cssi/SciSciGPT-SciSciNet huggingface dataset:
Hepatocyte growth factor is a preferred in vitro substrate for human hepsin, a membrane-anchored serine protease implicated in prostate and ovarian cancers

Hepsin is a membrane-anchored, trypsin-like serine protease with prominent expression in the human liver and tumours of the prostate and ovaries. To better understand the biological functions of hepsin, we identified macromolecular substrates employing a tetrapeptide PS-SCL (positional scanning-synthetic combinatorial library) screen that rapidly determines the P1-P4 substrate specificity. Hepsin exhibited strong preference at the P1 position for arginine over lysine, and favoured threonine, leucine or asparagine at the P2, glutamine or lysine at the P3, and proline or lysine at the P4 position. The relative activity of hepsin toward individual AMC (7-amino-4-methylcoumarin)-tetrapeptides was generally consistent with the overall peptide profiling results derived from the PC-SCL screen. The most active tetrapeptide substrate Ac (acetyl)-KQLR-AMC matched with the activation cleavage site of the hepatocyte growth factor precursor sc-HGF (single-chain HGF), KQLR downward arrowVVNG (where downward arrow denotes the cleavage site), as identified by a database analysis of trypsin-like precursors. X-ray crystallographic studies with KQLR chloromethylketone showed that the KQLR peptide fits well into the substrate-binding cleft of hepsin. This hepsin-processed HGF induced c-Met receptor tyrosine phosphorylation in SKOV-3 ovarian cancer cells, indicating that the hepsin-cleaved HGF is biologically active. Activation cleavage site mutants of sc-HGF with predicted non-preferred sequences, DPGR downward arrowVVNG or KQLQ downward arrowVVNG, were not processed, illustrating that the P4-P1 residues can be important determinants for substrate specificity. In addition to finding macromolecular hepsin substrates, the extracellular inhibitors of the HGF activator, HAI-1 and HAI-2, were potent inhibitors of hepsin activity (IC50 4+/-0.2 nM and 12+/-0.5 nM respectively). Together, our findings suggest that the HGF precursor is a potential in vivo substrate for hepsin in tumours, where hepsin expression is dysregulated and may influence tumorigenesis through inappropriate activation and/or regulation of HGF receptor (c-Met) functions.
Polymorphism and drug availability. Solubility relationships in the methylprednisolone system

The thermodynamic relationships involving polymorphism and solubility were examined in some detail and applied to experimental results with the methylprednisolone system. The solubilities of the two crystal forms of this steroid were determined in water, decyl alcohol, and dodecyl alcohol at various temperatures. The solubility ratios for the two forms were generally found to be independent of the solvent in accordance with theory. At room temperatures the activity of the more energetic form of the drug was found to be the order of 80% greater than that of the more stable form. The heat, entropy, and temperature of transition were calculated from the data, and the possible molecular factors involved in polymorphism were considered. Further work of exploratory nature involving cloudpoint determinations indicate that much more energetic crystal forms are probable.
Effect of exercise training on the ability of the rat heart to tolerate hydrogen peroxide

Objective: The purpose of this study was to determine whether exercise training could precondition the myocardium against hydrogen peroxide (H2O2)-induced damage. Methods: Male Fischer 344 rats ran on a treadmill for 9 weeks (60 min/day, 22 m/min, 6° grade, 5 days/week). Isolated perfused working hearts from exercise trained (ET, n = 8) and sedentary (SED, n = 10) animals were perfused with 150 μM H2O2. Results: Pre-H2O2 baseline values for cardiac external work (COxSP), coronary flow (CF), and lactate dehydrogenase (LDH) release were similar between groups. At 5 min of H2O2, COxSP was unchanged from baseline but CF was increased 30% in SED and 46% in ET ( P <0.05 vs. SED). COxSP began to decline similarly thereafter in both groups, dropping to 20% of baseline at 20 min. CF in ET remained higher than SED throughout ( P <0.05). LDH leakage remained near baseline during the first 15 min of H2O2 exposure, but was elevated ( P <0.05) 72% in SED and 40% in ET after 20 min, and was 2.2-fold greater in SED than ET ( P <0.05) after 25 min. Heat shock protein 70 was 2.1-fold greater in ET than SED ( P <0.05), but ET did not change catalase and glutathione peroxidase. Conclusions: The results of this study indicate that chronic moderate exercise will enhance coronary flow and attenuate the development of myocardial injury when exposed to H2O2, but will not affect H2O2-induced decrease in pump function.
Protanomaly without darkened red is deuteranopia with rods.

Abstract The Rayleigh match, a color match between a mixture of 545 + 670 nm lights and 589 nm light in modern instruments, is the definitive measurement for the diagnosis of inherited red–green color defects. All trichromats, whether normal or anomalous, have a limited range of 545 + 670 nm mixtures they perceive to match 589 nm: a typical color-normal match range is about 50–55% of 670 nm in the mixture (deutan mode), while deuteranomals have a range that includes mixtures with less 670 nm than normal and protanomals a range that includes mixtures with more 670 nm than normal. Further, the matching luminance of the 589 nm light for deuteranomals is the same as for normals but for protanomals is below normal. An example of an unexpected Rayleigh match, therefore, is a match range above normal (typical of protanomaly) and a normal luminance setting for 589 nm (typical of deuteranomaly), a match called protanomaly “when the red end of the spectrum is not darkened” [Pickford, R.W. (1950). Three pedigrees for color blindness. Nature, 165, 182.]. In this case, Rayleigh matching does not yield a clear diagnosis. Aside from Pickford, we are aware of only one other report of a similar observer [Pokorny, J., & Smith, V. C. (1981). A variant of red–green color defect. Vision Research, 21, 311–317]; this study predated modern genetic techniques that can reveal the cone photopigment(s) in the red–green range. We recently had the opportunity to conduct genetic and psychophysical tests on such an observer. Genetic results predict he is a deuteranope. His Rayleigh match is consistent with L cones and a contribution from rods. Further, with a rod-suppressing background, his Rayleigh match is characteristic of a single L-cone photopigment (deuteranopia).
MRG1, the product of a melanocyte-specific gene related gene, is a cytokine-inducible transcription factor with transformation activity

Identification of cytokine-inducible genes is imperative for determining the mechanisms of cytokine action. A cytokine-inducible gene, mrg1 [melanocyte-specific gene (msg1) related gene], was identified through mRNA differential display of interleukin (IL) 9-stimulated and unstimulated mouse helper T cells. In addition to IL-9, mrg1 can be induced by other cytokines and biological stimuli, including IL-1α, -2, -4, -6, and -11, granulocyte/macrophage colony-stimulating factor, interferon γ, platelet-derived growth factor, insulin, serum, and lipopolysaccharide in diverse cell types. The induction of mrg1 by these stimuli appears to be transient, with induction kinetics similar to other primary response genes, implicating its role in diverse biological processes. Deletion or point mutations of either the Box1 motif (binds Janus kinase 1) or the signal transducer and activator of transcription 3 binding site-containing region within the intracellular domain of the IL-9 receptor ligand binding subunit abolished or greatly reduced mrg1 induction by IL-9, suggesting that the Janus kinase/signal transducer and activator of transcription signaling pathway is required for mrg1 induction, at least in response to IL-9. Transfection of mrg1 cDNA into TS1, an IL-9-dependent mouse T cell line, converted these cells to IL-9-independent growth through a nonautocrine mechanism. Overexpression of mrg1 in Rat1 cells resulted in loss of cell contact inhibition, anchorage-independent growth in soft agar, and tumor formation in nude mice, demonstrating that mrg1 is a transforming gene. MRG1 is a transcriptional activator and may represent a founding member of an additional family of transcription factors.
Responses of resident male Dendrobates pumilio to territory intruders

Male Dendrobates pumilio are territorial, and vocalize in the presence of intruders. Territory displays are energetically expensive, and residents should modify display behavior according to costs and benefits associated with social contexts of intrusions by conspecifics. Activity censuses found no significant difference in the proportions of male and female D. pumilio found at various times of day, but a higher proportion of animals that were active at 0730 were male. Resident males exhibited a significantly greater mean call group duration when faced with male intruders in the morning than in the afternoon but did not respond differently to male or female intruders. This may reflect greater potential benefits of repelling territorial intruders in the morning than in the afternoon and use of the same territorial displays to defend territory boundaries as well as to attract potential mates. No significant differences were found in responses of resident males to familiar and unfamiliar conspecifics, which suggests that both neighbors and strangers may compete with residents for territory and mates.
Statistical implications of pooling RNA samples for microarray experiments

Microarray technology has become a very important tool for studying gene expression profiles under various conditions. Biologists often pool RNA samples extracted from different subjects onto a single microarray chip to help defray the cost of microarray experiments as well as to correct for the technical difficulty in getting sufficient RNA from a single subject. However, the statistical, technical and financial implications of pooling have not been explicitly investigated. Modeling the resulting gene expression from sample pooling as a mixture of individual responses, we derived expressions for the experimental error and provided both upper and lower bounds for its value in terms of the variability among individuals and the number of RNA samples pooled. Using "virtual" pooling of data from real experiments and computer simulations, we investigated the statistical properties of RNA sample pooling. Our study reveals that pooling biological samples appropriately is statistically valid and efficient for microarray experiments. Furthermore, optimal pooling design(s) can be found to meet statistical requirements while minimizing total cost. Appropriate RNA pooling can provide equivalent power and improve efficiency and cost-effectiveness for microarray experiments with a modest increase in total number of subjects. Pooling schemes in terms of replicates of subjects and arrays can be compared before experiments are conducted.
Functional magnetic resonance imaging of symptom provocation in obsessive-compulsive disorder.

Background: The new technique of functional magnetic resonance imaging was used to investigate the mediating neuroanatomy of obsessive-compulsive disorder symptoms. Methods: Ten patients with obsessive-compulsive disorder and 5 normal subjects were studied via functional magnetic resonance imaging during control and provoked conditions. Data analysis entailed parametric and nonparametric statistical mapping. Results: Statistical maps (nonparametric;P Conclusions: Results of functional magnetic resonance imaging were consistent with past studies of obsessive-compulsive disorder that used other functional neuroimaging modalities. However, paralimbic and limbic activations were more prominent in the present study.
Natural Capital and Labor Allocation: Mangrove-Dependent Households in Thailand

Many poor rural households exploit natural resources, and losses in natural capital may affect their participation in outside employment. The analysis of this article confirms that both mangrove area and the type of mangrove-dependent activity pursued by coastal households in Thailand have significant influences on the participation decision of adult males and females, the wages that they receive for outside employment, and the number of hours worked. Controlling mangrove deforestation could reduce the negative impacts on household labor allocation, but it will require a new institutional framework for coastal mangrove management inducing cooperation between government and coastal households. Investments in female education and training could improve their outside employment prospects and wage rates.
A matched filter network for estimating pulse arrival times

Pulse arrival times are often close to the arrival times of pulses at nearby positions. A method that estimates arrival times from a series of closely related receptions has been developed. It combines the matched filter with the minimum path algorithm of network programming. In an environment where noise is present, the arrival time estimates using traditional matched filter processing degrade, owing to arrival time jumps equal to a period of the carrier. Results obtained from experimental and simulated pulses demonstrate that the method removes the jumps while retaining smaller-scale arrival time fluctuations that are of interest. >
The U.S. Decennial Census: Politics and Political Science

Political scientists make heavy use of census statistics but have given scant attention to the politics behind the production of those statistics. Key issues that merit analytic attention by political science include vote dilution, the policy of population growth and composition, distributional accuracy and census undercounts, the establishment of statistical races, the color-blind challenge to the ethnoracial classification, the political independence of federal statistics, the important distinction between the scientific production and the political use of the census and other statistical products, public concern about government intrusiveness, and the shift from survey and census data to administrative and digital data.
The Secularisation of Religious Symbolism: The Irish Case

There exists a rich sociological literature dealing with secularisation. Such nineteenth‐century sociologists as Weber and Durkheim and twentieth‐century sociologists as Greeley, Bellah, Berger and Wilson have contributed. Berger refers to secularisation as “the process by which sectors of society and culture are removed from the domination of religious institutions and symbols”, while Wilson defines it as “the process whereby religious thinking, practices and institutions lose social significance”. These definitions represent the thrust of academic thinking about secularisation. Generally, social scientists interpret secularisation as the decline of religiosity — a movement from faith to reason. They cite numerous indicators of the change: decline in such areas as church attendance, praying, use of religious rites and rituals, recruitment to the church bureaucracy, church construction. Often they suggest a kind of inevitability relating to urbanisation and industrialisation. The focus of the process involves man becoming less concerned with the spiritual and more concerned with the mundane. Eventually, the spiritual becomes irrelevant; the Age of Enlightenment triumphs over the Age of Faith.
Children with disturbances in sensory processing: a pilot study examining the role of the parasympathetic nervous system.

This study was a preliminary investigation of parasympathetic nervous system (PNS) functioning in children with disturbances in sensory processing. The specific aims of this study were to (1) provide preliminary data about group differences in parasympathetic functions, as measured by the vagal tone index, between children with disturbances in sensory processing and those without; (2) determine effect size and power needed for future studies; and (3) to lay the foundation for further examination of the relations of parasympathetic functioning and functional behavior in children with disturbances in sensory processing. Participants were 15 children, nine with disturbances in sensory processing and six typically developing children. Heart period data were continuously collected for a 2-minute baseline and during administration of the 15-minute Sensory Challenge Protocol, a unique laboratory protocol designed to measure sensory reactivity (Miller, Reisman, McIntosh, & Simon, 2001). Groups were compared on vagal tone index, heart period, and heart rate using two-tailed, independent sample t tests. Children with disturbances in sensory processing had significantly lower vagal tone than the typically developing sample (t(13) = 2.4, p = .05). Statistical power analysis indicated that, for future studies, a sample size of 20 in each group would yield adequate statistical power. Although the number of subjects in this pilot study is small, the results from this study support further investigations of parasympathetic functions and functional behavior in children with disturbances in sensory processing.
Symbolic convergence and abolitionism: A terministic reinterpretation

In The Force of Fantasy, Ernest Bormann creates a misleading dichotomy between evangelical, conversionary abolitionists and secular, radical abolitionists. By relying on superseded historical interpretation, he has constructed a narrative based on this dichotomy which leads to confusion about the origins and dynamics of abolitionist rhetoric. This essay seeks to amend Bormann's narrative by employing terministic analysis to trace the development of radical abolitionism to its origins in evangelical religion. Such analysis can enrich our understanding of abolitionist rhetoric and point to new directions for research in rhetorical movement studies.
Tumor Induced Angiogenesis: Effect of Platelet Derived Growth Factor (PDGF), Pentoxifylline, Sodium Diethyldithiocarbamate, Epsilon Amino Caproic Acid and Tranexamic Acid

Most solid malignant tumors induce the formation of new blood vessels from the host into the tumor. Without this effect, most tumors are unable to propagate. This effect appears to be induced by tumor produced angiogenesis factors (Folkman et. al., 1971, 1974, 1974a, 1975; Brem et. al., 1975, 1976; Greenblatt et. al., 1968; Gullino, 1978, 1981; Langer et. al., 1976, 1981; Giambrone et. al., 1973; Eisenstein et. al., 1973). The extensive literature on angiogenesis has recently been reviewed by Klinworth (1991) and Rifkin and Klagsbrun (1987).
CCP Estimation of Dynamic Discrete/Continuous Choice Models with Generalized Finite Dependence and Correlated Unobserved Heterogeneity

This paper investigates conditional choice probability es timation of dynamic structural discrete and continuous choice models. I extend the concept of finite dependence in a way that accommodates non-stationary, irreducible transition probabilities. I show that under this new definition of finite dependence, one-peri od dependence is obtainable in any dynamic structural model. This finite dependence prop erty also provides a convenient and computationally cheap representation of the optimality conditions for the continuous choice variables. I allow for a general form of discrete-valued unobserved heterogeneity in utilities, transition probabilities, an d production functions. The unobserved heterogeneity may be correlated with the observable state variables. I show the estimator is root-n‐asymptotically normal. I develop a new and computationally cheap algorithm to compute the estimator. I apply our method to estimate a model of education and labor supply choices to investigate properties of t he distribution of returns to education, using data from the National Longitudinal Survey of Youth 1979.
CS1: where is visual basic?

This paper attempts to study the dichotomy that exists between the acceptance of Visual Basic in the programming community and rejection of Visual Basic in the academic community. The study looks at the position of Visual Basic the academic and business communities and looks at the factors leading to the reluctance of academia to accept Visual Basic as a viable language for CS1 and CS2 classes and gives arguments as to why it should be considered.
Comparing and decomposing the determinants of multiple health outcomes in southern and northeastern US states using county data

Objectives To investigate whether regional health disparities could explain health outcome differences between US regions. Methods The 2010–2012 County Level Raking database, which contains measures on health outcomes and factors for the US states, are used in this study. First, a regional comparison of the determinants of various health outcome measures (premature death rates, low birth weight rate and mean unhealthy days) is undertaken. Next, using the Blinder–Oaxaca decomposition method, the differences in health outcomes are partitioned into the portion explained by regional health factor endowments and the portion unexplained. Key findings Obesity rate and access to care determinants impact strongly each region's health outcomes. Half of the differences in clinically assessed (premature death rates and low birth weight rates) measures are unexplained by health endowments. The explained portion for the self-assessed (unhealthy days) outcomes is small. Conclusions Study findings both justify the imperatives of accounting for regional variations in order to strengthen policy inferences of research findings and suggest the prevalence of regional disparities in health outcomes. It is important to focus on region-specific preventive care. More effective public education and information strategies raising population awareness to the health hazards of obesity are in order. Greater access to various health services personnel should be provided to the relevant population. Implications are discussed for pharmaceutical care.
Early ambulation after the surgical treatment of idiopathic scoliosis.

From January 1968 through June 1970, 106 consecutive patients in the age range from twelve to twenty years had surgical treatment of their idiopathic scoliosis under the same management regimen. This consisted of careful articular-process fusion, usually in a preoperative cast, combined with Harrington instrumentation and addition of autogenous iliac-crest bone graft; careful application of a modified Risser-Cotrel cast and ambulation on an average of ten days following surgery; cast change at four to five months, and then removal of all support at an average of nine months following surgery. Follow-up averaged nineteen months. Correction obtained on the day of surgery compared with final correction standing out of plaster revealed an average loss of only 5 degrees. The pseudarthrosis rate was 4.7 per cent.
Trend of monthly temperature and daily extreme temperature during 1951–2012 in New Zealand

Among several variables affecting climate change and climate variability, temperature plays a crucial role in the process because its variations in monthly and extreme values can impact on the global hydrologic cycle and energy balance through thermal forcing. In this study, an analysis of temperature data has been performed over 22 series observed in New Zealand. In particular, to detect possible trends in the time series, the Mann-Kendall non-parametric test was first applied at monthly scale and then to several indices of extreme daily temperatures computed since 1951. The results showed a positive trend in both the maximum and the minimum temperatures, in particular, in the autumn-winter period. This increase has been evaluated faster in maximum temperature than in minimum one. The trend analysis of the temperature indices suggests that there has been an increase in the frequency and intensity of hot extremes, while most of the cold extremes showed a downward tendency.
Deterritorializing Utopia: The Possibility of Techno-Utopias in Societies of Control

The literature on technology, both broadly and in public administration, crafts its visions of utopia out of modern assumptions of the Enlightenment. The move into postmodernity has resulted in the emergence of conditions under which the deployment of technology results in paradoxes that simultaneously increase and reduce freedom. The use of technology, whether to improve centralized coordination and create efficient systems free of human messiness or to mitigate probabilistic risk in complex systems, both controls and frees those within the system. A Deleuzian notion of technology, informed by Foucault’s ideas of heterotopias and care of the self, both describes this emerging structure of control and opens up the possibility of a deployment of technology that opens space for action that fits the anti-essentialist aspects of pragmatism and extends the progressive possibilities of democratic practice.
Some questions on the nature and function of cranial and caudal neurosecretory systems in non-mammalian vertebrates.

Publisher Summary There are two separable cranial (hypothalamic) neurosecretory systems in vertebrates: one originating in the preoptic (and homologous) nuclei and the other in the lateral tuberal nuclei. However, in teleosts, the median eminence is at most residual and there is a specialized system of neurosecretory innervation of adenohypophysial cells. Innervation of the adenohypophysis, especially of the pars intermedia, occurs in other vertebrates as well. Some hypophysiotropic control systems differ among the several vertebrate groups. Nothing definitive is known about the chemistry of nonmammalian hypophysiotropins. A caudal neurosecretory system is probably present in all fish groups except cyclostomes and lungfishes, although the urophysis is characteristic only of teleosts. The function of this system is still unknown, but principles with smooth muscle contracting, hypotensive, and hydrosmotic effects are located in and released from the urophysis. The hydrosmotic effect is probably due to arginine vasotocin; the other factors, although peptidic, are not related to neurohypophysial octapeptides. Proteins unique to the urophysis can be demonstrated and undergo changes in response to certain stimuli. An increasing amount of pharmacological information on urophysial principles is available, but the physiology of the system remains essentially unknown.
Transitions, Realignments, and Focus Shifts: Possibilities for Biopsychosocial Care in the Electronic Health Record Era:

The healthcare system in the United States is currently evolving in response to a diverse range of inter-related economic and political pressures. In this article, we discuss three important macro-level transitions (volume to value, clinician-centric to patient-centered care, and individual to population) and their implications for the practice of medicine, health information technology (HIT), and clinical training. Specifically, challenges and opportunities for advancing the use of the biopsychosocial model in clinical practice and teaching in this new, electronic health record (EHR) era of medicine are highlighted. While much work needs to be done to leverage the potential of EHR/HIT systems, their potential to improve population health and patient experience while controlling the costs of care is great. As primary care clinicians and behavioral scientists navigating this changing healthcare landscape, we should continue to strive to deliver high-quality, patient-centered care. Insisting that future generations of EHR/HIT systems support a biopsychosocial approach is part of this mission.
Abstract 5388: Targeting, biodistribution, and in vivo effects of MV-muPA, a novel oncolytic measles virus fully retargeted against uPAR in syngeneic, immunocompetent cancer models

The Edmonston vaccine strain of measles virus (MV-Edm) is a promising oncolytic agent whose mechanisms of cytotoxicity, safety and efficacy are well established. A prerequisite for the clinical development of retargeted oncolytic viruses is the preclinical understanding of virus-host-tumor interactions in vivo. Unfortunately, this requirement has not yet been met in the measles virotherapy field, because of the lack of validated models and vectors able to target murine tumors or tissues. Our goals are to investigate the tumor selectivity and virus-host interactions of a novel oncolytic MV retargeted against murine uPA receptor in syngeneic immunocompetent cancer models. We have recently rescued and characterized novel oncolytic measles viruses fully retargeted against murine (MV-muPA) urokinase receptor. The murine specific virus offers the unique opportunity for in vivo characterization of virus-tumor-host interactions -as it relates to safety and efficacy-, in syngeneic models with an intact immune system. Efficient MV-muPA viral infection, replication and cytotoxicity were demonstrated in murine tumor cells (4T1, MC38 and CT26), whereas MV-muPA did not induce significant infection and cytotoxicity in B16F10 and TSA murine cancer cells. To validate MV-muPA as a therapeutic vector in syngeneic models, we assessed the antitumor effects of MV-muPA in immunocompetent models of murine colon cancer (CT26). Four intravenous administration of MV-muPA (2×10e6 PFUs) resulted in significant inhibition of tumor progression in treated animals. Successful tumor targeting after IV administration was demonstrated by IHC analysis of MV-N protein in resected tumors. No visible adverse events were observed in treated animals compared to controls. To characterize the biodistribution of MV-muPA in an immunocompetent model, 4T1 bearing BALB/C mice were treated with MV-muPA (2×10e6 PFUs) twice via tail vein. After five days virus treatment, tumors and major organs were removed for histological analysis (HE 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5388. doi:10.1158/1538-7445.AM2011-5388
Surgical management of spastic diplegia in cerebral palsy.

SPASTIC diplegia is a form of cerebral palsy characterized by spastic weakness exclusively or primarily of the lower extremities.1 , 2 This disorder of movement and posture is particularly important because it afflicts the majority of patients with cerebral palsy, and its associated motor disabilities are almost invariably permanent.2 Pathogenesis Spastic diplegia is directly related to premature birth and low birth weight.3 , 4 Cerebral palsy in premature children is manifested as spastic diplegia in about 70 percent of the cases.5 At least one third and perhaps 65 percent of all patients with spastic diplegia were born prematurely.3 The remainder are born at term. . . .
Hepatitis vaccination of adults

Active and passive immunization are the mainstay of hepatitis A and B prevention. The indication for active hepatitis B vaccination is acknowledged in adults travelling or working in endemic areas. Passive hepatitis A prevention with immunoglobulins is now indicated only in exceptional cases. While adolescents in Switzerland aged between 11 and 15 years will in future undergo general hepatitis B vaccination, in adults the indication is confined to risk groups. These are principally medical personnel or other groups in close contact with infected persons. Hepatitis B immunoglobulin prophylaxis remains confined to high-risk cases. No active vaccine against hepatitis C is to be expected in the foreseeable future.
Vorinostat Induced Cellular Stress Disrupts the Balance Between p38 MAPK and Erk Pathways Leading to Apoptosis in WM Cells.

Abstract 3740 Poster Board III-676 Despite advances, Waldenstrom9s Macroglobulinemia (WM) remains incurable, and novel agents are urgently needed. Histone deacetylase (HDACs) are involved in transcription regulation and signal transduction of cells through a genome wide alteration in histone modification and other proteins, leading to significant increase in cellular stress in tumor cells. We therefore examined the activity of Vorinostat, a histone deacetylase inhibitor (HDAC-I), and dissected its pro-apoptotic molecular pathways in WM cells. Vorinostat exhibited dose dependent killing of both primary, bone marrow derived WM cells, as well as BCWM.1 WM cells with an LD50 of 3.5 to 5uM using Annexin V and PI staining. Vorinostat induced apoptosis in WM cells through activation of specific caspases at different time points. Caspase 3, 6, 8, and 9 were activated after 24 hours of Vorinostat. Even though caspase 7 is downstream of caspase 3, we observed that caspase 7 was activated earlier, starting at 6 hours. We therefore hypothesized that the regulators of caspase 7 may be affected by Vorinostat at an earlier time point. Further investigation confirmed that there was significant down-regulation of inhibitor of apoptosis (IAP) family members, including c-IAP1, c-IAP2, XIAP and Livin after 12 hours of treatment with Vorinostat, and may elude to greater sensitivity for IAPs in modulating Caspase 7 versus Caspase 3 in WM cells. We also studied the stress pathways including Erk, JNK and P38 pathways in Vorinostat treated WM cells. Activated p38, phospho-p38, was upregulated starting at 12 hours, while phopho-Erk abruptly decreased following 24 hours of treatment with Vorinostat. There was minimal change in the activity of JNK pathway following Vorinostat treatment. The activation of the p38 pathway coincided with a reduction in c-IAP1, c-IAP2, XIAP and Livin following treatment of WM cells with Vorinostat for 12 hours. Taken together, these studies support that stress induced apoptosis in WM cells is mediated through disruption in the balanced activity between the Erk and p38 MAPK pathways. Vorinostat induced cellular stress results in the activation of p38 MAPK pathway and a reduction of the IAP family members, leading to early activation of caspase 7. While the inhibition of Erk pathway by Vorinostat results in delayed activation of caspase 3, 6, 8, and 9 at 24 hours, the collective signaling strength of p38 activation as well as inhibition of Erk likely determines the apoptotic fate WM cells upon Vorinostat treatment. Disclosures: No relevant conflicts of interest to declare.
Long-Term Outcome and Perspectives of Laparoscopic Fundoplication

The ability to perform a fundoplication laparoscopically since 1991 has changed the surgical approach to patients with gastroesophageal reflux disease (GERD). Laparoscopic antireflux surgery remains an excellent option in patients with severe GERD. Laparoscopic Nissen fundoplication offers less morbidity and mortality than the open procedure with at least the same short-term outcome and better results compared to medical therapy. The rate of conversion to an open procedure is now close to zero. Appropriate preoperative investigation, patient selection and adequate discussion of risks are important in securing a good outcome and long-term patient satisfaction. Some patients have continuing symptoms, but more than 90% of patients remain satisfied with their decision to undergo surgery. This excellent success rate is maintained for up to 20 years after open fundoplication and indications are that this should be the same after the laparoscopic procedure [1], [2]. Long-term results of laparoscopic fundoplication will be discussed under various headings.
The interaction of Munc 18 (p67) with the p10 domain of p35 protects in vivo Cdk5/p35 activity from inhibition by TFP5, a peptide derived from p35

In a series of studies, we have identified TFP5, a truncated fragment of p35, the Cdk5 kinase regulatory protein, which inhibits Cdk5/p35 and the hyperactive Cdk5/p25 activities in test tube experiments. In cortical neurons, however, and in vivo in Alzheimer's disease (AD) model mice, the peptide specifically inhibits the Cdk5/p25 complex and not the endogenous Cdk5/p35. To account for the selective inhibition of Cdk5/p25 activity, we propose that the "p10" N-terminal domain of p35, absent in p25, spares Cdk5/p35 because p10 binds to macromolecules (e.g., tubulin and actin) as a membrane-bound multimeric complex that favors p35 binding to Cdk5 and catalysis. To test this hypothesis, we focused on Munc 18, a key synapse-associated neuronal protein, one of many proteins copurifying with Cdk5/p35 in membrane-bound multimeric complexes. Here we show that, in vitro, the addition of p67 protects Cdk5/p35 and has no effect on Cdk5/p25 activity in the presence of TFP5. In cortical neurons transfected with p67siRNA, we also show that TFP5 inhibits Cdk5/p35 activity, whereas in the presence of p67 the activity is protected. It does so without affecting any other kinases of the Cdk family of cyclin kinases. This difference may be of significant therapeutic value because the accumulation of the deregulated, hyperactive Cdk5/p25 complex in human brains has been implicated in pathology of AD and other neurodegenerative disorders.
The role of ethylene in abscission of sweet orange promoted by exogenous application of the abscission agent 5-chloro-3-methyl-4-nitro-1H-pyrazole (CMNP)

ABSTRACTMature ‘Valencia’ fruit were treated with 5-chloro-3-methyl-4-nitro-1H-pyrazole (CMNP), and the ethylene inhibitors aminoethoxy vinyl glycine (AVG) and silver thiosulfate (STS), to assess involvement of ethylene in abscission via CMNP. Fruit detachment force (FDF) and ethylene evolution were measured over time. Accumulation of the ethylene precursor 1-aminocyclopropane-1-carboxylate (ACC) in peel upon CMNP application was assessed and impact of application of ACC on FDF was estimated when applied 1 cm away from the abscission zone (AZ), to determine its potential as a signaling molecule in promoting fruit loosening. CMNP when applied alone reduced FDF by 50%. AVG and STS inhibited fruit loosening considerably at 500 µM and 10 mM, respectively, when applied with 2 mM CMNP. ACC accumulation in peel was highest 2 days after CMNP application, which preceded the maximum decline in FDF which occurred a day later, indicating that ACC serves as a potential signaling molecule that triggers abscission in th...
TIE: An Algorithm for Incrementally Evolving Taxonomy for Text Data

Taxonomy is an effective mean of organizing, managing and accessing large amount of information available in today's digital world. However, data in today's digitally connected world is growing at a rapid pace. Taxonomy represents theme inherent in a data set. So, taxonomy should evolve and reflect changes occurred in the data set, otherwise, it could not represent theme of the underlying data set accurately. Many automatic techniques are available that are generating taxonomy effectively for large to small data sets but, very less focus has been made on the evolution of taxonomy. In this paper, we propose a novel Taxonomy Incremental Evolution (TIE) algorithm that can incrementally evolve an existing taxonomy, whenever new documents are added in underlying data set, rather than regenerating a taxonomy from scratch. The proposed methodology can rest on top of any of the available clustering based automatic taxonomy generation techniques and incrementally evolve an existing taxonomy. We tested the TIE algorithm, in comparison to regeneration, on a text data set belonging to computing domain. The results obtained show that evolution is a better approach as compared to regeneration, as far as time efficiency is considered. Moreover, lexical and hierarchical quality of the evolved taxonomy found to be equally comparable to the regenerated taxonomy. Thus, the TIE algorithm can give an updated taxonomy in a considerably shorter period of time.
Exposure Cessation During Adulthood Did Not Prevent Immunotoxicity Caused by Developmental Exposure to Low-Level Trichloroethylene in Drinking Water.

Exposure to the water pollutant trichloroethylene (TCE) can promote autoimmunity in both humans and rodents. Using a mouse model we have shown that chronic adult exposure to TCE at 500 μg/ml in drinking water generates autoimmune hepatitis in female MRL+/+ mice. There is increasing evidence that developmental exposure to certain chemicals can be more toxic than adult exposure. This study was designed to test whether exposure to a much lower level of TCE (0.05 μg/ml) during gestation, lactation, and early life generated autoimmunity similar to that found following adult exposure to higher concentrations of TCE. When female MRL+/+ mice were examined at postnatal day (PND) 259 we found that developmental/early life exposure [gestational day 0 to PND 154] to TCE at a concentration 10 000 fold lower than that shown to be effective for adult exposure triggered autoimmune hepatitis. This effect was observed despite exposure cessation at PND 154. In concordance with the liver pathology, female MRL+/+ exposed during development and early life to TCE (0.05 or 500 μg/ml) generated a range of antiliver antibodies detected by Western blotting. Expression of proinflammatory cytokines by CD4+ T cells was also similarly observed at PND 259 in the TCE-exposed mice regardless of concentration. Thus, exposure to TCE at approximately environmental levels from gestational day 0 to PND 154 generated tissue pathology and CD4+ T cell alterations that required higher concentrations if exposure was limited to adulthood. TCE exposure cessation at PND 154 did not prevent the immunotoxicity.
On estimating axial high cycle fatigue behavior by rotating beam fatigue testing: Application to A356 aluminum alloy castings

Abstract Three methods available in the literature to estimate the axial S-N curve from the rotating bending fatigue performance were summarized. Axial and rotating bending fatigue tests were conducted at various alternating stresses on specimens excised from A356 aluminum alloy castings in the high cycle fatigue range. These data were used to assess the effectiveness of the models. Among the three models, the one developed by Manson and Muralidharan did not provide good estimates of the axial fatigue performance from rotating bending data. The geometric correction factor proposed by Philipp yielded the best fit, however, did not alter the Basquin exponent whereas the one proposed by Halford and Manson provided a poor estimate. Only the model proposed by Esin provided accurate estimates of fatigue performance as well as the Basquin exponent.
Is the shadow economy a bane or boon for economic growth

This paper uses the theoretical framework developed by Feder (1983) and Ram (1986) to examine interactions (i.e. externalities and intersectoral factor productivity differentials) between the official and unofficial sectors of the economy. Results from the empirical analysis, using data on over 100 countries from 1970 to 2008, suggest that the marginal externality effect of growth in the unofficial sector on the official sector is positive. Further, input productivities are higher in the unofficial sector relative to the official sector. These results are robust using alternate measures of the (unobserved) unofficial economy and across level of development.
Knowledge requires belief – and it doesn’t? On belief as such and belief necessary for knowledge

Does knowledge entail belief? This paper argues that the answer depends on how one interprets ‘belief’. There are two different notions of belief: belief as such and belief for knowledge. They ofte...
A Rare Case of Cerebellar Ataxia Due to Voltage-Gated Calcium Channel and Glutamic Acid Decarboxylase Autoantibodies

BACKGROUND Autoimmune cerebellar ataxia can be paraneoplastic in nature or can occasionally present without evidence of an ongoing malignancy. The detection of specific autoantibodies has been statistically linked to different etiologies. CASE REPORT A 55-year-old African-American woman with hypertension and a past history of morbid obesity and uncontrolled diabetes status post gastric bypass four years prior to the visit (with significantly improved body mass index and hemoglobin A1c controlled at the time of the clinical encounter) presented to the office complaining of gradual onset of unsteadiness and recurrent falls for the past three years, as well as difficulties coordinating routine daily activities. The neurologic exam showed moderate dysarthria and ataxic gait with bilateral dysmetria and positive Romberg test. Routine laboratory test results were only remarkable for a mild elevation of erythrocyte sedimentation rate, and most laboratory and imaging tests for common causes of ataxia failed to demonstrate an etiology. Upon further workup, evidence of anti-voltage-gated calcium channel and anti-glutamic acid decarboxylase antibody was demonstrated. She was then treated with intravenous immunoglobulins with remarkable clinical improvement. CONCLUSIONS We present a case of antibody-mediated ataxia not associated with malignancy. While ataxia is rarely related to autoantibodies, in such cases it is critical to understand the etiology of this disabling condition in order to treat it correctly. Clinicians should be aware of the possible association with specific autoantibodies and the necessity to rule out an occult malignancy in such cases.
Mechanisms involved in hemoglobin-mediated oxidation of lipids in washed fish muscle and inhibitory effects of phospholipase A2.

Hemoglobin (Hb) is a lipid oxidation promoter in fish muscle. Phospholipase A2 (PLA2; EC 3.1.1.4) is linked to an increased resistance to lipid oxidation of frozen-thawed cod fillets via an unknown mechanism. The present study aimed to investigate the mechanism of Hb-mediated lipid oxidation with a focus on ferryl Hb and methemoglobin (metHb), the pro-oxidative Hb species, and to examine how porcine pancreatic PLA2 inhibits Hb-mediated lipid oxidation in washed cod muscle (WCM). Lipid hydroperoxides (LOOHs) and thiobarbituric acid reactive substances (TBARS) were measured as primary and secondary lipid oxidation products, respectively. The formation of metHb and ferryl Hb was also monitored.; Results: Ferryl Hb and metHb formed during the Hb-mediated lipid oxidation. PLA2 inhibited the formation of LOOHs and TBARS and suppressed the formation of metHb and ferryl Hb. WCM was pre-oxidized by hemin to increase the amount of LOOHs. PLA2 promoted the depletion of LOOHs in the pre-oxidized WCM with limited TBARS formation at the expense of the heme moiety of Hb.; Conclusion: The results of the present study suggest that ferryl Hb may play a role in Hb-mediated lipid oxidation and that PLA2 from pig pancreas may work together with Hb as a novel antioxidant with an ability to remove pre-formed LOOHs from a lipid substrate. © 2017 Society of Chemical Industry.; © 2017 Society of Chemical Industry.
Women’s motivations to sew clothing for themselves

Participation in home sewing sewing is undergoing a resurgence in participation with a growing number of women choosing to sew their garments instead of buying readily available fast fashion. The purpose of this grounded theory study was to understand the current motivations of an ethnically diverse sample of women who sew garments for themselves. The in-depth interview data from 15 interviews revealed personal fulfillment to be the overarching reason for their sewing participation. Personal fulfillment was achieved through investment, control, and empowerment that provided the women with accomplishment, a creative outlet, and stress relief. Theoretical perspectives of prosumerism, craft consumer and do-it-yourself consumption uses and gratification theory were applied to better understand the motivations of these women to sew garments for themselves.
Overcoming adversity—a critical step toward career satisfaction and leadership in academic surgery

Abstract The experiences of life are what shape us. This article relays stories of adversity and resiliency as experienced and told by members of our own surgical community at the Academic Surgical Congress in Las Vegas, NV in February 2017. We aim to express in words the lessons of each experience so that others can learn about life and leadership.
Catchment Areas and Community Outreach and Engagement: The New Mandate for NCI-Designated Cancer Centers

In 2012 (PAR 12-298), the NCI Funding Opportunity Announcement (FOA) required that designated cancer centers identify and describe their Catchment Area (CA) and document ongoing research that specifically addresses the cancer burden, risk factors, incidence, morbidity, mortality, and inequities, in