gebhart/patrepeval huggingface dataset:
Nearly-Linear Time Algorithms for Preconditioning and Solving Symmetric, Diagonally Dominant Linear Systems (2006)

We present a randomized algorithm that, on input a symmetric, weakly diagonally dominant n-by-n matrix A with m nonzero entries and an n-vector b, produces a y such that $\norm{y - \pinv{A} b}_{A} \leq ε\norm{\pinv{A} b}_{A}$ in expected time $O (m \log^{c}n \log (1/ε)),$ for some constant c. By applying this algorithm inside the inverse power method, we compute approximate Fiedler vectors in a similar amount of time. The algorithm applies subgraph preconditioners in a recursive fashion. These preconditioners improve upon the subgraph preconditioners first introduced by Vaidya (1990). For any symmetric, weakly diagonally-dominant matrix A with non-positive off-diagonal entries and $k \geq 1$, we construct in time $O (m \log^{c} n)$ a preconditioner B of A with at most $2 (n - 1) + O ((m/k) \log^{39} n)$ nonzero off-diagonal entries such that the finite generalized condition number $κ_{f} (A,B)$ is at most k, for some other constant c. In the special case when the nonzero structure of the matrix is planar the corresponding linear system solver runs in expected time $ O (n \log^{2} n + n \log n \ \log \log n \ \log (1/ε))$. We hope that our introduction of algorithms of low asymptotic complexity will lead to the development of algorithms that are also fast in practice.
gp39-CD40 interactions are essential for germinal center formation and the development of B cell memory. (1994)

gp39, the ligand for CD40 expressed on activated CD4+ T helper cells, is required for the generation of antibody responses to T-dependent (TD) antigens. Treatment of mice with anti-gp39 in vivo inhibits both primary and secondary antibody formation to TD, but not T-independent antigens. However, the role of this receptor-ligand pair in the development of germinal centers and the generation of B cell memory is as yet undefined. Using an antibody to gp39, this study examines the in vivo requirement for gp39-CD40 interactions in the induction of germinal center formation, as well as in the generation of B cell memory. Animals were immunized, treated in vivo with anti-gp39, and evaluated using immunohistochemical staining for the presence of splenic germinal centers 9-11 d after immunization. The results demonstrate that the formation of germinal centers was completely inhibited as a result of treatment with anti-gp39. Moreover, adoptive transfer experiments demonstrate that the generation of antigen-specific memory B cells is also inhibited as a consequence of blocking gp39-CD40 interactions. Taken together, the data demonstrate that gp39-CD40 interactions are critical not only for the generation of antibody responses, but also in the development of B cell memory.
The Human SHIP Gene Is Differentially Expressed in Cell Lineages of the Bone Marrow and Blood (1997)

The macrophage colony-stimulating factor receptor and several other hematopoietic growth factor receptors induce the tyrosine phosphorylation of a 145- to 150-kD protein in murine cells. We have previously cloned a cDNA for the murine 150-kD protein, SHIP, and found that it encodes a unique signaling intermediate that binds the SHC PTB domain through at least one tyrosine phosphorylated (NPXY) site in the carboxyl-terminal region. SHIP also contains several potential SH3 domain-binding sites, an SH2 domain for binding other tyrosine phosphorylated proteins, and an enzymatic activity that removes the phosphate from the 5 position of phosphatidylinositol 3,4,5-phosphate or from inositol 1,3,4,5-phosphate. SHIP has a negative effect on cell growth and therefore loss or modification may have profound effects on hematopoietic cell development. In this study, we have cloned a cDNA for human SHIP and examined mRNA and protein expression of SHIP and related species in bone marrow and blood cells. Flow cytometry indicates that at least 74% of immature CD34+ cells express SHIP cross-reacting protein species, whereas within the more mature population of CD33+ cells, only 10% of cells have similar expression. The majority of T cells react positively with the anti-SHIP antibodies, but significantly fewer B cells are positive. Immunoblotting detects up to seven different cross-reacting SHIP species, with peripheral blood mononuclear cells exhibiting primarily a 100-kD protein and a CD34+ acute myeloblastic leukemia expressing mainly 130-kD and 145-kD forms of SHIP. Overall, these results indicate that there is an enormous diversity in the size of SHIP or SHIP-related mRNA and protein species. Furthermore, the expression of these protein species changes according to both the developmental stage and differentiated lineage of the mature blood cell.
Virological Features and Clinical Manifestations Associated with Human Metapneumovirus: A New Paramyxovirus Responsible for Acute Respiratory‐Tract Infections in All Age Groups (2002)

The virological features and clinical findings associated with the new human metapneumovirus (HMPV) were examined retrospectively in Canadian patients hospitalized for various respiratory conditions since 1993. Thirty-eight previously unidentified respiratory viruses isolated from rhesus monkey kindey (LLC-MK2) cells were found to be positive for HMPV by reverse-transcription polymerase chain reaction, and those strains clustered in 2 phylogenetic groups. Children aged <5 years and elderly subjects aged >65 years represented 35.1% and 45.9% of the HMPV-infected cases, respectively. In hospitalized children, the most frequent diagnoses were pneumonitis (66.7%) and bronchiolitis (58.3%), whereas bronchitis and/or bronchospasm (60%) and pneumonitis (40%) were most commonly seen in elderly subjects. Of the 15 patients with pneumonitis, 4 (26.7%) had immunosuppressive conditions and 6 (40%) were infants aged <15 months. These findings suggest that HMPV can be associated with severe lower-respiratory-tract infections in very young children, the elderly, and immunocompromised patients.
A Novel, Killed-Virus Nasal Vaccinia Virus Vaccine (2007)

Live-virus vaccines for smallpox are effective but have risks that are no longer acceptable for routine use in populations at minimal risk of infection. We have developed a mucosal, killed-vaccinia virus (VV) vaccine based on antimicrobial nanoemulsion (NE) of soybean oil and detergent. Incubation of VV with 10% NE for at least 60 min causes the complete disruption and inactivation of VV. Simple mixtures of NE and VV (Western Reserve serotype) (VV/NE) applied to the nares of mice resulted in both systemic and mucosal anti-VV immunity, virus-neutralizing antibodies, and Th1-biased cellular responses. Nasal vaccination with VV/NE vaccine produced protection against lethal infection equal to vaccination by scarification, with 100% survival after challenge with 77 times the 50% lethal dose of live VV. However, animals protected with VV/NE immunization did after virus challenge have clinical symptoms more extensive than animals vaccinated by scarification. VV/NE-based vaccines are highly immunogenic and induce protective mucosal and systemic immunity without the need for an inflammatory adjuvant or infection with live virus.
Efficacy and safety of diclofenac diethylamine 1.16% gel in acute neck pain: a randomized, double-blind, placebo-controlled study (2013)

ClinicalTrials.gov identifier: NCT01335724.
Spatiotemporal characterization of rhythmic activity in rat spinal cord slice cultures (2001)

Rat spinal networks generate a spontaneous rhythmic output directed to motoneurons under conditions of increased excitation or of disinhibition. It is not known whether these differently induced rhythms are produced by a common rhythm generator. To investigate the generation and the propagation of rhythmic activity in spinal networks, recordings need to be made from many neurons simultaneously. Therefore extracellular multisite recording was performed in slice cultures of embryonic rat spinal cords grown on multielectrode arrays. In these organotypic cultures most of the spontaneous neural activity was nearly synchronized. Waves of activity spread from a source to most of the network within 35-85 ms and died out after a further 30-400 ms. Such activity waves induced the contraction of cocultured muscle fibres. Several activity waves could be grouped into aperiodic bursts. Disinhibition with bicuculline and strychnine or increased excitability with high K(+) or low Mg(2+) solutions could induce periodic bursting with bursts consisting of one or several activity waves. Whilst the duration and period of activity waves were similar for all protocols, the duration and period of bursts were longer during disinhibition than during increased excitation. The sources of bursting activity were mainly situated ventrally on both sides of the central fissure. The pathways of network recruitment from one source were variable between bursts, but they showed on average no systematic differences between the protocols. These spatiotemporal similarities under conditions of increased excitation and of disinhibition suggest a common spinal network for both types of rhythmic activity.
BACE1 Suppression by RNA Interference in Primary Cortical Neurons (2004)

Extracellular deposition of amyloid-beta (Abeta) aggregates in the brain represents one of the histopathological hallmarks of Alzheimer's disease (AD). Abeta peptides are generated from proteolysis of the amyloid precursor proteins (APPs) by beta- and gamma-secretases. Beta-secretase (BACE1) is a type I integral membrane glycoprotein that can cleave APP first to generate C-terminal 99- or 89-amino acid membrane-bound fragments containing the N terminus of Abeta peptides (betaCTF). As BACE1 cleavage is an essential step for Abeta generation, it is proposed as a key therapeutic target for treating AD. In this study, we show that small interfering RNA (siRNA) specifically targeted to BACE1 can suppress BACE1 (but not BACE2) protein expression in different cell systems. Furthermore, BACE1 siRNA reduced APP betaCTF and Abeta production in primary cortical neurons derived from both wild-type and transgenic mice harboring the Swedish APP mutant. The subcellular distribution of APP and presenilin-1 did not appear to differ in BACE1 suppressed cells. Importantly, pretreating neurons with BACE1 siRNA reduced the neurotoxicity induced by H2O2 oxidative stress. Our results indicate that BACE1 siRNA specifically impacts on beta-cleavage of APP and may be a potential therapeutic approach for treating AD.
Mobile ad hoc networking and the IETF (1999)

This is a continuing article in a series [2, 3, 4, 5] providing a snapshot of work underway within the Mobile Ad hoc Networks (manet) Working Group (WG) of the Internet Engineering Task Force (IETF) [1]. This article summarizes proceedings of the last manet WG meeting held in December 1998 and presents issues currently under discussion within the WG.
Differential IgG-binding characteristics of staphylococcal protein A, streptococcal protein G, and a chimeric protein AG. (1989)

Various Gram-positive bacteria express different types of IgG-binding receptors, each of which displaying certain unique binding properties. To evaluate specificity and avidity aspects of the differential binding pattern, a set of competitive binding assays was employed, by using staphylococcal protein A (SPA), streptococcal protein G (SPG), and a chimeric protein AG. These receptors were analyzed, in a reciprocal fashion, for binding and inhibition of binding to a selected panel of polyclonal and monoclonal Ig. Results of the study reveal that a majority of the determinants on human and bovine IgG, recognized by SPA and SPG, are either coextensive or closely overlapping. Accordingly, a minor portion of the determinants appear to be unique in the sense that a particular determinant(s) is selectively identified by one of the two receptors. Binding assays involving purified Fc fragments from human IgG, suggest that SPG shows exclusive specificity for an Fab region determinant(s) not recognized by SPA, whereas the Fc determinants for SPA and SPG are identical or overlapping. Furthermore, one of the IgG subclasses of bovine origin appears to be seen by the SPG receptor only. The competition study also demonstrates that the novel chimeric protein AG receptor shows higher or equal avidity for variants of human IgG molecules compared to the best of its parental constituents. It can thus be deduced that chimeric receptors might be useful as optimized tools for immunologic applications.
A Metal-Free DOTA-Conjugated 18F-Labeled Radiotracer: [18F]DOTA-AMBF3-LLP2A for Imaging VLA-4 Over-Expression in Murine Melanoma with Improved Tumor Uptake and Greatly Enhanced Renal Clearance (2019)

DOTA is commonly used for radiometal chelation in molecular imaging. Yet in the absence of a radiometal, DOTA is hypothesized to promote renal clearance of <sup>18</sup>F-labeled peptide tracers. In light of an increasing interest in the use of F18 for PET, here the effect of DOTA is evaluated for the first time with an <sup>18</sup>F-labeled tracer and is found to significantly improve the quality of images acquired through positron emission tomography (PET). We chose to image the peptide LLP2A that recognizes the transmembrane protein very-late antigen 4 (VLA-4) that is overexpressed by many cancers. Since it is known that [<sup>18</sup>F]RBF<sub>3</sub>-PEG<sub>2</sub>-LLP2A derivatives gave low tumor uptake values and significant GI tract accumulation, this ligand thus represents an ideal means of testing the additive effects of a DOTA group on clearance while permitting a facile, user-friendly, one-step <sup>18</sup>F-labeling. A newly designed RBF<sub>3</sub>-LLP2A bioconjugate with an appended DOTA moiety increased tumor uptake nearly 3-fold and reduced GI accumulation by more than 10-fold. The DOTA-AMBF<sub>3</sub>-PEG<sub>2</sub>-LLP2A was radiolabeled by isotope exchange and was purified by semiprep HPLC and C18 cartridge elution. Male C57BL/6J mice bearing B16-F10 melanoma tumors that overexpress the VLA-4 target were used to evaluate [<sup>18</sup>F]DOTA-AMBF<sub>3</sub>-PEG<sub>2</sub>-LLP2A using a combination of static and dynamic PET scans, biodistribution studies, and blocking controls at 1 h post injection (p.i.). The precursor peptide was synthesized and <sup>18</sup>F-labeled to provide formulations with mean (±SD) radiochemical purities of 95.9 ± 1.8%, in radiochemical yields of 4.8 ± 2.9% having molar activities of 131.7 ± 50.3 GBq/μmol. In vivo static PET images of [<sup>18</sup>F]DOTA-AMBF<sub>3</sub>-PEG<sub>2</sub>-LLP2A provided clear tumor visualization, and biodistribution studies showed that tumor uptake was 9.46 ± 2.19% injected dose per gram of tissue (%ID/g) with high tumor/muscle and tumor/blood contrast ratios of ∼8 and ∼10, respectively. Blocking confirmed the specificity of [<sup>18</sup>F]DOTA-AMBF<sub>3</sub>-PEG<sub>2</sub>-LLP2A to VLA-4 in the tumor and the bone marrow. Dynamic PET showed clearance of [<sup>18</sup>F]DOTA-AMBF<sub>3</sub>-PEG<sub>2</sub>-LLP2A mainly via the renal pathway, wherein accumulation in the intestines was reduced 10-fold compared to our previously investigated LLP2A's, while spleen uptake was at levels similar to previously reported LLP2A-chelator radiotracers. [<sup>18</sup>F]DOTA-AMBF<sub>3</sub>-PEG<sub>2</sub>-LLP2A represents a promising VLA-4 radiotracer and provides key evidence as to how a DOTA appendage can significantly reduce GI uptake in favor of urinary excretion. Implications for the development of dual-isotope theranostics that exploit the use fluorine-18 for imaging and DOTA to chelate therapeutic metal cations for therapy are discussed.
Glucosamine and Chondroitin for Treatment of Osteoarthritis (2000)

Trials of glucosamine and chondroitin preparations for OA symptoms demonstrate moderate to large effects, but quality issues and likely publication bias suggest that these effects are exaggerated. Nevertheless, some degree of efficacy appears probable for these preparations.
Growth stimulation of Rous sarcoma virus‐transformed BHK cells by biotin and serum lipids (1982)

Biotin or a serum lipid extract stimulated proliferation of G1 arrested Rous sarcoma virus-transformed BHK cells in modified Eagle's MEM (BM). The cells could be maintained continuously in BM plus biotin (BMB), but not in BM plus serum lipid extract (BM X L). Avidin inhibited growth stimulation when added to BMB, but did not inhibit growth when added to BM X L. 14C-acetate incorporation into total cellular lipids was stimulated in BMB, but not in BM. Thin-layer chromatography of the labeled cellular lipid extract indicated that relatively large amounts of 14C-acetate were incorporated into phosphatidylserine and little into the other major phospholipids. In the neutral lipids, the largest amount of incorporation was in cholesterol. G1 arrested cells multiplied rapidly in BM supplemented with dialyzed serum (BM X DS), but they did not multiply in BM with delipidized serum (BM X DLS). The addition of biotin or serum lipid extract to BM X DLS stimulated growth. Growth stimulation in BM X DLS by biotin was inhibited by avidin, but avidin had no effect on growth stimulation by serum lipid extract. Biotin stimulated additional multiplication in BM X DS and avidin inhibited this additional growth stimulation. These results suggest that growth stimulation requires lipids supplied by serum lipids or by de novo synthesis stimulated by biotin. In the absence of serum, the stimulation of the synthesis of growth factor(s) by biotin are also required for continuous multiplication.
Multiple levels of regulation of megakaryocytopoiesis. (1989)

A working hypothesis for the regulation of megakaryocytopoiesis is described on the basis of current data. The hypothesis proposes that in vivo megakaryocytes are generated by 1) the expansion of clonable progenitor cells into immature megakaryocytes by locally produced (and regulated) interleukin-3 (IL-3) and 2) the development and maturation of immature megakaryocytes by a dual system; by a lineage specific mechanism involving thrombopoietic stimuli in the steady state and thrombocytopenic conditions, and by a lineage nonspecific mechanism via IL-3 in damaged or reconstituting marrow. The hypothesis predicts that if IL-3 is a significant in vivo regulator of megakaryocyte formation and development, receptor for IL-3 should be present on megakaryocytes and may be vestigially on platelets. Small but significant levels of 125I IL-3 were found to bind to platelets from normal mice. The level of binding on platelets was found to be enhanced sevenfold from mice that had received high levels of irradiation followed by bone marrow transplantation. This contrasted with a twofold increase in the level of binding to platelets from mice made acutely thrombocytopenic with antiplatelet serum. The data suggest that IL-3 may be involved in the in vivo regulation of murine megakaryocytopoiesis and may be a significant factor in rebound thrombopoiesis following bone marrow damage.
Fluorescence spectral properties of cyanine dye labeled DNA near metallic silver particles (2003)

Recent studies have demonstrated that silver metallic particles can increase the quantum yield and decrease the lifetimes of nearby fluorophores. These studies are extended to double stranded DNA oligomers labeled with N,N'-(dipropyl)-tetramethylindocarbocyanine (Cy3) or N,N-(dipropyl)-tetramethylindodicarbocyanine (Cy5). The proximity to silver particles increases the apparent quantum yields and decreases the lifetimes of the double helical DNA 23-mer labeled individually with Cy3 or Cy5. The decreased lifetimes are accompanied by apparently increased photostability of the labeled oligomers near silver particles. Because of spatial averaging across the sample these results are likely to significantly underestimate the effects of silver particles on labeled DNA localized at an optimal distance from the metallic surface. These results suggest that DNA arrays fabricated on substrates with silver particles can display increased sensitivity and photostability in the analysis of gene expression.
Interplay of angiotensin II and angiotensin(1–7) in the regulation of matrix metalloproteinases of human cardiocytes (2008)

Angiotensin II (Ang II) is a critical effector in the renin-angiotensin system (RAS), which modulates cardiovascular homeostasis, and the matrix metalloproteinases (MMPs) and tissue inhibitors of matrix metalloproteinases (TIMPs) related metabolism of extracellular matrix (ECM). Angiotensin(1-7) [Ang(1-7)] is another bioactive peptide in the RAS and is considered to have opposite effects to Ang II. However, the modulation of MMPs and TIMPs by Ang(1-7) is largely unclear in cardiocytes, and the antagonistic effects of Ang(1-7) on Ang II-mediated expression of MMPs and TIMPs have yet to be identified. In the present study, we examined the transcript expression of MMPs and TIMPs in human cardiac fibroblasts (HCF) and myocytes (HCM) after Ang II or Ang(1-7) stimulation, and analysed the antagonistic effects of Ang(1-7) to Ang II. The results show that Ang II decreased transcript expression of MMP-1, MMP-2, TIMP-1, TIMP-2 and TIMP-3, but upregulated MMP-9 expression in the HCF cells. Transcript expression of MMP-9 and TIMP-2 was downregulated by Ang(1-7) in the same cells. In the HCM cells, Ang II induced MMP-1 and MMP-9 overexpression but MMP-2 was downregulated. All of the examined MMPs and TIMPs, except MMP-9, were markedly decreased by Ang(1-7). In the studies of antagonistic effects of Ang(1-7) to Ang II, Ang(1-7) counteracted the effects of Ang II-mediated regulation on MMP-9 and TIMP-1 in the HCF cells compared with the control group. The regulations of all examined MMPs by Ang II were reversed to basal expression by Ang(1-7) in the HCM cells. Our results suggest that Ang(1-7) and Ang II have opposite and antagonistic effects on regulation of transcription of MMPs and TIMPs in primary cultures of human cardiocytes. These effects lead to increased ratios of MMPs to TIMPs after Ang II stimulation and decreased ratios of MMPs to TIMPs after Ang(1-7) stimulation; effects which may partly depend of the type of cardiac cells. These results suggest a potential role for Ang(1-7) in attenuatating cardiac damage in Ang II-induced ECM remodelling.
Simulation and design of field emitters (1990)

Electron emission characteristics for the cone and wedge generic field emitter structures are described. Effects of variations in emitter geometry on electron current, spectral and temporal dispersion of electron emission, and emitter heating are calculated analytically and by computer simulation. Several guidelines for emitter design are suggested.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>