gebhart/patrepeval huggingface dataset:
Adenovirus-Mediated Herpes Simplex Virus Thymidine Kinase/Ganciclovir Gene Therapy in Patients with Localized Malignancy: Results of a Phase I Clinical Trial in Malignant Mesothelioma (1998)

Malignant pleural mesothelioma is a fatal neoplasm that is unresponsive to standard modalities of cancer therapy. We conducted a phase I dose-escalation clinical trial of adenoviral (Ad)-mediated intrapleural herpes simplex virus thymidine kinase (HSVtk)/ganciclovir (GCV) gene therapy in patients with mesothelioma as a model for treatment of a localized malignancy. The goals of this phase I trial were to assess the safety, toxicity, and maximally tolerated dose of intrapleural Ad.HSVtk, to examine patient inflammatory response to the viral vector, and to evaluate the efficiency of intratumoral gene transfer. Twenty-one previously untreated patients were enrolled in this single-arm, dose-escalation study with viral doses ranging from 1 x 10(9) plaque-forming units (pfu) to 1 x 10(12) pfu. A replication-incompetent recombinant adenoviral vector containing the HSVtk gene under control of the Rous sarcoma virus (RSV) promoter-enhancer was introduced into the pleural cavity of patients with malignant mesothelioma followed by 2 weeks of systemic therapy with GCV at a dose of 5 mg/kg twice a day. The initial 15 patients underwent thoracoscopic pleural biopsy prior to, and 3 days after, vector delivery. The last six patients underwent only the post-vector instillation biopsy. Dose-limiting toxicity was not reached. Side effects were minimal and included fever, anemia, transient liver enzyme elevations, and bullous skin eruptions, as well as a temporary systemic inflammatory response in those receiving the highest dose. Strong intrapleural and intratumoral immune responses were generated. Using RNA PCR, in situ hybridization, immunohistochemistry, and immunoblotting, HSVtk gene transfer was documented in 11 of 20 evaluable patients in a dose-related fashion. This study demonstrates that intrapleural administration of an adenoviral vector containing the HSVtk gene is well tolerated and results in detectable gene transfer when delivered at high doses. Further development of therapeutic trials for treatment of localized malignancy using this vector is thus warranted.
Therapeutic Alternatives for Subacute Peripheral Arterial Occlusion Comparison by Outcome, Length of Stay, and Hospital Charges (1991)

Thrombolytic therapy using streptokinase or urokinase has been shown to be a viable alternative to surgical thrombectomy in patients with subacute peripheral arterial occlusion. Urokinase is associated with higher success and lower complication rates than streptokinase, but the cost of urokinase is at least seven times higher. To address questions of utility and effectiveness in the treatment of subacute peripheral arterial occlusions, the authors designed a retrospective study of patients treated either by surgical thrombectomy (n = 70), thrombolysis with streptokinase (n = 19), or thrombolysis with urokinase (n = 22). Outcome of therapy, length of hospital stay, and total hospital charges in the three groups were examined. Treatment successes in the three groups, defined as complete clearing of the occluded segment with patency maintained for 60 days, were 76% for thrombectomy, 32% for streptokinase, and 64% for urokinase. Total duration of hospitalization was 21.1, 21.3, and 11.5 days (P less than .05), respectively. Mean charges for thrombolytic agents were $690 for streptokinase and $6429 for urokinase. Mean total hospital charges, however, were $25,978 for streptokinase, $22,203 for urokinase, and $25,336 for thrombectomy (P = NS). The higher cost of urokinase, then, accounted for the similar total charges, despite the shortened length of stay. These results suggest that urokinase is cost-effective compared to streptokinase for subacute peripheral arterial occlusion. Compared to thrombectomy, thrombolysis with urokinase has a marginally lower patency rate at 60 days, but a significantly shorter length of hospital stay.
Phylogenetic Divergence of CD47 Interactions with Human Signal Regulatory Protein α Reveals Locus of Species Specificity (2006)

Cell-cell interactions between ubiquitously expressed integrin-associated protein (CD47) and its counterreceptor signal regulatory protein (SIRPalpha) on phagocytes regulate a wide range of adhesive signaling processes, including the inhibition of phagocytosis as documented in mice. We show that CD47-SIRPalpha binding interactions are different between mice and humans, and we exploit phylogenetic divergence to identify the species-specific binding locus on the immunoglobulin domain of human CD47. All of the studies are conducted in the physiological context of membrane protein display on Chinese hamster ovary (CHO) cells. Novel quantitative flow cytometry analyses with CD47-green fluorescent protein and soluble human SIRPalpha as a probe show that neither human CD47 nor SIRPalpha requires glycosylation for interaction. Human CD47-expressing CHO cells spread rapidly on SIRPalpha-coated glass surfaces, correlating well with the spreading of primary human T cells. In contrast, CHO cells expressing mouse CD47 spread minimally and show equally weak binding to soluble human SIRPalpha. Further phylogenetic analyses and multisite substitutions of the CD47 Ig domain show that human to cow mutation of a cluster of seven residues on adjacent strands near the middle of the domain decreases the association constant for human SIRPalpha to about one-third that of human CD47. Direct tests of cell-cell adhesion between human monocytes and CD47-displaying CHO cells affirm the species specificity as well as the importance of the newly identified binding locus in cell-cell interactions.
UV polymerization of hydrodynamically shaped fibers (2011)

Most natural and man-made fibers have circular cross-sections; thus the properties of materials composed of non-circular fibers are largely unexplored. We demonstrate the technology for fabricating fibers with predetermined cross-sectional shape. Passive hydrodynamic focusing and UV polymerization of a shaped acrylate stream produced metre-long fibers for structural and mechanical characterization.
Lack of lymphangiogenesis in human primary cutaneous melanoma. Consequences for the mechanism of lymphatic dissemination. (1997)

Cutaneous melanoma has an initial preference for lymphatic spread. Remarkably, melanoma progression toward this metastasizing phenotype is accompanied by intense blood vessel angiogenesis (hemangiogenesis), but lymphangiogenesis, the formation of new lymph vessels in the tumor, has never been reported. To investigate how primary melanoma cells interact with the existing lymphatic microvasculature, and whether lymphangiogenesis occurs, an immunostaining was developed that differentially decorates blood and lymph vessels in frozen tissue sections. The density and distribution of both these vessel types in and around thin (< or = 1.5 mm) and thick (> or = 1.5 mm) primary melanoma lesions and in normal and uninvolved skin were determined. Although especially in thick melanoma lesions a significant increase in blood vessel density was observed, lymphatic density remained unaltered, showing that lymphangiogenesis did not occur. Morphological analysis indicated, however, that melanoma progression is accompanied by a sequence of events that involves hemangiogenesis supporting tumor expansion, especially in the vertical growth phase. Often, stromal sepia are formed around the blood capillaries in the tumor neovasculature protecting them from invasion. Lymph vessels inside the tumor were infrequently observed. However, subepidermal lymph vessels often seemed to be entrapped and penetrated by the expanding tumor mass. In this way, hemangiogenesis, as the driving force behind tumor expansion, might indirectly increase the chance of lymphatic invasion in the absence of lymphangiogenesis. This model explains the paradox that, although melanoma metastasis seems to require angiogenesis, a consistent relation of prognosis with blood capillary density in primary cutaneous melanoma is lacking.
5-Azacytidine Selectively Increases γ-Globin Synthesis in a Patient with β+Thalassemia (1982)

5-Azacytidine is a cytidine analogue that is capable of activating repressed genes in tissue-culture cells and has been shown to increase hemoglobin-F production in anemic baboons. This drug was administered to a patient with severe beta-thalassemia in an attempt to stimulate hemoglobin-F production. After seven days of 5-azacytidine treatment, gamma-globin synthesis increased approximately sevenfold, temporarily normalizing the patient's unbalanced globin synthesis. Erythropoiesis became more effective, leading to a temporary increase in the absolute reticulocyte count (from 5000 to 22,000 per cubic millimeter) and in hemoglobin concentration (from 8.0 to 10.8 g per deciliter). Hypomethylation of bone-marrow DNA near both the gamma-globin and epsilon-globin genes was directly demonstrated. At the time of peak drug effect, about 7000 gamma-globin messenger RNA molecules were present per erythroid bone-marrow cell, in contrast to 10 to 15 epsilon-globin messenger RNA molecules per cell. 5-Azacytidine selectivity increases gamma-globin synthesis and therefore provides a new approach to the treatment of severe beta-thalassemia. Further studies will be required to evaluate the efficacy, risks, and long-term toxicity of 5-azacytidine (or related compounds) before this approach can be used as a therapy for patients with disorders of hemoglobin synthesis.
The role of cytokines in rheumatoid arthritis. The Croonian Lecture 1995. (1997)

Des recherches ont montre la relation entre l'arthrite rhumatoide et les genes du systene HLA, ainsi que le role des interleukines 1 et 6 et du facteur necrose tumorale alpha dans le developpement de la maladie
Competitive routing in multiuser communication networks (1993)

The authors consider a communication network shared by several selfish users. Each user seeks to optimize its own performance by controlling the routing of its given flow demand, giving rise to a noncooperative game. They investigate the Nash equilibrium of such systems. For a two-node multiple links system, uniqueness of the Nash equilibrium is proven under reasonable convexity conditions. It is shown that this Nash equilibrium point possesses interesting monotonicity properties. For general networks, these convexity conditions are not sufficient for guaranteeing uniqueness, and a counterexample is presented. Nonetheless, uniqueness of the Nash equilibrium for general topologies is established under various assumptions.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
A neutralizing anti-TGF-beta1 antibody promotes proliferation of CD34+Thy-1+ peripheral blood progenitors and increases the number of transduced progenitors. (1998)

The subset of blood cells that expresses both CD34 and Thy1 (CD90) cell surface molecules is enriched in hematopoietic stem cell activity and can be obtained from the peripheral blood of cancer patients after mobilization by chemotherapy and granulocyte colony-stimulating factor (G-CSF). Because transforming growth factor-beta1 (TGF-beta1) is a potent inhibitor of hematopoietic progenitor proliferation and differentiation, in this study we analyzed the impact of neutralizing TGF-beta1 activity during culture and retroviral transduction of CD34+Thy1+ cells. When purified CD34+Thy1+ cells were cultured in the presence of a neutralizing antibody against TGF-beta1, the percentage of cycling cells, proliferation, and absolute number of clonogenic progenitors were increased in comparison to the cultures performed without the addition of antibody. Antibody-mediated neutralization of TGF-beta1 during retroviral transduction performed by coculture of CD34+Thy1+ cells with a MFG-S-nlsLacZ retroviral vector-producing cell line did not affect the percentage of transduced progenitors as assessed by direct X-Gal staining of colonies in clonogenic assays. However, due to the better expansion of CD34+Thy1+ cells in the presence of anti-TGF-beta1, the absolute number of transduced progenitors recovered at the end of the culture was increased.
Current and Potential Applications of Clinical 13C MR Spectroscopy (2008)

In this article, the current and potential clinical roles of (13)C magnetic resonance spectroscopy (MRS) and (13)C magnetic resonance spectroscopic imaging are presented, with a focus on applications to prostate cancer and hyperpolarized (13)C spectroscopic imaging. The advantages of (13)C MRS have been its chemical specificity and lack of background signal, with the major disadvantage being its inherently low sensitivity and the subsequent inability to acquire data at a high-enough spatial and temporal resolution to be routinely applicable in the clinic. The approaches to improving the sensitivity of (13)C spectroscopy have been to perform proton decoupling and to use endogenous (13)C-labeled or enhanced metabolic substrates. With these nominal increases in signal-to-noise ratio, (13)C MRS using labeled metabolic substrates has shown diagnostic promise in patients and has been approved by the Food and Drug Administration. The development of technology that applies dynamic nuclear polarization to generate hyperpolarized (13)C-labeled metabolic substrates, and the development of a process for delivering them into living subjects, have totally changed the clinical potential of MRS of (13)C-labeled metabolic substrates. Preliminary preclinical studies in a model of prostate cancer have demonstrated the potential clinical utility of hyperpolarized (13)C MRS.
International Approaches to Advancing Biospecimen Science (2011)

Biospecimen quality is affected by a number of preanalytical factors that may or may not be obvious to the investigator. These factors are introduced through multiple biospecimen collection, processing, and storage procedures, which can differ dramatically within and between medical institutions and biorepositories. Biospecimen Science is the emerging field of study that is attempting to quantify and control such variability. A variety of efforts are under way around the world to establish research programs, evidence-based biospecimen protocols, and standards to improve the overall quality of biospecimens for research.
The First Dinitrile Frameworks of the Rare Earth Elements:∞3[LnCl3(1,4-Ph(CN)2)] and∞3[Ln2Cl6(1,4-Ph(CN)2)], Ln = Sm, Gd, Tb, Y; Access to Novel Metal-Organic Frameworks by Solvent Free Synthesis in Molten 1,4-Benzodinitrile (2008)

The three-dimensional frameworks infinity(3)[LnCl3(1,4-Ph(CN)2)] of the lanthanides Ln = Sm (1), Gd (2), Tb (3), and infinity(3)[Ln2Cl6(1,4-Ph(CN)2)] for the group 3 metal Y (4) were obtained as single crystalline materials by the reaction of the anhydrous chlorides of the referring rare earth elements with a melt of 1,4-benzodinitrile. No additional solvents were used for the reactions. The dinitrile ligand is strongly coordinating and substitutes parts of the chlorine coordination. The Ln halide structures are reduced to two-dimensional networks, whereas coordination of both nitrile functions to the metal ions renders bridging in the third direction accessible. This enables formation of new metal organic framework (MOF) structure types with the large 1,4-benzodinitrile spacers interlinking infinity (2)[LnCl3] planes. In comparison to 1,4-Ph(CN)2 the mono functional benzonitrile ligand does not constitute framework structures, which is underlined by comparison with a reaction of yttrium chloride with PhCN resulting in the molecular complex [Y2Cl6(PhCN)6] (5) with end-on coordination PhCN ligands. The coordination spheres of the rare earth ions consist of double capped (infinity(3)[LnCl3(1,4-Ph(CN)2)] (1-3)) as well as single capped trigonal prisms (infinity(3)[Ln2Cl6(1,4-Ph(CN)2)] (4)) of chloride ions and N[triple bond]C groups while 5 displays edge sharing pentagonal bipyramids as coordination polyhedra. Sm (1), Gd (2), and Tb (3) exhibit isotypic framework structures with intercrossing dinitrile ligands. The group 3 metal Y (4) gives a framework with a coplanar arrangement of ligands and a lower ligand content. The largest cavities within the MOF structures of 1-4 have diameters of 3.9-8.0 A. All compounds were identified by single crystal X-ray analysis. Mid IR, Far IR, and Raman spectroscopy, microanalyses and simultaneous Differential Thermal Analysis-Thermogravimetry (DTA/TG) were also carried out to characterize the products. Crystal data for infinity(3)[LnCl3(1,4-Ph(CN)2)] (1-3): Pnma, T = 170(2) K; Sm (1): a = 7.172(1) A, b = 22.209(3) A, c = 6.375(1) A, V = 1015.4(3) A(3), R1 for F(o) > 4sigma(F(o)) = 0.032, wR2 = 0.079. Gd (2): a = 7.116(1) A, b = 22.147(4) A, c = 6.345(1) A, V = 1000.0(3) A(3), R1 for F(o) > 4sigma(F(o)) = 0.033, wR2 = 0.085. Tb (3): a = 7.090(2) A, b = 22.140(4) A, c = 6.325(2) A, V = 992.8(3) A(3), R1 for F(o) > 4sigma(F(o)) = 0.025, wR2 = 0.061. Crystal data for infinity (3)[Y2Cl6(1,4-Ph(CN)2)] (4): P1, T = 170(2) K; a = 6.653(2) A, b = 6.799(2) A, c = 9.484(2) A, V = 397.9(2) A(3), R1 for F(o) > 4sigma(F(o)) = 0.027, wR2 = 0.069. Crystal data for [Y2Cl6(PhCN)6] (5): P2(1)/c, T = 170(2) K; a = 9.767 (2) A, b = 12.304(3) A, c = 19.110(4) A, V = 2294.8(8) A(3), R1 for F(o) > 4sigma(F(o)) = 0.041, wR2 = 0.092.
M Cell Transport of Vibrio cholerae from the Intestinal. Lumen into Peyer's Patches: A Mechanism for Antigen Sampling and for Microbial Transepithelial Migration (1986)

Viable Vibrio cholerae O1 were inoculated into the intestinal lumen of nonimmune rabbits. The vibrios were phagocytosed by M cells over Peyer's patch lymphoid follicles, carried in vesicles through the epithelium, and discharged among underlying lymphocytes and macrophages. Autoradiography of V. cholerae labeled with [2-3H]adenine confirmed transport. Indigenous bacteria with and without capsules were also taken up from control loops and carried through M cells into Peyer's patches. V. cholerae killed by acidification, formalin, heat, or UV irradiation were not taken up, a result that may have relevance for development of oral vaccines. Ruthenium red stain revealed gaps in the layer of mucus over M cells, glycocalyx bridging the space between vibrios and M cell microvilli, and knobby projections over membranes of M cell microvilli; these projections were not found over absorptive cells. M cells thus convey viable enteric microbes, including V. cholerae that are not otherwise invasive, into intestinal lymphoid tissue, where mucosal immune responses are initiated. Uptake and transport by M cells may also assist certain pathogenic bacteria in traversing the mucosal barrier and initiating systemic infection.
Cis‐analysis of a seed protein gene promoter: the conservative RY repeat CATGCATG within the legumin box is essential for tissue‐specific expression of a legumin gene (1992)

A 2.4 kb fragment containing the 5'-flanking region and the 5'-noncoding sequence of the Vicia faba legumin gene LeB4 mediates high level seed-specific expression in transgenic tobacco plants. Deleted derivatives of this legumin upstream sequence were fused to the npt-II reporter gene to determine the tissue-specific activity of the chimeric constructs in stably transformed tobacco plants. The results indicate the presence of positive regulatory, enhancer-like cis elements within 566 bp of the upstream sequence. Most importantly, however, these elements are only fully functional in conjunction with the core motif CATGCATG of the legumin box around position -95, since destruction of the motif by a 6 bp deletion in an otherwise intact 2.4 kb upstream sequence drastically reduces expression in seeds. At the same time, low level expression in leaves is observed. The occurrence of similar CATGCATG consensus cis elements with alternating purine and pyrimidine base pairs in front of several other plant genes suggests a functional role of the motif in a wider range of plant promoters.
Hedgehog Signaling Regulates Brain Tumor-Initiating Cell Proliferation and Portends Shorter Survival for Patients with PTEN-Coexpressing Glioblastomas (2008)

The identification of brain tumor stem-like cells (BTSCs) has implicated a role of biological self-renewal mechanisms in clinical brain tumor initiation and propagation. The molecular mechanisms underlying the tumor-forming capacity of BTSCs, however, remain unknown. Here, we have generated molecular signatures of glioblastoma multiforme (GBM) using gene expression profiles of BTSCs and have identified both Sonic Hedgehog (SHH) signaling-dependent and -independent BTSCs and their respective glioblastoma surgical specimens. BTSC proliferation could be abrogated in a pathway-dependent fashion in vitro and in an intracranial tumor model in athymic mice. Both SHH-dependent and -independent brain tumor growth required phosphoinositide 3-kinase-mammalian target of rapamycin signaling. In human GBMs, the levels of SHH and PTCH1 expression were significantly higher in PTEN-expressing tumors than in PTEN-deficient tumors. In addition, we show that hyperactive SHH-GLI signaling in PTEN-coexpressing human GBM is associated with reduced survival time. Thus, distinct proliferation signaling dependence may underpin glioblastoma propagation by BTSCs. Modeling these BTSC proliferation mechanisms may provide a rationale for individualized glioblastoma treatment.
Procedure for Determining Maximum Sustainable Power Generated by Microbial Fuel Cells (2005)

Power generated by microbial fuel cells is computed as a product of current passing through an external resistor and voltage drop across this resistor. If the applied resistance is very low, then high instantaneous power generated by the cell is measured, which is not sustainable; the cell cannot deliver that much power for long periods of time. Since using small electrical resistors leads to erroneous assessment of the capabilities of microbial fuel cells, a question arises: what resistor should be used in such measurements? To address this question, we have defined the sustainable power as the steady state of power delivery by a microbial fuel cell under a given set of conditions and the maximum sustainable power as the highest sustainable power that a microbial fuel cell can deliver under a given set of conditions. Selecting the external resistance that is associated with the maximum sustainable power in a microbial fuel cell (MFC) is difficult because the operator has limited influence on the main factors that control power generation: the rate of charge transfer at the current-limiting electrode and the potential established across the fuel cell. The internal electrical resistance of microbial fuel cells varies, and it depends on the operational conditions of the fuel cell. We have designed an empirical procedure to predict the maximum sustainable power that can be generated by a microbial fuel cell operated under a given set of conditions. Following the procedure, we change the external resistors incrementally, in steps of 500 omega every 10, 60, or 180 s and measure the anode potential, the cathode potential, and the cell current. Power generated in the microbial fuel cell that we were using was limited by the anodic current. The anodic potential was used to determine the condition where the maximum sustainable power is obtained. The procedure is simple, microbial fuel cells can be characterized within an hour, and the results of the measurements can serve many purposes, such as: (1) estimating power generation in various MFCs, (2) comparing power generation in MFCs using different electroactive reactants, (3) quantifying the effects of the operational regime on the power generation in MFCs, and finally, (4) the purpose for which the procedure was designed, optimizing the performance of existing MFCs.