gebhart/patrepeval huggingface dataset:
Presence and Performance Within Virtual Environments (1995)

Recent developments in display technology, specifically head-mounted displays slaved to the user’s head position, techniques to spatialize sound, and computer-generated tactile and kinesthetic feedback allow humans to experience impressive visual, auditory, and tactile simulations of virtual environments. However, while technological advancements in the equipment to produce virtual environments have been quite impressive, what is currently lacking is a conceptual and analytical framework in which to guide research in this developing area. What is also lacking is a set of metrics which can be used to measure performance within virtual environments and to quantify the level of presence experienced by participants of virtual worlds. Given the importance of achieving presence in virtual environments, it is interesting to note that we currently have no theory of presence, let alone a theory of virtual presence (feeling like you are present in the environment generated by the computer) or telepresence (feeling like you are actually “there” at the remote site of operation). This in spite of the fact that students of literature, the graphic arts, the theater arts, film, and TV have long been concerned with the observer’s sense of presence. In fact, one might ask, what do the new technological interfaces in the virtual environment domain add, and how do they affect this sense, beyond the ways in which our imaginations (mental models) have been stimulated by authors and artists for centuries? Not only is it necessary to develop a theory of presence for virtual environments, it is also necessary to develop a basic research program to investigate the relationship between presence and performance using virtual environments. To develop a basic research program focusing on presence, several important questions need to be addressed. The first question to pose is, how do we measure the level of presence experienced by an operator within a virtual environment? We need to develop an operational, reliable, useful, and robust measure of presence in order to evaluate various techniques used to produce virtual environments. Second, we need to determine when, and under what conditions, presence can be a benefit or a detriment to performance.
The effects of corruption on administrative performance : illustrations from development countries (1983)

This study is one in a series of papers devoted to issues of development management in the search for greater efficiency in setting and pursuing developing goals. The widespread occurrence of corruption in developing countries, whereby public money is illicitly diverted for private gain, has raised substantial concern. The particular circumstances of developing countries as well as government monopoly of economic activities, conditions of political softness, widespread poverty and socioeconomic inequalities, ambivalence toward the legitimacy of governmental organizations, and systematic maladministration appear to be conducive to corruption. The data shows that corruption has a deleterious effect on administrative performance and economic and political development. The paper suggests counteraction measures ranging from commissions of inquiry, ombudsmen to investigate citizen complaints, courses and seminars, to simplification of administrative and financial procedures.
Jitter performance in ethernet passive optical networks (2005)

Ethernet passive optical networks (EPONs) have emerged as one of the most promising access network technologies. Propelled by rapid price declines in fiber optics and Ethernet components, these architectures combine the latest in optical and electronic advances and are poised to become the dominant means of delivering gigabit broadband connectivity to homes over a unified single platform. As this technology matures, related quality of service (QoS) issues are becoming a key concern. This paper proposes a novel dynamic scheduling algorithm, termed hybrid granting protocol (HGP), to support different QoS in EPON. Specifically, the proposed dynamic scheduling algorithm minimizes packet delay and jitter for delay and delay-variation sensitive traffic (e.g., voice transmissions) by allocating bandwidth in a grant-before-report (GBR) fashion. This considerably improves their performance without degrading QoS guarantees for other service types. Detailed simulation experiments are presented to validate the effectiveness of the proposed algorithm.
Association of IL-21 Cytokine With Severity of Primary Sjögren Syndrome Dry Eye (2015)

Our findings suggest that severity of primary SS dry eye is associated with IL-21.
K- and N-Ras Are Geranylgeranylated in Cells Treated with Farnesyl Protein Transferase Inhibitors (1997)

The association of mutant forms of Ras protein with a variety of human cancers has stimulated intense interest in therapies based on inhibiting oncogenic Ras signaling. Attachment of Ras proteins to the plasma membrane is required for effective Ras signaling and is initiated by the enzyme farnesyl protein transferase. We found that in the presence of potent farnesyl protein transferase inhibitors, Ras proteins in the human colon carcinoma cell line DLD-1 were alternatively prenylated by geranylgeranyl transferase-1. When H-Ras, N-Ras, K-Ras4A, and K-Ras4B were expressed individually in COS cells, H-Ras prenylation and membrane association were found to be uniquely sensitive to farnesyl transferase inhibitors; N- and K-Ras proteins incorporated the geranylgeranyl isoprene group and remained associated with the membrane fraction. The alternative prenylation of N- and K-Ras has significant implications for our understanding of the mechanism of action of farnesyl protein transferase inhibitors as anti-cancer chemotherapeutics.
Dimerization via Tandem Leucine Zippers Is Essential for the Activation of the Mitogen-activated Protein Kinase Kinase Kinase, MLK-3 (1998)

Mixed lineage kinase-3 (MLK-3) is a mitogen-activated kinase kinase kinase that mediates stress-activating protein kinase (SAPK)/c-Jun NH2-terminal kinase activation. MLK-3 and other MLK family kinases are characterized by the presence of multiple protein-protein interaction domains including a tandem leucine/isoleucine zipper (LZs) motif. Leucine zippers are known to mediate protein dimerization raising the possibility that the tandem leucine/isoleucine zippers may function as a dimerization motif of MLK-3. Using both co-immunoprecipitation and nonreducing SDS-polyacrylamide gel electrophoresis, we demonstrated that MLK-3 forms disulfide bridged homo-dimers and that the LZs motif is sufficient for MLK-3 homodimerization. We next asked whether MLK-3 utilizes a dimerization-based activation mechanism analogous to that of receptor tyrosine kinases. We found that dimerization via the LZs motif is a prerequisite for MLK-3 autophosphorylation. We then demonstrated that co-expression of Cdc42 lead to a substantial increase in MLK-3 dimerization, indicating that binding by this GTPase may induce MLK-3 dimerization. Moreover, the LZs minus form of MLK-3 failed to activate the downstream target SAPK, and expression of a MLK-3 LZs polypeptide was found to block SAPK activation by wild type MLK-3. Taken together, these findings indicate that dimerization plays a pivotal role in MLK-3 activation.
High Divergence of the Precursor Peptides in Combinatorial Lanthipeptide Biosynthesis (2014)

Lanthionine-containing peptides (lanthipeptides) are a rapidly growing family of polycyclic peptide natural products belonging to the large class of ribosomally synthesized and post-translationally modified peptides (RiPPs). These compounds are widely distributed in taxonomically distant species, and their biosynthetic systems and biological activities are diverse. A unique example of lanthipeptide biosynthesis is the prochlorosin synthetase ProcM from the marine cyanobacterium Prochlorococcus MIT9313, which transforms up to 29 different precursor peptides (ProcAs) into a library of lanthipeptides called prochlorosins (Pcns) with highly diverse sequences and ring topologies. Here, we show that many ProcM-like enzymes from a variety of bacteria have the capacity to carry out post-translational modifications on highly diverse precursor peptides, providing new examples of natural combinatorial biosynthesis. We also demonstrate that the leader peptides come from different evolutionary origins, suggesting that the combinatorial biosynthesis is tied to the enzyme and not a specific type of leader peptide. For some precursor peptides encoded in the genomes, the leader peptides apparently have been truncated at the N-termini, and we show that these N-terminally truncated peptides are still substrates of the enzymes. Consistent with this hypothesis, we demonstrate that about two-thirds of the ProcA N-terminal sequence is not essential for ProcM activity. Our results also highlight the potential of exploring this class of natural products by genome mining and bioengineering.
Protein Chip Discovery of Secreted Proteins Regulated by the Phosphatidylinositol 3-Kinase Pathway in Ovarian Cancer Cell Lines (2006)

Ovarian cancer has the highest mortality among the gynecologic malignancies. The phosphatidylinositol 3-kinase (PI3K) pathway is frequently activated, leading to increased cell survival. This study aimed to identify secreted proteins regulated by the PI3K pathway in ovarian cancer cell lines. Surface-enhanced laser desorption-ionization time-of-flight mass spectrometry with cation-exchange protein-chips was used to analyze secreted proteins from five ovarian cancer cell lines (SKOV-3, PE01, OVCAR-3, OV167, and OV207). To activate the PI3K pathway, cells were treated with 50 ng/mL epidermal growth factor (EGF) with or without 10 micromol/L LY294002, a PI3K inhibitor. Proteins induced by EGF and inhibited by LY294002, in the m/z range 7,500 to 9,500, were purified chromatographically, identified by peptide mass fingerprinting and NH(2)-terminal sequencing, and confirmed by immunodepletion. Two immunologically related proteins, m/z approximately 8,385 and 8,922, were identified as truncated and intact forms, respectively, of interleukin 8, a chemokine previously shown to be elevated in serum of ovarian cancer patients. Another protein, m/z 7,866, was identified as CXC chemokine ligand 1 (CXCL1) or GRO-alpha, a chemokine associated with melanoma formation and some epithelial cancers. EGF-stimulated CXCL1 levels were variably decreased by mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase kinase and p38 MAPK inhibition in the five cell lines, but only LY294002 fully reversed the EGF effect in all cell lines. Immunoreactive CXCL1 levels in 160 conditioned media were highly correlated with corresponding peak intensities at m/z 7,866 by mass spectrometry, indicating the quantitative nature of these analyses. We conclude that proteomic analysis of cell models of human disease may facilitate the discovery of pathway-dependent proteins.
Regulation of the proprotein convertase subtilisin/kexin type 9 in intestinal epithelial cells (2009)

Proprotein convertase subtilisin/kexin type 9 (PCSK9) posttranslationally promotes the degradation of the low-density lipoprotein receptor (LDLr) in hepatocytes and increases plasma LDL cholesterol. It is not clear, however, whether PCSK9 plays a role in the small intestine. Here, we characterized the patterns of variations of PCSK9 and LDLr in fully differentiated Caco-2/15 cells as a function of various potential effectors. Cholesterol (100 microM) solubilized in albumin or micelles significantly downregulated PCSK9 gene (30%, P<0.05) and protein expression (50%, P<0.05), surprisingly in concert with a decrease in LDLr protein levels (45%, P<0.05). Cells treated with 25-hydroxycholesterol (50 microM) also displayed significant reduction in PCSK9 gene (37%, P<0.01) and protein (75% P<0.001) expression, whereas LDLr showed a decrease at the gene (30%, P<0.05) and protein (57%, P<0.01) levels, respectively. The amounts of PCSK9 mRNA and protein in Caco-2/15 cells were associated to the regulation of 3-hydroxy-3-methylglutaryl-CoA reductase and sterol regulatory element binding protein-2 (SREBP-2) that can transcriptionally activate PCSK9 via sterol-regulatory elements located in its proximal promoter region. On the other hand, depletion of cholesterol content by hydroxypropyl-beta-cyclodextrin upregulated PCSK9 transcripts (20%, P<0.05) and protein mass (540%, P<0.001), in parallel with SREBP-2 protein levels. The addition of bile acids (BA) taurocholate and deoxycholate to the apical culture medium lowered PCSK9 gene expression (25%, P<0.01) and raised PCSK9 protein expression (30%, P<0.01), respectively, probably via the modulation of farnesoid X receptor. Furthermore, unconjugated and conjugated BA exhibited different effects on PCSK9 and LDLr. Altogether, these data indicate that intestinal PCSK9 is highly modulated by sterols and emphasize the distinct effects of BA species.
Mcl-1, a Bcl-2 Family Member, Delays the Death of Hematopoietic Cells Under a Variety of Apoptosis-Inducing Conditions (1997)

Mcl-1 is a member of the Bcl-2 family that was identified based on increased expression in myeloblastic leukemia cells undergoing differentiation. Mcl-1 was previously found to be similar to Bcl-2 in causing a delay in apoptotic cell death in Chinese hamster ovary cells. The work described here was aimed at determining whether Mcl-1 could also exert such an effect in hematopoietic cells, because endogenous Mcl-1 expression is prominent in the hematopoietic system. A further aim was to assess the effects of Mcl-1 in cells exposed to a variety of cytotoxic stimuli, because Bcl-2 is known to have a broad spectrum of activity. To approach these aims, FDC-P1 murine myeloid progenitor cells were transfected with vectors driving either constitutive or inducible expression of Mcl-1. The introduced Mcl-1 gene was found to cause a prolongation of viability under various conditions that cause apoptotic cell death, including exposure to cytotoxic agents (the chemotherapeutic drug etoposide, calcium ionophore, or UV irradiation) and the withdrawal of required growth factors. In addition, Mcl-1 was found to interact with Bax, a member of the Bcl-2 family that promotes cell death as a homodimer but that can heterodimerize with Bcl-2 to promote cell viability. Although Mcl-1 prolonged cell viability, it did not prevent eventual cell death upon continuous exposure to a cytotoxic agent. Prolongation of viability was maximal when expression of Mcl-1 was induced before the application of the apoptotic stimulus, although some increase occurred if Mcl-1 was induced shortly thereafter and before overt apoptosis. Taken as a whole, these findings provide further parallels between Mcl-1 and Bcl-2, showing that Mcl-1 can interact with Bax in hematopoietic FDC-P1 cells and can prolong cell viability under a variety of cytotoxic conditions.
Potent anti‐tumor responses to immunization with dendritic cells loaded with tumor tissue and an NKT cell ligand (2010)

Cancer immunotherapy is well tolerated and specific, but its efficacy remains variable. To enhance anti-tumor CD8(+) T-cell responses induced by immunization with antigen-loaded dendritic cells (DCs), we explored the impact of eliciting a potent source of T-cell help from activated invariant natural killer (NK)-like T cells (iNKT cells) using the specific glycolipid ligand alpha-galactosylceramide (alpha-GalCer). As cytokines released by iNKT cells may drive proliferation of CD4(+)CD25(+) regulatory T cells (Tregs), we assessed this immunization strategy in animals treated with anti-CD25 antibody to inactivate Treg function. Combining DC immunization with iNKT cell activation was found to significantly enhance anti-tumor activity, which was improved further by the prior inactivation of Tregs. The improved anti-tumor activity with Treg inactivation was associated with a prolonged proliferative burst of responding CD8(+) T cells. We could find no evidence that inclusion of alpha-GalCer in the vaccine enhanced Treg numbers, or that the 'helper' function of iNKT cells was improved in the absence of Treg activity. Rather, the two activities appeared to act independently to improve the tumor-specific T-cell response. Inactivating regulatory T cells and eliciting iNKT cell activation are therefore two useful strategies that can be used in combination to improve anti-tumor immunization with antigen-loaded DCs.
Carcinoembryonic antigen (CEA)-specific T-cell activation in colon carcinoma induced by anti-CD3 x anti-CEA bispecific diabodies and B7 x anti-CEA bispecific fusion proteins. (1999)

Two bispecific recombinant molecules, an anti-CD3 x anti-carcinoembryogenic antigen (CEA) diabody and a B7 x anti-CEA fusion protein, were tested for their capacity to specifically activate T cells in the presence of CEA-expressing colon carcinoma cells. T-cell activation by the anti-CD3 x anti-CEA diabody required close contact to CEA-positive cells and resulted in diabody-mediated cytotoxicity against the target cells. Additionally, CD28-mediated costimulation in combination with anti-CD3 x anti-CEA diabodies induced activation of autologous T cells in CEA-positive primary colon carcinoma specimens, as determined by flow cytometry. The high specificity of the bispecific diabody approach could be further enhanced by the use of B7 x anti-CEA fusion proteins because the costimulatory CD28-signaling to the T cells strictly depended on the expression of CEA on the target cells. We demonstrate that displaying engagement sites for the T-cell antigens CD3 and CD28 on the surface of colon carcinoma cells is a suitable way to activate and retarget T cells in a highly tumor-specific manner. For clinical purposes, B7 x anti-tumor-associated antigen (TAA) fusion proteins, which are equally effective but more specific compared with anti-CD28 monoclonal anti-bodies, thus may improve the tumor specificity of anti-CD3 x anti-TAA bispecific antibodies. Furthermore, B7-negative tumors can be converted into B7-positive tumors by B7 x anti-TAA fusion proteins without the need for B7 gene transfer to the malignant cells.
Flow-Mediated Regulation of Endothelin Receptors in Cocultured Vascular Smooth Muscle Cells: An Endothelium-Dependent Effect (1997)

The objective of this study was to determine the effect of pulsatile flow on endothelin (ET) receptor expression in vascular smooth muscle cells (VSMC) cocultured with endothelial cells (EC). Using a perfused transcapillary coculture system which permits the chronic exposure of cultured EC and VSMC to physiological shear stresses, cocultures were exposed to stepwise increases in flow up to (1) 2 ml/min (low flow: 0.5 dyn/cm2) or (2) 44 ml/min (high flow: 15 dyn/cm2) and maintained for 72 h before SMC and EC were harvested separately. There was a significant increase in [125I]-ET-1 binding in cocultured VSMC exposed to high flow as compared to low flow (Bmax: 75 +/- 22 vs. 152 +/- 10 fmol [125I]ET-1 bound/mg protein) in the absence of any change in the affinity (KD) of ET-1 for its receptor. ET-1 peptide mRNA levels were significantly decreased in EC exposed to high flow. The increase in [125I]ET-1 binding was associated with an increase in ET-A and ET-B receptor mRNA levels and was EC dependent as [125I]ET-1 binding in monocultured VSMC was the same, regardless of flow conditions. However, the amount of [125I]ET-1 binding on VSMC cultured in the absence of EC was significantly greater than that on cocultured VSMC. High flow caused a significant increase in endothelial nitric oxide synthase (NOS) activity in EC and prostacyclin levels in the perfusing medium. Flow-mediated upregulation of ET receptors was diminished by treatment with NG-nitro-L-arginine-methyl ester, a NOS inhibitor, whereas indomethacin, a cyclooxygenase inhibitor, had no significant effect. Collectively, these data suggest that flow-induced changes in ET receptor expression in VSMC are endothelium dependent and are in part mediated by nitric oxide. Modulation of ET receptor expression by EC may thus represent an important mechanism whereby hemodynamic forces regulate vessel wall function.
Vapor levitation epitaxy (1985)

InP and InGaAs-InGaAsP alloys lattice-matched to InP are crucial to the fabrication of optical sources and detectors that operate at wavelengths of minimum loss and dispersion of currently available optical fibers (1.55 and 1.3 μm). Optimization and economical production of these devices require precise control of layer thickness and composition across large-area wafers. We have developed a new vapor phase epitaxial technique that is particularly well-suited to the growth of such multilayer structures required for long-wavelength optoelectronic applications.
Anti-GD2 Antibody Therapy for GD2-Expressing Tumors (2010)

In the development of novel immune therapies for high-risk cancers, one goal is to find tumor targets that are not widely shared by normal cells. One such target is the surface disialoganglioside GD2. This antigen is expressed on the surface of a variety of tumors for which no curative therapies exist for patients with advanced disease. In childhood, the most common GD2-expressing tumor is neuroblastoma. GD2 is also expressed on several other high-risk tumors, including those of neuroectodermal or epithelial origin, virtually all melanomas, and approximately 50% of tumor samples from osteosarcoma and soft-tissue sarcomas. Because of the tumor-selective expression of this molecule, it is an attractive target for tumor-specific therapies such as antibody therapy. Over the last 2 decades, several anti-GD2 antibodies have been developed. To reduce both the toxicity of the antibody and the development of human anti-mouse antibodies (HAMA), research efforts have primarily focused on exploring anti-GD2 antibodies that have progressively more human elements while at the same time reducing the mouse components. This review will examine antibodies currently undergoing clinical testing as well as the most recent advances to improve antibody therapy for patients with GD2-expressing tumors.
Analysis of a Model for Excitation of Myelinated Nerve (1976)

Excellent models have been presented in the literature which relate membrane potential to transverse membrane current and which describe the propagation of action potentials along the axon, for both myelinated and nonmyelinated fibers. There is not, however, an adequate model for nerve excitation which allows one to compute the threshold of a nerve fiber for pulses of finite duration using electrodes that are not in direct contact with the fiber. This paper considers this problem and presents a model of the electrical properties of myelinated nerve which describes the time course of events following stimulus application up to the initiation of the action potential. The time-varying current and potential at all nodes can be computed from the model, and the strength-duration curve can be determined for arbitrary electrode geometries, although only the case of a monopolar electrode is considered in this paper. It is shown that even when the stimulus is a constant-current pulse, the membrane current at the nodes varies considerably with time. The strength-duration curve calculated from the model is consistent with previously published experimental data, and the model provides a quantitative relationship between threshold and fiber diameter which shows there is less selectivity among fibers of large diameter than those of small diameter.