gebhart/patrepeval huggingface dataset:
In Vitro Expansion of Polycythemia Vera Progenitors Favors Expansion of Erythroid Precursors without JAK2 V617F Mutation. (2005)

Abstract A single acquired point mutation of JAK2 1849G&amp;gt;T (V617F), a tyrosine kinase with a key role in signal transduction from growth factor receptors, is found in 70%–97% of patients with polycythemia vera (PV). In the studies of tyrosine kinase inhibitors on JAK2 1849G&amp;gt;T (see Gaikwad et all abstract at this meeting) we decided to study the possible therapeutic effect of these agents using native in vitro expanded cells from peripheral blood. To our surprise, the in vitro expansion of PV progenitors preferentially augmented cells without JAK2 1849G&amp;gt;T mutation. We used a 3 step procedure to amplify erythroid precursors in different stages of differentiation from the peripheral blood of 5 PV patients previously found to be homozygous or heterozygous for the JAK2 1849G&amp;gt;T mutation. In the first step (days 1–7), 106/ml MNCs were cultured in the presence of Flt-3 (50 ng/ml), Tpo (100 ng/ml), and SCF (100 ng/ml). In the second step (days 8–14), the cells obtained on day 7 were re-suspended at 106/ml in the same medium with SCF (50 ng/ml), IGF-1 (50 ng/ml), and 3 units/ml Epo. In the third step, the cells collected on day 14 were re-suspended at 106/ml and cultured for two more days in the presence of the same cytokine mixture as in the step 2 but without SCF. The cultures were incubated at 37oC in 5% CO2/95% air atmosphere and the medium renewed every three days to ensure good cell proliferation. The expanded cells were stained with phycoerythrin-conjugated anti-CD235A (glycophorin) and fluorescein isothiocyanate-conjugated anti-human-CD71 (transferrin receptor) monoclonal antibodies and analyzed by flow cytometry. The cells were divided by their differential expression of these antigens into 5 subgroups ranging from primitive erythroid progenitors (BFU-Es and CFU-Es) to polychromatophilic and orthochromatophilic erythroblasts; over 70% of harvested cells were early and late basophilic erythroblasts. The proportion of JAK2 1849G&amp;gt;T mutation in clonal PV granulocytes (GNC) before in vitro expansion and in expanded erythroid precursors was quantitated by pyrosequencing (Jelinek, Blood in press) and is depicted in the Table. These data indicate that in vitro expansion of PV progenitors favors expansion of erythroid precursors without JAK2 V617F mutation. Since three PV samples were from females with clonal granulocytes, erythrocytes, and platelets, experiments were underway to determine if the in vitro expanded erythroid cells were clonal PV cells without JAK2 V617F mutation, or derived from polyclonal rare circulating normal hematopoietic progenitors. The Proportion of JAK2 T Allele Patients GNC T Allele (%) Expanded Cells T Allele (%) PV1 (Female) 81 10 PV2 (Male) 77 28 PV3 (Male) 44 42 PV4 (Female) 78 19 PV5 (Female) 78 28
Essential role for proteinase-activated receptor-2 in arthritis (2003)

Using physiological, pharmacological, and gene disruption approaches, we demonstrate that proteinase-activated receptor-2 (PAR-2) plays a pivotal role in mediating chronic inflammation. Using an adjuvant monoarthritis model of chronic inflammation, joint swelling was substantially inhibited in PAR-2-deficient mice, being reduced by more than fourfold compared with wild-type mice, with virtually no histological evidence of joint damage. Mice heterozygous for PAR-2 gene disruption showed an intermediate phenotype. PAR-2 expression, normally limited to endothelial cells in small arterioles, was substantially upregulated 2 weeks after induction of inflammation, both in synovium and in other periarticular tissues. PAR-2 agonists showed potent proinflammatory effects as intra-articular injection of ASKH95, a novel synthetic PAR-2 agonist, induced prolonged joint swelling and synovial hyperemia. Given the absence of the chronic inflammatory response in the PAR-2-deficient mice, our findings demonstrate a key role for PAR-2 in mediating chronic inflammation, thereby identifying a novel and important therapeutic target for the management of chronic inflammatory diseases such as rheumatoid arthritis.
Tumor evasion of the immune system: inhibiting p38 MAPK signaling restores the function of dendritic cells in multiple myeloma (2005)

Dendritic cells (DCs) from patients with cancer are functionally defective, but the molecular mechanisms underlying these defects are poorly understood. In this study, we used the murine 5TGM1 myeloma model to examine the effects and mechanisms of tumor-derived factors on the differentiation and function of DCs. Myeloma cells or tumor culture conditioning medium (TCCM) were shown to inhibit the differentiation and function of BM-derived DCs (BMDCs), as evidenced by the down-regulated expression of DC-related surface molecules, decreased IL-12, and compromised capacity of the cells to activate allospecific T cells. Moreover, TCCM-treated BMDCs were inferior to normal BMDCs at priming tumor-specific immune responses in vivo. Neutralizing antibodies against IL-6, IL-10, and TGF-beta partially abrogated the effects. TCCM treatment activated p38 mitogen-activated protein kinase (MAPK) and Janus kinase (JNK) but inhibited extracellular regulated kinase (ERK). Inhibiting p38 MAPK restored the phenotype, cytokine secretion, and function of TCCM-treated BMDCs. BMDCs from cultures with TCCM and p38 inhibitor was as efficacious as normal BMDCs at inducing tumor-specific antibody, type 1 T cell, and cytotoxic T lymphocyte (CTL) responses and at prolonging mouse survival. Thus, our results suggested that tumor-induced p38 MAPK activation and ERK inhibition in DCs may be a new mechanism for tumor evasion and that regulating these pathways during DC differentiation provides new strategies for generating potent DC vaccines for immunotherapy in patients with cancer.
Hook-associated proteins essential for flagellar filament formation in Salmonella typhimurium (1984)

The hooks of the flagella of Salmonella typhimurium were purified by a newly developed method, using a flaL mutant without a filament, and the hook components were analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. As a result, we detected three protein species in addition to hook protein. We call these three proteins hook-associated proteins (HAPs). Their molecular weights were 59,000 for HAP1, 53,000 for HAP2, and 31,000 for HAP3. The HAP1/hook protein/HAP3/HAP2 molar ratio, calculated from their relative amounts and their molecular weights, was 1:10:1.1:0.53. The compositions of HAPs were analyzed in the hooks from the other filamentless mutants which were defective in H1 H2, flaV, flaU, or flaW. Hooks from the H1 H2 mutant had the same HAP composition as hooks from the flaL mutant. Hooks from the flaV mutants contained HAP1 and HAP3. Hooks from the flaU mutants contained HAP1. Hooks from the flaW mutants contained a very small amount of HAP3. From these results, the process of hook morphogenesis and the genes responsible for each step were postulated. Electron micrographs of hooks from the filamentless mutants showed that hooks which contained all three HAPs had a sharp clawlike tip, whereas hooks lacking any HAP had a flat tip. Electron micrographs of hooks treated with antibody against the hook protein showed that each claw-shaped end was not covered with antibody. These results strongly suggest that all three HAPs or at least some of them are located at the claw-shaped end and play an essential role in filament formation.
Effect of pelleting on the recalcitrance and bioconversion of dilute-acid pretreated corn stover under low- and high-solids conditions (2013)

Background: Knowledge regarding the performance of densified biomass in biochemical processes is limited. The effects of densification on biochemical conversion are explored here. Results: Pelleted corn stover samples were generated from bales that were milled to 6.35 mm. Low-solids acid pretreatment and simultaneous saccharification and fermentation were performed for pelleted and ground stover (6.35 and 2 mm) formats. Monomeric xylose yields were significantly higher for pellets (∼60%) than for ground formats (∼38%). Pellets achieved approximately 84% of theoretical ethanol yield; ground stover formats had similar profiles, reaching approximately 68% theoretical ethanol yield. Pelleted and 6.35-mm ground stover were evaluated using a ZipperClave® reactor under high-solids, process-relevant conditions for multiple pretreatment severities (Ro); feedstock reactivity increased slightly following combined pretreatment and enzymatic hydrolysis for three of five severities tested. Conclusion: Pelleting did not render corn stover more recalcitrant to dilute-acid pretreatment under low- or high-solids conditions, and even enhanced ethanol yields.
Comparison of Platelet-Rich Plasma, Stromal Vascular Fraction (SVF), or SVF with an Injectable PLGA Nanofiber Scaffold for the Treatment of Osteochondral Injury in Dogs (2017)

Stromal vascular fraction (SVF) contains a small number of mesenchymal stem cells and has been used as a treatment for osteoarthritis and cartilage injury. Due to limited evidence of successful cartilage regeneration with injected stem cell therapies, there is interest in combining cellular therapies with injectable scaffolding materials to increase intra-articular residence times of stem cells and improve tissue regeneration. However, the safety of intra-articular injection of SVF combined with injectable scaffolds is unestablished. Also, it is unclear if SVF therapy is superior to more easily prepared biologics, such as platelet-rich plasma (PRP). The purpose of this study was to assess the safety of SVF when combined with an injectable poly(L-lactide-co-glycolide) nanofiber scaffold and to provide a comparison of SVF therapy to PRP. A total of 12 Beagles had osteochondral defects created in both medial femoral condyles and 4 dogs each were allocated to treatment groups of SVF (<i>n</i> = 4), SVF plus PLGA scaffolding (<i>n</i> = 4), or leukoreduced PRP (<i>n</i> = 4). One knee in each dog received treatment, and the contralateral knee was sham treated with saline. Dogs were assessed over a 6-month period, and outcome measures included functional, radiographic, biochemical, and histological assessments. PRP treatment resulted in improvements in lameness scores and objective kinetic assessments of function. There were no statistically significant improvements in function, cartilage biochemical composition, or histology for SVF-treated knees. The combination of SVF and the injectable PLGA scaffold had worse outcomes than other groups including sham treatment based upon functional, biochemical, and histological assessments, raising concerns over the safety of this scaffold for intra-articular injection.
Increased rat cardiac angiotensin converting enzyme activity and mRNA expression in pressure overload left ventricular hypertrophy. Effects on coronary resistance, contractility, and relaxation. (1990)

We compared the activity and physiologic effects of cardiac angiotensin converting enzyme (ACE) using isovolumic hearts from male Wistar rats with left ventricular hypertrophy due to chronic experimental aortic stenosis and from control rats. In response to the infusion of 3.5 X 10(-8) M angiotensin I in the isolated buffer perfused beating hearts, the intracardiac fractional conversion to angiotensin II was higher in the hypertrophied hearts compared with the controls (17.3 +/- 4.1% vs 6.8 +/- 1.3%, P less than 0.01). ACE activity was also significantly increased in the free wall, septum, and apex of the hypertrophied left ventricle, whereas ACE activity from the nonhypertrophied right ventricle of the aortic stenosis rats was not different from that of the control rats. Northern blot analyses of poly(A)+ purified RNA demonstrated the expression of ACE mRNA, which was increased fourfold in left ventricular tissue obtained from the hearts with left ventricular hypertrophy compared with the controls. In both groups, the intracardiac conversion of angiotensin I to angiotensin II caused a comparable dose-dependent increase in coronary resistance. In the control hearts, angiotensin II activation had no significant effect on systolic or diastolic function; however, it was associated with a dose-dependent depression of left ventricular diastolic relaxation in the hypertrophied hearts. These novel observations suggest that cardiac ACE is induced in hearts with left ventricular hypertrophy, and that the resultant intracardiac activation of angiotensin II may have differential effects on myocardial relaxation in hypertrophied hearts relative to controls.
Temperature, Frequency, and Load Level Correction Factors for Backcalculated Moduli Values (1989)

It is a well-established fact that moduli values backcalculated from deflection data of one particular NDT device will be different from those of another device. Although disconcerting at first glance, this should not be surprising to the pavement engineer. NDT devices often use widely different load levels and loading frequencies. Combining this with the complex nature of pavement materials and the fact that data are often collected under different temperature and moisture conditions emphasizes the need for theoretically sound procedures for converting measured values to standard levels of load, temperature, and loading frequency. This is the subject of this paper. In this paper are the results of a recently completed Texas Transportation Institute study on nondestructive testing. One of the major recommendations of that study are standardized guidelines for applying temperature, frequency, and load level corrections. These will be described in detail, and typical examples will be given. Of particular interest are the load level correction factors. These are demonstrated in case studies which compare backcalculated moduli values from the Dynaflect, the Dynatest falling weight deflectometer, and the Road Rater 2000.
Bioenergetics of lactic acid bacteria: cytoplasmic pH and osmotolerance (1987)

Lactic acid bacteria maintain a cytoplasm that is more alkaline than the medium, but whose pH decreases as the medium is acidified during growth and fermentation. Streptococci generally acidify the cytoplasm from approximately pH 7.6 to 5.7 (external pH 4.5) before growth and then fermentation cease. The internal enzyme machinery of these anaerobic fermenters thus tolerates a fairly wide range in internal proton concentration. Lactobacilli tolerate a significantly more acidic cytoplasmic pH of 4.4 (external pH 3.5). However, when the cytoplasmic pH decreases below a threshold pH, which depends on the organism cellular functions are inhibited. Fermentation end-products, such as organic acids or alcohols, exert their deleterious effects by bringing about acidification of the cytoplasm below the permissible pH. Organic acids, which act as protonophores, or solvents, which perturb membrane phospholipids, at high concentrations increase the inward leak of H+ so that H+ efflux is not rapid enough to alkalinize the cytoplasm. The membrane pH gradient is thus dissipated.
Nuclear Import of Histone Deacetylase 5 by Requisite Nuclear Localization Signal Phosphorylation (2010)

Histone deacetylase 5 (HDAC5), a class IIa deacetylase, is a prominent regulator of cellular and epigenetic processes that underlie the progression of human disease, ranging from cardiac hypertrophy to cancer. Although it is established that phosphorylation mediates 14-3-3 protein binding and provides the essential link between HDAC5 nucleo-cytoplasmic shuttling and transcriptional repression, thus far only four phospho-acceptor sites have been functionally characterized. Here, using a combinatorial proteomics approach and phosphomutant screening, we present the first evidence that HDAC5 has at least 17 in vivo phosphorylation sites within functional domains, including Ser278 and Ser279 within the nuclear localization signal (NLS), Ser1108 within the nuclear export signal, and Ser755 in deacetylase domain. Global and targeted MS/MS analyses of NLS peptides demonstrated the presence of single (Ser278 and Ser279) and double (Ser278/Ser279) phosphorylations. The double S278/279A mutation showed reduced association with HDAC3, slightly decreased deacetylation activity, and significantly increased cytoplasmic localization compared with wild type HDAC5, whereas the S278A and S1108A phosphomutants were not altered. Live cell imaging revealed a deficiency in nuclear import of S278/279A HDAC5. Phosphomutant stable cell lines confirmed the cellular redistribution of NLS mutants and revealed a more pronounced cytoplasmic localization for the single S279A mutant. Proteomic analysis of immunoisolated S278/279A, S279A, and S259/498A mutants linked altered cellular localization to changes in protein interactions. S278/279A and S279A HDAC5 showed reduced association with the NCoR-HDAC3 nuclear corepressor complex as well as protein kinase D enzymes, which were potentiated in the S259/498A mutant. These results provide the first link between phosphorylation outside the known 14-3-3 sites and downstream changes in protein interactions. Together these studies identify Ser279 as a critical phosphorylation within the NLS involved in the nuclear import of HDAC5, providing a regulatory point in nucleo-cytoplasmic shuttling that may be conserved in other class IIa HDACs-HDAC4 and HDAC9.
Mucosal surface pH of the large intestine of the rat and of normal and inflamed large intestine in man. (1987)

The surface pH of rat distal colonic mucosa and human rectal mucosa was measured in vitro using first a small pH electrode with a flattened tip. In buffer with pH 7.56 the mean rat colonic surface pH was 6.72. Lowering the buffer pH in steps resulted in a small fall in surface pH, the values being buffer pH 7.06 surface pH 6.64, buffer pH 6.58 surface pH 6.61 and finally buffer pH 6.09 surface pH 6.39. Similar results were obtained with a buffer where butyrate, 30 mmol/l replaced chloride and when a CO2/bicarbonate buffer was used. During the time taken for the study transmural potential difference only changed by 1-2 mV. Serosal surface pH changed with buffer pH, suggesting that the maintained surface pH is a property of the mucosal surface only. The surface pH of human rectal mucosa was similar to that of rat distal colonic mucosa. As buffer pH fell from pH 7.51 to 5.96 mucosal surface pH only fell from pH 6.80 to 6.26. The values obtained in ulcerative proctitis did not differ from normal mucosa. Secondly pH microelectrodes were used to measure the juxta mucosal pH and the pH-microclimate thickness when luminal pH was controlled. The microclimate had a pH 6.63 adjacent to the mucosa with a thickness of 840 micron. The importance of mucus in maintaining the microclimate was shown by n-acetyl cysteine thinning and prostaglandin E2 thickening the layer. These results describe a surface microclimate in the large intestine of appreciable thickness and a constant juxta mucosal pH. Luminal pH changes produce only a small change in microclimate pH.
Automatic segmentation of colonic polyps in CT colonography based on knowledge-guided deformable models (2003)

An automatic method to segment colonic polyps from CT colonography is presented. The method is based on a combination of knowledge-guided intensity adjustment, fuzzy c-mean clustering, and deformable models. The input is a set of polyp seed points generated by filters on geometric properties of the colon surface. First, the potential polyp region is enhanced by a knowledge-guided adjustment. Then, a fuzzy c-mean clustering is applied on a 64*64 pixel sub-image around the seed. Fuzzy membership functions for lumen air, polyp tissues and other tissues are computed for each pixel. Finally, the gradient of the fuzzy membership function is used as the image force to drive a deformable model to the polyp boundary. The segmentation process is first executed on the 2D transverse slice where the polyp seed is located, and then is propagated to neighboring slices to construct a 3D representation of the polyp. Manual segmentation is performed on the same polyps and treated as the ground truth. The automatically generated segmentation is compared with the ground truth segmentation to validate the accuracy of the method. Experimental results showed that the average overlap between the automatic segmentation and manual segmentation is 76.3%. Given the complex polyp boundaries and the small size of the polyp, this is a good result both visually and quantitatively.
A SIMPLE AND EFFICIENT METHOD FOR PURIFICATION OF INFECTIOUS RECOMBINANT ADENOVIRUS (1994)

Recently, the adenovirus expression vector attracts much attention for the application to gene therapy and the method to purify and concentrate adenovirus without loss of infectivity has become very important, especially for animal experiments and gene therapy of humans. In this report, we show a simple and efficient method for purifying infectious adenovirus. The method consists of sequential centrifugation in CsCl step gradients without loss of infectivity and can be completed in one day. The method maintained the viral infectivity after 10-fold concentration and seemed to remove more than 99.9% of carried-over proteins. We showed also that the buffers for dialyzing the purified virions influenced the stability of infectivity. The buffers of 10 mM HEPES-1 mM EDTA-10% glycerol and PBS(-)-10% glycerol resulted in higher stability than did 10 mM HEPES-1 mM MgCl2-10% glycerol. The method is may be useful in many applications of recombinant adenovirus.
Going Deeper: a Taxonomy of 3D on the Tabletop (2007)

Extending the tabletop to the third dimension has the potential to improve the quality of applications involving 3D data and tasks. Recognizing this, a number of researchers have proposed a myriad of display and input metaphors. However a standardized and cohesive approach has yet to evolve. Furthermore, the majority of these applications and the related research results are scattered across various research areas and communities, and lack a common framework. In this paper, we survey previous 3D tabletops systems, and classify this work within a newly defined taxonomy. We then discuss the design guidelines which should be applied to the various areas of the taxonomy. Our contribution is the synthesis of numerous research results into a cohesive framework, and the discussion of interaction issues and design guidelines which apply. Furthermore, our work provides a clear understanding of what approaches have been taken, and exposes new routes for potential research, within the realm of interactive 3D tabletops.
An Interleave-Division multiplexing (IDM) based modulation for 3GPP LTE downlink (2008)

Interleave-Division Multiple-Access (IDMA) is an efficient multiple access technique to improve high spectrum efficiency for cellular communications. In this paper IDM-based modulation (called layered modulation (LM)) is proposed for OFDM systems. The idea of LM is to multiplex multiple parallel layers of data streams by performing repetition and layer-specific interleaver on each layer. Since LM code bits are fully distributed in time-frequency plane, by the aid of low-complexity chip-by-chip interference cancellation time-frequency diversity can be well exploited in LM. Applying LM to 3GPP LTE downlink, we compare LM to M-PSK/QAM modulation. Numerical results show that the LM can achieve superior performance over M-PSK/QAM. The performance gain over QPSK, 8PSK and 16QAM is 1.1dB, 2.2dB and 0.6dB, respectively.