gebhart/patrepeval huggingface dataset:
Survival and low-grade glioma: the emergence of genetic information (2015)

Significant gaps exist in our understanding of the causes and clinical management of glioma. One of the biggest gaps is how best to manage low-grade (World Health Organization [WHO] Grade II) glioma. Low-grade glioma (LGG) is a uniformly fatal disease of young adults (mean age 41 years), with survival averaging approximately 7 years. Although LGG patients have better survival than patients with high-grade (WHO Grade III or IV) glioma, all LGGs eventually progress to high-grade glioma and death. Data from the Surveillance, Epidemiology and End Results (SEER) program of the National Cancer Institute suggest that for the majority of LGG patients, overall survival has not significantly improved over the past 3 decades, highlighting the need for intensified study of this tumor. Recently published research suggests that historically used clinical variables are not sufficient (and are likely inferior) prognostic and predictive indicators relative to information provided by recently discovered tumor markers (e.g., 1p/19q deletion and IDH1 or IDH2 mutation status), tumor expression profiles (e.g., the proneural profile) and/or constitutive genotype (e.g., rs55705857 on 8q24.21). Discovery of such tumor and constitutive variation may identify variables needed to improve randomization in clinical trials as well as identify patients more sensitive to current treatments and targets for improved treatment in the future. This article reports on survival trends for patients diagnosed with LGG within the United States from 1973 through 2011 and reviews the emerging role of tumor and constitutive genetics in refining risk stratification, defining targeted therapy, and improving survival for this group of relatively young patients.
Rabbit tumor necrosis factor: mechanism of action (1981)

Rabbit tumor necrosis factor (TNF) was examined for effects on normal and transformed cells in culture. Several assays for killing of L-929 cell targets were developed, and their sensitivities were compared. Normal cells were not killed by TNF, and the discrimination between normal and transformed cells was shown not to be due to a cell cycle-dependent mechanism. TNF killing of L-929 cells was delayed for 10 to 12 h and thereafter showed concentration and time-dependent increases in cytolysis. Actinomycin D or cycloheximide treatment of L-929 cells resulted in an enhancement of the rate of cell killing as well as a shortening of the preceding lag period. TNF killing of L-929 cells was temperature dependent; cells were considerably more resistant to lysis at 25 degrees C and showed enhanced killing at 39 degrees C as compared to 37 degrees C controls. The slope of the dose curve showed less than single-hit kinetics. A model for cell killing whose general features incorporate both the specificity and catalytic properties of an enzymatic reaction is proposed for TNF action.
Are biosimilars really generics? (2010)

Biosimilars should not be brought to market using the same procedure applied to generics, and existing and future regulation should prevent inappropriate and automatic substitution of a biosimilar for a reference biopharmaceutical product.
Molecular cloning and expression of hybridoma growth factor in Escherichia coli. (1987)

Human monocytes produce a factor that supports the growth of B lymphocyte hybridoma cells, termed hybridoma growth factor (HGF). By using expression cloning in Escherichia coli of complementary DNA derived from human monocyte-poly(A+) RNA, we selected seven clones producing HGF activity as measured in a bioassay, based on the induction of proliferation of the HGF-dependent B cell hybridoma B9. Sequence analysis of the cDNA revealed that HGF is identical with interferon-beta 2, 26,000 protein, and B cell stimulatory factor-2. One of the active clones contained a cDNA that encoded a recombinant product lacking the 28-amino acid long signal peptide and the first 15 amino acids of the mature protein. Antibodies against the recombinant HGF inhibited the biologic activity of recombinant HGF as well as of monocyte-derived HGF.
Concentrations of IGF-I and IGFBP-3 and Brain Tumor Risk in the European Prospective Investigation into Cancer and Nutrition (2011)

Factors of the IGF axis might be involved in the etiology of some types of brain tumors.
Oligodendrocyte substratum adhesion modulates expression of adenylate cyclase-linked receptors. (1988)

The molecular mechanisms of myelin formation/reformation in the central nervous system are unknown. In previous work we have demonstrated that mature oligodendrocytes (OLG) respond to a signal(s), elicited by their adhesion to a substratum, by turning on a myelinogenic metabolism. Events occurring within 24 hr of adhesion include generation of diacylglycerol, activation of protein kinase C, phosphorylation of myelin basic protein, and enhanced synthesis of myelin lipids and proteins. To elucidate the mechanism(s) of signal transduction, we have investigated whether OLG-substratum interaction influences the level of basal cAMP and the expression of receptors coupled to adenylate cyclase. By using ovine brain OLG we have found that adhesion to a polylysine-coated surface for 24 hr increased the basal level of cAMP 2-fold and altered the expression (assessed by cAMP production) of receptors coupled to adenylate cyclase. Isoproterenol (beta-adrenergic agonist) augmented cAMP from 4 to 26 pmol/mg of protein in adhering OLG but had no such effect in nonattached OLG. Adhesion of OLG was accompanied by rapid synthesis of ethanolamine plasmalogen, a class of lipids believed to be associated with beta-adrenergic receptors. Nonattached OLG responded to prostaglandin E1 with only a 3-fold stimulation in their cAMP content; in attached OLG, 6-fold stimulation was observed. In contrast, vasoactive intestinal polypeptide elicited a 3-fold increase in cAMP in nonattached OLG but, following 24 hr of attachment, OLG did not respond to vasoactive intestinal polypeptide. The increase of cellular cAMP levels was accompanied by a 2.5-fold gain in protein kinase A. OLG-substratum adhesion resulted also in phosphorylation of the OLG/myelin protein, 2',3'-cyclic nucleotide 2'-phosphodiesterase, which proved to be a substrate for cAMP and phospholipid-, Ca2+-dependent protein kinases. These findings, in conjunction with our earlier work, implicate cAMP and diacylglycerol in signaling myelinogenesis; they suggest that phosphorylation/dephosphorylation of myelin basic protein and 2',3'-cyclic nucleotide 2'-phosphodiesterase may be key processes in the cascade of events that are initiated by adhesion of OLG to a polylysine surface (possibly acting as a surrogate for axons) and culminate in the reformation of myelin.
Herpes simplex virus-induced stromal keratitis: role of T-lymphocyte subsets in immunopathology (1989)

Herpetic stromal keratitis (SK), a frequent cause of visual impairment, is considered to represent an immune-mediated inflammatory response to persistent herpes simplex virus virions or subcomponents within the corneal stroma. The experimental disease in mice involves the essential participation of T lymphocytes, but the role of T-lymphocyte subsets in either mediating or controlling the disease is uncertain. In this report, rat monoclonal antibodies were used to selectively deplete mice in vivo of CD4+ (helper-inducer) and CD8+ (cytotoxic-suppressor) T-cell populations and the effect on herpetic SK was evaluated. As measured by flow cytometry, mice treated with anti-CD4 monoclonal antibody (GK 1.5) were greater than 95% depleted of CD4+ T lymphocytes and mice treated with anti-CD8 monoclonal antibody (2.43) were 90% depleted of CD8+ T lymphocytes. Depleted and nonspecific mouse ascites-treated control mice were infected topically on the corneas with herpes simplex virus type 1, and the induction of various immune parameters during the acute infection was evaluated. CD4+-depleted mice failed to produce either a significant antiviral antibody or delayed-type hypersensitivity response but were capable of producing normal cytotoxic T-lymphocyte responses. In contrast, CD8+-depleted mice produced antiviral antibody and delayed-type hypersensitivity responses comparable with those in control animals, but cytotoxic T-lymphocyte responses were markedly reduced. Clinical observations of the corneas revealed that SK in CD4+-depleted mice was significantly reduced, whereas in CD8+-depleted mice SK developed more rapidly, was more severe, and involved a greater percentage of mice. These observations implicate the CD4+ T-lymphocyte subset as the principal mediators of SK and CD8+ T lymphocytes as possible regulators that control the severity of SK.
Spatial heterodyne spectrometer: modeling and interferogram processing for calibrated spectral radiance measurements (2013)

This work presents a radiometric model of a spatial heterodyne spectrometer (SHS) and a corresponding interferogram-processing algorithm for the calculation of calibrated spectral radiance measurements. The SHS relies on Fourier Transform Spectroscopy (FTS) principles, and shares design similarities with the Michelson Interferometer. The advantages of the SHS design, including the lack of moving parts, high throughput, and instantaneous spectral measurements, make it suitable as a eld-deployable instrument. Operating in the long-wave infrared (LWIR), the imaging SHS design example included provides the capability of performing chemical detection based on re ectance and emissivity properties of surfaces of organic compounds. This LWIR SHS model outputs realistic, interferometric data and serves as a tool to nd optimal SHS design parameters for desired performance requirements and system application. It also assists in the data analysis and system characterization. The interferogram-processing algorithm performs at- elding and phase corrections as well as apodization before recovering the measured spectral radiance from the recorded interferogram via the Inverse Fourier Transform (IFT). The model and processing algorithm demonstrate results comparable to those in the literature with a noise-equivalent change in temperature of 0.35K. Additional experiments show the algorithm's real-time processing capability, indicating the LWIR SHS system presented is feasible.
A Quantitative Analysis and Performance Study for Similarity-Search Methods in High-Dimensional Spaces (1998)

For similarity search in high-dimensional vector spaces (or ‘HDVSs’), researchers have proposed a number of new methods (or adaptations of existing methods) based, in the main, on data-space partitioning. However, the performance of these methods generally degrades as dimensionality increases. Although this phenomenon-known as the ‘dimensional curse’-is well known, little or no quantitative a.nalysis of the phenomenon is available. In this paper, we provide a detailed analysis of partitioning and clustering techniques for similarity search in HDVSs. We show formally that these methods exhibit linear complexity at high dimensionality, and that existing methods are outperformed on average by a simple sequential scan if the number of dimensions exceeds around 10. Consequently, we come up with an alternative organization based on approximations to make the unavoidable sequential scan as fast as possible. We describe a simple vector approximation scheme, called VA-file, and report on an experimental evaluation of this and of two tree-based index methods (an R*-tree and an X-tree).
Parkinson's disease, motoneuron disease and Alzheimer's disease: origins and interrelationship. (1990)

The cause of neurodegenerative disease is considered. For Alzheimer's disease, Parkinson's disease, and motoneuron disease, accumulating evidence over the last 3 years indicates that (a) the usual etiological mechanisms involve a subclinical lesion which kills some neurons and reduces the life expectation of their surviving neighbors, and (b) there may be more than one cause for each of the idiopathic syndromes now termed AD, PD, and MND.
Real-time automatic tag recommendation (2008)

Tags are user-generated labels for entities. Existing research on tag recommendation either focuses on improving its accuracy or on automating the process, while ignoring the efficiency issue. We propose a highly-automated novel framework for real-time tag recommendation. The tagged training documents are treated as triplets of (words, docs, tags), and represented in two bipartite graphs, which are partitioned into clusters by Spectral Recursive Embedding (SRE). Tags in each topical cluster are ranked by our novel ranking algorithm. A two-way Poisson Mixture Model (PMM) is proposed to model the document distribution into mixture components within each cluster and aggregate words into word clusters simultaneously. A new document is classified by the mixture model based on its posterior probabilities so that tags are recommended according to their ranks. Experiments on large-scale tagging datasets of scientific documents (CiteULike) and web pages del.icio.us) indicate that our framework is capable of making tag recommendation efficiently and effectively. The average tagging time for testing a document is around 1 second, with over 88% test documents correctly labeled with the top nine tags we suggested.
Cloning and Characterization ofvuuA, a Gene Encoding theVibrio vulnificusFerric Vulnibactin Receptor (2000)

The ability of Vibrio vulnificus to acquire iron from the host has been shown to correlate with virulence. Many iron transport genes are regulated by iron, and in V. vulnificus, transcriptional regulation by iron depends on the fur gene. The N-terminal amino acid sequence of a 72-kDa iron-regulated outer membrane protein purified from a V. vulnificus fur mutant had 53% homology with the first 15 amino acids of the mature protein of the Vibrio cholerae vibriobactin receptor, ViuA. In this report, we describe the cloning, DNA sequence, mutagenesis, and analysis of transcriptional regulation of the structural gene for VuuA, the vulnibactin receptor of V. vulnificus. Analysis of the DNA sequence of the vuuA promoter region demonstrated a sequence identical to the upstream Fur box of V. cholerae viuA. Northern blot analysis showed that the transcript was strongly regulated by iron. The amino acid sequence of VuuA was 74% identical to the sequence of V. cholerae ViuA and was homologous to those of several TonB-dependent outer membrane receptors. An internal deletion of the V. vulnificus vuuA gene resulted in the loss of expression of the 72-kDa protein and the loss of the ability to use transferrin or vulnibactin as a source of iron. This mutant showed reduced virulence in an infant mouse model. Introduction of a plasmid containing the complete viuA coding sequence and 342 bp of upstream DNA into the mutant restored ferric vulnibactin and ferric transferrin utilization to the mutant.
Pyoderma gangrenosum in childhood (1984)

• A review of our records disclosed eight children with pyoderma gangrenosum. All had associated inflammatory bowel disease, and four had arthritis. In three patients the bowel disease was severe and required resection of portions of the affected bowel. The cutaneous lesions had a chronic course (average duration, 2½ years), and systemic therapy was required in seven cases. Previously reported cases of pyoderma gangrenosum in children are reviewed, and the management of this skin disorder in childhood is discussed. (<i>Arch Dermatol</i>1984;120:757-761)
Composites Reinforced in Three Dimensions by Using Low Magnetic Fields (2012)

The orientation and distribution of reinforcing particles in artificial composites are key to enable effective reinforcement of the material in mechanically loaded directions, but remain poor if compared to the distinctive architectures present in natural structural composites such as teeth, bone, and seashells. We show that micrometer-sized reinforcing particles coated with minimal concentrations of superparamagnetic nanoparticles (0.01 to 1 volume percent) can be controlled by using ultralow magnetic fields (1 to 10 milliteslas) to produce synthetic composites with tuned three-dimensional orientation and distribution of reinforcements. A variety of structures can be achieved with this simple method, leading to composites with tailored local reinforcement, wear resistance, and shape memory effects.
Delayed postischemic hypothermia: a six month survival study using behavioral and histological assessments of neuroprotection (1995)

In the gerbil, brief global forebrain ischemia induces profound habituation and working memory impairments that stem from delayed hippocampal CA1 death. Short duration postischemic hypothermia has been shown to reduce CA1 loss, but such reports are controversial, as it is thought that protection may be transient. The purpose of this study was to investigate whether prolonged postischemic hypothermia provided long-term CA1 and functional neuroprotection. Previously, 90% of anterior CA1 neurons were rescued (30 d survival) when 24 hr of hypothermia (32 degrees C) was induced 1 hr following a 5 min occlusion that otherwise produced more than 95% loss (Colbourne and Corbett, 1994). We now find about 70% CA1 savings with this same hypothermic treatment in gerbils that survived for 6 months postischemia. While this is a significant reduction from 30 day survival (medial CA1 only), it nonetheless shows, for the first time, persistent, if not permanent neuroprotection, especially in middle and lateral CA1. In addition, in non-treated animals, ischemia impaired learning in an open field and T-maze for up to 6 months. Postischemic hypothermia significantly reduced these deficits. Hypothermia (32 degrees), when initiated 4 hr after ischemia, rescued approximately 12% of CA1 neurons at 6 months with a slight behavioral benefit. Milder hypothermia (34 degrees C, 1-25 hr postischemia, 30 d survival) also reduced habituation impairments and saved approximately 60% of CA1 neurons. Similar trends were found at more caudal CA1 levels. These results clearly show that postischemic hypothermia provides effective and long-lasting neuroprotection, which depends upon the delay to initiation, duration, and degree of cooling and survival time. The protracted functional and histological benefit observed justifies further basic and clinical investigation.
Glucocorticoid‐Induced TNFR‐Related (GITR) Protein and Its Ligand in Antitumor Immunity: Functional Role and Therapeutic Modulation (2010)

The ability of the tumor necrosis factor receptor (TNFR) family member GITR to modulate immune responses has been the subject of multiple studies. Initially thought to be critically involved in governing functions of regulatory T cells, GITR and its ligand GITRL have meanwhile been found to modulate the reactivity of various different cell types and to influence a broad variety of immunological conditions including the immune response against tumors. Not only GITR, but also GITRL is capable of transducing signals, and the consequences of GITR-GITRL interaction may vary among different effector cell types, differ upon signal transduction via the receptor, the ligand, or both, depend on the level of an ongoing immune response, and even differ among mice and men. In this paper, we address available data on GITR and its ligand in immune responses and discuss the role and potential therapeutic modulation of this molecule system in antitumor immunity.
Soft biological materials and their impact on cell function (2006)

Most organs and biological tissues are soft viscoelastic materials with elastic moduli ranging from on the order of 100 Pa for the brain to 100 000 Pa for soft cartilage. Biocompatible synthetic materials already have many applications, but combining chemical compatibility with physiologically appropriate mechanical properties will increase their potential for use both as implants and as substrates for tissue engineering. Understanding and controlling mechanical properties, specifically softness, is important for appropriate physiological function in numerous contexts. The mechanical properties of the substrate on which, or within which, cells are placed can have as large an impact as chemical stimuli on cell morphology, differentiation, motility, and commitment to live or die.
Magnetic Properties of Anodic Oxide Coatings on Aluminum Containing Electrodeposited Co and Co‐Ni (1975)

Cobalt and Co‐Ni alloy were electrodeposited into the micropores of various kinds of anodic oxide films on aluminum. Fine granular metals precipitated on the barrier layer and formed columnar structures. Although the films of cobalt or nickel showed remarkable magnetic anisotropies perpendicular to the surface, the alloy films which consisted of approximately 50% cobalt showed a strong anisotropy along the horizontal direction. Coercive forces ranged from about 500 to about 1100 oe and the density of residual magnetization rose above 1000 gauss. The films may have applications in magnetic memories and recording devices.
Potent and Selective Inhibition of Zinc Aminopeptidase A (EC 3.4.11.7, APA) by Glutamyl Aminophosphinic Peptides:  Importance of Glutamyl Aminophosphinic Residue in the P1 Position (2000)

Through the development of a new chemical strategy, aminophosphinic peptides containing a pseudoglutamyl residue (Glu Psi(PO2-CH2)Leu-Xaa) in the N-terminal position were synthesized and evaluated as inhibitors of aminopeptidase A (APA). The most potent inhibitor developed in this study, Glu Psi(PO2-CH2)Leu-Ala, displayed a Ki value of 0.8 nM for APA, but was much less effective in blocking aminopeptidase N (APN) (Ki = 31 microM). The critical role of the glutamyl residue in this phosphinic peptide, both in potency and selectivity, is exemplified by the P1 position analogue, Ala Psi(PO2-CH2)Leu-Ala, which exhibited a Ki value of 0.9 microM toward APA but behaved as a rather potent inhibitor of APN (Ki = 25 nM). Glu Psi(PO2-CH2)Leu-Xaa peptides are poor inhibitors of angiotensin converting enzyme (Ki values higher than 1 microM). Depending on the nature of the Xaa residue, the potency of these phosphinic peptides toward neutral endopeptidase 24-11 varied from 50 nM to 3 microM. In view of the in vivo role of APA in the formation of brain angiotensin III, one of the main effector peptides of the renin angiotensin system in the central nervous system, highly potent and selective inhibitors of APA may find important therapeutic applications soon.
Therapeutic Effects of Antibodies Against Adhesion Molecules in Murine Collagen Type II-Induced Arthritis (1995)

Adhesion molecules play important roles in immune reactions and inflammatory processes and may constitute attractive targets for immunomodulatory approaches. In this study, blocking mAbs against a series of adhesion molecules were tested for their therapeutic effect on developing arthritis in a mouse model. MAbs were given for a period of 4 weeks at the time of exspected incidence of visible disease symptoms, i.e. 4 weeks after priming with collagen type II. A significant reduction of incidence down to values of 13% and 29% of the controls was obtained with mAbs against CD44 and alpha 4-integrin, respectively, during an observation time of 13 weeks. MAbs against CD4 and LFA-1 resulted only in weaker, non-significant effects or a delay in the incidence. MAbs against other molecules including L-selectin, ICAM-1 or VCAM-1 were not effective. The development of antibodies against collagen type II, collagen type I, proteoglycans and the immunogen, bovine collagen type II was affected by mAb treatment to a different extent. In this case, the anti CD4 mAb was the most effective, followed by the anti alpha 4-antibodies in most cases, whereas anti CD44 showed less clear effects on the development of humoral responses. In a skin delayed type hypersensitivity model analyzed for comparison, mAbs against LFA-1/ICAM-1 and alpha 4-integrin showed the largest effects on ear swelling. These data show that mAbs against several adhesion molecules are able to block selectively distinct aspects of immune reactions, and that CD44 and alpha 4-integrins could be promising targets for an immunotherapy of rheumatoid arthritis with receptor-interfering agents.