gebhart/patrepeval huggingface dataset:
Hsp90 inhibition increases p53 expression and destabilizes MYCN and MYC in neuroblastoma (2010)

Neuroblastoma is a childhood cancer that exhibits either a favorable or an unfavorable phenotype. MYCN and MYC are oncoproteins that play crucial roles in determining the malignancy of unfavorable neuroblastoma. The Hsp90 superchaperone complex assists in the folding and function of a variety of oncogenic client proteins. Inhibition of Hsp90 by small molecule inhibitors leads to the destabilization of these oncogenic proteins and consequently suppresses tumor malignancy. Nonetheless, little is known about the effect of Hsp90 inhibition on the stability of MYCN and MYC proteins. In this study, we investigated the effect of Hsp90 inhibition on the phenotype of unfavorable neuroblastoma cells including its effect on MYCN and MYC expression. Two MYCN-amplified neuroblastoma cell lines (IMR5 and CHP134) and two non-MYCN-amplified cell lines (SY5Y and SKNAS) were used to address the effect of Hsp90 inhibition on the malignant phenotype of neuroblastoma. It was found that Hsp90 inhibition in neuroblastoma cell lines resulted in significant growth suppression, a decrease in MYCN and MYC expression, and an increase in the expression of p53. In the TP53-mutated SKNAS cell line, Hsp90 inhibition enhanced the expression of the favorable neuroblastoma genes EFNB2, MIZ-1 and NTRK1 (TrkA). In addition, Hsp90 inhibition reduced HDAC6 expression and enhanced tubulin acetylation. Together our data suggest that Hsp90 inhibition suppresses the growth of neuroblastoma through multiple cellular pathways and that MYC/MYCN destabilization is among the important consequences of Hsp90 inhibition.
Investigation of Methods for Seven-Membered Ring Synthesis:  A Practical Synthesis of 4-Oxo-5,6,7,8-tetrahydro-4H-cyclohepta[b]furan-3-carboxylic Acid (2001)

Several synthetic routes to 4-oxo-5,6,7,8-tetrahydro-4H-cyclohepta[b]furan-3-carboxylic acid (1) are described, and the scale-up issues with each route are discussed. Seven-membered ring formation is a key issue with these syntheses, and several strategies are presented, including preparation from cycloheptane-1,3-dione, ring-expansion routes, Dieckmann cyclization, acetylene-furan [4 + 2] cycloaddition, and Friedel−Crafts cyclization. Two of the routes were scaled in the pilot plant to provide kilogram quantities of the title compound. The first scale-up route is outlined in Scheme 2 and utilizes a ring-expansion strategy to prepare cycloheptane-1,3-dione from cyclopentanone, via a [2 + 2] cycloaddition between dichloroketene and the silyl enol ether of cyclopentanone. The diketone is converted to the title compound by condensation with ethyl bromopyruvate and base, followed by acid hydrolysis. This route was efficient on laboratory scale but encountered problems upon scale-up due to a competing fragmentation pathway in the Zn/AcOH-mediated retro-aldol of cyclobutanone 11. The second, more successful scale-up route is described in Scheme 15, and involves Friedel−Crafts acylation of 3-carboethoxyfuran selectively at the 5-position. Reduction, lactonization, and hydrogenolysis provide acid 43, which is cyclized via a second Friedel−Crafts reaction to form the seven-membered ketone.
Compiler-directed dynamic voltage/frequency scheduling for energy reduction in microprocessors (2002)

Dynamic voltage and frequency scaling of the CPU has been identified as one of the most effective ways to reduce energy consumption of a program. This paper discusses a compilation strategy that identifies scaling opportunities without significant overall performance penalty. Simulation results show CPU energy savings of 3.97%-23.75% for the SPECfp95 benchmark suite with a performance penalty of at most 2.53%.
Construction of a shuttered time-of-flight mass spectrometer for selective ion detection (1989)

By placing a pulsed, high-voltage steering plate between the ion source and detector in a time-of-flight mass spectrometer, the signal-to-noise ratio of the mass of interest is improved by more than an order of magnitude. This improvement arises from (1) suppression of ions of other masses formed at the same time as the ion of interest and (2) suppression of ions formed at different times and different locations whose arrival time at the detector is nearly coincident with the mass of interest. The advantages of this simple device are demonstrated in the detection of molecular hydrogen in the presence of other species.
The use of intravitreal corticosteroids, evidence-based and otherwise (2006)

Intravitreal triamcinolone acetonide provides a potent short-term treatment for persistent macular edema and may be a useful adjunctive treatment for choroidal neovascularization. It remains to be determined whether intravitreal corticosteroids can provide long-term visual gain or stabilization. The side-effect profile of intravitreal corticosteroids is significant with corticosteroid-induced intraocular pressure rises. With longer-term studies, the rate of posterior subcapsular cataract formation is higher than previously reported, and there is a small but potential risk of endophthalmitis.
Applications of Casimir forces: Nanoscale actuation and adhesion (2020)

Here, we discuss possible applications of the Casimir forces in micro- and nanosystems. The main part of this paper is devoted to actuation with quantum fluctuations and to the relative contribution of van der Waals and Casimir interactions to adhesion. Switching between the amorphous and crystalline states of phase change materials could generate force contrast sufficient for actuation, though for practical applications, the influence of protective capping layers and volume compression have to be better understood. Resilience against the pull-in instability is also a critical point defined by the material choice, dissipation in the system, and roughness of the surfaces. The adhesion induced by the Casimir forces is omnipresent, and it can play a pivotal role in unwanted stiction demanding deeper understanding. The open problems are the distance upon contact and the relative area of the real contact since both of them control the adhesion. An experiment designed to answer these questions is briefly discussed.
Chimerism of the Transplanted Heart (2002)

Our results show a high level of cardiac chimerism caused by the migration of primitive cells from the recipient to the grafted heart. Putative stem cells and progenitor cells were identified in control myocardium and in increased numbers in transplanted hearts.
High-Dose Regimen of Interleukin-2 and Interferon-Alpha in Combination with Lymphokine-Activated Killer Cells in Patients with Metastatic Renal Cell Cancer (1997)

Seventy-two patients with metastatic renal cell cancer were treated with the combination of high-dose interleukin-2 (IL2), interferon-alpha (IFN alpha), and lymphokine-activated killer cells (LAK). Seventeen patients were entered in a feasibility part of the study (protocol 1) and 55 in an efficacy part (protocol 2). Protocol 2 differed from protocol 1 in the addition of IFN alpha to the first 5 days of IL2 infusion. Each patient was planned to receive two induction cycles. IL2, 18 MIU/m2/day, was administered continuously i.v. on days 1-5, and IFN alpha, 5 MIU/m2/day (protocol 2), was administered i.m. on days 1-5, followed by three daily lymphaphereses on days 7-9. On day 12, treatment was resumed with IL2 and IFN alpha on days 12-15 and LAK reinfusions on days 12-14. In protocol 1, three complete (CR) and one partial (PR) responses were achieved (response rate 24%). The median duration of response and the median survival were 18.1 and 13.9 months, respectively. The 3-year survival was 35%. Of the 51 evaluable patients in protocol 2, 6 achieved a CR and 13 a PR (response rate 37%). The median duration of response was 11.1 months. The median survival was 16.9 months. The 3-year survival was 35%. There were three treatment-related deaths. Other severe toxicities included hypotension, cardiotoxicity, pulmonary edema, renal toxicity, and infectious complications. In the two induction cycles, only 54 and 42% of the planned doses could be administered. We conclude that the use of high-dose regimens of IL2 and IFN alpha is not warranted, unless we can define more accurately which patients may experience long-term survival as a result of treatment.
The Structure of T-Cell Epitopes (1987)

We have reviewed here studies using synthetic peptides to analyze some of the properties of T-cell epitopes. Several general conclusions can be drawn. First, T-cell epitopes can usually be defined by linear sequences of about seven amino acids. However, the observation that increasing peptide length often results in increased antigenic potency has suggested that antigenicity may crucially depend upon the ability of peptides to adopt appropriate secondary structures. Two models for the prediction of T-cell epitopes on the basis of primary sequence data alone were discussed. Biophysical studies on the association of peptides with Ia molecules have shown that antigenic peptides bind directly to Ia; the evidence suggests that a binary association between Ia and peptide occurs in the absence of specific T-cells. Finally, a hypothesis to explain the observation that B-cells and T-cells generally recognize distinct epitopes on multideterminant antigens has been examined.
Cell binding and internalization by filamentous phage displaying a cyclic Arg-Gly-Asp-containing peptide. (1994)

Ligands that bind mammalian cell surface integrins with high affinity can mediate cellular internalization. We show that particles of the bacteriophage fd that display the cyclic integrin-binding peptide sequence GGCRGDMFGC in a proportion of their major coat protein subunits bind to cells and are efficiently internalized. In the displayed peptide the conformation of the RGD motif is restricted within a hairpin loop formed by a disulfide bridge between the 2 cysteine residues. Cellular internalization of phage was demonstrated by confocal and non-confocal immunofluorescence microscopy of tissue-cultured cells incubated with phage particles. The phage were contained in juxtanuclear vesicles in the same serial sections as transferrin receptor but were not colocalized with the cell surface marker alkaline phosphatase. Cell binding and internalization was inhibited by preincubation of cells with the integrin-binding peptide GRGDSP, whereas the control peptide GRGESP had no inhibitory effect. These results indicate that cyclic integrin-binding peptides can be used to target and enter cells and that it should be possible to exploit such peptides for the introduction of DNA, drugs, or other macromolecules.
Design, implementation and evaluation of audio for a location aware augmented reality game (2010)

In this paper, the development and implementation of a rich sound design, reminiscent of console gaming for a location aware game, Viking Ghost Hunt (VGH) is presented. The role of audio was assessed with particular attention to the effect on immersion and emotional engagement. Because immersion also involves the interaction and the creation of presence (the feeling of being in a particular place) these aspects of the sound design were also investigated. Evaluation of the game was undertaken over a three-day period with the participation of 19 subjects. The results gained imply that audio plays an important role in immersing a player within the game space and in emotionally engaging with the virtual world. However, challenges in regards to GPS inaccuracy and unpredictability remain, as well as device processor constraints, in order to create an accurate audio sound field and for the real-time rendering of audio files.
Structural transition and enhanced phase transition properties of Se doped Ge2Sb2Te5 alloys (2015)

Amorphous Ge₂Sb₂Te₅ (GST) alloy, upon heating crystallize to a metastable NaCl structure around 150°C and then to a stable hexagonal structure at high temperatures (≥250°C). It has been generally understood that the phase change takes place between amorphous and the metastable NaCl structure and not between the amorphous and the stable hexagonal phase. In the present work, it is observed that the thermally evaporated (GST)1-xSex thin films (0 ≤ x ≤ 0.50) crystallize directly to the stable hexagonal structure for x ≥ 0.10, when annealed at temperatures ≥ 150°C. The intermediate NaCl structure has been observed only for x < 0.10. Chemically ordered network of GST is largely modified for x ≥ 0.10. Resistance, thermal stability and threshold voltage of the films are found to increase with the increase of Se. The contrast in electrical resistivity between the amorphous and crystalline phases is about 6 orders of magnitude. The increase in Se shifts the absorption edge to lower wavelength and the band gap widens from 0.63 to 1.05 eV. Higher resistance ratio, higher crystallization temperature, direct transition to the stable phase indicate that (GST)1-xSex films are better candidates for phase change memory applications.
Oxygen and Oxidation Promote the Release of Nitric Oxide from Sydnonimines (1989)

The antianginal effect of sydnonimines is believed to be due to the release of nitric oxide (NO) from inactive prodrugs. The first step in the transformation of the sydnonimine SIN-1 is the hydroxyl ion-dependent conversion to SIN-1A that occurs almost immediately at neutral pH. However, the subsequent process of NO release from SIN-1A is not yet understood. Therefore, the spontaneous degradation of SIN-1A in aqueous solutions was studied by chemical and pharmacological means. Measurement of the oxygen content of a freshly prepared SIN-1A solution revealed a rapid decrease of the oxygen concentration. The oxygen-consuming process was accompanied by a decrease in SIN-1A concentration and a progressive formation of NO and SIN-1C. SIN-1A was stable under nitrogen, labile under air, and very unstable under pure oxygen. Thus, oxygen is an important reactant in the decomposition of SIN-1A. The question of whether or not oxygen is essential for NO release was studied by investigating the effect of other oxidants. The oxidants potassium hexacyanoferrate, cupric sulfate, and lead tetraacetate augmented the conversion of SIN-1A to SIN-1C and increased the relaxing effect on isolated pulmonary arteries used to bioassay NO. Therefore, an oxidative process is essential for the release of NO from sydnonimines.
Epidermal growth factor receptor activation induces nuclear targeting of cyclooxygenase-2, basolateral release of prostaglandins, and mitogenesis in polarizing colon cancer cells (1997)

Nonsteroidal antiinflammatory drugs reduce the risk of colon cancer, possibly via cyclooxygenase (COX) inhibition. The growth factor-inducible COX-2, which is overexpressed in neoplastic colonic tissue, is an attractive target to mediate this effect. Herein we have exploited the ability of a human colon cancer cell line, HCA-7 Colony 29, to polarize when cultured on Transwell (Costar) filters to study COX-2 production and the vectorial release of prostaglandins (PGs). Administration of type alpha transforming growth factor to the basolateral compartment, in which the epidermal growth factor receptor (EGFR) resides, results in a marked induction of COX-2 immunoreactivity at the base of the cells and the unexpected appearance of COX-2 in the nucleus. The increase in COX-2 protein is associated with a dose- and time-dependent increase in PG levels in the basolateral, but not apical, medium. Amphiregulin is the most abundantly expressed EGFR ligand in these cells, and the protein is present at the basolateral surface. EGFR blockade reduces baseline COX-2 immunoreactivity, PG levels, and mitogenesis in a concentration-dependent manner. Two specific COX-2 inhibitors, SC-58125 and NS 398, also, in a dose-dependent manner, attenuate baseline and type alpha transforming growth factor-stimulated mitogenesis, although PG levels are decreased > 90% at all concentrations of inhibitor tested. These findings show that activation of the EGFR stimulates COX-2 production and its translocation to the nucleus, vectorial release of PGs, and mitogenesis in polarized HCA-7 Colony 29 cells.
Polarization-sensitive Fourier domain optical coherence tomography (2005)

A fiber based polarization-sensitive Fourier domain optical coherence tomography system was demonstrated. The complex fringe signal containing amplitude and phase information was acquired by cancellation of DC and autocorrelation terms as well as the mirror image using an electro-optic phase modulator. The Stokes vectors of the reflected and scattered light from sample were determined by processing the analytical complex fringe signals from two perpendicular polarization-detection channels. From the Stokes vectors for four different input polarization states, the birefringence image and the polarization diversity intensity image were obtained.
Influenza A (H3N2) Outbreak, Nepal (2005)

In July 2004, an outbreak of influenza A (H3N2) was detected at 3 Bhutanese refugee camps in southeastern Nepal. Hemagglutination inhibition showed that approximately 40% of the viruses from this outbreak were antigenically distinct from the A/Wyoming/3/03 vaccine strain. Four amino acid differences were observed in most of the 26 isolates compared with the A/Wyoming/3/2003 vaccine strain. All 4 substitutions are located within or adjacent to known antibody-binding sites. Several isolates showed a lysine-to-asparagine substitution at position 145 (K145N) in the hemagglutinin molecule, which may be noteworthy since position 145 is located within a glycosylation site and adjacent to an antibody-binding site. H3N2 viruses continue to drift from the vaccine strain and may remain as the dominant strains during the 2005-2006 influenza season. Thus, the 2005-2006 Northern Hemisphere vaccine strain was changed to A/California/7/2004, a virus with all 4 amino acid substitutions observed in these Nepalese isolates.
Connection between Poly-β-Hydroxybutyrate Biosynthesis and Growth on C 1 and C 2 Compounds in the Methylotroph Methylobacterium extorquens AM1 (2001)

Several DNA regions containing genes involved in poly-beta-hydroxybutyrate (PHB) biosynthesis and degradation and also in fatty acid degradation were identified from genomic sequence data and have been characterized in the serine cycle facultative methylotroph Methylobacterium extorquens AM1. Genes involved in PHB biosynthesis include those encoding beta-ketothiolase (phaA), NADPH-linked acetoacetyl coenzyme A (acetyl-CoA) reductase (phaB), and PHB synthase (phaC). phaA and phaB are closely linked on the chromosome together with a third gene with identity to a regulator of PHB granule-associated protein, referred to as orf3. phaC was unlinked to phaA and phaB. Genes involved in PHB degradation include two unlinked genes predicted to encode intracellular PHB depolymerases (depA and depB). These genes show a high level of identity with each other at both DNA and amino acid levels. In addition, a gene encoding beta-hydroxybutyrate dehydrogenase (hbd) was identified. Insertion mutations were introduced into depA, depB, phaA, phaB, phaC, and hbd and also in a gene predicted to encode crotonase (croA), which is involved in fatty acid degradation, to investigate their role in PHB cycling. Mutants in depA, depB, hbd, and croA all produced normal levels of PHB, and the only growth phenotype observed was the inability of the hbd mutant to grow on beta-hydroxybutyrate. However, the phaA, phaB, and phaC mutants all showed defects in PHB synthesis. Surprisingly, these mutants also showed defects in growth on C(1) and C(2) compounds and, for phaB, these defects were rescued by glyoxylate supplementation. These results suggest that beta-hydroxybutyryl-CoA is an intermediate in the unknown pathway that converts acetyl-CoA to glyoxylate in methylotrophs and Streptomyces spp.
PAC-1: a Mitogen-Induced Nuclear Protein Tyrosine Phosphatase (1993)

Tyrosine phosphorylation of proteins is required for signal transduction in cells and for growth regulation. A mitogen-induced gene (PAC-1) has been cloned from human T cells and encodes a 32-kilodalton protein that contains a sequence that defines the enzymatic site of known protein phosphotyrosine phosphatases (PTPases). Other than this sequence, PAC-1 is different from several other known related PTPases exemplified by PTP-1b. PAC-1 is similar to a phosphatase induced by mitogens or heat shock in fibroblasts, a yeast gene, and a vaccinia virus-encoded serine-tyrosine phosphatase (VH1). PAC-1 was predominantly expressed in hematopoietic tissues and localized to the nucleus in transfected COS-7 cells and in mitogen-stimulated T cells.
Pernicious Anemia (1988)

• When patients are examined for possible cobalamin deficiency, great stress is often placed on the presence or absence of macrocytosis and anemia and on how low the serum cobalamin level is. The present study, however, shows that only 45 (64%) of 70 consecutively diagnosed patients with pernicious anemia, the most common cause of cobalamin deficiency, had very low cobalamin levels (74 pmol/L [or 100 ng/L]). Anemia was absent in 13 (19%) of the patients, and macrocytosis was absent in 23 (33%) of the patients; such absence was particularly common when cobalamin levels were only slightly or moderately low (74 to 184 pmol/L). Coexisting iron deficiency was responsible for the absence of macrocytosis in nine patients. Of the ten patients with neither anemia nor macrocytosis, neurological disturbance was prominent in six, including four whose only noticeable abnormality was cerebral. These observations indicate that macrocytosis and anemia, two classic features of pernicious anemia, may be overstressed in our diagnostic approach. All subnormal serum cobalamin results are best viewed as pathological until proved otherwise. Emphasis on only very low cobalamin levels risks delaying the diagnosis of pernicious anemia in a substantial proportion of cases, particularly in those without anemia or macrocytosis. (<i>Arch Intern Med</i>1988;148:1712-1714)
[The primary structure of a crystalline monoclonal immunoglobulin kappa-type L-chain, subgroup I (Bence-Jones protein Rei.); isolation and characterization of the tryptic peptides; the complete amino acid sequence of the protein; a contribution to the elucidation of the three-dimensional structure of antibodies, in particular their combining site (author's transl)]. (1975)

Bence-Jones protein Rei. was isolated from the urine of a plasmacytoma patient by precipitation with ammonium sulfate and purified by ion exchange chromatography. The determination of the molecular weight showed that the protein was present in its monomeric form. The preparation cotained a minor fraction, which consisted of the dimer of the variable parts and was characterized by its ability to crystallize. X-ray data with a resolution on the atomic level could be achieved and allowed, together with the known primary structure, the construction of a three-dimensional model, which also gave an insight into the antigen binding site. It consists of the hypervariable regions, which form a pocket 15 A in diameter lying between the two monomers at the ends of the molecules. Sequence studies were performed with tryptic peptides which were purified by chromatographic procedures and aligned in homology to other kappa-chains. The protein belongs to subgroup I on the basis of its characteristic amino acid sequence and follows a highly regular pattern of amino acid exchanges. Its sequence is in agreement with an evolutionary origin of antibody variability.