gebhart/patrepeval huggingface dataset:
Structural Basis of Inhibitor Specificity of the Human Protooncogene Proviral Insertion Site in Moloney Murine Leukemia Virus (PIM-1) Kinase (2005)

The kinase PIM-1 plays a pivotal role in cytokine signaling and is implicated in the development of a number of tumors. The three-dimensional structure of PIM-1 is characterized by an unique hinge region which lacks a second hydrogen bond donor and makes it particularly important to determine how inhibitors bind to this kinase. We determined the structures of PIM-1 in complex with bisindolylmaleimide (BIM-1) and established the structure-activity relationship (SAR) for this inhibitor class. In addition, we screened a kinase targeted library and identified a number of high affinity inhibitors of PIM-1 such as imidazo[1,2-b]pyridazines, pyrazolo[1,5-a]pyrimidines, and members of the flavonoid family. In this paper we present an initial SAR of the identified scaffolds determined on the basis of a thermostability shift assay, calorimetric binding data, and biochemical assays which may find applications for the treatment of PIM-1 dependent cancer types.
Effect of dipalmitoylphosphatidylcholine vesicle curvature on the reaction with human apolipoprotein A-I. (1982)

Large unilamellar vesicles of dipalmitoylphosphatidylcholine (DPPC) were prepared by sonication and were fractionated by gel filtration on Sepharose Cl-2B in the size range from 180- to 380-A Stokes radii. Negatively stained electron micrographs of these preparations indicated the presence of unilamellar, spheroidal structures of the expected size. Fluorescence polarization of diphenylhexatriene, dissolved in the vesicles, revealed progressively broader phase transitions, shifted to lower temperatures for vesicles of decreasing sizes. The fractionated unilamellar vesicles and multilamellar vesicles of DPPC were reacted with human apolipoprotein A-I at 41 degrees C for periods from 1 to 120 h. The reaction mixtures were then passed through a Bio-Gel A-5m column to separate unreacted lipid vesicles and protein from micellar complexes of DPPC with apolipoprotein A-I. Smaller vesicles were much more reactive than larger vesicles or multilamellar vesicles with the apolipoprotein. This difference in reactivity was explained by the increasing bilayer curvature of smaller vesicles which changes the packing of DPPC molecules in the bilayer and facilitates its penetration by the apolipoprotein.
Efficient induction of differentiation and growth inhibition in IDH1 mutant glioma cells by the DNMT Inhibitor Decitabine (2013)

Mutation in the IDH1 or IDH2 genes occurs frequently in gliomas and other human malignancies. In intermediate grade gliomas, IDH1 mutation is found in over 70% of tumors. These mutations impart the mutant IDH enzyme with a neomorphic activity - the ability to synthesize 2-hydroxyglutarate (2-HG). This ability leads to a reprogramming of chromatin state, a block in differentiation, and the establishment of the glioma hypermethylator phenotype (G-CIMP). It has been hypothesized but not proven that the extensive DNA methylation that occurs in G-CIMP tumors helps maintain and "lock in" glioma cancer cells in a dedifferentiated state. Here, we tested this hypothesis by treating patient derived IDH1 mutant glioma initiating cells (GIC) with non-cytotoxic, epigenetically targeted doses of the DNMT inhibitor decitabine. Global methylome analysis of treated IDH1 mutant GICs showed that DAC treatment resulted in reversal of DNA methylation marks induced by IDH and the re-expression of genes associated with differentiation. Accordingly, treatment of IDH1 mutant glioma cells resulted in a dramatic loss of stem-like properties and efficient adoption of markers of differentiation, effects not seen in decitabine treated IDH wild-type GICs. Induction of differentiation was much more efficient than that seen following treatment with a specific inhibitor of mutant IDH enzyme (Agios). Decitabine also decreased replicative potential and tumor growth in vivo. Reexpression of polycomb regulated genes accompanied these DAC-induced phenotypes. In total, our data indicates that targeting the pathologic DNA methylation in IDH mutant cells can reverse mutant IDH induced hypermethylation and block in differentiation and promote tumor control. These findings have substantial impact for exploring new treatment strategies for patients with IDH mutant gliomas.
Potentiation of cytotoxic cancer therapies by TNP‐470 alone and with other anti‐angiogenic agents (1994)

The ability of TNP-470, a synthetic analog of fumagillin which has been described as an anti-angiogenic agent, to potentiate cytotoxic cancer therapies was investigated in vivo in the murine FSaIIC fibrosarcoma and the Lewis lung carcinoma. TNP-470 was more toxic toward FSaIIC tumor cells from tumors treated in vivo than toward bone-marrow CFU-GM from the same animals. TNP-470 had a dose-modifying effect on the toxicity of cyclophosphamide toward FSaIIC tumor cells which amounted to an 8-fold increase in tumor-cell killing at a cyclophosphamide dose of 500 mg/kg. Treatment with TNP-470 and minocycline increased the permeability of the FSaII fibrosarcoma in vivo to the fluorescent dye Hoechst 33342 and increased the killing of both the bright and the dim tumor cells by cyclophosphamide. TNP-470, especially in combination with minocycline, formed a highly effective modulator combination for treatment of the Lewis lung carcinoma with cytotoxic cancer therapies against primary and metastatic disease. The combination of TNP-470/minocycline and cyclophosphamide led to 40 to 50% long-term survivors in Lewis-lung-carcinoma-bearing animals. Our results indicate that the use of anti-angiogenic modulators in cancer therapy is a very promising area for further study.
Desmin Aggregate Formation by R120G αB-Crystallin Is Caused by Altered Filament Interactions and Is Dependent upon Network Status in Cells (2004)

The R120G mutation in alphaB-crystallin causes desmin-related myopathy. There have been a number of mechanisms proposed to explain the disease process, from altered protein processing to loss of chaperone function. Here, we show that the mutation alters the in vitro binding characteristics of alphaB-crystallin for desmin filaments. The apparent dissociation constant of R120G alphaB-crystallin was decreased while the binding capacity was increased significantly and as a result, desmin filaments aggregated. These data suggest that the characteristic desmin aggregates seen as part of the disease histopathology can be caused by a direct, but altered interaction of R120G alphaB-crystallin with desmin filaments. Transfection studies show that desmin networks in different cell backgrounds are not equally affected. Desmin networks are most vulnerable when they are being made de novo and not when they are already established. Our data also clearly demonstrate the beneficial role of wild-type alphaB-crystallin in the formation of desmin filament networks. Collectively, our data suggest that R120G alphaB-crystallin directly promotes desmin filament aggregation, although this gain of a function can be repressed by some cell situations. Such circumstances in muscle could explain the late onset characteristic of the myopathies caused by mutations in alphaB-crystallin.
Influences of Green Supply Chain Management Practices on Organizational Sustainable Performance (2014)

This research discusses Taiwan’s electrical and electronic industries by considering the European Union Restriction of Hazardous Substances Directive (RoHS), Waste Electrical and Electronic Equipment (WEEE), Eco-design of End Use Equipment (EuE), etc., which are regarded as the green standards for green supply chain managerial practices for the sustainable organizations. The research adopts literature survey, in-depth interviews, and questionnaire surveys. The research uses the software “Statistics Package for Social Science” (SPSS) to analyze the materials and to verify the hypotheses, and Structural Equation Modeling (SEM) of the pathway analysis model to confirm the constructs. The empirical study’s results demonstrated that European Union RoHS, WEEE, EuE, and other related environmental protection standards. Their strategies for green design, green innovation, green manufacturing, green purchasing, green services practices are Green Supply Chain Management (GSCM) practiced by Taiwan’s electrical and electronic manufacturers and will positively affect the economic, environmental, and social performances of a certain organization
ROMP-Generated Oligomeric Sulfonyl Chlorides as Versatile Soluble Scavenging Agents (2002)

[reaction: see text] A new method for homogeneous nucleophilic scavenging employing oligomeric sulfonyl chloride (OSC) reagents is described. The method utilizes OSC to rapidly scavenge a variety of amines that are present in excess. The OSC reagents are generated from ROM polymerization of 2-chlorosulfonyl-5-norbornene utilizing the second generation Grubbs catalyst to produce oligomers of varying size as stable, free-flowing powders. Following the scavenging event, these oligomers are precipitated with ethyl acetate leaving products in excellent yield and purity.
Simultaneous loading of 200 sample lanes for DNA sequencing on vertical and horizontal, standard and ultrathin gels (1997)

We have developed a simple and efficient technique for automated parallel loading of >/=200 lanes on a 30 cm-wide gel in automated DNA sequencing, using porous filter materials and an associated manual or robotic system. The samples are loaded onto the teeth of a comb made of the porous material. The comb, with samples, is inserted directly above the straight edge of the polymerized gel. The samples are driven from the comb into the gel by the applied electrical field. A particularly advantageous aspect of this method is the elimination of the thin gel walls separating the sample wells in the standard gel loading technique. The time for sample loading is significantly reduced to a few minutes. The loading technique is applicable to horizontal or vertical systems, with standard or ultrathin gels.
Magnetic-assisted triboelectric nanogenerators as self-powered visualized omnidirectional tilt sensing system (2014)

The triboelectric nanogenerator (TENG) is a promising device in energy harvesting and self-powered sensing. In this work, we demonstrate a magnetic-assisted TENG, utilizing the magnetic force for electric generation. Maximum power density of 541.1 mW/m(2) is obtained at 16.67 MΩ for the triboelectric part, while the electromagnetic part can provide power density of 649.4 mW/m(2) at 16 Ω. Through theoretical calculation and experimental measurement, linear relationship between the tilt angle and output voltage at large angles is observed. On this basis, a self-powered omnidirectional tilt sensor is realized by two magnetic-assisted TENGs, which can measure the magnitude and direction of the tilt angle at the same time. For visualized sensing of the tilt angle, a sensing system is established, which is portable, intuitive, and self-powered. This visualized system greatly simplifies the measure process, and promotes the development of self-powered systems.
Role of hormone-sensitive lipase in β-adrenergic remodeling of white adipose tissue (2007)

Free fatty acids (FFA) are important extracellular and intracellular signaling molecules and are thought to be involved in beta-adrenergic-induced remodeling of adipose tissue, which involves a transient inflammatory response followed by mitochondrial biogenesis and increased oxidative capacity. This work examined the role of hormone-sensitive lipase (HSL), a key enzyme of acylglycerol metabolism, in white adipose tissue (WAT) remodeling using genetic inactivation or pharmacological inhibition. Acute treatment with the beta(3)-adrenergic agonist CL-316,243 (CL) induced expression of inflammatory markers and caused extravasation of myeloid cells in WAT of wild-type (WT) mice. HSL-knockout (KO) mice had elevated inflammatory gene expression in the absence of stimulation, and acute injection of CL did not further recruit myeloid cells, nor did it further elevate inflammatory gene expression. Acute pharmacological inhibition of HSL with BAY 59-9435 (BAY) had no effect on inflammatory gene expression in WAT or in cultured 3T3-L1 adipocytes. However, BAY prevented induction of inflammatory cytokines by beta-adrenergic stimulation in WAT in vivo and in cultured 3T3-L1 adipocytes. Chronic CL treatment stimulated mitochondrial biogenesis, expanded oxidative capacity, and increased lipid droplet fragmentation in WT mice, and these effects were significantly impaired in HSL-KO mice. In contrast to HSL-KO mice, mice with defective signaling of Toll-like receptor 4, a putative FFA receptor, showed normal beta-adrenergic-induced remodeling of adipose tissue. Overall, results reveal the importance of HSL activity in WAT metabolic plasticity and inflammation.
A tyrosine‐phosphorylated 12‐amino‐acid sequence of enteropathogenic Escherichia coli Tir binds the host adaptor protein Nck and is required for Nck localization to actin pedestals (2002)

Enteropathogenic Escherichia coli (EPEC) and enterohaemorrhagic E. coli (EHEC) each promote the reorganization of actin into filamentous pedestal structures beneath attached bacteria during colonization of the intestinal epithelium. Central to this process is the translocation of the protein Tir (translocated intimin receptor) into the plasma membrane of host cells, where it interacts with the bacterial outer membrane protein intimin and triggers cellular signalling events that lead to actin rearrangement. Actin signalling by EPEC Tir requires a tyrosine residue, Y474, which is phosphorylated in the host cell. In contrast, EHEC Tir lacks this residue and generates pedestals independently of tyrosine phosphorylation. Consistent with this difference, recent work indicates that EHEC Tir cannot functionally replace EPEC Tir. To identify the role that tyrosine phosphorylation of EPEC Tir plays in actin signalling, we generated chimeric EHEC/EPEC Tir proteins and identified a 12-residue sequence of EPEC Tir containing Y474 that confers actin-signalling capabilities to EHEC Tir when the chimera is expressed in EPEC. Nck, a mammalian adaptor protein that has been implicated in the initiation of actin signalling, binds to this sequence in a Y474 phosphorylation-dependent manner and is recruited to the pedestals of EPEC, but not of EHEC.
Human immunodeficiency virus type 1 and 2 envelope glycoproteins oligomerize through conserved sequences (1997)

Hetero-oligomerization between human immunodeficiency virus type 2 (HIV-2) envelope glycoprotein (Env) truncation mutants and epitope-tagged gp160 is dependent on the presence of gp41 transmembrane protein (TM) amino acids 552 to 589, a putative amphipathic alpha-helical sequence. HIV-2 Env truncation mutants containing this sequence were also able to form cross-type hetero-oligomers with HIV-1 Env. HIV-2/HIV-1 hetero-oligomerization was, however, more sensitive to disruption by mutagenesis or increased temperature. The conservation of the Env oligomerization function of the HIV-1 and HIV-2 alpha-helical sequences suggests that retroviral TM alpha-helical motifs may have a universal role in oligomerization.
Recording and controlling the 4D light field in a microscope using microlens arrays (2009)

By inserting a microlens array at the intermediate image plane of an optical microscope, one can record four-dimensional light fields of biological specimens in a single snapshot. Unlike a conventional photograph, light fields permit manipulation of viewpoint and focus after the snapshot has been taken, subject to the resolution of the camera and the diffraction limit of the optical system. By inserting a second microlens array and video projector into the microscope's illumination path, one can control the incident light field falling on the specimen in a similar way. In this paper, we describe a prototype system we have built that implements these ideas, and we demonstrate two applications for it: simulating exotic microscope illumination modalities and correcting for optical aberrations digitally.
[Differentially expressed genes between upward and downward progressing types of nasopharyngeal carcinoma]. (2008)

The gene expression patterns are significantly different between upward and downward progressing types of NPC. The expression of DIO2 gene is higher in the downward progressing type than in upward progressing type, which may be closely related to the metastasis potential of NPC.
Large and persistent electrical currents enter the transected lamprey spinal cord. (1980)

The electrical currents at the surface of the proximal portion of an isolated and transected lamprey spinal cord were measured with an extracellular vibrating probe. Soon after transection, currents of about 0.5 mA/cm2 enter the cut surface of the spinal cord. These currents fall to about a quarter of their initial value within an hour; within the next 2 days they gradually decline from about 100 microA/cm2 to about 4 microA/cm2; they then remain constant up to 6 days posttransection, when the measurements were ended. The pattern of current entry included substantial peaks opposite (and presumably into) the cut ends of giant axons. Response to changes in the ionic composition of the medium indicates that about half of the injury current consists of Na+, and that much of the rest may consist of Ca2+. The measured influx of ions, which adds up to several coulombs per cm2 in a few days, should radically alter the ionic composition of the terminal few millimeters of neural tissue. Thus it may be important in the degenerative and regenerative responses of neurons to axotomy.
Adaptation and communicative design. (2006)

Two theoretical frameworks that examine the nature of adaptability and mutual influence in interaction, interpersonal deception theory and interaction adaptation theory, were used to derive hypotheses concerning patterns of interaction that occur across time in truthful and deceptive conversations. Two studies were conducted in which senders were either truthful or deceptive in their interactions with a partner who increased or decreased involvement during the latter half of the conversation. Results revealed that deceivers felt more anxious and were more concerned about self-presentation than truthtellers prior to the interaction and displayed less initial involvement than truthtellers. Patterns of interaction were also moderated by deception. Deceivers increased involvement over time but also reciprocated increases or decreases in receiver involvement. However, deceivers were less responsive than truthtellers to changes in receiver behavior. Finally, partner involvement served as feedback to senders regarding their own performance.
Does ultrasound examination when the cervix is unfavorable improve the prediction of failed labor induction? (2004)

Compared with the Bishop score, cervical length by ultrasound is not a better predictor for the outcome of labor induction in an unfavorable cervix. Nevertheless, the Bishop score appears to be of poor predictive value for failed induction of labor.
Structural features in the HIV-1 repeat region facilitate strand transfer during reverse transcription (2001)

Two obligatory DNA strand transfers take place during reverse transcription of a retroviral RNA genome. The first strand transfer is facilitated by terminal repeat (R) elements in the viral genome. This strand-transfer reaction depends on base pairing between the cDNA of the 5'R and the 3'R. There is accumulating evidence that retroviral R regions contain features other than sequence complementarity that stimulate this critical nucleic acid hybridization step. The R region of the human immunodeficiency virus type 1 (HIV-1) is relatively extended (97 nt) and encodes two well-conserved stem-loop structures, the TAR and poly(A) hairpins. The role of these motifs was studied in an in vitro strand-transfer assay with two separate templates, the 5'R donor and the 3'R acceptor, and mutants thereof. The results indicate that the upper part of the TAR hairpin structure in the 5'R donor is critical for efficient strand transfer. This seems to pose a paradox, as the 5'R template is degraded by RNase H before strand transfer occurs. We propose that it is not the RNA hairpin motif in the 5'R donor, but rather the antisense motif in the ssDNA copy, which can also fold a hairpin structure, that is critical for strand transfer. Mutation of the loop sequence in the TAR hairpin of the donor RNA, which is copied in the loop of the cDNA hairpin, reduces the transfer efficiency more than fivefold. It is proposed that the natural strand-transfer reaction is enhanced by interaction of the anti-TAR ssDNA hairpin with the TAR hairpin in the 3'R acceptor. Base pairing can occur between the complementary loops ("loop-loop kissing"), and strand transfer is completed by the subsequent formation of an extended RNA-cDNA duplex.
Unlimited‐volume stacking of ions in capillary electrophoresis. Part 1: Stationary isotachophoretic stacking of anions (2008)

An online technique for stacking based on the generation of a stationary isotachophoretic (sITP) boundary is presented. By balancing the anodic migration of an ITP boundary with a cathodic EOF, a stationary boundary is formed that can be used to indefinitely concentrate analytes according to ITP principles during electrokinetic injection. The ITP boundary is created by using an electrolyte containing a leading ion (chloride) and a suitable terminating ion added to the sample (2-morpholinoethanesulphonic acid, MES). Destacking and separation are achieved simply by replacement of the sample vial with electrolyte. The formation and stabilisation of the sITP boundary were evaluated through computer simulation which revealed that the pH had little impact upon the formation of the sITP boundary, but did govern the position at which it becomes stationary. Simulations also demonstrated that similar results were obtained when the capillary was initially filled with sample/terminator or leader/electrolyte, which was also supported by experimental results. Using 100 mM Cl(-), 200 mM Tris, pH 8.05 as the leader/electrolyte and adding 100 mM MES, 200 mM Tris, pH 8.05 to the sample, the sITP boundary was established after 5 min at -20 kV and was stable for at least 60 min. This provided detection limits for NO(2) (-), NO(3) (-) and SCN(-) of 0.05-0.66 ppb, which are 10,000 times lower than hydrodynamic injection and 10-50 times lower than other stacking approaches used for these inorganic ions.
Evidence for octupole correlations in Xe-117 (1996)

High spin states in neutron-deficient Xe-117 have been studied by using High spin states in neutron-deficient Xe-117 have been studied by using
IFN-α Induces Early Lethal Lupus in Preautoimmune (New Zealand Black × New Zealand White)F1 but Not in BALB/c Mice (2005)

Recent studies indicate that IFN-alpha is involved in pathogenesis of systemic lupus erythematosus. However, direct proof that IFN-alpha is not only necessary, but also sufficient to induce lupus pathogenicity is lacking. In this study, we show that in vivo adenovector-mediated delivery of murine IFN-alpha results in preautoimmune (New Zealand Black (NZB) x New Zealand White (NZW))F(1), but not in normal, mice, in a rapid and severe disease with all characteristics of systemic lupus erythematosus. Anti-dsDNA Abs appeared as soon as day 10 after initiation of IFN-alpha treatment. Proteinuria and death caused by glomerulonephritis occurred in all treated mice within, respectively, approximately 9 and approximately 18 wk, at a time when all untreated (NZB x NZW)F(1) did not show any sign of disease. IFN-alpha in vivo induced an overexpression of B lymphocyte stimulator in circulation at similar levels in both the preautoimmune and the normal mouse strains. All effects elicited by IFN-alpha were dose dependent. (NZB x NZW)F(1) infused with purified murine IFN-alpha also showed acceleration of lupus. Thus, prolonged expression of IFN-alpha in vivo induces early lethal lupus in susceptible animals.