gebhart/patrepeval huggingface dataset:
IMC-C225, an anti-epidermal growth factor receptor monoclonal antibody, for treatment of head and neck cancer (2001)

Squamous cell carcinoma (SCC) of the head and neck (H&N) remains a clinical challenge due to its high rate of locoregional disease recurrence. The importance of the epidermal growth factor receptor (EGFR) in the development and progression of many solid tumours (including SCC of the H&N) is well understood; increased expression is associated with enhanced tumour invasion, resistance to chemotherapy and decreased patient survival. Several approaches have been developed to achieve EGFR blockade as an anticancer treatment strategy, including an anti-EGFR monoclonal antibody (mAb), IMC-C225, which competitively binds to the extracellular receptor site to prevent binding by natural EGFR ligands (EGF and TGF-alpha). Preclinical studies evaluating this chimeric mAb in human cancer cell lines in vitro and human tumour xenografts in vivo have demonstrated its potent antitumour activity. The clinical efficacy of IMC-C225 appears to involve multiple anticancer mechanisms, including inhibition of cell cycle progression, induction of apoptosis, anti-angiogenesis, inhibition of metastasis and its ability to enhance the response to chemotherapy and radiation therapy. Phase I studies of IMC-C225 combined with chemotherapy or radiation for SCC of the H&N demonstrate excellent response rates in patients with recurrent or refractory disease. Phase II and III trials examining the efficacy and safety of these combinations are currently underway. To date, IMC-C225 has been well-tolerated, with skin rashes and allergic reactions being the most clinically important adverse events reported. IMC-C225 displays dose-dependent elimination characteristics and a half-life of approximately 7 days. Current recommendations for dosing include a 400 mg/m2 loading dose, followed by weekly infusions of 250 mg/m2.
Importance of software component characterization for better software reusability (2006)

Component-based software development (CBSD) is the process of assembling existing software components in an application such that they interact to satisfy a predefined functionality. This approach can potentially be used to reduce software development costs, assemble systems rapidly, and reduce the maintenance overhead. One of the key challenges faced by software developers is to make component-based development (CBD) an efficient and effective approach. Since components are to be reused across various products and product-families, components must be characterized and tested properly. The present paper is a survey paper and firstly, it discusses CBD and related issues that help improving software reuse. Testing of third party components is a very difficult task in the absence a properly characterized software component. Besides improving software reusability, component characterization also provides better understanding of architecture, better retrieval, better usage and better cataloguing. This paper mainly discusses the essence of proper component characterization that ultimately helps the developers in software reuse, which is highly desirable in component-based software development. Further, paper also discusses other benefits of component characterization that are most essential in component-based development.
Rupture of Polyacrylamide Gel in a Tube in Response to Aqueous Pressure Gradients (2009)

Hydro‐gel and the evolution of its strength as the gel matures from the state of aqueous fluid to the state of viscoelastic solid provides opportunity to employ hydro‐gel in certain critical applications, such as sealing of fractures or high permeability streaks in a hydrocarbon reservoir. The mature gel, inside the channel, helps in diverting the injected water into an un‐swept oil bearing zone. For the gel treatment to be effective, the gel layer inside the channel has to resist failure under water pressure. This article describes evaluation of the strength of Cr(III)–partially hydrolyzed polyacrylamide gel, formed in transparent tubes. A pressure gradient was imposed on the gel by injecting water on one end of the tube, leaving the other end open to atmosphere. Pressure gradient that increased with time caused shear deformation, and bulging of gel at the outlet end of the tube. At a threshold pressure, the deformation culminated to a rupture at the center of the gel, and subsequent burst of water through the outlet. Rupture was visualized using colored water that fingered through the center of the gel, leaving the rest of the gel intact. Rupture pressure, similar to the ultimate strength of a material, is defined for the gel layer. The rupture pressure was found to increase with the length, and decrease with the width of aperture. A theoretical model in support of this trend is presented here. When the pressure was built up fast, the rupture took place at a much smaller pressure. In case of pressure build‐up over a long period of time, rupture pressure became independent of the duration of build‐up. The effect of the rate of pressure build‐up is analyzed using the concept of viscoelasticity. Also, the rupture model is extended to the situations where the porous media hinder the free movement of gel at the outlet, and allow partial movement of gel laterally through the surrounding wall.
Histone deacetylase 6 interacts with the microtubule‐associated protein tau (2008)

Histone deacetylase 6 (HDAC6), a unique cytoplasmic deacetylase, likely plays a role in neurodegeneration by coordinating cell responses to abnormal protein aggregation. Here, we provide in vitro and in vivo evidence that HDAC6 interacts with tau, a microtubule-associated protein that forms neurofibrillary tangles in Alzheimer's disease. This interaction is mediated by the microtubule-binding domain on tau and the Ser/Glu tetradecapeptide domain on HDAC6. Treatment with tubacin, a selective inhibitor of tubulin deacetylation activity of HDAC6, did not disrupt HDAC6-tau interaction. Nonetheless tubacin treatment attenuated site-specific tau phosphorylation, as did shRNA-mediated knockdown of HDAC6. Proteasome inhibition potentiated HDAC6-tau interactions and facilitated the concentration and co-localization of HDAC6 and tau in a perinuclear aggresome-like compartment, independent of HDAC6 tubulin deacetylase activity. Furthermore, we observed that in Alzheimer's disease brains the protein level of HDAC6 was significantly increased. These findings establish HDAC6 as a tau-interacting protein and as a potential modulator of tau phosphorylation and accumulation.
Protocol Operations for Version 2 of the Simple Network Management Protocol (SNMPv2) (1996)

This document specifies an Internet standards track protocol for the Internet community, and requests discussion and suggestions for improvements. Please refer to the current edition of the "Internet Official Protocol Standards" (STD 1) for the standardization state and status of this protocol. Distribution of this memo is unlimited.
Enhanced Anti-influenza Agents Conjugated with Anti-inflammatory Activity (2012)

Influenza therapy with a single targeted compound is often limited in efficacy due to the rapidly developed drug resistance. Moreover, the uncontrolled virus-induced cytokines could cause the high mortality of human infected by H5N1 avian influenza virus. In this study, we explored the novel dual-targeted bifunctional anti-influenza drugs formed by conjugation with anti-inflammatory agents. In particular, the caffeic acid (CA)-bearing zanamivir (ZA) conjugates ZA-7-CA (1) and ZA-7-CA-amide (7) showed simultaneous inhibition of influenza virus neuraminidase and suppression of pro-inflammatory cytokines. These ZA conjugates provided remarkable protection of cells and mice against influenza infections. Intranasal administration of low dosage (<1.2 μmol/kg/day) of ZA conjugates exhibited much greater effect than the combination therapy with ZA and the anti-inflammatory agents in protection of the lethally infected mice by H1N1 or H5N1 influenza viruses.
Gram negative species associated with active destructive periodontal lesions (1985)

Apical subgingival plaque samples were taken from 19 subjects exhibiting active destructive periodontal disease. The predominant cultivable Gram negative species from 50 active sites were compared to 69 inactive sites of comparable pocket depth and attachment level loss. Active disease sites were chosen which showed a significant loss of attachment within a two-month interval. Proportions of Gram negative rods were higher in active periodontal disease sites than in inactive sites. Species which were found to be significantly elevated only in active sites were Bacteroides intermedius, "fusiform" Bacteroides, Actinobacillus actinomycetemcomitans and Wolinella recta. Fusobacterium nucleatum, Capnocytophaga gingivalis and Eikenella corrodens were found in significantly increased proportions in active sites of some subjects and inactive sites of others.
Temporal stability of adaptive 3D radial MRI using multidimensional golden means (2009)

Breast tumor diagnosis requires both high spatial resolution to obtain information about tumor morphology and high temporal resolution to probe the kinetics of contrast uptake. Adaptive sampling of k-space allows images in dynamic contrast-enhanced (DCE)-magnetic resonance imaging (MRI) to be reconstructed at various spatial or temporal resolutions from the same dataset. However, conventional radial approaches have limited flexibility that restricts image reconstruction to predetermined resolutions. Golden-angle radial k-space sampling achieves flexibility in-plane with samples that are incremented by the golden angle, which fills two-dimensional (2D) k-space with radial spokes that have a relatively uniform angular distribution for any time interval. We extend this method to three-dimensional (3D) radial sampling, or 3D-Projection Reconstruction (3D-PR) using multidimensional golden means, which are derived from modified Fibonacci sequences by an eigenvalue approach. We quantitatively compare this technique to conventional 3D radial methods in terms of the fluctuation in error caused by undersampling artifacts, and show that the golden 3D-PR method can substantially improve the temporal stability of quantitative measurements made from dynamic images when compared to conventional 3D radial approaches of k-space sampling.
Ataluren (PTC124) Induces Cystic Fibrosis Transmembrane Conductance Regulator Protein Expression and Activity in Children with Nonsense Mutation Cystic Fibrosis (2010)

In children with nonsense mutation CF, ataluren can induce functional CFTR production and is well tolerated.
PINK1 Is Necessary for Long Term Survival and Mitochondrial Function in Human Dopaminergic Neurons (2008)

Parkinson's disease (PD) is a common age-related neurodegenerative disease and it is critical to develop models which recapitulate the pathogenic process including the effect of the ageing process. Although the pathogenesis of sporadic PD is unknown, the identification of the mendelian genetic factor PINK1 has provided new mechanistic insights. In order to investigate the role of PINK1 in Parkinson's disease, we studied PINK1 loss of function in human and primary mouse neurons. Using RNAi, we created stable PINK1 knockdown in human dopaminergic neurons differentiated from foetal ventral mesencephalon stem cells, as well as in an immortalised human neuroblastoma cell line. We sought to validate our findings in primary neurons derived from a transgenic PINK1 knockout mouse. For the first time we demonstrate an age dependent neurodegenerative phenotype in human and mouse neurons. PINK1 deficiency leads to reduced long-term viability in human neurons, which die via the mitochondrial apoptosis pathway. Human neurons lacking PINK1 demonstrate features of marked oxidative stress with widespread mitochondrial dysfunction and abnormal mitochondrial morphology. We report that PINK1 plays a neuroprotective role in the mitochondria of mammalian neurons, especially against stress such as staurosporine. In addition we provide evidence that cellular compensatory mechanisms such as mitochondrial biogenesis and upregulation of lysosomal degradation pathways occur in PINK1 deficiency. The phenotypic effects of PINK1 loss-of-function described here in mammalian neurons provides mechanistic insight into the age-related degeneration of nigral dopaminergic neurons seen in PD.
Nitrated alpha‐synuclein‐activated microglial profiling for Parkinson’s disease (2007)

Microglial neuroinflammatory processes play a primary role in dopaminergic neurodegeneration for Parkinson's disease (PD). This can occur, in part, by modulation of glial function following activation by soluble or insoluble modified alpha-synuclein (alpha-syn), a chief component of Lewy bodies that is released from affected dopaminergic neurons. alpha-Syn is nitrated during oxidative stress responses and in its aggregated form, induces inflammatory microglial functions. Elucidation of these microglial function changes in PD could lead to new insights into disease mechanisms. To this end, PD-associated inflammation was modeled by stimulation of microglia with aggregated and nitrated alpha-syn. These activated microglia were ameboid in morphology and elicited dopaminergic neurotoxicity. A profile of nitrated, aggregated alpha-syn-stimulated microglia was generated using combinations of genomic (microarrays) and proteomic (liquid chromatography-tandem mass spectrometry, differential gel electrophoresis, and protein array) assays. Genomic studies revealed a substantive role for nuclear factor-kappa B transcriptional activation. Qualitative changes in the microglial proteome showed robust increases in inflammatory, redox, enzyme, and cytoskeletal proteins supporting the genomic tests. Autopsy brain tissue acquired from substantia nigra and basal ganglia of PD patients demonstrated that parallel nuclear factor-kappa B-related inflammatory processes were, in part, active during human disease. Taken together, the transcriptome and proteome of nitrated alpha-syn activated microglia, shown herein, provide new potential insights into disease mechanisms.
Filgrastim Improves Survival in Lethally Irradiated Nonhuman Primates (2012)

Leukocyte growth factors (LGF), such as filgrastim, pegfilgrastim and sargramostim, have been used to mitigate the hematologic symptoms of acute radiation syndrome (ARS) after radiation accidents. Although these pharmaceuticals are currently approved for treatment of chemotherapy-induced myelosuppression, such approval has not been granted for myelosuppression resulting from acute radiation exposure. Regulatory approval of drugs used to treat radiological or nuclear exposure injuries requires their development and testing in accordance with the Animal Efficacy Rule, set forth by the U.S. Food and Drug Administration. To date, filgrastim is the only LGF that has undergone efficacy assessment conducted under the Animal Efficacy Rule. To confirm the efficacy of another LGF with a shorter dosing regimen compared to filgrastim, we evaluated the use of pegfilgrastim (Neulasta(®)) in a lethal nonhuman primate (NHP) model of hematopoietic acute radiation syndrome (H-ARS). Rhesus macaques were exposed to 7.50 Gy total-body irradiation (the LD(50/60)), delivered at 0.80 Gy/min using linear accelerator 6 MV photons. Pegfilgrastim (300 μg/kg, n = 23) or 5% dextrose in water (n = 23) was administered on day 1 and 8 postirradiation and all animals received medical management. Hematologic and physiologic parameters were evaluated for 60 days postirradiation. The primary, clinically relevant end point was survival to day 60; secondary end points included hematologic-related parameters. Pegfilgrastim significantly (P = 0.0014) increased 60 day survival to 91.3% (21/23) from 47.8% (11/23) in the control. Relative to the controls, pegfilgrastim also significantly: 1. decreased the median duration of neutropenia and thrombocytopenia; 2. improved the median time to recovery of absolute neutrophil count (ANC) ≥500/μL, ANC ≥1,000/μL and platelet (PLT) count ≥20,000/μL; 3. increased the mean ANC at nadir; and 4. decreased the incidence of Gram-negative bacteremia. These data demonstrate that pegfilgrastim is an additional medical countermeasure capable of increasing survival and neutrophil-related parameters when administered in an abbreviated schedule to a NHP model of lethal H-ARS.
Alzheimer's disease: current knowledge, management and research. (1997)

Alzheimer's disease is a common neurological condition, appearing as early as age 40 but increasing dramatically in incidence over age 85. Different genetic factors are at play, modified by events over a lifetime. Clinical diagnosis is possible through careful history taking with a reliable informant and a minimum number of laboratory tests. A relatively predictable natural history can be observed, with progression through stages of cognitive loss, functional impairment and behavioural disinhibition or apathy. New medications such as donepezil offer hope for improving or stabilizing symptoms. Such treatment can be administered by primary care physicians with experience in the diagnosis and management of Alzheimer's disease. Disease stabilization, or even prevention, may be possible in the future.
COMPARATIVE MOLECULAR BIOLOGY OF LAMBDOID PHAGES (1994)

Lambdoid phages are natural relatives of phage lambda. As a group, they are highly polymorphic in DNA sequence and biological specificity. Specificity differences have played a key role in identifying the specific sequences recognized by the N and Q antitermination proteins, the initiator O for DNA synthesis, the terminase system Nv1-A for cutting DNA during packaging, and the cI repressor protein. Variations that go beyond specificity differences are seen in packaging mechanism (headful in P22, specific cutting in lambdoid coliphages), in early control (terminator protein and phage-independent antitermination in HK022, phage-specific antitermination in lambda), in repression control (antirepressor operon in P22, absent in other lambdoid phages) and murein-degrading enzymes (transglycosylase in lambda, lysozyme in other lambdoid phages). Sequence comparisons indicate that recombination among lambdoid phages is frequent in nature.
Investigation of the performance of the General Electric ADVANCE positron emission tomograph in 3D mode (1996)

Performance measurements of the General Electric ADVANCE Positron Emission Tomograph operating with the septa retracted (3D mode) were made. All reconstructions were performed with the GE ADVANCE 3D package. Performance tests were carried out with: the NEMA phantoms; a 3D Hoffman phantom; a Data Spectrum torso phantom with lung and cardiac inserts; and the "Utah" 3D evaluation phantom. Data collected included: transaxial and axial resolution, uniformity, recovery coefficients, count rate performance, dead time accuracy, and effect of scatter correction.
Derivation of Insulin-Producing Beta-Cells from Human Pluripotent Stem Cells (2014)

Human embryonic stem cells have been advanced as a source of insulin-producing cells that could potentially replace cadaveric-derived islets in the treatment of type 1 diabetes. To this end, protocols have been developed that promote the formation of pancreatic progenitors and endocrine cells from human pluripotent stem cells, encompassing both embryonic stem cells and induced pluripotent stem cells. In this review, we examine these methods and place them in the context of the developmental and embryological studies upon which they are based. In particular, we outline the stepwise differentiation of cells towards definitive endoderm, pancreatic endoderm, endocrine lineages and the emergence of functional beta-cells. In doing so, we identify key factors common to many such protocols and discuss the proposed action of these factors in the context of cellular differentiation and ongoing development. We also compare strategies that entail transplantation of progenitor populations with those that seek to develop fully functional hormone expressing cells in vitro. Overall, our survey of the literature highlights the significant progress already made in the field and identifies remaining deficiencies in developing a pluripotent stem cell based treatment for type 1 diabetes.
Cloning and Characterization of a Lymphoid-Specific, Inducible Human Protein Tyrosine Phosphatase, Lyp (1999)

Protein tyrosine phosphatases act in conjunction with protein kinases to regulate the tyrosine phosphorylation events that control cell activation and differentiation. We have isolated a previously undescribed human phosphatase, Lyp, that encodes an intracellular 105-kD protein containing a single tyrosine phosphatase catalytic domain. The noncatalytic domain contains four proline-rich potential SH3 domain binding sites and an NXXY motif that, if phosphorylated, may be recognized by phosphotyrosine binding (PTB) domains. Comparison of the Lyp amino acid sequence with other known proteins shows 70% identity with the murine phosphatase PEP. The human Lyp gene was localized to chromosome 1p13 by fluorescence in situ hybridization analysis. We also identified an alternative spliced form of Lyp RNA, Lyp2. This isoform encodes a smaller 85-kD protein with an alternative C-terminus. The lyp phosphatases are predominantly expressed in lymphoid tissues and cells, with Lyp1 being highly expressed in thymocytes and both mature B and T cells. Increased Lyp1 expression can be induced by activation of resting peripheral T lymphocytes with phytohemagglutinin or anti-CD3. Lyp1 was found to be constitutively associated with the proto-oncogene c-Cbl in thymocytes and T cells. Overexpression of lyp1 reduces Cbl tyrosine phosphorylation, suggesting that it may be a substrate of the phosphatase. Thus, Lyp may play a role in regulating the function of Cbl and its associated protein kinases.
Bimetal Strip Hydrogen Gas Detectors (1969)

It is shown that bimetal strips which use palladium—silver alloys as the active component are sensitive detectors of gaseous hydrogen. Concentrations of hydrogen in STP nitrogen as low as 50 ppm have been detected with this technique. Fast response times are obtained at bimetal strip operating temperatures of 200–300°C. The experimentally observed steady state behavior of these strips is in good agreement with theory.
Nuclear Entry of Activated MAPK Is Restricted in Primary Ovarian and Mammary Epithelial Cells (2010)

ERK1/2 activation is dissociated from nuclear entry, which is a rate limiting step in primary cells and in vivo, and the restriction of nuclear entry is disrupted in transformed cells by the increased expression of nuclear pores and/or nuclear transport factors.