cssi/SciSciGPT-SciSciNet huggingface dataset:
Effects of Dexmedetomidine on Systemic and Coronary Hemodynamics in the Anesthetized Dog

Abstract In addition to central effects, which are the basis of their use in anesthesiology, α 2 -adrenergic agonists have direct peripheral cardiovascular effects. Dexmedetomidine (DM) has been found to depress cardiac function in dogs, even after autonomic denervation. The present experiments evaluated the effects of DM on coronary flow, myocardial oxygen extraction, and cardiac function in intact, open chest dogs under enflurane anesthesia. Heart rate (HR), mean arterial pressure (MAP), left ventricular end-diastolic pressure (LVEDP), the first derivative of systolic left ventricular pressure (dP/dt max ), and flow in the left anterior descending coronary artery (CBF) were measured and continuously recorded. Cardiac output (CO), plasma catecholamines (CA), hemoglobin and oxygen saturation in arterial, mixed venous, and coronary sinus blood were measured at intervals. Cardiac index (CI), systemic vascular resistance index (SVRI), regional coronary vascular resistance (CVR), and oxygen concentration differences across the systemic [C(a-v)O 2 ], and coronary [C(acs)O 2 ) circulations were calculated. DM doses of 0.25, 0.5, 1.0, 2.0, and 4.0 μg/kg were given IV at 20-minute intervals. Measurements and samples were taken at peak drug effects and just prior to the next dose. The α 2 -antagonist atipamezole, 0.5 mg/kg, was given after the last dose of DM. DM caused immediate dose-dependent increases in SVRI, CVR, LVEDP, C(a-v)O 2 , and C(a-cs)O 2 , and decreases in HR, and Cl, with recovery between doses. DP/dt max declined after the first two doses and stabilized thereafter, as plasma CA fell to minimal levels. Atipamezole completely reversed all changes. The decreases in dP/dt max and CA from initial doses of DM are attributed to a decrease in sympathetic outflow from the CNS, whereas the continuing decline in Cl, coupled with increased LVEDP without further decline in systolic contractility, may have reflected diastolic dysfunction.
Is Speed of Information Processing Related to Fluid or to Crystallized Intelligence

Abstract Speed of information processing was examined in relation to the theory of fluid and crystallized intelligence. Sixty sixth grade children completed the Standard Progressive Matrices test and the Mill Hill Vocabulary scale, both untimed, as measures of fluid and crystallized intelligence, and three RT tasks: Memory Scanning, Picture Identification, and Sentence-Picture Comparison. As predicted, RT parameters, with the exception of slope on two tasks, were negatively correlated with scores on both tests. There were no consistent differences between the two tests in the size of correlations with RT, and partial correlations, eliminating the effects of fluid and crystallized intelligence respectively, failed to support any causal relationship between fluid and crystallized intelligence in either direction. Some limitations of the research, specifically in the possible effect of error rates on the speed-intelligence relationship, and in the application to individuals of task parameters derived from group performance, are noted.
Radiofrequency ablation for nondysplastic Barrett’s esophagus: certainly not for all

Combined with EMR of visible lesions, radiofrequency ablation (RFA) has revolutionized the treatment of highgrade dysplasia (HGD) and intramucosal adenocarcinoma in Barrett’s esophagus (BE). EMR and RFA are preferred over esophagectomy in patients with HGD and intramucosal adenocarcinoma because studies show similar survival with significantly less morbidity. 1,2 In a randomized controlled trial, RFA resulted in a significant decrease in the progression of HGD and low-grade dysplasia (LGD) to cancer compared with endoscopic surveillance. 3 LGD is a difficult target because of inconsistent pathology interpretation, but LGD confirmed by expert pathologists is increasingly seen as an important marker of high risk of progression to HGD and cancer. In a recently published randomized controlled trial of patients with confirmed LGD, RFA significantly reduced progression to HGD and cancer compared with surveillance. 4 The proven benefits of RFA in patients with dysplasia elicited enthusiastic proposals to broaden the indication for RFA to nondysplastic BE (NDBE). 5 After all, it is only a short leap from the success of endoscopic therapy for BE with dysplasia to infer that RFA would also decrease the progression to cancer in NDBE. Why not wield RFA like the sword of Alexander to cut through the Gordian knot of sampling error and variable pathology that confounds and limits the impact of our current practice of endoscopic surveillance for NDBE? It is easy to be sympathetic to this notion, but there are major problems with it. Although there is published, highquality, level-one evidence for a protective effect of RFA in BE with HGD and LGD, no such data are available for RFA of NDBE. There are no randomized controlled trials of RFA versus surveillance in NDBE because the necessarily large numbers of patients required makes proposed budgets for such studies too expensive to fund. Meanwhile, recent and cumulative experiences with RFA have added to our understanding of long-term outcomes and limitations. Many questions of risk-to-benefit and cost-to-benefit must be considered when recommending RFA for most patients with NDBE. The central issue is the low incidence of cancer developing in patients with NDBE. For NDBE, the most recent estimates of progression to cancer are less than the longaccepted .5% per year. A meta-analysis in 2012 estimated the rate at .33% per year. 6 In a multicenter outcomes study, most cases of BE with HGD and cancer were diagnosed at the index endoscopy or within the first year after diagnosis (prevalent cases). Of 1204 cases followed after 1 year, the incidence rate of cancer was .27% per year. 7 Progression of NDBE to cancer seems to be cumulative but certainly not linear, with a lifetime risk of cancer estimated to be as low as 1%. The implication of treating all NDBE patients with RFA is that millions of people would receive RFA unnecessarily.
Excess Mortality Following Hip Fracture: The Role of Underlying Health Status

Summary We evaluated the long-term excess mortality associated with hip fracture, using prospectively collected data on pre-fracture health and function from a nationally representative sample of U.S. elders. Although mortality was elevated for the first six months following hip fracture, we found no evidence of long-term excess mortality.
The Impact of Managed Care on Efforts to Prevent Development of Serious Emotional Disturbance in Young Children

The purpose of this article is to present selected findings from a case study of systemic facilitators of, and barriers to, full implementation of Project Success. This project was designed to prevent the development of serious emotional disturbance (SED) in at-risk children in the early elementary grades. The project involved (1) an intervention composed of classroom interventions, use of multiple services located on school grounds, and provision of case management services to the children and their families; and (2) a qualitative case study of systemic facilitators and barriers regarding implementation of the intervention. This article focuses on the second component, specifically on how and why the move toward managed care in provision of mental health services in general and in the Medicaid program in particular frustrated efforts to prevent the development of SED in young children with existing emotional and behavioral problems.
Differential expression of olfactory genes in the southern house mosquito and insights into unique odorant receptor gene isoforms

The southern house mosquito, Culex quinquefasciatus, has one of the most acute and eclectic olfactory systems of all mosquito species hitherto studied. Here, we used Illumina sequencing to identify olfactory genes expressed predominantly in antenna, mosquito’s main olfactory organ. Less than 50% of the trimmed reads generated by high-quality libraries aligned to a transcript, but approximately 70% of them aligned to the genome. Differential expression analysis, which was validated by quantitative real-time PCR on a subset of genes, showed that approximately half of the 48 odorant-binding protein genes were enriched in antennae, with the other half being predominantly expressed in legs. Similar patterns were observed with chemosensory proteins, “plus-C” odorant-binding proteins, and sensory neuron membrane proteins. Transcripts for as many as 43 ionotropic receptors were enriched in female antennae, thus making the ionotropic receptor family the largest of antennae-rich olfactory genes, second only to odorant receptor (OR) genes. As many as 177 OR genes have been identified, including 36 unique transcripts. The unique OR genes differed from previously annotated ORs in internal sequences, splice variants, and extended N or C terminus. One of the previously unknown transcripts was validated by cloning and functional expression. When challenged with a large panel of physiologically relevant compounds, CquiOR95b responded in a dose-dependent manner to ethyl 2-phenylacteate, which was demonstrated to repel Culex mosquitoes, and secondarily to citronellal, a known insect repellent. This transcriptome study led to identification of key molecular components and a repellent for the southern house mosquito.
ATRP of butyl acrylates from functionalized carbon black surfaces

The functionalization of carbon black surface with atom transfer radical polymerization (ATRP) initiating sites and subsequent ATRP of n-butyl acrylate (n-BA) and t-butyl acrylate (t-BA) from the surface of carbon black is reported. The polymerizations were carried out using CuBr/N,N,N′,N″,N″-pentamethyldiethylenetriamine as the primary catalytic system in anisole at 70 °C. The initiator density on carbon black surface was tuned and the effect of initiator density on the polymers grafted on the surface was illustrated. Polymerizations were also performed in the presence of a sacrificial initiator to indirectly monitor the molecular weight evolution of polymers formed in the system. Block copolymerization of t-BA initiated from poly(n-BA) grafted carbon black was conducted to achieve water-dispersible carbon black composites after cleavage of the t-butyl groups. © 2005 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 43: 4695–4709, 2005
Analysis of single‐locus tests to detect gene/disease associations

A goal of association analysis is to determine whether variation in a particular candidate region or gene is associated with liability to complex disease. To evaluate such candidates, ubiquitous Single Nucleotide Polymorphisms (SNPs) are useful. It is critical, however, to select a set of SNPs that are in substantial linkage disequilibrium (LD) with all other polymorphisms in the region. Whether there is an ideal statistical framework to test such a set of 'tag SNPs' for association is unknown. Compared to tests for association based on frequencies of haplotypes, recent evidence suggests tests for association based on linear combinations of the tag SNPs (Hotelling T(2) test) are more powerful. Following this logical progression, we wondered if single-locus tests would prove generally more powerful than the regression-based tests? We answer this question by investigating four inferential procedures: the maximum of a series of test statistics corrected for multiple testing by the Bonferroni procedure, T(B), or by permutation of case-control status, T(P); a procedure that tests the maximum of a smoothed curve fitted to the series of of test statistics, T(S); and the Hotelling T(2) procedure, which we call T(R). These procedures are evaluated by simulating data like that from human populations, including realistic levels of LD and realistic effects of alleles conferring liability to disease. We find that power depends on the correlation structure of SNPs within a gene, the density of tag SNPs, and the placement of the liability allele. The clearest pattern emerges between power and the number of SNPs selected. When a large fraction of the SNPs within a gene are tested, and multiple SNPs are highly correlated with the liability allele, T(S) has better power. Using a SNP selection scheme that optimizes power but also requires a substantial number of SNPs to be genotyped (roughly 10-20 SNPs per gene), power of T(P) is generally superior to that for the other procedures, including T(R). Finally, when a SNP selection procedure that targets a minimal number of SNPs per gene is applied, the average performances of T(P) and T(R) are indistinguishable.
Harnessing creativity: Creating a business proposal competition for medical students

Dear SirIt has been hypothesized that there is a close link between medical practice outcomes and creativity (Weisz & Albury 2010). At Tulane, we are interested in fostering student creativity to s...
Some Selected Thoughts Old and New on Soliton-Black Hole Connections in 2d Dilaton Gravity

We discuss in an expository style some results,old and new,regarding connections between solitons and black holes in 2d dilaton gravity, for both Lorentzian and Euclidean metrics. Black hole vacua (the ground state or mass zero case), and non sine-Gordon solitons such as dissipatons (solutions of a resonance nonlinear Schrodinger equation) are also considered.
An Introduction to Molecular Pathology of the Head and Neck

As we learn more and more about the molecular pathogenesis of tumors, assays in molecular diagnostics are permeating into the clinical every-day practice of anatomic pathology. This means that tumors we used to diagnose with a 1-line diagnosis and an assessment of margins are now quickly becoming more complicated in both the workup and the reporting. The pathologist must now go beyond the hematoxylin-eosin slide and the usual tumor parameters and now take into account diagnostic, prognostic, and therapeutic markers that might be available. No matter what the organ system, the anatomic pathologist is well suited to take on the role of pulling together diverse information from various biological assays, and interpreting results in the context of the morphologic diagnoses. While there are challenges, particularly because of the rapid and constant evolution of the standard of care, this role will also be one of the most important and rewarding ones that we can have, as we continue to lead and participate in the diagnosis management of our patients’ diseases. In the head and neck, there has been an explosion of important information at the molecular level, both about tumors and inflammatory conditions. This has spanned across almost every anatomic subsite in the head and neck, as well as across tumor types and conditions. Exciting new developments in molecular pathology have challenged some basic tumor classifications, have elucidated new entities, and have changed the way we manage and treat some common conditions. Perhaps the most exciting developments have been in the area of new treatments that are based either on better molecular classification and understanding of disease, or based on novel therapeutic targets. There are new biomarkers being described and clinically validated regularly. From inflammatory conditions, to benign neoplastic entities, to common and rare tumors, our diagnostic algorithms are changing rapidly along with our growing understanding of molecular pathogenesis. The following collection of articles covers new information about the molecular etiology of some common and uncommon head and neck lesions that we face in clinical practice. While there is a focus on the known and evolving molecular pathogenesis, the authors have also highlighted the clinical practical applications that the pathologist must consider when reporting these entities. Though not comprehensive or exhaustive, these selections give us insight into specific entities and also reveal the rapid evolution that we can expect in the coming decade, as we strive to incorporate more and more molecular diagnostics into the routine anatomic pathology work we do in practice.
Corporate investments and growth options

Real options theory models certain corporate investments as investments in growth options, yet there is little direct evidence on whether firms actually capture growth option value from these investments. In the current paper, we attempt to bridge this empirical gap, and we also examine the conditions under which the growth option value embedded in such investments is enhanced. Results from a sample of manufacturing firms during 1989–2000 reveal that investments in research and development and joint venture (JV) investments contribute to firms' growth option values. We also show that, among JVs of different ownership structures, only minority JVs increase growth option value. Our findings affirm options theory's assertion that real options can help firms capture valuable upside opportunities, they highlight the value of examining contingencies that drive option value, and they also point to the challenges firms face in realizing the unique benefits the theory emphasizes. Copyright © 2007 John Wiley & Sons, Ltd.
Patterns of Change in Marital Satisfaction over the Newlywed Years.

Although marital satisfaction starts high and declines for the average newlywed, some spouses may follow qualitatively distinct trajectories. Using eight self-reports of satisfaction collected over 4 years from 464 newlywed spouses, we identified five trajectory groups, including patterns defined by high intercepts and no declines in satisfaction, moderate intercepts and minimal declines, and low intercepts and substantial declines. The groups varied systematically in their 4- and 10-year divorce rates, and wives tended to follow more satisfying trajectories than their husbands. Personality traits, stress, aggression, and communication behaviors assessed shortly after marriage discriminated among groups in expected directions. We conclude by outlining theoretical and practical implications of identifying distinct and predictable patterns of change in relationship satisfaction.
Mandated Correctional Training: A Task Analysis Approach to Curriculum Design:

Pursuant to legislation mandating that correctional officers in Georgia be trained and certified, a task analysis was devised and executed to assess training needs. The purpose of the Task Analysis was to produce usable data to assist in the development of basic training curricula for correctional officers in the state. Data were produced for four categories of institutions: state corrections, county correctional institutions, city/county jails and youth development centers. The task analysis provided solid, apparently valid data which were used in the subsequent development of three training curricula packages.
Mitosis is swell

Cell volume and dry mass are typically correlated. However, in this issue, Zlotek-Zlotkiewicz et al. (2015. J. Cell Biol. http://dx.doi.org/10.1083/jcb.201505056) and Son et al. (2015. J. Cell Biol. http://dx.doi.org/10.1083/jcb.201505058) use new live-cell techniques to show that entry to mitosis coincides with rapid cell swelling, which is reversed before division.
Increased Risk of Cerebrovascular Disease Among Patients With Neurofibromatosis Type 1: Population-Based Approach.

Background and Purpose— Although neurofibromatosis type 1 (NF1) may be associated with an incompletely understood vasculopathy, relative odds of stroke in this population is not known. Methods— Using the 1998 to 2009 US Nationwide Inpatient Sample, we performed a case–control study matching cases of NF1 to controls without such a diagnosis. We then compared the odds of stroke between the 2 groups. We used multivariable logistic regression to adjust for known or suspected confounders. Results— NF1 was associated with younger mean age at the time of stroke (41 versus 48) and a lower prevalence of stroke risk factors among adult patients. Pediatric patients with NF1, however, were more likely to have hypertension. Patients with NF1 were significantly more likely to be diagnosed with any stroke (odds ratio, 1.2; P <0.0001) than the general population. The odds of intracerebral hemorrhage were greatest among hemorrhagic stroke types analyzed (odds ratio, 1.9; P <0.0001). In the pediatric NF1 population, the odds of intracerebral hemorrhage were more dramatically elevated (odds ratio, 8.1; P <0.0001). The odds of ischemic stroke were also increased with NF1 in the pediatric (odds ratio, 3.4; P <0.0001) but not in the adult population. Conclusions— When compared with the general population, the odds of any type of stroke are significantly increased for patients with NF1, both adult and pediatric. This risk is most notable for hemorrhagic strokes although it is also increased for ischemic strokes in children. Physicians should be aware of the increased risk of stroke in this population, and consider stroke as a potential cause of new neurological symptoms.
Intercity Buses: The Forgotten Mode

The debate over President Obama's fantastically expensive high-speed rail program has obscured the resurgence of a directly competing mode of transportation: intercity buses. Entrepreneurial immigrants from China and recently privatized British transportation companies have developed a new model for intercity bus operations that provides travelers with faster service at dramatically reduced fares.New-model bus companies save money by selling tickets over the Internet and loading and unloading passengers at curbsides rather than in expensive bus stations. They speed service by running most buses non-stop between major cities rather than making numerous intermediate stops. Some companies distinguish themselves from their competition by providing leather seats, free wireless Internet, more legroom, and — in a few cases — onboard meal service and movies.In 2006, scheduled intercity bus service reached its lowest level in decades, yet intercity buses still carried almost three times as many passenger miles as Amtrak. Since then, intercity buses have become the nation's fastest-growing transportation mode, with ridership growing almost twice as fast as Amtrak.Intercity buses carry at least 50 percent more passenger miles than Amtrak in Amtrak's showcase Northeast Corridor. They do so with almost no subsidies and at fares that are about a third of Amtrak's regular train fares and little more than 10 percent of Amtrak's high-speed Acela fares. Intercity buses are safe and environmentally friendly, suffering almost 80 percent fewer fatalities per billion passenger miles than Amtrak and using 60 percent less energy per passenger mile than Amtrak.Policymakers can encourage expansion of intercity bus services by ending subsidies to Amtrak and minimizing regulatory barriers to new bus start-ups. Cities concerned about congestion and parking problems caused by curbside bus operations can sell curb rights — the right to load and unload passengers at various locations — at prices equal to the market rate for parking. Federal and state agencies can enforce existing safety rules but should hesitate to impose new rules that could increase costs and reduce competition without clear safety gains.
Body Shape and Size Concerns and Diet Culture in Urban Adolescents Attending Suburban High Schools

BODY SHAPE AND SIZE CONCERNS AND DIET CULTURE IN URBAN ADOLESCENTS ATTENDING SUBURBAN HIGH SCHOOLS Alice Woolverton, MS , Allegra L. Spalding, BA , Natasha K. Warikoo, PhD , Erin C. Dunn, ScD , Tracy K. Richmond, MD, MPH, FSAHM. Boston Children’s Hospital; Harvard Graduate School of Education; Massachusetts General Hospital, Harvard Medical School; Boston Children’s Hospital, Harvard Medical School.
Local Taxes and Levies as Financial Basis for Local Government in Ukraine

Sio straipsnio tikslas isanalizuoti savivaldybių renkamų mokescių ir rinkliavų vaidmenį užtikrinant vietos savivaldos institucijų biudžetine autonomiją Ukrainoje ir pateikti siūlymus kaip tobulinti mokescių sistemą vietos lygmeniu. Pagrindinė problema susijusi su savivaldybių renkamais mokesciais ir rinkliavomis yra ta, kad siuo metu ji neužtikrina finansinės vietos savivaldos institucijų autonomijos. Straipsnyje pateikiama Ukrainos Mokescių kodekso kaitos analizė apimanti savivaldybių renkamų mokescių ir rinkliavų struktūrą, nuosavybės apmokestinimo ypatybes, vieningojo mokescio rinkimą, ir rinkliavas už automobilių parkavimą. Identifikuojami naujosios savivaldybių renkamų mokescių ir rinkliavų sistemos privalumai bei trūkumai ir pateikiami siūlymai tolimesniam sistemos tobulinimui.
Abstract B84: NADPH oxidase 1 (NOX1) and related NOX isoforms as key mediators of NFκB signaling in colon cancer

B84 NADPH oxidase/dual-oxidase (Nox/Duox) family members have been implicated in nuclear factor kappa-B (NFκB)-mediated inflammation and inflammation-associated pathologies. In rats given 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) alternating with a high-fat diet, Nox1, Nox4 and Duo2, but not Nox2, were over-expressed in colon tumors at 1 year, as shown by quantitative RT-PCR and immunoblotting. Over-expression of Nox/duox isoforms coincided with increased nuclear NFκB protein, and elevated levels of downstream targets IL-1β, IL6, TNF-α and TNFR1. Over-expression of Nox1 and activation of NFκB also occurred at early stages of colon carcinogenesis, prior to tumor development. Nox/Duox isoforms were over-expressed in primary human colon cancers and in several human colorectal cancer cell lines. In HT29 cells, silencing of Nox1 inhibited nuclear translocation and DNA binding activity of NFκB, attenuated downstream targets IL1β, c-myc, and cyclin D1, and blocked lipopolysaccharide-induced phosphorylation of IκB kinaseα/β, resulting in G1 arrest. We conclude that the Nox1-NFκB pathway is important in colon tumorigenesis, and that Nox1 may provide a target for novel therapeutic strategies against colon cancer development. Citation Information: Cancer Prev Res 2008;1(7 Suppl):B84.
The Formation & the Development of Yellow Rice Wine Flavor

Yellow rice wine is Chinese proprietary wine product. The seven main decisive factors of yellow rice wine flavor cover ecological environment,raw materials and auxilliary materials,saccharifying fermenting agents,caramel color,wine-making techniques,wine-making equipments and wine-drinking culture. The formation process of yellow rice wine flavor in China (produced by grains) could be divided into four stages: beginning stage,forming stage,fixing stage and development stage. (Tran.by YUE Yang)
Enzymes as Drug Targets

This chapter considers how enzymes can be therapeutic drug targets. The most common therapeutic approach to enzyme control is inhibition; there are four general classes of enzyme inhibition based on the relative affinity of the inhibitor for the enzyme and the enzyme–substrate complex. Competitive inhibition describes inhibitors that have exclusive affinity for the enzyme and compete for substrate binding. Mixed inhibitors bind to the enzyme and the enzyme–substrate complex with different affinity. Non-competitive inhibitors bind equally well to the enzyme and enzyme–substrate complex. Uncompetitive inhibitors bind only to the enzyme–substrate complex. There are special considerations for the blockade of enzymes in cells in that concentrations may differ (from the extracellular medium). In addition, enzyme inhibitors may have no effect until the enzyme is active metabolically under in vivo conditions. Finally, the topic of irreversible enzyme inhibition, enzyme activation and the special cases of drug action on intracellular enzymes is considered.
Therapeutic Peptides and Proteins: Formulation, Processing, and Delivery Systems, Second Edition

Upon publication of the first edition of Therapeutic Peptides and Proteins ten years ago there were only 19 biotechology medicines on the market. Currently there are more than 100, with at least 400 more in various stages of development. That alone would be grounds for a new edition. Add to that the fact that it is still difficult to find up
The Role of G-protein Coupled Receptor Proteolytic Site (GPS) Cleavage in Polycystin-1 Biogenesis, Trafficking and Function

ABSTRACT Polycystin-1 (PC1) is encoded by PKD1, the principal gene mutated in autosomal dominant polycystic kidney disease (ADPKD). The protein regulates terminal differentiation of tubular structures in the kidney and is required to maintain their structural integrity. A fundamental property of PC1 is post-translational modification by cis-autoproteolytic cleavage at the G-protein coupled receptor proteolytic site (GPS) motif located at the base of the extracellular ectodomain. Defective cleavage likely plays a significant role in the pathogenesis of ADPKD. In mouse models, GPS cleavage of PC1 is essential for the integrity of the distal nephron segments during the postnatal period. While the exact cellular and biochemical functions of PC1 have yet to be fully elucidated, its trafficking and function must be precisely regulated at the subcellular level to ensure proper structure and function of the kidney. Recent evidence shows that GPS cleavage plays a central role in PC1 biogenesis, trafficking and function in vivo. GPS cleavage results in the N-terminal fragment (PC1NTF) and C-terminal fragment (PC1CTF), which remain non-covalently associated to form a heterodimeric PC1 molecule. Cleavage is required for ciliary trafficking of PC1, which occurs in a two-step mechanism. First, PC1 interacts with polycystin-2 (PC2) in the ER and binds Rabep1. PC1/2 complex formation is required for transition of PC1 to the trans-Golgi compartment. Second, once arriving at the trans-Golgi, PC1/2-bound Rabep1 recruits GGA1 and the small GTPase Arl3 sequentially for ciliary targeting. In the absence of cleavage, the PC1/2 complex cannot reach the trans-Golgi. This article will discuss the roles of GPS cleavage for PC1 structure, trafficking and function that are relevant for normal activity of polycystin-1 and in cystogenesis of ADPKD.
Electrical energy storage: Materials challenges and prospects

Rapid increases in global energy use and growing environmental concerns have prompted the development of clean and sustainable alternative energy technologies. Electrical energy storage (EES) is critical for efficiently utilizing electricity produced from intermittent, renewable sources such as solar and wind, as well as for electrifying the transportation sector. Rechargeable batteries are prime candidates for EES, but widespread adoption requires optimization of cost, cycle life, safety, energy density, power density, and environmental impact, all of which are directly linked to severe materials challenges. This article presents a brief overview of the electrode materials currently used in lithium-ion batteries, followed by the challenges and prospects of next-generation insertion-reaction electrodes and conversion-reaction electrodes with a Li+ working ion. Finally, we discuss future directions involving solid electrolytes, multi-electron transfer hosts, and other working ions.
Angioimmunoblastic T-cell lymphoma: the many faced lymphoma

Angioimmunoblastic T-cell lymphoma (AITL) is an uncommon subtype of mature peripheral T-cell lymphoma (PTCL). The history of AITL is much longer and deeper than the literature would suggest given the many names that have preceded it. Advanced-stage disease is common with uncharacteristic laboratory and autoimmune findings that often slow or mask the diagnosis. Significant strides in the immunohistochemical and molecular signature of AITL have brought increased ability to diagnose this uncommon type of PTCL. The 2016 World Health Organization classification of lymphoid neoplasms recently acknowledged the complexity of this diagnosis with the addition of other AITL-like subsets. AITL now resides under the umbrella of nodal T-cell lymphomas with follicular T helper phenotype. Induction strategies continue to focus on increasing complete remission rates that allow more transplant-eligible patients to proceed toward consolidative high-dose therapy and autologous stem cell rescue with improving long-term survival. There are several clinical trials in which recently approved drugs with known activity in AITL are paired with induction regimens with the hope of demonstrating long-term progression-free survival over cyclophosphamide, doxorubicin, vincristine, and prednisone. The treatment of relapsed or refractory AITL remains an unmet need. The spectrum of AITL from diagnosis to treatment is reviewed subsequently in a fashion that may one day lead to personalized treatment approaches in a many-faced disease.
TFEB inhibits endothelial cell inflammation and reduces atherosclerosis

Atherosclerosis, or the buildup of fatty plaques in blood vessels, can lead to high blood pressure and heart attacks. Lu et al. found that, in cultured endothelial cells, the transcription factor TFEB reduced oxidative stress and inflammation, two processes thought to contribute to the development of atherosclerosis. When fed a high-fat diet, mice that overexpressed TFEB in endothelial cells developed smaller atherosclerotic lesions than their control littermates on the same diet. Thus, treatments that enhance the activity of TFEB in endothelial cells could reduce the development of atherosclerosis. Furthermore, because the anti-inflammatory effect of TFEB in endothelial cells was independent of its role in autophagy, a process in which cells digest macromolecules and organelles, these results highlight new roles for this transcription factor.
Heat up and failure of BWR upper internals during a severe accident

Abstract In boiling water reactors, the shroud dome, separators, and dryers above the core are made of approximately 100,000 kg of stainless steel. During a severe accident in which the coolant boils away and exothermic oxidation of zirconium occurs, gases (steam and hydrogen) are superheated in the core region and pass through the upper internals. In this scenario, the upper internals can also be heated by thermal radiation from the hot degrading core. Historically, models of the upper internals have been relatively simple in severe accident codes. The upper internals are typically modeled in MELCOR as two lumped volumes with simplified heat transfer characteristics and no structural integrity considerations, and with limited ability to oxidize, melt, and relocate. The potential for and the subsequent impact of the upper internals to heat up, oxidize, fail, and relocate during a severe accident was investigated. A higher fidelity representation of the shroud dome, steam separators, and steam driers was developed in MELCOR v1.8.6 by extending the core region upwards. The MELCOR modeling effort entailed adding 45 additional core cells and control volumes, 98 flow paths, and numerous control functions. The model accounts for the mechanical loading and structural integrity, oxidation, melting, flow area blockage, and relocation of the various components. Consistent with a previous study, the results indicate that the upper internals can reach high temperatures during a severe accident sufficient to lose their structural integrity and relocate. The additional 100 metric tons of stainless steel debris influences the subsequent in-vessel and ex-vessel accident progression.
The Enduring Power of the Sports Broadcasting Act

This chapter examines a little-known, but vitally important statutory antitrust exemption for the U.S. professional sports industry: the Sports Broadcasting Act of 1961 (SBA). Under the SBA, league-wide television contracts between one of the four major U.S. sports leagues and an over-the-air broadcast television network are immune from challenge under federal antitrust law. As a result, the SBA has had a significant influence in helping to shape the way in which sports are broadcast in the United States today. At the same time, because sports leagues value the protection afforded by the SBA, the threat of repealing the statute has also given Congress the leverage necessary over the years to challenge various league activities viewed as harmful to the public interest. Thus, the SBA plays an important role in helping to shape professional-sports-related public policy in the United States today.
Exosomes carrying immunoinhibitory proteins and their role in cancer.

Summary Recent emergence of exosomes as information carriers between cells has introduced us to a new previously unknown biological communication system. Multi-directional cross-talk mediated by exosomes carrying proteins, lipids and nucleic acids between normal cells, cells harbouring a pathogen or cancer and immune cells has been instrumental in determining outcomes of physiological as well as pathological conditions. Exosomes play a key role in the broad spectrum of human diseases. In cancer, tumour-derived exosomes carry multiple immunoinhibitory signals, disable anti-tumour immune effector cells and promote tumour escape from immune control. Exosomes delivering negative signals to immune cells in cancer, viral infections, autoimmune or other diseases may interfere with therapy and influence outcome. Exosomes can activate tissue cells to produce inhibitory factors and thus can suppress the host immune responses indirectly. Exosomes also promise to be non-invasive disease biomarkers with a dual capability to provide insights into immune dysfunction as well as disease progression and outcome.
An Examination of Strategies for the Prevention of Gender-Based Violence at Four-Year Institutions of Higher Education

ABSTRACTAlthough gender-based violence prevention programs at institutions of higher education (IHEs) are mandated by federal legislation, research focusing on the prevalence or content of programming is limited. The present exploratory research examines campus websites for a nationally representative sample of Title IX eligible IHEs that offer at least a four-year degree (n = 389), assessing whether IHEs offer prevention programs and whether programs include information cited in federal legislation or adhere to best practices. Differences in programming are also examined across IHE types. Results demonstrate that most IHEs report offering prevention pro- grams (86%), but that differences do exist across IHE type: 97% of public nonprofit IHEs report programming compared to 46% of tribal institutions. Disparities also exist across IHE types regarding the content of programming. Results highlight the need to advance prevention programming to better align with “what works” in prevention science or what is ex...
Characterization of fluid inclusions encaged in quartz veins of Parsoi Formation, central India

The study focuses on analysis of primary and secondary fluid inclusions present in quartz veins hosted in the phyllites to explore the stress and temperature conditions at the time of formation of metasediment sequences of the of Parsoi Formation, central India. The results reveal the two-phase liquid-rich fluid inclusions that indicate that the intrusions of quartz veins in phyllite may have taken place between the temperature from 168.8°C to 256.3°C with an average of 205.55°C from a magmatic moderately saline fluid (3.7 to 18.29 wt. % NaCl equiv.). The final ice-melting temperatures ranges from -14.6°C to -2.2°C which indicate that the aqueous fluids are mainly H2O-NaCl. The density distribution of fluid inclusions rich in liquid H2O only are unimodel and low in natures and appears to be entrapped between pressure 1.666 to 2.125 kbar at depth of 200m. The study supports epithermal nature of fluid inclusions. The characteristic of fluid inclusions along with lithological and structural peculiarities, nature of structural features may be helpful in exploring the future potential zone of gold mineralization in similar types of area.
Global Distribution of Active Volcanoes

Abstract Approximately 1,550 subaerial volcanoes in the world today are thought to have erupted in the last 10,000 years, and thousands more volcanoes ring the seafloor. These active volcanoes mainly occur in curvilinear belts that define tectonic plate boundaries. Hundreds of millions of people live on the flanks of active volcanoes and could suffer the acute affects of even a moderate-sized eruption. Island arc nations such as Indonesia, the Philippines, and Japan host the largest populations within 100 km of an active volcano; Indonesia prompts further distinction as having the most explosive eruptions on record as well as the greatest number of eruption-related fatalities. The Volcanoes of the World database (version 4.1) maintained by Smithsonian's Global Volcanism Program, documents more than 10,000 Holocene eruptions, yet only six eruptions account for more than half of the total quantified fatalities. The assembled data bring into relief large gaps in our understanding of the risks posed by volcanoes and the need for more research into volcanic hazards, risks, and timescales.
Anticoagulation in Venous Thromboembolism

Venous thromboembolism (VTE) is a highly prevalent and potentially dangerous condition. While anticoagulation is the mainstay of therapy, thrombolytic therapy may be utilized in the acute setting for select patients. In this chapter, we review the risk factors for development of VTE and the key decision-making considerations for treatment. We highlight the role of acute therapies, such as thrombolytics, as well as appropriate selection of oral anticoagulants. Key advantages and disadvantages of warfarin and the direct oral anticoagulants are summarized. We review key aspects for chronic anticoagulation management, including the use of formal anticoagulation clinics. Finally, we discuss approaches to VTE recurrence risk stratification and the selection of antithrombotic agents for secondary VTE prevention. Numerous tables and figures outline decision-making steps and provide summary data from pivotal randomized trials in VTE management.
Differentiating Bilateral Symptomatic Hand Osteoarthritis From Rheumatoid Arthritis Using Sonography When Clinical and Radiographic Features Are Nonspecific: A Case Report.

Abstract Objective The purpose of this report is to describe a patient with bilateral symptomatic hand osteoarthritis (OA) originally thought to be rheumatoid arthritis (RA) based on clinical and radiographic features. Clinical Features A 48-year-old woman presented with bilateral hand pain, stiffness, swelling, and redness in the proximal and distal interphalangeal joints of 1 year’s duration. Laboratory analysis and plain film radiography were equivocal. These findings necessitated the use of diagnostic ultrasound, which revealed no synovitis or erosions in the joints of the hand, so a diagnosis of bilateral symptomatic hand OA was rendered. Intervention and Outcome A trial of conservative care consisting of mobilizations, instrument-assisted soft tissue therapy, and laser therapy was given. At 1-month follow-up, the patient regained full pain-free range of motion and strength and returned to complete work activity. Conclusion This case report demonstrated that hand OA can present with nonspecific inflammatory-like clinical features. These findings require further testing, in which case ultrasound imaging may be valuable to differentiate OA from RA. Using ultrasound to make this diagnosis may guide management, with rheumatology referral for RA and conservative care for OA.
Targeting the β2-integrin LFA-1, reduces adverse neuroimmune actions in neuropathic susceptibility caused by prenatal alcohol exposure

Recently, moderate prenatal alcohol exposure (PAE) was shown to be a risk factor for peripheral neuropathy following minor nerve injury. This effect coincides with elevated spinal cord astrocyte activation and ex vivo immune cell reactivity assessed by proinflammatory cytokine interleukin (IL) -1β protein expression. Additionally, the β2-integrin adhesion molecule, lymphocyte function-associated antigen-1 (LFA-1), a factor that influences the expression of the proinflammatory/anti-inflammatory cytokine network is upregulated. Here, we examine whether PAE increases the proinflammatory immune environment at specific anatomical sites critical in the pain pathway of chronic sciatic neuropathy; the damaged sciatic nerve (SCN), the dorsal root ganglia (DRG), and the spinal cord. Additionally, we examine whether inhibiting LFA-1 or IL-1β actions in the spinal cord (intrathecal; i.t., route) could alleviate chronic neuropathic pain and reduce spinal and DRG glial activation markers, proinflammatory cytokines, and elevate anti-inflammatory cytokines. Results show that blocking the actions of spinal LFA-1 using BIRT-377 abolishes allodynia in PAE rats with sciatic neuropathy (CCI) of a 10 or 28-day duration. This effect is observed (utilizing immunohistochemistry; IHC, with microscopy analysis and protein quantification) in parallel with reduced spinal glial activation, IL-1β and TNFα expression. DRG from PAE rats with neuropathy reveal significant increases in satellite glial activation and IL-1β, while IL-10 immunoreactivity is reduced by half in PAE rats under basal and neuropathic conditions. Further, blocking spinal IL-1β with i.t. IL-1RA transiently abolishes allodynia in PAE rats, suggesting that IL-1β is in part, necessary for the susceptibility of adult-onset peripheral neuropathy caused by PAE. Chemokine mRNA analyses from SCN, DRG and spinal cord reveal that increased CCL2 occurs following CCI injury regardless of PAE and BIRT-377 treatment. These data demonstrate that PAE creates dysregulated proinflammatory IL-1β and TNFα /IL-10 responses to minor injury in the sciatic-DRG-spinal pain pathway. PAE creates a risk for developing peripheral neuropathies, and LFA-1 may be a novel therapeutic target for controlling dysregulated neuroimmune actions as a consequence of PAE.
Screening Modalities for Women at Intermediate and High Risk for Breast Cancer

Breast cancer screening is critically important to detect malignancy at an early stage. Annual mammography remains the gold standard as the imaging modality for patients with an average breast cancer risk. However, women with increased breast cancer risk benefit from supplemental screening using additional imaging modalities. This review summarizes the current recommendations within this patient population. Analysis from ACRIN 6666 demonstrated that the cancer detection rate of ultrasound is comparable to mammography with an increased amount of invasive and node-negative cancers detected. Supplemental ultrasound increased the sensitivity and cancer detection rate in the J-START randomized controlled trial. Abbreviated breast MRI and ultrafast breast MRI have demonstrated effective cancer detection performance in the high-risk population. Women with increased breast cancer risk benefit from supplemental screening using digital breast tomosynthesis, ultrasound, and breast MRI. Molecular breast imaging may be considered in some patients.
Interaction Networks: Generating High Level Hints Based on Network Community Clusterings

We introduce a novel data structure, the Interaction Network, for representing interaction-data from open problem solving environment tutors. We show how using network community detecting techniques are used to identify subgoals in problems in a logic tutor. We then use those community structures to generate high level hints between subgoals. The preliminary results show that using network analysis techniques are promising for exploring and understanding user data from open problem solving environments.