cssi/SciSciGPT-SciSciNet huggingface dataset:
Dual inhibition of JAK2V617F and BCR-ABLT315I by a novel class of non-ATP competitive kinase inhibitors

A240 Cytokines mediate hematopoietic cell growth and differentiation via the JAK-STAT pathway and aberrations in this pathway have been found to result in leukemogenesis. Thus, point mutations in the JAK2 kinase have been shown to be the causative molecular event in certain myeloproliferative disorders identifying JAK2 as a new molecular target for drug discovery. Here we report the discovery of a new class of kinase inhibitors, α-benzoyl styryl benzyl sulfides, which possess potent kinase inhibitory activity and exhibit cytotoxicity to human tumor cells. One of the compounds that belong to this class, ON 044580 was found to be a potent inhibitor of mutant JAK2 kinase and was non-ATPcompetitive. In vivo, it readily inhibited the proliferation of JAK2V617F-positiveleukemic cells and blocked the phosphorylation of JAK2 and STAT5. Interestingly, this compound was also found to inhibit the kinase activity of both wild type and imatinib resistant (T315I) forms of the BCR-ABL kinase, which share STAT5 as a substrate with JAK2. The novel mechanism of kinase inhibition exhibited by these compounds that renders them effective against mutant forms of kinases such as the BCR-ABL-T315I mutant also makes them important alternative agents for treatment of leukemias that are resistant to ATP-competitive agents which are currently in the market. Herein, we report the synthesis of a novel 4-(2-(4-bromobenzylthio)ethanoyl)benzoic acid (ON 044580), which possess potent kinase inhibitory activity and exhibit cytotoxicity to human tumor cells that express oncogenic kinases such as JAK2-V617F and BCR-ABL.
The role of law in addressing mental health-related aspects of disasters and promoting resilience

Law plays a critical role in emergency preparedness and disaster response by establishing an infrastructure for the response and facilitating coordination among the federal, state, and local governments. Once a disaster occurs, certain legal mechanisms are activated to ensure that individuals' needs for mental health care are met, both for pre-existing and emergent conditions. This includes the rapid deployment of mental health care personnel and the implementation of crisis counseling programs in affected regions. By facilitating an influx of resources, including personnel, supplies, and financial assistance, the law can help communities quickly rebound and return to a sense of normal. Drawing on examples from the United States, this article illustrates the diverse ways in which the law simultaneously addresses mental health-related aspects of disasters and promotes resilience within affected communities. Language: en
Think and Suggest: Bringing the Real World to the Legal Writing Classroom

Legal education is experiencing its biggest shake-up in decades. Applications to law school are down about 45 percent since 2009, and millennials—more than any previous generation—are rejecting law school. This ‘crisis’ has caused much soul searching in the legal academy, but the problems are clear: We are using the same old approach to teaching students that schools used over 100 years ago, tuition is higher than ever, and traditional legal jobs are scarce. So how can we fix this? – Montre D. Carodine 1
Collective behaviour in some 1f7/2 even-even nuclei

Low-lying excited states of some of the 1f7/2 even-even nuclei have been calculated employing the simple asymmetric rotor-vibrator model. The results obtained are in agreement with experiments and another fairly complicated calculation. The collective behaviour indicated here should encourage more experiments specially on transition probability.
Critical Evaluation of Turbulence Modeling with the Flux Correction Method on Strand Grids

In this work, we examine the accuracy of the flux correction method for resolving turbulent flows on a strand based volume-mesh. The method uses a robust “negative” Spalart-Allmaras model to achieve turbulence closure of the Reynolds-Averaged NavierStokes equations. Flux correction is employed along body surfaces coupled with source terms containing derivatives in the strand direction to achieve high-order of accuracy. To demonstrate the method’s capabilities, we assess flow over three geometries, including a three-dimensional bump, an infinite wing, and a hemisphere-cylinder configuration. Comparison to results obtained from established codes show that the turbulent flux correction scheme accurately predicts both subsonic and transonic turbulent flows and accurately captures flow properties such as pressure, velocity profiles, shock location, and strength.
Robustness of reliable change indices to variability in Parkinson’s disease with mild cognitive impairment

Ability to identify change is crucial for measuring response to interventions and tracking disease progression. Beyond psychometrics, investigations of Parkinson's disease with mild cognitive impairment (PD-MCI) must consider fluctuating medication, motor, and mental status. One solution is to employ 90% reliable change indices (RCIs) from test manuals to account for account measurement error and practice effects. The current study examined robustness of 90% RCIs for 19 commonly used executive function tests in 14 PD-MCI subjects assigned to the placebo arm of a 10-week randomized controlled trial of atomoxetine in PD-MCI. Using 90% RCIs, the typical participant showed spurious improvement on one measure, and spurious decline on another. Reliability estimates from healthy adults standardization samples and PD-MCI were similar. In contrast to healthy adult samples, practice effects were minimal in this PD-MCI group. Separate 90% RCIs based on the PD-MCI sample did not further reduce error rate. In the present study, application of 90% RCIs based on healthy adults in standardization samples effectively reduced misidentification of change in a sample of PD-MCI. Our findings support continued application of 90% RCIs when using executive function tests to assess change in neurological populations with fluctuating status.
Optical dielectric functions of wurtzite III-V semiconductors

Optical properties of semiconductors can exhibit strong polarization dependence due to crystalline anisotropy. A number of recent experiments has shown that the photoluminescence intensity in free standing nanowires is polarization dependent. One contribution to this effect is the anisotropy of the dielectric function due to the fact that most nanowires crystalize in the wurtzite form. While little is known experimentally about the band structures of wurtzite phase III-V semiconductors, we have previously predicted the bulk band structure of nine III-V semiconductors in the wurtzite phase. Here, we predict the frequency dependent dielectric functions for nine non-nitride wurtzite phase III-V semiconductors (AlP, AlAs, AlSb, GaP, GaAs, GaSb, InP, InAs, and InSb).Their complex dielectric functions are calculated in the dipole approximation for light polarized parallel and perpendicular to the $c$axis of the crystal. Momentum matrix elements are evaluated on a dense grid of special $k$ points using empirical pseudopotential wave functions. Corrections to the momentum matrix elements, to account for the missing core states, are made using a scaling factor which is determined from the zinc-blende polytypes. Simple analytic expressions are provided for the dispersion relations in the vicinity of the respective fundamental absorption edges.
Preserving and maintaining optimal peri-implant soft-tissue complex for function and aesthetics.

MPH, MS, diplomate, American Board of Periodontology; fellow, International Congress of Oral Implantologists; and lecturer, University of California-Los Angeles School of Dentistry, one of the key elements of implant maintenance and longevity is good physiological architecture of the gingiva, specifically, an abundance of keratinized tissue, and adequate thickness of tissue fibers to form an appropriate environment for implants. Good physiological architecture of the gingiva yields both functional and cosmetic benefits. Kim notes, “One way to achieve these results is through manipulation of good lab designs, but an additional aid is following, when possible, a one-stage protocol, which is allowed by many currently marketed implant systems.” Standard healing abutments have parallel wall sides and a certain angle of flare that does not reflect the emergence profile of natural teeth or proper implant restoration. Therefore, Kim says, customized healing abutments can be used as part of a one-stage protocol. He continues, “Even a provisional restoration can be used, either in function or non-function, and constructed from various materials. Acrylic resin is the most economical and easiest to manipulate, but the restoration can be cast even from metal if need be.” When this one-stage approach is followed, the gingival tissues can be modified during the integration phase and then afterward for the final prosthesis—but only if careful planning is undertaken, since perfect embrasure form can be derived from the use of a resin abutment only if there is a limit, Kim says, “to adding and subtracting as you go.” Occasionally, when cases require bone augmentation at the implant site, the peri-implant tissue contour impression and transfer technique is performed in conjunction with what Kim calls a calcium sulfate compaction technique for peri-implant guided bone regeneration.
A Sea Change Off the Coast of Maine: Common Pool Resources as Cultural Property

In groundbreaking and award-winning research, social scientists have documented the power of small groups to manage common pool resources (CPRs). That research concludes that collective or communal ownership of CPRs may be optimal in certain circumstances. While group- and community-level rights have also sometimes been conceived in property law terms, these accounts have not focused on whether and how to protect existing groups whose successful management of CPRs has been documented. The idea that such a movement might occur, and what form it should take, is ripe for consideration and evaluation. In this Article, I use an initiative currently being advanced by a community of Maine lobstermen to create and illustrate a model that might be broadly used for the recognition of group-level property rights in communities, or other groups, that are the de facto stewards of common pool resources. Describing both when and how such a community-level right might be recognized and what its substantive contours should be, the Article draws not only from the recent social science research that recognizes the benefits of small group management of CPRs, but also from the growing field of cultural property rights, in which group-level rights have already been embraced in both domestic and international law.
Methamphetamine Regulation of Firing Activity of Dopamine Neurons.

Methamphetamine (METH) is a substrate for the dopamine transporter that increases extracellular dopamine levels by competing with dopamine uptake and increasing reverse transport of dopamine via the transporter. METH has also been shown to alter the excitability of dopamine neurons. The mechanism of METH regulation of the intrinsic firing behaviors of dopamine neurons is less understood. Here we identified an unexpected and unique property of METH on the regulation of firing activity of mouse dopamine neurons. METH produced a transient augmentation of spontaneous spike activity of midbrain dopamine neurons that was followed by a progressive reduction of spontaneous spike activity. Inspection of action potential morphology revealed that METH increased the half-width and produced larger coefficients of variation of the interspike interval, suggesting that METH exposure affected the activity of voltage-dependent potassium channels in these neurons. Since METH has been shown to affect Ca2+ homeostasis, the unexpected findings that METH broadened the action potential and decreased the amplitude of afterhyperpolarization led us to ask whether METH alters the activity of Ca2+-activated potassium (BK) channels. First, we identified BK channels in dopamine neurons by their voltage dependence and their response to a BK channel blocker or opener. While METH suppressed the amplitude of BK channel-mediated unitary currents, the BK channel opener NS1619 attenuated the effects of METH on action potential broadening, afterhyperpolarization repression, and spontaneous spike activity reduction. Live-cell total internal reflection fluorescence microscopy, electrophysiology, and biochemical analysis suggest METH exposure decreased the activity of BK channels by decreasing BK-α subunit levels at the plasma membrane. SIGNIFICANCE STATEMENT Methamphetamine (METH) competes with dopamine uptake, increases dopamine efflux via the dopamine transporter, and affects the excitability of dopamine neurons. Here, we identified an unexpected property of METH on dopamine neuron firing activity. METH transiently increased the spontaneous spike activity of dopamine neurons followed by a progressive reduction of the spontaneous spike activity. METH broadened the action potentials, increased coefficients of variation of the interspike interval, and decreased the amplitude of afterhyperpolarization, which are consistent with changes in the activity of Ca2+-activated potassium (BK) channels. We found that METH decreased the activity of BK channels by stimulating BK-α subunit trafficking. Thus, METH modulation of dopamine neurotransmission and resulting behavioral responses is, in part, due to METH regulation of BK channel activity.
Abstract TMP80: Relationship Between Neutrophil/Lymphocyte Ratio and Post-stroke Depression

Background: Depression is a leading cause of disability post-stroke. Nearly a third of stroke victims suffer from depression after event occurrence. Post-stroke depression hinders physical rehabili...
GIST Hemorrhagic Metastases

Gastrointestinal stromal tumors (GIST) most commonly originate in the stomach or small intestine. PET/MR imaging improves the detection of GIST and metastatic disease and is excellent at assessing response to therapy.
NMDA and AMPA glutamate receptor antagonists in the treatment of human malignant glioma xenografts

4562 Human glioma cell lines secrete high levels of the excitatory neurotransmitter glutamate (Glu); early published work has shown that glutamate stimulates glioma cell growth, and both NMDA and AMPA glutamate receptor antagonists decreased the proliferation of human glioma cells in vitro. Glu-releasing strains of rat glioma have been shown to form larger and more invasive xenografts, and NMDA receptor antagonists slowed the growth of orthotopic rat glioma xenografts. However, these compounds have not been well evaluated against human malignant glioma xenografts. We used heterotopic and orthotopic models of human glioma in immunocompromised mice to evaluate the efficacy of GYKI-53773 (talampanel, IVAX), an AMPA-subtype Glu receptor antagonist, and memantine, an NMDA-subtype antagonist. When tested against a panel of four subcutaneous human glioma xenografts, one-day gavage dosing regimens of talampanel did not result in statistically-significant tumor growth delay or regressions in tumor volume. Chronic intraperitoneal dosing of talampanel in six glioma lines and one ependymoma line led to a small number of regressions in D212MG (11.1% of samples), D245MG (10%), D245MG (PR) (procarbazine resistant, 8.3%), and D612EP (22.2%) xenografts without statistically-significant growth delays. The reported inhibition of glioma expansion by Glu receptor antagonists may be due to blockade of tumor cell receptors or to inhibition of the excitotoxic death of adjacent normal neurons. Therefore, we hypothesized that these agents may inhibit the expansion of neuron-encased intracranial glioma xenografts more than that of subcutaneous tumors. D54MG and D245MG, human glioma lines that express high levels of AMPA and NMDA receptors, were used in intracranial xenograft trials. Talampanel caused a 9.1% increase (p = 0.5) and memantine caused a 13.0% increase (p = 0.342) in median lifespan of mice bearing orthotopic D245MG xenografts. These preliminary results indicated that NMDA blockade might be more effective than AMPA blockade. In an orthotopic D54MG xenograft model, memantine (30 mg/kg IP BID) produced significant increases in median host animal lifespan of 16.5% (p = 0.016) and 11.9% (p = 0.018), in duplicate experiments. Studies currently underway will determine if higher doses of memantine will result in dose-dependent increases in the lifespan of animals bearing intracranial glioma xenografts.
Pilot Trial of a Comprehensive Summer Psychosocial Treatment for High-Functioning Young Children with ASD

This study examined the feasibility and preliminary outcomes of a comprehensive summer psychosocial treatment (summerMAXyc) for high-functioning young children, ages 4–6 years, with ASD (HFASD). The 5-week treatment, conducted 5 days per week, 6 h per day, included skills instruction and therapeutic activities targeting social/social-communication skills, facial-emotion recognition, and interest expansion. A behavioral system was implemented to increase skills acquisition and maintenance and reduce ASD symptoms and problem behaviors. Feasibility was supported in high levels of treatment fidelity and child, parent, and staff clinician satisfaction. Significant post-treatment improvements were found for 9 of 10 outcome measures including parent and staff clinician ratings of targeted social/social-communication skills, ASD symptoms, and broader adaptive social and communication skills, and staff clinician ratings of daily living skills. Results suggested that summerMAXyc was feasible and may yield positive outcomes for 4–6 year olds with HFASD.
Bundles over projective spaces and algebraic curvature tensors

Let R(π) be the skew-symmetric curvature operator introduced by Stanilov. Previous authors studied Riemannian metrics where R(π) has pointwise constant eigenvalues - these have been classified in dimensions \( m\ge4 \) and \( m\ne7 \). We study a complex analogue of this question. Let J be an almost complex structure and assume that R(π)J = JR(π) for every J invariant 2 plane π. We use bundle theory to restrict the eigenvalue structure as a first step towards a classification.
Simulation in General Surgery

Simulation in general surgery has had many advances in recent years. From the development of a variety of simulators to the creation of national skills curricula, the establishment of the accredited education institute network, and the refinement of assessment tools and metrics, the progress achieved signals a very bright future for the field. Surgical simulation will continue bringing the education and assessment of surgical trainees and practicing surgeons to new levels and is destined to improve patient care and outcomes.
The Peripheral Nervous System

The mammalian nervous system is divisible into the central nervous system (CNS) and the peripheral nervous system (PNS). The CNS, consisting of brain and spinal cord, is linked to all parts of the body by the PNS, which transmits signals to and from the CNS.
Lipidomics Profiling of Myelin

Lipidomics is a powerful approach that can provide quantitative characterization of hundreds of lipid species from biological samples. Recent studies have highlighted the value of lipidomics to study myelin biology. This chapter provides a detailed description for the application of multidimensional mass spectrometry shotgun lipidomics (MDMS-SL) to neuroscience research and particularly to the analysis of brain lipidomes with a particular emphasis on myelin lipids, from sample preparation to bioinformatics analyses. Sample preparation includes brain sample harvesting, homogenization, and lipid extraction. Lipid content is determined and quantified, in an unbiased manner and with wide coverage, using MDMS-SL. Overall, the approach described herein is applicable for whole brain tissue or specific brain regions (e.g., hippocampus, cerebellum), and is expected to yield new insights on various aspects of myelin biology and lipid metabolism.
Prevalence of Substance Use, Housing Instability, and Self-Perceived Preparation for Independence Among Current and Former Foster Youth

This study assesses prevalence of substance use, and the impact of housing instability. and independence preparation on substance use in two samples: youth currently in-care and former foster youth. Both samples were from a mid-Atlantic state with youth currently in-care residing in rural jurisdictions and former foster youth residing in the state’s largest urban jurisdiction. A cross-sectional design utilizing paper and web-based surveys was used to collect data. Findings indicate youth in-care are consuming substances that are on average with national prevalence statistics. However, former foster youth are consuming substances at alarmingly high rates well above the national prevalence. A high rate of housing instability after leaving child welfare was reported for former foster youth. In addition, greater preparation for independence among former foster youth was associated with less substance usage. Implications for social work practice, independence preparation, and life skills classes are presented.
Standardized Psychosocial Assessment Before Left Ventricular Assist Device Implantation

Background: Before consideration of advanced cardiac therapies, guidelines recommend a comprehensive multidisciplinary examination, including psychosocial assessment. The Stanford Integrated Psycho...
Copper(II)-catalyzed silyl conjugate addition to α,β-unsaturated conjugated compounds: Brønsted base-assisted activation of Si-B bond in water.

A mild method for the installation of the dimethylphenylsilyl group on the β-carbon of electron-deficient olefins is reported. In the presence of a catalytic amount of copper(II) (1 mol %) and amin...
CXCR3-CXCL9: It's All in the Tumor.

In this issue of Immunity, Chow et al. (2019) show that the CXCR3-CXCL9 axis is required for reinvigoration of intratumoral CD8+ T cell responses in response to PD-1 blockade and demonstrate that local guidance to dendritic cells, rather than recruitment of T cells into the tumor, underlies the importance of this chemokine axis.
Differences in Emotional Reactions to Social Media Content: The Role of Location and Content Type

Individuals in diaspora tend to engage and interact with the people of their origin. Afghans in the 1980s and 90s, still one of the largest diaspora communities, used traditional channels such as Radio and Television to communicate with their loved ones inside Afghanistan. The Internet facilitated changing their mode of communication to near real-time updates. Diaspora and local communities engage in the same Social Awareness Streams (SAS), but there is a lack of research focusing on difference and similarities of these communities. This paper investigates the differences in emotional disclosure and expression between diaspora and local communities in Afghanistan using data from 'Afghanistan My Passion', the largest public Afghan Facebook community page. We investigate a corpus of 2,165 Persian language words considering the location and gender of the social media user. This work provides the first analysis towards understanding differences in diaspora and local communities' emotional reactions to social media content and extends the body of literature on Persian language sentiment analysis.
Fusion applications for lithium: wall conditioning in magnetic confinement devices

The application of lithium to plasma facing components (PFCs) has been widely used to improve plasma performance in magnetic confinement devices. The ability of lithium to retain hydrogen isotopes has been exploited to lower wall recycling. Low recycling leads to high edge plasma temperatures, and decreased temperature gradients reduce the free energy source for microinstabilities that cause transport. A variety of techniques have been developed to introduce lithium into fusion research devices, and its beneficial effects have been observed in their plasmas. The mechanism for the retention of hydrogen isotopes has been elucidated by detailed surface science studies, and 'first principles' molecular dynamics simulations. The remaining challenges primarily pertain to long pulse operation. Our knowledge of erosion, transport, and redeposition needs to improve for the mixed material PFCs lithium creates. Flowing liquid lithium systems also must be demonstrated for the replenishable lithium walls that fusion reactors require.
Urban Teachers’ Perspectives of Strengths and Needs: The Promise of Teacher Responsive Professional Development

This study examines urban high school teachers’ perceptions (N = 50) of their strengths and needs in supporting diverse students in their classrooms. Qualitative analysis of responses revealed the emergence of four thematic categories: enactment of positive teacher dispositions; external challenges affecting student learning; strengths in the classroom environment and; effective instructional practices to support high needs students. We discuss the use of the findings of teachers’ perceptions as integrated in a teacher responsive professional development model built on culturally responsive student-centered teaching and focused on teacher involvement that includes collaborative decision-making, collective construction of effective practice, and a growth driven approach.
Different Types of Theories by Level of Abstraction in Nursing: A Discussion Paper.

Background and purpose Despite different labels used to refer to different types of nursing theories by different authors, agreements were made on three major types of theories by level of abstraction. The purpose of this analysis was to discuss the characteristics of the three major types of nursing theories by level of abstraction that were published in refereed journals and to propose directions for future theoretical development in nursing. Methods An integrated literature review was conducted using PUBMED, CINAHL, and PsycINFO. A total of 116 articles were included in this analysis. The retrieved articles were sorted by the type of theories (by level of abstraction), and analyzed in terms of scope, theorizing process, specificity and abstraction, contextual understanding, links to research and practice, and diversity and generalizability. Finally, themes reflecting the characteristics of the three major types of nursing theories were extracted and discussed. Results A total of 17 themes were found. Although most of the themes reflected what were known about these theories, there were three new findings. First, all the grand theories that were reviewed tended to have more specific foci rather than explaining general nature, mission, or goals of nursing. Second, middle-range theories were developed based on various types/levels of theories using various sources for theorizing. Third, situation-specific theories began to be used to generate propositions and tested through statistical and qualitative analyses. Implications for practice The efforts to try to link nursing theories to nursing practice need to be continued through further development and evaluation of the theories regardless of the types of theories.
Young Firms and Monetary Policy Transmission

We investigate the role of business dynamism in the transmission of monetary policy by exploitingthe variation in firm demographics across U.S. states. Using local projections, we find that a larger fraction of young firms significantly mutes the effects of monetary policy on the labor market and personal income over the medium term. The firm entry rate and the employment share of young firms are key factors underpinning these results, which are robust to a battery of robustness tests. We develop a heterogeneous-firm model with age-dependent financial frictions that rationalizes the empirical evidence.
Foliar Photodegradation in Pesticide Fate Modeling: Development and Evaluation of the Pesticide Dissipation from Agricultural Land (PeDAL) Model.

Pesticide dissipation from plant surfaces depends on a variety of factors including meteorological conditions, the pesticide’s physicochemical properties, and plant characteristics. Models already exist for describing pesticide behavior in agriculture fields; however, they do not account for pesticide-specific, condition-specific foliar photodegradation and the importance of this component in such models has not yet been investigated. We describe here the Pesticide Dissipation from Agricultural Land (PeDAL) model, which combines (a) multiphase partitioning to predict volatilization, (b) a new kinetics module for predicting photodegradation on leaf surfaces under varying light conditions based on location and timing, and (c) a generic foliar penetration component. The PeDAL model was evaluated by comparing measured pesticide dissipation rates from field experiments, described as the time for the pesticide concentration on leaves to decrease by half (DT₅₀), to ones generated by the model when using the reported field conditions. A sensitivity analysis of the newly developed foliar photodegradation component was conducted. We also showed how the PeDAL could be used by applicators and regulatory agencies. First, we used the model to examine how pesticide application timing affects dissipation rates. Second, we demonstrated how the model can be used to produce emission flux values for use in atmospheric dispersion and transport models.
Differential effects of the 2015 American Cancer Society guidelines on screening mammography exams based on socioeconomic status.

10539Background: Guidelines for screening mammography have changed several times since initiation of regular screening mammography in the 1970’s. Most recently, in 2015, the American Cancer Society...
Corticosteroid use and its impact on the efficacy of immunotherapy in multiple tumor types.

e14583Background: Studies have suggested that concurrent corticosteroid use may decrease the efficacy of immunotherapy for cancer treatment, however, the data remains limited. The purpose of this s...
New mAbs facilitate quantification of secreted equine TNF-α and flow cytometric analysis in monocytes and T cells.

Abstract Tumor necrosis factor-α (TNF-α) is a pleiotropic cytokine, that is involved in acute inflammation and is employed as a biomarker of inflammatory diseases in several species for which reliable quantification is available. We aimed to develop suitable tools to quantify TNF-α in equine samples. We generated two new mAbs against equine TNF-α (clones 48 and 292), evaluated their specificity for this cytokine, and confirmed detection of native TNF-α in stimulated equine PBMC. The TNF-α mAbs were paired in a fluorescent bead-based assay for quantification of equine TNF-α. The TNF-α assay had a wide quantification range of 12 pg/mL - 38.4 ng/mL. In addition, TNF-α mAb 48 was used for a detailed analysis of TNF-α production in PBMC by intracellular staining and flow cytometry. TNF-α was expressed by CD14+ monocytes after LPS stimulation and by monocytes and lymphocytes after polyclonal stimulation with PMA and ionomycin in vitro. TNF-α expressing lymphocytes consisted mainly of CD4+ T cells. CD8+ T cells and other lymphocytes also expressed TNF-α. The new mAbs evaluated here for soluble and intracellular TNF-α will enable the detailed analysis of this important pro-inflammatory cytokine during equine immune responses and inflammatory diseases of the horse.
A case of recalcitrant linear morphea responding to subcutaneous abatacept

Introduction:Linear morphea is an inflammatory condition that is often treated with systemic glucocorticoids and methotrexate, with mycophenolate mofetil being used as an alternative agent. However...
Revertant mutation V48G alters conformational dynamics of highly drug resistant HIV protease PRS17.

Abstract Drug resistance is a serious problem for controlling the HIV/AIDS pandemic. Current antiviral drugs show several orders of magnitude worse inhibition of highly resistant clinical variant PRS17 of HIV-1 protease compared with wild-type protease. We have analyzed the effects of a common resistance mutation G48V in the flexible flaps of the protease by assessing the revertant PRS17V48G for changes in enzyme kinetics, inhibition, structure, and dynamics. Both PRS17 and the revertant showed about 10-fold poorer catalytic efficiency than wild-type enzyme (0.55 and 0.39 μM−1min−1 compared to 6.3 μM−1min−1). Clinical inhibitors, amprenavir and darunavir, showed 2-fold and 8-fold better inhibition, respectively, of the revertant than of PRS17, although the inhibition constants for PRS17V48G were still 25 to 1,200-fold worse than for wild-type protease. Crystal structures of inhibitor-free revertant and amprenavir complexes with revertant and PRS17 were solved at 1.3–1.5 A resolution. The amprenavir complexes of PRS17V48G and PRS17 showed no significant differences in the interactions with inhibitor, although changes were observed in the conformation of Phe53 and the interactions of the flaps. The inhibitor-free structure of the revertant showed flaps in an open conformation, however, the flap tips do not have the unusual curled conformation seen in inhibitor-free PRS17. Molecular dynamics simulations were run for 1 μs on the two inhibitor-free mutants and wild-type protease. PRS17 exhibited higher conformational fluctuations than the revertant, while the wild-type protease adopted the closed conformation and showed the least variation. The second half of the simulations captured the transition of the flaps of PRS17 from a closed to a semi-open state, whereas the flaps of PRS17V48G tucked into the active site and the wild-type protease retained the closed conformation. These results suggest that mutation G48V contributes to drug resistance by altering the conformational dynamics of the flaps.
Abstract WP88: Predictors of Outcome for Procedural Perforation During Coiling of Intracranial Aneurysms: A Single Center Experience

Background: Despite significant advances in coil embolization of intracranial aneurysms (IA), intra-procedural perforation (IPP) remains a dreaded complication associated with significant morbidity (up to 50%) and mortality (up to38%). Objective: In this study, we sought to analyze all IPP during IA coiling at our center over a 10 year period to determine what characteristics may predict outcome. Methods: This is a retrospective chart review of 1029 consecutive patients who underwent IA coiling from January 2002-May 2012. Variables evaluated included clinical presentation, aneurysm location, morphological aspects and neurological outcomes at discharge. Good outcomes were defined as modified Rankin scale (mRS) 1-3. Results: IPP occurred in 24 patients (2.3% of the cohort). Of all IPP, 83% occurred in previously ruptured IA, 17% in unruptured IA. This corresponded to an overall IPP rate of 4% and 0.8% respectively. Overall morbidity at discharge (mRS 4,5) was 31.8% and mortality 8.3%. Overall, good outcome was noted in 44.4% immediately post-procedure and 68.2% at discharge. Among patients with unruptured IA and those with good Hunt-Hess (HH) grade (1-3), 92% had good outcome at discharge vs. 54.6% with poor HH, p=0.03. Patients with proximal IA (proximal to internal carotid artery bifurcation or close to basilar artery stem) had better discharge outcomes (41.7%) than distal IA (33.3%), p= 0.04; this was statistically significant after controlling for HH in logistic regression analysis. Between 2002-2007, balloon-assisted coiling (BAC) was utilized in only 20% of IPP cases and 2 mortalities were recorded. After 2007, BAC was used in 60% of IPP cases with no subsequent mortalities. Conclusion: It appears that the incidence of IPP is very low, with good outcomes occurring in a significant portion of the patients. Patients with good neurological exam at presentation are likely to have good discharge outcomes despite IPP. Proximal IA are associated with better discharge outcomes: IPP in this location may be easier to control endovascularly. Techniques like BAC allow for prompt hemostasis once IPP occurs, and might reduce mortality rates.
Cost optimization of thermoelectric materials for power generation: The case for ZT at (almost) any cost

Abstract We quantify the tradeoff between ZT and materials cost for thermoelectric energy scavengers, considering 31 real materials. It is nearly always practical to aggressively miniaturize the legs until the overall system cost is limited by the heat exchangers and ceramic spreader plates. For thermoelectric materials costing less than C crit . ‴ ∼ 1 $/cm3 (∼100 $/kg), the material might as well be free, and even costs as high as ∼10 $/cm3 (∼1000 $/kg) may still be acceptable. Thus, the materials goal is maximizing ZT at (almost) any cost.
Parenchymal manifestations of acute cerebrovenous occlusion

We report our experience with 29 patients with acute durai sinus and/or deep venous thrombosis, correlating their clinical presentation to their radiologic findings, and using dural sinus pressure to gauge severity and staging.
Factors Influencing Willingness to Recommend a Visit to Water-Enhanced Tourist Attractions in Central-European Mountainous and Submontane Landscapes

The aim of the chapter is to reveal the predictors of likelihood of recommendation for a visit to water-enhanced tourist attractions in Central-European mountainous and submontane landscapes. Pull motivation, push motivation, on-site experience and perception of site quality were chosen as potential factors and multiple linear regression was used as the method. Pleasant ‘natural’ environment, heritage and culture, and accessibility were found to be factors of pull motivation; social-gathering and escape as factors of push motivation; pleasure and arousal as factors of experience; and rarity, irregularity and novelty as factors of perceived quality. The forward selection of multiple linear regressions found the pleasure experience as the main predictor for willingness to recommend. Others are: pull motivation regarding types of attractions and site quality regarding rarity and novelty.
Attenuation to Control Gene Expression

Bacteria use a variety of strategies to regulate transcription elongation in response to changes in their environment. Several of these regulatory events are classified as transcription attenuation mechanisms, which involve regulated transcription termination to control expression of downstream genes. In most cases, two alternative RNA secondary structures, an antiterminator and an intrinsic terminator, share nucleotides in common such that their formation is mutually exclusive. Thus, the level of expression of the downstream genes depends on the frequency that the antiterminator forms in the nascent transcript. Transcription attenuation mechanisms in general are separated into two categories. The first category involves situations in which the action of a regulatory molecule promotes transcription termination, with the default situation being transcription readthrough. The second category involves situations in which the action of the regulatory molecule promotes transcription readthrough (antitermination), with the default situation being transcription termination. Transcription attenuation controls the expression of several amino acid biosynthetic and catabolic operons. These mechanisms are often controlled by the efficiency of leader peptide synthesis in Gram-negative bacteria, whereas Gram-positive organisms often use RNA binding proteins or tRNA molecules to determine whether the RNA will fold into the antiterminator or terminator structures. Several examples of transcription attenuation also exist in which an antisense RNA is responsible for controlling plasmid copy number. In addition, small metabolites participate in transcription attenuation mechanisms of a wide variety of bacterial genes by binding directly to the nascent transcript.
The X pinch as a point source for point-projection x-ray radiography

Point-projection radiography of dense plasmas and other objects using an X pinch as the x-ray source is discussed. An X pinch, generated using two or more wires that cross and touch, in the form of an X, as the load of a pulsed power generator, reliably produces a small, bright x-ray radiation source very near the original cross point of the wires. Taking advantage of the small source size (in some cases &#60;2 µm at energies above a few keV), radiographs of objects can be obtained without using pinholes. In addition, the short x-ray emission duration (&#60;20 ps in some cases for energies above a few keV) of the X pinch radiation enables sharp radiographs of rapidly changing dense plasmas. Detailed measurements of the emission characteristics of X pinches made using different wire materials and in different energy ranges using a set of x-ray diagnostics with high temporal and spatial resolution are presented. A comparison of the radiated energy and the imaging properties of two and up to seven wire X pinches are discussed. The application of the X pinch x-ray source for phase-contrast x-ray radiography of low absorption objects is demonstrated.
Taxes and Physicians' Use of Ancillary Health Labor

Recent papers have examined the effect of taxes on the labor supply of high income individuals and on the demand for employee labor; entrepreneurs' decisions to hire workers are seen to be quite sensitive to changes in marginal tax rates. However, little is known about the applicability of these findings to physician services. We posit a straightforward model of physician utility-maximization, where physician-employers jointly choose own work effort and other labor inputs. There is no theoretical prediction about the sign or magnitude of the cross-price effects of changes in physicians' tax rates on their choice of ancillary labor inputs. We estimate the impact of taxation of physician income on both the extensive and intensive margins using state-level variation in marginal income tax rates to identify the effects. We also examine the sensitivity of total and per worker compensation to variation in marginal tax rates.
Student’s t Distribution

The Student’s t distribution or t distribution defines a family of continuous probability distributions. It has a wide range of applications in probability, statistics, and other fields of sciences. It was first developed by Willieam S. Gosset (1908) in his work on “the probable error of a mean,” published by him under the nom de plume of Student. Further developments continued with the contributions of Fisher (1925) and others later. For detailed discussions on the development of the t distribution and its usages, see, example, Pearson (1967, 1970), Eisenhart (1979), Box (1981), Patel and Read (1982), Johnson et al. (1995), Wiper et al. (2005), Finner (2008), and Zabell (2008), and references therein. The graph of the probability density function of the Student’s t distribution is a symmetric and bell-shaped curve, differing for different sample sizes. The Student’s \(t\) distribution has mean \(=0\) and standard deviation is greater 1 for degrees of freedom greater than 2 and it does not exists for 1 and 2 degrees of freedom. As the sample size \(n\;\rightarrow \infty \), the Student’s t distribution approaches the standard normal distribution. If we compare the z-table and t table, we can see that the percentile points for of normal distribution and Student \(-t\) distribution for large degrees of freedom are approximately equal.
The Survival of Marginally-Distressed Firms: Evidence on the Duration of Turnaround

In this paper, we examine firms with established profitability that suddenly experience financial distress and subsequently return to a profitable position. Our interest lies in the speed with which a firm reverses from a loss position to a position of income and we focus on the duration of time that elapses between the year of the initial loss and the year in which the firm returns to profitability. We refer to firms with established profitability that suddenly experience financial distress and subsequently return to a profitable position as being marginally-distressed. The results in our paper suggest that the likelihood as well as the speed of recovery of a distressed firm changes over time as the associated managerial responses change. We also provide empirical evidence on factors that help explain variations in the time to turnaround of marginally-distressed firms. This latter result is particularly important from the perspective of a firm manager in identifying strategies for survival. It is also important from the perspective of an investor interested in predicting the likelihood and speed of turnaround of a distressed firm. Specifically we find that large firms are able to turnaround faster than small firms possibly due to their higher resilience and greater flexibility. We also find that while capital expenditures, increases in liquidity, and increases in employees have a positive impact on the speed of recovery, increases in long-term debt and increases in selling, general, and administrative expenses impede the speed of recovery.
On the behavioral H/sub /spl infin// control problem: an abstract

The H/sub /spl infin// problem in the behavioral setting has been introduced by Willems and Trentelman (1995). We propose a new solution of this problem. The proposed method makes use of the tangential Nevanlinna-Pick (NP) problem, which computationally, can be solved efficiently using linear matrix inequality methods.
A distributed cooperative power allocation method for campus buildings

We propose a coordination algorithm for cooperative power allocation among a collection of commercial buildings within a campus. We describe a typical commercial building Heating, Ventilation, and Air Conditioning (HVAC) system, and utilize Model Predictive Control (MPC) to characterize its power flexibility. The power allocation problem is formulated as a cooperative game using the Nash Bargaining Solution (NBS) concept, in which buildings cooperatively maximize the product of their utilities subject to their local flexibility constraints and a total power limit set by the campus coordinator. To solve the optimal allocation problem, a distributed protocol is designed using dual decomposition of the Nash bargaining problem. Numerical simulations are performed to demonstrate the efficacy of our proposed allocation method.
Star chambers will result in injustice.

Jon Turney's generally favourable review of my book The Baltimore Case offers the judgement that the affair was "not of enormous significance, except for the victims" (Nature 395, 30–31; 1998). That is to miss the point of historical importance of the case, and a major point of the book. The case had great significance for the civil rights of scientists charged with fraud.
A novel full-angle scanning light scattering profiler to quantitatively evaluate forward and backward light scattering from intraocular lenses

Glare, glistenings, optical defects, dysphotopsia, and poor image quality are a few of the known deficiencies of intraocular lenses (IOLs). All of these optical phenomena are related to light scatter. However, the specific direction that light scatters makes a critical difference between debilitating glare and a slightly noticeable decrease in image quality. Consequently, quantifying the magnitude and direction of scattered light is essential to appropriately evaluate the safety and efficacy of IOLs. In this study, we introduce a full-angle scanning light scattering profiler (SLSP) as a novel approach capable of quantitatively evaluating the light scattering from IOLs with a nearly 360° view. The SLSP method can simulate in situ conditions by controlling the parameters of the light source including angle of incidence. This testing strategy will provide a more effective nonclinical approach for the evaluation of IOL light scatter.