gebhart/patrepeval huggingface dataset:
Activation of the alternate pathway of human complements by rabbit cells. (1974)

The hemolysis of sheep red blood cells (SRBC) occurs via the classical complement pathway and is blocked by ethylene glycol bis-amino tetraacetate (EGTA). By contrast, fresh normal human serum in EGTA buffer was found to cause >90% hemolysis of unsensitized rabbit red blood cells (RaRBC) at a final dilution of 1:15. Absorbing human serum with RaRBC at 0°C will remove only 45% of this hemolytic activity and the same activity is present in human hypogammaglobulinemic serum. When rabbit lymphocytes were incubated with human serum in EGTA buffer, complement fixation occurred on their surface which was demonstrated with radiolabeled antibodies to human C3 or as “blocking” of the complement receptor. With purified complement components it was shown that the EGTA buffer completely blocked C1 but not C4, C2, or the late complement components. These findings show that a rabbit cell surface component can activate the alternate pathway of complement in human serum and suggest that this activation does not involve antibody.
Hypermethylation of tumor suppressor genes in cancer (1999)

Hypermethylation of tumor suppressor genes and other genes functionally important in the neoplastic process is a recently recognized process. This epigenetic process is characterized by loss of function of these genes associated with transcriptional loss in the absence of structural alterations. The growing list of genes inactivated by promoter region hypermethylation provide an opportunity to examine the patterns of inactivation of such genes and provide clues as to the roles these events play in the neoplastic process.
Nanotechnology in the targeted drug delivery for bone diseases and bone regeneration (2013)

Nanotechnology is a vigorous research area and one of its important applications is in biomedical sciences. Among biomedical applications, targeted drug delivery is one of the most extensively studied subjects. Nanostructured particles and scaffolds have been widely studied for increasing treatment efficacy and specificity of present treatment approaches. Similarly, this technique has been used for treating bone diseases including bone regeneration. In this review, we have summarized and highlighted the recent advancement of nanostructured particles and scaffolds for the treatment of cancer bone metastasis, osteosarcoma, bone infections and inflammatory diseases, osteoarthritis, as well as for bone regeneration. Nanoparticles used to deliver deoxyribonucleic acid and ribonucleic acid molecules to specific bone sites for gene therapies are also included. The investigation of the implications of nanoparticles in bone diseases have just begun, and has already shown some promising potential. Further studies have to be conducted, aimed specifically at assessing targeted delivery and bioactive scaffolds to further improve their efficacy before they can be used clinically.
Comparative Study of in Vitro and in Vivo Modulation of Lactogenic and Somatotropic Receptors by Native Human Growth Hormone and Its Modified Analog Prepared by Recombinant Deoxyribonucleic Acid Technology (1987)

A modified analog of human GH (hGH), prepared by recombinant DNA technology, that lacks 13 amino acids at the amino terminus (Met14hGH), was able to compete with [125I]hGH for binding to lactogenic receptors in Nb2-11C rat lymphoma cells, to somatotropic receptors in IM-9 human lymphocytes, and to both lactogenic and somatotropic receptors in the microsomal fraction of virgin female rat liver. Exposure of intact Nb2 or IM-9 cells to Met14hGH did not reduce the number of surface or intracellular receptors, as compared to the control without hormone. A parallel exposure to 500-fold lower concentrations of hGH resulted in 77-93% reduction in both surface and intracellular receptors. In contrast to [125I]hGH, [125I]Met14hGH was not taken up by the intact Nb2 lymphoma cells. Infusion of anesthetized female virgin rats for 3 h with hGH down-regulated both lactogenic and somatotropic receptors in the liver. A similar infusion with up to 200-fold higher amounts of Met14hGH did not lower the number of total receptors, indicating lack of down-regulation. Some decrease in the binding to free receptors was observed, suggesting that Met14hGH is capable of binding to liver receptors in vivo.
Resistance-Associated Loss of Viral Fitness in Human Immunodeficiency Virus Type 1: Phenotypic Analysis of Protease and gag Coevolution in Protease Inhibitor-Treated Patients (1998)

We have studied the phenotypic impact of adaptative Gag cleavage site mutations in patient-derived human immunodeficiency virus type 1 (HIV-1) variants having developed resistance to the protease inhibitor ritonavir or saquinavir. We found that Gag mutations occurred in a minority of resistant viruses, regardless of the duration of the treatment and of the protease mutation profile. Gag mutations exerted only a partial corrective effect on resistance-associated loss of viral fitness. Reconstructed viruses with resistant proteases displayed multiple Gag cleavage defects, and in spite of Gag adaptation, several of these defects remained, explaining the limited corrective effect of cleavage site mutations on fitness. Our data provide clear evidence of the interplay between resistance and fitness in HIV-1 evolution in patients treated with protease inhibitors.
Density of gap states of silicon grain boundaries determined by optical absorption (1983)

The results of optical absorption measurements on fine-grain polycrystalline-silicon thin films indicate that the singly occupied dangling silicon bond lies 0.65±0.15 eV below the conduction-band minimum in the grain boundary. The grain boundary band gap is ∼1.0 eV and there is evidence for exponential tailing of the band edges. The optical absorption was determined by photothermal deflection spectroscopy. The dangling silicon bond density has been measured on polycrystalline-silicon thin films as a function of hydrogen passivation of the grain boundaries and on silicon-on-saphhire films. The optical absorption exhibits a defect shoulder which varies as the dangling bond density.
Formal Synthesis of FPA, a Kainoid Amino Acid, via Ketyl Radical Cyclization (2002)

The formal synthesis of FPA, a kainoid amino acid, was performed through the SmI 2 induced ketyl radical cyclization as the key step.The stereoselectivity was inverted in the presence or absence of the proton source.Kainoid amino acids, such as kainic acid (1), domoic acid (2), acromelic acids A and B (3, 4), MFPA (5), and FPA (6), show potent neuroexcitatory activity in mammalian central nervous systems. 1 Due to their activity, they are useful probes in the neuroscience fields.Recently, a shortage of kainic acid, which has
The RAR1 Interactor SGT1, an Essential Component of R Gene-Triggered Disease Resistance (2002)

Plant disease resistance (R) genes trigger innate immune responses upon pathogen attack. RAR1 is an early convergence point in a signaling pathway engaged by multiple R genes. Here, we show that RAR1 interacts with plant orthologs of the yeast protein SGT1, an essential regulator in the cell cycle. Silencing the barley gene Sgt1 reveals its role in R gene-triggered, Rar1-dependent disease resistance. SGT1 associates with SKP1 and CUL1, subunits of the SCF (Skp1-Cullin-F-box) ubiquitin ligase complex. Furthermore, the RAR1-SGT1 complex also interacts with two COP9 signalosome components. The interactions among RAR1, SGT1, SCF, and signalosome subunits indicate a link between disease resistance and ubiquitination.
Atorvastatin with or without an Antibody to PCSK9 in Primary Hypercholesterolemia (2012)

In a randomized trial involving patients with primary hypercholesterolemia, adding SAR236553 to either 10 mg of atorvastatin or 80 mg of atorvastatin resulted in a significantly greater reduction in LDL cholesterol than that attained with 80 mg of atorvastatin alone. (Funded by Sanofi and Regeneron Pharmaceuticals; ClinicalTrials.gov number, NCT01288469.).
Efficacy of Prothrombin-Complex Concentrates in Hemophiliacs with Antibodies to Factor VIII (1980)

The therapeutic efficacy of prothrombin-complex concentrates in patients with hemophilia and inhibitors (antibodies) to factor VIII has been increasingly debated. We therefore entered 51 hemophiliacs with factor VIII inhibitors into a double-blind randomized crossover study to compare two commercial prothrombin-complex concentrates (Konyne and Proplex) and an albumin placebo. Acute hemarthrosis of the elbow, knee, or ankle was treated with a single dose of a test preparation and assessed six hours later with objective and subjective criteria. In all measurements the concentrates were significantly more effective than the placebo. The data indicate that although prothrombin-complex concentrates, when used in a single dose, are only partially effective in the treatment of joint hemorrhage in hemophiliacs with inhibitors, their continued use for acute hemarthrosis is justified in the absence of any other effective and readily available therapy for this disorder.
Human natural killer cells with polyclonal lectin and immunoglobulinlike receptors develop from single hematopoietic stem cells with preferential expression of NKG2A and KIR2DL2/L3/S2 (2001)

The stage of progenitor maturation and factors that determine the fate and clonal acquisition of human natural killer (NK) cell receptors during development are unknown. To study human NK cell receptor ontogeny, umbilical cord blood CD34(+)/Lin(-)/CD38(-) cells were cultured with a murine fetal liver line (AFT024) and defined cytokines. In the absence of lymphocyte-stimulating cytokines or when contact with AFT024 was prohibited, NK cell progeny were killer immunoglobulinlike receptor (KIR) and CD94 lectin receptor negative. In contrast, efficient NK cell differentiation and receptor acquisition was dependent on direct contact of progenitors with AFT024 and the addition of interleukin-15 (IL-15) or IL-2 but not IL-7. To address the question of whether receptor acquisition was determined at the stem cell level, single CD34(+)/Lin(-)/CD38(-) progenitors were studied. More than 400 single cell progeny were analyzed from cultures containing IL-15 or IL-2 and NK cells were always polyclonal, suggesting that receptor fate is determined beyond an uncommitted progenitor and that receptor-negative NK cells acquire class I-recognizing receptors after lineage commitment. KIR2DL2/L3/S2 was expressed more than KIR2DL1/S1 or KIR3DL1, and NKG2A was the dominant CD94 receptor, independent of whether the stem cell source contained the respective major histocompatibility complex class I ligand, suggesting a nonrandom sequence of receptor acquisition. The conclusion is that NK receptor fate is determined after NK cell commitment, does not require stromal presentation of human class I alleles, and is clonally stable after expression but dynamic because new receptors are acquired over time. (Blood. 2001;98:705-713)
A Gene Expression Map of the Arabidopsis Root (2003)

A global map of gene expression within an organ can identify genes with coordinated expression in localized domains, thereby relating gene activity to cell fate and tissue specialization. Here, we present localization of expression of more than 22,000 genes in the Arabidopsis root. Gene expression was mapped to 15 different zones of the root that correspond to cell types and tissues at progressive developmental stages. Patterns of gene expression traverse traditional anatomical boundaries and show cassettes of hormonal response. Chromosomal clustering defined some coregulated genes. This expression map correlates groups of genes to specific cell fates and should serve to guide reverse genetics.
Breath Hydrogen Testing (1988)

Department of Pediatrics Louisiana State Univesity Medical School New Orleans, Louisiana U.S.A. Department of Pediatrics University of Kansas College of Health Sciences Kansas City. Kansas U.S.A.
Human alpha-L-iduronidase: cDNA isolation and expression. (1991)

alpha-L-Iduronidase (IDUA; EC 3.2.1.76) is a lysosomal hydrolase in the metabolic pathway responsible for the degradation of the glycosaminoglycans heparan sulfate and dermatan sulfate. A deficiency of IDUA in humans leads to the accumulation of these glycosaminoglycans and results in the lysosomal storage disorder mucopolysaccharidosis type I. We have isolated and sequenced cDNA clones containing part of the human IDUA coding region and used PCR from reverse-transcribed RNA to obtain the full IDUA sequence. Analysis of the predicted 653-amino acid precursor protein shows that IDUA has a 26-amino acid signal peptide that is cleaved immediately prior to the amino terminus of the 74-kDa polypeptide present in human liver IDUA. The protein sequence contains six potential N-glycosylation sites. Northern blot analysis with IDUA cDNA detected only a single 2.3-kilobase mRNA species in human placental RNA; however, PCR analysis of fibroblast, liver, kidney, and placental RNA showed the existence of alternatively spliced mRNA from the IDUA gene. Southern blot analysis failed to detect major deletions or gene rearrangements in any of the 40 mucopolysaccharidosis type I patients studied. Expression of a full-length IDUA cDNA construct in Chinese hamster ovary cells produced human IDUA protein at a level 13-fold higher than, and with a specific activity comparable to, IDUA present in normal human fibroblasts.
Hybrid paraplegic standing with the Cochlear FES-22 implantable stimulator and Andrews FRO braces: a follow-up (2002)

The re-designed Cochlear FES-22 implantable stimulator has received considerable development in both hardware and software over the past four years. The implanted subject, a T-10 paraplegic male (CS), is able to exercise his knee and hip extensors for 20 minutes before onset of muscle fatigue. Subject CS has been able to stand using the Cochlear FES-22 stimulator with the Andrews FRO braces for up to 27 1/2 minutes during a 41 1/2 minute session with 3 standing periods. The longest single standing period achieved was 18 1/2 minutes. The stimulation to the knee extensors can be removed in excess of 90% of the stance. Subject CS has been able to lift over 5 lb. at arms length to above shoulder level, while maintaining his posture with the knee extensor stimulation off.
Lipid composition and sensitivity of Prototheca wickerhamii to membrane-active antimicrobial agents (1979)

The lipid composition of Prototheca wickerhamii ATCC 16529 is presented and discussed in relation to the unique susceptibility of the organism to drugs of three membrane-active antimicrobial classes: the polyenes, the polymyxins, and the imidazoles. The presence of ergosterol in the neutral lipid fraction of the membrane is likely responsible for the exquisite susceptibility to amphotericin B. The presence of a large quantity of free fatty acids in the membrane appears responsible for imidazole susceptibility. The membrane determinants of polymyxin B susceptibility are less well defined.
Polymerase chain reaction for detection of human cytomegalovirus infection in a blood donor population (1991)

We have used the polymerase chain reaction (PCR) to analyse 420 normal donor blood samples taken at a city centre donation site. Three sets of human cytomegalovirus (HCMV) primers specific to the HXLF6, immediate early and late antigen gp64 genes, of the alpha, beta and gamma antigen coding regions respectively, were used to allow for the possibility of sequence variation. There was perfect correlation between the three sets of primers. Latex agglutination and enzyme-linked immunosorbent assay (ELISA) were also employed to provide data for a comparative study. The complete data show that infection with human cytomegalovirus is not only age related but is also sex related. The female population examined using PCR reached a peak infection rate of 80% by the age of 40-50 years whereas the male population reached a 98% infection rate following an almost linear increase with age. Latex agglutination data shows a similar picture although the infection rate peaks around 20% lower than with PCR. The data shows an increase in sensitivity using the PCR rather than the serology although the clinical significance of this has yet to be determined. The work presented here also demonstrates the suitability of the polymerase chain reaction as a potential diagnostic and epidemiological tool.
Confirmation of a Susceptibility Locus for Crohnʼs Disease on Chromosome 16 (1997)

Crohn's disease and ulcerative colitis are related complex genetic disorders producing chronic intestinal inflammation. A susceptibility locus for Crohn's disease, IBDI (inflammatory bowel disease), has been implicated on chromosome 16. To evaluate IBDI in a different population using alternative methodology, we tested markers in the region of IBDI. Seventy-two relative pairs with Crohn's disease only, 23 mixed relative pairs (one relative having Crohn's disease, the other, ulcerative colitis), and 5 relative pairs with ulcerative colitis were genotyped in the region of IBDI. Our population consisted of white Americans, with 29% of families of Ashkenazi Jewish descent. Among the Crohn's disease pairs, we found evidence for linkage at IBDI using multipoint analysis, p = 0.0082. Negative linkage scores were obtained for mixed and ulcerative colitis-only relative pairs. For the entire data set, including mixed relative pairs and relative pairs with ulcerative colitis, there was no significant evidence of linkage. No difference was observed in the evidence of linkage between Jewish and non-Jewish families. Our studies confirm that IBDI represents a susceptibility locus for Crohn's disease, but not ulcerative colitis.
Ultra low voltage complementary metal oxide semiconductor (ULV-CMOS) circuits: bulk CMOS operation below threshold (V/sub TO/) (2002)

To achieve greater reduction in inverter operating voltage and power consumption, ULV-CMOS circuits operating with supply voltages of 900 mV and lower were implemented using bulk processed CMOS transistors. The low voltage operation was achieved by applying the input to both the gate and body of the CMOS transistors. The input voltage forward biases the body to source junction(s), which in turn lowers the V/sub T/'s (threshold voltage) and makes the lower voltage operation possible. A flip-flop and a three stage inverter chain using this technique have been demonstrated.
Mouse models for melanoma: a personal perspective (2009)

Complex biological processes often require in vivo analysis, and many important research advances have been made using mice as a model for the study of various biological systems. Cutaneous melanomas are tumors originating from skin melanocytes, which are present in hair follicles, and interfollicular epidermal and dermal layers. Until recently, mouse melanoma models were largely based on transplantation models, i.e. transplantation of either syngeneic or xenogeneic melanoma cells into wild type or genetically modified animals. More recently, however, the use of novel technologies specifically modifying the genome allows for the generation of mouse strains, which may develop spontaneous melanoma. Nevertheless, it should be kept in mind that animal models provide only an approximation of reality in humans. In this review, we will discuss a representative selection of currently available transplantation and transgenic melanoma models; despite the fact that this selection will be biased by personal experience, we are confident to demonstrate how the use of mouse melanoma models facilitates translational research in several biomedical disciplines.
Dithioesters in atom-transfer radical polymerization (2006)

Phenyl dithioacetates and bis(isobutyl) dithiocarbamates of Cu(II) and Ti(IV) were studied as chain-transfer agents in the controlled free-radical polymerization of methyl methacrylate and styrene. It was shown that the above compounds strongly decelerate the polymerization of at least one of the monomers. When Cu(II) bis(isobutyl) dithiocarbamate was used in an equivalent ratio with an initiator, the polymerization of MMA proceeded as a well-controlled process and yielded a monodisperse polymer. In other cases, when the concentration of the salt was reduced by two or more times, the most reliable feature of controlled polymerization was observed; that is, the molecular mass of the polymer increased linearly and progressively with an increase in the monomer conversion. The results obtained confirmed that dithiocarboxylate and dithiocarbamate groups can, similarly to halides, interact with transition-metal compounds through ligand-(atom)-transfer redox reactions.
Clinical Pharmacokinetics of Oral Controlled-Release 5-Fluorocytosine (2009)

5-Fluorocytosine (5FC) is an oral antifungal that is currently used in combination with amphotericin B to treat Cryptococcus neoformans meningoencephalitis. The oral dosing of 5FC could be optimized by the use of a controlled-release (CR) formulation. The objective of the current study was to develop two prototype 5FC-CR formulations and evaluate the single-dose (1,500-mg) serum pharmacokinetic profiles of those formulations relative to the profile of the commercially available, immediate-release 5FC product (Ancobon) by the use of a phase 1, open-label, randomized, three-phase, crossover pharmacokinetic study design. Hydroxypropyl methylcellulose was utilized as the rate-controlling matrix to compound the 5FC-CR tablets. The two prototype 5FC-CR formulations demonstrated 80% release at 13.0 and 18.4 h, respectively, whereas the immediate-release product demonstrated 80% release at 0.28 h, as determined in vitro by the United States Pharmacopeia apparatus 2 dissolution method. Five subjects completed all three phases of the study without any adverse events. The mean maximum concentration, the area under the curve from time zero to 24 h, and the area under the curve from time zero to infinity were approximately 50% lower (P < 0.01) with the 5FC-CR formulations than with the immediate-release 5FC product. However, no statistically significant differences in the minimum concentrations at 24 h were noted between the formulations. The gastric absorption profile of 5FC-CR was well predicted by in vitro dissolution. Future exploration of a gastroretentive 5FC-CR formulation could overcome the marked lack of bioequivalence observed in the present study.
Long conjugated 2-nitrobenzyl derivative caged anticancer prodrugs with visible light regulated release: preparation and functionalizations (2012)

A series of anticancer prodrugs with different chemical functional groups were prepared, in which the styryl conjugated 2-nitrobenzyl derivatives were introduced as the phototrigger to regulate the drug (chlorambucil) release. Compared to the common 4,5-dimethoxy-2-nitrobenzyl caged compounds, most of the prodrugs exhibited large and redshifted one-photon absorption within the visible range. One-photon excitation for the drug release was studied by measuring UV-vis absorption, FT-IR, and HPLC spectra, which suggested that chlorambucil was released effectively and precisely by manipulating external light conditions. And the introduction of different functional groups made this type of prodrug a good platform to further react with some typical drug carriers and to further form excellent visible light responsive drug delivery systems. Moreover, the drug also could be effectively released under the excitation of two-photon at 800 nm with comparable photorelease efficiencies.