gebhart/patrepeval huggingface dataset:
Sexually Transmitted Diseases and Tubal Pregnancy (1990)

The risk of tubal pregnancy associated with seropositivity to Chlamydia trachomatis or following a diagnosis of gonorrhea, genital herpes, trichomoniasis, genital warts, or nonspecific vaginal infection was evaluated in a study of this condition among women who were members of a prepaid health plan. A total of 264 women who had a tubal pregnancy between 1981 and 1986 were interviewed about their history of these sexually transmitted diseases (STDs). Their responses were compared to those of 715 women who were matched by age and county of residence but were otherwise randomly selected from the enrollment files of the health plan. Chlamydia antibody status was known in a sample of 135 cases and 192 controls. Although more cases reported a history of gonorrhea, trichomoniasis, and non-specific vaginal infections than did controls, only a modestly elevated risk for trichomoniasis remained after logistic regression was used to adjust for the effects of age, reference year, race, presence of contraception at reference date, seropositivity to Chlamydia trachomatis, and a history of other STDs. By contrast, among women for whom Chlamydia trachomatis antibody status was assessed, presence of antibody was associated with a two-fold increase in the risk of tubal pregnancy after adjusting for the effects of the previously enumerated variables. These findings confirm the relevance of Chlamydia trachomatis as a risk factor for ectopic pregnancy, and they also underscore the importance of adjustment for the influence of other STDs when evaluating the association between a specific STD and the occurrence of tubal pregnancy.
Alpha‐1‐antitrypsin inhibits human immunodeficiency virus type 1 (2001)

Several observations suggest the existence of potent endogenous suppressors of human immunodeficiency virus type 1 (HIV-1) production, and inhibitors of serine proteases may participate in this effect. Alpha-1-antitrypsin (AAT) is the most abundant circulating serine protease inhibitor. Physiological AAT concentrations inhibited HIV-1 production in chronically infected U1 monocytic cells, reduced virus replication in freshly infected peripheral blood mononuclear cells, and blocked infection of permissive HeLa cells. In U1 cells, AAT suppressed activation of the HIV-1-inducing transcription factor NF-kappaB. Similar results were obtained using CE-2072, a synthetic inhibitor of host serine proteases. HIV-1 did not replicate in blood obtained from healthy volunteers, but marked replication was observed in blood from individuals with hereditary AAT deficiency. These results identify AAT as a candidate circulating HIV-1 inhibitor in vivo. Two different mechanisms of AAT-induced HIV-1 inhibition were identified, including reduced HIV-1 infectivity and blockade of HIV-1 production. A novel host-pathogen interaction is suggested, and an alternative strategy to treat HIV-1-related disease may be possible.
Linear hashing with overflow-handling by linear probing (1985)

Linear hashing is a file structure for dynamic files. In this paper, a new, simple method for handling overflow records in connection with linear hashing is proposed. The method is based on linear probing and does not rely on chaining. No dedicated overflow area is required. The expansion sequence of liner hashing is modified to improve the performance, which requires changes in the address computation. A new address computation algorithm and an expansion algorithm are given. The performance of the method is studied by simulation. The algorithms for the basic file operations are very simple, and the overall performance is competitive with that of other variants of linear hashing.
Cloning of a novel putative G‐protein‐coupled receptor (NLR) which is expressed in neuronal and lymphatic tissue (1993)

A novel G-protein-coupled receptor was isolated from mouse and rat neuronal and lymphatic tissues. The amino acid sequence of the rat receptor (rNLR) shows an overall homology of 80% to a recently cloned receptor from Burkitt's lymphoma cells (BLR1) which is exclusively expressed in lymphatic tissues [(1992) Eur. J. Immunol. 22, 2795]. Much less homology between rNLR and BLR1 was observed at the N-terminus (about 40%), whereas rNLR and the mouse homologue mNLR show 92% amino acid identity. Northern blot analysis of NLR revealed a predominant 5.5 kb mRNA species in various brain regions and neuronal cell lines, whereas in the spleen a 3 kb transcript is predominant. This distribution suggests a role of NLR in the nervous and immune systems.
Effect of Antigen Coating Conditions on Enzyme-Linked Immunosorbent Assay for Detection of Immunoglobulin G Antibody to Neisseria meningitidis Serogroup Y and W135 Capsular Polysaccharide Antigens in Serum (2003)

Human sera collected from 28 consenting adult volunteers were used to define assay conditions for meningococcal vaccine clinical trial serology. Immunoassay parameters were optimized with these test sera and the standard reference serum, CDC1992. Coating conditions for serogroup Y and W135 polysaccharide antigens were found to influence the predicted serum immunoglobulin G (IgG) antibody concentrations. Sera that displayed IgG antibody binding profiles most unlike that of CDC1992 were influenced the most by coating conditions. Our results suggest that presentation of specific epitopes is influenced by antigen-coating concentrations for serogroup Y and W135 polysaccharides.
Efficient Payload Delivery by a Bispecific Antibody–Drug Conjugate Targeting HER2 and CD63 (2016)

Antibody-drug conjugates (ADC) are designed to be stable in circulation and to release potent cytotoxic drugs intracellularly following antigen-specific binding, uptake, and degradation in tumor cells. Efficient internalization and routing to lysosomes where proteolysis can take place is therefore essential. For many cell surface proteins and carbohydrate structures on tumor cells, however, the magnitude of these processes is insufficient to allow for an effective ADC approach. We hypothesized that we could overcome this limitation by enhancing lysosomal ADC delivery via a bispecific antibody (bsAb) approach, in which one binding domain would provide tumor specificity, whereas the other binding domain would facilitate targeting to the lysosomal compartment. We therefore designed a bsAb in which one binding arm specifically targeted CD63, a protein that is described to shuttle between the plasma membrane and intracellular compartments, and combined it in a bsAb with a HER2 binding arm, which was selected as model antigen for tumor-specific binding. The resulting bsHER2xCD63<sub>his</sub> demonstrated strong binding, internalization and lysosomal accumulation in HER2-positive tumor cells, and minimal internalization into HER2-negative cells. By conjugating bsHER2xCD63<sub>his</sub> to the microtubule-disrupting agent duostatin-3, we were able to demonstrate potent cytotoxicity of bsHER2xCD63<sub>his</sub>-ADC against HER2-positive tumors, which was not observed with monovalent HER2- and CD63-specific ADCs. Our data demonstrate, for the first time, that intracellular trafficking of ADCs can be improved using a bsAb approach that targets the lysosomal membrane protein CD63 and provide a rationale for the development of novel bsADCs that combine tumor-specific targeting with targeting of rapidly internalizing antigens. Mol Cancer Ther; 15(11); 2688-97. ©2016 AACR.
Cloning-Free PCR-Based Allele Replacement Methods (1997)

Efficient homologous recombination permits the directed introduction of specific mutations into the yeast genome. Here we describe a cloning-free, PCR-based allele replacement method that simplifies allele transfer between yeast strains. The desired allele from one strain is amplified by PCR, along with a selectable/counterselectable marker. After transformation, the resident allele in the target strain is replaced by creating a duplication of the new allele. Selection for direct repeat recombinants results in a single copy of the new allele in the target strain. Specifically, the desired allele is amplified by PCR with a pair of adaptamers, which are chimeric oligonucleotides that are used to amplify the allele and differentially tag its 5' and 3' ends. These tags allow the directed fusion to two different, but overlapping, regions of an appropriately tagged selectable/counterselectable marker after a second round of PCR amplification. Following cotransformation of the two fusion fragments into yeast, homologous recombination efficiently generates a duplication of the amplified allele flanking the intact selectable marker in the genome. After counterselection, only the desired allele is retained as a result of direct repeat recombination. A simple modification of this method allows the creation of de novo mutations in the genome.
Elliptical defected core photonic crystal fiber with high birefringence and negative flattened dispersion (2012)

We propose a novel design of photonic crystal fiber (PCF) using an elliptical air hole in the core as a defected core in order to enhance the performance of modal birefringence and to control the properties of chromatic dispersion at the same time. From the simulation results, it is shown that the proposed fiber has high birefringence up to the order of 10(-2), negative flattened chromatic dispersion in a broad range of wavelengths, and low confinement loss less than that of the single mode fiber. The outstanding advantage of the proposed PCF is that high birefringence, negative flattened dispersion, and low confinement loss can be achieved just by adding a small sized elliptical air hole in the core to the elliptical air hole PCF, especially at the same time.
Orexin receptor subtype activation and locomotor behaviour in the rat (2009)

We conclude that orexin A exerts its effects on locomotor behaviour via both the OX(1)R and OX(2)R and that agonism or antagonism of only one of these receptors for therapeutic purposes (i.e. sleep disorders) would not provide selectivity in terms of associated behavioural side effects.
SPF overview (2004)

Spam, scams and worms all use e-mail forgery. Put a stop to it with the new mark of quality for your domain.
Outer Retinal Degeneration (2004)

There has been substantial progress toward an electronic retinal prosthesis, but fully functional, long-lasting devices are not on the immediate horizon.
APRIL, BCMA and TACI proteins are abnormally expressed in non-small cell lung cancer (2016)

Lung cancer is the leading cause of cancer-associated mortality. Non-small cell lung cancer (NSCLC) accounts for >80% of lung cancers. The overall survival for NSCLC is dismal, with a 5-year survival of <5% for patients. Thus, identifying an effective biomarker for early diagnosis of lung cancer is the first essential step to reduce mortality. It has been recognized that certain inflammatory and immune responses are important in lung cancer development and prevention. The present study demonstrated that, in NSCLC, a proliferation-inducing ligand (APRIL), B-cell maturation antigen (BCMA)and transmembrane activator and CAML interactor (TACI) proteins are abnormally expressed by immunohistochemistry, reverse transcription-quantitative polymerase chain reaction and western blotting. In addition, the expression of APRIL, BCMA and TACI were observed to be involved in extracellular signal-regulated kinase (ERK)1/2 activation in A549 cells. Overall, the present study provides evidence that APRIL and its receptors, BCMA and TACI, may play roles in the biological processes of NSCLC tumors through the ERK1/2 signaling pathway.
Levitt and Tapley's technological basis of radiation therapy : practical clinical applications (1992)

Intended for radiation oncologists and therapy technicians, this book reflects advances in the technology and practice of both diagnostic and therapeutic radiology. Approaches to the treatment of cancer have been modified utilizing multiple modalities as well as combinations of external beam and brachytherapy. Chapters new to this edition include discussions of diagnostic techniques in determining tumour size and location, soft tissue sarcomas and simulation. The importance of accurate localization, adequate dosage and reproducability of the daily treatment fields as essential to quality radiation therapy is stressed.
PROLONGATION OF CARDIAC ALLOGRAFT SURVIVAL IN MURINE RECIPIENTS TREATED WITH A DIPHTHERIA TOXIN RELATED INTERLEUKIN-2 FUSION PROTEIN (1989)

A diphtheria toxin-related IL-2 fusion gene has been constructed that encodes a 68KD recombinant toxin in which the diphtheria toxin receptor-binding domain has been replaced with amino acids 2-133 of IL-2. This chimeric IL-2 toxin is cytotoxic for cells expressing the high-affinity IL-2 receptor but not for cells lacking this receptor. The ability of this IL-2 toxin to prolong allograft survival was examined in a murine vascularized, heterotopic heart transplant model in the strain combination B10.BR into C57B1/10. When given at a dose of 1.0 micrograms/day for 10 days, the IL-2 toxin significantly prolonged allograft survival in all recipients. CRM-45, a fragment of diphtheria toxin missing the binding domain, was ineffective, confirming the specificity of the therapy. The results demonstrate that this IL-2 toxin, which targets activated T cells expressing the IL-2 receptor, will prolong allograft survival, offering a new option for immunosuppressive therapy.
Congruence Between Existing Prevention Programs and Research on Risk Factors and Mechanisms of Noncontact ACL Injury (2007)

ACL-Loading Mechanisms and Risk Factors for Noncontact ACL Injury Mechanically, ACL injury occurs when excessive loading is applied on the ACL. A noncontact ACL injury occurs when the person him- or herself generates great forces or moments at the knee that apply excessive loading on the ACL. To und
[Imaging diagnosis of hepatocellular carcinoma]. (2005)

In patients with chronic liver disease, hepatocellular carcinomas are developed from regenerative nodule via dysplastic nodule and early hepatocellular carcinoma to advanced hepatocellular carcinoma during multistep hepatocarcinogenesis. In this article, imaging findings of various imaging modalities are described pertaining to the above mentioned hepatocellular nodules occurring in the cirrhotic liver, correlating with pathologic findings.
Characteristics of medial temporal lobe epilepsy: I. Results of history and physical examination (1993)

In order to more precisely define a syndrome of medial temporal lobe epilepsy, histories and physical findings were evaluated in 67 patients studied with intracranial electrodes who had medial temporal seizure onset and became seizure free following temporal lobectomy. Patients with circumscribed, potentially epileptogenic mass lesions were excluded. Fifty-four patients (81%) had histories of convulsions during early childhood or infancy, 52 of which were associated with fever. Complicated febrile seizures occurred in 33 (94%) of the 35 patients in whom detailed descriptions of the febrile seizures were available. Bacterial (5) or viral (2) central central nervous system infections were present in 7 patients with seizures and fevers. Other less common, but probably significant, risk factors included head trauma (10%) and birth trauma (3%). Only 5 patients had no apparent risk factors. The mean age at habitual seizure onset was 9 years. All patients had complex partial seizures, with half having only complex partial seizures. The other half also had secondarily generalized tonic-clonic seizures, but these were never the predominant seizure type. Only 3 patients had histories of convulsive status epilepticus and no patient had a history of nonconvulsive status epilepticus. All but 3 patients reported auras before some or all of their seizures, with an abdominal visceral sensation being by far the most common type of aura (61%). Of the 60 patients with identified risk factors, all but 2 had an interval between the presumed cerebral insult and the development of habitual seizures, with a mean seizure-free interval of 7.5 years.(ABSTRACT TRUNCATED AT 250 WORDS)
Charomids: cosmid vectors for efficient cloning and mapping of large or small restriction fragments. (1986)

Charomids are cosmid vectors up to 52 kilobases (kb) long, bearing 1-23 copies of a 2-kb spacer fragment linked in head-to-tail tandem arrays. Like cosmids and lambda phage, charomids can be packaged in vitro for efficient introduction into bacteria. Charomids contain a polylinker with nine unique restriction sites for cloning and can be used without preparing vector arms. Using a charomid of appropriate size, one can clone inserts of any size up to 45 kb. For example, charomid 9-36 (9 cloning sites, 36 kb long) is too small to be packaged efficiently without an insert and can be used to clone fragments of 2-16 kb. The structure of charomids facilitates restriction mapping of the insert DNA and, after cloning, all the spacer fragments can be removed easily. After enrichment by size fractionation in an agarose gel, a specific single-copy genomic sequence can be cloned rapidly from approximately 3 micrograms of DNA. Using charomid 9-36, we have cloned and mapped an amplified novel DNA fragment from a cell line resistant to N-(phosphonoacetyl)-L-aspartate and carrying about 100 copies of the CAD (carbamoyl-phosphate synthetase/aspartate carbamoyltransferase/dihydroorotase) gene. The fragment lies at the center of an inverted duplication of this gene.
Deciphering the mechanism underlying late-onset Alzheimer disease (2012)

Despite tremendous investments in understanding the complex molecular mechanisms underlying Alzheimer disease (AD), recent clinical trials have failed to show efficacy. A potential problem underlying these failures is the assumption that the molecular mechanism mediating the genetically determined form of the disease is identical to the one resulting in late-onset AD. Here, we integrate experimental evidence outside the 'spotlight' of the genetic drivers of amyloid-β (Aβ) generation published during the past two decades, and present a mechanistic explanation for the pathophysiological changes that characterize late-onset AD. We propose that chronic inflammatory conditions cause dysregulation of mechanisms to clear misfolded or damaged neuronal proteins that accumulate with age, and concomitantly lead to tau-associated impairments of axonal integrity and transport. Such changes have several neuropathological consequences: focal accumulation of mitochondria, resulting in metabolic impairments; induction of axonal swelling and leakage, followed by destabilization of synaptic contacts; deposition of amyloid precursor protein in swollen neurites, and generation of aggregation-prone peptides; further tau hyperphosphorylation, ultimately resulting in neurofibrillary tangle formation and neuronal death. The proposed sequence of events provides a link between Aβ and tau-related neuropathology, and underscores the concept that degenerating neurites represent a cause rather than a consequence of Aβ accumulation in late-onset AD.
T lymphocyte development in the absence of Fcϵ receptor Iγ subunit: analysis of thymic‐dependent and independent αβ and γδ pathways (1996)

During fetal development, early thymocyte progenitors transiently express low affinity Fc receptors for IgG (Fc gamma R) of both Fc gamma RII and III isoforms. Only the Fc gamma RIII isoform requires association of an Fc gamma RIII (CD16) alpha subunit with an Fc epsilon RI gamma homodimer for surface expression. To address the role of Fc gamma R in ontogeny, we studied thymic development in Fc epsilon RI gamma-/- mice. We fine that day 14.5 CD4-CD8- double-negative (DN) fetal thymocytes of Fc epsilon RI gamma-/- mice express mRNA of both Fc gamma RIIb1 and Fc gamma RIII. Surface expression of Fc gamma RII/III is readily detected on these cells. It appears that Fc gamma RIIb1, whose surface expression is Fc epsilon RI gamma independent, replaces Fc gamma RIII during thymic development in these animals. Moreover, subsequent development into CD4+CD8+ double-positive and CD4+CD8- and CD4-CD8+ single-positive subsets appears normal even in the absence of Fc epsilon RI gamma. However, alterations were noted in adult animals among the DN alpha beta TCR+ thymocytes and peripheral splenic DN T cells as well as CD8 alpha alpha + intestinal intraepithelial lymphocytes (iIEL). In contrast to conventional T lymphocytes, which do not express either Fc gamma RIII or Fc epsilon RI gamma, DN alpha beta TCR+ thymocytes and extrathymically derived alpha beta TCR+ and gamma delta TCR+ CD8 alpha alpha + beta- iIEL express TCR which incorporate Fc epsilon RI gamma as one of their subunits. Consistent with this, the TCR levels of these cells are lower than the TCR levels on cells from wild-type C57BL/6 mice. Despite the reduction in the level of surface TCR, the development of these cells was unaltered by the absence of Fc epsilon RI gamma. Thus, we observed alterations in adult DN alpha beta TCR+ thymocytes, splenic DN alpha beta TCR+ and DN gamma delta TCR+ large granular lymphocytes (LGL), and alpha beta TCR+ and gamma delta TCR+ CD8 alpha alpha+beta- iIEL, but no detectable changes in their major fetal thymic developmental pathways. Cultivation of peripheral DN alpha beta TCR+ and DN gamma delta TCR+ cells from Fc epsilon RI gamma-/- mice with interleukin-2 generates LGL which mediate natural killer activity. Unlike LGL from wild-type C57BL/6 mice, LGL from Fc epsilon RI gamma-/- mice lack Fc gamma RIII expression and could not mediate antibody-dependent cellular cytotoxicity through Fc gamma RIII.
Nucleotide sequence of the pntA and pntB genes encoding the pyridine nucleotide transhydrogenase of Escherichia coli (1986)

A 3240-base-pair DNA fragment spanning the pyridine nucleotide transhydrogenase (pnt) genes of Escherichia coli has been sequenced. The sequence contains two open-reading frames, pntA and pntB of 1506 and 1386 base pairs, coding for the transhydrogenase alpha and beta subunits, respectively. The coding sequences are preceded by a promoter-like structure and are most likely co-transcribed. Each coding sequence is preceded by a Shine-Dalgarno sequence. The amino-terminal amino acid sequences were determined from the purified alpha and beta subunits of the transhydrogenase. These sequences agree with those predicted from the nucleotide sequences of the pntA and pntB genes. The predicted relative molecular masses of 53906 (alpha) and 48667 (beta) are close to the values obtained by analysis of the subunits by sodium dodecyl sulfate/polyacrylamide gel electrophoresis. Several hydrophobic regions large enough to span the cytoplasmic membrane were observed in each subunit. These results indicate that transhydrogenase is an intrinsic membrane protein.
Nerve lesions and the generation of pain (2001)

This review addresses the issue of how axotomy of peripheral nerve fibers leads to pain and hyperalgesia. The point of axotomy (the nerve injury site), the dorsal root ganglia, and the dorsal horn of the spinal cord are candidate sites for generation of the pain signal that is likely to be critical for maintaining the neuropathic pain state. This review considers neuropathic pain from a "systems" perspective, tracing concepts of neuropathic pain from the work of Henry Head to the present. Surprisingly, the nerve injury site and the dorsal root ganglion belonging to a transected spinal nerve do not give rise to spontaneous activity in putative C-fiber nociceptors. The intact nociceptor belonging to adjacent uninjured spinal nerves, however, does acquire abnormal spontaneous activity and a chemical sensitivity to catechols. It is suggested that partially denervated tissues in the nerve, skin, and other locations may release substances that, in turn, sensitize the intact nociceptors. These abnormalities in the intact nociceptor, which arise in the context of Wallerian degeneration, probably play a role in creating or maintaining the abnormal pain state. These considerations probably also apply to the understanding of pain arising in other neuropathies. The findings relative to the "intact" nociceptor provide a rationale by which to understand how therapies distal to the nerve injury site may diminish pain.