gebhart/patrepeval huggingface dataset:
CTLA-4 blockade in tumor models: an overview of preclinical and translational research. (2013)

Cytotoxic T lymphocyte antigen-4 (CTLA-4) is a key negative regulator of T cell activation. A complex integration of positive and negative co-stimulatory signals in the well-defined B7:CD28/CTLA-4 pathway modulates the generation and maintenance of immune responses. Inhibiting negative regulation through binding of CTLA-4 has been shown to promote stimulation of adaptive immunity and potentiation of T cell activation. CTLA-4-blocking antibodies have demonstrated efficacy in various murine malignancy models when administered as monotherapy; additionally, they have shown synergistic anti-tumor activity when utilized with other agents, such as vaccines, chemotherapy, and radiation. Preclinical studies have supported the rationale for current clinical development of anti-CTLA-4 antibodies, including ipilimumab and tremelimumab, as novel therapeutic strategies to augment anti-tumor immunity in cancer. Both ipilimumab and tremelimumab have been evaluated extensively in melanoma; notably, ipilimumab was recently approved as monotherapy for the treatment of advanced melanoma. Tremelimumab is currently undergoing evaluation in phase II trials as monotherapy in melanoma and malignant mesothelioma, while ipilimumab is under clinical investigation in phase II and III trials in various tumor types, including in melanoma, prostate, and lung cancers as monotherapy and with other therapeutic modalities, such as chemotherapy and radiation. In this review, we will provide a detailed overview of preclinical advances that have delineated many features of CTLA-4 and have helped define its role in T cell response. We will also highlight clinical application of anti-CTLA-4 therapy in cancer and describe knowledge gaps that future studies may address.
Why conversational agents should catch the eye (2000)

We studied whether the gaze direction of users indicates whom they are speaking or listening to in multiparty conversations. Results show when someone is listening or speaking to individuals, there is indeed a high probability that the person looked at is the person listened (p=88%) or spoken to (p=77%). We implemented these findings in a multi-agent conversational system that uses eye input to gauge which agent the user is listening or speaking to.
Gene dose effect reveals no Gs-coupled A2A adenosine receptor reserve in murine T-lymphocytes: studies of cells from A2A-receptor-gene-deficient mice (2001)

Agonist binding to extracellular A2A adenosine receptors (A2ARs) inhibits the activation of virtually all tested functions of T-cells and can induce apoptosis in thymocytes. The evaluation of levels of expression of these immunosuppressive receptors is expected to clarify whether the absence of spare A2ARs (no ‘receptor reserve’) might be one of the mechanisms of attenuation of the effects of extracellular adenosine on T-cells. A2A transcript is found in T-cells and functional receptors can be demonstrated, but the density of receptor on T-cells is too low to be detected by radioligand binding. Studies of direct radioligand binding to murine brain with the selective A2AR agonist [3H]CGS21680 (2-{4-[(2-carboxyethyl)-phenyl]ethylamino}-5′-N-ethylcarboxamidoadenosine) established that striata levels of A2AR are virtually absent from A2A knock-out mice. Mice that are heterozygous (A2AR+/-) for the A2AR express significantly decreased levels of A2AR. To test for the presence of spare receptors in T-cells we took advantage of this gene dose effect and examined whether the decrease in the number of receptors in thymocytes from A2AR+/- mice was proportionately reflected in a decrease in the functional cAMP response of T-cells to adenosine. cAMP accumulation and apoptosis induced by adenosine and by A2AR agonist are of a lower magnitude in T-cells from A2AR+/- heterozygous mice than in T-cells from A2AR+/+ littermate control mice. These results indicate that there is no A2AR reserve in murine T-cells. Strongly decreased adenosine-triggered cAMP increases were detected in thymocytes from A2AR-/- mice, suggesting that A2B adenosine receptors cannot fully compensate for the loss of A2ARs in murine T-cells. We conclude that the number of A2ARs is the limiting factor in determining the maximal cAMP response of T-lymphocytes to extracellular adenosine, thereby minimizing the immunosuppressive effects of extracellular adenosine.
Inhibiting the Deubiquitinating Enzymes (DUBs) (2014)

The diverse roles of deubiquitinating enzymes, or DUBs, in determining the fate of specific proteins continue to unfold. Concurrent with the revelation of DUBs as potential therapeutic targets are publications of small molecule inhibitors of these enzymes. In this review, we summarize these molecules and their associated data and suggest additional experiments to further validate and characterize these compounds. We believe the field of drug discovery against DUBs is still in its infancy, but advances in assay development, biophysical techniques, and screening libraries hold promise for identifying suitable agents that could advance into the clinic.
Advances in the Pathogenesis, Diagnosis, and Treatment of Thrombotic Thrombocytopenic Purpura (2003)

Thrombotic thrombocytopenic purpura (TTP) and the hemolytic uremic syndrome (HUS) are both characterized by thrombocytopenia, microangiopathic hemolysis, and organ dysfunction. Other disorders occasionally present with similar manifestations. Recent studies have demonstrated that deficiency in the von Willebrand factor cleaving protease ADAMTS13, due to genetic mutations or autoimmune inhibitors, causes TTP. Molecular cloning of ADAMTS13 elucidates the structure of the protease, raising the prospect for advances in diagnosis and treatment of the disease. Assay of ADAMTS13 activity distinguishes TTP from HUS and other types of thrombotic microangiopathy (TMA); therefore, the term TTP/HUS should be avoided because it obscures the known or potential differences among the various types of TMA.
Human TRBP and PACT Directly Interact with Each Other and Associate with Dicer to Facilitate the Production of Small Interfering RNA (2007)

Mammalian Dicer interacts with double-stranded RNA-binding protein TRBP or PACT to mediate RNA interference and micro-RNA processing. TRBP and PACT are structurally related but exert opposite regulatory activities on PKR. It is not understood whether TRBP and PACT are simultaneously required for Dicer. Here we show that TRBP directly interacts with PACT in vitro and in mammalian cells. TRBP and PACT form a triple complex with Dicer and facilitate the production of small interfering RNA (siRNA) by Dicer. Knockdown of both TRBP and PACT in cultured cells leads to significant inhibition of gene silencing mediated by short hairpin RNA but not by siRNA, suggesting that TRBP and PACT function primarily at the step of siRNA production. Taken together, these findings indicate that human TRBP and PACT directly interact with each other and associate with Dicer to stimulate the cleavage of double-stranded or short hairpin RNA to siRNA. Our work significantly alters the current model for the assembly and function of the Dicer-containing complex that generates siRNA and micro-RNA in human.
Nucleotide sequence of the Escherichia coli gap gene (1985)

A 1523-base-pair DNA fragment, spanning the gap gene from Escherichia coli, has been sequenced. It contains an open-reading frame whose length (330 amino acids) is in agreement with D-glyceraldehyde-3-phosphate dehydrogenase (GAPDH) molecular mass. This coding sequence is preceded by a Shine-Dalgarno complementary sequence and by two overlapping promoter-like structures. The codon usage within gap is consistent with that expected for a gene which is strongly expressed. The amino acid sequence of the E. coli GAPDH, deduced from the DNA sequence, contains all the amino acids postulated to play a functional role in GAPDH. Comparison of the E. coli enzyme with enzymes from other species reveals different evolutionary behaviour of the NAD+-binding domain and of the catalytic domain of GAPDH. The E. coli enzyme is found to be more similar to eucaryotic enzymes than to enzymes from thermophilic bacteria. This observation is discussed in terms of adaptation to growth at high temperature.
Analyst Forecasting Errors and Their Implications for Security Analysis: An Alternative Perspective (1996)

Dreman and Berry, in the May/June 1995 Financial Analysts Journal, offered a perspective on analyst earnings forecast errors and their implications for security analysis. Among other arguments, they contended that the errors are too large to be reliably used by investors, the forecasts are less accurate than forecasts by time-series models, the errors are increasing over time, the analysts' forecasts are too optimistic, and the investment community relies too heavily on analyst forecasts. This article provides an alternative perspective on these issues. The argument is that analysts' forecast errors are within 3 percent of an appropriate benchmark (namely, stock price), that their forecasts generally are significantly more accurate than forecasts by naive or sophisticated time-series models, that analyst forecast errors have not been increasing over time, that analysts have been too pessimistic in recent years, and that the investment community, by placing too much weight on forecasts made by time-series models, relies too little on analysts' forecasts.
Antitumor Activity of Bacterial Infection. II. Effect of <italic>Listeria monocytogenes</italic> onGrowth of a Guinea Pig Hepatoma (1975)

Growth of a guinea pig hepatoma was suppressed when tumor cells were mixed with viable Listeria monocytogenes (LM) before intradermal (id) injection into syngeneic recipients. Heat-killed LM were less effective than viable organisms in suppressing tumor growth. A vaccine containing oil droplets and LM cell walls lacked antitumor activity. Intratumor injection of viable LM on the 7th day after id injection of tumor cells prolonged survival of guinea pigs that did not succumb to LM infection. After intratumor injection of 0.6 times 10-8-1.0 times 10-8 LM, 5 of 22 guinea pigs died from acute infection (23 percent). In the 17 survivors, 3 tumors regressed completely (18 percent). Animals surviving injections of LM and tumor cells were immune to a second challenge with tumor cells. Immunization ofguinea pigs with an intravenous injection of LM decreased the mortality from intratumor injection of LM, but the intratumor injection of LM failed to cure a significant fraction of LM-immune animals bearing 7-day hepatoma transplants. BCG was more effective than LM in producing tumor regression. Synergism between LM and BCG was not observed, and simultaneous intratumor injection of BCG and LM was no more effective than intratumor injection of BCG alone in the treatment of 12-day tumor transplants.
HT-1080 fibrosarcoma cell matrix degradation and invasion are inhibited by the matrix-associated serine protease inhibitor TFPI-2/33 kDa MSPI (1998)

The urokinase-urokinase receptor system plays a dominant role in the degradation and invasion of extracellular matrix (ECM) by tumor cells. In this system, urokinase bound to its cell receptor converts plasminogen to plasmin, a broad-spectrum serine protease that participates in the degradation and invasion of connective tissues by tumor cells. In this study, we evaluated whether these activities of plasmin are inhibited by a newly characterized human 32 kDa recombinant serine protease inhibitor called trypsin/tissue factor pathway inhibitor-2 (rTFPI-2). We found that rTFPI-2 dose-dependently inhibited fluid-phase plasmin as well as plasmin generated on the ECM and/or the cell surface of HT-1080 fibrosarcoma cells. The degradation of radiolabeled matrix as well as Matrigel invasion by these tumor cells is also inhibited by rTFPI-2 in a dose-dependent fashion. We have reported that rTFPI-2 is identical to 33 kDa extracellular matrix-associated serine protease inhibitor (33 kDa MSPI), whereas the 31 and 27 kDa MSPIs are under-glycosylated forms of the 33 kDa MSPI. We therefore evaluated the ability of MSPIs from the ECM of dermal fibroblasts to inhibit plasmin and found that the plasmin activity was effectively blocked by the MSPIs. We have also evaluated whether the HT-1080 cells synthesize and secrete the MSPIs and found that the synthesis and secretion of the MSPIs was undetectable in these cells. Collectively, our results suggest that rTFPI-2/33 kDa MSPI inhibits plasmin on the tumor cell and ECM surfaces as well as the degradation and invasion of matrix by HT-1080 fibrosarcoma cells.
Response of Atrial Fibrillation to Pulmonary Vein Antrum Isolation Is Directly Related to Resumption and Delay of Pulmonary Vein Conduction (2005)

The majority of patients with drug-free cure show no PV-LA conduction recurrence. Substantial A-PV delay is seen in patients able to maintain sinus rhythm on antiarrhythmic medication or cured of AF compared with patients who fail PVAI.
Bilateral Leg Edema, Obesity, Pulmonary Hypertension, and Obstructive Sleep Apnea (2000)

Bilateral leg edema in obese primary care patients is associated with both OSA and modest pulmonary hypertension. If these findings are generalizable, then bilateral leg edema may be an important clinical marker for underlying OSA.
Decision feedback equalizers: Concepts towards design guidelines (1987)

A quantitative and qualitative analysis of the stochastic dynamics of the blind adaptation of decision feedback equalizers (DFEs) operating on noiseless communication channels is presented. The overall goal, not yet acheived, is to identify channel classes for which DFE use is a practical option. Averaging analysis is invoked to predict the existence and location of undesirable attraction points to the adaptation algorithm. The parameter space in which adaptation takes place is shown to be subdivided into a large but finite set of convex polytopes when the channel can be modelled as a finite impulse response filter. With each polytope we show that the parameters describing the averaged equation are fixed. Further, for every point in a given polytope the error performance is described by a single finite state Markov process. Hence, the adaptive dynamics and the error properties of a noiseless DFEs do not depend continuously with the operating point in parameter space but rather only as a function of polytope membership. The possibility arises of the algorithm becoming hung at an inappropiate attraction point.
Visual Selection and the Human Frontal Eye Fields: Effects of Frontal Transcranial Magnetic Stimulation on Partial Report Analyzed by Bundesen's Theory of Visual Attention (2011)

While the frontal eye fields (FEF) are traditionally associated with eye movements, recent work indicates possible roles in controlling selective visual processing. We applied 10 Hz bursts of transcranial magnetic stimulation (TMS) over left or right human FEF while subjects performed a partial-report task that allowed quantitative estimates of top-down control and other parameters affecting visual performance. Participants selectively reported digits in a relevant color (targets) but not those in an irrelevant color (nontargets) from a brief masked display. A target could appear alone or together with an accompanying item (nontarget or target) in the same or opposite hemifield. Targets were normally identified better when presented with a nontarget than with another target, indicating prioritization of task-relevant targets and thus top-down control. We found this usual pattern of results without TMS, and also with TMS over left FEF. However, during right FEF TMS, the detrimental impact of accompanying distractors increased. Formal analysis in terms of Bundesen's (1990) theory of visual attention confirmed that right FEF TMS diminished the top-down control parameter for both hemifields, indicating an FEF role in top-down selection even for targets defined by the nonspatial property of color. Direct comparison with our previous findings for parietal TMS (Hung et al., 2005) confirmed the distinct role of FEF in top-down control, plus right-hemisphere predominance for this in humans.
Crosslinking of collagen gels by transglutaminase (2004)

Collagen is commonly used as a tissue-engineering scaffold, yet its in vivo applications are limited by a deficiency in mechanical strength. The purpose of this work was to explore the utilization of a unique enzymatic crosslinking procedure aimed at improving the mechanical properties of collagen-based scaffold materials. Type I bovine collagen gel was crosslinked by transglutaminase, which selectively mediates the chemical reaction between glutamine and lysine residues on adjacent protein fibers, thus providing covalent amide bonds that serve to reinforce the three-dimensional matrix. The degree of crosslinking was verified by thermal analysis and amine group content. The denaturation temperature of crosslinked collagen reached a maximum of 66 +/- 1 degrees C. The chemical reaction was confirmed to be noncytotoxic with respect to bone marrow stromal cells acquired from New Zealand White rabbits. Tube-shaped cellular constructs fashioned from crosslinked collagen and bone marrow stromal cells were found to have burst pressures significantly higher than their noncrosslinked analogs (71 +/- 4 mmHg vs. 46 +/- 3 mmHg; p < 0.01). Thus, the transglutaminase mediated reaction served to successfully strengthen collagen gels while remaining benign toward cells.
Modeling of electromagnetic effects from mask topography at full-chip scale (2005)

Polarization and other complex electromagnetic effects that arise because of mask topography are becoming increasingly more important to model. Commercial lithography simulation tools that operate on small layout areas of order 1-10&mu;m<sup>2</sup> have advanced models requiring solution of Maxwell’s three-dimensional boundary problem. However, this technique is not viable for full-chip modeling. Here, we show results that demonstrate the accuracy of domain decomposition method adapted for full-chip modeling of mask topography effects. The intensity error relative to the complete 3D solution is shown to be < 3%.
Regulation of the Acetoin Catabolic Pathway Is Controlled by Sigma L in Bacillus subtilis (2001)

Bacillus subtilis grown in media containing amino acids or glucose secretes acetate, pyruvate, and large quantities of acetoin into the growth medium. Acetoin can be reused by the bacteria during stationary phase when other carbon sources have been depleted. The acoABCL operon encodes the E1alpha, E1beta, E2, and E3 subunits of the acetoin dehydrogenase complex in B. subtilis. Expression of this operon is induced by acetoin and repressed by glucose in the growth medium. The acoR gene is located downstream from the acoABCL operon and encodes a positive regulator which stimulates the transcription of the operon. The product of acoR has similarities to transcriptional activators of sigma 54-dependent promoters. The four genes of the operon are transcribed from a -12, -24 promoter, and transcription is abolished in acoR and sigL mutants. Deletion analysis showed that DNA sequences more than 85 bp upstream from the transcriptional start site are necessary for full induction of the operon. These upstream activating sequences are probably the targets of AcoR. Analysis of an acoR'-'lacZ strain of B. subtilis showed that the expression of acoR is not induced by acetoin and is repressed by the presence of glucose in the growth medium. Transcription of acoR is also negatively controlled by CcpA, a global regulator of carbon catabolite repression. A specific interaction of CcpA in the upstream region of acoR was demonstrated by DNase I footprinting experiments, suggesting that repression of transcription of acoR is mediated by the binding of CcpA to the promoter region of acoR.
The chicken fast skeletal troponin I gene: exon organization and sequence (1986)

The gene encoding the fast skeletal isoform of the chick troponin I (sTnI) protein has been sequenced and its organization into exons and introns established. The gene is approximately 4.5 kb in length and composed of 8 exons, the first of which contains solely 5' untranslated sequence. In addition to its major mRNA product, there is evidence that the sTnI gene encodes a second mRNA, present at low abundance levels in embryonic skeletal muscle. Sl nuclease protection and primer extension experiments indicate that the low abundance mRNA is initiated approximately 47 nucleotides upstream of the major transcriptional initiation site. Both mRNAs appear to encode identical sTnI polypeptides. A comparison of nucleotide sequence in the 5' flanking region of several muscle-specific genes, including the sTnI gene, reveals a heptanucleotide consensus sequence, 5'-CATTCCT-3', which is conserved in the 5' flanking regions of many vertebrate contractile protein genes.
Are angiogenic factors, cytokines, and soluble adhesion molecules prognostic factors in patients with renal cell carcinoma? (1997)

Angiogenesis has an important role in the progression of solid tumors. Therefore, we measured the blood levels (ELISA) of angiogenic factors [basic fibroblast growth factor (bFGF), hepatocyte growth factor/scatter factor, and vascular endothelial growth factor (VEGF)] and soluble adhesion molecules [E-selectin, intercellular adhesion molecule (ICAM-1), platelet endothelial cell adhesion molecule-1, and vascular cell adhesion molecule-1] in 76 consecutive patients with untreated renal cell carcinoma and 41 healthy controls to evaluate their prognostic value. The serum levels of bFGF, hepatocyte growth factor, and VEGF were significantly higher in patients with renal cancer than they were in healthy subjects. bFGF and VEGF values were significantly higher in patients with disseminated cancer (N+ and/or M+) than they were in those with undisseminated (M-N-) cancer: median = 27 pg/ml, range = 5-118, n = 15 versus median = 8 pg/ml, range = 1-149, n = 61 (P = 10(-4)) for bFGF; and median = 883 pg/ml, range = 200-2317, n = 15 versus median = 278 pg/ml, range = 0-1704, n = 61 (P = 0.006) for VEGF. The blood levels of ICAM-1 and vascular cell adhesion molecule-1 were significantly higher, and the levels of E-selectin and platelet endothelial cell adhesion molecule-1 were significantly lower in patients with renal cancer than they were in controls. Plasma ICAM-1 was higher in metastatic patients (M+) than they were in nonmetastatic (M-) patients: median = 687 ng/ml, range = 294-1091, n = 12 versus median = 408 ng/ml, range = 217-1375, n = 64 (P = 10(-4)). ICAM-1 and bFGF blood values were correlated with the size of the primary tumor. The interleukin 6 and tumor necrosis factor-alpha (TNF-alpha) values of these patients have been previously published and are included in the survival analysis. Univariate analysis showed that bFGF, ICAM-1, interleukin 6, and TNF-alpha, before treatment, were prognostic factors. In multivariate analysis for proportional hazard regression, only TNF-alpha was an independent prognostic indicator, with a normal plasma TNF-alpha being highly predictive for a good prognosis in patients with untreated renal cell carcinoma.