gebhart/patrepeval huggingface dataset:
Nerve growth factor stimulates a protein kinase in PC-12 cells that phosphorylates microtubule-associated protein-2. (1990)

Some of the effects of nerve growth factor (NGF) may be mediated by changes in protein phosphorylation. We have identified a protein kinase from PC-12 cells that catalyzes the phosphorylation of pig brain microtubule-associated protein (MAP)-2 in vitro. This activity is stimulated 2-4-fold in extracts from cells treated with NGF or epidermal growth factor (EGF). The partial purification and characterization of this MAP kinase indicate that it is distinct from previously described NGF-stimulated protein kinases. The NGF-stimulated kinase activity is unaffected by direct addition to the assay of the heat-stable cAMP-dependent kinase peptide inhibitor, staurosporine, or K-252A, is slightly stimulated by heparin and is inhibited by sodium fluoride and calcium ions. Treatment of cells with NGF increases the activity of the kinase within 2 min. The activity declines after 10 min, and a second phase of activation is observed at 20-30 min. Comparison of its behavior on gel permeation and sucrose density gradients indicates a molecular mass in the range of 40,000 daltons. The kinase activity is specific for ATP as substrate with a Km of 12 microM. Although the pathway of activation of MAP kinase by NGF is unknown, the stimulation can be reversed by treatment of the enzyme with alkaline phosphatase, suggesting that activation involves phosphorylation of the kinase itself. The properties and hormone sensitivity of the PC-12 MAP kinase suggest that it is similar to the previously identified, growth factor-sensitive MAP kinase from 3T3-L1 adipocytes.
From Host to Phage Metabolism: Hot Tales of Phage T4’s Takeover of E. coli (2018)

The mechanisms by which bacteriophage T4 converts the metabolism of its <i>E. coli</i> host to one dedicated to progeny phage production was the subject of decades of intense research in many labs from the 1950s through the 1980s. Presently, a wide range of phages are starting to be used therapeutically and in many other applications, and also the range of phage sequence data available is skyrocketing. It is thus important to re-explore the extensive available data about the intricacies of the T4 infection process as summarized here, expand it to looking much more broadly at other genera of phages, and explore phage infections using newly-available modern techniques and a range of appropriate environmental conditions.
Nucleic Acid Sequence-Based Amplification, a New Method for Analysis of Spliced and Unspliced Epstein-Barr Virus Latent Transcripts, and Its Comparison with Reverse Transcriptase PCR (1998)

Nucleic acid sequence-based amplification (NASBA) assays were developed for direct detection of Epstein-Barr virus (EBV) transcripts encoding EBV nuclear antigen 1 (EBNA1), latent membrane proteins (LMP) 1 and 2, and BamHIA rightward frame 1 (BARF1) and for the noncoding EBV early RNA 1 (EBER1). The sensitivities of all NASBAs were at least 100 copies of specific in vitro-generated RNA. Furthermore, 1 EBV-positive JY cell in a background of 50,000 EBV-negative Ramos cells (the relative sensitivity) was detected by using the EBNA1, LMP1, and LMP2 NASBA assays. The relative sensitivity of the EBER1 NASBA was 100 EBV-positive cells, which was probably related to the loss of small RNA molecules during the isolation. The BARF1 and LMP2 NASBAs were evaluated on clinical material. BARF1 expression was found in 6 of 7 nasopharyngeal carcinomas (NPC) but in 0 of 22 Hodgkin's disease (HD) cases, whereas LMP2 expression was found in 7 of 7 NPCs and in 17 of 22 HD cases. For detection of EBNA1 transcripts in HLs (n = 12) and T- and B-cell non-Hodgkin's lymphomas (n = 3 and n = 2, respectively), NASBA was compared with reverse transcriptase (RT) PCR. Two samples were positive only with NASBA, and two other samples were positive only with RT-PCR; for all other samples, the RT-PCR and NASBA results were in agreement. We conclude that NASBA is suitable for sensitive and specific detection of the above-mentioned EBV transcripts, regardless of their splicing patterns and the presence of EBV DNA. The EBNA1, LMP2, and BARF1 NASBAs developed in this study proved to be reliable assays for detection of the corresponding transcripts in EBV-positive clinical material.
Progress and challenges towards targeted delivery of cancer therapeutics (2018)

Targeted delivery approaches for cancer therapeutics have shown a steep rise over the past few decades. However, compared to the plethora of successful pre-clinical studies, only 15 passively targeted nanocarriers (NCs) have been approved for clinical use and none of the actively targeted NCs have advanced past clinical trials. Herein, we review the principles behind targeted delivery approaches to determine potential reasons for their limited clinical translation and success. We propose criteria and considerations that must be taken into account for the development of novel actively targeted NCs. We also highlight the possible directions for the development of successful tumor targeting strategies.
The effect on drinking of peptide precursors and of shorter chain peptide fragments of angiotensin II injected into the rat's diencephalon (1971)

1. Recently it has been shown that injection of angiotensin II into the anterior diencephalon causes the rat to drink water. In the present experiments the dipsogenic action of a number of other substances including substances related to angiotensin was tested.2. Injection of 0.001 Goldblatt u. renin into the angiotensin-sensitive region causes the water-replete rat to drink. Drinking is slower in onset and continues for longer than after injection of angiotensin II.3. Synthetic tetradecapeptide renin substrate and angiotensin I were as effective as angiotensin II at causing water-replete rats to drink.4. beta-aspartic acid(1)-valine(5)-angiotensin II was also fully effective; but the D-arginine substituted octapeptide was much less effective.5. The (2-8) heptapeptide retained about 50% of the dipsogenic activity of the octapeptide, whereas the absence of phenylalanine at the other end of the peptide chain in the (1-7) heptapeptide results in an inactive compound.6. The (3-8) hexapeptide and the (4-8) pentapeptide, both of which have phenylalanine at the end of the chain, and the (1-4) and (5-8) tetrapeptide fragments of angiotensin II showed only a slight action on intake of water.7. Kallikrein, bradykinin, adenosine-3'5-cyclic phosphate, vasopressin and oxytocin caused no drinking when injected into the angiotensin-sensitive region.8. It is concluded that the requirements for the dipsogenic activity of angiotensin are the same as those for its other biological actions with the qualification that the precursor peptides are also active, presumably because they give rise to angiotensin II locally.
Prevention of diabetes in NOD mice at a late stage by targeting OX40/OX40 ligand interactions (2004)

Autoreactive T cells play a major role in the development of insulin-dependent diabetes mellitus, suggesting that costimulatory molecules that regulate T cell responses might be essential for disease progression. In NOD mice, CD28/B7 and CD40/CD40 ligand (L) interactions control the onset of diabetes from 2 to 4 weeks of age, but blocking these molecules has little effect after this time. Hence, it is possible that other ligand/receptor pairs control a later phase of disease. We now show that OX40 is expressed on CD4 and CD8 T cells several weeks prior to islet destruction, which is initiated around weeks 12-14, and that OX40L is present on dendritic cells in both secondary lymphoid organs and the pancreas from 11 to 13 weeks of age. Blocking OX40L at 6, 9, or 15 weeks after birth had little effect on disease; however, inhibiting OX40/OX40L interactions at week 12, or continuous treatment from week 12 onwards, significantly reduced the incidence of diabetes. Histological examination showed that islet destruction was prevented and insulitis reduced by targeting OX40L. These studies show that OX40/OX40L interactions form a late checkpoint in diabetes development and suggest that these molecules are realistic targets for therapeutic intervention.
Phase I Study of PARP Inhibitor ABT-888 in Combination with Topotecan in Adults with Refractory Solid Tumors and Lymphomas (2011)

A phase I trial of ABT-888 (veliparib), a PARP inhibitor, in combination with topotecan, a topoisomerase I-targeted agent, was carried out to determine maximum tolerated dose (MTD), safety, pharmacokinetics, and pharmacodynamics of the combination in patients with refractory solid tumors and lymphomas. Varying schedules and doses of intravenous topotecan in combination with ABT-888 (10 mg) administered orally twice a day (BID) were evaluated. Plasma and urine pharmacokinetics were assessed and levels of poly(ADP-ribose) (PAR) and the DNA damage marker γH2AX were measured in tumor and peripheral blood mononuclear cells (PBMC). Twenty-four patients were enrolled. Significant myelosuppression limited the ability to coadminister ABT-888 with standard doses of topotecan, necessitating dose reductions. Preclinical studies using athymic mice carrying human tumor xenografts also informed schedule changes. The MTD was established as topotecan 0.6 mg/m²/d and ABT-888 10 mg BID on days one to five of 21-day cycles. Topotecan did not alter the pharmacokinetics of ABT-888. A more than 75% reduction in PAR levels was observed in 3 paired tumor biopsy samples; a greater than 50% reduction was observed in PBMCs from 19 of 23 patients with measurable levels. Increases in γH2AX response in circulating tumor cells (CTC) and PBMCs were observed in patients receiving ABT-888 with topotecan. We show a mechanistic interaction of a PARP inhibitor, ABT-888, with a topoisomerase I inhibitor, topotecan, in PBMCs, tumor, and CTCs. Results of this trial reveal that PARP inhibition can modulate the capacity to repair topoisomerase I-mediated DNA damage in the clinic.
HLA-DRB1 association in Turkish psoriasis vulgaris patients (2003)

Psoriasis vulgaris (PV) is a skin disease present in 1–3% of the Caucasoid population [1]. Although genetic, immunological and environmental factors foster PV, there is evidence that immune system activation plays a central role in keratinocyte hyperproliferation, a typical feature of psoriasis. Moreover, actively dividing T cells accumulate in psoriatic lesions, apart from the presence of a variety of other antigen-presenting, effector and inflammatory cells in psoriatic skin [2]. Peptide presentation by MHC class II molecules is important in human autoimmune diseases. Most of these autoimmune diseases are genetically linked to particular alleles of the class II molecules, and much sequence information has also accumulated on the polymorphisms in these genes. In some autoimmune diseases almost all of the patients carry particular alleles of MHC class II genes (e.g. pemphigus vulgaris). In other autoimmune diseases several different MHC class II alleles carry increased risk, presumably because different MHC class II molecules present the relevant peptide(s) to T cells [3]. Studies have shown psoriasis susceptibity loci on chromosomes as follows: 1, 2, 3, 4, 6th, 8th, 16, 17, 19 and 20. As seen with most autoimmune diseases, psoriasis is found on 6p and associated with allelic component of the major histocompatibility complex [4]. HLA antigens are analysed in different populations and PV has been associated with several HLA class I and class II specifities [5–9]. Among these class I phenotypes Cw6 and B57 have been most consistently reported. The alleles corresponding to these phenotypes are in linkage disequilibrium in normal individuals and compose the proximal class I end of an ancestral haplotype called EH57.1. The class II side of EH57.1 ancestral haplotype contains DRB1* 07 and some other DRB1 alleles [10]. Studies suggest several genetic backgrounds for PV [11]. The first choice is that more than one allele at a single locus may confer susceptibility. The second is that alleles at more than one locus within the HLA region may also confer susceptibility. The true disease locus could be linked to, but separate from, one or more known HLA genes. Although present HLA association information tends to support the last-mentioned hypothesis, it does not in fact rule out the first two. A close linkage between HLA class III and PV has been reported in an Indian population [12]. This study investigates HLA-DRB1 association with PV in a Turkish population.
A Test of the Immunoreactive Theory for the Origin of Neurodevelopmental Disorders in the Offspring of Women with Immune Disorder (1994)

Gualtieri and Hicks (1985) proposed that male vulnerability for neurodevelopmental disorders (NDs) was partially due to intrauterine immune attack of the fetus. One group of mothers with heightened immunoreactivity might be women with immune disorder. This was tested within an epidemiological sample of 17,283 mother/child pairs. Maternal immune disorders considered were ulcerative colitis or asthma. NDs in the child included: cerebral palsy, mental retardation, seizures, articulation disorder, reading, or arithmetic disability, verbal or performance aptitude deficits, and attention deficit disorder. Unlike prior studies, we controlled for demographic perinatal variables that might confound interpretation of the data. Results indicated that immune dysfunction in the mother, be it autoimmune (ulcerative colitis) or defensive (asthma) was not associated with an increased incidence of any NDs in the offspring, but mothers with ulcerative colitis did have a disproportionate number of offspring who were non-right handed. Few variables discriminated between the children of ulcerative colitis mothers who became right handed when compared to those who did not. We suggest that a) only certain maternal autoimmune disorders such as systemic lupus erythematosus (but not ulcerative colitis or asthma) elevate the risk of intrauterine immune attack and b) the elevated rate of non-right handed offspring among ulcerative colitis mothers was not an instance of immune attack but instead represents some kind of genetic association.
The Complete Exosome Workflow Solution: From Isolation to Characterization of RNA Cargo (2013)

Exosomes are small (30-150 nm) vesicles containing unique RNA and protein cargo, secreted by all cell types in culture. They are also found in abundance in body fluids including blood, saliva, and urine. At the moment, the mechanism of exosome formation, the makeup of the cargo, biological pathways, and resulting functions are incompletely understood. One of their most intriguing roles is intercellular communication--exosomes function as the messengers, delivering various effector or signaling macromolecules between specific cells. There is an exponentially growing need to dissect structure and the function of exosomes and utilize them for development of minimally invasive diagnostics and therapeutics. Critical to further our understanding of exosomes is the development of reagents, tools, and protocols for their isolation, characterization, and analysis of their RNA and protein contents. Here we describe a complete exosome workflow solution, starting from fast and efficient extraction of exosomes from cell culture media and serum to isolation of RNA followed by characterization of exosomal RNA content using qRT-PCR and next-generation sequencing techniques. Effectiveness of this workflow is exemplified by analysis of the RNA content of exosomes derived from HeLa cell culture media and human serum, using Ion Torrent PGM as a sequencing platform.
Nonlinear joint power spectrum based optical correlation (1989)

A nonlinear joint transform image correlator is investigated. The Fourier transform interference intensity is thresholded to provide higher correlation peak intensity and a better defined correlation spot. Analytical expressions for the thresholded joint power spectrum are provided. The effects of nonlinearity at the Fourier plane on the correlation signals at the output plane are investigated. The correlation signals are determined in terms of nonlinear characteristics of the spatial light modulator (SLM) at the Fourier plane. We show that thresholding the interference intensity results in a sum of infinite harmonic terms. Each harmonic term is envelope modulated due to the nonlinear characteristics of the device and phase modulated by m times the phase modulation of the nonthresholded joint power spectrum. The correct phase information about the correlation signal is recovered from the first-order harmonic of the thresholded interference intensity. We show that various types of autocorrelation signal can be produced simply by varying the severity of the nonlinearity and without the need to synthesize the specific matched filter. For example, the autocorrelation signal produced by a phase-only matched filter can be obtained by selecting the appropriate nonlinearity.
Design and characteristics of holographic neural photo-stimulation systems (2009)

Computer-generated holography is an emerging technology for stimulation of neuronal populations with light patterns. A holographic photo-stimulation system may be designed as a powerful research tool or a compact neural interface medical device, such as an optical retinal prosthesis. We present here an overview of the main design issues including the choice of holographic device, field-of-view, resolution, physical size, generation of two- and three-dimensional patterns and their diffraction efficiency, choice of algorithms and computational effort. The performance and characteristics of a holographic pattern stimulation system with kHz frame rates are demonstrated using experimental recordings from isolated retinas.
Dual Add-on Therapy in Type 2 Diabetes Poorly Controlled With Metformin Monotherapy: A Randomized Double-Blind Trial of Saxagliptin Plus Dapagliflozin Addition Versus Single Addition of Saxagliptin or Dapagliflozin to Metformin (2014)

In this first report of adding a well-tolerated combination of saxagliptin plus dapagliflozin to background metformin therapy in patients poorly controlled with metformin, greater improvements in glycemic control were obtained with triple therapy by the dual addition of saxagliptin and dapagliflozin than dual therapy with the addition of saxagliptin or dapagliflozin alone.
Stromal Cell–Derived Factor-1α Plays a Critical Role in Stem Cell Recruitment to the Heart After Myocardial Infarction but Is Not Sufficient to Induce Homing in the Absence of Injury (2004)

SDF-1/CXCR4 interactions play a crucial role in the recruitment of BMDCs to the heart after MI and can further increase homing in the presence, but not in the absence, of injury.
New IBD genetics: common pathways with other diseases (2011)

Complex disease genetics has been revolutionised in recent years by the advent of genome-wide association (GWA) studies. The chronic inflammatory bowel diseases (IBDs), Crohn's disease and ulcerative colitis have seen notable successes culminating in the discovery of 99 published susceptibility loci/genes (71 Crohn's disease; 47 ulcerative colitis) to date. Approximately one-third of loci described confer susceptibility to both Crohn's disease and ulcerative colitis. Amongst these are multiple genes involved in IL23/Th17 signalling (IL23R, IL12B, JAK2, TYK2 and STAT3), IL10, IL1R2, REL, CARD9, NKX2.3, ICOSLG, PRDM1, SMAD3 and ORMDL3. The evolving genetic architecture of IBD has furthered our understanding of disease pathogenesis. For Crohn's disease, defective processing of intracellular bacteria has become a central theme, following gene discoveries in autophagy and innate immunity (associations with NOD2, IRGM, ATG16L1 are specific to Crohn's disease). Genetic evidence has also demonstrated the importance of barrier function to the development of ulcerative colitis (HNF4A, LAMB1, CDH1 and GNA12). However, when the data are analysed in more detail, deeper themes emerge including the shared susceptibility seen with other diseases. Many immune-mediated diseases overlap in this respect, paralleling the reported epidemiological evidence. However, in several cases the reported shared susceptibility appears at odds with the clinical picture. Examples include both type 1 and type 2 diabetes mellitus. In this review we will detail the presently available data on the genetic overlap between IBD and other diseases. The discussion will be informed by the epidemiological data in the published literature and the implications for pathogenesis and therapy will be outlined. This arena will move forwards very quickly in the next few years. Ultimately, we anticipate that these genetic insights will transform the landscape of common complex diseases such as IBD.
Two RNA-binding Domains Determine the RNA-binding Specificity of Nucleolin (1997)

Nucleolin is an abundant nucleolar RNA-binding protein that seems to be involved in many aspects of ribosome biogenesis. Nucleolin contains four copies of a consensus RNA-binding domain (CS-RBD) found in several other proteins. In vitro RNA-binding studies previously determined that nucleolin interacts specifically with a short RNA stem-loop structure. Taken individually, none of the four CS-RBDs interacts significantly with the RNA target, but a peptide that contains the first two adjacent CS-RBDs (R12) is sufficient to account for nucleolin RNA-binding specificity and affinity. The full integrity of these two domains is required, since N- or C-terminal deletion abolishes the specific interaction with the RNA. Mutation of conserved amino acids within the RNP-1 sequence of CS-RBD 1 or 2 drastically reduces the interaction with the RNA, whereas mutation of the analogous residues in CS-RBDs 3 and 4 has no effect in the context of the R1234G protein (which corresponds to the C-terminal end of nucleolin). Our results demonstrate that nucleolin RNA-binding specificity is the result of a cooperation between two CS-RBDs (RBDs 1 and 2) and also suggests a direct or indirect involvement of the RNP-1 consensus sequence of both CS-RBDs in the recognition of the RNA target.
Proton Exchange Membrane Fuel Cells with Carbon Nanotube Based Electrodes (2003)

The use of multiwalled carbon nanotubes as a platinum support for proton exchange membrane fuel cells has been investigated as a way to reduce the cost of fuel cells through an increased utilization of platinum. Carbon nanotubes were selectively grown directly on the carbon paper by chemical vapor deposition with electrodeposited cobalt catalyzing the growth of the carbon nanotubes. The as-prepared carbon nanotubes were employed as the support for the subsequent platinum catalyst, which is electrodeposited on the carbon nanotubes. Physicochemical and electrochemical characterizations were conducted to identify the morphologies of the cobalt, the carbon nanotubes, and the electrodeposited platinum on the carbon nanotubes. The feasibility of a fuel cell using the carbon nanotube-based electrodes was demonstrated.
Evolutionary development of advanced liquid crystal spatial light modulators (1989)

Taking into account recent developments and present trends in devices and component technologies, the future development of electrically addressed liquid crystal spatial light modulators is considered. In particular, the combination of single-crystal-silicon active backplane and chiral smectic C liquid crystal technologies is shown to be promising. The ultimate limitations of such technologies for producing faster devices of higher complexity and functionality are assessed, and an advanced device, presently under development, is described.
RETRACTED: Interleukin‐6 protects LNCaP cells from apoptosis induced by androgen deprivation through the Stat3 pathway (2004)

These results indicate that IL-6 protects androgen sensitive LNCaP cells from apoptosis induced by androgen deprivation, and Stat3 activation play an important role in IL-6-mediated anti-apoptosis in prostate cancer cells.