gebhart/patrepeval huggingface dataset:
Loss of heterozygosity on chromosome 6p21.2 as a potential marker for recurrence after radiotherapy of human cervical cancer. (2000)

Cervical carcinomas develop as a result of multiple genetic alterations, and specific alterations lead to specific clinical behavior. However, the effect of such alterations on the recurrence of cervical cancer after radiotherapy remains unknown. Chromosome arm 6p is one of those most frequently involved in a loss of heterozygosity (LOH) in patients with cervical carcinoma. The aim of this study was to identify the correlation between the LOH on chromosome 6p21.2 and the recurrence of cervical cancer after radiotherapy. A total of 62 patients with cervical cancer (stage I, 4 patients; stage II, 9 patients; stage III, 37 patients; and stage IV, 12 patients) were included in this study. All patients were treated with definitive radiotherapy. We analyzed specimens from the tumors and venous blood of all patients. Tumors and normal DNA were analyzed by PCR for genetic losses at three polymorphic microsatellite loci (D6S276, D6S1624, and D6S1583). Chromosome 6p21.2 is involved in the LOH in 46.8% (29 of 62) of the informative carcinomas. Ten patients had a local recurrence, 4 had distant metastases, and 13 had both local recurrence and distant metastases after radiotherapy. To evaluate the relationship between the recurrence after radiotherapy and LOH on chromosome 6p21.2, we divided the patients into those with cancer recurrence (n = 27) and those without recurrence (n = 35). LOH on chromosome 6p21.2 was correlated with recurrence after radiotherapy (P = 0.006). The tumors in patients with recurrence were significantly larger than those in patients without recurrence (P = 0.003). However, there was no correlation between the sizes and stages of tumors and the LOH on chromosome 6p21.2. In addition, both overall survival and relapse-free survival were significantly worse for the patients with LOH as compared with those without LOH (P = 0.02 and P = 0.002, respectively). The results of this study suggest that LOH on 6p21.2 is correlated with recurrence of cervical carcinoma after radiotherapy.
Prerequisites as Outcomes:Thomas Hobbes and the Paradoxes of Political Origins (1997)

To encounter the work of Thomas Hobbes is to encounter a deep aversion toward ambiguity. Both as a methodological concern and as a substantive position, a distrust of interpretative openness pervades Leviathan and the other principal texts of Hobbes. For him, the defusing and transcending and confining of ambiguity were the means by which his chief aim could be fulfilled—the aim of nurturing social concord. Without the taming of interpretative multiplicity and inconstancy, the dampening of societal strife could not proceed.
Wound-induced accumulation of mRNA containing a hevein sequence in laticifers of rubber tree (Hevea brasiliensis). (1990)

Hevein is a chitin-binding protein that is present in laticifers of the rubber tree (Hevea brasiliensis). A cDNA clone (HEV1) encoding hevein was isolated by using the polymerase chain reaction with mixed oligonucleotides corresponding to two regions of hevein as primers and a Hevea latex cDNA library as a template. HEV1 is 1018 base pairs long and includes an open reading frame of 204 amino acids. The deduced amino acid sequence contains a putative signal sequence of 17 amino acid residues followed by a 187-amino acid polypeptide. This polypeptide has two striking features. The amino-terminal region (43 amino acids) is identical to hevein and shows homology to several chitin-binding proteins and to the amino termini of wound-inducible proteins in potato and poplar. The carboxyl-terminal portion of the polypeptide (144 amino acids) is 74-79% homologous to the carboxyl-terminal region of wound-inducible genes of potato. Wounding, as well as application of the plant hormones abscisic acid and ethylene, resulted in accumulation of hevein transcripts in leaves, stems, and latex but not in roots.
Insertion Mutations in Herpes Simplex Virus 1 Glycoprotein H Reduce Cell Surface Expression, Slow the Rate of Cell Fusion, or Abrogate Functions in Cell Fusion and Viral Entry (2009)

Of the four required herpes simplex virus (HSV) entry glycoproteins, the precise role of gH-gL in fusion remains the most elusive. The heterodimer gH-gL has been proposed to mediate hemifusion after the interaction of another required glycoprotein, gD, with a receptor. To identify functional domains of HSV-1 gH, we generated 22 randomized linker-insertion mutants. Analyses of 22 gH mutants revealed that gH is relatively tolerant of insertion mutations, as 15 of 22 mutants permitted normal processing and transport of gH-gL to the cell surface. gH mutants that were not expressed well at the cell surface did not function in fusion or viral entry. The screening of gH mutants for function revealed the following: (i) for wild-type gH and some gH mutants, fusion with nectin-1-expressing target cells occurred more rapidly than with herpesvirus entry mediator (HVEM)-expressing target cells; (ii) some gH mutants reduced the rate of cell fusion without abrogating fusion completely, indicating that gH may play a role in governing the kinetics of fusion and may be responsible for a rate-limiting first stage in HSV-1 fusion; and (iii) only one gH mutant, located within the short cytoplasmic tail, completely abrogated function, indicating that the gH cytoplasmic tail is crucial for cell fusion and viral infectivity.
15-PGDH inhibitors: the antiulcer effects of carbenoxolone, pioglitazone and verapamil in indomethacin induced peptic ulcer rats. (2013)

The antiulcer properties of pioglitazone and verapamil are, in part, consequences of their inhibitory effect on the enzyme 15-PGDH, responsible for PGs degradation, and the resultant prolongation of PGE2 biological activity in rat stomach mucosa.
Therapeutic options directed against platelet activating factor, eicosanoids and bradykinin in sepsis (1998)

Various autacoids, including the eicosanoids, platelet activating factor (PAF) and bradykinin, have been implicated in the pathogenesis of sepsis and septic shock. The precise role of these compounds as mediators of the diffuse inflammatory state characteristic of sepsis remains to be determined, but, in animal models, beneficial effects have been observed as a result of treatment with various inhibitors of eicosanoid biosynthesis or antagonists of PAF or bradykinin receptors. To date, however, it has been impossible to translate these encouraging results from animal models into convincingly positive results in the clinical setting.
T-Lymphocyte Dysregulation in Asthma (1994)

In this paper, we have reviewed the evidence suggesting that T-cell dysregulation is important in the pathogenesis of asthma. The history, clinical presentation, and an overview of the appropriate management of asthma have been briefly reviewed. T cells obtained from the airways of asthmatics display signs of activation; these changes mirror the intramural inflammation found at biopsy. There is debate about the importance of T helper/suppressor ratios in this population of cells, but alterations in these ratios have been noted with experimental allergen exposure, as well as during acute asthma attacks; some of these changes revert toward normal with steroid therapy. The division of T helper lymphocytes into Th1 and Th2 cells, first described in studies of murine immunology, appear to be relevant in humans, particularly in allergic disease. Although IL-4 and IL-5, prototypical Th2 cytokines, have been most clearly implicated in asthma, there is some evidence supporting a role for Th1 cells/cytokines as well.
Inactivation of the antiapoptotic phosphatidylinositol 3-kinase-Akt pathway by the combined treatment of taxol and mitogen-activated protein kinase kinase inhibition. (2002)

Paclitaxel (Taxol) activates a number of signal transduction pathways that lead to apoptosis. In contrast, paclitaxel also activates cell survival pathways, such as the Raf-mitogen-activated protein kinase kinase (MEK)-extracellular signal-regulated kinase (ERK) pathway. Previously, we have shown that inhibition of MEK combined with paclitaxel treatment causes an impressive enhancement of apoptosis in various tumor cell lines. Here, we find that the combination of paclitaxel with a MEK inhibitor leads to a dramatic inactivation of the antiapoptotic Akt (protein kinase B) kinase. The decrease in Akt is not reflected at the protein or mRNA level but rather attributed to kinase inactivation. To confirm that inactivation of Akt is significant, a constitutively active Akt mutant was introduced and shown to reverse tumor cell apoptosis. Further analysis upstream of Akt shows that treatment with the combination of paclitaxel and MEK inhibitor down-regulates PI3K activity more than either agent alone. The direct pharmacological inhibition of phosphatidylinositol 3-kinase (PI3K) similarly enhances paclitaxel-induced tumor apoptosis in a dose-dependent manner. Our results suggest the combination of paclitaxel and MEK inhibitor leads to down-regulation of the PI3K-Akt signaling in addition to the proapoptotic effects of paclitaxel and MEK inhibitor alone. Overall, these findings render the combined use of paclitaxel with MEK inhibitors, or paclitaxel with PI3K inhibitors, as a promising new strategy for cancer chemotherapy.
Functional Analysis of the C-terminal Extension of Telomerase Reverse Transcriptase (2002)

Telomerase is an RNA-protein complex responsible for the extension of one strand of telomere terminal repeats. The catalytic protein subunit of telomerase, known generically as telomerase reverse transcriptase (TERT), exhibits significant homology to reverse transcriptases (RTs) encoded by retroviruses and retroelements. The mechanisms of telomerase may therefore be similar to those of the conventional reverse transcriptases. In this report, we explore potential similarity between these two classes of proteins in a region with no evident sequence similarity. Previous analysis has implicated a C-terminal domain of retroviral RTs (known as the "thumb" domain) in template-primer binding and in processivity control. The equivalent region of TERTs, although similar to one another, does not exhibit significant sequence homology to retroviral RTs. However, we found that removal of this region of yeast TERT similarly resulted in a decrease in the stability of telomerase-DNA complex and in the processivity of telomerase-mediated nucleotide addition. Moreover, the C-terminal domain of TERT exhibits a nucleic acid binding activity when recombinantly expressed and purified. Finally, amino acid substitutions of conserved residues in this region of TERT were found to impair telomerase activity and processivity. We suggest that mechanistic similarity between telomerase and retroviral RTs may extend beyond the regions with apparent sequence similarity.
T-cell-depleted allogeneic bone marrow transplantation in adults with acute nonlymphocytic leukemia in first remission (1992)

Abstract We prospectively evaluated the efficacy of T-cell-depleted bone marrow transplantation (BMT) in adults with de novo acute nonlymphocytic leukemia (ANLL) in first complete remission (CR), with regard to relapse-free survival and incidence of graft-versus-host disease (GvHD). Thirty-one patients older than 16 years (range, 16.5 to 43.2) received T-cell-depleted grafts for this purpose from related HLA/MLC- compatible donors. Twelve of the patients were older than 30 years at the time of transplantation. Patients were prepared with hyperfractionated total body irradiation (HFTBI; 1,375 to 1,500 cGy) and high-dose cyclophosphamide (120 mg/kg). T cells were removed from the marrow grafts by a two-step soybean lectin agglutination and sheep red blood cell (sRBC)-rosette procedure, achieving a 2.5- to 3-log depletion of clonable T lymphocytes. No additional prophylaxis against GvHD was administered. The median age at transplantation was 28.8 years; the median interval from diagnosis to transplantation was 3.8 months, and from CR was 2.7 months. Seventy-four percent received consolidation after remission induction therapy. The product-limit estimate of disease-free survival (DFS) at 3 years is 45% (95% confidence interval [CI], 24% to 66%), and the cause-specific probability of relapse is 13%. The median follow-up of the survivors is 72 months (range, 34.5 to 95.6). Median time to achieve a sustained absolute neutrophil count of 500 or greater was 16 days, and to maintain an untransfused platelet count of 20,000 or greater was 20 days. Five patients suffered immune-mediated graft rejection. Three patients developed grade I to II acute GvHD limited to the skin, which resolved promptly with brief courses of systemic steroids. None of the patients has developed clinically apparent chronic GvHD or a secondary lymphoproliferative disorder, and no patient is receiving immunosuppressive therapy. T-cell-depleted BMT by the method reported here is a favorable option as postremission therapy for adults with de novo ANLL in first remission who have an HLA/MLC-compatible related donor, and it is not associated with an increased risk of relapse posttransplant.
Superconducting Y–Ba–Cu–O Films with Tc&gt;70 K Prepared by Thermal Decomposition Technique of Y-, Ba-, and Cu-2ethylhexanoates (1987)

Abstract High Tc superconducting Y–Ba–Cu–O films with Tc(end)&amp;gt;70 K were prepared on yttria stabilized zirconia substrates by the thermal decomposition technique using Y-, Ba-, and Cu-2ethylhexanoates. The observed Tc(onset) was 95 K and Tc(end) was 72 K, and they are currently the highest Tc values for films obtained from organic acid salts.
SNP and mutation discovery using base-specificcleavage and MALDI-TOF mass spectrometry (2003)

Abstract Motivation: Single Nucleotide Polymorphisms (SNPs) are believed to contribute strongly to the genetic variability in living beings, in particular their disease or drug side effect predispositions. Mutation-induced sequence variations are playing an important role in the development of cancer, among others. From this, it is clear that SNP and mutation discovery is of great interest in today’s Life Sciences. Currently, such discovery is often performed utilizing electrophoresis-based Sanger Sequencing. Discovery of SNPs can also be performed by multiple sequence alignment of publicly available sequence data, but recent studies indicate that only a small percentage of SNPs can be discovered using this approach and, in particular, that SNPs with low frequency are often missed. Other SNP discovery methods only indicate the presence of a SNP in a sample region, but fail to resolve its characterization and localization. Results: We present a method to discover mutations and SNPs using base-specific cleavage and mass spectrometry. An amplicon of known reference sequence with length usually between 100 and 1000 nt is amplified, transcribed, and cleaved using base-specific endonucleases such as RNAse A or T1. The resulting cleavage products (or fragments) are analyzed by MALDI-TOF mass spectrometry and, comparing the measured spectra with those predicted in-silico, the goal is to discover and pinpoint sequence variations of the sample sequence compared to the reference sequence. A time-efficient algorithm for discovering sequence variations is presented that enables fast analysis of such variations even if the sample sequence differs significantly from the reference sequence. Contact: boecker@CeBiTec.uni-bielefeld.de *Currently at AG Genome Informatics, Technische Fakultät, Universität Bielefeld, Germany.
Vibro-acoustic tissue mammography (2002)

A novel method for detection and imaging of microcalcifications in breast tissue is presented. The method, called vibro-acoustography, uses the radiation force of ultrasound to vibrate tissue at low (kHz) frequency and utilizes the resulting response to produce images that are related to the hardness of the tissue. The method is tested on human breast tissues. The resulting vibro-acoustographic images are in agreement with corresponding X-ray mammography images of the specimens. The existence of microcalcifications in locations indicated by vibro-acoustography is confirmed by histology. Microcalcifications as small as 110 microm in diameter are detected by this method. Resulting vibro-acoustographic images show microcalcifications with high contrast with respect to the background soft tissue. Structures such as dense sclerotic tissue do not seem to interfere with detection of microcalcifications.
Silver Sulfadiazine—A New Topical Therapy for Pseudomonas in Burns (1968)

AFTER thermal burns local and systemic infection, especially with<i>Pseudomonas aeruginosa</i>, is a major cause of death. The use of soluble sodium sulfonamides in wounds and burns was investigated during World War II,<sup>1</sup>and in studies of extensive burns,<sup>2</sup>topical antibacterial therapy was combined with treatment for the burn wound by using a neutralized mixture of tannic acid and sodium sulfadiazine. Although the results were good, emphasis shifted to the role of sodium salts in systemic therapy in an era of disbelief in the efficacy of local antibacterial therapy. As predicted in 1952 by Meleney,<sup>3</sup>there is now a renaissance of topical antibacterial therapy with the introduction of dilute silver nitrate solutions<sup>4</sup>and mafenide-containing ointments.<sup>5</sup>Both agents are effective in burn wound sepsis, especially that caused by<i>P aeruginosa</i>, but both also produce characteristic fluid and electrolyte alterations. The hypotonic (29.4 millimol/liter) silver nitrate solution
Functional properties of a new crosslinked hemoglobin designed for use as a red cell substitute (1989)

A new crosslinking agent, bis-pyridoxal tetraphosphate, (bis-PL)P4, was used to prevent dissociation of the hemoglobin (Hb) tetramer. Yields in excess of 75 percent of intramolecularly crosslinked (bis-PL)P4Hb have been obtained using stoichiometric amounts of the crosslinking reagent. Some functional properties of (bis-PL)P4Hb have been evaluated in vitro and in vivo. Oxygen affinity was substantially reduced (p50 = 31 torr at 37 degrees C, pH 7.4, pCO2 = 40 torr), while the Bohr coefficient was -0.27 of H+ per mol of O2. Owing to its right-shifted dissociation curve, (bis-PL)P4Hb still yielded a p50 of 15 torr at a low temperature (16 degrees C), as compared with only 3 torr for normal adult Hb (HbA). Clearance of (bis-PL)P4Hb from plasma was significantly delayed (t1/2 = 171 min, at a dose of 0.2 g/kg of body weight compared with that of HbA (t1/2 = 54 min). Heart rate, mean arterial blood pressure, and respiration remained stable or returned to normal values within hours after bolus injection of the hemoglobin. The (bis-PL)P4Hb was not excreted in the urine, in contrast to HbA (21% of the total dose of HbA appeared in the urine within the first 2 hrs). These results show that the covalent beta-beta crosslink prevents the renal excretion of (bis-PL)P4Hb, thereby significantly prolonging vascular retention. These properties, together with an increased ability to unload O2, make (bis-PL)P4Hb a promising new candidate as a red cell substitute.
'Natural' search user interfaces (2011)

Users will speak rather than type, watch video rather than read, and use technology socially rather than alone.
Treatment of advanced medullary thyroid carcinoma with a combination of cyclophosphamide, vincristine, and dacarbazine (1994)

Our experience suggests that CVD chemotherapy has moderate activity and is well tolerated in patients with advanced MTC. Additional prospective studies of this regimen for MTC are required.
Characterization of the T-Cell Response to Coxsackievirus B4 (2002)

Most of the evidence linking enterovirus (EV) infection with the development and/or acceleration of type 1 diabetes is indirect. Few studies have examined T-cell responses to these viruses, and therefore the nature of the viral targets and the immune cells involved in antiviral responses remain unclear. In the present study, we examined the characteristics of the T-cell response to the EV Coxsackievirus B4 (CVB4) in patients with type 1 diabetes and healthy control subjects. We find that CVB4-specific T-cells preferentially target the envelope proteins VP1, VP2, and VP3, and that the response to these and other CVB4 proteins differs markedly in type 1 diabetic patients compared with nondiabetic control subjects. The frequency of T-cell proliferative responses against VP2 was significantly reduced in type 1 diabetic patients compared with control subjects, especially in patients tested near to diagnosis (P < 0.001). In contrast, median levels of gamma-interferon (IFN-gamma) production by T-cells in response to the CVB4 antigens tested were generally high in new-onset type 1 diabetic patients, who produced significantly higher levels in response to VP3 compared with healthy subjects (P < 0.05) and patients with long-standing disease (P < 0.05). New-onset type 1 diabetic patients also had higher levels in response to P2C compared with healthy subjects (P < 0.005) and to VP2 compared with patients with long-standing disease (P < 0.05). These results suggest that the quality of the immune response to CVB4 antigens differs significantly between type 1 diabetic patients and control subjects, with a predominance of primed effector (IFN-gamma-producing) memory cells near to disease diagnosis. The data are consistent with the notion that the diagnosis of type 1 diabetes is associated with recent or persistent exposure to EV antigens.
Filtering edges for gray-scale displays (1981)

While simple line-drawing techniques produce “jagged” lines on raster images, more complex anti-aliasing, or filtering, techniques use gray-scale to give the appearance of smooth lines and edges. Unfortunately, these techniques are not frequently used because filtering is thought to require considerable computation. This paper presents a simple algorithm that can be used to draw filtered lines; the inner loop is a variant of the Bresenham point-plotting algorithm. The algorithm uses table lookup to reduce the computation required for filtering. Simple variations of the algorithm can be used to draw lines with different thicknesses and to smooth edges of polygons.
Multirate digital filters, filter banks, polyphase networks, and applications: a tutorial (1990)

The basic concepts and building blocks in multirate digital signal processing (DSP), including the digital polyphase representation, are reviewed. Recent progress, as reported by several authors in this area, is discussed. Several applications are described, including subband coding of waveforms, voice privacy systems, integral and fractional sampling rate conversion (such as in digital audio), digital crossover networks, and multirate coding of narrowband filter coefficients. The M-band quadrature mirror filter (QMF) bank is discussed in considerable detail, including an analysis of various errors and imperfections. Recent techniques for perfect signal reconstruction in such systems are reviewed. The connection between QMF banks and other related topics, such as block digital filtering and periodically time-varying systems, is examined in a pseudo-circulant-matrix framework. Unconventional applications of the polyphase concept are discussed.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>