gebhart/patrepeval huggingface dataset:
Anti‐PEGimmunity: emergence, characteristics, and unaddressed questions (2015)

The modification of protein and nanoparticle therapeutics with polyethylene glycol (PEG), a flexible, uncharged, and highly hydrophilic polymer, is a widely adopted approach to reduce RES clearance, extend circulation time, and improve drug efficacy. Nevertheless, an emerging body of literature, generated by numerous research groups, demonstrates that the immune system can produce antibodies that specifically bind PEG, which can lead to the 'accelerated blood clearance' of PEGylated therapeutics. In animals, anti-PEG immunity is typically robust but short-lived and consists of a predominantly anti-PEG IgM response. Rodent studies suggest that the induction of anti-PEG antibodies (α-PEG Abs) primarily occurs through a type 2 T-cell independent mechanism. Although anti-PEG immunity is less well-studied in humans, the presence of α-PEG Abs has been correlated with reduced efficacy of PEGylated therapeutics in clinical trials. The prevalence of anti-PEG IgG and reports of memory immune responses, as well as the existence of α-PEG Abs in healthy untreated individuals, suggests that the mechanism(s) and features of human anti-PEG immune responses may differ from those of animal models. Many questions, including the incidence rate of pre-existing α-PEG Abs and immunological mechanism(s) of α-PEG Ab formation in humans, must be answered in order to fully address the potential complications of anti-PEG immunity.
Cellular and Molecular Aspects of Human CD34+ CD38-Precursors: Analysis of a Primitive Hematopoietic Population (2000)

Hematopoiesis is a complex, highly regulated process in which a small number of primitive stem cells produce all the mature blood and immune cells required by an animal throughout its life. In this review, we summarize current understanding of human CD34+ CD38- cells, a small subclass of hematopoietic cells, which is enriched for primitive precursors, including stem cells. This review emphasizes functional, molecular and immunophenotypic characteristics of the cells and includes some of the factors which are believed to regulate the survival, growth and differentiation of this important class of cells.
Use of avian retroviral vectors to introduce transcriptional regulators into mammalian cells for analyses of tumor maintenance (2003)

A key issue in cancer biology is whether genetic lesions involved in tumor initiation or progression are required for tumor maintenance. This question can be addressed with mouse models that conditionally express oncogenic transgenes, i.e., under the control of tetracycline (tet)-dependent transcriptional regulators. We have developed a system for studying tumor maintenance by using avian retroviral [i.e., replication-competent avian leukosis virus long terminal repeat with splice acceptor (RCAS)] vectors to deliver the reverse tet transcriptional transactivator (rtTA) gene to somatic mammalian cells. rtTA can regulate any transgene in which the protein coding sequence is preceded by a tet-operator (tet-o); RCAS viruses infect only cells engineered to express ectopically the avian retroviral receptor, TVA. One vector, RCAS-rtTA-IRES-GFP, also encodes GFP to identify infected cells. Infection of cells from beta-actin TVA transgenic mice with this vector permits efficient regulation of tet-responsive transgenes. Sarcomas arise when p53-deficient murine embryonic fibroblasts carrying beta-actin TVA and tet-o-K-ras4bG12D transgenes are infected with RCAS-rtTA-IRES-GFP and introduced into nude mice treated with the tet analog, doxycycline (dox); when dox is withdrawn, K-ras4bG12D levels fall, cells undergo apoptosis, and tumors regress. Regression can be prevented by means of a genetic complementation assay in which tumors are superinfected before dox withdrawal with other RCAS viruses, such as those carrying an active allele of K-ras. Many TVA and tet-regulated transgenic mice have been generated; thus, this method for somatic cell-specific and temporally controlled gene expression may have broad applications for the study of oncogenesis and tumor maintenance, as well as other cell functions and development.
Gene therapy targeted by radiation preferentially radiosensitizes tumor cells. (1994)

Transcriptional regulation of the promoter/enhancer region of the Egr-1 gene is activated by ionizing radiation. We linked DNA sequences from the promotor region of Egr-1 to a complementary DNA sequence which encodes human tumor necrosis factor (TNF) alpha, a radiosensitizing cytokine. The Egr-TNF construct was transfected into a human cell line of hematopoietic origin, HL525, which was used in an experimental animal system. HL525 (clone 2) cells containing the Egr-TNF construct which exhibits radiation induction of TNF-alpha were injected into human xenografts of the radioresistant human squamous cell carcinoma cell line SQ-20B. Animals treated with radiation and clone 2 demonstrated an increase in tumor cures compared with animals treated with radiation alone or unirradiated animals given injections of clone 2 alone. No increase in local or systemic toxicity was observed in the combined treatment group. The combination of gene therapy and radiation therapy enhances tumor cures without increasing normal tissue toxicity and is a new paradigm for cancer treatment.
Characterization of aStaphylococcus aureusSurface Virulence Factor That Promotes Resistance to Oxidative Killing and Infectious Endocarditis (2010)

Staphylococcus aureus is a prominent human pathogen and a leading cause of community- and hospital-acquired bacterial infections worldwide. Herein, we describe the identification and characterization of the S. aureus 67.6-kDa hypothetical protein, named for the surface factor promoting resistance to oxidative killing (SOK) in this study. Sequence analysis showed that the SOK gene is conserved in all sequenced S. aureus strains and homologous to the myosin cross-reactive antigen of Streptococcus pyogenes. Immunoblotting and immunofluorescence analysis showed that SOK was copurified with membrane fractions and was exposed on the surface of S. aureus Newman and RN4220. Comparative analysis of wild-type S. aureus and an isogenic deletion strain indicated that SOK contributes to both resistance to killing by human neutrophils and to oxidative stress. In addition, the S. aureus sok deletion strain showed dramatically reduced aortic valve vegetation and bacterial cell number in a rabbit endocarditis model. These results, plus the suspected role of the streptococcal homologue in certain diseases such as acute rheumatic fever, suggest that SOK plays an important role in cardiovascular and other staphylococcal infections.
A resampling-based meta-analysis for detection of differential gene expression in breast cancer (2008)

The proposed meta-analysis approach has the ability to detect a set of differentially expressed genes with the least amount of within-group variability, thus providing highly stable gene lists for class prediction. Increased statistical power and stringent filtering criteria used in the present study also make identification of novel candidate genes possible and may provide further insight to improve our understanding of breast cancer development.
New hepatitis C virus (HCV) genotyping system that allows for identification of HCV genotypes 1a, 1b, 2a, 2b, 3a, 3b, 4, 5a, and 6a (1997)

Recent studies have focused on whether different hepatitis C virus (HCV) genotypes are associated with different profiles of pathogenicity, infectivity, and response to antiviral therapy. The establishment of a simple and precise genotyping system for HCV is essential to address these issues. A new genotyping system based on PCR of the core region with genotype-specific PCR primers for the determination of HCV genotypes 1a, 1b, 2a, 2b, 3a, 3b, 4, 5a, and 6a was developed. A total of 607 samples (379 from Japan, 63 from the United States, 53 from Korea, 35 from Taiwan, 32 from China, 20 from Hong Kong, 15 from Australia, 6 from Egypt, 3 from Bangladesh, and 1 from South Africa) were tested by both the assay of Okamoto et al. (H. Okamoto, Y. Sugiyama, S. Okada, K. Kurai, Y. Akahane, Y. Sugai, T. Tanaka, K. Sato, F. Tsuda, Y. Miyamura, and M. Mayumi, J. Gen. Virol. 73:673-679, 1992) and this new genotyping system. Comparison of the results showed concordant results for 539 samples (88.8%). Of the 68 samples with discordant results, the nucleotide sequences of the HCV isolates were determined in 23, and their genotypes were determined by molecular evolutionary analysis. In all 23 samples, the assignment of genotype by our new genotyping system was correct. This genotyping system may be useful for large-scale determination of HCV genotypes in clinical studies.
Attenuation of the Obesity Syndrome of ob/ob Mice by the Loss of Neuropeptide Y (1996)

The obesity syndrome of ob/ob mice results from lack of leptin, a hormone released by fat cells that acts in the brain to suppress feeding and stimulate metabolism. Neuropeptide Y (NPY) is a neuromodulator implicated in the control of energy balance and is overproduced in the hypothalamus of ob/ob mice. To determine the role of NPY in the response to leptin deficiency, ob/ob mice deficient for NPY were generated. In the absence of NPY, ob/ob mice are less obese because of reduced food intake and increased energy expenditure, and are less severely affected by diabetes, sterility, and somatotropic defects. These results suggest that NPY is a central effector of leptin deficiency.
Augmentation of Left Ventricular Contractility by Cardiac Sympathetic Neural Stimulation (2010)

Cardiac nerve fibers that innervate the left ventricle are amenable to transvenous electric catheter stimulation. This may permit direct interference with and modulation of the sympathetic tone of the left ventricle.
A Synthetic Overview of New Molecules with 5-HT1A Binding Affinities (2003)

The present review discusses the synthetic strategies of new ligands exhibiting mainly 5-HT(1A)binding affinities. Specifically we focused our attention in the synthesis of compounds structurally related to arylpiperazine, 2-aminotetralin, and benzopyran derivatives.
One Athlete, One Nation, Two Flags: Cathy Freeman and Australia's search for aboriginal reconciliation (2008)

This paper will examine the career of athletics champion Catherine Astrid Salome Freeman (better known as Cathy) and how it has affected perceptions of Australia. In lighting the cauldron at the Opening Ceremony of the Sydney 2000 Olympic Games and winning her historic 400 metre race before a record Olympic crowd of 112,524, Freeman became one of Australia's most admired and respected athletes. Her celebrated win at the Sydney Games was Australia's 100th gold medal at an Olympic event and the first individual gold medal for an indigenous Australian. This article examines a number of mediated signs and symbols surrounding Cathy Freeman between 1994 and 2000, and how these images were played out in wider discussions about the future of the Australian nation-state. While the paper focuses on some of Freeman's high profile events between 1994 and 2000, some developments since 2000 will be briefly discussed where relevant.
Development of Greenbiochemistry (2003)

Abstract For Abstract see ChemInform Abstract in Full Text.
CD4+ T-Cell–Mediated Mechanisms of Corneal Allograft Rejection: Role of Fas-Induced Apoptosis (2004)

The results suggest that CD4(+) T cells function directly as effector cells and not as helper cells in the rejection of corneal allografts. Although the corneal endothelium is highly susceptible to Fas-induced apoptosis, this is apparently not the primary mechanism of CD4(+) T-cell-dependent rejection.
Exploiting Collective Effects of Multiple Optoelectronic Devices Integrated in a Single Fiber (2009)

The opportunities and challenges of realizing sophisticated functionality by assembling many nanoscale devices, while covering large areas, remain for the most part unrealized and unresolved. In this work, we demonstrate the successful fabrication of an eight-device cascaded optoelectronic fiber structure in which components down to 100 nm are individually electrically addressed and can operate collectively to deliver novel functionality over large area coverage. We show that a tandem arrangement of subwavelength photodetecting devices integrated in a single fiber enables the extraction of information on the direction, wavelength, and potentially even color of incident radiation over a wide spectral range in the visible regime. Finally, we fabricated a 0.1 square meter single plane fiber assembly which uses polychromatic illumination to extract images without the use of a lens, representing an important step toward ambient light imaging fabrics.
Modeling and Simulation of Genetic Regulatory Systems: A Literature Review (2002)

In order to understand the functioning of organisms on the molecular level, we need to know which genes are expressed, when and where in the organism, and to which extent. The regulation of gene expression is achieved through genetic regulatory systems structured by networks of interactions between DNA, RNA, proteins, and small molecules. As most genetic regulatory networks of interest involve many components connected through interlocking positive and negative feedback loops, an intuitive understanding of their dynamics is hard to obtain. As a consequence, formal methods and computer tools for the modeling and simulation of genetic regulatory networks will be indispensable. This paper reviews formalisms that have been employed in mathematical biology and bioinformatics to describe genetic regulatory systems, in particular directed graphs, Bayesian networks, Boolean networks and their generalizations, ordinary and partial differential equations, qualitative differential equations, stochastic equations, and rule-based formalisms. In addition, the paper discusses how these formalisms have been used in the simulation of the behavior of actual regulatory systems.
Self-Similar Propagation and Amplification of Parabolic Pulses in Optical Fibers (2000)

Ultrashort pulse propagation in high gain optical fiber amplifiers with normal dispersion is studied by self-similarity analysis of the nonlinear Schrödinger equation with gain. An exact asymptotic solution is found, corresponding to a linearly chirped parabolic pulse which propagates self-similarly subject to simple scaling rules. The solution has been confirmed by numerical simulations and experiments studying propagation in a Yb-doped fiber amplifier. Additional experiments show that the pulses remain parabolic after propagation through standard single mode fiber with normal dispersion.
Regulation of 3’ IgH enhancers by a common set of factors, including kappa B-binding proteins (1996)

Targeted disruption of the p50 subunit of NF-kappa B resulted in isotype class switch defects resembling those observed in mice in which the downstream IgH enhancer 3'alpha E(hs1,2) was deleted. We postulated that kappa B binding proteins may regulate class switching by interacting with 3'alpha E(hs1,2) or with other IgH 3' enhancers with which 3'alpha E(hs1,2) synergizes. kappa B binding sites were identified in 3'alpha E(hs1,2) and 3' alpha-hs4, the distal 3' IgH enhancer. A kappa B binding site within 3'alpha E(hs1,2) contributes to at least half the activity of the enhancer in plasma cells, while the same kappa B binding site participates in the complex repression of the enhancer in B cells. In the case of 3'alpha-hs4, a kappa B binding complex activates the enhancer in pre-B, B cells and plasma cells. Additional binding sites within 3'alpha-hs4 for factors known to regulate 3'alpha E(hs1,2), including Oct-1 and BSAP, were identified, and their contribution to 3'alpha-hs4 regulation during B cell development was assessed. Oct-1 positively regulates the enhancer in pre-B and B cells, while BSAP is a repressor in pre-B cells and an activator at the B cell stage. These studies identify kappa B binding proteins as key modulators of 3'alpha E(hs1,2) and 3'alpha-hs4, and suggest coregulation of the two enhancers by a common set of factors.
Persistent Activation of Stat3 Signaling Induces Survivin Gene Expression and Confers Resistance to Apoptosis in Human Breast Cancer Cells (2006)

We identify Survivin as a direct downstream target gene of Stat3 in human breast cancer cells that is critical for their survival in culture. Our findings suggest that activated Stat3 signaling contributes to breast cancer progression and resistance to chemotherapy by, at least in part, inducing expression of the antiapoptotic protein, Survivin.
Efficient checkpoint/verification patterns (2015)

Errors have become a critical problem for high-performance computing. Checkpointing protocols are often used for error recovery after fail-stop failures. However, silent errors cannot be ignored, and their peculiarity is that such errors are identified only when the corrupted data is activated. To cope with silent errors, we need a verification mechanism to check whether the application state is correct. Checkpoints should be supplemented with verifications to detect silent errors. When a verification is successful, only the last checkpoint needs to be kept in memory because it is known to be correct. In this paper, we analytically determine the best balance of verifications and checkpoints so as to optimize platform throughput. We introduce a balanced algorithm using a pattern with p checkpoints and q verifications, which regularly interleaves both checkpoints and verifications across same-size computational chunks. We show how to compute the waste of an arbitrary pattern, and we prove that the balanced algorithm is optimal when the platform MTBF (mean time between failures) is large in front of the other parameters (checkpointing, verification and recovery costs). We conduct several simulations to show the gain achieved by this balanced algorithm for well-chosen values of p and q, compared with the base algorithm that always perform a verification just before taking a checkpoint ( p = q = 1), and we exhibit gains of up to 19%.
Cellular and biochemical characterization of VX-710 as a chemosensitizer (1997)

VX-710 or (S)-N[2-Oxo-2-(3,4,5-trimethoxyphenyl)acetyl]-piperidine-2-carboxylic acid 1,7-bis(3-pyridyl)-4-heptyl ester, a novel non-macrocyclic ligand of the FK506-binding protein FKBP12, was evaluated for its ability to reverse P-glycoprotein-mediated multidrug resistance in vitro. VX-710 at 0.5-5 microM restored sensitivity of a variety of multidrug resistant cells to the cytotoxic action of doxorubicin, vincristine, etoposide or paclitaxel, including drug-selected human myeloma and epithelial carcinoma cells, and human MDR1 cDNA-transfected mouse leukemia and fibroblast cells. Uptake experiments showed that VX-710 at 0.5-2.5 microM fully restored intracellular accumulation of [14C]doxorubicin in multidrug resistant cells, suggesting that VX-710 inhibits the drug efflux activity of P-glycoprotein. VX-710 effectively inhibited photoaffinity labeling of P-glycoprotein by [3H]azidopine or [125I]iodoaryl azidoprazosin with EC50 values of 0.75 and 0.55 microM. Moreover, P-glycoprotein was specifically labeled by a tritiated photoaffinity analog of VX-710 and unlabeled VX-710 inhibited analog binding with an EC50 of 0.75 microM. VX-710 also stimulated the vanadate-inhibitable P-glycoprotein ATPase activity 2- to 3-fold in a concentration-dependent manner with an apparent k(a) of 0.1 microM. These data indicate that a direct, high-affinity interaction of VX-710 with P-glycoprotein prevents efflux of cytotoxic drugs by the MDR1 gene product in multidrug resistant tumor cells.
Desorption electrospray ionization mass spectrometry: Imaging drugs and metabolites in tissues (2008)

Ambient ionization methods for MS enable direct, high-throughput measurements of samples in the open air. Here, we report on one such method, desorption electrospray ionization (DESI), which is coupled to a linear ion trap mass spectrometer and used to record the spatial intensity distribution of a drug directly from histological sections of brain, lung, kidney, and testis without prior chemical treatment. DESI imaging provided identification and distribution of clozapine after an oral dose of 50 mg/kg by: i) measuring the abundance of the intact ion at m/z 327.1, and ii) monitoring the dissociation of the protonated drug compound at m/z 327.1 to its dominant product ion at m/z 270.1. In lung tissues, DESI imaging was performed in the full-scan mode over an m/z range of 200-1100, providing an opportunity for relative quantitation by using an endogenous lipid to normalize the signal response of clozapine. The presence of clozapine was detected in all tissue types, whereas the presence of the N-desmethyl metabolite was detected only in the lung sections. Quantitation of clozapine from the brain, lung, kidney, and testis, by using LC-MS/MS, revealed concentrations ranging from 0.05 microg/g (brain) to a high of 10.6 microg/g (lung). Comparisons of the results recorded by DESI with those by LC-MS/MS show good agreement and are favorable for the use of DESI imaging in drug and metabolite detection directly from biological tissues.
Natural therapies for ocular disorders, part one: diseases of the retina. (1999)

Diseases of the retina are the leading causes of blindness throughout the world. Evidence points to potential benefit from nutritional and botanical interventions for the prevention and treatment of several of these conditions, including macular degeneration, diabetic retinopathy, retinopathy of the newborn, and retinitis pigmentosa. Epidemiological evidence points to the potential of antioxidant vitamins E and C, carotenoids, zinc, and selenium in the prevention and possible treatment of macular degeneration. In addition, dietary components such as red wine-high in important flavonoids-and fruits and vegetables high in carotenoids appear to offer some protection. While diabetic retinopathy can best be prevented by maintaining good blood sugar control, there are a number of nutrients and botanicals which may help prevent and treat retinopathy by inhibiting protein glycosylation, stabilizing collagen, decreasing capillary permeability, and providing important antioxidant effects. Extensive research on the use of vitamin E for the prevention of retrolental fibroplasia (retinopathy of the newborn), despite yielding promising results, has not resulted in incorporation of vitamin E into conventional standards of care protocols. Retinitis pigmentosa resembles the retinal damage seen in taurine-deficient cats. While patients with retinitis pigmentosa do not appear to be deficient in taurine, they appear to have faulty cellular uptake of this important amino acid. Disturbed utilization of vitamin A also appears to play a part in retinitis pigmentosa, and a subgroup of patients benefit from supplementation.
Effect of high-dose thymidine infusions in patients with mycosis fungoides (1981)

The antitumor effect of thymidine has been demonstrated in patients with leukemia and lymphoma. This report summarizes the treatment of three patients with mycosis fungoides, a chronic T-cell lymphoma. Four courses of thymidine (75 g/m2/day) were administered by continuous infusion for 4-7 days. Steady-state serum thymidine levels were in the range of 1-3 mM. Associated toxicities were minimal and consisted of milk headache and anorexia. Myelosuppression was manifested by transient declines in the peripheral leukocyte count. One patient had extensive clearing of diffuse erythematous plaques on the trunk and extremities that persisted for over one month. A second patient had partial clearing of plaques that persisted for two weeks following therapy and a third patient had a minimal response with 25% reduction in lymphadenopathy and noduloulcerative lesions. These responses indicate the effectiveness of thymidine as a single agent in the treatment of mycosis fungoides.