gebhart/patrepeval huggingface dataset:
Recombinant human hyaluronidase (rHuPH20): an enabling platform for subcutaneous drug and fluid administration (2007)

The extracellular matrix is a significant barrier to the effective subcutaneous delivery of many drugs, limiting both pharmacokinetic parameters and injection volumes. The space outside adipocytes in the hypodermis is not a fluid, but rather a solid extracellular matrix of collageneous fibrils embedded within a glycosaminoglycan-rich viscoelastic gel that buffers convective forces. The extracellular matrix limits the volume of drug that can be injected at a single site, as well as the rate and amount that reach the vascular compartment. A fully human recombinant DNA-derived hyaluronidase enzyme (rHuPH20) has been developed to leverage the historical efficacy of animal testes extract-derived spreading factors to reversibly modify the hypodermis, in light of discovery of the human hyaluronidase gene family. The application of this technology to increase both injection volumes and bioavailability from subcutaneous injection may overcome some key limitations of this route of administration in multiple settings of care.
Recombinant Antibody Color Resulting from Advanced Glycation End Product Modifications (2014)

Recombinant antibodies produced in Chinese hamster ovary (CHO) cells often exhibit a slight yellow-brown color, but the molecular basis for this color has remained elusive. We predicted that the color results from post-translational modifications on the antibody, because colored species were found to coelute with antibody products during size exclusion chromatography. Previously, modification by oxidation and advanced glycation end products (AGEs) had been shown to give rise to colored and fluorescent species whose spectral properties are in agreement with the spectral properties of CHO-derived recombinant antibodies. To test whether these modifications give rise to the color exhibited in our CHO-derived antibodies, we searched for 8 different oxidation and 28 different glycation and AGE modifications by mass spectrometry in a variety of samples exhibiting varying color intensities. Oxidation and glycation modifications correlated weakly with color in a subset of samples, but several AGEs exhibited a strong correlation with product color in all samples tested. This strong correlation with sample color was verified for a specific AGE, carboxymethyllysine, by ELISA, thus validating the mass spectrometry data. These data indicate that AGEs are at least partially responsible for the color seen in CHO-derived recombinant antibodies.
Remote Ischemic Preconditioning and Postoperative Renal Dysfunction (2015)

To the Editor The Editorial by Drs Pan and Sheikh-Hamad1 accompanied the study by Zarbock et al2 showing a beneficial effect of remote ischemic preconditioning on the incidence of postoperative renal dysfunction in high-risk patients undergoing cardiac surgery.
Modulation of the Cell Growth Regulator mTOR by Epstein-Barr Virus-Encoded LMP2A (2005)

Control of translation initiation is one means by which cells regulate growth and proliferation, with components of the protein-synthesizing machinery having oncogenic potential. Expression of latency protein LMP2A by the human tumor virus Epstein-Barr virus (EBV) activates phosphatidylinositol 3-kinase/Akt located upstream of an essential mediator of growth signals, mTOR (mammalian target of rapamycin). We show that mTOR is activated by expression of LMP2A in carcinoma cells, leading to wortmannin- and rapamycin-sensitive inhibition of the negative regulator of translation, eukaryotic initiation factor 4E-binding protein 1, and increased c-Myc protein translation. Intervention by this DNA tumor virus in cellular translational controls is likely to be an integral component of EBV tumorigenesis.
Handbook of Psychiatric Measures (2000)

Preface. Acknowledgements. About the CD-ROM. Section I: Introduction to the Handbook. Organization and use of the handbook. Psychometric properties: concepts of reliability and validity. Considerations in choosing, using, and interpreting a measure for a particular clinical context. Cultural factors nfluencing the selection, use, and interpretation of psychiatric measures. Section II: General Measures (Non-Disorder Specific). Diagnostic measures for adults. General psychiatric symptoms measures. Mental health status, functioning, and disabilities measures. General health status, functioning, and disabilities measures. Quality of life measures. Adverse effects measures. Patient perceptions of care measures. Stress and life events measures. Family risk factor measures. Suicide risk measures. Section III: Measures Related To DSM-IV Diagnostic Categories. Child and adolescent measures for diagnosis and screening. Symptom-specific measures for disorders usually first diagnosed in infancy, childhood, or adolescence. Child and adolescent measures of functional status. Measures for delirium and the behavioral symptoms of cognitive disorders. Neuropsychiatric measures for cognitive disorders. Substance use disorder measures. Psychotic disorders measures. Mood disorders measures. Anxiety disorders measures. Somatoform and factitious disorders and malingering measures. Dissociative disorders measures. Measures of sexual dysfunction and disorders. Eating disorders measures. Sleep disorders measures. Impulse-control disorders measures. Personality disorders, personality traits, and defense mechanisms measures. Aggression measures. Appendix A: DSM-IV-TR classification. Appendix B: list of measures included on the CD-ROM. Appendix C: index of measures. Appendix D: index of abbreviations for measures. General index.
[Effect of chlorpyrifos residue in red soil on crops]. (2006)

The pot cultivation experiment method, integrating with laboratory analysis, was employed for exploring the influence of chlorpyrifos residue in red soil on growth of wheat and oil-seed rape seedlings, and the uptake of crops to chlorpyrifos residue. The results show that, wheat seedlings and oil-seed rape seedlings can absorb chlorpyrifos residue from soil to reach the concentration of 0.257 to approximately 4.50 microg/g and 0.249 to approximately 2.021 microg/g, respectively, 20 days later since chlorpyrifos was introduced into the pots, on condition that the initial concentration of chlorpyrifos residue in red soil was 1 to approximately 10 microg/g. The initial concentration of chlorpyrifos residue in red soil equivalent to or below 10 micro/g has not significant influence on growth of wheat seedlings. Similarly, the concentration equivalent to or below 5 microg/g has not significant influence on growth of oil-seed rape seedlings. The degradation rate in oil-seed rape rhizosphere soil is 1.4 to approximately 4.2 times more than in that in unvegetated soil. The amount of bacterium and fungus in oil-seed rape rhizosphere is 3.18 times and 1.84 times as much as these in unvegetated soil, respectively. However, there is no substantial difference of actinomyces between in rhizosphere soil and in unvegetated soil. Compared with unvegetated soil, pH in rhizosphere soil is lowered by 0. 19 to approximately 0.23.
Distinct Induction Patterns and Functions of Two Closely Related Interferon-inducible Human Genes, ISG54 and ISG56 (2006)

Human P54 and P56 proteins are tetratricopeptide proteins that are encoded by two closely related genes, ISG54 and ISG56. These genes are induced strongly but transiently when cells are treated with interferons or double-stranded RNA or infected with a variety of viruses. We observed that, although double-stranded RNA or Sendai virus infection induced the two genes with similar kinetics, their induction kinetics in response to interferon-beta were quite different. The induction kinetics by virus infection were also different between two cell lines. Functionally the two proteins were similar. Like P56, P54 bound to the translation initiation factor eIF3 and inhibited translation. However, unlike P56, P54 bound to both the "e" and the "c" subunits of eIF3. Consequently, P54 inhibited two functions of eIF3. Like P56, it inhibited the ability of eIF3 to stabilize the eIF2 x GTP x Met-tRNA(i) ternary complex. But in addition, it also inhibited the formation of the 48 S pre-initiation complex between the 40 S ribosomal subunit and the 20 S complex composed of eIF3, ternary complex, eIF4F, and mRNA. Thus, although similar in structure, the human P54 and P56 proteins are induced differently and function differently.
Complete Replacement of the Mitochondrial Genotype in a Bos indicus Calf Reconstructed by Nuclear Transfer to a Bos taurus Oocyte (2001)

Due to the exclusively maternal inheritance of mitochondria, mitochondrial genotypes can be coupled to a particular nuclear genotype by continuous mating of founder females and their female offspring to males of the desired nuclear genotype. However, backcrossing is a gradual procedure that, apart from being lengthy, cannot ascertain that genetic and epigenetic changes will modify the original nuclear genotype. Animal cloning by nuclear transfer using host ooplasm carrying polymorphic mitochondrial genomes allows, among other biotechnology applications, the coupling of nuclear and mitochondrial genotypes of diverse origin within a single generation. Previous attempts to use Bos taurus oocytes as hosts to transfer nuclei from unrelated species led to the development to the blastocyst stage but none supported gestation to term. Our aim in this study was to determine whether B. taurus oocytes support development of nuclei from the closely related B. indicus cattle and to examine the fate of their mitochondrial genotypes throughout development. We show that indicus:taurus reconstructed oocytes develop to the blastocyst stage and produce live offspring after transfer to surrogate cows. We also demonstrate that, in reconstructed embryos, donor cell-derived mitochondria undergo a stringent genetic drift during early development leading, in most cases, to a reduction or complete elimination of B. indicus mtDNA. These results demonstrate that cross-subspecies animal cloning is a viable approach both for matching diverse nuclear and cytoplasmic genes to create novel breeds of cattle and for rescuing closely related endangered cattle.
Tumor-specific lysis of human renal cell carcinomas by tumor-infiltrating lymphocytes: modulation of recognition through retroviral transduction of tumor cells with interleukin 2 complementary DNA and exogenous alpha interferon treatment. (1993)

Two cytotoxic effector cell populations were isolated from a patient with renal cell carcinoma. The tumor-infiltrating lymphocytes comprised a population of highly specific, major histocompatibility complex-restricted, cytotoxic T lymphocytes (CTL). An autologous non-major histocompatibility complex-restricted lymphokine-activated killer (LAK) cell population was generated by culturing the peripheral blood lymphocytes with high doses of recombinant interleukin 2 (rIL-2). The capacity of these two effector cell types to lyse cytokine-modulated autologous tumor cells was compared in vitro. A complementary DNA for rIL-2 was introduced into the tumor cells by retroviral transduction, and tumor cells secreting low doses of rIL-2 were isolated. The CTL recognition of these tumor cells was enhanced, compared to unmodified tumor cells, whereas LAK cell recognition was unchanged or slightly reduced. Pretreatment of tumor cells with exogenous alpha interferon led to an up-regulation of some major histocompatibility complex class I molecules and to slightly better recognition by the CTL; little effect on LAK cell recognition was observed. CTL were found to be 50-150-fold more effective than LAK cells in lysing autologous tumor cell lines or clones modulated with both rIL-2 and alpha interferon. The assessment of a patient's cytotoxic immune capacity directed against genetically modified autologous tumor cells in vitro provides important insight for cytokine-mediated gene therapy of cancer.
Terpenoids as Potential Anti-Alzheimer’s Disease Therapeutics (2012)

Alzheimer's disease (AD) is one of the most well-known neurodegenerative diseases and explains 50-60% of dementia in patients. The prevalence rate of AD is positively correlated with age and AD affects ≥ 40% of those over 85 years old. The major AD therapeutics available on the market are acetylcholinesterase inhibitors, such as tacrine and donepezil. New therapeutic agents that can block the disease-inducing mechanisms are essential. Diverse efforts have been made to discover anti-AD agents from natural sources. In this review article, we describe some representative terpenoids such as ginsenosides, gingkolides, and canabinoids as potential anti-AD agents. These compounds exhibit promising in vitro and in vivo biological activities, but are still waiting clinical trials. Additionally, we also discuss some terpenoids including cornel iridoid glycoside, oleanolic acid, tenuifolin, cryptotanshinone, and ursolic acid, which are under investigation for their in vitro and in vivo animal studies.
Characterization of human variable domain antibody fragments against the U1 RNA‐associated A protein, selected from a synthetic and a patient‐derived combinatorial V gene library (1996)

This is the first study describing recombinant human antibody fragments directed to the U1 RNA-associated A protein (U1A). Three anti-U1A antibody fragments (Fab) were isolated from a semi-synthetic human Fab library and one anti-U1A single-chain variable fragment (scFv) was isolated from a library which was derived from the IgG-positive splenic lymphocytes of an autoimmune patient. Competition studies with autoantibodies against the U1 small nuclear ribonucleoprotein (snRNP) particle from patients with systemic lupus erythematosus (SLE) and SLE-overlap syndromes revealed that U1A binding of these antibody fragments can be inhibited by about 40% of the patient sera. All antibody fragments recognized the native U1 snRNP in immunoprecipitation assays. Two of three Fab clones as well as the scFv clone derived from the repertoire of an autoimmune patient use the same heavy chain germ-line gene DP-65. Epitope mapping revealed that these three clones appear to recognize an identical epitope domain present on the C-terminal RNP motif of the U1A protein. The DP-65 heavy chain gene is used in less than 1% of the B cells in healthy individuals, while three out of four anti-U1A antibody fragments use this gene. This points to a restricted VH gene usage in the case of U1A, suggesting that the DP-65 heavy chain has a natural shape complementarity to the U1A protein.
Isolation, characterization, and genetic profiling of subpopulations of olfactory ensheathing cells from the olfactory bulb (2011)

Olfactory ensheathing cells (OECs) play a crucial role during neurogenesis of primary olfactory neurons. Transplantation of OECs is considered as a promising new therapy for central nervous system repair. Nevertheless, OECs are constituted of distinct subpopulations and their role during neurogenesis is not clearly understood. In particular, OECs from the olfactory bulb (OB) constitute a heterogeneous, but not yet isolated and characterized, population of cells. In our study, flow cytometry analyses of primary OB cultures, based on cell surface expression of low-affinity nerve growth factor receptor (p75), reveal the presence of two distinct populations of OECs. Indeed, some of them express a high level of p75 (P75High) and the other a low level of p75 (P75Low). Effects of OB microenvironment were assessed, and we were able to show that fibroblasts mediate the induction of these two populations through the secretion of soluble factors. To characterize P75High and P75Low OECs, cells were sorted based on their differential expression of p75. Microarray analyses revealed that P75High OECs overexpress genes implicated in modulation of extracellular matrix and cell sorting, whereas P75Low OECs overexpress genes involved in regulation of the inflammatory response and axonal guidance. These results permit, for the first time, to isolate the two distinct subpopulations of OECs from OB, and suggest their specific role during neurogenesis.
Helium reemission during implantation of silicon carbide (1983)

Reemission has been measured during implantation of 1 keV and 20 keV helium ions in CVD SiC at room temperature and at 600 °C. The reemission behavior depends strongly on target temperature as well as ion energy, and there exists a close relationship between the reemission behavior and surface features. The flaking of CVD SiC is explained by crack propagation through the implanted layer, with gas pressure being the driving force for cracking. The effects on the reemission behavior of prebombardment with helium ions having continuous energy distribution have been also measured.
Ultrasonic visualization of norplant® subdermal contraceptive devices (1985)

This article describes the first use of ultrasound in locating in vivo NORPLANT subdermal contraceptive implants. Providing low dose, continuous contraception for women. the NORPLANT system utilizes Silastic tubing filled with levonorgestrel. The progestin-filled tubing is not radiopaque. Anticipating the large scale use of NORPLANT subdermal implants, the potential, but rare problem of difficult localization of an implant is recognized. The feasibility of using ultrasound for the painless and safe localization of NORPLANT rods and capsules is demonstrated.
Reticuloendotheliosis viruses and derived vectors. (1995)

In most human gene therapy trials, the tools of gene delivery are retroviral vectors. All current vectors are derived from murine leukemia virus (MLV). Although this system is suitable for delivering a large variety of genes into different tissues, it also has its limitations and is not adequate for all potential applications of human gene therapy. Thus, attempts are underway in many laboratories to develop other gene delivery tools. Potential agents range from non-viral based gene delivery systems (eg liposomes) to other viral vectors such as those derived from adenoviruses, adeno-associated viruses, herpes simplex virus, and several other viruses. Furthermore, the development of other, non-MLV retroviral vector systems, including one derived from HIV, is in progress in several laboratories. In this article, reticuloendotheliosis viruses and their vector systems are reviewed, and their possible use in human gene therapy is discussed.
The sequence A??-(154 ??? 159) of fibrinogen is capable of accelerating the t-PA catalysed activation of plasminogen (1991)

The rate of activation of plasminogen by tissue-type plasminogen activator (t-PA) is greatly increased by fibrin, but much less by fibrinogen. Fibrin(ogen) fragments such as the fibrin(ogen) cyanogen bromide fragment FCB-2 and FCB-5, and a synthetic peptide with the sequence of fibrinogen A alpha-(148-160), a constituent of FCB-2, also have rate-enhancing properties. In order to find a possibly smaller, still stimulating site within A alpha-(148-160) we synthesized successive linear amino-terminally acylated hexapeptides [i.e. A alpha-(148-153), A alpha-(149-154)'d, .... A alpha-(155-160)] from the sequence A alpha-(148-160). The only hexapeptide within the sequence A alpha-(148-160) capable of enhancing the rate of plasminogen-to-plasmin conversion by t-PA appears to be the amino-terminally acylated peptide comprising the sequence A alpha-(154-159). This peptide enhances the plasminogen activation rate six-fold; half-maximal activation rate is reached at a peptide concentration of 56 microM.
Administration of a Synthetic TLR4 Agonist Protects Mice from Pneumonic Tularemia (2008)

Francisella tularensis is a Gram-negative intracellular pathogen that causes the zoonosis tularemia. Because F. tularensis LPS causes weak TLR4 activation, we hypothesized that administration of a synthetic TLR4 agonist, aminoalkyl glucosaminide phosphate (AGP), would boost the innate immune system and compensate for reduced TLR4 stimulation. Intranasal administration of AGPs induced intrapulmonary production of proinflammatory cytokines and chemokines. Mice treated with AGPs before and after inhalation of Francisella novicida exhibited augmented cytokine and inflammatory responses to infection; reduced bacterial replication in lung, liver, and spleen; and increased survival, whereas all PBS-treated control mice died within 4 days of infection, all AGP-treated mice showed prolonged time-to-death, and 30-60% of AGP-treated mice survived. The protective effect of AGP was lost in mice lacking IFN-gamma. Long-term survivors developed specific Th1 splenocyte responses and specific Abs dominated by IgG2 isotypes. Survivors were fully protected from rechallenge with aerosolized F. novicida. Thus, preventive administration of AGP successfully modulated innate immune responses to aerosolized F. novicida, leading to protective immunity to pneumonic tularemia. This is the first report of the protective effect of a TLR ligand on resistance to F. novicida-induced pneumonic tularemia.
Birth weight and blood pressure: cross sectional and longitudinal relations in childhood (1995)

Birth weight rather than placental ratio is the early life factor most importantly related to blood pressure in childhood. The results support the possibility of "amplification" of the relation between birth weight and blood pressure, particularly in girls.
Magnetic Field Alignment of Ordered Silicate-Surfactant Composites and Mesoporous Silica (1997)

Macroscopic orientational ordering of the pores of condensed hexagonal mesostructured silica (MCM-41) was achieved through alignment of an unpolymerized, hexagonal, lyotropic silicate-surfactant liquid crystal in a high magnetic field. This alignment was preserved after polymerization of the silicate species by acid treatment. Subsequent calcination to remove the surfactant yielded a mesoporous silica solid that retained both macroscopic pore alignment and mesoscale periodicity. Potential applications of such liquid crystal processing strategies range from the formation of anisotropic silica-based bulk ceramics to the production of oriented mesoporous thin films for chemical sensors, separations, catalysis, or host-guest applications.
Intracisternal Type A Particle-Mediated Activation of the Notch4/int3 Gene in a Mouse Mammary Tumor: Generation of Truncated Notch4/int3 mRNAs by Retroviral Splicing Events (1999)

The int3 oncogene was discovered as a frequent target in mouse mammary tumor virus-induced mammary tumors and encodes the intracellular domain of a Notch4/int3 protein. In one spontaneous mammary tumor, no. 9, that developed in a BALB/c mouse, we have found an insertion of a 1.2-kb sequence, consisting of a 5' long terminal repeat and gag sequences of an intracisternal type A particle (IAP) as well as an extra copy of the Notch4/int3 genomic sequences containing exons 23 and 24, into the intron between exons 24 and 25 of the Notch4/int3 gene. In this tumor, unique splicing events between the IAP and the Notch4/int3 sequences generated two types of IAP-Notch4/int3 fusion transcripts encoding two different portions of the intracellular domain of Notch4/int3 proteins: one with a RAM domain and the other without. Interestingly, these two proteins showed different subcellular localizations in a mouse mammary epithelial cell line, HC-11.