cssi/SciSciGPT-SciSciNet huggingface dataset:
Can we predict the response to epidermal growth factor receptor targeted therapy

Epidermal growth factor receptor (EGFR) targeted therapy interferes with a molecular pathway that significantly regulates tumor growth, progression, and survival. Several clinical trials on EGFR targeted therapy revealed objective responses, and also improved survival in patients with different solid tumors. However, considerable differences in therapeutic efficacy were recognized across patient populations that might rely on specific characteristics of the individual patient, the tumor dependence on the EGFR pathway or alternative signaling pathways. Therefore, molecular markers that predict responsiveness to the specific targeted therapy are essential. Predictive markers will help to identify which individual patients might benefit the most from targeted therapy, and thus will help to increase efficacy and decrease toxicities. The occurrence of an acne-like skin rash was the first clinical surrogate marker in EGFR targeted therapy significantly associated with response rate. In gastrointestinal cancer patients promising predictive molecular markers have now been identified within the EGFR signaling pathway. K-ras mutations are associated with resistance to EGFR monoclonal antibodies (mAbs) in metastatic colorectal cancer patients. Moreover, high gene expression levels of EGFR ligands amphiregulin and epiregulin are indicative for improved progression-free survival (PFS) in response to EGFR targeted therapy. Favorable response to EGFR targeted therapy has been correlated with low gene expression levels of vascular endothelial growth factor (VEGF). Furthermore, germline polymorphisms within the genes of epidermal growth factor (EGF) and EGFR, cyclooxygenase-2 (Cox-2), cyclin D1, and FCGR2A/3A are of predictive value. However, these first encouraging findings are limited mostly due to the small patient numbers evaluated in retrospective studies. Thus, large prospective clinical trials are needed to validate these data.
Heterosis for myelin content is limited to the central nervous system

We have recently described a murine model for studying aspects of myelination (Seyfried and Yu, 1980; Ebato et al., 1983; Miskimins et al., 1986). This mouse shows hypermyelination during the period of most active synthesis of myelin, 9 to 21 days post-natal. The myelin parameters showing an increase were all measured in the central nervous system. We investigated here whether this effect extends into the peripheral nervous system. Our results indicate that the hypermyelination is limited to the central nervous system.
Evolution of the antiretroviral restriction factor TRIMCyp in Old World primates.

The retroviral restriction factor TRIMCyp, which is a fusion protein derived from the TRIM5 gene, blocks replication at a post-entry step. Among Old World primates, TRIMCyp has been found in four species of Asian macaques, but not in African monkeys. To further define the evolutionary origin of Old World TRIMCyp, we examined two species of baboons (genus Papio) and three additional macaque species, including M. sylvanus, which is the only macaque species found outside Asia, and represents the earliest diverging branch of the macaque lineage. None of four P. cynocephalus anubis, one P. hamadryas, and 36 M. sylvanus had either TRIMCyp mRNA or the genetic features required for its expression. M. sylvanus genomic sequences indicated that the lack of TRIMCyp in this species was not due to genetic homogeneity among specimens studied and revealed the existence of four TRIM5α alleles, all distinct from M. mulatta and Papio counterparts. Together with existing data on macaque evolution, our findings indicate that TRIMCyp evolved in the ancestors of Asian macaques approximately 5–6 million years before present (ybp), likely as a result of a retroviral threat. TRIMCyp then became fixed in the M. nemestrina lineage after it diverged from M. nigra, approximately 2 million ybp. The macaque lineage is unique among primates studied so far due to the presence and diversity of both TRIM5 and TRIMCyp restriction factors. Studies of these antiviral proteins may provide valuable information about natural antiviral mechanisms, and give further insight into the factors that shaped the evolution of macaque species.
The importance of information security spending: an economic approach

Information security is a growing concern for today's businesses though it does not always get enough attention. One problem is justifying the budget necessary to properly protect information systems. This paper explores why information security should be a priority for businesses and deals with how a security expert can model potential losses for their organization. There is no silver bullet for modeling security risks so this paper discusses various methods that can be used as guidelines for professionals to make well informed decisions. Not all losses are able to be modeled correctly and for this reason they may be overlooked or improperly understood by an organization. Non-financial losses such as the potential for stock devaluation due to damaged reputations are also explored.
Caspase-3 inhibition preserves myocardial geometry and long-term function after infarction.

Background Cardiac remodeling after infarction is characterized by progressive ventricular dilation and functional impairment. Although surgical and percutaneous revascularization strategies may prevent remodeling, not all patients are candidates for these procedures. Apoptosis in the border-zone myocardium is thought to be critical to the remodeling process, and caspase-3 is a downstream effector of apoptosis. We hypothesized that inhibition of caspase-3 activity might limit dysfunction and remodeling after permanent coronary artery ligation. Methods FVB male mice underwent permanent ligation of the left anterior descending coronary artery. Immediately before surgery and for 7 subsequent days, animals were treated daily with 3 mg/kg DEVD-CHO, a cell-permeable inhibitor of caspase-3 ( n = 16), or vehicle ( n = 28). At 2 weeks and 6 weeks, echocardiography was performed and ventricular dimensions and function were assessed. At 8 weeks, invasive hemodynamic measurements were made and the animals were sacrificed. Results There was a trend toward improved survival in the inhibitor-treated group compared to the vehicle-treated group (56.3% versus 21.4%, P = 0.07). Infarct size at the time of sacrifice was comparable in both groups. At both 2 and 6 weeks, left ventricular dimensions, including end-diastolic and end-systolic diameters, were less in inhibitor-treated animals. Fractional shortening was higher at 6 weeks in the inhibitor-treated animals (22.1 ± 6.0% versus 15.0 ± 6.0%, P = 0.02). Invasive hemodynamic parameters at 8 weeks were comparable, with the exception of diastolic blood pressure, which was less in the inhibitor group. Conclusion Treatment with a caspase-3 inhibitor improved survival and prevented ventricular dilation and dysfunction after permanent coronary artery occlusion.
Photodeformable spherical hybrid nanoparticles.

We report the first synthesis of spherical nanoparticles of a bridged polysilsesquioxane. The hard, brittle nanoparticles are prepared by a simple sol−gel polymerization without surfactants or templates. Particle size ranges from 50 to 100 nm. The organic component of these hybrid nanoparticles is composed of a photolabile coumarin dimer. Irradiation with UV light dissociates the photodimer resulting in rupture of the cross-links and subsequent deformation and eventual “melting” of the nanoparticles.
Clinical Evaluation of a Multiple-Gene Sequencing Panel for Hereditary Cancer Risk Assessment

Purpose Multiple-gene sequencing is entering practice, but its clinical value is unknown. We evaluated the performance of a customized germline-DNA sequencing panel for cancer-risk assessment in a representative clinical sample. Methods Patients referred for clinical BRCA1/2 testing from 2002 to 2012 were invited to donate a research blood sample. Samples were frozen at −80° C, and DNA was extracted from them after 1 to 10 years. The entire coding region, exon-intron boundaries, and all known pathogenic variants in other regions were sequenced for 42 genes that had cancer risk associations. Potentially actionable results were disclosed to participants. Results In total, 198 women participated in the study: 174 had breast cancer and 57 carried germline BRCA1/2 mutations. BRCA1/2 analysis was fully concordant with prior testing. Sixteen pathogenic variants were identified in ATM, BLM, CDH1, CDKN2A, MUTYH, MLH1, NBN, PRSS1, and SLX4 among 141 women without BRCA1/2 mutations. Fourteen participants carried 15 ...
Anti-inflammatory agents and renal function

The purpose of this review is to provide an overview of the effect of traditional nonsteroidal anti-inflammatory drugs (NSAIDs) and cyclooxygenase (COX)-specific-2 inhibitors (coxibs) on renal function. Both COX isoforms (COX-1 and COX-2) constitutively are expressed in the adult mammalian kidney and contribute to the biosynthesis of prostaglandins (PGs). Inhibition of COX activity in the kidney by NSAIDs has relatively mild consequences in healthy individuals, but can lead to serious adverse events in patients whose renal function is PG dependent. Most studies have reported transient decreases in sodium excretion upon initiation of therapy with either traditional NSAIDs or coxibs. In patients whose renal function is dependent on prostanoids, both nonselective NSAIDs and coxibs can affect the glomerular filtration rate. Changes in renal function may result in hypertension and edema. Several studies have compared the effects of traditional NSAIDs, celecoxib, and rofecoxib on blood pressure and incidence of edema, but the results have not been consistent, as the trials used different clinical models and study designs. No trials to date have been performed with rigorous study designs that allow meaningful drug comparisons at comparably effective doses. In consequence, patients who are at risk for adverse renal events should be monitored with the same caution when receiving coxibs as when receiving treatment with nonselective NSAIDs. They include patients with congestive heart failure or renal or hepatic disease, as well as those of advanced age receiving therapy with diuretics or angiotensin-converting enzyme (ACE) inhibitors.
Head and neck cancers on CT: preliminary study of treatment response assessment based on computerized volume analysis.

OBJECTIVE. The objective of our study was to investigate the feasibility of computerized segmentation of lesions on head and neck CT scans and evaluate its potential for estimating changes in tumor volume in response to treatment of head and neck cancers.MATERIALS AND METHODS. Twenty-six CT scans were retrospectively collected from the files of 13 patients with 35 head and neck lesions. The CT scans were obtained from an examination performed before treatment (pretreatment scan) and an examination performed after one cycle of chemotherapy (posttreatment scan). Thirteen lesions were primary site cancers and 22 were metastatic lymph nodes. An experienced radiologist (radiologist 1) marked the 35 lesions and outlined each lesion's 2D contour on the best slice on both the pre- and posttreatment scans. Full 3D contours were also manually extracted for the 13 primary tumors. Another experienced radiologist (radiologist 2) verified and modified, if necessary, all manually drawn 2D and 3D contours. An in-house-de...
Background and current knowledge of Chlamydia pneumoniae and atherosclerosis.

Attributes of Chlamydia pneumoniae of potential importance to a relationship with atherosclerosis are described. Among these are that C. pneumoniae is not new. It is unique. It is a pathogen with which everyone is infected, and it is difficult to treat. It causes immunopathology, myocarditis, and endocarditis and chronicity is a hallmark of Chlamydia infection. Current knowledge of the relation of C. pneumoniae and atherosclerosis comes from observational (e.g., seroepidemiology and tissue studies) and experimental studies. The limitations of the serologic studies of chronic infection are noted as is the conclusive demonstration of an association of C. pneumoniae and atherosclerosis by the repeated and frequent finding of the organism in atherosclerotic tissue. Experimental studies are needed to determine if the association is causal. Such studies should include animal models, basic mechanisms, and secondary prevention antibiotic treatment trials.
Understanding the relationship between entrepreneurial orientation and strategic learning capability: an empirical investigation

This research explores the relationship between strategic learning capability—a firm's proficiency at generating, and then acting on, strategic knowledge—and entrepreneurial orientation (EO). While theory posits the inevitably of building strategic learning capability from behaving entrepreneurially, there is little empirical research to validate this proposition and even less understanding of how and why EO contributes to strategic learning capability. Empirical results from 110 manufacturing firms confirm the direct effect of EO on strategic learning capability, and support is found for three constructs—structural organicity, market responsiveness, and strategy formation mode—that fully mediate the EO-strategic learning capability relationship. Copyright © 2009 Strategic Management Society.
Pneumoperitoneum does not influence trocar site implantation during tumor manipulation in a solid tumor model

The purpose of this study was to assess tumor implantation at abdominal wound sites following manipulation of a solid abdominal tumor. GW-39 human colon cancer cells were injected into the omentum of golden Syrian hamsters. At 2 weeks, an omental tumor was harvested and animals were randomized to bivalve (A), crush (B), strip (C), or excision (D), with or without pneumoperitoneum. Four 5-mm trocars were inserted into the abdomen, and the tumor was reinserted through the midline, swept through four quadrants, and removed. The incision was closed and pneumoperitoneum at 7 mmHg was maintained for 10 min. Tumor implantation at wound sites was documented at 7 weeks. Implantation at trocar sites was 53 and 49% with and without pneumoperitoneum in the manipulated groups (A, B, C), respectively (p = 0.993). Implantation at trocar sites was reduced in the control group (D) at 9 and 10% with and without pneumoperitoneum, respectively (p < 0.001). Tumor implantation at trocar sites is due to spillage of tumor during manipulation and not to pneumoperitoneum.
The Rgg Regulator of Streptococcus pyogenes Influences Utilization of Nonglucose Carbohydrates, Prophage Induction, and Expression of the NAD-Glycohydrolase Virulence Operon

The expression of many virulence-associated genes in Streptococcus pyogenes is controlled in a growth phase-dependent manner. Unlike the model organisms Escherichia coli and Bacillus subtilis, such regulation is apparently not dependent upon alternative sigma factors but appears to rely on complex interactions among several transcriptional regulators, including Rgg. The purpose of this study was to identify changes in gene expression associated with inactivation of the rgg gene in S. pyogenes strain NZ131 (serotype M49). To this end, the transcriptomes of wild-type and rgg mutant strains were analyzed during both the exponential and postexponential phases of growth using Affymetrix NimbleExpress gene chips. Genomewide differences in transcript levels were identified in both phases of growth. Inactivation of rgg disrupted coordinate expression of genes associated with the metabolism of nonglucose carbon sources, such as fructose, mannose, and sucrose. The changes were associated with an inability of the mutant strain to grow using these compounds as the primary carbon source. Bacteriophage transcript levels were also altered in the mutant strain and were associated with decreased induction of at least one prophage. Finally, transcripts encoding virulence factors involved in cytolysin-mediated translocation of NAD-glycohydrolase, including the immunity factor IFS and the cytolysin (streptolysin O [SLO]), were more abundant in the mutant strain, which correlated with the amount of NADase and SLO activities in culture supernatant fluids. The results provide further evidence that Rgg contributes to growth phase-dependent gene regulation in strain NZ131.
WIDESPREAD PHAGOCYTOSIS OF CILIATES AND OTHER PROTISTS BY MARINE MIXOTROPHIC AND HETEROTROPHIC THECATE DINOFLAGELLATES1

An electron microscopic examination of large amorphous inclusions located in a variety of photosynthetic thecate dinoflagellates (Alexandrium ostenfeldii (Paulsen) Balech et Tangen, Gonyaulax diegensis Kofoid, Scrippsiella sp., Ceratium longipes (Bailey) Gran, and Prorocentrum micans Ehrenberg) and a nonphotosynthetic thecate species (Amylax sp.) revealed each inclusion to be a food vacuole, the majority of which were ingested ciliate prey. Recognizable features of these ciliates included linear arrays of basal bodies and cilia consistent with oligotrich polykinetid structure, characteristic macronuclei, chloroplasts (evidently kleptoplastids), cup-shaped starch plates, and cylindrical extrusomes. Three species contained (apparent) nonciliate prey: Scrippsiella sp., whose food vacuoles consistently contained unusual and complex extrusome-like cylindrical bodies having a distinctive six-lobed, multilayered structure; P. micans, which contained an unidentified encysted cell; and a single A. ostenfeldii cell, containing a Dinophysis sp. dinoflagellate cell. Several food vacuoles of ciliate origin had a red hue. This, together with the resemblance of A. ostenfeldii cells to planozygotes, suggests that similar structures previously identified as accumulation bodies may in fact be food vacuoles and that feeding may in some cases be associated with sexual processes.
The left spectrum, the Levitzki radical, and noncommutative schemes.

Abstract This note contains a brief exposition of the basics of a noncommutative version of affine, quasi-affine, and projective algebraic geometry. In this version, to any associative ring (with unity) a quasi-affine (resp. affine) left scheme is assigned. The notion of the left spectrum of a ring plays the key role.
Efficacy of phosphodiesterase type 5 inhibitor treatment in men with erectile dysfunction and dyslipidemia: a post hoc analysis of the vardenafil statin study.

ABSTRACT Introduction Dyslipidemia occurs often in subjects with erectile dysfunction (ED), but there is little information about how this condition affects ED treatment responses. Aim To determine whether low-density lipoprotein cholesterol (LDL-C) levels, total cholesterol (TC)/high-density lipoprotein cholesterol (HDL-C) ratio; or the presence of metabolic syndrome influenced efficacy of vardenafil in men with ED and dyslipidemia. Methods Post hoc subgroup analysis of a 12-week study of the influence of lipid levels and presence of metabolic syndrome on the efficacy of vardenafil as measured by International Index of Erectile Function-Erectile Function (IIEF-EF) domain score, responses to Sexual Encounter Profile (SEP) SEP2 and SEP3 questions, duration of erection leading to successful intercourse, and erection duration regardless of the answer to SEP3. Lipid values were obtained at study start, after patients had received at least 3 months of therapy with a statin. Main Outcome Measures Outcomes in subjects with LDL-C Results Vardenafil improved all endpoints evaluated compared with placebo in all subgroups, however, nominally significant treatment by subgroup interaction terms did not follow a distinct pattern. Increasing LDL-C ( P = 0.033), but not TC/HDL-C ratio or metabolic syndrome, was associated with an increase in treatment response measured by the IIEF-EF domain score. Responses to SEP3 were nominally influenced by LDL-C levels ( P = 0.019), but were not significantly influenced by TC/HDL-C ratio, or the metabolic syndrome. Only higher TC/HDL-C ratios (≥3.5) were associated with larger treatment differences in duration of erection leading to successful intercourse ( P =0.028). Conclusions Vardenafil was effective in men with dyslipidemia regardless of LDL-C levels, TC/HDL-C ratio, and/or presence of metabolic syndrome. Despite the known presence of ED and dyslipidemia, other cardiovascular risk factors were apparently not aggressively managed. Miner MM, Barnes A, and Janning S. Efficacy of phosphodiesterase type 5 inhibitor treatment in men with erectile dysfunction and dyslipidemia: A post hoc analysis of the vardenafil statin study.
An analysis of learning data which distinguishes between initial preference and learning ability

Several sets of learning data furnished by I. Krechevsky have been analyzed in terms of meaningful parameters of the learning curve, and the changes in the frequency distributions of these parameters with changes in the experimental conditions have been studied. One of the parameters represents the animal's initial preference for the light or dark, the other represents learning ability. The analysis shows that destruction of about ten or fifteen per cent. of the cortex, increases the animal's preference for the light and decreases the learning ability slightly. By ordinary methods of analysis, it is not possible to discover thatboth initial preference and learning ability have been changed by any given factor.
Assessing Parent-Child Relationship Disorders in Clinical Practice: The Child's Point of View

This paper presents two short-form scales that measure the degree or magnitude of problems children have in their relationships with their parents. The scales were designed for use in research and in clinical settings to monitor and evaluate the client's response to treatment through repeated administrations. Both-scales have a reliability in excess of .90 as well as good discriminant and construct validity, and both have been used in clinical practice where they were found to be important adjuncts to the conduct and the evaluation of treatment.
Mortality in Schizophrenia—The Iowa Record-Linkage Study: A Comparison with General Population Mortality

Mortality data from 0- to 10-year follow-up of 688 schizophrenic patients were obtained through a record-linkage process and compared with that of the general population of the State of Iowa. Results show that the risk for mortality was most pronounced during the first two years following hospital discharge and among men and women younger than 40 years of age, although women continued to show excess risk after age 40 as well. Deaths occurring from cancer, heart disease, other natural causes, and accidents were not excessive, but mortality from suicide was significantly excessive for both men and women. Total mortality for schizophrenic patients was > 2.5 times expectation (standardized mortality ratio = 2.53, χ 2 = 25.00, p
The Value of Relationship Strength in Segmenting Casino Patrons

AbstractIncreased competition in the gaming industry has resulted in the need for casinos to identify consumer segments that will be most receptive to their communications. In the past, casinos have traditionally used behavioral variables (i.e., frequency of visits, amount of money wagered, etc.) to segment and target customers. However, recent work in segmentation advocates the value of also segmenting customers based on attitudinal variables (i.e., commitment, affect, etc.). The purpose of this study was to explore attitudinal measures of relationship strength to segment casino patrons. Based on a qualitative research design, we used indicators of relationship strength to identify four potential and unique segments. Strategic implications for both online and brick-and-mortar casino marketers are proposed for each segment.
Immunolocalization of a 25-kilodalton protein in mouse testis and epididymis.

We have recently observed that a polyclonal antibody raised against a mouse epididymal luminal fluid protein (MEP 9) recognizes a 25-kDa antigen in mouse testis and epididymis [Rankin et al., Biol Reprod 1992; 46:747-766]. This antigen was localized by light and electron microscopic immunohistochemistry. The immunoreactivity in the testis was found in the residual cytoplasm of the elongated spermatids, in the residual bodies, and in the cytoplasmic droplets of spermatozoa. In the epididymis, the epithelial principal cells were stained from the distal caput to the distal cauda. Immunogold labeling in the principal cells showed diffuse distribution without preferential accumulation in either the endocytic or the secretory apparatus of the cells. In the epididymal lumen, the immunoreactivity was restricted to the sperm cytoplasmic droplets. No membrane-specific labeling was observed in luminal spermatozoa, cytoplasmic droplets, or isolated sperm plasma membranes. Three weeks after hemicastration or severance of the efferent ducts, a normal distribution of the immunoreactive sites was found in the epididymis. Immunoreactivity. was also detected in the epididymal epithelium of immature mice as well as in that of XXSxr male mice having no spermatozoa in the epididymis. These results suggest that the inununoreactivity seen in the principal cells originates from synthesis rather than endocytosis of the testicular protein from disrupted cytoplasmic droplets. Furthermore, these results suggest that the 25-kDa protein is synthesized independently by both testis and epididymis.
Effect of Obesity on Clinical and Radiographic Outcomes Following Reconstruction of Stage II Adult Acquired Flatfoot Deformity

Background:Obesity is a known risk factor for the development of adult acquired flatfoot deformity (AAFD), but obesity’s effects on outcomes following AAFD reconstruction are unknown. We hypothesiz...
The Role and Types of Job Search Strategies as Career Growth Tool for Mid-Career Professionals:

This study examines whether and how job search strategies mediate the relationship between core self-evaluations (CSE) and career growth for mid-career professionals. Using a path analysis approach to analyze a national sample of mid-career professionals (N = 269), results revealed that CSE was positively related to the direct job search strategy (i.e., contacting employers directly) and negatively to the networking job search strategy (i.e., contacting friends/relatives). Interestingly, the direct job search strategy was positively related to both a recent promotion and salary increase (i.e., objective career growth), while the networking job search strategy was positively related to increased job satisfaction (i.e., subjective career growth). Findings also indicated that CSE was positively related to salary increase and a recent promotion. These findings suggest that job search strategies are one mechanism through which individual differences, such as CSE, can influence mid-career professionals’ career ...
Detecting Alien Genes in Bacterial Genomesa

: We present new methods for calculating codon bias of a group of genes or an individual gene relative to a standard gene class. This method is suitable for identifying alien (e.g., horizontally transferred) and highly expressed genes. In yeast and several bacterial genomes, highly expressed genes typically include ribosomal protein genes, elongation factors, chaperonins (heat shock proteins), and a subset of genes involved in glycolysis generally essential in exponential growth. Highly expressed genes of the Synechocystis genome feature several photosystem II genes, and highly expressed genes in several methanogens (Methanococcus jannaschii, M. thermoautotrophicum) are essential for methanogenesis. Alien genes mostly consist of ORFs of unknown function, transposases, prophage genes, and restriction/modification enzymes. Notably, nuclear ribosomal proteins of yeast are highly expressed, whereas mitochondrial ribosomal protein genes appear to be alien genes. Alien genes often occur in clusters, suggesting in these cases that transfer events entail several genes.
Numerical study of light scattering by a boundary-layer flow

Temperature inhomogeneities in free, isotropic turbulence have the effect of scattering light in near-forward angles. We investigate numerically modifications of free turbulence by a rigid wall and its effect on the propagation of light through turbulence. The wall is a 5 cm optical window placed at the leading edge of an instrument towed with speeds of 0.1 and 1 m/s in free turbulence. The turbulent flow field presents inhomogeneities of an embedded passive scalar (Pr = 7, temperature in water), which are modified by the boundary layer developing on the window. We find that the developing laminar boundary layer has a negligible effect on light scattering for the investigated geometry when considered in terms of the volume-scattering function (differential cross section). This indicates that the boundary layer is not an obstacle for optical measurements of turbulence.
Uptake of modified low-density lipoproteins alters actin distribution and locomotor forces in macrophages

It is postulated that macrophage-derived foam cells accumulate in the arterial wall because they lose the ability to migrate after excessive ingestion of modified forms of low-density lipoproteins (LDL). To assess changes in locomotor force generating capacity of foam cells, we measured isometric forces in J774A.1 macrophages after cholesterol loading with oxidized (Ox-LDL) or aggregated (Agg-LDL) LDL using a novel magnetic force transducer. Ox-LDL loading reduced the ability of J774A.1 macrophages to generate isometric forces by 50% relative to control cells. Changes in force frequency consistent with reduced motility were detected as well. Agg-LDL loading was also detrimental to J774A.1 motility but to a lesser extent than Ox-LDL. Ox-LDL loading significantly reduced total actin levels and induced changes in the F-actin to G-actin distribution, whereas Agg-LDL loaded cells had significantly increased levels of total actin. These data provide evidence that cholesterol loading and subsequent accumulation decreases macrophage motility by reducing the cells' force generating capacity and that Ox-LDL appears to be more effective than Agg-LDL in disrupting the locomotor machinery.
Adjuvant radiation therapy for early stage seminoma: Proton versus photon planning comparison and modeling of second cancer risk

Abstract Purpose Given concerns of excess malignancies following adjuvant radiation for seminoma, we evaluated photon and proton beam therapy (PBT) treatment plans to assess dose distributions to organs at risk and model rates of second cancers. Materials and methods Ten stage I seminoma patients who were treated with conventional para-aortic AP–PA photon radiation to 25.5Gy at Massachusetts General Hospital had PBT plans generated (AP–PA, PA alone). Dose differences to critical organs were examined. Risks of second primary malignancies were calculated. Results PBT plans were superior to photons in limiting dose to organs at risk. PBT decreased dose by 46% (8.2Gy) and 64% (10.2Gy) to the stomach and large bowel, respectively ( p p Conclusions In this study, the use of protons provided a favorable dose distribution with an ability to limit unnecessary exposure to critical normal structures in the treatment of early-stage seminoma. It is expected that this will translate into decreased acute toxicity and reduced risk of second cancers, for which prospective studies are warranted.
Imperfect Credit Markets, Household Wealth Distribution, and Development

This article discusses some key results in the theoretical literature on credit market imperfections, household wealth distribution, and development by conducting three types of analysis, which progressively build on one another. The first, a single dynasty model, explains how a household may be caught in a poverty trap because of credit market imperfections but says little about the effects of distribution on development. The second, a model of interacting dynasties with a fixed threshold, explains a collective poverty trap, with path dependence in the wealth distribution dynamics, but says little about the effects of inequality on development, owing to its absolute notion of the rich and the poor. The third, models of interacting dynasties with variable thresholds, offers a richer framework for understanding the dynamics of inequality and development under credit market imperfections, owing to its relative notion of the rich and poor.
Pyoderma gangrenosum: A case report of bilateral dorsal hand lesions and literature review of management:

Pyoderma gangrenosum is a great masquerader in wound diagnosis and management. Frequently misdiagnosed as a necrotizing infection, the elusive nature of its etiology and pathogenesis has thwarted the establishment of a standardized management algorithm, leaving immunosuppressant therapies as the mainstay of treatment. The present report describes a 61-year-old woman presenting with temporally discrete bilateral dorsal hand lesions successfully managed with distinctive multimodality therapies. The initial lesion was managed under the auspices of a necrotizing process using a combination of hyperbaric oxygen therapy and skin grafting with a negative-pressure dressing, both individually demonstrated to be effective for prompt wound stabilization and coverage. A subsequent contralateral hand lesion was similarly managed as a necrotizing infection before a diagnosis of pyoderma gangrenosum was considered. Stabilization and eventual resolution was achieved using intravenous and topical steroids followed by hyperbaric oxygen therapy, again highlighting the benefits of multimodality therapy in the setting of pyoderma gangrenosum.
Soft-tissue injury by mercury from a broken thermometer. A case report and review of the literature.

A case of soft-tissue injury to the hand resulting from an accident with a mercury thermometer in which there was no serious untoward effect other than a local fibrous and lymphoreticular reaction is described. Other instances of similar soft-tissue injuries from the literature, illustrating the unpredictable and sometimes fatal consequences of such accidents, are reviewed. Injuries with metallic mercury through iatrogenic means, or by self-administration into arteries, veins, and gastrointestinal tract, are also mentioned.
Glucose transport by isolated plasma membranes of the bovine blood-brain barrier.

Luminal and abluminal endothelial plasma membrane vesicles were isolated from bovine cerebral microvessels, the site of the blood-brain barrier. Glucose transport across each membrane was measured ...
EXPERIMENTAL STUDIES OF THE EVOLUTIONARY SIGNIFICANCE OF SEXUAL REPRODUCTION. IV. EFFECT OF NEIGHBOR RELATEDNESS AND APHID INFESTATION ON SEEDLING PERFORMANCE.

To investigate the effect of neighbor relatedness in seedling populations, propagules of six Anthoxanthum odoratum parents, produced from a reciprocal diallel cross, were planted into the parental source population, a mown field. The propagules were either surrounded by four unrelated neighbors in a 1 cm square, four sibling neighbors, or no neighbors. About 45% of the emerging seedlings were attacked by aphids (Schizaphis graminum). Aphid infestation significantly reduced seedling survivorship and did not differ with parental genotype or neighbor relatedness; plants without neighbors had a slightly higher infestation risk. Plants without neighbors had lower survivorship than those surrounded by unrelated neighbors although this difference was only significant for plants infested by aphids. When infested by aphids, plants surrounded by siblings had lower survivorship than plants surrounded by non-relatives, suggesting the operation of minority advantage. These results are consistent with the frequency-dependent selection hypothesis for the evolution and maintenance of sexual reproduction.
Flux-Assisted Preparation of Powdered Bismuth Superconductors

Results are presented on efforts to prepare both the 80K, Bi2CaSr2Cu2Oz (2122), and 11 OK, (Bi,Pb)2Ca2Sr2Cu3Oz (2223), transition temperature bismuth superconducting species in either phase pure or nearly phase pure, powdered form using either equimolar NaCI-KCI or NaBiOz as molten fluxes. Data are presented on the effects of variation of the reaction temperature and duration, solvent content, relative CaO and CuO contents, and of post-synthesis anneals of the product materials.
The Endorsement Effect: An Examination of Statewide Political Endorsements in the 2008 Democratic Caucus and Primary Season:

Presidential candidates often pursue the endorsements of elected officials hoping to boost the candidate’s chances of electoral success. But do these endorsements really enhance electoral outcomes? This study pays special attention to endorsements by sitting U.S. senators, U.S. House members, and governors in the 2008 Democratic presidential nominating season. Evidence is found of a statistically significant relationship between endorsements and the state-level vote share. Other significant variables include momentum, a state’s racial and elderly composition, the type of selection process, and the number of campaign events each candidate held in the state.
Control Oriented Modeling of 6-DOF Hypersonic Vehicle Dynamics

The derivation of a control-design model (CDM) of the 6-DOF rigid body dynamics of a hypersonic vehicle is presented in this paper. The development of the CDM is based on curve t approximation of the forces and moments on the vehicle, making the model suitable for control design. In order to have an implementable curve t algorithm, the forces and moments have been divided into their
Do African-American men need separate prostate cancer screening guidelines?

In 2012, the United States Preventative Services Task Force issued new guidelines recommending that male U.S. residents, irrespective of race, no longer be screened for prostate cancer. In African American men, the incidence of prostate cancer is almost 60 % higher and the mortality rate is two to three times greater than in Caucasians. The purpose of this study is to reduce African American men's prostate cancer burden by demonstrating they need separate screening guidelines. We performed a PubMed search using the keywords: African American, Prostate cancer, Outcomes, Molecular markers, Prostate-specific Antigen velocity, PSA density, and to derive data relevant to our hypothesis. In our literature review, we identified several aspects of prostate cancer that are different in Caucasian and African American men. These included prostate cancer incidence and outcome, the clinical course of the disease, serum PSA levels, genetic differences, and social barriers. It's also important to note that the USPSTF guidelines were based on two studies, one of which reported that only 4 % of its participants were African American. The other did not report demographic information, but used participants from seven European countries with small African American populations. Given the above, we conclude that separate prostate cancer screening guidelines are greatly necessary to help save the lives of African Americans.
Teaching to the test: developing an assessment tool for novice echocardiographers.

Focused critical care echocardiography (FCCE) is a powerful tool that allows for the rapid assessment of several important physiologic states quickly, inexpensively, and (seemingly) without risk to the patient. FCCE, performed by non-cardiologists, has gained popularity over the past several decades, and today many residencies and fellowship programs are incorporating some echocardiography into their curriculum. In addition, there are a large number of established physicians who are learning to incorporate FCCE into their practice. Finding ways, therefore, to ensure a minimum standard of operator competence is a crucial step to safeguard quality and patient safety.
Left ventricular function after mitral valve replacement. Comparative studies following resection or preservation of chordae tendineae.

Summary Left ventricular function curves were inscribed and the first derivative of the left ventricular pressure pulse measured at constant heart rate and aortic pressure before and immediately after mitral valve replacement in 20 dogs. In 10 animals the mitral valve and its supporting structures were excised, and in 10 they were preserved. Mitral valve replacement, with or without resection of the chordae tendineae and papillary muscles, had no significant acute effect on left ventricular performance.
A1 segment hypoplasia associated with cerebral infarction after anterior communicating artery aneurysm rupture.

Background Congenital hypoplasia or absence of the A1 segment of the anterior cerebral artery (ACA) has been associated with increased incidence of berry aneurysms at the anterior communicating artery (Acom) complex. It is not known, however, whether this anatomic variant also predisposes patients to complications after aneurysmal subarachnoid hemorrhage. Methods Patients were included for analysis if they presented to our institution for clipping or coiling of an Acom aneurysm between the years of 2001 and 2013. Patients were deemed to have cerebral infarction if a new hypodensity in a vascular distribution was visualized on CT imaging. The association between A1 segmental abnormalities and radiologic infarction was subsequently evaluated in a risk-adjusted manner using stepwise multivariable logistic regression analysis. Results Of 145 patients who presented with aneurysmal subarachnoid hemorrhage after rupture of an Acom aneurysm, 31 (21.4%) had a hypoplastic or absent A1 segment. On univariate analysis, there was a trend toward an increased rate of radiologic infarction in patients with A1 segment abnormalities (OR=2.11, 95% CI: 0.93-4.79; P=0.0757). On multivariable analysis, a hypoplastic or absent A1 segment was significantly associated with an increased rate of radiologic infarction (OR=2.54, 95% CI: 1.02-6.43; P=0.0466). Conclusions Our results suggest that a hypoplastic or absent A1 segment is associated with cerebral infarction following subarachnoid hemorrhage from ruptured Acom aneurysms, indicating a potential need for heightened vigilance and a reduced threshold for therapeutic intervention in patients harboring this abnormality.
Marginal Cost Pricing and Social Investment Criteria for Electricity Undertakings

Marginal cost pricing—which for many years appeared to be something of a theoretician’s toy, with little application to reality—has been the subject of revived interest in recent years, largely as the result of the efforts by Electricite de France to put the precept into practice. In this paper, we will review the basic principles governing the marginal cost pricing of electricity, and shall attempt to elaborate upon them at a few critical points.
Students’ acceptance and readiness for E-learning in Northeastern Thailand

The study explored student readiness for online learning in the Northeast of Thailand, using the Unified Theory of Acceptance and Use of Technology (UTAUT). The survey also explored students’ self-regulation, computing devices ownership, and level of familiarity with education-related technologies. The responses imply that students have a slightly positive perception toward e-learning. They use mobile technologies extensively, and have experience using social media; but are unfamiliar with other collaborative e-learning tools. A discussion includes recommendations for cultural context and the design of e-learning in Thailand.
Differential ability of mutant H-RAS and mutant K-RAS to enhance radiation-induced signaling and cell survival

1297 Previous studies have shown that ionizing radiation causes activation of ERBB1 and downstream signaling pathways in carcinoma cells in two waves: the first wave as an initial response to radiation exposure, the second due to the autocrine actions of TGF alpha. We have examined the impact, in an isogenic background, of mutant active H-RAS and mutant active K-RAS on the expression of autocrine growth factors, ERBB family receptors, radiation-induced activation of downstream signaling pathways and radiation-induced reduction of clonogenic survival. HCT116 cells, wild type and mutant K-RAS deleted, were transfected with vector control and mutant H-RAS plasmids, respectively. Clones were isolated and studied. Deletion of mutant K-RAS enhanced expression of ERBB1 and ERBB3, and expression of mutant H-RAS further enhanced ERBB1 and ERBB3 levels. Deletion of mutant K-RAS abolished expression of epiregulin whereas expression of mutant H-RAS enhanced expression of heregulin without restoring epiregulin expression. The levels of TGF alpha and HB-EGF remained approximately constant. Radiation caused phasic activation of ERK1/2 and AKT in wild type cells that were abolished in mutant K-RAS deleted cells. The introduction of mutant H-RAS into mutant K-RAS deleted cells restored basal and radiation-stimulated ERK1/2 and AKT activation, which in the case of AKT, was greater than that observed in wild type cells expressing mutant K-RAS. Mutant H-RAS cells had a higher plating efficiency and were more radio-resistant than wild type cells. Thus loss of mutant K-RAS expression and introduction of mutant H-RAS promoted increased expression of ERBB3 and its ligand heregulin that correlated with enhanced AKT activation and elevated radio-resistance. Thus mutant RAS isoforms may differentially alter the ability of cells to respond to irradiation by altering the levels of ERBB receptors, their ligands and the activation downstream signaling pathways.
Variable competitive effects of fungicide resistance in field experiments with a plant pathogenic fungus

Classic evolutionary theory suggests that mutations associated with antimicrobial and pesticide resistance result in a fitness cost in the absence of the selective antimicrobial agent or pesticide. There is experimental evidence to support fitness costs associated with resistance to anti-microbial compounds and pesticides across many biological disciplines, including human pathology, entomology, plant sciences, and plant pathology. However, researchers have also found examples of neutral and increased fitness associated with resistance, where the effect of a given resistance mutation depends on environmental and biological factors. We used Zymoseptoria tritici, a model evolutionary plant pathogenic fungus, to compare the competitive ability of fungicide-resistant isolates to fungicide-sensitive isolates. We conducted four large-scale inoculated winter wheat experiments at Oregon State University agriculture experiment stations. We found a significant change in the frequency of fungicide resistance over time in all four experiments. The direction and magnitude of these changes, however, differed by experimental location, year of experiment, and inoculum resistance treatment (fungicide-resistant, resistant/sensitive mixture, and fungicide-sensitive). These results suggest that the competitive ability of resistant isolates relative to sensitive isolates varied depending upon environmental conditions, including the initial frequency of resistant individuals in the population.
Attribution Patterns in Women With and Without Orgasmic Difficulties

People with sexual problems are more likely to attribute negative sexual experiences to themselves, in contrast with sexually functional individuals who attribute negative sexual experiences to external factors such as the circumstance or situation. We investigated attribution patterns in women reporting difficult or absent orgasm—a group only minimally investigated in this regard—to determine whether they differed from women without orgasmic problems. Using an internet-based approach, we compared attribution responses of 376 women with orgasmic difficulty with 367 women without orgasmic difficulty to five sexual scenarios, two presenting positive sexual experiences and three presenting negative sexual experiences. Women with orgasmic difficulty were more likely to take blame for any negative sexual experience, including ones not related to orgasmic difficulty. They were also more likely to attribute responsibility to their partner’s lack of skill, whereas orgasmic women attributed negative outcomes more ...