gebhart/patrepeval huggingface dataset:
Immunoglobulin E–independent Major Histocompatibility Complex–restricted T Cell Peptide Epitope–induced Late Asthmatic Reactions (1999)

Intradermal administration of short overlapping peptides derived from chain 1 of the cat allergen Fel d 1 (FC1P) that did not cross-link IgE, elicited isolated late asthmatic reactions with no visible early or late cutaneous response in 9/40 cat-allergic asthmatics. Four of the nine were human histocompatibility leukocyte antigen DR13-positive, as compared with only 1/31 nonreactors. The other five reactors expressed either DR1 or DR4. To confirm major histocompatibility complex restriction, fibroblast cell lines transfected with HLA-DR molecules were used to present FC1Ps to cat allergen-specific T cell lines derived from subjects before peptide injection. FC1P3 (peptide 28-44 of Fel d 1 chain 1) was recognized in the context of DR13 alleles (DRB1*1301, 1302) and induced specific T cell proliferation and IL-5 production. T cells from a DR1(+) responder proliferated and produced IL-5 in the presence of FC1P3 and DR1 (DRB1*0101) fibroblast cell lines, whereas T cells from a DR4(+) subject recognized FC1P2 (peptide 22-37) when presented by DRB1*0405. We conclude that short, allergen-derived peptides can directly initiate a major histocompatibility complex-restricted, T cell-dependent late asthmatic reaction, without the requirement for an early IgE/mast cell-dependent response, in sensitized asthmatic subjects.
Divergence and convergence of TGF‐β/BMP signaling (2001)

The transforming growth factor-beta (TGF-beta) superfamily includes more than 30 members which have a broad array of biological activities. TGF-beta superfamily ligands bind to type II and type I serine/threonine kinase receptors and transduce signals via Smad proteins. Receptor-regulated Smads (R-Smads) can be classified into two subclasses, i.e. those activated by activin and TGF-beta signaling pathways (AR-Smads), and those activated by bone morphogenetic protein (BMP) pathways (BR-Smads). The numbers of type II and type I receptors and Smad proteins are limited. Thus, signaling of the TGF-beta superfamily converges at the receptor and Smad levels. In the intracellular signaling pathways, Smads interact with various partner proteins and thereby exhibit a wide variety of biological activities. Moreover, signaling by Smads is modulated by various other signaling pathways allowing TGF-beta superfamily ligands to elicit diverse effects on target cells. Perturbations of the TGF-beta/BMP signaling pathways result in various clinical disorders including cancers, vascular diseases, and bone disorders.
Real‐Time Caustics (2003)

Abstract We present a new algorithm to render caustics. The algorithm discretizes the specular surfaces into samplepoints. Each of the sample points is treated as a pinhole camera that projects an image of the incoming lightonto the diffuse receiver surfaces. Anti‐aliasing is performed by considering the local surface curvature at thesample points to filter the projected images. The algorithm can be implemented using programmable texturemapping hardware. It allows to render caustics in fully dynamic scenes in real‐time on current PC hardware. Categories and Subject Descriptors: I.3.3 [Computer Graphics]: Picture/Image Generation — Display Algorithms;I.3.7 [Computer Graphics]: Three‐Dimensional Graphics and Realism
Nivolumab (N) plus ipilimumab (I) as first-line (1L) treatment for advanced (adv) NSCLC: 2-yr OS and long-term outcomes from CheckMate 012. (2017)

9093 Background: The fully human anti–PD-1 antibody N offers long-term OS benefit in patients (pts) with previously treated adv NSCLC. Adding I (anti–CTLA-4 antibody) to N has been shown to improve clinical activity vs either agent alone in multiple tumor types. We present long-term data for 1L N+I treatment of pts with adv NSCLC from CheckMate 012. Methods: In two cohorts in this phase 1 study, pts with recurrent stage IIIb/IV, chemotherapy-naive NSCLC and ECOG PS 0–1 received N 3 mg/kg Q2W combined with I 1 mg/kg Q12W (n=38) or Q6W (n=39) until disease progression, unacceptable toxicity, or consent withdrawal. The primary endpoint was safety and tolerability. Secondary endpoints included investigator-assessed ORR (RECIST v1.1) and PFS. Exploratory endpoints included OS and efficacy by tumor PD-L1 expression. Results: In the N+I Q12W and N+I Q6W cohorts, respectively, 42% and 31% of pts experienced grade 3–4 treatment-related (TR) AEs; 18% in each cohort discontinued due to any-grade TRAEs. The most frequently reported any-grade TRAEs were pruritus (26%) and diarrhea (21%) with N+I Q12W, and fatigue (26%) and diarrhea (23%) with N+I Q6W. There were no TR deaths. N+I showed promising efficacy (table). While efficacy was enhanced with increasing PD-L1 expression, activity was noted in pts with &lt;1% PD-L1 (table). Of 6 complete responses (CRs), 3 were in pts with &lt;1% PD-L1. Conclusions: 1L therapy with N+I demonstrates a manageable safety profile and promising, durable efficacy (including pathological CRs) in adv NSCLC; efficacy was enhanced in pts with ≥1% PD-L1 tumor expression. Longer follow-up data, including 2-yr OS and characteristics of long-term survivors, will be presented. Clinical trial information: NCT01454102. [Table: see text]
The role of humoral immunity in Cryptosporidium spp. infection. Studies with B cell-depleted mice. (1990)

Cryptosporidiosis has become an important infection in man, particularly among very young or immunocompromised individuals. Here, the protective role of antibody responses to Cryptosporidium was examined using a well established murine model of cryptosporidiosis. Although normal neonatal BALB/c mice exhibited good IgM and IgG serum antibody responses, no correlation could be drawn between the intensity of these responses and the severity or duration of cryptosporidiosis. Moreover, B cell-deficient (anti-mu-treated) neonatal BALB/c mice did not differ from untreated or normal rabbit Ig-treated, age-matched controls in the onset, peak, or duration of cryptosporidiosis. The apparent absence of a role for antibody in these self resolving infections was supported by the lack of susceptibility of anti-mu-treated adult BALB/c to attempted infection with doses of Cryptosporidium 10 times the dose required to infect 100% of normal (Ig producing) neonates. The results suggest that the role of specific in vivo antibody responses in the resolution of murine infection with this coccidian parasite is minor and that the likelihood of success for cryptosporidial vaccines aimed solely at enhancing in vivo antibody production may be limited.
Tissue-specific expression of apolipoprotein A-I (ApoA-I) is regulated by the 5′-flanking region of the human ApoA-I gene. (1988)

We have isolated and characterized a 2.5-kilobase pairs genomic DNA fragment which includes the 5'-flanking region and the first and second exons of the human apolipoprotein (apo) A-I gene. The major transcriptional start site was determined by primer extension analysis and is 235 base pairs (bp) upstream from the AUG translational start codon in liver and 234 bp upstream in the intestine. TATA box-like and CAT box-like sequences and two GC box sequences are present in the intestine 30, 108, 220, and 440 bp upstream, respectively, from the transcriptional start site. Fragments of 570 bp (-487 to +71) and 2.15 kilobase pairs (-2067 to +99) containing the 5'-flanking region of the apoA-I gene were fused upstream to the bacterial chloramphenicol acetyltransferase (CAT) gene. These constructs, designated pA-I(0.6)CAT and pA-I(2.2)CAT, respectively, were introduced into human oral epithelial cells (KB), mouse NIH 3T3 cells, Chinese hamster ovary (CHO) cells, human hepatoma cells (Hep G2), human duodenal epithelial cells (Hutu 80), and human colonic epithelial cells (Caco-2) by calcium phosphate coprecipitation. When compared with control vectors, highly efficient CAT expression of both the pA-I(0.6)CAT and pA-I(2.2)CAT constructs were observed only in cells derived from the liver (Hep G2) and intestine (Caco-2), which is consistent with the tissue specificity of expression of the native gene. Analysis of deletion mutants of the human apoA-I 5'-flanking region revealed that: 1) the region from -250 to -199 bp, from -487 to -413 bp, and -1021 to -691 bp upstream from the transcriptional start site contain sequences required for maximum gene expression; and 2) the regions from -2067 to -1476 bp and -199 to -80 bp contain the sequences required for tissue-specific repression of apoA-I gene expression in non-apoA-I producing cells.
Mapping the epitope of a functional P-selectin monoclonal antibody (LYP20) to a short complement-like repeat (SCR 4) domain: use of human–mouse chimaera and homologue-replacement mutagenesis (1998)

P-selectin (CD62P), an adhesion molecule localized in platelet alpha-granules and endothelial cell Weibel-Palade bodies, is rapidly expressed on the surface of activated cells. This adhesion molecule, a member of the selectin family, mediates leucocyte interactions with activated platelets or endothelial cells. The aim of this study was to identify and characterize the epitope of a functional blocking P-selectin monoclonal antibody (mAb), LYP20. LYP20 recognizes human or rat, but not mouse, P-selectin. Human/mouse chimaeras and wild-type constructs, modified by homologue replacement mutagenesis, were expressed in COS cells. Blocking anti-(P-selectin) mAbs (G1, G3 or CLB-thromb/6) were observed, by flow cytometry, to bind to the lectin-like domain. In contrast, LYP20 was found to bind to one of the P-selectin short complement-like repeats (SCR domain 4). Homologue replacement mutagenesis of SCR domain 4 (region delineated by amino acid residues 359-457) identified three amino acids (Cys412-->Ser, Cys416-->Ser or Arg415-->Lys) as being implicated in the LYP20 epitope. Deleting the region bearing the LYP20 epitope, from a wild-type CD62P construct, showed a decrease in polymorphonuclear leucocyte (PMNL) binding to transfected COS cells. In addition, mutation of one of the three amino acids, implicated in the LYP20 epitope, markedly affected PMNL binding to transfected COS cells but did not affect the binding of mAbs G1 and CLB-thromb/6. These results are the first to indicate (1) that a functional blocking anti-P-selectin mAb binds to SCR 4, a site other than the lectin-like/epidermal growth factor-like domain, and (2) that SCR domain 4 has a functional role in P-selectin-leucocyte interactions.
Specific human cellular immunity to bcr-abl oncogene-derived peptides (1996)

Chronic myelogenous leukemia (CML) cells are characterized by a t(9;22) translocation, which can encode one of two chimeric P210 bcr-abl fusion proteins, comprising products of either the b2a2 or the b3a2 exon junction. The junctional sequences represent potentially immunogenic tumor-specific antigens. Despite their intracellular location, the fusion proteins might be recognized immunologically by T lymphocytes if peptides, derived from these unique sequences, are capable of presentation by the major histocompatibility complex molecules. We previously found that four peptides, 9 to 11 amino acids long, spanning the b3a2 CML breakpoint bind with high or intermediate affinity to purified HLA class I molecules A3, A11, B8, or both A3 and A11. We tested the ability of these peptides to elicit specific class I restricted cytotoxic T lymphocytes (CTLs) in vitro in HLA-matched healthy donors. In addition, a longer b3a2 CML-breakpoint-derived peptide, 25 aminoacids in length (b3a2-25), was studied for its ability to induce peptide-specific, class II-mediated, T-cell proliferation. In four of four HLA-A3 donors tested, CML-A3/A11-peptide specific CTLs were induced that killed an allogeneic HLA-A3-matched peptide pulsed leukemia cell line. In two of three HLA-A3 donors, the CML-A3/A11 peptide was able to induce killing of autologous and allogeneic HLA-matched peptide-pulsed peripheral blood mononuclear cells (PBMC). CML-A3 peptide induced peptide specific CTLs in one of the four HLA A3 donors tested. No killing was observed in two HLA-B8 and two HLA-A11 donors. PBMC from seven donors were also tested for anti b3a2-25 peptide proliferation in a thymidine incorporation assay. Specific proliferation was detected in three donors, all of the HLA-DR11 haplotype. These data represent the first evidence of a cytolytic human immune response against CML bcr-abl oncogene-derived peptides and provide a rationale for developing peptide-based vaccines for this disease.
Antioxidant Properties of Catechins and Green Tea Extracts in Model Food Emulsions (1997)

Extraction of green tea with hot water provided an extract that was highly effective as an antioxidant for an oil-in-water emulsion at pH 5.5 during prolonged storage (40 days). Other components besides epigallocatechin gallate (EGCG) and epicatechin gallate (ECG) made important contributions to the antioxidant activity of the extract in an oil-in-water emulsion, since ECG, when pure, had no significant antioxidant activity (p > 0.05) and EGCG was completely oxidized within 15 days. Myricetin had a greater antioxidant effect in this system than EGCG or ECG at a concentration of 10-4 M in the absence of ferric ions, but all three flavonoids exhibited prooxidant effects in the presence of ferric ions. Keywords: Antioxidants; epigallocatechin gallate; epicatechin gallate; green tea; emulsions
Multiple Hypothesis Tracking Revisited (2015)

This paper revisits the classical multiple hypotheses tracking (MHT) algorithm in a tracking-by-detection framework. The success of MHT largely depends on the ability to maintain a small list of potential hypotheses, which can be facilitated with the accurate object detectors that are currently available. We demonstrate that a classical MHT implementation from the 90's can come surprisingly close to the performance of state-of-the-art methods on standard benchmark datasets. In order to further utilize the strength of MHT in exploiting higher-order information, we introduce a method for training online appearance models for each track hypothesis. We show that appearance models can be learned efficiently via a regularized least squares framework, requiring only a few extra operations for each hypothesis branch. We obtain state-of-the-art results on popular tracking-by-detection datasets such as PETS and the recent MOT challenge.
Phase I/II Evaluation of Nevirapine Alone and in Combination with Zidovudine for Infection with Human Immunodeficiency Virus (1995)

In these Phase I/II open-label clinical trials, 62 persons with human immunodeficiency virus type 1 (HIV-1) infection and CD4+ cell counts < 400/mm3 received nevirapine at doses of 12.5, 50, and 200 mg/day, alone or in combination with zidovudine, 200 mg q8h. Nevirapine was well tolerated in the doses tested. Mean steady-state trough levels were 0.23, 1.1, and 1.9 micrograms/ml for the 12.5, 50, and 200 mg/day doses, respectively. Early suppression of p24 antigen levels and increase in CD4+ cell count were reversed following rapid emergence of virus less susceptible to nevirapine. Resistant strains were isolated from all participants by 8 weeks. Nevertheless, reduction of p24 antigen levels to < 50% of baseline values persisted for 12 weeks or more in four of seven persons who received 200 mg nevirapine/day in combination with zidovudine: these individuals had been antigenemic on long-term zidovudine therapy. This study demonstrates a direct relationship between drug resistance and effects on surrogate markers in HIV-1 infection.
Architecture Tradeoffs in High Density Microstimulators for Retinal Prosthesis (2005)

Electrical stimulation of retinal neurons has been identified as a form of visual prosthesis to restore vision in blind patients affected by retinitis pigmentosa (RP) and age-related macular degeneration (AMD) through several studies and experiments. This paper presents the different architectures of microstimulator for high density retinal prosthesis considering both the biomedical and circuit perspectives. The choices for the key aspects of the microstimulator - location of the chip in the eye, electrode configuration, method of stimulation, demultiplexing, stimulation sequence, and communication protocol - are discussed along with the associated tradeoffs for each of them. In addition, a 60-output microstimulator for an implantable retinal prosthesis to be used in future clinical trials, fabricated in 1.2-mum CMOS technology and its measurement results are presented. The chip consists of 60 independently programmable output drivers and a digital controller for managing run-time and configuration data
A Versatile Set of Aminooxy Amino Acids for the Synthesis of Neoglycopeptides (2003)

Four N-alkylaminooxy amino acids have been synthesized in 22-56% overall yield from readily available amino acid precursors. Each amino acid can be efficiently incorporated into peptides using Boc-chemistry-based solid-phase peptide synthesis, and in three of the four cases the resulting peptides can be chemoselectively glycosylated at the aminooxy side chains to generate neoglycopeptides. The range of N-alkylaminooxy amino acids prepared allows attachment of sugars at two-, three-, or four-atom distances from the peptide backbone, and each ensures that attached sugars adopt cyclic conformations. These derivatives provide convenient access to arrays of biologically relevant neoglycopeptides that may be used to probe the influence of attached sugars on the structure and function of peptides and proteins.
Trusted Computing Platforms: TCPA Technology in Context (2002)

As businesses stake their very existence on the Internet, PCs, PDAs, and other key computing platforms, the trustworthiness of these platforms has become a vital concern. In response, the Trusted Computing Platform Alliance (TCPA) has delivered a complete specification for building trusted computing platforms atop trusted hardware. In Trusted Computing Platforms, leaders of the initiative illuminate TCPA for every systems developer and decision-maker. They place TCPA in context, outlining its goals, techniques, and powerful implications for the future. What trusted computing platforms are, how they work, and what problems they will solve Transforming standard platforms into trusted platforms cost-effectively Scenarios for managers: TCPA applications in the security-focused business Protected storage: how TCPA can ensure the confidentiality of stored data Software integrity: ensuring that a system's software environment hasn't been tampered with Trust mechanisms in a trusted platform: functional descriptions, advantages, and overhead Trusted platforms in practice: TCPA for developers and technical professionals How trusted platforms can be used to protect user privacy The TCPA initiative: its history, status, and next steps forwardBacked by an extraordinary range of industry leaders, TCPA offers the first complete, cost-effective, and globally applicable solution for trusted computing. Whether you develop new systems or apply them in business or government, you need to understand this technology-and with this book, you will.
Isolation, Microinjection, and Transfer of Mouse Blastocysts (2003)

Genetically modified mice by means of homologous recombination in embryonic stem (ES) cells are generated by injection of manipulated ES cells into recipient blastocysts. The injected blastocysts, following reintroduction into recipient foster mice, will produce chimeric mice in which the manipulated ES cells populate the germline and transmit the induced mutation to the offspring. Crossing of the chimeras' offspring bearing the targeted mutation in heterozygosis will ultimately produce mice homozygous for the specific genetic mutation. Here we describe the steps and procedures required to generate the chimeric mice leading to the transfer of a genetic mutation to the mouse germline.
Natural variants of the human papillomavirus type 16 E6 protein differ in their abilities to alter keratinocyte differentiation and to induce p53 degradation (1996)

Three naturally occurring variant human papillomavirus type 16 (HPV-16) E6 proteins, which contained amino acid substitutions predominantly near the N terminus, exhibited significant differences in their abilities to abrogate keratinocyte differentiation in response to serum and calcium and to induce the degradation of p53 in vitro. One variant surpassed the reference E6 protein in its ability to abrogate keratinocyte differentiation responses, whereas another showed a reduction in this activity. Interestingly, the biological activities of the HPV-16 E6 proteins and their abilities to induce p53 degradation in vitro were directly correlated. These results demonstrate that naturally occurring variants of HPV-16 differ in biological and biochemical properties which might result in differences in pathogenicity.
S100A1 Expression in Ovarian and Endometrial Endometrioid Carcinomas Is a Prognostic Indicator of Relapse-Free Survival (2009)

We sought to investigate the expression levels of S100A1 in ovarian cancer cell lines and tissues to correlate S100A1 with subtype, stage, grade, and relapse-free survival. S100A1 messenger RNA and protein were up-regulated in ovarian cancer cell lines and tumors compared with normal ovarian cell lines and tissues by gene microarray analysis, reverse transcriptase-polymerase chain reaction, quantitative reverse transcriptase-polymerase chain reaction, and Western immunoblotting. In the study, 63.7% of serous, 21.2% of clear cell, 11.2% of endometrioid, and 3% of mucinous ovarian (1/31) cancers were S100A1+ by immunohistochemical staining of tissue microarrays (n = 500). S100A1 expression increased with increasing Silverberg grade but not stage in serous tumors. Endometrial tissue microarrays (n = 127) were 9.4% S100A1+; no correlation with stage or grade and S100A1 was found. In the endometrioid subtype of ovarian and endometrial cancers, relapse-free survival was decreased for patients with S100A1+ tumors. These data suggest that S100A1 is a marker for poor prognosis of endometrioid subtypes of cancer.
Boolean functions: with engineering applications and computer programs (1989)

Modern systems engineering (e. g. switching circuits design) and operations research (e. g. reliability systems theory) use Boolean functions with increasing regularity. For practitioners and students in these fields books written for mathe maticians are in several respects not the best source of easy to use information, and standard books, such as, on switching circuits theory and reliability theory, are mostly somewhat narrow as far as Boolean analysis is concerned. Further more, in books on switching circuits theory the relevant stochastic theory is not covered. Aspects of the probabilistic theory of Boolean functions are treated in some works on reliability theory, but the results deserve a much broader interpre tation. Just as the applied theory (e. g. of the Laplace transform) is useful in control theory, renewal theory, queueing theory, etc., the applied theory of Boolean functions (of indicator variables) can be useful in reliability theory, switching circuits theory, digital diagnostics and communications theory. This book is aimed at providing a sufficiently deep understanding of useful results both in practical work and in applied research. Boolean variables are restricted here to indicator or O/l variables, i. e. variables whose values, namely 0 and 1, are not free for a wide range of interpretations, e. g. in digital electronics 0 for L ==low voltage and 1 for H == high voltage.
Impaired plasticity of cortical dendritic spines in P301S tau transgenic mice (2013)

Dendritic spine plasticity and morphology are altered in layer V cortical neurons of P301S tau transgenic mice in vivo. This does not coincide with the detection of hyperphosphorylated tau in dendritic spines.