gebhart/patrepeval huggingface dataset:
Treating autoimmune disease by targeting CD8+T suppressor cells (2009)

Current treatments for autoimmune disease are hampered by the non-specificity of immunomodulatory interventions, having to accept broad suppression of immunoresponsiveness with potentially serious side effects, such as infection or malignancy. The development of antigen-specific approaches, downregulating pathogenic immune responses while maintaining protective immunity, would be a major step forward. One possible approach involves the targeting of physiological regulatory mechanisms, such as inhibitory CD8 T cells that are now recognized to fine-tune many aspects of immune responses. CD8 T suppressor (Ts) cells may directly inhibit other T cells or condition antigen-presenting cells in such a way that immune amplification steps are dampened. The promise of CD8 Ts cells lies in their potential to disrupt host-injurious immune responses in a targeted fashion. For therapeutic purposes, such CD8 Ts cells could either be generated in vitro and transferred into the host or their numbers and activity could be modulated by treating the patient with established or novel immunomodulators. Emerging evidence shows that several subsets of CD8 Ts cells exist. While there is still considerable uncertainty about the molecular mechanisms through which CD8 Ts cells can reset immune responses to protect the host, their potential diagnostic and therapeutic use is intriguing and has generated renewed interest.
[Improving effect of huperzine A on discrimination performance in aged rats and adult rats with experimental cognitive impairment]. (1988)

Huperzine A (Hup-A) , a new alkaloid extracted from Huperzia serrata, is a reversible acetylcholinesterase inhibitor. By using Y-maze method, the rats were traincd to escape foot shocks by going to the light arca (safe area). The criterion of learning or memory retention was met when the rat chose the light area 10 trials in succession. The effects of Hup-A on learning and memory retention processes of brightness discrimination were studied in this paper. The results were as follows; 1) Hup-A (O.1 mg/kg ip or 0.3 mg/kg ig) given 20 min before hypercapnia prevented the CO2-induced impairment of learning of brightness discrimination tasks in rats. This improving effect was also seen with physostigmine (Phys) 0.2 mg/kg ip. 2) Hup-A 0.1-0.3 mg/kg ip immediately after training improved memory retention process in aged rats (over 18 month-old), but neither Phys 0.2 nor HupA O.05 or 0.2 mg/kg did in adult rats. 3) when the adult rats were given Hup-A 0.4 mg/kg ig and scopolamine 0.5 mg/kg ip immediately after training and tested 1 h after medicatiop, the scopolamine-induced amnesia was reversed by Hup-A. Under the same condition, the effective dose of Phys was 0.7 mg/kg ig. These results show that the improving effects of Hup-A on learning and memory retention processes are superior to those of Phys. Hup-A should be of therapeutic value in improving cognitive function in human.
Schulterinstabilität nach primärem Gelenkersatz (1999)

Auffällig ist, daß die Inzidenz in den verschiedenen Arbeiten, die über Instabilitäten nach Schultergelenkersatz berichten weitgestreut zwischen 0 und 38% ist. Dies kann möglicherweise durch die unterschiedliche Interpretation, wann eine Instabilität vorliegt, bedingt sein. Einige Autoren zählen die kraniale Migration bei Verlust oder Dysfunktion der Rotatorenmanschette zur Instabilität, wohingegen andere nur die frühe vordere, hintere oder inferiore Instabilität in diesem Zusammenhang nennen.
Pattern Diversity with Multi-mode Circular Patch Antennas in Clustered MIMO Channels (2005)

The throughput that a MIMO channel can support is a function of different array parameters. Another technique, for miniaturized antenna designs, is polarization/pattern diversity where the antennas are designed to radiate with orthogonal radiation patterns and polarizations as a means to create uncorrelated channels across different array elements. The benefits of pattern diversity have been shown by L. Dong et al. (2003). That analysis, however, did not use realistic channel models. We aim to extend the analysis of Dong et al. to clustered channel models, adopted by the IEEE 802.11n standard body for wireless local area networks (WLANs). We analyze MIMO arrays consisting of circular microstrip antennas to enable pattern diversity and compare their performance against conventional uniform linear arrays. We also model the effect of mutual coupling and measure the performance degradation produced by the near-field effects. We briefly review the channel model and the properties of circular microstrip antennas. Then, we analytically compute the spatial correlation coefficients and evaluate the MIMO channel capacity. Pattern diversity yields better performance than space diversity.
Viral gene therapy strategies: from basic science to clinical application (2005)

A major impediment to the successful application of gene therapy for the treatment of a range of diseases is not a paucity of therapeutic genes, but the lack of an efficient non-toxic gene delivery system. Having evolved to deliver their genes to target cells, viruses are currently the most effective means of gene delivery and can be manipulated to express therapeutic genes or to replicate specifically in certain cells. Gene therapy is being developed for a range of diseases including inherited monogenic disorders and cardiovascular disease, but it is in the treatment of cancer that this approach has been most evident, resulting in the recent licensing of a gene therapy for the routine treatment of head and neck cancer in China. A variety of virus vectors have been employed to deliver genes to cells to provide either transient (eg adenovirus, vaccinia virus) or permanent (eg retrovirus, adeno-associated virus) transgene expression and each approach has its own advantages and disadvantages. Paramount is the safety of these virus vectors and a greater understanding of the virus-host interaction is key to optimizing the use of these vectors for routine clinical use. Recent developments in the modification of the virus coat allow more targeted approaches and herald the advent of systemic delivery of therapeutic viruses. In the context of cancer, the ability of attenuated viruses to replicate specifically in tumour cells has already yielded some impressive results in clinical trials and bodes well for the future of this approach, particularly when combined with more traditional anti-cancer therapies.
Receptor-mediated endocytosis of epidermal growth factor by hepatocytes in the perfused rat liver: ligand and receptor dynamics. (1984)

We have used biochemical and morphological techniques to demonstrate that hepatocytes in the perfused liver bind, internalize, and degrade substantial amounts of murine epidermal growth factor (EGF) via a receptor-mediated process. Before ligand exposure, about 300,000 high-affinity receptors were detectable per cell, displayed no latency, and co-distributed with conventional plasma membrane markers. Cytochemical localization using EGF coupled to horseradish peroxidase (EGF-HRP) revealed that the receptors were distributed along the entire sinusoidal and lateral surfaces of hepatocytes. When saturating concentrations of EGF were perfused through a liver at 35 degrees C, ligand clearance was biphasic with a rapid primary phase of 20,000 molecules/min per cell that dramatically changed at 15-20 min to a slower secondary phase of 2,500 molecules/min per cell. During the primary phase of uptake, approximately 250,000 molecules of EGF and 80% of the total functional receptors were internalized into endocytic vesicles which could be separated from enzyme markers for plasma membranes and lysosomes on sucrose gradients. The ligand pathway was visualized cytochemically 2-25 min after EGF-HRP internalization and a rapid transport from endosomes at the periphery to those in the Golgi apparatus-lysosome region was observed (t 1/2 approximately equal to 7 min). However, no 125I-EGF degradation was detected for at least 20 min. Within 30 min after EGF addition, a steady state was reached which lasted up to 4 h such that (a) the rate of EGF clearance equaled the rate of ligand degradation (2,500 molecules/min per cell); (b) a constant pool of undegraded ligand was maintained in endosomes; and (c) the number of accessible (i.e., cell surface) receptors remained constant at 20% of initial values. By 4 h hepatocytes had internalized and degraded 3 and 2.3 times more EGF, respectively, than the initial number of available receptors, even in the presence of cycloheximide and without substantial loss of receptors. All of these results suggest that EGF receptors are internalized and that their rate of recycling to the surface from intracellular sites is governed by the rate of entry of ligand and/or receptor into lysosomes.
Polypyrrole Nanotubes Conjugated with Human Olfactory Receptors: High‐Performance Transducers for FET‐Type Bioelectronic Noses (2009)

Get a whiff of this: Human olfactory receptor (hOR)-conjugated polypyrrole (PPy) nanotubes were integrated into the field-effect transistor (FET) sensor platform for the fabrication of high-performance bioelectronic noses (see picture, S = source, D = drain). The device can translate and amplify hOR-odorant interaction into a detectable signal, and it showed highly sensitive and specific responses toward a target odorant.
Financial Impact of Health Promotion Programs: A Comprehensive Review of the Literature (2001)

There are good correlational data to suggest that high levels of stress, excessive body weight, and multiple risk factors are associated with increased health care costs and illness-related absenteeism. The associations between seat belt use, cholesterol, diet, hypertension, and alcohol abuse and absenteeism and health care expenditures are either mixed or unknown. Health promotion programs are associated with lower levels of absenteeism and health care costs, and fitness programs are associated with reduced health care costs.
Radiation Therapy with Tositumomab (B1) Anti-CD20 Monoclonal Antibody Initiates Extracellular Signal-Regulated Kinase/Mitogen-Activated Protein Kinase–Dependent Cell Death that Overcomes Resistance to Apoptosis (2008)

These findings indicate that RT and type II anti-CD20 mAb combine to stimulate a prodeath function of the MEK-ERK1/2 pathway, which is able to overcome apoptotic resistance potentially explaining the efficacy of this modality in treating patients with chemoresistant disease.
Vitronectin governs the interaction between plasminogen activator inhibitor 1 and tissue-type plasminogen activator (1991)

The serpin plasminogen activator inhibitor 1 (PAI-1) is the fast acting inhibitor of plasminogen activators (tissue-type (t-PA) and urokinase type-PA) and is an essential regulatory protein of the fibrinolytic system. Its P1-P1' reactive center (R346 M347) acts as a bait for tight binding to t-PA/urokinase-type PA. In vivo, PAI-1 is encountered in complex with vitronectin, an interaction known to stabilize its activity but not to affect the second-order association rate constant (k1) between PAI-1 and t-PA. Nevertheless, by using PAI-1 reactive site variants (R346M, M347S, and R346M M347S), we show that the binding of vitronectin to the PAI-1 mutant proteins improves plasminogen activator inhibition. In the absence of vitronectin the PAI-1 R346M mutants are virtually inactive toward t-PA (k1 less than 1 x 10(3) M-1 s-1). In contrast, in the presence of vitronectin the rate of association increases about 1,000-fold (k1 of 6-8 x 10(5) M-1 s-1). This inhibition coincides with the formation of serpin-typical, sodium dodecyl sulfide-stable t-PA.PAI-1 R346M (R346M M347S) complexes. As evidenced by amino acid sequence analysis, the newly created M346-M/S347 peptide bond is susceptible to attack by t-PA, similar to the wild-type R346-M347 peptide bond, indicating that in the presence of vitronectin M346 functions as an efficient P1 residue. In addition, we show that the inhibition of t-PA and urokinase-type PA by PAI-1 mutant proteins is accelerated by the presence of the nonprotease A chains of the plasminogen activators.
AKT/PKB signaling mechanisms in cancer and chemoresistance (2005)

During the past decade, Akt (also known as protein kinase B, PKB) has been extensively studied. It regulates a variety of cellular processes by mediating extracellular (mitogenic growth factor, insulin and stress) and intracellular (altered tyrosine receptor kinases, Ras and Src) signals. Activation of Akt by these signals is via its pleckstrin homology (PH) domain binding to products of phosphatidylinositol 3-kinase (PI3K). This process is negatively regulated by a dual phosphatase PTEN tumor suppressor. Today, more than 30 Akt substrates have been identified. These phosphorylation events mediate the effects of Akt on cell survival, growth, differentiation, angiogenesis, migration and metabolism. Further, PI3K/PTEN/Akt pathway is frequently altered in many human malignancies and overexpression of Akt induces malignant transformation and chemoresistance. Thus, the Akt pathway is a major target for anti-cancer drug development. This review focuses on Akt signaling mechanism in oncogenesis and chemoresistance, and ongoing translational efforts to therapeutically target Akt.
Circulating Bacterial-Derived DNA Fragments and Markers of Inflammation in Chronic Hemodialysis Patients (2009)

Circulating BDNAs are associated with higher levels of C-reactive protein and IL-6 in HD patients.
Patient-Specific Neutralizing Antibody Responses to Herpes Simplex Virus Are Attributed to Epitopes on gD, gB, or Both and Can Be Type Specific (2015)

We previously showed that people infected with HSV produce neutralizing Abs directed against gD or a combination of gD+gB (and in one case, gD+gB+gC, which was HSV-1 specific). In this more extensive study, we again found that gD or gD+gB can account for the virus neutralizing response and critical epitopes of one or both of these proteins are represented in sera of naturally infected humans. However, we also found that some individuals produced a strong response against gB alone. In addition, we identified type-specific contributions to HSV neutralization from both gD and gB. Contributions from the other entry glycoproteins, gC and gH/gL, were minimal and limited to HSV-1 neutralization. Knowing the variations in how humans see and mount a response to HSV will be important to vaccine development.
Why Are Proteins Charged? Networks of Charge–Charge Interactions in Proteins Measured by Charge Ladders and Capillary Electrophoresis (2006)

Almost all proteins contain charged amino acids. While the function in catalysis or binding of individual charges in the active site can often be identified, it is less clear how to assign function to charges beyond this region. Are they necessary for solubility? For reasons other than solubility? Can manipulating these charges change the properties of proteins? A combination of capillary electrophoresis (CE) and protein charge ladders makes it possible to study the roles of charged residues on the surface of proteins outside the active site. This method involves chemical modification of those residues to generate a large number of derivatives of the protein that differ in charge. CE separates those derivatives into groups with the same number of modified charged groups. By studying the influence of charge on the properties of proteins using charge ladders, it is possible to estimate the net charge and hydrodynamic radius and to infer the role of charged residues in ligand binding and protein folding.
Recombination in Eukaryotic Single Stranded DNA Viruses (2011)

Although single stranded (ss) DNA viruses that infect humans and their domesticated animals do not generally cause major diseases, the arthropod borne ssDNA viruses of plants do, and as a result seriously constrain food production in most temperate regions of the world. Besides the well known plant and animal-infecting ssDNA viruses, it has recently become apparent through metagenomic surveys of ssDNA molecules that there also exist large numbers of other diverse ssDNA viruses within almost all terrestrial and aquatic environments. The host ranges of these viruses probably span the tree of life and they are likely to be important components of global ecosystems. Various lines of evidence suggest that a pivotal evolutionary process during the generation of this global ssDNA virus diversity has probably been genetic recombination. High rates of homologous recombination, non-homologous recombination and genome component reassortment are known to occur within and between various different ssDNA virus species and we look here at the various roles that these different types of recombination may play, both in the day-to-day biology, and in the longer term evolution, of these viruses. We specifically focus on the ecological, biochemical and selective factors underlying patterns of genetic exchange detectable amongst the ssDNA viruses and discuss how these should all be considered when assessing the adaptive value of recombination during ssDNA virus evolution.
Pilot Two-Way CATV Systems (1975)

Pilot two-way CATV systems have been mounted in the United States largely to assess the marketability of various interactive services (e.g., subscriber response) and to assess technical problems over operating CATV systems. Such tests were at their peak in the early 1970's. Twelve systems which have been publicly tested are considered briefly. Three of these, the Theta-Com subscriber response system (SRS), the Coaxial Scientific Telecinema system, and the MITRE MITRIX system, are considered in some detail.
Serial propagation of Creutzfeldt-Jakob disease in guinea pigs. (1976)

The transmission and serial propagation of Creutzfeldt-Jakob disease from man to guinea pigs are reported. The latency, symptomatology, and morphology of the infection during the first four passages are presented. The incubation period between the first and subsequent passages was halved. One hundred percent take, morbidity, and mortality were achieved in all inoculated animals. All guinea pigs developed a subacute spongiform virus encephalopathy with marked neuronal destruction in the cerebral cortex and subcortical grey structures. The neuronal loss resulted in cerebral atrophy and hydrocephalus ex vacuo.
Evolutionary Stochastic Gradient Descent for Optimization of Deep Neural Networks (2018)

We propose a population-based Evolutionary Stochastic Gradient Descent (ESGD) framework for optimizing deep neural networks. ESGD combines SGD and gradient-free evolutionary algorithms as complementary algorithms in one framework in which the optimization alternates between the SGD step and evolution step to improve the average fitness of the population. With a back-off strategy in the SGD step and an elitist strategy in the evolution step, it guarantees that the best fitness in the population will never degrade. In addition, individuals in the population optimized with various SGD-based optimizers using distinct hyper-parameters in the SGD step are considered as competing species in a coevolution setting such that the complementarity of the optimizers is also taken into account. The effectiveness of ESGD is demonstrated across multiple applications including speech recognition, image recognition and language modeling, using networks with a variety of deep architectures.
Cell‐Sorting Technology (2000)

The first five chapters of this text describe the state-of-the-art for these rapidly evolving technologies. They cover both theoretical considerations and practical application issues that should be of interest to both instrument designers and end users. This chapter provides a review of cell-sorting technology and serves as an introduction to those not already well acquainted with the field. It is followed by chapters covering high-speed cell sorting, rare-event detection, clinical applications of high-speed cell sorting, and MEMS-based cell-handling systems. Taken together, this suite of chapters offers a comprehensive presentation of the recent advances in cell-sorting instrumentation and provides some insight into emerging technologies in this important area.
Ammonia-Hyperproducing Bacteria from New Zealand Ruminants (1998)

Pasture-grazed dairy cows, deer, and sheep were tested for the presence of ammonia-hyperproducing (HAP) bacteria in roll tubes containing a medium in which tryptone and Casamino Acids were the sole nitrogen and energy sources. Colonies able to grow on this medium represented 5.2, 1.3, and 11.6% of the total bacterial counts of dairy cows, deer, and sheep, respectively. A total of 14 morphologically distinct colonies were purified and studied further. Restriction fragment length polymorphisms of 16S rRNA genes indicated that all isolates differed from the previously described HAP bacteria, Clostridium aminophilum, Clostridium sticklandii, and Peptostreptococcus anaerobius. Carbon source utilization experiments showed that five isolates (C2, D1, D4, D5, and S1) were unable to use any, or very few, of the carbon sources tested. Biochemical tests and phylogenetic analyses of 16S ribosomal DNA sequences indicated that all isolates were monensin sensitive; that D1 and S1 belonged to the genus Peptostreptococcus, that D4 and D5 belonged to the family Bacteroidaceae, where D4 was similar to Fusobacterium necrophorum; and that C2 was most similar to an unidentified species from the genus Eubacterium. Growth on liquid medium containing tryptone and Casamino Acids as the sole nitrogen and energy source showed that D1, D4, and S1 grew rapidly (specific growth rates of 0.40, 0.35, and 0.29 h-1, respectively), while C2 and D5 were slow growers (0.25 and 0.10 h-1, respectively). Ammonia production rates were highest in D1 and D4, which produced 945.5 and 748.3 nmol/min per mg of protein, respectively. Tests of individual nitrogen sources indicated that D1 and D4 grew best on tryptone, S1 grew equally well on Casamino Acids or tryptone, and C2 and D5 grew poorly on all nitrogen sources. The intact proteins casein and gelatin did not support significant growth of any of the isolates. These isolates extend the diversity of known HAP rumen bacteria and indicate the presence of significant HAP bacterial populations in pasture-grazed New Zealand ruminants.
Nuclear expression of the Y-box binding protein, YB-1, as a novel marker of disease progression in non-small cell lung cancer. (2001)

Transcription factor Y-box binding protein 1 (YB-1) that binds to the inverted CCAAT box is involved not only in transcription of various genes but also in cell proliferation and DNA repair. We determined whether localization of YB-1 in either the nucleus or cytoplasm could serve as a prognostic marker for patients with non-small cell lung cancer (NSCLC). In 196 NSCLC patients, expression of YB-1 protein in the nucleus or cytoplasm was immunohistochemically evaluated. Of the 196 tumors examined, 88 (44.9%) were positive for YB-1 expression in the nucleus. Nuclear YB-1 expression significantly correlated with T factor, lymph node metastasis, and stage of the disease. Patients with a nuclear YB-1 tumor had a poorer prognosis than did those with a cytoplasmic YB-1 tumor in all of the NSCLC patients (P = 0.0494) and in patients with squamous cell carcinoma (P = 0.0313) but not in patients with adenocarcinomas. Nuclear localization of the YB-1 protein may prove to be an important factor of disease progression for patients with NSCLC, in particular, in cases of squamous cell carcinoma.