gebhart/patrepeval huggingface dataset:
Modifying Lipid Rafts Promotes Regeneration and Functional Recovery (2014)

Ideal strategies to ameliorate CNS damage should promote both neuronal survival and axon regeneration. The receptor Neogenin promotes neuronal apoptosis. Its ligand prevents death, but the resulting repulsive guidance molecule a (RGMa)-Neogenin interaction also inhibits axonal growth, countering any prosurvival benefits. Here, we explore strategies to inhibit Neogenin, thus simultaneously enhancing survival and regeneration. We show that bone morphogenetic protein (BMP) and RGMa-dependent recruitment of Neogenin into lipid rafts requires an interaction between RGMa and Neogenin subdomains. RGMa or Neogenin peptides that prevent this interaction, BMP inhibition by Noggin, or reduction of membrane cholesterol all block Neogenin raft localization, promote axon outgrowth, and prevent neuronal apoptosis. Blocking Neogenin raft association influences axonal pathfinding, enhances survival in the developing CNS, and promotes survival and regeneration in the injured adult optic nerve and spinal cord. Moreover, lowering cholesterol disrupts rafts and restores locomotor function after spinal cord injury. These data reveal a unified strategy to promote both survival and regeneration in the CNS.
Functional Expression and Characterization of Tetrachloroethene Dehalogenase From Geobacter sp. (2018)

Reductive dehalogenase (RDase) consists of two parts, RdhA and RdhB. RdhA is the catalytic subunit, harboring a cobalamin cofactor and two Fe-S clusters. RdhA is anchored to the cytoplasmic membrane via the membrane anchoring subunit, RdhB. There are many genes encoding RDases in the genome of organohalide-respiring bacteria, including <i>Dehalococcoides</i> spp. However, most genes have not been functionally characterized. Biochemical studies on RDases have been hampered by difficulties encountered in their expression and purification. In this study, we have expressed, purified and characterized RdhA of RDase for tetrachloroethene (PceA) from <i>Geobacter</i> sp. PceA was expressed as a fusion protein with a trigger factor tag in <i>Escherichia coli</i>. PceA was purified and denatured in aerobic condition. Subsequently, this protein was refolded in the presence of FeCl<sub>3</sub>, Na<sub>2</sub>S and cobalamin in anaerobic condition. The reconstituted PceA exhibited dechlorination ability for tetrachloroethene. UV-Vis spectroscopy has shown that it contains cobalamin and Fe-S clusters. Since this method requires anaerobic manipulation only in the reconstituting process and has a relatively high yield, it will enable further biochemical studies of RDases.
Optimal Segmentation for Piecewise RF Power Amplifier Models (2016)

Accurate modeling of an RF power amplifier and/or its inverse is the core element of every digital predistortion system. An interesting alternative to the family of classic polynomial models are piecewise models, which divide the magnitude range into segments and define gain/phase-distortion through complex-valued functions on a per-segment basis. Naturally, the question arises whether a well-chosen non-uniform segmentation outperforms straightforward uniform segmentation and whether the benefit outweighs the extra effort. This work has two contributions: First, the segmentation that is optimal in the least-squares sense is determined jointly with the model coefficients and its benefit in terms of linearization improvement is demonstrated through measurements on a Doherty power amplifier. Second, a reduced-complexity approach with negligible performance loss is proposed.
Dispersing carbomers, mixing technology matters! (2022)

Mixing dry carbomer powder with water using magneto-hydrodynamic mixing yielded carbomer dispersions with higher viscosity and increased storage modulus as compared to conventional high shear mixing. <sup>1</sup>H NMR spectroscopy demonstrated this to be induced by a different water distribution, accompanied by lower ionization and higher degradation of the polymer in case of high shear mixing. This investigation reveals <sup>1</sup>H MAS NMR to provide suitable sensitivity and resolution to detect structural changes induced in organic polymers during their hydration.
Engineered ligand‐based VEGFR antagonists with increased receptor binding affinity more effectively inhibit angiogenesis (2016)

Pathologic angiogenesis is mediated by the coordinated action of the vascular endothelial growth factor (VEGF)/vascular endothelial growth factor receptor 2 (VEGFR2) signaling axis, along with crosstalk contributed by other receptors, notably α<sub>v</sub>β<sub>3</sub> integrin. We build on earlier work demonstrating that point mutations can be introduced into the homodimeric VEGF ligand to convert it into an antagonist through disruption of binding to one copy of VEGFR2. This inhibitor has limited potency, however, due to loss of avidity effects from bivalent VEGFR2 binding. Here, we used yeast surface display to engineer a variant with VEGFR2 binding affinity approximately 40-fold higher than the parental antagonist, and 14-fold higher than the natural bivalent VEGF ligand. Increased VEGFR2 binding affinity correlated with the ability to more effectively inhibit VEGF-mediated signaling, both in vitro and in vivo, as measured using VEGFR2 phosphorylation and Matrigel implantation assays. High affinity mutations found in this variant were then incorporated into a dual-specific antagonist that we previously designed to simultaneously bind to and inhibit VEGFR2 and α<sub>v</sub>β<sub>3</sub> integrin. The resulting dual-specific protein bound to human and murine endothelial cells with relative affinities of 120 ± 10 pM and 360 ± 50 pM, respectively, which is at least 30-fold tighter than wild-type VEGF (3.8 ± 0.5 nM). Finally, we demonstrated that this engineered high-affinity dual-specific protein could inhibit angiogenesis in a murine corneal neovascularization model. Taken together, these data indicate that protein engineering strategies can be combined to generate unique antiangiogenic candidates for further clinical development.
The Role of Heparan Sulfate and TLR2 in Cytokine Induction by Hepatitis B Virus Capsids (2005)

In an article published September 1, 2005, Cooper et al. ([1][1]) demonstrated that HBV nucleocapsids bind to PMA-treated THP-1 cells, an interaction that resulted in the secretion of cytokines. A critical role for the C-terminal arginine-rich domains of nucleocapsids in both processes was suggested
Chlorocresol: an activator of ryanodine receptor-mediated Ca2+ release. (1993)

In the present study we investigated the effect of the compound chlorocresol on intracellular Ca2+ homeostasis. Three different systems that have been shown to express the ryanodine receptor Ca2+ channel were chosen, i.e., skeletal muscle sarcoplasmic reticulum, cerebellar microsomes, and PC12 cells. In skeletal muscle sarcoplasmic reticulum, 4-chloro-m-cresol was found to be a potent activator of Ca2+ release mediated by a ruthenium red/caffeine-sensitive Ca2+ release channel. In cerebellar microsomes, this compound released Ca2+ from an inositol-1,4,5-trisphosphate-insensitive store, suggesting that there too it was acting at the ryanodine receptor level. When tested on PC12 cells, chlorocresol released Ca2+ from a caffeine- and thapsigargin-sensitive intracellular store. In addition, the compound was capable of releasing Ca2+ after pretreatment of PC12 cells with bradykinin, suggesting that it acts on a channel contained within an intracellular Ca2+ store that is distinct from that sensitive to inositol-1,4,5-trisphosphate. Structure-activity relationship analyses suggest that the chloro and methyl groups in chlorocresols are important for the activation of the ryanodine receptor Ca2+ release channel.
Organized monolayers of polycyclic aromatic quinones (1988)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTOrganized monolayers of polycyclic aromatic quinonesP. W. Kenny, L. L. Miller, S. F. Rak, T. H. Jozefiak, W. C. Christopfel, J. H. Kim, and R. A. UphausCite this: J. Am. Chem. Soc. 1988, 110, 13, 4445–4446Publication Date (Print):June 1, 1988Publication History Published online1 May 2002Published inissue 1 June 1988https://pubs.acs.org/doi/10.1021/ja00221a072https://doi.org/10.1021/ja00221a072research-articleACS PublicationsRequest reuse permissionsArticle Views143Altmetric-Citations25LEARN 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
A Simple Prediction Algorithm for the Lagrangian Motion in Two-Dimensional Turbulent Flows (2002)

A new algorithm is suggested for prediction of a Lagrangian particle position in a stochastic flow, given observations of other particles. The algorithm is based on linearization of the motion equations and appears to be efficient for an initial tight cluster and small prediction time. A theoretical error analysis is given for the Brownian flow and a stochastic flow with memory. The asymptotic formulas are compared with simulation results to establish their applicability limits. Monte Carlo simulations are carried out to compare the new algorithm with two others: the center-of-mass prediction and a Kalman filter--type method. The algorithm is also tested on real data in the tropical Pacific.
The underlying mechanisms by which PTSD symptoms are associated with cardiovascular health in male UK military personnel: The ADVANCE cohort study (2023)

Post-Traumatic Stress Disorder (PTSD) has been identified as an independent risk factor for cardiovascular disease, but the mechanisms of this relationship are not well understood. This study investigates the associations between PTSD symptom clusters (hyperarousal, intrusive thoughts, avoidance behaviours and emotional numbing) and mechanisms of cardiovascular disease including cardiometabolic effects, inflammation, and haemodynamic functioning. In the ADVANCE study cohort of UK male military personnel, 1111 participants were assessed for PTSD via questionnaire and cardiovascular risk via venous blood sampling, pulse wave analysis and dual energy x-ray absorptiometry between 2015 and 2020. Variable selection procedures were conducted to assess which of the symptom clusters if any were associated with cardiovascular risk outcomes. Associations were confirmed via robust regression modelling. Avoidance behaviours were associated with greater systolic Blood Pressure (BP) (Adjusted Coefficient (AC) 0.640 (95% Confidence Interval (CI) 0.065, 1.149). Emotional numbing was associated with greater estimated glucose disposal rate (AC -0.021 (95%CI -0.036, -0.005). Hyperarousal was associated with greater levels of (log)triglycerides (exponentiated-AC 1.009 (95%CI 1.002, 1.017). Intrusive thoughts were associated with greater visceral adipose tissue (AC 0.574 (95%CI 0.020, 1.250). Nonlinear relationships were observed between emotional numbing with heart rate and intrusive thoughts with systolic BP. Limited evidence is present for symptom associations with lipoproteins and pulse wave velocity. No associations were observed between PTSD symptom clusters and high sensitivity c-reactive protein, diastolic BP, total cholesterol, or haemoglobin fasting glucose. In conclusion, symptom clusters of PTSD were associated with increased cardiovascular risk via cardiometabolic and haemodynamic functioning mechanisms, but not inflammation.
Oxidative Protein Damage and Degradation in Lymphocytes from Patients Infected with Human Immunodeficiency Virus (1997)

It has been proposed that oxidative stress is the common mediator of apoptotic cell death in AIDS. However, mechanistic relationships between oxidative damage and cell death are far from clear. It is reported here that the mitogenic activation of T lymphocytes from human immunodeficiency virus-positive subjects involves perturbation of redox balance, as indicated by the increase in hydroethydine intracellular oxidation and manganese superoxide dismutase adaptive induction. Principal molecular targets of oxidative injury are cellular proteins whose content in carbonyl groups increases together with a dramatic increase in degradation of newly synthesized proteins catalyzed by the ATP- and ubiquitin-dependent proteolytic system. The major consequence of this metabolic anomaly is the decrease in protein cell mass leading to cells that are smaller than normal at lethal mitosis.
Updated Results of a Phase I Study of Flavopiridol in Acute Leukemias Using a Novel, Pharmacokinetically Derived Schedule: Clinical Activity Including Hyperacute Tumor Lysis Syndrome (TLS), Pharmacokinetics (PK), and Pharmacodynamics (PD). (2006)

Abstract Flavopiridol is a cyclin-dependent kinase inhibitor that induces apoptosis in acute leukemia cell lines. In earlier studies with flavopiridol in several malignancies, plasma concentrations of flavopiridol were not reached or maintained at sufficient levels to induce apoptosis due to unexpectedly high levels of bound drug in human serum relative to fetal calf serum used in preclinical studies. PK modeling in chronic lymphocytic leukemia (CLL) cells cultured in human plasma in vitro indicated that administering flavopiridol by 30 minute intravenous (IV) bolus followed by 4 hour continuous IV infusion (CIVI) would achieve sustained in vivo plasma drug concentration and time exposure similar to that necessary to induce apoptosis. We designed a phase I dose escalation trial in acute leukemias of single agent flavopiridol given as a 30 minute bolus followed by a 4 hour CIVI on days 1–3 with the ability to repeat cycles every 21 days; 16 patients (pts) have been enrolled to date. Dose escalation was as follows (bolus dose/4 hr CIVI dose in mg/m2): 20/30 (n=3), 30/35 (n=7), 30/50 (n=3), and 40/60 (n=3). Based on prior experience with flavopiridol at our institution in CLL, aggressive measures for the prevention and management of hyperacute tumor lysis syndrome (TLS) were employed. Pts had relapsed/refractory AML (N=12) and ALL (N=4), and were 25–78 yrs old (median age 64 yrs). Average plasma levels were 1.0–2.5 μM at the first three dose levels during the infusion (N=13) and declined with terminal half-lives comparable to previously reported 72 hr and more recent 4.5 hr infusions. Clinically significant TLS occurred in 2/16 pts with chemical evidence of lysis in 4 additional pts. A dose-limiting toxicity (renal failure) occurred at dose level 4 (40 mg/m2 bolus/60 mg/m2 CIVI), and the level is currently being expanded. Treatment was otherwise well tolerated. Downregulation of Mcl-1 protein by standard immunoblotting at 4 and/or 24 hrs was demonstrated in blood and/or bone marrow cells of 6/10 patients Anti-leukemic activity including transient reductions in WBCs/circulating blasts (n=7), bone marrow blasts (n=2), and platelet transfusion independence (n=1) was observed. Two received a second course of therapy, but no pt experienced an objective response by standard criteria. The current dose level exceeds that previously given in ongoing CLL studies; dose escalation to identify the maximum tolerated dose using this pharmacokinetically derived schedule in acute leukemia continues. Given the activity of this drug as a single agent, combination studies with conventional chemotherapy or other novel agents in acute leukemias should be considered.
[P2–053]: CYCLIC D‐ENANTIOMERIC PEPTIDE TARGETING AMYLOID‐BETA IN ALZHEIMER's DISEASE (2017)

To decrease the levels of toxic Amyloid-beta (Aβ) species in the brain, we have developed and designed D-enantiomeric peptides. Here, we investigated a cyclic D-enantiomeric peptide's (cycP) aptitude as an Alzheimer's disease (AD) drug by in vitro, ex vivo and in vivo experiments. Especially, cycP's ability to cross the blood brain barrier (BBB) to a higher extent than its linear equivalent (linP) is of advantage. Furthermore, cycP's pharmacokinetic profile, proteolytic stability and plasma protein binding properties were characterized. CycP's impact on cell viability (MTT test), Aβ fibril formation (Thioflavin T assay), proteolytic stability in murine plasma, brain-homogenate and human liver microsomes (thin layer chromatography (TLC)) and plasma protein binding to human serum albumin (HSA) and α1-acid-glycoprotein (AGP) (TRANSIL(R) Binding Kits) were investigated. To determine cycP's concentration-time-profile, a mixture of 3H-labelled and non-labelled peptide was administered to wildtype mice. The negative impact of Aβ on cell viability could be reduced and Aβ fibril formation could be clearly decelerated by cycP. Proteolytic stability tests showed that cycP was not degraded within 24 h. Plasma protein binding of cycP was stronger to AGP than to HSA and the fraction unbound after binding to HSA and AGP was about 2–3 %. Two hours after administration, cycP concentrations in the brain were up to ten times higher than linP concentrations although concentrations in plasma were similar for both peptides. Additionally, cycP showed longer half-life than linP. Oral cycP administration resulted in a constant concentration-time-profile in plasma and brain with high bioavailability. In vitro and ex vivo experiments showed promising results for cycP as a non-toxic, Aβ-targeting AD drug. As cycP concentrations in the brain were considerably higher than linP concentrations while plasma concentrations were in the same range, cycP seems to pass the BBB more efficiently than linP. This is fundamental for an Aβ-targeting AD-drug. In fact, an increased mobility to pass the BBB and high oral bioavailability probably allow administration of lower doses for cycP treatment, further reducing the risk of adverse side effects.
New Pinning Strategies for Second-Generation Wires (2013)

In the last several years, second-generation (2G) superconducting wires have been considered for applications in rotating machines operating in the 20-40 K temperature range in 1-3 T magnetic fields. Here, we outline several novel strategies for improving the low-temperature performance of second-generation wires by utilizing the in-plane strain of thick YBCO layers manufactured by the reel-to-reel metal-organic deposition (MOD) method. First, we show that he strain-induced pinning mechanism analysis, based on the Eshelby model of the elastically-strained composites, predicts that small YBCO grain size is a critical component of a strong pinning architecture. Second, we describe how the in-plane strain can be controlled by processing parameters. Systematic changes of the in-plane structure and YBCO grain size are mapped with respect to the YBCO stability line and the Cu <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sub> O-CuO line on the Bormann-Hammond diagram. It is demonstrated that the optimum critical current density is the result of a trade-off between YBCO grain coupling and the strain-induced pinning.
Microstructured optical fiber refractive index sensor (2010)

We describe a dual-core microstructured optical fiber designed for refractive index sensing of fluids. We show that by using the exponential dependence of intercore coupling on analyte refractive index, both large range and high sensitivity can be achieved in the one device. We also show that selective filling of the microstructure with analyte can increase the device sensitivity by approximately 1 order of magnitude.
Ion-ion proton transfer reactions of bio-ions involving noncovalent interactions: Holomyoglobin (1997)

Multiply protonated horse skeletal muscle holomyoglobin and apomyoglobin have been subjected to ion-ion proton transfer reactions with anions derived from perfluoro-1,3-dimethylcyclohexane in a quadrupole ion trap operated with helium as a bath gas at 1 mtorr. Neither the apomyoglobin nor holomyoglobin ions show any sign of fragmentation associated with charge state reduction to the 1 + charge state. This is particularly noteworthy for the holomyoglobin ions, which retain the noncovalently bound heme group. For example, no sign of heme loss is associated with charge state reduction from the 9 + charge state of holomyoglobin to the 1 + charge state despite the eight consecutive highly exothermic proton transfer reactions required to bring about this charge change. This result is consistent with calculations that show the combination of long ion lifetime and the high ion-helium collision rate relative to the ion-ion collision rate makes fragmentation unlikely for high mass ions in the ion trap environment even for noncovalently bound complexes of moderate binding strength. The ion-ion proton transfer rates for holo- and apomyoglobin ions of the same charge state also were observed to be indistinguishable, which supports the expectation that ion-ion proton transfer rates are insensitive to ion structure and are determined primarily by the attractive Coulomb field.
Clinical trial: benefits and risks of immunomodulators and maintenance infliximab for IBD‐subgroup analyses across four randomized trials (2009)

Concomitant immunomodulators did not improve efficacy or pharmacokinetics in IBD patients who received maintenance infliximab.
Amplification of the MLL gene on double minutes, a homogeneously staining region, and ring chromosomes in five patients with acute myeloid leukemia or myelodysplastic syndrome (2000)

Gene amplification is one of the mechanisms for activating proto-oncogenes resulting in an enhanced expression of the corresponding gene product. By fluorescence in situ hybridization (FISH), amplification of the proto-oncogene MLL has been described only in seven patients with acute myeloid leukemia (AML). We report five new patients (four had de novo AML, one had a de novo myelodysplastic syndrome) displaying different mechanisms of MLL amplification, suspected by G-banding and confirmed by FISH analysis. In two patients, MLL was amplified on double-minute chromosomes (dmins). In both cases, an interstitial deletion in 11q23 including the MLL gene was associated with the occurrence of the dmins containing MLL. As a rarely described mechanism, MLL amplification in the form of size-variable ring chromosomes was observed in two patients. Remodeling of the ring chromosomes leads to multiple copies of MLL and obviously provided a selective growth advantage. In one of the two cases with ring chromosomes, the centromeric alpha-satellite DNA of the ring chromosome was not detectable. Our fifth patient showed the unique finding of MLL amplification within a uniformly (homogeneously?) stained region in interaction with amplified ribosomal DNA sequences. Also, one of the patients with ring chromosomes exhibited the amplification of ribosomal DNA on the ring chromosomes. The transcriptionally active genes for ribosomal RNA could probably enhance the expression of MLL. In one of our five patients, we found the new combination of concomitant amplification of the proto-oncogenes MLL and MYC.