cssi/SciSciGPT-SciSciNet huggingface dataset:
PERICYTE CHANGES IN BRANCH RETINAL VEIN OCCLUSION

The model of experimental branch vein occlusion (BVO) in the monkey offers the opportunity to examine retinal capillaries under stress. Electron microscopic morphometry was done on 812 capillaries of 13 eyes of cynomolgus monkeys, comparing 579 capillary collaterals of 9 BVO eyes with 233 normal capillaries of 4 control eyes. The tissue underwent the myosin subfragment-1 technique to decorate and quantify bundles of actin filaments in capillary pericytes. The duration of BVO was 2-48 months. Capillary collaterals of BVO eyes had an enlarged caliber, endothelial hyperplasia, and pericyte hypertrophy, but no proportional increase in basement membrane area. Collaterals near the inner plexiform layer (IPL) had a greater wall thickness, pericyte coverage, and actin coverage than collaterals near the outer plexiform layer (OPL). Pericyte hypertrophy was proportionate to caliber increase in OPL vessels and exceeded caliber increase only in IPL vessels. Actin coverage was proportional with the vessel dilation and size of pericyte cytoplasm in all vessels. These findings indicate that capillary collaterals in BVO are not equipped morphologically for an increased regulatory role in microvascular flow beyond their normal function. Invest Ophthalmol Vis Sci 32:1455-1463,1991 For more than a century, pericytes have been suspected of being contractile and involved in regulating capillary blood flow. 1 " 4 The subsequent demonstration in vascular pericytes of filamentous actin 5 " 7 typical of smooth muscle cells, 8 of myosin and of troporhyosin, 7 - 910 and of adhesion plaques linking pericytes and endothelial cells" confirmed that pericytes share biochemical similarities with smooth muscle cells and are structurally specialized for contraction of the microvascular wall. Moreover, retinal pericytes have been shown to contract in vitro during normal growth 12 or in response to Mg adenosine triphosphate 13 and to relax in response to the actin filament disrupting agent, cytochalasin B. 12 In vivo indirect evidence for pericyte influence on retinal capillary blood flow was reported in experimental systemic hypertension. Although brain capillaries broke down, retinal capillaries remained intact, permitting the interpretation that the comparatively high number of contractile retinal pericytes may have counteracted the increase of hydrostatic pressure and
Ten Steps for Preparing MBA Learners for Business and Management

In the past few decades, business schools have realized that traditional graduate degrees in business such as an M.A. in business administration are not marketable because of their program design. Therefore, most business schools around the world are now focusing on the star of the business school’s product portfolio, the MBA program. The goal of the MBA program is to prepare learners for business and management. This paper presents the ten steps that business school must take to prepare the learner for business and management. The paper is a triggered research paper, and the research concludes that business schools must foster a culture of continuous learning, and work with facilitators (faculty), corporate partners, and accrediting agencies as a team to prepare MBA learners for the world of business and management.
The relation between peer victimization and changes in trauma symptoms in adolescents

THE RELATION BETWEEN PEER VICTIMIZATION AND CHANGES IN TRAUMA SYMPTOMS IN ADOLESCENTS By Anh-Thuy H. Le, B.S. A thesis submitted in partial fulfillment of the requirements for the degree of Master of Science, at Virginia Commonwealth University. Virginia Commonwealth University, 2014 Director: Albert D. Farrell Professor of Psychology Department of Psychology Peer victimization has been shown to negatively impact youth functioning and may be especially damaging during adolescence, given the increased importance of peers. However, there is a dearth of longitudinal research examining trauma symptomatology as an outcome of peer victimization with low-income, ethnic minority adolescents. The present study investigated this relation in a predominantly African American sample of 684 students assessed at five time points between the fall of their sixth grade and seventh grade school years. Growth mixture models grouped participants with similar victimization trajectories, and latent growth models related growth trajectories of physical and relational victimization to changes in trauma symptoms. Although initial levels of victimization were unrelated to changes in trauma symptoms over time, increasing victimization was associated with increasing trauma symptoms. These findings provide insight into the relation between peer victimization and trauma in an underserved sample of adolescents, with important implications for prevention efforts.
Neighborhood Environments and Cognitive Decline Among Middle-Aged and Older People in China.

Objectives Despite the growing interest in the effects of neighborhood environments on cognitive function, most studies on older people are based on cross-sectional survey data from developed countries. This study examines the relationship between neighborhood environments and decline in cognitive function over time among middle-aged and older people in China and whether this relationship varies between rural and urban residents. Methods The three waves of China Health and Retirement Longitudinal Study (CHARLS 2011-2015) were used. The sample included 12,131 respondents living in 298 rural villages and 4,059 respondents living in 150 urban communities. Three-level linear growth curve models were estimated to track trajectories of cognitive change over a 4-year period. Results Chinese older people who lived in neighborhoods with more handicap access, more bus lines, employment service, and higher socioeconomic status (SES) had slower cognitive decline. Neighborhood basic infrastructures, number of days that roads were unpassable, outdoor exercise facilities, and average social activity participation were associated with baseline cognitive function in both rural and urban areas, but neighborhood environments had more impact on cognitive decline among rural older adults than urban older adults. Discussions Findings from this study call for increased infrastructure development and community building programs in rural China.
1-Amino-2'-fucosyllactose inhibits biofilm formation by Streptococcus agalactiae.

2′-Fucosyllactose (2′-FL) is a ubiquitous oligosaccharide in human milk. Importantly, this carbohydrate promotes the growth of several strains of Bifidobacteria, a class of beneficial gut commensal, and inhibits epithelial binding of pathogens. In light of these protective effects, we elected to evaluate the potential of 2′-FL to serve as an antibacterial agent against Group B Streptococcus (GBS). While 2′-FL was devoid of any substantial antimicrobial or antibiofilm activity, conversion of 2′-FL to its reducing end β-amine provided a novel antibiofilm compound.
The Development of the Fear Response Circuitry of the Brain: A Neurodevelopmental Case for Family Counseling:

This article describes the early life social regulation of the fear circuitry in the brain. In this article, the authors discuss the link between the quality of the caregiving environment and the d...
"A night already devoid of stars": Illuminating the Violent Darkness in Kyle Baker's Nat Turner

In my essay I argue Kyle Baker’s 2008 graphic novel Nat Turner delivers a complex reimaging of history, which positions readers to confront an Antebellum past that produced few undamaged heroes. Recent criticism surrounding Baker’s work has split on how to understand Turner’s actions, but I argue Baker neither wholly celebrates nor condemns the rebellion. Instead, he focuses on the overwhelming violence that characterized Turner’s nineteenth century environment. The insurrection then becomes a natural part of a devastating cycle of violence caused by enslavement, and Turner himself is cast as a man who is simply acting rationally within a deeply troubled reality. Therefore, while Baker’s characterization of Turner and his rebellion does not leave readers with clear answers or heroes, it does offer a deeper understanding of slavery’s all-consuming violence and continuing impact on the nation.
Challenges of the Transition: A Case of Noncompliance in an Adult with Congenital Heart Disease

There are more adults than children living with congenital heart disease (CHD) due to improvements in surgical and medical CHD management today. In 2011, though, fewer than 30% of adult CHD patients were following up with specialized providers. An ineffective transition from pediatric to adult-focused medical care can result in lapses in CHD medical care, patient noncompliance, and increased risk of late complications. Early involvement of a palliative care team offers development of autonomy, identification of potential barriers to care, and support for patient and family that may improve transition success and quality of life in CHD patients.
Teaching Autistic Adolescents and Young Adults to Drive: Perspectives of Specialized Driving Instructors.

Abstract Background: Limited transportation access may curtail education, occupational training, social, and community engagement opportunities for autistic adolescents. Nearly one-third of autisti...
Engaging Residents in Planning a Community Garden: A Strategy for Enhancing Participation Through Relevant Messaging

Understanding residents’ perceptions and preferences regarding health promotion and community development strategies is vital. Community gardens, often collaborative community-engaged projects, are designed to be healthy places where neighbors gather; however, they have the potential to be much more. The purpose of the study was to gauge public support for a community garden in South Omaha and prioritize messaging strategies regarding the potential benefits of a garden. To that end, a bilingual online survey that assessed interest in, perceived benefits of, purposes for, and functional attributes to co-locate in a community garden was conducted. Through this process, we learned about the value of developing local data, importance of using an asset-based framework, understanding community perceptions about potential benefits, balancing community research endeavors, and developing partnerships to expand the reach of a project. Developing community research strategies and appropriate messaging in collaboration with community members and partners is critical to the success of community health promotion initiatives.
Gate-tunable Epsilon-near-zero meta-structures (Conference Presentation)

The optical response of epsilon-near-zero (ENZ) materials has been a topic of significant interest in the last few years as the electromagnetic field inside media with near-zero permittivity has been shown to exhibit unique optical properties, including strong electromagnetic wave confinement, non-reciprocal magneto-optical effects, and abnormal nonlinearity. These ultrathin ENZ materials are promising for the enhancement of quantum emission for optical sensing and enhanced absorption/emittivity for energy harvesting. This talk will review our recent development on a gate-tunable conducting oxide epsilon-near-zero meta-structures. I will present our recent development on the use of gate-tunable materials, transparent conducting oxides, to demonstrate an electrically tunable ultrathin ENZ perfect absorber enabled by the excitation of ENZ mode. In addition, I will present the active control of emissive properties of quantum emitters and enhanced optical nonlinearity in hybrid ENZ-plasmonic heterostructures.
Online information seeking behaviors of breast cancer patients before and after diagnosis: From website discovery to improving website information.

Abstract Despite the internet being a common place breast cancer patients seek information, navigating this Wild West of content can be challenging. The present study analyzed open-ended data from breast cancer survivors (n = 77) regarding their online information seeking behaviors when looking for breast cancer information to help inform the creation of improved online educational materials. Participants were asked what prompted them to seek information, which websites and search terms they used both before and after diagnosis, what information was useful, what misinformation was found, and what they would like to see improved. Results indicated symptoms, tests, or diagnoses prompt women to seek breast cancer information online, and that many different search terms and websites are used. More search terms and websites were utilized after diagnosis compared to before diagnosis, but the most common search terms and websites did not change much from before to after diagnosis. Cancer specific and general medical websites were the most popular. The most useful information related to treatment, obtaining information from other breast cancer survivors, statistics, and positively-valenced information. Though misinformation was not reported by many participants, some mentioned outdated survival rates, inaccurate information about alternative treatments, and other breast cancer patients’ experiences that did not align with their own. Participants desired improvements in treatment information, more factual information, a guide, and information that is easy to understand. Creation of a guide and use of search engine optimization to help breast cancer patients navigate this online information could be beneficial.
Environmental relative humidity affects Schirmer tear test results in normal dogs.

Objective To investigate the effects of environmental temperature and relative humidity on tear test results in dogs. Animals studied 22 normal dogs. Procedures Routine Schirmer tear tests (STT1) and phenol red thread tests (PRTT) were administered to normal dogs in four environmental conditions with different relative humidity (RH) and temperature (T). Environmental conditions (mean ± SD) included the following: normal indoor (RH = 49 ± 4%, T = 72 ± 2°F), outdoor (RH = 62 ± 11%, T = 85 ± 6°F), indoor high humidity (RH = 85 ± 6%, T = 71 ± 1°F), and indoor low humidity (RH = 39 ± 2%, T = 76 ± 1°F). ANCOVA models were used to assess for significant associations between tear test readings and RH/T (P Results A significant, direct positive relationship between RH and STT1 results was detected (y = 0.04909*X + 19.11, P = .006) but not between T and STT1. There was no significant relationship between PRTT and RH or T. Conclusions These results suggest that STT1 but not PRTT is affected by RH and that T does not influence STT1 or PRTT results in normal dogs. RH is unlikely, however, to cause clinically significant effects on STT1 readings in normal dogs when performed in average indoor conditions. Future studies should investigate the influence of RH on STT1 readings obtained in dogs with keratoconjunctivitis sicca.
Synthesis and characterization of [125I]TZ6544, a promising radioligand for investigating sphingosine-1-phosphate receptor 2.

Abstract Introduction Sphingosine-1-phosphate receptor 2 (S1PR2) activation exerts a critical role in biological abnormalities and diseases. A suitable radiotracer will advance our understanding of S1PR2 pathophysiology of diseases. The objective of this study is to evaluate the potential of iodine-125 labeled [125I]TZ6544 to be used for screening new compounds binding toward S1PR2, and assessing the changes of S1PR2 expression in the kidney of streptozotocin-induced diabetic rats. Methods [125I]TZ6544 was synthesized from borate precursor by copper (II)-catalyzed iodization reaction with [125I]NaI. [125I]TZ6544 was characterized using human recombinant S1PR2 cell membrane and biodistribution studies of [125]TZ6544 were performed on Wistar rats that were euthanized at 5 and 30 min post-injection. A rat model of diabetes was induced by IV injection of streptozotocin (55 mg/kg). In vitro autoradiography studies, immunostaining, and enzyme-linked immunosorbent assay (ELISA) analysis were performed in both diabetic and control rats. Results Radiosynthesis of [125I]TZ6544 was achieved successfully with good radiochemical yields of ~47% and high radiochemical purity of >99%. [125I]TZ6544 is a potent ligand in vitro for S1PR2 with Kd value of 4.31 nM. [125I]TZ6544 and [32P]-labeled endogenous S1P provided comparable IC50 values in radioactive competitive binding assays against known S1PR2 ligands. Compared to control, the kidney of diabetic rats had increased uptake of [125I]TZ6544, which could be reduced by a S1PR2 antagonist, JTE-013. Immunostaining and ELISA analysis confirmed that the diabetic rat had increased S1PR2 expression in the kidney. Conclusions [125I]TZ6544 was synthesized successfully in high yields, and in vitro evaluation suggested [125I]TZ6544 has high potential to be used for screening new S1PR2 compounds and investigating the pathophysiology of S1PR2 functions. The availability of [125I]TZ6544 may facilitate the development of therapeutics and imaging agents targeting S1PR2. Advances in knowledge [125I]TZ6544 showed increased expression of S1PR2 in diabetic rat kidney and can be used to determine binding potency of S1PR2 compounds.
Do early trends in oak barrens fire treatment predict later outcomes? Insights from three decades of vegetation monitoring

Vegetation structure, species diversity, and composition have been monitored at a fire-treatment and a fire-free control unit of a dry oak barrens and woodland complex in southern Illinois, USA, over a 29-year period and five burns. The restoration hypothesis is that fire management would result in different trends for vegetation parameters of conservation interest between fire treatment and control units, that before–after differences would be greater with fire management, and that early trends provide a reliable predictor for later outcomes. This study examines effectiveness of management in achieving restoration goals and uses response to the first two burns and monitoring results over the first seven years as an estimation period to test whether early trends with fire treatment are a reliable predictor for outcomes following three additional burns over the following 22 years. Trends differed between fire-treatment and control units for all parameters measured, and before–after differences were greater at the fire treatment unit. However, trends at the fire-treatment unit during the estimation period were a poor predictor of later outcomes. Tree density and basal area declined more than expected while ground-layer species density, richness, diversity, and percent cover did not keep pace with expectations of increase. Trends at the control unit were more predictable; however, tree basal area declined more than expected, possibly due to an outbreak of rapid white oak mortality disease, and decline of ground-layer species density was less than predicted from the early estimation period. Results suggested that fire alone can be effective at restoring woodland and barrens natural areas and that a fire return interval of about every four years would be optimal for maintaining composition and diversity in this specific oak barrens habitat. However, burns followed immediately by severe drought possibly can have negative interactions, resulting in declines of ground-layer species diversity.
Landscape governance: the prospects for the SITES rating system

Landscape is a synthesis of the cultural and natural processes of a place. As such, landscapes provide a suitable framework for governance that promotes sustainability and resilience. Any landscape holds the possibility to both improve and regenerate the natural benefits and services of ecosystems. The Sustainable Sites Initiative was an interdisciplinary group effort which developed a rating system that advances best practices for landscape design. The system, called SITES, is grounded in the ecosystem services concept. Advantages of SITES include its credibility, replicability, and scalability. Administered by Green Business Certification Inc., SITES is being used by the cities of New York, Chicago, and Atlanta, the state of Rhode Island, and the US. General Services Administration to guide design decisions toward sustainable outcomes. These practical applications in landscape governance help inform socio-ecological practice and theory.
Ultraviolet germicidal irradiation of the inner bore of a CT gantry.

PURPOSE: To investigate the feasibility and practicality of ultraviolet (UV) germicidal irradiation of the inner bore of a computed tomography (CT) gantry as a means of viral decontamination. METHOD: A UV lamp (PADNUT 38 W, 253 nm UV-C light tube) and UV-C dosimeter (GENERAL UV-C Digital Light Meter No. UV512C) were used to measure irradiance throughout the inner bore of a CT scanner gantry. Irradiance (units µW/cm2 ) was related to the time required to achieve 6-log viral kill (10-6 survival fraction). RESULTS: A warm-up time of ~120 s was required for the lamp to reach stable irradiance. Irradiance at the scan plane (z = 0 cm) of the CT scanner was 580.9 µW/cm2 , reducing to ~350 µW/cm2 at z = ±20 cm toward the front or back of the gantry. The angular distribution of irradiation was uniform within 10% coefficient of variation. A conservative estimate suggests at least 6-log kill (survival fraction ≤ 10-6 ) of viral RNA within ±20 cm of the scan plane with an irradiation time of 120 s from cold start. More conservatively, running the lamp for 180 s (3 min) or 300 s (5 min) from cold start is estimated to yield survival fraction <<10-7 survival fraction within ±20 cm of the scan plane. CONCLUSION: Ultraviolet irradiation of the inner bore of the CT gantry can be achieved with a simple UV-C lamp attached to the CT couch. Such practice could augment manual wipe-down procedures, improve safety for CT technologists or housekeeping staff, and could potentially reduce turnover time between scanning sessions.
Partners' Consensus About Joint Effort and COVID-19 Prevention Among Sexual Minority Men.

The current study examined the relevance of relationship functioning to partners' agreement or consensus about joint effort surrounding COVID-19 prevention. Interdependence theory has been widely used to understand how relationship partners influence health behavior, including how sexual minority male (SMM) couples regulate HIV risk. Couples with better relationship functioning tend to be more successful at negotiating joint (shared) goals and subsequently accomplishing them. The study recruited 134 cis-male, SARS-CoV-2 negative adults in relationships with cis-male partners from phone-based social networking applications. Participants completed an online survey assessing relationship functioning (Perceived Relationship Components Questionnaire), COVID-19 prevention behaviors, and risk perceptions. Partners' consensus around joint COVID-19 prevention effort was assessed using an adapted version of the Preferences for Sexual Health Outcomes scale. Path analyses indicated that consensus for joint prevention effort predicted social distancing (B = 0.23; p = .001) and the number of other COVID-19 prevention behaviors engaged in (B = 0.17; p = .003) above and beyond perceived risk and relationship functioning. Relationship satisfaction predicted higher levels of consensus for joint COVID-19 prevention effort (B = 0.40; p = .029). Findings suggest that the theoretical foundations of successful HIV prevention interventions that utilize joint goal formation may generalize to the prediction of COVID-19 prevention behavior and may be leveraged to mitigate the risk of SARS-CoV-2 infection among SMM in relationships. Interventions that overlook the potential for dyadic regulation of health behavior may miss opportunities to capitalize on shared coping resources and fail to address relational barriers to prevention.
Garlic Scape (Allium sativum L.) Extract Decreases Adipogenesis by Activating AMK-Activated Protein Kinase During the Differentiation in 3T3-L1 Adipocytes.

Regulating adipogenesis and lipogenesis in white adipose tissue (WAT) is an efficient strategy to reduce obesity. This study investigates whether garlic scape extract (GSE) has anti-adipogenic and ...
Ethical Compass: Settlement Fever: Lawyers, Have You Updated Your Philosophical Map?

This column is the second in my three-part series about settlement fever. The focus of this column is on how settlement fever is incentivizing you, an ethical lawyer, to expand your legal mindset when you engage with your clients to help resolve their disputes. Have you updated your philosophical map lately?
Optimal Long-Term Financial Contracting with Privately Observed Cash Flows

We characterize the optimal long-term financial contract in a setting in which a risk-neutral agent with limited capital seeks financing for a project that pays stochastic cash flows over many periods. These cash flows are observable to the agent but not to investors. The agent can be induced to pay investors via the threat of the loss of control of the project. After solving for the contract as an optimal mechanism, we demonstrate that it can be implemented by a combination of equity, long-term debt and a line of credit - very simple, standard securities. Thus our model provides a theory of capital structure, capturing both optimal debt maturity and debt vs. equity financing. Equity is issued to investors and is also used for the agent's compensation. In equilibrium, the agent may default on the debt and control of the project may pass to debt holders. The optimal capital structure is robust in the sense that it is independent of the amount financed and under certain circumstances, independent of the severity of the moral hazard problem. We also show how our characterization applies to settings in which the agent undertakes hidden effort, or can alter the risk of cash flows.
Abstract P333: Diabetes: Coronary Heart Disease Risk Equivalent or Risk Factor? The REasons for Geographic and Racial Differences in Stroke Study

Evidence is mixed regarding whether diabetes confers an equivalent risk of coronary heart disease (CHD) as prior myocardial infarction (MI). We assessed the hypotheses that 1) diabetes is a CHD risk equivalent and 2) severe diabetes is a CHD risk equivalent in the REasons for Geographic and Racial Differences in Stroke study population (30,239 black and white US adults ≥ 45 years recruited 2003-2007 with follow-up through 2011 for CHD). Diabetes at baseline was assessed using blood glucose (fasting ≥ 126 mg/dL or non-fasting ≥ 200 mg/dL) or self-reported use of diabetes medication. CHD at baseline was assessed using electrocardiogram evidence of MI or self-report of MI or revascularization. The primary exposure groups were diabetes only, CHD only, both diabetes and CHD, and neither CHD nor diabetes at baseline. We further stratified individuals with diabetes only at baseline by self-reported insulin use or albuminuria (urinary albumin-to-creatinine ratio ≥ 30 mg/g) to identify more severe diabetes. We con...
Turbulence Measurement Study

The capability of a modified commercially available electromagnetic water current meter was evaluated for measurement of parameters necessary to quantify turbulent flow. Values of turbulence intensity were measured, and Fourier analyses of their oscillograph recordings were performed to obtain the spectral distribution of the energy. Field tests were then conducted at three locations selected on the basis of their differences in flow regime. The results showed that values of turbulent intensity for flows between very high to light turbulence levels ranged from 0.71 to 0.06, respectively, and the Fourier analysis of the data shows the energy to be concentrated generally below 5 Hz. This instrument can be used to obtain relative values of turbulent intensity and spectral information from field measurement.
Intake of trans fatty acid isomers found in ruminant fat versus industrial sources differentially impact concentrations of fatty acids in erythrocytes (1025.17)

Evidence suggests concentration of trans fatty acids (TFA) in erythrocyte (RBC) membranes is strongly predictive of coronary heart disease (CHD) risk. Some data suggest a direct association with in...
Learning from the History of the Field

This essay reviews some of the early work on the study of media industries, emphasizing the historic precedents for media industry studies that more recent research sometimes neglects or even forgets. It briefly identifies some classic studies that should providefoundations for current research. While new developments in media industries are continually introduced, the essay argues that new research approaches should at least acknowledge (and perhaps even draw insights from) these historical precedents.
Formation of 6-keto-PGF1α by collecting tubule cells isolated from rabbit renal papillae

Abstract Homogeneous populations of collecting tubule epithelial cells have been isolated from rabbit renal papillae by a sequence of procedures involving: (a) dissociation of the tissue by mincing and treatment with trypsin; (b) destruction of contaminating non-collecting tubule cells by differential lysis in hypotonic media and (c) collection and washing by repeated centrifugation. The isolated cells have been characterized as being derived from the collecting tubules on the basis of anatomical source, size and histological staining for both NADH diaphorase activity and cyclooxygenase antigenicity. The cells are judged to be viable by several criteria including their ability to exclude both trypsin and vital dyes, their capacity to metabolize glucose and leucine and their ability to retain distinctive morphology following 10–14 days in culture media. Homogenates of freshly isolated collecting tubule cells when incubated with [3H]-arachidonic acid yielded radioactive products identified by thin-layer chromatographic behavior in multiple solvent systems as 6-keto-PGF1α, PGF2α, PGE2, PGD2 and a monohydroxy acid, probably HHT. No lipoxygenase-like activity was detected. At arachidonate concentrations of 2 μM or less, the major product was 6-keto-PGF1α; while at substrate concentrations of greater than 10 μM , PGE2 was the major radioactive prostaglandin formed. Similar distributions of products were observed when homogenates of dissociated renal papillae enriched in medullary interstitial cells were incubated with arachidonic acid. Our results indicate that collecting tubule cells do contain significant prostacyclin synthetase activity and suggest that PGI2 plays a role in the function of mammalian collecting tubules.
Targeting Hsp90: small-molecule inhibitors and their clinical development

The Hsp90 multichaperone complex has important roles in the development and progression of malignant transformation. Several small-molecule inhibitors of Hsp90 of diverse chemotypes have shown potent antitumor activity in a wide-range of malignancies, and are currently in clinical or late-stage preclinical investigation. This review intends to update the reader on advances made over the past two years in the clinical development of Hsp90 inhibitors in advanced cancers. It will refer to the two 17-AAG formulations, tanespimycin and IPI-504, and to synthetic small molecules, among which are the purine-scaffold Hsp90 inhibitor CNF2024/BIIB021, the isoxazole derivative VER-52296/NVP-AUY922, and the carbazol-4-one benzamide derivative SNX-5422, and will present our current knowledge on their clinical performance.
Kinetic studies in the biosolubilization of lignite

Abstract The rates at which lignite is solubilized by the extracellular products of Penicillium fungi, including RWL-5 and four substrains isolated from RWL-5, and Streptomyces flavovirens were examined. The effects of lignite surface oxidation on lignite solubilizability were also examined. Comparison of data generated from studies with the two microorganisms suggested that S. flavovirens solubilized lignite in a more alkaline environment than that of the Penicillium strain RWL-5. The rate of biosolubilization by RWL-5 in an oxygen-enriched atmosphere was almost twice that in air. Two substrain isolates exhibited biosolubilization rates approximately two times as great as that of the parent strain.
A Subsequent Human Neural Progenitor Transplant into the Degenerate Retina Does Not Compromise Initial Graft Survival or Therapeutic Efficacy

PURPOSE Stem and progenitor cell transplantation provides a promising clinical application for treating degenerative retinal diseases, including age-related macular degeneration (AMD) and retinitis pigmentosa (RP). Our previous studies have shown that a single subretinal injection of human cortical-derived neural progenitor cells (hNPCctx) into cyclosporine-treated Royal College of Surgeons (RCS) rats preserved both photoreceptors and visual function. However, it is still unknown whether nonautologous progenitor cell readministration for sustained vision is efficacious and safe in terms of the initial graft initiating an immune response to a subsequent graft. METHODS A cell suspension containing 3×104 hNPCctx into one eye of cyclosporine-treated RCS rats at postnatal day 21 (P21), followed by a second transplantation at P95 into the previously untreated fellow eye. RESULTS hNPCctx delayed photoreceptor degeneration and preserved visual function, as measured by electroretinography (ERG), optokinetic response (OKR), and luminance threshold recordings (LTRs). Visual function and photoreceptors of the initially treated eye were still preserved 6 weeks after hNPCctx were injected into the second eye. Antibodies against T-cell markers showed that CD3, CD4, and CD8 T cells were not detected at P90 and P140 in most cases. No detectable level of anti-nestin antibody was found in serum by enzyme-linked immunosorbent assay (ELISA). CONCLUSIONS This xenograft study with cyclosporine-treated animals demonstrates that readministration of hNPCctx into the fellow eye did not induce anti-graft immune responses or lower therapeutic efficacy of hNPCctx in preserving vision. Thus, readministration of progenitor cells to sustain long-term efficacy may be an option for long-term therapies of retinal degeneration. TRANSLATIONAL RELEVANCE Redosing neural progenitors do not affect the efficacy of the initial grafts in protecting vision or induce unwanted immune responses.
The effects of nearest neighbor interactions on the evaporation rate of cloud particles

Abstract A modified images method is presented and used to determine the vapor density field in arrays of up to nine “quasi-stationary” evaporating particles. The evaporation rate of each particle in an array is calculated as a function of the particle separation. Correction factors to Maxwell's evaporation rate expression to account for nearest neighbor interactions are proposed. The “R 2 -law” is assessed and found to be only approximately correct when applied to interacting particles.
Hydrogeophysical Investigations at Hidden Dam, Raymond, California

Self-potential and direct current resistivity surveys are carried out at the Hidden Dam site in Raymond, California to assess present-day seepage patterns and better understand the hydrogeologic mechanisms that likely influence seepage. Numerical modeling is utilized in conjunction with the geophysical measurements to predict variably-saturated flow through typical two-dimensional dam cross-sections as a function of reservoir elevation. Several different flow scenarios are investigated based on the known hydrogeology, as well as information about typical subsurface structures gained from the resistivity survey. The flow models are also used to simulate the bulk electrical resistivity in the subsurface under varying saturation conditions, as well as the self-potential response using petrophysical relationships and electrokinetic coupling equations. The self-potential survey consists of 512 measurements on the downstream area of the dam, and corroborates known seepage areas on the northwest side of the dam. Two directcurrent resistivity profiles, each approximately 2,500 ft (762 m) long, indicate a broad sediment channel under the northwest side of the dam, which may be a significant seepage pathway through the foundation. A focusing of seepage in low-topography areas downstream of the dam is confirmed from the numerical flow simulations, which is also consistent with past observations. Little evidence of seepage is identified from the self-potential data on the southeast side of the dam, also consistent with historical records, though one possible area of focused seepage is identified near the outlet works. Integration of the geophysical surveys, numerical modeling, and observation well data provides a framework for better understanding seepage at the site through a combined hydrogeophysical approach.
Material tailoring in finite torsional deformations of axially graded Mooney–Rivlin circular cylinder:

We study direct and material tailoring (or inverse) problems for finite torsional deformations of a solid circular cylinder made of a Mooney–Rivlin material with the two elastic moduli continuously varying in the axial direction and deformed by applying equal and opposite torques on its two end faces. We note that a Mooney–Rivlin material is isotropic and incompressible. For the direct problem, we derive the condition that the two material moduli must satisfy in order for the problem to have a solution. In particular, it is shown that finite torsional deformations can be produced if one modulus equals the negative one-half of the other one. For the material tailoring problem, we find the axial variation of the two material moduli to produce finite torsional deformations with prescribed axial variation of the angle of twist per unit length.
Transverse shear-induced gradient diffusion in a dilute suspension of spheres

We study the shear-induced gradient diffusion of particles in an inhomogeneous dilute suspension of neutrally buoyant spherical particles undergoing a simple shearing motion, with all inertia and Brownian motion effects assumed negligible. An expansion is derived for the flux of particles due to a concentration gradient along the directions perpendicular to the ambient flow. This expression involves the average velocity of the particles, which in turn is expressed as an integral over contributions from all possible configurations. The integral is divergent when expressed in terms of three-particle interactions and must be renormalized. For the monolayer case, such a renormalization is achieved by imposing the condition of zero total macroscopic flux in the transverse direction whereas, for the three-dimensional case, the additional constraint of zero total macroscopic pressure gradient is required. Following the scheme of Wang, Mauri & Acrivos (1996), the renormalized integral is evaluated numerically for the case of a monolayer of particles, giving for the gradient diffusion coefficient 0.077γa2c¯2, where is the applied shear rate, a the radius of the spheres and c¯ their areal fraction.
Respiratory psychophysiology in hypertension research.

The pathogenesis of hypertension results from an interaction of genetic and environmental factors. Behavioral factors might participate in sodium sensitive forms of hypertension via a cascade of physiological responses triggered by conditioned inhibition of breathing. When an individual decreases ventilation sufficient to increase pCO2 but not sufficient to activate chemoreceptor reflexes, plasma pH decreases transiently to stimulate a renal mechanism that can expand plasma volume via sodium retention. The combination of high resting pCO2 and high sodium intake elevates resting blood pressure in laboratory animals and healthy human participants. In the natural environment, this mechanism seems to be more important for the development of hypertension in women than in men, perhaps due to differential expression of anger and aggression. Studies are needed to clarify the role of breathing pattern in individual differences in resting pCO2 and the effects of breathing interventions on salt sensitivity and sodiu...
Tolstoy and Wittgenstein: The Life Outside of Time

Etude du probleme philosophique et existentiel que se pose Wittgenstein a travers sa theorie de la valeur de la vie et son attitude ethique face au monde. Mesurant l'influence biographique et textuelle de Tolstoi sur le jeune philosophe, l'A. met en evidence l'analogie entre la conception de vie hors du temps chez l'ecrivain, et la conception de la vie de la connaissance chez Wittgenstein.
Continuous glucose monitoring system for early detection of graft dysfunction in allogenic islet transplant recipients.

Background There are no effective indicators of graft dysfunction in islet transplantation. This study evaluated the role of the Continuous Glucose Monitoring System (CGMS) as an early indicator of graft dysfunction in islet transplant recipients.
Pain after Spinal Cord Injury: A Review of Classification, Treatment Approaches, and Treatment Assessment

Pain is a prevalent consequence of spinal cord injury (SCI) that can persist for years after the injury and can have a significant impact on physical and emotional function and quality of life. There are a variety of types of pain that may develop after a SCI, including those of primarily nociceptive origin and those of primarily neuropathic origin. Recommendations for diagnostic and treatment strategies have been varied in part because of the lack of a universal classification system and in part because of the biopsychosocial nature of pain. The most recent taxonomy for pain after SCI is described herein. Pain-management strategies, including pharmacological, interventional, and psychological treatments, also are described. For neuropathic pain in SCI, anticonvulsant agents and tricyclic antidepressants often are tried, but these treatments have had limited success in many patients, and alternative interventions (eg, massage therapy, acupuncture, meditation) often are just as successful. Treatment of nociceptive pain after SCI often includes nonsteroidal antiinflammatory agents and acetaminophen, but correction of underlying etiologies and behavior adjustments also should be implemented if possible. An overview of self-report pain questionnaires and scales is also presented to provide the clinician and researcher with a set of tools to evaluate the efficacy of pain interventions.
Correlation of some thermodynamic properties of the lanthanide and actinide metals

Some of the thermodynamic and spectroscopic properties of the metals M of the lanthanide and actinide series are correlated. The enthalpy of sublimation at 298.15 K, ΔHos(M), the standard enthalpy of formation of the metal aquo ion at 298.15 K, ΔHof{M(III), aq}, and the difference in energy ΔE(M) between the lowest lying energy level of the trivalent fns2d1 electronic configuration and the lowest lying energy level of the divalent fn + 1s2 configuration of the neutral gaseous atoms are treated. Previously reported results most likely to be found in error are pointed out, and best values of ΔHos(M) and ΔHof{M(III), aq} for each member of the lanthanide and actinide series are presented. The trends observed in ΔHos(M) and ΔHof{M(III), aq} across each series are discussed in relation to the number of valence electrons per atom in the crystalline metals and in the gaseous metal atoms.
Research methods for meta-analyses

Meta-analysis uses numerical tools to pool data and to estimate a summary effect size for the comparison of two interventions from a set of randomised controlled trials identified in a systematic review. An effect size is a single number that expresses the difference in outcome from the interventions. The most commonly used effect sizes for dichotomous outcomes, for example, mortality, are the odds ratio and the relative risk. The results of a meta-analysis are usually presented in a complex figure, known as a forest plot, which shows both the individual studies and the summary statistics. Sensitivity analyses are performed to clarify the effect of the experimental design bias on the effect size. Clinical and statistical heterogeneity of the included studies are explored by the additional tools of fixed effect versus random effects models and subgroup analyses.
Inhibition of the neutrophilic infiltrate of experimental tubulointerstitial nephritis in the Brown-Norway rat by decomplementation

Abstract Anti-tubular basement membrane (TBM) antibody-associated tubulointerstitial nephritis (TIN) in Brown-Norway rats is induced by immunization with bovine TBM antigens and adjuvants. The lesion is characterized by linear deposition of IgG and C3 along the TBM with sequential neutrophil (Days 8–9)- and mononuclear (Day 10 and after)-dominated inflammatory infiltrates. To study the complement dependent of the infiltrative process, immunized rats were decomplemented with cobra venom factor (CVF). The CVF treatment did not affect the production or renal deposition of anti-TBM antibodies. CVF markedly reduced the neutrophilic inflammatory infiltrate. In rats immunized with suboptimal doses of soluble bovine TBM antigens to produce a mild lesion, decomplementation also decreased the mononuclear inflammatory infiltrates on Days 10–13. In rats immunized optimally with particulate TBM to induce maximally severe TIN, decomplementation did not affect the mild mononuclear cell infiltrate on Days 8 and 9 but did somewhat reduce the subsequent mononuclear infiltrate on Days 10 and 12. These results demonstrate that the anti-TBM antibody- and C3-associated neutrophilic inflammatory infiltrate is largely complement dependent. The early mononuclear cell infiltrate that was unmodified by CVF treatment may be dependent on complement-independent humoral events or related to cell-mediated immune events. A portion of the later mononuclear inflammatory infiltrate could be dependent on the preceding neutrophilic inflammatory phase.
Joint space height correlates with arthroscopic grading of wrist arthritis

Background Osteoarthritis of the radiocarpal joints is commonly encountered by hand surgeons. To date, there is no well-defined method of radiographically grading osteoarthritis of the wrist.
Meta-analysis of consumer's willingness-to-pay premiums for certified wood products

Consumers’ willingness to pay (WTP) price premiums for environmentally certified wood products has been frequently estimated using stated preference methods. Estimates of WTP premiums for certified wood products over non-certified options reported in the literature range from 1.0% to 39.3%. This paper describes a meta-analysis used to determine the key factors associated with WTP price premium estimates by examining data from 19 different studies conducted around the world. Results of Bayesian hierarchical models show that frequently purchased wood products and wood products with lower base prices tend to capture higher percentage premiums. Survey administration method was also a statistically significant factor influencing variations in WTP estimates. Results show that conjoint analysis elicited inflated WTP estimates toward certified wood products compared with contingent valuation methods. Reported WTP estimates have increased in recent years. Recommendations to reduce the error of WTP estimates toward certified wood products and improve the validity of experimental studies are provided.
An experimental study of mass transfer in pulse reversal plating

An experimental study has been made of the limiting pulse current density for a periodic pulse reversal plating of copper on a rotating disc electrode from an acidic copper sulfate bath containing 0.05m CuSO4 and 0.5M H2SO4. The measurements were made over a range of the electrode rotational speeds of 400–2500 r.p.m., pulse periods of 1–100 ms, cathodic duty cycles of 0.25–0.9, and dimension-less anodic pulse reversal current densities of 0 to 50. The experimental limiting pulse current data were compared to the theoretical prediction of Chin's mass transfer model. A satisfactory agreement was obtained over the range of a dimensionless pulse period ofDT/δ 2=0.001−1; the root mean square deviation between the theory and 128 experimental data points was ±8.5%.