cssi/SciSciGPT-SciSciNet huggingface dataset:
Imaging α-Hemolysin with Molecular Dynamics: Ionic Conductance, Osmotic Permeability, and the Electrostatic Potential Map

alpha-Hemolysin of Staphylococcus aureus is a self-assembling toxin that forms a water-filled transmembrane channel upon oligomerization in a lipid membrane. Apart from being one of the best-studied toxins of bacterial origin, alpha-hemolysin is the principal component in several biotechnological applications, including systems for controlled delivery of small solutes across lipid membranes, stochastic sensors for small solutes, and an alternative to conventional technology for DNA sequencing. Through large-scale molecular dynamics simulations, we studied the permeability of the alpha-hemolysin/lipid bilayer complex for water and ions. The studied system, composed of approximately 300,000 atoms, included one copy of the protein, a patch of a DPPC lipid bilayer, and a 1 M water solution of KCl. Monitoring the fluctuations of the pore structure revealed an asymmetric, on average, cross section of the alpha-hemolysin stem. Applying external electrostatic fields produced a transmembrane ionic current; repeating simulations at several voltage biases yielded a current/voltage curve of alpha-hemolysin and a set of electrostatic potential maps. The selectivity of alpha-hemolysin to Cl(-) was found to depend on the direction and the magnitude of the applied voltage bias. The results of our simulations are in excellent quantitative agreement with available experimental data. Analyzing trajectories of all water molecule, we computed the alpha-hemolysin's osmotic permeability for water as well as its electroosmotic effect, and characterized the permeability of its seven side channels. The side channels were found to connect seven His-144 residues surrounding the stem of the protein to the bulk solution; the protonation of these residues was observed to affect the ion conductance, suggesting the seven His-144 to comprise the pH sensor that gates conductance of the alpha-hemolysin channel.
Assessing the population-level prevention effect of emergency department-based HIV testing in the United States: a research framework and commentary.

The effect of highly active antiretroviral therapy in HIV/ AIDS care on patient-level morbidity and mortality is without question, and HIV counseling and testing is an essential step on the pathway to accessing such care. For these reasons, the Institute of Medicine has stated that HIV treatment is so essential it should become a public health entitlement program, and many individuals and organizations have promoted strategic expansion of HIV testing services. Less well defined is the effect expanded HIV testing in emergency departments (EDs) might have on HIV transmission in the United States at the population level. Hsu and Walensky carefully reviewed the literature on the cost-effectiveness of expanded HIV testing in EDs in the United States and found no full-scale cost-utility studies exactly on this point. In this commentary, I outline a framework for assessing the possible population-level impact of expanded HIV testing in EDs during a 1-year period and observe how the articles in this section of the special issue can provide key parameters for that framework. It has been estimated that there are 119.2 million ED visits annually in the United States. If we extrapolate from the study by Hudepohl et al, we might approximate that there are 3.178 ED visits per year per patients of these facilities. Taken together, these estimates suggest that roughly 37.5 million people visit EDs each year in the United States. The Kaiser Family Foundation has estimated that approximately 21% of people in the United States have been tested for HIV in the past year, leaving 79% not tested in the past 12 months. Hence, roughly 29.6 million visitors to EDs in the United States might not have been tested for HIV in the last year. Of course, this estimate of 21% may not be equally distributed across individuals visiting and not visiting EDs in the past year. In this issue, Hudepohl et al estimated that approximately 6.95% (11,502/165,512) of patients in the ED in their study were offered, agreed to, and actually received HIV testing. If we extrapolate this percentage and apply it to the 29.6 million ED patients not tested in the past year, we might see 2,058,965 such individuals tested in an ED HIV testing program similar to the one conducted by Hudepohl et al. The estimate of 6.95% m
Competency-Based Resident Education

Over the course of the last decade fundamental changes have occurred in residency training. The basis of these changes has been rooted in the desire to simultaneously improve the quality of the learning experience while decreasing the demands of training on resident lifestyle. The ACGME Outcomes Project was initiated in 1999 with the intent of facilitating such change in medical education. Before its introduction, assessment of residency training sites focused on the processes, resources, and reputation of an individual program, but failed to assess how effectively a program used those assets. The stated goal of the ACGME Outcomes Project has been to drive an evolution of this process-oriented form of education to one that is based on outcomes that measure the effect of the educational experience. This article is a brief overview of current efforts to achieve this goal.
Development of Non-Birefringent Optical Adhesives

Abstract The birefringence compensation technique1 has been employed through polymer blending for the development of non-birefringent optical adhesives. It has been found that trimellitic anhydride(TMA)-cured polymethylmethacylate(PMMA)/Epoxy EPON-828) as a possible system resulted in phase separation due to polymerization2. To circumvent the problem of polymerization-induced phase separation, a copolymer system comprised of methylmethacrylate(MMA) and glycidylmethacrylate(GMA) was synthesiztd3. The MMA-co-GMA copolymer was subsequently blended with EPON-828, then cured thermally with TMA. The cured blend films showed single glass transition at all compositions and optical transparency suggestive of miscible character. These optical adhesive blends showed zero birefringence or zero optical retardation at compositions between 60–70-wt% copolymer. The zero Birefringence afforded by the compensation of the intrinsic birefringence of the constituent polymer chains may be attributed to the complete miscibility...
Stoichiometric arginine binding in the oxygenase domain of inducible nitric oxide synthase requires a single molecule of tetrahydrobiopterin per dimer.

Abstract In addition to its catalytic roles, the nitric oxide synthase (NOS) cofactor tetrahydrobiopterin (H4B) is required for substrate binding and for stabilization of the dimeric structure. We expressed and purified the core of the iNOS oxygenase domain consisting of residues 75–500 (COD iNOS ) in the presence (H4B + ) and absence (H4B − ) of this cofactor. Both forms bound stoichiometric amounts of heme (>0.9 heme per protein subunit). H4B − COD iNOS was unable to bind arginine, gave an unstable ferrous carbonyl adduct, and was a mixture of monomer and dimer. H4B + COD iNOS bound arginine, gave a stable ferrous carbonyl adduct, and was exclusively dimeric. The H4B cofactor content of this species was only one per dimer yet this was sufficient to form two competent arginine binding sites as determined by optical stoichiometric titrations.
Vascular endothelial growth factor–induced elimination of the type 1 interferon receptor is required for efficient angiogenesis

Angiogenesis is stimulated by vascular endothelial growth factor (VEGF) and antagonized by type 1 interferons, including IFN-α/β. On engaging their respective receptors (VEGFR2 and IFNAR), both stimuli activate protein kinase D2 (PKD2) and type 1 IFNs require PKD2 activation and recruitment to IFNAR1 to promote the phosphorylation-dependent ubiquitination, down-regulation, and degradation of the cognate receptor chain, IFNAR1. Data reveal that PKD2 activity is dispensable for VEGF-stimulated down-regulation of VEGFR2. Remarkably, VEGF treatment promotes the recruitment of PKD2 to IFNAR1 as well as ensuing phosphorylation, ubiquitination, and degradation of IFNAR1. In cells exposed to VEGF, phosphorylation-dependent degradation of IFNAR1 leads to an inhibition of type 1 IFN signaling and is required for efficient VEGF-stimulated angiogenesis. Importance of this mechanism for proangiogenic or antiangiogenic responses in cells exposed to counteracting stimuli and the potential medical significance of this regulation are discussed.
The gene encoding protein kinase SEK1 maps to mouse chromosome 11 and human chromosome 17.

Abstract We report the mapping of the human and mouse genes encoding SEK1 (SAPK/ERK kinase-1), a newly identified protein kinase that is a potent physiological activator of the stress-activated protein kinases. The human SERK1 gene was assigned to human chromosome 17 using genomic DNAs from human–rodent somatic cell hybrid lines. A specific human PCR product was observed solely in the somatic cell line containing human chromosome 17. The mouseSerk1gene was mapped to chromosome 11, closely linked toD11Mit4,using genomic DNAs from a (C57BL/6J ×Mus spretus)F1×M. spretusbackcross.
BARTONELLA BODIES IN THE BLOOD OF A NON-SPLENECTOMIZED DOG

A non-splenectomized dog, on a vitamin-adequate basal diet, in the course of a plasmapheresis experiment, developed an uncontrollable anemia associated with the presence of bodies in or on the erythrocytes, indistinguishable from the descriptions of Bartonella canis. The normal plasma protein level of 7.3 per cent was reduced to 4.1 per cent by diet and the removal of 5354 ml. of whole blood in 33 bleedings. The Bartonella infection was transferred to a splenectomized dog by an intravenous injection of whole blood. Each animal was apparently sterilized by one injection of neoarsphenamine equivalent to 15 mg. per kilo weight. It is possible that the spleen liberates some substance into the blood stream which has an inhibitory effect upon a latent Bartonella infection and that this protective substance was diminished by the many bleedings associated with the lowering of plasma proteins in the non-splenectomized dog and was lacking in the inoculated splenectomized dog.
Enhanced Performance of Li-Ion Batteries via Modified Reference Governors and Electrochemical Models

This paper examines reference governor (RG) methods for satisfying state constraints in Li-ion batteries. Mathematically, these constraints are formulated from a first principles electrochemical model. Consequently, the constraints explicitly model specific degradation mechanisms, such as lithium plating, lithium depletion, and overheating. This contrasts with the present paradigm of limiting measured voltage, current, and/or temperature. The critical challenges, however, are that: 1) the electrochemical states evolve according to a system of nonlinear partial differential equations, and 2) the states are not physically measurable. Assuming available state and parameter estimates, this paper develops RGs for electrochemical battery models. The results demonstrate how electrochemical model state information can be utilized to ensure safe operation, while simultaneously enhancing energy capacity, power, and charge speeds in Li-ion batteries.
The inducibility and ontogeny of rat liver UDP- glucuronyltransferase toward furosemide

Furosemide (F) conjugation with glucuronic acid is the main pathway of F metabolism in humans and experimental animals. In order to study rat liver microsomal UDP-glucuronyltransferase (UDP-GT) activity towards F we developed an in vitro assay in which the conjugation product, furosemide 1-0-acyl glucuronide (FG) was separated and quantitatively determined by reverse phase high pressure liquid chromatography. The optimal conditions of the reaction were established and the apparent Km for F and UDP-glucuronic acid (UDPGA) were 0.22 and 1.76 mM, respectively. Substrate inhibition of UDP-GT toward F occurred at F concentrations higher than 1.5 mM. Developmental changes in F glucuronidation were compared to the ontogeny of UDP GT activity toward two other acceptors, 1-naphthol and estrone that are known to have different patterns of maturation. F glucuronidation was 26% of adult activity at 18 days of gestation, reached 48% at birth and gradually increased to 250% of adult activity at 22 days of age. Glucuronidation of 1-naphthol and estrone attained 87% and 44% of adult activity at 22 days of gestation, 37% and 66% in six-day-old rats and 100% and 427% of adult activity in 22-day-old rats, respectively. The effect of 3-methylcholanthrene (3-MC), phenobarbital (PB) and pregnenolone-16 alpha-carbonitrile (PCN) on F UDP-GT was studied and compared to their effect on 1-naphthol and estrone glucuronidation. PB, 3-MC and PCN increased F-UDP-GT activity to 208%, 282% and 342% of vehicle-treated animals, respectively, while F pretreatment did not affect the conjugation of F. In comparison, 1-naphthol glucuronidation was preferentially induced by 3-MC (4.4-fold of control) while estrone glucuronidation was induced by PB and PCN (4.9- and 2.5-fold of control, respectively). These studies suggest that several forms of UDP-GT activities, which differ in their ontogeny and inducibility patterns, are involved in the glucuronidation of F in vitro.
IICPS 2014 workshop keynote: Computing through failures and cyber attacks: Case for resilient smart power grid

Rapid proliferation of cyber physical systems (CPS) in our society makes them an attractive target for miscreants, in particular when CPS monitors and controls physical processes within a critical infrastructure such as power grid or water distribution. By integrating computation and physical processes in a tight control loop, CPS enables rapid response to changes in the controlled environment. However, regardless of how well a system is engineered, it is a matter of time for it to fail and hence, computing through failures and cyber-attacks becomes a norm rather than an exception. This talk first discusses challenges in achieving resilient smart cyber physical systems using examples from: (i) empirical studies on impact of failures/attacks on SCADA (Supervisory Control and Data Acquisition) systems used in power grid and (ii) data on real attacks on a commercial CPS. Then, we use an example of the SCADA deployed in the power grid, where a sophisticated attacker exploits system vulnerabilities and issues malicious control commands to drive remote facilities into an unsecure state without exhibiting any protocol-level anomalies. In order to detect such attacks, methods that combine system knowledge on both cyber and physical infrastructure in the power grid are needed to estimate execution consequences of control commands and thus, to reveal attacker's malicious intentions. We present an example method to address the challenge.
The pattern of recovery of erythropoiesis in heavily irradiated mice receiving transplants of fetal liver.

SummaryThe recovery of erythropoiesis in heavily irradiated mice receiving fetal liver was compared with that of mice receiving adult bone marrow. The number of cells was adjusted so that each group received a comparable number of cfu. Red cell production as judged by both iron incorporation and peripheral reticulocyte values began earlier in the fetal liver transplant than after adult bone marrow. Further, the extent of erythroid colonization of the bone marrow appeared greater in recipients of fetal tissue than adult. These differences in the recovery pattern suggest that stem cell regulation of fetal erythropoiesis differs from that of the adult.
Flow of informational RNA from cytoplasmic poly(A)-containing particles to polyribosomes in Artemia salina cysts at early stages of development

Abstract When Artemia salina cysts are incubated at 28°C in artificial seawater, the pool of cytoplasmic mRNA as measured by the [3H]poly(U) hybridization technique is depleted, and a parallel increase in the polysome bound mRNA is observed. The shift of informational RNA from subribosomal particles to polyribosomes occurs without a significant increase in the amount of poly(A)-containing RNA per embryo, at least during the first hours of development. In order to ascertain whether resumption of development is due mainly to utilization of preformed mRNA, the polypeptides synthesized in a wheat germ lysate under the direction of cyst cytoplasmic mRNA were compared with those obtained using polysomal mRNA from developed embryos (1 and 4 hr). The complex pattern of proteins synthesized in vitro was resolved into 70–80 radioactive spots by two-dimensional gel electrophoresis and was shown to be almost identical in unincubated and incubated cysts, except for a few novel spots. Our results do not exclude that early transcription of a few mRNA species could play a role in the activation of metabolic processes which occur when development is resumed.
Behçet‐type vasculopathy in a patient without the diagnostic features of Behçet disease

Behcet's disease is a multisystem inflammatory disorder which may involve the vascular system. The vasculopathy of Behcet's disease is distinctive among the vasculitides in that it involves both arteries and veins, and vessels of all sizes. Most published diagnostic criteria for Behcet's disease include the classic triad of orogenital ulceration and ocular inflammation. In this report, we describe a patient who had a vasculopathy fitting the Behcet's disease type, but who lacked the other characteristic or diagnostic features of Behcet's disease. This case illustrates an unusual presentation and natural history of a complex vasculitic disease.
Identifying spike-timing dependent plasticity in spike train models of synaptically-coupled neuronal ensembles.

Identifying plasticity in cortical neural ensembles is important in studying systems neuroscience to permit tracking the dynamics of biological cortical networks during learning and behavior. Recently, we proposed an algorithm to identify clusters of neurons that exhibit functional interdependency in local and global contexts across multiple time scales. In this paper, we examine the applicability of the algorithm to identify and track functional plasticity in a probabilistic point process model of integrate and fire neural network with time varying synaptic coupling. Three types of coupling between the neurons are considered: auto-inhibition, cross-inhibition, and excitation. A stimulus-dependent synaptic plasticity is induced randomly to mimic artificial sensory inputs. The results demonstrate that when the stimulus input duration increases such that new synaptic coupling occurs between otherwise uncoupled neurons, the algorithm correctly identifies the change in the circuit topology indicated by the number of clusters of functionally interdependent neurons and their labels. We report the clustering performance of the approach applied to simulated data with spontaneous activity as well as a stimulus driven activity across multiple trials.
MODULATION WAVELENGTH DEPENDENCE OF THE INTERDIFFUSION IN AMORPHOUS Si/Ge MULTILAYER FILMS

Compositionally modulated amorphous Si/Ge thin films with repeat lengths (wavelengths) between 4.8 nm and 5.83 nm have been prepared using ion beam sputtering. The interdiffusion coefficient was determined from the decrease in the (000) x-ray satellite intensities with annealing, and was found to be relatively large, so that it could easily be measured without crystallization occurring. The effect of copper and oxygen impurities was found to be negligible. The dependence of the interdiffusivity on the modulation wavelength is similar to that of an ordering system. The temperature and wavelength dependence in the range T = 550–630 K is described by Dλ = 1.47×10−10 m.s−1 exp(−1.6 eV/kT)(1−21.8/λ2(nm)). It is suggested that diffusion is governed by the breaking of one bond near a pre-existing dangling bond.
Dynamic VM migration: assessing its risks & rewards using a benchmark

Dynamic migration of virtual machines (VMs) across physical servers has the potential to increase the utilization of the servers and hence drive down the data center costs. However, IT practitioners are leery of using this capability for increasing resource utilization due to concerns about the impact of such migrations on the performance of the applications, particularly the response times seen by the users of the applications. The relative newness to the industry of many of the tools used to automate VM migrations for resource utilization; data from researchers; as well as the recommendations from some analysts justify such caution and warrant quantifying the risks as well as potential rewards before deciding how aggressively this capability should be adopted. This paper will discuss the requirements for a benchmark to be used for such quantification. We will also discuss adaptations to SPECvirt_sc2010, originally developed as a single server benchmark, to meet these requirements. We will also present risk-reward quantifications obtained using this benchmark for a simple case and the broader use of the benchmark for other cases.
Effects of seasonality and farm proximity to forest on Hymenoptera in Tarrazú coffee farms

The management of natural vegetation and forested habitat within agricultural areas can be important for bolstering ecosystem services. In coffee agro-ecosystems, proximate forested habitat can provide resources for Hymenoptera that contribute to crop pollination and biological control of pests. We conducted a field study on 12 coffee farms in the highlands of Tarrazu, Costa Rica over a period of 3 years during both dry (flowering) and rainy (nonflowering) seasons. We compared the abundance of Hymenoptera observed around coffee plants on farms that were either isolated from or immediately adjacent to substantial forest habitat. Our results demonstrated a seasonally dependent response, with higher numbers of Hymenoptera observed in adjacent farms than in isolated farms during dry seasons, but no difference in the numbers in isolated farms and adjacent farms during rainy seasons. We discuss the implications of these findings with respect to the potential pollination and biological control benefits associate...
Formal design of communication checkers for ICCP using UPPAAL

Vulnerabilities in key communication protocols that drive the daily operations of the power grid may lead to exploits that could potentially disrupt its safety-critical operation and may result in loss of power, consequent financial losses, and disruption of crucial power-dependent services. This paper focuses on the Inter Control Center Communications Protocol, (ICCP), which is the protocol used among control centers for data exchange and control. We discuss use of UPPAAL in formal modeling of portions of ICCP. Specifically, we present an iterative process and framework for the design and formal verification of tailored checking mechanisms that protect resource-exhaustion vulnerabilities in the protocol standard from attacks and exploits. We discuss insights we gained and lessons we learned when modeling the protocol functionalities and running the UPPAAL model checker to prove critical security and safety properties, and we discuss the overall success of this approach.
Combination Therapy with MK-801 and α-Phenyl-tert-butyl-nitrone Enhances Protection against Ischemic Neuronal Damage in Organotypic Hippocampal Slice Cultures

Abstract In vitrocombinations of MK-801, an NMDA receptor antagonist, and α-phenyl-tert-butyl-nitrone (PBN), a free radical scavenger, have been tested for possible additive neuroprotective effects against anoxia/hypoglycemia (Ax/Hg)-induced neuronal damage. Rat organotypic hippocampal slice cultures were exposed to Ax/Hg for different lengths of time to vary the severity of the insult. Cell death (CD) was assessed using propidium iodide fluorescence and expressed as a percentage of the total neuronal cells present. Pretreatment with PBN alone (500 μM) provided significant protection against moderate ischemic injury and reduced CD from 65% in controls to 2% in the treated group (P
Spatio-temporal variation of periphyton biomass and accumulation in a temperate spring-fed stream

Spatio-temporal variation of plant populations often can demonstrate synchronous patterns, particularly within highly connected landscapes. Periphyton biomass (chlorophyll a) and net accumulation were measured at five sites in a spring-fed fourth-order stream located in central Pennsylvania with a mixed land-uses watershed (Spring Creek, USA) to characterize longitudinal variation within the stream. Samples were collected at three-week intervals over one year to describe seasonal patterns of periphyton biomass and net production (n = 17 per site). Spring Creek periphyton biomass and net accumulation increased dramatically from the headwaters to downstream (range 10–1,000 mg/m2). The downstream reaches had exceptionally large algal biomass (chlorophyll a > 300 mg/m2) and potential for rapid turnover. Varying degrees of seasonality were observed among the sites, with upstream sites showing more temporal variation but no distinct seasonal pattern. Despite this, large-scale disturbances within the watershed seem to promote synchrony among sites throughout the stream as reflected by close correlations in chlorophyll values (Pearson correlation coefficient r > 0.50).
Effects of novelty‐reducing preparation on exploratory behavior and cognitive learning in a science museum setting

The purpose of this study was to examine the relationships between (a) novelty and exploratory behavior, (b) novelty and cognitive learning, and (c) exploratory behavior and cognitive learning in science museums. Sixty-four sixth-grade public school students participated in a posttest-only control group design. The control group received a treatment designed to decrease the novelty of a field trip setting through a vicarious exposure while the placebo group received an informative but not novelty-reducing treatment. Both groups then visited the field site where they were videotaped. Statistical analyses were conducted on both dependent variables with socioeconomic status and academic achievement as covariates, novelty-reducing preparation as the independent variable, and gender as moderator variable. Exploratory behavior was shown to be positively correlated with cognitive learning. Significant differences were detected for exploratory behavior. For both dependent variables, gender by treatment group interaction was significant with novelty-reducing preparation shown to be highly effective on boys but having no effect on girls.
Effects of concurrent access to a single concentration or multiple concentrations of ethanol on the intake of ethanol by male and female periadolescent alcohol-preferring (P) rats

Abstract The objectives of this study were to assess the effects of access to different concentrations of ethanol and sex of the animal on ethanol consumption during periadolescence [postnatal days (PNDs) 30–60] in alcohol-preferring (P) rats. On PND 28, female and male P pups were single housed in hanging stainless steel cages with ad libitum access to water and food. Beginning on PND 30, the rats were also given access to either a single concentration [15% volume/volume (vol./vol.)] or multiple concentrations [10%, 20%, and 30% (vol./vol.)] of ethanol. Differences between sex (male vs. female) and ethanol conditions (single concentration vs. multiple concentrations), for the average amount of ethanol consumed for each week (starting on PND 33) of access, were examined. Analyses of the data for ethanol drinking revealed significant ( P
Neuronal change: Compensatory acclimation of the contribution of an electrogenic pump to the resting potential

1. The resting potential of the lateral giant neuron in the buccal ganglia of the fresh water snailHelisoma trivolvis becomes more negative with an increase in temperature (Fig. 1). 2. The degree to which the resting potential varies over 3 to 30° C is dependent upon the previous acclimation temperature of the experimental subject (Fig. 6A). 3. Temperature acclimation (at 5 and 25° C) partially compensates for the temperature dependence of the resting potential. 4. The resting potential can be dissected into ionic permeability and metabolic pump components by the use of ouabain, a specific inhibitor of sodium pump activity (Fig. 2). The contribution of the sodium pump to the resting potential is found to be the main component responsible for the resting potential acclimation (Fig. 6B). 5. Such compensatory temperature acclimation would enable the lateral giant neuron to maintain its function as effector of salivary gland activity over a wide range of environmental temperatures.
Parental Conflict During Divorce as an Indicator of Adjustment and Future Relationships: A Retrospective Sibling Study

We assessed parental conflict during divorce and divorce stories, quality of relationship among siblings during divorce, and attitudes about romantic relationships later in life. Thirty-two undergraduate female participants (18–23 years old) whose parents divorced during the 7 to 13 year old age range completed the Sibling Relationship Questionnaire and an adapted version of the Adult Divorce and Sibling Relationship Interview. Older sibling participants endorsed higher levels of dominance toward younger siblings, more caretaking behavior, and higher levels of parental conflict than younger siblings. Analyses revealed overt conflict exposure related to less confidence in relationship sustainability as young adults. Content analysis demonstrated relationship formation problems and trust in partners.
Co-Occurring Presenting Problems in African American College Clients Reporting Racial Discrimination Distress

Ethnic minority students’ perceptions of racism may be associated with a host of secondary emotional, interpersonal, and academic difficulties that can nevertheless be the chief reason these students seek treatment at a counseling center. This study examined archival data from the Presenting Problems Checklist completed by 1555 African American clients seen at the counseling centers of 7 predominantly White Midwestern universities. Findings of ordinal correlations (Kendall’s tau-b) suggested that, for both men and women, perceived racial discrimination was associated with a broad range of co-occurring presenting problems, including academic (e.g., performance anxiety, adjustment to university), interpersonal (dating concerns), psychological/emotional (perfectionism, depression, suicide risk), and existential concerns (confusion in beliefs/values, spiritual/religious concerns). Separate analyses conducted for men and women suggested some sex differences; for example, irritability/anger had the strongest correlation with perceived discrimination for men, whereas for women the strongest correlation was for procrastination. Awareness of the full range of likely sequelae of racial discrimination could improve psychologists’ assessment and intervention efforts and lead to a better understanding of how perceived racism affects students’ functioning in multiple areas.
On staggering techniques and the non-staggered Z-grid scheme

A new staggered-grid momentum-based numerical scheme that is equivalent to the non-staggered Z-grid scheme for linearized shallow water equations is proposed. Utilizing the equivalence between the staggered/non-staggered discrete vorticity-divergence fields and the discrete velocity fields, the equivalent vorticity-divergence formulations of some of the existing staggered-grid schemes, namely the C-grid, D-grid, CD-grid, and co-volume schemes are derived. The strengths and weaknesses of these schemes are discussed from the perspectives of their new formulations.
Efavirenz-mediated induction of omeprazole metabolism is CYP2C19 genotype dependent

Efavirenz increases CYP2C19- and CYP3A-mediated omeprazole metabolism. We hypothesized that CYP2C19 and CYP2B6 genetic polymorphisms influence the extent of induction of omeprazole metabolism by efavirenz. Healthy subjects (n=57) were administered a single 20 mg oral dose of omeprazole on two occasions: with a single 600 mg efavirenz dose; and after a 17-day treatment with efavirenz (600 mg per day). DNA was genotyped for CYP2C19*2, *3 and *17 alleles and CYP2B6*6, *4 and *9 alleles using Taqman assays. Omeprazole, its enantiomers and metabolites were measured by liquid chromatography/tandem mass spectrometry. Our results showed that efavirenz increased omeprazole clearances in all CYP2C19 genotypes in non-stereoselective manner, but the magnitude of induction was genotype dependent. Metabolic ratios of 5-hydroxylation of omeprazole were reduced in extensive and intermediate metabolizers of CYP2C19 (P<0.05). No significant associations were observed between CYP2B6 genotypes and induction by efavirenz on omeprazole metabolism. Our data indicate how interplays between drug interactions and CYP2C19 genetic variations may influence systemic exposure of CYP2C19 substrates.
The effects of noncontingent and self-administered cytisine on body weight and meal patterns in male Sprague-Dawley rats.

Abstract Rationale Increased appetite and weight gain after cessation are deterrents for quitting smoking. Pharmacotherapies that can reduce this weight gain in ex-smokers would be invaluable, and yet are not well studied in this context. Objective To examine the effects of extended daily exposure to intravenous cytisine, an alpha4beta2 nAChR partial agonist used for smoking cessation in some European countries, on body weight and patterns of food intake in rats. Methods In the first experiment, programmed infusions of cytisine were administered over 15 h per day. Food intake, meal patterns, and weight change were examined relative to a vehicle-infused group during treatment, and in a post-cytisine phase. The second experiment examined the effects of cytisine on food intake, meal patterns, and weight change when substituted for nicotine in a self-administration protocol. Rats self-administered nicotine and cytisine during alternating four day periods, and changes in body weight, drug infusions, and meal patterns were compared between drugs and during an extinction phase. Results In the first experiment, cytisine-treated rats ate less and gained less weight than those that received the vehicle. This occurred primarily by a reduced frequency of meals. In the 12 day post-cytisine phase, animals maintained a lower body weight relative to controls throughout. In the second experiment, total pellet intake increased during cytisine substitution relative to nicotine and animals self-administered cytisine significantly less than nicotine. However, cytisine substitution maintained decreases in food intake and weight gain compared to baseline via decreases in total pellet intake and meal size. Conclusion Cytisine administration results in decreased weight gain and changes in meal patterns dependent upon mode and pattern of administration and a previous history of nicotine administration.
Using Ethical Reasoning to Amplify the Reach and Resonance of Professional Codes of Conduct in Training Big Data Scientists

The use of Big Data—however the term is defined—involves a wide array of issues and stakeholders, thereby increasing numbers of complex decisions around issues including data acquisition, use, and sharing. Big Data is becoming a significant component of practice in an ever-increasing range of disciplines; however, since it is not a coherent “discipline” itself, specific codes of conduct for Big Data users and researchers do not exist. While many institutions have created, or will create, training opportunities (e.g., degree programs, workshops) to prepare people to work in and around Big Data, insufficient time, space, and thought have been dedicated to training these people to engage with the ethical, legal, and social issues in this new domain. Since Big Data practitioners come from, and work in, diverse contexts, neither a relevant professional code of conduct nor specific formal ethics training are likely to be readily available. This normative paper describes an approach to conceptualizing ethical reasoning and integrating it into training for Big Data use and research. Our approach is based on a published framework that emphasizes ethical reasoning rather than topical knowledge. We describe the formation of professional community norms from two key disciplines that contribute to the emergent field of Big Data: computer science and statistics. Historical analogies from these professions suggest strategies for introducing trainees and orienting practitioners both to ethical reasoning and to a code of professional conduct itself. We include two semester course syllabi to strengthen our thesis that codes of conduct (including and beyond those we describe) can be harnessed to support the development of ethical reasoning in, and a sense of professional identity among, Big Data practitioners.
Impact of Parent Education Groups on Family Environment.

Abstract This study assesses the nature of change over time in the family environment of parents attending Adlerian parent education groups and determines whether these groups foster democratic parental attitudes and behavior toward children.
Comparison of characteristics of future myocardial infarctions in women with baseline high versus baseline low levels of high-sensitivity C-reactive protein.

High-sensitivity C-reactive protein (hs-CRP) has previously been shown to be an independent predictor for the development of cardiovascular disease. However, little is known about the association between hs-CRP and the severity of cardiovascular events that occur. This study compared characteristics of incident myocardial infarctions (MIs) in 40 initially healthy women with very high baseline hs-CRP levels (>7.5 mg/L) with infarctions in 40 women with very low hs-CRP levels (≤1 mg/L). At baseline, very high hs-CRP was associated with a clinical diagnosis of hypertension, higher body mass index, lower high-density lipoprotein, and higher triglycerides. Our analysis found that the 2 study groups had similar proportions of ST-segment elevations on electrocardiograms, peak cardiac enzyme levels, postinfarct left ventricular function, and burden of coronary atherosclerosis seen on angiography. However, subjects with very high hs-CRP levels developed infarctions significantly sooner than those with very low hs-CRP levels (median time to event 4.45 vs 6.64 years, respectively, p
Selection of gamma delta T cells with canonical T-cell antigen receptors in fetal thymus.

Abstract Two gamma delta T-cell subsets that are generated in the fetal thymus and selectively localize in epidermis and uterus-vagina-tongue epithelia exhibit remarkable homogeneity in their (T-cell) antigen receptors (TCR). In the present study, we show that cells expressing the canonical gamma delta TCR are also generated in fetal thymus organ cultures. Treatment of these cultures with anti-gamma delta TCR antibodies did not prevent gamma delta T-cell development but led to a striking increase in the frequency of noncanonical in-frame sequences. We conclude from this finding that cells expressing the canonical TCR accumulate selectively as a result of TCR-mediated positive selection in the fetal thymus.
HEMODYNAMIC EFFECTS OF CHRONIC PARTIAL URETERAL OBSTRUCTION (CPUO) IN THE NEWBORN GUINEA PIG

To evaluate the hemodynamic effects of CPUO and reduced renal mass in the neonate, 38 guinea pigs were subjected to left (L) CPUO within the first 48 h of life, 17 of which underwent concurrent right (R) uninephrectomy (NX). Eight sham-operated and 8 NX animals were controls. At 23±2 days of age, L renal blood flow (RBF, ml/min), filtration fraction (FF, %), glcmerular filtration rate (GFR, ml/min) and percent of RBF to the outer third of renal cortex (OCRBF) were measured using microsphere and clearance techniques. Resulting hydronephrosis was variable in animals with CPUO, and each group was divided into Mild and Severe obstruction for ureteral diameter < 3 mm and ≥3 mm respectively. Results were as follows (mean ± SE, *p <0.05 vs Control):
From city club to nation state: business networks in American political development

Although cities were given no role in the constitutional order of the United States, the new nation posed the same potential threats to the accumulation of capital and wealth as European monarchs posed to long-powerful urban centers. In mobilizing for self-protection and advancement, American business developed new practices and discourses of citizenship that sustained a central role for the community as the locus of social provision. The strategy combined opportunity-hoarding through restricted membership in civic groups and obligation-hoarding through the alignment of diverse networks of voluntarism with this civic core. The linkage of business interests to this hybrid charitable-civic configuration constituted a source of resistance to nationalizing tendencies driven by demands for social protection. This alternative model of social provision and civic organization sustained a distinctive pattern of political membership and state development. By fiercely defending the capacity of privately governed civic networks to provide substantial social support, this history of business influence through community organizations lives on in the partial and fragmented character of the American welfare state.
Abstract 3077: Nek3/Vav2 modulation of the expression of genes involved in breast cancer pathogenesis

The pituitary hormone prolactin (PRL) is generally recognized for its role in breast growth and differentiation; however, a role for PRL in the pathogenesis of breast cancer has emerged from epidemiological studies and basic science research using both human breast cancer cells and animal models. Activation of the prolactin receptor (PRLr) by PRL contributes to the growth, survival, and motility of human breast cancer cells. PRLr stimulation by PRL results in the activation of multiple signaling complexes including serine/threonine kinase Nek3 and guanine nucleotide exchange factor Vav2. Nek3 is necessary for the activation of Vav2, and Nek3 knockdown results in decreased cytoskeletal re-organization, cell motility, and cell invasion in PRL-stimulated human breast cancer cells. The overexpression of a kinase inactive form of Nek3 in human breast cancer cells results in increased apoptosis, indicating a pro-survival function for Nek3. Furthermore, Nek3 expression is increased in malignant vs. normal human breast tissue. These data make the Nek3/Vav2 complex an interesting target for novel breast cancer therapeutics. To this end, a greater understanding of the role of Nek3/Vav2 in breast cancer pathogenesis is necessary. We hypothesized that the Nek3/Vav2 complex modulates PRL-driven expression of genes involved in the pathogenesis of breast cancer. In these studies, luciferase assays and quantitative PCR were used to evaluate the effects of gain- or loss-of-function of Nek3/Vav2 on the expression of CISH (cytokine-inducible SH2-containing protein). Gain- or loss-of-function of Nek3/Vav2 was found to alter the expression of CISH in response to PRL in both MCF7 and T47D human breast cancer cell lines. The CISH promoter has 4 binding sites for the transcription factor Stat5, which is known to contribute to malignant transformation and tumor growth in breast cancer. Luciferase assay showed that gain- or loss-of-function of Nek3 was also found to alter the activation of a reporter construct containing the lactogenic hormone response element which consists of six tandem Stat5 DNA-binding elements. This suggests that Nek3/Vav2 modulates the PRL-driven expression of CISH by regulating activity of the transcription factor Stat5. Gain- or loss-of-function of Nek3/Vav2 was not found to alter the subcellular localization of Stat5 in response to PRL. Ongoing studies are examining the mechanism of Nek3/Vav2 modulation of PRL-responsive gene expression in breast cancer cells. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3077. doi:1538-7445.AM2012-3077
Die Auflösungsgeschwindigkeiten einiger Metalle in Jodlösungen und ihre Beziehung zur Diffusionstheorie

1. Die Losungsgeschwindigkeiten von Cadmium; Eisen, Nickel und Kobalt in ahnlichen Jodlosungen sind gemessen worden und haben sich als gleich erwiesen. Dies Ergebnis erweitert die Liste der Metalle, die sich nach einer fruheren Untersuchung mit gleicher Geschwindigkeit losen, von 5 auf 8, namlich Hg, Cu, Ag, Zn, Cd, Fe, Ni, Co.
Computer simulations to model Mendel's laws on inheritance in computational biology

The present paper uses the computational power of Microsoft Excel 2007 software system to perform interactive simulations for advanced undergraduate and first year graduate students in biology, biochemistry, biophysics, microbiology and medicine in college and university classroom setting. We developed the required computer algorithm, which uses a built-in pseudo-random number generating function, to computer model two basic Mendel's Laws of heredity in evolution for plant and animal species. The results of simulations corroborate the experimental observations of Mendel's research on inheritance in Pisum hybrid species.
Many-body perturbation theory applied to hydrogen fluoride

Abstract Pair contributions to the electronic correlation energy of the hydrogen fluoride molecule are computed using many-body perturbation theory (MBPT) with a basis set of Slater orbitals on both atomic centers. Summation of all two-body diagrams through third order gives ≈ 93% of the total correlation energy at the equilibrium internuclear separation. However, including certain higher-order effects, by means of denominator shifts, gives a correlation energy of −0.3691 hartree, or ≈ 97% of the correlation energy.
A Stopped Flow Transient Kinetic Analysis of Substrate Binding and Catalysis in Escherichia coli d-3-Phosphoglycerate Dehydrogenase

Pre-steady state, stopped flow analysis of Escherichia coli d-3-phosphoglycerate dehydrogenase was performed by following the fluorescence of protein tryptophan and the fluorescence resonance energy transfer from protein tryptophan to bound NADH. The results indicate that binding of substrates is ordered, with coenzyme, NADH, binding first. Furthermore, the analysis indicated that there are two sets of sites on the tetrameric enzyme that can be differentiated by their kinetic behavior. NADH binding was consistent with an initial binding event followed by a slow conformational change for each site. The slow conformational change is responsible for the apparent tight binding of NADH to the apoenzyme but is too slow to participate in the catalytic cycle when the enzyme is rapidly turning over. Subsequent binding of the substrate, α-ketoglutarate, was characterized by a rapid equilibrium binding event followed by a conformational change for each site. Catalysis in the direction of NAD+ reduction showed a distinct burst of activity followed by a slow rate of turnover, indicating that the rate-limiting step is after hydride transfer. Catalysis in the direction of NADH oxidation did not display burst kinetics, indicating that the rate-limiting step is at or before the hydride transfer step. The burst data indicated that the rate of NAD+ reduction (3.8 s–1) is similar to the kcat of the enzyme (2–3 s–1) in that direction. However, analysis of the reaction with deuterated NADH failed to show an effect on the velocity of the reaction with a VH/VD = 1.07 ± 0.06. None of the other rates determined by stopped flow analysis could account for the kcat of the enzyme in either direction (forward kcat = 0.01 s–1, reverse kcat = 2–3 s–1), suggesting that the rate-limiting step in both directions is a conformational change in the enzyme that is not detected optically.