gebhart/patrepeval huggingface dataset:
Sequence and in vitro expression of the M2 gene of turkey rhinotracheitis pneumovirus (1992)

Negative-stranded virion RNA and oligonucleotide primers complementary to fusion (F) protein gene sequences were used to generate cDNA clones, revealing that the gene 5'-proximal to the F protein corresponded to the M2 (22K) gene, as in respiratory syncytial (RS) virus. The transcription start signal, GGGACAAGU, was identical to that of the F and matrix (M) proteins of turkey rhinotracheitis virus (TRTV). There were two sequences with the potential to function as transcription termination/poly(A) signals, located at nucleotides 751 to 762 and 777 to 787; 15 clones derived from mRNA indicated that the first of these sequences formed the major signal. Part of the next downstream (5') gene was sequenced; unlike mammalian pneumoviruses the TRTV M2 gene did not overlap the beginning of the 5'-proximal gene. Northern blotting indicated that infected Vero cells contained less M2 mRNA than F mRNA and that about half of the M2 mRNA was present as a F-M2 dicistronic mRNA. The M2 gene contained two overlapping open reading frames (ORFs 1 and 2), as with RS virus. ORF 1 comprised 558 nucleotides with the coding potential for a 186 amino acid polypeptide, M(r) 20959, eight or nine residues shorter than for human RS virus strains. The overall amino acid identity was 40%, the N-terminal one-third of the proteins sharing 62% of residues, the remainder 29%. A hydropathy plot of the TRTV M2 protein had close similarity to that of the M2 or RS virus. The protein was predicted to have a basic character with no N-terminal signal sequence or other major highly hydrophobic sequences. In vitro translation of a transcript comprising both ORFs 1 and 2 produced a single product of apparent M(r) 23000, corresponding to the M2 product of ORF 1. Site-directed mutagenesis confirmed that this product was derived from ORF 1 and that frameshifting was not involved. The second ORF was expressed only from a transcript which lacked the AUG codons of ORF 1 and, although occupying a similar position to that in the RS virus M2 gene, had virtually no amino acid identity in its 73 residue length and was approximately 25% shorter than the corresponding RS virus ORF 2. The hydropathy plot of the potential products of the second ORFs of TRTV and RS virus showed little resemblance. Taken together these results suggest that ORF 2 is unlikely to be expressed in vivo.(ABSTRACT TRUNCATED AT 400 WORDS)
Selection of internalization‐deficient cells by interleukin‐2‐Pseudomonas exotoxin chimeric protein: the cytoplasmic domain of the interleukin‐2 receptor β chain does not contribute to internalization of interleukin‐2 (1993)

To study the structural basis of ligand-induced receptor-mediated internalization of interleukin-2 (IL-2), a strategy has been developed to generate variant T cells that are deficient in internalization of this cytokine. IL-2 receptor (IL-2R) alpha- and beta-bearing EL4 cells, that express high-affinity IL-2R and internalize IL-2, were treated with low doses of IL-2-Pseudomonas exotoxin chimeric protein (IL-2-PE40). This treatment resulted in isolation of a variant (CX1) that was unable to express high-affinity IL-2R or internalize IL-2. Transfection of CX1 with the IL-2R beta cDNA led to surface expression of IL-2R beta and high-affinity IL-2R as well as the ability to internalize IL-2. This finding indicates that the absence of the beta subunit was the sole defect in CX1 responsible for its failure to internalize IL-2. By transfecting CX1 with mutated beta cDNA, several CX1 transfectants were produced that expressed a beta-subunit that lacked all amino acids of the intracytoplasmic region. These transfectants expressed high-affinity IL-2R and internalized IL-2 at a rate comparable to cells expressing wild-type beta-chain. These results demonstrate that internalization of IL-2 is independent of any signals contained in the intracytoplasmic tail of the beta subunit and raise the possibility that such signals may be entirely contained within the gamma subunit.
KIR2DL4 Differentially Signals Downstream Functions in Human NK Cells through Distinct Structural Modules (2008)

KIR2DL4 (2DL4) is a member of the killer cell Ig-like receptor (KIR) family in human NK cells. It can stimulate potent cytokine production and weak cytolytic activity in resting NK cells, but the mechanism for 2DL4-mediated signaling remains unclear. In this study we characterized the signaling pathways stimulated by 2DL4 engagement. In a human NK-like cell line, KHYG-1, cross-linking of 2DL4 activated MAPKs including JNK, ERK, and p38. Furthermore, 2DL4 cross-linking resulted in phosphorylation of IkappaB kinase beta (IKKbeta) and the phosphorylation and degradation of IkappaBalpha, which indicate activation of the classical NF-kappaB pathway. Engagement of 2DL4 was also shown to activate the transcription and translation of a variety of cytokine genes, including TNF-alpha, IFN-gamma, MIP1alpha, MIP1beta, and IL-8. Pharmacological inhibitors of JNK, MEK1/2 and p38, blocked IFN-gamma, IL-8, and MIP1alpha production, suggesting that MAPKs are regulating 2DL4-mediated cytokine production in a nonredundant manner. Activation of both p38 and ERK appear to be upstream of the stimulation of NF-kappaB. Mutation of a transmembrane arginine in 2DL4 to glycine (R/G mutant) abrogated FcepsilonRI-gamma association, as well as receptor-mediated cytolytic activity and calcium responses. Surprisingly, the R/G mutant still activated MAPKs and the NF-kappaB pathway and selectively stimulated the production of MIP1alpha, but not that of IFN-gamma or IL-8. In conclusion, we provide evidence that the activating functions of 2DL4 can be compartmentalized into two distinct structural modules: 1) through transmembrane association with FcepsilonRI-gamma; and 2) through another receptor domain independent of the transmembrane arginine.
LOW LEVEL LASER THERAPY IN PATIENTS WITH VENOUS ULCERS: (1996)

The effectiveness of low level laser therapy in accelerating would healing has been clinically well documented. We report our experience treating 42 patients with resistant venous ulcers (ulcus cruris) due to chronic venous insufficiency syndrome, using low level laser therapy (LLLT). Full granulation and closure of the ulcers was achieved in 36 patients, two of whom had a recurrence after two years. Complete wound closure in 85.7% of our patients is attributed to the biostimulating effect of laser therapy.
Negative group-velocity dispersion using refraction (1984)

It is shown that a negative contribution to the group-velocity dispersion always accompanies angular dispersion. We describe structures, such as slabs and prisms, that use this contribution to provide adjustable group-velocity dispersion. We discuss, in particular, considerations regarding incorporation of these structures with a laser resonator. A description of possible submillimeter semiconductor devices is also given.
miRNA-221 promotes cutaneous squamous cell carcinoma progression by targeting PTEN (2019)

Taken together, the obtained results indicated that miR-221 plays an oncogenic function in CSCC by targeting PTEN and further suggest that miR-221 may be a potential target for CSCC diagnosis and treatment.
Purification of a Modified Form of Bovine Antithrombin III as an HIV-1 CD8+ T-cell Antiviral Factor (2002)

CD8(+) T-cells secrete soluble factor(s) capable of inhibiting both R5- and X4-tropic strains of human immunodeficiency virus type 1 (HIV-1). CCR5 chemokine ligands, released from activated CD8(+) T-cells, contribute to the antiviral activity of these cells. These CC-chemokines, however, do not account for all CD8(+) T-cell antiviral factor(s) (CAF) released from these cells, particularly because the elusive CAF can inhibit the replication of X4 HIV-1 strains that use CXCR4 and not CCR5 as a coreceptor. Here we demonstrate that activated CD8(+) T-cells of HIV-1-seropositive individuals modify serum bovine antithrombin III into an HIV-1 inhibitory factor capable of suppressing the replication of X4 HIV-1. These data indicate that antithrombin III may play a role in the progression of HIV-1 disease.
Estimates of echo correlation and measurement bias in acoustic radiation force impulse imaging (2003)

Acoustic radiation force impulse (ARFI) imaging is a novel imaging modality in which pulses from a diagnostic ultrasound scanner are used to displace tissue and track its motion. The region displaced has lateral and elevational dimensions of similar scale to the ultrasound beams used to track the motion. Therefore, there is a range of tissue displacements present within the tracking beam, leading to decorrelation of the echo signal. Expressions are derived for the expected value of the displacement estimate and the cross-correlation at the expected displacement. Numerical simulations confirm the analytical model.
Total fecal microbiota transplantation alleviates high-fat diet-induced steatohepatitis in mice via beneficial regulation of gut microbiota (2017)

Non-alcoholic steatohepatitis (NASH) is an epidemic metabolic disease with limited therapeutic strategies. Cumulative data support the pivotal role of gut microbiota in NASH. Here, we investigated the hypothesis regarding whether fecal microbiota transplantation (FMT) is effective in attenuating high-fat diet (HFD)-induced steatohepatitis in mice. Mice were randomized into control, HFD and HFD + FMT groups. After an 8-week HFD, FMT treatment was initiated and carried out for 8 weeks. The gut microbiota structure, butyrate concentrations of the cecal content, liver pathology and intrahepatic lipid and cytokines were examined. Our results showed that after FMT, the gut microbiota disturbance was corrected in HFD-fed mice with elevated abundances of the beneficial bacteria Christensenellaceae and Lactobacillus. FMT also increased butyrate concentrations of the cecal content and the intestinal tight junction protein ZO-1, resulting in relief of endotoxima in HFD-fed mice. Steatohepatitis was alleviated after FMT, as indicated by a significant decrease in intrahepatic lipid accumulation (reduced Oli-red staining, decreased intrahepatic triglyceride and cholesterol), intrahepatic pro-inflammatory cytokines, and the NAS score. Accordingly, intrahepatic IFN-γ and IL-17 were decreased, but Foxp3, IL-4 and IL-22 were increased after FMT intervention. These data indicate that FMT attenuated HFD-induced steatohepatitis in mice via a beneficial effect on the gut microbiota.
Microfluidic actuation by modulation of surface stresses (2003)

We demonstrate the active manipulation of nanoliter liquid samples on the surface of a glass or silicon substrate by combining chemical surface patterning with electronically addressable microheater arrays. Hydrophilic lanes designate the possible routes for liquid migration while activation of specific heater elements determine the trajectories. The induced temperature fields spatially modulate the liquid surface tension thereby providing electronic control over the direction, timing, and flow rate of continuous streams or discrete drops. Temperature maps can be programed to move, split, trap, and mix ultrasmall volumes without mechanically moving parts and with low operating voltages of 2–3 V. This method of fluidic actuation allows direct accessibility to liquid samples for handling and diagnostic purposes and provides an attractive platform for palm-sized and battery-powered analysis and synthesis.
Relationship between inflammatory biomarkers and depressive symptoms during late pregnancy and the early postpartum period: a longitudinal study (2016)

Our study supports previous reports from the literature showing no relationship between inflammatory biomarkers and depressive symptoms during late pregnancy, early postpartum, or across time. Our study is the first to observe an association between late pregnancy levels of IL-6 and IL-10 and postpartum depressive symptoms. Further studies with larger samples are required to confirm these findings.
Synthesis of 6,7‐dimethoxypyrimido[4,5‐b]‐indoles as potential antihypertensive agents (1988)

Abstract Using ethyl 5,7‐dimethoxy‐2‐amino‐3‐indolecarboxylate as a synthon, routes are described for the synthesis of the title compounds bearing alkylamino moieties in the 2 and 4‐positions. Some of the compounds displayed antihypertensive activity.
Cancer spread and micrometastasis development: Quantitative approaches for in vivo models (2002)

Death from cancer is usually due to metastasis. Fortunately, most cells that escape from a primary tumor fail to form metastases. Identifying reasons for this failure will help development of anti-metastatic therapies. Intravital videomicroscopy (IVVM) can be used to observe cancer cells injected into live animals. Co-injected microspheres can be used to assess cell survival. These techniques have been used to show that circulating tumor cells generally arrest in the microcirculation and may extravasate with high efficiency. While many tumor cells may survive in a secondary site, only a small subset form micrometastases and only a subset of these micrometastases persist to form vascularized macrometastases. Furthermore, solitary tumor cells may remain dormant for long periods of time in secondary sites. These findings suggest that metastatic growth and angiogenesis are prime targets for anti-metastatic therapy.
Cytokine Gene Transfer Enhances Herpes Oncolytic Therapy in Murine Squamous Cell Carcinoma (2001)

Replication-competent, attenuated herpes simplex viruses (HSV) have been demonstrated to be effective oncolytic agents in a variety of malignant tumors. Cytokine gene transfer has also been used as immunomodulatory therapy for cancer. To test the utility of combining these two approaches, two oncolytic HSV vectors (NV1034 and NV1042) were designed to express the murine GM-CSF and murine IL-12 genes, respectively. These cytokine-carrying variants were compared with the analogous non-cytokine-carrying control virus (NV1023) in the treatment of murine SCC VII squamous cell carcinoma. All three viruses demonstrated similar infection efficiency, viral replication, and cytotoxicity in vitro. SCC VII cells infected by NV1034 and NV1042 effectively produced GM-CSF and IL-12, respectively. In an SCC VII subcutaneous flank tumor model in immunocompetent C3H/HeJ mice, intratumoral injection with each virus caused a significant reduction in tumor volume compared with saline injections. The NV1042-treated tumors showed a striking reduction in tumor volume compared with the NV1023- and NV1034-treated tumors. On subsequent rechallenge in the contralateral flank with SCC VII cells, 57% of animals treated with NV1042 failed to develop tumors, in comparison with 14% of animals treated with NV1023 or NV1034, and 0% of naive animals. The increased antitumor efficacy seen with NV1042 in comparison with NV1023 and NV1034 was abrogated by CD4(+) and CD8(+) lymphocyte depletion. NV1042 is a novel, attenuated, oncolytic herpesvirus that effectively expresses IL-12 and elicits a T lymphocyte-mediated antitumor immune response against murine squamous cell carcinoma. Such combined oncolytic and immunomodulatory strategies hold promise in the treatment of cancer.
Complement activation during systemic lupus erythematosus: C3A and C5a anaphylatoxins circulate during exacerbations of disease (1986)

To determine whether activated complement components appear in the circulation of patients with systemic lupus erythematosus (SLE), we measured C5a and C3a by radioimmunoassay. Mean C5a concentration in the plasma of acutely ill SLE patients was 46.0 ng/ml, compared with 17.1 ng/ml in normal controls (P less than 0.01). Mean C3a concentration in patients with severe disease was 526 ng/ml, compared with 134 ng/ml in controls (P less than 0.01). In patients with moderately active SLE, the mean C3a concentration, but not the mean C5a concentration, was also elevated. In addition, C3a was elevated in 15 or 21 patients with active SLE, whereas low levels of C3 or C4 were noted in only 7 of these 21 patients. We conclude that the measurement of complement-derived anaphylatoxins may be useful in the management of patients with SLE. In addition, we suggest that these circulating mediators may contribute to the pathogenesis of vascular injury in patients with the disease.
Microarray-Based Cell-Free DNA Analysis Improves Noninvasive Prenatal Testing (2014)

NIPT using microarrays delivers more accurate cfDNA analysis than next-generation sequencing and can be performed in less time.
Paradigmenwechsel bei der Alzheimer-Krankheit: Intrazelluläre Aggregation von Amyloid-beta verursacht den Zellverlust unabhängig von extrazellulären Plaques (2008)

Vermehrte Hinweise deuten auf eine wichtige Rolle von intraneuronalem A&amp;#946; als Auslöser der pathologischen Kaskade hin, welche zu Neurodegeneration und schließlich zur Alzheimer-Demenz mit ihren typischen klinischen Symptomen wie Gedächtnisverlust und Veränderung der Persönlichkeit führt. Die Amyloid-A&amp;#946;-Plaques haben keine toxische Funktion und ihre Anzahl und Lokalisation korreliert nicht mit Zellverlust und kognitiver Beeinträchtigung. Die vorliegende Übersicht fokussiert auf das APP/PS1KI-Mausmodell, da es als einziges Modell einen massiven Nervenzellverlust im Hippokampus zeigt. Der hohe Nervenzellverlust, die Hippokampusatrophie und der synaptische Funktionsverlust entwickeln sich aufgrund der intraneuronalen Amyloid-Pathologie und nicht als Folge der extrazellulären Plaque-Ablagerungen. Dieser Befund stellt das gängige therapeutische Konzept der Reduzierung von extrazellulären Plaques in Frage.
Expression of a single-chain HLA class I molecule in a human cell line: presentation of exogenous peptide and processed antigen to cytotoxic T lymphocytes. (1996)

We have synthesized a recombinant gene encoding a single-chain HLA-A2/beta 2-microglobulin (beta 2m) molecule by linking beta 2m through its carboxyl terminus via a short peptide spacer to HLA-A2 (A*0201). This gene has been expressed in the beta 2m-deficient colorectal tumor cell line DLD-1. Transfection of this cell with the single-chain construct was associated with conformationally correct cell surface expression of a class I molecule of appropriate molecular mass. The single-chain HLA class I molecule presented either exogenously added peptide or (after interferon-gamma treatment) endogenously processed antigen to an influenza A matrix-specific, HLA-A2-restricted cytotoxic T-lymphocyte line. The need for interferon gamma for the processing and presentation of endogenous antigen suggests that DLD-1 has an antigen-processing defect that can be up-regulated, a feature that may be found in other carcinomas. Our data indicate that single-chain HLA class I constructs can form functional class I molecules capable of presenting endogenously processed antigens. Such molecules should be of use for functional studies, as well as providing potential anticancer immunotherapeutic agents or vaccines.
GENETIC ALGORITHM MODEL FOR PROFIT MAXIMIZATION OF GENERATING COMPANIES IN DEREGULATED ELECTRICITY MARKETS (2009)

In deregulated and rapidly changing electricity markets, there is strong interest on how to solve the new price-based unit commitment (PBUC) problem used by each generating company to optimize its generation schedule in order to maximize its profit. This article proposes a genetic algorithm (GA) solution to the PBUC problem. The advantages of the proposed GA are: 1) flexibility in modeling problem constraints because the PBUC problem is not decomposed either by time or by unit; 2) smooth and easier convergence to the optimum solution thanks to the proposed variable fitness function which not only penalizes solutions that violate the constraints but also this penalization is smoothly increasing as the number of generations increases; 3) easy implementation to work on parallel computers, and 4) production of multiple unit commitment schedules, some of which may be well suited to situations that may arise quickly due to unexpected contingencies. The method has been applied to systems of up to 120 units and the results show that the proposed GA constantly outperforms the Lagrangian relaxation PBUC method for systems with more than 60 units. Moreover, the difference between the worst and the best GA solution is very small, ranging from 0.10% to 0.49%.
Directional Relays for Multi-Hop Cooperative Cognitive Radio Networks (2013)

In this paper, we investigate power allocation and beamforming in a relay assisted cognitive radio (CR) network. Our objective is to maximize the performance of the CR network while limiting interference in the direction of the primary users (PUs). In order to achieve these goals, we first consider joint power allocation and beamforming for cognitive nodes in direct links. Then, we propose an optimal power allocation strategy for relay nodes in indirect transmissions. Unlike the conventional cooperative relaying networks, the applied relays are equipped with directional antennas to further reduce the interference to PUs and meet the CR network requirements. The proposed approach employs genetic algorithm (GA) to solve the optimization problems. Numerical simulation results illustrate the quality of service (QoS) satisfaction in both primary and secondary networks. These results also show that notable improvements are achieved in the system performance if the conventional omni-directional relays are replaced with directional ones.
Platelet isoforms of platelet-derived growth factor stimulate fibroblasts to contract collagen matrices. (1989)

Fibroplasia and angiogenesis are essential components of tissue repair when substantial tissue has been lost at a site of injury. Platelets and monocyte/macrophages accumulate at these sites and release a variety of growth factors that are thought to initiate and sustain the repair. Often the involved tissue contracts, a process that can markedly reduce the amount of fibroplasia and angiogenesis necessary for the reestablishment of organ integrity. Such tissue contraction occurs over hours or days, a much slower time course than the rapid, reversible contraction of muscle tissue. Fibroblasts, which are rich in f-actin bundles, appear to be responsible for wound contraction. However, the signals that stimulate contraction are not known. Using cultured fibroblasts, which are also rich in f-actin bundles, we demonstrate the platelet and monocyte isoforms of platelet-derived growth factor (PDGF; AB and BB) but not PDGF-AA, can stimulate fibroblasts to contract collagen matrix in a time course similar to that of wound contraction. In addition, PDGF appears to be the predominant fibroblast/collagen gel contraction activity released from platelets. Vasoactive agonists known to stimulate smooth and striated muscle contraction do not stimulate fibroblast-driven collagen gel contraction.
Rig is a novel Ras-related protein and potential neural tumor suppressor (2002)

The Ras superfamily consists of a large group of monomeric GTPases demonstrating homology to Ras oncoproteins. Although structurally similar, Ras-superfamily proteins are functionally diverse. Whereas some members exhibit oncogenic properties, others may serve as tumor suppressors. We have identified a novel Ras-related protein that suppresses cell growth and have designated it Rig (Ras-related inhibitor of cell growth). Overexpression of Rig inhibited Ras-mediated cellular transformation and activation of downstream signaling in NIH 3T3 cells. rig mRNA is expressed at high levels in normal cardiac and neural tissue. However, Rig protein expression is frequently lost or down-regulated in neural tumor-derived cell lines and primary human neural tumors. Moreover, expression of exogenous Rig in human astrocytoma cells suppressed growth. Rig has a C-terminal CAAX motif that codes for posttranslational modification by both farnesyl and geranylgeranyl isoprenoid lipids. Consequently, Rig may play a role in the cellular response to farnesyl transferase inhibitors. Rig bears 63% overall sequence homology to a recently described Ras-family member Noey2, a tumor suppressor in breast and ovarian tissue. Therefore, Rig and Noey2 may represent a new subfamily of Ras-like tumor suppressors.