cssi/SciSciGPT-SciSciNet huggingface dataset:
Abstract 488: Acute Fluvastatin Pleiotropy Is Mevalonate Independent

Objectives Thrombospondin 1 (TSP1) is a matricellular glycoprotein present in injured arteries, and acts as a chemoattractant for vascular smooth muscle cells (VSMC). Migration of VSMCs to an area of injury plays a role in the development of intimal hyperplasia. We have recently shown that acute treatment of VSMCs with statins leads to a decrease in TSP1-induced VSMC chemotaxis. The purpose of this study was to determine whether the acute statin effect is dependent on the mevalonate pathway or is a pleiotropic effect. Methods Quiescent VSMCs were treated for 20 hours (standard time) or 20 minutes (acute treatment) with 100μM mevalonolactone, 0.5 μM fluvastatin, or mevalonolactone and fluvastatin combined. Migration of VSMCs towards 20 μg/ml TSP1 was assessed using a modified Boyden microchemotaxis chamber. Data was recorded as cells migrated per 5 high power fields and converted to percent positive control. Extracellular signal-regulated kinase 1/2 (ERK 1/2) activation was determined by Western blot. Densitometry is presented as percent positive control. Results TSP1 induced VSMC migration compared to SFM, 100% + 7.6 vs. 35.3% + 4.5. Treatment with fluvastatin for 20 hours (34.3% + 6.9) or 20 minutes (38.4% + 9) inhibited TSP1-induced VSMC migration. 20 hour mevalonate treatment together with fluvastatin restored the migratory effect of TSP1, 81% +9.9, p=0.11. Addition of mevalonate to acute fluvastatin treatment, did not reverse the anti-migratory effect of fluvastatin compared to TSP1 alone, 35.6% + 9.9, p Conclusion These data indicate long-term fluvastatin inhibition of TSP1 stimulated migration is at least partially dependent on the mevalonate pathway. In contrast, acute fluvastatin inhibition of TSP1-induced chemotaxis involves an alternate pathway resulting in pleiotropic statin effects. Previous studies found that standard treatment time with statins inhibited ERK 1/2 activation. Our current study found that acute fluvastatin inhibition of TSP1-induced chemotaxis does not appear to be ERK1/2 dependent.
Audiologists' communication behaviour during hearing device management appointments.

AbstractObjective: The aim of this exploratory study was to describe audiologist communication behaviours during appointments for hearing device monitoring and management before and after participation in counselling skills training. Design: The study used a longitudinal design with three assessment points over 6 months. Study sample: The sample included 10 audiologists and audiology graduate students interacting in a professional setting with their clients. Results: Audiologists reported improvement in their counselling skills from pre-training to follow-up, which was consistent with objective findings that audiologist relative speaking time decreased from pre-training to post-training as well as from pre-training to follow-up. Observer-rated scores of participants’ counselling skills; however, yielded no significant differences across time. Conclusions: Some improvement was noted in audiologists’ counselling behaviour following a 1-day communication skills workshop and continued learning support. It is ...
MANDATORY RETIREMENT AND THE CONSUMPTION PUZZLE: DISENTANGLING PRICE AND QUANTITY DECLINES

This study investigates changes in household consumption at retirement based on a comprehensive, diary-based household survey from China. We focus on disentangling price changes from quantity changes at retirement. The mandatory retirement policy in China provides a quasi-experimental setting for nonparametric identification of the true causal effects of fully anticipated retirement. Using a regression discontinuity design, we find that food expenditure declines at retirement, particularly among the less-educated group. We further show that this decline is driven by a reduction in prices rather than quantities. These findings, along with a documented increase in shopping time for food upon retirement among the less-educated households, are consistent with a time allocation model in which education enhances the value of leisure. (JEL J26, C21)
The Digital Humanities and Teaching Iberian and Latin American Music History

Instructors of music history today often seek resources to strengthen their ability to responsibly include Spanish, Portuguese, and Latin American topics in their course offerings. As one mode of engagement, this essay considers how ongoing projects in the digital humanities can facilitate the serious teaching of Iberian and Latin American topics in music studies by introducing students to digitized primary source material, online databases, and other resources relevant in the field. It also notes that existing digital resources present pedagogical challenges at the undergraduate level, as many humanities projects tend to be geared toward younger students or toward professional academics.
UX Practitioners' Engagement with Intermediate-Level Knowledge

Scholars have repeatedly called for the knowledge production efforts of the HCI research community to have resonance with the needs of practitioners. These efforts, reified in approaches such as "implications for design," annotated portfolios, and other forms of intermediate-level knowledge have begun to take hold within the research community, yet it is unclear if and how these forms of knowledge are used to actually support user experience (UX) practice. In this study, we analyzed resources shared via URLs that pointed to articles on external websites within a practitioner-focused Reddit community. Using Lowgren's taxonomy of intermediate-level knowledge, we identified the forms of knowledge these resources represent, and use this analysis as a provocation for future exploration into the types of knowledge practitioners desire and use to support their practice.
Implementing a Multidisciplinary Approach to Treating Tuberous Sclerosis Complex: A Case Report.

Objective:Tuberous sclerosis complex is expressed throughout the body, resulting in a range of clinical manifestations that can be challenging to manage.Results:The authors report a patient who pre...
Twelve-month prospective cohort study of patients with severe traumatic brain injury and their relatives: Coping, satisfaction with life and neurological functioning.

ABSTRACTBackground: To examine the associations between the functioning of patients with severe traumatic brain injury (TBI), and their relatives’ coping style and quality of life across 12 months post-injury.Methods: Prospective, population-based cohort study assessing 188 patients with severe TBI (Abbreviated Injury Scale of the head region [HAIS] score >3), and their relatives, 3, 6 and 12 months post-injury. Data were drawn from a larger national study run in Switzerland (2007–2011). Patient assessment: Glasgow Coma Outcome Scale Extended (GOSE), Patient Competency Rating Scale for Neurorehabilitation (PCRS-NR). Relative assessment: Health-Related Quality of Life (HRQoL; 12-item short form health survey [SF-12]), Coping Inventory for Stressful Situations (CISS). Mixed linear models were run separately for ages >50 and ≤50 (i.e. bimodal distribution).Results: Patients’ GOSE score was associated with relatives’ reported mental SF-12 scores across age (ps < 0.01). Relatives’ CISS was associated with pati...
CHAPTER 5 – The Mechanism of V(D)J Recombination

This chapter describes a series of site-specific recombination of events, termed as “V(D)J” recombination reaction, the biochemistry of the cleavage reactions, the activities of the recombination of activating gene (RAG) proteins, and the components of the nonhomologous end joining(NHEJ) deoxyribonucleic acid (DNA) repair pathway. V(D)J serves to assemble antigen receptor genes from arrays of gene segments. In broad terms, rearrangement is initiated by the lymphoid-specific V(D)J recombinase composed of therecombination activating gene 1 and 2 (RAG1 and RAG2) proteins. Together, RAG1 and RAG2 bind the recombination signal sequences (RSS) that flank each gene segment and introduce a double-strand break (DSB) between the RSS and the flanking coding DNA. The DNA ends generated by cleavage are asymmetrical, with the coding end covalently sealed into a hairpin, and the signal end is presented as a 5´ phosphorylated blunt DNA end. This first stage of V(D)J rearrangement is the point at which most of the regulation of the recombination reaction is imposed. Joining of the broken DNA, generated by RAG cleavage, is mediated by components of NHEJ DNA repair pathway.
Moisture-induced aggregation of lyophilized insulin

A critical problem in the storage and delivery of pharmaceutical proteins is aggregation in the solid state induced by elevated temperature and moisture. These conditions are particularly relevant for studies of protein stability during accelerated storage or for proteins loaded in polymeric delivery devices in vivo. In the present investigation, we have found that, when exposed to an environment simulating these conditions, lyophilized insulin undergoes both covalent and noncovalent aggregation. The covalent process has been elucidated to be intermolecular thiol-catalyzed disulfide interchange following β-elimination of an intact disulfide bridge in the insulin molecule. This process is accelerated by increasing the temperature and water content of the insulin powder or by performing lyophilization and/or dissolution of insulin in alkaline media. The aggregation can be ameliorated by the presence of Cu 2+ , which presumably catalyzes the oxidization of free thiols. The water sorption isotherm for insulin reveals that the extent of aggregation directly correlates with the water uptake by the lyophilized insulin powder, thus pointing to the critical role of protein conformational mobility in the aggregation process.
Material Requirements for Nonlinear Third Order Phenomena in Waveguides

Publisher Summary This chapter discusses the requirements for guided wave switching devices. Semiconductors, organics, and fibers have been used to implement all-optical guided wave switching devices, with varying degrees of success. The waveguide geometries used can be separated into two basic types. In the simplest, that of a nonlinear Mach–Zehnder interferometer, an input signal is split into two separate propagation paths (channels), which are interfered after some distance to produce a signal output. The relative nonlinear phase shift and therefore, the interference condition when the channels are recombined depend on the input power. The key concept here is that the signals in the two channels propagate and acquire nonlinear phase shifts independently of one another. This device that is the basis of the nonlinear loop mirror has been demonstrated successfully in fibers. The other class of switching geometries involves the interaction of two co-propagating or counter-propagating modes, either in two coupled or a single waveguide(s).
Evolution of Melatonin Function: A Hypothesis

ABSTRACT Melatonin has many ascribed functions, many of which are involved in the entraining or reinforcement of various rhythms in vertebrates. A hypothesis concerning the evolution of a biological timing function for melatonin is outlined as well as some background information supporting the hypothesis. Also presented are some avenues of investigation which may be used to test the hypothesis so that it may be either accepted and modified or rejected.
Determination of the Mechanical Properties of the Contractile System in Arterial Smooth Muscle Using Classical Muscle Models

Classically the mechanics of muscle have been represented in terms of its ability to develop isometric force. With regard to the role of vascular smooth muscle in the control of circulatory function a more appropriate measure of mechanics is its ability to shorten. This conclusion follows from the fact that the resistance to blood flow is an inverse function of blood vessel radius which is determined by the shortening of vascular smooth muscle cells under conditions of constant load. In fact, such a representation may not be completely appropriate since the contraction of vascular smooth muscle in vivo produces not only changes in blood vessel dimensions but also changes in transmural pressure which would affect the load against which the cells contract. Isometric force development and isotonic or isobaric shortening represent two different measures of the same physical-chemical processes in muscle with different independent variables maintained constant1. As such, some relationship must exist between these two measures of smooth muscle cell mechanics.
Arachidonic Acid Metabolism in the Skin

The prostaglandins and related arachidonate metabolites are not normally synthesized or stored to any extent in body tissues. Increased levels are brought about by rapid biosynthesis in response to a variety of chemical, physical and hormonal factors. This synthesis or arachldonlc acid cascade is complex and includes several enzymes that are affected by endogenous and/or exogenous regulatory factors. Generally, molecular oxygen is inserted into a polyunsaturated fatty acid with acyl chain rearrangement to form the various structures. The principle end products of the various branches of the pathway are the prostaglandins, the thromboxanes, prostacyclin, the hydroperoxy and hydroxyfatty acids, and the leukotrlenes. All are derived from the essential fatty acids in the diet.
Modulation of the assembly of immunoglobulin subunits by J chain.

Because J chain is present in polymeric and not monomeric immunoglobulin molecules and since it is released from polymers when they are reduced to subunits, it has been suggested that J chain plays an important role in the assembly of both IgA and IgM polymers. J chain has been reported (1) to have a high half cystine content (10–12 per mole), and there are, therefore, sufficient cysteine residues to undergo disulfide bond formation with each of the subunits in a pentameric immunoglobulin molecule. Consistent with this thesis are quantitative estimates of the amount of J chain in IgM and IgA suggesting that there is one J chain per mole of polymer regardless of the polymeric size.
Monoclonal gammopathy in a child with leukemia.

This paper describes the case history of a boy found to suffer from acute blastic leukemia at the age of two years. Manifestations of an intracranial localization of the leukemic process occurred several times in the course of the next 18 months; a generalized relapse responded well to therapy. The boy subsequently developed a severe refractory virus infection of the skin and suffered a few other virus infections, without any of the usual changes in the morphology of the blood. A few weeks later he developed a monoclonal gammopathy of the IgG class type L with Bence Jones proteinuria, likewise of type L. The possible causes of this clinical course and of the paraproteinemia are discussed.
Metabolic Liver Disease: Part 2

This chapter will review three genetically determined diseases: alpha-1 antitrypsin deficiency, Wilson disease, and hereditary hemochromatosis. Liver disease associated with cystic fibrosis and other disorders of iron storage are also reviewed.
Role of MCP-1 and CCR2 in ethanol-induced neuroinflammation and neurodegeneration in the developing brain

Neuroinflammation and microglial activation have been implicated in both alcohol use disorders (AUD) and fetal alcohol spectrum disorders (FASD). Chemokine monocyte chemoattractant protein 1 (MCP-1) and its receptor C-C chemokine receptor type 2 (CCR2) are critical mediators of neuroinflammation and microglial activation. FASD is the leading cause of mental retardation, and one of the most devastating outcomes of FASD is the loss of neurons in the central nervous system (CNS). The underlying molecular mechanisms, however, remain unclear. We hypothesize that MCP-1/CCR2 signaling mediates ethanol-induced neuroinflammation and microglial activation, which exacerbates neurodegeneration in the developing brain. C57BL/6 mice and mice deficient of MCP-1 (MCP-1−/−) and CCR2 (CCR2−/−) were exposed to ethanol on postnatal day 4 (PD4). Neuroinflammation, and microglial activation, and neurodegeneration in the brain were evaluated by immunohistochemistry and immunoblotting. A neuronal and microglial co-culture system was used to evaluate the role of microglia and MCP-1/CCR2 signaling in ethanol-induced neurodegeneration. Specific inhibitors were employed to delineate the involved signaling pathways. Ethanol-induced microglial activation, neuroinflammation, and a drastic increase in the mRNA and protein levels of MCP-1. Treatment of Bindarit (MCP-1 synthesis inhibitor) and RS504393 (CCR2 antagonist) significantly reduced ethanol-induced microglia activation/neuroinflammation, and neuroapoptosis in the developing brain. MCP-1−/− and CCR2−/− mice were more resistant to ethanol-induced neuroapoptosis. Moreover, ethanol plus MCP-1 caused more neuronal death in a neuron/microglia co-culture system than neuronal culture alone, and Bindarit and RS504393 attenuated ethanol-induced neuronal death in the co-culture system. Ethanol activated TLR4 and GSK3β, two key mediators of microglial activation in the brain and cultured microglial cells (SIM-A9). Blocking MCP-1/CCR2 signaling attenuated ethanol-induced activation of TLR4 and GSK3β. MCP-1/CCR2 signaling played an important role in ethanol-induced microglial activation/neuroinflammation and neurodegeneration in the developing brain. The effects may be mediated by the interaction among MCP-1/CCR2 signaling, TLR4, and GSK3β.
Integrated care, shared electronic records, and the psychology profession: a cautionary tale for counseling centers

Inadequate attention has been paid to the implications for clients and professional psychology resulting from use of electronic records in outpatient integrated care settings. Affecting clients, th...
No room at the inn: Use of maternal-child simulation when hospital clinical is restricted.

BACKGROUND This qualitative, educational, and phenomenological study examined practical nursing (PN) students entering the maternal-child component of the nursing program. With the limited availability of hospital sites, students were unable to attain hands-on hospital experience. To bridge this gap in nursing education, strategies utilizing maternal-child high-fidelity simulation (HFS) were implemented as an effective intervention. METHODS One group of students (n = 10) participated for this pilot project over one semester as part of their curriculum. Normal and emergency simulation training related to childbirth was reviewed first with lecture, then observing, practicing, and critiquing classmates during HFS exercises. RESULTS Students unanimously expressed increased confidence, awareness, and proficiency with obstetrical HFS. Instead of memorizing, active learning promoted understanding and retaining concepts. Examination scores reflected passing grades for the entire cohort. CONCLUSION This simulation pedagogical approach with a paradigm shift from low-fidelity simulation focusing on skills to HFS active learning incorporating the whole person with real-life clinical scenarios can be achieved in PN education. Instructor flexibility with strategies to adapt HFS to the learning environment of PN students promotes critical thinking, analysis, and problem-solving skills that can have a positive impact on academic and clinical performance.
Prospective Analysis of Vegetable Amount and Variety on the Risk of All-Cause and Cause-Specific Mortality among US Adults, 1999–2011

The Dietary Guidelines for Americans 2015–2020 (DGA) provides recommendations for consuming a specific amount and variety of vegetables, but no studies have assessed the relationship between DGA-recommended vegetable variety and risk of mortality. We prospectively assessed the relationship between vegetable amount and variety and the risk of mortality using nationally-representative survey data (n = 29,133). Hazard ratios were estimated using survey-weighted, multivariate, Cox-proportional hazards models. Mean follow-up time was 6.5 years (12.8 years maximum). Total deaths from all causes were 2861, which included 829 deaths from cardiometabolic disease (556 coronary heart disease, 170 stroke, and 103 diabetes). Compared to individuals who reported consuming the greatest amount of vegetables daily, those with the least intake had a 78% greater risk of mortality from all causes (HR: 1.78, 95% CI: 1.29–2.47), a 68% greater risk of death from cardiovascular disease (1.68, 1.08–2.62), and an 80% greater risk of death from coronary heart disease (1.80, 1.09–2.08). No relationships were observed between vegetable variety and risk of all-cause or cause-specific mortality. Greater vegetable amount, but not variety, was associated with a reduced risk of mortality from all causes, cardiovascular disease, and coronary heart disease. Additional large-scale longitudinal studies with repeated measures of dietary exposure are needed.
Feedback Can Be Less Stressful: Medical Trainee Perceptions of Using the Prepare to ADAPT (Ask-Discuss-Ask-Plan Together) Framework.

Introduction Meaningful feedback is essential for effective medical education, yet the feedback process has been consistently problematic for both learners and faculty. Emerging research on feedback highlights the importance of the learner, relationships, and culture for feedback to improve performance. We used the theory of self-regulated learning to develop the Prepare to Ask-Discuss-Ask-Plan Together (Prepare to ADAPT) framework to improve the feedback processes and investigated learner perceptions of this innovative feedback framework. Methods Qualitative thematic analysis of structured interviews of nine trainees participating in training on the Prepare to ADAPT feedback framework. Results The framework appeared primarily to potentially decrease learner anxiety and stress around the feedback process by providing a simple, structured discourse pattern. We identified five contributing themes: (1) increased efficiency of the feedback process; (2) formation of coaching/teamwork relationships; (3) facilitation of reflection and goal identification; (4) increased frequency of the feedback; (5) increased usefulness of the feedback. Discussion The Prepare to ADAPT framework may help decrease stress and anxiety of the feedback by clarifying the process, applying a structure, and developing coaching relationships. The framework was found to be easy to use and increased the number of effective feedback conversations in this exploratory study.
Confocal Imaging of Double-Stranded RNA and Pattern Recognition Receptors in Negative-Sense RNA Virus Infection

Double-stranded (ds) RNA is produced as a replicative intermediate during RNA virus infection. Recognition of dsRNA by host pattern recognition receptors (PRRs) such as the retinoic acid (RIG-I) like receptors (RLRs) RIG-I and melanoma differentiation-associated protein 5 (MDA-5) leads to the induction of the innate immune response. The formation and intracellular distribution of dsRNA in positive-sense RNA virus infection has been well characterized by microscopy. Many negative-sense RNA viruses, including some arenaviruses, trigger the innate immune response during infection. However, negative-sense RNA viruses were thought to produce low levels of dsRNA, which hinders the imaging study of PRR recognition of viral dsRNA. Additionally, infection experiments with highly pathogenic arenaviruses must be performed in high containment biosafety level facilities (BSL-4). The interaction between viral RNA and PRRs for highly pathogenic RNA virus is largely unknown due to the additional technical challenges that researchers need to face in the BSL-4 facilities. Recently, a monoclonal antibody (Mab) (clone 9D5) originally used for pan-enterovirus detection has been found to specifically detect dsRNA with a higher sensitivity than the traditional J2 or K1 anti-dsRNA antibodies. Herein, by utilizing the 9D5 antibody, we describe a confocal microscopy protocol that has been used successfully to visualize dsRNA, viral protein and PRR simultaneously in individual cells infected by arenavirus. The protocol is also suitable for imaging studies of dsRNA and PRR distribution in pathogenic arenavirus infected cells in BSL4 facilities.
Comparative Study of AODV And OLSR Routing Protocols

In this paper, we have implemented two routing algorithms over Mobile Ad-hoc Network (MANET) for wireless network. First is Ad-hoc On-Demand Distance Vector (AODV) routing protocol and second is Optimized Link State Routing Algorithm (OLSR) routing protocol. These algorithms enable the way for optimization of the routing parameters. These algorithms take into account the merits and demerits of both the protocols in the mobile network. Herein, we used Network Simulator- ns-2 and Xilinx (version 10.1) for Very High-Speed Integrated Circuit (VHSIC) hardware description language implementation of AODV and OLSR routing algorithms in wireless ad-hoc network. Experimental analysis has been done to compare the performance of both algorithms. In ns-2 software, the algorithm aims at improving the performance parameters of routing such as delay, throughput, jitter, and also added OLSR patch to run OLSR routing algorithm. In Xilinx software, algorithm aims at improving the performance parameter of routing such as macrocells, product term, register used, pin, functional block and memory used.
Exploring diet and status in the Medieval and Modern periods of Asturias, Spain, using stable isotopes from bone collagen

This study explored the relationship between paleodietary patterns and social inequality in rural human populations from Medieval (AD 600–1499) and Modern (AD 1500–1800) Asturias, Spain. Diets were investigated through stable carbon and nitrogen isotopes from a sample of burials from eight cemetery sites (n = 80). Social status was inferred by burial location, where individuals interred within church buildings (ad sanctos) were compared to those buried in cemeteries. While Medieval and Modern society was strongly hierarchical, burial location is only one factor in determining the status and diet of individuals. It was hypothesized that ad sanctos burials would have elevated δ15N values as a reflection of high-status individuals consuming protein-rich diets in comparison to lower-status peasant populations; however, results found no significant differences in δ15N values between those buried in ad sanctos compared to those buried in cemeteries. Rather, the results of our paleodietary reconstruction indicate that the difference in δ13C values is statistically significant between burial location, where ad sanctos burials have more elevated δ13C than commoner individuals. These elevated δ13C values suggest that those buried in places of prestige often consumed a different diet (more C4 resources) from than those buried outside of church walls.
Imagine This: An Object Starting a Revolution: The Radio, Exiled Voice, and the Mute Poet in Communist Romania

This paper analyzes the role played by Radio Free Europe in redistributing sound inside Romania, a country which experienced one of the most repressive communist regimes in Eastern Europe. By following the work of Monica Lovinescu, a cultural critic and writer, and Ana Blandiana, a poet, and leaning heavily on the theoretical framework provided by Giorgio Agamben, this paper uncovers the potential of disembodied voices. Voice, therefore, drives the revolution, providing the Romanian population with a means of escape, a means with which to reclaim their words and thus begin making demands for change. Two types of sounds/voices will be discussed in this paper, exiled sound and muted sound. This paper challenges the prevailing notions that Romania was a country without an effective intellectual/cultural public sphere which thus prevented it from fully partaking in the "Carnival of Revolution" of 1989. Introduction Imagine this: whispers, murmurs, secrets, noiselessness, rumors, hints, undertones, silence. Now this: literature, sound, voice, music, news, politics, discussions, poetry. If each of these imaginings makes up two distinct worlds, the first introduces a muted space, made up of taciturn individuals, silent bodies walking as if they had lost their voices to disease or a gunshot wound. The second world introduces the space of intellect and creativity, the space for voices to argue and receive one another, made up of individuals which communicate through words, written and spoken, through sounds, musical
The Role of Housing Environment and Dietary Protein Source on the Gut Microbiota of Chicken

The gut microbiota of chicken has received much attention due to its importance for bird health, food safety, and performance. In the United States, the impending transition to cage-free housing environments has raised many questions about its consequences for poultry health, productivity, and welfare. Therefore, we investigated how housing environments and feed composition affect the poultry gut microbiome. Such data is necessary to inform the design of production systems that promote health and food safety. In this study, we investigated the cecal microbiome of both caged and cage-free laying hens that were fed either an industry-standard soy-based versus a soy-free diet. Caged hens were housed in standard industry-style layer cages with one bird per cage, and cage-free hens were housed in a poultry barn with an outdoor enclosed yard with multiple hens per pen. Our study showed significant differences in the gut microbiota between cage-free and caged environments. Cage free housing generated higher diversity compared to caged housing. Furthermore, we observed a synergistic interaction of soy-based feed in cage-free housing, as the cage-free soy group showed the highest alpha diversity, whereas the caged-soy group showed the lowest diversity overall.
Geometric machine learning informed by ground truth: Recovery of conformational continuum from single-particle cryo-EM data of biomolecules

This work is based on the manifold-embedding approach to study biological molecules exhibiting continuous conformational changes. Previous work established a method capable of reconstructing 3D movies and accompanying energetics of atomic-level structures from single-particle cryo-EM images of macromolecules displaying multiple conformational degrees of freedom. Here, we introduce an unsupervised geometric machine learning approach that is informed by detailed heuristic analysis of manifolds formed by simulated heterogeneous cryo-EM datasets generated from an atomic structure. These simulated data were generated with increasing complexity to account for multiple conformational motions, state occupancies and typical microscope parameters in a wide range of signal-to-noise ratios. Using these datasets as ground-truth, we provide detailed exposition of our findings using several conformational motions while exploring the available parameter space. Guided by these insights, we build a framework to leverage the high-dimensional geometric information obtained towards reconstituting a quasi-continuum of conformational states in the form of a free-energy landscape and respective 3D density maps for all states therein. As shown by a direct comparison of results, this framework offers substantial improvements relative to the previous work.
Resveratrol Treatment Reverses Mild Angiotensin II-Induced Hypertension, but Not by Increased Natriuresis

Resveratrol is a phenol that reduces blood pressure in animal models of hypertension, but a mechanism is unknown. We reported resveratrol is a renal vasodilator that increases nitric oxide bioavail...
Cell Sources for Cartilage Tissue Engineering

Adult stem or progenitor cells have now been detected in most tissues of the body, including those relevant to the musculoskeletal system – bone marrow, bone, periosteum, cartilage, synovium, adipose and muscle. The cells of most tissues have been shown to have at least chondrogenic, osteogenic and adipogenic differentiation potential, and in some tissues, certain subfractions with greater differentiation potential are now described. Despite these advances, the relationship between the various cells of the different tissues is unclear, as is their relative importance in the field of regenerative medicine. There still remains a need for specific markers for these stem cell populations. Furthermore, to harness the therapeutic potential of stem cells for the treatment of skeletal pathologies, novel technologies need to be developed to isolate these cells effectively and efficiently.
Medium Chain Fatty Acid Binding to Human Plasma Albumin

Abstract The binding of hexanoic, octanoic, and decanoic acids to defatted human plasma albumin was measured by equilibrium dialysis at 37° in a calcium-free Krebs-Ringer phosphate buffer, pH 7.4. The results were analyzed in terms of multiple stepwise equilibria. For each of the albumin binding sites, the magnitude of the equilibrium constants increased as the chain length of the acid increased: decanoate g octanoate g hexanoate. The first six equilibrium constants ranged from 1.5 x 104 to 4.7 x 10 for hexanoate, from 3.4 x 104 to 1.2 x 103 for octanoate, and from 105 to 3.4 x 103 for decanoate. In each case, the equilibrium constants occurred in a generally descending order, suggesting that major cooperative binding effects do not occur over the physiologically important range of fatty acid-albumin molar ratios. The equilibrium constants calculated for each of the three acids could not be grouped in a common way in terms of classes of binding sites, indicating that a single, uniform class-site binding model cannot be applied to these medium chain fatty acids. Octanoate binding was relatively insensitive to pH changes over the range of 6.0 to 8.2. Decanoate binding also was similar at pH 6.5 and 7.4. A decrease in octanoate binding occurred when the albumin was acetylated or when the medium contained 6 m urea. Octanoate binding also was decreased when either palmitate or oleate was added to albumin, suggesting that medium chain fatty acid transport may be influenced by changes in the plasma long chain free fatty acid concentration.
Safety or Control?: Workplace Organization and Occupational Health:

Using labor process theory and epidemiologic models as a framework, this study analyzed relationships between task exposures, worker labor process control, perceived safety climate, and three dependent measures of adverse occupational health: workplace injury, exhaustion, and health status among a national sample of employed adults (n = 1,607). Multivariate analyses confirmed that task demands of heavy labor were associated with workplace injury above baseline individual and job characteristics. Consistent with previous research, results indicated worker control was associated with increased health. Reliable co-workers were associated with less exhaustion, and working fast was associated with greater exhaustion. My results implied that increased safety climate was associated with fewer injuries, less exhaustion, and increased health. Safety climate did not account for associations between task exposures, labor process control, and work place injury or exhaustion. Results suggested that part of the influen...
Bending and radial deformation of lipid tubules on self-assembled thiol monolayers

Lipid tubules represent a hollow, cylindrical supramolecular structure formed by rolled-up lipid bilayers. We find that the lipid tubules of 1,2-bis(tricosa-10,12-diynoyl)-sn-glycero-3-phosphocholine can be bent into a loopike shape by the shrinking contact line of droplets on self-assembled monolayers (SAMs) of 1-dodecanethiol. The persistence length of individual lipid tubules is estimated to be approximately 41 microm. The radial deformation of the lipid tubules on SAMs is studied under applied load using atomic force microscope. The stiffness of the tubules in the radial direction is found to increase when the number of the lipid bilayers in the tubule wall increases.
Gr-1+ CD11b+ Myeloid-derived Suppressor Cells Suppress Inflammation and Promote Insulin Sensitivity in Obesity

Activation of immune cells, including macrophages and CD8+ T cells, contributes significantly to the advancement of obesity and its associated medical complications, such as atherosclerosis, insulin resistance, and type 2 diabetes. However, how the activation of these immune cells is regulated in vivo remains largely unexplored. Here we show that a group of immature myeloid cells with cell surface markers of Gr-1+ CD11b+ are highly enriched in peripheral tissues (i.e. liver and adipose tissues) during obesity. Down-regulation of these cells in obese animals significantly increases inflammation and impairs insulin sensitivity and glucose tolerance, whereas elevation of these cells via adoptive transfer has the opposite effects. Mechanistically, we show that under obese conditions, the Gr-1+ cells suppress proliferation and induce apoptosis of CD8+ T cells and are capable of skewing differentiation of macrophages into insulin-sensitizing, alternatively activated M2 macrophages. Taken together, our study demonstrates that immature myeloid cells provide a checks-and-balances platform to counter proinflammatory immune cells in the liver and adipose tissue during obesity to prevent overt immune responses.
Conditions, processes and consequences of technology use: a case study

Abstract The conditions, processes and consequences of technology implementation were explored in order to develop a holistic view of technology use in a typical elementary school (ages 6-11 years). This qualitative case study employed a symbolic interactionist conceptual framework, an interpretivist research paradigm and analytic induction strategies. Assertions generated from the process of analytic induction suggest that even when conditions appear ripe for transformational uses of technology, these uses often do not occur. The study raises questions about whether school-wide transformational uses of technology can occur without an organized reform effort and whether the conditions for transformational use of technology advocated in the literature are sufficient to facilitate such use. The study also supports the need to consider stages of adoption when planning for technology integration within a school and adds another dimension to the question of whether constructivist teaching strategies enable tra...
Reactivity of the M4S6+ (M = Mo, W) cluster with CO and NH3 in the gas-phase: An experimental and DFT study

Abstract Gas-phase M x S y + (M = Mo, W) cluster ions were generated by reactive sputtering using a magnetron cluster source. Adsorption of CO and NH3 were used to confirm the stoichiometry of the more prominent M x S y + (M = Mo, W) clusters. For the most abundant M 4 S 6 + cluster, the adsorption experiments are consistent with a calculated structure in which the metal atoms are arranged in an internal tetrahedron surrounded by bridging S-atoms. Binding energies for the consecutive addition of CO and NH3 were also calculated and found to be consistent with the observed cluster adduct stability.
Efficacy and toxicity of d-penicillamine in low-level lead poisoning

In a retrospective cohort study we reviewed our experience using D-penicillamine in children with low-level lead poisoning (whole blood lead levels 25 to 40 micrograms/dL) to determine its efficacy and the incidence of side effects. Two groups were compared: treated subjects (n = 84) were treated with penicillamine at a mean daily dose of 27.5 mg/kg; control subjects (n = 37) received no chelation therapy. Over a prechelation observation period of 60 days, lead levels (PbB) did not change in either group. With a mean period of 76 days of D-penicillamine therapy, PbB fell in treated patients by 33% (P less than 0.001). In 64 patients (76%), PbB was reduced to a currently acceptable range (less than or equal to 25 micrograms/dL). There were eight treatment failures (10%). In control subjects, mean PbB did not change significantly over 119 days of observation. Fourteen control subjects eventually required conventional chelation with calcium disodium ethylene-diaminetetraacetic acid, and 17 were lost to follow-up. Use of D-penicillamine was associated with an adverse reaction in 28 cases (33%); transient leukopenia occurred in eight, rash in seven, transient platelet count depression in seven, enuresis in three, and abdominal pain in two. Treatment was terminated prematurely in eight cases (10%) because of an adverse reaction. We conclude that D-penicillamine is effective therapy for selected children with low-level plumbism, but adverse effects can complicate or prevent its use in some patients.
MEASUREMENT OF THE MAGNETIC MOMENT OF THE PROTON IN BOHR MAGNETONS

An experimental determination of the ratio of the precession frequency of the proton, ${\ensuremath{\omega}}_{p}={\ensuremath{\mu}}_{p}{H}_{0}$, to the cyclotron frequency, ${\ensuremath{\omega}}_{e}=\frac{e{H}_{0}}{\mathrm{mc}}$ of a free electron in the same magnetic field has been carried out. The result, $\frac{{\ensuremath{\omega}}_{p}}{{\ensuremath{\omega}}_{e}}$, is the magnitude of the proton magnetic moment, ${\ensuremath{\mu}}_{p}$, in Bohr magnetons, since ${\ensuremath{\gamma}}_{p}=\frac{2{\ensuremath{\mu}}_{p}}{\ensuremath{\hbar}}$.Possible sources of systematic error were carefully investigated and in view of the results of this investigation and the high internal consistency of the data it is felt that the true ratio, uncorrected for diamagnetism, lies within the range $\frac{{\ensuremath{\omega}}_{e}}{{\ensuremath{\omega}}_{p}}=657.475\ifmmode\pm\else\textpm\fi{}0.008$. If the diamagnetic correction to the field at the proton for the hydrogen molecule is applied here the proton moment in Bohr magnetons becomes ${\ensuremath{\mu}}_{p}=(1.52101\ifmmode\pm\else\textpm\fi{}0.00002)\ifmmode\times\else\texttimes\fi{}{10}^{\ensuremath{-}3}(\frac{e\ensuremath{\hbar}}{2mc})$.
SYNAPTONEMAL COMPLEXES IN RED ALGAE1,2

SUMMARY The presence of synaptonemal complexes in the nuclei of young tetraspore mother cells is described for the first time in the red algae. Synaptonemal complexes were found in Janczewskia gardneri Setchell, Levringiella gardneri Setchell, Gonimophyllum skottsbergii Setchell, and Polycoryne gardneri Setchell. The synaptonemal complexes consist of 2 lateral, dark-staining elements from which small fibrils extend to form a less densely staining central element. With minor variations, the dimensions and structure of these synaptonemal complexes correspond to those found in other organisms.
Electromagnetic self-energy of quarks confined to a sphere

Abstract We calculate the electromagnetic energy shift, δω, of a massless fermion confined to a sphere. We find δω > 0, in agreement with our previous result for a slab, and in disagreement with the sign needed to obtain the right value of the neutron-proton mass difference in a model in which the hadron consists of confined massless quarks. We consider the effect of a bare mass for the confined quarks, and show that it is then possible for δω to be negative.
“I'm Not Sure We're Ready for This …”: Working With Families Toward Facilitating Healthy Sexuality for Individuals With Autism Spectrum Disorders

Navigating adolescence can be extremely difficult, especially for teens who are also dealing with the core symptoms of autism spectrum disorders (ASDs). Adolescence can also be a difficult time period for parents who struggle to know how best to support their teen. The present study aimed to (a) acquire information via focus groups about the concerns and service needs of parents regarding the sexuality development of their youth with ASDs and (b) evaluate the effectiveness of an 8-week parent sexuality-education curriculum. Themes that emerged from the parent focus groups are discussed along with outcomes from the parent education curriculum.
"The Purity of My Blood Cannot Put Food on My Table": Changing Attitudes Towards Interracial Marriage in Nineteenth-Century Buenos Aires

Lorenzo Barbosa had a big problem with his daughter Josefa. In June 1821, in Buenos Aires, young Josefa Barbosa was in love with Pascual Cruz. What bothered Lorenzo was that Pascual was a mulatto, while the Barbosa family was white. When the couple asked his permission to marry, Lorenzo vehemently opposed the union and withheld his consent. He was acting within his rights, since minor children (men and women younger than 25 and 23 respectively) were required by law to obtain parental permission to marry. To bolster his case, Lorenzo invoked the power of a colonial law issued in 1778, known as the Royal Pragmatic on marriage, which gave parents the right to block their children's marriages to “unequal partners.” Even though Buenos Aires had broken away from Spain in 1810, most colonial laws regarding family life, including the pragmatic, continued in force into the national period. But just as in colonial times, children retained the right to challenge parental opposition in court. If they chose to do so, the resulting case was known as a disenso .
Cortical cheiro-oral syndrome: a revisit of clinical significance and pathogenesis.

Abstract Objectives A restricted neurological deficit is not uncommon in patients with cortical lesions. However, in cheiro-oral syndrome (COS) associated with cortical involvement, the topographic disparity of the cheiral and oral representation area is hardly explained by the restricted sensorium at the homolateral mouth angle/lip and finger/hand, with sparing of the facial structures. Patients and methods In order to elucidate the factors of clinical significance and pathogenesis in cortical COS, 11 patients with COS associated with contralateral cortical lesions were analyzed, and the cases of similar patients described in the literature were reviewed. Results In our patients, the etiologies of COS were infarct, subdural hematoma, meningioma, and vascular malformation. The lesions were sizable enough to involve areas beyond the postcentral gyrus of the parietal lobe. A cortical sensory sign was detected in only six patients. Their paroxysmal sensorium without exacerbation on stimulus was in contrast to the clinical features of COS associated with thalamic lesions. Five patients suffered worsening of their neurological deficits without a parallel expansion of their infarct or hemorrhage. Removal of the hematoma or tumor in four patients rapidly abolished their sensorium. Conclusion Cortical COS is a warning sign of a potentially life-threatening etiology. Since there is a high frequency of exacerbation, COS should be carefully investigated, as a paucity of associated clinical signs was found in our patients. Paroxysmal sensorium signifies possible cortical involvement. Rapid decompression within the “golden period” is encouraged. It seems that the interaction between previously existing vascular compromise, sensory plasticity, and neuronal vulnerability predisposes patients to this peculiar sensory disorder. Epileptogenesis is unlikely. Thus, a reconsideration of COS in clinical practice is warranted.
Acute lethality in irradiated flour beetles: Evidence against a role of bacterial infection☆

Abstract The time course of mortality and the mean survival time of flour beetles dying after X-irradiation varied slightly in different strains and species. Within a given strain, however, both minimum and mean survival time were independent of dose over a wide range of exposures and independent of percent mortality. These findings suggest the operation of a single mode of death in irradiated beetles, in contrast to the “hierarchy of modes of death” recognized in irradiated mammals. Invasion of blood and tissues by enteric bacteria which gain entrance through the damaged intestinal lining, and subsequent spread of such infection, have been implicated in the lethal syndrome of irradiated mammals. The present investigation indicates that bacterial invasion does not contribute to the death of irradiated beetles. This conclusion is based on the lack of influence on survival of (1) administration of neomycin at levels which eliminated virtually all bacteria from the insects, (2) crowding or isolation, or (3) maintenance of irradiated beetles on medium in which other beetles previously had been raised. In addition, analysis of the distribution of deaths among a large number of vials each containing a small number of beetles disclosed no deviation from expectation based on random distribution; thus it seems unlikely that there is any “spread” of contagion within vials.