gebhart/patrepeval huggingface dataset:
Sequential coexpression of the multidrug resistance genes MRP and mdr1 and their products in VP-16 (etoposide)-selected H69 small cell lung cancer cells. (1995)

Resistance to drugs included in the multidrug-resistance phenotype has been attributed to overexpression of either mdr1 or MRP genes and their products in numerous cell lines, while coexpression, to our knowledge, has not previously been reported in the same cells. Human small cell lung cancer H69/VP cells were developed by continuous incubation in increasing doses of VP-16. In reverse transcription-PCR assays we found over-expression of both mdr1 and multidrug-resistance protein (MRP) genes, and immunoblots showed both elevated P-glycoprotein and MRP in H69/VP cells. Double immunocytochemical staining demonstrated the expression of both MRP and P-glycoprotein in the same cells, indicating that the observations do not result from the selection of two independent clones. Examination of early passages of H69/VP cells showed that overexpression of MRP mRNA occurred prior to mdr1. Thus, cell lines and clinical samples in the future should be tested for both mdr1/P-glycoprotein and MRP since a positive result for one of the phenotypes does not preclude the existence of the other.
Anti-α4 integrin therapy for multiple sclerosis (2005)

The symptoms, severity, and course of multiple sclerosis (MS) vary among patients, leading to complex treatment issues. In recent years, research has focused on specific adhesion molecules that participate in the activation and function of lymphocytes, especially the migration of these cells to sites of inflammation. In particular, the integrin, very late activation antigen (VLA)-4, has been implicated in mediating adhesion and migration of immune cells through interaction with its ligand, vascular cell adhesion molecule (VCAM)-1. VLA-4 is comprised of alpha4/beta1 and is critical in mediating Th-1 cell migration in the animal model of MS, experimental autoimmune encephalomyelitis, and has been the target of several recent clinical trials in MS. The humanized monoclonal antibody to alpha4 integrin, natalizumab (Tysabri, Biogen Idec/Elan), was recently approved in the United States for the treatment of relapsing MS. The authors discuss the mechanisms by which alpha4 integrins alter lymphocyte function as a rationale for anti-alpha4 integrin use in MS.
Cloning and regulation of a mRNA specifically expressed in the preadipose state (1989)

A cDNA library of Ob1771 preadipocytes was constructed, and a cDNA clone designated pOb24 was isolated by differential screening. The pOb24 mRNA, 6 kilobases in length, rose sharply in early differentiating Ob1771 and 3T3-F442A cells and decreased thereafter. In mouse adipose tissue, it was present at a high level in stromal-vascular cells (containing adipose precursor cells) and at a low level in mature adipocytes. Thus, pOb24 mRNA appears to be both in vitro and in vivo an unique marker of the preadipose state, i.e. of cell commitment during adipose cell differentiation. In contrast to glycerol-3-phosphate dehydrogenase mRNA, the emergence of pOb24 mRNA in Ob1771 cells required neither growth hormone or triiodothyronine as obligatory hormones nor insulin as a modulating hormone. Comparative studies of the expression of pOb24 and dihydrofolate reductase genes during the cell cycle suggest that arrest at the G1/S boundary was critical for the entry into the preadipose state. Tumor necrosis factor and transforming growth factor-beta were able to induce a large decrease of pOb24 mRNA level in growth-arrested Ob1771 cells. This decrease was shown to be only confined to early differentiating, glycerol-3-phosphate dehydrogenase negative cells as no decrease of pOb24 mRNA level was observed in glycerol-3-phosphate dehydrogenase positive cells. This result suggests that signals generated by tumor necrosis factor and transforming growth factor-beta have no effect on a commitment-related gene in late differentiated cells.
Nephrotoxicity and drug interaction of vancomycin. (2). (1996)

Vancomycin hydrochloride (VCM) has an antibacterial action against Gram positive bacteria, e.g., Methicillin-resistant Staphylococcus aureus (MRSA). In the clinical situation, there are patients with serious infections, being infected with not only MRSA, but also with Gram negative bacteria like Pseudomonas aeruginosa. Because VCM has the adverse reaction of nephrotoxicity, we are apprehensive about using VCM with other antibiotics, which might increase this problem. Therefore, the nephrotoxic effects and pharmacokinetics of VCM were examined in rabbits and compared with those in rabbits administered with VCM and other antibiotics. Responses indicating nephrotoxicity such as increases of serum creatinine concentration and BUN and morphological changes of the kidney were induced by the single injection of VCM at 300 mg/kg, i.v. In contrast, no abnormality of clinical data and morphological alteration were observed in the groups injected with VCM and imipenem (IPM)-cilastatin sodium (CS), flomoxef sodium (FMOX) or fosfomycin sodium (FOM). This was not true for groups injected with VCM and ceftazidime, cefpimizole sodium (CPIZ) or cefoperazone sodium. Clearance of VCM increased obviously in the groups injected with VCM and IPM-CS, FMOX or FOM, but decreased in those given VCM and CPIZ. Since the renal concentrations of VCM in the groups that were administered VCM with IPM-CS, FMOX or FOM were lower than that in the control group, IPM-CS, FMOX and FOM may decrease the nephrotoxicity of VCM by inhibiting its uptake into the kidney.
The structure of the yeast ribosomal RNA genes. I. The complete nucleotide sequence of the 18S ribosomal RNA gene from Saccharomyces cerevisiae (1980)

The cloned 18 S ribosomal RNA gene from Saccharomyces cerevisiae have been sequenced, using the Maxam-Gilbert procedure. From this data the complete sequence of 1789 nucleotides of the 18 S RNA was deduced. Extensive homology with many eucaryotic as well as E. coli ribosomal small subunit rRNA (S-rRNA) has been observed in the 3'-end region of the rRNA molecule. Comparison of the yeast 18 S rRNA sequences with partial sequence data, available for rRNAs of the other eucaryotes provides strong evidence that a substantial portion of the 18 S RNA sequence has been conserved in evolution.
Interaction of porcine vasoactive intestinal peptide with dispersed pancreatic acinar cells from the guinea pig. Binding of radioiodinated peptide. (1976)

We have used 125I-labeled vasoactive intestinal peptide (VIP) to study the kinetics, stoichiometry, and chemical specificity with which the labeled peptide binds to dispersed acinar cells prepared from guinea pig pancreas. Binding of 125I-VIP to pancreatic acinar cells was moderately rapid, reversible, specific, saturable, and depended on incubation temperature. Deterioration of 125I-VIP incubated with pancreatic acinar cells at 37 degrees was reflected in a decrease in acid-precipitable radioactivity and in the amount of tracer which could bind to fresh acinar cells. On the other hand, 125I-VIP bound to pancreatic acinar cells appeared to be protected from deterioration. VIP and secretin but not glucagon or COOH-terminal octapeptide of cholecystokinin inhibited binding of 125I-VIP to pancreatic acinar cells. The dose-response curve for inhibition of 125I-VIP binding by VIP or secretin was biphasic and suggested that pancreatic acinar cells have two classes of binding sites: (a) a relatively small number of sites with a high affinity for VIP and a low affinity for secretin, and (b) a relatively large number of sites with a low affinity for VIP and a high affinity for secretin. The difference between the relative affinities of VIP and secretin for the high affinity VIP binding sites appears to be primarily attributable to the NH2-terminal portions of these molecules since synthetic COOH-terminal fragments VIP 14-28, VIP 15-28, and secretin 14-27 were equipotent in inhibiting 125I-VIP binding. On the other hand, secretin 5-27, [6-tyrosine] secretin and native secretin were equipotent in inhibiting binding of 125I-VIP to its high affinity site, and these three peptides were 5 times more potent than secretin 14-27 but 10,000 times less potent than native VIP.
Role of biomarkers in studies of presymptomatic Alzheimer's disease (2005)

The technical development of biomarkers that are used for presymptomatic AD diagnosis and for longitudinally measuring disease severity is evolving rapidly. Ethical and privacy considerations must be made before such biomarkers can be applied routinely to asymptomatic populations.
Reduced Glucose Transporter at the Blood‐Brain Barrier and in Cerebral Cortex in Alzheimer Disease (1989)

We studied the hexose transporter protein of the frontal and temporal neocortex, hippocampus, putamen, cerebellum, and cerebral microvessels (which constitute the blood-brain barrier) in Alzheimer disease and control subjects by reversible and covalent binding with [3H]cytochalasin B and by immunological reactivity. In Alzheimer disease subjects, we found a marked decrease in the hexose transporter in brain microvessels and in the cerebral neocortex and hippocampus, regions that are most affected in Alzheimer disease, but there were no abnormalities in the putamen or cerebellum. Hexose transporter reduction in cerebral microvessels of Alzheimer subjects is relatively specific because other enzyme markers of brain endothelium were not significantly altered. The low density of the hexose transporter at the blood-brain barrier and in the cerebral cortex in Alzheimer disease may be related to decreased in vivo measurements of cerebral oxidative metabolism.
The Prevalence and Incidence of Clinical and Asymptomatic Lyme Borreliosis in a Population at Risk (1991)

A past history of clinical Lyme borreliosis and the 6-month incidence of clinical and asymptomatic Lyme borreliosis was studied prospectively in a high-risk population. In the spring, blood samples were drawn from 950 Swiss orienteers, who also answered a questionnaire. IgG anti-Borrelia burgdorferi antibodies were detected by ELISA. Positive IgG antibodies were seen in 248 (26.1%), in contrast to 3.9%-6.0% in two groups of controls (n = 101). Of the orienteers, 1.9%-3.1% had a past history of definite or probable clinical Lyme borreliosis. Six months later a second blood sample was obtained from 755 participants, 558 (73.9%) of whom were seronegative initially; 45 (8.1%) had seroconverted from negative to positive. Only 1 (2.2%) developed clinical Lyme borreliosis. Among all participants, the 6-month incidence of clinical Lyme borreliosis was 0.8% (6/755) but was much higher (8.1%) for asymptomatic seroconversion (45/558). In conclusion, positive Lyme serology was common in Swiss orienteers, but clinical disease occurred infrequently.
Facial Temperature in Migraine, Tension-Vascular and Tension Headache (1984)

The relationship between clinical features and changes in the extracranial circulation was studied during 209 separate attacks of headache affecting the anterior part of the head. Extracranial vascular changes were assessed thermographically and by the change in headache intensity when pressure was applied over the superficial temporal and common carotid arteries. In unilateral headaches, increased heat loss from the affected frontotemporal region was observed most frequently in attacks which were temporarily relieved by compression of the superficial temporal artery; thermographic asymmetry disappeared as the headache abated. Although such headaches were associated more frequently with migrainous features than attacks which did not respond to arterial compression, many headaches with clinical features of migraine had no vascular component detectable by thermography or vascular compression. Furthermore, the response to arterial compression was not consistent from one headache to another in the same patient. It was concluded that extracranial vascular changes recur intermittently in headache-prone patients, depending on the severity of pain and association with other features commonly regarded as migrainous. However, there was no clear demarcation point between entities diagnosed clinically as "migraine" and "tension headache".
Identification and function of neonatal Fc receptor in mammary gland of lactating mice (1999)

In addition to its proposed function in regulating serum IgG levels, the MHC class I-related neonatal Fc receptor (FcRn) is known to play a role in IgG transfer across rodent yolk sac and neonatal intestine. In contrast to humans, for which transplacental transfer of IgG appears to be the only mechanism of maternal IgG delivery, the transmission of IgG in mice occurs both antenatally (yolk sac) and neonatally (transport from mother's milk across intestinal epithelial cells). In the current study, a possible role for FcRn in regulating IgG transfer into milk has been investigated. FcRn has been shown to be present in functional form in the mammary gland of lactating mice, and is localized to the epithelial cells of the acini. Analysis of the transfer of Fc fragments and IgG which have different affinities for FcRn indicate that, unexpectedly, these proteins are transferred in inverse correlation with their binding affinity for FcRn. Thus, in the lactating mammary gland FcRn appears to play a role in recycling IgG in a mode that may have relevance to FcRn trafficking during the maintenance of constant serum IgG levels.
Cell surface antigens of chemically induced sarcomas of the mouse. I. Murine leukemia virus-related antigens and alloantigens on cultured fibroblasts and sarcoma cells: description of a unique antigen on BALB/c Meth A sarcoma. (1977)

As background for a serological definition of the unique antigens of chemically induced sarcomas, we have typed a series of fibroblast and sarcoma cell lines of BALB/c and C57BL/6 origin by cytoxicity and absorption tests for murine leukemia virus (MuLV)-related cell surface antigens and known alloantigens. 7 of the 17 cultured lines expressed the range of cell surface antigens associated with MuLV (GIX, GCSA, gp70, p30), and this was invariably associated with MuLV production. In nonproducer lines of C57BL/6 (but not BALB/c) origin, a MuLV-gp70-like molecule was found on the surface of fibroblasts and sarcoma cells. The alloantigenic phenotype of these MuLV+ and MuLV- cell lines was H-2D+, H-2K+, Thy-1.2+ or -, PC.1+ or -, Lyt-1.2-, Lyt-2.2-, Ia.7-, and TL.2-. A unique antigen was defined on the BALB/c ascites sarcoma Meth A with antisera prepared in BALB/c or (BALB/c X C57BL/6)F1 mice. Tissue culture lines derived from this tumor were MuLV-, which facilitated serological study of the antigen. Absorption analysis indicated that the antigen was restricted to Meth A; it could not be detected in normal or fetal BALB/c tissue MuLV+ or MuLV- fibroblast lines, 12 syngeneic or allogeneic sarcomas, or normal lymphoid cells from 13 different inbred mouse strains.
Therapeutic advances in Huntington's Disease (2015)

Huntington's disease is a rare hereditary degenerative disease with a wide variety of symptoms that encompass movement, cognition, and behavior. The genetic mutation that causes the disease has been known for more than 20 y, and animal models have illuminated a host of intracellular derangements that occur downstream of protein translation. A number of clinical trials targeting these metabolic consequences have failed to produce a single effective therapy, although clinical trials continue. New strategies targeting the protein at the level of transcription, translation, and posttranslational modification and aggregation engender new hope that a successful strategy will emerge, but there is much work ahead. Some of the clinical manifestations of the illness, particularly chorea, affective symptoms, and irritability, are amenable to palliative strategies, but physicians have a poor evidence base on which to select the best agents. Clinical trials since 2013 have dashed hopes that coenzyme Q10 or creatine might have disease-modifying properties but suggested other agents were safe or hinted at efficacy (cysteamine, selisistat, hydroxyquinoline) and could proceed into later-stage disease modification trials. The hunt for effective symptom relief suggested that pridopidine might be shown effective given the right outcome measure. This review summarizes recent progress in HD and highlights promising new strategies for slowing disease progression and relieving suffering in HD.
Predictors of answer quality in online Q&A sites (2008)

Question and answer (Q&A) sites such as Yahoo! Answers are places where users ask questions and others answer them. In this paper, we investigate predictors of answer quality through a comparative, controlled field study of responses provided across several online Q&A sites. Along with several quantitative results concerning the effects of factors such as question topic and rhetorical strategy, we present two high-level messages. First, you get what you pay for in Q&A sites. Answer quality was typically higher in Google Answers (a fee-based site) than in the free sites we studied, and paying more money for an answer led to better outcomes. Second, we find that a Q&A site's community of users contributes to its success. Yahoo! Answers, a Q&A site where anybody can answer questions, outperformed sites that depend on specific individuals to answer questions, such as library reference services.
Regulatory and Signaling Properties of the Vav Family (2000)

X.R.B. is a Sinsheimer Scholar for Cancer Research whose own work is supported by the National Cancer Institute (CA7373501), the Baldwin Foundation for Breast Cancer Research, and the Association for International Cancer Research.
Synthesis, in Vitro Biological Evaluation and Oral Bioavailability of 9-[2-(Phosphonomethoxy)Propyl]Adenine (PMPA) Prodrugs (1997)

Potentially orally bioavailable prodrugs of the antiretroviral agent 9-[2-(phosphonomethoxy)propyl]adenine (PMPA) were evaluated. Alkyl methyl carbamates were synthesized by alkylation of PMPA with the corresponding alkyl chloromethyl carbonate and N-alkyl chloromethyl carbamate reagents. The prodrugs were evaluated for in vitro antiviral activity in addition to chemical and enzymic stability. The inhibition of human immunodeficiency virus type 1 (HIV-1) strain IIIB replication in MT-2 cells by the carbonate prodrugs was found to be 2.5-500-fold increased compared to PMPA. The alkyl methyl carbonates, except t-butyl methyl carbonate, had reasonable chemical stability at pH 2.2 and 7.4, but were rapidly converted to the corresponding monoester of PMPA in the presence of dog plasma. The alkyl methyl carbamate prodrugs such as N-t-butyl methyl carbamate were found to have high stability in vitro. Based on its chemical stability and good oral bioavailability, bis(POC)PMPA (isopropyl methyl carbonate) was chosen as a clinical candidate.
Neuromagnetic assessment of pathophysiologic brain activity induced by minor head trauma. (1999)

MSI indicated brain dysfunction in significantly more patients with postconcussive symptoms than either EEG or MR imaging (P < .01). The presence of excessive abnormal low-frequency magnetic activity provides objective evidence of brain injury in patients with postconcussive syndromes and correlates well with the degree of symptomatic recovery.
Edaravone (Radicava): A Novel Neuroprotective Agent for the Treatment of Amyotrophic Lateral Sclerosis. (2018)

Edaravone (Radicava): a novel neuroprotective agent for the treatment of amyotrophic lateral sclerosis.
Optical wavelength shifting by traveling-wave electrooptic modulation (1993)

Optical wavelength shifting of 1.054-nm laser pulses in excess of +or- 10 wavenumbers (+or- 300 GHz) was demonstrated. The wavelength shifter consists of synchronous microwave and optical waveguides fabricated monolithically on LiNbO/sub 3/. An optical pulse experiences a constant refractive index gradient that travels with the pulse and causes the wavelength shift.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Magnetic shielding and exotic spin-dependent interactions (2016)

Experiments searching for exotic spin-dependent interactions typically employ magnetic shielding between the source of the exotic field and the interrogated spins. We explore the question of what effect magnetic shielding has on detectable signals induced by exotic fields. Our general conclusion is that for common experimental geometries and conditions, magnetic shields should not significantly reduce sensitivity to exotic spin-dependent interactions, especially when the technique of comagnetometry is used. However, exotic fields that couple to electron spin can induce magnetic fields in the interior of shields made of a soft ferromagnetic or ferrimagnetic material. This induced magnetic field must be taken into account in the interpretation of experiments searching for new spin-dependent interactions and raises the possibility of using a flux concentrator inside magnetic shields to amplify exotic spin-dependent signals.
On the beamforming performance of large-scale antenna arrays (2012)

The paper investigates the beamforming (BF) performance of large, potentially unconstrained in size antenna arrays when equipped with arbitrarily many elements. A realistic BF criterion namely the average BF gain is revisited and employed to understand the BF performance of large-scale antennas above a user clutter. Simulation results show diminishing average BF gain returns as the number of antennas increases in low angle spread outdoor channels.
Mechano-electronic Superlattices in Silicon Nanoribbons (2009)

Significant new mechanical and electronic phenomena can arise in single-crystal semiconductors when their thickness reaches nanometer dimensions, where the two surfaces of the crystal are physically close enough to each other that what happens at one surface influences what happens at the other. We show experimentally that, in silicon nanomembranes, through-membrane elastic interactions cause the double-sided ordering of epitaxially grown nanostressors that locally and periodically highly strains the membrane, leading to a strain lattice. Because strain influences band structure, we create a periodic band gap modulation, up to 20% of the band gap, effectively an electronic superlattice. Our calculations demonstrate that discrete minibands can form in the potential wells of an electronic superlattice generated by Ge nanostressors on a sufficiently thin Si(001) nanomembrane at the temperature of 77 K. We predict that it is possible to observe discrete minibands in Si nanoribbons at room temperature if nanostressors of a different material are grown.
Poly(3-Hydroxybutyrate) Synthesis by Recombinant Escherichia coli arcA Mutants in Microaerobiosis (2006)

We assessed the effects of different arcA mutations on poly(3-hydroxybutyrate) (PHB) synthesis in recombinant Escherichia coli strains carrying the pha synthesis genes from Azotobacter sp. strain FA8. The arcA mutations used were an internal deletion and the arcA2 allele, a leaky mutation for some of the characteristics of the Arc phenotype which confers high respiratory capacity. PHB synthesis was not detected in the wild-type strain in shaken flask cultures under low-oxygen conditions, while ArcA mutants gave rise to polymer accumulation of up to 24% of their cell dry weight. When grown under microaerobic conditions in a bioreactor, the arcA deletion mutant reached a PHB content of 27% +/- 2%. Under the same conditions, higher biomass and PHB concentrations were observed for the strain bearing the arcA2 allele, resulting in a PHB content of 35% +/- 3%. This strain grew in a simple medium at a specific growth rate of 0.69 +/- 0.07 h(-1), whereas the deletion mutant needed several nutritional additives and showed a specific growth rate of 0.56 +/- 0.06 h(-1). The results presented here suggest that arcA mutations could play a role in heterologous PHB synthesis in microaerobiosis.