gebhart/patrepeval huggingface dataset:
Inhibition of HIV-1 replication and NF-x B activity by cysteine and cysteine derivatives (1991)

HIV-1 proviral DNA contains two binding sites for the transcription factor NF-kappa B. HIV-1-infected individuals have, on average, abnormally high levels of tumour necrosis factor alpha (TNF alpha) and abnormally low plasma cysteine levels. We therefore investigated the effects of cysteine and related thiols on HIV-1 replication and NF-kappa B expression. The experiments in this report show that cysteine or N-acetylcysteine (NAC) raise the intracellular glutathione (GSH) level and inhibit HIV-1 replication in persistently infected Molt-4 and U937 cells. However, inhibition of HIV-1 replication appears not to be directly correlated with GSH levels. Cysteine and NAC also inhibit NF-kappa B activity as determined by electrophoretic mobility shift assays and chloramphenicol acetyl-transferase (CAT) gene expression under control of NF-kappa B binding sites in uninfected cells. This suggests that the cysteine deficiency in HIV-1-infected individuals may cause an over-expression of NF-kappa B-dependent genes and enhance HIV-1 replication. NAC may be considered for the treatment of HIV-1-infected individuals.
Jamming prokaryotic cell-to-cell communications in a model biofilm (2008)

We report on the physical parameters governing prokaryotic cell-to-cell signaling in a model biofilm. The model biofilm is comprised of bacteria that are genetically engineered to transmit and receive quorum-sensing (QS) signals. The model is formed using arrays of time-shared, holographic optical traps in conjunction with microfluidics to precisely position bacteria, and then encapsulated within a hydrogel that mimics the extracellular matrix. Using fluorescent protein reporters functionally linked to QS genes, we assay the intercellular signaling. We find that there isn't a single cell density for which QS-regulated genes are induced or repressed. On the contrary, cell-to-cell signaling is largely governed by diffusion, and is acutely sensitive to mass-transfer to the surroundings and the cell location. These observations are consistent with the view that QS-signals act simply as a probe measuring mixing, flow, or diffusion in the microenvironment of the cell.
Spatial filter for increasing the depth of focus (1985)

The Strehl ratio, in the form of McCutchen's theorem, is employed to design a spatial filter that increases the depth of focus. Computer-simulated images show the increment in focal depth.
Interleukin-9 Induces Tyrosine Phosphorylation of Insulin Receptor Substrate-1 via JAK Tyrosine Kinases (1995)

Interleukin (IL)-9 stimulates the proliferation of a variety of hematopoietic lineages through its interaction with a receptor of the cytokine receptor superfamily. In the studies presented here, we have begun to characterize the downstream signaling pathways activated by IL-9. In addition to the activation of JAK1 and JAK3 tyrosine kinases, IL-9, unlike most hematopoietic cytokines but similar to IL-4, induces the tyrosine phosphorylation of a 170-kDa protein that is related to the insulin receptor substrate-1 (IRS-1). We further demonstrate for the first time that IRS-1 is not only associated with JAK1 but also tyrosine phosphorylated and functionally involved in IL-9 signaling in TS1 lymphocytes transfected with the murine IRS-1 cDNA. Cotransfection studies and in vitro experiments directly demonstrate that JAK1, JAK2, or JAK3 is capable of tyrosine phosphorylating IRS-1, suggesting a functional role for these kinases in vivo. Lastly, we demonstrate that IL-9 induces the tyrosine phosphorylation of Stat3 and in this regard differs from IL-4, which triggers tyrosine phosphorylation of Stat6. Taken together, these results strongly suggest that IL-9 and IL-4 utilize common and unique signaling pathways via inducing the similar and distinct tyrosine-phosphorylated proteins.
Survival effect of ciliary neurotrophic factor (CNTF) on chick embryonic motoneurons in culture: comparison with other neurotrophic factors and cytokines (1990)

In previous studies, it has been demonstrated that ciliary neurotrophic factor (CNTF) has a potent survival effect on various populations of neurons in culture, in particular, neurons isolated from chick ciliary, dorsal root sensory, and sympathetic ganglia (Barbin et al., 1984). After recent investigations demonstrated that CNTF prevents the degeneration of motoneurons in newborn rats after axonal lesion (Sendtner et al., 1990), the question arose as to whether CNTF also has a survival effect on embryonic chick motoneurons at the developmental stage where physiological cell death occurs. To study this, it was essential to develop an isolation and culture procedure for the survival of chick E6 spinal motoneurons in which non-neuronal cells were eliminated and the motoneurons were highly enriched. In these cultures, virtually all of the initially plated motoneurons survived for at least 3 d in the presence of muscle extract, which was chosen as a positive control. Retrograde labeling of the motoneurons prior to their isolation showed that there is more than an 80% enrichment for motoneurons by the method used. The retrogradely labeled neurons also fulfilled the morphological criteria (diameter of neurons, appearance of processes) to identify motoneurons independent of retrograde labeling. Under these conditions, CNTF at a concentration of 1.5 ng/ml (EC50, 0.023 ng/ml) supported maximally 64% of the initially plated spinal motoneurons after 3 d and 53% after 6 d (the longest time period investigated). Other neurotrophic factors, such as NGF, brain-derived neurotrophic factor (BDNF), and neurotrophin-3, had no survival effect at all, even at concentrations up to 10 micrograms/ml for NGF and BDNF.(ABSTRACT TRUNCATED AT 250 WORDS)
Cyclin-dependent kinase 6 (CDK6) amplification in human gliomas identified using two-dimensional separation of genomic DNA. (1997)

DNA amplification is a common mechanism invoked by many human tumors to elicit overexpression of genes whose products are involved in drug resistance or cell proliferation. Although amplified regions in tumor DNA may exceed several megabases in size, segments of amplicons with a high probability of containing gene sequences may be amenable to detection by restriction landmark genomic scanning (RLGS), a high-resolution DNA analysis that separates labeled NotI fragments in two dimensions. Here, we tested this by applying RLGS to matched samples of glioma and normal brain DNA and found tumor-specific amplification of the gene encoding cyclin-dependent kinase 6 (CDK6), an observation not previously reported in human tumors. The CDK6 gene has been localized to chromosome 7q21-22, but in the gliomas studied here, it was not coamplified with either the syntenic MET (7q31) or epidermal growth factor receptor (7p11-p12) genes, suggesting that this may be part of a novel amplicon in gliomas. We then corroborated this finding by identifying both amplification-associated and amplification-independent increases in CDK6 protein levels in gliomas relative to matched normal brain samples. These data implicate the CDK6 gene in genomic amplification and illustrate the potential of RLGS for the more general identification and cloning of novel genes that are amplified in human cancer.
The Signature Sequence of Voltage-gated Potassium Channels Projects into the External Vestibule (1996)

A highly conserved motif, GYGD, contributes to the formation of the ion selectivity filter in voltage-gated K+ channels and is thought to interact with the scorpion toxin residue, Lys27. By probing the pore of the Kv1.3 channel with synthetic kaliotoxin-Lys27 mutants, each containing a non-natural lysine analog of a different length, and using mutant cycle analysis, we determined the spatial locations of Tyr400 and Asp402 in the GYGD motif, relative to His404 located at the base of the outer vestibule. Our data indicate that the terminal amines of the shorter Lys27 analogs lie close to His404 and to Asp402, while Lys27 itself interacts with Tyr400. Based on these data, we developed a molecular model of this region of the channel. The junction between the outer vestibule and the pore is defined by a ring ( approximately 8-9-A diameter) formed from alternating Asp402 and His404 residues. Tyr400 lies 4-6 A deeper into the pore, and its interaction with kaliotoxin-Lys27 is in competition with K+ ions. Studies with dimeric Kv1.3 constructs suggest that two Tyr400 residues in the tetramer are sufficient to bind K+ ions. Thus, at least part of the K+ channel signature sequence extends into a shallow trough at the center of a wide external vestibule.
Needle free injection technology: A complete insight (2015)

Needle free injection technology (NFIT)is an extremely broad concept which include a wide range of drug delivery systems that drive drugs through the skin using any of the forces as Lorentz, Shock waves, pressure by gas or electrophoresis which propels the drug through the skin, virtually nullifying the use of hypodermic needle. This technology is not only touted to be beneficial for the pharma industry but developing world too find it highly useful in mass immunization programmes, bypassing the chances of needle stick injuries and avoiding other complications including those arising due to multiple use of single needle. The NFIT devices can be classified based on their working, type of load, mechanism of drug delivery and site of delivery. To administer a stable, safe and an effective dose through NFIT, the sterility, shelf life and viscosity of drug are the main components which should be taken care of. Technically superior needle-free injection systems are able to administer highly viscous drug products which cannot be administered by traditional needle and syringe systems, further adding to the usefulness of the technology. NFIT devices can be manufactured in a variety of ways; however the widely employed procedure to manufacture it is by injection molding technique. There are many variants of this technology which are being marketed, such as Bioject(®) ZetaJetTM, Vitajet 3, Tev-Tropin(®) and so on. Larger investment has been made in developing this technology with several devices already being available in the market post FDA clearance and a great market worldwide.
Die Erfahrung deutscher Volontäre mit dem israelisch-palästinensischen Konflikt: Positionierung, emotionale Ambivalenz und emotionale Nähe (2013)

Diese Studie untersucht, inwiefern sich die mentalen Konfliktmodelle von jungen Deutschen während eines Freiwilligendienstes in Israel oder Palästina verändern. 33 deutsche Freiwillige beantworteten einen Fragebogen zur Positionierung, emotionalen Ambivalenz und emotionalen Nähe bezüglich des israelisch-palästinensischen Konfliktes, bevor sie Deutschland verließen. Nach ungefähr vier Monaten nahmen sie an einer zweiten Befragung teil. Obwohl die Untersuchung nicht repräsentativ ist, konnte gezeigt werden, dass beinahe die Hälfte der Teilnehmer ihre Position zum israelisch-palästinensischen Konflikt während ihres Aufenthaltes vor Ort veränderte. Die Ergebnisse bestätigen Befunde vorangegangener Studien und weisen darauf hin, dass die emotionale Nähe zu der einen oder der anderen Konfliktpartei eine wichtige Rolle bei der Positionierung zum Konflikt spielt. Insbesondere die Teilnehmer, die eine größere emotionale Nähe zu den Palästinensern entwickelten, nahmen eine deutliche pro-palästinensische Haltung ein.
Epiplakin Gene Analysis in Mouse Reveals a Single Exon Encoding a 725-kDa Protein with Expression Restricted to Epithelial Tissues (2003)

Based on cDNA cloning and sequencing, human epiplakin has been classified as a member of the plakin protein family of cytolinkers. We report here the characterization of the mouse epiplakin gene locus and the isolation of full-length mouse epiplakin cDNA using BAC vectors. We found that the protein is encoded by a single remarkably large exon (>20 kb) that consists of a series of 0.8-1.5-kb-long DNA repeats, eight of which are virtually identical. Consequently, mouse epiplakin contains 16 plakin repeat domains, three more than reported for the human protein and eight more than predicted for the mouse protein based on the contig characterized by the Mouse Genome Sequencing Consortium. Using antibodies raised to a highly conserved repeating epiplakin sequence domain, we show that the protein in cells is expressed in its full length (725 kDa), and we provide evidence that the size of human epiplakin previously may have been underestimated. In addition we show on transcript and protein levels that epiplakin is restricted to epithelial tissues and that its gene maps to mouse chromosome 15 (human chromosome 8). This study lays the groundwork for future genetic approaches aimed at defining the biological role of this unique protein.
Processing of β-Secretase by Furin and Other Members of the Proprotein Convertase Family (2001)

The amyloid peptide is the main constituent of the amyloid plaques in brain of Alzheimer's disease patients. This peptide is generated from the amyloid precursor protein by two consecutive cleavages. Cleavage at the N terminus is performed by the recently discovered beta-secretase (Bace). This aspartyl protease contains a propeptide that has to be removed to obtain mature Bace. Furin and other members of the furin family of prohormone convertases are involved in this process. Surprisingly, beta-secretase activity, neither at the classical Asp(1) position nor at the Glu(11) position of amyloid precursor protein, seems to be controlled by this maturation step. Furthermore, we show that Glu(11) cleavage is a function of the expression level of Bace, that it depends on the membrane anchorage of Bace, and that Asp(1) cleavage can be followed by Glu(11) cleavage. Our data suggest that pro-Bace could be active as a beta-secretase in the early biosynthetic compartments of the cell and could be involved in the generation of the intracellular pool of the amyloid peptide. We conclude that modulation of the conversion of pro-Bace to mature Bace is not a relevant drug target to treat Alzheimer's disease.
Optimization of Annealing Temperature To Reduce Bias Caused by a Primer Mismatch in Multitemplate PCR (2001)

To reduce PCR bias derived from a primer mismatch, the effect of the annealing temperature on the product ratio was investigated by denaturing gradient gel electrophoresis analysis of PCR products from a mixture of perfect-match and one-mismatch templates. These templates were generated by PCR from Pediococcus acidilactici for one mismatch and Micrococcus luteus for the perfect match. PCRs showed that the bias was reduced at lower temperatures. An environmental sample was also examined.
Chemoattractant receptor cross talk as a regulatory mechanism in leukocyte adhesion and migration (1997)

Leukocytes express multiple chemoattractant receptors that can trigger adhesion and direct their migration. Regulation of such proadhesive and migratory responses must often occur in a complex cytokine milieu in vivo, in which multiple receptors may be engaged simultaneously or sequentially, Here we have examined the interplay between interleukin-8 (IL-8) receptor and formyl peptide receptor (fPR)-stimulation and its consequences for leukocyte adhesion and chemotactic responses. IL-8 has no significant effect on fMLP-stimulated adhesion and migration of human neutrophils, indicating that leukocytes have the potential to respond to sequential proadhesive and chemoattractant stimuli during homing and targeted migration. In contrast, fMLP at > or = 10 nM totally abrogated proadhesive and chemoattractant responses to IL-8, a trnas effect to which the fPR itself is relatively resistant. N-formyl peptides are released by invasive bacteria and lysed cells, and the dominance of the fPR may ensure that signals from these terminal phagocyte targets can override host-derived recruitment signaling through IL-8 and other chemokine receptors. Asymmetric inhibition of adhesion-triggering responses is also observed in lymphoid cells transfected with IL-8 receptor A and fPR, but in this cellular context chemotactic responses are bidirectionally abrogated, suggesting the potential for downstream desensitization of motility programs as well. Cross talk between chemoattractant receptors and their signaling pathways may help target leukocyte migration in the context of complex chemoattractant arrays in vivo.
Fc gamma RIIA alleles are heritable risk factors for lupus nephritis in African Americans. (1996)

Allelic variants of Fc gamma R confer distinct phagocytic capacities providing a mechanism for heritable susceptibility to immune complex disease. Human Fc gamma RIIa has two codominantly expressed alleles, R131 and H131, which differ substantially in their ability to ligate human IgG2. The Fc gamma RIIa-H131 is the only human Fc gamma R which recognizes IgG2 efficiently and optimal IgG2 handling occurs only in the homozygous state. Therefore, since immune complex clearance is essential in SLE, we hypothesized that Fc gamma RIIA genes are important disease susceptibility factors for SLE, particularly lupus nephritis. In a two-stage cross-sectional study, we compared the distribution of Fc gamma RIIA alleles in African Americans with SLE to that in African American non-SLE controls. A pilot study of 43 SLE patients and 39 controls demonstrated a skewed distribution of Fc gamma RIIA alleles, with only 9% of SLE patients homozygous for Fc gamma RIIa-H131 compared with 36% of controls (odds ratio, 0.18; 95% CI, 0.05-0.69, P = 0.009). This was confirmed with a multicenter study of 214 SLE patients and 100 non-SLE controls. The altered distribution of Fc gamma RIIA alleles was most striking in lupus nephritis. Trend analysis of the genotype distribution showed a highly significant decrease in Fc gamma RIIA-H131 as the likelihood for lupus nephritis increased (P = 0.0004) consistent with a protective effect of the Fc gamma RIIA-H131 gene. The skewing in the distribution of Fc gamma RIIA alleles identifies this gene as a risk factor with pathophysiologic importance for the SLE diathesis in African Americans.
A Role for Human SPα as a Pattern Recognition Receptor (2005)

Human Sp alpha is a soluble protein belonging to group B of the scavenger receptor cysteine-rich (SRCR) superfamily for which little functional information is available. It is expressed by macrophages present in lymphoid tissues (spleen, lymph node, thymus, and bone marrow), and it binds to myelomonocytic and lymphoid cells, which suggests that it may play an important role in the regulation of the innate and adaptive immune systems. In the present study we show that recombinant human Sp alpha (rSp alpha) binds to the surface of several gram-positive and gram-negative bacterial strains. Competition studies indicated that such binding is mediated by the recognition of lipoteichoic acid (LTA) and lipopolysaccharide (LPS), respectively, through nonoverlapping sites on the Sp alpha molecule. The most conserved part of LPS (2-keto-3-deoxyoctulosonic acid and lipid A) was shown to be involved in the recognition by Sp alpha. Bacterial binding studies using the SRCR domain 1 of Sp alpha showed that this domain retains both the LPS and LTA binding activities, indicating that both bacterial interacting sites are retained in a single SRCR domain. Furthermore, rSp alpha induced aggregation of gram-positive and gram-negative bacteria strains. On the other hand, rSp alpha inhibited tumor necrosis factor-alpha secretion by human monocytes stimulated with LPS or LTA. Binding of Sp alpha to conserved components of bacterial surfaces and modulation of the monocyte response indicate that this molecule is an active constituent of the innate immune response of the host.
Amplitudes of Accommodation of Primate Lenses Refilled With Two Types of Inflatable Endocapsular Balloons (1993)

The greater yield of accommodation with the nonaccommodation balloon is consistent with the recent theory on the mechanism of accommodation. Although the obtained accommodation was a small fraction of values determined prior to the operation and the small amplitude of accommodation decreased over time, the feasibility of refilling the lens with an inflatable endocapsular balloon, allowing at least some accommodation in the eyes of youthful primates, was demonstrated. Applied to humans, this procedure may allow accommodation following cataract surgery.
Selective transfer of individual human chromosomes to recipient cells. (1985)

Two hypoxanthine phosphoribosyltransferase-deficient human cell lines, D98/AH-2 and HT1080-6TG, were stably transfected with pSV2 gpt, a plasmid containing the selectable marker Escherichia coli xanthine-guanine phosphoribosyl transferase (Eco gpt). Hypoxanthine-aminopterin-thymidine-resistant transformants arose with a frequency of ca. 10(-6) and contained mostly single, but occasionally multiple, copies of the plasmid sequences. These transformants actively express the Eco gpt marker. Single chromosomes from two different HT1080 gpt transformants and one D98 gpt transformant, containing the integrated plasmid sequences, were transferred via microcell-mediated chromosome transfer to hypoxanthine phosphoribosyl transferase-deficient mouse A9 cells. The transferred human chromosomes were identified as 2, 4, and 22, by using a combination of G-11 staining, G-banding, isoenzyme analysis, and in situ hybridization. This system is being used to create a library of interspecies microcell hybrid clones, each clone containing a unique single human chromosome in a mouse background. The complete library will represent the entire human karyotype.
ENCRYPTION-BASED PROTECTION PROTOCOLS FOR INTERACTIVE USER-COMPUTER COMMUNICATION (1976)

This thesis develops a complete set of protocols, which utilize a block cipher, e.g., the NBS data encryption standard, for protection interactive user-computer communication over physically unsecured channels. The use of the block cipher protects against disclosure of message contents to an intruder, and the protocols provide for the detection of message stream modification and dental of message service by an intruder.
New Evidence of Premature Oxidative DNA Damage: Mitochondrial DNA Deletion in Gingival Tissue of Patients With Periodontitis (2006)

The overproduction of ROS by activated polymorphonuclear leukocytes in chronic inflammation may lead to premature oxidative damage of the mtDNA. In this study, the occurrence of the 5-kbp mtDNA deletion in 24 periodontitis subjects may be evidence of premature oxidative DNA damage.