gebhart/patrepeval huggingface dataset:
Gene therapy for adenosine deaminase–deficient severe combined immune deficiency: clinical comparison of retroviral vectors and treatment plans (2012)

We conducted a gene therapy trial in 10 patients with adenosine deaminase (ADA)-deficient severe combined immunodeficiency using 2 slightly different retroviral vectors for the transduction of patients' bone marrow CD34(+) cells. Four subjects were treated without pretransplantation cytoreduction and remained on ADA enzyme-replacement therapy (ERT) throughout the procedure. Only transient (months), low-level (< 0.01%) gene marking was observed in PBMCs of 2 older subjects (15 and 20 years of age), whereas some gene marking of PBMC has persisted for the past 9 years in 2 younger subjects (4 and 6 years). Six additional subjects were treated using the same gene transfer protocol, but after withdrawal of ERT and administration of low-dose busulfan (65-90 mg/m(2)). Three of these remain well, off ERT (5, 4, and 3 years postprocedure), with gene marking in PBMC of 1%-10%, and ADA enzyme expression in PBMC near or in the normal range. Two subjects were restarted on ERT because of poor gene marking and immune recovery, and one had a subsequent allogeneic hematopoietic stem cell transplantation. These studies directly demonstrate the importance of providing nonmyeloablative pretransplantation conditioning to achieve therapeutic benefits with gene therapy for ADA-deficient severe combined immunodeficiency.
Electron Transport in AlGaN/GaN Heterostructures Grown by Plasma-Assisted Molecular Beam Epitaxy (2000)

High quality AlGaN/GaN heterostructures have been grown by rf plasma-assisted molecular beam epitaxy (MBE) on n-type GaN templates grown on sapphire by metalorganic chemical vapor deposition (MOCVD). By optimizing the AlGaN thickness and the Al content, record low temperature mobilities have been achieved. Temperature and magnetic field dependent Hall effect, and Shubnikov-de Haas oscillations, were used to probe the two-dimensional electron gas (2DEG) with consistent results. The unintentionally doped Al 0.09 Ga 0.91 N heterostructures exhibit a measured 77 K Hall mobility of 24,000 cm 2 /V·s ( n sh =2.5×10 12 ), 12 K mobility of 52,000 cm 2 /V·s and ∼4 K mobility of 60,000 cm 2 /V·s ( n sh =2.25×10 12 ), all records for this material system. The magnetic field dependent Hall effect revealed carriers from the bulk GaN freeze out and that a single carrier system is dominant below 80 K.
Comparison of time-resolved and -unresolved measurements of deoxyhemoglobin in brain. (1988)

Continuous (CW) and pulsed light were used for the noninvasive measurement of hemoglobin oxygenation in tissues. A dual wavelength method of continuous illumination spectroscopy used 760 nm (deoxyhemoglobin peak) and 800 nm (an oxyhemoglobin-deoxyhemoglobin isosbestic point) to measure the kinetics and extent of oxyhemoglobin deoxygenation in brains during mild ischemia/hypoxia. Absorption and scattering were modeled in an artificial milk/yeast blood system, which gave an exponential relationship between absorption and optical path length to a depth of 7 cm. Time-resolved spectroscopy (10-ps resolution) afforded a display of the times and distances of arrival of photons emitted by the cat brain in response to a 10-ps input pulse. The emitted photons rose to a peak in a fraction of a nanosecond and declined exponentially over a few nanoseconds. The half-time of exponential decay corresponds to photon migration over a distance of 4 cm. Exponential light emission continued for several more nanoseconds when the brain was encased by the skull, which plays a key role in prolonging light emission. The exponential decline of light intensity has a value [exp(-microL)], where L is the path length determined from the time/distance scale and mu is the characteristic of the migration of light in the brain. The factor mu is increased by increasing absorption, and mu' = epsilon C where epsilon and C are the Beer-Lambert parameters of extinction coefficient (epsilon) and concentration (C). Thus, deoxyhemoglobin can be quantified in brain tissues.
Core structure of the envelope glycoprotein GP2 from Ebola virus at 1.9-Å resolution (1999)

Ebola virions contain a surface transmembrane glycoprotein (GP) that is responsible for binding to target cells and subsequent fusion of the viral and host-cell membranes. GP is expressed as a single-chain precursor that is posttranslationally processed into the disulfide-linked fragments GP1 and GP2. The GP2 subunit is thought to mediate membrane fusion. A soluble fragment of the GP2 ectodomain, lacking the fusion-peptide region and the transmembrane helix, folds into a stable, highly helical structure in aqueous solution. Limited proteolysis studies identify a stable core of the GP2 ectodomain. This 74-residue core, denoted Ebo-74, was crystallized, and its x-ray structure was determined at 1.9-A resolution. Ebo-74 forms a trimer in which a long, central three-stranded coiled coil is surrounded by shorter C-terminal helices that are packed in an antiparallel orientation into hydrophobic grooves on the surface of the coiled coil. Our results confirm the previously anticipated structural similarity between the Ebola GP2 ectodomain and the core of the transmembrane subunit from oncogenic retroviruses. The Ebo-74 structure likely represents the fusion-active conformation of the protein, and its overall architecture resembles several other viral membrane-fusion proteins, including those from HIV and influenza.
ESAT-6 Subunit Vaccination againstMycobacterium tuberculosis (2000)

The ESAT-6 antigen from Mycobacterium tuberculosis is a dominant target for cell-mediated immunity in the early phase of tuberculosis (TB) in TB patients as well as in various animal models. The purpose of our study was to evaluate the potential of ESAT-6 in an experimental TB vaccine. We started out using dimethyl dioctadecylammonium bromide (DDA), an adjuvant which has been demonstrated to be efficient for the induction of cellular immune responses and has been used successfully before as a delivery system for TB vaccines. Here we demonstrate that, whereas immune responses to both short-term-culture filtrate and Ag85B are efficiently induced with DDA, this adjuvant was inefficient for the induction of immune responses to ESAT-6. Therefore, we investigated the modulatory effect of monophosphoryl lipid A (MPL), an immunomodulator which in different combinations has demonstrated strong adjuvant activity for both cellular and humoral immune responses. We show in the present study that vaccination with ESAT-6 delivered in a combination of MPL and DDA elicited a strong ESAT-6-specific T-cell response and protective immunity comparable to that achieved with Mycobacterium bovis BCG.
Vitamin E succinate inhibits NF‐κB and prevents the development of a metastatic phenotype in prostate cancer cells: Implications for chemoprevention (2007)

Our findings propose a potential mechanism of VES-mediated anti-tumor activity and support the role of vitamin E analogs as potential chemopreventative agents against prostate cancer.
Family 19 Chitinase ofStreptomyces griseusHUT6037 Increases Plant Resistance to the Fungal Disease (2003)

Chitinase C (ChiC) is the first bacterial family 19 chitinase discovered in Streptomyces griseus HUT6037. In vitro, ChiC clearly inhibited hyphal extension of Trichoderma reesei but a rice family 19 chitinase did not. In order to investigate the effects of ChiC as an increaser of plant resistance to fungal diseases, the chiC gene was introduced into rice plants under the control of the increased CaMV 35S promoter and a signal sequence from the rice chitinase gene. Transgenic plants were morphologically normal. Resistance to leaf blast disease caused by Magnaporthe grisea was evaluated in R1 and R2 generations using a spray method. Ninety percent of transgenic rice plants expressing ChiC had higher resistance than non-transgenic plants. Disease resistance of sibling plants within the same line was correlated with the ChiC expression levels. ChiC produced in rice plants accumulated intercellularly and had the hydrolyzing activity against glycol chitin.
The Electra KrF laser program (2002)

Electra is a repetitively pulsed, electron-beam pumped, Krypton Fluoride (KrF) laser that will develop the technologies that can meet the Inertial Fusion Energy (IFE) requirements for durability, efficiency, and cost. Electra will have a 30 cm/spl times/30 cm optical aperture, an output of 400-900 Joules, and run at 5 Hz. The main amplifier will be pumped with two 30 cm/spl times/100 cm e-beams, each with V=500 kV, I=110 kA, and t=100 nsec (flat top). The components that need to be developed are: a durable and efficient pulsed power system; a durable electron beam emitter; a long life, transparent pressure foil structure (hibachi); a laser gas recirculator; and long life optical windows. The technologies developed on Electra will be directly scalable to a full size fusion power plant beam line. We have built a first generation pulsed power system that can produce the necessary pulsed power parameters and repetition rate. This system has operated at 5 Hz for 90000 shots (e.g. five hours), which is more than ample to develop the laser components. This paper gives an overview of the Electra program, and then concentrate on the results of our research on electron beam generation, transport, and deposition. This includes evaluation of various cathode and hibachi structures, as well as KrF laser modeling.
The desA gene of the cyanobacterium Synechocystis sp. strain PCC6803 is the structural gene for delta 12 desaturase (1993)

The desA gene of the cyanobacterium Synechocystis sp. strain PCC6803 was expressed in Escherichia coli, which does not contain any fatty acid desaturase. The product of the desA gene catalyzed the desaturation of fatty acids at the delta 12 position. This result demonstrates that desA is the structural gene for a delta 12 desaturase.
Hematopoietic growth factors: biology and clinical application. (1990)

A number of recently identified cytokines have been implicated in the development of blood cells and their functional activation. These include granulocyte colony-stimulating factor (G-CSF), granulocyte/macrophage colony-stimulating factor (GM-CSF), macrophage colony-stimulating factor (M-CSF), and interleukins-1, -3, and -6. The two that have been studied most extensively clinically are G- and GM-CSF. Biologic differences between these two agents have important implications for their use in particular clinical settings. Whereas G-CSF for the most part has demonstrated lineage specificity in stimulating production of neutrophil granulocytes, GM-CSF stimulates production of all types of granulocytes and is a potent activator of monocytes and macrophages as well. In addition, GM-CSF has been found to induce other cytokines, such as tumor necrosis factor and interleukin-1. Functional differences such as influencing neutrophil migration have also been noted; GM-CSF can be a potent inhibitor of neutrophil migration. The interaction of these and other cytokines in inflammation and injury is the determinant of the ultimate clinical outcome. Potential clinical applications for these growth factors are discussed, and specific clinical studies during which recombinant human G-CSF was used are reviewed.
The c-MYC oncoprotein as a treatment target in cancer and other disorders of cell growth (2003)

The c-MYC proto-oncogene is essential for cellular proliferation but, paradoxically, may also promote cell death. Deregulated expression of c-MYC is present in most, if not all, human cancers, and is associated with a poor prognosis. However, given that human tumours at diagnosis generally carry multiple genetic lesions that have accumulated during (although they are not necessarily essential for) tumour progression, it has proved difficult to attribute a specific role to any given single factor or indeed to explore the therapeutic potential of selectively mitigating their biological functions. Regulatable transgenic mouse models of oncogenesis have shed light on these issues, influenced our thinking about cancer and provided encouragement for the future development of cancer therapies based on targeting individual oncogenes such as c-MYC. Although still in its infancy, encouraging results have been reported using antisense oligodeoxynucleotide-based methods, as well as other approaches to interfere with MYC expression both in vitro and in vivo.
Synthesis of Plasmepsin II Inhibitors – Potential Antimalarial Agents (2003)

A new series of plasmepsin II (PM II) inhibitors has been prepared based on 4-aminopiperidine-tert-butyl-carbamate (1). These compounds might be useful as antimalarial drugs acting via a new mechanism, and therefore be less susceptible to parasite resistance now often observed with current antimalarial therapies. Some of the final compounds prepared exhibited encouraging inhibitory activity towards PM II.
Bioinspired Growth of Crystalline Carbonate Apatite on Biodegradable Polymer Substrata (2002)

Mineralization in biological systems is a widespread, yet incompletely understood phenomenon involving complex interactions at the biomacromolecule-mineral nucleus interface. This study was aimed at understanding and controlling mineral formation in a poly(alpha-hydroxy ester) model system, to gain insight into biological mineralization processes and to develop biomaterials for orthopaedic tissue regeneration. We specifically hypothesized that providing a high surface density of anionic functional groups would enhance nucleation and growth of bonelike mineral following exposure to simulated body fluids (SBF). Polymer surface functionalization was achieved via hydrolysis of 85:15 poly(lactide-co-glycolide) (PLG) films. This treatment led to an increase in surface carboxylic acid and hydroxyl groups, resulting in a substantial increase in polymer surface energy from 42 to 49 dynes/cm2. Treated polymers exhibited a 3-fold increase in heterogeneous mineral grown and growth of a continuous mineral film on the polymer surface. The mineral grown on PLG surfaces is a carbonate apatite, the major mineral component of vertebrate bone tissue. Mineral crystal size and morphology were dependent on the solution characteristics but unaffected by the degree of surface prehydrolysis. The mechanism of heterogeneous carbonate apatite growth was examined via ion binding assays, which indicated that calcium binding is mediated independently by the presence of soluble phosphate counterions and surface functional groups. These findings indicate that poly(alpha-hydroxy ester) materials can be readily mineralized using a biomimetic process, and that the impetus for mineral nucleation in this system appears more complicated than the simple electrostatic interactions proposed in previous biomineralization theory.
Transient Impairment of Hippocampus-dependent Learning and Memory in Relatively Low-Dose of Acute Radiation Syndrome is Associated with Inhibition of Hippocampal Neurogenesis (2008)

Neurogenesis in the adult hippocampus, which occurs constitutively, is vulnerable to ionizing radiation. In the relatively low-dose exposure of acute radiation syndrome (ARS), the change in the adult hippocampal function is poorly understood. This study analyzed the changes in apoptotic cell death and neurogenesis in the DGs of hippocampi from adult ICR mice with single whole-body gamma-irradiation using the TUNEL method and immunohistochemical markers of neurogenesis, Ki-67 and doublecortin (DCX). In addition, the hippocampus-dependent learning and memory tasks after single whole-body gamma-irradiation were examined in order to evaluate the hippocampus-related behavioral dysfunction in the relatively low-dose exposure of ARS. The number of TUNEL-positive apoptotic nuclei in the dentate gyrus (DG) was increased 6-12 h after acute gamma-irradiation (a single dose of 0.5 to 4 Gy). In contrast, the number of Ki-67- and DCX-positive cells began to decrease significantly 6 h postirradiation, reaching its lowest level 24 h after irradiation. The level of Ki-67 and DCX immunoreactivity decreased in a dose-dependent manner within the range of irradiation applied (0-4 Gy). In passive avoidance and object recognition memory test, the mice trained 1 day after acute irradiation (2 Gy) showed significant memory deficits, compared with the sham controls. In conclusion, the pattern of the hippocampus-dependent memory dysfunction is consistent with the change in neurogenesis after acute irradiation. It is suggested that a relatively low dose of ARS in adult ICR mice is sufficiently detrimental to interrupt the functioning of the hippocampus, including learning and memory, possibly through the inhibition of neurogenesis.
Evaluation of the type I signal peptidase as antibacterial target for biofilm-associated infections of Staphylococcus epidermidis (2009)

The development of antibacterial resistance is inevitable and is a major concern in hospitals and communities. Moreover, biofilm-grown bacteria are less sensitive to antimicrobial treatment. In this respect, the Gram-positive Staphylococcus epidermidis is an important source of nosocomial biofilm-associated infections. In the search for new antibacterial therapies, the type I signal peptidase (SPase I) serves as a potential target for development of antibacterials with a novel mode of action. This enzyme cleaves off the signal peptide from secreted proteins, making it essential for protein secretion, and hence for bacterial cell viability. S. epidermidis encodes three putative SPases I (denoted Sip1, Sip2 and Sip3), of which Sip1 lacks the catalytic lysine. In this report, we investigated the active S. epidermidis SPases I in more detail. Sip2 and Sip3 were found to complement a temperature-sensitive Escherichia coli lepB mutant, demonstrating their in vivo functional activity. In vitro functional activity of purified Sip2 and Sip3 proteins and inhibition of their activity by the SPase I inhibitor arylomycin A(2) were further illustrated using a fluorescence resonance energy transfer (FRET)-based assay. Furthermore, we demonstrated that SPase I not only is an attractive target for development of novel antibacterials against free-living bacteria, but also is a feasible target for biofilm-associated infections.
PROLONGED SKIN HOMOGRAFT AND HETEROGRAFT SURVIVAL IN PATIENTS WITH NEOPLASTIC DISEASE (1960)

SNYDERMAN, REUVEN K. M.D.; MILLER, DANIEL G. M.D.; LIZARDO, JESUS G. M.D. Author Information
HLA-A31- and HLA-Aw68-restricted cytotoxic T cell responses to a single hepatitis B virus nucleocapsid epitope during acute viral hepatitis. (1993)

We have recently developed the technology to identify and characterize the human histocompatibility leukocyte antigen (HLA) class I-restricted, CD8+ cytotoxic T lymphocyte (CTL) response to hepatitis B virus (HBV)-encoded antigens in patients with acute viral hepatitis. CTL are expanded in vitro by stimulation with HBV-derived synthetic peptides and selected by restimulation with a panel of HLA-matched stable transfectants that express the corresponding HBV protein. We have recently reported the existence of an HLA-A2-restricted, CD8+ CTL response to an epitope located between residues 18 and 27 of the HBV nucleocapsid core antigen (HBcAg). We now report the discovery of a CTL epitope located between HBcAg residues 141 and 151 that completely overlaps a critical domain in the viral nucleocapsid protein that is essential for its nuclear localization and genome packaging functions as well as processing of the precore protein. The CTL response to this epitope is dually restricted by the HLA-A31 and HLA-Aw68 alleles, which, unexpectedly, appear to use a common binding motif based on the results of alanine substitution and competition analysis, and the binding properties of these two alleles predicted from their known primary sequence, and from the three-dimensional structure of HLA-Aw68. We have also demonstrated that the HBV-specific CTL response to this epitope is polyclonal during acute viral hepatitis, since these two restriction elements can present the HBcAg 141-151 epitope to independent CTL clones derived from a single patient; and that the CTL response is multispecific, since HLA-A2-restricted and HLA-Aw68-restricted CTL responses to HBcAg 18-27 and HBcAg 141-151, respectively, have been identified to coexist in another patient. The foregoing argue against the emergence of CTL escape mutants as a significant problem during HBV infection, especially at this locus, where mutations might be incompatible with viral replication. Finally, our data suggest an association between the HBV-specific CTL response and viral clearance, and they have implications for the design of immunotherapeutic strategies to terminate HBV infection in chronically infected patients.
Genetically modified bone marrow‐derived dendritic cells expressing tumor‐associated viral or “self” antigens induce antitumor immunity in vivo (1997)

The clinical application of synthetic tumor peptide-based vaccines is currently limited to patients with specified major histocompatibility complex (MHC) class I alleles. Such logistic limitations may be overcome using tumor gene-based approaches. Here we describe the effective generation of dendritic cells (DC) expressing tumor peptide-MHC complexes as a result of particle-mediated transfer of genes encoding tumor-associated antigens (TAA). Bone marrow-derived DC were transfected with plasmid DNA encoding the tumor-associated viral antigen E7 derived from human papilloma virus (HPV) 16. When applied as a vaccine, these genetically modified DC induced antigen-specific CD8+ cytotoxic T lymphocytes (CTL) in vivo and promoted the rejection of a subsequent, normally lethal challenge with an HPV 16-transformed tumor cell line. Of greatest interest, immunization of mice with syngeneic DC genetically modified to enhance their presentation of a constitutive "self" epitope derived from the tumor-suppressor gene product p53 caused a significant reduction in the in vivo growth of a chemically induced p53-positive sarcoma. These results suggest that cancer vaccines consisting of DC genetically modified to express TAA of viral or "self" origin effectively induce antitumor immunity in vivo.