gebhart/patrepeval huggingface dataset:
The A53T α-Synuclein Mutation Increases Iron-Dependent Aggregation and Toxicity (2000)

Parkinson9s disease (PD) is the most common motor disorder affecting the elderly. PD is characterized by the formation of Lewy bodies and death of dopaminergic neurons. The mechanisms underlying PD are unknown, but the discoveries that mutations in α-synuclein can cause familial PD and that α-synuclein accumulates in Lewy bodies suggest that α-synuclein participates in the pathophysiology of PD. Using human BE-M17 neuroblastoma cells overexpressing wild-type, A53T, or A30P α-synuclein, we now show that iron and free radical generators, such as dopamine or hydrogen peroxide, stimulate the production of intracellular aggregates that contain α-synuclein and ubiquitin. The aggregates can be identified by immunocytochemistry, electron microscopy, or the histochemical stain thioflavine S. The amount of aggregation occurring in the cells is dependent on the amount of α-synuclein expressed and the type of α-synuclein expressed, with the amount of α-synuclein aggregation following a rank order of A53T &gt; A30P &gt; wild-type &gt; untransfected. In addition to stimulating aggregate formation, α-synuclein also appears to induce toxicity. BE-M17 neuroblastoma cells overexpressing α-synuclein show up to a fourfold increase in vulnerability to toxicity induced by iron. The vulnerability follows the same rank order as for aggregation. These data raise the possibility that α-synuclein acts in concert with iron and dopamine to induce formation of Lewy body pathology in PD and cell death in PD.
Acute liver failure (2008)

Acute liver failure (ALF) is a rare but challenging clinical syndrome with multiple causes; a specific etiology cannot be identified in 15% of adult and 50% of pediatric cases. The course of ALF is variable and the mortality rate is high. Liver transplantation is the only therapy of proven benefit, but the rapidity of progression and the variable course of ALF limit its use. Currently in the United States, spontaneous survival occurs in approximately 45%, liver transplantation in 25%, and death without transplantation in 30% of adults with ALF. Higher rates of spontaneous recovery (56%) and transplantation (31%) with lower rates of death (13%) occur in children. The outcome of ALF varies by etiology, favorable prognoses being found with acetaminophen overdose, hepatitis A, and ischemia (approximately 60% spontaneous survival), and poor prognoses with drug-induced ALF, hepatitis B, and indeterminate cases (approximately 25% spontaneous survival). Excellent intensive care is critical in management of patients with ALF. Nonspecific therapies are of unproven benefit. Future possible therapeutic approaches include N-acetylcysteine, hypothermia, liver assist devices, and hepatocyte transplantation. Advances in stem cell research may allow provision of cells for bioartificial liver support. ALF presents many challenging opportunities in both clinical and basic research.
Synthesis, Antiviral Activity and Pharmacokinetics of P1/P1′ Substituted 3‐Aminoindazole Cyclic Urea HIV Protease Inhibitors. (2003)

Abstract For Abstract see ChemInform Abstract in Full Text.
Structure, organization, and chromosomal mapping of the human macrophage scavenger receptor gene. (1993)

Macrophage scavenger receptors (MSR) mediate the binding, internalization, and processing of a wide range of negatively charged macromolecules. Functional MSR are trimers of two C-terminally different subunits that contain six functional domains. We have cloned an 80-kilobase human MSR gene and localized it to band p22 on chromosome 8 by fluorescent in situ hybridization and by genetic linkage using three common restriction fragment length polymorphisms. The human MSR gene consists of 11 exons, and two types of mRNAs are generated by alternative splicing from exon 8 to either exon 9 (type II) or to exons 10 and 11 (type I). The promoter has a 23-base pair inverted repeat with homology to the T cell element. Exon 1 encodes the 5'-untranslated region followed by a 12-kilobase intron which separates the transcription initiation and the translation initiation sites. Exon 2 encodes a cytoplasmic domain, exon 3, a transmembrane domain, exons 4 and 5, an alpha-helical coiled-coil, and exons 6-8, a collagen-like domain. The position of the gap in the coiled coil structure corresponds to the junction of exons 4 and 5. These results show that the human MSR gene consists of a mosaic of exons that encodes the functional domains. Furthermore, the specific arrangement of exons played a role in determining the structural characteristics of functional domains.
On-line signature verification using local shape analysis (2004)

This paper presents a novel approach to the on-line signature verification using local shape analysis. First, segment the input signature into several segments using HMM (hidden Markov model). Then, combine two adjacent segments to form a long segment and get its spectral and tremor information using FFT (fast Fourier transformation). At last, accept it or reject it based on the similarity between the spectral and its prototype. In addition, we proposed a novel initialization algorithm to avoid the local optimal of the HMM's re-estimation and a novel algorithm to avoid losing the important information at cusps in preprocessing. Combining the local shape analysis with the local time-based comparison, we get promising experimental results.
Wide-band channel modelling using a spatial model (2002)

This paper describes the application of a spatial model for the multipath radio channel to wide-band channel modelling. The spatial model models the geographical distribution of scatterers around the transmitter and receiver, and hence predicts the distribution of delay, amplitude, and direction of arrival of multipath components at the receiver. We model the arrival of multipath components within the power-delay profile as a Poisson process, and find an expression for the Poisson parameter in terms of the scatterer density, showing that it is a function of the excess delay of the component. Hence we construct randomly-assigned power-delay profiles, useful for system simulation, and also derive an averaged power-delay profile for the channel.
Molecular defect in the membrane skeleton of blood bank-stored red cells. Abnormal spectrin-protein 4.1-actin complex formation. (1986)

During liquid preservation under blood bank conditions, red cell membranes inexorably undergo damage that decreases erythrocyte survival after transfusion. Accordingly, we have surveyed membrane skeletal protein interactions during storage. We uncovered a decrease in the in vitro formation of spectrin-actin complex in the absence (50%) or presence (60%) of protein 4.1. Actual formation of the spectrin-actin-protein 4.1 complex fell in a linear fashion during the storage period. This fall in spectrin-actin interaction tightly correlated with the decline in total red cell phospholipid (R = 0.9932) measured simultaneously. This decrement of spectrin-actin association could be restored to greater than 70% of normal values by preincubation of stored spectrin with 50 mM dithiothreitol. This storage injury to spectrin-actin interaction might weaken the membrane skeleton and lead to decreased red cell survival. In vitro reversibility of the damage by reducing agents suggests a possible new direction for prolonging the shelf life of stored blood.
The Use of Gamma-Linolenic Acid in Diabetic Neuropathy (1992)

EF4 is an entirely new approach to the management of diabetic neuropathy. EF4 (providing gamma-linolenic acid or gamolenic acid, GLA) has been shown to reverse existing diabetic neuropathy in trials in seven centres. Diabetic animals and humans have a reduced ability to convert dietary linoleic acid to GLA. GLA and its metabolites are required for normal neuronal structure and function and a normal microcirculation. The lack of GLA and its metabolites may play a major role in the development of the neuropathy. EF4 helps to correct the biochemical defects, restores levels of GLA metabolites towards normal and produces highly significant clinical and neurophysiological improvements in diabetic neuropathy.
Cell-Mediated Immunity in Marek's Disease Virus-Infected Chickens Genetically Selected for High and Low Concentrations of Plasma Corticosterone (1980)

Lines of chickens genetically selected for high (HPC)-and low-plasma corticosterone (LPC) titers were assessed for cell-mediated immunity during Marek's disease tumorigenesis. Lymphocyte transformation (using phytohemagglutinin and 2,4-dinitrofluorobenzene-bovine serum complex) and mitogen-induced cellular cytotoxicity were evaluated with peripheral blood leukocytes. Chickens from the LPC line showed a greater lymphocyte transformation response than those from the HPC line. All tumor-bearing chickens demonstrated a markedly suppressed blastogenic response. Although the blastogenic response was suppressed in those chickens infected with Marek's disease virus but not having gross tumors when compared with the steroid level, this response was greater than that of chickens with tumors and less than that of normal controls. In comparison with LPC-line chickens, HPC-line chickens demonstrated a decreased mitogen-induced cellular cytotoxicity. A decreased mitogen-induced cellular cytotoxicity was observed in both steroid lines concomitant with the onset and severity of tumors. The impaired cell-mediated response observed in the HPC line was associated with an increased tumor incidence and a greater mortality than that observed in the LPC line. Metyrapone, a chemical which blocks adrenal corticosterone synthesis, transiently enhanced mitogen-induced cellular cytotoxicity and initiated tumor regression in chickens debilitated with Marek's disease tumors.
Reducing data communication overhead for DOACROSS loop nests (1994)

If the iterations of a loop nest cannot be partitioned into independent tasks, data communication for data dependence is inevitable in order to execute them on parallel machines. This kind of loop nest is referred to as a DOACROSS loop nest.
Two new components fromGnetum pendulum (2008)

Two new compounds, 3-O-(13-hydroxy-9Z,11E,15E-octadecatrienoyl) cycloeucalenol (1) and 24'-hydroxy-tetracosyl ferulate (2), together with one known compound, tetracosyl ferulate (3), were isolated from the dried stems of Gnetum pendulum. The two new compounds were structurally elucidated by spectroscopic and chemical methods.
Cloning and Sequencing of a Full-Length cDNA of Mouse N-Acetylglucosamine (β1–4)Galactosyltransferase1 (1988)

A full-length cDNA clone for mouse N-acetylglucosamine (β 12–4)galactosyltransferase (β1–4GT) [EC 2.4.1.90] and several clones diverged from the β12–4GT cDNA were isolated from a mouse F9 cDNA library and then sequenced. The fβ1–4GT cDNA has an open reading frame consisting of 399 amino acids. The homology at the amino acid level is 80 and 91% as to the partial sequences of bovine and human milk β12–4GT respectively. The general enzyme structure of the β1–4GT seems to be similar to that of a rat β-galactoside (α2–6) sialyltransferase. Junctions of the common and divergent regions of cDNA have dinucleotides, AG, suggesting that the variety of cDNA clones is generated through alternative splicing.
Muscle recruitment with intrafascicular electrodes (1991)

We have studied muscle recruitment with Teflon-insulated, 25 microns diameter, Pt-Ir intrafasicular electrodes implanted in nerves innervating the gastrocnemius and soleus muscles of cats. The purpose of this study was to measure the performance of these bipolar electrodes, which had been designed to optimize their ability to record unit activity from peripheral nerves, as stimulating electrodes. Recruitment curves identified the optimal stimulus configuration as a biphasic rectangular pulse, with an interphase separation of about 500 microseconds and a duration of about 50 microseconds. The current required for a half-maximal twitch contraction was on the order of 50 microA. Current and charge densities needed for stimulation were well below levels believed to be safe for the tissue and electrode materials involved. When the spinal reflex pathway was interrupted by crushing the nerve, the force produced by a given stimulus changed in some cases, but not in others, implying that the spinal reflex contribution was not the same in all the implants. We conclude that intrafascicular recording electrodes are also a potentially valuable technology for functional neuromuscular stimulation, and warrant further development.
JQ1 affects BRD2-dependent and independent transcription regulation without disrupting H4-hyperacetylated chromatin states (2018)

The bromodomain and extra-terminal domain (BET) proteins are promising drug targets for cancer and immune diseases. However, BET inhibition effects have been studied more in the context of bromodomain-containing protein 4 (BRD4) than BRD2, and the BET protein association to histone H4-hyperacetylated chromatin is not understood at the genome-wide level. Here, we report transcription start site (TSS)-resolution integrative analyses of ChIP-seq and transcriptome profiles in human non-small cell lung cancer (NSCLC) cell line H23. We show that di-acetylation at K5 and K8 of histone H4 (H4K5acK8ac) co-localizes with H3K27ac and BRD2 in the majority of active enhancers and promoters, where BRD2 has a stronger association with H4K5acK8ac than H3K27ac. Although BET inhibition by JQ1 led to complete reduction of BRD2 binding to chromatin, only local changes of H4K5acK8ac levels were observed, suggesting that recruitment of BRD2 does not influence global histone H4 hyperacetylation levels. This finding supports a model in which recruitment of BET proteins via histone H4 hyperacetylation is predominant over hyperacetylation of histone H4 by BET protein-associated acetyltransferases. In addition, we found that a remarkable number of BRD2-bound genes, including MYC and its downstream target genes, were transcriptionally upregulated upon JQ1 treatment. Using BRD2-enriched sites and transcriptional activity analysis, we identified candidate transcription factors potentially involved in the JQ1 response in BRD2-dependent and -independent manner.
Beta 2-adrenergic receptor-stimulated increase in cAMP in rat heart cells is not coupled to changes in Ca2+ dynamics, contractility, or phospholamban phosphorylation. (1994)

Previous studies have shown that both beta 1- and beta 2-adrenergic receptors (AR) are present in rat ventricular myocytes, but stimulation of these receptor subtypes elicits qualitatively different cellular responses (Xiao, R.-P., and Lakatta, E. G. (1993) Circ. Res. 73, 286-300). In the present study, the biochemical mechanism underlying the distinct beta AR subtype actions have been investigated. Although both beta 1AR and beta 2AR stimulation increased total cellular cAMP in suspensions of rat ventricular myocytes to a similar extent, the maximum elevation of the membrane bound cAMP by beta 2AR stimulation was only half of that induced by beta 1AR stimulation, suggesting that stimulation the beta AR subtypes leads to different compartmentation of cAMP. The effects of beta 1AR stimulation on Ca2+ transient (indexed by the transient increase in indo-1 fluorescence ration after excitation) and contraction amplitude (measured via photodiode array) and their kinetics closely paralleled the increase in cAMP. In contrast, the increase in both membrane bound and total cAMP content after beta 2AR stimulation were completely dissociated from the effects of beta 2AR stimulation to increase the amplitudes of cytosolic Ca2+ transient and contraction. Furthermore, beta 2AR stimulation did not phosphorylate phospholamban to the same extent as did beta 1AR stimulation. This finding provides a mechanism for the failure of beta 2AR stimulation to accelerate the kinetics of the Ca2+i (cytosolic Ca2+) transient and contraction. These results indicate that the effects of beta 2AR stimulation on Ca2+i transient and contraction are uncoupled from the cAMP production and cAMP-dependent protein phosphorylation and indicate that, in addition to coupling to adenylate cyclase, beta 2AR stimulation also activates other signal transduction pathway(s) to produce changes in cytosolic Ca2+ and contraction.
Clinical Practice Guidelines for Clostridium difficile Infection in Adults and Children: 2017 Update by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA) (2017)

A panel of experts was convened by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA) to update the 2010 clinical practice guideline on Clostridium difficile infection (CDI) in adults. The update, which has incorporated recommendations for children (following the adult recommendations for epidemiology, diagnosis, and treatment), includes significant changes in the management of this infection and reflects the evolving controversy over best methods for diagnosis. Clostridium difficile remains the most important cause of healthcare-associated diarrhea and has become the most commonly identified cause of healthcare-associated infection in adults in the United States. Moreover, C. difficile has established itself as an important community pathogen. Although the prevalence of the epidemic and virulent ribotype 027 strain has declined markedly along with overall CDI rates in parts of Europe, it remains one of the most commonly identified strains in the United States where it causes a sizable minority of CDIs, especially healthcare-associated CDIs. This guideline updates recommendations regarding epidemiology, diagnosis, treatment, infection prevention, and environmental management.
A fast channel-tunable optical transmitter for ultrahigh-speed all-optical time-division multiaccess networks (1996)

This paper describes the design and the experimental demonstration of a novel fast channel tunable optical transmitter which is suitable for ultrahigh-speed all-optical time-division multiaccess (TDMA) networks. This optical transmitter is capable of performing fast channel tuning and data modulation in a simple and cost-effective way without using the expensive optical modulators and optical switches. By employing this transmitter, together with the proposed destructive writing scheme, ultrahigh-speed channel multiplexing with relaxed synchronization requirements for data access can be achieved. The demonstrated prototype can be arbitrarily tuned to any one of the 16 1-Gb/s channels in a 16-Gb/s all-optical TDMA network with a channel switching time of less than 5 ns. This is suitable for use in most high-speed optical time-division multiplexed (TDM) systems and tunable-channel multiaccess (TCMA) networks.
Computerized three-dimensional stereotaxic removal of small central nervous system lesions in patients (1980)

The authors describe the results of their recently reported computer-based stereotaxic surgical technique for the indentification, enhancement, three-dimensional reconstruction, localization, and removal of small central nervous system lesions. This technique has been applied to patients with various types of central nervous system pathology, and representative cases are reported.
Soy oil based versus alternative lipid emulsions for parenterally fed preterm infants (2011)

This is a protocol for a Cochrane Review (Intervention). The objectives are as follows: Primary objectives To compare the effects of soybean oil based lipid emulsions (SO‐LE) versus alternative LE (olive oil based LE (OO‐LE), medium chain triglyceride (MCT) oil based LE, structured LE, fish oil based LE or multi‐combination LE) on: a) death, b) physical growth, c) chronic lung disease, and d) long term neuro‐developmental outcomes in parenterally fed preterm infants. We would like to do separate comparisons for SO‐LE and each of the different alternatives wherever the studies are available. Each available lipid emulsion type will be compared separately with SO‐LE giving us five comparison groups: SO‐LE versus OO‐LE; SO‐LE versus MCT‐LE (pure MCT‐LE and mixed MCT/LCT‐LE); SO‐LE versus structured lipids (structured MCT/LCT‐LE); SO‐LE versus FO‐LE; SO‐LE versus multi‐combination LE. We would also consider studies which compare one non‐soy alternative to another as a separate analysis, if feasible. Secondary objectives To compare the effects of SO‐LE versus alternative LE (OO‐LE, MCT‐LE, structured LE, FO‐LE or multi‐LE) on morbidities associated with prematurity and PNALD in parenterally fed preterm infants. Subgroup analysis will be performed based on: a) population type {gestational age (< 30 weeks, ≥ 30 weeks); gender; birth weight (≤ 1000 g, > 1000g); congenital malformations} and b) intervention type, early (≤ 3 days) versus late (4 to 7 days) introduction of LE; low dose (≤ 2 g/kg/day) versus high dose LE (> 2 g/kg/day); maximum dose from day 1 versus gradual increment of LE.
Therapeutic options in cutaneous melanoma: latest developments (2011)

Melanoma is a malignancy that is highly curable in the early stages but has devastating consequences in later stages due to lack of response to traditional treatments. Improved understanding of the basic science of tumorigenesis has helped lead to novel targeted therapies which are producing beneficial results in patients with melanoma. Enhancement of the immune system by blockade of the cytotoxic T-lymphocyte associated antigen-4 by the monoclonal antibody ipilimumab is now approved by the United States Food and Drug Administration (FDA) for use in patients with unresectable melanoma. The approval of this drug was based on the first ever data in melanoma showing an improvement in overall survival. New advances in targeting components of the mitogen-activated protein kinase pathway are showing impressive responses in clinical trials in most patients harboring activating mutations in BRAF. Thus, this is a new era in the management of melanoma and we review the recent progress made in treating patients with advanced disease.
New Guidelines to Evaluate the Response to Treatment in Solid Tumors (2000)

Anticancer cytotoxic agents go through a process by which their antitumor activity-on the basis of the amount of tumor shrinkage they could generate-has been investigated. In the late 1970s, the International Union Against Cancer and the World Health Organization introduced specific criteria for the codification of tumor response evaluation. In 1994, several organizations involved in clinical research combined forces to tackle the review of these criteria on the basis of the experience and knowledge acquired since then. After several years of intensive discussions, a new set of guidelines is ready that will supersede the former criteria. In parallel to this initiative, one of the participating groups developed a model by which response rates could be derived from unidimensional measurement of tumor lesions instead of the usual bidimensional approach. This new concept has been largely validated by the Response Evaluation Criteria in Solid Tumors Group and integrated into the present guidelines. This special article also provides some philosophic background to clarify the various purposes of response evaluation. It proposes a model by which a combined assessment of all existing lesions, characterized by target lesions (to be measured) and nontarget lesions, is used to extrapolate an overall response to treatment. Methods of assessing tumor lesions are better codified, briefly within the guidelines and in more detail in Appendix I. All other aspects of response evaluation have been discussed, reviewed, and amended whenever appropriate.