gebhart/patrepeval huggingface dataset:
Isolation and identification of an α2 subclass lymphotoxin (LT) subunit from the high-molecular-weight (complex) human LT class (1984)

The high-molecular-weight (MW) complex class (MW = greater than or equal to 200,000) of lymphotoxin (LT) may be involved in the process of lymphocyte-mediated cytolysis. This LT class was produced by concanavalin A-stimulated human adenoid and tonsil lymphocytes in vitro and purified approximately 1000 fold by a scheme employing lectin affinity chromatography on concanavalin A-Sepharose, negative hydrophobic affinity chromatography on phenyl-Sepharose, and molecular sieving on Ultrogel AcA 44. A cell-lytic subunit, termed C-alpha toxin, was dissociated from this partially purified complex LT (Cx) preparation. The identification of C-alpha toxin as an alpha 2 LT form was established by its comigration with the alpha 2 LT form during native polyacrylamide gel electrophoresis (PAGE), molecular sieving, and isoelectricfocusing. In addition, C-alpha toxin was neutralized by antiserum raised against purified alpha 2 LT, and the latter was neutralized by antiserum raised against C-alpha toxin. Furthermore, preliminary evidence indicates that both alpha 2 LT and C-alpha toxin are composed of peptides with apparent MW of approximately 69,000. Additional data indicate the Cx LT form is composed of alpha 2 LT and other subunits.
Significant improvement of electron mobility in organic thin-film transistors based on thiazolothiazole derivative by employing self-assembled monolayer (2007)

n -type organic thin-film transistors based on a thiazolothiazole derivative were fabricated on a SiO2 gate insulator treated with n-alkyl self-assembled monolayers (SAMs), which were composed of various alkyl chain lengths. The field-effect electron mobility increased depending on the alkyl chain length of the SAMs. A long alkyl chain significantly improved the on current and electron mobility. The highest electron mobility of 1.2cm2∕Vs and on/off ratio of 107 were achieved with an alkyl chain longer than that of tetradecyl-trichlorosilane. This result is attributed to the suppression of the influence of electron trap sites on the SiO2 gate insulator by employing the SAM with the long alkyl chain.
IL-7 receptor blockade reverses autoimmune diabetes by promoting inhibition of effector/memory T cells (2012)

To protect the organism against autoimmunity, self-reactive effector/memory T cells (T(E/M)) are controlled by cell-intrinsic and -extrinsic regulatory mechanisms. However, how some T(E/M) cells escape regulation and cause autoimmune disease is currently not understood. Here we show that blocking IL-7 receptor-α (IL-7Rα) with monoclonal antibodies in nonobese diabetic (NOD) mice prevented autoimmune diabetes and, importantly, reversed disease in new-onset diabetic mice. Surprisingly, IL-7-deprived diabetogenic T(E/M) cells remained present in the treated animals but showed increased expression of the inhibitory receptor Programmed Death 1 (PD-1) and reduced IFN-γ production. Conversely, IL-7 suppressed PD-1 expression on activated T cells in vitro. Adoptive transfer experiments revealed that T(E/M) cells from anti-IL-7Rα-treated mice had lost their pathogenic potential, indicating that absence of IL-7 signals induces cell-intrinsic tolerance. In addition to this mechanism, IL-7Rα blockade altered the balance of regulatory T cells and T(E/M) cells, hence promoting cell-extrinsic regulation and further increasing the threshold for diabetogenic T-cell activation. Our data demonstrate that IL-7 contributes to the pathogenesis of autoimmune diabetes by enabling T(E/M) cells to remain in a functionally competent state and suggest IL-7Rα blockade as a therapy for established T-cell-dependent autoimmune diseases.
MEK Inhibition Leads to PI3K/AKT Activation by Relieving a Negative Feedback on ERBB Receptors (2012)

The phosphoinositide 3-kinase (PI3K)/AKT and RAF/MEK/ERK signaling pathways are activated in a wide range of human cancers. In many cases, concomitant inhibition of both pathways is necessary to block proliferation and induce cell death and tumor shrinkage. Several feedback systems have been described in which inhibition of one intracellular pathway leads to activation of a parallel signaling pathway, thereby decreasing the effectiveness of single-agent targeted therapies. In this study, we describe a feedback mechanism in which MEK inhibition leads to activation of PI3K/AKT signaling in EGFR and HER2-driven cancers. We found that MEK inhibitor-induced activation of PI3K/AKT resulted from hyperactivation of ERBB3 as a result of the loss of an inhibitory threonine phosphorylation in the conserved juxtamembrane domains of EGFR and HER2. Mutation of this amino acid led to increased ERBB receptor activation and upregulation of the ERBB3/PI3K/AKT signaling pathway, which was no longer responsive to MEK inhibition. Taken together, these results elucidate an important, dominant feedback network regulating central oncogenic pathways in human cancer.
The influence of abnormally high reservoir attenuation on the AVO signature (2005)

The direct detection of hydrocarbons with the seismic technique is one of the main goals of current geophysical research. Amongst the many direct hydrocarbon indicators which have been proposed, the AVO technique has received by far the greatest attention in the literature. The technique has inspired confidence in large part through its ability to relate the observed phenomena directly to rock and fluid properties through robust seismic modeling and rock physics relationships.
造成的不平均：美国的工薪危机：评论 (2000)

奥卡姆的威廉的警句经常被乱用，当这位哲人说：“不要增殖假设”时。他的意思可能不是说。任何现象的第一个似乎合理的解释在所有其它的解释之上。经济学职业是那些用似乎合理代替研究，用重复代替证据，最知名的集中的一个产地。在加尔布雷斯新近的一本著作中。他揭露了近来经济的神话中更固执的且更有突害的一个。
Autophagy inhibitor Lys05 has single-agent antitumor activity and reproduces the phenotype of a genetic autophagy deficiency (2012)

Autophagy is a lysosome-dependent degradative process that protects cancer cells from multiple stresses. In preclinical models, autophagy inhibition with chloroquine (CQ) derivatives augments the efficacy of many anticancer therapies, but CQ has limited activity as a single agent. Clinical trials are underway combining anticancer agents with hydroxychloroquine (HCQ), but concentrations of HCQ required to inhibit autophagy are not consistently achievable in the clinic. We report the synthesis and characterization of bisaminoquinoline autophagy inhibitors that potently inhibit autophagy and impair tumor growth in vivo. The structural motifs that are necessary for improved autophagy inhibition compared with CQ include the presence of two aminoquinoline rings and a triamine linker and C-7 chlorine. The lead compound, Lys01, is a 10-fold more potent autophagy inhibitor than HCQ. Compared with HCQ, Lys05, a water-soluble salt of Lys01, more potently accumulates within and deacidifies the lysosome, resulting in impaired autophagy and tumor growth. At the highest dose administered, some mice develop Paneth cell dysfunction that resembles the intestinal phenotype of mice and humans with genetic defects in the autophagy gene ATG16L1, providing in vivo evidence that Lys05 targets autophagy. Unlike HCQ, significant single-agent antitumor activity is observed without toxicity in mice treated with lower doses of Lys05, establishing the therapeutic potential of this compound in cancer.
Recognition and Response in the Plant Immune System (2003)

Molecular communication between plants and potential pathogens determines the ultimate outcome of their interaction. The directed delivery of microbial molecules into and around the host cell, and the subsequent perception of these by the invaded plant tissue (or lack thereof), determines the difference between disease and disease resistance. In theory, any foreign molecule produced by an invading pathogen could act as an elicitor of the broad physiological and transcriptional re-programming indicative of a plant defense response. The diversity of elicitors recognized by plants seems to support this hypothesis. Additionally, these elicitors are often virulence factors from the pathogen recognized by the host. This recognition, though genetically as simple as a ligand-receptor interaction, may require additional host proteins that are the nominal targets of virulence factor action. Transduction of recognition probably requires regulated protein degradation and results in massive changes in cellular homeostasis, including a programmed cell death known as the hypersensitive response that indicates a successful, if perhaps over-zealous, disease resistance response.
Directional Resolution of Synthetic Holliday Structures by the Cre Recombinase (2001)

The Cre recombinase of bacteriophage P1 cleaves its target site, loxP, in a defined order. Recombination is initiated on one pair of strands to form a Holliday intermediate, which is then resolved by cleavage and exchange of the other pair of strands to yield recombinant products. To investigate the influence of the loxP sequence on the directionality of resolution, we constructed synthetic Holliday (chi) structures containing either wild-type or mutant lox sites. We found that Cre preferentially resolved the synthetic wild-type chi structures on a particular pair of strands. The bias in the direction of resolution was dictated by the asymmetric loxP sequence since the resolution bias was abolished with symmetric lox sites. Systematic substitutions of the loxP site revealed that the bases immediately 5' to the scissile phosphodiester bonds were primarily responsible for the directionality of resolution. Interchanging these base pairs was sufficient to reverse the resolution bias. The Cre-lox co-crystal structures show that Lys(86) makes a base-specific contact with guanine immediately 5' to one of the scissile phosphates. Substituting Lys(86) with alanine resulted in a reduction of the resolution bias, indicating that this amino acid is important for establishing the bias in resolution.
Production of Plant Non-protein Amino Acids by Recombinant Enzymes of Sequential Biosynthetic Reactions in Bacteria. (1997)

We constructed the co-expression vector, pFK4, in which two cDNAs encoding serine acetyltransferase (SATase) and beta-(pyrazol-1-yl)-L-alanine/L-cysteine synthase (beta-PA/CSase) from Citrullus vulgaris (watermelon) were over-expressed under the transcriptional control of T7 promoter in Escherichia coli. Accumulation of both SATase and beta-PA/CSase in soluble extracts of E. coli was confirmed by immunoblotting. The high enzymatic activities of SATase and L-cysteine synthase (CSase) were detected in cell-free extracts of E. coli carrying pFK4. The activities of the formation of beta-PA and L-mimosine, plant non-protein amino acids, from O-acetyl-L-serine (OAS) and the precursor heterocyclic compounds, pyrazole and 3,4-dihydroxypyridine, were also found in the extracts. beta-PA was also produced in vivo from L-serine and pyrazole as precursors by E. coli cells transformed with pFK4. beta-PA was accumulated mainly in the extra-cellular culture medium. The pronounced accumulation of L-cysteine and L-methionine was observed in the cells transformed with pFK4. Additionally, we also constructed vectors which carried chimeric genes encoding fusion proteins of SATase and beta-PA/CSase. However, the fusion proteins tended to form insoluble inclusion bodies and thus to exhibit only weak enzymatic activities. The successful results of pFK4 shows the way to create a new sequential biosynthetic pathway of plant specific amino acids in bacterial cells by means of recombinant DNA technology.
Measles Virus Epitope Presentation by HLA: Novel Insights into Epitope Selection, Dominance, and Microvariation (2015)

Immunity to infections with measles virus (MV) can involve vigorous human leukocyte antigen (HLA) class I-restricted CD8(+) cytotoxic T cell (CTL) responses. MV, albeit regarded monotypic, is known to undergo molecular evolution across its RNA genome. To address which regions of the MV proteome are eligible for recognition by CD8(+) CTLs and how different HLA class I loci contribute to the epitope display, we interrogated the naturally processed and presented MV peptidome extracted from cell lines expressing in total a broad panel of 16 different common HLA-A, -B, and -C molecules. The repertoire and abundance of MV peptides were bona fide identified by nanoHPLC-MS/MS. -Eighty-nine MV peptides were discovered and assignment to an HLA-A, -B, or -C allele, based on HLA-peptide affinity prediction, was in most cases successful. Length variation and presentation by multiple HLA class I molecules was common in the MV peptidome. More than twice as many unique MV epitopes were found to be restricted by HLA-B than by HLA-A, while MV peptides with supra-abundant expression rates (>5,000 cc) were rather associated with HLA-A and HLA-C. In total, 59 regions across the whole MV proteome were identified as targeted by HLA class I. Sequence coverage by epitopes was highest for internal proteins transcribed from the MV-P/V/C and -M genes and for hemagglutinin. At the genome level, the majority of the HLA class I-selected MV epitopes represented codons having a higher non-synonymous mutation rate than silent mutation rate, as established by comparison of a set of 58 unique full length MV genomes. Interestingly, more molecular variation was seen for the epitopes expressed at rates ≥1,000 cc. These data for the first time indicate that HLA class I broadly samples the MV proteome and that CTL pressure may contribute to the genomic evolution of MV.
Angiotensin converting enzyme inhibitors and the cardiovascular system. (1992)

ACE inhibitors are uniquely valuable first-line antihypertensive agents, especially in patients with cardiovascular risk.
A stacked memory device on logic 3D technology for ultra-high-density data storage (2011)

We have demonstrated, for the first time, a novel three-dimensional (3D) memory chip architecture of stacked-memory-devices-on-logic (SMOL) achieving up to 95% of cell-area efficiency by directly building up memory devices on top of front-end CMOS devices. In order to realize the SMOL, a unique 3D Flash memory device and vertical integration structure have been successfully developed. The SMOL architecture has great potential to achieve tera-bit level memory density by stacking memory devices vertically and maximizing cell-area efficiency. Furthermore, various emerging devices could replace the 3D memory device to develop new 3D chip architectures.
Linkage mapping of benign familial infantile convulsions (BFIC) to chromosome 19q (1997)

Benign familial infantile convulsions (BFIC) are an autosomal-dominant epileptic syndrome characterized by an age of onset within the first year of life. Although they were first reported in families of Italian descent, BFIC have also been described in non-Italian families. We have mapped the BFIC gene to chromosome 19 by linkage analysis in five Italian families with a maximum two-point lod score of 6.36 at D19S114; maximum multipoint lod scores > 8 were obtained for the interval D19S250-D19S245. BFIC are therefore the third idiopathic partial epileptic syndrome to be mapped on the human genome.
Efficient Extraction of Robust Image Features on Mobile Devices (2007)

Recent convergence of imaging sensors and general purpose processors on mobile phones creates an opportunity for a new class of augmented reality applications. Robust image feature extraction is a crucial enabler of this type of systems. In this article, we discuss an efficient mobile phone implementation of a state-of-the-art algorithm for computing robust image features called SURF. We implement several improvements to the basic algorithm that significantly improve its performance and reduce its memory footprint making the use of this algorithm on the mobile phone practical. Our prototype implementation has been applied to several practical applications such as image search, object recognition and augmented reality applications.
How Were Motorways Specified? A Comment on the Special Section on Roads (2012)

A motorway is universally defined as a road specifically provided for motor traffic, with dual carriageways separating oncoming traffic, with all intersections grade-separated, and with no access from abutting properties.1 However, these three papers on motorway history will suggest that this definition is not nearly as simple and straightforward as we might previously have assumed. The papers are each significant contributions to our understanding of European motorway development and usefully present the planning and development of motorways from very different perspectives.
Phorbol ester-induced expression, phosphorylation, and translocation of protein-tyrosine-phosphatase 1C in HL-60 cells. (1994)

PTP1C, a protein-tyrosine-phosphatase (PTP) containing two Src homology 2 domains, is expressed at high levels in HL-60 human promyelocytic leukemia cells. It represents 0.15% of total protein in a postnuclear extract and corresponds to approximately 70% of phosphatase activity measured with p-nitrophenyl phosphate at pH 5.0. Upon differentiation of HL-60 cells to macrophages induced by phorbol 12-myristate 13-acetate (PMA), the activity and expression levels of PTP1C increase 2- to 3-fold. Furthermore, PTP1C is phosphorylated on serine residues upon PMA treatment. While the enzyme localizes entirely in the cytosolic fraction in untreated cells, 30-40% is found in a particulate fraction following differentiation. Immunofluorescent staining of differentiated cells before and after digitonin treatment indicates that the bound enzyme localizes on the plasma membrane. The time courses of induction and translocation of PTP1C correlate with the differentiation process. The PMA-induced differentiation is inhibited by sodium orthovanadate, suggesting the PTPs are required for this process.
CD4+ T cells from peripheral blood of a melanoma patient recognize peptides derived from nonmutated tyrosinase. (1998)

Tyrosinase is an antigen that is expressed by normal melanocytes as well as melanoma cells, against which responses by autologous T cells have been detected. Although CD4+ T cells play an important role in tumor immunity in animal tumor models, little information about CD4+ T-cell immunity against human tumors exists. Here, we report that CD4+ T cells from the peripheral blood of a patient with melanoma respond to synthetic peptides derived from nonmutated tyrosinase. T-cell clones were generated that recognized the tyrosinase p386-406 peptide when it was presented by the HLA-DR15 (DRB1*1501) molecule. The CD4+ T-cell clone also recognized autologous EBV-transformed B-lymphoblastoid cell lines that had been pulsed with the lysate of melanoma cells. The synthetic tyrosinase p386-406 peptide was capable of binding to HLA-DR15 (DRB1*1501) molecules on cell surface of DR15 homozygous cells. Thus, the finding that nonmutated tyrosinase peptides are immunogenic in a melanoma patient may provide the basis for the development of cancer immunotherapy, based on knowledge of synthetic tumor-associated peptide antigens.
Studies on the Specific Fibrinolytic Effect of Human Extrinsic (Tissue-Type) Plasminogen Activator in Human Blood and in Various Animal Species in Vitro (1981)

Human extrinsic (tissue-type) plasminogen activator (EPA) was highly purified from the culture fluid of a human melanoma cell line, both as a one-chain or as a two-chain molecule. Its specific fibrinolytic effect on human whole blood clots or plasma clots with different degrees of fibrin crosslinking was evaluated in an in vitro system, composed of a 125I-fibrin labeled clot, hanging in circulating human plasma. After infusion of EPA (30 IU per ml over 3 hrs), non-crosslinked clots lysed more extensively (75-100 percent in 5 hrs) than totally-crosslinked clots (50-65 percent), and no difference was found between one-chain or two-chain EPA. The extent of lysis of totally-crosslinked human or animal plasma clots hanging in autologous plasma induced by EPA varied markedly form one species ot the other. When 90 IU of EPA were infused over 3 hrs, crosslinked human plasma clots dissolved for over 95 percent within 5 hrs. Under comparable conditions, the degree of lysis was 80 percent in primate plasma (cynomolgus fascicularis), 60 percent in cat and rabbit plasma, 30 percent in dog plasma and only 10 percent in rat plasma. Systemic activation of the fibrinolytic system in the circulating plasmas was minor and dose-dependent in all species, but complete fibrinogen breakdown was not observed in any species following infusion of up to 90 IU EPA per ml plasma. It is concluded that the human system is more susceptible to EPA induced fibrinolysis than the other animal systems which were investigated, and that even totally-crosslinked clots can be lysed after infusion of EPA.
T-cells for tumor therapy can be obtained from antigen-loaded sponge implants. (1994)

The aim of the current study was to evaluate the therapeutic use of tumor-specific T-cells obtained from s.c. Ag (antigen)-loaded sponge implants. Naive C57BL/6 mice were implanted with small, polyurethane sponges containing irradiated FBL-3 tumor cells. On day 10, cells that had accumulated in the sponges were harvested and tested for specific cytolytic and proliferative function in vitro. The results demonstrated that CD8+ and CD4+ T-cells immune to FBL-3 could both be primed in and obtained from the Ag-loaded sponge implants. Limiting dilution analysis demonstrated that the frequency of FBL-3-specific cytotoxic T-lymphocytes elicited from Ag-loaded sponges was four times greater than the frequency from draining lymph nodes and at least 50 times greater than from spleen and peripheral blood. Tumor-specific T-cells could similarly be obtained from Ag-loaded sponges implanted into previously primed mice and into mice bearing disseminated FBL-3. In both circumstances, elicited T-cells exhibited much higher cytolytic activity than T-cells from sponges implanted in naive mice, indicating an in situ accumulation and expansion of primed T-cells in response to the antigen stimulation. Tumor-specific T-cells obtained from Ag-loaded sponge implants could be grown long-term in vitro by periodic restimulation with irradiated FBL-3 and low concentrations of interleukin 2. Adoptive transfer of the resultant expanded T-cell lines into mice with disseminated FBL-3 revealed that cultured sponge-infiltrating T-cells could mediate effective antitumor therapy. Thus, in vivo immunization with Ag-loaded sponges provides a potentially useful technique for procuring primed, Ag-specific T-cells for tumor therapy.
A Simple and Robust Mutation Strategy for the Metropolis Light Transport Algorithm (2002)

This paper presents a new mutation strategy for the Metropolis light transport algorithm, which works in the unit cube of pseudo-random numbers instead of mutating in the path space. This transformation makes the integrand have lower variation and thus increases the acceptance probability of the mutated samples. Higher acceptance ratio, in turn, reduces the correlation of the samples, which increases the speed of convergence. We use both local mutations that choose a new random sample in the neighborhood of the previous one, and global mutations that make ``large steps'', and find the samples independently. Local mutations smooth out the result, while global mutations guarantee the ergodicity of the process. Due to the fact that samples are generated independently in large steps, this method can also be considered as a combination of the Metropolis algorithm with a classical random walk. If we use multiple importance sampling for this combination, the combined method will be as good at bright regions as the Metropolis algorithm and at dark regions as random walks. The resulting scheme is robust, efficient, but most importantly, is easy to implement and to combine with an arbitrary random-walk algorithm.