gebhart/patrepeval huggingface dataset:
In vitro optimization of 2′-OMe-4′-thioribonucleoside–modified anti-microRNA oligonucleotides and its targeting delivery to mouse liver using a liposomal nanoparticle (2013)

MicroRNAs (miRNAs) are small noncoding RNAs that regulate gene expression post-transcriptionally. Previous studies, which characterized miRNA function, revealed their involvement in fundamental biological processes. Importantly, miRNA expression is deregulated in many human diseases. Specific inhibition of miRNAs using chemically modified anti-miRNA oligonucleotides (AMOs) can be a potential therapeutic strategy for diseases in which a specific miRNA is overexpressed. 2'-O-Methyl (2'-OMe)-4'-thioRNA is a hybrid type of chemically modified oligonucleotide, exhibiting high binding affinity to complementary RNAs and high resistance to nuclease degradation. Here, we evaluate 2'-OMe-4'-thioribonucleosides for chemical modification on AMOs. Optimization of the modification pattern using a variety of chemically modified AMOs that are perfectly complementary to mature miR-21 revealed that the uniformly 2'-OMe-4'-thioribonucleoside-modified AMO was most potent. Further investigation showed that phosphorothioate modification contributed to long-term miR-122 inhibition by the 2'-OMe-4'-thioribonucleoside-modified AMO. Moreover, systemically administrated AMOs to mouse using a liposomal delivery system, YSK05-MEND, showed delivery to the liver and efficient inhibition of miR-122 activity at a low dose in vivo.
TREM‐1 promotes survival during septic shock in mice (2007)

Triggering receptor expressed on myeloid (TREM)-1 is integral to the inflammatory response occurring during septic shock, although its precise function has yet to be determined. Here we show that in vivo silencing of TREM-1 using siRNA duplexes in a fecal peritonitis mouse model resulted in a blunted inflammatory response and increased mortality. This was associated with impaired bacterial clearance related to marked inhibition of the neutrophil oxidative burst. By contrast, TREM-1-silenced mice were highly resistant to a lethal endotoxin challenge, while partial silencing of TREM-1 in the bacterial peritonitis model produced a significant survival benefit. These data highlight the crucial role of the TREM-1 pathway in mounting an adequate inflammatory and cytotoxic response to polymicrobial sepsis, and both the therapeutic promise and potential risks of its modulation.
Metabolic studies on erythropoietin (EP): II. The role of liver and kidney in the metabolism of Ep. (1981)

Half plasma disappearance time (HDT) of endogenous erythropoietin (Ep) was measured in single rats, using an in vitro assay system for EP. In rats treated with the hepatotoxic agent d-Galactosamine-HCl (GalN), a small but significant elevation of HDT was found as compared with control rats (164 and 105 min, respectively). In bilaterally nephrectomized rats mean HDT was significantly elevated: 266 min. Combination of nephrectomy and GalN treatment did not result in a significant further elongation of HDT (mean = 301 min). In experiments using isolated liver perfusion, rat livers (with and without GalN treatment) were shown to be unable to change perfusate Ep titre during 4 h of perfusion. It is concluded that hepatic degradation of Ep in rats is only minimal. The kidney however is important in the catabolism of Ep.
Hyperphosphorylation-Induced Tau Oligomers (2013)

In normal adult brain the microtubule associated protein (MAP) tau contains 2-3 phosphates per mol of the protein and at this level of phosphorylation it is a soluble cytosolic protein. The normal brain tau interacts with tubulin and promotes its assembly into microtubules and stabilizes these fibrils. In Alzheimer disease (AD) brain tau is three to fourfold hyperphosphorylated. The abnormally hyperphosphorylated tau binds to normal tau instead of the tubulin and this binding leads to the formation of tau oligomers. The tau oligomers can be sedimented at 200,000 × g whereas the normal tau under these conditions remains in the supernatant. The abnormally hyperphosphorylated tau is capable of sequestering not only normal tau but also MAP MAP1 and MAP2 and causing disruption of the microtubule network promoted by these proteins. Unlike Aβ and prion protein (PrP) oligomers, tau oligomerization in AD and related tauopathies is hyperphosphorylation-dependent; in vitro dephosphorylation of AD P-tau with protein phosphatase 2A (PP2A) inhibits and rehyperphosphorylation of the PP2A-AD P-tau with more than one combination of tau protein kinases promotes its oligomerization. In physiological assembly conditions the AD P-tau readily self-assembles into paired helical filaments. Missense tau mutations found in frontotemporal dementia apparently lead to tau oligomerization and neurofibrillary pathology by promoting its abnormal hyperphosphorylation. Dysregulation of the alternative splicing of tau that alters the 1:1 ratio of the 3-repeat: 4-repeat taus such as in Down syndrome, Pick disease, and progressive supranuclear palsy leads to the abnormal hyperphosphorylation of tau.
Neural and marrow—derived stromal cell sphere transplantation in a rat model of traumatic brain injury (2002)

Rats that received NMSCS transplants had reduced lesion volume and showed improved motor and neurological function when compared with control groups 14 days after the treatment. These results suggest that transplantation of this novel biological material (NMSCS) may be useful in the treatment of TBI.
Inactivation of glutathione peroxidase by nitric oxide leads to the accumulation of H 2 O 2 and the induction of HB‐EGF via c‐Jun NH 2 ‐terminal kinase in rat aortic smooth muscle cells (2001)

ABSTRACT We describe the effect of nitric oxide (NO) on the expression of the heparin‐binding EGF‐like growth factor (HB‐EGF), a potent chemoattractant and mitogen for smooth muscle cells, and its anti‐apoptotic effect against NO cytotoxicity. Previous studies have shown that glutathione peroxidase (GPx), a major peroxide scavenging enzyme is selectively inactivated by an NO donor, S ‐nitroso‐ N ‐acetyl‐DL‐penicillamine (SNAP), in vitro and in vivo and results in the accumulation of peroxide (6, 7). The SNAP or peroxynitrite induces HB‐EGF through the inactivation of GPx and the accumulation of peroxide. This induction is accompanied by JNK and c‐Jun/AP‐1 activation. The blocking of the HB‐EGF induction by curcumin, c‐jun antisense oligonucleotide, and a dominant‐negative mutant of JNK1 provides support for these results. A longer pretreatment of rat aortic smooth muscle cells (RASMCs) by SNAP induces HB‐EGF and reduces the TNFα+actinomycin D‐induced apoptosis. This protection is blocked by antisense HB‐EGF s‐oligonucleotide. These findings indicate that the induction of HB‐EGF by NO would be an adaptive response as an autocrine protective factor against apoptosis by NO in RASMCs.
Short Amyloid-β (Aβ) Immunogens Reduce Cerebral Aβ Load and Learning Deficits in an Alzheimer's Disease Mouse Model in the Absence of an Aβ-Specific Cellular Immune Response (2006)

Amyloid-beta (Abeta) immunotherapy lowers cerebral Abeta and improves cognition in mouse models of Alzheimer's disease (AD). A clinical trial using active immunization with Abeta1-42 was suspended after approximately 6% of patients developed meningoencephalitis, possibly because of a T-cell reaction against Abeta. Nevertheless, beneficial effects were reported in antibody responders. Consequently, alternatives are required for a safer vaccine. The Abeta1-15 sequence contains the antibody epitope(s) but lacks the T-cell reactive sites of full-length Abeta1-42. Therefore, we tested four alternative peptide immunogens encompassing either a tandem repeat of two lysine-linked Abeta1-15 sequences (2xAbeta1-15) or the Abeta1-15 sequence synthesized to a cross-species active T1 T-helper-cell epitope (T1-Abeta1-15) and each with the addition of a three-amino-acid RGD (Arg-Gly-Asp) motif (R-2xAbeta1-15; T1-R-Abeta1-15). High anti-Abeta antibody titers were observed in wild-type mice after intranasal immunization with R-2xAbeta1-15 or 2xAbeta1-15 plus mutant Escherichia coli heat-labile enterotoxin LT(R192G) adjuvant. Moderate antibody levels were induced after immunization with T1-R-Abeta1-15 or T1-Abeta1-15 plus LT(R192G). Restimulation of splenocytes with the corresponding immunogens resulted in moderate proliferative responses, whereas proliferation was absent after restimulation with full-length Abeta or Abeta1-15. Immunization of human amyloid precursor protein, familial AD (hAPP(FAD)) mice with R-2xAbeta1-15 or 2xAbeta1-15 resulted in high anti-Abeta titers of noninflammatory T-helper 2 isotypes (IgG1 and IgG2b), a lack of splenocyte proliferation against full-length Abeta, significantly reduced Abeta plaque load, and lower cerebral Abeta levels. In addition, 2xAbeta1-15-immunized hAPP(FAD) animals showed improved acquisition of memory compared with vehicle controls in a reference-memory Morris water-maze behavior test that approximately correlated with anti-Abeta titers. Thus, our novel immunogens show promise for future AD vaccines.
Electronic PMD mitigation-from linear equalization to maximum-likelihood detection (2002)

In a comparative study post-detection signal processing performed by transversal-filter, decision-feedback-equalizer, the concatenation of both, or maximum-likelihood sequence detection is analyzed for PMD penalty reduction. Optical noise sources and second-order PMD are taken into account.
Ester groups as effective ligands in chelate-controlled additions of cuprates and Grignard reagents to chiral .beta.-formyl esters to form .gamma.-lactones. (1993)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTEster groups as effective ligands in chelate-controlled additions of cuprates and Grignard reagents to chiral .beta.-formyl esters to form .gamma.-lactones.Hans Ulrich Reissig, Hubert Angert, Thomas Kunz, Agnes Janowitz, Gabriele Handke, and Emanuel Bruce-AdjeiCite this: J. Org. Chem. 1993, 58, 23, 6280–6285Publication Date (Print):November 1, 1993Publication History Published online1 May 2002Published inissue 1 November 1993https://pubs.acs.org/doi/10.1021/jo00075a022https://doi.org/10.1021/jo00075a022research-articleACS PublicationsRequest reuse permissionsArticle Views396Altmetric-Citations31LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Antibody binding to CD5 (Tp67) and Tp44 T cell surface molecules: effects on cyclic nucleotides, cytoplasmic free calcium, and cAMP-mediated suppression. (1986)

T cells can be activated to proliferate by antibodies to the T cell antigen receptor or the molecularly associated CD3 complex if monocytes are present. We have shown previously that monoclonal antibodies to the human T cell differentiation antigens CD5 (Tp67) and Tp44 each augment and prolong proliferative responses of anti-CD3-activated T cells, even in the absence of monocytes. Here we show that the functional and biochemical mechanisms of CD5 and Tp44 signal transmission are distinct. T cell proliferation is suppressed by agents that increase the concentration of intracellular cAMP. We found that antibody binding to the Tp44 surface molecule overcomes this suppression, whereas antibody binding to CD5 does not, indicating that ligand-Tp44 interaction changes T cell sensitivity to cAMP-mediated growth inhibition. The ability of anti-CD3, anti-Tp44, and anti-CD5 monoclonal antibodies to directly alter cyclic nucleotide levels in the Jurkat T cell line was examined. Anti-CD3 alone caused a rapid four- to sixfold increase in cAMP levels, but did not affect cGMP levels. However, anti-Tp44 and anti-CD5 each caused a rapid three- to fourfold increase in cGMP levels without affecting cAMP levels. In other experiments, cytoplasmic free calcium levels were measured in resting T cells after CD5 or Tp44 stimulation by using the dye indo-1 and flow cytometry. This sensitive method showed that anti-CD5 alone caused an increase in cytoplasmic calcium free levels within 3 min of antibody addition, whereas anti-Tp44 had no effect. Finally, anti-Tp44 and IL 1 each augmented proliferation of phorbol ester-stimulated lymphocytes, whereas anti-CD5 did not. The effects of IL 1 and Tp44 could be further distinguished in that the effect of anti-Tp44 was resistant to inhibition by dBcAMP whereas IL 1 was not. These data suggest that the receptor function of both Tp44 and CD5 involves changes in cyclic nucleotides levels, and that the mechanism by which anti-Tp44 and anti-CD5 antibodies affect T cell proliferative responses may be related to their selective effects on cGMP levels and cytoplasmic calcium concentrations.
Structuring contention-based channel access in wireless sensor networks (2006)

In a wireless network using CSMA for MAC, packet collisions can result either because of the vulnerability stemming from the idle channel detection delay of the radio device or because of the hidden terminal problem. Both of these collision scenarios can be addressed by applying some additional structure to carrier sense-based channel access, sacrificing throughput to improve collision protection. Specifically, we assign a unique time slice to each contending transmitter that is designed to allow collision-free access to each data slot while still using carrier sense as the mechanism to determine channel state. The width of each time slice is equal to the idle channel detection delay of the radio. We prepend a fixed-length time interval to each transmitted packet whose length is proportional to the idle channel detection delay of the radio device and the node density. We discuss this method of channel access including tradeoffs and requirements, and analyze the performance in comparison with existing MAC strategies.
Randomized, Double-Blind Study of SR142801 (Osanetant). A Novel Neurokinin-3 (NK3) Receptor Antagonist in Panic Disorder with Pre- and Posttreatment Cholecystokinin Tetrapeptide (CCK-4) Challenges (2005)

With regard to efficacy of outcome, the compound was not significantly different from placebo. However, post-CCK-4 plasma prolactin concentrations showed a significant difference between placebo and SR142801.
New schemes for improved opto-electronic oscillator (2003)

We have demonstrated a compact Opto-Electronic Oscillator (OEO) with integrated laser and modulator, and miniature amplifier and filter. Also we have successfully implemented a carrier suppression noise reduction technique with an optical fiber delay line, and applied the technique to reduce the close-to-carrier 1/f noise in a double loop OEO. Finally, we have demonstrated an OEO with a submillimeter microspherical resonator in place of kilometers of fiber delay. Further improvements of these techniques are expected in the near future.
XomaZyme-CD5 immunotoxin in conjunction with partial T cell depletion for prevention of graft rejection and graft-versus-host disease after bone marrow transplantation from matched unrelated donors. (1994)

Patients who receive bone marrow transplants from unrelated donors have a high incidence of graft-versus-host disease (GVHD). If the donor marrow is first T cell-depleted, the everity of GVHD declines but the risk of rejection rises. In an attempt to prevent both graft rejection and GVHD, we included an anti-T cell antibody-toxin conjugate (CD-5-Ricin; XomaZyme H65) in the transplant conditioning regimen. After receiving a partially T cell-depleted marrow, patients then received a second course of immunotoxin as additional GVHD prophylaxis. Eight recipients of unrelated donor marrow transplants were studied. All engrafted (ANC > 500 x 10(6)/l by day 15, range 13-20 days). One patient had grade II skin GVHD and one developed grade IV disease but the other six patients had no acute GVHD. However, there was high morbidity and mortality from virus infections associated with a sluggish return of CD4 and CD8 T cells into the normal range. Four patients died from virus disease (CMV, n = 2; EBV, n = 1; adenovirus, n = 1) and the remaining patients had frequent documented viral illnesses during the first year. We conclude that improvement in the outcome of unrelated donor marrow transplantation will require strategies which prevent rejection and GVHD coupled with attempts to accelerate immune reconstitution.
Reducing costs (2004)

After reading this chapter you will be able to: distinguish the two generic strategies of cost leadership and product differentiation identify the main cost drivers understand the relationship between a price strategy and a cost leadership strategy understand what is meant by a focused cost leadership strategy understand the nature of a technological system and its relationship to the organization of an enterprise realize how short-lived any cost or price leadership can be KeywordsExchange RateCompetitive AdvantagePrice StrategyCost DriverDifferential PriceThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
Anti-NKG2D mAb: A New Treatment for Crohn’s Disease? (2017)

Crohn's disease (CD) and ulcerative colitis (UC) are immunologically-mediated, debilitating conditions resulting from destructive inflammation of the gastrointestinal tract. The pathogenesis of IBD is incompletely understood, but is considered to be the result of an abnormal immune response with a wide range of cell types and proteins involved. Natural Killer Group 2D (NKG2D) is an activating receptor constitutively expressed on human Natural Killer (NK), γδ T, mucosal-associated invariant T (MAIT), CD56⁺ T, and CD8⁺ T cells. Activation of NKG2D triggers cellular proliferation, cytokine production, and target cell killing. Research into the NKG2D mechanism of action has primarily been focused on cancer and viral infections where cytotoxicity evasion is a concern. In human inflammatory bowel disease (IBD) this system is less characterized, but the ligands have been shown to be highly expressed during intestinal inflammation and the following receptor activation may contribute to tissue degeneration. A recent phase II clinical trial showed that an antibody against NKG2D induced clinical remission of CD in some patients, suggesting NKG2D and its ligands to be of importance in the pathogenesis of CD. This review will describe the receptor and its ligands in intestinal tissues and the clinical potential of blocking NKG2D in Crohn's disease.
Level of Acrylamide Precursors Asparagine, Fructose, Glucose, and Sucrose in Potatoes Sold at Retail in Italy and in the United States (2006)

ABSTRACT The free amino acid asparagine and the reducing sugars glucose and fructose has been reported to serve as precursors for the heat‐induced formation of potentially toxic acrylamide in a variety of plant‐based food. To contribute to our knowledge about the levels of these precursors, we used ion‐exchange chromatography to measure free asparagine and high‐performance liquid chromatography (HPLC) to measure free glucose, fructose, and sucrose in 9 potato varieties sold at retail in Italy and in 22 varieties sold in the United States. Asparagine levels (in mmol/kg of fresh wt) ranged from 1.17 for the Agata potatoes to 57.65 Russet potatoes, a 49.3‐fold variation from lowest to highest value. The corresponding levels for fructose ranged from 1.73 (Fingerling Ozette) to 33.63 (Red), a 19.4‐fold variation from the lowest to the highest value. For glucose, the concentration ranged from 1.11 (Jelli) to 34.73 (Yukon Gold B) potatoes, a 31.3‐fold variation from lowest to highest value. The corresponding values for sucrose ranged from 1.16 (Fingerling Ozette) to 40.61 (Marabel) potatoes, a 35fold variation. The American potato varieties Kennebec, White, and Fingerling Ozette and the Italian potato varieties Agria, Merit, and Marabel had very low levels of both asparagine and reducing sugars. The results may enable consumers, restaurants, and processors to select commercial potatoes with low levels of acrylamide precursors for baking or frying.
Production, purification, crystallization and preliminary X-ray analysis of adeno-associated virus serotype 8 (2005)

Adeno-associated viruses (AAVs) are actively being developed for clinical gene-therapy applications and the efficiencies of the vectors could be significantly improved by a detailed understanding of their viral capsid structures and the structural determinants of their tissue-transduction interactions. AAV8 is approximately 80% identical to the more widely studied AAV2, but its liver-transduction efficiency is significantly greater than that of AAV2 and other serotypes. The production, purification, crystallization and preliminary X-ray crystallographic analysis of AAV8 viral capsids are reported. The crystals diffract X-rays to 3.0 A resolution using synchrotron radiation and belong to the hexagonal space group P6(3)22, with unit-cell parameters a = 257.5, c = 443.5 A. The unit cell contains two viral particles, with ten capsid viral protein monomers per crystallographic asymmetric unit.
Oxidative DNA Damage in Rats with Diabetes Induced by Alloxan and Streptozotocin (1999)

The role of oxidative stress in the initiation and the complication of diabetes was examined by monitoring blood glucose increase and oxidative DNA damage in rats treated with alloxan or streptozotocin (STZ). Oxidative DNA damage was assessed by quantitating 8-oxo-2'-deoxyguanosine ( excreted in urine and the accumulated in pancreas DNA. Both alloxan and STZ treatments resulted in an abrupt increase in blood glucose and significant increases in urinary and pancreatic . Pretreatment of buthionine sulfoximine (BSO), a glutathione-depleting agent, slightly potentiated the increase of blood glucose and urinary in the alloxan- and STZ-treated rats. Furthermore, the BSO pretreatment caused significant amplification of pancreatic increase in the rats. On the other hand, pretreatment with 1,10- phenanthroline (o-phen), a chelator of divalent cations, showed different results between alloxan- and STZ-treated rats. The o-phen pretreatment completely blocked diabetes and the increase of by alloxan treatment, while it potentiated the increase of blood glucose and by STZ treatment. The results demonstrate that the causative effect of alloxan on diabetes may be the generation of reactive oxygen species through a Fenton type reaction, but that of STZ may not.