Na+/K(+)-ATPase transport activity.

Cultured mouse cerebral microvessel endothelial cells have a large intracellular myo-inositol content and rapidly take up extracellular myo-inositol. Myo-inositol uptake occurs by a high- and low-affinity transport system. Both transport systems appear to be Na+-dependent. The high- and low-affinity transport systems have a Km of 11 and 198 μmol/L and a Vmax of 47 and 381 pmol/min/mg protein, respectively. Acute exposure of cultured cells to 30 mmol/L d-glucose or d-galactose causes a decrease in myo-inositol uptake. The acute effect of glucose and galactose on myo-inositol uptake is sensitive to the extracellular myo-inositol concentration. The acute effect of glucose is apparently due to a competitive inhibition of high-affinity myo-inositol transport and has a Ki of 21 mmol/L. l-Glucose is more effective than d-glucose in decreasing myo-inositol uptake. In contrast, 2-deoxyglucose or 3-0-methylglucose does not acutely inhibit myo-inositol uptake. This suggests that the hydroxyl groups on carbons 2 and 3 of glucose are necessary for inhibitory activity. Chronic exposure of cells to media containing 136.4 μmol/L myo-inositol and 30 mmol/L glucose has no effect on myo-inositol accumulation from the extracellular fluid, myo-inositol incorporation into inositol phospholipids, or total myo-inositol content. Chronic exposure of the cells to media containing 30 mmol/L glucose causes only a small increase in the intracellular sorbitol content. In contrast, chronic exposure of the cells to media containing 30 mmol/L galactose causes a large increase in galactitol content and a decrease in myo-inositol accumulation, myo-inositol incorporation into inositol phospholipids, and intracellular myo-inositol content. Sorbinil treatment of the galactose-supplemented media protects the cells form changes in myo-inositol metabolism and content. Chronic exposure of the cells to media containing 30 mmol/L glucose or 30 mmol/L galactose causes a decrease in ouabain-sensitive Na+K+-ATPase transport activity, which is corrected by the addtion of sorbinil to the media. Chronic exposure of the cells to media containing 45 mmol/L glucose, but not galactose, causes an increase in PGE2 production. These studies suggest that acute or chronic exposure of cultured microvessel endothelial cells to increased concentrations of glucose or galactose causes a decrease in myo-inositol uptake by different mechanisms. Chronic exposure of the cells to increased concentrations of glucose or galactose causes alterations in endothelial cell properties, including Na+K+-ATPase transport activity and eicosanoid synthesis. The data are not clearly supportive of polyol accumulation and myo-inositol depletion as being responsible for the decrease in Na+K+ pump activity.
Residue-Level Interrogation of Macromolecular Crowding Effects on Protein Stability

Theory predicts that macromolecular crowding affects protein behavior, but experimental confirmation is scant. Herein, we report the first residue-level interrogation of the effects of macromolecular crowding on protein stability. We observe up to a 100-fold increase in the stability, as measured by the equilibrium constant for folding, for the globular protein chymotrypsin inhibitor 2 (CI2) in concentrations of the cosolute poly(vinylpyrrolidone) (PVP) that mimic the protein concentration in cells. We show that the increased stability is caused by the polymeric nature of PVP and that the degree of stabilization depends on both the location of the individual residue in the protein structure and the PVP concentration. Our data reinforce the assertion that macromolecular crowding stabilizes the protein by destabilizing its unfolded states.
Rhipicephalus sanguineus: amino acid composition of egg shell.

Abstract Acid hydrolysis of the protein fraction of a batch of egg shells of Rhipicephalus sanguineus was followed by determination of the amino acids in the hydrolysate. Using thin layer chromatography, the amino acids—lysine, arginine, aspartic acid, serine, glycine, glutamic acid, alanine, threonine, valine, tyrosine, isoleucine, and leucine were identified. Alkaline hydrolysis of the fraction followed by TLC revealed the presence of tryptophane. Chitin was revealed utilizing a chitosan test.
Hoarseness Misattributed to Reflux: Sources and Patterns of Error

Objective:This study aimed to identify voice disorders commonly misidentified as reflux and sources of such misattribution.Study Design:Retrospective chart review.Methods:Twenty-six patients carryi...
Sex Differences and Personality Factors in Responsivity to Pain

This study investigated the relationship between measured levels of masculinity-femininity, social desirability, and responsivity to pain in men and women. The literature suggests that the two personality variables might provide an explanation for the common findings of higher pain thresholds and tolerances in men than in women. A significant interaction was found between masculinity-femininity and sex for pain thresholds. Analysis of this interaction indicated that for men, but not women, there was a significant correlation between masculinity-femininity and pain, where higher masculinity was associated with higher pain thresholds. However, this finding did not account for the sex difference in pain threshold. The sex of the subject remained a significant predictor of both pain thresholds and tolerances after allowing for the influence of masculinity-femininity, social desirability, and their associated interactions.
Surveillance, epidemiology, and end results analysis of 2677 cases of uterine sarcoma 1989-1999.

Abstract Objective . To determine the association of race with incidence, histology, treatment, and survival in women with uterine sarcoma during the period 1989–1999. Methods . Uterine sarcomas were defined as leiomyosarcoma, carcinosarcoma, high-grade endometrial stromal sarcoma (HGESS), adenosarcoma, and sarcoma not otherwise specified (NOS). We used cases from Surveillance, Epidemiology, and End Results (SEER) program to compare uterine sarcoma among women >35 years of age. Using data from 1989 to 1999, we compared race-specific age-adjusted incidences, histological distributions, extent of disease at diagnosis, and race-specific survival. Results . During the period of 1989–1999, 2677 women were diagnosed with uterine sarcoma, 2098 (78%) of whom were white and 420 (16%) of whom were black, and 159 (6%) of whom were of other races. The overall age-adjusted incidence for blacks was twice that of whites and more than twice that of women of other races (7/10 5 vs. 3.6/10 5 vs. 2.7/10 5 , P 5 for blacks vs. 0.91/10 5 for whites, and 0.89 for women of other races, P 5 for blacks, vs. 1.7/10 5 for whites, and 0.99 for women of other races, P P Conclusions . Adjuvant therapy improved survival for women with stage II–IV disease. Survival of black and white patients who received comparable treatment was similar.
Continuous monitoring and intrafraction target position correction during treatment improves target coverage for patients undergoing SBRT prostate therapy.

Purpose To compare the potential benefits of continuous monitoring of prostate position and intervention (CMI) using 2-mm displacement thresholds during stereotactic body radiation therapy (SBRT) treatment to those of a conventional image-guided procedure involving single localization prior to treatment. Methods and Materials Eighty-nine patients accrued to a prostate SBRT dose escalation protocol were implanted with radiofrequency transponder beacons. The planning target volume (PTV) margin was 5 mm in all directions, except for 3 mm in the posterior direction. The prostate was kept within 2 mm of its planned position by the therapists halting dose delivery and, if necessary, correcting the couch position. We computed the number, type, and time required for interventions and where the prostate would have been during dose delivery had there been, instead, a single image-guided setup procedure prior to each treatment. Distributions of prostate displacements were computed as a function of time. Results After the initial setup, 1.7 interventions per fraction were required, with a concomitant increase in time for dose delivery of approximately 65 seconds. Small systematic drifts in prostate position in the posterior and inferior directions were observed in the study patients. Without CMI, intrafractional motion would have resulted in approximately 10% of patients having a delivered dose that did not meet our clinical coverage requirement, that is, a PTV D95 of >90%. The posterior PTV margin required for 95% of the dose to be delivered with the target positioned within the PTV was computed as a function of time. The margin necessary was found to increase by 2 mm every 5 minutes, starting from the time of the imaging procedure. Conclusions CMI using a tight 2-mm displacement threshold was not only feasible but was found to deliver superior PTV coverage compared with the conventional image-guided procedure in the SBRT setting.
The Melodramas of Globalization

This article posits a homology between (1) the developmentalist logic endemic to hegemonic discourses of globalization and (2) the logic of the `too late' that drives the melodrama genre, to argue that the experience of globalization is, itself, highly melodramatic. Focusing on the far-reaching transformations of the Mumbai-based film industry and its global epiphenomenon `Bollywood', the article critically analyzes the hooplas and anxieties that structure contemporary Indian cultural nationalism. Countering overarching prognoses of global homogenization, it draws attention to the myriad ground-level transactions through which difference is capitalized and managed. This understanding of melodrama as the persistence of difference helps explain the continuing popularity of the genre in the global South.
Do legumes and non-legumes tree species affect soil properties in unmanaged forests and plantations in Costa Rican dry forests?

Abstract Legume tree species, which are abundant in tropical dry forests, may be a critical regulator of soil nutrient dynamics because of their high foliar nitrogen (N) and potential for symbiotic N fixation. We investigated whether three legume tree species ( Acosmium panamense , Dalbergia retusa , and Gliricidia sepium ) have distinct soil chemistry under their crowns compared to nearby non-legume species ( Rehdera trinervis , Swietenia macrophylla , and Quercus oleoides ) when grown in two habitats: a diverse secondary forest or in 18-yr old monoculture plantations in northwestern Costa Rica. We quantified soil moisture, pH, labile carbon (C), inorganic N (NH 4 + and NO 3 − ), net N mineralization rates, total C and N, δ 15 N signature and enzyme activity. We predicted that legumes would have higher soil nutrient availability under their crowns, but that this effect would be more pronounced in plantations, where tree species diversity is low. In the forest, soils under Dalbergia had the highest values of total C and N, and extractable nitrate, whereas soils under Acosmium the highest N mineralization rates. The activity of acid phosphatase enzymes varied among the soils under different species in both habitats, with the highest activity in the soils under the legume Acosmium at the forest site. In the plantations, Acosmium had the highest values for total soil C and N, labile C, and potential N mineralization rates. We conclude that 1) the legume species did not have consistent effects as a functional group, possibly due to different amounts of nodulation in individuals within species, and 2) as hypothesized, the magnitude of the species effect was more pronounced in the plantations than in the diverse secondary forest.
Three dimensional finite element analysis of damage accumulation in composite laminate

A three dimensional finite-element computer program has been developed to analyze layered fiber-reinforced composite laminate. This program is capable of: (1) calculating the detailed stress distribution, (2) identifying the damage zone and mode of failure, (3) analyzing the damage accumulation, and (4) determining the ultimate strength of the composite laminate.
Effect of rearing condition on in vitro RNA synthesis by brain chromatin.

Whole brain chromatin from enriched, isolated, or standard colony rats was measured for its capacity to support RNA synthesis in vitro. Chromatin from rats environmentally enriched from 28 to 60 days of age supported less RNA synthesis than did chromatin from the corresponding isolated and standard colony animals. However, when the differential rearing was maintained from 28 to 88 days of age, no rearing-related differences in chromatin-supported RNA synthesis were observed. These results are discussed in terms of environmental modulation of brain development.
The impact of thrombocytopenia from temozolomide and radiation in newly diagnosed adults with high-grade gliomas.

Temozolomide (TMZ) administered daily with radiation therapy (RT) for six weeks, followed by adjuvant TMZ for six months, has become standard therapy for patients with glioblastoma multiforme (GBM). After several newly diagnosed patients at our institution developed severe (grade 3–4), prolonged thrombocytopenia, we conducted a retrospective review to define the incidence, depth, and duration of thrombocytopenia associated with this therapy. We reviewed the medical records and laboratory data of all adult patients with newly diagnosed high-grade gliomas who started treatment with this regimen between June 2004, when the regimen was first used at our institution, and August 2005. Of the 52 patients who met the criteria for this review, grade 3–4 thrombocytopenia occurred in 10 (19%; 95% CI, 10%–33%). In eight patients, the thrombocytopenia was attributable to concurrent daily TMZ and RT. The median duration of grade 3–4 thrombocytopenia was 32 days (range, 1–389 days). Five patients (10%) required platelet transfusions, two (4%) have required continued biweekly platelet transfusions for over six months, and nine (17%) discontinued therapy because of thrombocytopenia. Grade 3–4 thrombocytopenia occurred in 25% of women and 14% of men. Grade 3–4 neutropenia and anemia were noted in 10% and 8% of patients, respectively, and were not clinically significant. Between 15% and 20% of our newly diagnosed patients receiving TMZ and RT developed severe (grade 3–4) and potentially irreversible thrombocytopenia. The factors that predispose patients to this toxicity have yet to be determined. This toxicity should be considered when (1) prescribing this regimen to patient populations where a clinical benefit has yet to be shown, (2) contemplating empirical escalations of the dose or duration of TMZ, or (3) combining it with other potentially myelosuppressive therapies.
Metabolomics: integration of a new "omics" with clinical pharmacology.

The term “pharmacometabolomics” was coined in 2006 to reflect the potential of the predrug metabolomic signature to predict the postdrug response. Metabolomics can be used to examine the contribution of nongenomic factors, such as the environment, diet, or the gut microbiome, to the overall drug response. As such, the complexity of human biology afforded by metabolomics can complement genomic approaches, ultimately moving the discipline of clinical pharmacology closer to full implementation of personalized medicine. Clinical Pharmacology & Therapeutics (2013); 94 5, 547–551. doi:10.1038/clpt.2013.166
Nitric oxide, but not interleukin-1, mediates the local blood flow response to lipopolysaccharide in rabbit skin.

Abstract Lipopolysaccharide can mimic many aspects of the inflammatory response to gram-negative bacteria. In rabbit and rat skin, lipopolysaccharide induces neutrophil accumulation and an increase in blood flow. Interleukin-1, tumor necrosis factor-α and the vasodilator, nitric oxide (NO) have been implicated in the biological responses to lipopolysaccharide and gram-negative bacteria. In the present study, we characterized the local vascular response to E. coli lipopolysaccharide in rabbit skin and investigated its dependence on de novo protein synthesis, NO, interleukin-1 and neutrophils. The local vascular response to the intradermal injection of lipopolysaccharide was determined by measuring changes in local blood flow with a laser-Doppler flowmeter. Injections of lipopolysaccharide (3, 10 and 30 μg/site) induced a dose-related increase in blood flow, with a maximum at 2 h. The response to 10 μg/site lipopolysaccharide was abolished by co-injection of actinomycin D (4 × 10 −9 mol/site), reduced by 60% by N G -nitro-L-arginine methyl ester (10 −7 mol/site) and suppressed by 82% in rabbits pretreated with dexamethasone (2 mg/kg, i.v.). However, the lipopolysaccharide-induced increase in blood flow was not affected by co-injection of recombinant human interleukin-1 receptor antagonist (7.0 × 10 −11 mol/site) or by systemic neutrophil depletion. These results demonstrate that lipopolysaccharide causes delayed vasodilation of the rabbit cutaneous microvasculature which depends on protein synthesis and involves in part the release of NO. However, this response does not depend on interleukin-1 or neutrophils. The vasolidator effect of lipopolysaccharide may involve the expression of the inducible form of NO synthase in the vessel wall, through a mechanism independent of interleukin-1.
The Synthesis and Biological Activity of Certain 4′-Thionucleosides

Abstract Results are presented on the synthesis and biological activity of several types of 4′-thionucleosides as potential anticancer agents. Detailed studies on the mechanism of action of 4′-thiothymidine are also presented.
Investigating the anharmonicity of lattice vibrations in water-containing molecular crystals through the terahertz spectroscopy of L-serine monohydrate.

The influence of cocrystallized H2O molecules on the terahertz (THz) spectra and corresponding computational treatment of hydrated molecular crystals was investigated in the study of protonated and deuterium-substituted l-serine·H2O. The THz spectra of both solids have been measured in the range of 10 to 90 cm−1, with simulations of the crystalline structure and THz vibrational modes performed using solid-state density functional theory. Significant and systematic overestimations of the predicted vibrational frequencies were observed in all calculations. Evidence provided by the comparison of the experimental and calculated vibrational frequencies for both the protonated and deuterated l-serine·H2O solids indicates the presence of significant anharmonicity in the observed lattice vibrations. The results suggest that vibrational anharmonicity may play a much larger role in the interpretation of the THz spectra of hydrates in contrast to their corresponding anhydrous forms.
On Side-Chain Conformational Entropy of Proteins

The role of side-chain entropy (SCE) in protein folding has long been speculated about but is still not fully understood. Utilizing a newly developed Monte Carlo method, we conducted a systematic investigation of how the SCE relates to the size of the protein and how it differs among a protein's X-ray, NMR, and decoy structures. We estimated the SCE for a set of 675 nonhomologous proteins, and observed that there is a significant SCE for both exposed and buried residues for all these proteins—the contribution of buried residues approaches ∼40% of the overall SCE. Furthermore, the SCE can be quite different for structures with similar compactness or even similar conformations. As a striking example, we found that proteins' X-ray structures appear to pack more “cleverly” than their NMR or decoy counterparts in the sense of retaining higher SCE while achieving comparable compactness, which suggests that the SCE plays an important role in favouring native protein structures. By including a SCE term in a simple free energy function, we can significantly improve the discrimination of native protein structures from decoys.
An investigation of 2-amino-4-chlorobenzenethiol hydrochloride as a spectrophotometric reagent for the determination of molybdenum

Abstract 2-Amino-4-chlorobenzenethiol hydrochloride forms a green precipitate with molybdenum VI at pH 2. The precipitate can be extracted into chloroform and has an absorbance maximum at 720 mμ. The sensitivity of the reaction is 0.0054 μg of molybdenum per cm 2 for log I 0 /I = 0·001. Development of the spectrophotornetric method for the determination of molybdenum included a study of the effect of pH, reagent concentration, rate of complex formation and extraction, temperature and conformity to Beer's law. The method has been applied to the determination of molybdenum in steel and cast iron.