gebhart/patrepeval huggingface dataset:
Preparation of Neural Progenitors from Bone Marrow and Umbilical Cord Blood (2003)

The bone marrow is clearly much more than a reservoir of stem cells that repopulates blood cell lineages throughout life. The marrow also contains nonhematopoietic stem cells, which are much more versatile than previously appreciated. These nonhematopoietic stem/progenitor cells are found in the bone marrow stromal cell (BMSC) population. BMSCs also are known as colony-forming unit fibroblasts and mesenchymal stem cells (MSCs). MSCs also can be generated from umbilical cord blood and other tissues. MSCs have been shown to express properties of neuroectodermal cells in vitro by many researchers and in vivo after transplantation into the brain and spinal cord. Many investigators have developed variations on the original method described 6 years ago for the preparation of neural progenitors from BMSCs. We bring up to date the materials and procedures used to prepare BMSCs from bone marrow and from human umbilical cord blood for the induction of neural progenitor cells and subsequent differentiation into neurons and glia.
Precise Instruction Scheduling (2005)

Pipeline depths in high performance dynamically scheduled microprocessors are increasing steadily. In addition, level 1 caches are shrinking to meet latency constraints- but more levels of cache are being added to mitigate this performance impact. Moreover, the growing schedule-toexecute-window of deeply pipelined processors has required the use of speculative scheduling techniques. When these effects are combined, we are faced with performance degradation and increased power consumption due to load misscheduling, particularly when considering instructions dependent on in-flight loads. In this paper, we propose a scheduler for such processors. Instead of non-selectively speculating, the scheduler predicts the execution delay of an instruction and issues them accordingly. This, in return, can eliminate the issuing of some operations that will otherwise be squashed. Clearly, load operations constitute an important obstacle in predicting the latency of instructions, because their latencies are not known until the cache access stage, which happens later in the pipeline. Our proposed techniques can estimate the arrival of cache blocks in various locations of the cache hierarchy, thereby enabling more precise scheduling of instructions
Raman scattering from polymerizing styrene. I. Vibrational mode analysis (1981)

The frequencies and intensities of the Raman spectrum of thermally polymerizing styrene were measured in order to confirm (or correct) the mode assignments in the literature and to observe the effect of polymerization on the Raman active modes. The spectra were measured over a period of three weeks while an originally highly purified sample of monostryrene was kept at about 100 °C. The polymer vibrations are identified with their monomer ’’origins’’ which are in turn compared to known benzene (or benzene derivatives) and ethylene (or vinyl group) vibrations.
Efficacy of urate oxidase (uricozyme) in tumour lysis induced urate nephropathy (1998)

Urate oxidase (uricozyme) is an enzyme of non-human origin capable of oxidizing human uric acid to allantoin, a highly soluble product at renal tubule pH. We report its efficacy in three patients with acute urate nephropathy due to tumour lysis in chronic lymphatic leukaemia and high grade lymphoma. Two patients had an additional obstructive nephropathy due to ureteric urate crystals. An intravenous infusion (100 units/kg in 50 ml saline over 30 min) was given for between two and five consecutive days. All patients showed a rapid fall in serum urate levels with associated diuresis, correction of metabolic disturbance and full resolution of uraemia within a week. The treatment was well tolerated and caused a rapid resolution of clinical symptoms in all cases. We review the literature relating to the use of this agent both in the treatment of hyperuricaemic acute renal failure and gouty arthritis.
Biosynthesis, Characterization, and Efficacy in Retinal Degenerative Diseases of Lens Epithelium-derived Growth Factor Fragment (LEDGF1–326), a Novel Therapeutic Protein (2013)

For vision-threatening retinitis pigmentosa and dry age-related macular degeneration, there are no United States Food and Drug Administration (FDA)-approved treatments. We identified, biosynthesized, purified, and characterized lens epithelium-derived growth factor fragment (LEDGF1-326) as a novel protein therapeutic. LEDGF1-326 was produced at about 20 mg/liter of culture when expressed in the Escherichia coli system, with about 95% purity and aggregate-free homogeneous population with a mean hydrodynamic diameter of 9 ± 1 nm. The free energy of unfolding of LEDGF1-326 was 3.3 ± 0.5 kcal mol(-1), and melting temperature was 44.8 ± 0.2 °C. LEDGF1-326 increased human retinal pigment epithelial cell viability from 48.3 ± 5.6 to 119.3 ± 21.1% in the presence of P23H mutant rhodopsin-mediated aggregation stress. LEDGF1-326 also increased retinal pigment epithelial cell FluoSphere uptake to 140 ± 10%. Eight weeks after single intravitreal injection in Royal College of Surgeons (RCS) rats, LEDGF1-326 increased the b-wave amplitude significantly from 9.4 ± 4.6 to 57.6 ± 8.8 μV for scotopic electroretinogram and from 10.9 ± 5.6 to 45.8 ± 15.2 μV for photopic electroretinogram. LEDGF1-326 significantly increased the retinal outer nuclear layer thickness from 6.34 ± 1.6 to 11.7 ± 0.7 μm. LEDGF1-326 is a potential new therapeutic agent for treating retinal degenerative diseases.
Nanoalloys:  From Theory to Applications of Alloy Clusters and Nanoparticles (2008)

Le nanoleghe sono sistemi di taglia nanometrica formati da due o più specie atomiche. In questo lavoro sono trattati gli aspetti strutturali e termodinamici e la cinetica di crescita per un'ampia scelta di sistemi.
Assembly Properties of the Human Immunodeficiency Virus Type 1 CA Protein (2004)

During retroviral maturation, the CA protein oligomerizes to form a closed capsid that surrounds the viral genome. We have previously identified a series of deleterious surface mutations within human immunodeficiency virus type 1 (HIV-1) CA that alter infectivity, replication, and assembly in vivo. For this study, 27 recombinant CA proteins harboring 34 different mutations were tested for the ability to assemble into helical cylinders in vitro. These cylinders are composed of CA hexamers and are structural models for the mature viral capsid. Mutations that diminished CA assembly clustered within helices 1 and 2 in the N-terminal domain of CA and within the crystallographically defined dimer interface in the CA C-terminal domain. These mutations demonstrate the importance of these regions for CA cylinder production and, by analogy, mature capsid assembly. One CA mutant (R18A) assembled into cylinders, cones, and spheres. We suggest that these capsid shapes occur because the R18A mutation alters the frequency at which pentamers are incorporated into the hexagonal lattice. The fact that a single CA protein can simultaneously form all three known retroviral capsid morphologies supports the idea that these structures are organized on similar lattices and differ only in the distribution of 12 pentamers that allow them to close. In further support of this model, we demonstrate that the considerable morphological variation seen for conical HIV-1 capsids can be recapitulated in idealized capsid models by altering the distribution of pentamers.
Glycoprotein H of human cytomegalovirus is a major antigen for the neutralizing humoral immune response (1996)

A recombinant baculovirus expressing glycoprotein H (gpUL75) of human cytomegalovirus was used to examine the humoral immune response in naturally infected individuals. Recombinant baculovirus infected insect cells produced two forms of gH with molecular masses of 78-82 kDa and 94 kDa. The 94 kDa polypeptide was modified by high mannose oligosaccharide side-chains as shown by reduction in molecular mass after treatment with endoglycosidases H and F. The 78-82 kDa protein represented the non-glycosylated precursor which was resistant to the enzymes. In contrast to gH expressed in mammalian cells, the recombinant baculovirus expressed gH was transported to the cell surface. Glycoprotein H produced in insect cells was reactive with human convalescent sera and all tested neutralizing monoclonal antibodies recognizing either linear or conformational epitopes. Antibodies reacting with insect cell derived gH were detected in 96 percent of HCMV seropositive human sera. Using insect cells infected with the gH expressing recombinant baculovirus as immunoabsorbent, between 0 percent and 58 percent of the total virus neutralizing activity was removed from sera of individuals with a past HCMV infection. gH must therefore be considered a major antigen for the induction of neutralizing antibodies during natural infection.
Topoisomerase 2β: A Promising Molecular Target for Primary Prevention of Anthracycline-Induced Cardiotoxicity (2013)

Anthracyclines are powerful chemotherapy agents that are still widely used today. However, their clinical use is limited by the development of dose-dependent cardiotoxicity. Recently, we showed that topoisomerase 2β (Top2β) is required for anthracycline to induce DNA double-strand breaks and changes in the transcriptome, leading to mitochondrial dysfunction and generation of reactive oxygen species. Furthermore, deleting Top2β from cardiomyocytes prevented the development of anthracycline-induced cardiotoxicity in mice. On the basis of this molecular insight, new strategies should be developed to prevent anthracycline-induced cardiotoxicity. First, Top2α-specific anthracyclines should be tested to determine whether they will spare the heart. Second, Top2β should be studied as a potential biomarker to predict risk of developing cardiotoxicity before anthracycline treatment. Third, inhibiting and deleting Top2β in the heart should also be tested as primary prevention strategies. We propose that Top2β is a promising molecular target that can be used to design interventions to prevent anthracycline-induced cardiotoxicity.
Immunoglobulin domain crossover as a generic approach for the production of bispecific IgG antibodies (2011)

We describe a generic approach to assemble correctly two heavy and two light chains, derived from two existing antibodies, to form human bivalent bispecific IgG antibodies without use of artificial linkers. Based on the knobs-into-holes technology that enables heterodimerization of the heavy chains, correct association of the light chains and their cognate heavy chains is achieved by exchange of heavy-chain and light-chain domains within the antigen binding fragment (Fab) of one half of the bispecific antibody. This "crossover" retains the antigen-binding affinity but makes the two arms so different that light-chain mispairing can no longer occur. Applying the three possible "CrossMab" formats, we generated bispecific antibodies against angiopoietin-2 (Ang-2) and vascular endothelial growth factor A (VEGF-A) and show that they can be produced by standard techniques, exhibit stabilities comparable to natural antibodies, and bind both targets simultaneously with unaltered affinity. Because of its superior side-product profile, the CrossMab(CH1-CL) was selected for in vivo profiling and showed potent antiangiogenic and antitumoral activity.
ChemInform Abstract: Effect of Molecular Sieves in the Liquid‐Phase Synthesis of Nucleotides via the Phosphoramidite Method. (2002)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Effects of Bicarbonates and Film-Forming Polymers on Cucurbit Foliar Diseases (1992)

The inhibitory effects of sodium, potassium, and ammonium bicarbonates (NaHCO 3 , KHCO 3 and NH 4 HCO 3 , respectively) alone and in combination with SunSpray Ultra-Fine Spray Oil (SS) on powdery mildew, caused by Sphaerotheca fuliginea; gummy stem blight, caused by Didymella bryoniae; Alternaria leaf blight, caused by Alternaria cucumerina; and Ulocladium leaf spot, caused by Ulocladium cucurbitae, were studied. SS oil performed consistently better than ForEverGreen, Masbrane, Crop Life, Vapor Gard, Nu-Film 17, and Bio-Film for powdery mildew control in cucumber and pumpkin(.)
Colorectal Cancer Consensus Molecular Subtypes Translated to Preclinical Models Uncover Potentially Targetable Cancer Cell Dependencies (2017)

<b>Purpose:</b> Response to standard oncologic treatment is limited in colorectal cancer. The gene expression-based consensus molecular subtypes (CMS) provide a new paradigm for stratified treatment and drug repurposing; however, drug discovery is currently limited by the lack of translation of CMS to preclinical models.<b>Experimental Design:</b> We analyzed CMS in primary colorectal cancers, cell lines, and patient-derived xenografts (PDX). For classification of preclinical models, we developed an optimized classifier enriched for cancer cell-intrinsic gene expression signals, and performed high-throughput <i>in vitro</i> drug screening (<i>n</i> = 459 drugs) to analyze subtype-specific drug sensitivities.<b>Results:</b> The distinct molecular and clinicopathologic characteristics of each CMS group were validated in a single-hospital series of 409 primary colorectal cancers. The new, cancer cell-adapted classifier was found to perform well in primary tumors, and applied to a panel of 148 cell lines and 32 PDXs, these colorectal cancer models were shown to recapitulate the biology of the CMS groups. Drug screening of 33 cell lines demonstrated subtype-dependent response profiles, confirming strong response to EGFR and HER2 inhibitors in the CMS2 epithelial/canonical group, and revealing strong sensitivity to HSP90 inhibitors in cells with the CMS1 microsatellite instability/immune and CMS4 mesenchymal phenotypes. This association was validated <i>in vitro</i> in additional CMS-predicted cell lines. Combination treatment with 5-fluorouracil and luminespib showed potential to alleviate chemoresistance in a CMS4 PDX model, an effect not seen in a chemosensitive CMS2 PDX model.<b>Conclusions:</b> We provide translation of CMS classification to preclinical models and uncover a potential for targeted treatment repurposing in the chemoresistant CMS4 group. <i>Clin Cancer Res; 24(4); 794-806. ©2017 AACR</i>.
Up-regulation of caveolin expression by cytotoxic agents in drug-sensitive cancer cells (2003)

Caveolin 1 expression is down-regulated in various cancer cell lines. Interestingly, in several drug-resistant cancer cells, a strong induction of caveolin 1 expression has been reported, suggesting a role for caveolin 1 in the acquisition and/or the maintenance of the multidrug-resistance phenotype. Here, we show, in drug-sensitive lung cancer cells (A549, Calu-6 or NCI-H69), that exposure to cytotoxic drugs (taxol, doxorubicin or etoposide) is sufficient to strongly up-regulate caveolin 1 and 2 protein levels. This up-regulation is sustained even 1 week after drug removal. Our results suggest that caveolin up-regulation is an early cellular response to a cytotoxic stress taking place before drug resistance.
Persistence of Multiple Tumor-Specific T-Cell Clones Is Associated with Complete Tumor Regression in a Melanoma Patient Receiving Adoptive Cell Transfer Therapy (2004)

The authors recently reported that adoptive immunotherapy with autologous tumor-reactive tumor infiltrating lymphocytes (TILs) immediately following a conditioning nonmyeloablative chemotherapy regimen resulted in an enhanced clinical response rate in patients with metastatic melanoma. These observations led to the current studies, which are focused on a detailed analysis of the T-cell antigen reactivity as well as the in vivo persistence of T cells in melanoma patient 2098, who experienced a complete regression of all metastatic lesions in lungs and soft tissues following therapy. Screening of an autologous tumor cell cDNA library using transferred TILs resulted in the identification of novel mutated growth arrest-specific gene 7 (GAS7) and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) gene transcripts. Direct sequence analysis of the expressed T-cell receptor beta chain variable regions showed that the transferred TILs contained multiple T-cell clonotypes, at least six of which persisted in peripheral blood for a month or more following transfer. The persistent T cells recognized both the mutated GAS7 and GAPDH. These persistent tumor-reactive T-cell clones were detected in tumor cell samples obtained from the patient following adoptive cell transfer and appeared to be represented at higher levels in the tumor sample obtained 1 month following transfer than in the peripheral blood obtained at the same time. Overall, these results indicate that multiple tumor-reactive T cells can persist in the peripheral blood and at the tumor site for prolonged times following adoptive transfer and thus may be responsible for the complete tumor regression in this patient.
Factors Influencing Recombinant Adeno-Associated Virus Production (1998)

Recombinant adeno-associated virus (rAAV) is produced by transfecting cells with two constructs: the rAAV vector plasmid and the rep-cap plasmid. After subsequent adenoviral infection, needed for rAAV replication and assembly, the virus is purified from total cell lysates through CsCl gradients. Because this is a long and complex procedure, the precise titration of rAAV stocks, as well as the measure of the level of contamination with adenovirus and rep-positive AAV, are essential to evaluate the transduction efficiency of these vectors in vitro and in vivo. Our vector core is in charge of producing rAAV for outside investigators as part of a national network promoted by the Association Française contre les Myopathies/Généthon. We report here the characterization of 18 large-scale rAAV stocks produced during the past year. Three major improvements were introduced and combined in the rAAV production procedure: (i) the titration and characterization of rAAV stocks using a stable rep-cap HeLa cell line in a modified Replication Center Assay (RCA); (ii) the use of different rep-cap constructs to provide AAV regulatory and structural proteins; (iii) the use of an adenoviral plasmid to provide helper functions needed for rAAV replication and assembly. Our results indicate that: (i) rAAV yields ranged between 10(11) to 5 x 10(12) total particles; (ii) the physical particle to infectious particle (measured by RCA) ratios were consistently below 50 when using a rep-cap plasmid harboring an ITR-deleted AAV genome; the physical particle to transducing particle ratios ranged between 400 and 600; (iii) the use of an adenoviral plasmid instead of an infectious virion did not affect the particles or the infectious particles yields nor the above ratio. Most of large-scale rAAV stocks (7/9) produced using this plasmid were free of detectable infectious adenovirus as determined by RCA; (iv) all the rAAV stocks were contaminated with rep-positive AAV as detected by RCA. In summary, this study describes a general method to titrate rAAV, independently of the transgene and its expression, and to measure the level of contamination with adenovirus and rep-positive AAV. Furthermore, we report a new production procedure using adenoviral plasmids instead of virions and resulting in rAAV stocks with undetectable adenovirus contamination.
Fibrin glue from stored human plasma. An inexpensive and efficient method for local blood bank preparation. (1987)

European surgeons have used fibrin glue extensively during thoracic, cardiovascular, and general surgical operations. Until now, however, it has been available only as a commercial preparation made from pooled human plasma, and it has not been approved by the U.S. Food and Drug Administration for use in the United States because of a high associated risk of hepatitis and acquired immune deficiency syndrome. Methods of obtaining fibrinogen, an essential component of fibrin glue, from cryoprecipitate or fresh frozen plasma have been published recently. However, the cryoprecipitate method results in relatively low concentrations of fibrinogen, which can reduce glue effectiveness. The fresh frozen plasma method is more expensive and does not meet the standards of the American Association of Blood Banks for the "closed" system required for safe handling and management of blood component products. Both the cryoprecipitate and the fresh frozen plasma methods result in waste of unstable clotting factors. These factors are necessary to replace human plasma clotting deficiencies but are not necessary for the production of fibrin glue. The authors have developed an efficient, high-concentration blood bank method for producing and maintaining a local supply of a safer and less expensive but equally effective material derived from stored human plasma. This material is produced using approved blood bank techniques for a "closed" system in blood component production, thus reducing the risks of contamination and infection, and its fibrinogen concentration is higher than that of standard cryoprecipitate. The cost of 1 unit of this fibrin glue is comparable to that for 1 unit of cryoprecipitate and less than that for 1 unit of fresh frozen plasma.(ABSTRACT TRUNCATED AT 250 WORDS)
Mechanism of Mo-Dependent Nitrogenase (2009)

Nitrogen-fixing bacteria catalyze the reduction of dinitrogen (N(2)) to two ammonia molecules (NH(3)), the major contribution of fixed nitrogen to the biogeochemical nitrogen cycle. The most widely studied nitrogenase is the molybdenum (Mo)-dependent enzyme. The reduction of N(2) by this enzyme involves the transient interaction of two component proteins, designated the iron (Fe) protein and the MoFe protein, and minimally requires 16 magnesium ATP (MgATP), eight protons, and eight electrons. The current state of knowledge on how these proteins and small molecules together effect the reduction of N(2) to ammonia is reviewed. Included is a summary of the roles of the Fe protein and MgATP hydrolysis, information on the roles of the two metal clusters contained in the MoFe protein in catalysis, insights gained from recent success in trapping substrates and inhibitors at the active-site metal cluster FeMo cofactor, and finally, considerations of the mechanism of N(2) reduction catalyzed by nitrogenase.
Microdevices in Medicine (2000)

The application of microelectromechanical systems (MEMS) to medicine is described. Three types of biomedical devices are considered, including diagnostic microsystems, surgical microsystems, and therapeutic microsystems. The opportunities of MEMS miniaturization in these emerging disciplines are considered, with emphasis placed on the importance of the technology in providing a better outcome for the patient and a lower overall health care cost. Several case examples in each of these areas are described. Key aspects of MEMS technology as it is applied to these three areas are described, along with some of the fabrication challenges.
Satori: enlightened page sharing (2009)

We introduce Satori, an efficient and effective system for sharing memory in virtualised systems. Satori uses enlightenments in guest operating systems to detect sharing opportunities and manage the surplus memory that results from sharing. Our approach has three key benefits over existing systems: it is better able to detect short-lived sharing opportunities, it is efficient and incurs negligible overhead, and it maintains performance isolation between virtual machines.

We present Satori in terms of hypervisor-agnostic design decisions, and also discuss our implementation for the Xen virtual machine monitor. In our evaluation, we show that Satori quickly exploits up to 94% of the maximum possible sharing with insignificant performance overhead. Furthermore, we demonstrate workloads where the additional memory improves macrobenchmark performance by a factor of two.