cssi/SciSciGPT-SciSciNet huggingface dataset:
Increased ghrelin sensitivity and calorie consumption in subordinate monkeys is affected by short-term astressin B administration.

Animals chronically exposed to stressors with access to diets high in fat and sugar consume and prefer these diets, a result consistent with the association between stress and comfort food ingestion in humans. As social subordination in rhesus monkeys provides an ethologically relevant translational model of psychosocial stress, we tested the hypothesis that differences in food intake between dominant and subordinate female monkeys are due to corticotropin-releasing hormone-(CRH) induced alteration in sensitivity to ghrelin, a potent orexigenic signal. We assessed food intake of animals given a choice between a low (LCD) and high calorie diet (HCD) in response to 4-day treatment with the CRH receptor antagonist, astressin B, and to an acute treatment of ghrelin. Ghrelin stimulated intake of LCD in subordinates but did not further increase consumption of HCD, whereas ghrelin decreased LCD consumption without affecting HCD intake in dominant females. Astressin B decreased cortisol levels and increased preference for and intake of the HCD in subordinates and decreased calorie intake and HCD preference in dominant animals. These results suggest that increased caloric intake by subordinates may, in part, be explained by a greater sensitivity to postprandial increases in ghrelin and that CRH receptor antagonism leading to a decrease in cortisol has mixed effects on food choice depending on an individual’s stress background.
Safety and Tolerability of Long-term Propafenone Therapy for Supraventricular Tachyarrhythmias*

An important issue regarding the long-term use of antiarrhythmic drugs concerns the safety of these agents, particularly with regard to cardiac toxicity. Propafenone is an effective drug for preventing supraventricular tachyarrhythmia, but the incidence of side effects during longterm therapy in patients with such arrhythmias has not been adequately reported. A total of 480 patients received oral propafenone as therapy for symptomatic atrial fibrillation, atrial flutter, or supraventricular tachycardia. During the follow-up (mean 14.4 months), 290 patients (60%) discontinued propafenone therapy, but in only 70 patients (15%) was the reason for discontinuation an adverse drug reaction. Overall, 284 patients (59%) experienced at least 1 adverse reaction, and the incidence was related to dose and age >65 years. The overall incidence of side effects was not related to structural heart disease; however, cardiovascular toxicity including arrhythmia aggravation, congestive heart failure, and serious conduction disturbances occurred more often in those with heart disease (20% vs 13%). Sixteen patients died during drug therapy, but in only 1 case was the drug considered contributory. For patients with a supraventricular arrhythmia, propafenone was well tolerated and was infrequently discontinued because of side effects. The incidence of serious cardiac toxicity when propafenone was used to treat supraventricular arrhythmia was low, and these side effects were more frequent in patients with structural heart disease.
Targeting a fixed percentage of granulocyte differentiation using experiments designed via nonlinear model predictive control

Previous efforts to control cellular differentiation have been largely experimental. Although some mathematical models for this process exist, rarely has a quantitative approach been employed to design experiments that predictably direct the cell fate. As an initial step towards this aim, a control strategy for sustaining a desired constant level of differentiated human promyelocytic leukemia (HL60) cells is proposed. Nonlinear model predictive control is applied using a model of HL60 cell differentiation which reflects the dominant observable cell states along the known granulocyte/monocyte differentiation pathway. After implementing changes identified by a preliminary experimental trial, the experimental realization of the controller successfully achieved the target differentiation level and demonstrated the need for a quantitative approach to experiment design.
Glutamine deamidation destabilizes human γD-crystallin and lowers the kinetic barrier to unfolding

Human eye lens transparency requires life long stability and solubility of the crystallin proteins. Aged crystallins have high levels of covalent damage, including glutamine deamidation. Human γD-crystallin (HγD-Crys) is a two-domain β-sheet protein of the lens nucleus. The two domains interact through interdomain side chain contacts, including Gln-54 and Gln-143, which are critical for stability and folding of the N-terminal domain of HγD-Crys. To test the effects of interface deamidation on stability and folding, single and double glutamine to glutamate substitutions were constructed. Equilibrium unfolding/refolding experiments of the proteins were performed in guanidine hydrochloride at pH 7.0, 37 °C, or urea at pH 3.0, 20 °C. Compared with wild type, the deamidation mutants were destabilized at pH 7.0. The proteins populated a partially unfolded intermediate that likely had a structured C-terminal domain and unstructured N-terminal domain. However, at pH 3.0, equilibrium unfolding transitions of wild type and the deamidation mutants were indistinguishable. In contrast, the double alanine mutant Q54A/Q143A was destabilized at both pH 7.0 and 3.0. Thermal stabilities of the deamidation mutants were also reduced at pH 7.0. Similarly, the deamidation mutants lowered the kinetic barrier to unfolding of the N-terminal domain. These data indicate that interface deamidation decreases the thermodynamic stability of HγD-Crys and lowers the kinetic barrier to unfolding due to introduction of a negative charge into the domain interface. Such effects may be significant for cataract formation by inducing protein aggregation or insolubility.
Properties of Selected Poultry Products Treated with a Tenderizing Marinade

Abstract Poultry muscles injected with a tenderizing marinade were evaluated for quality characteristics. Turkey drumsticks, baking hens, and roasters were injected with either 3 or 5% (based upon weight of the meat) of a marinade containing .05% papain. After injection, the meat was allowed to equilibrate for 2 hr at 4 C and then oven baked or cooled in a microwave oven. All meat products injected with papain were significantly more tender (shear press and taste panel) than the controls. Products injected with 5% marinade were more tender than those injected with 3% marinade. Sensory characteristics were unaffected by the papain.
CHEMOTACTIC SIGNALING PATHWAYS IN NEUTROPHILS: FROM RECEPTOR TO ACTIN ASSEMBLY

In this review, we present an overview of the signaling elements between neutrophil chemotactic receptors and the actin cytoskeleton that drives cell motility. From receptor-ligand interactions, activation of heterotrimeric G-proteins, their downstream effectors PLC and PI-3 kinase, the activation of small GTPases of the Rho family, and their regulation of particular cytoskeletal regulatory proteins, we describe pathways specific to the chemotaxing neutrophil and elements documented to be important for neutrophil function.
Increased Fibronectin Expression in Sturge-Weber Syndrome Fibroblasts and Brain Tissue

Sturge-Weber syndrome (SWS) is a neurocutaneous disorder that presents with a facial port-wine stain and a leptomeningeal angioma. Fibronectin expression regulates angiogenesis and vasculogenesis and participates in brain tissue responses to ischemia and seizures. We therefore hypothesized that abnormal gene expression of fibronectin and other extracellular matrix genes would be found in SWS brain tissue and SWS port-wine skin fibroblasts. Fibronectin gene and protein expression from port-wine‐ derived fibroblasts were compared with that from normal skin-derived fibroblasts of four individuals with SWS using microarrays, reverse transcriptase‐ PCR, Western analysis, and immunocytochemistry. Fibronectin gene and/or protein expression from eight SWS surgical brain samples was compared with that in two surgical epilepsy brain samples and six postmortem brain samples using microarrays, reverse transcriptase‐PCR, and Western analysis. The gene expression of fibronectin was significantly increased (p 0.05) in the SWS port-wine‐ derived fibroblasts compared with that of fibroblasts from SWS normal skin. A trend for increased protein levels of fibronectin in port-wine fibroblasts was found by Western analysis. No difference in the pattern of fibronectin staining was detected. The gene expression of fibronectin was significantly increased (p 0.05), and a trend for increased fibronectin protein expression was found in the SWS surgical brain samples compared with the postmortem controls. These results suggest a potential role for fibronectin in the pathogenesis of SWS and in the brain’s response to chronic ischemic injury in SWS. The reproducible differences in fibronectin gene expression between the SWS port-wine‐ derived fibroblasts and the SWS normal skin-derived fibroblasts are consistent with the presence of a hypothesized somatic mutation underlying SWS. (Pediatr Res 53: 762–769, 2003)
Marriage and Bourgeois Respectability

Feminist critics of the institution of marriage point to its tendency to reproduce and solidify a gendered division of labor, norms of dependency and protection, and mandated monogamy. While I support the feminist call for a decoupling of state benefits, such as rights to health care and legal proxy, from the institution of marriage in light of discrimination against same-sex couples who are denied the right to marry, in this essay I draw attention to a separate but related issue. I focus here on what I consider one of the most troubling aspects of marriage for feminists, one highlighted by Simone de Beauvoir in her classic and still timely critique of marriage in The Second Sex (1952): the fact that marriage automatically confers bourgeois respectability on its participants. Even as we oppose antigay marriage legislation and recognize that marriage can protect vulnerable parties by guaranteeing health care, equity upon divorce, tax benefits, and so forth, feminists must continue to refuse the bourgeois respectability that is so deeply linked with the institution of marriage. Having the state accord legitimacy to some kinds of intimate relationships and consensual sex, but not others, goes against basic ideas of feminist freedom articulated most convincingly, I argue, by Beauvoir. While arguing this position, however, I will also ask whether only the relatively privileged are able to refuse the bourgeois respectability that marriage promises.
Receiver designs and channel characterization for multi-spot high-bit-rate wireless infrared communications

This paper addresses one of the most promising candidates for high-speed in-house wireless communications, namely, the multi-spot diffusing configuration (MSDC). Since it uses the optical infrared medium for data transmission, it has the inherent potential for achieving very high capacities. The channel characteristics in MSDC are simulated and the causes for channel distortion are analyzed. Then, conditions for creation of a virtually ideal channel are derived. It is shown that the 3-dB channel bandwidth can be extended up to beyond 2 GHz. This bandwidth comes at the cost of a poor power efficiency. In order to compensate for that, a novel receiver optical front-end design is proposed and its performance is analyzed. Taking advantage of the unique properties of the holographic optical elements, the conventional optical front-end, consisting of a concentrator and a filter, is replaced by a single holographic curved mirror. The utilization of such a holographic optical element improves the signal-to-shot noise ratio by up to 18.5 dB.
Critical competitive strategy issues every entrepreneur should consider before going into business

The topic of formulating and implementing competitive strategy is usually considered from the perspective of a large, well established, and oftentimes multi-divisional corporation. Achieving a sustainable competitive advantage, however, is every bit or even more critical to the survival of smaller startup businesses. Although much research has been performed on how startup companies create value for their constituencies and on how they launch products, few attempts have been made to apply classical large-company strategy ideas to startups. In this paper we consider eleven distinct differences between how large, established firms and their smaller startup counterparts consider strategy initiatives with an eye to guiding entrepreneurs toward higher probabilities of success. The eleven differences are building on market strengths, size of market, relationship to resources, presence of constraints, visibility of and by competitors, investor expectations, shareholder/investor risk tolerance, process, portfolio management, triage, and time horizon for results.
Glucose tolerance and skeletal muscle gene expression in response to alternate day fasting.

Objective: Alternate day fasting may extend lifespan in rodents and is feasible for short periods in nonobese humans. The aim of this study was to examine the effects of 3 weeks of alternate day fasting on glucose tolerance and skeletal muscle expression of genes involved in fatty acid transport/oxidation, mitochondrial biogenesis, and stress response. Research Methods and Procedures: Glucose and insulin responses to a standard meal were tested in nonobese subjects (eight men and eight women; BMI, 20 to 30 kg/m2) at baseline and after 22 days of alternate day fasting (36 hour fast). Muscle biopsies were obtained from a subset of subjects (n = 11) at baseline and on day 21 (12-hour fast). Results: Glucose response to a meal was slightly impaired in women after 3 weeks of treatment (p < 0.01), but insulin response was unchanged. However, men had no change in glucose response and a significant reduction in insulin response (p < 0.03). There were no significant changes in the expression of genes involved in mitochondrial biogenesis or fatty acid transport/oxidation, although a trend toward increased CPT1 expression was observed (p < 0.08). SIRT1 mRNA expression was increased after alternate day fasting (p = 0.01). Discussion: Alternate day fasting may adversely affect glucose tolerance in nonobese women but not in nonobese men. The gene expression results indicate that fatty acid oxidation and mitochondrial biogenesis are unaffected by alternate day fasting. However, the increased expression in SIRT1 suggests that alternate day fasting may improve stress resistance, a commonly observed feature of calorie-restricted rodents.
The C-ND tree: a multidimensional index for hybrid continuous and non-ordered discrete data spaces

Contemporary database applications often perform queries in hybrid data spaces (HDS) where vectors can have a mix of continuous valued and non-ordered discrete valued dimensions. To support efficient query processing for an HDS, a robust indexing method is required. Existing indexing techniques to process queries efficiently either apply to continuous data spaces (e.g., the R-tree) or non-ordered discrete data spaces (e.g., the ND-tree). No techniques directly indexing vectors in HDSs have been reported in the literature. In this paper, we propose a new multidimensional indexing technique, called the C-ND tree, to directly index vectors in an HDS. To build such an index, we first introduce some essential geometric concepts (e.g., hybrid bounding rectangle) in HDSs. The C-ND tree structure and the relevant tree building and query processing algorithms based on these geometric concepts in HDSs are then presented. Strategies have been suggested to make the values in continuous dimensions and non-ordered discrete dimensions comparable and controllable. Novel node splitting heuristics which exploit characteristics of both continuous and discrete dimensions are proposed. Performance of the C-ND tree is compared with that of linear scan, R*-tree and ND-tree using range queries on hybrid data. Experimental results demonstrate that the C-ND tree is quite promising in supporting range queries in HDSs.
Mutations affecting regulation of methionine biosynthetic genes isolated by use of met-lac fusions.

Abstract Fusions of the lac genes to the promoters of four structural genes in the methionine biosynthetic pathway, metA, metB, metE, and metF, were obtained by the use of the Mu d(Ap lac) bacteriophage. The levels of beta-galactosidase in these strains could be derepressed by growth under methionine-limiting conditions. Furthermore, growth in the presence of vitamin B12 repressed the synthesis of beta-galactosidase in strains containing a fusion of lacZ to the metE promoter, phi(metE'-lacZ+). Mutations affecting the regulation of met-lac fusions were generated by the insertion of Tn5. Tn5 insertions were obtained at the known regulatory loci metJ and metK. Interestingly, a significant amount of methionine adenosyltransferase activity remained in the metK mutant despite the fact that the mutation was generated by an insertion. Several Tn5-induced regulatory mutations were isolated by screening for high-level beta-galactosidase expression in a phi(metE'-lacZ+) strain in the presence of vitamin B12. Tn5 insertions mapping at the btuB (B12 uptake), metH (B12 dependent tetrahydropteroylglutamate methyltransferase), and metF (5,10-methylenetetrahydrofolate reductase) loci were obtained. The isolation of the metH mutant was consistent with previous suggestions that the metH gene product is required for the repression of metE by vitamin B12. The metF::Tn5 insertion was of particular interest since it suggested that a functional metf gene product was also needed for repression of metE by vitamin B12.
Disseminating quality improvement: study protocol for a large cluster-randomized trial.

Background: Dissemination is a critical facet of implementing quality improvement in organizations. As a field, addiction treatment has produced effective interventions but disseminated them slowly and reached only a fraction of people needing treatment. This study investigates four methods of disseminating quality improvement (QI) to addiction treatment programs in the U.S. It is, to our knowledge, the largest study of organizational change ever conducted in healthcare. The trial seeks to determine the most cost-effective method of disseminating quality improvement in addiction treatment. Methods: The study is evaluating the costs and effectiveness of different QI approaches by randomizing 201 addiction-treatment programs to four interventions. Each intervention used a web-based learning kit plus monthly phone calls, coaching, face-to-face meetings, or the combination of all three. Effectiveness is defined as reducing waiting time (days between first contact and treatment), increasing program admissions, and increasing continuation in treatment. Opportunity costs will be estimated for the resources associated with providing the services. Outcomes: The study has three primary outcomes: waiting time, annual program admissions, and continuation in treatment. Secondary outcomes include: voluntary employee turnover, treatment completion, and operating margin. We are also seeking to understand the role of mediators, moderators, and other factors related to an organization’s success in making changes. Analysis: We are fitting a mixed-effect regression model to each program’s average monthly waiting time and continuation rates (based on aggregated client records), including terms to isolate state and intervention effects. Admissions to treatment are aggregated to a yearly level to compensate for seasonality. We will order the interventions by cost to compare them pair-wise to the lowest cost intervention (monthly phone calls). All randomized sites with outcome data will be included in the analysis, following the intent-to-treat principle. Organizational covariates in the analysis include program size, management score, and state. Discussion: The study offers seven recommendations for conducting a large-scale cluster-randomized trial: provide valuable services, have aims that are clear and important, seek powerful allies, understand the recruiting challenge, cultivate commitment, address turnover, and encourage rigor and flexibility.
Improved learning of structural support vector machines: training with latent variables and nonlinear kernels

Structured output prediction in machine learning is the study of learning to predict complex objects consisting of many correlated parts, such as sequences, trees, or matchings. The Structural Support Vector Machine (Structural SVM) algorithm is a discriminative method for structured output learning that allows flexible feature construction with robust control for overfitting. It provides state-of-art prediction accuracies for many structured output prediction tasks in natural language processing, computational biology, and information retrieval. This thesis explores improving the learning of structured prediction rules with structural SVMs in two main areas: incorporating latent variables to extend their scope of application and speeding up the training of structural SVMs with nonlinear kernels. In particular, we propose a new formulation of structural SVM, called Latent Structural SVM, that allows the use of latent variables, and an algorithm to solve the associated non-convex optimization problem. We demonstrate the generality of our new algorithm through several structured output prediction problems, showing improved prediction accuracies with new alternative problem formulations using latent variables. In addition to latent variables, the use of nonlinear kernels in structural SVMs can also improve their expressiveness and prediction accuracies. However their high computational costs during training limit their wider application. We explore the use of approximate cutting plane models to speed up the training of structural SVMs with nonlinear kernels. We provide a theoretical analysis of their iteration complexity and their approximation quality. Experimental results show improved accuracy-sparsity tradeoff when compared against several state-of-art approximate algorithm for training kernel SVMs, with our algorithm having the advantage that it is readily applicable to structured output prediction problems.
Laboratory Experimentation with Organizations: A Reappraisal

This article begins with two statements which summarize why laboratory experiments are either sensible or senseless. The author then discusses how the laboratory can be used to think more imaginatively about organizations. He notes that the lab setting allows researchers to make use of experimental simulations that field work does not allow and that researchers can also manipulate their variables in the lab. He addresses researchers that have criticized laboratory research techniques in studying organizations by noting the lack of research on complex organizations and urging work in that field.
In Search of Decay in Verbal Short-Term Memory

Is forgetting in the short term due to decay with the mere passage of time, interference from other memoranda, or both? Past research on short-term memory has revealed some evidence for decay and a plethora of evidence showing that short-term memory is worsened by interference. However, none of these studies has directly contrasted decay and interference in short-term memory in a task that rules out the use of rehearsal processes. In this article the authors present a series of studies using a novel paradigm to address this problem directly, by interrogating the operation of decay and interference in short-term memory without rehearsal confounds. The results of these studies indicate that short-term memories are subject to very small decay effects with the mere passage of time but that interference plays a much larger role in their degradation. The authors discuss the implications of these results for existing models of memory decay and interference.
Automatic alarm correlation for fault identification

In communication networks, a large number of alarms exist to signal any abnormal behavior of the network. As network faults typically result in a number of alarms, correlating these different alarms and identifying their source is a major problem in fault management. The alarm correlation problem is of major practical significance. Alarms that have not been correlated may not only lead to significant misdirected efforts, based on insufficient information, but may cause multiple corrective actions (possibly contradictory) as each alert is handled independently. The paper proposes a general framework to solve the alarm correlation problem. The authors introduce a new model for faults and alarms based on probabilistic finite state machines. They propose two algorithms. The first one acquires the fault models starting from possibly incomplete and incorrect date. The second one correlates alarms in the presence of multiple faults and noisy information. Both algorithms have polynomial time complexity, use an extension of the Viterbi algorithm to deal with the corrupted data, and can be implemented in hardware. As an example, they are applied to analyse faults using data generated by the ANS (Advanced Network and Services, Inc.)/NSF T3 network.
Ubiquinone biosynthesis in microorganisms

The quinoid nucleus of the benzoquinone, ubiquinone (coenzyme Q; Q), is derived from the shikimate pathway in bacteria and eukaryotic microorganisms. Ubiquinone is not considered a vitamin since mammals synthesize it from the essential amino acid tyrosine. Escherichia coli and other Gram-negative bacteria derive the 4-hydroxybenzoate required for the biosynthesis of Q directly from chorismate. The yeast, Saccharomyces cerevisiae, can either form 4-hydroxybenzoate from chorismate or tyrosine. However, unlike mammals, S. cerevisiae synthesizes tyrosine in vivo by the shikimate pathway. While the reactions of the pathway leading from 4-hydroxybenzoate to Q are the same in both organisms the order in which they occur differs. The 4-hydroxybenzoate undergoes a prenylation, a decarboxylation and three hydroxylations alternating with three methylation reactions, resulting in the formation of Q. The methyl groups for the methylation reactions are derived from S-adenosylmethionine. While the prenyl side chain is formed by the 2-C-methyl-D-erythritol 4-phosphate (non-mevalonate) pathway in E. coli, it is formed by the mevalonate pathway in the yeast.
Left atrial appendage fibroelastoma.

A 59-year-old woman suffered sudden left hemiparesis that resolved after several hours. She had a history of hypertension and atrial septal defect repair at the age of 29 but had no history of arrhythmia or other heart disease. Physical examination …
Essentials of Musculoskeletal Imaging

Thomas R. Johnson and Lynne S. Steinbach, editors. Rosemont, Illinois: American Academy of Orthopaedic Surgeons; 2004. 927 pages. $115.00 ($95.00 AAOS member, $85.00 resident). Having hit upon a recipe for success with the initial book in its Essentials series (Essentials of Musculoskeletal Care), the American Academy of Orthopaedic Surgeons has enlisted a superb team of editors from the fields of orthopaedics and radiology to oversee the publication of Essentials of Musculoskeletal Imaging, a comprehensive yet concise reference text. Form follows function in this easy-to-use reference …
Intentional islanding and adaptive load shedding to avoid cascading outages

Predetermined islanding scenarios along with automated load shedding schemes are applied once a prospective cascading outage condition is predicted. If required, additional distributed generation at specified locations in the system is also determined. The choice of different islands along with loads to be shed is then made available to the operator so as to be armed for action in case the system security is compromised. Determination of line outages that lead to disastrous consequences, intentional islanding schemes, and load shedding schemes have been explored individually. A plan integrating these defense mechanisms coupled with the possibility of using distributed generation where and when available is presented via case studies. Results obtained from the application of this technique indicate that it can be a powerful approach for secure operation of power systems.
Metabolism studies with DL-[α-14C]ergothioneine.

The metabolism of DL-[α-14C]ergothioneine (the betaine of thiolhistidine) was studied in the intact rat. The conversion to respiratory CO2 was extremely low (0.14% of dose in 6 h). Labeling of amino acids of liver protein was small (2–6%), of the liver non-protein fraction rather high (17–31%). Of the former, glutamic and aspartic acids, arginine and histidine accounted for almost all the radioactivity, whereas radioactivity of the liver non-protein fraction could be accounted for almost entirely by herzynine (the betaine of histidine). The latter compound also contributed almost one-third of the radioactivity of urine, another third being due to unchanged ergothioneine. The conversion of herzynine to ergothioneine was found to be exceedingly low, as tested by injection of labeled herzynine and isolation of urinary ergothioneine.
Use of Ghrelin and Ghrelin Receptor Agonists in Cancer- and Chemotherapy-Induced Cachexia

The Cancer Anorexia-Cachexia Syndrome (CACS) is present in up to 80% of cancer patients decreasing their quality of life and survival. Nevertheless, treatments for this condition are lacking. Ghrelin and its mimetics appear promising in the treatment of CACS. Ghrelin increases growth hormone/IGF-1 levels, body weight, and appetite, and decreases energy expenditure in healthy subjects. Also, animal and human studies have shown favorable anabolic effects of ghrelin in the setting of cancer. In preliminary studies, anamorelin, an orally available ghrelin mimetic, also seems to improve weight loss in cancer cachexia patients. Furthermore, in animal models of cisplatin-induced cachexia and emesis, ghrelin infusion stabilizes appetite, increases weight, and improves GI side effects. In several short-term studies ghrelin was found to be safe; however, long-term safety of ghrelin and ghrelin mimetics has not yet been fully established. In summary, more studies are needed looking into the long-term safety and efficacy of ghrelin and its mimetics in cancer patients and other chronic diseases associated with cachexia.
Reconstructing edge-disjoint paths faster

For a simple undirected graph with n vertices and m edges, we consider a data structure that given a query of a pair of vertices u , v and an integer k ? 1 , it returns k edge-disjoint u v -paths. The data structure takes O ? ( n 3.375 ) time to build, using O ( m n 1.5 log n ) space, and each query takes O ( k n ) time, which is optimal and beats the previous query time of O ( k n α ( n ) ) .
The role of neuropeptides in immunoregulatory processes

Among the various non-neuronal cell types known to produce and make use of neuropeptides, those of the immune system have received much attention in recent years. Comparative studies in vertebrates and invertebrates have shown that some of these compounds, especially opioid peptides, are engaged in receptor-mediated autoregulating processes of the immune system as well as the exchange of information with the neuroendocrine system. Most of those activities observed are immunostimulatory, as determined by their effects on conformational changes indicative of immunocyte activation, cellular motility, and phagocytosis. In cooperation with cytokines, opiate alkaloids, and certain regulatory enzymes (neutral endopeptidase 24.11), they form an effective network of messenger molecules. The immunostimulatory effects observed in this system are balanced (counteracted) by the primarily inhibitory influence of morphine and related opiates. These signals are mediated by several types of receptors with different degrees of selectivity. Among them the recently identified, opioid insensitive µ3 receptor deserves attention on account of its specificity for opiate alkaloids.
Congenic strains of RCS rats with inherited retinal dystrophy

Two congenic strains of RCS rats, RCS-p/+ and RCS-c, have been developed that differ from the parental strain at genetic loci affecting pigmentation. Inbred RCS rats are pink-eyed, while RCS-p/+ rats produce segregating litters of pink-eyed (p/p) and black-eyed (p/+) offspring, and RCS-c rats are albinos. All the strains are homozygous for the mutant form of the retinal dystrophy gene. The black eye pigment in RCS-p/+ rats slows the progression of the retinal degeneration by about 10 days in the posterior retina and by about 30-35 days in the peripheral retina in the superior half of the eye. No slowing of the disease occurs in the inferior half of the eye along the vertical meridian. All the strains are similar in body weight and litter size, and show a low incidence of cataract and microphthalmia.
Interaction of Mycoplasma gallisepticum with Chicken Tracheal Epithelial Cells Contributes to Macrophage Chemotaxis and Activation

Mycoplasma gallisepticum colonizes the chicken respiratory mucosa and mediates a severe inflammatory response hallmarked by subepithelial leukocyte infiltration. We recently reported that the interaction of M. gallisepticum with chicken tracheal epithelial cells (TECs) mediated the upregulation of chemokine and inflammatory cytokine genes in these cells (S. Majumder, F. Zappulla, and L. K. Silbart, PLoS One 9:e112796, http://dx.doi.org/10.1371/journal.pone.0112796). The current study extends these observations and sheds light on how this initial interaction may give rise to subsequent inflammatory events. Conditioned medium from TECs exposed to the virulent Rlow strain induced macrophage chemotaxis to a much higher degree than the nonvirulent Rhigh strain. Coculture of chicken macrophages (HD-11) with TECs exposed to live mycoplasma revealed the upregulation of several proinflammatory genes associated with macrophage activation, including interleukin-1β (IL-1β), IL-6, IL-8, CCL20, macrophage inflammatory protein 1β (MIP-1β), CXCL-13, and RANTES. The upregulation of these genes was similar to that observed upon direct contact of HD-11 cells with live M. gallisepticum. Coculture of macrophages with Rlow-exposed TECs also resulted in prolonged expression of chemokine genes, such as those encoding CXCL-13, MIP-1β, RANTES, and IL-8. Taken together, these studies support the notion that the initial interaction of M. gallisepticum with host respiratory epithelial cells contributes to macrophage chemotaxis and activation by virtue of robust upregulation of inflammatory cytokine and chemokine genes, thereby setting the stage for chronic tissue inflammation.
An algorithm for frequency-dependent principal component spectral analysis

Summary Principal component analysis (PCA) can be used to generate frequency-dependent spectral attributes for improved delineation and visualization of frequencydependent features. A Varimax (Kaiser, 1958) PCA rotation algorithm relates individual principal components (PCs) to characteristic frequency bands. Synthetic and field data results show that Varimax rotated PC spectral attributes effectively respond to geological variations. For a synthetic wedge model, Varimax rotated PC spectral attributes serve well as a thickness indicator. For a real data case, a karst related sink hole is delineated better using Varimax rotated PC attributes than by conventional spectral decomposition or conventional principal component analysis.
Abstract 1766: Investigating Chk1 biology with selective oral Chk1 inhibitor.

Chk1 inhibitor as a chemo-potentiator in cancer therapy was proposed more than 10 years ago. Most of the first generation i.v. dosing chk1 inhibitors were terminated in clinical trials recently. The second generation oral chk1 inhibitors were just launched by several companies. However, many questions in Chk1 biology remain unclear, which is important to guide Pfizer to develop oral chk1 inhibitor in the future. Chk1 biology team investigated preclinical scheduling, biomarker, combination strategy, TGI, primary indication and patient selection with chk1 tool compounds. Biomarker is critical in evaluating POM in clinical trial phase I. Significant target modulations and dose responses of biomarkers p-Chk1 345, r-H2AX, cleaved-PARP were observed in both in vitro and in vivo studies, suggesting their potential application in clinical setting. The scheduling study indicated its importance in chk1 project. Both administration of chk1 inhibitor soon after chemotherapy and sustained inhibition of chk1 robustly improved efficacy in Miapaca2 pancreatic cancer model. There was no clear patient selection strategy for Chk1 clinical trials in the past. To investigate the primary indication and patient selection, 6 indications were indentified according to clinical trial results and human tumor tissue genomics, more than 100 cancer cell lines were screened with either chk1 inhibitor alone or in combination with SOC. 75%(12/16) cell lines in mesothelioma and 44% (4/9) in endometrial carcinoma demonstrated significant synergy in the combination treatment. Next generation sequencing and SiRNA library screening in DNA damage repair genes (DDR) will be used to clarify the mechanisms. In summary, we have identified treatment schedule and potential new indications for Chk1 inhibitor, which could significantly increase efficacy, lower toxicity, and improve probability of success in clinical trials. Citation Format: Zhenxiong Wang. Investigating Chk1 biology with selective oral Chk1 inhibitor. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1766. doi:10.1158/1538-7445.AM2013-1766
Paleoecological Characteristics of the Carboniferous Phylloid Algal Buildups in Southern Guizhou

The Carboniferous phylloid algal buildups are widespread and well exposed in southern Guizhou. A unique depositional sequence consists of phylloid algal buildups, bioclastic banks and mud facies affected by frequent changes of depositional environments. The phylloid algae that grow on the margin of carbonate platform prefer to live in clean water with medium turbulence. Therefore the phylloid algae must be a narrow spectrum of ecological environment. Adjacent two leaves of phylloid algae rarely are tightly together in the growth-form and the spaces between two leaves are often filled with sparry calcite. It indicates that phylloid algae thallus should be a certain tenacity and intensity. The worm may be taked part in the construction of buildup substrate, and they are the pioneer of phylloid algal buildup.
Do Fools Rush In? The Importance of Transactional Due Diligence in M&A

After signing an acquisition agreement, acquiring firms conduct transactional due diligence to identify potential material adverse events and breaches of target firm representations and warranties. When detected, these outcomes of due diligence provide acquiring firms the contractual right to terminate the transaction or renegotiate a lower purchase price. However, acquirers face pressure to complete M&A transactions quickly and cut the transactional due diligence process short. Based on a survival analysis of terminated and completed M&A transactions, I find that less extensive transactional due diligence is associated with lower post-acquisition profitability, a higher probability of post-acquisition goodwill impairments, and lower quality fair value estimates for the acquired assets and liabilities. These findings highlight transactional due diligence as an important factor explaining cross-sectional variation in post-acquisition performance and financial reporting.
Recent Advances in the Catalytic Synthesis of α-Ketoamides

α-Ketoamides and their derivatives are key constituents of natural products, biologically relevant molecules, drug and drug candidates, and functional materials. Further, they are versatile and valuable intermediates and synthons in a number of functional group transformations and total syntheses. In recent years tremendous growth has been realized in the development of synthetic methods for α-ketoamide preparation and their applications in synthetic and medicinal chemistry. Among the various catalytic methods of α-ketoamide formation, two approaches, namely double aminocarbonylation and oxidative amidation, have received much more attention and have been greatly studied because of the ready availability of the starting materials, use of carbon monoxide (CO) as a direct source of carbonyl functionalities, and use of molecular oxygen (O2) or air as a green terminal oxidant and/or reactants. Catalyzed α-ketoamide formation can be roughly classified into metal- and nonmetal-catalyzed processes. In the contex...
High-power lasers: applications in mesospheric remote sensing and astronomy (R. V. Pole Memorial Plenary Lecture)

For more than 20 years lidar systems have been used to study the chemistry and dynamics of the upper atmosphere above 70 km altitude. A variety of important minor atmospheric constituents have resonance lines in the near IR to near UV region of the optical spectrum which can be probed with exceptional sensitivity and resolution using resonance fluorescence lidar techniques. The most widely studied have been atomic Na, Fe, Li, K, Ca, and Ca+. Sodium is especially important because the fine structure of the D2 resonance line can now be probed with sufficient spectral resolution to deduce temperature and Doppler winds. To be most useful for studies related to global change issues, measurements of these constituents and parameters must be obtained with high resolution and accuracy. Measurement resolution ~100 s and ~100 m and accuracies ~1 K, ~0.5 m/s, and ~1% in density are needed. This performance can be achieved with laser power levels ~10 W, linewidths <100 MHz, and frequency stability better than 1 MHz. In the field of astronomy, sodium lidar techniques are now being developed for creating artificial guide stars in the upper atmosphere that can be used with ground based adaptive telescopes to compensate image distortion caused by atmospheric turbulence. To create a laser guide star that is sufficiently small and bright to adaptively compensate a 2 m class telescope, also requires power levels ~10 W. The required pulse rate is ~100 pps, the pulse length is ~50 microsec, the optium bandwidth is ~600 MHz, and the beam divergence can be no larger than a few microrad. The laser requirements for both of these applications present significant challenges to the laser designer. Some of the current designs and their limitations are discussed.
Are reverse payments and pay-for-delay settlements business as usual or an anticompetitive practice?

Cash payments and other arrangements between patent holders and their competitors in exchange for a delayed market entry interfere with free-market principles and keep product prices at a premium, which affects payers, governments, healthcare providers and especially patients.
Large-Scale and Big Optimization Based on Hadoop

Integer Linear Programming (ILP) is among the most popular optimization techniques found in practical applications, however, it often faces computational issues in modeling real-world problems. Computation can easily outgrow the computing power of standalone computers as the size of problem increases. The modern distributed computing releases the computing power constraints by providing scalable computing resources to match application needs, which boosts large-scale optimization. This chapter presents a paradigm that leverages Hadoop, an open-source distributed computing framework, to solve a large-scale ILP problem that is abstracted from real-world air traffic flow management. The ILP involves millions of decision variables, which is intractable even with existing state-of-the-art optimization software package. Dual decomposition method is used to separate variables into a set of dual subproblems that are smaller ILPs with lower dimensions, the computation complexity is downsized. As a result, the subproblems are solvable with optimization tools. It is shown that the iterative update on Lagrangian multipliers in dual decomposition method can fit into the Hadoop’s MapReduce programming model, which is designed to allocate computations to cluster for parallel processing and collect results from each node to report aggregate results. Thanks to the scalability of the distributed computing, parallelism can be improved by assigning more working nodes to the Hadoop cluster. As a result, the computational efficiency for solving the whole ILP problem is not impacted by the input size.
Library buildings in a digital age, why bother?

L'ere de l'electronique n'a pas fait diminuer la frequentation des bibliotheques. L'auteur cite 10 points a mettre en avant pour defendre les projets de construction ou d'extension des bâtiments de bibliotheques, vis-a-vis de l'administration. Les avantages d'un espace physique d'information comprennent les nouvelles fonctions des bibliotheques, des considerations de cout, les inconvenient du format numerique et le role de l'imagination et du contexte dans le lieu de connaissance que constitue une bibliotheque.
PERSISTENT INFECTIONS OF BUNYAVIRUSES IN AEDES ALBOPICTUS

ABSTRACT Persistent infections have been established in Aedes albopictus cell cultures with Inkoo virus or Uukuneimi virus. Both of these cultures are resistant to homologous infection but are susceptible to heterologous infection. Both persistently infected cell populations show no CPE and are producing low levels of virus or viral particles after more than 20 cell passages. Co-infections of Aedes albopictus cells with standard virus and virus from Inkoo persistently infected cells show a decrease in the initial production of plaque forming units. Similar experiments in BHK (WI-2) cells show no such decrease. RNA purified from either virus particles or infected cell cytoplasms obtained from persistently infected cells reveals several small RNA species not found during infection of vertebrate cells. The possible significance of these findings to the horizontal transmission of arboviruses in nature is discussed.
Economic Burden of Inpatient Admission of Ankle Fractures

Background:Ankle fractures are among the most prevalent traumatic orthopaedic injuries. A large proportion of patients sustaining operative ankle fractures are admitted directly from the emergency ...
An Empirical Study of Related-Party Lending

Related-party transactions, where one of the parties is owned or controlled by the other, are often regarded as a way to tunnel funds out of firms. This paper provides the first empirical evidence on a specific channel through which related-party lending may benefit borrowers, namely its ability to ease financing frictions. Using a hand-collected sample of 294 loans from related parties to U.S. firms, I identify the drivers of related-party lending and investigate its impact on borrowers. I show that related-party lending mitigates adverse selection at times when a firm is more likely to be credit rationed by unrelated parties. The incidence of related-party loans is positively linked to the degree of financing constraints and lack of transparency that aggravates these constraints. I find that interest rates on loans from related parties (management) are 1.9% (2.6%) higher compared to loans from unrelated parties which I attribute to a premium for loss of diversification required by related-party lenders. I also find that informed lending has a strong signalling effect: the likelihood of obtaining additional debt financing increases by 32.8% in the quarter following a related-party loan. Collectively, this evidence suggests that borrowers agree to "invest" in an expensive loan from related parties in order to increase their chances of obtaining debt financing in the future.