gebhart/patrepeval huggingface dataset:
Characterization of adenovirus particles made by deletion mutants lacking the fiber gene (1988)

H2dl802, H2dl807, and H5dl1021 are defective deletion mutants of human adenovirus which do not make the capsid protein fiber yet which can make substantial amounts of virus particles. Virions made by the mutants contain very little fiber (which comes from helper virus contaminants in the deletion virus stocks): less than 6% as much as that contained by wild-type virions. This demonstrates that fiber is not an essential structural component of the adenovirus virion and suggests that fiber is nonessential for virion assembly. These fiber-deficient particles are poorly adsorbed to cells, consistent with the proposed role of fiber in virus attachment. Further, virion protein precursors, including that of the virion protease, are poorly processed in these particles, suggesting a relationship between the presence of fiber and the maturation of the virus particle.
The Role of Antiapoptotic Bcl-2 Family Members in Endothelial Apoptosis Elucidated with Antisense Oligonucleotides (1999)

In this study, we utilized potent antisense oligonucleotides to examine the role of two Bcl-2 family members found in human umbilical vein endothelial cells (HUVEC). The first, A1, is thought to be a TNF-alpha-inducible cytoprotective gene, and the second, Bcl-XL, is constitutively expressed. Inhibition of the constitutive levels of Bcl-XL caused 10-25% of the cell population to undergo apoptosis and increased the susceptibility of cells to treatment with low concentrations of staurosporin or ceramide. The caspase inhibitor benzyloxycarbonyl-Val-Ala-Asp(OMe)-CH2 prevented DNA fragmentation and DeltaYm loss caused by Bcl-XL inhibition or Bcl-XL inhibition combined with staurosporin. However, disruption of DeltaYm caused by Bcl-XL inhibition combined with ceramide treatment was not inhibited by benzyloxycarbonyl-Val-Ala-Asp(OMe)-CH2, although DNA fragmentation was completely prevented. Taken together, these results demonstrate a direct protective role for Bcl-XL under normal resting conditions and under low level apoptotic challenges to HUVEC. Furthermore, Bcl-XL protects cells from caspase-dependent and -independent mechanisms of DeltaYm disruption. In contrast to Bcl-XL, A1 inhibition did not show a marked effect on the susceptibility of HUVEC to undergo apoptosis in response to TNF-alpha, ceramide, or staurosporin. These results demonstrate that although A1 may be a cytoprotective gene induced by TNF-alpha, it is not primarily responsible for HUVEC resistance to this cytokine.
ChemInform Abstract: SYNTHESIS OF SOME ALKYL PHOSPHITE COMPLEXES OF PLATINUM AND THEIR STRUCTURAL AND SPECTRAL CHARACTERIZATION (1984)

Abstract Die Pum‐phosphit‐Komplexe (II) werden durch Reduktion von Tetrachloroplatinat (I) mittels Phosphiten unter gleichzeitigem Chlorid‐Ersatz erhalten.
N-(Phosphonacetyl)-l-Aspartate, a Potent Transition State Analog Inhibitor of Aspartate Transcarbamylase, Blocks Proliferation of Mammalian Cells in Culture (1974)

Abstract N-(phosphonacetyl)-l-aspartate (PALA) is an analog of the activated complex for the reaction catalyzed by aspartate transcarbamylase and has previously been shown to be a potent and specific inhibitor of the enzymes from Escherichia coli and mouse spleen. PALA is now shown to be a potent inhibitor of de novo pyrimidine nucleotide biosynthesis in five lines of mammalian cells in culture. When the concentration of PALA in the medium is 10-4 m, simian virus 40-transformed hamster cells do not divide and, within about 2 days, have detached from the culture dishes and appear dead. The toxicity of 10-4 m PALA is prevented completely if 10-4 m uridine is present in the medium, showing that PALA inhibits uridylic acid biosynthesis specifically. The same effect can be observed with the other cell lines. When the external concentration of radioactive PALA is in the range 10-4 to 10-5 m, its concentration in the cytosol is approximately equal to the external concentration. Most of the PALA recovered from cells remains undegraded. In crude cell extracts, the Ki for PALA is about 1 x 10-9 m at 37° and pH 7.5. Addition of 1 x 10-7 m PALA in vitro to an extract of transformed hamster cells inhibits by 60% the incorporation of radioactivity from CO2 into UMP and CMP; approximately 10-6 m PALA is required to give comparable inhibition of incorporation from carbamyl-P. Higher concentrations give virtually complete inhibition in both cases. These results suggest that PALA may find clinical use in suppressing cellular proliferation. A small number of the virus-transformed hamster cells become resistant to 10-4 m PALA in culture and retain resistance after they are grown for many generations in the absence of the drug. Resistance is accompanied by a large increase in aspartate transcarbamylase activity.
Integrated optical approach to trapped ion quantum computation (2009)

Recent experimental progress in quantum information processing with trapped ions have demonstrated most of the fundamental elements required to realize a scalable quantum computer. The next set of challenges lie in realization of a large number of qubits and the means to prepare, manipulate and measure them, leading to error-protected qubits and fault tolerant architectures. The integration of qubits necessarily require integrated optical approach as most of these operations involve interaction with photons. In this paper, we discuss integrated optics technologies and concrete optical designs needed for the physical realization of scalable quantum computer.
IL-11 Activates Human Endothelial Cells to Resist Immune-Mediated Injury (2000)

IL-11, a gp130-signaling cytokine, is protective in several in vivo models of immune-mediated and inflammatory injury. HUVECs express IL-11 receptor alpha-chain and gp130. Human IL-11 causes rapid (2-10 min) tyrosine phosphorylation of gp130. IL-11 at 0.1 and 10 ng/ml induces tyrosine phosphorylation of STAT3 and STAT1, respectively, although maximal responses require 50 ng/ml. Phospho-STAT3 and phospho-STAT1 levels peak rapidly (2.5 min) and disappear by 60 min. The p42 and p44 mitogen-activated protein kinases (MAPKs) are phosphorylated in response to 0.3 ng/ml IL-11 with maximal activation at 30 ng/ml IL-11. Phosphorylation of p42 and p44 MAPKs, which can be prevented by a mitogen-activated protein/extracellular signal-related kinase kinase-1 inhibitor, peaks by 15-20 min and largely disappears by 40 min. IL-11 does not activate NF-kappaB nor does it inhibit NF-kappaB activation by TNF. Similarly, IL-11 neither induces E-selectin or ICAM-1 nor blocks induction by TNF. Although IL-11 does not alter class I MHC complex molecule expression, pretreatment with 0.5 ng/ml IL-11 partially protects HUVECs against lysis by allospecific class I MHC-restricted cytolytic T lymphocytes or by anti-class I MHC Ab plus heterologous C. IL-11-induced cytoprotection is protein synthesis dependent and may depend on mitogen-activated protein/extracellular signal-related kinase kinase-1. Our results indicate that low (i.e., STAT3- and MAPK-activating) concentrations of IL-11 confer resistance to immune-mediated injury in cultured HUVECs without inhibiting proinflammatory responses.
Rating Systems in the Evaluation of Knee Ligament Injuries (1985)

Many different methods of evaluating disability after knee ligament injury exist. Most of them differ in design. Some are based on only patients' symptoms. Other include patients' symptoms, activity grading, performance in a test, and clinical findings. The rating in these evaluating systems can be either numerical, as in a score, or binary, with yes/no answers. Comparison between a symptom-related score and a score of more complex design showed that the symptom-related score gave a more differentiated picture of the disability. It was also shown that the binary rating system gave less detailed information than a score and that differences in a binary rating can depend on at what level the symptoms are regarded as "significant." A new activity grading scale, where work and sport activities were graded numerically, was constructed as complement to the functional score. When evaluating knee ligament injuries, stability testing, functional knee score, performance test, and activity grading are all important. However, the relative importance varies during the course of treatment, and therefore they should not all be included in one and the same score.
Presymptomatic cognitive deficits in individuals at risk of familial Alzheimer's disease. A longitudinal prospective study (1998)

A longitudinal study of asymptomatic individuals at risk of autosomal dominant familial Alzheimer's disease was performed to assess the earliest clinical and neuropsychological features of the disease. Over a 6-year period, 63 subjects underwent serial assessments. During the study, 10 subjects developed symptoms of episodic memory loss and subsequently progressed to fulfil criteria for possible or probable Alzheimer's disease. The mean time (+/-SD) from first assessment to the appearance of symptoms was 2.6+/-1.4 years. The subjects who remained well were similar to those who became clinically affected in terms of age, family history and initial Mini-Mental State Examination. Individuals who later became clinically affected already had significantly lower verbal memory (P=0.003) and performance IQ (P=0.030) scores at their first assessment, when they were ostensibly unaffected. Subsequent assessments showed progressive decline in multiple cognitive domains. Blinded assessment of serial imaging revealed the appearance of diffuse cerebral and medial temporal lobe atrophy in subjects only once they were clinically affected. These findings imply that in familial Alzheimer's disease cognitive decline predates symptoms by several years and that verbal memory deficits precede more widespread deterioration. This may have implications for the detection and treatment of Alzheimer's disease at an early stage.
5GNOW: non-orthogonal, asynchronous waveforms for future mobile applications (2014)

This article provides some fundamental indications about wireless communications beyond LTE/LTE-A (5G), representing the key findings of the European research project 5GNOW. We start with identifying the drivers for making the transition to 5G networks. Just to name one, the advent of the Internet of Things and its integration with conventional human-initiated transmissions creates a need for a fundamental system redesign. Then we make clear that the strict paradigm of synchronism and orthogonality as applied in LTE prevents efficiency and scalability. We challenge this paradigm and propose new key PHY layer technology components such as a unified frame structure, multicarrier waveform design including a filtering functionality, sparse signal processing mechanisms, a robustness framework, and transmissions with very short latency. These components enable indeed an efficient and scalable air interface supporting the highly varying set of requirements originating from the 5G drivers.
p300 Functions as a Coactivator for the Peroxisome Proliferator-activated Receptor α (1997)

The integrator protein, p300, was demonstrated to interact with mouse peroxisome proliferator-activated receptor alpha in a ligand-enhanced manner. The PPARalpha-interacting domain of p300 was mapped to amino acids 39-117 which interacted strongly with PPARalpha but did not interact with retinoic acid receptor-gamma or retinoid X receptor-alpha. Amino acids within the carboxyl terminus of PPARalpha as well as residues within the hinge region were required for ligand-dependent interaction with p300. p300 enhanced the transcriptional activation properties of PPARalpha and, therefore, can be considered a bona fide coactivator for this nuclear receptor. These observations extend the group of p300-interacting proteins to include mPPARalpha and further characterize the molecular mechanisms of PPARalpha-mediated transcriptional regulation.
Development of a transgenic mouse system for the analysis of stages in liver carcinogenesis using tissue-specific expression of SV40 large T-antigen controlled by regulatory elements of the human alpha-1-antitrypsin gene. (1989)

alpha-1-Antitrypsin (AAT) is the major antiprotease in human plasma; it is synthesized primarily in hepatocytes and to a lesser extent in several nonhepatic tissues. Under the control of regulatory elements of the human AAT gene, expression of SV40-large tumor antigen (T-ag) in transgenic mice occurred in the liver, stomach, pancreas, and kidney. Among seven founder transgenic animals, six developed liver carcinoma, four showed gastric neoplasia, and one developed pancreatic carcinoma. In three animals the kidneys showed glomerular or tubular epithelial hyperplasia but no malignancy. A stable transgenic line, 1812, was established. Members of this line reproducibly develop liver tumors by 10 weeks of age but do not exhibit any phenotypic changes in other tissues. Histological changes leading to liver tumor formation occurred with predictable kinetics and could be classified into four distinct stages: (a) embryonal/fetal stage, no recognizable histological changes; (b) newborn to 2 weeks of age, hyperplastic hepatocytes with reduced amounts of cytoplasm but no nuclear alterations; (c) between 3 and 8 weeks of age, diffuse liver cell dysplasia without observable tumor nodules; and (d) 8 weeks of age and thereafter, hepatocellular carcinomas in a background of liver dysplasia. Embryonic and newborn liver tissue showed uniform, high level expression of T-ag in the majority of hepatocytes by immunohistochemistry, whereas the dysplastic and tumoral stages were characterized by considerable variation in both the intensity of T-ag staining and the proportion of T-ag-positive cells. Immunoprecipitation analyses showed that T-ag was complexed with cellular protein p53 in all tumor samples. This study showed that SV40 T-ag expression in the liver resulted in cellular hyperplasia and dysplasia; additional event(s) apparently were required for progression to neoplasia. Those cooperating events occurred with predictable kinetics. This transgenic mouse system displays several similarities with human liver disease and provides a practical model for the study of separate steps in hepatocarcinogenesis.
Chemokines and Chemokine Receptors: Potential Therapeutic Targets in Multiple Sclerosis (2004)

Multiple sclerosis (MS) is a common inflammatory and demyelinating disease of the central nervous system (CNS), which causes progressive neurological disability. The disease is characterised pathologically by destruction of the myelin sheaths, which surround nerve fibres in the CNS. It is believed that this tissue damage in the brain and spinal cord of MS patients is caused by an inflammatory response that is initiated when autoreactive T cells, specific for myelin antigens, cross the blood-brain barrier and detect their antigen within the CNS. As a result, most therapies to date have been immunosuppressive and/or anti-inflammatory in nature, targeting the processes involved in activation and migration of leukocytes and promotion of the immune response. Over the last decade, a family of chemotactic cytokines called chemokines, have been found to be involved in the trafficking of leukocytes in both the normal and pathological states. The expression of these chemokines and their receptors is increased during the acute phase of MS and also in the animal model of MS, experimental autoimmune encephalomyelitis (EAE). As a result, these chemokines have become an emerging focus for research into novel therapeutics for EAE and ultimately MS. This review will briefly describe the structure and function of chemokines and their receptors, before discussing the latest advances in developing pharmacological agents to block the effects of chemokines involved in promoting the inflammatory response in EAE and MS.
Fully 3D list‐mode time‐of‐flight PET image reconstruction on GPUs using CUDA (2011)

A list-mode ToF OSEM library was developed on the GPU-CUDA platform. Our studies show that the GPU reformulation is considerably faster than a single-threaded reference CPU method especially for ToF processing, while producing virtually identical images. This new method can be easily adapted to enable more advanced algorithms for high resolution PET reconstruction based on additional information such as depth of interaction (DoI), photon energy, and point spread functions (PSFs).
Functional analysis of the essential bifunctional tobacco enzyme 3-dehydroquinate dehydratase/shikimate dehydrogenase in transgenic tobacco plants (2007)

In plants, the shikimate pathway occurs in the plastid and leads to the biosynthesis of aromatic amino acids. The bifunctional 3-dehydroquinate dehydratase/shikimate dehydrogenase (DHD/SHD) catalyses the conversion of dehydroquinate into shikimate. Expression of NtDHD/SHD was suppressed by RNAi in transgenic tobacco plants. Transgenic lines with <40% of wild-type activity displayed severe growth retardation and reduced content of aromatic amino acids and downstream products such as cholorogenic acid and lignin. Dehydroquinate, the substrate of the enzyme, accumulated. However, unexpectedly, so did the product, shikimate. To exclude that this finding is due to developmental differences between wild-type and transgenic plants, the RNAi approach was additionally carried out using a chemically inducible promoter. This approach revealed that the accumulation of shikimate was a direct effect of the reduced activity of NtDHD/SHD with a gradual accumulation of both dehydroquinate and shikimate following induction of gene silencing. As an explanation for these findings the existence of a parallel extra-plastidic shikimate pathway into which dehydroquinate is diverted is proposed. Consistent with this notion was the identification of a second DHD/SHD gene in tobacco (NtDHD/SHD-2) that lacked a plastidic targeting sequence. Expression of an NtDHD/SHD-2-GFP fusion revealed that the NtDHD/SHD-2 protein is exclusively cytosolic and is capable of shikimate biosynthesis. However, given the fact that this cytosolic shikimate synthesis cannot complement loss of the plastidial pathway it appears likely that the role of the cytosolic DHD/SHD in vivo is different from that of the plastidial enzyme. These data are discussed in the context of current models of plant intermediary metabolism.
Matrix-induced fragmentation of P3'-N5' phosphoramidate-containing DNA: high-throughput MALDI-TOF analysis of genomic sequence polymorphisms (2001)

Chemical and enzymatic approaches were used to produce polynucleotide fragments containing acid-labile internucleotide P3'-N5' phosphoramidate bonds, either in a surface-bound form or in solution. The primer extension reaction utilizing 5'-amino-5'-deoxynucleoside 5'-triphosphates generates polynucleotides that can be fragmented into short, easy-to-analyze pieces simply by being premixed with the acidic matrices typically used for MALDI-TOF mass spectrometry of nucleic acids. This leads to detection procedures that are simple, robust and easy to automate. Utilizing this approach, a polymorphic site in the human ADRB3 gene was interrogated. Primer extensions with phosphoramidate analogs of dNTPs allowed for unambiguous discrimination of all possible genotypes.
Rheumatoid arthritis: relation of serum C-reactive protein and erythrocyte sedimentation rates to radiographic changes. (1977)

Serum C reactive protein (CRP) levels and erythrocyte sedimentation rates (ESR) were measured in 56 patients with rheumatoid arthritis. Radiographical damage, based on a count of erosions, was significantly more likely to occur when serum CRP and ESR were persistently raised, irrespective of the presence or absence of rheumatoid factor. Measurements of both CRP and ESR were more helpful than either alone, but CRP was probably the more informative. Serial measurements of CRP and ESR provide a reliable means of discriminating between drugs that provide symptomatic relief only and those with a more profound effect in rheumatoid arthritis.
A Practical Guide to Market Assessment (2005)

The authors address the fundamental question, "How does one analyze the potential of a given product for a given market?" A review of the literature suggests that numerous authors have proposed a relatively consistent set of questions that need to be addressed, information sought and key issues to consider when conducting market assessments. The goal of this paper is to review this literature and assemble a set of references that provide insights on how to analyze the market potential of agricultural and food products. This process is of growing importance as U.S. agricultural producers and processors seek to market differentiated products, seek out direct marketing opportunities and focus on meeting consumer preferences for food product attributes.
Tumor necrosis factor alpha and interleukin 1beta are responsible for in vitro myocardial cell depression induced by human septic shock serum. (1996)

Previous studies have demonstrated the presence of myocardial depression in clinical and experimental septic shock. This depression is associated with the presence of a circulating myocardial depressant substance with physical characteristics consistent with cytokines. The present study utilized an in vitro myocardial cell assay to examine the role of various human recombinant cytokines, including tumor necrosis factor (TNF)alpha and interleukin (IL)1beta, in depression of cardiac myocyte contractile function induced by serum from humans with septic shock. The extent and velocity of electrically paced rat cardiac myocytes in tissue culture was quantified by a closed loop video tracking system. Individually, TNF-alpha and IL-1beta each caused significant concentration-dependent depression of maximum extent and peak velocity of myocyte shortening in vitro. In combination, TNF-alpha and IL-1beta induced depression of myocardial cell contractility at substantially lower concentrations consistent with a synergistic effect. Using immunoabsorption, removal of both TNF-alpha and IL-1beta (but not either alone) from the serum of five patients with acute septic shock and marked reversible myocardial depression resulted in elimination of serum myocardial depressant activity. IL-2, -4, -6, -8, -10, and interferon gamma failed to cause significant cardiac myocyte depression over a wide range of concentrations. These data demonstrate that TNF-alpha and IL-1beta cause depression of myocardial cell contraction in vitro and suggest that these two cytokines act synergistically to cause sepsis-associated myocardial depression in humans.
Revisions to the staging and classification of mycosis fungoides and Sézary syndrome: a proposal of the International Society for Cutaneous Lymphomas (ISCL) and the cutaneous lymphoma task force of the European Organization of Research and Treatment of Cancer (EORTC) (2007)

The ISCL/EORTC recommends revisions to the Mycosis Fungoides Cooperative Group classification and staging system for cutaneous T-cell lymphoma (CTCL). These revisions are made to incorporate advances related to tumor cell biology and diagnostic techniques as pertains to mycosis fungoides (MF) and Sézary syndrome (SS) since the 1979 publication of the original guidelines, to clarify certain variables that currently impede effective interinstitution and interinvestigator communication and/or the development of standardized clinical trials in MF and SS, and to provide a platform for tracking other variables of potential prognostic significance. Moreover, given the difference in prognosis and clinical characteristics of the non-MF/non-SS subtypes of cutaneous lymphoma, this revision pertains specifically to MF and SS. The evidence supporting the revisions is discussed as well as recommendations for evaluation and staging procedures based on these revisions.