gebhart/patrepeval huggingface dataset:
NF-κB as a Therapeutic Target in Multiple Myeloma (2002)

We have shown that thalidomide (Thal) and its immunomodulatory derivatives (IMiDs), proteasome inhibitor PS-341, and As(2)O(3) act directly on multiple myeloma (MM) cells and in the bone marrow (BM) milieu to overcome drug resistance. Although Thal/IMiDs, PS-341, and As(2)O(3) inhibit nuclear factor (NF)-kappaB activation, they also have multiple and varied other actions. In this study, we therefore specifically address the role of NF-kappaB blockade in mediating anti-MM activity. To characterize the effect of specific NF-kappaB blockade on MM cell growth and survival in vitro, we used an IkappaB kinase (IKK) inhibitor (PS-1145). Our studies demonstrate that PS-1145 and PS-341 block TNFalpha-induced NF-kappaB activation in a dose- and time-dependent fashion in MM cells through inhibition of IkappaBalpha phosphorylation and degradation of IkappaBalpha, respectively. Dexamethasone (Dex), which up-regulates IkappaBalpha protein, enhances blockade of NF-kappaB activation by PS-1145. Moreover, PS-1145 blocks the protective effect of IL-6 against Dex-induced apotosis. TNFalpha-induced intracellular adhesion molecule (ICAM)-1 expression on both RPMI8226 and MM.1S cells is also inhibited by PS-1145. Moreover, PS-1145 inhibits both IL-6 secretion from BMSCs triggered by MM cell adhesion and proliferation of MM cells adherent to BMSCs. However, in contrast to PS-341, PS-1145 only partially (20-50%) inhibits MM cell proliferation, suggesting that NF-kappaB blockade cannot account for all of the anti-MM activity of PS-341. Importantly, however, TNFalpha induces MM cell toxicity in the presence of PS-1145. These studies demonstrate that specific targeting of NF-kappaB can overcome the growth and survival advantage conferred both by tumor cell binding to BMSCs and cytokine secretion in the BM milieu. Furthermore, they provide the framework for clinical evaluation of novel MM therapies based upon targeting NF-kappaB.
Hepatocyte growth factor specifically binds to sulfoglycolipids (1994)

Hepatocyte growth factor (HGF) is a heparin-binding pleiotropic factor that acts on a variety of epithelial cells. The interaction of human HGF with glycolipids was studied by overlaying them with 125I-HGF on thin layer chromatograms and by a solid-phase assay using lipids adsorbed on microtiter plates. Among various glycolipids tested, HGF was found to bind to sulfoglycolipids, including galactosylceramide sulfate (SM4), lactosylceramide sulfate (SM3), and gangliotriaosylceramide bis-sulfate. In contrast, HGF failed to bind to gangliosides or neutral glycolipids. HGF binding to SM4 was strongly inhibited by dextran sulfate, heparin, and fucoidan, whereas neither keratan sulfate nor hyaluronic acid had any inhibitory activity. When glycolipids from a renal cancer cell line, SMKT-R3, which overexpresses sulfoglycolipids, were developed on a thin layer chromatogram, SM4 and SM3 were the only glycolipids that bound HGF. We further examined the effect of the incorporation of glycolipids into SMKT-R3 cells on HGF binding to the cells. The incorporation of SM4 into the cells enhanced HGF binding to SMKT-R3 cells, while that of galactosylceramide, a precursor of SM4, had no effect. These observations indicated that SM4 exogenously incorporated into the cell membranes could react with HGF and suggested that endogenous sulfoglycolipids on SMKT-R3 cells might function as reservoirs for HGF.
Structural Basis for Selective Recognition of Oligosaccharides by DC-SIGN and DC-SIGNR (2001)

Dendritic cell specific intracellular adhesion molecule-3 (ICAM-3) grabbing nonintegrin (DC-SIGN), a C-type lectin present on the surface of dendritic cells, mediates the initial interaction of dendritic cells with T cells by binding to ICAM-3. DC-SIGN and DC-SIGNR, a related receptor found on the endothelium of liver sinusoids, placental capillaries, and lymph nodes, bind to oligosaccharides that are present on the envelope of human immunodeficiency virus (HIV), an interaction that strongly promotes viral infection of T cells. Crystal structures of carbohydrate-recognition domains of DC-SIGN and of DC-SIGNR bound to oligosaccharide, in combination with binding studies, reveal that these receptors selectively recognize endogenous high-mannose oligosaccharides and may represent a new avenue for developing HIV prophylactics.
Effects of trans MUFA from dairy and industrial sources on muscle mitochondrial function and insulin sensitivity (2008)

Epidemiological studies suggest that chronic consumption of trans MUFA may alter muscle insulin sensitivity. The major sources of dietary trans MUFA (dairy fat vs. industrially hydrogenated oils) have different isomeric profiles and thus probably different metabolic consequences. These effects may involve alterations in muscle mitochondrial oxidative capacity, which may in turn promote insulin resistance if fatty acid oxidation is reduced. We report that in Wistar rats, an 8 week diet enriched (4% of energy intake) in either dairy, industrial, or control MUFA did not alter insulin and glucose responses to an intraperitoneal glucose tolerance test (1g/kg). In C2C12 myotubes, vaccenic and elaidic acids did not modify insulin sensitivity compared with oleic acid. Furthermore, the ex vivo total, mitochondrial and peroxisomal oxidation rates of [1-(14)C]oleic, vaccenic, and elaidic acids were similar in soleus and tibialis anterior rat muscle. Finally, an 8 week diet enriched in either dairy or industrial trans MUFA did not alter mitochondrial oxidative capacity in these two muscles compared with control MUFA but did induce a specific reduction in soleus mitochondrial ATP and superoxide anion production (P<0.01 vs. control). In conclusion, dietary trans MUFA of dairy or industrial origin have similar effects and do not impair muscle mitochondrial capacity and insulin sensitivity.
Reduced Prefrontal Glutamate/Glutamine and γ-Aminobutyric Acid Levels in Major Depression Determined Using Proton Magnetic Resonance Spectroscopy (2007)

For the first time, GABA and Glx concentrations were compared between unmedicated depressed adults and controls in prefrontal ROIs. The abnormal reductions in Glx and GABA concentrations found in the MDD sample were compatible with findings from postmortem histopathologic studies, indicating that glial cell density is reduced in the same areas in MDD.
Adaptive postfiltering for quality enhancement of coded speech (1995)

An adaptive postfiltering algorithm for enhancing the perceptual quality of coded speech is presented. The postfilter consists of a long-term postfilter section in cascade with a short-term postfilter section and includes spectral tilt compensation and automatic gain control. The long-term section emphasizes pitch harmonics and attenuates the spectral valleys between pitch harmonics. The short-term section, on the other hand, emphasizes speech formants and attenuates the spectral valleys between formants. Both filter sections have poles and zeros. Unlike earlier postfilters that often introduced a substantial amount of muffling to the output speech, our postfilter significantly reduces this effect by minimizing the spectral tilt in its frequency response. As a result, this postfilter achieves noticeable noise reduction while introducing only minimal distortion in speech. The complexity of the postfilter is quite low. Variations of this postfilter are now being used in several national and international speech coding standards. This paper presents for the first time a complete description of our original postfiltering algorithm and the underlying ideas that motivated its development.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Liposomes as sterile preparations and limitations of sterilisation techniques in liposomal manufacturing (2013)

Liposomes have been widely researched as a delivery system and there have been many manufacturing techniques used in the production of liposomal preparations, the most common being extrusion method which will be introduced in this paper. However because of the unique properties of liposomes and their susceptibility to chemical and physical degradation, sterilisation remains an unresolved issue in the manufacturing of liposome-based formulations. It is especially pertinent in the pharmaceutical industry where liposomes are commonly prepared for intravenous administration. Currently, filtration and aseptic manufacturing are recommended for the preparation of sterile liposomal products. Newer aseptic manufacturing techniques such as dense gas techniques have been devised to eliminate the need for terminal sterilisation. This paper will highlight the limitations of the conventional techniques that are specific to the liposome preparation under the respective sterilisation conditions specified by the 2011 British Pharmacopoeia to achieve 10−6 Sterility Assurance Level, as well as modifications incorporated in the newer sterilisation technologies to overcome these limitations. This paper will introduce these techniques in brief, including their advantages and limitations.
Mutants of the Bacteriophage MS2 Coat Protein That Alter Its Cooperative Binding to RNA (1995)

An RNA binding assay measuring cooperative protein binding has been used to evaluate the effects of mutations in the MS2 phage coat protein expected to disrupt capsid assembly. By using the crystal structure of the virus as a guide, six different mutations in the FG loop structure were selected in which hydrophobic residues were replaced with charged residues. Most of these proteins form capsids in Escherichia coli, but not in an in vitro assembly assay, suggesting that interdimer interactions are weaker than wild type. These mutant proteins reduce the free energy of cooperative protein binding to a double-hairpin RNA from its wild-type value of -1.9 kcal/mol. Several of the variants that have large effects on cooperativity have no effect on RNA affinity, suggesting that protein-RNA interactions can be affected independently of dimer-dimer interactions. The V75E;A81G protein, which shows no measurable cooperativity, binds operator RNA equally well as the wild-type protein under a variety of buffer conditions. Because this protein also exhibits similar specificity for variant RNA sequences, it will be useful for studying RNA binding properties independent of capsid assembly.
Furan-2-ylmethylene Thiazolidinediones as Novel, Potent, and Selective Inhibitors of Phosphoinositide 3-Kinase γ (2006)

Class I phosphoinositide 3-kinases (PI3Ks), in particular PI3Kgamma, have become attractive drug targets for inflammatory and autoimmune diseases. Here, we disclose a novel series of furan-2-ylmethylene thiazolidinediones as selective, ATP-competitive PI3Kgamma inhibitors. Structure-based design and X-ray crystallography of complexes formed by inhibitors bound to PI3Kgamma identified key pharmacophore features for potency and selectivity. An acidic NH group on the thiazolidinedione moiety and a hydroxy group on the furan-2-yl-phenyl part of the molecule play crucial roles in binding to PI3K and contribute to class IB PI3K selectivity. Compound 26 (AS-252424), a potent and selective small-molecule PI3Kgamma inhibitor emerging from these efforts, was further profiled in three different cellular PI3K assays and shown to be selective for class IB PI3K-mediated cellular effects. Oral administration of 26 in a mouse model of acute peritonitis led to a significant reduction of leukocyte recruitment.
Ninety-Day Survival Rate of Patients with Sepsis Relates to Programmed Cell Death 1 Genetic Polymorphism rs11568821 (2014)

Data provide first associative evidence for PD-1 rs11568821 as a prognostic indicator in patients with sepsis.
Components of Broussonetia kazinoki Sieb. I Structures of two new isoprenylated flavans and five new isoprenylated 1,3-diphenylpropane derivatives. (1986)

Two new isoprenylated flavans, kazinols E and H, and five new isoprenylated 1, 3-diphenyl-propane derivatives, kazinols C, D, F, G, and K, were isolated from the extract of the root bark of Broussonetia kazinoki SIEB. (Japanese name, Kimekozo, Moraceae). On the basis of chemical and spectral evidence, the structures of kazinols E and H were shown to be 3 and 6, respectively, and the structures of kazinols C, D, F, G, and K to be 1, 2, 4, 5, and 7, respectively.
Effects of tomato paste extracts on cell proliferation, cell-cycle arrest and apoptosis in LNCaP human prostate cancer cells (2005)

Since tomato consumption is associated with decreased risk of prostate cancer, cell proliferation, cell cycle progression and apoptosis by LNCaP human prostate cancer cells might elucidate action of tomatoes. To discover possible bioactive fractions of tomatoes, whole tomato paste and its water and hexane extract were used and biomarkers of carcinogenesis were measured. After 6, 24 and 48 hr of incubation, cells were harvested and determined cell growth. Tomato paste hexane extract inhibited cell proliferation by 33% compared to the control after 48 hr incubation. Whole tomato paste and its water extract showed only modest growth inhibition. Tomato paste hexane extract at 5 microM lycopene increased G2/M-phase of the cell cycle from 13 to 28% and decreased S-phase cells from 45 to 29%. Apoptosis was observed at the 5 microM hexane extract at the late stages during 24 and 48 hr treatment. Tomato, therefore, deserves study as a potential chemopreventive/chemotherapeutic agent.
Au55[P(C6H5)3]12CI6 — ein Goldcluster ungewöhnlicher Größe (1981)

Abstract Die Reduktion von C 6 H 5 ) 3 PAuCl mit B 2 H 6 in Benzol ergibt Au 9 , 2 [P(C 6 H 5 ) 3 ] 2 Cl, das mittels Molmassebestimmungen als Au 55 [P(C 6 H 5 ) 3 ] 12 Cl 6 charakterisiert wurde. Ein einfaches Modell, beruhend auf einer Anordnung dichtest gepackter Goldatome, führt zu einem Goldcluster, dessen Aufbau mit der ungewöhnlichen chemischen Zusammensetzung in guter Übereinstimmung ist. Das Mößbauer‐Spektrum der Verbindung zeigt vier Sorten von Goldatomen: einen metallischen Anteil (Au 13 ‐Kern), durch P(C 6 H 5 ) 3 ‐bzw. Cl‐Liganden Koordinierte Au‐Atome, sowie unkoordi‐niertes Oberflächengold. Mit Brom und lod läß sich der Komplex zu (C 6 H 5 ) 3 PAuCl, (C 6 H 5 ) 3 PAuBr( I ) und metallischem Gold abbauen. Die Thermolyse bei 50°C führt quantitativ zu [(C 6 H 5 ) 3 P] 2 AuCl und Gold.
Dengue Virus Evolution and Virulence Models (2007)

Dengue virus transmission has increased dramatically in the past 2 decades, making this virus one of the most important mosquito-borne human pathogens. The emergence of dengue hemorrhagic fever in most tropical countries has made its control a public health priority, but no vaccines or treatments exist. Little is understood about dengue virus pathogenesis, because no other animals develop symptoms of disease, and research, therefore, has been limited to studies involving patients. Although epidemiologic and evolutionary studies have pointed to host and viral factors in determining disease outcome, only recently developed models could prove the importance of viral genotypes in causing severe epidemics. The influence of host immune status and mosquito vectorial capacity are also being tested in mathematical models to determine virus population dynamics. Therefore, new technologies are allowing us to better understand how specific virus variants cause more disease than others, and these virus variants should be targeted for detection, control, and treatment.
Flight path planning of UAV based on heuristically search and genetic algorithms (2005)

Flight path planning of UAV is a complicated optimum problem. The research in this field is usually classified as two directions: optimal path planning without considering the computation cost and real-time suboptimal path planning. Aimed at the two problems, this paper presents two methods of path planning of UAV. One method is based on heuristically search. In this method, we search the threat net by using A-star algorithm. A shortest suboptimum path is obtained, which is composed of the lines on the Voronoi diagram, and then considering the UAV's turn constraint, the path can be smoothed by geometry method. The other method is based on genetic algorithm and potential fields technology. Because potential fields, however popular, have shortcomings, viz, trap situations due to local minima, the genetic algorithm is introduced. In this method, Firstly, construct the threats' Delaunay triangle net based on the principle of nearest neighborhood and a safe planning path goes across the lines of the triangles. Then designate each point (position of a threat) on the left of the path a index 0 and on the right 1 and only designate the points of line which is not passed the same symbol. Thus, based on the directions of passing the lines of Delaunay triangle, a kind of encoding is designed on the principle of "Left 0, Right 1". At last, a global planning path can obtained by the genetic algorithm and potential fields technology. At the same time, simulation results of the two path planning methods are given.
Regulated expression of a diphtheria toxin A-chain gene transfected into human cells: possible strategy for inducing cancer cell suicide. (1986)

As an alternative to directing plant or bacterial toxins to surface receptors, we are investigating the possibility of killing tumor cells by the expression of an exogenously introduced toxin gene (i.e., cell suicide). Tissue-specific gene regulatory elements might thus be exploited to achieve selective killing. To assess the feasibility of such an approach, we have transfected human cells (HeLa, B-lymphoblastoid, and 293 cells) with plasmids containing the diphtheria toxin A-chain (DT-A) coding sequence. The presence of the DT-A sequence lowered the level of transient expression of chloramphenicol acetyltransferase from a cotransfected plasmid, pSV2cat. This expression level in B-cells was further diminished by the inclusion of an immunoglobulin enhancer in the DT-A plasmid. In cotransfection experiments with a DT-A plasmid lacking an enhancer, chloramphenicol acetyltransferase expression was much more strongly inhibited in 293 cells (which express adenovirus E1A and E1B products) than in the other cell types; furthermore, the presence of the DT-A sequence eliminated recovery of G418-resistant 293 cell transformants after transfection with a plasmid containing the neo selectable marker. These results suggest that cell-specific regulatory mechanisms can be exploited to achieve selective cell killing by expression of an introduced toxin gene.
IL-15Rα expression on CD8+T cells is dispensable for T cell memory (2003)

The generation and maintenance of immunological memory requires the activation, expansion, and persistent proliferation of antigen-specific T cells. Recent work suggests that IL-15 may be important for this process. Surprisingly, we now find that expression of the high-affinity receptor for IL-15, IL-15R alpha, on T cells is dispensable for the generation or maintenance of memory CD8(+) T cells. By contrast, IL-15R alpha expression on cells other than T cells is absolutely critical for this function. These findings may be related to IL-15R alpha's ability to present IL-15 in trans to low-affinity IL-15R beta gamma(c) receptors on memory CD8(+) T cells. These unexpected results provide insights into how IL-15R alpha supports memory CD8(+) T cells.
A Prospective Study of the Value of Monitoring Heparin Treatment with the Activated Partial Thromboplastin Time (1972)

Two hundred and thirty-four patients treated with continuous intravenous infusions of heparin were studied prospectively to seek a relation between the activated partial thromboplastin time (APTT) and recurrent venous thromboembolism or bleeding during treatment. One hundred and sixty-two patients were treated for venous thromboembolism and the remaining 72 for other diseases. The heparin dose was adjusted to keep the APTT between 1 1/2 and 2 1/2 times control levels. The five patients with venous thromboembolism in whom recurrence developed had a significantly lower APTT than patients without recurrence even though they received similar amounts of heparin. No recurrence developed in any patient with a mean APTT within the therapeutic range. Bleeding occurred in 19 patients whose mean heparin dose and APTT were similar to those of patients without bleeding. Thus, recurrence of venous thromboembolism during heparin treatment appears to be rare if the APTT is prolonged to 1 1/2 times or more control values at all times.
In Vitro and In Vivo Photocytotoxicity of Boron Dipyrromethene Derivatives for Photodynamic Therapy (2010)

To understand the effects of substitution patterns on photosensitizing the ability of boron dipyrromethene (BODIPY), two structural variations that either investigate the effectiveness of various iodinated derivatives to maximize the "heavy atom effect" or focus on the effect of extended conjugation at the 4-pyrrolic position to red-shift their activation wavelengths were investigated. Compounds with conjugation at the 4-pyrrolic position were less photocytotoxic than the parent unconjugated compound, while those with an iodinated BODIPY core presented better photocytotoxicity than compounds with iodoaryl groups at the meso-positions. The potency of the derivatives generally correlated well with their singlet oxygen generation level. Further studies of compound 5 on HSC-2 cells showed almost exclusive localization to mitochondria, induction of G(2)/M-phase cell cycle block, and onset of apoptosis. Compound 5 also extensively occluded the vasculature of the chick chorioallantoic membrane. Iodinated BODIPY structures such as compound 5 may have potential as new photodynamic therapy agents for cancer.