gebhart/patrepeval huggingface dataset:
Increasing vitamin C content of plants through enhanced ascorbate recycling (2003)

Vitamin C (ascorbic acid) is essential to prevent disease associated with connective tissue (e.g., scurvy), improves cardiovascular and immune cell functions, and is used to regenerate alpha-tocopherol (vitamin E). In contrast to most animals, humans lack the ability to synthesize ascorbic acid as a result of a mutation in the last enzyme required for ascorbate biosynthesis. Vitamin C, therefore, must be obtained from dietary sources and, because it cannot be stored in the body, it must be obtained regularly. Once used, ascorbic acid can be regenerated from its oxidized form in a reaction catalyzed by dehydroascorbate reductase (DHAR). To examine whether overexpression of DHAR in plants would increase the level of ascorbic acid through improved ascorbate recycling, a DHAR cDNA from wheat was isolated and expressed in tobacco and maize, where DHAR expression was increased up to 32- and 100-fold, respectively. The increase in DHAR expression increased foliar and kernel ascorbic acid levels 2- to 4-fold and significantly increased the ascorbate redox state in both tobacco and maize. In addition, the level of glutathione, the reductant used by DHAR, also increased, as did its redox state. These results demonstrate that the vitamin C content of plants can be elevated by increasing expression of the enzyme responsible for recycling ascorbate.
Exploring the Use of Human Pluripotent Stem Cells to Create Functional Pancreatic \(\beta\) Cells (2013)

Directed differentiation of human pluripotent stem cells (hPSCs) has the potential to produce human cell types that can be used for disease modeling and cell transplantation. Two key challenges in the differentiation from hPSCs to \\(\\beta\\) cells are the specification from pancreatic progenitors to insulin-expressing \\((INS^+\n)\\) cells and the maturation of \\(INS^+\\) cells into glucose responsive β cells. To address the first, two high-content chemical screens identified PKC inhibitors as inducers of \\(INS^+\\) cells from pancreatic progenitors. PKC inhibition generated up to tenfold more \\(INS^+\\) cells while PKC agonists blocked differentiation into \\(INS^+\\) cells. Transplantation of \\(PKC\\beta\\) inhibitor-treated pancreatic progenitors, containing higher \nproportions of endocrine progenitors and endocrine cells, resulted in mature \\(\\beta\\) cells showing higher levels of glucose-stimulated human c-peptide production in vivo. This indicates that in vitro derived \\(INS^+\\)\ncells might be competent to mature into functional \\(\\beta\\) cells. To address the second challenge, we first studied mouse and human \\(\\beta\\) cell maturation in vivo. Postnatal mouse \\(\\beta\\) cell maturation was marked by an increase in the glucose threshold for insulin secretion and by expression of the gene urocortin 3. To study human \\(\\beta\\) cell maturation, a Method for Analyzing RNA following Intracellular Sorting (MARIS) was developed and used for transcriptional profiling of sorted human fetal and adult \\(\\beta\\) cells. Surprisingly, transcriptional differences between human fetal and adult \\(\\beta\\) cells did not resemble differences between mouse fetal and adult \\(\\beta\\) cells, calling into question inter-species homology at the late stages of development. A direct comparison between hPSC-derived \\(INS^+\\) cells, and \\(\\beta\\) cells produced during human development is essential to validate directed differentiation and provide a roadmap for maturation of hPSC-derived \\(INS^+\\) cells. Genome-wide transcriptional analysis of sorted \\(INS^+\\) cells derived from three hPSC-lines suggest that different lines produce highly similar \\(INS^+\\) cells, confirming robustness of directed differentiation protocols. Furthermore, nonfunctional hPSC-derived \\(INS^+\\) cells resemble human fetal \\(\\beta\\) cells, which are distinct from adult \\(\\beta\\) cells. We therefore suggest that in vitro directed differentiation mimics normal human development and reveal differences in gene expression that may account for the functional differences between hPSC-derived \\(INS^+\\) cells and true \\(\\beta\\) cells.
Toxicity and Efficacy of Defined Doses of CD4+ Donor Lymphocytes for Treatment of Relapse After Allogeneic Bone Marrow Transplant (1998)

Donor lymphocyte infusions (DLI) can induce remissions in patients who have relapsed after allogeneic bone marrow transplantation (BMT). However, DLI frequently also result in significant acute and/or chronic graft-versus-host disease (GVHD). Several clinical and experimental lines of evidence have suggested that CD8+ T cells play a critical role in the pathogenesis of GVHD. To develop methods to reduce the incidence of GVHD associated with DLI, we administered defined numbers of CD4+ donor T cells after ex vivo depletion of CD8+ lymphocytes to 40 patients with relapsed hematologic malignancies after allogeneic BMT. Cohorts of patients received 0.3, 1.0, or 1.5 × 108CD4+ cells/kg. Overall, 12 of 38 patients (32%) evaluable for toxicity developed acute or chronic GVHD. However, 6 of 27 patients (22%) receiving 0.3 × 108 CD4 cells/kg developed GVHD compared with 6 of 11 patients (55%) who received ≥1.0 × 108 CD4 cells/kg (P = .07). Treatment-related mortality was low (3%), with 1 death related to infection in the setting of immunosuppression for GVHD. Disease responses after CD4+ DLI were documented in 15 of 19 patients (79%) with early-phase chronic myelogenous leukemia (CML) relapse, 5 of 6 patients (83%) with relapsed multiple myeloma, and 1 patient with myelodysplasia. For patients with early-phase CML relapse, the Kaplan-Meier probability of achieving complete cytogenetic remission was 87% and the probability of complete molecular response was 78% at 1 year after DLI. The median time to complete cytogenetic response and molecular response in patients with CML was 13 weeks (range, 9 to 30 weeks) and 34 weeks (range, 10 to 56 weeks), respectively. The median time to response in patients with multiple myeloma was 26 weeks (range, 15 to 62 weeks). All patients in this trial who developed GVHD demonstrated tumor regression, but the presence of GVHD was not required for patients to achieve a response, because 48% of responding patients never developed evidence of GVHD. Two patients with CML who did not respond at dose level 1 subsequently achieved complete cytogenetic remission after a second infusion of CD8-depleted cells at dose level 2. In patients with evidence of mixed hematopoietic chimerism who achieved a complete remission after DLI, cytogenetic analysis of marrow cells also demonstrated conversion to complete donor hematopoiesis in all evaluable patients. These studies suggest that relatively low numbers of CD8-depleted donor lymphocytes are effective in inducing complete remissions in patients with stable-phase CML and multiple myeloma who have relapsed after allogeneic BMT. Because of the relatively low risk of toxicity associated with the infusion of defined numbers of CD4+donor cells, further studies can be undertaken in the setting of persistent minimal residual disease to prevent relapse after allogeneic BMT.
Relationship between RGS5 expression and differentiation and angiogenesis of gastric carcinoma (2010)

RGS5 expression level in gastric carcinoma is associated with the differentiation and MVD of the tumor, and may be used as an important parameter for determining the prognosis of gastric carcinoma patients.
Docetaxel in non-small cell lung cancer: a review (2003)

Docetaxel (Taxotere, Aventis Pharma), a semisynthetic taxane targeting the beta-subunit of tubulin, has broad spectrum anticancer activity including non-small cell lung cancer (NSCLC). It is synergistic with platinum and radiation in preclinical models and has been tested clinically in every stage of NSCLC. Docetaxel-platinum combinations have an efficacy comparable to other newer-agent platinum doublets as first-line therapy in advanced NSCLC, and has been approved for use in this setting. Docetaxel was initially approved for NSCLC in the second-line setting following two Phase III trials demonstrating improved survival and quality of life. Ongoing clinical trials are investigating how best to combine docetaxel with thoracic radiotherapy in locally advanced disease. Preliminary studies evaluating docetaxel in the pre-operative setting have also been completed. Ongoing studies are focused on confirming the results observed with consolidation docetaxel in locally advanced NSCLC (SWOG 9504) and docetaxel in combination with molecularly targeted agents. This paper will review the pharmacology, preclinical, clinical and pharmacoeconomic data supporting the use of docetaxel in the treatment NSCLC.
Experimental Study on Sprayed FRP System for Strengthening Reinforced Concrete Beams (2012)

The purpose of this study is to develop a new technique for strengthening and repairing existing concrete structures with sprayed fiber-reinforced polymers (FRP) by mixing chopped carbon or glass fibers with epoxy or vinyl ester resins in open air and randomly spraying the mixture onto the concrete surface with compressed air. The use of sprayed FRP for repair and strengthening purposes using epoxy or vinyl ester resins has never been fully investigated. In this study, tensile testing was conducted on material specimens to determine the optimum length of chopped carbon or glass fibers and the mixture ratio of fiber, epoxy, and vinyl ester resin for sprayed FRP. These variables were adjusted to produce a material strength equivalent to that of one FRP sheet. The optimal length of glass and carbon chopped fibers was determined to be 38 mm, and the optimal mixture ratio of chopped fiber to resin was found to be 1:2. The thickness of sprayed FRP required to provide the same strengthening effect as one FRP sheet was also calculated. During this study, experiments were conducted to evaluate the strengthening/repair effects of the sprayed FRP on flexural beams, shear beams, and damaged beams. The results showed that the strengthening effect of sprayed FRP on the flexural and shear specimens was similar to those of one FRP sheet. The maximum strength of the damaged beams reinforced by sprayed FRP was approximately the same as that of the reinforced flexural and shear beams. Moreover, existing design equations for FRP sheets were found to be applicable to flexural beams reinforced with sprayed FRP. The shear beam specimens could be safely designed using the coefficient of shear strength reduction α= 0.18, determined to result in computed values that most closely approximate the experimental values. Overall, the sprayed FRP technique was found to be suitable for strengthening existing reinforced concrete buildings.
Induced Foxp3+ regulatory T cells: a potential new weapon to treat autoimmune and inflammatory diseases? (2011)

Foxp3(+) T regulatory cells (Tregs) consisting of natural and induced Treg subsets play a crucial role in the maintenance of immune homeostasis against self-antigen. The actions designed to correct defects in numbers or functions of Tregs may be therapeutic in the treatment of autoimmune diseases. While recent studies demonstrated that natural Tregs are instable and dysfunctional in the inflammatory condition, induced Tregs (iTregs) may have a different feature. Here we review the progress of iTregs, particularly focus on their stability and function in the established autoimmune diseases. The advantage of iTregs as therapeutics used under inflammatory conditions is highlighted. Proper generation and manipulation of iTregs used for cellular therapy may provide a promise for the treatment of many autoimmune and inflammatory diseases.
Molecular characterization of hpuAB, the haemoglobin–haptoglobin‐utilization operon of Neisseria meningitidis (1997)

We previously identified HpuB, an 85 kDa Fe-repressible protein required for utilization of Fe from, and binding to, haemoglobin and the haemoglobin-haptoglobin complex. The gene for hpuB was cloned from Neisseria meningitidis strain DNM2 and the predicted amino acid sequence indicates that HpuB is an outer membrane receptor belonging to the TonB family of high-affinity transport proteins. A second open reading frame, predicted to encode a 34.8 kDa lipoprotein, was discovered 5' to hpuB, and was designated hpuA. HpuA was identified in a total-membrane-protein preparation by construction of a mutant lacking HpuA. Acylation of HpuA was confirmed by [3H]-palmitic acid labelling of meningococci. Consensus promoter sequences were not apparent 5' to hpuB. The hpuA insertion mutation exerted a polar effect, abolishing expression of hpuB, suggesting that hpuA and hpuB are co-transcribed. The 3.5 kb polycistronic hpuAB mRNA was identified and shown to be transcriptionally repressed by iron. The transcriptional start site was identified 33 nucleotides 5' to the hpuA translational start site, appropriately positioned around consensus promoter and ferric uptake regulator (Fur)-box sequences. The structure of this operon suggests that HpuA-HpuB is a two-component receptor analogous to the bipartite transferrin receptor TbpB-TbpA.
Development of an anti-adhesive vaccine for Pseudomonas aeruginosa targeting the C-terminal region of the pilin structural protein. (1995)

This study describes the development of passive and active vaccines directed at the Pseudomonas aeruginosa pilus adhesin. Passive immunization studies were carried out with P. aeruginosa strain K pilus-specific (PK3B, PK99H) and cross-reactive (PAK-13) monoclonal antibodies (MAbs). When A.BY/SnJ mice were passively immunized with a pilus-specific MAb (PK99H), which inhibited pilus-mediated adherence to respiratory epithelial cells, mice challenged with 5 x LD 50 of P. aeruginosa were completely protected while mice were not protected when animals were passively immunized with a pilus specific MAb (PK3B), which did not inhibit pilus adherence to epithilial cells. MAb PAK-13 was found to cross-react with the C-terminal portion of pili of different strains of P. aeruginosa. When mice were passively immunized with MAb PAK-13, subsequent challenge with KB7 (3 x LD50), PAO (8 x LD50) and PAK (3 x LD50) strains of P. aeruginosa resulted in a 70%, 60% and 90% protection of the mice, respectively. MAb PK99H has been previously shown to recognize a linear antigenic epitope consisting of the sequence DEQFIPK. This epitopic peptide was conjugated to protein carriers using different coupling strategies. Use of an appropriate adjuvant and the correct conjugation strategy were critical for raising high affinity antipeptide antisera. In a comparison of Freund's, alum, and Adjuvax, as adjuvants for a peptide-tetanus toxoid conjugate vaccine, highest titers for the synthetic peptide component of the conjugate were obtained with Adjuvax, while highest titers for the carrier protein components were obtained with Freund's. Of the four peptide-conjugates used in this study, only the C-terminal conjugated peptide failed to produce antibodies that bind to native antigen and did not protect mice in active immunization experiments (no survivors at 80 h in the mouse infection model). Conformationally restricted peptide conjugates in which the peptide was conjugated to the carrier at both ends provided better protection in mice challenged with lethal doses of P. aeruginosa than either N- or C-terminal linked peptide-conjugates. The pilus adhesin plays a critical role in P. aeruginosa pathogenesis and this is an excellent vaccine target for either active or passive immunization strategies.
Telemedicine and Distributed Medical Intelligence (1996)

Recent trends in health care informatics and telemedicine indicate that systems are being developed with a primary focus on technology and business, not on the process of medicine itself. The authors present a new model of health care information, distributed medical intelligence, which promotes the development of an integrative medical communication system addressing the process of providing expert medical knowledge to the point of need. The model incorporates audio, video, high-resolution still images, and virtual reality applications into an integrated medical communications network. Three components of the model (care portals, Docking Station, and the bridge) are described. The implementation of this model at the East Carolina University School of Medicine is also outlined.
A multi-analyte serum test for the detection of non-small cell lung cancer (2010)

Here, we report the development of a serum algorithm with high specificity for classifying patients with NSCLC against cohorts of various 'high-risk' individuals. A high rate of false positives was observed within the cohort in which patients had non-neoplastic lung nodules, possibly as a consequence of the inflammatory nature of these conditions.
Early-onset ataxia with ocular motor apraxia and hypoalbuminemia (2002)

We found clinical heterogeneity in the patients with EAOH in this study. With the disease course, the choreiform movements tended to reduce in degree, and hypoalbuminemia became evident. Molecular analysis identified one insertion and two missense mutations including a novel missense one, which was located at a highly conserved amino acid residue in the aprataxin gene product.
Selective secretion of chemoattractants for haemopoietic progenitor cells by bone marrow endothelial cells: a possible role in homing of haemopoietic progenitor cells to bone marrow (1999)

To elucidate the mechanisms by which haemopoietic progenitor cells lodge in the bone marrow, we examined the secretion of chemoattractants for haemopoietic progenitor cells by bone marrow and lung endothelial cells. The bone marrow endothelial cells, but not lung endothelial cells, secreted chemoattractants for the haemopoietic progenitor cell line, FDCP-2, and normal haemopoietic progenitor cells. Checkerboard analysis demonstrated that the conditioned medium of the bone marrow endothelial cells had chemotactic activity and random motility-stimulating activity. The bone marrow endothelial cells expressed stromal-cell-derived factor-1 (SDF-1) mRNA and produced SDF-1 protein, whereas the lung endothelial cells did not. Adhesion of FDCP-2 cells to the bone marrow endothelial cells was partially inhibited by anti-SDF-1 antibody. These findings suggest that the chemoattractants for haemopoietic progenitor cells including SDF-1 and random motility-stimulating factor(s) selectively secreted by the bone marrow endothelial cells may contribute to the homing of haemopoietic progenitor cells to bone marrow.
Internal radiation therapy for patients with primary or metastatic hepatic cancer (1998)

The different approaches to internal radiation therapy that are reviewed in this article represent several ways in which radiation can be selectively targeted to hepatic tumors without undue radiation to the nontumorous liver. However, the efficacy of each of these therapies still needs to be evaluated in randomized controlled trials.
Real-Time Multi-Spectral Image Processing For Mapping Pigmentation In Human Skin (2001)

Real-time mapping pigmentation in human skin is expected to give useful information for reproducing various skin colors and monitoring human conditions in real time. In this research, the maps of melanin, oxy-hemoglobin and deoxy-hemoglobin densities in skin are estimated and displayed in real time from digital video signals by using three precomputed look up tables for color conversions. As the experiments to show the effectiveness of the proposed system, time dependent changes of pigmentation map in human hand are observed during the occlusion and release of middle finger, also during anaerobic by squat exercise. From the results of the experiments, human homeostasis for disturbance can be observed in real time.
Maturation of early endosomes and vesicular traffic to lysosomes in relation to membrane recycling (1995)

The controversy whether endocytic processing occurs by organellar maturation or by vesicular traffic has not been resolved. It is also not clear whether maturation continues to the stage of lysosomes, to what extent it involves a decrease in organellar fusogenicity, and how it relates to membrane recycling. Maturation and vesicular traffic imply distinct kinetics for the intermingling of endocytic markers after sequential endocytic uptake. We have studied the kinetics of intermingling of fluid-phase markers (fluorescein-labelled dextran and horseradish peroxidase) and cell surface-derived membrane (labelled by galactosylation) in organelles at early and late stages of the endocytic pathway in macrophage-like P388D1 cells. Intermingling declined by sigmoid kinetics, indicating that endosomes matured within about 3 minutes to become non-fusogenic towards early endosomes. During maturation about 60% of internalized membrane was recycled with T1/2 approximately 2 minutes. Whereas matured endosomes were non-fusogenic towards early endosomes and towards each other, a second phase of intermingling was observed upon delivery to lysosomes. This intermingling occurred by a first-order process (T1/2 approximately 4 minutes), concurrent with recycling of the remaining 40% of internalized membrane marker. These kinetic observations suggest a model for endocytic processing which reconciles maturation of early endosomes with the known function of carrier vesicles: Endocytic carrier vesicles do not bud off from permanent early endosomes as proposed for vesicular traffic, but are derived, together with recycling vesicles, from the maturation of early endosomes which are consumed by this process; these carrier vesicles subsequently mediate delivery to lysosomes by vesicular traffic during which the remaining surface-derived membrane is recycled.
Signal Transduction from the Extracellular Matrix. A Role for the Focal Adhesion Protein-tyrosine Kinase FAK. (1996)

The proliferation and differentiation of cells in higher organisms requires specific external signals. These can
Mechlorethamine, vincristine, and procarbazine chemotherapy for recurrent high-grade glioma in adults: a phase II study. (1990)

We undertook a phase II study of combination chemotherapy with mechlorethamine (nitrogen mustard) 6 mg/m2 intravenously day 1 and day 8, vincristine 2 mg intravenously day 1 and day 8, and procarbazine 100 mg/m2 orally days 1 through 14 (MOP) in adults with recurrent high-grade glioma. There were 31 patients entered and 27 patients assessable for response. The median age was 49 years old. All patients had prior maximal radiotherapy, and eight had previous chemotherapy. Responses were determined based on clinical and computed tomographic (CT) scan/magnetic resonance imaging (MRI) criteria. The response rate (partial response [PR] plus objective qualitative response [OQR] plus complete response [CR]) was 52% with one CR. The response rate was higher in patients with anaplastic astrocytoma as compared with glioblastoma multiforme (P less than .05). The median duration of response was 42 weeks. Median survival for all assessable patients was 30 weeks, and for responders, it was 60 weeks. Response was correlated with ability to decrease dexamethasone doses and improved performance status. Toxicity was mainly hematologic with leukopenia being common. There was one treatment-related death from listeria meningitis, and two patients developed Pneumocystis carinii pneumonia. There were three episodes of neutropenic fever. We conclude that MOP is active and merits further investigation in adult high-grade glioma.