gebhart/patrepeval huggingface dataset:
Intersections of pathways involving biotin and iron relative to therapeutic mechanisms for progressive multiple sclerosis. (2016)

While there are a variety of therapies for relapsing remitting multiple sclerosis (MS), there is a lack of treatments for progressive MS. An early study indicated that high dose biotin therapy has beneficial effects in approximately 12-15% of patients with progressive MS. The mechanisms behind the putative improvements seen with biotin therapy are not well understood, but have been postulated to include: 1) improving mitochondrial function which is impaired in MS, 2) increasing synthesis of lipids and cholesterol to facilitate remyelination, and 3) affecting gene expression. We suggest one reason that a greater percentage of patients with MS didn't respond to biotin therapy is the inaccessibility or lack of other nutrients, such as iron. In addition to biotin, iron (or heme) is necessary for energy production, biosynthesis of cholesterol and lipids, and for some protective mechanisms. Both biotin and iron are required for myelination during development, and by inference, remyelination. However, iron can also play a role in the pathology of MS. Increased deposition of iron can occur in some CNS structures possibly promoting oxidative damage while low iron levels can occur in other areas. Thus, the potential, detrimental effects of iron need to be considered together with the need for iron to support metabolic demands associated with repair and/or protective processes. We propose the optimal utilization of iron may be necessary to maximize the beneficial effects of biotin. This review will examine the interactions between biotin and iron in pathways that may have therapeutic or pathogenic implications for MS.
Resistance to Experimental Autoimmune Encephalomyelitis and Impaired T Cell Priming by Dendritic Cells in Src Homology 2 Domain-Containing Protein Tyrosine Phosphatase Substrate-1 Mutant Mice (2007)

Src homology 2 domain-containing protein tyrosine phosphatase (SHP) substrate-1 (SHPS-1) is a transmembrane protein that binds the protein tyrosine phosphatases SHP-1 and SHP-2 through its cytoplasmic region and is expressed on the surface of CD11c(+) dendritic cells (DCs) and macrophages. In this study, we show that mice that express a mutant form of SHPS-1 lacking most of the cytoplasmic region are resistant to experimental autoimmune encephalomyelitis (EAE) in response to immunization with a peptide derived from myelin oligodendrocyte glycoprotein (MOG (35-55)). The MOG (35-55)-induced proliferation of, and production of IFN-gamma, IL-2, and IL-17, by T cells from immunized SHPS-1 mutant mice were reduced compared with those apparent for wild-type cells. The abilities of splenic DCs from mutant mice to stimulate an allogenic MLR and to prime Ag-specific T cells were reduced. Both IL-12-stimulated and TLR-dependent cytokine production by DCs of mutant mice were also impaired. Finally, SHPS-1 mutant mice were resistant to induction of EAE by adoptive transfer of MOG (35-55)-specific T cells. These results show that SHPS-1 on DCs is essential for priming of naive T cells and the development of EAE. SHPS-1 is thus a potential therapeutic target in inflammatory disorders of the CNS and other autoimmune diseases.
Three-dimensional photopatterning of hydrogels using stereolithography for long-term cell encapsulation (2010)

Cell-encapsulated hydrogels with complex three-dimensional (3D) structures were fabricated from photopolymerizable poly(ethylene glycol) diacrylate (PEGDA) using modified 'top-down' and 'bottoms-up' versions of a commercially available stereolithography apparatus (SLA). Swelling and mechanical properties were measured for PEGDA hydrogels with molecular weights (M(w)) ranging from 700 to 10 000 Daltons (Da). Long-term viability of encapsulated NIH/3T3 cells was quantitatively evaluated using an MTS assay and shown to improve over 14 days by increasing the M(w) of the hydrogels. Addition of adhesive RGDS peptide sequences resulted in increased cell viability, proliferation, and spreading compared to pristine PEG hydrogels of the same M(w). Spatial 3D layer-by-layer cell patterning was successfully demonstrated, and the feasibility of depositing multiple cell types and material compositions into distinct layers was established.
Mutations in Lettuce Improvement (2011)

Lettuce is a major vegetable in western countries. Mutations generated genetic variations and played an important role in the domestication of the crop. Many traits derived from natural and induced mutations, such as dwarfing, early flowering, male sterility, and chlorophyll deficiency, are useful in physiological and genetic studies. Mutants were also used to develop new lettuce products including miniature and herbicide-tolerant cultivars. Mutant analysis was critical in lettuce genomic studies including identification and cloning of disease-resistance genes. Mutagenesis combined with genomic technology may provide powerful tools for the discovery of novel gene alleles. In addition to radiation and chemical mutagens, unconventional approaches such as tissue or protoplast culture, transposable elements, and space flights have been utilized to generate mutants in lettuce. Since mutation breeding is considered nontransgenic, it is more acceptable to consumers and will be explored more in the future for lettuce improvement.
Soluble, dimeric HLA DR4‐peptide chimeras: An approach for detection and immunoregulation of human type‐1 diabetes (2005)

Still there are no effective methods to predict or cure type 1 diabetes (T1D) in humans. Soluble, dimeric MHC class II-peptide (DEF) chimeras have potential for both early diagnosis and immunospecific therapy. DEF chimeras prevent and reverse diabetes in mice by stimulating antigen-specific type 1 T regulatory cell (Tr1)-like cells. We also showed that diabetes could be predicted by changes in the phenotype of autoreactive CD4 T cells in peripheral blood. Herein, we demonstrated that human DEF (HLA-DR*0401/Fcgamma1) chimeras expressing peptides of beta-cell antigens stimulate Tr1-like cells in blood of patients with T1D, non-diabetic relatives, and controls. Furthermore, the specific and stable binding of DEF chimeras to cognate TCR and CD4 coreceptor allowed quantification and phenotyping of autoreactive CD4 T cells in non-stimulated blood by FACS. Our results indicate that (1) autoreactive CD4 T cells to GAD65 autoantigen are commonly present in humans expressing diabetes-susceptible HLA-DR*0401 molecules; (2) these autoreactive T cells undergo avidity maturation upon encountering the self antigen early in life; (3) the disease is associated with an imbalance between autoreactive CD4+CD25+ and CD4+CD69+ T cells specific for GAD65. Based on this, we propose a model to explain the kinetics of autoreactive CD4 T cells in blood during the natural history of T1D.
Fabrication of Ordered Two-Dimensional Arrays of Micro- and Nanoparticles Using Patterned Self-Assembled Monolayers as Templates (1999)

A new method for the fabrication of ordered arrays of small particles is reported here. A combination of microcontact printing of SAMs, surface-templated self-assembly, and confined crystallization has been used to produce 2D arrays of micro- and nanoparticles. The method allows highly accurate control over size distribution and spatial arrangement for a broad range of substrates, such as CdS on Au, as shown in the Figure.
An Interleukin (IL)-10/IL-12 Immunoregulatory Circuit Controls Susceptibility to Autoimmune Disease (1998)

Cells of the innate immune system secrete cytokines early in immune responses that guide maturing T helper (Th) cells along appropriate lineages. This study investigates the role of cytokine networks, bridging the innate and acquired immune systems, in the pathogenesis of an organ specific autoimmune disease. Experimental allergic encephalomyelitis (EAE), a demyelinating disease of the central nervous system, is widely used as an animal model for multiple sclerosis. We demonstrate that interleukin (IL)-12 is essential for the generation of the autoreactive Th1 cells that induce EAE, both in the presence and absence of interferon gamma. The disease-promoting effects of IL-12 are antagonized by IL-10 produced by an antigen nonspecific CD4+ T cell which, in turn, is regulated by the endogenous production of IL-12. This unique immunoregulatory circuit appears to play a critical role in controlling Th cell differentiation and provides a mechanism by which microbial triggers of the innate immune system can modulate autoimmune disease.
Dynamic constraint satisfaction problems (1990)

Constraint satisfaction (CSP) is a powerful and extensively used framework for describing search problems. A CSP is typically defined as the problem of finding consistent assignment of values to a fixed set of variables given some constraints over these variables. However, for many synthesis tasks such as configuration and model composition, the set of variables that are relevant to a solution and must be assigned values changes dynamically in response to decisions made during the course of problem solving. In this paper, we formalize this notion as a dynamic constraint satisfaction problem that uses two types of constraints. Compatibility constraints correspond to those traditionally found in CSPs, namely, constraints over the values of variables. Activity constraints describe conditions under which a variable may or may not be actively considered as a part of a final solution. We present a language for expressing four types of activity constraints in terms of variable values and variables being considered. We then describe an implemented algorithm that enables tight interaction between constraints about variable activity and constraints about variable values. The utility of this approach is demonstrated for configuration and model composition tasks.
High-level expression of a bioengineered, cysteine-free hepatocyte-stimulating factor (interleukin 6)-like protein. (1988)

Hepatocyte-stimulating factor, interferon-beta 2, B-cell stimulation factor 2, and hybridoma/plasmacytoma growth factor are identical proteins presently referred to as interleukin 6 (IL-6). Through the use of synthetic oligonucleotide technology, we have constructed a biologically active recombinant IL-6 (rIL-6) gene based on the sequence of a human IL-6 cDNA. The synthetic gene encodes a cysteine-free, bioengineered rIL-6 protein that is expressed at high levels in Escherichia coli as a tripartite fusion protein. Cleavage of the fusion protein with collagenase releases a 23-kDa rIL-6 protein that can be easily purified to homogeneity. We show that the rIL-6 protein displays a range of biological activities similar to those of natural human IL-6, as demonstrated by its ability to (i) protect cells from viral infection, (ii) stimulate the synthesis of fibrinogen in rat FAZA 967 cells, and (iii) induce the terminal differentiation of B cells, resulting in elevated secretion of immunoglobulin.
An 80W AlGaN/GaN heterojunction FET with a field-modulating plate (2003)

An AlGaN/GaN heterojunction FET with a field-modulating plate (FP) has been fabricated on a SiC substrate. The gate breakdown voltage (BV/sub gd/) was improved from 50V to 160V by introducing an FP electrode. The highest BV/sub gd/ was obtained with an FP length of 1.0 /spl mu/m. A 4mm-wide unit-cell FET exhibited 32.5W (8.1W/mm) output power, 62% power-added efficiency, and 12.4 dB linear gain at a drain bias of 41V. The linear gain decreased with increasing the FP length, but the difference in the linear gain among FETs with various FP lengths decreased with increasing the drain bias. To the best of our knowledge, a power density of 8.1W/mm is the highest for GaN based FETs with over 1mm gate width. For a 24mm-wide 6-cell FET, an output power of 80.0W (3.3W/mm) was obtained with a linear gain of 8.5dB and a power-added efficiency of 42% at a drain bias of 31V.
Acetylcholinesterase-transgenic mice display embryonic modulations in spinal cord choline acetyltransferase and neurexin Iβ gene expression followed by late-onset neuromotor deterioration (1997)

To explore the possibility that overproduction of neuronal acetylcholinesterase (AChE) confers changes in both cholinergic and morphogenic intercellular interactions, we studied developmental responses to neuronal AChE overexpression in motoneurons and neuromuscular junctions of AChE-transgenic mice. Perikarya of spinal cord motoneurons were consistently enlarged from embryonic through adult stages in AChE-transgenic mice. Atypical motoneuron development was accompanied by premature enhancement in the embryonic spinal cord expression of choline acetyltransferase mRNA, encoding the acetylcholine-synthesizing enzyme choline acetyltransferase. In contrast, the mRNA encoding for neurexin-Ibeta, the heterophilic ligand of the AChE-homologous neuronal cell surface protein neuroligin, was drastically lower in embryonic transgenic spinal cord than in controls. Postnatal cessation of these dual transcriptional responses was followed by late-onset deterioration in neuromotor performance that was associated with gross aberrations in neuromuscular ultrastructure and with pronounced amyotrophy. These findings demonstrate embryonic feedback mechanisms to neuronal AChE overexpression that are attributable to both cholinergic and cell-cell interaction pathways, suggesting that embryonic neurexin Ibeta expression is concerted in vivo with AChE levels and indicating that postnatal changes in neuronal AChE-associated proteins may be involved in late-onset neuromotor pathologies.
TNF inhibitor therapy for rheumatoid arthritis (2012)

Immunotherapy has markedly improved treatment outcomes in rheumatoid arthritis (RA). Tumor necrosis factor (TNF)-α antagonists, such as infliximab (IFX), etanercept (ETN), adalimumab (ADA), golimumab (GOLI) and certolizumab pegol (CZP) have been widely used for the treatment of RA. IFX provides significant, clinically relevant improvement in physical function and the quality of life, inhibits progressive joint damage and sustains improvement in the signs and symptoms of patients with RA. ETN is effective and safe for patients with RA. Combination therapy with ETN plus methotrexate (MTX) reduces disease activity, decreases total joint score progression, slows the pace of joint destruction and improves function more effectively compared to any of the monotherapies. ADA with or without MTX also relieves the signs and symptoms of RA. CZP and GOLI expand the therapeutic schedule for patients with RA. The TNF-α inhibitors have similar efficacy, but distinct clinical pharmacokinetic and -dynamic properties. The common adverse events of these TNF-α antagonists include adverse reactions, infections and injection-site reaction. Additionally, these adverse events are mostly mild or moderate and their incidence is low. Certain patients exhibit a lack of response to anti-TNF-α therapies. Some patients may discontinue the initial drug and switch to a second anti-TNF-α agent. The shortage of clinical response to one agent may not predict deficiency of response to another. This review mainly addresses the latest developments of these biological agents in the treatment of RA.
Migraine prevention with a supraorbital transcutaneous stimulator (2013)

This study provides Class III evidence that treatment with a supraorbital transcutaneous stimulator is effective and safe as a preventive therapy for migraine.
Therapeutic drug monitoring: antiarrhythmic drugs (2001)

Antiarrhythmic agents are traditionally classified according to Vaughan Williams into four classes of action. Class I antiarrhythmic agents include most of the drugs traditionally thought of as antiarrhythmics, and have as a common action, blockade of the fast-inward sodium channel on myocardium. These agents have a very significant toxicity, and while they are being used less, therapeutic drug monitoring (TDM) does significantly increase the safety with which they can be administered. Class II agents are antisympathetic drugs, particularly the b-adrenoceptor blockers. These are generally safe agents which do not normally require TDM. Class III antiarrhythmic agents include sotalol and amiodarone. TDM can be useful in the case of amiodarone to monitor compliance and toxicity but is generally of little value for sotalol. Class IV antiarrhythmic drugs are the calcium channel blockers verapamil and diltiazem. These are normally monitored by haemodynamic effects, rather than using TDM. Other agents which do not fall neatly into the Vaughan Williams classification include digoxin and perhexiline. TDM is very useful for monitoring the administration (and particularly the safety) of both of these agents.
Distinct functions of DC-SIGN and its homologues L-SIGN (DC-SIGNR) and mSIGNR1 in pathogen recognition and immune regulation (2004)

Antigen presenting cells express C-type lectins that are involved in pathogen capture, processing and antigen presentation to induce immune responses against these pathogens. However, it is becoming clear that pathogens have evolved to subvert the function of some C-type lectins to escape immune surveillance. An important C-type lectin family is represented by DC-SIGN and its homologues in human and mouse. Here we discuss the structure in relation to the pathogen binding specificity of the SIGN receptors and the function of these receptors in mouse and humans.
HOXB13 Mediates Tamoxifen Resistance and Invasiveness in Human Breast Cancer by Suppressing ERα and Inducing IL-6 Expression (2013)

Most breast cancers expressing the estrogen receptor α (ERα) are treated successfully with the receptor antagonist tamoxifen (TAM), but many of these tumors recur. Elevated expression of the homeodomain transcription factor HOXB13 correlates with TAM-resistance in ERα-positive (ER+) breast cancer, but little is known regarding the underlying mechanism. Our comprehensive evaluation of HOX gene expression using tiling microarrays, with validation, showed that distant metastases from TAM-resistant patients also displayed high HOXB13 expression, suggesting a role for HOXB13 in tumor dissemination and survival. Here we show that HOXB13 confers TAM resistance by directly downregulating ERα transcription and protein expression. HOXB13 elevation promoted cell proliferation in vitro and growth of tumor xenografts in vivo. Mechanistic investigations showed that HOXB13 transcriptionally upregulated interleukin (IL)-6, activating the mTOR pathway via STAT3 phosphorylation to promote cell proliferation and fibroblast recruitment. Accordingly, mTOR inhibition suppressed fibroblast recruitment and proliferation of HOXB13-expressing ER+ breast cancer cells and tumor xenografts, alone or in combination with TAM. Taken together, our results establish a function for HOXB13 in TAM resistance through direct suppression of ERα and they identify the IL-6 pathways as mediator of disease progression and recurrence.
LYVE-1, a New Homologue of the CD44 Glycoprotein, Is a Lymph-specific Receptor for Hyaluronan (1999)

The extracellular matrix glycosaminoglycan hyaluronan (HA) is an abundant component of skin and mesenchymal tissues where it facilitates cell migration during wound healing, inflammation, and embryonic morphogenesis. Both during normal tissue homeostasis and particularly after tissue injury, HA is mobilized from these sites through lymphatic vessels to the lymph nodes where it is degraded before entering the circulation for rapid uptake by the liver. Currently, however, the identities of HA binding molecules which control this pathway are unknown. Here we describe the first such molecule, LYVE-1, which we have identified as a major receptor for HA on the lymph vessel wall. The deduced amino acid sequence of LYVE-1 predicts a 322-residue type I integral membrane polypeptide 41% similar to the CD44 HA receptor with a 212-residue extracellular domain containing a single Link module the prototypic HA binding domain of the Link protein superfamily. Like CD44, the LYVE-1 molecule binds both soluble and immobilized HA. However, unlike CD44, the LYVE-1 molecule colocalizes with HA on the luminal face of the lymph vessel wall and is completely absent from blood vessels. Hence, LYVE-1 is the first lymph-specific HA receptor to be characterized and is a uniquely powerful marker for lymph vessels themselves.
Relating Elderly, Child and Total Pedestrian Casualties to Several Urban Planning Characteristics (2001)

This research aims to establish separate relationships between elderly, child and total pedestrian casualties and urban planning characteristics in a number of zones in the capital city of Jordan, Amman. The considered characteristics for each zone included road density (ratio of street area to zone area), population density, length of streets, number of four-leg intersections, zonal population in thousands, number of green areas, total number of intersections, business rate (ratio of employees to the population), number of students in elementary schools in thousands, and length of public transit routes.The study revealed that elderly pedestrian casualties were significantly correlated with the population density and total population of each zone. The child pedestrian casualties were positively correlated with the population density, the zonal population and the number of students enrolled in elementary schools. However, total green areas were inversely proportional to child pedestrian casualties. The predicted models also indicated that the total pedestrian casualties were significantly correlated with the total population of the zone, number of four-leg intersections, population density, and total number of students enrolled in elementary schools in the considered zones.
Cell-cell cooperation in lymphocyte colony formation: studies in human allogeneic marrow transplantation. (1982)

The pace of restoration of phytohemagglutinin- (PHA) stimulated lymphocyte colony-forming response was investigated in 50 bone marrow transplant (BMT) recipients (49 allogeneic, 1 syngeneic) studied on 86 occasions. On the majority of occasions (28 of 48), patients studied early (3 to 8 wk) after BMT failed to make detectable lymphocyte colonies, whereas patients studied late (greater than 6 mo) after BMT displayed responses comparable to those of healthy adult volunteers. The sequential study of 10 of the 15 patients with positive lymphocyte colony-forming responses early after BMT revealed that this response is short-lived. The results of recipient donor mixing experiments and experiments involving the addition of the lymphokine interleukin 2 (IL 2) to recipient cells indicated that lymphocytes obtained from unresponsive recipients evaluated early after BMT can be driven to colony formation, and suggest that the major limiting component in such subjects is functional T help.
Graph partitioning into isolated, high conductance clusters (2008)

We consider the problem of decomposing a weighted graph with n vertices into a collection P of vertex disjoint clusters such that, for all clusters C ε P, the graph induced by the vertices in C and the edges leaving C, has conductance bounded below by φ. We show that for planar graphs we can compute a decomposition P such that |P| < n/ρ, where ρ is a constant, in O(log n) parallel time with O(n) work. Slightly worse guarantees can be obtained in nearly linear time for graphs that have fixed size minors or bounded genus. We show how these decompositions can be used in the first known linear work parallel construction of provably good preconditioners for the important class of fixed degree graph Laplacians. On a more theoretical note, we present upper bounds on the Euclidean distance of eigenvectors of the normalized Laplacian from the space of vectors which consists of the cluster-wise constant vectors scaled by the square roots of the total incident weights of the vertices.