gebhart/patrepeval huggingface dataset:
A method for accurate pH mapping with chemical exchange saturation transfer (CEST) MRI (2015)

Chemical exchange saturation transfer (CEST) MRI holds enormous promise for imaging pH. Whereas the routine CEST-weighted MRI contrast is complex and susceptible to confounding factors such as labile proton ratio, chemical shift, bulk water relaxation and RF saturation, ratiometric CEST imaging simplifies pH determination. However, the conventional ratiometric CEST (RCEST) MRI approach is limited to CEST agents with multiple exchangeable groups. To address this limitation, RF power-based ratiometric CEST (PRCEST) imaging has been proposed that ratios CEST effects obtained under different RF power levels. Nevertheless, due to concomitant RF saturation (spillover) effect, the recently proposed PRCEST imaging is somewhat dependent on parameters including bulk water relaxation time and chemical shift. Herein we hypothesized that RF power-based ratiometric analysis of RF spillover effect-corrected inverse CEST asymmetry (PRICEST) provides enhanced pH measurement. The postulation was verified numerically, and validated experimentally using an in vitro phantom. Briefly, our study showed that the difference between MRI-determined pH (pHMRI ) and electrode-measured pH being 0.12 ± 0.13 and 0.04 ± 0.03 for PRCEST and PRICEST imaging, respectively, and the newly proposed PRICEST imaging provides significantly more accurate pH determination than PRCEST imaging (P < 0.01, Wilcoxon signed-rank test). Notably, the exchange rate shows dominantly base-catalysed relationship with pH, independent of creatine concentration (P > 0.10, Analysis of Covariance). In addition, the derived labile proton ratio linearly scales with creatine concentration (P < 0.01, Pearson Regression). To summarize, PRICEST MRI provides concentration-independent pH imaging, augmenting prior quantitative CEST methods for accurate pH mapping. Copyright © 2015 John Wiley & Sons, Ltd.
Antibody-targeted chemotherapy with CMC-544: a CD22-targeted immunoconjugate of calicheamicin for the treatment of B-lymphoid malignancies (2003)

Antibody-targeted chemotherapy with gemtuzumab ozogamicin (CMA-676, a CD33-targeted immunoconjugate of N-acetyl-gamma-calicheamicin dimethyl hydrazide [CalichDMH], a potent DNA-binding cytotoxic antitumor antibiotic) is a clinically validated therapeutic option for patients with acute myeloid leukemia (AML). Here, we describe the preclinical profile of another immunoconjugate of CalichDMH, CMC-544, targeted to CD22 expressed by B-lymphoid malignancies. CMC-544 comprises a humanized IgG4 anti-CD22 monoclonal antibody (mAb), G5/44, covalently linked to CalichDMH via an acid-labile 4-(4'-acetylphenoxy) butanoic acid (AcBut) linker. Both CMC-544 and unconjugated G5/44 bound human CD22 with subnanomolar affinity. CMC-544, but not unconjugated G5/44, exerted potent cytotoxicity against CD22+ B-cell lymphoma (BCL) cell lines (inhibitory concentration of 50%: 6-600 pM CalichDMH). CMC-544 caused a potent inhibition of growth of small but established BCL xenografts leading to cures (therapeutic index > 10). CMC-544 prevented the establishment of BCL xenografts and also caused regression of large BCLs (> 1.5 g tumor mass). In contrast, unconjugated CalichDMH, unconjugated G5/44, and an isotype-matched control conjugate, CMA-676, were ineffective against these BCL xenografts. Thus, CD22-targeted delivery of CalichDMH is a potent and effective preclinical therapeutic strategy for BCLs. The strong antitumor profile of CMC-544 supports its clinical evaluation as a treatment option for B-lymphoid malignancies.
Differential effects of agarose and poly(lactic‐co‐glycolic acid) on dendritic cell maturation (2006)

Application of biomaterials in combination products in which the biomaterial is presented to the host with a biological component prompts the need for understanding the biomaterial-associated adjuvant effect in the immune response against antigens associated with such a product. We have previously demonstrated that a polymer commonly used in tissue engineering and vaccine delivery, poly(lactic-co-glycolic acid) (PLGA), exerts an adjuvant effect in vivo, which was supported by PLGA-induced dendritic cell (DC) maturation in vitro. In this study, the effects of agarose and PLGA on DC maturation were compared in vitro to establish differential biomaterial effects. Human monocyte-derived DCs were treated with agarose or PLGA microparticles or films, and their maturation effect was measured as expression of costimulatory and MHC class II molecules, allostimulatory capacity, and proinflammatory cytokine secretion. Direct comparison of DC maturation phenotype indicated that PLGA was a stronger stimulus of DC maturation than agarose, and this maturation was not affected by microparticle phagocytosis. However, agarose-treated DCs showed higher activation of nuclear factor kappaB (NFkappaB) 24 h after the initial stimulation of DCs. Taken together, these results demonstrate differential biomaterial effects on DC maturation, substantiating the maturation effect of PLGA, and provide screening methods for biomaterial adjuvant effect for applications in combination products.
PRIME: A Novel Processing-in-Memory Architecture for Neural Network Computation in ReRAM-Based Main Memory (2016)

Processing-in-memory (PIM) is a promising solution to address the "memory wall" challenges for future computer systems. Prior proposed PIM architectures put additional computation logic in or near memory. The emerging metal-oxide resistive random access memory (ReRAM) has showed its potential to be used for main memory. Moreover, with its crossbar array structure, ReRAM can perform matrix-vector multiplication efficiently, and has been widely studied to accelerate neural network (NN) applications. In this work, we propose a novel PIM architecture, called PRIME, to accelerate NN applications in ReRAM based main memory. In PRIME, a portion of ReRAM crossbar arrays can be configured as accelerators for NN applications or as normal memory for a larger memory space. We provide microarchitecture and circuit designs to enable the morphable functions with an insignificant area overhead. We also design a software/hardware interface for software developers to implement various NNs on PRIME. Benefiting from both the PIM architecture and the efficiency of using ReRAM for NN computation, PRIME distinguishes itself from prior work on NN acceleration, with significant performance improvement and energy saving. Our experimental results show that, compared with a state-of-the-art neural processing unit design, PRIME improves the performance by ~2360x and the energy consumption by ~895x, across the evaluated machine learning benchmarks.
Identification and Characterization of Phenylpyruvate Decarboxylase Genes in Saccharomyces cerevisiae (2003)

Catabolism of amino acids via the Ehrlich pathway involves transamination to the corresponding alpha-keto acids, followed by decarboxylation to an aldehyde and then reduction to an alcohol. Alternatively, the aldehyde may be oxidized to an acid. This pathway is functional in Saccharomyces cerevisiae, since during growth in glucose-limited chemostat cultures with phenylalanine as the sole nitrogen source, phenylethanol and phenylacetate were produced in quantities that accounted for all of the phenylalanine consumed. Our objective was to identify the structural gene(s) required for the decarboxylation of phenylpyruvate to phenylacetaldehyde, the first specific step in the Ehrlich pathway. S. cerevisiae possesses five candidate genes with sequence similarity to genes encoding thiamine diphosphate-dependent decarboxylases that could encode this activity: YDR380w/ARO10, YDL080C/THI3, PDC1, PDC5, and PDC6. Phenylpyruvate decarboxylase activity was present in cultures grown with phenylalanine as the sole nitrogen source but was absent from ammonia-grown cultures. Furthermore, the transcript level of one candidate gene (ARO10) increased 30-fold when phenylalanine replaced ammonia as the sole nitrogen source. Analyses of phenylalanine catabolite production and phenylpyruvate decarboxylase enzyme assays indicated that ARO10 was sufficient to encode phenylpyruvate decarboxylase activity in the absence of the four other candidate genes. There was also an alternative activity with a higher capacity but lower affinity for phenylpyruvate. The candidate gene THI3 did not itself encode an active phenylpyruvate decarboxylase but was required along with one or more pyruvate decarboxylase genes (PDC1, PDC5, and PDC6) for the alternative activity. The K(m) and V(max) values of the two activities differed, showing that Aro10p is the physiologically relevant phenylpyruvate decarboxylase in wild-type cells. Modifications to this gene could therefore be important for metabolic engineering of the Ehrlich pathway.
Readministration of Adenovirus Vector in Nonhuman Primate Lungs by Blockade of CD40-CD40 Ligand Interactions (2000)

The interaction between CD40 on B cells and CD40 ligand (CD40L) on activated T cells is important for B-cell differentiation in T-cell-dependent humoral responses. We have extended our previous murine studies of CD40-CD40L in adenoviral vector-mediated immune responses to rhesus monkeys. Primary immune responses to adenoviral vectors and the ability to readminister vector were studied in rhesus monkeys in the presence or absence of a transient treatment with a humanized anti-CD40 ligand antibody (hu5C8). Adult animals were treated with hu5C8 at the time vector was instilled into the lung. Immunological analyses demonstrated suppression of adenovirus-induced lymphoproliferation and cytokine responses (interleukin-2 [IL-2], gamma interferon, IL-4, and IL-10) in hu5C8-treated animals. Animals treated with hu5C8 secreted adenovirus-specific immunoglobulin M (IgM) levels comparable to control animals, but did not secrete IgA or develop neutralizing antibodies; consequently, the animals could be readministered with adenovirus vector expressing alkaline phosphatase. A second study was designed to examine the long-term effects on immune functions of a short course of hu5C8. Acute hu5C8 treatment resulted in significant and prolonged inhibition of the adenovirus-specific humoral response well beyond the time hu5C8 effects were no longer significant. These studies demonstrate the potential of hu5C8 as an immunomodulatory regimen to enable administration of adenoviral vectors, and they advocate testing this model in humans.
Gaining Control: Training Executive Function and Far Transfer of the Ability to Resolve Interference [retracted] (2008)

Functional brain-imaging data document overlapping sites of activation in prefrontal cortex across memory tasks, suggesting that these tasks may share common executive components. We leveraged this evidence to develop a training regimen and a set of transfer tasks to examine the trainability of a putative executive-control process: interference resolution. Eight days of training on high-interference versions of three different working memory tasks increased the efficiency with which proactive interference was resolved on those particular tasks. Moreover, an improved ability to resolve interference was also transferred to different working memory, semantic memory, and episodic memory tasks, a demonstration of far-transfer effects from process-specific training. Participants trained with noninterference versions of the tasks did not exhibit transfer. We infer that the transfer we demonstrated resulted from increased efficiency of the interference-resolution process. Therefore, this aspect of executive control is plastic and adaptive, and can be improved by training.
Horizons in Nutritional Science (2005)

The appetite-modulating peptide ghrelin is predominantly produced and secreted by the stomach and shows a strong growth hormone-releasing activity, which is mediated by the activation of the so-called growth hormone secretagogue type 1a receptor. Ghrelin is involved in the regulation of energy balance by increasing food intake and reducing fat utilization. Additionally, it stimulates lactotroph and corticotroph function, influences the pituitary gonadal axis, inhibits pro-inflammatory cytokine expression, controls gastric motility and acid secretion and influences pancreatic exocrine and endocrine function, as well as impacting on glucose metabolism. This review summarizes the known functions of ghrelin and its role in the regulation of the gut-brain axis.
Systemic and regional hemodynamic effects of cyclo-oxygenase and thromboxane synthetase inhibition in normal and hyperdynamic endotoxemic rabbits. (1988)

We tested the hypothesis that prostaglandins (PGs) and thromboxane (Tx) A2 are important mediators of the hemodynamic derangements occurring in a rabbit model of hyperdynamic endotoxicosis. Rabbits were injected with either normal saline (NS) or Escherichia coli lipopolysaccharide (LPS; 1-3 micrograms/kg) and studied 6 hr later. Cardiac index (CI) and regional blood flow were determined using thermodilution and radioactive microspheres, respectively. Systemic and regional hemodynamics were determined before and 40 min after administering indomethacin (cyclo-oxygenase inhibitor; 5 mg/kg), UK38485 (Tx synthetase inhibitor; 10 mg/kg), or NS. LPS increased CI (P = .0024) and decreased mean arterial pressure (P = .0031) and systemic vascular resistance index (P = .0001). LPS increased flow to the heart and small intestine and decreased flow to the hepatic artery and pancreas. The systemic and regional hemodynamic effects of indomethacin were similar in NS- and LPS-treated rabbits. UK38485 decreased perfusion of skeletal muscle and diaphragm in both endotoxemic and control animals. This agent increased splenic perfusion only in NS-treated rabbits. Plasma levels of 6-keto PGF1 alpha (PGI2 metabolite) were typically undetectable in both NS- and LPS-treated rabbits. These data do not support the hypothesis that PG's or TxA2 are major determinants of the hemodynamic perturbations that occur in this endotoxicosis model.
Identification and procaryotic expression of the gene coding for the highly immunogenic 28-kilodalton structural phosphoprotein (pp28) of human cytomegalovirus (1988)

Human cytomegalovirus contains a structural polypeptide that is 28 kilodaltons in apparent molecular size and is reactive in Western blot (immunoblot) analysis with the majority of human sera. The gene coding for this polypeptide was mapped on the genome of human cytomegalovirus strain AD169. A monoclonal antibody specific for the 28-kilodalton polypeptide was used to screen a cDNA library constructed from poly(A)+ RNA of human cytomegalovirus-infected cells in the procaryotic expression vector lambda gt11. Hybridization of cDNA with cosmid and plasmid clones mapped the gene to the HindIII R fragment. The gene was transcribed into a late 1.3-kilobase RNA. The nucleotide sequence of the coding region was determined. Parts of the 28-kilodalton polypeptide were expressed in Escherichia coli as hybrid proteins fused to beta-galactosidase. In Western blots these proteins were recognized by human sera. Antibodies raised against the hybrid proteins reacted specifically with the viral antigen in immunoprecipitations and Western blots. In vitro phosphorylation of HCMV virions and immunoprecipitation showed that the 28-kilodalton polypeptide was phosphorylated.
Suppression of colds in human volunteers challenged with rhinovirus by a new synthetic drug (R61837) (1989)

This report describes double-blind placebo-controlled trials of a new synthetic antirhinovirus drug, R61837, which showed it to be effective in suppressing colds in human volunteers challenged with rhinovirus type 9. In one trial, R61837 was given by intranasal spray six times a day, commencing 28 h before virus challenge; treatment continued for 4 days and one dose (total dose, 25 mg). This regimen suppressed symptoms until 48 h after medication ceased, at which time colds developed. In another trial, medication with R61837 commenced at 4 h before virus challenge and continued for a total of 6 days (total dose, 36 mg). The drug produced substantial reductions in both the mean daily clinical score and the mean daily nasal secretion weight compared with patients given the placebo. These differences reached statistical significance for 2 and 4 days, respectively. In a further trial, intranasal R61837 was not effective in treating colds even when given shortly after the onset of symptoms and in doses of up to 15 mg/day.
A massively scaleable decoder architecture for low-density parity-check codes (2003)

A massively scalable architecture for decoding low-density parity-check codes is presented in this paper. This novel architecture uses hardware scaling and memory partitioning to achieve a throughput of 100 Gbps. Simulation results show that this throughput is achieved without significant bit-error performance degradation.
Esters of 1-p-chlorobenzoyl-5-methoxy-2-methyl-3-indolylacetic acid (1980)

Reactions of imidazolide of 1- p -chlorobenzoyl-5-methoxy-2-methyl-3-indolylacetic acid, prepared from the acid and N,N'-carbonyldiimidazole, with the optically active forms of 2-phenyl-3-hydroxypropane acid and with the inactive forms of p -chloro-, p -isopropyl-, and p -isobutyl-2-phenyl-3-hydroxypropane acids gave the corresponding esters. The compounds were tested for antiinflammatory activity.
Connexin hemichannel blockade improves outcomes in a model of fetal ischemia (2011)

These data support the hypothesis that opening of connexin hemichannels is a significant mediator of postischemic white and gray matter dysfunction and injury.
Chlamydial and human heat shock protein 60s activate human vascular endothelium, smooth muscle cells, and macrophages (1999)

Both chlamydial and human heat shock protein 60s (HSP 60), which colocalize in human atheroma, may contribute to inflammation during atherogenesis. We tested the hypothesis that chlamydial or human HSP 60 activates human endothelial cells (ECs), smooth muscle cells (SMCs), and monocyte-derived macrophages. We examined the expression of adhesion molecules such as endothelial-leukocyte adhesion molecule-1 (E-selectin), intercellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1), and the production of the proinflammatory cytokine interleukin-6 (IL-6). We also tested whether either HSP 60 induces nuclear factor-kappaB (NF-kappaB), which contributes to the gene expression of these molecules. Either chlamydial or human HSP 60 induced E-selectin, ICAM-1, and VCAM-1 expression on ECs similar to levels induced by Escherichia coli lipopolysaccharide (LPS). Each HSP 60 also significantly induced IL-6 production by ECs, SMCs, and macrophages to an extent similar to that induced by E. coli LPS, as assessed by enzyme-linked immunosorbent assay (ELISA). In ECs, either HSP 60 triggered activation of NF-kappaB complexes containing p65 and p50 Rel proteins. Heat treatment abolished all these effects, but did not alter the ability of E. coli LPS to induce these functions. Chlamydial and human HSP 60s therefore activate human vascular cell functions relevant to atherogenesis and lesional complications. These findings help to elucidate the mechanisms by which a chronic asymptomatic chlamydial infection might contribute to the pathophysiology of atheroma.
Broadly targeted human cytomegalovirus-specific CD4 + and CD8 + T cells dominate the memory compartments of exposed subjects (2005)

Human cytomegalovirus (HCMV) infections of immunocompetent hosts are characterized by a dynamic, life-long interaction in which host immune responses, particularly of T cells, restrain viral replication and prevent disease but do not eliminate the virus or preclude transmission. Because HCMV is among the largest and most complex of known viruses, the T cell resources committed to maintaining this balance have never been characterized completely. Here, using cytokine flow cytometry and 13,687 overlapping 15mer peptides comprising 213 HCMV open reading frames (ORFs), we found that 151 HCMV ORFs were immunogenic for CD4(+) and/or CD8(+) T cells, and that ORF immunogenicity was influenced only modestly by ORF expression kinetics and function. We further documented that total HCMV-specific T cell responses in seropositive subjects were enormous, comprising on average approximately 10% of both the CD4(+) and CD8(+) memory compartments in blood, whereas cross-reactive recognition of HCMV proteins in seronegative individuals was limited to CD8(+) T cells and was rare. These data provide the first glimpse of the total human T cell response to a complex infectious agent and will provide insight into the rules governing immunodominance and cross-reactivity in complex viral infections of humans.
Neutrophil-Derived Heparin-Binding Protein (HBP/CAP37) Deposited on Endothelium Enhances Monocyte Arrest under Flow Conditions (2005)

In acute inflammation, infiltration of neutrophils often precedes a second phase of monocyte invasion, and data in the literature suggest that neutrophils may directly stimulate mobilization of monocytes via neutrophil granule proteins. In this study, we present a role for neutrophil-derived heparin-binding protein (HBP) in monocyte arrest on endothelium. Adhesion of neutrophils to bovine aorta endothelial cells (ECs) or HUVEC-triggered secretion of HBP and binding of the protein to the EC surface. Blockade of neutrophil adhesion by treatment with a mAb to CD18 greatly reduced accumulation of HBP. In a flow chamber model, immobilized recombinant HBP induced arrest of human monocytes or monocytic Mono Mac 6 (MM6) cells to activated EC or plates coated with recombinant adhesion molecules (E-selectin, P-selectin, VCAM-1). However, immobilized recombinant HBP did not influence arrest of neutrophils or lymphocytes. Treatment of MM6 cells with recombinant HBP evoked a rapid and clear-cut increase in cytosolic free Ca(2+) that was found to be critical for the HBP-induced monocyte arrest inasmuch as pretreatment with the intracellular calcium chelating agent BAPTA-AM abolished the evoked increase in adhesion. Thus, secretion of a neutrophil granule protein, accumulating on the EC surface and promoting arrest of monocytes, could contribute to the recruitment of monocytes at inflammatory loci.
Stimulation of homologous recombination in plants by expression of the bacterial resolvase RuvC (1999)

Targeted gene disruption exploits homologous recombination (HR) as a powerful reverse genetic tool, for example, in bacteria, yeast, and transgenic knockout mice, but it has not been applied to plants, owing to the low frequency of HR and the lack of recombinogenic mutants. To increase the frequency of HR in plants, we constructed transgenic tobacco lines carrying the Escherichia coli RuvC gene fused to a plant viral nuclear localization signal. We show that RuvC, encoding an endonuclease that binds to and resolves recombination intermediates (Holliday junctions) is properly transcribed in these lines and stimulates HR. We observed a 12-fold stimulation of somatic crossover between genomic sequences, a 11-fold stimulation of intrachromosomal recombination, and a 56-fold increase for the frequency of extrachromosomal recombination between plasmids cotransformed into young leaves via particle bombardment. This stimulating effect may be transferred to any plant species to obtain recombinogenic plants and thus constitutes an important step toward gene targeting.