gebhart/patrepeval huggingface dataset:
Detection of rare mutant K-ras DNA in a single-tube reaction using peptide nucleic acid as both PCR clamp and sensor probe (2006)

The major problem of using somatic mutations as markers of malignancy is that the clinical samples are frequently containing a trace amounts of mutant allele in a large excess of wild-type DNA. Most methods developed thus far for the purpose of tickling this difficult problem require multiple procedural steps that are laborious. We report herein the development of a rapid and simple protocol for detecting a trace amounts of mutant K-ras in a single tube, one-step format. In a capillary PCR, a 17mer peptide nucleic acid (PNA) complementary to the wild-type sequence and spanning codons 12 and 13 of the K-ras oncogene was used to clamp-PCR for wild-type, but not mutant alleles. The designated PNA was labeled with a fluorescent dye for use as a sensor probe, which differentiated all 12 possible mutations from the wild-type by a melting temperature (T(m)) shift in a range of 9 to 16 degrees C. An extension temperature of 60 degrees C and an opposite primer 97 nt away from the PNA were required to obtain full suppression of wild-type PCR. After optimization, the reaction detected mutant templates in a ratio of 1:10,000 wild-type alleles. Using this newly devised protocol, we have been able to detect 19 mutants in a group of 24 serum samples obtained from patients with pancreatic cancer. Taken together, our data suggest that this newly devised protocol can serve as an useful tool for cancer screening as well as in the detection of rare mutation in many diseases.
Establishment and characterization of an epithelial cell line from the rat submandibular gland (1989)

An epithelial cell line, RSMTx, has been established from the submandibular gland of weanling Fisher 344 rats by treatment of explanted tissue clumps with 3-methylcholanthrene. These cells exhibit a polygonal shape on light microscopy and a polar appearance, with desmosomes, terminal bar-like structures, surface microvilli and cytoplasmic interdigitations, when examined by electron microscopy. The cells react positively with an antiserum to cytoskeletal keratin, and a commercial monoclonal antibody to an "epithelial membrane antigen." An antiserum, prepared against early passage cells in hamsters, reacts primarily with ductal elements in tissue sections of submandibular gland, as does an antiserum prepared in mice with late passage cells. The cells are easily passaged and have been maintained for more than two years in continuous culture.
Selective inhibition of transcription of the Ets2 gene in prostate cancer cells by a triplex-forming oligonucleotide (2003)

The transcription factor Ets2 has a role in cancer development and represents an attractive therapeutic target. In this study, we designed a triplex-forming oligonucleotide (TFO) directed to a homopurine:homopyrimidine sequence in the Ets2 promoter. Transcription factors of the Sp family bound to this sequence and mutation of the Sp1 site reduced Ets2 promoter activity. The Ets2-TFO had high binding affinity for the target sequence and inhibited binding of Sp1/Sp3 to the overlapping site. This effect occurred with a high degree of sequence specificity. Mismatched oligonucleotides did not inhibit Sp1/Sp3 binding and mutations in the target sequence that abolished triplex formation prevented inhibition of Sp1/Sp3 binding by the TFO. The Ets2-TFO inhibited Ets2 promoter activity and expression of the endogenous gene in prostate cancer cells at nanomolar concentrations. The TFO did not affect reporter constructs with mutations in the TFO binding site and promoters of non-targeted genes. Expression of non-targeted genes was also not affected in TFO-treated cells. Collectively, these data demonstrated that the anti-transcriptional activity of the Ets2-TFO was sequence- and target-specific, and ruled out alternative, non-triplex mediated mechanisms of action. This anti-transcriptional approach may be useful to examine the effects of selective downregulation of Ets2 expression and may have therapeutic applications.
Safe operating area for 1200-V nonlatchup bipolar-mode MOSFET's (1987)

This paper reports the safe operating area (SOA) for 1200-V nonlatchup bipolar-mode MOSFET's. The measured SOA limit, in terms of current density and drain-voltage product, reached 2.5 × 10 <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">5</sup> W/cm <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> for 125°C-case temperature and 10-µs pulse operation conditions. It exceeded even the so-called "avalanche limit" for n-p-n bipolar transistors when the measurement was carried out under 25°C-case temperature conditions. These SOA's enable device protection from an abnormally large drain-current surge.
THE COMPLEMENT REGULATORS C1 INHIBITOR AND SOLUBLE COMPLEMENT RECEPTOR 1 ATTENUATE ACUTE LUNG INJURY IN RABBITS (2000)

Because activation of the complement system plays a major role in the pathogenesis of acute lung injury, the availability of new specific complement inhibitors represents a promising therapeutic approach. In the present study we investigated pulmonary edema formation and pulmonary artery pressure (PAP) in acute complement-induced lung injury for possible therapeutic impact of the complement regulators C1 inhibitor and soluble complement receptor 1. Eighteen isolated and ventilated rabbit lungs were perfused with pooled normal human serum (NHS, final concentration 35%) in Krebs-Henseleit buffer in a recirculating system. Lung weight gain and PAP were continuously recorded. Complement activation was blocked by the addition of C1 inhibitor (1.0 U/mL, n = 6) or sCR 1 (2.0 microg/mL, n = 6). Lungs that received NHS without inhibitors served as controls (n = 6). This study was performed according to the Helsinki Declaration and approved by the local government. Application of NHS resulted in an increase of PAP within 20 min from 8+/-2 to 42+/-6 mmHg, which was significantly (P < 0.05) decreased by C1-Inh (25+/-5 mmHg) and sCRI (20 +/-3 mmHg). Moreover, pulmonary edema formation after NHS, as assessed by overall weight gain, was reduced by both C1-Inh and sCR1, compared with controls. These findings were paralleled with significantly decreased thromboxane release rates and reduced tissue deposition of C3c and C5b-9. C1 inhibitor and sCR1 attenuate the complement-induced pulmonary capillary leakage and PAP increase, indicating the protective effect of complement inhibition in isolated perfused rabbit lungs.
Cryptography in OpenBSD: an overview (1999)

Cryptographic mechanisms are an important security component of an operating system in securing the system itself and its communication paths. Indeed, in many situations, cryptography is the only tool that can solve a particular problem, e.g., network-level security. While cryptography by itself does not guarantee security, when applied correctly, it can signi#cantly improve overall security. Since one of the main foci of the OpenBSD system is security,various cryptographic mechanisms are employed in a number of di#erent roles.
Mining from open answers in questionnaire data (2001)

Surveys are an important part of marketing and customer relationship management, and open answers (i.e., answers to open questions) in particular may contain valuable information and provide an important basis for making business decisions. We have developed a text mining system that provides a new way for analyzing open answers in questionnaire data. The product is able to perform the following two functions: (A) accurate extraction of characteristics for individual analysis targets, (B) accurate extraction of the relationships among characteristics of analysis targets. In this paper, we describe the working of our text mining system. It employs two statistical learning techniques: rule analysis and Correspondence Analysis for performing the two functions. Our text mining system has already been put into use by a number of large corporations in Japan in the performance of text mining on various types of survey data, including open answers about brand images, open answers about company images, complaints about products, comments written on home pages, business reports, and help desk records. In this it has been found to be useful in forming a basis for effective business decisions.
LIGHT SCATTERING FOR STRUCTURAL INVESTIGATIONS OF SILICA AEROGELS AND ALCOGELS (1989)

A scattering apparatus is described which allows the investigation of gels and aerogels with visible light. The correction formulas for various typical geometries are derived. Scattering data for silica aerogels with densities 71, 105 and 143 kg/m3 are provided ; the derived correlation lenghts ac are in the range 10 to 25 nm ; they show a systematic decrease with increasing density. We also provide results for light scattering in a sol-gel process.
Bone Marrow Transplantation without Myeloablation for Sickle Cell Disease (2001)

To the Editor: Bone marrow transplantation can eliminate sickle cell disease and halt end-organ damage.1,2 However, the applicability of the procedure is limited because of the toxic effects associated with conventional bone marrow transplantation. Nonmyeloablative conditioning regimens can decrease or eliminate such toxic effects.3–5 An eight-year-old girl with homozygous sickle cell disease had been receiving monthly transfusions and chelation therapy with deferoxamine since having a stroke three years earlier. Before the stroke, she had required three or four hospitalizations per year for vaso-occlusive crises and the acute chest syndrome. We treated the girl with a bone marrow transplant . . .
Self-Assembled Honeycomb Networks of Gold Nanocrystals (2001)

Size-monodisperse 35 Å diameter, sterically stabilized gold nanocrystals self-assemble into hexagonal networks, or two-dimensional honeycombs, during drop casting of a dispersion onto a substrate under the appropriate conditions. By changing the nanocrystal concentration prior to deposition, the microscopic morphology of self-assembled nanocrystal structures can be tuned from rings at high concentrations to honeycombs at low concentrations. The temperature dependence of the surface tension of the gold nanocrystal dispersions was measured using a ring tensiometer and found to depend on the particle concentration, particle size, and distribution. The morphological transition from rings to honeycombs appears to occur due to a transition from diffusive to convective fluid flow during solvent evaporation, which results directly from the surface tension and thermal conductivity differences between the dispersions.
Evidence for a catalytic role of glutamic acid 129 in the NAD-glycohydrolase activity of the pertussis toxin S1 subunit. (1993)

The S1 subunit of pertussis toxin is an ADP-ribosyl-transferase capable of transferring the ADP-ribose moiety of NAD+ to nucleotide-binding signal-transducing proteins of the Gi/G(o) family. In the absence of G proteins, the enzyme also catalyzes the hydrolysis of NAD+. Glu-129 was previously shown to be critical for both enzymatic activities. In this study, site-directed mutagenesis was used to make the conservative substitution of aspartate for Glu-129. The recombinant wild type and mutant proteins were purified to near homogeneity and used for enzymatic analyses. Kinetic experiments showed that the kcat of the mutant protein was about 200 times less than that of the wild type enzyme, whereas the Km for NAD+ of the two proteins were very similar, suggesting that Glu-129 is a catalytic residue for the NAD-glycohydrolase reaction of S1. This hypothesis was confirmed by a less than 2-fold change in Kd as measured by fluorescence quenching studies, indicating that the binding of NAD+ is not affected in the mutant protein in any important way. In another experiment, the replacement of Glu-129 by cysteine resulted in a disulfide bridge between Cys-129 and Cys-41 in rS1d-E129C, suggesting that the folding of the polypeptide chain is such that the catalytic Glu-129 residue is close to the amino-terminal NAD-binding site of S1. These findings imply that Glu-129 plays a key role in catalysis of the NAD-glycohydrolase reaction, possibly by electrostatically stabilizing a cationic transition state intermediate, or by serving as a general base to deprotonate the ADP-ribosyl acceptor substrates.
Fabrication of nanometer size photoresist wire patterns with a silver nanocrystal shadowmask (1999)

In this article, we present a new method for fabricating precisely defined nanometer scale photoresist wire patterns. The Langmuir technique was utilized to form high aspect ratio lamellae, or wire patterns, of Ag nanocrystals at the air/water interface, and these patterns were transferred onto resist-coated substrates as a Langmuir–Schaeffer film and as a shadowmask. The wire patterns were transferred to the photoresist material by spatially selective electron beam exposure on the Ag nanocrystal wire shadowmask. Monte Carlo simulation was done to estimate the electron stopping power for the Ag nanocrystal shadowmask at low voltage.
TRAF2 Must Bind to Cellular Inhibitors of Apoptosis for Tumor Necrosis Factor (TNF) to Efficiently Activate NF-κB and to Prevent TNF-induced Apoptosis (2009)

Tumor necrosis factor (TNF) receptor-associated factor-2 (TRAF2) binds to cIAP1 and cIAP2 (cIAP1/2) and recruits them to the cytoplasmic domain of several members of the TNF receptor (TNFR) superfamily, including the TNF-TNFR1 ligand-receptor complex. Here, we define a cIAP1/2-interacting motif (CIM) within the TRAF-N domain of TRAF2, and we use TRAF2 CIM mutants to determine the role of TRAF2 and cIAP1/2 individually, and the TRAF2-cIAP1/2 interaction, in TNFR1dependent signaling. We show that both the TRAF2 RING domain and the TRAF2 CIM are required to regulate NF-Binducing kinase stability and suppress constitutive noncanonical NF-B activation. Conversely, following TNFR1 stimulation, cells bearing a CIM-mutated TRAF2 showed reduced canonical NF-B activation and TNF-induced RIPK1 ubiquitylation. Remarkably, the RING domain of TRAF2 was dispensable for these functions. However, like the TRAF2 CIM, the RING domain of TRAF2 was required for protection against TNF-induced apoptosis. These results show that TRAF2 has anti-apoptotic signaling roles in addition to promoting NF-B signaling and that efficient activation of NF-B by TNFR1 requires the recruitment of cIAP1/2 by TRAF2.
Synthesis of (+)- and (−)-Tetrabenazine from the Resolution of α-Dihydrotetrabenazine (2009)

Abstract Tetrabenazine (1) was reduced with NaBH4 to α-dihydrotetrabenazine (2) and then resolved with di-p-toluoyl-L-tartrate and di-p-toluoyl-D-tartrate to subsequently give (+)- and (−)-α-dihydrotetrabenazine. The enantiomers were oxidized under Swern conditions to prepare samples of (+)-tetrabenazine and (−)-tetrabenazine. The samples were optically pure by chiral HPLC analysis.
Molecular cloning and construction of the coding region for human acetylcholinesterase reveals a G + C-rich attenuating structure. (1990)

To study the primary structure of human acetylcholinesterase (AcChoEase; EC 3.1.1.7) and its gene expression and amplification, cDNA libraries from human tissues expressing oocyte-translatable AcChoEase mRNA were constructed and screened with labeled oligodeoxynucleotide probes. Several cDNA clones were isolated that encoded a polypeptide with greater than or equal to 50% identically aligned amino acids to Torpedo AcChoEase and human butyrylcholinesterase (BtChoEase; EC 3.1.1.8). However, these cDNA clones were all truncated within a 300-nucleotide-long G + C-rich region with a predicted pattern of secondary structure having a high Gibbs free energy (-117 kcal/mol) downstream from the expected 5' end of the coding region. Screening of a genomic DNA library revealed the missing 5' domain. When ligated to the cDNA and constructed into a transcription vector, this sequence encoded a synthetic mRNA translated in microinjected oocytes into catalytically active AcChoEase with marked preference for acetylthiocholine over butyrylthiocholine as a substrate, susceptibility to inhibition by the AcChoEase inhibitor BW284C51, and resistance to the BtChoEase inhibitor tetraisopropylpyrophosphoramide. Blot hybridization of genomic DNA from different individuals carrying amplified AcChoEase genes revealed variable intensities and restriction patterns with probes from the regions upstream and downstream from the predicted G + C-rich structure. Thus, the human AcChoEase gene includes a putative G + C-rich attenuator domain and is subject to structural alterations in cases of AcChoEase gene amplification.
Renal Proximal Tubular Albumin Reabsorption: Daily Prevention of Albuminuria (1998)

Although the glomerular filtration coefficient of albumin is small, the daily filtered load can be as much as 8 g. To prevent such massive losses of albumin, quantitative reabsorption along the proximal tubules is accomplished by "receptor"-mediated endocytosis. Albumin reaches the lysosomes where it is degraded to amino acids.
Comparison of toxinotyping and PCR ribotyping of Clostridium difficile strains and description of novel toxinotypes (2001)

Toxinotyping and PCR ribotyping are two methods that have been used to type Clostridium difficile isolates. Toxinotyping is based on PCR-RFLP analysis of a 19 kb region encompassing the C. difficile pathogenicity locus. PCR ribotyping is based on comparison of patterns of PCR products of the 16S-23S rRNA intergenic spacer region. Representative strains (101) from a C. difficile PCR ribotype library and 22 strains from previously described toxinotypes were analysed to compare ribotyping with toxinotyping. Within this panel of strains all 11 toxinotypes (0-X) described previously and an additional 5 novel toxinotypes (XI-XV) were observed. PCR ribotyping and toxinotyping correlated well and usually all strains within a given ribotype had similar changes in toxin genes. The new toxinotype XI comprises strains that did not express toxins TcdA or TcdB at detectable levels, but contained part of the tcdA gene. Strains of toxinotype XII exhibit changes only in the 5' end of the tcdB gene. Toxinotype XIV is composed of strains that have a large insertion at the beginning of the tcdA gene. A total of 25 of the 89 tested PCR ribotypes of C. difficile contained variant strains. It was estimated that they represent 7.7% of the total number of strains in the Anaerobe Reference Unit collection.
Calcium-independent phosphodiesterase inhibitors as putative antidepressants: [3-(bicycloalkyloxy)-4-methoxyphenyl-2-imidazolidinones (1991)

The synthesis and biological properties of a novel series of selective calcium-independent phosphodiesterase inhibitors are described. These compounds also inhibit the specific binding of [3H]rolipram to rat brain membranes and exhibit efficacy in preclinical models of antidepressant activity in mice, such as reducing immobility in the forced-swim test and reversing reserpine-induced hypothermia. Imidazolidinones 4 and 16 were found to be the most potent compounds studied.
Peptide Secondary Structure Mimetics: Recent Advances and Future Challenges (1993)

An important goal of structural biochemistry is the reduction of complex molecules to small functional units that are amenable to high-resolution structural analysis and rapid modification. The dissection of multidomain proteins into small synthetic conformationally restricted components is an important step in the design of low molecular weight nonpeptides that mimic the activity of the native protein. Mimetics of critical functional domains might possess beneficial properties in comparison to the intact proteinaceous species with regard to specificity and therapeutic potential, and are valuable probes for the study of molecular recognition events. 1. Introduction 2. Peptidomimetic Discovery Strategies 3. The Secondary Structure Approach 4. First Generation Reverse Turn Mimetics 5. The Second Generation 6. Third Generation Mimetics 7. Conclusions
Management of Advanced Prostate Cancer (2000)

Most cases of advanced carcinoma of the prostate are hormonosensitive. The use of combined androgen blockade (CAB) seems to improve survival and quality of life, but only when combined with chemical castration by luteinizing-hormone-releasing hormone analog and without the use of steroidal antiandrogens. After CAB, further hormonal treatments remain efficacious, such as antiandrogen withdrawal followed by estrogens, aromatase inhibitors, and hormone-refractory prostate cancer multiple cytotoxic agents. For painful bone lesions, external beam radiotherapy, biphosphonates, and strontium 89 or samarium 153 provide pain relief. The use of new methods for the evaluation of response and quality of life will allow the rapid identification of effective treatments and permit powered phase III trials.
Managing Anger and Bullying Issues (2003)

This section discusses the issue of student's anger pathology, its reasons and impacts on the class. It also focuses on the various aspects of managing anger and the bullying issues of children with behaviour disorders.
Australian fish—An excellent source of both arachidonic acid and ω‐3 polyunsaturated fatty acids (1983)

The fatty acid methyl esters obtained by the esterification of total lipids extracted from 24 species of fin fish and 4 species of invertebrates caught in the rivers and coastal waters of southern Australia were analyzed by gas chromatography. The lipids of most species contained significant levels of arachidonic acid (0.7-15.8%) as well as the more common marine polyunsaturate, eicosapentaenoic acid (0.7-15.9%). The major ω6 fatty acid present in most species was 20∶4; however, other fatty acids of this series, including 18∶2, 22∶4 and 22∶5, were present. The level of total ω6 fatty acids ranged from 3.9 to 22.3% of the total lipid. In general, the level of total ω3 polyunsaturates was higher than the total ω6 fatty acids with levels of ω3 fatty acids ranging from 9.6 to 48.2%. Only 2 fish (barramundi and gurnard perch) had ω6/ω3 ratios greater than 1.0. Most of the Australian species examined contained low levels of fat (0.5-7.8% of fresh weight). Two species examined, callop (freshwater) and blue groper (marine) contained sufficient quantities of both fat (7.7 and 7.8%) and arachidonic acid (4.8 and 9.3%) to warrant consideration for commercial exploitation.
A randomised study of topical 5% imiquimod vs. topical 5-fluorouracil vs. cryosurgery in immunocompetent patients with actinic keratoses: a comparison of clinical and histological outcomes including 1-year follow-up (2007)

Imiquimod treatment of AK resulted in superior sustained clearance and cosmetic outcomes compared with cryosurgery and 5-FU. It should be considered as a first line therapy for sustained treatment of AK.