gebhart/patrepeval huggingface dataset:
Nucleotide excision repair rates in rat tissues (2003)

We have determined and compared nucleotide excision repair capability of several rat tissues by a method based on restoration of the transformation activity of UV-irradiated pBlueScript by incubation in repair-competent protein extracts. After 3 h of incubation, plasmid DNA was isolated and used to transform competent Escherichia coli cells. Damaged plasmids showed low transformation efficiency prior to incubation in repair-competent extracts. After incubation the transformation efficiency was restored to different extents permitting calculation of the repair capacity of the extracts. Our results showed that rapidly proliferating tissues such as liver, kidney and testis showed higher nucleotide excision repair capacity than slowly proliferating tissues such as heart, muscle, lung and spleen. When liver and splenocytes were stimulated to proliferation by partial hepatectomy and mitogen stimulation, their repair capability increased in parallel with the respective proliferative rates.
Effect of lactoferrin on interaction of Prevotella intermedia with plasma and subepithelial matrix proteins (1994)

A lactoferrin-binding protein with an estimated molecular mass of 57 kDa was identified in the cell envelope of Prevotella intermedia by gel electrophoresis and Western-blot analysis. Peroxidase-labeled bovine lactoferrin and human lactoferrin showed similar specific binding to this protein. Whole cells of P. intermedia were also examined for interactions with 5 125I-labeled plasma and subepithelial matrix proteins. A high degree of binding was found with fibronectin, collagen type I and type IV and laminin, whereas a moderate interaction was detected with fibrinogen. The ability of bovine lactoferrin to affect the interactions of the above proteins with P. intermedia was examined. In the presence of unlabeled bovine lactoferrin, a dose-dependent inhibition of binding was observed with all 5 proteins tested. Unlabeled bovine lactoferrin also dissociated the bacterial complexes with these proteins. The complexes with laminin or collagen type I were more effectively dissociated than fibronectin or fibrinogen, whereas the interaction with collagen type IV was affected to a lesser extent. A strain-dependent variation in the effect of bovine lactoferrin was observed. These data establish the presence of a specific lactoferrin-binding protein in the cell envelope of P. intermedia. The ability of lactoferrin to inhibit the binding of some plasma and subepithelial matrix proteins to P. intermedia could be a protective mechanism against the establishment of this pathogen in the periodontal pocket.
Impact of donor type on outcome of bone marrow transplantation for Wiskott-Aldrich syndrome: collaborative study of the International Bone Marrow Transplant Registry and the National Marrow Donor Program (2001)

Human leukocyte antigen (HLA)-identical sibling bone marrow transplantation is an effective treatment for Wiskott-Aldrich syndrome. However, most children with this disease lack such donors and many patients receive transplants from alternative donors. This study compared outcomes of HLA-identical sibling, other related donor, and unrelated donor transplantation for Wiskott-Aldrich syndrome. The outcome of 170 transplantations for Wiskott-Aldrich syndrome, from 1968 to 1996, reported to the International Bone Marrow Transplant Registry and/or National Marrow Donor Program were assessed. Fifty-five were from HLA-identical sibling donors, 48 from other relatives, and 67 from unrelated donors. Multivariate proportional hazards regression was used to compare outcome by donor type and identify other prognostic factors. Most transplant recipients were younger than 5 years (79%), had a pretransplantation performance score greater than or equal to 90% (63%), received pretransplantation preparative regimens without radiation (82%), and had non-T-cell-depleted grafts (77%). Eighty percent received their transplant after 1986. The 5-year probability of survival (95% confidence interval) for all subjects was 70% (63%-77%). Probabilities differed by donor type: 87% (74%-93%) with HLA-identical sibling donors, 52% (37%-65%) with other related donors, and 71% (58%-80%) with unrelated donors (P =.0006). Multivariate analysis indicated significantly lower survival using related donors other than HLA-identical siblings (P =.0004) or unrelated donors in boys older than 5 years (P =.0001), compared to HLA-identical sibling transplants. Boys receiving an unrelated donor transplant before age 5 had survivals similar to those receiving HLA-identical sibling transplants. The best transplantation outcomes in Wiskott-Aldrich syndrome are achieved with HLA-identical sibling donors. Equivalent survivals are possible with unrelated donors in young children.
Chronic disease long‐term drug prevention trials: Lessons from the Alzheimer's Disease Anti‐inflammatory Prevention Trial (ADAPT) (2007)

A randomized trial is a randomized trial. The basic ingredients do not change with different purposes whether for treatment or prevention of disease. Likewise, the problems and difficulties are mostly the same. But there are differences in approach and philosophy. Here we discuss problems in trials focused on healthy people to determine whether drugs can delay or prevent adverse health events, with the Alzheimer's Disease Anti-inflammatory Prevention Trial (ADAPT) as an example. An important difference separating treatment trials from prevention trials is the length of time needed to demonstrate a difference with treatment. Related to this is the risk-benefit calculus of the trial. Treatment trials are aimed at "curing" or ameliorating disease, for example, as with trials involving people with Alzheimer's disease (AD) dementia to determine whether treatment is useful in dealing with the AD-induced dementia. Like other treatment trials, those targeting AD dementia balance these benefits against the risks of treatment. But by contrast, benefit in prevention trials, if any, will be found only in the absence or delay in disease onset, often after years of continuous treatment. As in ADAPT, the separation in timing of risk versus benefit often brings difficult decisions about how long to continue the trial in the absence of any apparent benefit to treatment. Other difficulties similarly relate to the length of prevention trials. In hopes that some lessons learned from ADAPT will assist future prevention trials, especially in the elderly, we describe several conundrums and problems experienced in this trial and attempt when possible to extend our observations to the larger class of long-term drug prevention trials.
Send in the Cyborgs (2009)

Research Article| March 01 2009 Send in the Cyborgs Rob White Rob White Search for other works by this author on: This Site PubMed Google Scholar Film Quarterly (2009) 62 (3): 4–7. https://doi.org/10.1525/fq.2009.62.3.4 Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Twitter LinkedIn Tools Icon Tools Get Permissions Cite Icon Cite Search Site Citation Rob White; Send in the Cyborgs. Film Quarterly 1 March 2009; 62 (3): 4–7. doi: https://doi.org/10.1525/fq.2009.62.3.4 Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu nav search search input Search input auto suggest search filter All ContentFilm Quarterly Search This content is only available via PDF. ©© 2009 by the Regents of the University of California.2009 Article PDF first page preview Close Modal You do not currently have access to this content.
A Bispecific Diabody That Mediates Natural Killer Cell Cytotoxicity Against Xenotransplantated Human Hodgkin’s Tumors (1999)

CD16/CD30 bispecific monoclonal antibodies can induce remissions of Hodgkin's disease refractory to chemo- and radiotherapy. However, the development of human antimouse immunoglobulin antibodies and allergic reactions precludes repeated applications of the antibody. Moreover, problems of producing and purifying sufficient amounts of material limit the clinical practicability of this novel treatment approach. To overcome these obstacles, we have constructed a bispecific antibody in a diabody form that only employs the variable domains of the CD16/CD30 hybrid hybridoma. The diabody compared favorably with the parent CD16/CD30 bispecific antibody in its ability to activate and target natural killer cells in vitro. Its administration to mice bearing xenografted Hodgkin's lymphoma resulted in a marked regression of tumor growth, thus proving for the first time the capability of a diabody for immune recruitment in vivo. The CD16/CD30 diabody is a novel reagent that should considerably facilitate the immunotherapy of patients with refractory Hodgkin's lymphoma.
Neural Symbolic Machines: Learning Semantic Parsers on Freebase with Weak Supervision (2017)

Harnessing the statistical power of neural networks to perform language understanding and symbolic reasoning is difficult, when it requires executing efficient discrete operations against a large knowledge-base. In this work, we introduce a Neural Symbolic Machine (NSM), which contains (a) a neural "programmer", i.e., a sequence-to-sequence model that maps language utterances to programs and utilizes a key-variable memory to handle compositionality (b) a symbolic "computer", i.e., a Lisp interpreter that performs program execution, and helps find good programs by pruning the search space. We apply REINFORCE to directly optimize the task reward of this structured prediction problem. To train with weak supervision and improve the stability of REINFORCE we augment it with an iterative maximum-likelihood training process. NSM outperforms the state-of-theart on the WEBQUESTIONSSP dataset when trained from question-answer pairs only, without requiring any feature engineering or domain-specific knowledge.
Different affinity windows for virus and cancer‐specific T‐cell receptors: Implications for therapeutic strategies (2012)

T-cell destiny during thymic selection depends on the affinity of the TCR for autologous peptide ligands presented in the context of MHC molecules. This is a delicately balanced process; robust binding leads to negative selection, yet some affinity for the antigen complex is required for positive selection. All TCRs of the resulting repertoire thus have some intrinsic affinity for an MHC type presenting an assortment of peptides. Generally, TCR affinities of peripheral T cells will be low toward self-derived peptides, as these would have been presented during thymic selection, whereas, by serendipity, binding to pathogen-derived peptides that are encountered de novo could be stronger. A crucial question in assessing immunotherapeutic strategies for cancer is whether natural TCR repertoires have the capacity for efficiently recognizing tumor-associated peptide antigens. Here, we report a comprehensive comparison of TCR affinities to a range of HLA-A2 presented antigens. TCRs that bind viral antigens fall within a strikingly higher affinity range than those that bind cancer-related antigens. This difference may be one of the key explanations for tumor immune escape and for the deficiencies of T-cell vaccines against cancer.
In Vivo Microdialysis Study of the Penetration of Daptomycin into Soft Tissues in Diabetic versus Healthy Volunteers (2008)

Daptomycin is approved for the treatment of complicated skin and soft tissue infections, including diabetic wounds of the lower extremities, at a dose of 4 mg/kg of body weight once daily. For such localized tissue infections, drug concentrations in the interstitial space are an important determinant of successful therapy. In the diabetic population, peripheral arterial disease may limit antibiotic penetration into the target tissue. The objective of this study was to describe and compare the pharmacokinetic profiles of daptomycin in the interstitial fluid of soft tissues in diabetic and healthy volunteers by using in vivo microdialysis. Twelve subjects (six diabetic and six healthy) received a single 4-mg/kg dose of daptomycin intravenously. Samples of plasma and tissue were simultaneously collected over 24 h. Diabetic and healthy groups were matched in mean age (+/-10 years), gender ratio, mean weight (+/-10 kg), and creatinine clearance rate (+/-20 ml/min/1.73 m(2)). Pharmacokinetic parameters for plasma were similar between groups (P > 0.05). The mean peak drug concentrations +/- standard deviations in tissue were 4.3 +/- 3.3 microg/ml and 3.8 +/- 1.4 microg/ml for diabetic and healthy subjects, respectively. The degree of tissue penetration, defined as the ratio of the area under the free drug concentration-time curve for tissue to that for plasma, was 0.93 +/- 0.61 for diabetic subjects and 0.74 +/- 0.09 for healthy subjects (P = 0.46). Daptomycin at 4 mg/kg penetrated well into the soft tissue, reaching concentrations approximately 70 to 90% of those of the free drug in plasma. Moreover, these free, bioactive concentrations in tissue exceeded the MICs for staphylococci and streptococci over the 24-h dosing interval.
Vacuum-assisted closure for fasciotomy wounds following compartment syndrome of the leg. (2006)

This study evaluated the efficacy of vacuum-assisted closure (VAC) for treatment of fasciotomy wounds for traumatic compartment syndrome. The authors reviewed the records of a consecutive series of 34 patients who had compartment syndrome of the leg requiring the standard two-incision release of all four compartments and received the application of VAC therapy until the time of definitive wound closure or coverage. A matched series of 34 consecutive antecedent patients with the same entry criteria, except for the use of the VAC, were also studied and served as a control group. The main parameter of interest was the time to "definitive closure" (delayed primary closure with sutures or skin graft coverage) of the wounds. Of the 68 wounds in 34 patients managed with VAC, the average time to definitive closure for both the lateral and the medial wounds was 6.7 days. For the 70 wounds in the 34 control patients, the average time to definitive closure was 16.1 days. This difference in time to wound closure between the VAC group and the non-VAC group was statistically significant (p < .05). Subatmospheric treatment for compartment syndrome of the leg after fasciotomy theoretically helps to speed the resolution of the swelling and tissue edema that are often components of this clinical entity. Experimental work has shown vacuum-assisted wound management to be effective in hastening the resolution of wound edema, enhancing local blood flow, promoting granulation tissue, and thwarting bacterial colonization. These factors may account for its utility in the management of fasciotomy wounds in the setting of compartment syndrome of the leg.
Formate hydrogenlyase in the hyperthermophilic archaeon, Thermococcus litoralis (2008)

The formate dehydrogenase together with the membrane-bound [NiFe] hydrogenase formed a formate hydrogenlyase (formate dehydrogenase coupled hydrogenase, FDH-MHY) complex. The expression data suggested that its physiological role is linked to the removal of formate likely generated during anaerobic peptide fermentation.
Human Induced Pluripotent Stem Cells on Autologous Feeders (2009)

These results suggest that autologous fibroblasts can be not only a source for iPS cells but also be feeder layers. Our results provide a possibility to solve the dilemma by using isogenic fibroblasts as feeder layers of iPS cells. This is an important step toward the establishment of clinical grade iPS cells.
System on chip design methodology applied to system in package architecture (2003)

There are two competing technologies pursuing the 'holy grail' of complete system integration. Today, the most common method used to create the 'system' is to mount separately packaged ICs on a next-level substrate. Even with a low pin count, a package is typically several times larger than the IC, to accommodate the low wiring density on the PCB. High-performance systems, such as network processor systems, require high data bandwidth between key components and thus need an increased number of signal I/Os. Wide I/O busses switching at high speeds consequently require a larger number of power and ground pins to reduce switching noise. As a result, system performance is limited by increasing package size and the associated parasitic inductance and capacitance of the package and its connection on the PCB. System on chip (SoC) architecture attempts to integrate many functions, both analog and digital into a monolithic device. The successes are many, but so are the challenges. Many functions cannot be optimized due to the limitation of the semiconductor substrate used. Also, as defect density scales with area, the notion of integrating large scale functions (memory, switch fabrics) with small scale functions (rf devices) results in compounded yield impacts. System in Package (SiP) technology allows heterogeneous devices to be integrated into a small form factor. The integration technology includes embedded devices in the substrate and 3 dimensional chip-stacking approaches. By using a silicon based SiP, a copper/low K interconnect defined by lithographic processes on silicon offers very dense routing with high speed, low noise signal paths. The ICs used in the SiP can be designed to leverage the high density interconnect by optimizing both the core and the I/O of each device. Additionally, specialized devices can be designed specifically for the SiP architecture to take advantage of the high bandwidth and low latency features. Reducing chip-to-chip bus capacitance can dramatically decrease system power requirements and thermal dissipation. The lower bus power can be traded against higher bus frequency to improve performance at a fixed power level.
Web interfaces for mobile robots in public places (2000)

The growth of the World Wide Web provides unique opportunities to bring robots closer to people. The vision behind such endeavors ranges from relatively simple web-based inspections and surveillance applications to highly versatile applications that use robots connected to the web to establish a remote telepresence in dynamic and populated environments. In the latter scenario, robots play the role of a physical mediator, enabling remote people to acquire information, explore, manipulate, communicate, and interact physically with people far away. The article describes a series of web interfaces designed to remotely operate mobile robots in public places through the web. The design of these interfaces specifically addresses issues such as low bandwidth of interconnections, control brokering, and shared control as well as interaction with people in the robot's environment, which arise naturally in applications with web-based robot control. The interfaces have been tested extensively using two deployed service robots, which were installed as interactive tour guides in two museums. The article also discusses trade-offs and limitations of web-based robots that interact with people in populated public places.
Isolation and characterization of human bone marrow microvascular endothelial cells: hematopoietic progenitor cell adhesion (1994)

To examine potential mechanisms by which hematopoiesis may be regulated by endothelial cells within the bone marrow (BM) microenvironment, we have devised a technique for the in vitro study of the interaction of human BM microvascular endothelial cells (BMEC) with hematopoietic cells. Microvessels isolated by collagenase digestion of spicules obtained from filtered BM aspirate were plated on gelatin-coated plastic dishes, and colonies of endothelial cells grown from microvessel explants were further purified by Ulex europaeus lectin affinity separation. BMEC monolayers isolated by this technique grew in typical cobblestone fashion, stained positively with antibody to factor VIII/von Willebrand factor, and incorporated acetylated LDL. Immunohistochemical studies showed that BM microvessels and BMEC monolayers express CD34, PECAM, and thrombospondin. Incubation of resting BMEC with BM mononuclear hematopoietic cells resulted in the selective adhesion of relatively large numbers of CD34+ progenitor cells and megakaryocytes. The binding of purified BM-derived CD34+ progenitor cells to BMEC was dependent on divalent cations and was partially blocked by antibodies to CD34. IL-1 beta treatment of BMEC monolayers resulted in an increase of CD34+ progenitor cell adhesion by mechanisms independent of CD34 or divalent cations. BMEC exhibit specific affinity for CD34+ progenitor cells and megakaryocytes, suggesting that the BM microvasculature may play a role in regulating the trafficking, proliferation, and differentiation of lineage specific hematopoietic elements, and possibly of pluripotent stem cells within the CD34+ population.
Synthesis of Recombinant Peptides (1994)

The development of recombinant methods to clone and express genes of one organism in another organism has been one of the greatest advances in biology. More recently, refined methodologies have been utilized to clone and express peptides of diverse complexities into a variety of organisms.
Prominent role of TGF-β1 in thrombopoietin-induced myelofibrosis in mice (2002)

Several studies suggest an implication of transforming growth factor-beta1 (TGF-beta1) in the promotion of myelofibrosis associated with hematopoietic malignancies, but the involvement of this cytokine is not fully investigated. To test directly the impact of TGF-beta1 in the pathogenesis of myelofibrosis, bone marrow stem cells from homozygous TGF-beta1 null (TGF-beta1(-/-)) and wild-type (WT) littermates were infected with a retrovirus encoding the murine thrombopoietin (TPO) protein and engrafted into lethally irradiated wild-type hosts for long-term reconstitution. Over the 4 months of follow-up, TPO levels in plasma were markedly elevated in both groups of mice, and animals typically developed a myeloproliferative syndrome characterized by thrombocytosis, leukocytosis, splenomegaly, increased numbers of progenitors in blood, and extramedullary hematopoiesis. Severe fibrosis was observed in spleen and marrow from all the mice engrafted with WT cells. In contrast, none of the mice repopulated with TGF-beta1(-/-) cells (chimerism > 70%) showed deposition of reticulin fibers at any time during the follow-up. In accordance with the development of fibrosis, latent TGF-beta1 levels in plasma and extracellular fluid of the spleen from mice engrafted with WT cells were increased 6-fold and 4-fold, respectively, over levels found in normal hosts, whereas no increase over baseline levels could be demonstrated in animals undergoing transplantation with TGF-beta1(-/-) cells. These data provide evidence that TGF-beta1 produced by hematopoietic cells is pivotal for the pathogenesis of myelofibrosis that develops in mice with TPO overexpression.