gebhart/patrepeval huggingface dataset:
The CXC chemokines, IL-8 and IP-10, regulate angiogenic activity in idiopathic pulmonary fibrosis (1997)

Idiopathic pulmonary fibrosis (IPF) is a chronic and often fatal disorder. Fibroplasia and deposition of extracellular matrix are dependent, in part, on angiogenesis. We postulated that an imbalance exists in the expression of angiogenic (IL-8) vs angiostatic (IFN-gamma-inducible protein (IP-10)) CXC chemokines, which favors net angiogenesis in IPF. To test this hypothesis, we obtained open lung biopsies either from normal patients undergoing thoracic surgery for reasons other than interstitial lung disease (control) or from patients with IPF. We found that levels of IL-8 were greater from tissue specimens of IPF patients then from those of controls. In contrast, IP-10 levels were higher from tissue specimens obtained from control subjects than from those from IPF patients. When IL-8 or IP-10 was depleted from IPF tissue specimens, tissue-derived angiogenic activity was markedly reduced or enhanced, respectively. Immunolocalization of IL-8 demonstrated that the pulmonary fibroblast (PF) of IPF lung was the predominant cellular source of IL-8. Isolated PF from IPF patients constitutively produced more IL-8 and less IP-10 than control PF. Conditioned media from IPF-PFs demonstrated constitutive angiogenic activity that was attributable, in part, to IL-8. Depletion of IP-10 from IPF-PF CM resulted in an increase in corneal neovascularization. These findings support the notion that IL-8 and IP-10 are important factors that regulate angiogenic activity in IPF.
Multiplexing/Beamforming Switching for Coded MIMO in Spatially Correlated Channels Based on Closed-Form BER Approximations (2007)

This paper considers low-complexity coded multiple-input-multiple-output transmission in Rayleigh channels with correlation between antennas at both the transmitter and receiver. We consider statistical beamforming (SB) and spatial multiplexing (SM) with a zero-forcing receiver. We calculate the link-level capacity of both schemes with bit-interleaved coded modulation and derive accurate closed-form approximations to the bit error rate. We then show how the resulting expressions can be used in an adaptive algorithm to select the best combination of code rate, modulation format, and transmission scheme (SB or SM) in order to maximize throughput. Unlike other mode-switching schemes that require empirical lookup tables, this approach applies to any correlation scenario. Numerical studies are used to demonstrate the performance as a function of signal-to-noise ratio and correlation parameters.
Soya–a dietary source of the non-steroidal oestrogen equol in man and animals (1984)

The dietary origin of the weak oestrogen equol (7-hydroxy-3-(4'-hydroxyphenyl)-chroman) present in human urine has been investigated using gas chromatography-mass spectrometry. Feeding experiments with different food constituents and monitoring the urinary excretion of equol revealed that soya food yields more than 0.1 mg urinary equol/g flour ingested. From this source the glucoside of daidzein (4',7-dihydroxyisoflavone) has been isolated and identified as a precursor of equol. Both equol and daidzein were characterized as monoglucuronide conjugates in human urine and the concentration of urinary equol exceeded the concentrations of the classical oestrogens by 100- to 1000-fold after ingestion of a single meal containing soya protein. The potential biological significance of this result is discussed.
Dual labelling of circulating CD8 cells in patients with multiple sclerosis. (1989)

Peripheral blood T cell phenotypes have been analysed in serial samples from patients with multiple sclerosis, their unaffected relatives and controls using a panel of antibodies chosen to distinguish T suppressor and activated suppressor cells from other CD8 lymphocytes. Overall, the percentage of Leu 2a cells correlated with alterations in the Leu 2a/15 suppressor sub-population (r = 0.79, p less than 0.001). Fewer circulating Leu 2a and Leu 2a/15 positive cells were identified in multiple sclerosis patients than unaffected individuals but there was no alteration in percentage of activated (Leu 2a/DR) CD8 cells. These findings suggest that the fluctuations in CD8 cells, characteristic of patients with multiple sclerosis, are due to alterations in T suppressor phenotype; this may then lower the threshold for activation of other T cell subpopulations.
microRNA-29c and microRNA-223 down-regulation has in vivo significance in chronic lymphocytic leukemia and improves disease risk stratification (2009)

Aberrant expression of microRNAs has been recently associated with chronic lymphocytic leukemia (CLL) outcome. Although disease evolution can be predicted by several prognostic factors, a better outcome individualization in a given patient is still of utmost interest. Here, we showed that miR-29c and miR-223 expression levels decreased significantly with progression from Binet stage A to C were significantly lower in poor prognostic subgroups (defined by several prognostic factors) and could significantly predict treatment-free survival (TFS) and overall survival (OS). Furthermore, we developed a quantitative real-time polymerase chain reaction (qPCR) score combining miR-29c, miR-223, ZAP70, and LPL (from 0 to 4 poor prognostic markers) to stratify treatment and death risk in a cohort of 110 patients with a median follow-up of 72 months (range, 2-312). Patients with a score of 0/4, 1/4, 2/4, 3/4, and 4/4 had a median TFS of greater than 312, of 129, 80, 36, and 19 months, respectively (hazard ratio, HR(0/4 < 1/4 < 2/4 < 3/4 < 4/4) = 17.00, P < .001). Patients with a score of 0-1/4, 2-3/4, and 4/4 had a median OS of greater than 312, of 183 and 106 months, respectively (HR(0/4 < 1/4 < 2/4 < 3/4 < 4/4) = 13.69, P = .001). This score will help to identify, among the good and poor prognosis subgroups, patients who will need early therapy and thus will require a closer follow-up.
Regulation of expression of type II sodium-phosphate cotransporters by protein kinases A and C (1998)

The purpose of the present study was to determine the effect of protein kinase A and protein kinase C activation on the membrane expression of NaPi-4, the type II sodium-phosphate cotransporter in OK cells. NaPi-4 expression was measured using polyclonal antisera produced in rabbits against a peptide identical to the carboxy-terminal 12-amino acid sequence of NaPi-4. The antisera identified an apically localized protein by confocal imaging of intact OK cells and a broad band of 110-140 kDa by immunoblot analysis of OK cell membranes. Treatment of OK cells with parathyroid hormone (PTH) decreased the intensity of the 110- to 140-kDa band, which was detectable by 2 h, maximal by 4 h at 62%, and sustained for 24 h. 8-Bromo-cAMP (8-BrcAMP) inhibited NaPi-4 expression for up to 24 h by over 90%. However, phorbol 12-myristate 13-acetate inhibited NaPi-4 expression by less than 10%. PTH-(3-34), a fragment which stimulates only protein kinase C, inhibited phosphate transport but also had no effect on NaPi-4 expression. We conclude that protein kinase A but not protein kinase C inhibits sodium-phosphate uptake in OK cells by downregulation of NaPi-4 expression.
High-fidelity facial and speech animation for VR HMDs (2016)

Significant challenges currently prohibit expressive interaction in virtual reality (VR). Occlusions introduced by head-mounted displays (HMDs) make existing facial tracking techniques intractable, and even state-of-the-art techniques used for real-time facial tracking in unconstrained environments fail to capture subtle details of the user's facial expressions that are essential for compelling speech animation. We introduce a novel system for HMD users to control a digital avatar in real-time while producing plausible speech animation and emotional expressions. Using a monocular camera attached to an HMD, we record multiple subjects performing various facial expressions and speaking several phonetically-balanced sentences. These images are used with artist-generated animation data corresponding to these sequences to train a convolutional neural network (CNN) to regress images of a user's mouth region to the parameters that control a digital avatar. To make training this system more tractable, we use audio-based alignment techniques to map images of multiple users making the same utterance to the corresponding animation parameters. We demonstrate that this approach is also feasible for tracking the expressions around the user's eye region with an internal infrared (IR) camera, thereby enabling full facial tracking. This system requires no user-specific calibration, uses easily obtainable consumer hardware, and produces high-quality animations of speech and emotional expressions. Finally, we demonstrate the quality of our system on a variety of subjects and evaluate its performance against state-of-the-art real-time facial tracking techniques.
NARC-1/PCSK9 and Its Natural Mutants (2004)

The discovery of autosomal dominant hypercholesterolemic patients with mutations in the PCSK9 gene, encoding the proprotein convertase NARC-1, resulting in the missense mutations suggested a role in low density lipoprotein (LDL) metabolism. We show that the endoplasmic reticulum-localized proNARC-1 to NARC-1 zymogen conversion is Ca2+-independent and that within the zymogen autocatalytic processing site SSVFAQ [downward arrow]SIP Val at P4 and Pro at P3' are critical. The S127R and D374Y mutations result in approximately 50-60% and > or =98% decrease in zymogen processing, respectively. In contrast, the double [D374Y + N157K], F216L, and R218S natural mutants resulted in normal zymogen processing. The cell surface LDL receptor (LDLR) levels are reduced by 35% in lymphoblasts of S127R patients. The LDLR levels are also reduced in stable HepG2 cells overexpressing NARC-1 or its natural mutant S127R, and this reduction is abrogated in the presence of 5 mm ammonium chloride, suggesting that overexpression of NARC-1 increases the turnover rate of the LDLR. Adenoviral expression of wild type human NARC-1 in mice resulted in a maximal approximately 9-fold increase in circulating LDL cholesterol, while in LDLR-/- mice a delayed approximately 2-fold increase in LDL cholesterol was observed. In conclusion, NARC-1 seems to affect both the level of LDLR and that of circulating apoB-containing lipoproteins in an LDLR-dependent and -independent fashion.
Metal−Organic Frameworks with Exceptionally High Capacity for Storage of Carbon Dioxide at Room Temperature (2005)

Metal-organic frameworks (MOFs) show high CO2 storage capacity at room temperature. Gravimetric CO2 isotherms for MOF-2, MOF-505, Cu3(BTC)2, MOF-74, IRMOFs-11, -3, -6, and -1, and MOF-177 are reported up to 42 bar. Type I isotherms are found in all cases except for MOFs based on Zn4O(O2C)6 clusters, which reveal a sigmoidal isotherm (having a step). The various pressures of the isotherm steps correlate with increasing pore size, which indicates potential for gas separations. The amine functionality of the IRMOF-3 pore shows evidence of relatively increased affinity for CO2. Capacities qualitatively scale with surface area and range from 3.2 mmol/g for MOF-2 to 33.5 mmol/g (320 cm3(STP)/cm3, 147 wt %) for MOF-177, the highest CO2 capacity of any porous material reported.
Cloning and Characterization of Unusual Fatty Acid Desaturases from Anemone leveillei: Identification of an Acyl-Coenzyme A C20 Δ5-Desaturase Responsible for the Synthesis of Sciadonic Acid (2007)

The seed oil of Anemone leveillei contains significant amounts of sciadonic acid (20:3Delta(5,11,14); SA), an unusual non-methylene-interrupted fatty acid with pharmaceutical potential similar to arachidonic acid. Two candidate cDNAs (AL10 and AL21) for the C(20) Delta(5cis)-desaturase from developing seeds of A. leveillei were functionally characterized in transgenic Arabidopsis (Arabidopsis thaliana) plants. The open reading frames of both Delta(5)-desaturases showed some similarity to presumptive acyl-coenzyme A (CoA) desaturases found in animals and plants. When expressed in transgenic Arabidopsis, AL21 showed a broad range of substrate specificity, utilizing both saturated (16:0 and 18:0) and unsaturated (18:2, n-6 and 18:3, n-3) substrates. In contrast, AL10 did not show any activity in wild-type Arabidopsis. Coexpression of AL10 or AL21 with a C(18) Delta(9)-elongase in transgenic Arabidopsis plants resulted in the production of SA and juniperonic fatty acid (20:4Delta(5,11,14,17)). Thus, AL10 acted only on C(20) polyunsaturated fatty acids in a manner analogous to "front-end" desaturases. However, neither AL10 nor AL21 contain the cytochrome b(5) domain normally present in this class of enzymes. Acyl-CoA profiling of transgenic Arabidopsis plants and developing A. leveillei seeds revealed significant accumulation of Delta(5)-unsaturated fatty acids as acyl-CoAs compared to the accumulation of these fatty acids in total lipids. Positional analysis of triacylglycerols of A. leveillei seeds showed that Delta(5)-desaturated fatty acids were present in both sn-2 and sn-1 + sn-3 positions, although the majority of 16:1Delta(5), 18:1Delta(5), and SA was present at the sn-2 position. Our data provide biochemical evidence for the A. leveillei Delta(5)-desaturases using acyl-CoA substrates.
Synthesis and Reactivity of Laquinimod, a Quinoline-3-carboxamide:  Intramolecular Transfer of the Enol Proton to a Nitrogen Atom as a Plausible Mechanism for Ketene Formation (2006)

5-Chloro-N-ethyl-1,2-dihydro-4-hydroxy-1-methyl-2-oxo-N-phenyl-3-quinolinecarboxamide (laquinimod, 2) is an oral drug in clinical trials for the treatment of multiple sclerosis. The final step in the synthesis of 2 is a high-yielding aminolysis reaction of ester 1 with N-ethylaniline. An equilibrium exists between 1 and 2, and removal of formed methanol during the reaction is a prerequisite for obtaining high yields of 2 from 1. The reactivity of 1 and 2 is explained by a mechanistic model that involves a transfer of the enol proton to the exocyclic carbonyl substituent with concomitant formation of ketene 3. This proton transfer is especially facilitated for 2 because the intramolecular hydrogen bond to the carbonyl oxygen is weakened due to steric interactions. Both 1 and 2 undergo solvolosis reactions that obey first-order reaction kinetics, further supporting the theory that these two molecules are able to decompose unimolecularly into ketene 3. The solvent-dependent spectroscopic features of 2 indicate that the molecule mainly resides in two conformations. One conformation is favored in nonpolar solvents and is likely the result of intramolecular hydrogen bonding. The other conformation is favored in polar solvents and probably exhibits less intramolecular hydrogen bonding.
IgE-Antibody-Dependent Immunotherapy of Solid Tumors: Cytotoxic and Phagocytic Mechanisms of Eradication of Ovarian Cancer Cells (2007)

Abs have a paramount place in the treatment of certain, mainly lymphoid, malignancies, although tumors of nonhemopoietic origin have proved more refractory ones. We have previously shown that the efficacy of immunotherapy of solid tumors, in particular ovarian carcinoma, may be improved by the use of IgE Abs in place of the conventional IgG. An IgE Ab (MOv18 IgE) against an ovarian-tumor-specific Ag (folate binding protein), in combination with human PBMC, introduced into ovarian cancer xenograft-bearing mice, greatly exceeded the analogous IgG1 in promoting survival. In this study, we analyzed the mechanisms by which MOv18 IgE may exert its antitumor activities. Monocytes were essential IgE receptor-expressing effector cells that mediated the enhanced survival of tumor-bearing mice by MOv18 IgE and human PBMC. Monocytes mediated MOv18 IgE-dependent ovarian tumor cell killing in vitro by two distinct pathways, cytotoxicity and phagocytosis, acting respectively through the IgE receptors FcepsilonRI and CD23. We also show that human eosinophils were potent effector cells in MOv18 IgE Ab-dependent ovarian tumor cell cytotoxicity in vitro. These results demonstrate that IgE Abs can engage cell surface IgE receptors and activate effector cells against ovarian tumor cells. Our findings offer a framework for an improved immunotherapeutic strategy for combating solid tumors.
Autologous bone marrow transplantation for patients with acute myeloid leukaemia and acute lymphoblastic leukaemia--a comparison. (1987)

Forty-two patients with acute leukaemia were treated with autologous bone marrow transplantation (ABMT) using a combination chemotherapy protocol for bone marrow ablation. The response to high-dose chemotherapy and ABMT and its associated morbidity and mortality have been compared in 24 patients with acute myeloid leukaemia (AML) and 18 patients with acute lymphoblastic leukaemia (ALL). In 16 patients with AML treated with ABMT during first complete remission (CR), ten patients (62.5%) remain in unmaintained remission; median follow up is 32 months. In eight patients with ALL treated in first CR, only one remains in remission 32 months post-ABMT, with three patients dying non-leukaemic deaths. Fourteen of 18 patients (AML and ALL) treated after first remission have died of recurrent leukaemia, two died non-leukaemic deaths and two remain well 31 and 55 months post-ABMT; both have ALL. The length of hospital stay and the amount of blood product support were similar in both groups. Haematological recovery post-ABMT was delayed in patients with AML compared to patients with ALL but this difference was not significant. Rapidly progressive lung infection was thought to be the cause of four early deaths (4/18) in patients with ALL but none in patients with AML. Severe gram-negative infections were significantly more common in patients with AML.
CD28 engagement by B7/BB-1 induces transient down-regulation of CD28 synthesis and prolonged unresponsiveness to CD28 signaling (1993)

Costimulatory molecules on the APC regulate T cell growth by providing signals that regulate responses to TCR occupancy. One such molecule is B7/BB-1, which triggers a T cell activation pathway by binding the CD28 and/or CTLA-4 cell-surface molecules. Expression and signaling activity of CD28 have been shown to increase after T cell activation by various polyclonal activators. Here we show that CD28 expression and signaling activity in activated T cells decrease after ligand binding to CD28. Stimulation of CD28 on PHA- or PMA-activated T cells by cross-linked mAb 9.3 or by co-culture with B7+ Chinese hamster ovary (CHO) cells caused a marked reduction of CD28 mRNA levels within 4 h. The decrease in CD28 mRNA was transient, and by 24 h of CD28 stimulation, CD28 mRNA was found at approximately initial levels. In contrast, CTLA-4 mRNA levels were usually up-regulated by CD28 triggering. Cell-surface expression of CD28, but not CD2 or CD3, decreased by 12 to 24 h after addition of B7+ CHO cells, but returned to initial levels or higher by 48 h. The ability of CD28 cross-linking on PMA-activated CD4+ cells to trigger calcium mobilization was also reduced by treatment with B7+ CHO cells, and remained reduced even after cell-surface expression of CD28 returned to normal levels. Thus, engagement of the CD28 receptor by its natural ligand B7/BB-1 leads to a transient down-regulation of CD28 synthesis and a prolonged unresponsiveness to CD28 signaling. This represents a novel mechanism for regulation of costimulatory signals delivered by interactions of CD28 with the B7/BB-1 counter receptor.
Multiple Sigma Subunits and the Partitioning of Bacterial Transcription Space (2003)

Promoter recognition in eubacteria is carried out by the initiation factor sigma, which binds RNA polymerase and initiates transcription. Cells have one housekeeping factor and a variable number of alternative sigma factors that possess different promoter-recognition properties. The cell can choose from its repertoire of sigmas to alter its transcriptional program in response to stress. Recent structural information illuminates the process of initiation and also shows that the two key sigma domains are structurally conserved, even among diverse family members. We use the sigma repertoire of Escherichia coli, Bacillus subtilis, Streptomyces coelicolor, and cyanobacteria to illustrate the different strategies utilized to organize transcriptional space using multiple sigma factors.
Efficacy of systemic morpholino exon‐skipping in duchenne dystrophy dogs (2009)

This is the first report of widespread rescue of dystrophin expression to therapeutic levels in the dog model of DMD. This study also provides a proof of concept for systemic multiexon-skipping therapy. Use of cocktails of morpholino, as shown here, allows broader application of this approach to a greater proportion of DMD patients (90%) and also offers the prospect of selecting deletions that optimize the functionality of the dystrophin protein.
Polyhydroxystilbenes from the heartwood of Schotia brachypetala (1974)

From the heartwood of Schotia brachypetala trans-3,3′,4,5,5′-pentahydroxystilbene has been isolated as the major component and trans-3,3′,4,5′-tetrahydroxystilbene as the minor component. The methyl ethers of both stilbenes have been synthesized via a Wittig reaction. Traces of the cis-pentahydroxystilbene also occur in the wood.
The Measurement and Determinants of Brand Equity: A Financial Approach (1993)

This paper presents a technique for estimating a firm's brand equity that is based on the financial market value of the firm. Brand equity is defined as the incremental cash flows which accrue to branded products over unbranded products. The estimation technique extracts the value of brand equity from the value of the firm's other assets. This technique is useful for two purposes. First, the macro approach assigns an objective value to a company's brands and relates this value to the determinants of brand equity. Second, the micro approach isolates changes in brand equity at the individual brand level by measuring the response of brand equity to major marketing decisions. Empirically, we estimate brand equity using the macro approach for a sample of industries and companies. Then we use the micro approach to trace the brand equity of Coca-Cola and Pepsi over three major events in the soft drink industry from 1982 to 1986.
Reactions of nitrogen mustards with DNA. (1986)

This paper summarizes the mechanism of action and the covalent modifications of nucleic acids, nucleotides and nucleosides by nitrogen mustards. Nitrogen mustards react preferentially with guanine N7 in DNA in vitro. A few minor adducts have been characterized. Cross-links of nitrogen mustard and metabolites of cyclophosphamide that have been identified are diguanyl derivatives linked at N7. It is essential that studies of alkylation products in vivo be carried out, since characterization of alkylation products of cytostatic drugs should provide further insight into the mechanisms of cytotoxicity and, consequently, facilitate the development of more efficient anticancer agents. Furthermore, the monitoring of DNA adducts of therapeutic significance in patients may provide new avenues for the individualization of cancer therapy.