cssi/SciSciGPT-SciSciNet huggingface dataset:
Anniversary of the discovery/isolation of the yeast centromere by Clarke and Carbon

The first centromere was isolated 35 years ago by Louise Clarke and John Carbon from budding yeast. They embarked on their journey with rudimentary molecular tools (by today's standards) and little knowledge of the structure of a chromosome, much less the nature of a centromere. Their discovery opened up a new field, as centromeres have now been isolated from fungi and numerous plants and animals, including mammals. Budding yeast and several other fungi have small centromeres with short, well-defined sequences, known as point centromeres, whereas regional centromeres span several kilobases up to megabases and do not seem to have DNA sequence specificity. Centromeres are at the heart of artificial chromosomes, and we have seen the birth of synthetic centromeres in budding and fission yeast and mammals. The diversity in centromeres throughout phylogeny belie conserved functions that are only beginning to be understood.
Protein Composition Correlates with the Mechanical Properties of Spider (Argiope trifasciata) Dragline Silk

We investigated the natural variation in silk composition and mechanical performance of the orb-weaving spider Argiope trifasciata at multiple spatial and temporal scales in order to assess how protein composition contributes to the remarkable material properties of spider dragline silk. Major ampullate silk in orb-weaving spiders consists predominantly of two proteins (MaSp1 and MaSp2) with divergent amino acid compositions and functionally different microstructures. Adjust- ing the expression of these two proteins therefore provides spiders with a simple mechanism to alter the material properties of their silk. We first assessed the reliability and precision of the Waters AccQ-Tag amino acid composition analysis kit for determining the amino acid composition of small quantities of spider silk. We then tested how protein composition varied within single draglines, across draglines spun by the same spider on different days, and finally between spiders. Then, we correlated chemical composition with the material properties of dragline silk. Overall, we found that the chemical composition of major ampullate silk was in general homogeneous among individuals of the same population. Variation in chemical composition was not detectable within silk spun by a single spider on a single day. However, we found that variation within a single spider's silk across different days could, in rare instances, be greater than variation among individual spiders. Most of the variation in silk composition in our investigation resulted from a small number of outliers (three out of sixteen individuals) with a recent history of stress, suggesting stress affects silk production process in orb web spiders. Based on reported sequences for MaSp genes, we developed a gene expression model showing the covariation of the most abundant amino acids in major ampullate silk. Our gene expression model supports that dragline silk composition was mostly determined by the relative abundance of MaSp1 and MaSp2. Finally, we showed that silk composition (especially proline content) strongly correlated with some measures of mechanical performance, particularly how much fibers shrunk during supercontraction as well as their breaking strains. Our findings suggest that spiders are able to change the relative expression rates of different MaSp genes to produce silk fibers with different chemical compositions, and hence, different material properties.
Trees in polyhedral graphs

A graph is said to be d-polyhedral provided it is isomorphic with the graph formed by the vertices and edges of a d-dimensional bounded (convex) polyhedron (d-polyhedron). A k-tree is a connected acyclic graph in which each vertex is of valence ⩽k.
Staining Normal and Experimental Motor Nerve Terminals with Tetrazolium Salts

Nitroblue tetrazolium (NBT) has been used to stain motor nerve terminals and unmyelinated axons in vertebrate skeletal muscle, but undesirable background connective tissue coloration resulted. This procedure was improved by separation of the tetrazolium salt's binding from its subsequent reduction. By uncoupling the binding and reduction steps it was possible (1) to improve nerve terminal staining by using tetranitroblue tetrazolium (TNBT), (2) to counterstain and postfix in osmium tetroxide and (3) to enhance the overall tissue preservation. The separate binding and reduction procedure is compatible with postsynaptic acetylcholinesterase staining. Experimentally manipulated and diseased preparations can be successfully stained, and the requirements for optimal staining in each case are described.
Mothering While Black: Feminist Thought on Maternal Loss, Mourning and Agency in the African Diaspora

This essay is a discussion and analysis of key feminist ideas in the collection of articles for a special edition of Transforming Anthropology, entitled “Sorrow as Artifact”. The author discusses the importance of transnational and feminist perspectives in anthropological analyses and definitions of Black motherhood. The author also examines intersecting themes, including Black mothers’ responses to violence and loss throughout the African diaspora. The author also considers why Black motherhood matters and the roles of “other mothers” in the historic and ongoing Black freedom struggle.
An Artificial-Immune-Algorithm-Based QoS Multicast Routing Algorithm in IP/DWDM Optical Internet

In this paper,an artificial-immune-algorithm-based QoS multicast routing algorithm in IP/DWDM optical Internet is proposed.Given a QoS multicast request and the delay interval required by the group,an algorithm is pro- posed,being able to finda flexible QoS-based cost near-optimal routing tree.The proposed algorithm constructs the multicast tree based on artificial immune algorithm,and assigns wavelengths to the tree based on the wavelength graph ideas. It integrates routing and wavelength assignment into one single process,and also considers load balanc- ing.Simulation results have shown that it can construct a feasible and effective routing tree for group applications in IP/DWDM optical Internet.
THE EFFECT OF ACUTE RESPIRATORY AND METABOLIC ALKALOSIS ON CARDIAC OUTPUT AND PERIPHERAL RESISTANCE.

SUMMARY 1. Experiments were performed in animals to determine the effect of acutely induced respiratory and metabolic alkalosis on cardiac output, and peripheral resistance. 2. Acute respiratory alkalosis produced no change in cardiac output, peripheral resistance, or arterial blood pressure. 3. Acute metabolic alkalosis induced by injection of either hypertonic or isotonic sodium bicarbonate produced a marked increase in cardiac output with an accompanying fall in peripheral resistance but no change in arterial pressure or pulse rate. 4. Control experiments with injection of similar amounts of hypertonic or isotonic sodium chloride solution produced increases in cardiac output similar to those induced by sodium bicarbonate. 5. The elevation in cardiac output induced by intravenous administration of sodium bicarbonate solution appears to be largely explainable on the basis of increased blood volume and no specific effect of acute metabolic alkalosis on cardiac output was demonstrated.
Normal and Developmental Aspects of Masochism: Transcultural and Clinical Implications

Masochism in all its forms has challenged psychoanalytic theories of development a and treatment since Freud (1905, 1919, 1924). It might appear paradoxical to present a concept of normal masochism while masochism has been considered to be so pathological, but I have proposed this concept (Nakakuki 1982, 1984) as a part of normal mental functioning through my experience and study of "traditional" Japanese culture, which I believe contains the features of normal masochism. It is normal in that it represents Japanese adaptation to their cultural orientation and expectations.
Towards Understanding Multicultural Teams

Consider the following two anecdotes: A French-Senegalese manufacturing organization in Senegal was struggling with ways to increase production. The company’s leadership was mostly comprised of French and Italian expatriates. Following some initial efforts and calculations, the French production manager concluded that it was impossible to increase the production levels by 25%. Coincidentally, he fell ill during this time and his assistant, a Senegalese national, took over the negotiation and decision making temporarily. A Senegalese worker approached the assistant with a proposal that workers were willing to increase the daily production by 30% or more in return for two hours’ additional pay. The Senegalese assistant did some calculations and consulted some influential people and accepted the proposal. The daily production increased between 30 to 40%. Upon his return, the French production manager did not fully support the agreement since he thought that his authority had been undermined, which led to worker dissatisfaction and low morale. It was clear that both the Senegalese staff and expatriate managers were equally interested in increasing performance. However, they did not manage their cultural differences well and thus were not able to work effectively as a team.
654. Recombinant Gene and Cell Therapy With Serine-Histogranin and Endomorphin-1 for the Experimental Treatment of Chronic Neuropathic Pain

The insufficient pain relief provided by current pharmacotherapy for chronic neuropathic pain represents a serious medical problem. The development of new treatment strategies is therefore of a high clinical interest. The mechanisms underlying development of chronic pain include decrease in spinal tonic inhibition due to the dysfunction of GABA signaling and increase in excitatory signaling through glutamate NMDA receptors. Previous studies showed beneficial effect of the intraspinal transplantation of GABAergic neuronal precursor cells (NPCs) and of the intraspinal delivery of serine histogranin (SHG), an NMDA receptor antagonist. Moreover, our studies showed that combined injection of SHG with another analgesic peptide, endomorphin-1 (EM-1), potentiated analgesic effect of SHG. Endomorphins are highly selective for μ-opioid receptors and have been shown to decrease neuropathic pain in previous studies.Cells and gene therapy provides suitable tools for targeted delivery of therapeutic peptides thus minimizing adverse effect of systemic delivery. Here we attempted to simultaneously target inhibitory and excitatory pathways in the spinal cord of injured animals by using either recombinant cells or recombinant AAV vectors. Recombinant plasmid encoding single- and multi-SHG and EM-1 was engineered and successful production of recombinant peptides by transduced HEK 293 cells was analyzed by immunocytochemistry and FLISA. AAV vectors were used as carriers of recombinant cDNA and used for either transduction of NPC or for direct spinal injection. Clip compression injury of the spinal cord was use as a model of central neuropathic pain. Animals showing clear sign of pain-related behavior were used for intraspinal injection of either recombinant NPCs or recombinant AAVs. Animals were tested weekly to evaluate analgesic effect of the treatment. Two week post injection animals treated with rAAVs showed significant attenuation of tactile sensitivity compared to controls and the antinociceptive effect sustained up to 6 weeks post injection. Enhanced analgesic effect was observed in the group with 6SHG-EM1 construct compared to 1SHG-EM1. Animals treated with rNPCs did not display significant pain relief compared to nonrecombinant NPCs group. However, these results may be masked by a low survival rate of the transplanted cells. Better strategies for rNPC engineering are currently examined. The presence of SHG and EM (above the levels of controls animals) was detected by FLISA methods and by immunohistochemistry in the spinal cord of treated animals suggesting successful production of recombinant peptides.This study demonstrates that the beneficial effect of combined therapy in the management of chronic pain may be enhanced by using gene engineering tools to deliver therapeutic substances into CNS in a single step and minimize the need for extensive surgical interventions.
Acute kidney injury: A guide to diagnosis and management

Acute kidney injury is characterized by abrupt deterioration in kidney function, manifested by an increase in serum creatinine level with or without reduced urine output. The spectrum of injury ranges from mild to advanced, sometimes requiring renal replacement therapy. The diagnostic evaluation can be used to classify acute kidney injury as prerenal, intrinsic renal, or postrenal. The initial workup includes a patient history to identify the use of nephrotoxic medications or systemic illnesses that might cause poor renal perfusion or directly impair renal function. Physical examination should assess intravascular volume status and identify skin rashes indicative of systemic illness. The initial laboratory evaluation should include measurement of serum creatinine level, complete blood count, urinalysis, and fractional excretion of sodium. Ultrasonography of the kidneys should be performed in most patients, particularly in older men, to rule out obstruction. Management of acute kidney injury involves fluid resuscitation, avoidance of nephrotoxic medications and contrast media exposure, and correction of electrolyte imbalances. Renal replacement therapy (dialysis) is indicated for refractory hyperkalemia; volume overload; intractable acidosis; uremic encephalopathy, pericarditis, or pleuritis; and removal of certain toxins. Recognition of risk factors (e.g., older age, sepsis, hypovolemia/shock, cardiac surgery, infusion of contrast agents, diabetes mellitus, preexisting chronic kidney disease, cardiac failure, liver failure) is important. Team-based approaches for prevention, early diagnosis, and aggressive management are critical for improving outcomes.
Vein of Galen Aneurysmal Malformations

Vein of Galen aneurysmal malformations (VGAMs) are rare vascular malformations involving the median prosencephalic vein of Markowski, the precursor of the vein of Galen and the embryonic drainage of the choroid plexus. Although reported to comprise 30 % of pediatric vascular and 1 % of pediatric congenital anomalies [1], the exact incidence of VGAMs is difficult to quantify given the array of vascular pathology causing dilation of the median prosencephalic vein of Markowski or the vein of Galen [2]. In this chapter, we review relevant VGAM vascular anatomy and embryology, classifications schemes, clinical features and pathophysiology, and treatment strategies.
Racial Variation in Semen Quality at Fertility Evaluation.

Objective To identify racial differences in semen quality among men living in the same geographic area and seeking fertility evaluation. Methods Men obtaining a semen analysis for infertility evaluation or treatment between 2012 and 2016 at a single center were identified, and demographic data including height, weight, body mass index (BMI), and age were described. Mean semen parameters and the proportions of men with suboptimal parameters based on the World Health Organization's fifth edition criteria were also compared based on race. Multivariable regression analysis was conducted incorporating age, BMI, and year of evaluation. Further subanalyses based on BMI were subsequently performed. Results White men produced greater volumes of semen on average; however, Asian men had higher sperm concentrations and total sperm count. A lower proportion of Asian men compared to white men had semen quality in the suboptimal range for most semen parameters, whereas a higher proportion of white men were found to have azoospermia. Stratification by BMI groups attenuated the observed differences between whites and Asians, yet Asian male semen quality remained higher. Conclusion Among men evaluated for infertility at a single center, Asians had lower volume but higher sperm concentrations compared with whites, which was influenced by differences in azoospermia prevalence. Although anthropometric and demographic factors attenuated the differences, even after adjustment, the contrasts remained. Our study suggests that racial differences exist in semen quality at the time of infertility evaluation.
Progress and roadblocks in the search for brain-based biomarkers of autism and attention-deficit/hyperactivity disorder

Children with neurodevelopmental disorders benefit most from early interventions and treatments. The development and validation of brain-based biomarkers to aid in objective diagnosis can facilitate this important clinical aim. The objective of this review is to provide an overview of current progress in the use of neuroimaging to identify brain-based biomarkers for autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD), two prevalent neurodevelopmental disorders. We summarize empirical work that has laid the foundation for using neuroimaging to objectively quantify brain structure and function in ways that are beginning to be used in biomarker development, noting limitations of the data currently available. The most successful machine learning methods that have been developed and applied to date are discussed. Overall, there is increasing evidence that specific features (for example, functional connectivity, gray matter volume) of brain regions comprising the salience and default mode networks can be used to discriminate ASD from typical development. Brain regions contributing to successful discrimination of ADHD from typical development appear to be more widespread, however there is initial evidence that features derived from frontal and cerebellar regions are most informative for classification. The identification of brain-based biomarkers for ASD and ADHD could potentially assist in objective diagnosis, monitoring of treatment response and prediction of outcomes for children with these neurodevelopmental disorders. At present, however, the field has yet to identify reliable and reproducible biomarkers for these disorders, and must address issues related to clinical heterogeneity, methodological standardization and cross-site validation before further progress can be achieved.
Well Integrity Assessment of Monitoring Wells at an Active CO2-EOR Flood

Abstract Assessment of well integrity has become more important for CCS and CO 2 -EOR as it has become apparent that wells represent the most likely migration pathway for CO 2 to leave a CCS storage unit or a CO 2 -EOR reservoir. Although wells represent a migration pathway they are also the best vehicle for employing technology monitoring CO 2 injection and storage. This contradiction of being a potential migration path and key monitoring technology leads to a need to understand how monitoring wells may be similar or different in comparison to other types of wells with respect to migration risk. The maturation and completion US Department of Energy sponsored research projects presents an opportunity to assess the integrity of monitoring wells that have been exposed to injected CO 2 . This paper discusses an integrity assessment of two monitoring wells in an operating CO 2 -EOR flood in Mississippi, USA. It provides an early assessment of how monitoring equipment affects well integrity and isolation capacity. Each of the monitoring wells in this study were similarly constructed using both fiberglass and conventional steel casing. Each of the wells was instrumented with multiple monitoring technologies including, electrodes, pressure gauges, and temperature sensors on the outside of the casing. Control lines and cables were run from the surface on the outside of the long-string casing in each well to communicate with the monitoring equipment. A comprehensive logging, testing, and sampling program was developed to assess integrity in both wells. Ultrasonic well mapping was used to create radial maps of the location of cement, liquid, and gas behind the casing. Cement bond logging provided information on the casing-to-cement and cement-to-formation bonds for the long-string section. The logs showed that the monitoring equipment attached to the long-string casing is visible as continuous low acoustic impedance features and may represent a leakage risk. Cased-hole sidewall cores were collected and provided some validation of the log results and provide local information on the isolation capacity of the wells. The combination of information from the log data sets and cores was used to assess isolation capacity. The results of the study show that careful design and assessment of the materials used in monitoring well construction, the types of monitoring technology, and the location of monitoring technology within a well needs to be conducted with limiting migration potential and maximizing well integrity as objectives.
The Effect of Soft Tissue Injuries on Clinical Outcomes After Tibial Plateau Fracture Fixation.

Objective:To determine if ligamentous and meniscal injuries as determined by initial magnetic resonance imaging altered clinical outcomes after the fixation of tibial plateau fractures.Design:Comparative cohort study.Setting:Academic level I trauma center.Patients/Participants:Eighty-two patients fr
The microscopic theory of superconductivity

Key steps in the development of the microscopic understanding of superconductivity are discussed.
miR‐29 contributes to normal endothelial function and can restore it in cardiometabolic disorders

We investigated the role of microRNAs (miRNA) in endothelial dysfunction in the setting of cardiometabolic disorders represented by type 2 diabetes mellitus (T2DM). miR-29 was dysregulated in resistance arterioles obtained by biopsy in T2DM patients. Intraluminal delivery of miR-29a-3p or miR-29b-3p mimics restored normal endothelium-dependent vasodilation (EDVD) in T2DM arterioles that otherwise exhibited impaired EDVD Intraluminal delivery of anti-miR-29b-3p in arterioles from non-DM human subjects or rats or targeted mutation of Mir29b-1/a gene in rats led to impaired EDVD and exacerbation of hypertension in the rats. miR-29b-3p mimic increased, while anti-miR-29b-3p or Mir29b-1/a gene mutation decreased, nitric oxide levels in arterioles. The mutation of Mir29b-1/a gene led to preferential differential expression of genes related to nitric oxide including Lypla1. Lypla1 was a direct target of miR-29 and could abrogate the effect of miR-29 in promoting nitric oxide production. Treatment with Lypla1 siRNA improved EDVD in arterioles obtained from T2DM patients or Mir29b-1/a mutant rats or treated with anti-miR-29b-3p. These findings indicate miR-29 is required for normal endothelial function in humans and animal models and has therapeutic potential for cardiometabolic disorders.
Prognostic impact of perihepatic lymph node metastases in patients with resectable colorectal liver metastases.

BACKGROUND Although perihepatic lymph node metastases (PLNMs) are known to be a poor prognosticator for patients with colorectal liver metastases (CRLMs), optimal management remains unclear. This study aimed to determine the risk factors for PLNMs, and the survival impact of their number and location in patients with resectable CRLMs. METHODS Data on patients with CRLM who underwent hepatectomy during 2003-2014 were analysed retrospectively. Recurrence-free (RFS) and overall (OS) survival were calculated according to presence, number and location of PLNMs. Risk factors for PLNM were evaluated by logistic regression analysis. RESULTS Of 1485 patients, 174 underwent lymphadenectomy, and 54 (31·0 per cent) had PLNM. Ten patients (5·7 per cent) who had lymphadenectomy and 176 (13·4 per cent) who did not underwent repeat hepatectomy. Survival of patients with PLNM was significantly poorer than that of patients without (RFS: 5·3 versus 13·8 months, P < 0·001; OS: 20·5 versus 71·3 months; P < 0·001). Median OS was significantly better in patients with para-aortic versus hepatoduodenal ligament PLNMs (58·2 versus 15·5 months; P = 0·011). Patients with three or more PLNMs had significantly worse median OS than those with one or two (16·3 versus 25·4 months; P = 0·039). The presence of primary tumour lymph node metastases (odds ratio 2·35; P = 0·037) and intrahepatic recurrence requiring repeat hepatectomy (odds ratio 5·61; P = 0·012) were significant risk factors for PLNM on multivariable analysis. CONCLUSION Patients undergoing repeat hepatectomy and those with primary tumour lymph node metastases are at significant risk of PLNM. Although PLNM is a poor prognostic factor independent of perihepatic lymph node station, patients with one or two PLNMs have a more favourable outcome than those with more PLNMs.
Methylation of Carbohydrates with Methylsulfinyl Anion and Methyl Iodide in Dimethyl Sulfoxide: Methylation of Aerobacter aerogenes A3(S1) Capsular Polysaccharide and 3-O-α-d-Glucopyranosyluronic acid-d-mannose

Publisher Summary This chapter discusses the methylation of carbohydrates with methylsulfinyl anion and methyl iodide in dimethyl sulfoxide. Methylation of free hydroxyl groups involves a nucleophilic attack of alkoxides generated by action of base on the hydroxyl groups on an alkylating reagent to form the ether. The base used in this reaction, methylsulfinyl anion, is generated by the reaction of sodium hydride with dimethyl sulfoxide. When the anion is added to a solution of an oligo- or polysaccharide in dimethyl sulfoxide, free hydroxyls are converted completely to the alkoxide form. Addition of either methyl iodide or dimethyl sulfate to the alkoxide solution at 20° then gives complete etherification within a few minutes. The competing reaction between the excess methylsulfinyl anion and alkylating reagent does not interfere as long as the alkylating reagent is added in molar excess of the total base.
Biomaterials for Cell Immobilization

There are several major biomedical applications where the transplantation of immobilized cells is being employed to restore, maintain or improve tissue function. These strategies can be split into two main categories: the replacement of biochemical function only or the replacement of structurally functional tissue. As only chemical communication (e.g., diffusion of molecules) is required in the former, it is possible to deliver cells encapsulated in a nanoporous, immunoisolatory polymer membrane. The membranes is constructed such that there are pores large enough to allow for nutrients, waste and the bioactive factor to diffuse but not large enough as to allow immune cells to attack the cells within [1]. This strategy has mainly been employed to temporarily or permanently replace biochemical functions of the liver [2,3], pancreas [4,5], and provide local protein delivery in neurological disorders [6]. The second major strategy involves entrapping cells on a micro or macroporous polymer scaffold and promoting the formation of a new tissue that is structurally and functionally integrated with the surrounding tissue. The scaffold is constructed with a biocompatible material that degrades over time to leave only the integrated tissue in its place. Researchers have attempted to use this strategy with a variety of tissues, including skin [7,8,9], liver [10,11,12], pancreas [13], cornea [14], blood vessels [15,16], cartilage [17,18], heart [19], and bone [20,21].
Bis(2,6-dimethyl­phenyl isocyanide-κC)gold(I) tetra­fluorido­borate

In the title compound, [Au(C9H9N)2]BF4, the AuI cation adopts an almost linear AuC2 geometry. The cation is bowed due to crystal packing effects, and the dihedral angle between the xylyl rings is 52.3 (7)°.
Clinical research with adolescents: barriers and how to overcome them.

Purpose of review This review aims to emphasize the importance of including adolescents in research, outline current standards and evaluate barriers that prevent adolescent research. We also hope to provide some guidance and call for much needed additional direction in the field. Recent findings The absolute necessity for including adolescents in research has been an area of focus within the community of adolescent providers and care takers. Recent policy and support from major organizations has emphasized the importance of including this population in research but also pointed out many of the complexities. Summary Adolescent research is imperative to guiding policy and promoting evidence-based care. Current standards provide both guidance and barriers, yet more research is needed to further guide conduct of ethical research in this population.
Non-linear Systems

This chapter explores non-linear dynamics through simple mathematical models. Rather than solve or numerically integrate differential equations, a variety of graphical techniques in phase space are introduced to gain an intuitive and visual feel for the dynamics. Equilibrium points, velocity vectors, bifurcations, trajectories, and basins of attraction are introduced in one-dimensional systems. In two-dimensional systems, these concepts are expanded upon and nullclines and hysteresis are added, as well as the behavior of limit cycles and separatrices. Three-dimensional systems are explored in the context of chaotic and slow-fast systems. The ability for non-linear systems to display robustness and meta-stability are also discussed. Examples of non-linear dynamics are provided from weather, politics, evolutionary biology, music, art, and dance. More speculative applications include how the trajectories of attention may be a way to understand the nature of consciousness and how free will might exist in a deterministic world through chaotic unpredictability. The chapter concludes with questions for either reflection or group discussion as well as resources for further exploration.
Enterotoxigenic Escherichia coli Heat-Stable Toxin Increases the Rate of Zinc Release from Metallothionein and Is a Zinc- and Iron-Binding Peptide.

ABSTRACT Enterotoxigenic Escherichia coli (ETEC) is a major diarrheal pathogen in children in low- to middle-income countries. Previous studies have identified heat-stable enterotoxin (ST)-producing ETEC as one of the major diarrhea-causing pathogens in children younger than five years. In this study, we examined iron and zinc binding by both human and porcine ST variants and determined how host metallothionein could detoxify ST. We found that ST purified from ETEC culture supernatants eluted as a doublet during C18 reverse-phase chromatography. Leading edge fractions of the ST doublet were found to be devoid of iron, while trailing edge fractions of the ST doublet were found to contain measurable iron. Next, we found that purified ST could be reconstituted with iron under reducing and anaerobic conditions, and iron-bound ST attenuated the induction of cGMP in T84 epithelial cells. Moreover, we demonstrated that supernatants of ETEC 214-4 grown under increasing iron concentrations were only able to induce cGMP at iron concentrations greater than 5 μM. In vitro studies also demonstrated that ST binds zinc, and once bound, zinc removal from ST required denaturing conditions. Zinc-bound ST also failed to induce cGMP. We found that ST contributes disulfide bonds to the perceived oxidized glutathione pool, increases the rate of zinc release from metallothionein, and can be detoxified by metallothionein. Lastly, we showed ST induces transcriptional changes in genes previously shown to be regulated by deferoxamine. These studies demonstrate ST ETEC pathogenesis may be tied intimately to host mucosal metal status. IMPORTANCE Enterotoxigenic Escherichia coli (ETEC) is a major diarrheal pathogen in children in low- to middle-income countries, deployed military personnel, and travelers to regions of endemicity. The heat-stable toxin (ST) is a small nonimmunogenic secreted peptide with 3 disulfide bonds. It has been appreciated that dietary disulfides modulate intestinal redox potential and that ST could be detoxified using exogenous reductants. Using biochemical and spectroscopic approaches, we demonstrated that ST can separately bind iron and zinc under reducing conditions, thereby reducing ST toxicity. Moreover, we demonstrated that ST modulates the glutathione (GSH)/oxidized glutathione (GSSG) ratio and that ST should be considered a toxin oxidant. ST can be detoxified by oxidizing zinc-loaded metallothionine, causing free zinc to be released. These studies help lay a foundation to understand how diarrheal pathogens modulate intestinal redox potential and may impact how we design therapeutics and/or vaccines for the pathogens that produce them.
Improving High-Latitude and Cold Region Precipitation Analysis

Accurate estimation of precipitation is important for science and application. In high latitudes precipitation estimation is difficult due to several challenges in remote sensing of precipitation and sparseness of in situ observations. Furthermore, in situ observations can also have large errors, especially for measurement of snowfall that occurs frequently in high latitudes. Here, we show how CloudSat and the Gravity Recovery and Climate Experiment (GRACE) can provide additional information to refine our quantification of high latitude precipitation. We show this through case studies over ocean, Eurasia, Tibetan Plateau, and arctic basins. The results suggest that combination of CloudSat and GRACE can provide valuable information on quantifying snowfall accumulation that can also be used to assess gauge undercatch correction methods. Together with ongoing efforts under GPM to advance Level 2 precipitation retrievals and their combination, great opportunities exist to advance precipitation retrieval in high latitudes.
Ventral tegmental area GABA neurons mediate stress-induced anhedonia

Abstract Stressful experiences frequently precede depressive episodes1. Depression results in anhedonia, or disrupted reward-seeking, in most patients2. In humans3,4 and rodents5,6, stress can disrupt reward-seeking, providing a potential mechanism by which stress can precipitate depression7-9. Yet despite decades investigating how stress modulates dopamine neuron transmission between the ventral tegmental area (VTA) and nucleus accumbens (NAc), the underpinnings of the stress-anhedonia transition remain elusive10-13. Here we show that during restraint stress, VTA GABA neurons drive low frequency NAc LFP oscillations, rhythmically modulating NAc firing rates. The strength of these stress-induced NAc oscillations predict the degree of impaired reward-seeking upon release from restraint. Inhibiting VTA GABA neurons disrupts stress-induced NAc oscillations and reverses the effect of stress on reward-seeking. By contrast, mimicking these oscillations with rhythmic VTA GABA stimulation in the absence of stress blunts subsequent reward-seeking. These experiments demonstrate that VTA GABA inputs to the NAc are both necessary and sufficient for stress-induced decreases in reward seeking behavior, elucidating a key circuit-level mechanism underlying stress-induced anhedonia.
Iodate interactions with calcite: implications for natural attenuation

Solid-phase interactions and speciation are important to radioiodine transport in groundwater. At the Hanford Site in Southeastern Washington State, iodate (IO3−) is the main aqueous species in dilute radioiodine groundwater plumes. Like other oxyanions, IO3− may be incorporated into and/or adsorbed onto calcite, a common mineral at Hanford, decreasing its mobility in the environment. A series of macroscale batch experiments combined with solid-phase characterization were conducted to identify variables impacting time-dependent aqueous IO3− removal via calcite precipitation and determine the location of IO3− within the calcite crystal structure. Results demonstrated 11.5–97% aqueous IO3− removal during initial rapid calcite precipitation. Incorporation was apparently the main removal mechanism, although later slower precipitation and/or adsorption may have also contributed to IO3− removal. Using a higher concentration of the calcite-forming solutions (i.e., using 1 M vs. 0.1 M concentrations) resulted in an increase in the amount of precipitated calcite and a greater percentage of IO3− removed; however, calcite formed with lower molarity solutions resulted in higher IO3− mass (µg/g) removal. Solubility testing of laboratory-produced calcites showed only small differences in solubility for calcite with and without IO3− incorporated into the structure. Evidence collected from SEM/FIB and TEM/SAED suggested that the IO3− incorporated into calcite was present in regions close to the surface (implying potential easy release upon calcite dissolution).
Shareholder Wealth Effects of the Private Securities Litigation Reform Act of 1995

This paper investigates the reaction ofstock prices to enactment of the Private Securities LitigationReform Act of 1995 (PSLRA). Based on a sample of 489 high-technologyfirms, we find that the PSLRA was wealth-increasing, on average,and that the market reaction is more positive for firms at greatestrisk of being sued in a securities class action. However, wealso show that the PSLRA was less beneficial for firms likelyto be the subject of a meritorious lawsuit. Collectively, ourevidence implies that shareholders generally benefit from restrictionson private securities litigation, although these benefits aremitigated when other mechanisms for curbing fraudulent activityare inadequate.
Transgender surgery – Knowledge gap among physicians impacting patient care

Transgender surgeries are increasingly performed across the globe and in the United States. Although comprehensive centers exist, which are well equipped to cater and tailor to the needs of this population subset, quite often their resultant complications are handled at a different institution owing to the acuity of the condition. However, interestingly the psychosocial needs, medical pathophysiology, available surgical procedures, and their resultant complications are still not a part of the regular medical curriculum. This translates into inadequate care when physicians from vast majority of institutions that do not routinely perform transgender surgery encounter these patients with complications from gender-affirming surgeries. We present a case of a patient who underwent complex multiple gender-affirming surgeries, presenting to our emergency department with an acute abdomen; this resulted in a diagnostic and management dilemma and review of brief pertinent literature. We recommend that transgender medicine and its basics needs should be exposed to currently practicing physicians by continuing medical education, trainees and medical students alike via incorporation into their curriculum, to decrease health disparities among the lesbian, gay, bisexual, transgender, and queer community.
Teaching Multidisciplinary Research Methods at a Small Liberal Arts College

This chapter draws upon my experience teaching a multidisciplinary research methods course to political science and sociology majors. I describe how I found myself teaching such a course and trace my pedagogical evolution over my first three years as an early-career academic. The pedagogical approach that I developed over this period emphasizes the research process, with a focus on research design that is detached from a specific social science discipline. At the end of the chapter, I provide some strategies to assist instructors at institutions that currently have, or are considering, a multidisciplinary research methods curriculum. I find that while there are significant challenges in teaching such a course, it may be an effective means to pool faculty resources across adjacent disciplines.
The Global Epidemiology of AIDS

In 1981, the first cases of AIDS were recognized in previously healthy homosexual men residing in the United States. Within just a few years, thousands of cases were recognized in members of other high-risk groups, including injecting drug users (IDUs), hemophiliacs, and recipients of blood transfusions. The diversity of the global AIDS pandemic is also reflected in the heterogeneity of the viral subtypes of HIV. Recent studies have suggested that HIV entered the human population through multiple zoonotic infections from simian immunodeficiency virus (SIV)-infected nonhuman primates sometime in the early to mid-20th century. In 1985, a second human retrovirus associated with AIDS, HIV-2, was identified in West Africa. This virus has been found to have relatively high prevalence rates among hospitalized patients, female prostitutes, and patients who attend sexually transmitted disease (STD) clinics in several countries of West Africa. Sub-Saharan Africa represents the epicenter of the global HIV/AIDS pandemic. HIV/AIDS is now the leading cause of death in some countries of the Caribbean basin.
Fluid dynamic characterization of a novel branching anastomosis design

Geometric characteristics of a vascular anastomosis can have important biomechanical impacts, particularly in the hemodynamic context of wall shear stress (WSS). In this study, we propose a new branching anastomosis design, the Hybrid anastomosis, to connect a donor vessel to two recipient vessels. The central obstruction characteristic of the traditional Figure 8 anastomosis is mitigated by creating a recessed lumen at the bifurcation. Chicken vessels were used to create and test three Figure 8 and three Hybrid anastomoses ex vivo. Computational fluid dynamics (CFD) simulations of idealized anastomosis designs were then used to verify the experiments and further studied the WSS and WSS gradient (WSSG) profiles of the designs. Experimental results showed increased flow through the Hybrid anastomosis (0.40 ml/s vs. 0.23 ml/s). The mean suture time averaged 20 and 28 min for the Figure 8 and Hybrid anastomoses, respectively. CFD simulations agreed with the experiments; the simulations showed lower flow resi...
Range gate pull off (RGPO): detection, observability and /spl alpha/-/spl beta/ target tracking

This paper considers the range gate pull off (RGPO) tracking problem, an electronic counter measure (ECM) which is included in the Benchmark 96 Target Tracking Problem. In RGPO, the target senses the radar pulse and repeats it with a control delay. The amplified, repeated/delayed pulse results in a false range measurement with signal-to-noise (S/N) ratio larger than the real target range measurement confusing the radar/target detection and tracking process. A false range measurement, r/sup ft//sub k/, appears along with the true range measurement, r/sub k/, and depending on the controlled delay motion causes range tracking bias, velocity and/or acceleration pull-off {r/sub po/, v/sub po/, a/sub po/} and eventually lost target track. Fundamental characteristics of the RGPO are considered from a target tracking viewpoint: the nature of the RGPO, the detection of true and false range measurements, the tracking observability, and the RGPO range /spl alpha/-/spl beta/ tracking. It is shown that it is impossible to track the true target using the false range measurement. Ironically, it is also shown that the RGPO false measurements intended to defeat target tracking contains information which can be used to improve the true target track. A practical RGPO /spl alpha/-/spl beta/ matrix tracking process is presented which tracks both true and false targets with improved performance.
Temporal stability of polydipsia-hyponatremia

We evaluated temporal stability and outcome predictors associated with polydipsia-hyponatremia (PH). Severity of PH was measured on two occasions separated by at least 1 year in 25 chronic psychiatric inpatients (24 with schizophrenia). Three-quarters of the sample had clinically evident PH on follow-up. Follow-up PH severity was significantly related to intake severity and hospitalization length. Our findings suggest that PH may be a persistent condition with specific outcome predictors.
Weak interactions at high energies

We discuss the weak interactions from an $S$-matrix point of view in order to make some qualitative statements about high-energy behavior. In order to separate the weak interactions from others as much as possible, attention is focused on the weak interactions of leptons neglecting electromagnetism. We examine the consequences of imposing the constraints of unitarity and analyticity on weak amplitudes whose low-energy behavior is assumed to be correctly given by the usual Fermi theory (including the possibility of neutral currents). We first study corrections to the low-energy limit by using the Mandelstam iteration to express all lepton-lepton two-body scattering amplitudes to third order in the Fermi constant in terms of a small number of subtraction constants. We then speculate beyond perturbation theory. We discuss some consequences of forward dispersion relations and propose a mechanism for providing the necessary damping of weak amplitudes at high energies. The mechanism is the existence of the intermediate vector boson coupled weakly to leptons but interacting strongly with itself. We examine some consequences of this hypothesis.
The relationship of maternal beliefs about sex typing to maternal and young children's behavior

Possible links between maternal beliefs about children's sex-typed behavior and familial characteristics, mothers' interactions with their young children, and children's cognitive functioning were explored. One hundred and thirty-two mothers and their two-year-olds were seen; familial social class, birth order, and child gender were selection-criterion variables. Sex-typed beliefs were assessed by asking mothers to rate a number of qualities and interests as to whether or not each was more likely to occur in or be characteristic of boys or of girls, or was equally likely to be characteristic of boys and girls. Mothers rated qualities for two different age periods—toddlerhood and middle childhood. Mothers and toddlers were observed in a free play setting for 20 min. Responsivity and type of behavior emitted were assessed. The Bayley Scale of Infant Intelligence was given at 24 months. The findings were as follows: First, gender and social class were related to maternal beliefs about sex-typed characteristics. Second, maternal sex-typed beliefs were negatively related to active toy play and distal interaction, with this relationship significant for daughters but not sons. Third, daughters of low sex-typed mothers were more responsive and more likely to seek comfort than daughters of high sex-typed mothers. Fourth, daughters of mothers who had strong sex-typed beliefs had lower IQ scores at 24 months than did daughters of mothers with beliefs less strong; this relationship was not found for sons. Research on cross-sex behavior and enhanced cognitive functioning was reviewed as it relates to these findings.
Kaci Hickox: Public Health and the Politics of Fear

Kaci Hickox was a nurse who worked with persons who were infected with Ebola in West Africa. When she returned to the United States, the governors of New Jersey and Maine intervened to confine her to inpatient quarantine despite the fact that she was asymptomatic and had no serological evidence of infection. She defied the quarantine which resulted in enormous public attention and discussion of quarantine and public fear. This article summarizes the case discussing the history of the case, the government actions, and the final legal rulings.