gebhart/patrepeval huggingface dataset:
Peripheral white blood cell toxicity induced by broad spectrum cyclin‐dependent kinase inhibitors (2007)

Cyclin-dependent kinases (CDKs) have been pursued for more than a decade for the treatment of cancer. CDK inhibitors are expected to slow the rate of cell division and potentially increase the apoptotic fraction of rapidly dividing cells. Although CDK activity is often increased in tumors, normal dividing tissues are also susceptible to the cytostatic and cytotoxic effects of CDK inhibitor action. Therefore the typical toxicity profile associated with cytotoxic anti-cancer therapy, bone marrow suppression and gastrointestinal toxicity, is expected with CDK inhibitors. Bone marrow toxicity and the ensuing delayed peripheral leukocyte suppression often limit the therapeutic application of cytotoxic anticancer drugs. Here we characterize an unusual bone marrow-independent acute toxicity toward leukocytes from broad spectrum CDK inhibitors in monkeys and rodents. The potential combination of both acute and delayed immunosuppression would likely further restrict the application of these particular compounds. Since the cells targeted were non-proliferating, it was assumed that the toxicity was not driven by the intended pharmacological mechanism thereby facilitating the development of a testing strategy to identify compounds with a reduced potential for acute leukocyte toxicity. This testing strategy resulted in a CDK inhibitor void of bone marrow-independent leukocyte toxicity that is currently undergoing clinical testing.
Network-aware P2P file sharing over the wireless mobile networks (2007)

With the coming wireless mobile networks era and the popular use of P2P applications, how to improve the resource retrieval and discovery for P2P file sharing applications in wireless mobile networks becomes a critical issue. In this paper, we propose a novel network-aware P2P file architecture and related control schemes that can provide continuous resource retrieval and discovery for mobile users over the wireless network environment. The proposed architecture divides a P2P file sharing network into multiple network-aware clusters, in which peers are assigned to a network-aware cluster using a network prefix division. Accordingly, there are two designs for supporting mobile peers to retrieve files in wireless mobile networks. First, a novel file discovery control scheme named mobility-aware file discovery control (MAFDC) scheme is devised to obtain fresh status of shared peers and find the new resource providing peers in wireless mobile networks. Second, a resource provider selection algorithm is devised to enable a mobile peer to select new resource providing peers for continuous file retrieval.
A MEMS AC current sensor for residential and commercial electricity end-use monitoring (2009)

This paper presents a novel prototype MEMS sensor for alternating current designed for monitoring electricity end-use in residential and commercial environments. This new current sensor design is comprised of a piezoelectric MEMS cantilever with a permanent magnet mounted on the cantilever's free end. When placed near a wire carrying AC current, the magnet is driven sinusoidally, producing a voltage in the cantilever proportional to the current being measured. Analytical models were developed to predict the applicable magnetic forces and piezoelectric voltage output in order to guide the design of a sensor prototype. This paper also details the fabrication process for this sensor design. Released piezoelectric MEMS cantilevers have been fabricated using a four-mask process and aluminum nitride as the active piezoelectric material. Dispenser-printed microscale composite permanent magnets have been integrated, resulting in the first MEMS-scale prototypes of this current sensor design.
Non-destructive optical methods for assessing defects in production of Si or SiGe materials (2004)

Non-destructive techniques are ideal for process control and process development. They do not involve any special wafer treatment and the wafers can be further processed in the manufacturing line. A relatively new technique that can be applied to materials characterizations is room temperature photoluminescence (RT-PL). Defects can be revealed because of the enhanced non-radiative recombination at the defect site. The efficiency of detecting defects in SiGe was evaluated. Defects could be detected in blanket film SiGe layers, and there was a good correlation with bright field microscopy inspection and laser scanning methods. The effect of ex-situ cleaning, pre-bake and Boron doping conditions have been investigated. The results follow the expected trends, more defects for non-standard processing. The defects detected by RT-PL were confirmed using transmission electron microscopy (TEM). Defects could also be detected in part-processed patterned wafers, giving a direct indication of the material quality in product wafers.
Laboratory Testing of High-Pressure, High-Speed PDC Bits (1986)

ABSTRACT A high-speed drilling system has been developed which drills medium strength rocks at rates up to 1000 ft/hr (328 m/hr). This system uses special motors to operate high-pressure PDC bits at pressures up to 10,000 psi (69 MPa) and at speeds of 800 to 1000 RPM. High drilling rates were achieved due to the high rotary speeds and the use of PDC cutters to remove the rock ledges left on the hole bottom by the high-pressure jets.
5-Hydroxytryptamine 2B receptor regulates cell-cycle progression: Cross-talk with tyrosine kinase pathways (2000)

In this paper, we present evidence that activation of 5-hydroxytryptamine 2B (5-HT2B) receptors by serotonin (5-HT) leads to cell-cycle progression through retinoblastoma protein hyperphosphorylation and through activation of both cyclin D1/cdk4 and cyclin E/cdk2 kinases by a mechanism that depends on induction of cyclin D1 and cyclin E protein levels. The induction of cyclin D1 expression, but not that of cyclin E, is under mitogen-activated protein kinase (MAPK) control, indicating an independent regulation of these two cyclins in the 5-HT2B receptor mitogenesis. Moreover, by using the specific platelet-derived growth factor receptor (PDGFR) inhibitor AG 1296 or by overexpressing a kinase-mutant PDGFR, we show that PDGFR kinase activity is essential for 5-HT2B-triggered MAPK/cyclin D1, but not cyclin E, signaling pathways. 5-HT2B receptor activation also increases activity of the Src family kinase, c-Src, Fyn, and c-Yes. Strikingly, c-Src, but not Fyn or c-Yes, is the crucial molecule between the G(q) protein-coupled 5-HT2B receptor and the cell-cycle regulators. Inhibition of c-Src activity by 4-amino-5-(4-methylphenyl)-7-(t-butyl)pyrazolo[3,4-d]pyrimidine (PP1) or depletion of c-Src is sufficient to abolish the 5-HT-induced (i) PDGFR tyrosine kinase phosphorylation and MAPK activation, (ii) cyclin D1 and cyclin E expression levels, and (iii) thymidine incorporation. This paper elucidates a model of 5-HT2B receptor mitogenesis in which c-Src acts alone to control cyclin E induction and in concert with the receptor tyrosine kinase PDGFR to induce cyclin D1 expression via the MAPK/ERK pathway.
Epidermal Growth Factor Receptor in Glioma: Signal Transduction, Neuropathology, Imaging, and Radioresistance (2010)

Aberrant epidermal growth factor receptor (EGFR) signaling is common in cancer. Increased expression of wild type and mutant EGFR is a widespread feature of diverse types of cancer. EGFR signaling in cancer has been the focus of intense investigation for decades primarily for two reasons. First, aberrant EGFR signaling is likely to play an important role in the pathogenesis of cancer, and therefore, the mechanisms of EGFR-mediated oncogenic signaling are of interest. Second, the EGFR signaling system is an attractive target for therapeutic intervention. EGFR gene amplification and overexpression are a particularly striking feature of glioblastoma (GBM), observed in approximately 40% of tumors. GBM is the most common primary malignant tumor of the central nervous system in adults. In approximately 50% of tumors with EGFR amplification, a specific EGFR mutant (EGFRvIII, also known as EGFR type III, de2-7, Delta EGFR) can be detected. This mutant is highly oncogenic and is generated from a deletion of exons 2 to 7 of the EGFR gene, which results in an in-frame deletion of 267 amino acids from the extracellular domain of the receptor. EGFRvIII is unable to bind ligand, and it signals constitutively. Although EGFRvIII has the same signaling domain as the wild type receptor, it seems to generate a distinct set of downstream signals that may contribute to an increased tumorigenicity. In this review, we discuss recent progress in key aspects of EGFR signaling in GBM, focusing on neuropathology, signal transduction, imaging of the EGFR, and the role of the EGFR in mediating resistance to radiation therapy in GBM.
The Adrenergic Nervous System in Heart Failure (1984)

IN this issue of the Journal Cohn et al. report that in heart failure central venous plasma norepinephrine is directly related to mortality, and that plasma norepinephrine is the only one of several univariate predictors that independently correlates with mortality risk.1 These observations contribute to an expanding body of information that suggests that the behavior of the adrenergic nervous system may be an important variable in the natural history of heart-muscle disease and heart failure.Cardiovascular function is under the regulatory control of the adrenergic or sympathetic nervous system. As first noted by Cannon,2 increases in heart rate, force of . . .
Sensitivity analysis of the maximum likelihood direction finding algorithm (1989)

The maximum likelihood (ML) technique has been proposed for estimating the directions-of-arrival (DOA) of narrowband s4paI.s received by a sensor array. A flrst-order analysis is performed of the sensitivity of the ML direction-finding algorithm to system errors which cause differences between the array manifold used by the algorithm and the true array manifold The effect of such errors on the DOA estimates is investigated. The ability of the ML algorithm to resolve two closely spaced sources in the presence of phase and gain errors in the array elements or in the receivers, or errors in the element locations, is analyzed. A formula for computing the failure threshold of the algorithm as a function of source separation and other system parameters is derived and tested by simulation The analysis assumes that the exact covariance matrix of array element outputs is known (the infinite data case).
Topical immunomodulation under systemic immunosuppression: results of a multicentre, randomized, placebo-controlled safety and efficacy study of imiquimod 5% cream for the treatment of actinic keratoses in kidney, heart, and liver transplant patients (2007)

Imiquimod appears to be a safe alternative for the treatment of multiple actinic keratoses in patients with solid organ transplants. Efficacy was within the range previously observed in nontransplanted populations.
Aligning software processes with strategy (2006)

Although increasing evidence suggests that superior performance requires alignment between firms' strategies and production processes, it is not known if such alignment is relevant for software development processes. This study breaks new ground by examining how firms align their software processes, products, and strategies in Internet application development. Drawing upon the literatures in strategy, operations management, and information systems, we identify four dimensions that influence alignment: the business unit strategy, the level of product customization, the level of process customization, and the volume of customers. To examine how these dimensions are synchronized, we conducted detailed case studies of Internet application development in nine varied firms including both start-ups and established brick and mortar companies. Our analyses reveal that the firms in our study do use differing processes for Internet application development, and that many of the firms match their software process choices to product characteristics, customer volume, and business unit strategies. We develop concept maps for the firms that are in alignment to illustrate how managers configure specific product and process dimensions. We also offer potential explanations for why some firms are misaligned, such as attempting to execute incompatible strategies, the lack of coordination between marketing and production strategies, the too rapid expansion of process scope, and inflexible barriers to rapid adaptation of process. Our study contributes detailed insights into how software processes are customized to complement different types of product requirements and strategies.
Detecting and characterizing <i>N</i> -acyl-homoserine lactone signal molecules by thin-layer chromatography (1997)

Many Gram-negative bacteria regulate gene expression in response to their population size by sensing the level of acyl-homoserine lactone signal molecules which they produce and liberate to the environment. We have developed an assay for these signals that couples separation by thin-layer chromatography with detection using Agrobacterium tumefaciens harboring lacZ fused to a gene that is regulated by autoinduction. With the exception of N-butanoyl-L-homoserine lactone, the reporter detected acyl-homoserine lactones with 3-oxo-, 3-hydroxy-, and 3-unsubstituted side chains of all lengths tested. The intensity of the response was proportional to the amount of the signal molecule chromatographed. Each of the 3-oxo- and the 3-unsubstituted derivatives migrated with a unique mobility. Using the assay, we showed that some bacteria produce as many as five detectable signal molecules. Structures could be assigned tentatively on the basis of mobility and spot shape. The dominant species produced by Pseudomonas syringae pv. tabaci chromatographed with the properties of N-(3-oxohexanoyl)-L-homoserine lactone, a structure that was confirmed by mass spectrometry. An isolate of Pseudomonas fluorescens produced five detectable species, three of which had novel chromatographic properties. These were identified as the 3-hydroxy- forms of N-hexanoyl-, N-octanoyl-, and N-decanoyl-L-homoserine lactone. The assay can be used to screen cultures of bacteria for acyl-homoserine lactones, for quantifying the amounts of these molecules produced, and as an analytical and preparative aid in determining the structures of these signal molecules.
Efficient encoding of low-density parity-check codes (2001)

Low-density parity-check (LDPC) codes can be considered serious competitors to turbo codes in terms of performance and complexity and they are based on a similar philosophy: constrained random code ensembles and iterative decoding algorithms. We consider the encoding problem for LDPC codes. More generally we consider the encoding problem for codes specified by sparse parity-check matrices. We show how to exploit the sparseness of the parity-check matrix to obtain efficient encoders. For the (3,6)-regular LDPC code, for example, the complexity of encoding is essentially quadratic in the block length. However, we show that the associated coefficient can be made quite small, so that encoding codes even of length n/spl sime/100000 is still quite practical. More importantly, we show that "optimized" codes actually admit linear time encoding.
Stereoselective Synthesis of <scp>d</scp>-Desosamine and Related Glycals via Tungsten-Catalyzed Alkynol Cycloisomerization (2004)

Stereoselective synthesis of d-desosamine diacetate ester (iii, R = Ac) was achieved from the glycal (ii). generated by tungsten carbonyl-catalyzed cycloisomerization of the corresponding amino-alkynol (i). A wide variety of N-substituents (R, R') are compatible with the cycloisomerization, provided that at least one R or R' is an acyl derivative.
P2‐228: Cerebral perfusion in Alzheimer's disease using dynamic susceptibility contrast MRI (2008)

According to National Institute on Aging up to 4.5 million Americans suffer from Alzheimer's disease (AD), the most common neurodegenerative disease. Blood flow is a candidate marker for detecting early stages of AD because a decrease in cerebral perfusion has already been observed with perfusion MRI in AD using Arterial Spin Labeling (ASL) techniques. The DSC technique has the ability to provide cerebral blood flow (CBF), cerebral blood volume (CBV), and mean transit time (MTT) perfusion maps which can help distinguish reduced perfusion due to brain atrophy from vasoregulatory changes. Objective: To investigate the ability of DSC MRI with applications that combines bolus and infusion techniques to measure CBV, CBF, and MTT changes in subjects with AD. Ten AD subjects and ten Control Normal subjects were scanned on a GE Signa 1.5T MR. The imaging protocol included two injections of contrast agent (gadolinium): rapid bolus injection (65 μmol/kg at 3 mL/s) followed by a slow infusion (35 μmol/kg at 1 mL/s). For the bolus technique, the acquisition parameters were optimized for depicting temporal dynamics while a contrast infusion technique was optimized for measuring CBV. The CBF map was generated using the central volume principal, CBF=CBV/MTT. Perfusion maps were normalized to standard MNI space and smoothed with a 10mm FWHM Gaussian kernel using SPM5. The statistical maps generated showed perfusion differences among the AD and Control groups for the CBV, CBF, and MTT. A decrease in CBV perfusion is consistently seen in expected areas, including the Posterior Cingulate(PC), caudate, and thalamus (Fig 1.). A decrease in CBF is observed in the posterior cingulate(PC) and the thalamus(Fig 2). A decrease in MTT is observed in the caudate nucleus and thalamus. (Fig 3). The data support DSC MRI as a viable means for measuring perfusion changes in AD. The regions identified as hypoperfusion in AD subjects are consistent with prior studies using ASL and PET perfusion methods. An ROI analysis will be performed to observe the mean CBV, CBF, and MTT values in specific ROIs.
Evolution of collagen arthritis in mice is arrested by treatment with anti-tumour necrosis factor (TNF) antibody or a recombinant soluble TNF receptor. (1992)

Immunization of DBA/1 mice with type II collagen within complete Freund's adjuvant leads to arthritis, lasting more than 3 months. Injection of anti-tumour necrosis factor (TNF) IgG, 2 and 3 weeks after immunization prevented the development of arthritis in the following months. This treatment had no effect when started 2 months after induction of the disease. A soluble form of the human recombinant TNF receptor type-beta (rsTNFR-beta), continuously infused at a rate of 20 micrograms/day during the second and third week after immunization, also had a long-term protective effect. Anti-TNF antibody had no effect upon the production of anti-type II collagen antibodies. These results indicate that TNF is critically involved in an early phase of this arthritis.
VISTA Is a Novel Broad-Spectrum Negative Checkpoint Regulator for Cancer Immunotherapy (2014)

In the past few years, the field of cancer immunotherapy has made great progress and is finally starting to change the way cancer is treated. We are now learning that multiple negative checkpoint regulators (NCR) restrict the ability of T-cell responses to effectively attack tumors. Releasing these brakes through antibody blockade, first with anti-CTLA4 and now followed by anti-PD1 and anti-PDL1, has emerged as an exciting strategy for cancer treatment. More recently, a new NCR has surfaced called V-domain immunoglobulin (Ig)-containing suppressor of T-cell activation (VISTA). This NCR is predominantly expressed on hematopoietic cells, and in multiple murine cancer models is found at particularly high levels on myeloid cells that infiltrated the tumors. Preclinical studies with VISTA blockade have shown promising improvement in antitumor T-cell responses, leading to impeded tumor growth and improved survival. Clinical trials support combined anti-PD1 and anti-CTLA4 as safe and effective against late-stage melanoma. In the future, treatment may involve combination therapy to target the multiple cell types and stages at which NCRs, including VISTA, act during adaptive immune responses.
Cerebral lactic acidosis correlates with neurological impairment in MELAS (2004)

High levels of ventricular lactate, the brain spectroscopic signature of MELAS, are associated with more severe neurologic impairment.
Therapeutic efficacy of undenatured type‐II collagen (UC‐II) in comparison to glucosamine and chondroitin in arthritic horses<sup>1</sup> (2009)

The present investigation evaluated arthritic pain in horses receiving daily placebo, undenatured type II collagen (UC-II) at 320, 480, or 640 mg (providing 80, 120, and 160 mg active UC-II, respectively), and glucosamine and chondroitin (5.4 and 1.8 g, respectively, bid for the first month, and thereafter once daily) for 150 days. Horses were evaluated for overall pain, pain upon limb manipulation, physical examination, and liver and kidney functions. Evaluation of overall pain was based upon a consistent observation of all subjects during a walk and a trot in the same pattern on the same surface. Pain upon limb manipulation was conducted after the walk and trot. It consisted of placing the affected joint in severe flexion for a period of 60 sec. The limb was then placed to the ground and the animal trotted off. The response to the flexion test was then noted with the first couple of strides the animal took. Flexion test was consistent with determining clinically the degree of osteoarthritis in a joint. Horses receiving placebo showed no change in arthritic condition, while those receiving 320 or 480 or 640 mg UC-II exhibited significant reduction in arthritic pain (P < 0.05). UC-II at 480 or 640 mg dose provided equal effects, and therefore, 480 mg dose was considered optimal. With this dose, reduction in overall pain was from 5.7 +/- 0.42 (100%) to 0.7 +/- 0.42 (12%); and in pain upon limb manipulation from 2.35 +/- 0.37 (100%) to 0.52 +/- 0.18 (22%). Although glucosamine and chondroitin treated group showed significant (P < 0.05) reduction in pain compared with pretreated values, the efficacy was less compared with that observed with UC-II. In fact, UC-II at 480 or 640 mg dose was found to be more effective than glucosamine and chondroitin in arthritic horses. Clinical condition (body weight, body temperature, respiration rate, and pulse rate), and liver (bilirubin, GGT, and ALP) and kidney (BUN and creatinine) functions remained unchanged, suggesting that these supplements were well tolerated.
Binding of soluble form of fibroblast surface protein, fibronectin, to collagen (1977)

Fibronectin, a plasma protein immunologically identical with a major surface protein of normal fibroblasts, was found to bind to collagen and gelatin. A solid phase enzyme immunoassay was used for the binding tests. Collagen, gelatin or various control proteins were adsorbed to a plastic surface. Binding of fibronectin was detected using purified fibronectin antibodies conjugated to alkaline phosphatase. Circulating fibronectin and fibronectin obtained from fibroblast cultures both showed specific binding to collagen and gelatin. Preparative affinity chromatography of plasma on gelatin coupled to Sepharose gave electrophoretically and immunologically pure fibronectin in high yields. Malignantly transformed fibroblasts lack surface fibronectin. Our findings suggest the possibility that this results in a lack of anchorage to the surrounding intercellular matrix, which could contribute to the malignant growth behavior.