gebhart/patrepeval huggingface dataset:
Selective Expression of Purkinje-Cell Antigens in Tumor Tissue from Patients with Paraneoplastic Cerebellar Degeneration (1990)

Paraneoplastic cerebellar degeneration is a rare syndrome that occurs in patients with gynecologic cancer and is characterized by widespread loss of Purkinje cells. To determine whether Purkinje-cell antigens are selectively expressed in the tumors of patients with the syndrome, we examined tumor tissue from 10 patients whose serum contained anti-Purkinje-cell (anti-Yo) antibodies. The origins of the cancers were the breast (five patients), ovary (three), endometrium (one), and fallopian tube (one). We used as controls tumor tissue from 11 patients with ovarian cancer and 10 patients with breast cancer who were neurologically normal. Using immunohistochemical and Western blot analysis, we found that Purkinje-cell antigens were expressed in all the tumors from the 10 patients with paraneoplastic cerebellar degeneration but in none of the tumors from the 21 neurologically normal patients. When IgG from patients with paraneoplastic cerebellar degeneration was affinity-purified to cerebellar Purkinje-cell antigen, immunohistochemical analysis showed that it reacted specifically with the tumor tissue from those patients. We conclude that in patients with paraneoplastic cerebellar degeneration, the anti-Yo antibody results from an immune response to neural antigens expressed by the gynecologic tumors in the patients.
Pathogenesis and Diagnosis of Shiga Toxin-Producing Escherichia coli Infections (1998)

Since their initial recognition 20 years ago, Shiga toxin-producing Escherichia coli (STEC) strains have emerged as an important cause of serious human gastrointestinal disease, which may result in life-threatening complications such as hemolytic-uremic syndrome. Food-borne outbreaks of STEC disease appear to be increasing and, when mass-produced and mass-distributed foods are concerned, can involve large numbers of people. Development of therapeutic and preventative strategies to combat STEC disease requires a thorough understanding of the mechanisms by which STEC organisms colonize the human intestinal tract and cause local and systemic pathological changes. While our knowledge remains incomplete, recent studies have improved our understanding of these processes, particularly the complex interaction between Shiga toxins and host cells, which is central to the pathogenesis of STEC disease. In addition, several putative accessory virulence factors have been identified and partly characterized. The capacity to limit the scale and severity of STEC disease is also dependent upon rapid and sensitive diagnostic procedures for analysis of human samples and suspect vehicles. The increased application of advanced molecular technologies in clinical laboratories has significantly improved our capacity to diagnose STEC infection early in the course of disease and to detect low levels of environmental contamination. This, in turn, has created a potential window of opportunity for future therapeutic intervention.
WISQ: a restartable architecture using queues (1987)

In this paper, the WISQ architecture is described. This architecture is designed to achieve high performance by exploiting new compiler technology and using a highly segmented pipeline. By having a highly segmented pipeline, a very-high-speed clock can be used. Since a highly segmented pipeline will require relatively long pipelines, a way must be provided to minimize the effects of pipeline bubbles that are formed due to data and control dependencies. It is also important to provide a way of supporting precise interrupts. These goals are met, in part, by providing a reorder buffer to help restore the machine to a precise state. The architecture then makes the pipelining visible to the programmer/compiler by making the reorder buffer accessible and by explicitly providing that issued instructions cannot be affected by immediately preceding ones. Compiler techniques have been identified that can take advantage of the reorder buffer and permit a sustained execution rate approaching or exceeding one per clock. These techniques include using trace scheduling and providing a relatively easy way to “undo” instructions if the predicted branch path is not taken. We have also studied ways to further reduce the effects of branches by not having them executed in the execution unit. In particular, branches are detected and resolved in the instruction fetch unit. Using this approach, the execution unit is sent a stream of instructions (without branches) that are guaranteed to execute.
Targeting Cancer Cells: Controlling the Binding and Internalization of Antibody-Functionalized Capsules (2012)

The development of nanoengineered particles, such as polymersomes, liposomes, and polymer capsules, has the potential to offer significant advances in vaccine and cancer therapy. However, the effectiveness of these carriers has the potential to be greatly improved if they can be specifically delivered to target cells. We describe a general method for functionalizing nanoengineered polymer capsules with antibodies using click chemistry and investigate their interaction with cancer cells in vitro. The binding efficiency to cells was found to be dependent on both the capsule-to-cell ratio and the density of antibody on the capsule surface. In mixed cell populations, more than 90% of target cells bound capsules when the capsule-to-target cell ratio was 1:1. Strikingly, greater than 50% of target cells exhibited capsules on the cell surface even when the target cells were present as less than 0.1% of the total cell population. Imaging flow cytometry was used to quantify the internalization of the capsules, and the target cells were found to internalize capsules efficiently. However, the role of the antibody in this process was determined to enhance accumulation of capsules on the cell surface rather than promote endocytosis. This represents a significant finding, as this is the first study into the role antibodies play in internalization of such capsules. It also opens up the possibility of targeting these capsules to cancer cells using targeting molecules that do not trigger an endocytic pathway. We envisage that this approach will be generally applicable to the specific targeting of a variety of nanoengineered materials to cells.
Calcium Phosphate Transfection of Mammalian Cultured Cells (2003)

Calcium phosphate and DEAE-dextran reagents were incorporated into the first chemical methods that successfully transferred nucleic acid directly to cultured mammalian cells in a process referred to as transfection (1–4). Early transfection studies used viral RNA (1) and DNA (2,4), which, at that time, were relatively easy to propagate and purify, and allowed phenotypic discrimination of the transfected mammalian cells. Calcium phosphate coprecipitation and DEAE-dextran methods became widely used after cloning and manipulation of plasmid DNA became routine, and it was demonstrated that plasmid DNA was effectively transferred to cultured cells using these methods. Together with advancements in vector development came the introduction of additional transfection methods using chemical reagents such as liposomes (5,6), dendrimers (7,8), and cationic polymers (9,10), plus physical methods such as electroporation (11) and biolistic microparticle bombardment (12). However, the calcium phosphate coprecipitation technique still remains one of the most widely used in vitro transfection methods.
Immunity to TCR peptides in multiple sclerosis. II. T cell recognition of V beta 5.2 and V beta 6.1 CDR2 peptides. (1994)

The biased expression of V beta 5.2 and V beta 6.1 by T cells specific for myelin basic protein (BP) has led to our use of TCR peptides from these V gene sequences to induce anti-TCR immunity in patients with multiple sclerosis (MS). Injection of V beta 5.2-39-59 or V beta 6.1-39-59 peptides significantly increased the peptide specific T cell frequency in 7 of 11 MS patients, often with an accompanying delayed hypersensitivity reaction at the injection site. Here, we validate these cellular immune responses by characterizing TCR peptide specific T cells from an MS patient with biased V beta 5.2 expression in BP reactive T cells before treatment with TCR peptides, and from two MS patients in whom the frequencies of anti-TCR peptide specific T cells were significantly boosted after injection with low doses of TCR peptides. In both cases, T cell lines were established with relative ease, especially after boosting with the peptides. A V beta 5.2-39-59 reactive line responded selectively to the boosting peptide and was restricted by both MHC class I (HLA-B7) and MHC class II (HLA-DR2) molecules. Characterization of 22 clonal isolates revealed that the responding T cells were predominantly activated CD4+CD8lo, circulating memory cells restricted by either HLA-B7 or HLA-DR2, that utilized mainly V beta 4, V beta 6, V beta 12, and V beta 14, but not V beta 5.2 in their TCR. T cell isolates specific for V beta 6.1-39-59 possessed similar characteristics but contained specificities cross-reactive with an N-terminal sequence on V beta 5.2-39-59. Upon stimulation with peptide or Con A, the TCR peptide specific T cell lines had increased message production for IFN-gamma, GM-CSF, IL-4, IL-5, and to a lesser degree, IL-2. This lymphokine mRNA profile differed from a BP-specific T cell line that produced message for IFN-gamma and GM-CSF but low or absent levels of IL-4 and IL-5. The extensive parallels between human T cells specific for V beta 5.2 and V beta 6.1 CDR2 peptides and rat T cells specific for V beta 8.2 CDR2 peptide that are highly protective against experimental encephalomyelitis strengthen the rationale for the therapeutic use of TCR peptides in human autoimmunity.
A Non-cooperative Equilibrium for Supergames (1971)

Journal Article A Non-cooperative Equilibrium for Supergames Get access James W. Friedman James W. Friedman University of Rochester Search for other works by this author on: Oxford Academic Google Scholar The Review of Economic Studies, Volume 38, Issue 1, January 1971, Pages 1–12, https://doi.org/10.2307/2296617 Published: 01 January 1971
Metrifonate: A new agent for the treatment of Alzheimer’;s disease (1999)

The pharmacology, pharmacokinetics, clinical efficacy, and adverse effects of metrifonate, a long-acting cholinesterase inhibitor, are discussed. Attempts to correct the central cholinergic deficits associated with Alzheimer's disease have included administration of cholinergic precursors, cholinergic agonists, and cholinesterase inhibitors. To date, two reversible cholinesterase inhibitors-tacrine and donepezil-have been marketed. Metrifonate, an organophosphate, is converted nonenzymatically to 2,2-dichlorovinyl dimethyl phosphate (DDVP), the active enzyme inhibitor. DDVP produces irreversible inhibition of brain cholinesterase that lasts for several days; enzyme recovery is dependent on synthesis of new enzyme. Several preclinical studies have demonstrated cognition-enhancing effects of metrifonate in animals. Trials in humans have shown improvement on the Alzheimer's Disease Assessment Scale, in Mini-Mental State Examination scores, and in the Clinician's Interview-Based Impression of Change with caregiver input. Clinical improvement noted with metrifonate appears similar to that seen with other cholinesterase inhibitors. Adverse effects noted in clinical trials have been associated primarily with the gastrointestinal tract and have been mild. Metrifonate appears to be a promising agent for the treatment of the symptoms of Alzheimer's disease.
Self-Propagating, Molecular-Level Polymorphism in Alzheimer's ß-Amyloid Fibrils (2005)

Amyloid fibrils commonly exhibit multiple distinct morphologies in electron microscope and atomic force microscope images, often within a single image field. By using electron microscopy and solid-state nuclear magnetic resonance measurements on fibrils formed by the 40-residue beta-amyloid peptide of Alzheimer's disease (Abeta(1-40)), we show that different fibril morphologies have different underlying molecular structures, that the predominant structure can be controlled by subtle variations in fibril growth conditions, and that both morphology and molecular structure are self-propagating when fibrils grow from preformed seeds. Different Abeta(1-40) fibril morphologies also have significantly different toxicities in neuronal cell cultures. These results have implications for the mechanism of amyloid formation, the phenomenon of strains in prion diseases, the role of amyloid fibrils in amyloid diseases, and the development of amyloid-based nano-materials.
Reaction of organometallic reagents with 2'- and 3'-ketouridine derivatives: Synthesis of uracil nucleosides branched at the 2'- and 3'-positions. (1987)

The reaction of organolithium, Grignard, and organoaluminum reagents with 2'- and 3'-ketouridine derivatives was examined. For the reaction of 2', 5'-bis-0- (tert-butyldimethylsilyl) -3'-ketouridine, both organolithiums and organoaluminums seem to be practically useful. But only organoaluminums gave satisfactory yields in the reaction of 3', 5'-0- (tetraisopropyldisiloxan-1, 3-diyl) -2'-ketouridine.
Sucralfate affects the susceptibility of Helicobacter pylori to antimicrobial agents. (1995)

The results demonstrate that sucralfate enhances the anti-H. pylori activity of antibiotics and that this effect is comparable to that of omeprazole.
Vector integration is nonrandom and clustered and influences the fate of lymphopoiesis in SCID-X1 gene therapy (2007)

Recent reports have challenged the notion that retroviruses and retroviral vectors integrate randomly into the host genome. These reports pointed to a strong bias toward integration in and near gene coding regions and, for gammaretroviral vectors, around transcription start sites. Here, we report the results obtained from a large-scale mapping of 572 retroviral integration sites (RISs) isolated from cells of 9 patients with X-linked SCID (SCID-X1) treated with a retrovirus-based gene therapy protocol. Our data showed that two-thirds of insertions occurred in or very near to genes, of which more than half were highly expressed in CD34(+) progenitor cells. Strikingly, one-fourth of all integrations were clustered as common integration sites (CISs). The highly significant incidence of CISs in circulating T cells and the nature of their locations indicate that insertion in many gene loci has an influence on cell engraftment, survival, and proliferation. Beyond the observed cases of insertional mutagenesis in 3 patients, these data help to elucidate the relationship between vector insertion and long-term in vivo selection of transduced cells in human patients with SCID-X1.
Refactoring the Salmonella type III secretion system (2012)

Bacteria naturally contain a wide variety of multi-component molecular machines that perform complex functions such as chemotaxis, photosynthesis, chemical fixation, and protein secretion, all of which are potentially valuable to synthetic biologists for use in engineered organisms. However, in most cases, the gene clusters encoding these functions are complex and intricately regulated by the bacteria, making them difficult to reuse for new applications.One potential method to address these difficulties is refactoring: a process of recoding the genes for the purpose of simplification and re-use. Here, we present the methods, techniques and results of refactoring the Salmonella Pathogenicity Island I (SPI-1) Type III Secretion System (T3SS). The SPI-1 T3SS is used naturally by Salmonella to inject pathogenic effector agents into its host cell and, unlike the most commonly used secretion mechanisms in bacteria, is capable of transporting functional proteins through both membranes of the bacteria directly into the culture media. This function may enable such biotech applications as targeted peptide/drug delivery and continuous protein expression. In addition, the methods developed here should be broadly applicable to a wide range of bacterial gene-clusters.
Metastatic lesions from prostate cancer do not express oestrogen and progesterone receptors (1997)

Oestrogen receptors (ER) and progesterone receptors (PR) have been reported by several authors in the stromal cells of the human prostate. Controversial results exist on the expression of ER and PR in epithelial cells of the prostate. Some recent publications, in contrast to previous findings, have suggested that these receptors are also present in human prostate cancer cell lines derived from metastatic lesions. The expression of ER and PR in these cell lines has been re-examined to determine their presence in lymph node metastases from patients who did not receive any kind of endocrine therapy and in distant metastases obtained from patients who failed endocrine treatment. ER and PR expression in LNCaP, PC-3, and DU-145 cells was assessed by means of the reverse transcriptase-polymerase chain reaction, ligand binding assays, and immunohistochemistry. With all the techniques applied, the three cell lines were found to be negative for both ER and PR. Immunohistochemical analyses were performed in four lymph node metastases obtained at radical prostatectomy from patients who did not receive endocrine therapy and in 17 distant metastases obtained at palliative surgery from patients who failed endocrine therapy. All 21 metastases were negative for ER and PR on immunohistochemistry. These results do not support the recently developed concept that receptors for oestrogenic and progestagenic steroids are present in metastases from human prostate cancer.
Dioxanone-Fused Dienes Enable Highly Endo-Selective Intramolecular Diels–Alder Reactions (2015)

Intramolecular Diels-Alder reactions of dioxanone-fused (Z,Z)-dienes, available in a stereoselective manner from the corresponding alcohols are described. These dienes exhibited high reactivity and high levels of endo selectivity, giving functionalized trans-fused bicyclic compounds.
Effects of Using Virtual Reality and Virtual Avatar on Hand Motion Reconstruction Accuracy and Brain Activity (2017)

Reconstruction of a hand's motion with electroencephalography (EEG) signals is a challenging problem that has not been solved yet. Most related studies rely on a motion tracking system to record a sequence of hand coordinate values paired with biosignals, in order to train a mapping function between them. For amputees, this approach is not possible. There are also only a few studies about how different training techniques may affect the accuracy of a motion reconstruction system. A virtual avatar for presenting different upper limb motions was developed. Subjects were asked to follow the avatar's motion, while the subject's EEG and electromyography (EMG) signals were recorded and paired with avatar's hand trajectory values. This task was performed under three conditions: repeating the motion by memory, repeating the motion while watching it on a screen, and repeating the motion while seeing it in virtual reality (VR). We did not find any significant difference between the three conditions in terms of correlation values. Still, we found that using both EEG and EMG at the same time led to a better result than using only one of them. Additionally, significant differences were found in the EEG activity, suggesting that even if the task (moving the arm) was the same for the three conditions, the brain dynamics were different. Specifically, we found that using the VR resulted in a higher alpha desynchronization during the motion. Finally, our results, when only EEG signals were used, were comparable with other studies that have used a motion tracking system.
Regulation of hemolysin expression in Actinobacillus pleuropneumoniae serotype 1 by Ca2+ (1988)

Actinobacillus pleuropneumoniae, the causative agent of swine pleuropneumonia, secretes a hemolytic activity which is thought to be a factor involved in the pathogenesis of the disease. The biosynthesis of hemolysin by serotype 1 strain 4074 was strongly dependent on the activity of free Ca2+ in the growth medium. At activities of free Ca2+ below 50 microM, very low hemolytic activities could be detected in the growth medium and in cell extracts. Maximal hemolytic activities of up to 400 hemolytic units per ml could be measured in growth medium containing free Ca2+ activities above 3 mM. Other bivalent cations did not stimulate the production of hemolysin. Neither the growth rate nor the secretion of hemolysin was affected by increasing Ca2+ concentrations in the medium. The hemolysin of serotype 1 did not require Ca2+ as a cofactor for the lysis of erythrocytes. Ca2+ induced the expression of a 105-kilodalton protein, which was secreted. This protein comigrated with purified hemolysin on sodium dodecyl sulfate-polyacrylamide gel electrophoresis and exhibited hemolysin activity upon purification. Inhibition experiments with rifampin suggest that the hemolysin of A. pleuropneumoniae is regulated by Ca2+ at the transcriptional level. The threshold of hemolysin induction was around 700 microM free Ca2+, a concentration which is similar to that found in blood serum. The Ca2+-inducible hemolysin represents a novel type of positively regulated bacterial gene expression.
Dining activity analysis using a hidden Markov model (2004)

We describe an algorithm for dining activity analysis in a nursing home. Based on several features, including motion vectors and distance between moving regions in the subspace of an individual person, a hidden Markov model is proposed to characterize different stages in dining activities with certain temporal order. Using HMM model, we are able to identify the start (and ending) of individual dining events with high accuracy and low false positive rate. This approach could be successful in assisting caregivers in assessments of resident's activity levels over time.
Solid‐Phase Synthesis of DOTA–Peptides (2004)

A general synthetic route to two DOTA-linked N-Fmoc amino acids (DOTA-F and DOTA-K) is described that allows insertion of DOTA at any endo-position within a peptide sequence. Three model pentapeptides were prepared to test the general utility of these derivatives in solid-phase peptide synthesis. Both DOTA derivatives reacted smoothly by means of standard HBTU activation chemistry to the point of insertion of the DOTA amino acid, but extension of the peptide chain beyond the DOTA-amino acid insertion required the use of pre-activated C-pentafluorophenyl ester N-alpha-Fmoc amino acids. Three Gal-80 binding peptides (12-mers) were then prepared by using this methodology with DOTA positioned either at the N terminus or at one of two different internal positions;the binding of the resulting GdDOTA-12-mers to Gal-80 were compared. The methodology described here allows versatile, controlled introduction of DOTA into any location within a peptide sequence. This provides a potential method for the screening of libraries of DOTA-linked peptides for optimal targeting properties.