cssi/SciSciGPT-SciSciNet huggingface dataset:
Survival After Surgery for Renal Cell Carcinoma Metastatic to the Spine: Impact of Modern Systemic Therapies on Outcomes.

Background Modern medical management of metastatic renal cell carcinoma (RCC) includes therapies targeting tyrosine kinases, growth pathways (mammalian target of rapamycin (mTOR)), and immune checkpoints. Objective To test our hypothesis that patients with spinal metastases would benefit from postoperative systemic therapy despite presenting with disease that, in many cases, was resistant to prior systemic therapy. Methods This is an Institutional Review Board-approved clinical retrospective cohort analysis. A sample of adult patients with RCC metastatic to the spine who underwent operative intervention between January 2010 and December 2017 at 2 large academic medical centers was used in this study. Results We identified 78 patients with metastatic RCC in whom instrumented stabilization was performed in 79% and postoperative stereotactic radiosurgery was performed in 41% of patients. Of patients presenting with weakness or myelopathy, 93% noted postoperative improvement and 78% reported improvement in radicular and axial paraspinal pain severity. Increased overall survival (OS) (913 d (95% CI: 633-1975 d, n = 49) vs 222 d (95% CI: 143-1005 d, n = 29), P = .003) following surgery was noted in patients who received postoperative systemic therapy a median of 80 d (interquartile range 48-227 d) following the surgical intervention. Conclusion Postoperative outcomes and palliation of symptoms for metastatic RCC without targeted therapies in this cohort are similar to those reported in earlier series prior to the adoption of these systemic therapies. We observed a significantly longer OS among patients who received modern systemic therapies postoperatively. These findings have implications for the preoperative evaluation of patients with systemic disease who may have been deemed poor surgical candidates prior to the availability of these systemic therapies.
A radiomics platform for computing imaging features from µCT images of Thoroughbred racehorse proximal sesamoid bones: Benchmark performance and evaluation

BACKGROUND Proximal sesamoid bone (PSB) fractures are the most common fatal musculoskeletal injury in North American racehorses. Computed tomography has the potential to detect morphological changes in bone structure but can be challenging to analyse reliably and quantitatively. OBJECTIVES To develop a radiomics platform that allows the comparison of features from micro-CTs (µCT) of PSBs in horses that sustained catastrophic fractures with horses that did not. To compare features calculated with a radiomics approach with features calculated from a previously published study that used quantitative µCT in the same specimens. STUDY DESIGN Retrospective study of cadaver specimens of µCT images of PSBs using prospectively applied radiomics. METHODS Radiomics features were computed on standardised CT datasets to benchmark the software. Features from µCT images of PSBs from eight horses that sustained PSB fracture and eight controls were computed using the contralateral, intact forelimb from horses sustaining PSB fracture (cases, n = 19) and all available forelimbs for controls (n = 30). Two-hundred and fifteen radiomic features were calculated, and similar or comparable features were compared with those reported in a previous study that used the same specimens. RESULTS Morphologic features computed with the radiomics approach, such as volume, minor axis dimensions and anisotropy were highly correlated with previously published data. A high number of imperceptible radiomic features, such as entropy, coarseness and histogram features were also found to be significantly different (P < .01). The extent of the differences in image features for the cases and controls PSBs depends on radiomic calculation settings. MAIN LIMITATIONS Only datasets obtained from cadaver specimens were included in the study. CONCLUSIONS A radiomics approach for analysing µCT images of PSBs was able to identify and reproduce differences in image features in cases and controls. Furthermore, radiomics revealed many more imperceptible image features between cases and control PSBs.
Prediction of peptide binding to MHC Class I proteins in the age of deep learning

Prediction of antigens likely to be recognized by the immune system is a fundamental challenge for development of immune therapy approaches. We explore the utility of deep learning for in silico prediction of peptide binding affinity to major histocompatibiliy complex Type I molecules (pMHC-I binding). This process is a critical step in the immune system9s response to cancer cells, which may present highly specific neoantigen peptides bound to MHC proteins at the cell surface. With the advent of high-throughput sequencing and the recognition that somatic mutations in the exome can produce neoantigens, fast in silico prediction of these affinities has become increasingly relevant to precision cancer immunotherapy. We have developed five machine learning methods and use a benchmark from the Immune Epitope Database of experimental pMHC-I binding affinities to compare them to existing machine learning approaches. All methods were used to score, rank, and classify pMHC-I pairs. The best six methods, which include three of our own, were identified and found to make highly correlated predictions, even for individual pMHC-I pairs. The most effective deep learning methods were a gated recurrent unit and a long short-term memory neural network, enhanced by transfer learning. These methods can handle peptides of any length without the need for artificial lengthening or shortening and were substantially faster than the most widely-used standard neural networks. Major findings: The best in silico predictors of peptide major histocompatibility complex binding must be identified for application in precision cancer immunotherapy. We design and test a variety of machine learning methods for this purpose. We identify six best-in-class methods, three of our own design. Surprisingly, the best deep and standard machine learning methods make highly correlated predictions. Several standard methods run significantly slower and may have less utility as high-throughput sequence analysis for precision immunotherapy becomes more common. Performance of all methods varies by MHC allele, and most of this variance can be explained by data-driven, rather than biological properties. Increasing the quantity of publicly available experimental data has the potential to improve all machine learning methods applied to this problem, and in particular deep learning methods.
Sleep Apnea and Insomnia: Emerging Evidence for Effective Clinical Management

Comorbid insomnia and sleep apnea (COMISA) are the most common co-occurring sleep disorders and present many challenges to clinicians. This review provides an overview of the clinical challenges in the management of patients with COMISA, with a focus on recent evidence regarding the evaluation and treatment of COMISA. Innovations in the assessment of COMISA have used profile analyses or dimensional approaches to examine symptom clusters or symptom severity that could be particularly useful in the assessment of COMISA. Recent randomized controlled trials have provided important evidence about the safety and effectiveness of a concomitant treatment approach to COMISA using cognitive-behavioral therapy for insomnia (CBT-I) with positive airway pressure (PAP). Furthermore, patient-centered considerations that integrate patient characteristics, treatment preferences, and accessibility to treatment in the context of COMISA are discussed as opportunities to improve patient care. Based on these recent advances and clinical perspectives, a model for using multidisciplinary, patient-centered care is recommended to optimize the clinical management of patients with COMISA.
Network-Agnostic Knowledge Transfer for Medical Image Segmentation

Conventional transfer learning leverages weights of pre-trained networks, but mandates the need for similar neural architectures. Alternatively, knowledge distillation can transfer knowledge between heterogeneous networks but often requires access to the original training data or additional generative networks. Knowledge transfer between networks can be improved by being agnostic to the choice of network architecture and reducing the dependence on original training data. We propose a knowledge transfer approach from a teacher to a student network wherein we train the student on an independent transferal dataset, whose annotations are generated by the teacher. Experiments were conducted on five state-of-the-art networks for semantic segmentation and seven datasets across three imaging modalities. We studied knowledge transfer from a single teacher, combination of knowledge transfer and fine-tuning, and knowledge transfer from multiple teachers. The student model with a single teacher achieved similar performance as the teacher; and the student model with multiple teachers achieved better performance than the teachers. The salient features of our algorithm include: 1) no need for original training data or generative networks, 2) knowledge transfer between different architectures, 3) ease of implementation for downstream tasks by using the downstream task dataset as the transferal dataset, 4) knowledge transfer of an ensemble of models, trained independently, into one student model. Extensive experiments demonstrate that the proposed algorithm is effective for knowledge transfer and easily tunable.
Costly Trading, Managerial Myopia, and Long-Term Investment

The costly trade theory predicts that it is much more difficult to exploit long-term private information than short-term. Thus, there is less long-term information impounded in prices. The managerial myopia theory predicts that a variety of short-term pressures, including inadequate information on long-term projects, cause asymetrically-informed corporate managers to underinvest in long-term projects. The introduction of long-term options called LEAPS provides a natural experiment to jointly test both theories, which are otherwise difficult to test. We conduct an event study around the introduction of LEAPS for a given stock and test whether corporate investment in long-term R&D/Sales increases in the years following the introduction. We find that over a two year period of time LEAPS firms increase their R&D/Sales between 23% and 28% ($125-$152 million annually) compared to matching non-LEAPS firms. The difference depends on the matching technique used. Two other proxies for long-term investment find similar increases. We find that the increase is positively related to LEAPS volume. We also find that the increase is larger in firms where R&D plays a larger and more strategic role. These results provide both statistically and economically significant support for the costly trade and managerial myopia theories.
Kawahiva: do Diagnóstico de Vulnerabilidade à Documentação

Este texto trata da documentacao linguistica da lingua falada por varios povos amazonicos autodenominados Kawahiva. Mais especificamente, descreve-se o percurso pelo qual o Projeto de Documentacao Linguistica Kawahiva tem seguido, desde o censo sobre a vulnerabilidade da lingua ate o atual estagio, quando tecnicas de salvaguarda da sua cultura verbal foram implementadas. A construcao do quadro aqui relatado foi proporcionada por trabalhos de campo realizados no âmbito do Inventario Nacional de Diversidade Linguistica (INDL) com os Kawahiva em 2017, e do projeto de documentacao propriamente dito que computam um total de oito meses. Ao final, o leitor ganhara acesso ao reporte de uma parte importante do trabalho com os Kawahiva, qual seja, o diagnostico de vulnerabilidade que permitiu a implementacao do projeto voltado a salvaguarda da lingua.
Implicit Methods with Reduced Memory for Thermal Radiative Transfer.

This paper presents approximation methods for time-dependent thermal radiative transfer problems in high energy density physics. It is based on the multilevel quasidiffusion method defined by the high-order radiative transfer equation (RTE) and the low-order quasidiffusion (aka VEF) equations for the moments of the specific intensity. A large part of data storage in TRT problems between time steps is determined by the dimensionality of grid functions of the radiation intensity. The approximate implicit methods with reduced memory for the time-dependent Boltzmann equation are applied to the high-order RTE, discretized in time with the backward Euler (BE) scheme. The high-dimensional intensity from the previous time level in the BE scheme is approximated by means of the low-rank proper orthogonal decomposition (POD). Another version of the presented method applies the POD to the remainder term of P2 expansion of the intensity. The accuracy of the solution of the approximate implicit methods depends of the rank of the POD. The proposed methods enable one to reduce storage requirements in time dependent problems. Numerical results of a Fleck-Cummings TRT test problem are presented.
A Low-Sodium Diet Boosts Ang (1-7) Production and NO-cGMP Bioavailability to Reduce Edema and Enhance Survival in Experimental Heart Failure.

Sodium restriction is often recommended in heart failure (HF) to block symptomatic edema, despite limited evidence for benefit. However, a low-sodium diet (LSD) activates the classical renin-angiotensin-aldosterone system (RAAS), which may adversely affect HF progression and mortality in patients with dilated cardiomyopathy (DCM). We performed a randomized, blinded pre-clinical trial to compare the effects of a normal (human-equivalent) sodium diet and a LSD on HF progression in a normotensive model of DCM in mice that has translational relevance to human HF. The LSD reduced HF progression by suppressing the development of pleural effusions (p < 0.01), blocking pathological increases in systemic extracellular water (p < 0.001) and prolonging median survival (15%, p < 0.01). The LSD activated the classical RAAS by increasing plasma renin activity, angiotensin II and aldosterone levels. However, the LSD also significantly up-elevated the counter-regulatory RAAS by boosting plasma angiotensin converting enzyme 2 (ACE2) and angiotensin (1–7) levels, promoting nitric oxide bioavailability and stimulating 3′-5′-cyclic guanosine monophosphate (cGMP) production. Plasma HF biomarkers associated with poor outcomes, such as B-type natriuretic peptide and neprilysin were decreased by a LSD. Cardiac systolic function, blood pressure and renal function were not affected. Although a LSD activates the classical RAAS system, we conclude that the LSD delayed HF progression and mortality in experimental DCM, in part through protective stimulation of the counter-regulatory RAAS to increase plasma ACE2 and angiotensin (1–7) levels, nitric oxide bioavailability and cGMP production.
3D Analysis of Casting Surface Characterization Based on the Variogram Roughness Method

Casting surface specifications are commonly inspected via visual inspection. Since visual inspection is subjective, the results are not very reliable. Objective methods that could replace visual inspection for simple surface patches, and thus increased the reliability of the inspection process has been introduced. This paper continued the work on the variogram roughness method and adopted the method to produce reliable results for 3D scans of complete castings. This enables foundries to utilize existing 3D scanners used for dimensional inspection for surface roughness inspection of their castings and potentially using the same dataset for both needs. This paper will describe the function of this method and how it was adopted to whole castings. Tests will also be performed to validate the method in 3D. To accomplish this, the results from the validated method for flat surfaces were used to determine the surface roughness of flat surface patches on a cube. The cubes were created from plastic copies of the SCRATA comparators. Overall, comparable results to the previous method were possible. The highest deviations were seen for rough surfaces. Further, with its local roughness determination, the method can also be used as an input for automated surface finishing.
Practising what we preach: are knowledge management systems in practice really knowledge management systems?

Knowledge management systems (KMS) are predominant in both theory and practice. However, are the same systems discussed in theory actualised in practice? By comparing and contrasting KMS in theory and practice, this paper demonstrates that they are indeed dissimilar. In theory, KMS have both subjective and objective components. In practice, only the objective component of KMS appears to be actualized; hence, these KMS in practice are essentially organisational memory systems at best and not KMS at all.
Clinical diagnosis and risk stratification in patients with Brugada syndrome.

In patients with Brugada syndrome (BRS), especially those who are asymptomatic, preclinical diagnosis and risk stratification are vital to the prevention of the fatal ventricular arrhythmias. The initial optimism that a diagnosis of BRS could be made simply on the basis of distinct
Self-Tuning Adaptive Control using Fourier Series Neural Networks

A neural network architecture, called the Fourier Series Neural Network (FSNN), has been developed [1] for modeling unstructured dynamic systems using system input and output frequency spectrums. This paper addresses the issues concerning on-line implementation of self-tuning adaptive control using the FSNN as an estimator. An underlying controller design method based on the estimation of the system frequency response is proposed in the principle of the laglead compensation. The performance of this Neuro-Self-Tuning Regulator (NSTR) is evaluated using the performance parameters from the frequency domain such as the system bandwidth, phase margin and the gain margin. Simulations for the evaluation of the NSTR were conducted and the results are discussed.
Fixed point and selection theorems in hyperconvex spaces

It is shown that a set valued mapping T ∗ of a hyperconvex metric space M which takes values in the space of nonempty externally hyperconvex subsets of M always has a lipschitzian single valued selection T which satisfies d(T (x), T (y)) ≤ dH(T ∗(x), T ∗(y)) for all x, y ∈M . (Here dH denotes the usual Hausdorff distance.) This fact is used to show that the space of all bounded λ-lipschitzian self-mappings of M is itself hyperconvex. Several related results are also obtained.
Sedentary Behavior as a Risk Factor for Physical Frailty Independent of Moderate Activity: Results From the Osteoarthritis Initiative

Objectives. This prospective longitudinal study investigated the association between baseline objectively measured sedentary time and 2-year onset of physical frailty.Methods. We studied 1333 Osteoarthritis Initiative participants 55 to 83 years of age who were at risk for physical frailty, as assessed via low gait speed (< 0.6 m per second) or inability to perform a single chair stand. Baseline sedentary time was assessed through accelerometer monitoring. Hazard ratios (HRs) for physical frailty onset were estimated with discrete survival methods that controlled for moderate physical activity, sociodemographic characteristics, baseline gait and chair stand functioning, and health factors.Results. The incidence of physical frailty in this high-risk group was 20.7 per 1000 person-years. Greater baseline sedentary time (adjusted HR = 1.36 per sedentary hour; 95% confidence interval [CI] = 1.02, 1.79) was significantly related to incident physical frailty after control for time spent in moderate-intensity ac...
Giving a Voice to the Silent Mentally Ill Client: An Empirical Study of the Role of Counsel in the Civil Commitment Hearing

In the civil commitment arena, where a mentally ill person is allegedly a danger to the life or safety of themselves or of others and in need of in-patient care or treatment, there are two groups assigned to protect the people: one, the hospital presenter, who is responsible for investigating and presenting evidence and testimony at a hearing to secure admission to a psychiatric facility as an involuntary patient, the other, the lawyer, who represents and defends the allegedly mentally ill person from such involuntary civil commitment confinement. These are their stories.The attorney representing a mentally ill client at the involuntary admission hearing (IVA) often faces challenges in defining his role and responsibility toward his client and the community at large. There are occasions when a client's mental disorder makes it impossible to effectively communicate his desires and wishes to his lawyer. The client's ability to aid his attorney in preparing an adequate defense to the application for involuntary admission is severely compromised. There are occasions at the civil commitment hearing when the individual subject to the commitment is silent as a result of cognitive impairment, which places the attorney in the position of advocating a position without the input of the client. The hospital presenter who seeks the involuntary confinement into the psychiatric hospital is opposed by an attorney without clear instructions from the client as to how to proceed.This article will discuss and analyze the attorney's role in light of the silent or incapacitated mentally ill client. An historical perspective of the traditional role of counsel will be examined and compared with the guardian ad litem role. The American Bar Association (ABA) standards will be scrutinized to seek guidance in understanding the duty an attorney owes to competently represent his client and keep him informed as to the proceedings and abide by decisions made by the client in the legal proceedings at hand. When a client is a person under a disability, the role and responsibility of counsel are often complex and confused, thus this article will examine court decisions addressing the constitutional right to counsel, as well as seek guidance from state statutes addressing right to counsel at the civil commitment hearing as to the role of counsel at the hearing.
Amino Acids as Regulators of Gene Expression at the Level of mRNA Translation

Amino acids act through a number of signaling pathways and mechanisms to mediate control of gene expression at the level of mRNA translation. This report reviews recent findings that illustrate the manner through which amino acids act to regulate the initiation phase of mRNA translation. The report focuses on signaling pathways that involve the eukaryotic initiation factor-2 (eIF2) protein kinase, general control non-derepressing kinase-2 and the mammalian target of rapamycin (mTOR) protein kinase. It also describes the mechanisms through which amino acid-induced modulation of eIF2 phosphorylation and mTOR-mediated signaling cause derepression of translation of specific mRNAs and result in an overall change in the pattern of gene expression. Finally, it provides examples of mRNAs whose translation is modulated through these mechanisms.
Growth of a two-dimensional dielectric monolayer on quasi-freestanding graphene

Integrating graphene into device architectures requires interfacing graphene with dielectric materials. However, the dewetting and thermal instability of dielectric layers on top of graphene makes fabricating continuous graphene/dielectric interfaces challenging. Here, we show that yttria (Y(2)O(3))--a high-κ dielectric--can form a complete monolayer on platinum-supported graphene. The monolayer interacts weakly with graphene, but is stable to high temperatures. Scanning tunnelling microscopy reveals that the yttria layer exhibits a two-dimensional hexagonal lattice rotated by 30° relative to the hexagonal graphene lattice. X-ray photoemission spectroscopy measurements indicate a shift of the Fermi level in graphene on yttria deposition, which suggests that dielectric layers could be used for charge doping of metal-supported graphene.
Synthesis, Characterization, and Catalytic Activity of N-Heterocyclic Carbene (NHC) Palladacycle Complexes

Palladacycle dimers possessing bridging halides can be easily cleaved by using N-heterocyclic carbenes (NHCs) to generate novel monomeric complexes. The structure of one of these was determined by single-crystal diffraction study and consists of a square-planar coordination around the palladium center where the NHC ligand is trans to the amine of the palladacycle. The complex was found to be equally active in aryl amination and α-arylation of ketones even at very low catalyst loading (0.02 mol %). Primary and secondary alkyl/arylamines are equally active partners in coupling reactions.
Epitope spreading: a mechanism for progression of autoimmune disease.

Autoimmune diseases are typically characterized by a persistent inflammatory self-recognition process that ultimately leads to chronic progressive disability. Over the past several years we have addressed the fundamental question of why autoimmune diseases are chronic. Our working hypothesis in these studies has been that autoimmunity involves a continuous acquisition of new self-recognition events, thereby providing an inflammatory steady-state that leads to chronicity. This acquired T cell neoautoreactivity is commonly referred to as epitope spreading. By studying multiple sclerosis (MS) and its related animal model, experimental autoimmune encephalomyelitis (EAE), we have found that chronic progression of autoimmune disease is invariably linked to the development of an epitope-spreading process that manifests as a cascade of inflammatory T cell neoautoreactivities to a sequential series of predictable new target self-antigens. However, our most recent observations indicate that the emergence of epitope spreading is accompanied by a concurrent regression of the established primary autoreactivity associated with disease onset. Thus, our studies indicate that progression of autoimmune disease involves a shifting of T cell autoreactivity from primary initiating self-determinants to defined cascades of secondary determinants that sustain the inflammatory self-recognition process during progression to chronicity. Our data support the view that the natural development of self-recognition during autoimmune disease may best be understood when considered in the temporal context of an “epitope du jour” and “moving target” perspective.
Light Activation of Protein Splicing with a Photocaged Fast Intein

Intein-mediated protein splicing has found broad biotechnological applications. Herein, we describe our recent result in engineering a photoactivatable intein compatible with living mammalian cells. A photocaged cysteine amino acid residue was genetically introduced into a highly efficient Nostoc punctiforme (Npu) DnaE intein. The resulting photocaged intein was inserted into a red fluorescent protein (RFP) mCherry and a human Src tyrosine kinase to create inactive chimeric proteins. A light-induced photochemical reaction was able to reactivate the intein and trigger protein splicing. Active mCherry and Src were formed as observed by direct fluorescence imaging or imaging of an Src kinase sensor in mammalian cells. The genetically encoded photocaged intein is a general optogenetic tool, allowing effective photocontrol of primary structures and functions of proteins.
Epidermal growth and ribosomal RNA accumulation in regenerating mouse epidermis following abrasion.

Epidermal regeneration following abrasion of mouse skin can be divided into 2 phases. The first phase consists of a period of massive epidermal production. Epidermal wet weight in a standard area of skin increases over 6 × that of normal within 5 days after abrasion and remains at this level until about the 8th day. Associated with the increase in epidermal wet weight is a marked increase in total epidermal protein and DNA. The second phase, characterized by a period of regression, begins about 8 days after abrasion, during which the epidermis gradually returns to its normal thickness, and there is a gradual return toward normal levels of wet weight, total protein and DNA. Ribosomes accumulate in large numbers in epidermal cells during the period of massive epidermal production, as measured by the increases in rRNA/DNA and rRNA/gm epidermis. Ribosome accumulation reaches a peak of over 5 × that of normal by 5 days after abrasion, remains high for the next 3 days, and during the period of epidermal regression, gradually decreases approaching normal levels by 21 days after abrasion. A hypothesis is presented that the large accumulation of ribosomes, along with the other associated metabolic regulatory changes, acts as a "driving force" to keep epidermal cells proliferating and thus helps produce the epidermal hyperplasia.
The prehatching development of the thyroid gland of the fathead minnow, Pimephales promelas (Rafinesque)

Abstract The prehatching development of the thyroid gland in the fathead minnow, Pimephales promelas , has been studied using histochemical and autoradiographic methods. The thyroid arises as a solid nodular bud from the pharyngeal epithelium at the posterior border of the hyomandibular junction and then grows ventrocaudally into a tractus thyroglossus from which the follicles eventually form. During subsequent development, the follicles exhibit an exponential increase in number, migrate from the subhyoid region, become diffusely distributed throughout the pharynx and at ectopic loci, and show an increase in the size of the follicular lumina with an accumulation of colloid and a decrease in follicular cell heights due to follicular emptying. Autoradiographic studies suggest that the thyroid tissue traps and concentrates iodine prior to the appearance of histochemically demonstrable colloid. Histochemical observations suggest that the formation of thyroid follicles is preceded by the secretion of colloid in the intercellular space and into the tractus thyroglossus.
Calibration Of Beam Power Monitors For Laser Welding

Calibration of a Coherent Radiation Model 213 laser power sensor is reviewed. The calibration chain is traced from the National Bureau of Standards (NBS) through transfer calibrations to a working sensor. Uncertainty components in this chain, including those for use conditions, are combined to give a root-sum-square uncertainty of 7% for use of this device.
Growth and Properties of Lithium Salicylate Single Crystals

Optical quality lithium salicylate (LiSal) single crystals have been grown from water and methanol solutions for thermal neutron detection studies. The results of structural studies showed that LiSal crystallizes from water as a stable modification different from the monohydrate LiSal·H2O reported previously. Growth from methanol results in the formation of unstable crystals of LiSal·MeOH that quickly degrade in air due to the loss of methanol. Initial radiation detection tests showed a good neutron/gamma separation in water-grown modification making LiSal in its single crystal form a potential material for thermal neutron detection.
Angiopeptin, a Somatostatin Analogue, Inhibits Rat Coronary Artery and Aorta Smooth Muscle Cell Proliferation Induced by the Thromboxane A2 Mimetic U46619

Thromboxane A2 (TXA2) is a potent mitogenic agent. Its synthesis is increased in transplant patients during rejection episodes, which is the suspected etiology of accelerated transplant arteriosclerosis. Angiopeptin, a stable analogue of somatostatin, inhibits arterial myointimal thickening in a number of vascular balloon injury models of angioplasty and in vivo models of transplant arteriosclerosis. In this study, we investigated whether TXA2-induced smooth muscle cell proliferation is inhibited by Angiopeptin in vitro. Primary rat coronary and aorta smooth muscle cells were cultured in the presence of U46619, a TXA2 mimetic. Proliferation induced by U46619, as determined by 3H-thymidine incorporation, was abrogated by two specific thromboxane receptor antagonists, SQ 30741 and SQ 29548, indicating that the effect of U46619 on smooth muscle cells is a specific receptor-mediated response. We found Angiopeptin to inhibit proliferation following exposure of both coronary and aorta smooth muscle cells to varying concentrations of U46619 for 3 and 6 days. This study demonstrates that U46619 exerts a specific receptor-mediated response stimulating the rat coronary and aorta smooth muscle cell proliferation. This mitogenic effect is obtained by increasing the G1 to S transition rate. Angiopeptin inhibits thromboxane-induced cell proliferation to the same extent as a thromboxane antagonist. This inhibition is obtained by maintaining the noncycling fraction in that Angiopeptin prevents a progression from G0-G1 to S phase.
Design and tests for CLEO-II silicon vertex detector

We report on the design and prototype studies for a new double-sided silicon vertex detector for the CLEO-II experiment at CESR. To minimize multiple scattering, two new techniques are employed: (1) the detector is supported by low mass, low Z boron carbide foam U-channels; and (2) the preamplifiers are removed entirely from the tracking volume by using a second layer of metallization on the silicon to provide longitudinal readout traces for the transverse sense strips.
Analysis of aldehydes in excipients used in liquid/semi-solid formulations by gas chromatography–negative chemical ionization mass spectrometry

Abstract Monitoring of low-molecular-weight aldehyde levels in excipients used in liquid/semi-solid based capsule (LFC) dosage forms plays a critical role in the development of these pharmaceutical products. A simple, sensitive and specific method based on gas chromatography coupled with mass spectrometry (GC–MS) utilizing an Rtx-5MS capillary column was developed and validated for the detection and quantification of C1–C8 aliphatic aldehydes in LFC excipients at sub-μg/g levels. The proposed procedure is based on the derivatization of aldehydes in 10:1 (v/v) acetonitrile:water with O-2,3,4,5,6-(pentafluorobenzyl) hydroxylamine hydrochloride (PFBHA), followed by direct GC analysis of aldehyde-PFBHA-oxime derivatives with negative chemical ionization (NCI) MS detection. The method developed was successfully applied to the analysis of short chain aldehydes in 30 typical LFC excipients. An example case study on the formation and growth of aldehydes in these excipients under accelerated storage conditions is also reported.
Hybrid Electric Vehicles and Implications for Transportation Finance

Fuel efficiency improvements in the U.S. vehicle fleet are slowing growth in gasoline consumption. Although this is desirable with respect to goals for achieving energy security and environmental i...
Arthroscopic rotator cuff repair:Indications and technique

Abstract Arthroscopic repair of rotator cuff tears is now possible. By using the biomechanical principles of margin convergenceand the balance of force couples, even large cuff defects can be repaired. Suture anchors are particularly suitable for arthroscopic repairs, and a corkscrew anchor design lends itself to a trans-tendon approach
Dislocation-mediated melting in two dimensions

A theory of dislocation-mediated melting in two dimensions is described in detail, with an emphasis on results for triangular lattices on both smooth and periodic substrates. The transition from solid to liquid on a smooth substrate takes place in two steps with increasing temperatures. Dissociation of dislocation pairs first drives a transition out of a low-temperature solid phase, with algebraic decay of translational order and long-range orientational order. This transition is into a "liquid-crystal" phase characterized by exponential decay of translational order, but power-law decay of sixfold orientational order. Dissociation of disclination pairs at a higher temperature then produces an isotropic fluid. The behavior of the specific heat, structure factor, and various elastic constants near these transitions is worked out. We also discuss the applicability of our results to melting on a periodic substrate. Dislocation unbinding should describe melting of a "floating" (and, in general, incommensurate) adsorbate solid into a high-temperature fluid phase. The orientation bias imposed by the substrate can alter or eliminate the disclination-unbinding transition, however. Transitions from a floating solid into a low-temperature registered or partially registered phase can also be mapped onto the dislocation-unbinding transition, but only at certain special values of the coverage. Substrate reciprocallattice vectors play the role of Burger's vectors in this case.
Infinite-layer La Ni O 2 : Ni 1 + is not Cu 2 +

The Ni ion in $\mathrm{La}\mathrm{Ni}{\mathrm{O}}_{2}$ has the same formal ionic configuration $3{d}^{9}$ as does Cu in isostructural $\mathrm{Ca}\mathrm{Cu}{\mathrm{O}}_{2}$, but it is reported to be nonmagnetic and probably metallic whereas $\mathrm{Ca}\mathrm{Cu}{\mathrm{O}}_{2}$ is a magnetic insulator. From ab initio calculations we trace its individualistic behavior to (1) reduced $3d--2p$ mixing due to an increase of the separation of site energies $({\ensuremath{\epsilon}}_{d}--{\ensuremath{\epsilon}}_{p})$ of at least $2\phantom{\rule{0.3em}{0ex}}\mathrm{eV}$, and (2) important $\mathrm{Ni}\phantom{\rule{0.2em}{0ex}}3d(3{z}^{2}\ensuremath{-}{r}^{2})$ mixing with $\mathrm{La}\phantom{\rule{0.2em}{0ex}}5d(3{z}^{2}--{r}^{2})$ states that leads to Fermi surface pockets of $\mathrm{La}\phantom{\rule{0.2em}{0ex}}5d$ character that hole dope the $\mathrm{Ni}\phantom{\rule{0.2em}{0ex}}3d$ band. Correlation effects do not appear to be large in $\mathrm{La}\mathrm{Ni}{\mathrm{O}}_{2}$. However, ad hoc increase of the intra-atomic repulsion on the Ni site (using the $\mathrm{LDA}+\mathrm{U}$ method) is found to lead to a correlated state: (i) the transition metal $d({x}^{2}\ensuremath{-}{y}^{2})$ and $d(3{z}^{2}\ensuremath{-}{r}^{2})$ states undergo consecutive Mott transitions; (ii) their moments are antialigned leading (ideally) to a ``singlet'' ion in which there are two polarized orbitals; and (iii) mixing of the upper Hubbard $3d(3{z}^{2}--{r}^{2})$ band with the $\mathrm{La}\phantom{\rule{0.2em}{0ex}}5d(xy)$ states leaves considerable transition metal $3d$ character in a band pinned to the Fermi level. The magnetic configuration is more indicative of a ${\mathrm{Ni}}^{2+}$ ion in this limit, although the actual charge changes little with $U$.
Right ventricular performance in the fetus with hypoplastic left heart syndrome.

Background In the fetus with hypoplastic left heart syndrome (HLHS), the single right ventricle (RV) pumps the entire cardiac output in utero. By investigating RV performance in utero, we sought to determine the inherent capabilities of a single RV before the increased metabolic demands of postnatal life and surgical palliation. In addition, we sought to determine whether the presence or absence of a left ventricular cavity impacts on RV performance in fetal life. Methods Between November 2004 and December 2006, Doppler flow-derived measures of ventricular performance were obtained with echocardiography in 76 fetuses with normal cardiovascular system and in 48 age-matched fetuses with HLHS from 17 weeks until 40 weeks of gestation. The myocardial performance index, ventricular ejection force, and cardiac output were determined for both groups and compared using unpaired Student's t tests and regression analysis. Results In fetuses with HLHS, cardiac output was diminished by 20%, RV ejection force was elevated, and RV myocardial performance index was elevated compared with those of normal fetuses. The presence of a left ventricular cavity did not impact on RV performance in utero. Conclusions Fetuses with HLHS have preserved systolic performance but impaired diastolic performance compared with normal fetuses. The heart of a fetus with HLHS is less efficient than the normal heart in that ejection force of the RV is increased, but overall delivery of cardiac output is lower than normal. We conclude that patients with HLHS have inherent limitations in cardiac performance even before birth.
Relationship of ornithine decarboxylase to RNA polymerase i activity.

Abstract Ornithine decarboxylase activity can be rapidly elevated 50- to 100-fold by the administration of methylxanthine derivatives such as methylisobutylxanthine. This elevation occurs just prior to the increase in RNA polymerase I activity. Inhibitors of RNA synthesis and of protein synthesis suggest that any alteration in the ornithine decarboxylase response results in a similar alteration in the level of α-amanitin-insensitive RNA polymerase. Addition of a partially purified ornithine decarboxylase preparation to the RNA polymerase assay increased both the initial rate of 3H-UTP incorporation and the length of time that the polymerase assay was linear. It is suggested that ornithine decarboxylase is the labile protein that modulates the level of RNA polymerase I.
Harvesting in an uncertain world: impact of resource competition on harvesting dynamics

Abstract Different minimum resource levels ( R∗ ) of competitors can result in switches in competitive dominance mediated by predation on the competitors. A simple food-web model with two herbivores competing for a food resource but having different R∗ values was explored to determine the impact of the species' different R∗ on harvesting dynamics. When a superior competitor is harvested and the inferior competitor left unharvested, the superior competitor is driven to extinction by the inferior competitor once harvesting raises the shared resource to a level that the inferior competitor can survive. Yields to the predator then drop to zero for a very small change in harvesting effort. It was shown that these dramatic drops in yield will, in most cases, occur before the maximum sustained yield (MSY) inflexion point predicted without the inferior resource competitor. The maximum yield achieved by the superior competitor in the presence of the inferior competitor increased with the difference between the two species R∗ values (i.e. MSY ∝ R∗ s − R∗ i ). Therefore, high yields to a predator require either polyphagy (i.e. eating all competitors) or large differences in the R∗ of competitors. The second case is most likely to occur between species with different energetic requirements and, therefore, with different evolutionary lineages (i.e. bony fish versus invertebrates). However, even in this circumstance drops in yield are likely to occur before a MSY predicted without the inferior competitor. MSY predictions need to consider community dynamics and the minimum resource requirements of competing species.
A comparison of aversion therapies for nailbiting behavior

To compare the relative effectiveness of three alternative models of aversion therapy in modifying the biting behavior of chronic naibiters, subjects ( N =61) were randomly assigned to one of four groups: (1) shock, (2) negative practice, (3) bitter substance, and (4) attention-placebo control. Half of the subjects from each treatment condition were instructed to self-monitor their nailbiting throughout treatment. All groups experienced an increase in nail growth, with no significant difference among groups. However, self-monitoring subjects exhibited significantly greater increases in nail growth than non-self-monitoring subjects ( p p p
Movement of people across the landscape: a blurring of distinctions between areas, interests, and issues affecting natural resource management

Abstract The spread of development from cities into surrounding forests and farms continues to receive a great deal of attention from the media and resource managers in the US and other countries. However, suburban sprawl is just one of many inter-linked components of the movement of people across the landscape that influence resource management. Substantial changes are taking place in urban areas, fringe areas, and rural recreation/amenity areas. In this paper, we describe these changes, explore their commonalities and interconnectedness, and discuss the implications that they may have for natural resource management. What emerges is a blurring of the distinctions between what have traditionally been considered “urban” or “rural” problems with respect to natural resource issues, interest group concerns, and resource management strategies. Our findings suggest prospects for substantial changes in resource management and the public and private programs designed to support it. Among the emphasis areas for natural resource management that emerge with the changing distribution of people over the landscape are changes in management situations, management processes, and research needs. The changing management situations include increased emphasis on interface and intermix areas, restoring human-impacted natural areas, and addressing complex ecosystem problems. Changing management processes include adaptive forest management, working collaboratively with diverse landowners and other partners, interacting with citizens on a regular basis, and taking a landscape perspective on natural resources and their management. Questions for policy and program development and for research focus on a better understanding of linkages among management activities across the urban to rural landscape.
Pacing-induced changes in cardiac venous blood flow in normal subjects and patients with coronary artery disease.

To quantitate limitations of coronary blood flow in angina pectoris, great cardiac venous blood flow was measured by the thermodilution method of Ganz in 6 normal subjects and 28 patients with angina pectoris undergoing diagnostic coronary angiography. After resting measurements were obtained, atrial pacing was started at 100 beats/min and increased 10 beats/min every 2 minutes until appearance of the onset of angina, a heart rate of 150 beats/min or second degree atrioventricular block. A comparison of the hemodynamic data at rest and at the maximal rate revealed the systolic pressure-heart rate product increased 61 ± 4.2 percent (standard error of the mean), time-tension index 36 ± 3.4 percent and great cardiac venous blood flow 50 ± 7.1 percent in 23 patients who had angina during pacing (Group I). In five patients who did not have angina with pacing (Group II), systolic pressure-heart rate product increased 84 ± 13 percent, time-tension index 33 ± 10 percent, and great cardiac venous blood flow 83 ± 14 percent. In normal subjects (Group III) systolic pressure-heart rate product increased 76 ± 13.9 percent, time-tension index 36 ± 5.3 percent and great cardiac venous blood flow 102 ± 9.9 percent. Compared to Group III, Group I had a lesser rise in great cardiac venous blood flow ( P = 0.001) despite comparable increases in time-tension index and systolic pressure-heart rate product. Greater limitations in ability to increase great cardiac venous blood flow were evident in patients with severe extensive coronary disease. Twenty-four of the study patients also underwent a progressive bicycle-ergometer exercise test. Those able to perform high exercise loads had a significantly greater increase in great cardiac venous blood flow during atrial pacing than patients with low exercise capacity. Measurement of great cardiac venous blood flow appears to be a useful method for quantitating regional limitations of coronary blood flow.
A Systematic Comprehensive Computational Model for Stake Estimation in Mission Assurance - Applying Cyber Security Econometrics System (CSES) to Mission Assurance Analysis Protocol (MAAP)

In earlier works, we presented a computational infrastructure that allows an analyst to estimate the security of a system in terms of the loss that each stakeholder stands to sustain as a result of security breakdowns. In this paper, we discuss how this infrastructure can be used in the subject domain of mission assurance as defined as the full life-cycle engineering process to identify and mitigate design, production, test, and field support deficiencies of mission success. We address the opportunity to apply the Cyberspace Security Econometrics System (CSES) to Carnegie Mellon University and Software Engineering Institute’s Mission Assurance Analysis Protocol (MAAP) in this context.