gebhart/patrepeval huggingface dataset:
The Role of Th17 in Neuroimmune Disorders: Target for CAM Therapy. Part II (2009)

Decades of research went into understanding the role that Th1 autoreactive T-cells play in neuroinflammation. Here we describe another effector population, the IL-17-producing T-helper lineage (Th17), which drives the inflammatory process. Through the recruitment of inflammatory infiltration neutrophils and the activation of matrix metalloproteinases, IL-17, a cytokine secreted by Th17 cells, contributes to blood-brain barrier breakdown and the subsequent attraction of macrophages and monocytes into the nervous system. The entry of cells along with the local production of inflammatory cytokines leads to myelin and axonal damage. This activation of the inflammatory response system is induced by different pathogenic factors, such as gut bacterial endotoxins resulting in progressive neurodegeneration by Th17 cells. Through the understanding of the role of bacterial endotoxins and other pathogenic factors in the induction of autoimmune diseases by Th17 cells, CAM practitioners will be able to design CAM therapies targeting IL-17 activity. Targeted therapy can restore the integrity of the intestinal and blood-brain barriers using probiotics, N-acetyl-cysteine, α-lipoic acid, resveratrol and others for their patients with autoimmunities, in particular those with neuroinflammation and neurodegeneration.
Module Assembly for Protein‐Surface Recognition: Geranylgeranyltransferase I Bivalent Inhibitors for Simultaneous Targeting of Interior and Exterior Protein Surfaces (2008)

Synthetic chemical probes designed to simultaneously targeting multiple sites of protein surfaces are of interest owing to their potential application as site specific modulators of protein-protein interactions. A new approach toward bivalent inhibitors of mammalian type I geranylgeranyltransferase (GGTase I) based on module assembly for simultaneous recognition of both interior and exterior protein surfaces is reported. The inhibitors synthesized in this study consist of two modules linked by an alkyl spacer; one is the tetrapeptide CVIL module for binding to the interior protein surface (active pocket) and the other is a 3,4,5-alkoxy substituted benzoyl motif that contains three aminoalkyl groups designed to bind to the negatively charged protein exterior surface near the active site. The compounds were screened by two distinct enzyme inhibition assays based on fluorescence spectroscopy and incorporation of a [(3)H]-labeled prenyl group onto a protein substrate. The bivalent inhibitors block GGTase I enzymatic activity with K(i) values in the submicromolar range and are approximately one order of magnitude and more than 150 times more effective than the tetrapeptide CVIL and the methyl benzoate derivatives, respectively. The bivalent compounds 6 and 8 were shown to be competitive inhibitors, suggesting that the CVIL module anchors the whole molecule to the GGTase I active site and delivers the other module to the targeting protein surface. Thus, our module-assembly approach resulted in simultaneous multiple-site recognition, and as a consequence, synergetic inhibition of GGTase I activity, thereby providing a new approach in designing protein-surface-directed inhibitors for targeting protein-protein interactions.
Anti-cytotoxic T lymphocyte antigen-4 antibodies in melanoma (2013)

Approaches aimed at enhancement of the tumor specific response have provided proof for the rationale of immunotherapy in cancer, both in animal models and in humans. Ipilimumab, an anti-cytotoxic T lymphocyte antigen-4 (CTLA-4) antibody, is a new generation immunotherapeutic agent that has shown activity in terms of disease free and overall survival in metastatic melanoma patients. Its use was approved by the US Food and Drug Administration in March 2011 to treat patients with late stage melanoma that has spread or that cannot be removed by surgery. The mechanism of action of CTLA-4 antibodies in the activation of an antitumor immune response and selected clinical studies of ipilimumab in advanced melanoma patients are discussed. Ipilimumab treatment has been associated with immune related adverse events due to T-cell activation and proliferation. Most of these serious adverse effects are associated with the gastrointestinal tract and include severe diarrhea and colitis. The relationship between immune related adverse events and antitumor activity associated with ipilimumab was explored in clinical studies. Potential biomarkers predictive for clinical response and survival in patients treated with anti-CTLA-4 therapy are presently under investigation. Besides the conventional patterns of response and stable disease as defined by standard Response Evaluation Criteria in Solid Tumors criteria, in subsets of patients, ipilimumab has shown patterns of delayed clinical activity which were associated with an improved overall survival. For this reason a new set of response criteria for tumor immunotherapy has been proposed, which was termed immune related response criteria. These new criteria are presently used to better analyze clinical activity of immunotherapeutic regimens. Ipilimumab is currently under investigation in combination with other treatments, such as chemotherapy, target agents, radiotherapy, and other immuno-therapeutic regimens.
A study of factors affecting responses in electronic mail surveys (1997)

Electronic mail is becoming increasingly popular as a means to communicate information expediently and inexpensively. One use of electronic mail that has not been well researched is its viability as a tool for data collection. A handful of studies have focused on the differences that exist in responses and response rates of electronic mail surveying compared to other methods of surveying (telephone and postal mail). One area that has not been studied at all is the factors affecting the response rates of electronic mail surveys.\nThis research study sought to build upon the existing research base of what is known about using electronic mail surveys as a data collection tool. The purpose of the study was to examine various factors, which may be related to response rate for the electronic mail survey Specifically, the effects of prenotification, personalization of cover letters, and follow-up were the variables studied. Additionally examined was whether there are differences in surveying by regular mail and electronic mail in terms of response rate, time to respond, and the survey responses.\nA sample of 528 faculty and staff members from Western Michigan University was selected to take part in the study. The sample was divided into several treatment groups to study each of the independent variables: electronic prenotification message prior to electronic survey; personally addressed cover letter and electronic mail survey; generically addressed cover letter and electronic mail survey; no follow-up letter and survey for nonrespondents; follow -up letter and survey for nonrespondents; and personalized regular postal mail survey.\nFollow-up w as the variable that most influenced the response rate of the electronic mail survey. Only about one fourth of the sample that did not receive follow-up responded and over 50% o f the sample that did receive follow-up responded. Personalized regular mail surveys received a higher response rate than did electronic mail surveys (67% vs. 51%). Electronic m ail surveys w ith precorrespondence and personalization coupled with follow-up produced no differences in response rates when compared to the personalized regular mail survey. Electronic mail surveys were completed and returned on average at a faster rate than regular mail surveys (3 days vs 15 days).
A Survey of Antiviral Drugs for Bioweapons (2005)

Smallpox (variola major), and the haemorrhagic fever viruses (filoviruses and arenaviruses) are classified as Category A biowarfare agents by the Centers for Disease Control. Category A agents pose a significant risk to public health and national security because they can be easily disseminated by aerosol, although with the exception of variola, they are not easily transmitted from person to person. An attack with these viruses would result in high morbidity and mortality and cause widespread panic. With the exception of smallpox and Argentine haemorrhagic fever virus, there are no vaccines or approved treatments to protect against these diseases. In this review we focus on promising prophylactic, therapeutic and disease modulating drugs (see Figure 1 for select chemical structures).
High-precision pointing on large wall displays using small handheld devices (2013)

Rich interaction with high-resolution wall displays is not limited to remotely pointing at targets. Other relevant types of interaction include virtual navigation, text entry, and direct manipulation of control widgets. However, most techniques for remotely acquiring targets with high precision have studied remote pointing in isolation, focusing on pointing efficiency and ignoring the need to support these other types of interaction. We investigate high-precision pointing techniques capable of acquiring targets as small as 4 millimeters on a 5.5 meters wide display while leaving up to 93 % of a typical tablet device's screen space available for task-specific widgets. We compare these techniques to state-of-the-art distant pointing techniques and show that two of our techniques, a purely relative one and one that uses head orientation, perform as well or better than the best pointing-only input techniques while using a fraction of the interaction resources.
The composition of the murein of Escherichia coli. (1988)

Escherichia coli murein, the polymer from which the shape-maintaining structure of the cell envelope is made, shows unexpected complexity. The separation of murein building blocks with high performance liquid chromatography reveals about 80 different types of muropeptides. Their behavior in high performance liquid chromatography and their chemical structure are described. The complexity of E. coli murein is due to the free combination of seven different types of side chains (L-Ala-D-Glu-R with R = -OH, -m-A2pm, -m-A2pm-D-Ala, -m-A2 pm-Gly, -m-A2pm-D-Ala-D-Ala, -m-A2pm-D-Ala-Gly, -m-A2pm-Lys-Arg) with two types of cross-bridges (D-Ala-m-A2pm, -m-A2pm-m-A2pm). The novel type of cross-bridge, A2pm-A2pm, contains an L,D-peptide bond, as shown by Edman degradation and chemical analysis of the reaction products. The A2pm-A2pm cross-bridge is assumed to play a role in the adaptation of the cross-linkage of murein to different growth conditions of the cell. The structural data of E. coli murein agree best with a model of a thin, however multilayered, murein sacculus.
Parthenogenetic Activation of Porcine Oocytes by Electric Pulse and/or Butyrolactone I Treatment (1999)

The goal of the present research was to study the parthenogenetic activation of porcine oocytes following treatment with the specific cyclin-dependent kinase inhibitor butyrolactone I (BL I). In Experiment I, the effective dose of BL I was determined by the rates of the subsequent pronuclear formation in oocytes after the activation. In Experiment II, BL I was further tested alone or in combination with an electric pulse. The efficiency of the various treatments to induce activation and parthenogenetic development was examined. In Experiment III parthenogenetic development of activated oocytes in two different media was compared. Cleavage and blastocyst developmental rates were examined, and number of cells in the blastocysts was determined. Our results indicate that, in pig, the optimal activation dose for BL I was 150 microM; a combined electrical and BL I treatment resulted in superior cleavage rates compared to an electric pulse, 150 microM of BL I, or 200 microM of BL I alone (74%, 60%, 41%, and 42%, respectively; P < 0.05); and the rate of parthenogenetic development of activated oocytes to the blastocyst stage in mNCSU37 medium was significantly higher than that in Whitten's medium (59% vs. 5%, P < 0.05) and the resulting day-6 blastocysts had higher cell numbers (35.5 +/- 14.1 vs. 19.5 +/- 2.5). This activation protocol might be useful in porcine nuclear transfer experiments and for the generation of parthenogenetic fetuses.
Small Heat-Shock Protein Hsp20 Attenuates β-Agonist–Mediated Cardiac Remodeling Through Apoptosis Signal–Regulating Kinase 1 (2006)

Chronic stimulation of the beta-adrenergic neurohormonal axis contributes to the progression of heart failure and mortality in animal models and human patients. In cardiomyocytes, activation of the beta-adrenergic pathway has been shown to result in transiently increased expression of a cardiac small heat-shock protein Hsp20. The present study shows that cardiac overexpression (10-fold) of Hsp20 may protect the heart against beta-agonist-induced cardiac remodeling, associated with isoproterenol (50 mug/g per day) infusion for 14 days. Hsp20 attenuated the cardiac hypertrophic response, markedly reduced interstitial fibrosis, and decreased apoptosis. Contractility was also preserved in hearts with increased Hsp20 levels. These beneficial effects were associated with attenuation of the ASK1-JNK/p38 (apoptosis signal-regulating kinase 1/c-Jun NH(2)-terminal kinase/p38) signaling cascade triggered by isoproterenol, whereas there was no difference in either extracellular signal-related kinase 1/2 or Akt activation. Parallel in vitro experiments supported the inhibitory role of Hsp20 on enforced ASK1-JNK/p38 activation in both H9c2 cells and adult rat cardiomyocytes. Immunostaining studies also demonstrated that Hsp20 colocalizes with ASK1 in cardiomyocytes. Taken together, our findings indicate that (1) beta-agonist-induced cardiac injury is associated with activation of the ASK1-JNK/p38 cascade; (2) increased expression of Hsp20 attenuates the induction of remodeling, dysfunction, and apoptosis in response to sustained beta-adrenergic stimulation; and (3) the beneficial effects of Hsp20 are at least partially attributable to inhibition of the ASK1-signaling cascade.
Lack of MHC class I surface expression on neoplastic cells and poor activation of the secretory pathway of cytotoxic cells in oral squamous cell carcinomas (1999)

Cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells use the secretory pathway of perforin/granzymes to kill their target cells. In contrast to NK cells, CTL responses are MHC class I restricted. In this study we analysed the relative activation of CTL and NK cells in relation with MHC class I expression on oral squamous cell carcinomas (OSCCs). MHC class I expression was investigated in 47 OSCCs by immunohistochemistry using HCA2, HC10 and beta2-m antibodies. The presence of CTLs, NK cells, and its activation, was investigated in 21 of these OSCCs using respectively, CD8, CD57 and GrB7 antibodies. The Q-Prodit measuring system was used for quantification of cytotoxic cells. All OSCCs showed weak or absent staining of beta2-m on the cell surface. The absence of beta2-m was significantly associated with absent expression of MHC class I heavy chain as detected by HC10 antibody (P = 0.004). In tumour infiltrates CTLs always outnumbered NK cells, as reflected by the ratio CD57/CD8 being always inferior to one (mean: 0.19; SD: 0.15). The proportion of activated cytotoxic cells as detected by granzyme B expression was generally low (mean: 8.6%; SD 8.9). A clear correlation between MHC class I expression and the relative proportion of NK cells/CTLs was not found. This study shows that the majority of OSCCs show weak or absent expression of MHC class I molecules on the cell surface, possibly due to alterations in the normal beta2-m pathway. The low proportion of granzyme B-positive CTLs/NK cells indicates that the secretory pathway of cytotoxicity is poor in these patients. The lack of correlation between MHC class I expression and CTL/NK cell activation as detected by granzyme-B expression suggests that, next to poor antigen presentation, also local factors seem to determine the final outcome of the cytotoxic immune response.
A soluble form of human Delta-like-1 inhibits differentiation of hematopoietic progenitor cells (2000)

Two Notch ligand families, Delta and Serrate/Jagged, have been identified in vertebrates. Members of the Jagged family have been shown to affect in vitro hematopoiesis. To determine whether members of the Delta family might play a similar role in hematopoiesis, we examined the expression of mouse Delta-like-1 (mDll1). mDll1 protein was detected in whole marrow and in a marrow stromal cell line MS-5. At the RNA level, both mDll1 and Notch1 were seen in marrow precursor, differentiated hematopoietic, marrow stromal, and MS-5 cells. We isolated a cDNA encoding the human homologue of mDll1, designated human Delta-like-1 (hDll1). A soluble form of hDll1, hDll1(NDSL), containing the DSL domain and the N-terminal sequences, was expressed and purified from bacteria as a glutathione S-transferase (GST) fusion protein. We observed that hDll1(NDSL) delayed the acquisition of differentiation markers by murine hematopoietic progenitor cells (Lin-) cultured in vitro with cytokines. In addition, it promoted greater expansion (more than 3 times) of the primitive hematopoietic precursor cell population, measured in high-proliferative potential colony assay and day 12 colony-forming unit spleen (CFU-S) assay, than GST controls. We also observed that the percentage of apoptotic cells decreased and that the number of cells in the S-phase of the cell cycle increased in the cultures of Lin(-) cells with hDll1(NDSL). The effects of hDll1(NDSL) were blocked by antibody against the mouse counterpart of hDll1(NDSL), mDll1(NDSL). These observations demonstrate that hDll1 plays a role in mediating cell fate decisions during hematopoiesis. (Blood. 2000;95:1616-1625)
A survey of sensor planning in computer vision (1995)

A survey of research in the area of vision sensor planning is presented. The problem can be summarized as follows: given information about the environment as well as information about the task that the vision system is to accomplish, develop strategies to automatically determine sensor parameter values that achieve this task with a certain degree of satisfaction. With such strategies, sensor parameters values can be selected and can be purposefully changed in order to effectively perform the task at hand. The focus here is on vision sensor planning for the task of robustly detecting object features. For this task, camera and illumination parameters such as position, orientation, and optical settings are determined so that object features are, for example, visible, in focus, within the sensor field of view, magnified as required, and imaged with sufficient contrast. References to, and a brief description of, representative sensing strategies for the tasks of object recognition and scene reconstruction are also presented. For these tasks, sensor configurations are sought that will prove most useful when trying to identify an object or reconstruct a scene.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
EXPLORING THE ROLE OF MENTORING IN AGRICULTURAL ECONOMICS PH.D. TRAINING (1996)

Mentoring is used in many fields to prepare graduate students for a professional career. This study focuses on mentoring of Ph.D. students in agricultural economics, including the effects of mentoring on expected research output and students' satisfaction with time spent with their major professor. The sink-or-swim mentoring method seems to create the most discord among students and also negatively influences expected research output. The students' gender and citizenship seem to also impact expected output.
THE RELATIONSHIP BETWEEN GLUCOSINOLATE CONTENT OF CRUCIFEROUS PLANTS AND OVIPOSITION PREFERENCES OF HYLEMYA BRASSICAE (DIPTERA: ANTHOMYIIDAE) (1976)

Abstract Leaves of each of six cruciferous plant species investigated contained glucosinolates. There was no correlation between the total glucosinolate concentration of the species (identity of the glucosinolates unknown) and the oviposition response of the adult cabbage maggot, Hylemya brassicae (Bouché). Tests with chemical fractions isolated from rutabaga root tissue indicated that glucosinolates are the major, and perhaps the only, oviposition-inducing substances present in cruciferous plants. It is suggested that oviposition preferences are governed by the presence of some ’key’ glucosinolates and the absence of inhibitory chemicals.
Immunology in the clinic review series; focus on cancer: tumour-associated macrophages: undisputed stars of the inflammatory tumour microenvironment (2011)

Mononuclear phagocytes are cells of the innate immunity that defend the host against harmful pathogens and heal tissues after injury. Contrary to expectations, in malignancies, tumour-associated macrophages (TAM) promote disease progression by supporting cancer cell survival, proliferation and invasion. TAM and related myeloid cells [Tie2(+) monocytes and myeloid-derived suppressor cells (MDSC)] also promote tumour angiogenesis and suppress adaptive immune responses. These divergent biological activities are mediated by macrophages/myeloid cells with distinct functional polarization, which are ultimately dictated by microenvironmental cues. Clinical and experimental evidence has shown that cancer tissues with high infiltration of TAM are associated with poor patient prognosis and resistance to therapies. Targeting of macrophages in tumours is considered a promising therapeutic strategy: depletion of TAM or their 're-education' as anti-tumour effectors is under clinical investigation and will hopefully contribute to the success of conventional anti-cancer treatments.
Biochemical mechanism of HIV-I Vpr function. Specific interaction with a cellular protein. (1994)

vpr is an accessory gene of human immunodeficiency virus I (HIV-I). Although unnecessary for viral replication in T cell lines, growing evidence suggests that it is essential for virus replication in monocytes/macrophages and for replication in vivo. We expressed HIV-I vpr in Escherichia coli and purified Vpr by affinity chromatography. In a coprecipitation assay, the purified Vpr interacted specifically with a cellular protein designated as Vpr-interacting protein, or RIP. Mutational analysis suggested that this interaction required a domain rich in leucine/isoleucine residues and highly conserved between HIV-I and SIVmac Vprs. During transient expression in mammalian cells, HIV-I Vpr was localized in the nucleus. However, mutational analysis failed to identify in Vpr a typical nuclear localization signal rich in basic amino acid residues. Instead, Vpr nuclear localization seemed to correlate with Vpr interaction with RIP. Mutations in the C-terminal 20-amino acid region containing a cryptic nuclear localization signal did not abolish Vpr nuclear localization or interaction with RIP, whereas point mutations in the leucine/isoleucine-rich domain abolished Vpr interaction with RIP and rendered Vpr unstable during transient expression. These results suggest that RIP may be involved in Vpr function.