gebhart/patrepeval huggingface dataset:
Neural Mechanisms of Cutaneous Nociceptive Pain (2000)

Acute mechanical, thermal, and chemically induced pains in the skin are signalled by a set of specific nociceptive afferents, which encode the magnitude of the perceived pain by their discharge intensity. After tissue injury or inflammation, a number of changes in the properties of the primary afferent occur parallel to profound changes in the central nervous system. Primary hyperalgesia (within the area of tissue injury) is best explained by changes of the properties of primary nociceptive afferents, whereas secondary hyperalgesia (increased pain sensitivity outside the area of tissue injury) critically requires functional changes in the central nervous system. Collectively, these changes are the basis for the many forms of hyperalgesia that can present clinically as incident pain. Knowledge of the various types of hyperalgesia and their underlying mechanisms is required for better treatment of this challenging aspect of chronic pain.
Neuromodulation for cephalgias (2013)

Headaches (cephalgias) are a common reason for patients to seek medical care. There are groups of patients with recurrent headache and craniofacial pain presenting with malignant course of their disease that becomes refractory to pharmacotherapy and other medical management options. Neuromodulation can be a viable treatment modality for at least some of these patients. We review the available evidence related to the use of neuromodulation modalities for the treatment of medically refractory craniofacial pain of different nosology based on the International Classification of Headache Disorders, 2(nd) edition (ICHD-II) classification. This article also reviews the scientific rationale of neuromodulation application in management of cephalgias.
Direct synthesis of 8-aryl tetrahydroquinolines via pd-catalyzed ortho-arylation of arylureas in water (2012)

An efficient protocol for the direct synthesis of 8-arylated tetrahydroquinolines via Pd-catalyzed ortho-arylation of aryl ureas with aryl iodides was developed. The reaction proceeded smoothly in water under ligand-free and surfactant-free conditions, providing the desired products in high yields with remarkable functional group tolerance.
A Facile Nanoparticle Immunoassay for Cancer Biomarker Discovery (2011)

The molecular aberrations observed from this study may become new biomarkers for prostate cancer detection. The nanoparticle immunoassay reported here can be used as a convenient and general tool to screen and analyze serum proteins and to discover new biomarkers associated with cancer and other human diseases.
Thermolytic CpG-containing DNA oligonucleotides as potential immunotherapeutic prodrugs (2005)

A CpG-containing DNA oligonucleotide functionalized with the 2-(N-formyl-N-methyl)aminoethyl thiophosphate protecting group (CpG ODN fma1555) was prepared from phosphoramidites 1a-d using solid-phase techniques. The oligonucleotide behaved as a prodrug by virtue of its conversion to the well-studied immunomodulatory CpG ODN 1555 through thermolytic cleavage of the 2-(N-formyl-N-methyl)aminoethyl thiophosphate protecting group. Such a conversion occurred at 37 degrees C with a half-time of 73 h. The immunostimulatory properties of CpG ODN fma1555 were evaluated in two in vivo assays, one of which consisted of mice challenged in the ear with live Leishmania major metacyclic promastigotes. Local intradermal administration of CpG ODN fma1555 was as effective as that of CpG ODN 1555 in reducing the size of Leishmania lesions over time. In a different infectious model, CpG ODN 1555 prevented the death of Tacaribe-infected mice (43% survival) when administered between day 0 and 3 post infection. Administration of CpG ODN fma1555 three days before infection resulted in improved immunoprotection (60-70% survival). Moreover, co-administration of CpG ODN fma1555 and CpG ODN 1555 in this model increased the window for therapeutic treatment against Tacaribe virus infection, and thus supports the use of thermolytic oligonucleotides as prodrugs in the effective treatment of infectious diseases.
Collagen Matrices Enhance Survival of Transplanted Cardiomyoblasts and Contribute to Functional Improvement of Ischemic Rat Hearts (2006)

Collagen matrices enhance early survival of H9c2 cardiomyoblasts after transplantation into ischemic hearts and lead to improved LV function. Further optimization of the graft design should make restoration of large myocardial infarctions by tissue engineering approaches effective.
A rapid and convenient method for the preparation and storage of competent bacterial cells (1988)

Journal Article A rapid and convenient method for the preparation and storage of competent bacterial cells Get access C.T. Chung, C.T. Chung Laboratory of Infectious Diseases, National Institute of Allergy and Infectious DiseasesBethesda, MD 20892, USA Search for other works by this author on: Oxford Academic PubMed Google Scholar Roger H. Miller Roger H. Miller Laboratory of Infectious Diseases, National Institute of Allergy and Infectious DiseasesBethesda, MD 20892, USA Search for other works by this author on: Oxford Academic PubMed Google Scholar Nucleic Acids Research, Volume 16, Issue 8, 25 April 1988, Page 3580, https://doi.org/10.1093/nar/16.8.3580 Published: 25 April 1988 Article history Received: 15 March 1988 Published: 25 April 1988
Chloroplast Division and Expansion Is Radically Altered by Nuclear Mutations in Arabidopsis thaliana (1992)

We have isolated three mutants of Arabidopsis thaliana in which there is a sevenfold change in chloroplast number in fully expanded leaf mesophyll cells and increases and decreases in chloroplast number are compensated for by changes in chloroplast size. The changes are stably inherited in sexual crosses for three generations and mutant phenotypes are effected by changes at single recessive nuclear loci, termed arc loci. This is the first report of large, stably inherited changes in chloroplast number in higher plants, and represents a major advance toward the genetic dissection of the control of chloroplast division.
Specific Expression of a Tyrosine Kinase Gene, blk , in B Lymphoid Cells (1990)

Several pathways of transmembrane signaling in lymphocytes involve protein-tyrosine phosphorylation. With the exception of p56lck, a tyrosine kinase specific to T lymphoid cells that associates with the T cell transmembrane proteins CD4 and CD8, the kinases that function in these pathways are unknown. A murine lymphocyte complementary DNA that represents a new member of the src family has now been isolated and characterized. This complementary DNA, termed blk (for B lymphoid kinase), specifies a polypeptide of 55 kilodaltons that is related to, but distinct from, previously identified retroviral or cellular tyrosine kinases. The protein encoded by blk exhibits tyrosine kinase activity when expressed in bacterial cells. In the mouse and among cell lines, blk is specifically expressed in the B cell lineage. The tyrosine kinase encoded by blk may function in a signal transduction pathway that is restricted to B lymphoid cells.
A Review of Potential Cardiovascular Uses of Intravenous Glucagon Administration (1999)

Glucagon is a counter-regulatory hormone that is classically used to treat hypoglycemia. However, it can elicit the generation of cAMP within the myocardium to cause positive inotropic and chronotropic effects without the need for beta-1 adrenoceptor stimulation. Glucagon has been used extensively to treat beta-blocker overdose and has evidence for use in verapamil and imipramine overdose as well. Glucagon has been used as adjunctive therapy in shock situations and heart failure but is inferior to catecholamines. An interesting potential indication for glucagon is in treating postcountershock asystole.
Direct Activation of STING in the Tumor Microenvironment Leads to Potent and Systemic Tumor Regression and Immunity (2015)

Spontaneous tumor-initiated T cell priming is dependent on IFN-β production by tumor-resident dendritic cells. On the basis of recent observations indicating that IFN-β expression was dependent upon activation of the host STING pathway, we hypothesized that direct engagement of STING through intratumoral (IT) administration of specific agonists would result in effective anti-tumor therapy. After proof-of-principle studies using the mouse STING agonist DMXAA showed a potent therapeutic effect, we generated synthetic cyclic dinucleotide (CDN) derivatives that activated all human STING alleles as well as murine STING. IT injection of STING agonists induced profound regression of established tumors in mice and generated substantial systemic immune responses capable of rejecting distant metastases and providing long-lived immunologic memory. Synthetic CDNs have high translational potential as a cancer therapeutic.
Nativelike expression in the speech of long‐residencyL2 users: A study of multiword structures inL2English,French andSpanish (2014)

Nativelike expression in L 2 speech is investigated by comparing quantity and distribution of different types of multiword structures ( MWSs ) in the speech of very advanced L 2 speakers with native speakers. Swedish speakers of L 2 E nglish, L 2 F rench and L 2 S panish (average LOR in the UK , F rance and C hile 7–10 years) performing two oral tasks, a role play, and an online retelling task, are compared with matching native speakers, totalling 140,000 words. The L 2 groups were nativelike in their use of MWSs as social routines in the role play. Collocations, the dominant category in the retelling task, were underrepresented in all three L 2 groups compared to the native groups. Furthermore, the E nglish NNSs were nativelike on more measurements of MWSs than the F rench and S panish NNSs .
IgG and IgA content of vaginal fluid during the menstrual cycle. (1989)

Immunoglobulin levels in cervicovaginal secretions during the menstrual cycle have not been well characterized biochemically. We determined the IgG and IgA concentrations in vaginal fluid obtained by patient self-sampling with an Ovu-Trac aspirator. Vaginal fluid IgG levels were less than 1-270 mg/dL. On the average the levels of IgG were relatively high after menstruation, declined during the ovulatory phase and remained relatively low during most of the luteal phase. The IgA levels were less than 10 mg/dL, and many samples contained IgA at our assay's lower limits of detection (microradial immunodiffusion). The preovulatory and luteal phase levels of IgG and IgA in vaginal fluid were generally lower than those reported for cervical mucus, but the ovulatory phase IgG and IgA composition was comparable between vaginal fluid and cervical mucus.
Treating statin-intolerant patients (2011)

Statins are effective in reducing cardiovascular events and are safe for almost all patients. Nevertheless, intolerance to statins is frequently faced in clinical practice. This is mostly due to muscular symptoms (myalgia with or without increase of plasma creatinine kinase) and/or elevation of hepatic aminotransferases, which overall constitutes approximately two-thirds of reported adverse events during statin therapy. These side effects raise concerns in patients as well as in doctors and are likely to reduce patients' adherence and, as a consequence, the cardiovascular benefit. Therefore, it is mandatory that clinicians improve their knowledge on the clinical aspects of muscular and hepatic side effects of statin therapy as well as their ability to manage patients with statin intolerance. Besides briefly examining the clinical aspects and the mechanisms that are proposed to be responsible for the most common statin-associated side effects, the main purpose of this article is to review the available approaches to manage statin-intolerant patients. The first step is to determine whether the adverse events are indeed related to statin therapy. If so, lowering the dosage or changing statin, alternate dosing options, or the use of nonstatin compounds may be practical strategies. The cholesterol-lowering potency as well as the usefulness of these different approaches in treating statin-intolerant patients will be examined based on currently available data. However, the cardiovascular benefit of these strategies has not been well established, so their use has to be guided by a careful clinical assessment of each patient.
Inhibition of leukotriene function can modulate particulate‐induced changes in bone cell differentiation and activity (2001)

Aseptic loosening remains the major problem facing arthroplasty longevity with particulates from component materials touted as the cause of periprosthetic osteolysis. Proposed mechanisms in aseptic bone loss include: increased resorption, increased differentiation of osteoclasts (and/or macrophages locally), and decreased osteoblastic bone formation. Leukotrienes participate in osteoclastic bone resorption. We investigated inhibiting leukotrienes synthesis, using ICI 230487, to ameliorate the effects of particulates on osteoclast pit formation and also assessed the effects of alendronate, a bisphosphonate, on pit formation. Three particulates were used: ultra high molecular weight polyethylene (UHMWPE), polymethylmethacrylate (PMMA) and hydroxyapatite (HA). Osteoclast resorption was increased with UHMWPE, PMMA, and HA particles. Interventions with alendronate and ICI 230487 reduced particulate-induced osteoclast resorption. Both ICI 230487 and alendronate reduced osteoclast numbers at higher doses. To assess the effect of particulates on osteoclast and macrophage differentiation, mouse bone marrow was cultured and stained for tartrate resistant acid phosphatase colonies (TRAP+, osteoclasts) and nonspecific esterase positive colonies (NSE+, macrophage precursors). Particulates increased both TRAP+ and NSE+ colony formation. These increases were inhibited by ICI 230487. Particulates also inhibited osteoblast function assessed by the development of mineralized nodules and alkaline phosphatase positive (AP+) colony area. ICI 230487 partly protected osteoblast function from this particulate effect. Blockade of leukotriene production may prove a useful therapeutic intervention for particulate-induced aseptic loosening by inhibiting resorptive activity, reducing the pro-inflammatory cell populations induced and recruited by these particulates, as well as ameliorating the negative effects of inflammatory mediators on osteoblast function.© 2001 John Wiley & Sons, Inc. J Biomed Mater Res (Appl Biomater) 58: 406–414, 2001
Technetium-99m-human polyclonal IgG radiolabeled via the hydrazino nicotinamide derivative for imaging focal sites of infection in rats. (1990)

The biologic behavior of human polyclonal immunoglobulin (IgG) radiolabeled with technetium-99m (99mTc) by a novel method, via a nicotinyl hydrazine derivative, was evaluated in rats. Technetium-99m- and indium-111-IgG were co-administered to normal rats and biodistribution was determined at 2, 6, and 16 hr. The inflammation imaging properties of the two reagents were compared in rats with deep-thigh infection due to Escherichia coli. Blood clearance of both antibody preparations was well described by a bi-exponential function: (99mTc-IgG: t1/2 = 3.82 +/- 0.89 and 57.52 +/- 1.70 hr. 111In-IgG: 3.93 +/- 0.117 and 40.71 +/- 1.26 hr). Biodistributions in the solid organs were similar, however, small but statistically significant differences were detected: 99mTc-IgG greater than 111In-IgG in lung, liver, and spleen; 99mTc-IgG less than 111In-IgG in kidney and skeletal muscle (p less than 0.01). At all three imaging times, target-to-background ratio and percent residual activity for the two compounds were remarkably similar. These studies establish that human polyclonal IgG labeled with 99mTc via a nicotinyl hydrazine modified intermediate is equivalent to 111In-IgG for imaging focal sites of infection in experimental animals.
Donor lymphocyte infusion for relapsed chronic myelogenous leukemia: prognostic relevance of the initial cell dose (2002)

Donor lymphocyte infusion (DLI) can produce durable remissions in patients with chronic myelogenous leukemia (CML) who have a relapse after an allogeneic stem cell transplantation. However, the best modality to administer DLI is still unclear. The effect of the initial cell dose (ICD; ie, mononuclear cells x 10(8)/kg received in the first instance) on outcome was retrospectively analyzed in 298 of 344 patients treated with DLI at 51 centers. Patients were classified into 3 groups according to the ICD: 98 in group A (<or= 0.20), 107 in group B (0.21-2.0), and 93 in group C (> 2.0). Additional infusions were given to 62%, 20%, and 5% of patients in groups A, B, and C, respectively. A lower ICD was associated with less graft-versus-host disease (GVHD; A, 26%; B, 53%; C, 62%; P <.001), less myelosuppression (A, 10%; B, 23%; C, 24%; P =.01), and similar response rate (A, 78%; B, 73%; C, 70%; P =.48). Nonadjusted estimates of 3-year survival, failure-free survival, and DLI-related mortality were 84%, 66%, and 5% respectively, in group A; 63%, 57%, and 20% in group B; and 58%, 45%, and 22% in group C. Outcome analysis was adjusted for patient age, donor type, sex of donor, sex mismatch, disease phase at transplantation, T-cell depletion, interval from transplantation to DLI, GVHD prior to relapse, relapse type, and date of DLI. After adjustment, lower ICD was associated with less GVHD, less myelosuppression, same response rate, better survival, better failure-free survival, and less DLI-related mortality. Our results suggest that the first DLI dose should not exceed 0.2 x 10(8) mononuclear cells/kg.
Interactions of Lipopolysaccharide and Polymyxin Studied by NMR Spectroscopy (2009)

In the light of occurrence of bacterial strains with multiple resistances against most antibiotics, antimicrobial peptides that interact with the outer layer of Gram-negative bacteria, such as polymyxin (PMX), have recently received increased attention. Here we present a study of the interactions of PMX-B, -E, and -M with lipopolysaccharide (LPS) from a deep rough mutant strain of Escherichia coli. A method for efficient purification of biosynthetically produced LPS using reversed-phase high-performance liquid chromatography in combination with ternary solvent mixtures was developed. LPS was incorporated into a membrane model, dodecylphosphocholine micelles, and its interaction with polymyxins was studied by heteronuclear NMR spectroscopy. Data from chemical shift mapping using isotope-labeled LPS or labeled polymyxin, as well as from isotope-filtered nuclear Overhauser effect spectroscopy experiments, reveal the mode of interaction of LPS with polymyxins. Using molecular dynamics calculations the complex of LPS with PMX-B in the presence of dodecylphosphocholine micelles was modeled using restraints derived from chemical shift mapping data and intermolecular nuclear Overhauser effects. In the modeled complex the macrocycle of PMX is centered around the phosphate group at GlcN-B, and additional contacts from polar side chains are formed to GlcN-A and Kdo-C, whereas hydrophobic side chains penetrate the acyl-chain region.
A novel optical microscope for imaging large embryos and tissue volumes with sub-cellular resolution throughout (2016)

Current optical microscope objectives of low magnification have low numerical aperture and therefore have too little depth resolution and discrimination to perform well in confocal and nonlinear microscopy. This is a serious limitation in important areas, including the phenotypic screening of human genes in transgenic mice by study of embryos undergoing advanced organogenesis. We have built an optical lens system for 3D imaging of objects up to 6 mm wide and 3 mm thick with depth resolution of only a few microns instead of the tens of microns currently attained, allowing sub-cellular detail to be resolved throughout the volume. We present this lens, called the Mesolens, with performance data and images from biological specimens including confocal images of whole fixed and intact fluorescently-stained 12.5-day old mouse embryos.
Reliable stream transmission protocols in mobile computing environments (2002)

The popularity and usefulness of the Internet seem to grow exponentially every day. As a result of this rapid growth, mobile users expect to access the Internet's information resources and to communicate with other Internet users. However, providing efficient and reliable stream transmissions in mobile computing environments presents a significant obstacle to the development of mobile computing systems over the Internet. This paper presents three approaches — known as fast retransmissions, data interceptions, and packet interceptions — that can be used to improve the performance and reliability of transmission protocols in mobile computing environments. The paper also discusses how packet interception has become the most effective approach of the three and describes its implementation.
Definition of a new alpha satellite suprachromosomal family characterized by monomeric organization (1993)

We have analyzed more than 500 alphoid monomers either sequenced in our laboratory or available in the literature. Most of them belonged to the well studied suprachromosomal families 1, 2 and 3 characterized by dimeric (1 and 2) and pentameric (3) ancestral periodicities. The sequences that did not belong to the previously known families were subjected to further analysis. About a half of them formed a relatively homogenous family. Its members were on average 80.5% identical and 89.5% homologous to the M1 consensus sequence derived from this group (39 monomers). In the genome they do not form any ancestral periodicities other than a monomeric one, and are found at least in chromosomes 13, 14, 15, 21, 22 and Y. The newly defined family was termed suprachromosomal family 4. Comparison of all 10 alphoid monomeric groups identified so far showed that the M1 sequence is closely related to the J1-D2-W4-W5 homology grouping. Notably the African Green Monkey alpha satellite, also characterized by monomeric construction, appears to be a member of the same group.
TALEN-mediated genetic tailoring as a tool to analyze the function of acquired mutations in multiple myeloma cells (2014)

Multiple myeloma (MM) is a clonal plasma cell malignancy that is initiated by a number of mutations and the process of disease progression is characterized by further acquisition of mutations. The identification and functional characterization of these myelomagenic mutations is necessary to better understand the underlying pathogenic mechanisms in this disease. Recent advancements in next-generation sequencing have made the identification of most of these mutations a reality. However, the functional characterization of these mutations has been hampered by the lack of proper and efficient tools to dissect these mutations. Here we explored the possible utility of transcription activator-like effector nuclease (TALEN) genome engineering technology to tailoring the genome of MM cells. To test this possibility, we targeted the HPRT1 gene and found that TALENs are a very robust and efficient genome-editing tool in MM cells. Using cotransfected green fluorescent protein as an enrichment marker, single-cell subclones with desirable TALEN modifications in the HPRT1 gene were obtained in as little as 3-4 weeks of time. We believe that TALENs will greatly facilitate the functional study of somatic mutations in MM as well as other cancers.