gebhart/patrepeval huggingface dataset:
The Role of Endogenous NADPH Oxidases in Airway and Pulmonary Vascular Smooth Muscle Function (2003)

Reactive oxygen species generated from NADPH oxidase(s) in airway smooth muscle cells and pulmonary artery smooth muscle cells are important signaling intermediates. Nox4 appears to be the predominant gp91 homologue in these cells. However, expression of NADPH oxidase components is dependent on phenotype, and different homologues may be expressed during different functional states of the cell. NADPH oxidase(s) appear to be important not only for mitogenesis by these cells, but also for O(2) sensing. The regulation of NADPH oxidase(s) in airway and pulmonary artery smooth muscle cells has important implications for the pathobiochemistry of asthma and pulmonary vascular diseases.
Investigations into the Diffusion Behaviour of Polypeptides in Native Intestinal Mucus with Regard to their Peroral Administration (1996)

Beside enzymatic and absorption barriers, the diffusion barrier presented by the mucus layer covering the gastrointestinal epithelia has an important influence on the bioavailability of perorally administrated peptide and protein drugs. To obtain detailed information on this barrier, the diffusion behaviour of polypeptides in the range of 3.4 to 66 kDa and the influence of a mucolytic agent (N-acetylcysteine) was studied in native mucus gel from porcine small intestine during an incubation period of 5 h.



Since the percentage amount of protein that passed through the mucus was almost constant (1 ± 0.5%) between molecular masses of 12.4 and 66 kDa but increases significantly below these values, the margin for polypeptides passing through a layer of mucus 1 mm thick has to be no more than 12.4 kDa. Smaller polypeptides, 6.5 and 3.4 kDa, exhibited approximately two- and threefold diffusion rates, respectively. In the presence of 2% N-acetylcysteine (w/v) the diffusion rate of all tested polypeptides could be increased significantly. Depending on their respective molecular sizes, the permeability of the native mucus could be increased by 50% for large sized molecules (66 kDa) up to approximately three times for comparable small molecules (6.5 kDa).



The results demonstrate that the mucus covering gastrointestinal epithelia represents an almost insurmountable barrier to proteins with a molecular mass higher than 12.4 kDa but this can be reduced by the addition of appropriate mucolytic agents such as N-acetylcysteine.
Exploring algorithms using Balsa-II (1988)

The use of the Balsa-II algorithm animation environment to investigate the dynamic behavior of programs is discussed. Balsa-II is examined first from a user's perspective and then from a programmer's perspective. Some related systems are briefly considered.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
MECHANISMS AND KINETICS OF SELF-ASSEMBLED MONOLAYER FORMATION (2001)

Recent applications of various in situ techniques have dramatically improved our understanding of the self-organization process of adsorbed molecular monolayers on solid surfaces. The process involves several steps, starting with bulk solution transport and surface adsorption and continuing with the two-dimensional organization on the substrate of interest. This later process can involve passage through one or more intermediate surface phases and can often be described using two-dimensional nucleation and growth models. A rich picture has emerged that combines elements of surfactant adsorption at interfaces and epitaxial growth with the additional complication of long-chain molecules with many degrees of freedom.
Selective Induction of High Avidity CTL by Altering the Balance of Signals from APC (2003)

High avidity CTL are most effective at clearing viruses and cancer cells. Therefore, understanding the mechanisms involved in induction of high avidity CTL is critical for effective vaccines. However, no vaccine approach to selectively induce high avidity CTL in vivo has been discovered. In a new approach, signals from MHC class I (signal 1) and costimulatory molecules (signal 2) were adjusted by varying Ag dose and by use of recombinant poxvirus expressing a triad of costimulatory molecules (B7-1, ICAM-1, and LFA-3), respectively. Independent of CTL avidity, a strong signal 1 resulted in an increased frequency of CD8(+) CTL. However, a strong signal 2 was necessary for the induction of high avidity CD8(+) CTL that killed target cells more efficiently, and signal 2 played a more crucial role in the absence of a strong signal 1. Only CTL induced with strong signal 2 killed tumor cells endogenously expressing low levels of Ag. Signal 2 contributed to the induction of high avidity CD8(+) CTL in both primary and secondary responses. Thus, although signal 2 has been known to increase the quantity of CTL response, in this study we show that it also improves the quality of CTL response. Our data also suggested that dendritic cells play an important role in induction of high avidity CD8(+) CTL in vivo. This strategy to selectively induce higher avidity CTL may lead to more effective vaccines for viruses and cancer.
Targeted Retrograde Gene Delivery for Neuronal Protection (2002)

The cellular heterogeneity and complex circuitry of the central nervous system make it difficult to achieve precise delivery of experimental and therapeutic agents. We report here an in vivo retrograde gene delivery strategy to target mature projection neurons using adeno-associated virus, a vector with low toxicity and the capacity for long-term gene expression. Viral delivery to axon terminal fields in the hippocampus and striatum resulted in viral internalization, retrograde transport, and transgene expression in specific projection neurons in entorhinal cortex and substantia nigra. Retrograde delivery of the anti-apoptotic gene Bcl2l (also known as Bcl-xL) protected entorhinal projection neurons from subsequent damage-induced cell death. Given the broad distribution of neurons affected by neurodegenerative diseases, gene delivery to both the terminal fields and the projection neurons through retrograde infection provides for strategic therapeutic intervention at both levels of the neural circuit. This approach may also facilitate experimental studies of defined neural circuits.
Molecular indices of oxidative stress and mitochondrial dysfunction occur early and often progress with severity of Alzheimer's disease (2006)

Glucose uptake and energy metabolism in the brain are regulated by insulin and insulin-like growth factors (IGF). Recent studies demonstrated progressive deficiencies in brain insulin and IGF production and responsiveness, and linked these abnormalities to acetylcholine deficiency in Alzheimer's disease (AD). We extended this line of research by attempting to correlate the deficits in insulin/IGF signaling and energy production with mitochondrial dysfunction, oxidative injury, and compensatory cyto-protective responses in brains with different Braak Stage severities of AD. Real time quantitative RT-PCR analysis of frontal lobe tissue demonstrated significantly reduced expression of mitochondria-encoded Complex IV and V genes, with relative preservation of genes encoding Complexes I, II and III. In addition, AD was associated with significantly increased expression of the p53 pro-apoptosis gene, all 3 isoforms of nitric oxide synthase (NOS 1-3), and NADPH-oxidase (NOX) 1 and NOX 3, beginning early in the course of disease. Activation of cyto-protective mechanisms in AD brains was limited since the expression levels of uncoupling protein (UCP) 2, 4, and 5, and peroxisome-proliferator activated receptor (PPAR) alpha and delta genes were significantly reduced, whereas PPAR-gamma expression was selectively increased. The results demonstrate that AD is associated with early and striking increases in the molecular indices of oxidative stress, including up-regulation of NOS and NOX genes, which could impair the function of Complexes IV and V within the electron transport chain. The simultaneous reductions in cyto-protective mechanisms (UCP and PPAR), could allow oxidative injury to go unchecked and persist or increase over time. Adopting strategies to reduce the effects of NOS and NOX activities, and improve the actions of UCPs and PPARs may help in the treatment of AD.
The HSP90 inhibitor ganetespib potentiates the antitumor activity of EGFR tyrosine kinase inhibition in mutant and wild-type non-small cell lung cancer (2014)

Small molecule inhibitors of epidermal growth factor receptor (EGFR) tyrosine kinase activity, such as erlotinib and gefitinib, revolutionized therapy for non-small cell lung cancer (NSCLC) patients whose tumors harbor activating EGFR mutations. However, mechanisms to overcome the invariable development of acquired resistance to such agents, as well as realizing their full clinical potential within the context of wild-type EGFR (WT-EGFR) disease, remain to be established. Here, the antitumor efficacy of targeted EGFR tyrosine kinase inhibitors (TKIs) and the HSP90 inhibitor ganetespib, alone and in combination, were evaluated in NSCLC. Ganetespib potentiated the efficacy of erlotinib in TKI-sensitive, mutant EGFR-driven NCI-HCC827 xenograft tumors, with combination treatment causing significant tumor regressions. In erlotinib-resistant NCI-H1975 xenografts, concurrent administration of ganetespib overcame erlotinib resistance to significantly improve tumor growth inhibition. Ganetespib co-treatment also significantly enhanced antitumor responses to afatinib in the same model. In WT-EGFR cell lines, ganetespib potently reduced cell viability. In NCI-H1666 cells, ganetespib-induced loss of client protein expression, perturbation of oncogenic signaling pathways, and induction of apoptosis translated to robust single-agent activity in vivo. Dual ganetespib/erlotinib therapy induced regressions in NCI-H322 xenograft tumors, indicating that the sensitizing properties of ganetespib for erlotinib were conserved within the WT-EGFR setting. Mechanistically, combined ganetespib/erlotinib exposure stabilized EGFR protein levels in an inactive state and completely abrogated extracellular-signal-regulated kinase (ERK) and AKT signaling activity. Thus, selective HSP90 blockade by ganetespib represents a potentially important complementary strategy to targeted TKI inhibition alone for inducing substantial antitumor responses and overcoming resistance, in both the mutant and WT-EGFR settings.
Numerical Methods for Image Registration (2003)

Abstract This text provides an introduction to the theoretical, practical, and numerical aspects of image registration, with special emphasis on medical imaging. Given a so-called reference and template image, the goal of image registration is to find a reasonable transformation such that the transformed template is similar to the reference image. Image registration is utilized whenever information obtained from different viewpoints times and sensors needs to be combined or compared, and unwanted distortion needs to be eliminated. The book provides a systematic introduction to image registration and discusses the basic mathematical principles, including aspects from approximations theory, image processing, numerics, optimization, partial differential equations, and statistics, with a strong focus on numerical methods. A unified variational approach is introduced and enables a separation into data-related issues like image feature or image intensity-based similarity measures, and problem inherent regularization like elastic or diffusion registration. This general framework is further used for the explanation and classification of established methods as well as the design of new schemes and building blocks including landmark-, thin-plate-spline, mutual information, elastic, fluid, demon, diffusion, and curvature registration.
Refractory migraine in a headache clinic population (2011)

Refractory migraine is a relatively common and very disabling condition between the patients attended in a headache unit. The proposed operational criteria may be useful in identifying those patients who require care in headache units, the selection of candidates for combinations of prophylactic drugs or invasive treatments such as neurostimulation, but also to facilitate clinical studies in this patient group.
Preemptive Plasmapheresis and Recurrence of FSGS in High‐Risk Renal Transplant Recipients (2005)

Recurrent focal segmental glomerulosclerosis (FSGS) following transplantation is ascribed to the presence of a circulating FSGS permeability factor (FSPF). Plasmapheresis (PP) can induce remission of proteinuria in recurrent FSGS. This study addressed the efficacy of pre-transplant PP in decreasing the incidence of recurrence in high-risk patients. Ten patients at high-risk for FSGS recurrence because of rapid progression to renal failure (n = 4) or prior transplant recurrence of FSGS (n = 6) underwent a course of 8 PP treatments in the peri-operative period. Recurrences were identified by proteinuria >3 g/day and confirmed by biopsy. Seven patients, including all 4 with first grafts and 3 of 6 with prior recurrence, were free of recurrence at follow-up (238-1258 days). Final serum creatinine in 8 patients with functioning kidneys averaged 1.53 mg/dL. FSGS recurred within 3 months in 3 patients, each of whom had lost prior transplants to recurrent FSGS. Two of these progressed to end-stage renal disease (ESRD) and the third has significant renal dysfunction. Based on inclusion criteria, recurrence rates of 60% were expected if no treatment was given. Therefore, PP may decrease the incidence of recurrent FSGS in high-risk patients. Definitive conclusions regarding optimal management can only be drawn from larger, randomized, controlled studies.
Eicosapentaenoic acid and docosahexaenoic acid from fish oils: differential associations with lipid responses (2002)

Fish-oil supplementation can reduce circulating triacylglycerol (TG) levels and cardiovascular risk. This study aimed to assess independent associations between changes in platelet eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) and fasting and postprandial (PP) lipoprotein concentrations and LDL oxidation status, following fish-oil intervention. Fifty-five mildly hypertriacylglycerolaemic (TG 1.5-4.0 mmol/l) men completed a double-blind placebo controlled cross over study, where individuals consumed 6 g fish oil (3 g EPA+DHA) or 6 g olive oil (placebo)/d for two 6-week intervention periods, with a 12-week wash-out period in between. Fish-oil intervention resulted in a significant increase in the platelet phospholipid EPA (+491 %, P<0.001) and DHA (+44 %, P<0.001) content and a significant decrease in the arachidonic acid (-10 %, P<0.001) and gamma-linolenic acid (-24 %, P<0.001) levels. A 30 % increase in ex vivo LDL oxidation (P<0.001) was observed. In addition, fish oil resulted in a significant decrease in fasting and PP TG levels (P<0.001), PP non-esterified fatty acid (NEFA) levels, and in the percentage LDL as LDL-3 (P=0.040), and an increase in LDL-cholesterol (P=0.027). In multivariate analysis, changes in platelet phospholipid DHA emerged as being independently associated with the rise in LDL-cholesterol, accounting for 16 % of the variability in this outcome measure (P=0.030). In contrast, increases in platelet EPA were independently associated with the reductions in fasting (P=0.046) and PP TG (P=0.023), and PP NEFA (P=0.015), explaining 15-20 % and 25 % of the variability in response respectively. Increases in platelet EPA+DHA were independently and positively associated with the increase in LDL oxidation (P=0.011). EPA and DHA may have differential effects on plasma lipids in mildly hypertriacylglycerolaemic men.
Survival of Allogeneic Porcine Retinal Pigment Epithelial Sheets after Subretinal Transplantation (2004)

Allogeneic RPE grafts survive in the subretinal space up to 3 months after surgery, and the choriocapillaris remains patent in the transplant bed, although there are many heavily pigmented cells within the transplant bed that are Barr body negative by 3 months. Further work is needed to produce uniform repopulation of a sizable portion of Bruch's membrane with a monolayer of transplanted RPE.
Binding of herpes simplex virus to cellular heparan sulphate, an initial step in the adsorption process (1991)

It has been suggested that heparan sulphate has a receptor function in the initial phase of the attachment of herpes simplex virus (HSV) to cells. We have studied the influence of glycosaminoglycans on cell adsorption of, and plaque formation by, HSV-1 and HSV-2, with regard to the role of saccharide structure, chain length and charge density. Heparin and highly-sulphated heparan sulphate (1.5 sulphate groups/disaccharide unit), but neither chondroitin sulphate nor dermatan sulphate, were found to compete with the cellular receptor for attachment of HSV. Heparan sulphate preparations of low sulphate content (0.5 and 0.7 sulphate groups/disaccharide unit) failed to show any significant interaction with HSV. Oligosaccharides generated by partial deaminative cleavage of heparin were used to determine the minimum molecular size required for the binding of virus; the smallest oligosaccharide which reacted with HSV was composed of 10 monosaccharide units. The importance of charge density was demonstrated more directly by subfractionation of the heparin dodecasaccharide fraction by anion-exchange HPLC. The virus-binding capacities of the four resulting dodecasaccharide subfractions increased from the least sulphated to the most heavily sulphated fraction. The results reported are discussed in relation to virus-receptor interactions involved in the attachment of HSV, including the reported binding of HSV to the fibroblast growth factor receptor.
Differential CD4+versus CD8+T-Cell Responses Elicited by Different Poxvirus-Based Human Immunodeficiency Virus Type 1 Vaccine Candidates Provide Comparable Efficacies in Primates (2008)

Poxvirus vectors have proven to be highly effective for boosting immune responses in diverse vaccine settings. Recent reports reveal marked differences in the gene expression of human dendritic cells infected with two leading poxvirus-based human immunodeficiency virus (HIV) vaccine candidates, New York vaccinia virus (NYVAC) and modified vaccinia virus Ankara (MVA). To understand how complex genomic changes in these two vaccine vectors translate into antigen-specific systemic immune responses, we undertook a head-to-head vaccine immunogenicity and efficacy study in the pathogenic HIV type 1 (HIV-1) model of AIDS in Indian rhesus macaques. Differences in the immune responses in outbred animals were not distinguished by enzyme-linked immunospot assays, but differences were distinguished by multiparameter fluorescence-activated cell sorter analysis, revealing a difference between the number of animals with both CD4(+) and CD8(+) T-cell responses to vaccine inserts (MVA) and those that elicit a dominant CD4(+) T-cell response (NYVAC). Remarkably, vector-induced differences in CD4(+)/CD8(+) T-cell immune responses persisted for more than a year after challenge and even accompanied antigenic modulation throughout the control of chronic infection. Importantly, strong preexposure HIV-1/simian immunodeficiency virus-specific CD4(+) T-cell responses did not prove deleterious with respect to accelerated disease progression. In contrast, in this setting, animals with strong vaccine-induced polyfunctional CD4(+) T-cell responses showed efficacies similar to those with stronger CD8(+) T-cell responses.
ChemInform Abstract: METABOLITES OF MICROORGANISMS. PART 193. FERRITHIOCIN (1980)

Abstract Aus Extrakten des Stammes Tü 1998 von Streptomyces antibioticus wurde neben den Antibiotica β‐ und 7‐Rubromycin ein neuer Metabolit isoliert und Ferrithiocin genannt.
2002 Podiatric Practice Survey (2003)

This report presents the results of analyses of statistical data from 2,955 members of the American Podiatric Medical Association who responded to the 2002 Podiatric Practice Survey, conducted in April through May 2002.
NOTE ON THE EXPERIMENTAL USE OF RABIES VACCINE FOR MELANOMATOSIS (1950)

In May 1940 a 32 year old woman with a malignant melanoma 3 cm. in diameter and situated in the pretibial region had the lesion surgically excised on the mixed tumor service of the Memorial Hospital. An elective groin dissection six weeks later revealed no deposits of metastatic melanoma in regional nodes. In September 1942 three cutaneous melanotic nodules were excised from the same leg and thigh. In September 1943, after a dog bite, the patient received 14 injections of rabies vaccine. In April 1948 two additional melanotic nodules were removed from the skin on the ipsolateral side. At this writing, two years later, there had been no further evidence of recurrence. The long latent period of 5½ years intervening between the appearance of multiple metastases was so extraordinarily unusual that it excited considerable speculation among various members of the clinic staff concerning the cause of this inhibition. In a
HIV Gag protein conjugated to a Toll-like receptor 7/8 agonist improves the magnitude and quality of Th1 and CD8+T cell responses in nonhuman primates (2005)

Induction and maintenance of antibody and T cell responses will be critical for developing a successful vaccine against HIV. A rational approach for generating such responses is to design vaccines or adjuvants that have the capacity to activate specific antigen-presenting cells. In this regard, dendritic cells (DCs) are the most potent antigen-presenting cells for generating primary T cell responses. Here, we report that Toll-like receptor (TLR) agonists and ligands that activate DCs in vitro influence the magnitude and quality of the cellular immune response in nonhuman primates (NHPs) when administered with HIV Gag protein. NHPs immunized with HIV Gag protein and a TLR7/8 agonist or a TLR9 ligand [CpG oligodeoxynucleotides (CpG ODN)] had significantly increased Gag-specific T helper 1 and antibody responses, compared with animals immunized with HIV Gag protein alone. Importantly, conjugating the HIV Gag protein to the TLR7/8 agonist (Gag-TLR7/8 conjugate) dramatically enhanced the magnitude and altered the quality of the T helper 1 response, compared with animals immunized with HIV Gag protein and the TLR7/8 agonist or CpG ODN. Furthermore, immunization with the Gag-TLR7/8 conjugate vaccine elicited Gag-specific CD8+ T responses. Collectively, our results show that conjugating HIV Gag protein to a TLR7/8 agonist is an effective way to elicit broad-based adaptive immunity in NHPs. This type of vaccine formulation should have utility in preventive or therapeutic vaccines in which humoral and cellular immunity is required.
No evidence for allelic association between bipolar disorder and monoamine oxidase a gene polymorphisms (1995)

We have tested the hypothesis that DNA markers in the MAOA gene show allelic association with bipolar affective disorder. Eighty-four unrelated Caucasian patients with DSM III-R bipolar disorder and 84 Caucasian controls were typed for three markers in MAOA: a dinucleotide repeat in intron 2, a VNTR in intron 1, and an Fnu4HI RFLP in exon 8. No evidence for allelic association was observed between any of the markers and bipolar disorder.