gebhart/patrepeval huggingface dataset:
The Stress-inducted Proteins RTP801 and RTP801L Are Negative Regulators of the Mammalian Target of Rapamycin Pathway (2005)

The mammalian target of rapamycin (mTOR) is a serine/threonine kinase that plays an essential role in cell growth control. mTOR stimulates cell growth by phosphorylating p70 ribosomal S6 kinase (S6K) and eukaryote initiation factor 4E-binding protein 1 (4EBP1). The mTOR pathway is regulated by a wide variety of cellular signals, including mitogenic growth factors, nutrients, cellular energy levels, and stress conditions. Recent studies have proposed several mechanisms to explain how mTOR is regulated by growth factors and cellular energy levels. However, little is known as to how mTOR is regulated by stress conditions. We observed that two stress-induced proteins, RTP801/Redd1 and RTP801L/Redd2, potently inhibit signaling through mTOR. Our data support that RTP801 and RTP801L work downstream of AKT and upstream of TSC2 to inhibit mTOR functions. These results add a new dimension to mTOR pathway regulation and provide a possible molecular mechanism of how cellular stress conditions may regulate mTOR function.
Nanoindentation and contact stiffness measurement using force modulation with a capacitive load-displacement transducer (1999)

We have implemented a force modulation technique for nanoindentation using a three-plate capacitive load-displacement transducer. The stiffness sensitivity of the instrument is ∼0.1 N/m. We show that the sensitivity of this instrument is sufficient to detect long-range surface forces and to locate the surface of a specimen. The low spring mass (236 mg), spring constant (116 N/m), and damping coefficient (0.008 Ns/m) of the transducer allows measurement of the damping losses for nanoscale contacts. We present the experimental technique, important specimen mounting information, and system calibration for nanomechanical property measurement.
Structure of the angiotensin I-converting enzyme gene. Two alternate promoters correspond to evolutionary steps of a duplicated gene (1991)

Overlapping genomic clones containing the entire sequence of the human angiotensin I-converting enzyme (ACE) gene were isolated from a lamda phage human DNA library. This gene spans 21 kilobases (kb) and comprises 26 exons, ranging in size from 88 to 481 base pairs. Intron-exon boundaries were sequenced and the relative positions of the exons were mapped. The two different mRNAs transcribed from the ACE gene were assigned to their respective exons. The large endothelial type ACE mRNA (4.3 kb long) is transcribed from exon 1 to exon 26, excluding exon 13. The 3-kb long testicular ACE mRNA is transcribed from exon 13 to exon 26. Exon 13 encodes for the 67 amino acids of the NH2-terminal region of the testicular ACE, whereas downstream exons encode a sequence common to both isozymes. The gene duplication suggested by the internal homology of the endothelial ACE mRNA is now confirmed by the presence of two homologous clusters of eight exons (exons 4-11 and exons 17-24) having similar sizes and codon phases at exon-intron boundaries. The presence of two alternate promoters was investigated by ribonuclease protection assays. The different 5' ends of the two ACE transcripts revealed a promoter for the endothelial ACE mRNA in the 5'-flanking region of the first exon and a promoter for the testicular ACE mRNA situated in intron 12.
The Iron Chelator L1 Potentiates Oxidative DNA Damage in Iron-Loaded Liver Cells (1998)

Iron-mediated carcinogenesis is thought to occur through the generation of oxygen radicals. Iron chelators are used in attempts to prevent the long term consequences of iron overload. In particular, 1,2-dimethyl-3-hydroxypyrid-4-one (L1), has shown promise as an effective chelator. Using an established hepatocellular model of iron overload, we studied the generation of iron-catalyzed oxidative DNA damage and the influence of iron chelators, including L1, on such damage. Iron loading of HepG2 cells was found to greatly exacerbate hydrogen peroxide-mediated DNA damage. Desferrithiocin was protective against iron/hydrogen peroxide-induced DNA damage; deferoxamine had no effect. In contrast, L1 exposure markedly potentiated hydrogen peroxide-mediated oxidative DNA damage in iron-loaded liver cells. However, when exposure to L1 was maintained during incubation with hydrogen peroxide, L1 exerted a protective effect. We interpret this as indicating that L1's potential toxicity is highly dependent on the L1:iron ratio. In vitro studies examining iron-mediated ascorbate oxidation in the presence of L1 showed that an L1:iron ratio must be at least 3 to 1 for L1 to inhibit the generation of free radicals; at lower concentrations of L1 increased oxygen radical generation occurs. In the clinical setting, such potentiation of iron-catalyzed oxidative DNA damage at low L1:iron ratios may lead to long-term toxicities that might preclude administration of L1 as an iron chelator. Whether this implication in fact extends to the in vivo situation will have to be verified in animal studies.
Recognizing the Absence of Opposing Arguments in Persuasive Essays (2016)

In this paper, we introduce an approach for recognizing the absence of opposing arguments in persuasive essays. We model this task as a binary document classification and show that adversative transitions in combination with unigrams and syntactic production rules significantly outperform a challenging heuristic baseline. Our approach yields an accuracy of 75.6% and 84% of human performance in a persuasive essay corpus with various topics.
A new trajectory control of a flexible-link robot based on a distributed-parameter dynamic model (2004)

The objective of this study is to develop a new trajectory-tracking control method, free from the so-called spillover instability, for a flexible-link robot. Based on a distributed-parameter dynamic model (a partial differential equation), a new moment-feedback trajectory-tracking control scheme is designed for a one-link flexible robot having a payload at the free end, in which zero geometric boundary conditions at the hub end and non-zero dynamic boundary conditions at the free end are taken into account. The proposed control is then extended to an adaptive scheme to cope with parametric uncertainties. The proposed control is stable for trajectory-tracking control and asymptotically stable at desired goal positions, which is proven by using the Lyapunov stability theorem. In addition, the proposed trajectory-tracking control, based on a distributed-parameter dynamic model, does not have the spillover problem. Furthermore, the control performance is guaranteed regardless of the magnitude of desired angle of rotation, which does not require any additional actuators such as piezoelectric actuators on the link and boundary force or moment actuators at the free end. The effectiveness of the proposed control has been shown by experiments.
Textfinder: an automatic system to detect and recognize text in images (1999)

A robust system is proposed to automatically detect and extract text in images from different sources, including video, newspapers, advertisements, stock certificates, photographs, and checks. Text is first detected using multiscale texture segmentation and spatial cohesion constraints, then cleaned up and extracted using a histogram-based binarization algorithm. An automatic performance evaluation scheme is also proposed.
Masterminding B Cells (2015)

In 1999, Stephen Nutt, Barry Heavey, Antonius Rolink, and Meinrad Busslinger unveiled how Pax5 masterminds B cell development ([1][1]). In doing so, they significantly deepened understanding about how competition between transcription factors can dictate cell fate.

Their discovery emerged from a
Self-Assembly and Stress Relaxation in Acrylic Triblock Copolymer Gels (2007)

The structure and relaxation behavior of thermoreversible gels made with poly(methyl methacrylate)−poly(n-butyl acrylate)−poly(methyl methacrylate) [PMMA−PnBA−PMMA] triblock copolymers in 2-ethylhexanol, a midblock selective solvent, were studied by small-angle X-ray scattering (SAXS) and rheology. Effects of endblock length, endblock fraction, and gel concentration on the gel properties were investigated. A dramatic decrease in SAXS intensity was observed over a 20 °C interval where the gel transitions smoothly from elastic to viscous behavior. SAXS patterns were fit with a Percus−Yevick disordered hard-sphere model from which aggregation number and average domain spacing were calculated. Aggregation number increases with increasing gel concentration and endblock length. Increasing the endblock length from 9K to 25K increases the relaxation time of a gel with a polymer volume fraction of 0.15 by a factor of 106. For a given triblock endblock fraction and molecular weight, the micelle aggregation number is strongly correlated to the gel relaxation time. Arrhenius behavior with an effective activation energy of ∼550 kJ/mol was observed for all triblocks and concentrations. This very high effective energy barrier describes gels relaxation behavior over a 40 °C temperature range, where the relaxation times vary by a factor of 1010.
Galactofuranose in eukaryotes: aspects of biosynthesis and functional impact (2011)

Galactofuranose (Galf) is the five-membered ring form of galactose. It is widely distributed among several branches of the eukaryotic kingdom. This review highlights recent advances in our understanding of the biosynthesis and function of Galf-containing glycoconjugates in fungal Aspergillus spp. and the protozoan trypanosomatid parasites. We give an overview of the biosynthetic pathways leading to the production of glycolipids, glycoproteins and polysaccharides containing Galf in these species and their biological relevance. Remarkably, modification of the cell surface caused by Galf absence often results in morphological abnormalities and an impaired cell wall function in these organisms. Galf-deficient mutants are generally hypersensitive to drugs, exhibit a constitutive osmotic stress phenotype and/or have an attenuated virulence. Since Galf has never been found in mammals and higher plants, Galf-biosynthetic pathways have raised much interest as targets for drug development to combat microbial infections.
Acid-Labile Alpha Interferon (1983)

Many homosexual men with the acquired immunodeficiency syndrome (AIDS) have an unusual acid-labile form of human leukocyte, or alpha, interferon in their serum. Male patients with classic hemophilia treated with lyophilized clotting-factor concentrates are also at high risk for the development of AIDS. To determine whether the level of alpha interferon may be a preclinical marker of early subclinical disease, we examined stored plasma and serum from three hemophilic patients with AIDS. Persistently elevated levels of the acid-labile form of alpha interferon were found in all three patients. In two patients the appearance of circulating alpha interferon preceded the onset of clinical disease by 3 to 10 months. In contrast, alpha-interferon levels were not elevated in 43 of 46 unselected patients with hemophilia; three of these patients had transient elevations. These results suggest that acid-labile alpha interferon may be a marker that can be used to identify affected asymptomatic members of high-risk groups before the onset of clinical disease.
Delivering Small Interfering RNA for Novel Therapeutics (2008)

The gene silencing capability of RNA interference (RNAi) is being used to study individual gene's biological function and role in biochemical pathways. However, the efficacy of RNAi depends upon efficient delivery of the intermediates of RNAi, small interfering RNA (siRNA) oligonucleotides. The delivery challenge is even greater when the aim is to inhibit the expression of target genes in disease tissues. In vivo delivery of siRNA is complicated and challenging, and recent works on various animal disease models and early successes in human clinical trials are enlightening the tremendous potential of RNAi therapeutics. In this chapter, the latest developments of in vivo delivery of siRNA and the critical issues related to this effort are addressed.
The Minimal Replicator of Epstein-Barr Virus oriP (2000)

oriP is a 1.7-kb region of the Epstein-Barr virus (EBV) chromosome that supports the replication and stable maintenance of plasmids in human cells. oriP contains two essential components, called the DS and the FR, both of which contain multiple binding sites for the EBV-encoded protein, EBNA-1. The DS appears to function as the replicator of oriP, while the FR acts in conjunction with EBNA-1 to prevent the loss of plasmids from proliferating cells. Because of EBNA-1's role in stabilizing plasmids through the FR, it has not been entirely clear to what extent EBNA-1 might be required for replication from oriP per se, and a recent study has questioned whether EBNA-1 has any direct role in replication. In the present study we found that plasmids carrying oriP required EBNA-1 to replicate efficiently even when assayed only 2 days after plasmids were introduced into the cell lines 143B and 293. Significantly, using 293 cells it was demonstrated that the plasmid-retention function of EBNA-1 and the FR did not contribute significantly to the accumulation of replicated plasmids, and the DS supported efficient EBNA-1-dependent replication in the absence of the FR. The DS contains two pairs of closely spaced EBNA-1 binding sites, and a previous study had shown that both sites within either pair are required for activity. However, it was unclear from previous work what additional sequences within the DS might be required. We found that each "half" of the DS, including a pair of closely spaced EBNA-1 binding sites, had significant replicator activity when the other half had been deleted. The only significant DNA sequences that the two halves of the DS share in common, other than EBNA-1 binding sites, is a 9-bp sequence that is present twice in the "left half" and once in the "right half." These nonamer repeats, while not essential for activity, contributed significantly to the activity of each half of the DS. Two thymines occur at unique positions within EBNA-1 binding sites 1 and 4 at the DS and become sensitive to oxidation by permanganate when EBNA-1 binds, but mutation of each to the consensus base, adenine, actually improved the activity of each half of the DS slightly. In conclusion, the DS of oriP is an EBNA-1-dependent replicator, and its minimal active core appears to be simply two properly spaced EBNA-1 binding sites.
In Vivo Models of Inflammation (1999)

Purpose of In vivo Models of Inflammation is to provide the biomedical researcher in both the pharmaceutical industry and academia with a description of the state of the art animal model systems used to emulate diseases with components of inflammation. The aim of this second edition is to act as a complement to the first by describing and updating the standard models that are most utilized for specific disease areas. In addition, this 2nd edition includes new models exploring emerging areas of inflammation research. It provides detailed descriptions of the methodologies and uses of the most significant models. This includes current information regarding agents that demonstrate efficacy, those that do not and those that can be used as standard controls. The focus remains on those models that serve as pre-clinical correlates to human disease as well as those that represent components of the inflammatory response. New approaches to the development of future models in selected therapeutic areas have been highlighted. The focus on novel technologies that are vital for innovative in vivo research has also been expanded to include chapters on the use of transgenic and gene transfer technologies, nanotechnology, and stem cells. The book provides the scientist with an up-to-date reference manual for selecting the best animal model for their specific question. Chapters describing current regulations in the United States, United Kingdom, and Japan are also included
Odor-Induced Membrane Currents in Vertebrate-Olfactory Receptor Neurons (1989)

In olfactory receptor neurons, odor molecules cause a depolarization that leads to action potential generation. Underlying the depolarization is an ionic current that is the earliest electrical event in the transduction process. In two preparations, olfactory receptor neurons were voltage-clamped and stimulated with odors and this generator current was measured. In addition, a method was developed to estimate the time course and absolute concentration of odorants delivered to the receptor sites. With this method, olfactory neurons were found to have relatively high stimulus thresholds, steep dose-response relations, long latencies, and an apparent requirement for cooperativity at one or more steps in the pathway from odorant binding to activation of the generator current.
Emerging drugs for psoriasis (2006)

Psoriasis is a chronic immune-mediated inflammatory skin disease characterised by abnormal keratinocyte differentiation and proliferation. The immunopathogenesis is complex and novel evidence shows the involvement of both innate and adaptive immune response. Type 1 T cells and their effector cytokines play a pivotal role. Several drugs under preclinical and clinical development for psoriasis are directed against the immune response, targeting activation or proliferation of T cells, their trafficking and skin-homing, or effector cytokines. Among these, great attention has been given to TNF-alpha, following the demonstration of effectiveness of anti-TNF-alpha biologicals, and to IFN-gamma inducers. Another appealing approach concerns drugs capable of inducing immunological tolerance. Progress made in the recognition of intracellular events has prompted the development of small molecules and oligonucleotides that can inhibit specific molecular targets. There is, however, a plethora of other emerging drugs, clearly suggestive of the current interest for psoriasis, which are briefly described in this paper.
Humoral immune response to outer surface protein C of Borrelia burgdorferi in Lyme disease: role of the immunoglobulin M response in the serodiagnosis of early infection (1994)

We determined the humoral immune response to outer surface protein C (OspC) of Borrelia burgdorferi in patients with early or late manifestations of Lyme disease and investigated the use of this antigen in the serodiagnosis of early infection. The ospC gene from the low-passage human isolate 297, a North American B. burgdorferi strain, was used to make a recombinant maltose-binding protein (MBP)-OspC fusion protein for serologic tests. This gene showed 84 to 85% nucleotide sequence identity and 76 to 79% amino acid identity with ospC of B. burgdorferi B31 and 2591. The antibody responses to MBP-OspC were determined in serial sera from 15 patients with Lyme disease who were monitored for 4 to 12 years of illness, in single-serum samples from 189 patients with early or late manifestations of the disorder, and in serum samples from 106 control patients. Early in the infection, patients with erythema migrans or meningitis commonly had weak to strong immunoglobulin M (IgM) responses to OspC and sometimes weak to moderate IgG responses. Months to years later, weak to strong IgG reactivity with this protein was often apparent in patients with arthritis, but this response was weak or absent in patients with chronic neuroborreliosis. When acute- and convalescent-phase serum samples from patients with erythema migrans were tested for reactivity against MBP-OspC, the sensitivity of the IgM test was 73% and the specificity was 98%, with either enzyme-linked immunosorbent assay (ELISA) or Western blotting. We conclude that the majority of patients with Lyme disease have a prominent IgM response to OspC early in the illness, which is often followed by a prominent IgG response in patients with arthritis. For the serodiagnosis of early infection, the sensitivity and specificity of IgM ELISA and Western blotting were comparable or slightly improved when MBP-OspC was used as the antigen compared with tests in which spirochetal lysates were used.
Uterine papillary serous carcinoma (1982)

A review of 256 cases of pathologic Stage I uterine adenocarcinoma treated at Stanford University Hospital revealed 26 cases of uterine papillary serous carcinoma (UPSC), a clinically aggressive and morphologically distinct variant of adenocarcinoma which closely resembles ovarian papillary serous carcinoma. These lesions are easily recognized by microscopic examination and typically feature a high degree of cytologic anaplasia and a papillary growth pattern. Invasion of the lymphatics has been a frequent finding. The relapse rate among patients with pathologic Stage I UPSC was 50% (13/26), five times the rate which would have been predicted by the incidence of UPSC. Patients with Stage I UPSC fared significantly worse than the group of nonpapillary grade II or grade III adenocarcinomas (p less than 0.0001). Forty percent of Stage I UPSC patients had deep myometrial invasion, as compared with 12% of those with all other histologic types of adenocarcinoma (p = 0.001). Women with UPSC deeply invading the myometrium tended to do worse than those with deeply invasive lesions of the more usual endometrioid type as reflected by relapse rates (after surgery alone) of 63% and 30%, respectively. Of seven Stage I corpus carcinoma patients whose initial site of failure was in the upper abdomen, six had UPSC. Thus, UPSC shares the tendency of its ovarian counterpart to spread over peritoneal surfaces. In addition to the original study group of 26 Stage I patients, 34 patients with more advanced stages of UPSC were also reviewed. Of these, 26 have been followed and four survive. Eleven of these women presented or relapsed with abdominal carcinomatosis. UPSC is a clinically aggressive neoplasm which should be distinguished from other types of primary endometrial adenocarcinoma. In cases of invasive UPSC the mode of spread, similar to that of ovarian surface epithelial carcinomas, suggests the need for adjuvant upper abdominal and pelvic irradiation or effective chemotherapy.
First-principles study ofDXcenters in CdTe, ZnTe, andCdxZn1−xTe alloys (1995)

Large lattice relaxation models for DX centers in CdTe, ZnTe, and ${\mathrm{Cd}}_{\mathit{x}}$${\mathrm{Zn}}_{1\mathrm{\ensuremath{-}}\mathit{x}}$ Te alloys are examined through first-principles pseudopotential calculations. The calculated binding energies of DX centers for Al, Ga, In, Cl, Br, and I donor impurities in CdTe and their pressure and alloy dependence in ${\mathrm{Cd}}_{\mathit{x}}$${\mathrm{Zn}}_{1\mathrm{\ensuremath{-}}\mathit{x}}$Te are in good agreement with experimental data. Three distinct types of DX-like structures characterized by either bond rupture or bond compression are found for column VII donors. The relative stability of these structures is impurity and pressure dependent.
Differential expression of genes encoding the hypusine-containing translation initiation factor, elF-5A, in tobacco (1992)

Two Nicotiana plumbaginifolia cDNA clones, NeIF-5A1 and NeIF-5A2, encoding eukaryotic translation initiation factor eIF-5A (formerly called eIF-4D) were cloned by heterologous screening with Dictyostelium and human eIF-5A probes. eIF-5A is the only protein known to contain a unique amino acid modification, hypusine. Comparison of the Nicotiana deduced amino acid sequences with those of other eIF-5A polypeptides reveals conservation throughout the coding sequence, especially in the region of the hypusine residue. Transcript analysis reveals that NeIF-5A1 is preferentially expressed in photosynthetic tissues, while NeIF-5A2 is constitutively expressed in all plant tissues examined. A polyclonal antibody was raised against NeIF-5A1 overexpressed in E. coli. NeIF-5A1 antiserum crossreacts with an 18 kDa polypeptide doublet in all tobacco tissues examined. At least one polypeptide of ca. 18 kDa from a diversity of higher and lower plants crossreacts with NeIF-5A1 antiserum.