cssi/SciSciGPT-SciSciNet huggingface dataset:
Transcription factor series

Prokaryotic transcription can be recapitulated largely with a four-subunit RNA polymerase and naked DNA. By contrast, eukaryotic transcription requires a chromatin template, large multiprotein chromatin-remodeling and -modifying complexes, a 12-subunit RNA polymerase (for protein-coding genes), five general transcription (initiation) factors (individually comprising as many as nine subunits), a 20-subunit Mediator complex, diverse elongation factors, and a multitude of gene-specific regulatory proteins and accessory factors. This vast complexity enables the regulated transcription of tens of thousands of genes in higher organisms, and underlies development and cell differentiation.Discovery of the many dozens of eukaryotic transcription proteins has been the work of a generation of scientists in many laboratories across the world. Much remains uncertain, but due to key connections made in the past few years, a coherent picture has begun to emerge. A series of reviews on transcription factors beginning with that by Workman and co-workers on page 15 of this issue mark this watershed in transcription research.The reviews will be illustrative rather than comprehensive. The thousands of gene-specific transcription factors that bind to enhancer, operator and silencer elements in the genome will be represented by a few well-studied examples. Several reviews will describe the current excitement surrounding so-called cofactors, the chromatin-remodeling and -modifying complexes, and the giant Mediator that conveys regulatory information from enhancers and operators to promoters. Finally, there will be a review on the much-debated role of the transcription-initiation factor TFIID, and a review on the less-investigated but no-less-fascinating and important topic of elongation factors.As will become apparent from this series of reviews, no single solution has been found to the mystery of eukaryotic transcriptional regulation. Rather, regulation occurs at every step of the pathway from a physiologic signal to the appearance of a complete transcript. Gene-specific factors can be controlled by conversion to an active state and by translocation to the nucleus. Chromatin – through its fundamental subunit, the nucleosome – exerts a general negative-regulatory effect, accounting for the extinction of most gene expression in most cell types and enabling the broad specificity of the gene-activation process. Transcription per se starts with the processing and transmittal of regulatory information by Mediator to RNA polymerase, whereas completion of the transcript is controlled by elongation factors.A key area for future transcription factor research will be structural studies, at two levels, the higher-order organization of eukaryote chromosomes and high-resolution structural detail of the transcription machinery. Due to the vast size of the multiprotein complexes involved, these structural studies present a daunting challenge, which must be met for a full understanding of transcription factor biology to be achieved.
Liposomal Delivery of Oligodeoxynucleotides

We have previously demonstrated that liposome-incorporated methylphosphonate antisense oligodeoxynucleotides (oligos) specific for BCR-ABL can selectively inhibit the expression of p210Bcr-Abl protein and the proliferation of chronic myelogenous leukemia cells in vitro. Here, we show that liposome-entrapment of phosphodiester and phosphorothioate oligos specific for BCR-ABL can also selectively inhibit the proliferation of chronic myelogenous leukemia cells. We have studied the intracellular localization of liposomes by fluorescent microscopy and found that lipo-somes are readily taken up by leukemic cells and are localized in the cytoplasm, allowing increased access of oligos to target cells intracellularly. Liposomal oligos are not toxic to peripheral blood mononuclear cells nor to bone marrow progenitors isolated from normal hematological donors. These studies strongly suggest that liposomal delivery of oligos may indeed circumvent the major limitations that preclude the clinical development of antisen...
Axonal growth: where neurotrophins meet Wnts.

Axonal guidance is influenced by many cues, including polypeptide trophic factors, cytokines, diffusible attractants and repellents and changes in calcium. How these signals are conveyed and integrated is not well defined. Recent data suggest that molecules of the canonical Wnt signaling pathway may have direct actions on axonal growth through neurotrophin signaling. This surprising mechanism is supported by local inactivation of glycogen synthase kinase 3β (GSK-3β) by nerve growth factor through the integrin-linked kinase. Inhibition of GSK-3β provides a positive regulatory signal for the cytoskeleton re-arrangement involved in axon extension. Moreover, microtubule stabilization is stimulated by adenomatous polyposis coli protein, a downstream target of GSK3, in response to neurotrophins. Therefore, components of the Wnt signaling pathway are downstream of trophic factors, providing new insights into cytoskeletal regulatory events during axonal growth.
End-user tools for grid computing

The present work describes an approach to simplifying the development and deployment of applications for the Grid. Our approach aims at hiding accidental complexities (e.g., low-level Grid technologies) met when developing these kinds of applications. To realize this goal, the work focuses on the development of end-user tools using concepts of domain engineering and domain-specific modeling which are modern software engineering methods for automating the development of software. This work is an attempt to contribute to the long term research goal of empowering users, to create complex applications for the Grid without depending on the expertise of support teams or on hand-crafted solutions.
Liquid crystal visualization of the effects of crucible and crystal rotation on Cz melt flows

Abstract Liquid crystals have been used to visualize the temperature field in a simulated Czochralski system. A versatile image processing software has been developed to obtain radial and axial temperature gradients that allow a detailed analysis of momentum and energy transport. The change in the meridional temperature profile with a change in crucible rotation rate is found to be significant. The axial temperature gradient has been found to increase with the rotation rate. Crystal rotation for a low Re s case was studied to emphasize the interaction of buoyancy-driven and rotationally driven forces which makes the flow field susceptible to unstable behavior.
1277 TYPE I HYPERLIPIDEMIA IN A CAMBODIAN FAMILY

Four children and both parents were evaluated for hypertriglyceridemia (HTG)when “cream of tomato soup” blood was discovered on a routine screen. The parents, 31 and 36, and the children, ages 3-9, were asymptomatic without history of abdominal pain or xanthomas. Their diet was native Cambodian with American supplementation. They cooked with pork fat, ate ice cream and standard school lunches without symptoms. Three of the children and the father had elevated fasted triglycerides (TG) (2780, 4170, 2930, and 372 mg% - father). The mother's TG was 92 mg%. The HDL-cholesterol (HDL-C) was low in three children with Type I and in the father (12, 13, 12, and 20 mg% - father). The mother's HDL-C was 37 mg%. Utilizing radioimmunoassay, Apo CII was normal in all patients, apo AI was low in the 3 Type I children and in the HTG father. Post heparin hepatic lipase was normal in all patients 7.9-21.3, normals ±2 S.D. 2.5-32.5 μm FFA/ml/hr. Extra hepatic lipase (EHL) was decreased in the 3 Type I children and the HTG father 2.9-9.6, normal ±2 S.D., 11.9-29.9 μm FFA/ml/hr. There was a strong correlation between decreased HDL-C, decreased apo AI, and decreased EHL in this family. Type I hyperlipidemia was discovered in 3 children and decreased EHL in these 3 children and their father who are from Cambodia without xanthomata or symptoms of pancreatitis such as abdominal pain.
Brief neuroleptic discontinuation and clinical symptoms in Kraepelinian and non-Kraepelinian chronic schizophrenic patients.

Abstract Neuroleptic medication was abruptly discontinued in 24 male chronic schizophrenic patients who were subdivided on the basis of their history of illness into Kraepelinian ( n =8) and non-Kraepelinian ( n =16) subgroups. These patients were kept drug free for 6 weeks and then returned to treatment with haloperidol, 20 mg/day. Half of the non-Kraepelinian patients developed exacerbations of their symptoms, which quickly resolved when they were returned to medication, while none of the Kraepelinian patients showed a worsening of symptomatology. On- medication clinical severity failed to predict risk for exacerbation, with severity of exacerbation predicting the amount of improvement when returned to medication. The Kraepelinian patients were found to be much less variable than the non- Kraepelinian patients in their symptoms during both medication manipulations, suggesting that medication truly has a negligible effect on them.
Age differences in the perception of hierarchical structure in events

Everyday activities break down into parts and subparts, and appreciating this hierarchical structure is an important component of understanding. In two experiments we found age differences in the ability to perceive hierarchical structure in continuous activity. In both experiments, younger and older adults segmented movies of everyday activities into large and small meaningful events. Older adults’ segmentation deviated more from group norms than did younger adults’ segmentation, and older adults’ segmentation was less hierarchically organized than that of younger adults. Older adults performed less well than younger adults on event memory tasks. In some cases, measures of event segmentation discriminated between those older adults with better and worse memory. These results suggest that the hierarchical encoding of ongoing activity declines with age, and that such encoding may be important for memory.
PTV experiments of subcooled boiling flow through a vertical rectangular channel

Abstract Time resolved Particle Tracking Velocimetry (PTV) experiments were carried out to investigate turbulent, subcooled boiling flow of refrigerant HFE-301 through a vertical rectangular channel with one heated wall. Measurements were performed with liquid Reynolds numbers (based on the hydraulic diameter) of Re = 3309, 9929 and 16,549 over a wall heat flux range of 0.0–64.0 kW/m2. Turbulence statistics are inferred from PTV full-field velocity measurements. Quantities such as: instantaneous 2D velocity fields, time-averaged axial and normal velocities, axial and normal turbulence intensities, and Reynolds stresses are obtained. The present results agree well with previous studies and provides new information due to the full-field nature of the technique. This work is an attempt to provide turbulent subcooled boiling flow data for validation and improvement of two-phase flow computational models.
Notes on the genus Graphis (Graphidaceae: Lichenized Ascomycetes) in the coastal plain of southeastern North America

Abstract Notes on some species of Graphis s. str. occurring in the coastal plain of southeastern North America are presented. The use of the name G. pavoniana in the region is discussed. The following species are newly reported from North America: G. hyphosa (Georgia, South Carolina), G. intermedians (Georgia, Florida), G. oxyclada (Florida) and G. pinicola (Georgia, Florida). Graphis intermedians is also newly reported for the Neotropics. Two species with anthraquinone pigments in the lirellae are described as new to science: G. hodgesiana and G. tamiamiensis.
Inhibition of in Vitro Fertilization of Rabbit Ova by Trypsin Inhibitors

The inhibition of crystalline tyrpsin and chymotrypsin and the acrosomal trypsin-like enzyme by soybean and ovomucoid trypsin inhibitors was ivestigated. A concentration of 1.0mg/ml of soybean trypsin inhibitor was necessary for good inhibition of in vitro fertilization. There was a close correlation between inhibition of the acrosomal trypsin-like enzyme and inhibition of in vitro fertilization. This indicated that the acrosomal enzyme is the essential enzyme for penetration of the zona pellicida of the rabbit ovum.
Mechanism of Copper Transport and Delivery in Mammals: Review and Recent Findings

The distribution of dietary copper after its absorption from the intestinal tract appears to occur in two stages. In the first stage, copper moves from the intestinal mucosa to the liver and kidney, and in the second stage, it moves from the liver to peripheral tissues. Evidence for these two stages of distribution comes from tracing the path of radiocopper after its intraduodenal or intragastric intubation (or direct injection) into rats. Immediately after intraduodenal administration, radioactive tracer is found in the portal blood, where it attaches to albumin, and transcuprein. The involvement of albumin in the initial transport of incoming copper is well documented (Owen, 1965 and 1971; Marceau and Aspin, 1971; Campbell et al., 1981; Gordon et al., 1987), and albumin has long been known to carry a high affinity copper binding site at its N-terminus (Breslow, 1964; Lau and Sarkar, 1971). The Kd for human albumin has been measured as 10-17 M in the absence of amino acids, and 10-22 M in the presence of L-histidine. As it is by far the most abundant plasma protein, albumin can theoretically bind up to about 40 μg Cu per ml of plasma or serum (assuming about 42 mg of albumin per ml). Nevertheless, albumin is normally relatively unsaturated with copper, binding only about 150 ng Cu per ml in normal adult humans, or less than 15% of the total copper in blood plasma.
Development of a methodology to predict material properties from environmental exposure. II. Structural features

A general scheme is presented in the first part of this series in which degradation-induced changes in a polymer that are produced by exposure to an aggressive environment are linked to measurable kinetic parameters and molecular weight distribution variations. Although general in nature for all polymers and environments, the data were collected on bisphenol A polycarbonate that was degraded by elevated temperatures. A parameter, τ, the product of a kinetic rate constant, k, and the environmental exposure time, provided a metric that was suitable for superposition methods to reduce the data. τ was directly related to the molecular weight distribution shifting during environmentally induced changes. This article extends the methodology to structure–property correlations such as the relationship of the glass-transition temperature, rheology, and the tensile strength of polycarbonate after the environmental treatment. Again, in a universal fashion, the τ value (the degree of degradation) was sufficient to model the observed physical property changes with the amount of exposure to the hostile environment. As long as the kinetics of the process of change are amenable to a mathematical model and a quantitative measure of the change in a fundamental polymer parameter is available, this methodology should be applicable to any polymer in any environment. © 2002 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 40: 802–812, 2002
Future directions in treatment of joint disease in horses.

Osteoarthritis (OA) is one of the most economically important diseases facing equine practitioners. The loss of use associated with joint disease is a leading problem in the equine industry. In fact, a recent survey suggested that 60% of lameness issues are related to OA. For these reasons, equine joint disease research remains on the cutting edge of equine research and holds a promising future. In addition, the disease processes seem similar to those in people. The relation to human disease allows the equine researcher to use the human knowledge base regarding pathophysiology more closely as well as funding sources. The launch of the Bone and Joint Decade (2002– 2011) has helped to increase awareness, patient education, and resources available for research, with the final goal of improving diagnostics, treatment, and prevention of musculoskeletal disease not only in human beings but in the veterinary field as well. The facts that 300 billion dollars per year is spent on human musculoskeletal conditions and that one in three Americans have joint pain are quite gripping and certainly are compelling for research in this area [1]. Furthermore, many of the current medical and surgical options being developed for people have been pioneered in veterinary medicine, including the horse, because of similarities in pathophysiology. Although OA in all species is believed to be a multifactorial disease that is not well understood, significant advances are being made. This article presents areas of research that are relatively well developed but have not made it to commercialization or routine clinical practice and looks at new applications being investigated for people that may have an equine application.
Mechanically Tunable Three-Dimensional Elastomeric Network/Air Structures via Interference Lithography

We show how to employ an interference lithographic template (ILT) as a facile mold for fabricating three-dimensional bicontinuous PDMS (poly(dimethylsiloxane)) elastomeric structures and demonstrate the use of such a structure as a mechanically tunable PDMS/air phononic crystal. A positive photoresist was used to make the ILT, and after infiltration with PDMS, the resist was removed in a water-based basic solution which avoided PDMS swelling or pattern collapse occurring during the ILT removal process. Since the period of the structure is approximately 1 μm, the density of states of gigahertz phonons are altered by the phononic PDMS/air crystal. Brillouin light scattering (BLS) was employed to measure phononic modes of the structure as a function of mechanical strain. The results demonstrate that the phononic band diagram of such structures can be tuned mechanically.
California's New Vagrancy Laws: The Growing Enactment and Enforcement of Anti-Homeless Laws in the Golden State

Vagrancy laws conjure up a distant past when authorities punished people without a home or permanent residence. Whether the objects of pity or scorn, vagrants could be cited or jailed under laws selectively enforced against anyone deemed undesirable. Although such laws have generally been struck down by courts as unconstitutionally vague, today’s “vagrants” are homeless people, who face growing harassment and punishment for their presence in public.More than one in five homeless people in the country lives in California, and two-thirds are unsheltered. The state legislature has done little to respond to this widespread problem, forcing municipal governments to address homelessness with local laws and resources. Cities have responded by enacting and enforcing new vagrancy laws — a wide range of municipal codes that target or disproportionately impact homeless people.Through extensive archival research and case studies of several cities, the report presents detailed evidence of the growing enactment and enforcement of municipal anti-homeless laws in recent decades as cities engage in a race to the bottom to push out homeless people. It concludes with a call for a state-level solution to end the expensive and inhumane treatment of some of California's most vulnerable residents.
A chaotic limit cycle paradox

Duffing's equation with sinusoidal forcing produces chaos for certain combinations of the forcing amplitude and frequency. To determine the most chaotic response achieveable for given bounds on the input force, an optimal control problem was investigated to maximize the largest Lyapunov exponent, which in this case also corresponds to maximizing the Kaplan-Yorke Lyapunov fractal dimension. The resulting bang-bang optimal feedback controller yielded a bounded attractor with a positive largest Lyapunov exponent and a fractional Lyapunov dimension, indicating a chaotic strange attractor. Indeed, the largest Lyapunov exponent was approximately twice as large as that achieved with sinusoidal forcing at the same amplitude. However, the resulting attractor is just a stable limit cycle and is not chaotic or fractal at all! this contradicts the basic idea that a bounded attractor with at least one positive Lyapunov exponent must be chaotic and fractal.
Experiments of device failures in a spatial power-combining array

The performance of a spatial power-combining array with device failure is investigated. Experimental results show that the array still combines the power in the broadside direction when the DC open-circuit failure occurs. Analysis of measured radiation patterns indicated that the power radiated from the patch antenna attached to the failed device is much smaller than the power radiated from other patch antennas. The effects of the chip resistor and the RF impedance of failed device are discussed. >
Religion/Science/Fiction: Beyond the Final Frontier

Science fiction is conventionally assumed to be hostile to religion. This article argues that science fiction stories not only belie this assumption, but can even promote religious speculation. Science fiction’s techniques, the intervention by African American and other ethnic minority writers in the literature, and the use of science fiction in the college classroom, all call into question any definitive boundary between science and religion.
Markers of aging. Modeling the clocks that time us.

From a life span perspective, aging occurs from birth to death, may involve reversible changes, and is a complex process that occurs interactively at the biological, psychosocial, and societal leve...
Impact of Childhood Trauma on Treatment Outcome in the Treatment for Adolescents with Depression Study (TADS)

Objective The impact of childhood trauma was examined in 427 adolescents (54% girls, 74% Caucasian, mean=14.6, SD=1.5) with major depressive disorder participating in the Treatment for Adolescents with Depression Study (TADS). Method TADS compared the efficacy of cognitive behavioral therapy (CBT), fluoxetine (FLX), their combination (COMB), and placebo (PBO). Teens were separated into four trauma history groups: (1) no trauma; (2) trauma, no abuse; (3) physical abuse; (4), and sexual abuse. The effects of treatment and trauma history on depression severity across 12 weeks of acute treatment, as measured by the Children's Depression Rating Scale–Revised (CDRS-R), were examined. Results A significant trauma-by-treatment-by-time interaction indicated that trauma history moderated treatment. The Week 12 primary efficacy findings previously reported by TADS were replicated in the no trauma group ( n = 201): COMB=FLX > CBT=PBO. No significant differences in treatment arms were observed among the trauma, no abuse, or physical abuse group. Teens with a history of sexual abuse treated with COMB, FLX, and PBO showed significant and equivalent improvement on the CDRS-R (mean 45). Baseline suicidality and self-reported depression were significantly related to a history of sexual abuse. Conclusions The study was limited by the level of detail regarding childhood traumatic experiences. Results are discussed in terms of the implications for treating depressed adolescents with traumatic backgrounds. Clinical Trials Registry Information: Treatment for Adolescents with Depression Study; http://www.clinicaltrials.gov, NCT00006286.
Contributions of muscles and passive dynamics to swing initiation over a range of walking speeds

Stiff-knee gait is a common walking problem in cerebral palsy characterized by insufficient knee flexion during swing. To identify factors that may limit knee flexion in swing, it is necessary to understand how unimpaired subjects successfully coordinate muscles and passive dynamics (gravity and velocity-related forces) to accelerate the knee into flexion during double support, a critical phase just prior to swing that establishes the conditions for achieving sufficient knee flexion during swing. It is also necessary to understand how contributions to swing initiation change with walking speed, since patients with stiff-knee gait often walk slowly. We analyzed muscle-driven dynamic simulations of eight unimpaired subjects walking at four speeds to quantify the contributions of muscles, gravity, and velocity-related forces (i.e. Coriolis and centrifugal forces) to preswing knee flexion acceleration during double support at each speed. Analysis of the simulations revealed contributions from muscles and passive dynamics varied systematically with walking speed. Preswing knee flexion acceleration was achieved primarily by hip flexor muscles on the preswing leg with assistance from biceps femoris short head. Hip flexors on the preswing leg were primarily responsible for the increase in preswing knee flexion acceleration during double support with faster walking speed. The hip extensors and abductors on the contralateral leg and velocity-related forces opposed preswing knee flexion acceleration during double support.
Ligand-induced distortion of a tetranuclear manganese butterfly complex.

The reaction of the pentadentate Schiff-base ligand 1,3-bis(salicylideneamino)-2-propanol (salproH3) with [Mn3O(O2CR)6(py)3] (R = Me, Et, But) gives the corresponding tetranuclear manganese product [Mn4O2(O2CR)5(salpro)] (4MnIII). The syntheses, structure and magnetochemical characterization of these complexes are reported. The structure of the [Mn4(µ3-O)2]8+ is butterfly-like much more closed than in previous complexes with this core as a result of the alkoxide oxygen of the salpro ligand bridging the two wingtip Mn atoms. Variable-temperature, solid-state magnetic susceptibility studies reveal that these complexes possess S = 0 ground state spins. Fitting of the magnetic susceptibility data to the theoretical χMTvs. T expression derived for a C2v symmetry complex, assuming an isotropic Heisenberg spin-Hamiltonian and using the Van Vleck equation, revealed that the various exchange parameters are all antiferromagnetic, and the core thus experiences spin frustration effects.
On the relative importance of history and ecology in structuring communities of desert small animals

Several recent studies have compared small mammal community structure across multiple deserts on different continents. These studies have tacitly assumed that variation in community structure was greater between continents than within, and so have not evaluated variation across desert regions within continents. I evaluated several metrics of community structure and a model of community assembly for four desert regions in North America - the Great Basin, Mojave. Sonoran. and Chihuahuan Deserts in order to explicitly compare these metrics across these deserts. Additionally. I compared these results with similar analyses conducted on two desert regions in central Asia - the Gobi Desert and the Turan Desert Region to evaluate the relative magnitude of intra- vs inter-continental variation. Although the patterns observed are complex, they demonstrated marked heterogeneity in desert small mammal communities within North America. However, this heterogeneity is much less than that observed in inter-continental comparisons, in which Asian and North American deserts differ markedly. These results agree with other recent studies providing limited or no support for the existence of substantial convergence in community characteristics or ecological function across geographically distant regions. Rather, the results support the hypothesis that the common evolutionary history of faunas in globally disjunct landmasses has had a stronger influence on the evolution of communities and faunas than do regional variations in climate, physiography, etc. Whereas a common ecological setting may have large impacts on some facets of organismal structure (e.g., bipedalism in desert small mammals), common evolutionary history appears to have a more profound influence on local dynamics.
Classification using functional data analysis for temporal gene expression data

Motivation: Temporal gene expression profiles provide an important characterization of gene function, as biological systems are predominantly developmental and dynamic. We propose a method of classifying collections of temporal gene expression curves in which individual expression profiles are modeled as independent realizations of a stochastic process. The method uses a recently developed functional logistic regression tool based on functional principal components, aimed at classifying gene expression curves into known gene groups. The number of eigenfunctions in the classifier can be chosen by leave-one-out cross-validation with the aim of minimizing the classification error. Results: We demonstrate that this methodology provides low-error-rate classification for both yeast cell-cycle gene expression profiles and Dictyostelium cell-type specific gene expression patterns. It also works well in simulations. We compare our functional principal components approach with a B-spline implementation of functional discriminant analysis for the yeast cell-cycle data and simulations. This indicates comparative advantages of our approach which uses fewer eigenfunctions/base functions. The proposed methodology is promising for the analysis of temporal gene expression data and beyond. Availability: MATLAB programs are available upon request. Contact: [email protected] Supplementary information: Supplementary materials are available on the journal's website.
Dynamics of Agent Organizations: Application to Modeling Irregular Warfare

In this paper, we focus on computational modeling of adversarial activities and asymmetric warfare in a tactical setting. As a topic for simulation study, asymmetric warfare is an odd and ill-conditioned problem. Empirical data is scarce or one-sided, while the subject itself presents a constantly adapting and moving target that makes it a strategic priority to conceal its inner workings from the observers. To provide an insight into the dynamics of the asymmetric conflicts, one needs to constrain the model in rigorous social-scientific concepts, including those of organization theory, theory of collective action, and social network analysis. Our model, called NetMason, enables controlled experiments to replicate and analyze alternative policies of disruption of activities of terrorist organizations. In addition, sensitivity analysis with respect to behavioral assumptions can be easily performed.
Intracolonic zymosan produces visceral hyperalgesia in the rat that is mediated by spinal NMDA and non-NMDA receptors

The present study examined the effects of colonic inflammation on reflex responses to colorectal distension (CRD) in awake rats. Visceromotor responses (VMR) to CRD were recorded in rats that received either no treatment or intracolonic saline or zymosan. Three hours following zymosan treatment (25 mg/ml; 1 ml) VMR response magnitudes were significantly increased at all intensities of CRD tested (10-80 mmHg). The enhanced responses to CRD were attenuated in a dose-dependent fashion by intrathecal administration of the non-competitive N-methyl-D-aspartate (NMDA) receptor channel blocker MK-801 to 60% of control and by the non-NMDA receptor antagonist DNQX to less than 20% of control. The metabotropic receptor antagonist AP-3 was without effect. Signs of multi-focal colonic inflammation were clearly present 3 h after zymosan treatment, characterized by an ingress of inflammatory cells and damaged crypts in and around these foci. Taken together these findings suggest that tissue inflammation increases the sensitivity of the colon to mechanical stimuli, leading to enhanced responses to CRD. This enhancement involves the activation of spinal NMDA as well as non-NMDA receptors, but not metabotropic receptors.
Greater Discounting of Delayed Rewards in Young Adults with Family Histories of Alcohol and Drug Use Disorders: Studies from the Oklahoma Family Health Patterns Project

Background: Increased discounting of delayed rewards may be a premorbid characteristic and possible risk factor for alcohol and other drug use disorders; however, previous studies have found no or minimal differences in delay discounting in individuals at risk for substance use disorders based on family history. It is possible that increased delay discounting may be more closely associated with antisocial traits, evident in a subset of individuals with positive family histories of alcohol and drug use disorders, and that previous studies were underpowered for detecting subtle to modest overall group differences. Methods: In this study, we compared 143 young adults with family histories of alcohol and other drug use disorders (FH+) and 155 young adults with no such histories (FH)) on delay discounting and subsequently examined how delay discounting was related to antisocial traits and other selected psychological and demographic variables. Results: The FH+ group discounted delayed rewards more than the FH) group. Subsequent analyses revealed that increased delay discounting was correlated with having more parents and grandparents with alcohol and drug use disorders, more antisocial traits, more depressive tendencies and lower IQs, and lower income. After controlling for all these relationships, more antisocial traits and lower IQ still predicted greater delay discounting, and subsequent analysis revealed that the greater delay discounting in the FH+ group was mediated by this group’s greater number of individuals with antisocial traits. Conclusion: FH+ individuals who discount delayed rewards more may be at increased risk for developing alcohol and other drug use disorders; however, additional descriptive studies and longitudinal studies are needed.
Apolipoprotein B determines risk for recurrent coronary events in postinfarction patients with metabolic syndrome

The adult treatment panel III (ATP III) of the National Cholesterol Education Program recognizes metabolic syndrome (MS) as a secondary target for risk-reduction therapy given the well-known increase in risk of cardiovascular disease (CVD) by all MS components. We investigated potential CVD risk arising from 17 laboratory variables in postinfarction patients with MS by identifying such patients from the Thrombogenic Factors and Recurrent Coronary Events (THROMBO) study using slightly modified ATP III criteria for MS. This gave 272 patients with MS out of a total of 766 postinfarction patients without history of diabetes. Comparison between non-MS and MS patients using Kaplan-Meier analysis revealed no difference in outcome between groups. Additionally, a proportional hazards model applied to dichotomized laboratory parameters demonstrated only apoB as a significant predictor of risk for recurrent coronary events in MS patients with hazard ratio, 1.97 (95% CI; 1.08, 3.60; P < 0.05). We conclude that there is no difference in outcomes between non-MS and MS postinfarction patients; that apoB is significantly associated with risk for recurrent coronary events in postinfarction patients with MS; that further studies would be needed to recommend the routine determination of apoB in these patient groups.
Improving the Science of Regulatory Dispersion Models for Short-Range Applications

Atmospheric dispersion models used in assessing environmental impact and regulatory issues are often labeled “regulatory.” Such models are typically of a simple form due to their repeated use and the fast turnaround required. In the United States for example, models often are run for a year of hourly meteorological inputs to determine the highest or “worst-case” concentration for a source. Despite the simplicity requirement, however, regulatory models must be based on sound physical principles to generate confidence in their results.
An efficient diagnostic procedure based on recursive configuration of Dilated Benes Networks

Crosstalk is a major concern in switching networks such as dilated Benes networks (DBNs) consisting of electro-optical switches. There are many practical constraints which make efficient diagnosis of a DBN difficult. These constraints include (a) only the inputs and outputs of the network are accessible and (b) the crosstalk is both nonuniform among different switches as well as asymmetric for a given switch. We propose a diagnostic procedure that is amendable to automatic test generation. At its heart is a set of recursively defined network configurations that enable us to collect the power measurements at the outputs of the network in an accurate and yet efficient way. Based on these measurements, one may obtain the crosstalk measurements of each switch, which can in turn be used to calculate the signal-to-crosstalk ratio (SXR) of the network and identify switches having excessive crosstalk.
Nuclear Physics Applications of the Mössbauer Effect

If somewhere in the mid 1950s someone had made the comment to nuclear physicists studying nuclear decays that in 1958 a graduate student would discover a method that would ultimately allow measurements of certain γ-ray transitions in nuclei with resolutions as high as perhaps 10− 10 eV, the reaction would have been most likely a ridicule or worse. So unbelievable would such a prediction have seemed, but it did happen and the Mossbauer effect [1] provided yet another testimony to the wonders of physics!
IS FlowMap, a novel tool to examine blood flow changes induced by flow diverter stent treatment: initial experiences with pipeline cases.

Background Intracranial aneurysm flow diverting stents are a new endovascular treatment option for wide neck and large/giant aneurysms. Since August 2011, our center has integrated flow diverting stents into aneurysm treatment management. To further understand the effects of flow diverting stents, we developed the intracranial stent flow mapping program, which allows detailed, case by case, examination and comparison of blood flow changes within an aneurysm before and after stent treatment. Methods The Intracranial Stent Flow Mapping program (IS FlowMap) utilizes algorithms detecting movement changes between consecutive images. Sequences of catheter angiograms capturing the movement of injected contrast were used to map flow patterns and examine aneurysmal flow before and after stent implantation. Results A pilot study of this new technique in flow diverter (FD) stent treated aneurysms was performed. Four clinical aneurysms (two wide neck and two giant aneurysms) were analyzed by IS FlowMap. The characteristics of redirected flow in cases treated with one stent or two overlapping stents in the reconstructed vessels are presented. Distinct differences in flow impingement on the aneurysm wall, aneurysmal inflow, and flow circulation before and after FD stent treatment were found. Conclusions We present a novel approach to map blood flow motion within aneurysms and have shown the feasibility of the technique in clinical aneurysms. This new technology can help monitor flow changes induced by stents and study the relationship between the modified flow and treatment outcome.
NEARSHORE PLACEMENT OF SAND

A methodology that evaluates the influence of depth on the rate of onshore migration of sand placed in the nearshore is presented. The results appear appropriate for the Atlantic and Gulf coasts of the United States. Migration rate is found to be extremely dependent, to the 4th or Sth power, on the water depth. This implies that doubling the rate of migration requires placement in only about 15% less depth. It is argued that accounting for the net shoreward bottom stress due to the velocity asymmetry under finite-amplitude waves is the appropriate way to model the fate of nearshore placed sands.
Dirhodium paddlewheel with functionalized carboxylate bridges: new building block for self-assembly and immobilization on solid support.

A new dirhodium(II,II) paddlewheel complex, [Rh2(O2CC6H4COOC2H5)4] (1), has been synthesized using a predesigned functionalized carboxylate, namely, 4-(ethoxycarbonyl)benzoate. The target product has been crystallized from the acetone solution and structurally characterized as a bis-acetone adduct, [Rh2(O2CC6H4COOC2H5)4(OCMe2)2]·C6H14 (2). By utilizing the ability of dangling ester groups to coordinate to open axial ends of neighboring dirhodium units, 1 can self-assemble to form 2D networks upon crystallization from solutions of noncoordinating solvents such as chlorobenzene and chloroform. The resulting [Rh2(O2CC6H4COOC2H5)4]·2C6H5Cl (3) and [Rh2(O2CC6H4COOC2H5)4]·2CHCl3 (4) products have microporous solid state structures with the pores filled with the corresponding disordered solvent molecules. Notably, 3 and 4 represent unique examples of 2D extended frameworks based on dirhodium tetracarboxylate paddlewheel units devoid of any exogenous ligands. In solution, the dangling ends of carboxylate bridges ...
Confident assignment of site-specific glycosylation in complex glycoproteins in a single step.

A glycoprotein may contain several sites of glycosylation, each of which is heterogeneous. As a consequence of glycoform diversity and signal suppression from non- glycosylated peptides that ionize more efficiently, typical reversed-phase LC−MS and bottom−up proteomics database searching workflows do not perform well for identification of site-specific glycosylation for complex glycoproteins. We present an LC−MS system for enrichment, separation, and analysis of glycopeptides from complex glycoproteins (>4 N-glycosylation sequons) in a single step. This system uses an online HILIC enrichment trap prior to reversed-phase C18-MS analysis. We demonstrated the effectiveness of the system using a set of glycoproteins including human transferrin (2 sequons), human alpha-1-acid glycoprotein (5 sequons), and influenza A virus hemagglutinin (9 sequons). The online enrichment renders glycopeptides the most abundant ions detected, thereby facilitating the generation of high-quality data-dependent tandem mass spectra. The tandem mass spectra exhibited product ions from both glycan and peptide backbone dissociation for a majority of the glycopeptides tested using collisionally activated dissociation that served to confidently assign site-specific glycosylation. We demonstrated the value of our system to define site-specific glycosylation using a hemagglutinin containing 9 N-glycosylation sequons from a single HILIC-C18-MS acquisition.
Bayesian Tomographic Reconstruction Using Riemannian MCMC

This paper describes the use of Monte Carlo sampling for tomographic image reconstruction. We describe an efficient sampling strategy, based on the Riemannian Manifold Markov Chain Monte Carlo algorithm, that exploits the peculiar structure of tomographic data, enabling efficient sampling of the high-dimensional probability densities that arise in tomographic imaging. Experiments with positron emission tomography (PET) show that the method enables the quantification of the uncertainty associated with tomographic acquisitions and allows the use of arbitrary risk functions in the reconstruction process.
Actin exposure upon tissue injury is a targetable wound site-specific protein marker.

Abstract Background Identification of wound-specific markers would represent an important step toward damaged tissue detection and targeted delivery of biologically important materials to injured sites. Such delivery could minimize the amount of therapeutic materials that must be administered and limit potential collateral damage on nearby normal tissues. Yet, biological markers that are specific for injured tissue sites remain elusive. Methods In this study, we have developed an immunohistological approach for identification of protein epitopes specifically exposed in wounded tissue sites. Results Using ex-vivo tissue samples in combination with fluorescently-labeled antibodies we show that actin, an intracellular cytoskeletal protein, is specifically exposed upon injury. The targetability of actin in injured sites has been demonstrated in vivo through the specific delivery of anti-actin conjugated particles to the wounded tissue in a lethal rat model of grade IV liver injury. Conclusions These results illustrate that identification of injury-specific protein markers and their targetability for specific delivery is feasible. General significance Identification of wound-specific targets has important medical applications as it could enable specific delivery of various products, such as expression vectors, therapeutic drugs, hemostatic materials, tissue healing, or scar prevention agents, to internal sites of penetrating or surgical wounds regardless of origin, geometry or location.
Association of Socioeconomic Status and Race/Ethnicity With Treatment and Survival in Patients With Medullary Thyroid Cancer.

Importance Medullary thyroid cancer (MTC) is a relatively rare neoplasm of the thyroid but accounts for 14% of thyroid cancer–related deaths. Female sex, young age, and stage at presentation have been found to predict survival and treatment. However, patterns of survival and treatment by socioeconomic status and race/ethnicity have not been fully described. Objective To determine whether socioeconomic status and race/ethnicity are associated with survival and treatment in patients with MTC. Design, Setting, and Participants Data for 1647 patients with MTC from January 1, 1998, to December 31, 2011, in the Surveillance, Epidemiology, and End Results (SEER) Program registry were examined. Data analysis was conducted from June 1, 2013, to July 31, 2014. Main Outcomes and Measures Differences in receipt of thyroidectomy and lymph node examination by race/ethnicity were examined using logistic regression models. Overall and disease-specific survival were examined by race/ethnicity using Kaplan-Meier survival curves and adjusted Cox proportional hazards regression models. Results Of the 1647 patients with MTC were 1192 white (72.4%), 139 black (8.4%), 222 Hispanic (13.5%), and 94 other races/ethnicities (5.7%). Of these, 1539 (93.4%) underwent surgical treatment. There were no differences in receipt of thyroidectomy by race/ethnicity; however, black patients (adjusted odds ratio, 0.61; 95% CI, 0.39-0.93) and female patients (adjusted odds ratio, 0.76; 95% CI, 0.59-0.99) were less likely to undergo lymph node examination compared with non-Hispanic white and male patients. Black patients had lower overall (adjusted hazard ratio, 2.40; 95% CI, 1.45-3.98) and disease-specific survival (adjusted hazard ratio, 2.9; 95% CI, 1.64-5.14) compared with non-Hispanic white patients. Conclusions and Revelance In this population-based study of patients with MTC, black patients were less likely to have lymph node examination following surgery. Furthermore, Hispanic and black patients had poorer overall and disease-specific survival compared with non-Hispanic white patients after accounting for clinical factors. Racial/ethnic disparities exist in the type of treatment as well as outcomes in patients with MTC.
Pharmacy's influence and opportunity in public health.

Many current students and graduates of pharmacy programs are familiar with the “Oath of a Pharmacist,” in which the beneficent vows of our profession are outlined for current and future practitioners.[1][1] I am particularly inspired by the first proclaimed intention, “I will consider the
Fusion of Acid Oxides for Potentially Radiation-Resistant Waste Forms

Skull melting of groups VA and VB acid oxides with alkali metal oxides and urania leads to compounds with a good ability to retain radionuclides and establishes immunity to radiation damage. Substitution of neptunium and plutonium for uranium should not diminish these desirable properties. For hexavalent transplutonic elements, even at high oxygen fugacities and oxide activities, acid character losses and the reducing nature of radiation suggest the lower valences (III and IV) will be the stable states. Plutonium becomes the pivotal radionuclide when valence stability in a radiation field is considered.
Rapidly converging image covariance estimation for FBP reconstruction methods

We propose a new estimator for covariance between pixels in x-ray CT images reconstructed using algorithms of the filtered backprojection type. Our new estimator is unbiased and is found to have significantly lower variance than the conventional unbiased estimator. We demonstrate the accuracy of our new estimator for both fan-beam and cone-beam reconstruction via Monte Carlo simulation. Moreover, we provide an analytical expression for the estimator variance and verify it numerically with Monte Carlo simulation.