cssi/SciSciGPT-SciSciNet huggingface dataset:
Effects of thioridazine on transmembrane potential and contractile characteristics of guinea pig hearts.

Abstract The effects of thioridazine on intrinsic rate and contractile characteristics of isolated intrinsically beating atria, and the transmembrane potential and contractile characteristics of electrically stimulated strips of right ventricle were determined. Increasing concentrations of thioridazine altered intrinsic rates, transmembrane potentials, and contractile characteristics similar to that reported for quinidine. Parenteral pretreatment of guinea pigs with 30 mg/kg thioridazine 30 min and 24 hr prior to in vitro experiments modified norepinephrine-induced changes in tissue characteristics. Parenterally administered thioridazine also decreased the incidence of norepinephrine-induced arrythmias by 30%. Thioridazine altered cardiac function by decreasing intrinsic rhythmicity, prolonging the plateau and duration of action potentials, and depressing contractility.
Combined compression and denoising of images using vector quantization

Compression of a noisy source is usually a two stage problem, involving the operations of estimation (denoising) and quantization. A survey of literature on this problem reveals that for the squared error distortion measure, the best possible compression strategy is to subject the noisy source to an optimal estimator followed by an optimal quantizer for the estimate. What we present in this paper is a simple but sub-optimal vector quantization (VQ) strategy that combines estimation and compression in one efficient step. The idea is to train a VQ on pairs of noisy and clean images. When presented with a noisy image, our VQ-based system estimates the noise variance and then performs joint denoising and compression. Simulations performed on images corrupted by additive, white, Gaussian noise show significant denoising at various bit rates. Results also indicate that our system is robust enough to handle a wide range of noise variations, while designed for a particular noise variance.
Allylamine cardiovascular toxicity: VI. subcellular distribution in rat aortas

The cardiovascular toxin allylamine (3-aminopropene) has been shown to concentrate in elastic and muscular tissues. In this study the 14C-moiety of [14C]allylamine was traced in aortas of adult Sprague-Dawley rats after intravenously injecting 30 microCi of [14C]allylamine (spec. act. = 0.4 mCi/mM). At 5, 10, 15 and 20 min after injection 33.3-29.8% of the 14C-moiety was sequestered in aortas; at 30 min 16.8% was still present. Subcellular fractionation of the postnuclear supernatant by isopycinic centrifugation in sucrose demonstrated that 5 min after administration of [14C]allylamine, the 14C-moiety displayed a modal density peak of 1.20 g/ml. Similar activities were observed up to 30 min exposure. This modal density was similar to the distribution pattern of mitochondria based on analysis of malate dehydrogenase activities. As early as 20 min post-exposure, mitochondrial malate dehydrogenase activities of aortic mitochondria decreased, while cytosolic malate dehydrogenase activities increased, suggesting mitochondrial membrane perturbation. We suggest that the subcellular site for allylamine injury to the aorta is the mitochondrion.
Charge exchange collisions of deuterium in a rubidium vapor target

Abstract The equilibrium fraction of D − ions formed when D + ions are incident on a Rb vapor target has been measured for energies of the incident ion in the range 1.1–40 keV. The equilibrium fraction of D − ions emerging from a Rb target is 19% when D + ions with an energy of 1.1 keV are incident. The equilibrium fraction decreases as the energy of the incident ion increases in the energy range of 1.1–40 keV. The charge transfer cross section σ +0 for the reaction D + + Rb → D 0 + Rb + is also reported. The cross section is 1.14 × 10 −14 cm 2 when the incident D + ion has an energy of 1.5 keV, and the cross section falls rapidly with increasing energy reaching the value 9.4 × 10 −16 cm 2 at 40 keV.
Dihomogammalinolenic acid, but not eicosapentaenoic acid, activates washed human platelets

Abstract Dihomogammalinolenic acid (2.5–20 μM) added to suspensions of washed human platelets induces platelet shape change and the formation of 1,2-diacylglycerol and phosphatidic acid, indicating the activation of phospholopase C. It also stimulates the phosphorylation of a 40 kDa protein, indicating the activation of protein kinase C. Dihomogammalinolenic acid is converted mainly to 12-hydroxyheptadecadienoic acid and to a smaller extent to prostaglandin E 1 and thromboxane B 1 . Small quantities of the lipoxygenase product 12-hydroxyeicosatrienoic acid are also observed. Indomethacin, by blocking platelet cyclooxygenase, prevents the activation of phospholipase C, protein kinase C, and platelet shape change induced by dihomogammalinolenic acid. Compound UK 38485, a specific thromboxane synthetase inhibitor, does not block platelet activation induced by dihomogammalinolenic acid. The results indicate that endoperoxides derived from dihomogammalinolenic acid, such as prostaglandin G 1 or prostaglandin H 1 , may be responsible for the stimulation of phospholipase C and protein kinase C, and for the induction of platelet shape change. Eicosapentaenoic acid does not activate platelets and is poorly metabolized by platelet cyclooxygenase and lipoxygenase. Eicosapentaenoic acid is a better inhibitor of platelet activation induced by various agonist in washed platelets than dihomogammalinolenic acid. Eicosapentaenoic acid and dihomogammalinolenic acid are, however, equally effective in inhibiting aggregation induced by collagen in platelet-rich plasma. We suggest that eicosapentaenoic acid might be a better antithrombotic agent than dihomogammalinolenic acid.
A group-based brief intervention for surgery patients with high-risk substance use

Abstract Objective This study examined the feasibility and efficacy of a psychosocial intervention to address high-risk substance use in patients scheduled for elective surgery. Method A group-format intervention, based on motivational interviewing principles, was provided prior to elective surgery to 107 participants with at-risk substance use, identified using the Alcohol Use Disorders Identification Test — Condensed (AUDIT-C) and self-report of illicit drug use. Patient satisfaction was assessed with an anonymous survey. Within-subject comparisons of substance use at baseline and at a postoperative follow-up evaluation were conducted. A control group of 67 surgery patients reporting high-risk substance use completed baseline assessments and received usual care. Medical outcomes and measures of utilization were compared between groups. Results Patient satisfaction with the brief intervention was high. A paired t test comparing average pre- and post-AUDIT-C scores showed significant reduction in substance use postsurgery ( t =9.94, P =.000), and participants reported intention to maintain reduced substance use levels. Between-group analyses revealed no significant differences in medical complications or utilization. Conclusion Findings suggest that a group-based intervention for substance use disorder can be implemented as part of preoperative care and may contribute to decreased substance use prior to and following surgery. Further work is needed to identify methods to reduce adverse medical outcomes in surgical patients.
Structure of vapor-phase deposited Al-Ge thin films and Al-Ge intermediate layer bonding of Al-based microchannel structures

Al-based high-aspect-ratio microscale structures (HARMS) are basic building blocks for all-Al microdevices. Bonding of Al-based HARMS is essential for device assembly. In this paper, bonding of Al-based HARMS to flat Al plates using Al-Ge thin film intermediate layers is investigated. The structure of sputter codeposited Al-Ge thin films was studied by high-resolution transmission electron microscopy as a function of the average film composition. The structure of the interface region between Al-based HARMS bonded to flat Al plates is studied by combining focused ion beam sectioning and scanning electron microscopy. An extended bonding interface region, ∼100 μm in width, is observed and suggested to result from liquidus/solidus reactions as well as diffusion of Ge in solid Al at the bonding temperature of 500 °C. The extended interface region is suggested to be beneficial to Al-Al bonding via Al-Ge intermediate layers.
Characterization of microvascular endothelial cells isolated from the dermis of adult mouse tails

Dermal microvascular endothelial cells (DMECs) play an important role in physiological and pathophysiological processes such as wound healing, cell differentiation, antigen-presentation, inflammation, tumor metastasis, and diabetes. The study of these processes requires a suitable and accessible in vitro model, such as murine DMECs (mDMECs). However, since these cells are difficult to isolate and propagate, some of their properties are not fully characterized. We isolated these cells from C57BL/6J adult mouse tail skin and purified them using magnetic sorting. Then, we tested several culture conditions and oxygen concentrations for mDMEC growth and propagation. After obtaining optimal culture conditions, we characterized the expression of EC markers and compared such expression with an established murine microvascular EC line (EOMA). Our results indicate that mDMECs isolated from mouse tails expressed most of the characteristic EC markers such as von Willebrand Factor (vWF), CD31, Tie1, Tie2, ANGPT1, ANGPT2, FLK-1, FLT-1, and VEGF-A. Further characterization demonstrated that these cells also expressed proteins involved in organogenesis such as bone morphogenetic proteins-2, -4 (BMP-2/-4), and their receptor (BMPR1A). Surprisingly, higher expression of vWF, ANGPT1, and BMP-2 was observed in mDMECs compared to EOMA cells. For mDMEC in vitro propagation, we found a twofold increase in cell proliferation in cells that grew at 1% O(2) compared to those cells that grew at standard 20% O(2.) Therefore, the method described herein for mDMECs isolation and propagation allowed us to analyze in more detail their biological properties that can be relevant for the study of pathological processes using mouse models.
“Infatuated Barbarians as They Are:” Pro-slavery Challenges to the First Amendment in the 1830s, Mob Violence, and Associated Links

(2011). “Infatuated Barbarians as They Are:” Pro-slavery Challenges to the First Amendment in the 1830s, Mob Violence, and Associated Links. Free Speech Yearbook: Vol. 45, No. 1, pp. 95-109.
Studies on catechol-O-methyltransferase in rat brain using two-dimensional gel electrophoresis

The presence of catechol-O-methyltransferase (COMT) in the rat brain was studied using a combination of two-dimensional gel electrophoresis (2-DE), protein blotting and a specific antiserum. Two major immunoreactive proteins were identified-one with mol. wt 23 kdalton and an isoelectric point of 5.2, the other of mol. wt 25 kdalton and an isoelectric point of 5.1. In addition, multiple lower molecular weight immunoreactive proteins, possibly corresponding to breakdown products of the enzyme, were also detected. The 23 kdalton form of COMT, which is probably the soluble form of the enzyme, is a major protein visible on silver-stained 2-D gels of rat brain. In contrast, the other proteins recognized by the antiserum were not detected by the silver stain. These results demonstrate, using 2-DE, that at least two distinct forms of catechol-O-methyltransferase are present in rat brain. In addition, since one of these proteins is stained by silver, these results also serve to identify another protein visible on 2-D electrophoretograms of rat brain.
Splenic arteriovenous fistula. A rare lesion causing bleeding esophageal varices, ascites, and diarrhea

We report the case of a 39-year-old woman with portal hypertension caused by a splenic arteriovenous fistula that was diagnosed by Doppler ultrasound and splenic arteriography. She presented with esophageal variceal hemorrhage and was initially treated with sclerotherapy. Ascites and secretory diarrhea then developed. At laparotomy portal pressure was 60 cm H2O but fell to 26 cm H2O after the fistula was resected with a splenectomy. All symptoms disappeared shortly thereafter, and the patient has remained well for the past two years.
CHILD SEXUAL ABUSE IN THE CATHOLIC CHURCH How Situational Crime Prevention Strategies Can Help Create Safe Environments

Research on child sexual abuse often focuses on offenders, particularly on explanations of the etiology and maintenance of their abusive behavior. A recent study by Smallbone and Wortley suggests, ...
Addressing Parents’ Concerns: Do Vaccines Cause Allergic or Autoimmune Diseases?

Anecdotal case reports and uncontrolled observational studies in the medical literature claim that vaccines cause chronic diseases such as asthma, multiple sclerosis, chronic arthritis, and diabetes. Several biolog- ical mechanisms have been proposed to explain how vaccines might cause allergic or autoimmune diseases. For example, allergic diseases might be caused by pre- vention of early childhood infections (the "hygiene hy- pothesis"), causing a prolongation of immunoglobulin E-promoting T-helper cell type 2-type responses. How- ever, vaccines do not prevent most common childhood infections, and large well-controlled epidemiologic stud- ies do not support the hypothesis that vaccines cause allergies. Autoimmune diseases might occur after immu- nization because proteins on microbial pathogens are similar to human proteins ("molecular mimicry") and could induce immune responses that damage human cells. However, wild-type viruses and bacteria are much better adapted to growth in humans than vaccines and much more likely to stimulate potentially damaging self- reactive lymphocytes. Consistent with critical differences between natural infection and immunization, well-con- trolled epidemiologic studies do not support the hypoth- esis that vaccines cause autoimmunity. Flaws in proposed biological mechanisms that explain how vaccines might cause chronic diseases are consistent with the findings of many well-controlled large epide- miologic studies that fail to show a causal relationship. Pediatrics 2003;111:653- 659; vaccines, vaccine safety, asthma, allergies, multiple sclerosis, diabetes, chronic ar- thritis.
High-Breakdown-Voltage GaN Vertical Schottky Barrier Diodes with Field Plate Structure

Gallium nitride (GaN) vertical Schottky barrier diodes (SBDs) with a SiNx field plate (FP) structure on low-dislocation-density GaN substrates have been designed and fabricated. We have successfully achieved the SBD breakdown voltage (Vb) of 680V with the FP structure, in contrast to that of 400V without the FP structure. There was no difference in the forward current-voltage characteristics with a specific on-resistance (Ron) of 1.1mcm2. The figure of merit V2b/Ron of the SBD with the FP structure was 420MWcm-2. The FP structure and the high quality drift layers grown on the GaN substrates with low dislocation densities have greatly contributed to the obtained results.
Retinal neuroprotection by growth factors: a mechanistic perspective.

For more than a decade it has been known that certain growth factors inhibit apoptosis in genetically determined and experimental models of inner and outer retinal degeneration. The molecular mechanisms underlying these protective effects and the signaling that supports the survival of photoreceptors and retinal ganglion cells in these models have recently come under more in depth investigation. This paper reviews our current understanding of the balance of pro- and antiapoptotic signals that determine cell fate in the retina and how the activation of key signal transduction pathways by specific classes of neurotrophins protects retinal neurons.
Inhibitory Actions Unified by Network Integration

Cortical function is regulated by a strikingly diverse array of local-circuit inhibitory neurons. We evaluated how optogenetically activating somatostatin- and parvalbumin-positive interneurons subtractively or divisively suppressed auditory cortical cells' responses to tones. In both awake and anesthetized animals, we found that activating either family of interneurons produced mixtures of divisive and subtractive effects and that simultaneously recorded neurons were often suppressed in qualitatively different ways. A simple network model shows that threshold nonlinearities can interact with network activity to transform subtractive inhibition of neurons into divisive inhibition of networks, or vice versa. Varying threshold and the strength of suppression of a model neuron could determine whether the effect of inhibition appeared divisive, subtractive, or both. We conclude that the characteristics of response inhibition specific to a single interneuron type can be "masked" by the network configuration and cellular properties of the network in which they are embedded.
Observer-based output feedback control of discrete-time Lur'e systems with sector-bounded slope-restricted nonlinearities

Many well studied classes of dynamical systems such as actuator-constrained linear systems and dynamic artificial neural networks can be written as discrete-time Lur'e systems with sector-bounded and/or slope-restricted nonlinearities. Two types of observer-based output feedback control design methods are presented and analyzed with regard to robustness to model uncertainties and insensitivity to output disturbances. The controller designs are formulated in terms of linear matrix inequalities (LMIs) that are solvable with standard software. The design equations are illustrated in numerical examples.
Microstructure of Trabecular Bone in a Mouse Model for Down Syndrome

Down syndrome (DS) is caused by trisomy of human chromosome 21 (Hsa21) and results in a suite of dysmorphic phenotypes, including effects on the postcranial skeleton and the skull. We have previously demonstrated parallels in the patterns of craniofacial dysmorphology in DS and in the Ts65Dn mouse model for DS. The specific mechanisms underlying the production of these changes in craniofacial shape remain unknown. High-resolution computed tomography scan data were collected for the presphenoid bone of euploid and aneuploid mice. Three-dimensional morphometric parameters of trabecular bone were quantified and compared between euploid and aneuploid mice using nonparametric statistical tests. Aneuploid presphenoid bones were smaller than those of their euploid littermates and had lower bone volume fraction and fewer, more rod-like trabeculae. The differences in cancellous bone structure suggest that bone development, perhaps including bone modeling and remodeling, is affected by aneuploidy. These differences may contribute to the observed dysmorphology of skull and postcranial skeletal phenotypes in DS.
Short-term weight loss and hepatic triglyceride reduction: evidence of a metabolic advantage with dietary carbohydrate restriction

Background: Individuals with nonalcoholic fatty liver disease (NAFLD) have excess intrahepatic triglycerides. This is due, in part, to increased hepatic synthesis of fat from carbohydrates via lipogenesis. Although weight loss is currently recommended to treat NAFLD, little attention has been given to dietary carbohydrate restriction. Objective: The aim of this study was to determine the effectiveness of 2 wk of dietary carbohydrate and calorie restriction at reducing hepatic triglycerides in subjects with NAFLD. Design: Eighteen NAFLD subjects (n = 5 men and 13 women) with a mean (6SD) age of 45 6 12 y and a body mass index (in kg/m 2 ) of 35 6 7 consumed a carbohydrate-restricted (,20 g/d) or calorierestricted (1200–1500 kcal/d) diet for 2 wk. Hepatic triglycerides were measured before and after intervention by magnetic resonance spectroscopy. Results: Mean (6SD) weight loss was similar between the groups (24.0 6 1.5 kg in the calorie-restricted group and 24.6 6 1.5 kg in the carbohydrate-restricted group; P = 0.363). Liver triglycerides decreased significantly with weight loss (P , 0.001) but decreased significantly more (P = 0.008) in carbohydrate-restricted subjects (255 6 14%) than in calorie-restricted subjects (228 6 23%). Dietary fat (r = 0.643, P = 0.004), carbohydrate (r = 20.606, P = 0.008), posttreatment plasma ketones (r = 0.755, P = 0.006), and respiratory quotient (r = 20.797, P , 0.001) were related to a reduction in liver triglycerides. Plasma aspartate, but not alanine, aminotransferase decreased significantly with weight loss (P , 0.001). Conclusions: Two weeks of dietary intervention (’4.3% weight loss) reduced hepatic triglycerides by ’42% in subjects with NAFLD; however, reductions were significantly greater with dietary carbohydrate restriction than with calorie restriction. This may have been due, in part, to enhanced hepatic and whole-body oxidation. This trial was registered at clinicaltrials.gov as NCT01262326. Am J Clin Nutr doi: 10.3945/ajcn.110.007674.
NIM811 (N-Methyl-4-isoleucine Cyclosporine), a Mitochondrial Permeability Transition Inhibitor, Attenuates Cholestatic Liver Injury but Not Fibrosis in Mice

Cholestasis causes hepatocyte death, possibly because of mitochondrial injury. This study investigated whether NIM811 (N-methyl-4-isoleucine cyclosporine), an inhibitor of the mitochondrial permeability transition (MPT), attenuates cholestatic liver injury in vivo. Cholestasis was induced in mice by bile duct ligation (BDL). NIM811 was gavaged (20 mg/kg) before BDL and daily (10 mg/kg) afterward. Mitochondrial depolarization, cell death, and MPT onset were assessed by intravital confocal/multiphoton microscopy of rhodamine 123, propidium iodide, and calcein. After BDL, serum alanine aminotransferase (ALT), hepatic necrosis, and apoptosis all increased. NIM811 decreased ALT, necrosis, and apoptosis by 60 to 86%. In vehicle-treated mice at 6 h after BDL, viable hepatocytes with depolarized mitochondria were 18/high-power field (hpf), and nonviable cells were approximately 1/hpf, showing that depolarization preceded necrosis. Calcein entered mitochondria after BDL, indicating MPT onset in vivo. NIM811 decreased depolarization by 72%, prevented calcein entry into mitochondria, and blocked release of cytochrome c. Hepatic tumor necrosis factor alpha, transforming growth factor-beta1, procollagen alpha1(I) mRNA, alpha-smooth muscle actin, and Sirius red staining for collagen increased after BDL but were not different in vehicle- and NIM811-treated mice. Taken together, NIM811 decreased cholestatic necrosis and apoptosis but did not block fibrosis, indicating that the MPT plays an important role in cholestatic cell death in vivo.
Attention-deficit/hyperactivity disorder evaluation and diagnosis: A practical approach in office practice

Attention-deficit/hyperactivity disorder is the most common neurobehavioral disorder of childhood, with most children maintaining symptoms of ADHD as adolescents and as adults. It is among the most common chronic conditions that primary care pediatricians see. Progress in brain imaging, genetics, neuropsychology, and molecular biology of ADHD reveals complex interactions between neurologic mechanisms, genetics, and environmental influences. Core behaviors seen in children with ADHD include hyperactivity, impulsivity, and inattention. The DSM-IV standard for diagnosis emphasized the importance of documenting that these behaviors occur at school and in the home, the chronicity of symptoms, and the connection between the behaviors and impairments in educational achievement or social development. The complex nature of this disorder is indicated by the observation that children and adolescents with ADHD have associated conditions, such as learning disorders, anxiety, oppositional behaviors, and depression. The AAP practice guideline on the evaluation and diagnosis of school-aged children with ADHD provides primary care pediatricians with a scientific foundation for assessing children with behavior and learning problems. Attention to accurate documentation of behaviors, coexisting learning disorders and mental health conditions, and the development of office practices that support the diagnostic process will ensure that children receive an appropriate and comprehensive assessment.
Trans-species learning of cellular signaling systems with bimodal deep belief networks

Motivation: Model organisms play critical roles in biomedical research of human diseases and drug development. An imperative task is to translate information/knowledge acquired from model organisms to humans. In this study, we address a trans-species learning problem: predicting human cell responses to diverse stimuli, based on the responses of rat cells treated with the same stimuli. Results: We hypothesized that rat and human cells share a common signal-encoding mechanism but employ different proteins to transmit signals, and we developed a bimodal deep belief network and a semi-restricted bimodal deep belief network to represent the common encoding mechanism and perform trans-species learning. These ‘deep learning’ models include hierarchically organized latent variables capable of capturing the statistical structures in the observed proteomic data in a distributed fashion. The results show that the models significantly outperform two current state-of-the-art classification algorithms. Our study demonstrated the potential of using deep hierarchical models to simulate cellular signaling systems. Availability and implementation: The software is available at the following URL: http://pubreview.dbmi.pitt.edu/TransSpeciesDeepLearning/. The data are available through SBV IMPROVER website, https://www.sbvimprover.com/challenge-2/overview, upon publication of the report by the organizers. Contact: ude.ttip@auhgnix Supplementary information: Supplementary data are available at Bioinformatics online.
THE EFFECT OF TESTOSTERONE PROPIONATE ON THE GENITAL TRACT OF THE IMMATURE FEMALE RAT

Butenandt and Kudzus (1) have noted that certain androgens, when injected into immature female rats, cause premature opening of the vagina. This observation has been interpreted as indicating that these androgens possess, by virtue of similarity in chemical structure to the estrogens, estrogenic properties (2). There is, furthermore, some experimental evidence to indicate that certain of the androgens may be converted in the body to an estrogenic substance (3). In contrast to these experimental investigations we find that the estrus cycle can be suppressed by means of testicular extracts (4), and by testosterone (5, 6). Korenchevsky and his co-workers (7), Nelson and Gallagher (8) and others, have shown that androgens cause hypertrophy of the uterus and vagina of adult spayed, as well as intact, rats. Nelson and Merckel (3) have observed that testosterone, androsterone, dehydroandrosterone and androstanedione failed to produce vaginal cornification in spayed rats. However, testosterone and androstanedione...
Specifications of ideal prototype filters for designing linear phase FIR filters

To design a linear phase FIR filter using a window technique, the infinite impulse response of an ideal filter to approximate a desired specifications must be truncated to a finite length. The parameters associated with this technique are the length of the impulse response and the type of the truncation window. We discuss another parameter, the specification of the frequency response of the ideal prototype filter. We show that a given specification may be met with a shorter length of the truncated impulse response, if the ideal filter is properly specified.
Changing channels for tobacco control with youth: developing an intervention for working teens

Worksites represent an untapped resource for reaching teens with tobacco control messages, given that 80% of teens have held at least one job by the time they graduate from high school. This paper presents formative research findings from a methods development study aimed at designing and testing a tobacco control intervention targeting working teens. Formative research included qualitative methods as well as quantitative data from a cross-sectional survey of teens employed in 10 participating grocery stores. Contrary to our a priori hypothesis, smoking rates among employed youth in this study were not higher than statewide averages and most of the teen workers were still in school, indicating that worksite interventions, at least in this setting, represent an alternative or adjunct to school-based programs, but do not necessarily capture a unique population. Employed teen tobacco use patterns and work characteristics that emerged from our formative research are presented in this paper, and may be useful in planning future worksite interventions for employed teens.
Social Skills Training of LD Adolescents: A Generalization Study.

The purpose of this study was to determine the reliability of role playing as a device for assessing generalization of social skills training and to determine the extent to which LD adolescents gen...
ON UREA FORMATION IN PRIMITIVE FISHES

In 1828, Friedrich Wohler obtained urea by heating ammonium cyanate, this being the first deliberate extracorporeal synthesis of an organic compound by man. A century passed before Krebs and Henseleit (1932) demonstrated the biosynthesis of urea by mammalian liver through a process they termed the “ornithine cycle”. It is fitting and historically instructive to note that between these two scientific achievements Salkowski (1877–78) provided the lead article in Hoppe-Seyler’s new journal, his Zeitschrift fur physiologische Chemie’, “On the process of urea formation in animals and the influence on this by ammonium salts.” Now, somewhat more than a half-century since the discovery of the ornithine cycle, we are still working on the details of how it operates. This cycle, which we will refer to here as the ornithine-urea cycle (reasons for which will become evident later), has been, and continues to be, the framework for a legion of studies in comparative biochemistry and physiology.
Autocatalytic replication of polymers

Abstract We construct a simplified model for the chemistry of molecules such as polypeptides or single stranded nucleic acids, whose reactions can be restricted to catalyzed cleavage and condensation. We use this model to study the spontaneous emergence of autocatalytic sets from an initial set of simple building blocks, for example short strands of amino acids or nucleotides. When the initial set exceeds a critical diversity, autocatalytic reactions generate large molecular species in abundance. Our results suggest that the critical diversity is not very large. Autocatalytic sets formed in this way can be regarded as primitive connected metabolisms, in which particular species are selected if their chemical properties are advantageous for the metabolism. Such autocatalytic sets may have played a crucial role in the origin of life, providing a bridge from simple molecular species to complex proteins and nucleic acids. Many of our results are experimentally testable.
Negligence’s X Factor

This brief paper argues that it is helpful to reconceptualize the famous “Hand Formula” as an equation. To translate the inequality relation of the Hand Formula into an equation, one only needs to add a variable, x. Doing so is illuminating in many ways, as it allows us to quantify exactly how negligent a party is. Consideration of the x factor allows the Hand Formula to be a better teaching and research vehicle.
Abstract 15492: ADAM12 Modifies Severity of Peripheral Arterial Disease; Evidence From Preclinical and Human Studies

Objective: Peripheral arterial disease (PAD) results from atherosclerotic occlusion in the arteries of the lower extremities. Recent evidence suggests genetic factors may affect severity of PAD in the setting of an occlusion, however the specific genes involved are not known. We previously showed a locus on mouse chromosome 7 (LSq-1) modified PAD severity. The goal of this study was to identify the function of a leading candidate gene within this locus. Method: Perfusion recovery following experimental PAD was analyzed in 9 mouse strains. Haplotype blocks were generated based on SNP alleles common in strains that recover well but absent in strains that recover poorly. Gene expression was assessed by quantitative RT-PCR. Effect of gain or loss of our candidate gene was assessed in vitro and in vivo. In a human cohort with critical limb ischemia (CLI, N=162) and intermittent claudication (IC, N=627), tagged SNPs were genotyped for association with CLI using multivariable logistic regression. Results: We identified 4 haplotype blocks containing 25 genes of which 4 were expressed at higher levels in ischemic hind limbs of mice that recover well (C57BL/6) compared to expression in mice that recover poorly (Balb/c). Of the 4 genes, ADAM12 showed the most differential expression with (>3 fold) up-regulation in ischemic endothelial cells (EC). In simulated ischemia, in vitro, over expression of ADAM12 in EC’s increased cell proliferation and survival. “Knock down” of ADAM12 by shRNA decreased AKT phosphorylation, impaired EC proliferation and increased apoptosis in simulated ischemia. In vivo, augmentation of ADAM12 expression in Balb/c hind limbs by gene transfer improved perfusion recovery following experimental PAD (change in perfusion = 81%±6.5 vs 40%±7.6 p=0.001). Moreover “knock down” of ADAM12 in C57BL/6 hind limbs impaired perfusion recovery (79%±4.5 vs 95%±3.3 p=0.01). Lastly, in humans, RS1471244 in ADAM12 was strongly associated with CLI (odds ratio 2.4 [95% CI 1.5-4.0), p=0.0006 for dominant model; OR 2.2 [1.3-3.5], p=0.002 for additive model), even after adjustment for diabetes. Conclusion: ADAM12 is a gene that is associated with PAD outcomes in mice and humans likely through modulation of endothelial cell proliferation and survival.
DPAC measurement of the hyperfine fields in100RhCo and100RhFe

Using the 85–75 keV γγ-cascade of100Rh, we report the first DPAC measurement of the hyperfine field in100RhCo and100RhFe. Our results were made possible by continued improvement in time resolution using BaF2 scintillators. At room temperature we obtained fields of 420.6(1.3) kG and 540.4(1.5) kG for100RhCo and100RhFe, respectively. The former revises an earlier spin echo result by Kontani and Itoh by ∼9%; the latter is consistent with the work of Matthiaset al. using resonant destruction of angular correlations.
Immunoelectrophoresis of Serum in “Lupoid” Hepatitis.

SummaryImmuno- and paper strip electrophoresis of serum proteins were performed on 6 patients with “lupoid” hepatitis and compared with the findings in 13 patients with Laennec's cirrhosis. The following changes were observed in “lupoid” hepatitis: There was a decrease in albumin, alphas haptoglobin, alpha2-beta1 lipoproteins and beta1 A globulin and an elevation in alpha2 M, beta2 A, beta2 M and gamma globulins. Immunoelectrophoresis in Laennec's cirrhosis revealed only an increase in beta2 A, beta2 M and gamma globulins. Paper strip electrophoresis revealed in both diseases a decrease in the albumin fraction and an increase in gamma globulins. The significance of these alterations in the serum proteins is discussed. The beta1 A globulin has been identified with one of the components of the complement and is diminished both in SLE and in “lupoid” hepatitis. This suggests that a similar immunologic process is operating in both diseases.
‘We’re, like, a cute rugby team’: How whiteness and heterosexuality shape women’s sense of belonging in rugby:

This article considers how race and sexuality mutually inform the ways women experience their sense of belonging in sport. An examination of how white and heterosexual privilege structure belonging...
Home Hemodialysis and Satellite Hemodialysis

More than thirty years ago, hemodialysis was the first high-technology health care treatment to be transferred to the home and carried out by the patient with the help of a family member or other individual. Originally undertaken primarily for financial reasons, it soon became obvious that home hemodialysis increased the opportunity for patient independence and rehabilitation and provided an improved quality of life compared with patients dialyzing in a hospital or other outpatient dialysis facility. As financing improved for the treatment of end-stage renal disease (ESRD), the use of home hemodialysis declined and outpatient hemodialysis became the predominant treatment. Now, perhaps, the time is coming for home hemodialysis to come into its own again
Stimulation of Wnt/β-catenin signaling pathway with Wnt agonist reduces organ injury after hemorrhagic shock.

Background Hemorrhagic shock is a leading cause of morbidity and mortality in surgery and trauma patients. Despite a large number of preclinical trials conducted to develop therapeutic strategies against hemorrhagic shock, there is still an unmet need exist for effective therapy for hemorrhage victims. Wnt/β-catenin signaling controls developmental processes and cellular regeneration owing to its central role in cell survival and proliferation. We therefore hypothesized that the activation of Wnt signaling reduces systemic injury caused by hemorrhagic shock.
Ekta: an efficient DHT substrate for distributed applications in mobile ad hoc networks

Distributed hash tables (DHTs) have proven to be a novel and efficient platform for building a variety of scalable and robust distributed applications like content sharing and location in the Internet. Similar to those in the Internet, distributed applications and network services in mobile ad hoc networks (MANETs) can potentially benefit from the deployment of a DHT. However, bandwidth limitations, node mobility, and multi access interference pose unique challenges to deploying such DHTs in MANETs. In this paper, we first study how to efficiently implement DHTs in MANETs. We explore two disparate design options: the simple approach of directly overlaying a DHT on top of a MANET multi-hop routing protocol, and Ekta which integrates a DHT with a multi-hop routing protocol at the network layer. Second, we examine the efficiency of DHT substrates in supporting applications in MANETs by examining the performance of a resource discovery application built on top of Ekta with one that directly uses physical layer broadcast. Such a study answers the fundamental question of whether a DHT substrate can be more efficient in supporting applications than a physical layer broadcast-based protocol, since in MANETs, DHT protocols effectively rely on physical layer broadcast to discover and maintain routes.
Crizotinib inhibits hyperpolarization-activated cyclic nucleotide-gated channel 4 activity

Sinus bradycardia is frequently observed in patients treated with crizotinib, a receptor tyrosine kinase inhibitor used for the treatment of anaplastic lymphoma kinase (ALK)-rearranged non-small cell lung cancer (NSCLC). We investigated whether crizotinib could influence heart rate (HR) through direct cardiac effects. The direct effect of crizotinib on HR was studied using ECG analysis of Langendorff-perfused mouse hearts. The whole-cell patch clamp technique was used to measure the effects of crizotinib on the hyperpolarization-activated funny current, If, in mouse sinoatrial node cells (SANCs) and hyperpolarization-activated cyclic nucleotide-gated channel 4 (HCN4) activity in HEK-293 cells stably expressing human HCN4. Crizotinib resulted in a dose-dependent reduction in HR in isolated intact mouse hearts with a half maximal inhibitory concentration (IC50) of 1.7 ± 0.4 μmol/L. Because ECG analysis revealed that crizotinib (0–5 μmol/L) resulted in significant reductions in HR in isolated mouse hearts without changes in PR, QRS, or QT intervals, we performed whole-cell patch clamp recordings of SANCs which showed that crizotinib inhibited If which regulates cardiac pacemaker activity. Crizotinib resulted in diminished current density of HCN4, the major molecular determinant of If, with an IC50 of 1.4 ± 0.3 μmol/L. Crizotinib also slowed HCN4 activation and shifted the activation curve to the left towards more hyperpolarized potentials. Our results suggest that crizotinib’s effects on HCN4 channels play a significant role in mediating its observed effects on HR.
A 50+ year search for effective, efficient and engaging instruction

In this paper I will chronicle my 50+ year career, from my interest in making education more effective, to an epiphany about theories, and some of my published work that, for a time, gained the attention of others in the field of instructional technology. My extensive experience with computer-assisted learning covers early efforts to teach concepts to attempts to design automated authoring systems. My most recent work attempts to identify underlying principles common to most theories of instruction. The professional press publishes reports of theory, research, data, prescriptions, and opinions, but seldom do we get the back story. Where did these ideas originate? What events led to a particular theoretical or research approach? What were the challenges—personal and interpersonal—that affected a given approach, theory or research study? In this paper, in addition to identifying a few of the most notable contributions to this literature, I will provide some of the back story that contributed to my career and inspired or significantly influenced my work. I will also highlight some of the lessons learned along the way. Download the PDF and read more...
MULTIVARIATE DENSITY ESTIMATION BY DISCRETE MAXIMUM PENALIZED LIKELIHOOD METHODS

The graphical representation of a multivariate random sample by a probability density function is a useful one. The parametric approach to fitting a density function, such as the multivariate Gaussian, is not robust against incorrect specification of the parametric form. Nonparametric density estimation, on the other hand, providesconsistent approximations for a large class of well-behaved “true” sampling densities. The authors have previously developed a univariate nonparametric density estimator that is a continuous piecewise linear function that optimizes a discrete maximum penalized likelihood criterion. This estimator is pointwise consistent almost surely and Monte Carlo studies indicate good small-sample approximation properties. In the present paper, we present two methods of extending the univariate algorithm to higher dimensions. In the first method, the criterion is extended directly to higher dimensions. In the second method, the eigenvectors of the estimated covariance matrix are used to provide a pseudo-independent linear transformation. Then the univariate algorithm is applied to each of the pseudo-independent dimensions and the multivariate estimate is easily obtained. The latter method is illustrated with multimodal data.
Information needs for anime recommendation: analyzing anime users' online forum queries

Despite the increasing consumption and popularity of audio-visual materials and non-textual information, recommendation-based information retrieval research regarding these materials remains limited. To provide robust recommendation services to users, it is critical to understand how users describe their needs when they seek audio- visual materials. We conducted a content analysis of 396 recommendation threads from Anime News Network online forums to identify 19 common information features used in these requests. Work, Theme, and Genre were the most frequently mentioned features when users described anime they were seeking. Findings also show Audience as an important anime information need. Together, these form a distinct set of interests, vital to understanding the information needs of anime users.
Oxidative Damage: DNA Repair and Inducible Resistance

Free radicals and activated oxygen species are generated in a variety of ways. For example, most of the biological effects of ionizing radiations can be ascribed to the oxygen radicals they produce, such as superoxide anion (O2 \(\overline \bullet \)) and hydroxyl radical (·OH) (1). Such radicals are also produced deliberately by macrophages during inflammatory responses, evidently as a means of destroying invading cells (2). It seems likely that the normal reduction of O2 to water by cytochrome C oxidase might inadvertently release intracellular activated oxygen. Indeed, bacteria devoid of superoxide dismutase, which destroys O2 \(\overline \bullet \), display a strongly increased spontaneous mutation frequency in aerated but not in hypoxic culture (3). This apparent production of oxygen radicals under normal aerobic conditions underscores the need to understand the nature of the cellular defenses against oxidative damage. We are investigating the mechanisms that cells employ to avert oxidative damage and to correct such damage when it does occur.
Challenges of Implementing Integrated Programs for Underrepresented Students in STEM: A Study of the CSU STEM Collaboratives.

With emerging evidence about the efficacy of integrated support programs for college students and increasing attention nationally to creating such programs, it is important to understand implementa...
Feasibility and Outcomes of Femoral Vein Harvest for Dialysis Access and Arterial Reconstruction

Abstract Background We describe the feasibility and long-term outcomes of using femoral vein (FV) for arteriovenous fistula (AVF) and lower extremity bypass (LEB) creation. Methods All patients undergoing AVF or LEB using autogenous FV by a single surgeon (April 2006 to September 2013) were reviewed. Perioperative (30-d) complications and long-term outcomes are described. Results Forty-four patients underwent vascular reconstruction with FV (AVF = 27 and LEB = 17). Perioperative morbidity was 43.2%, including harvest site infection and or seroma in 15.9%. No patients suffered from compartment syndrome or venous thromboembolic event. At median follow-up of 50.0 mon, overall patency was 70.4% for AVF (primary = 37.0% and secondary = 70.3%) and 76.5% for LEB (primary = 70.6% and secondary = 76.5%). Long-term lower extremity swelling occurred in 18.2% of patients. Conclusions Perioperative morbidity following FV harvest is high, but long-term patency rates are excellent. FV harvest is feasible and should be considered as a valid conduit in patients without useable great saphenous vein or other more commonly used sources of autogenous vein.
Mimicry in viceroy butterflies is dependent on abundance of the model queen butterfly

Mimics should not exist without their models, yet often they do. In the system involving queen and viceroy butterflies, the viceroy is both mimic and co-model depending on the local abundance of the model, the queen. Here, we integrate population surveys, chemical analyses, and predator behavior assays to demonstrate how mimics may persist in locations with low-model abundance. As the queen becomes less locally abundant, the viceroy becomes more chemically defended and unpalatable to predators. However, the observed changes in viceroy chemical defense and palatability are not attributable to differing host plant chemical defense profiles. Our results suggest that mimetic viceroy populations are maintained at localities of low-model abundance through an increase in their toxicity. Sharing the burden of predator education in some places but not others may also lower the fitness cost of warning signals thereby supporting the origin and maintenance of aposematism.