gebhart/patrepeval huggingface dataset:
Ligand-directed retroviral targeting of human breast cancer cells. (1995)

We explored the feasibility of designing retroviral vectors that can target human breast cancer cells with characteristic receptors via ligand-receptor interaction. The ecotropic Moloney murine leukemia virus envelope was modified by insertion of sequences encoding human heregulin. Ecotropic virus, which normally does not infect human cells, when pseudotyped with the modified envelope protein now crosses species to infect human breast cancer cell lines that overexpress HER-2 (human epidermal growth factor receptor; also called ERBB2) and HER-4 (also called ERBB4), while human breast cancer cell lines expressing low levels of these receptors remain resistant to infection. Since about 20% of human breast cancers overexpress HER-2 and some of breast cancer cell lines overexpress both HER-2 and HER-4, cell-specific targeting of retroviral vectors may provide a different approach for in vivo gene therapy of this type of breast cancer.
Oral tolerance (2005)

Multiple mechanisms of tolerance are induced by oral antigen. Low doses favor active suppression, whereas higher doses favor clonal anergy/deletion. Oral antigen induces T-helper 2 [interleukin (IL)-4/IL-10] and Th3 [transforming growth factor (TGF)-beta] T cells plus CD4+CD25+ regulatory cells and latency-associated peptide+ T cells. Induction of oral tolerance is enhanced by IL-4, IL-10, anti-IL-12, TGF-beta, cholera toxin B subunit, Flt-3 ligand, and anti-CD40 ligand. Oral (and nasal) antigen administration suppresses animal models of autoimmune diseases including experimental autoimmune encephalitis, uveitis, thyroiditis, myasthenia, arthritis, and diabetes in the non-obese diabetic (NOD) mouse, plus non-autoimmune diseases such as asthma, atherosclerosis, graft rejection, allergy, colitis, stroke, and models of Alzheimer's disease. Oral tolerance has been tested in human autoimmune diseases including multiple sclerosis (MS), arthritis, uveitis, and diabetes and in allergy, contact sensitivity to dinitrochlorobenzene (DNCB), and nickel allergy. Although positive results have been observed in phase II trials, no effect was observed in phase III trials of CII in rheumatoid arthritis or oral myelin and glatiramer acetate (GA) in MS. Large placebo effects were observed, and new trials of oral GA are underway. Oral insulin has recently been shown to delay onset of diabetes in at-risk populations, and confirmatory trials of oral insulin are being planned. Mucosal tolerance is an attractive approach for treatment of autoimmune and inflammatory diseases because of lack of toxicity, ease of administration over time, and antigen-specific mechanisms of action. The successful application of oral tolerance for the treatment of human diseases will depend on dose, developing immune markers to assess immunologic effects, route (nasal versus oral), formulation, mucosal adjuvants, combination therapy, and early therapy.
Assessment of Internet voice transport with TCP (2006)

Abstract We investigate whether the current best‐effort technology of Internet stands up to the high quality standards of real‐time voice communication. More precisely, we assess VoIP quality within the context of transport protocol support and efficiency. Initially, we focus on TCP and UDP supportive role from the perspective of VoIP performance. Applying our metric for real‐time performance, we reach the outcome that UDP is always not the protocol of choice for VoIP, since it occasionally exhibits inadequate performance. Beyond that, we evaluate a solution‐framework based on TCP protocols, which favour real‐time traffic. Based on our measurements, we assess the efficiency of the associated congestion control and congestion avoidance mechanisms in terms of VoIP performance. We also study the effect of packet size on protocol behaviour and VoIP quality. Furthermore, we investigate VoIP traffic friendliness, as well as potential tradeoffs between protocol performance and fairness. Copyright © 2006 John Wiley &amp; Sons, Ltd.
Neuroprotective effect of dexmedetomidine in a murine model of traumatic brain injury (2018)

No FDA approved pharmacological therapy is available that would reduce cell death following traumatic brain injury (TBI). Dexmedetomidine (Dex) is a highly selective agonist of alpha-2 adrenergic receptors and has demonstrated neuroprotective effects in hippocampal slice cultures undergoing direct impact. However, no one has tested whether Dex, in addition to its sedative action, has neuroprotective effects in an animal model of TBI. Thus, in the present study, we investigated the effects of Dex on an animal model of TBI. Mice received different doses of Dex (1, 10, or 100 µg/kg bodyweight, n = 10 each group) or saline as control at 1 hour and 12 hours following TBI. The mice treated with Dex lost less cortical tissue than the control mice. Further analysis found that Dex treatment reduced cell death in the cortex and the hippocampus measured by Fluoro-Jade B (FJB) staining, prevented axonal degeneration detected by immunostaining with antibody against β-amyloid precursor protein (β-APP), and protected synapses from elimination with synaptophysin staining. Taken together, in an in vivo murine model of TBI, Dex at the dose of 100 µg/kg not only prevented tissue lesion and cell death, but also reduced axonal injury and synaptic degeneration caused by TBI.
Specific proteolytic cleavage of recombinant Norwalk virus capsid protein (1995)

Norwalk virus (NV) causes epidemic outbreaks of acute nonbacterial gastroenteritis in humans. The NV capsid is made up of a single protein, and expression of the capsid protein in baculovirus recombinants results in spontaneous assembly of the protein into virus-like particles (X. Jiang, M. Wang, D. Y. Graham, and M. K. Estes, J. Virol. 66:6527-6532, 1992). We have investigated whether the NV capsid protein undergoes a specific proteolytic cleavage. Recombinant NV (rNV) particles were digested with trypsin to determine if a specific cleavage occurred. A predominant band with a molecular weight of approximately 32,000 (32K protein) was observed when trypsin-treated rNV was electrophoresed on sodium dodecyl sulfate-polyacrylamide gels. Determination of the N-terminal sequence of this band showed that a trypsin-specific cleavage occurred at amino acid residue 227. Early studies identified two proteins with molecular weights of 59,000 and 30,000 (59K and 30K proteins) in the stool of NV-infected volunteers that were reactive with postinfection antiserum. (H. B. Greenberg, J. R. Valdesuso, A. R. Kalica, R. G. Wyatt, V. J. McAuliffe, A. Z. Kapikian, and R. M. Chanock, J. Virol. 37:994-999, 1981). We hypothesized that the 32K rNV cleavage product might be analogous to the 30K soluble protein detected in stools of NV-infected volunteers. Immunoprecipitation of soluble protein from these stool extracts with a rabbit polyclonal antiserum made against rNV, and Western blot detection with a mouse polyclonal antiserum made against rNV, revealed a single band with an apparent molecular weight of 30,000 that migrated similarly to the trypsin cleavage product observed in vitro. The N terminus of this band was identical to that of the 32K cleavage product of rNV capsid protein. These data show that the 30K protein in stool is produced by specific cleavage of the NV capsid protein in vivo. Trypsin cleavage of isolated soluble rNV 58K capsid protein and of assembled particles showed that only soluble 58K capsid protein is susceptible to cleavage. The presence of a large amount of soluble capsid protein may influence the immune response to or pathogenicity of NV infections.
An Essential Role for Tumor Necrosis Factor in Natural Killer Cell–mediated Tumor Rejection in the Peritoneum (1998)

Natural killer (NK) cells are thought to provide the first line of defence against tumors, particularly major histocompatibility complex (MHC) class I- variants. We have confirmed in C57BL/6 (B6) mice lacking perforin that peritoneal growth of MHC class I- RMA-S tumor cells in unprimed mice is controlled by perforin-dependent cytotoxicity mediated by CD3(-) NK1.1(+) cells. Furthermore, we demonstrate that B6 mice lacking tumor necrosis factor (TNF) are also significantly defective in their rejection of RMA-S, despite the fact that RMA-S is insensitive to TNF in vitro and that spleen NK cells from B6 and TNF-deficient mice are equally lytic towards RMA-S. NK cell recruitment into the peritoneum was abrogated in TNF-deficient mice challenged with RMA-S or RM-1, a B6 MHC class I- prostate carcinoma, compared with B6 or perforin-deficient mice. The reduced NK cell migration to the peritoneum of TNF-deficient mice correlated with the defective NK cell response to tumor in these mice. By contrast, a lack of TNF did not affect peptide-specific cytotoxic T lymphocyte-mediated rejection of tumor from the peritoneum of preimmunized mice. Overall, these data show that NK cells delivering perforin are the major effectors of class I- tumor rejection in the peritoneum, and that TNF is specifically critical for their recruitment to the peritoneum.
Preliminary data from a multi-arm expansion study of MEDI4736, an anti-PD-L1 antibody. (2014)

3002^ Background: Checkpoint blockade of the PD-1/PD-L1 and CTLA-4 pathways has shown to be active in multiple tumor types. MEDI4736 is a human IgG1 monoclonal antibody which binds specifically to PD-L1, preventing binding to PD-1 and CD80. In phase I, MEDI4736 showed acceptable safety (no maximal tolerated dose identified). With evidence of clinical activity in phase I, an expansion study was initiated in multiple cancer types including NSCLC, melanoma (cutaneous and ocular), gastroesophageal, hepatocellular carcinoma, pancreatic, SCCHN and triple negative breast cancer. Methods: 10 - 20 pts were initially enrolled per tumor type, with expansion allowed upon observation of clinical activity. MEDI4736 was administered as 10 mg/kg IV every 2 weeks for 12 months. Retreatment was permitted for progression after 12 months of therapy. Response was assessed by RECIST v1.1. Results: The expansion cohorts were initiated in Sep 2013. As of Jan 17, 2014, 151 pts had received ≥1 dose of MEDI4736. Safety data are available for 105 pts (median age 60y; 36-84), 59% male, ECOG 0/1 (27%/71%), with a median of 3 (1-8) prior treatments, who received a median of 3 (1-8) doses. The safety profile was consistent with previous reports. Treatment-related AEs occurred in 33% of pts, with related ≥ Grade 3 AEs in 7%; none led to discontinuation of study drug. The most frequently observed treatment-related AEs were fatigue (13%), nausea (8%), rash (6%), vomiting (5%), and pyrexia (5%). One pt developed Grade 2 pneumonitis which resolved with drug interruption and steroids. There were no reports of colitis or hyperglycemia of any grade. With a median follow-up of 6 weeks, tumor shrinkage is already detectable in multiple tumor types including pts with melanoma, pancreatic, head and neck, and gastroesophageal cancer. The study continues to enroll pts and generate more mature follow-up data. Conclusions: Preliminary data in expansion suggest the safety of MEDI4736 is acceptable, even in heavily pre-treated pts. Early evidence of clinical activity was reported in multiple tumor types. Further evaluation of MEDI4736 as monotherapy and in combination with a variety of immunomodulators and targeted agents is ongoing. Clinical trial information: NCT01693562.
Reduced low frequency noise in electron beam evaporated MgO magnetic tunnel junctions (2010)

We compare low frequency noise in magnetic tunnel junctions with MgO barriers prepared by electron-beam evaporation with those prepared by radiofrequency sputtering, both showing a high tunneling magnetoresistance. The normalized noise parameter in the parallel state of junctions with evaporated barriers is at least one order of magnitude lower than that in junctions with sputtered barriers, and exhibits a weaker bias dependence. The lowest normalized noise is in the 10−11 μm2 range. A lower density of oxygen vacancies acting as charge trap states in the evaporated MgO is responsible for the lower noise.
Epidermal hydration of psoriasis plaques and the relation to scaling. Measurement of electrical conductance and transepidermal water loss (1987)

Seventy-seven plaques of ten patients with psoriasis vulgaris were studied with measurement of electrical conductance (3.5 MHz), measurement of transepidermal water loss (TEWL), and clinical scoring of erythema, induration and scaling. Uninvolved skin of the same body region served as control. Findings were very distinct with decreased conductance and increased TEWL. Plaques with no or mild scaling did not differ from grossly scaly plaques. Scales of psoriasis do not seem to exert any major occlusive effect on the water evaporation. The inverse relation between conductance and TEWL indicates reduced water-holding capacity of psoriatic epidermis, being a very common feature.
Glucocorticoid treatment inhibits apoptosis in human neutrophils. Separation of survival and activation outcomes. (1995)

We examined the direct effects of glucocorticoid treatment on neutrophil survival and function in vitro. Four different glucocorticoids caused a dose-dependent inhibition of apoptosis leading to increased survival of neutrophils. Maximal effects were found with dexamethasone at 10(-6) M, 16.6 +/- 6.2 vs 54.6 +/- 6.9, at 24 h (p < 0.05). Nonglucocorticoid steroids did not modulate apoptosis in neutrophils. Furthermore, the effect was inhibited in a dose-dependent manner by the glucocorticoid antagonist RU 486. Glucocorticoid-treated neutrophils produced significantly more superoxide in response to FMLP than untreated controls (p < 0.05). However, both basal and stimulated superoxide production were less than that found with freshly isolated cells. Such lack of priming or activation by glucocorticoids is in contrast to previous experience when increased survival was accompanied by cell activation. When compared with other stimuli, the effect of glucocorticoids at 24 h was similar to that of LPS but less than that of granulocyte-macrophage colony-stimulating factor (GM-CSF), 52 +/- 4, 57 +/- 6, and 70 +/- 4, respectively (p < 0.05). When added in combination, dexamethasone did not increase survival with LPS, but did augment the effect of GM-CSF, suggesting diversity in the mechanisms by which these stimuli regulate apoptosis. These data indicate that glucocorticoids can augment the effector potential of neutrophils by prolonging their survival and functional responsiveness, and such treatment might be detrimental in vivo because of delay in neutrophil apoptosis and in ultimate clearance of them from tissues.
Measuring proteins and voids in proteins (2002)

Common geometric models for proteins and other molecules are the space filling diagram, the solvent accessible surface, and the molecular surface. We describe software that computes metric properties of these models, including volume and surface area. It also measures voids or empty space enclosed by the protein, and it keeps track of surface area contributions of individual atoms. The software is based on 3-dimensional alpha complexes and on inclusion-exclusion formulas with terms derived from the simplices in this complex.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Color Doppler ultrasound imaging of lower-extremity venous disease (1989)

A color Doppler ultrasound imaging device was used to evaluate 475 patients with suspected lower-extremity venous thrombosis. Occlusive and nonocclusive femoral and popliteal thrombi were detected in 200 studies (42%). In phase 1 of the study (240 examinations), peripheral augmentation with the use of periodic calf compression was required to show color flow throughout the femoropopliteal venous segment. In phase 2 (235 examinations), with a software upgrade to enhance detectability of slow flow, spontaneous flow could be appreciated in the normal, partly thrombosed, and recanalized femoral popliteal veins without augmentation. Augmentation was often necessary to view tibioperoneal veins. Of the total study group, conventional venography was performed for correlation in 47 patients. In the other patients, clinicians relied on the color Doppler test for the definitive diagnosis of the presence or absence of femoral popliteal venous thrombosis and treated these patients on the basis of the color Doppler test result. In the femoral veins, color Doppler studies and venography agreed in all 12 positive and 35 negative cases. In the popliteal veins, there was agreement in five isolated popliteal thromboses and in 10 femoral popliteal thromboses; there were two false-negative color Doppler studies of isolated popliteal thromboses. In four patients, Doppler studies detected nonocclusive thrombus not evident on venography. Color Doppler imaging is easy to perform and does not require augmentation to view color flow in the femoropopliteal venous segment. Eccentric thrombus and partially canalized thrombus can be shown. Initial experience suggests color Doppler imaging may be useful in the detection of tibioperoneal venous thrombosis.
Effects of human serum on transport of testosterone and estradiol into rat brain (1980)

The effect in vivo of the plasma proteins in human serum on the transport of [3H]testosterone (T), [3H]-dihydrotestosterone (DHT), and [3H]estradiol (E2) through the brain capillary wall, i.e., the blood-brain barrier, was studied in anesthetized rats using a tissue-sampling-single-injection technique, In the absence of plasma proteins, approximately 90% of plasma T, DHT, or E2 was transported into brain on a single pass after a bolus carotid injection of labeled hormone. Serum was obtained from 57 patients in seven different clinical conditions: pregnancy, oral contraceptive use, thin and obese postmenopausal, follicular phase female, hirsutism, and normal male; the level (mean +/- SD) of sex hormone-binding globulin (SHBG) varied from 17 +/- 5 nM (hirsutism) to 323 +/- 83 nM (pregnancy). When the carotid injection solution was made 67% serum, the amount of T, DHT, or E2 transported into brain was inhibited in proportion to the concentration of SHBG. Among the patient groups, an overall linear inverse correlation between the mean SHBG level and the mean extraction of unidirectional influx of testosterone (r = 0.99) and estradiol (r = 0.98) was observed. These studies indicate that a) the undirectional clearance by brain of both testosterone and estradiol is inversely related to the SHBG level and b) the fraction of hormone transported into brain greatly exceeds the free (dialyzable) moiety and is essentially equal to the albumin-bound fraction of plasma testosterone or estradiol.
Neurochemistry of aging. 2. Design, synthesis and biological evaluation of halomethyl analogs of choline with high affinity choline transport inhibitory activity (1991)

The design, synthesis, and testing of several halomethyl analogues of choline and acetylcholine as potential cholinotoxins is described. The compounds were evaluated for their ability to inhibit high-affinity choline transport and their affinity toward postsynaptic muscarinic receptors. Among the analogues tested, bromomethyl and iodomethyl analogues of choline were found to be the most potent inhibitors of the high affinity choline transport system. Introduction of a beta-methyl group in the halomethyl analogues drastically reduced their potencies. The bromomethyl and iodomethyl analogues were further investigated for their effects on choline acetyltransferase activity, acetylcholinesterase activity and QNB binding. Neither compound possesses significant ability to alter any of the above cholinergic markers, except at very high concentrations. These results suggest that the bromomethyl and iodomethyl choline analogues may be used as specific inhibitors of the presynaptic high-affinity choline transport system.
Late-breaking abstract: Inhaled calcium salts reduce tobacco smoke induced airway inflammation and improve lung pathology (2011)

Rationale: Acute exacerbations (AE) of COPD are associated with bacterial and viral infection, however no available therapy broadly targets infection to prevent AEs. We have developed a novel host-targeted therapy based on the inhalation of dry powder (DP) calcium (Ca) salts that is broadly anti-infective and applicable to AE control. The goal of this study was to evaluate the impact of inhaled Ca salts on inflammation in an acute model of tobacco smoke (TS) exposure. Methods: C57BL6 mice were exposed to TS for 4d or 11d. Treatments with salt-based DP (40μmol/kg) were delivered by inhalation exposure. A p38 MAP kinase inhibitor (100μg/kg) was used as a positive control. Mice were euthanized 24h after the last TS exposure, BAL cells were quantified and histopathology performed. Results: In a 4d exposure model, treatment with Ca-based DP (PUR118) once daily 1h or 6h before TS reduced inflammatory cells [for 1h, macrophages (52%) and neutrophils (62%)] compared to control DP (p&lt;0.01). Treatment with magnesium (Mg)-based DP 1h before TS reduced macrophages 21% (p&lt;0.05); however, neither Mg nor sodium treatment reduced neutrophils. In an 11d exposure model, PUR118 reduced inflammation in prophylactic or therapeutic dosing regimes and markedly reduced the severity and incidence of peri-vascular and peri-bronchiolar inflammation, bronchiolitis, alveolitis, and pneumonitis by histopathological analysis. Conclusions: Ca-based DP reduced TS induced inflammation and improved lung pathology with equivalent efficacy to the p38 MAP kinase inhibitor. By targeting the infectious cause of AEs and baseline airway inflammation, inhaled Ca DP provides a novel multi-pronged approach for AE control.
Mass spectrometry of perdeuterated molecules of biological origin. Fatty acid esters from Scenedesmus obliquus (1970)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTMass spectrometry of perdeuterated molecules of biological origin. Fatty acid esters from Scenedesmus obliquusJames A. McCloskey and Gernot WendtCite this: Biochemistry 1970, 9, 25, 4854–4866Publication Date (Print):December 8, 1970Publication History Published online1 May 2002Published inissue 8 December 1970https://doi.org/10.1021/bi00827a005RIGHTS & PERMISSIONSArticle Views105Altmetric-Citations21LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit PDF (1 MB) Get e-Alerts Get e-Alerts
Celiac plexus block for pancreatic cancer pain in adults (2011)

Although statistical evidence is minimal for the superiority of pain relief over analgesic therapy, the fact that CPB causes fewer adverse effects than opioids is important for patients. Further studies and RCTs are recommended to demonstrate the potential efficacy of a less invasive technique under EUS guidance.