gebhart/patrepeval huggingface dataset:
Teachers' smoking. (1979)

Children take up smoking for many reasons and it is suggested that the example set by schoolteachers may have some influence. Smoking by male teachers appears to have some effect on boys' smoking, particularly in their first two years at secondary school. Thus, in any comprehensive study of what causes children to take up smoking and in any attempt to prevent this by means of health education, the influence of teachers as well as that of relatives and friends must be considered.
Mechanism of Action of a 16‐Membered Macrolide (1981)

Rosaramicin is a new macrolide antibiotic with activity similar to that of erythromycin. In this paper, we describe the synthesis of [3H]dihydrorosaramicin and show by sucrose gradient centrifugation, gel exclusion chromatography and equilibrium dialysis that rosaramicin and its dihydroderivative bind specifically to the 70-S ribosome and 50-S ribosomal subunit of Escherichia coli. Binding to the 30-S subunit is not detectable. The parameters of the binding interaction were evaluated by equilibrium dialysis. The affinities of E. coli ribosomes for rosaramicin and dihydrorosaramicin are in good agreement with the minimal inhibitory concentration of these drugs for microorganisms.
Recognition properties of a panel of human recombinant Fab fragments to the CD4 binding site of gp120 that show differing abilities to neutralize human immunodeficiency virus type 1 (1994)

Six recombinant human Fab fragments that were derived from the same human immunodeficiency virus type 1 (HIV-1)-infected individual and are directed against the CD4 binding site (CD4bs) of the gp120 envelope glycoprotein were studied. A range of neutralizing activity against the HIV-1 (HXBc2) isolate was observed, with Fab b12 exhibiting the greatest potency among the Fabs tested. The neutralizing potency of Fab b12 was better than that of monoclonal whole antibodies directed against the third variable (V3) region of gp120. To explore the basis for the efficient neutralizing activity of b12, the recognition of a panel of HIV-1 gp120 mutants by the six Fabs was studied. The patterns of sensitivity to particular gp120 amino acid changes were similar for all six Fabs to those seen for anti-CD4bs monoclonal antibodies derived from HIV-1-infected individuals by conventional means. In addition, recognition by Fab b12 demonstrated an atypical sensitivity to changes in the V1 and V2 variable regions. Next, the binding of the Fabs to monomeric gp120 and to the envelope glycoprotein complex was examined. Neither the binding properties of the b12 Fab to monomeric gp120 nor the ability of the Fab to compete with soluble CD4 for monomeric gp120 binding appeared to account for the greater neutralizing potency. However, both quantitative and qualitative differences between the binding of b12 and that of less potent Fabs to the cell surface envelope glycoprotein complex were observed. Relative to less potently neutralizing Fabs, Fab b12 exhibited a higher affinity for a subpopulation of cell surface envelope glycoproteins, the conformation of which was best approximated by the mature gp120 glycoprotein. Apparently, subtle differences in the gp120 epitope recognized allow some members of the group of anti-CD4bs antibodies to bind to the functionally relevant envelope glycoprotein complex and to neutralize virus more efficiently.
Studies on the epizootiology of canine coronavirus (1993)

The seroprevalence and, or, incidence of canine coronavirus infection was determined in several dog populations in the UK. Seroprevalence ranged from 76 per cent for a rescue kennel to 100 per cent in a commercial breeding colony. In the rescue kennel there was no difference in seroprevalence of the virus between dogs less than or more than four months of age. In the breeding colony, subclinical seroconversion occurred between six and 10 weeks of age. The virus was isolated from faecal samples from 45 of 100 dogs in the rescue kennel; it was isolated from 73 per cent of the dogs with diarrhoea and from 43 per cent of those which did not have diarrhoea. In field cases of acute, mainly haemorrhagic diarrhoea in pet dogs, eight of 32 were positive for canine coronavirus. No canine coronavirus was isolated from either clinically healthy pet dogs in a boarding kennel or from non-diarrhoeic pet dogs examined at the University of Liverpool Small Animal Hospital. It would appear that although canine coronavirus is widespread, the role of the virus in canine enteritis is still equivocal.
VENOUS NEEDLE DISLODGEMENT: HOW TO MINIMISE THE RISKS (2008)

Although haemodialysis (HD) has become a routine treatment, adverse side effects, and occasionally life threatening clinical complications, still happen. Venous needle dislodgment (VND) is one of the most serious accidents that can occur during HD. If the blood pump is not stopped, either by activation of the protective system of the dialysis machine or manually, the patient can bleed to death within minutes. Fatal and near-fatal blood loss due to VND have been described in the literature (ECRI 1998; Sandroni 2005; Mactier & Worth 2007), but published reports represent only the tip of the ice berg, as such incidents are normally handled at a local or national level. The European Dialysis and Transplant Nurses Association/European Renal Care Association (EDTNA/ERCA) has produced 12 practice recommendations to help reduce the risk of VND and detect blood leakage as early as possible. A poster summarising these recommendations has been created (Van Waeleghem et al. 2008).
Superposition coding for linear operator channels over finite fields (2012)

A coding approach based on the superposition structure is proposed for linear operator channels. Under a subspace decoding rule, a lower bound on the maximum achievable rate of this coding approach is characterized. Under the subspace decoding rule, this coding approach is capacity achieving for a class of linear operator channels, and it can potentially achieve higher rates than the subspace coding approach.
Assessment of the Economic Burden of COPD in the U.S.: A Review and Synthesis of the Literature (2006)

The costs of chronic obstructive pulmonary disease (COPD) pose a major economic burden to the United States. Studies evaluating COPD costs have generated widely variable estimates; we summarized and critically compared recent estimates of the annual national and per-patient costs of COPD in the U.S. Thirteen articles reporting comprehensive estimates of the direct costs of COPD (costs related to the provision of medical goods and services) were identified from searches of relevant primary literature published since 1995. Few papers reported indirect costs of COPD (lost work and productivity). The National Heart, Lung, and Blood Institute (NHLBI) provides the single current estimate of the total (direct plus indirect) annual cost of COPD to the U.S., $38.8 billion in 2005 dollars. More than half of this cost ($21.8 billion) was direct, aligning with the $20-26 billion range reported by two other recent analyses of large national datasets. For per-patient direct costs (in $US 2005), studies using recent data yield attributable cost estimates (costs deemed to be related to COPD) in the range of $2,700-$5,900 annually, and excess cost estimates (total costs incurred by COPD patients minus total costs incurred by non-COPD patients) in the range of $6,100-$6,600 annually. Studies of both national and per-patient costs that use data approximately 8-10 years old or older have produced estimates that tend to deviate from these ranges. Cost-of-illness studies using recent data underscore the substantial current cost burden of COPD in the U.S.
Comparison of the specificities and catalytic activities of hammerhead ribozymes and DNA enzymes with respect to the cleavage of BCR-ABL chimeric L6 (b2a2) mRNA (1997)

With the eventual goal of developing a treatment for chronic myelogenous leukemia (CML), attempts have been made to design hammerhead ribozymes that can specifically cleave BCR-ABL fusion mRNA. In the case of L6 BCR-ABL fusion mRNA (b2a2 type; BCR exon 2 is fused to ABL exon 2), which has no effective cleavage sites for conventional hammerhead ribozymes near the BCR-ABL junction, it has proved very difficult to cleave the chimeric mRNA specifically. Several hammerhead ribozymes with relatively long junction-recognition sequences have poor substrate-specificity. Therefore, we explored the possibility of using newly selected DNA enzymes that can cleave RNA molecules with high activity to cleave L6 BCR-ABL fusion (b2a2) mRNA. In contrast to the results with the conventional ribozymes, the newly designed DNA enzymes, having higher flexibility for selection of cleavage sites, were able to cleave this chimeric RNA molecule specifically at sites close to the junction. Cleavage occurred only within the abnormal BCR-ABL mRNA, without any cleavage of the normal ABL or BCR mRNA. Thus, these chemically synthesized DNA enzymes seem to be potentially useful for application in vivo , especially for the treatment of CML, if we can develop exogenous delivery strategies.
Spatial light interference tomography (SLIT) (2011)

We present spatial light interference tomography (SLIT), a label-free method for 3D imaging of transparent structures such as live cells. SLIT uses the principle of interferometric imaging with broadband fields and combines the optical gating due to the micron-scale coherence length with that of the high numerical aperture objective lens. Measuring the phase shift map associated with the object as it is translated through focus provides full information about the 3D distribution associated with the refractive index. Using a reconstruction algorithm based on the Born approximation, we show that the sample structure may be recovered via a 3D, complex field deconvolution. We illustrate the method with reconstructed tomographic refractive index distributions of microspheres, photonic crystals, and unstained living cells.
BRCA1 Activates a G2-M Cell Cycle Checkpoint following 6-Thioguanine–Induced DNA Mismatch Damage (2007)

Human DNA mismatch repair (MMR) is involved in the response to certain chemotherapy drugs, including 6-thioguanine (6-TG). Consistently, MMR-deficient human tumor cells show resistance to 6-TG damage as manifested by a reduced G(2)-M arrest and decreased apoptosis. In this study, we investigate the role of the BRCA1 protein in modulating a 6-TG-induced MMR damage response, using an isogenic human breast cancer cell line model, including a BRCA1 mutated cell line (HCC1937) and its transfectant with a wild-type BRCA1 cDNA. The MMR proteins MSH2, MSH6, MLH1, and PMS2 are similarly detected in both cell lines. BRCA1-mutant cells are more resistant to 6-TG than BRCA1-positive cells in a clonogenic survival assay and show reduced apoptosis. Additionally, the mutated BRCA1 results in an almost complete loss of a G(2)-M cell cycle checkpoint response induced by 6-TG. Transfection of single specific small interfering RNAs (siRNA) against MSH2, MLH1, ATR, and Chk1 in BRCA1-positive cells markedly reduces the BRCA1-dependent G(2)-M checkpoint response. Interestingly, ATR and Chk1 siRNA transfection in BRCA1-positive cells shows similar levels of 6-TG cytotoxicity as the control transfectant, whereas MSH2 and MLH1 siRNA transfectants show 6-TG resistance as expected. DNA MMR processing, as measured by the number of 6-TG-induced DNA strand breaks using an alkaline comet assay (+/-z-VAD-fmk cotreatment) and by levels of iododeoxyuridine-DNA incorporation, is independent of BRCA1, suggesting the involvement of BRCA1 in the G(2)-M checkpoint response to 6-TG but not in the subsequent excision processing of 6-TG mispairs by MMR.
Phase II trial of bevacizumab and erlotinib in patients with recurrent malignant glioma (2010)

Vascular endothelial growth factor (VEGF) and epidermal growth factor receptor (EGFR) signaling are established contributors to malignant glioma (MG) biology. We, therefore, evaluated bevacizumab, a humanized anti-VEGF monoclonal antibody, in combination with the EGFR tyrosine kinase inhibitor erlotinib, in this phase 2 study for recurrent MG patients (www. ClinicalTrials.gov, NCT00671970). Fifty-seven patients (n 5 25, glioblastoma [GBM]; n 5 32, anaplastic glioma [AG]) were enrolled. The primary endpoint was 6-month progression-free survival (PFS-6). Overall survival (OS), radiographic response, pharmacokinetics, and correlative biomarkers were the secondary endpoints. Patients were stratified based on the concurrent use of enzyme-inducing antiepileptic drugs (EIAEDs). Bevacizumab (10 mg/kg) was given intravenously every 2 weeks. Erlotinib was orally administered daily at 200 mg/day for patients not on EIAEDs and 500 mg/day for patients on EIAEDs. PFS-6 and median OS were 28% and 42 weeks for GBM patients and 44% and 71 weeks for AG patients, respectively. Twelve (48%) GBM patients and 10 (31%) AG patients achieved a radiographic response. Erlotinib pharmacokinetic exposures were comparable between EIAED and non-EIAED groups. Rash, mucositis, diarrhea, and fatigue were common but mostly grades 1 and 2. Among GBM patients, grade 3 rash, observed in 32%, was associated with survival benefit, whereas elevated hypoxia-inducible factor-2 alpha and VEGF receptor-2 levels were associated with poor survival. Bevacizumab plus erlotinib was adequately tolerated in recurrent MG patients. However, this regimen was associated with similar PFS benefit and radiographic response when compared with other historical bevacizumab-containing regimens.
Safety and Immunogenicity in Neonatal Mice of a HyperattenuatedListeriaVaccine Directed against Human Immunodeficiency Virus (2002)

CD8(+) T cells are a major component of the adaptive response of a host to infections by viruses and other intracellular pathogenic agents. However, because of the intrinsic immaturity of the immune system of neonatal animals, neonates are highly sensitive to a variety of pathogens and may be unable to respond in a protective manner. Here we explore whether a hyperattenuated strain of Listeria monocytogenes that can be used as a live vaccine vector in adults is safe and able to induce an effective response in neonates. We answer both questions affirmatively.
A new model of temporary focal neocortical ischemia in the rat. (1992)

For unanesthetized normothermic rats, cerebral blood flow reductions to 10-20% of baseline resulted in maximal infarction once ischemic durations exceeded 2-3 hours. To be effective, experimental therapies aimed at lessening infarct size or restoring blood flow must be initiated within this critical time interval.
Structure−Activity Relationships of the Melanocortin Tetrapeptide Ac-His-DPhe-Arg-Trp-NH2 at the Mouse Melanocortin Receptors:  Part 2 Modifications at the Phe Position (2002)

The melanocortin pathway is an important participant in skin pigmentation, steroidogenesis, obesity, energy homeostasis and exocrine gland function. The centrally located melanocortin-3 and melanocortin-4 receptors (MC3R, MC4R) are involved in the metabolic and food intake aspects of energy homeostasis and are stimulated by melanocortin agonists such as α-melanocyte stimulation hormone (α-MSH). The melanocortin agonists contain the putative message sequence “His-Phe-Arg-Trp,” and it has been well-documented that inversion of chirality of the Phe to DPhe results in a dramatic increase in melanocortin receptor potency. Herein, we report a tetrapeptide library, based upon the template Ac-His-DPhe-Arg-Trp-NH2, consisting of 26 members that have been modified at the DPhe7 position (α-MSH numbering) and pharmacologically characterized for agonist and antagonist activity at the mouse melanocortin receptors MC1R, MC3R, MC4R, and MC5R. The most notable results of this study include the identification of the tetrapeptide Ac-His-(pI)DPhe-Arg-Trp-NH2 that is a full nanomolar agonist at the mMC1 and mMC5 receptors, a mMC3R partial agonist with potent antagonist activity (pA2 = 7.25, Ki = 56 nM) and, but unexpectedly, is a potent agonist at the mMC4R (EC50 = 25 nM). This ligand possesses novel melanocortin receptor pharmacology, as compared to previously reported peptides, and is potentially useful for in vivo studies to differentiate MC3R vs MC4R physiological roles in animal models, such as primates, where “knockout” animals are not viable options. The DNal(2‘) substitution for DPhe resulted in a mMC3R partial agonist with antagonist activity (pA2 = 6.5, Ki = 295 nM) and a mMC4R (pA2 = 7.8, Ki = 17 nM) antagonist possessing 60- and 425-fold decreased potency, respectively, as compared with SHU9119 at these receptors. Examination of this DNal(2‘)-containing tetrapeptide at the F254S and F259S mutant mMC4Rs resulted in agonist activity of this mMC4R tetrapeptide antagonist, similar to that observed for the SHU9119 peptide, supporting our previously proposed hypothesis that the Phe 254 and 259 transmembrane six receptor residues are important for differentiating melanocortin sequence-based MC4R antagonists vs the agouti-related protein (AGRP) sequence-based antagonists.
Identification of a Naturally Occurring Peroxidase-Lipoxygenase Fusion Protein (1997)

A distant relative of catalase that is specialized for metabolism of a fatty acid hydroperoxide was identified. This heme peroxidase occurs in coral as part of a fusion protein, the other component of which is a lipoxygenase that forms the hydroperoxide substrate. The end product is an unstable epoxide (an allene oxide) that is a potential precursor of prostaglandin-like molecules. These results extend the known chemistry of catalase-like proteins and reveal a distinct type of enzymatic construct involved in the metabolism of polyunsaturated fatty acids.
On the molecular origins of the chronic myeloproliferative disorders: it all makes sense (2005)

The chronic myeloproliferative diseases, polycythemia vera (PV), essential thrombocythemia (ET), chronic idiopathic myelofibrosis (IMF), and chronic myelogenous leukemia (CML), were grouped into a spectrum of pathogenetically related disorders of varying clinical manifestations by Dameshek in 1951.[
A Novel Ubiquitin-Specific Protease, UBP43, Cloned from Leukemia Fusion Protein AML1-ETO-Expressing Mice, Functions in Hematopoietic Cell Differentiation (1999)

Using PCR-coupled subtractive screening-representational difference analysis, we have cloned a novel gene from AML1-ETO knockin mice. This gene is highly expressed in the yolk sac and fetal liver of the knockin mice. Nucleotide sequence analysis indicates that its cDNA contains an 1,107-bp open reading frame encoding a 368-amino-acid polypeptide. Further protein sequence and protein translation analysis shows that it belongs to a family of ubiquitin-specific proteases (UBP), and its molecular mass is 43 kDa. Therefore, we have named this gene UBP43. Like other ubiquitin proteases, the UBP43 protein has deubiquitinating enzyme activity. Protein ubiquitination has been implicated in many important cellular events. In wild-type adult mice, UBP43 is highly expressed in the thymus and in peritoneal macrophages. Among nine different murine hematopoietic cell lines analyzed, UBP43 expression is detectable only in cell lines related to the monocytic lineage. Furthermore, its expression is regulated during cytokine-induced monocytic cell differentiation. We have investigated its function in the hematopoietic myeloid cell line M1. UBP43 was introduced into M1 cells by retroviral gene transfer, and several high-expressing UBP43 clones were obtained for further study. Morphologic and cell surface marker examination of UBP43/M1 cells reveals that overexpression of UBP43 blocks cytokine-induced terminal differentiation of monocytic cells. These data suggest that UBP43 plays an important role in hematopoiesis by modulating either the ubiquitin-dependent proteolytic pathway or the ubiquitination state of another regulatory factor(s) during myeloid cell differentiation.
Photovoltaic conversion of laser power to electrical power (1986)

Photovoltaic laser to electric converters are attractive for use with a space-based laser power station. This paper presents the results of modeling studies for a silicon vertical junction converter used with a Nd laser. A computer code was developed for the model and this code was used to conduct a parametric study for a Si vertical junction converter consisting of one p-n junction irradiated with a Nd laser. These calculations predict an efficiency over 50 percent for an optimized converter.
Dynamics of Seed Transmission of Plant Pathogens (1966)

Beneficial microbes in the microbiome of plant roots improve plant health. Induced systemic resistance (ISR) emerged as an important mechanism by which selected plant growth–promoting bacteria and fungi in the rhizosphere prime the whole plant body for ...Read More
Constitutive HER2 Signaling Promotes Breast Cancer Metastasis through Cellular Senescence (2013)

Senescence, a terminal cell proliferation arrest, can be triggered by oncogenes. Oncogene-induced senescence is classically considered a tumor defense barrier. However, several findings show that, under certain circumstances, senescent cells may favor tumor progression because of their secretory phenotype. Here, we show that the expression in different breast epithelial cell lines of p95HER2, a constitutively active fragment of the tyrosine kinase receptor HER2, results in either increased proliferation or senescence. In senescent cells, p95HER2 elicits a secretome enriched in proteases, cytokines, and growth factors. This secretory phenotype is not a mere consequence of the senescence status and requires continuous HER2 signaling to be maintained. Underscoring the functional relevance of the p95HER2-induced senescence secretome, we show that p95HER2-induced senescent cells promote metastasis in vivo in a non-cell-autonomous manner.
Brief Electrical Stimulation Promotes Nerve Regeneration Following Experimental In-Continuity Nerve Injury (2018)

The application of brief ES for in-continuity nerve injury promotes faster recovery, although in a rat model where regeneration distances are short the control group ultimately recovers to a similar degree. Brief EF requires further evaluation as a promising therapy for in-continuity nerve injuries in humans.
Antigen processing in vivo and the elicitation of primary CTL responses. (1995)

CD8+ T lymphocytes (TCD8+) play an important role in cellular immune responses. TCD8+ recognize MHC class I molecules complexed to peptides of 8 to 10 residues derived largely from cytosolic proteins. Proteins are generally thought to be fragmented in the cytoplasm and delivered to nascent class I molecules in the endoplasmic reticulum (ER) by a peptide transporter encoded by the MHC. To explore the extent to which TCD8+ induction in vivo is limited by proteolysis or peptide transport into the ER, mice were immunized with recombinant vaccinia viruses containing mini-genes encoding antigenic peptides (bypassing the need for proteolysis), or these peptides with a NH2-terminal ER insertion sequence (bypassing the requirements for both proteolysis and transport). Additionally, mice were immunized with recombinant vaccinia viruses encoding rapidly degraded fragments of proteins. We report that limitations in induction of TCD8+ responses vary among Ags: for some, full length proteins are as immunogenic as other forms tested; for others, maximal responses are induced by peptides or by peptides targeted to the ER. Most importantly, in every circumstance examined, targeting peptides to the ER never diminished, and in some cases greatly enhanced, the TCD8+ immune response and provide an important alternative strategy in the design of live viral or naked DNA vaccines for the treatment of cancer and infectious diseases.