gebhart/patrepeval huggingface dataset:
CERTAIN REACTIONS OF GAMMA KETONIC ACIDS (1934)

A considerable number of highly substituted acrylic acids or their lactols have been synthesized, and the Grignard reagent used to differentiate between the two possible structures. Acetyl chloride was found to be a satisfactory confirmatory agent, giving chlorides with the lactols, but not reacting with the open-chain acids. From the available evidence it is concluded that the differences may be attributed to cis-trans isomerism.Two other series of ketonic acids were investigated with both reagents; the Grignard reagent indicated mostly open-chain structures. The use of acetyl chloride led to a variety of products; by varying the procedure, dimers of undetermined structure, unsaturated lactones, enolic acetates, and methyl esters were obtained.Cyclohexanone gave cyclohexenyl acetate with acetyl chloride.The mechanism of the reactions is discussed, as well as the evidence for the possible structures of derivatives of levulinic acid. A mechanism is suggested to account for the formation of enolic esters and unsaturated lactones of enolized ketonic acids.
Cheese-like Food Production from Various Nuts (2009)

Nuts are rich in vegetable proteins and lipids, and can be easily made into a milk-like emulsion such as coconut milk or hemp milk. In this study we attempted to produce a cheese-like food from various nuts instead of from cows’ milk. First, we investigated the curdling activity of various proteases on emulsions made individually from 13 species of nuts. The proteases bromelain, papain, subtilisin, thermolysin and a protease from E. faecalis could curdle the milk-like emulsion made from 12 species of nuts. The emulsions made from hemp nuts, coconuts, almonds, pine nuts and macadamia nuts curdled especially well. We then successfully produced cheese-like foods from 6 species of nuts (hemp nuts, coconuts, almonds, pine nuts, cashew nuts and macadamia nuts). Compared to cheese made from cows’ milk these nut-cheeses were softer, the curd yield from the emulsion was almost the same, the protein content was lower and the lipid content was higher. Hemp nut cheese was the most similar to cows’ milk-cheese in its composition and gave the highest yield of cheese among all of the tested nuts.
Identifying topics by position (1997)

This paper addresses the problem of identifying likely topics of texts by their position in the text. It describes the automated training and evaluation of an Optimal Position Policy, a method of locating the likely positions of topic-bearing sentences based on genre-specific regularities of discourse structure. This method can be used in applications such as information retrieval, routing, and text summarization.
An $n^{5/2} $ Algorithm for Maximum Matchings in Bipartite Graphs (1973)

The present paper shows how to construct a maximum matching in a bipartite graph with n vertices and m edges in a number of computation steps proportional to $(m + n)\sqrt n $.Keywordsalgorithmalgorithmic analysisbipartite graphscomputational complexitygraphsmatching
T cells from CLL patients exhibit features of T-cell exhaustion but retain capacity for cytokine production (2012)

T-cell exhaustion, originally described in chronic viral infections, was recently reported in solid and hematologic cancers. It is not defined whether exhaustion contributes to T-cell dysfunction observed in chronic lymphocytic leukemia (CLL). We investigated the phenotype and function of T cells from CLL patients and age-matched controls. CD8+ and CD4+ T cells from CLL patients had increased expression of exhaustion markers CD244, CD160, and PD1, with expansion of a PD1+BLIMP1HI subset. These molecules were most highly expressed in the expanded population of effector T cells in CLL. CLL CD8+ T cells showed functional defects in proliferation and cytotoxicity, with the cytolytic defect caused by impaired granzyme packaging into vesicles and nonpolarized degranulation. In contrast to virally induced exhaustion, CLL T cells showed increased production of interferon-γ and TNFα and increased expression of TBET, and normal IL2 production. These defects were not restricted to expanded populations of cytomegalovirus (CMV)–specific cells, although CMV seropositivity modulated the distribution of lymphocyte subsets, the functional defects were present irrespective of CMV serostatus. Therefore, although CLL CD8+ T cells exhibit features of T-cell exhaustion, they retain the ability to produce cytokines. These findings also exclude CMV as the sole cause of T-cell defects in CLL.
Contribution of CD4+ and CD8+ T cells to graft-versus-host disease and graft-versus-leukemia reactivity after transplantation of MHC-compatible bone marrow. (1991)

A murine model of allogeneic bone marrow (BM) transplantation was used to determine the relative importance of CD4+ and CD8+ T cells in establishing donor T cell chimerism and in the development of graft-versus-host (GVH) and graft-versus-leukemia (GVL) reactivity. Mature donor T cells were essential for complete chimerism when host mice (AKR, H-2k) were conditioned with suboptimal irradiation (9 Gy = LD50). Transplantation of donor BM (B10.BR, H-2k) resulted in mixed chimerism, whereas mice given BM containing additional T cells developed into complete and stable chimeras. Depletion of T cell subsets was associated with an increase in the frequency of mixed chimerism. The incidence of lethal GVHD was dependent on the number of T cells added to the BM inoculum. Ex vivo depletion of CD4+ T cells eliminated GVH-associated mortality. Removal of CD8+ T cells had no effect on overall survival. In contrast to the GVH results, removal of either CD4+ or CD8+ T cells compromised GVL reactivity, indicating that an optimal GVL response required both CD4+ and CD8+ T cells. T cell-subset depletion did not interfere with the induction of donor-host tolerance in these chimeras and may have facilitated its development. The loss of GVH/GVL effector cells as a result of T cell depletion and the development of donor-host tolerance may act synergistically to prevent or suppress GVH and GVL reactivity.
Assessment of the Cerebral Ischemic/Reperfusion Injury after Cardiac Arrest (2010)

The cerebral damage after cardiac arrest is thought to arise both from the ischemia during the cardiac arrest but also during reperfusion. It is the degree of cerebral damage which determines the outcome in patients. This thesis focuses on the cerebral damage after cardiac arrest. In two animal studies, positron emission tomography (PET) was used to measure cerebral blood flow, oxygen metabolism and oxygen extraction in the brain. After restoration of spontaneous circulation (ROSC) from five or ten minutes of cardiac arrest there was an immediate hyperperfusion, followed by a hypoperfusion which was most evident in the cortex. The oxygen metabolism decreased after ROSC with the lowest values in the cortex. The oxygen extraction was high at 60 minutes after ROSC, indicating an ischemic situation. After ten minutes of cardiac arrest, there was a hyperperfusion in the cerebellum. In 31 patients resuscitated after cardiac arrest and treated with hypothermia for 24 hours, blood samples were collected from admission until 108 hours after ROSC. The samples were analyzed for different biomarkers in order to test the predictive value of the biomarkers. The patients were assessed regarding their neurological outcome at discharge from the intensive care unit and after six months. Brain derived neurotrophic factor (BDNF) and glial fibrillary acidic protein (GFAP) was not associated with outcome. Neuron specific enolase (NSE) concentrations were higher among those with a poor outcome with a sensitivity of 57% and a specificity of 93% when sampled 96 hours after ROSC. S-100B was very accurate in predicting outcome; after 24 hours after ROSC it predicted a poor outcome with a sensitivity of 87% and a specificity of 100%. Tau protein predicted a poor outcome after 96 hours after ROSC with a sensitivity of 71% and a specificity of 93%.
Shal‐type channels contribute to the Ca2+‐independent transient outward K+ current in rat ventricle. (1997)

1. The hypothesis that Kv4.2 and Kv4.3 are two of the essential K+ channel isoforms underlying the Ca2+-independent transient outward K+ current (It) in rat ventricle has been tested using a combination of electrophysiological measurements and antisense technology in both native myocytes and a stably transfected mammalian cell line, mouse Ltk- cells (L-cells). 2. The transient outward currents generated by Kv4.2 channels in L-cells exhibit rapid activation and inactivation properties similar to those produced by It in rat ventricular cells. The current-voltage relationships and the voltage dependence of steady-state inactivation are also very similar in these two preparations. However, the recovery from inactivation of Kv4.2 is much slower (time constant, 378 ms) than that of It in rat ventricular cells (58 ms). 3. The K+ current due to Kv4.2 can be blocked by millimolar concentrations of 4-aminopyridine in L-cells; a similar pharmacological response has been observed in rat ventricular myocytes. 4. Quinidine inhibits Kv4.2 in L-cells and It in rat ventricular cells in a similar fashion. In L-cells quinidine reduced the amplitude of Kv4.2 and accelerated its time course of inactivation, suggesting that quinidine may act as an open channel blocker of Kv4.2, as has been described for It in rat ventricle. 5. To provide further independent evidence that Kv4.2 and Kv4.3 channel isoforms contribute to It in rat ventricular cells, the effects of 20-mer antisense phosphorothioate oligodeoxynucleotides directed against Kv4.2 and Kv4.3 mRNAs were examined in ventricular myocytes isolated from 14- and 20-day-old rats, and in L-cells. In both preparations, Kv4.2 antisense pretreatment significantly reduced the transient outward K+ current (by approximately 55-60%). Similar reduction of It was produced by the Kv4.3 antisense oligonucleotide on the 14-day-old rat myocytes. 6. In 14-day rat ventricular cells, combination of Kv4.2 and Kv4.3 antisense oligonucleotides did not produce a significantly larger reduction of It than that observed after pretreatment with either antisense oligonucleotide alone. 7. L-cells stably transfected with Kv4.2 were treated with Kv4.3 antisense oligonucleotide to evaluate the possibility of cross-reactivity between Kv4.3 antisense and Kv4.2 mRNA. This antisense treatment produced no change in It, verifying the lack of cross-reactivity. 8. These biophysical and pharmacological results together with the antisense data show that Kv4.2 and Kv4.3 are essential components of the Ca2+-independent transient outward K+ current, It, in rat ventricular myocytes.
Discovery of Risdiplam, a Selective Survival of Motor Neuron-2 ( SMN2 ) Gene Splicing Modifier for the Treatment of Spinal Muscular Atrophy (SMA) (2018)

SMA is an inherited disease that leads to loss of motor function and ambulation and a reduced life expectancy. We have been working to develop orally administrated, systemically distributed small molecules to increase levels of functional SMN protein. Compound 2 was the first SMN2 splicing modifier tested in clinical trials in healthy volunteers and SMA patients. It was safe and well tolerated and increased SMN protein levels up to 2-fold in patients. Nevertheless, its development was stopped as a precautionary measure because retinal toxicity was observed in cynomolgus monkeys after chronic daily oral dosing (39 weeks) at exposures in excess of those investigated in patients. Herein, we describe the discovery of 1 (risdiplam, RG7916, RO7034067) that focused on thorough pharmacology, DMPK and safety characterization and optimization. This compound is undergoing pivotal clinical trials and is a promising medicine for the treatment of patients in all ages and stages with SMA.
Functional domains within FEN-1 and RAD2 define a family of structure-specific endonucleases: implications for nucleotide excision repair. (1994)

Structure-specific nucleases catalyze critical reactions in DNA replication, recombination, and repair. Recently, a structure-specific endonuclease, FEN-1, has been purified and shown to cleave DNA flap structures. Here, we describe the cloning of the murine FEN-1 gene. The nucleotide sequence of FEN-1 is highly homologous to the Saccharomyces cerevisiae genes YKL510 and RAD2. We show that YKL510 and a truncated RAD2 protein are also structure-specific endonucleases. The substrate specificity of the truncated RAD2 protein implicates branched DNA structures as important intermediates in nucleotide excision repair. The polarity of these branched DNA structures allows us to predict the placement of DNA scissions by RAD2 and RAD1/RAD10 in this reaction.
Jellyfish green fluorescent protein as a reporter for virus infections (1995)

The gene encoding green fluorescent protein (GFP) of Aequorea victoria was introduced into the expression cassette of a virus vector based on potato virus X (PVX). Host plants of PVX inoculated with PVX.GFP became systemically infected. Production of GFP in these plants was detected initially between 1 and 2 days postinoculation by the presence of regions on the inoculated leaf that fluoresced bright green under UV light. Subsequently, this green fluorescence was evident in systemically infected tissue. The fluorescence could be detected by several methods. The simplest of these was by looking at the UV-illuminated plants in a darkened room. The PVX.GFP-infected tissue has been analysed either by epifluorescence or confocal laser scanning microscopy. These microscopical methods allow the presence of the virus to be localized to individual infected cells. It was also possible to detect the green fluorescence by spectroscopy or by electrophoresis of extracts from infected plants. To illustrate the potential application of this reporter gene in virological studies a derivative of PVX.GFP was constructed in which the coat protein gene of PVX was replaced by GFP. Confocal laser scanning microscopy of the inoculated tissue showed that the virus was restricted to the inoculated cells thereby confirming earlier speculation that the PVX coat protein is essential for cell-to-cell movement. It is likely that GFP will be useful as a reporter gene in transgenic plants as well as in virus-infected tissue.
Identification of Biological Tissues by Rapid Evaporative Ionization Mass Spectrometry (2010)

The newly developed rapid evaporative ionization mass spectrometry (REIMS) provides the possibility of in vivo, in situ mass spectrometric tissue analysis. The experimental setup for REIMS is characterized in detail for the first time, and the description and testing of an equipment capable of in vivo analysis is presented. The spectra obtained by various standard surgical equipments were compared and found highly specific to the histological type of the tissues. The tissue analysis is based on their different phospholipid distribution; the identification algorithm uses a combination of principal component analysis (PCA) and linear discriminant analysis (LDA). The characterized method was proven to be sensitive for any perturbation such as age or diet in rats, but it was still perfectly suitable for tissue identification. Tissue identification accuracy higher than 97% was achieved with the PCA/LDA algorithm using a spectral database collected from various tissue species. In vivo, ex vivo, and post mortem REIMS studies were performed, and the method was found to be applicable for histological tissue analysis during surgical interventions, endoscopy, or after surgery in pathology.
Incremental Learning From Stream Data (2011)

Recent years have witnessed an incredibly increasing interest in the topic of incremental learning. Unlike conventional machine learning situations, data flow targeted by incremental learning becomes available continuously over time. Accordingly, it is desirable to be able to abandon the traditional assumption of the availability of representative training data during the training period to develop decision boundaries. Under scenarios of continuous data flow, the challenge is how to transform the vast amount of stream raw data into information and knowledge representation, and accumulate experience over time to support future decision-making process. In this paper, we propose a general adaptive incremental learning framework named ADAIN that is capable of learning from continuous raw data, accumulating experience over time, and using such knowledge to improve future learning and prediction performance. Detailed system level architecture and design strategies are presented in this paper. Simulation results over several real-world data sets are used to validate the effectiveness of this method.
The chimeric anti-CD20 antibody rituximab induces apoptosis in B-cell chronic lymphocytic leukemia cells through a p38 mitogen activated protein–kinase–dependent mechanism (2002)

Antibodies against CD20 can activate complement and induce antibody-dependent cellular cytotoxicity (ADCC) in B lymphocytes. In B-cell lines, such antibodies also induce apoptosis. In this study, the expression and function of CD20 on B-cell chronic lymphocytic leukemia (B-CLL) cells were analyzed. Flow cytometric analysis demonstrated that B-CLL cells express CD20 with a fluorescence intensity that is significantly weaker than that of normal CD5(+) and CD5(-) B cells and that of malignant CD5(-) low-grade non-Hodgkin lymphoma cells. A small population of cells from healthy donors that have an expression pattern of CD5 and CD20 identical to that of B-CLL cells were identified, and this population was confirmed to be of T lineage, not B lineage. Culture of freshly isolated B-CLL cells in the presence of the chimeric anti-CD20 antibody rituximab and a cross-linking F(ab)(2) fragment, resulted in dose- and time-dependent induction of apoptosis. The induction of apoptosis occurred under conditions in which the influence of complement activation and ADCC was negligible. Cross-linking of rituximab induced strong and sustained phosphorylation of the 3 mitogen activated protein (MAP) kinases c-Jun NH2-terminal protein kinase, extracellular signal-regulated kinase, and p38. Introduction of the p38 inhibitor SB203580 into the system completely blocked signaling downstream of p38, as evidenced by the absence of MAPKAP K2 activity, and significantly reduced the degree of anti-CD20-induced apoptosis. These results demonstrate that cross-linking of rituximab bound to CD20 on freshly isolated B-CLL cells induces apoptosis through a signaling pathway that is dependent on p38 MAP-kinase activation.
Patient-Derived Xenograft Models: An Emerging Platform for Translational Cancer Research (2014)

PDX models are increasingly used in translational cancer research. These models are useful for drug screening, biomarker development, and the preclinical evaluation of personalized medicine strategies. This review provides a timely overview of the key characteristics of PDX models and a detailed discussion of future directions in the field.
Specific expression and methylation of SLIT1, SLIT2, SLIT3, and miR-218 in gastric cancer subtypes (2016)

SLIT has been suggested as a key regulator of cancer development and a promising therapeutic target for cancer treatment. Herein, we analyzed expression and methylation of SLIT1/SLIT2/SLIT3 in 11 gastric cancer cell lines, 96 paired gastric tumors and adjacent normal gastric tissues, and 250 gastric cancers provided by The Cancer Genome Atlas. Methylation of SLIT1/SLIT2/SLIT3 was found both in early gastric cancers, and in advanced gastric cancers. Even normal gastric tissue showed increased methylation of SLIT1 and SLIT3 that correlated with patient age. Furthermore, epigenetic inactivation of SLIT occurred in a gastric cancer subtype-dependent manner. SLIT2 and SLIT3 expression was reduced in Epstein-Barr virus-positive and microsatellite instability subtypes, but increased in the genomically stable subtype. Expression of miR‑218 correlated negatively with methylation of SLIT2 or SLIT3. These findings suggest that a molecular subtype-specific therapeutic strategy is needed for targeting SLITs and miR-218 in treatment of gastric cancer.
Who's got the floor? (1981)

ABSTRACT This study into the nature of “the floor” actually began as an open-ended inquiry into sex differences that might occur beyond the sentence level in the multi-party interaction of five informal committee meetings. Technical difficulties prompted the trying out of several different transcription displays, most of which failed to capture the “feel” of the interaction and each of which biased (in its own way) the perception of what had actually gone on. The type of unconventional display eventually used was intended to show the floor holder in the center of the page, flanked by co-occurring talk. Because there were many episodes for which a single floor holder could not be identified, the primary focus of the study shifted to the nature of the floor itself. Questions about sex differences became a secondary and succeeding focus. In the analysis, “floor” and “turn” were distinguished on the basis of “participant-sense” rather than technical criteria. Two kinds of floors were subjectively identified: F1, a singly developed floor; and F2, a collaborative venture where several people seemed to be either operating on the same wavelength or engaging in a free-for-all. The two kinds of floors were differentiated objectively by such features as quantity and frequency participation, language functions, number of nonturn utterances, overlaps, and pauses. There were indeed sex/language differences, but these were related to the type of floor being developed. Men took more and longer turns and did more of the joking, arguing, directing, and soliciting of responses F1 's. Turn length and frequency differences were neutralized in F2's, and certain language functions were used by women to a greater extent in F2's than in F1 's. (Conversational analysis, gender and language, qualitative research methodology.)
Tri-polar concentric ring electrode development for Laplacian electroencephalography (2006)

Brain activity generates electrical potentials that are spatio-temporal in nature. Electroencephalography (EEG) is the least costly and most widely used noninvasive technique for diagnosing many brain problems. It has high temporal resolution, but lacks high spatial resolution. In an attempt to increase the spatial selectivity, researchers introduced a bipolar electrode configuration utilizing a five-point finite difference method (FPM) and others applied a quasi-bipolar (tri-polar with two elements shorted) concentric electrode configuration. To further increase the spatial resolution, the authors report on a tri-polar concentric electrode configuration for approximating the analytical Laplacian based on a nine-point finite difference method (NPM). For direct comparison, the FPM, quasi-bipolar method (a hybrid NPM), and NPM were calculated over a 400 x 400 mesh with 1/400 spacing using a computer model. A closed-form analytical computer model was also developed to evaluate and compare the properties of concentric bipolar, quasi-bipolar, and tri-polar electrode configurations, and the results were verified with tank experiments. The tri-polar configuration and the NPM were found to have significantly improved accuracy in Laplacian estimation and localization. Movement-related potential (MRP) signals were recorded from the left prefrontal lobes on the scalp of human subjects while they performed fast repetitive movements. Disc, bipolar, quasi-bipolar, and tri-polar electrodes were used. MRP signals were plotted for all four electrode configurations. The signal-to-noise ratio and spatial selectivity of the MRP signals acquired with the tri-polar electrode configuration were significantly better than the other configurations.
[Effect of C5-siRNA silencing receptor C5 on myocardial ischemia injury in rats]. (2010)

C5-siRNA could attenuate myocardial ischemia injury in rats by reducing inflammatory cell infiltration and expression of C5.