gebhart/patrepeval huggingface dataset:
Neuropathic Pain: A Maladaptive Response of the Nervous System to Damage (2009)

Neuropathic pain is triggered by lesions to the somatosensory nervous system that alter its structure and function so that pain occurs spontaneously and responses to noxious and innocuous stimuli are pathologically amplified. The pain is an expression of maladaptive plasticity within the nociceptive system, a series of changes that constitute a neural disease state. Multiple alterations distributed widely across the nervous system contribute to complex pain phenotypes. These alterations include ectopic generation of action potentials, facilitation and disinhibition of synaptic transmission, loss of synaptic connectivity and formation of new synaptic circuits, and neuroimmune interactions. Although neural lesions are necessary, they are not sufficient to generate neuropathic pain; genetic polymorphisms, gender, and age all influence the risk of developing persistent pain. Treatment needs to move from merely suppressing symptoms to a disease-modifying strategy aimed at both preventing maladaptive plasticity and reducing intrinsic risk.
InkSeine (2007)

Using a notebook to sketch designs, reflect on a topic, or capture and extend creative ideas are examples of active note taking tasks. Optimal experience for such tasks demands concentration without interruption. Yet active note taking may also require reference documents or emails from team members. InkSeine is a Tablet PC application that supports active note taking by coupling a pen-and-ink interface with an in situ search facility that flows directly from a user's ink notes (Fig. 1). InkSeine integrates four key concepts: it leverages preexisting ink to initiate a search; it provides tight coupling of search queries with application content; it persists search queries as first class objects that can be commingled with ink notes; and it enables a quick and flexible workflow where the user may freely interleave inking, searching, and gathering content. InkSeine offers these capabilities in an interface that is tailored to the unique demands of pen input, and that maintains the primacy of inking above all other tasks.
Sequence and functional analysis of the Streptomyces phaeochromogenes plasmid pJV1 reveals a modular organization of Streptomyces plasmids that replicate by rolling circle (1995)

pJV1 is an 11 kb, high-copy-number conjugative Streptomyces phaeochromogenes plasmid that replicates by the rolling circle mechanism (RCR). Sequencing combined with functional analysis of deletion, insertion and frameshift mutations was used to characterize the genes involved in plasmid transfer and chromosome mobilization (Cma), the single-strand origin for RCR and an associated strong incompatibility (Sti) determinant. pJV1 contains two essential transfer genes whose expression is regulated by an adjacent repressor gene with similarity to the GntR family of regulators. A consensus sequence specific for the helix-turn-helix motifs of repressor proteins of Streptomyces plasmids is proposed. Unregulated expression of the transfer genes by inactivation of the repressor is lethal. Three additional genes increase intramycelial plasmid spread resulting in pock formation but, unlike the essential transfer genes, are not required for Cma. The pJV1 transfer genes and their regulatory region, but not the minimal replication region encoding the double-strand replication origin and replication protein, are similar in their sequence and arrangement to those of the Streptomyces nigrifaciens plasmid pSN22, revealing a modular organization of Streptomyces RCR plasmids.
Alveolar Macrophages Inhibit Retrovirus-Mediated Gene Transfer to Airway Epithelia (1997)

Gene transfer with integrating vectors such as recombinant retrovirus has the potential to correct inherited lung diseases permanently. As a gene therapy target, the pulmonary epithelium presents several challenges to vector delivery in vivo. Many of the host defenses that have evolved to prevent infection from inhaled bacteria or viruses represent potential barriers to gene transfer to the lung. We performed in vitro studies to determine whether two components of the innate immune system of the lung, airway surface fluid and alveolar macrophages, inhibit retroviral gene transfer to airway epithelia. Human alveolar macrophages obtained by bronchoalveolar lavage from normal subjects were left untreated or activated with lipopolysaccharide (LPS) for 3 hr in the presence of subconfluent human bronchial epithelial cells (HBE); than 4 x 10(5) cfu DA-luciferase retrovirus was added. Three days after infection, luciferase activity was measured in cell lysates. When the epithelial cells were co-cultured with LPS-activated macrophages, retroviral gene transfer to HBE cells was reduced by approximately 60%. Nonactivated macrophages decreased the transfection to approximately 55% of control values. In control experiments with either activated or inactivated macrophages but without epithelia, no luciferase activity was detected, suggesting that terminally differentiated alveolar macrophages are not infected by the recombinant retrovirus. Pretreatment of alveolar macrophages with dexamethasone restored gene transfer to approximately 60% of control values. In contrast, incubation of retrovirus with airway surface fluid had no inhibitory effect on gene transfer. These experiments document that AM inhibit retrovirus-mediated gene transfer to airway epithelia in vitro, and may represent a barrier to retroviral gene transfer in vivo. These barriers may be overcome, at least partially, with pharmacological agents.
Global transcription profiling reveals differential responses to chronic nitrogen stress and putative nitrogen regulatory components in Arabidopsis (2007)

Differentially expressed genes identified provide additional insights into the coordination of the complex N responses of plants and the components of the N response mechanism. Putative N regulatory elements were identified to reveal possible new components of the regulatory network for plant N responses. A better understanding of the complex regulatory network for plant N responses will help lead to strategies to improve N use efficiency.
Catheter-based prostacyclin synthase gene transfer prevents in-stent restenosis in rabbit atheromatous arteries (2003)

PGIS gene transfer accelerated re-endothelialization, and attenuated neointimal formation after stent implantation in atheromatous rabbit arteries, at least in part, via increased production of VEGF protein.
Poly(ionic liquid)s: Polymers expanding classical property profiles (2011)

In recent years, polymeric/polymerized ionic liquids or poly(ionic liquid)s (PILs) were found to take an enabling role in some fields of polymer chemistry and material science. PILs combine the unique properties of ionic liquids with the flexibility and properties of macromolecular architectures and provide novel properties and functions that are of huge potential in a multitude of applications, including solid ionic conductor, powerful dispersant and stabilizer, absorbent, precursor for carbon materials, porous polymers, etc. So far, the preparation of PILs with various forms in cations and anions has mostly focused on the conventional free radical polymerization of IL monomers. Recent progress in the preparation of PILs via controlled/“living” radical polymerizations points out an unprecedented opportunity to precisely design and control macromolecular architecture of IL species on a meso-/nanoscale within a polymer matrix. There are also newly emerging polymerization techniques that have appeared for the preparation of PILs which have further pushed the limit of the design of PILs. In this review, we try to summarize the current preparative strategies of PILs, providing a systematic and actual view on the polymer chemistry behind. A discussion of the properties and applications of PILs constitutes the second part of this review.
The extensibility framework in Microsoft StreamInsight (2011)

Microsoft StreamInsight (StreamInsight, for brevity) is a platform for developing and deploying streaming applications, which need to run continuous queries over high-data-rate streams of input events. StreamInsight leverages a well-defined temporal stream model and operator algebra, as the underlying basis for processing long-running continuous queries over event streams. This allows StreamInsight to handle imperfections in event delivery and to provide correctness guarantees on the generated output. StreamInsight natively supports a diverse range of off-the-shelf streaming operators. In order to cater to a much broader range of customer scenarios and applications, StreamInsight has recently introduced a new extensibility infrastructure. With this infrastructure, StreamInsight enables developers to integrate their domain expertise within the query pipeline in the form of user defined modules (functions, operators, and aggregates). This paper describes the extensibility framework in StreamInsight; an ongoing effort at Microsoft SQL Server to support the integration of user-defined modules in a stream processing system. More specifically, the paper addresses the extensibility problem from three perspectives: the query writer's perspective, the user defined module writer's perspective, and the system's internal perspective. The paper introduces and addresses a range of new and subtle challenges that arise when we try to add extensibility to a streaming system, in a manner that is easy to use, powerful, and practical. We summarize our experience and provide future directions for supporting stream-oriented workloads in different business domains.
Tissue-specific and convergent metabolic transformation of cancer correlates with metastatic potential and patient survival (2016)

Cancer cells undergo a multifaceted rewiring of cellular metabolism to support their biosynthetic needs. Although the major determinants of this metabolic transformation have been elucidated, their broad biological implications and clinical relevance are unclear. Here we systematically analyse the expression of metabolic genes across 20 different cancer types and investigate their impact on clinical outcome. We find that cancers undergo a tissue-specific metabolic rewiring, which converges towards a common metabolic landscape. Of note, downregulation of mitochondrial genes is associated with the worst clinical outcome across all cancer types and correlates with the expression of epithelial-to-mesenchymal transition gene signature, a feature of invasive and metastatic cancers. Consistently, suppression of mitochondrial genes is identified as a key metabolic signature of metastatic melanoma and renal cancer, and metastatic cell lines. This comprehensive analysis reveals unexpected facets of cancer metabolism, with important implications for cancer patients' stratification, prognosis and therapy.
T helper type 17 pathway suppression by appendicitis and appendectomy protects against colitis (2013)

Appendicitis followed by appendectomy (AA) at a young age protects against inflammatory bowel disease (IBD). We wanted to characterize the role of the T helper type 17 (Th17) system involved in this protective effect. AA was performed on 5-week-old male BALB/c mice and distal-colon samples were harvested. Mice with two laparotomies each served as sham-sham (SS) controls. RNA was extracted from four individual colonic samples per group (AA and SS groups) and each sample microarray-analysed and reverse transcription-polymerase chain reaction (RT-PCR)-validated. Gene-set enrichment analysis (GSEA) showed that the Th17 recruitment factor gene CCL20 was significantly suppressed at both 3 days post-AA and 28 days post-AA. Although Th17 cell development differentiation factor genes TGF-β2 and TGF-β3 were significantly up-regulated 3 days post-AA, GSEA 28 days post-AA showed that AA down-regulated 29 gene-sets associated with TGF-β1, TGF-β2 and TGF-β3 in contrast to none up-regulated with any of these genes. GSEA showed substantial down-regulation of gene-sets associated with Th17 lymphocyte recruitment, differentiation, activation and cytokine expression in the AA group 28 days post-AA. We conclude that Th17-system cytokines are kept under control by AA via down-regulation of proinflammatory CCL20, a rapid down-regulation of pro-Th17 cell differentiation genes TGF-β2 and TGF-β3, suppression of RORC-associated gene-sets, increased protective STAT1 expression and suppression of 81 'pro-Th17' system gene-sets. AA suppresses the Th17 pathway leading to colitis amelioration. Further characterization of Th17-associated genes and biological pathways will assist in the development of better therapeutic approaches in IBD management.
Man in Space Communications System (1966)

Reliable communications are essential to success of the Lunar Excursion Module (LEM) mission in the Apollo program. This paper describes the communications system to provide the communications necessary for both in-flight and lunar-stay modes of operation. Features of the S-band transmission link between earth and the LEM vehicle, and the VHF transmission link between the Command Module and the LEM vehicle are discussed. The signal processor, S-band and VHF transceivers, S-band power amplifier, and steerable and erectable antenna assemblies comprising the communications system are described.
Rituximab for rheumatoid arthritis refractory to anti–tumor necrosis factor therapy: Results of a multicenter, randomized, double‐blind, placebo‐controlled, phase III trial evaluating primary efficacy and safety at twenty‐four weeks (2006)

At 24 weeks, a single course of rituximab with concomitant MTX therapy provided significant and clinically meaningful improvements in disease activity in patients with active, longstanding RA who had an inadequate response to 1 or more anti-TNF therapies.
Antibiotic prophylaxis of postoperative endophthalmitis. (1979)

Nonconcurrent analysis of 45,954 cataract operations performed by a single surgeon indicates that periocular injection of penicillin combined with multiple preoperative applications of topical chloramphenicol-sulphadimidine reduced the incidence of postoperative endophthalmitis by 72%. Periocular penicillin alone was ineffective. A concurrent masked randomized study of 6,618 cataract operations confirms the efficacy of combined prophylaxis and demonstrates that the topical regimen, by itself, is as ineffective as isolated penicillin prophylaxis.
Adding Genes to the RNA Genome of Vesicular Stomatitis Virus: Positional Effects on Stability of Expression (2002)

Gene expression of the nonsegmented negative strand (NNS) RNA viruses is controlled primarily at the level of transcription by the position of the genes relative to the single transcriptional promoter. We tested this principle by generating engineered variants of vesicular stomatitis virus in which an additional, identical, transcriptional unit was added to the genome at each of the viral gene junctions. Analysis of transcripts confirmed that the level of transcription was determined by the position of the gene relative to the promoter. However, the position at which a gene was inserted affected the replication potential of the viruses. Adding a gene between the first two genes, N and P, reduced replication by over an order of magnitude, whereas addition of a gene at the other gene junctions had no effect on replication levels. All genes downstream of the inserted gene had decreased levels of expression, since transcription of the extra gene introduced an additional transcriptional attenuation event. The added gene was stably maintained in the genome upon repeated passage in all cases. However, expression of the added gene was stable at only three of the four positions. In the case of insertion between the N and P genes, a virus population arose within two passages that had restored replication to wild-type levels. In this population, expression of the additional gene as a monocistronic mRNA was suppressed by mutations at the end of the upstream (N) gene that abolished transcriptional termination. Because transcription is obligatorily sequential, this prevented transcription of the inserted downstream gene as a monocistronic mRNA and resulted instead in polymerase reading through the gene junction to produce a bicistronic mRNA. This eliminated the additional attenuation step and restored expression of all downstream genes and viral replication to wild-type levels. These data show that transcriptional termination is a key element in control of gene expression of the negative strand RNA viruses and a means by which expression of individual genes may be regulated within the framework of a single transcriptional promoter. Further, these results are directly relevant to the use of NNS viruses as vectors and vaccine delivery agents, as they show that the level of expression of an added gene can be controlled by its insertion position but that not all positions of insertion yield stable expression of the added gene.
A new principle of RNA folding based on pseudoknotting (1985)

Tertiary interactions involving hairpin or interior loops of RNA can lead to extended quasi-continuous double helical stem regions, consisting of coaxially stacked segments of duplex RNA, bridged by single-stranded connections. This type of compact folding plays a role in various strategic regions of RNA molecules. Their role in ribosome functioning, RNA splicing and recognition of tRNA-like structures is discussed.
Association of anthracyclines and synthetic hexanucleotides. Structural factors influencing sequence specificity (1989)

The equilibrium and kinetic aspects of the interaction between four anthracyclines and two synthetic self-complementary hexanucleotides was investigated by fluorescence detection. Two of the studied anthracyclines are widely used antitumor drugs: doxorubicin (1, formerly adriamycin) and daunorubicin (2, formerly daunomycin). The other two, 9-deoxydoxorubicin (3) and 3'-deamino-3'-hydroxy-4'-epidoxorubicin (4), are doxorubicin analogues with modifications of the chemical groups that have been proposed as responsible for sequence specificity (Chen, K.-X., Gresh, N. and Pullman, B. (1985). J. Biomol. Struct. Dyn. 3, 445-466). One of the oligonucleotides, d(CGTACG), is identical to that used in the high resolution x-ray structure determination of the daunorubicin intercalative complex (Wang, A. H.-J., Ughetto, G., Quigley, G. J. & Rich, A. (1987). Biochemistry 26, 1152-1163). Binding to this hexanucleotide is compared with intercalation into the d(CGCGCG) duplex, revealing sequence preferences of the four anthracyclines. Taking into account the anthracycline aggregation and the dissociation of the hexanucleotide double standard form, results can be interpreted with a model that assumes complete fluorescence quenching at intercalative sites containing the CG base pair, and a large residual fluorescence after intercalation within the TpA fragment. All four anthracyclines show preferential intercalation at sites near the ends of both hexanucleotide duplexes, partly as a result of positive cooperativity in the formation of di-intercalated species at these sites. Within the limits of experimental error, complete site specificity for the CpG fragment is found in the intercalation of 1 and 2 into d(CGTACG) duplex, whereas analogues 3 and 4 give increasing evidence of intercalation at other sites including the fluorescence-preserving TpA fragment. Site specificity is less pronounced in the association with d(CGCGCG), when cooperativity is taken into account. Kinetic data corroborate the results of equilibrium studies and are interpreted with a mechanism that includes formation of an intermediate bound species followed by drug redistribution to preferential sites. Finally, from a comparison of pertinent site binding constants, approximate free energy contributions to sequence specific DNA interaction, due to C9-OH on the aglycone and -NH3+ on daunosamine, are estimated not to exceed 2 kcal/mol.
Importance of Extracellular Polymeric Substances fromThiobacillus ferrooxidansfor Bioleaching (1998)

Leaching bacteria such as Thiobacillus ferrooxidans attach to pyrite or sulfur by means of extracellular polymeric substances (EPS) (lipopolysaccharides). The primary attachment to pyrite at pH 2 is mediated by exopolymer-complexed iron(III) ions in an electrochemical interaction with the negatively charged pyrite surface. EPS from sulfur cells possess increased hydrophobic properties and do not attach to pyrite, indicating adaptability to the substrate or substratum.
Food allergy. (1997)

The evaluation of adverse reactions to foods involving abnormal immune responses to food allergens remains an important part of the practice of allergy and immunology. Approximately 5% of children younger than 3 years and 1.5% of the general population experience food allergic disorders, indicating that about 4 million Americans suffer from food allergies. The evaluation of adverse reactions to foods depends on a careful clinical history, diagnostic studies including appropriate skin testing or in vitro testing with food extracts, and/or endoscopy and biopsy. The mainstay of therapy remains avoidance of incriminated foods and education to deal with inadvertent exposures. Experience over the past decade suggests that the ready availability and early introduction of highly allergenic foods (eg, peanuts and nuts) into the diet will only increase the number of individuals suffering from hypersensitivity reactions to foods. Research has focused on the identification and characterization of allergenic proteins and the development of new therapeutic strategies, eg, plasmid DNA vaccines, to treat these disorders.
Kurzzeit-Immuntherapie mit Baumpollen-Allergoiden und dem Adjuvans Monophosphoryl Lipid-A – Ergebnisse einer randomisierten, doppelblinden, plazebokontrollierten Multicenterstudie (2002)

Specific immunotherapy (SIT) is considered as the only causal treatment of IgE-mediated allergies apart from allergen avoidance. In this randomized, placebo-controlled, double-blind study, efficacy and tolerability of a preseasonal short-term immunotherapy with 4 injections was evaluated in patients with tree-pollen allergy. Eighty-four patients with clinically relevant seasonal allergic rhinitis, conjunctivitis and/or asthma sensitised to birch/alder/hazel pollen were enrolled. The active group received 4 injections of L-tyrosine-adsorbed tree pollen allergoids plus 50 μg/ml monophosphoryl lipid-A (MPL; n = 57). The placebo injections consisted ofL-tyrosine-solution (2%) in excipient solution (n = 27). The combined symptom-/medication score served as a primary endpoint. Changes in skin reactivity measured by titrated skin prick test and blood levels of pollen-specific IgG and IgE antibodies served as secondary endpoints. There was a significant advantage in favour of the active treatment for the combined symptom-/medication score (p = 0.028). Titrated skin prick testing revealed a significant reduction of skin sensitivity after therapy (p < 0.01) and a significant decrease of mean sum of wheal areas in the active group compared to placebo (p = 0.03). Already 2 weeks after active treatment, levels of specific IgG rose significantly (p < 0.01). An increase of specific IgE during and after pollen season was only observed in the placebo group (p < 0.01). The tolerability of the therapy was good. There were no reports of serious or severe adverse events. In this study, the efficacy and tolerability of a short-term immunotherapy with 4 injections was shown. The application of this short-term therapy may improve acceptance by patients and encourage wider application of SIT in the treatment of IgE-mediated allergies.