gebhart/patrepeval huggingface dataset:
Conversion of Thyrotropin Heterodimer to a Biologically Active Single-Chain* (1998)

TSH and the gonadotropins, FSH, LH, and CG are a family of heterodimeric glycoprotein hormones composed of a common alpha-subunit noncovalently linked to a hormone specific beta-subunit. Assembly of alpha- and beta-subunits is essential for hormone-specific posttranslational modifications, receptor binding, and bioactivity. Structure-function studies of TSH and gonadotropins using site-directed mutagenesis can often affect folding, assembly, and secretion of the hormone. To circumvent these difficulties, recently, the gonadotropin heterodimers were converted to single chains. Here we converted the hTSH heterodimer to a biologically active single chain by genetically fusing the amino terminal end of the common alpha-subunit to the carboxyl terminal end of hTSHbeta in the presence or absence of hCGbeta carboxyl terminal peptide (CTP), which was used as a linker. Wild-type hTSH and the single chains were expressed in Chinese hamster ovary (CHO) cells, and they were efficiently secreted. Although the secretion rate of the single chain was 3-fold higher than that of hTSH wild-type. Moreover, the secretion of the single chain in the presence of the CTP linker was dramatically increased. On the other hand, receptor binding and in vitro bioactivity of the single chains were similar to that of hTSH wild-type. These data indicate the potential of the single chain approach to further investigate structure-function relationships of TSH.
Human Skin Fibroblasts Derived from Papillary and Reticular Dermis: Differences in Growth Potential in Vitro (1979)

Papillary fibroblasts, when compared to reticular fibroblasts from the same skin specimen, exhibit greater proliferative capacities in vitro. These results demonstrate a difference in function between morphologically similar cells obtained from the same tissue. Such findings represent an important consideration in the study of cell aging in vitro.
Progeny Analysis of Glyphosate Selected Transgenic Soybeans Derived from Agrobacterium‐Mediated Transformation (2000)

Glyphosate selection has been implemented into an Agrobacterium ‐mediated transformation system for soybean [ Glycine max (L.) Merr.]. Cotyledonary explants were excised from 5‐d‐old seedlings and inoculated with an Agrobacterium strain carrying the CP4 gene, which confers tolerance to the herbicide Roundup, and the β‐glucuronidase (GUS) gene. Explants were selected on sublethal levels of glyphosate during shoot initiation and elongation. Glyphosate tolerant shoots were identifiable after 8 to 12 wk of selection. Coexpression of GUS occurred in approximately 80% of the primary transformants (R 0 ). The R 0 plants were fully fertile, with no apparent phenotypic abnormalities. Progeny analysis from 81 independent transgenic soybean events derived from glyphosate selection demonstrated that the majority of the transformants transmitted the transgenes as a single functional locus.
MR‐guided laser‐induced thermal therapy (LITT) for recurrent glioblastomas (2012)

Focal tumor control was performed safely using minimally invasive LITT with real-time MRTI control. LITT could be considered as salvage therapy for high-grade recurrent gliomas if a 1-day treatment is considered useful for a few weeks gain in survival. Larger experience will be required to define indications for such infiltrative disease and accurately determine a potentially significant survival gain in good neurological condition associated with this 1-day procedure.
Transforming Growth Factor-β Receptor Mutations and Pulmonary Arterial Hypertension in Childhood (2005)

The cause of PAH presenting in childhood is heterogeneous in nature, with genetic defects of transforming growth factor-beta receptors playing a critical role.
Precision oncology for patients with advanced cancer: the challenges of malignant snowflakes (2015)

Precision oncology implies customizing treatment to the unique molecular and biologic characteristics of each individual and their cancer. Its implementation is being facilitated by remarkable technological advances in genomic sequencing, as well as the increasing availability of targeted and immunotherapeutic drugs. Yet, next generation sequencing may be a disruptive technology in that its results suggest that classic paradigms for clinical research and practice are a poor fit with the complex reality encountered in metastatic malignancies. Indeed, it is evident that advanced tumors have heterogeneous molecular landscapes that mostly differ between patients. Traditional modes of clinical research/practice are drug centered, with a strategy of finding commonalities between patients so that they can be grouped together and treated similarly. However, if each patient with metastatic cancer has a unique molecular portfolio, a new patient-centered, N-of-one approach that utilizes individually tailored treatment is needed.
Novel Peptidomimetics Containing a Vinyl Ester Moiety as Highly Potent and Selective Falcipain-2 Inhibitors (2009)

This paper describes the synthesis and biological evaluation of a new class of peptidomimetic falcipain-2 inhibitors based on a 1,4-benzodiazepine scaffold combined with various alpha,beta-unsaturated electrophilic functions such as vinyl-ketone, -amide, -ester, and -nitrile. The profile of reactivity of this class of derivatives has been evaluated and 4c, containing a vinyl ester warhead, proved to be a highly potent and selective falcipain-2 inhibitor.
Age‐induced mitochondrial DNA point mutations are inadequate to alter metabolic homeostasis in response to nutrient challenge (2020)

Mitochondrial dysfunction is frequently associated with impairment in metabolic homeostasis and insulin action, and is thought to underlie cellular aging. However, it is unclear whether mitochondrial dysfunction is a cause or consequence of insulin resistance in humans. To determine the impact of intrinsic mitochondrial dysfunction on metabolism and insulin action, we performed comprehensive metabolic phenotyping of the polymerase gamma (PolG) D257A "mutator" mouse, a model known to accumulate supraphysiological mitochondrial DNA (mtDNA) point mutations. We utilized the heterozygous PolG mutator mouse (PolG<sup>+/mut</sup> ) because it accumulates mtDNA point mutations ~ 500-fold > wild-type mice (WT), but fails to develop an overt progeria phenotype, unlike PolG<sup>mut/mut</sup> animals. To determine whether mtDNA point mutations induce metabolic dysfunction, we examined male PolG<sup>+/mut</sup> mice at 6 and 12 months of age during normal chow feeding, after 24-hr starvation, and following high-fat diet (HFD) feeding. No marked differences were observed in glucose homeostasis, adiposity, protein/gene markers of metabolism, or oxygen consumption in muscle between WT and PolG<sup>+/mut</sup> mice during any of the conditions or ages studied. However, proteomic analyses performed on isolated mitochondria from 12-month-old PolG<sup>+/mut</sup> mouse muscle revealed alterations in the expression of mitochondrial ribosomal proteins, electron transport chain components, and oxidative stress-related factors compared with WT. These findings suggest that mtDNA point mutations at levels observed in mammalian aging are insufficient to disrupt metabolic homeostasis and insulin action in male mice.
Histatins, a novel family of histidine-rich proteins in human parotid secretion. Isolation, characterization, primary structure, and fungistatic effects on Candida albicans. (1988)

Histatins 1, 3, and 5 from human parotid secretion were isolated by gel filtration on Bio-Gel P-2 and reverse phase high performance liquid chromatography. The complete amino acid sequences of histatins determined by automated Edman degradation of the proteins, Staphylococcus aureus V8 protease, and tryptic peptides, are as follows: (Sequence: see text). Histatins 1, 3, and 5 contain 38, 32, and 24 amino acid residues, have molecular weights of 4929, 4063, and 3037, respectively, and contain 7 residues of histidine. Histatin 1 contains 1 mol of phosphate/mol of protein; histatins 3 and 5 lack phosphate. With the exception of Glu (residue 4) and Arg (residue 11) in histatin 1, the first 22 amino acid residues of all three histatins are identical, and the carboxyl-terminal 7 residues of histatins 1 and 3 are also identical. The sequence, -Glu-Phe-Pro-Phe-Tyr-Gly-Asp-Tyr-Gly- (residues 23-29), in histatin 1 is absent in histatin 3; and the sequence, -Gly-Tyr-Arg- (residues 23-25), in histatin 3 is absent in histatin 1. The complete sequence of histatin 5 is contained within the amino terminal 24 residues of histatin 3. The structural data suggest that histatins 1 and 3 are derived from different structural genes, whereas histatin 5 is a proteolytic product of histatin 3. All three histatins exhibit the ability to kill the pathogenic yeast, Candida albicans.
Nanotailored Crystalline Morphology in Hexagonally Perforated Layers of a Self-Assembled PS-b-PEO Diblock Copolymer (2002)

Nanoscale tailored polymer crystalline morphology is studied in a polystyrene-b-poly(ethylene oxide) (PS-b-PEO) diblock copolymer with number-average molecular weights for the PS and PEO blocks being 17 000 and 11 000 g/mol, respectively. The PEO volume fraction is 0.39. After large amplitude planar reciprocating shear, a hexagonally perforated layer (HPL) structure is obtained. Since the glass transition temperature of the PS blocks (72 °C) is higher than the PEO crystal melting temperature (∼51 °C when the crystallization temperature, Tc, is lower than 40 °C), the PEO block crystallization is confined within the HPL structure. The PEO crystal (the c axis) orientation within this complex confined environment is investigated using simultaneous synchrotron two-dimensional small-angle and wide-angle X-ray scattering (SAXS and WAXS) methods. The PEO crystal orientations with respect to the layer plane (or the {000l}) of the HPL structure have been found to be dependent upon Tc. At very low Tcs (below −50 °C), the PEO crystals have a random orientation. Between −50 °C ≤ Tc ≤ −10 °C, the PEO crystal c axes preferentially orient parallel to the layer plane. Above Tc = 0 °C, the crystal c axes orient inclined to the layer plane of the HPL structure, and the tilt angle with respect to the layer plane increases with Tc. Contrary to the confined polymer crystallization in nanolamellar structure, however, the c axis orientation perpendicular to the layer plane is not found at least up to Tc = 40 °C in this HPL confined environment. Meanwhile, the ribbonlike PEO crystal growth is specifically tailored along the {101̄0} planes of the hexagonal PS perforations. Apparent crystallite size analyses using the Scherrer equation confirm the one-dimensional crystal growth at high Tcs. Using time-resolved WAXS experiments, the crystal orientation is observed to occur in the early stage of crystallization with a crystallinity of ∼7 wt %. Based on the results of specifically designed self-seeding experiment, the crystal orientation is determined by the crystal growth (surface nucleation) in the confined HPL phase rather than the preorientation of primary nuclei.
Design considerations for low switching voltage crossing channel switches (1988)

Demonstrates both theoretically and experimentally that low switching voltage, in comparison to those characterizing other modulators, can be obtained with single-mode crossing channel structures at the wavelength of 1.32 mu m. Design considerations for obtaining the low switching voltage are presented.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
<title>Embedding interactive external program objects within open-distributed hypermedia documents</title> (1995)

The World-Wide-Web (WWW) has created a new paradigm for online information retrieval by providing immediate and ubiquitous access to digital information of any type from data repositories located throughout the world. The web's development enables not only effective access for the generic user, but also more efficient and timely information exchange among scientists and researchers. We have extended the capabilities of the web to provide an improvement to the current paradigm for interacting with inline images, and to allow multidimensional image datasets to be embedded, together with realtime interactive viewers, within WWW documents. Those datasets can then be accessed via our modified version of NCSA's Mosaic WWW browser. This paper will provide a brief background on the World-Wide-Web, and overview of the extensions necessary to support these new data types and a description of an implementation of this approach in a WWW-compliant distributed visualization system.
ExceLint: automatically finding spreadsheet formula errors (2018)

Spreadsheets are one of the most widely used programming environments, and are widely deployed in domains like finance where errors can have catastrophic consequences. We present a static analysis specifically designed to find spreadsheet formula errors. Our analysis directly leverages the rectangular character of spreadsheets. It uses an information-theoretic approach to identify formulas that are especially surprising disruptions to nearby rectangular regions. We present ExceLint, an implementation of our static analysis for Microsoft Excel. We demonstrate that ExceLint is fast and effective: across a corpus of 70 spreadsheets, ExceLint takes a median of 8 seconds per spreadsheet, and it significantly outperforms the state of the art analysis.
Line narrowing of terahertz vibrational modes for organic thin polycrystalline films within a parallel plate waveguide (2006)

Waveguide terahertz time-domain spectroscopy is used to demonstrate the narrowing of vibrational lines for a thin polycrystalline film of 1,2-dicyanobenzene in a parallel plate metal waveguide. When compared to corresponding linewidths for 1,2-dicyanobenzene in a pellet sample at room temperature, the linewidths for the waveguide film are found to be significantly sharper. For measurements near 77K, a dramatic line narrowing is observed for the waveguide film, yielding linewidths as much as five times sharper than found in the pellet. These effects are attributed to much smaller inhomogeneous broadening in the waveguide film and result in a more informative spectrum.
Mutations in the small heterodimer partner gene are associated with mild obesity in Japanese subjects (2001)

Mutations in several genes encoding transcription factors of the hepatocyte nuclear factor (HNF) cascade are associated with maturity-onset diabetes of the young (MODY), a monogenic form of early-onset diabetes mellitus. The ability of the orphan nuclear receptor small heterodimer partner (SHP, NR0B2) to modulate the transcriptional activity of MODY1 protein, the nuclear receptor HNF-4alpha, suggested SHP as a candidate MODY gene. We screened 173 unrelated Japanese subjects with early-onset diabetes for mutations in this gene and found five different mutations (H53fsdel10, L98fsdel9insAC, R34X, A195S, and R213C) in 6 subjects as well as one apparent polymorphism (R216H), all present in the heterozygous state. Interestingly, all of the subjects with the mutations were mildly or moderately obese at onset of diabetes, and analysis of the lineages of these individuals indicated that the SHP mutations were associated with obesity rather than with diabetes. Therefore, an additional group of 101 unrelated nondiabetic subjects with early-onset obesity was screened for mutations in the SHP gene. Two of the previously observed mutations (R34X and A195S) and two additional mutations (R57W and G189E) were identified in 6 subjects, whereas no mutations were identified in 116 young nondiabetic lean controls (P = 0.0094). Functional studies of the mutant proteins show that the mutations result in the loss of SHP activity. These results suggest that genetic variation in the SHP gene contributes to increased body weight and reveal a pathway leading to this common metabolic disorder in Japanese.
A comparison of polyssacharides from strains of Aureobasidium pullulans (1990)

Production of pullulan by five strains of Aureobasidium pullulans was compared in three media with three carbohydrate sources. Our goal was to screen strains and media to obtain pullulan in maximal yield, purity, and stability. Pullulan yields and properties were strongly affected by strain specificity, but a single medium performed best with most strains. Sucrose was the preferred carbohydrate for all five strains. A “color variant” strain of Aureobasidium, NRRL Y-12974, possibly representing a distinct species, produced a polysaccharide of intermediate molecular weight which was stable during storage at 4°C, heating to 100°C, and high shearing action. This polysaccharide was 70% pullulanase sensitive and contained the least contaminating melanin pigment.
High birefringence and wide nematic range bis-tolane liquid crystals (1999)

Several dialkyl and fluoro bis-tolane liquid crystals were synthesized and their physical properties evaluated. These highly conjugated liquid crystals exhibit a wide nematic range, small heat fusion enthalpy, high birefringence, and relatively low viscosity. Their excellent compatibility with commercial cyano mixtures makes these liquid crystals attractive for many electro-optic applications.
Fine-Needle Aspiration of Thyroid Nodules: Proteomic Analysis To Identify Cancer Biomarkers (2008)

At present, the clinical and pathological analysis used in the diagnosis of papillary thyroid cancer (PTC) are insufficient to discern tumor behavior, and new diagnostic and prognostic markers need to be identified. In this study, we performed a comparative proteome analysis to examine the global changes of fine needle aspiration fluid (FNA) protein patterns of two variants of malignant PTC (classical variant PTC (cPTC) and tall cell variant PTC (TCV)) with respect to the controls. Changes in protein expression were identified using two-dimensional electrophoresis (2DE) and peptide mass fingerprinting via MALDI-TOF mass spectrometry (MS), as well as Western blot analysis. A statistical significant up-regulation of 17 protein spots in cPTC and/or TCV with respect to controls was demonstrated. These proteins included transthyretin precursor (TTR), ferritin light chain (FLC), proteasome activator complex subunit 1 and 2, alpha-1-antitrypsin precursor, glyceraldehyde-3-phosphate dehydrogenase (GAPDH), lactate dehydrogenase chain B (LDH-B), apolipoprotein A1 precursor (Apo-A1), annexin A1, DJ-1 protein and cofilin-1. In addition, 12 protein spots were found exclusively in cPTC and three exclusively in TCV. These latter proteins (ferritin heavy chain (FHC), peroxiredoxin 1 (PRX1) and 6-phosphogluconate dehydrogenase (6-PDGH)) correspond to stress response proteins and, until now, had not been described in thyroid tumors. These findings illustrate the potential use of FNA proteomics to identify protein changes associated with thyroid cancer and to advance potential protein biomarkers in the diagnostic classification of the disease.
The p53 Isoform Δp53 Lacks Intrinsic Transcriptional Activity and Reveals the Critical Role of Nuclear Import in Dominant-Negative Activity (2007)

The transcription factor p53 is one of the most frequently mutated tumor suppressors. Recent progress has unraveled several novel isoforms of p53. Intriguingly, one of the p53 isoform, Deltap53, which lacks part of the DNA binding domain, was reported to be transcriptionally active toward some p53 target genes and is critical for the intra-S phase checkpoint. Here, we show that, in contrast to full-length p53, ectopically expressed Deltap53 neither transactivated the promoters of p21(CIP1/WAF1) or murine double minute-2 (MDM2) nor repressed the cyclin B1 promoter in unstressed H1299 cells. Due to the deletion of a nuclear localization signal, Deltap53 was not imported into the nucleus. Engineering of nuclear localization signals to Deltap53 restored nuclear accumulation. However, the nuclear-targeting Deltap53 remained inactive, indicating that the lack of intrinsic activity of Deltap53 was not simply due to subcellular localization but to its incomplete DNA binding domain. Similar to p53, Deltap53 was subjected to MDM2-mediated ubiquitination/proteolysis. The cytoplasmic localization of Deltap53 correlated with the instability of the protein because forcing Deltap53 into the nucleus increased its stability. Although Deltap53 could form a complex with p53 and stimulated the cytoplasmic retention of p53, it was not a robust inhibitor of p53. Targeting Deltap53 into the nucleus enhanced the dominant-negative activity of Deltap53. These observations underscore the critical role of subcellular localization in the dominant-negative action of p53.
cDNA and deduced amino acid sequence of human PK‐120, a plasma kallikrein‐sensitive glycoprotein (1995)

PK-120 is a substrate for plasma kallikrein (PK), recently purified from human plasma. Here we have established the cDNA sequence for human PK-120 mRNA. The deduced amino sequence of PK-120 revealed that it consists of 902 amino acid residues with a calculated mass of 116,423 Da. The putative cleavage sites by PK have been proposed, suggesting that PK-120 may be a precursor of a bioactive peptide. Most interestingly, PK-120 showed significant sequence identities to heavy chains (HCs) of the inter-alpha-trypsin inhibitor (ITI) superfamily.
Silyl-Mediated Halogen/Halogen Displacement in Pyridines and Other Heterocycles (2002)

Heating with bromotrimethylsilane converts 2-chloropyridine into 2-bromopyridine and 2-chloro-6-methylpyridine into 2-bromo-6-methylpyridine. Both 2-chloropyridines and 2-bromopyridines give the corresponding iodo compound when treated with in situ generated iodotrimethylsilane. Although 3- and 4-chloropyridine are completely inert, 2,4-dichloropyridine undergoes the halogen/halogen exchange simultaneously at the 2- and 4-position. Halogen displacement takes place exclusively at the 2-position with 2,3-dichloropyridine and 2,5-dichloropyridine. In agreement with the intermediacy of N-trimethylsilylpyridinium salts as a prerequisite for the occurrence of halogen exchange, neither 2-fluoropyridine and 2-fluoro-6-methylpyridine nor any 2,6-dihalopyridine reacts. Finally, bromine/chlorine and iodine/chlorine substitution can also be accomplished with 2- or 4-chloroquinoline, 1-chloroisoquinoline, 2-chloropyrimidine, chloropyrazine and 2,3-dichloroquinoxaline as substrates. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2002)
Somatic Cell Nuclear Transfer: Recent Progress and Challenges (2002)

Somatic cell nuclear transfer (NT) offers new and exciting opportunities in many areas of research and biotechnology. However, the field as a whole is still in its infancy, with continuing inefficiencies in the process proving many early expectations premature. The technical steps of NT are complex, and success is highly susceptible to minor variations. Furthermore, the biological process of reprogramming is not fully understood, making it difficult to optimize the protocols for providing ideal recipient oocytes and donor cells. In this paper, we describe recent advances and novel approaches, which resulted in progress during the last year, including the birth of cloned piglets and farm animals with precise genetic changes. Key problems hindering further progress are addressed.