gebhart/patrepeval huggingface dataset:
Inhibitors of sterol synthesis. Metabolism-based design and construction of a new analog of 3 beta-hydroxy-5 alpha-cholest-8(14)-en-15-one and its effects in cultured mammalian cells and in rats. (1995)

3 beta-Hydroxy-5 alpha-cholest-8(14)-en-15-one (I) is a potent regulator of cholesterol metabolism. In the present study, the 7 alpha-methyl-25,26,26,26,27,27,27-heptafluoro analog (X) of I has been synthesized with the goal of blocking not only the side chain oxidation of I but also its conversion to cholesterol. X was prepared in seven steps from the known 7 alpha-methyl analog (IX) of I. Treatment of the acetate of IX with a mixture of trifluoroacetic anhydride, hydrogen peroxide, and sulfuric acid gave 3 beta-acetoxy-7 alpha-methyl-24-hydroxy-5 alpha-chol-8(14)-en-15-one (XII) in remarkably high (68%) yield. Dehydration of XII via the orthonitrophenylselenide to the 23-ene, followed by addition of (CF3)2CFI gave (23R)-3 beta-acetoxy-7 alpha-methyl-23-iodo-25,26,26,26,27,27,27-heptafluoro-5 alpha-cholest-8(14)-en-15-one (XV). Reductive deiodination of XV with tributyltin hydride, followed by hydrolysis of the acetate gave 3 beta-hydroxy-7 alpha-methyl-25,26,26,26,27,27,27-heptafluoro-5 alpha-cholest-8(14)-en-15-one (X). The F7-7 alpha-methyl-15-ketosterol X lowered the levels of 3-hydroxy-3-methylglutaryl coenzyme A reductase activity in CHO-K1 cells with a potency equivalent to that of I. X showed significant hypocholesterolemic action upon oral administration to rats, with a potency far in excess of the 7 alpha-methyl-15-ketosterol IX lacking the F7 substitution. In marked contrast to I, X showed little or no suppression of food consumption in rats. Upon oral administration of X to rats, low levels of X (relative to cholesterol), characterized by chromatographic and gas chromatography-mass spectrometric methodologies, were observed in serum, liver, and small intestine. No material was observed with the expected properties of F7-7-methylcholesterol (or potential intermediates in its possible formation from X). In contrast to I, X lowered serum cholesterol levels at dosages at which no effect on food consumption was observed.
Cloning of cDNA for Canine Interleukin-18 and Canine Interleukin-1beta Converting Enzyme and Expression of Canine Interleukin-18 (1999)

Cloning of canine interleukin-18 (IL-18) and canine interleukin-1beta converting enzyme (ICE) cDNA was carried out by using murine IL-18 cDNA and human ICE cDNA, respectively, as probes. Sequence homology to known sequences of human, mouse, or rat genes was noted at nucleotide and amino acid levels. Canine IL-18 mRNA was expressed in various canine organs, whereas canine ICE mRNA was expressed in only a few, particularly in the brain and testis. Cloned canine IL-18 cDNA was expressed in Escherichia coli. The resulting protein promoted induction of canine interferon-y (IFN-y) from stimulated canine lymphocytes. Canine IL-18 and canine IL-12 produced canine IFN-gamma synergistically. Canine IL-18 suppressed the growth of tumor cells transplanted in SCID mice. Cloned canine IL-18 should prove useful as an anticancer agent.
Automatic tracking of neuro vascular tree paths (2006)

3-D analysis of blood vessels from volumetric CT and MR datasets has many applications ranging from examination of pathologies such as aneurysm and calcification to measurement of cross-sections for therapy planning. Segmentation of the vascular structures followed by tracking is an important processing step towards automating the 3-D vessel analysis workflow. This paper demonstrates a fast and automated algorithm for tracking the major arterial structures that have been previously segmented. Our algorithm uses anatomical knowledge to identify the start and end points in the vessel structure that allows automation. Voxel coding scheme is used to code every voxel in the vessel based on its geodesic distance from the start point. A shortest path based iterative region growing is used to extract the vessel tracks that are subsequently smoothed using an active contour method. The algorithm also has the ability to automatically detect bifurcation points of major arteries. Results are shown for tracking the major arteries such as the common carotid, internal carotid, vertebrals, and arteries coming off the Circle of Willis across multiple cases with various data related and pathological challenges from 7 CTA cases and 2 MR Time of Flight (TOF) cases.
Data related to the synthesis, characterization and electrochemical performance of high capacity sodium manganese periodate electrodes (2019)

Sodium manganese periodate compounds were synthesized to serve as high capacity cathodes. The composition and morphology of resulting products were characterized by scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDX), X-ray Diffraction (XRD) and thermogravimetric analysis (TGA). Composite cathodes made from the synthesized periodates were used to fabricate batteries with zinc anode and acetic acid electrolyte. Electrode formulations were optimized using nanocarbon conductive additives. For the full design and mechanism related to the sodium manganese periodate electrode with specific capacity as high as 750 mAh g<sup>-1</sup>, please refer to our research article "High Capacity Aqueous Periodate Batteries Featuring a Nine-Electron Transfer Process" [1].
High contrast scanning nano‐Raman spectroscopy of silicon (2007)

Abstract We have demonstrated that scanning nano‐Raman spectroscopy (SNRS), generally known as tip‐enhanced Raman spectroscopy (TERS), with side illumination optics can be effectively used for analysis of silicon‐based structures at the nanoscale. Even though the side illumination optics has disadvantages such as difficulties in optical alignment and shadowing by the tip, it has the critical advantage that it may be used for the analysis of nontransparent samples. A key criterion for making SNRS effective for imaging Si samples is the optimization of the contrast between near‐field and far‐field (background) Raman signals. This has been achieved by optimizing the beam polarization, resulting in an order of magnitude improvement in the contrast. We estimate the lateral resolution of our Raman images to be ∼20 nm. Copyright © 2007 John Wiley & Sons, Ltd.
Gradual Increase of miR156 Regulates Temporal Expression Changes of Numerous Genes during Leaf Development in Rice       (2012)

The highly conserved plant microRNA, miR156, is an essential regulator for plant development. In Arabidopsis (Arabidopsis thaliana), miR156 modulates phase changing through its temporal expression in the shoot. In contrast to the gradual decrease over time in the shoot (or whole plant), we found that the miR156 level in rice (Oryza sativa) gradually increased from young leaf to old leaf after the juvenile stage. However, the miR156-targeted rice SQUAMOSA-promoter binding-like (SPL) transcription factors were either dominantly expressed in young leaves or not changed over the time of leaf growth. A comparison of the transcriptomes of early-emerged old leaves and later-emerged young leaves from wild-type and miR156 overexpression (miR156-OE) rice lines found that expression levels of 3,008 genes were affected in miR156-OE leaves. Analysis of temporal expression changes of these genes suggested that miR156 regulates gene expression in a leaf age-dependent manner, and miR156-OE attenuated the temporal changes of 2,660 genes. Interestingly, seven conserved plant microRNAs also showed temporal changes from young to old leaves, and miR156-OE also attenuated the temporal changes of six microRNAs. Consistent with global gene expression changes, miR156-OE plants resulted in dramatic changes including precocious leaf maturation and rapid leaf/tiller initiation. Our results indicate that another gradient of miR156 is present over time, a gradual increase during leaf growth, in addition to the gradual decrease during shoot growth. Gradually increased miR156 expression in the leaf might be essential for regulating the temporal expression of genes involved in leaf development.
Multifunctional and High Affinity Polymer Ligand that Provides Bio-Orthogonal Coating of Quantum Dots (2016)

We detail the design of hydrophilic metal-coordinating ligands and their use for the effective coating of luminescent quantum dots (QDs). The ligand design exploits the specific, reagent-free nucleophilic addition reaction of amine-modified molecules toward maleic anhydride to introduce several lipoic acid metal anchors, hydrophilic zwitterion moieties, and specific reactive groups along a poly(isobutylene-alt-maleic anhydride) (PIMA) chain. Tunable reactive groups tested in this study include azide, biotin, carboxyl, and amine. Cap exchange with these multilipoic acid ligands via a photochemical ligation strategy yields homogeneous QD dispersions that are colloidally stable over several biologically relevant conditions and for extended periods of time. The zwitterionic coating yields compact nanoparticle size and imparts nonsticky surface properties onto the QDs, preventing protein absorption. The introduction of a controllable number of reactive groups allows conjugation of the QDs to biomolecules via bio-orthogonal coupling chemistries including (1) attachment of the neurotransmitter dopamine to QDs via amine-isothiocyanate reaction to produce a platform capable of probing interactions with cysteine in proteins, based on charge transfer interactions; (2) self-assembly of biotinylated QDs with streptavidin-dye; and (3) ligation of azide-functionalized QDs to cyclooctyne-modified transferrin via copper-free click chemistry, used for intracellular delivery. This ligand design strategy can be used to prepare an array of metal-coordinating ligands adapted for coating other inorganic nanoparticles, including magnetic and plasmonic nanomaterials.
TRIP Titanium Alloy Design (2020)

Building on successful development experience of transformation induced plasticity (TRIP) steels, an analogous concept was taken to design high performance titanium alloys. This article describes a computational design framework of novel near-α TRIP titanium alloys with both high yield strength and fracture toughness for naval structural applications using a systems design approach integrating processing/structure/properties/performance relations. Predictive models including a transformation stability model based on Olson-Cohen heterogeneous martensite nucleation theory for titanium alloys was proposed. Integration of the models with CALPHAD software and databases enables parametric design optimization to meet design objectives. The developed models were calibrated with experimental measurements.
Structural basis for recognition of the central conserved region of RSV G by neutralizing human antibodies (2018)

Respiratory syncytial virus (RSV) is a major cause of severe lower respiratory tract infections in infants and the elderly, and yet there remains no effective treatment or vaccine. The surface of the virion is decorated with the fusion glycoprotein (RSV F) and the attachment glycoprotein (RSV G), which binds to CX3CR1 on human airway epithelial cells to mediate viral attachment and subsequent infection. RSV G is a major target of the humoral immune response, and antibodies that target the central conserved region of G have been shown to neutralize both subtypes of RSV and to protect against severe RSV disease in animal models. However, the molecular underpinnings for antibody recognition of this region have remained unknown. Therefore, we isolated two human antibodies directed against the central conserved region of RSV G and demonstrated that they neutralize RSV infection of human bronchial epithelial cell cultures in the absence of complement. Moreover, the antibodies protected cotton rats from severe RSV disease. Both antibodies bound with high affinity to a secreted form of RSV G as well as to a peptide corresponding to the unglycosylated central conserved region. High-resolution crystal structures of each antibody in complex with the G peptide revealed two distinct conformational epitopes that require proper folding of the cystine noose located in the C-terminal part of the central conserved region. Comparison of these structures with the structure of fractalkine (CX3CL1) alone or in complex with a viral homolog of CX3CR1 (US28) suggests that RSV G would bind to CX3CR1 in a mode that is distinct from that of fractalkine. Collectively, these results build on recent studies demonstrating the importance of RSV G in antibody-mediated protection from severe RSV disease, and the structural information presented here should guide the development of new vaccines and antibody-based therapies for RSV.
Determinants of exercise performance in normal men with externally imposed expiratory flow limitation (2002)

To understand how externally applied expiratory flow limitation (EFL) leads to impaired exercise performance and dyspnea, we studied six healthy males during control incremental exercise to exhaustion (C) and with EFL at approximately 1. We measured volume at the mouth (Vm), esophageal, gastric and transdiaphragmatic (Pdi) pressures, maximal exercise power (W(max)) and the difference (Delta) in Borg scale ratings of breathlessness between C and EFL exercise. Optoelectronic plethysmography measured chest wall and lung volume (VL). From Campbell diagrams, we measured alveolar (PA) and expiratory muscle (Pmus) pressures, and from Pdi and abdominal motion, an index of diaphragmatic power (W(di)). Four subjects hyperinflated and two did not. EFL limited performance equally to 65% W(max) with Borg = 9-10 in both. At EFL W(max), inspiratory time (TI) was 0.66s +/- 0.08, expiratory time (TE) 2.12 +/- 0.26 s, Pmus approximately 40 cmH2O and DeltaVL-DeltaVm = 488.7 +/- 74.1 ml. From PA and VL, we calculated compressed gas volume (VC) = 163.0 +/- 4.6 ml. The difference, DeltaVL-DeltaVm-VC (estimated blood volume shift) was 326 ml +/- 66 or 7.2 ml/cmH2O PA. The high Pmus and long TE mimicked a Valsalva maneuver from which the short TI did not allow recovery. Multiple stepwise linear regression revealed that the difference between C and EFL Pmus accounted for 70.3% of the variance in DeltaBorg. DeltaW(di) added 12.5%. We conclude that high expiratory pressures cause severe dyspnea and the possibility of adverse circulatory events, both of which would impair exercise performance.
Steam as the working fluid for power recovery from exhaust gases by means of screw expanders (2011)

Rankine cycle systems, using steam as a working fluid, are not well suited to the recovery of power from heat sources in the 300–450 °C temperature range, such as internal combustion engine exhaust gases, mainly due to the relatively large enthalpy of vaporization of water. Admitting the steam to the expander as vapour approximately 50 per cent dry, would be preferable but turbines cannot be used to expand vapours from this state. However, screw expanders can operate well in this mode. It is shown that, apart from being environmentally benign and free from flammability risks, a screw-driven wet steam cycle system can recover power from engine exhaust gases, with comparable efficiencies to turbine-driven systems using organic fluids at a significantly lower cost per unit output.
AT-53 * PHASE I/II STUDY OF DIANHYDROGALACTITOL IN PATIENTS WITH RECURRENT MALIGNANT GLIOBLASTOMA MULTIFORME (GBM) (2014)

Median survival for patients with recurrent GBM is <6 months. Front-line systemic therapy is temozolomide but resistance due to O6-methylguanine-DNA-methyltransferase (MGMT) activity is implicated in poor outcomes. Dianhydrogalactitol (VAL-083) is a structurally unique bi-functional DNA alkylating agent that accumulates in brain tumor tissue. In in vitro studies, VAL-083 demonstrated activity in pediatric and adult GBM cell lines, as well as GBM cancer stem cells. Notably, VAL-083 overcomes resistance to MGMT in vitro. Previous clinical studies suggest that VAL-083 has anti-tumor activity against a range of tumors, including GBM. In light of extensive safety data from clinical trials and promising efficacy in CNS tumors, we initiated a new clinical study to establish the maximum tolerated dose (MTD) and identify a dose and dosing regimen for future efficacy trials in GBM. Early in the development of VAL-083, a cumulative IV dose of 125 mg/m2 delivered in a 35 day cycle in combination with radiation was shown superior to radiation alone in brain cancer (Eagan, et al. 1979). In the present study, the cumulative dose in a 33 day cycle ranges from 9 mg/m2 (cohort 1) to 240 mg/m2 (cohort 7). Six dose cohorts have completed the trial with no drug-related serious adverse events: MTD was not yet reached. Enrollment for cohort 7 (33 day cumulative dose: 240 mg/m2) has been initiated and higher doses may be explored; the results will determine the design of the safety and efficacy registration trial. METHODS: Open-label, single-arm Phase I/II dose-escalation study in patients with histologically-confirmed initial diagnosis of malignant GBM. The study utilizes a 3 + 3 dose-escalation design. Patients receive VAL-083 IV on days 1, 2, and 3 of a 21 day cycle. GBM patients previously been treated with surgery and/or radiation, if appropriate, must have failed both bevacizumab and temozolomide, unless contraindicated. ClinicalTrials.gov Identifier NCT01478178.
Polyacrylic acid-modified zinc phosphate conversion coatings for corrosion protection of steel (1989)

Polyacrylic acid, p(AA), electrolyte macromolecules diffused into crystalline zinc phosphate (Zn{center dot}Ph) conversion coatings that are precipitated onto cold-rolled steel by dissolution- recrystallization processes, enhance the corrosion protection of steel. One of the specific subserviences was that, when the NaOH- dissolution of Zn{center dot}Ph is considered, the Zn-OOC electrostatic bonds at p(AA)-Zn{center dot}Ph interfaces are transformed into Na{sup {plus minus}}OOC ionic bonds which associate with the salt complexed macromolecules. Another is the intermolecular chemical reactions between p(AA) and polymeric topcoats. These contributions relate directly to a lower cathodic delamination rate. 9 refs., 6 figs., 2 tabs.
Rationally Designed Integrin β3 Mutants Stabilized in the High Affinity Conformation (2008)

Integrins are important cell surface receptors that transmit bidirectional signals across the membrane. It has been shown that a conformational change of the integrin beta-subunit headpiece (i.e. the beta I domain and the hybrid domain) plays a critical role in regulating integrin ligand binding affinity and function. Previous studies have used coarse methods (a glycan wedge, mutations in transmembrane contacts) to force the beta-subunit into either the open or closed conformation. Here, we demonstrate a detailed understanding of this conformational change by applying computational design techniques to select five amino acid side chains that play an important role in the energetic balance between the open and closed conformations of alphaIIbbeta3. Eight single-point mutants were designed at these sites, of which five bound ligands much better than wild type. Further, these mutants were found to be in a more extended conformation than wild type, suggesting that the conformational change at the ligand binding headpiece was propagated to the legs of the integrin. This detailed understanding of the conformational change will assist in the development of allosteric drugs that either stabilize or destabilize specific integrin conformations without occluding the ligand-binding site.
Novel Single-Cell-Level Phenotypic Assay for Residual Drug Susceptibility and Reduced Replication Capacity of Drug-Resistant Human Immunodeficiency Virus Type 1 (2004)

Human immunodeficiency virus type 1 (HIV-1)-infected individuals who develop drug-resistant virus during antiretroviral therapy may derive benefit from continued treatment for two reasons. First, drug-resistant viruses can retain partial susceptibility to the drug combination. Second, therapy selects for drug-resistant viruses that may have reduced replication capacities relative to archived, drug-sensitive viruses. We developed a novel single-cell-level phenotypic assay that allows these two effects to be distinguished and compared quantitatively. Patient-derived gag-pol sequences were cloned into an HIV-1 reporter virus that expresses an endoplasmic reticulum-retained Env-green fluorescent protein fusion. Flow cytometric analysis of single-round infections allowed a quantitative analysis of viral replication over a 4-log dynamic range. The assay faithfully reproduced known in vivo drug interactions occurring at the level of target cells. Simultaneous analysis of single-round infections by wild-type and resistant viruses in the presence and absence of the relevant drug combination divided the benefit of continued nonsuppressive treatment into two additive components, residual virus susceptibility to the drug combination and selection for drug-resistant variants with diminished replication capacities. In some patients with drug resistance, the dominant circulating viruses retained significant susceptibility to the combination. However, in other cases, the dominant drug-resistant viruses showed no residual susceptibility to the combination but had a reduced replication capacity relative to the wild-type virus. In this case, simplification of the regimen might still allow adequate suppression of the wild-type virus. In a third pattern, the resistant viruses had no residual susceptibility to the relevant drug regimen but nevertheless had a replication capacity equivalent to that of wild-type virus. In such cases, there is no benefit to continued treatment. Thus, the ability to simultaneously analyze residual susceptibility and reduced replication capacity of drug-resistant viruses may provide a basis for rational therapeutic decisions in the setting of treatment failure.
Binary Multi-View Clustering (2018)

Clustering is a long-standing important research problem, however, remains challenging when handling large-scale image data from diverse sources. In this paper, we present a novel Binary Multi-View Clustering (BMVC) framework, which can dexterously manipulate multi-view image data and easily scale to large data. To achieve this goal, we formulate BMVC by two key components: compact collaborative discrete representation learning and binary clustering structure learning, in a joint learning framework. Specifically, BMVC collaboratively encodes the multi-view image descriptors into a compact common binary code space by considering their complementary information; the collaborative binary representations are meanwhile clustered by a binary matrix factorization model, such that the cluster structures are optimized in the Hamming space by pure, extremely fast bit-operations. For efficiency, the code balance constraints are imposed on both binary data representations and cluster centroids. Finally, the resulting optimization problem is solved by an alternating optimization scheme with guaranteed fast convergence. Extensive experiments on four large-scale multi-view image datasets demonstrate that the proposed method enjoys the significant reduction in both computation and memory footprint, while observing superior (in most cases) or very competitive performance, in comparison with state-of-the-art clustering methods.