gebhart/patrepeval huggingface dataset:
Active Learning for Multi-Objective Optimization (2013)

In many fields one encounters the challenge of identifying, out of a pool of possible designs, those that simultaneously optimize multiple objectives. This means that usually there is not one optimal design but an entire set of Pareto-optimal ones with optimal tradeoffs in the objectives. In many applications, evaluating one design is expensive; thus, an exhaustive search for the Pareto-optimal set is unfeasible. To address this challenge, we propose the Pareto Active Learning (PAL) algorithm which intelligently samples the design space to predict the Pareto-optimal set. Key features of PAL include (1) modeling the objectives as samples from a Gaussian process distribution to capture structure and accomodate noisy evaluation; (2) a method to carefully choose the next design to evaluate to maximize progress; and (3) the ability to control prediction accuracy and sampling cost. We provide theoretical bounds on PAL’s sampling cost required to achieve a desired accuracy. Further, we show an experimental evaluation on three real-world data sets. The results show PAL’s effectiveness; in particular it improves significantly over a state-of-the-art multi-objective optimization method, saving in many cases about 33% evaluations to achieve the same accuracy. Proceedings of the 30 th
The Chemistry of Oxovanadium(IV) (1965)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTThe Chemistry of Oxovanadium(IV)Joel SelbinCite this: Chem. Rev. 1965, 65, 2, 153–175Publication Date (Print):April 1, 1965Publication History Published online1 May 2002Published inissue 1 April 1965https://pubs.acs.org/doi/10.1021/cr60234a001https://doi.org/10.1021/cr60234a001research-articleACS PublicationsRequest reuse permissionsArticle Views2634Altmetric-Citations489LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Novel Bcl-2 Homology-3 Domain-like Sequences Identified from Screening Randomized Peptide Libraries for Inhibitors of the Pro-survival Bcl-2 Proteins (2009)

Interactions between Bcl-2 homology-3 (BH3)-only proteins and their pro-survival Bcl-2 family binding partners initiate the intrinsic apoptosis pathway. These interactions are mediated by a short helical motif, the BH3 domain, on the BH3-only protein, which inserts into a hydrophobic groove on the pro-survival molecule. To identify novel peptidic ligands that bind Mcl-1, a pro-survival protein relative of Bcl-2, both human and mouse Mcl-1 were screened against large randomized phage-displayed peptide libraries. We identified a number of 16-mer peptides with sub-micromolar affinity that were highly selective for Mcl-1, as well as being somewhat selective for the species of Mcl-1 (human or mouse) against which the library was panned. Interestingly, these sequences all strongly resembled natural BH3 domain sequences. By switching residues within the best of the human Mcl-1-binding sequences, or extending beyond the core sequence identified, we were able to alter the pro-survival protein interaction profile of this peptide such that it now bound all members tightly and was a potent killer when introduced into cells. Introduction of an amide lock constraint within this sequence also increased its helicity and binding to pro-survival proteins. These data provide new insights into the determinants of BH3 domain:pro-survival protein affinity and selectivity.
Urokinase-Type Plasminogen Activator System in Breast Cancer (2004)

The prognostic value of components of the urokinase-type plasminogen activator (uPA) system, its receptor uPAR (CD87), and plasminogen activator inhibitors PAI-1 and PAI-2 is well established. We studied the predictive value of these proteolytic factors by evaluating the association of their tumor expression level and the efficacy of tamoxifen therapy in patients with recurrent breast cancer. The antigen levels of the four factors were determined by ELISA in cytosols prepared from estrogen receptor-positive primary breast tumors of 691 hormone-naive breast cancer patients with recurrent disease and treated with tamoxifen as first-line systemic therapy. High tumor levels of uPA (P < 0.001), uPAR (P < 0.01), and PAI-1 (P = 0.01) were associated with a lower efficacy of tamoxifen therapy. In the multivariable analysis, uPA (P < 0.001) provided additional information independent of the traditional predictive factors to predict benefit from tamoxifen therapy. High levels of uPA, uPAR, and PAI-1 predicted a shorter progression-free survival (PFS) on tamoxifen in an analysis of the first 9 months of therapy. However in the analysis during the total follow-up period, high PAI-2 levels (P = 0.01) showed a longer response to tamoxifen. In conclusion, uPA, uPAR, and PAI-1, components of the urokinase system, are predictive for the efficacy of tamoxifen therapy in patients treated for recurrent breast cancer. Knowledge of their tumor expression levels might be helpful for future individualized therapy protocols, including possible new-targeted therapies based on the interference in the urokinase system.
mRNA expression patterns of the cGMP‐hydrolyzing phosphodiesterases types 2, 5, and 9 during development of the rat brain (2003)

Recent evidence indicates that cGMP plays an important role in neural development and neurotransmission. Since cGMP levels depend critically on the activities of phosphodiesterase (PDE) enzymes, mRNA expression patterns were examined for several key cGMP-hydrolyzing PDEs (type 2 [PDE2], 5 [PDE5], and 9 [PDE9]) in rat brain at defined developmental stages. Riboprobes were used for nonradioactive in situ hybridization on sections derived from embryonic animals at 15 days gestation (E15) and several postnatal stages (P0, P5, P10, P21) until adulthood (3 months). At all stages PDE9 mRNA was present throughout the whole central nervous system, with highest levels observed in cerebellar Purkinje cells, whereas PDE2 and PDE5 mRNA expression was more restricted. Like PDE9, PDE5 mRNA was abundant in cerebellar Purkinje cells, although it was observed only on and after postnatal day 10 in these cells. In other brain regions, PDE5 mRNA expression was minimal, detected in olfactory bulb, cortical layers, and in hippocampus. PDE2 mRNA was distributed more widely, with highest levels in medial habenula, and abundant expression in olfactory bulb, olfactory tubercle, cortex, amygdala, striatum, and hippocampus. Double immunostaining of PDE2, PDE5, or PDE9 mRNAs with the neuronal marker NeuN and the glial cell marker glial fibrillary acidic protein revealed that these mRNAs were predominantly expressed in neuronal cell bodies. Our data indicate that three cGMP-hydrolyzing PDE families have distinct expression patterns, although specific cell types coexpress mRNAs for all three enzymes. Thus, it appears that differential expression of PDE isoforms may provide a mechanism to match cGMP hydrolysis to the functional demands of individual brain regions.
A convolutional neural network cascade for face detection (2015)

In real-world face detection, large visual variations, such as those due to pose, expression, and lighting, demand an advanced discriminative model to accurately differentiate faces from the backgrounds. Consequently, effective models for the problem tend to be computationally prohibitive. To address these two conflicting challenges, we propose a cascade architecture built on convolutional neural networks (CNNs) with very powerful discriminative capability, while maintaining high performance. The proposed CNN cascade operates at multiple resolutions, quickly rejects the background regions in the fast low resolution stages, and carefully evaluates a small number of challenging candidates in the last high resolution stage. To improve localization effectiveness, and reduce the number of candidates at later stages, we introduce a CNN-based calibration stage after each of the detection stages in the cascade. The output of each calibration stage is used to adjust the detection window position for input to the subsequent stage. The proposed method runs at 14 FPS on a single CPU core for VGA-resolution images and 100 FPS using a GPU, and achieves state-of-the-art detection performance on two public face detection benchmarks.
Cerebral monitoring during carotid endarterectomy using near-infrared diffuse optical spectroscopies and electroencephalogram (2011)

Intraoperative monitoring of cerebral hemodynamics during carotid endarterectomy (CEA) provides essential information for detecting cerebral hypoperfusion induced by temporary internal carotid artery (ICA) clamping and post-CEA hyperperfusion syndrome. This study tests the feasibility and sensitivity of a novel dual-wavelength near-infrared diffuse correlation spectroscopy technique in detecting cerebral blood flow (CBF) and cerebral oxygenation in patients undergoing CEA. Two fiber-optic probes were taped on both sides of the forehead for cerebral hemodynamic measurements, and the instantaneous decreases in CBF and electroencephalogram (EEG) alpha-band power during ICA clamping were compared to test the measurement sensitivities of the two techniques. The ICA clamps resulted in significant CBF decreases (-24.7 ± 7.3%) accompanied with cerebral deoxygenation at the surgical sides (n = 12). The post-CEA CBF were significantly higher (+43.2 ± 16.9%) than the pre-CEA CBF. The CBF responses to ICA clamping were significantly faster, larger and more sensitive than EEG responses. Simultaneous monitoring of CBF, cerebral oxygenation and EEG power provides a comprehensive evaluation of cerebral physiological status, thus showing potential for the adoption of acute interventions (e.g., shunting, medications) during CEA to reduce the risks of severe cerebral ischemia and cerebral hyperperfusion syndrome.
Abscisic Acid Accelerates Adaptation of Cultured Tobacco Cells to Salt (1985)

Adaptation of tobacco (Nicotiana tabacum L. var Wisconsin 38) cells to NaCl was accelerated by (+/-) abscisic acid (ABA). In medium with 10 grams per liter NaCl, ABA stimulated the growth of cells not grown in medium with NaCl (unadapted, S-0) with an increasing response from 10(-8) to 10(-4) molar. ABA (10(-5) molar) enhanced the growth of unadapted cells in medium with 6 to 22 grams per liter NaCl but did not increase the growth of cells previously adapted to either 10 (S-10) or 25 (S-25) grams per liter NaCl unless the cells were inoculated into medium with a level of NaCl higher than the level to which the cells were adapted. The growth of unadapted cells in medium with Na(2)SO(4) (85.5 millimolar), KCl (85.5 or 171 millimolar), K(2)SO(4) (85.5 millimolar) was also stimulated by ABA. ABA (10(-8)-10(-4) molar) did not accelerate the growth of unadapted cells exposed to water deficits induced by polyethylene glycol (molecular weight 8000) (5-20 grams per 100 milliliters), sorbitol (342 millimolar), mannitol (342 millimolar) or sucrose (342 millimolar). These results suggest that ABA is involved in adaptation of cells to salts, and is not effective in promoting adaptation to water deficits elicited by nonionic osmotic solutes.
Simple method for purifying choleragenoid, the natural toxoid of Vibrio cholerae (1977)

Choleragenoid, a nontoxic aggregate of the B subunit of cholera toxin, has been purified from concentrated culture filtrates in a single step by ion-exchange chromatography on phosphocellulose or other cation-exchange resins. This procedure is far simpler than others currently used to isolate choleragenoid and yields a preparation essentially free from nucleic acid, lipopolysaccharide, toxin, and other proteins present in the crude culture filtrates. The purified choleragenoid retained the specific receptor-binding capacity of the toxin but exhibited no enterotoxic activity by either the ileal loop assay or the skin permeability assay. This purification methods may therefore be superior to others currently used for obtaining choleragenoid for immunization or other purposes.
The N-myc oncogene in human neuroblastoma cells: down-regulation of an angiogenesis inhibitor identified as activin A. (2000)

Angiogenesis, the formation of new blood vessels, is seen during embryonic development and tumor progression, but the mechanisms have remained unclear. Recent data indicate that developmental and tumor angiogenesis can be induced by cellular oncogenes, leading to the enhanced activity of molecules stimulating angiogenesis. However, activated oncogenes might also facilitate angiogenesis by down-regulating endogenous inhibitors of angiogenesis. We report here that enhanced expression of the N-myc oncogene in human neuroblastoma cells down-regulates an inhibitor of endothelial cell proliferation, identified by amino acid sequencing as being identical with activin A, a developmentally regulated protein. Down-regulation appears to involve interaction of the N-Myc protein with the activin A promoter. In addition, activin A inhibits both endothelial cell proliferation in vitro and angiogenesis in vivo, and it induces hemorrhage in vivo. We suggest that the N-myc-induced down-regulation of activin A could contribute to developmental and tumor angiogenesis.
Inhibition of Caspases Prevents Ototoxic and Ongoing Hair Cell Death (2002)

Sensory hair cells die after acoustic trauma or ototoxic insults, but the signal transduction pathways that mediate hair cell death are not known. Here we identify several important signaling events that regulate the death of vestibular hair cells. Chick utricles were cultured in media supplemented with the ototoxic antibiotic neomycin and selected pharmacological agents that influence signaling molecules in cell death pathways. Hair cells that were treated with neomycin exhibited classically defined apoptotic morphologies such as condensed nuclei and fragmented DNA. Inhibition of protein synthesis (via treatment with cycloheximide) increased hair cell survival after treatment with neomycin, suggesting that hair cell death requires de novo protein synthesis. Finally, the inhibition of caspases promoted hair cell survival after neomycin treatment. Sensory hair cells in avian vestibular organs also undergo continual cell death and replacement throughout mature life. It is unclear whether the loss of hair cells stimulates the proliferation of supporting cells or whether the production of new cells triggers the death of hair cells. We examined the effects of caspase inhibition on spontaneous hair cell death in the chick utricle. Caspase inhibitors reduced the amount of ongoing hair cell death and ongoing supporting cell proliferation in a dose-dependent manner. In isolated sensory epithelia, however, caspase inhibitors did not affect supporting cell proliferation directly. Our data indicate that ongoing hair cell death stimulates supporting cell proliferation in the mature utricle.
ALK and ROS1 as a joint target for the treatment of lung cancer: a review. (2013)

Rearrangements of the anaplastic lymphoma kinase (ALK) have been described in multiple malignancies, including non-small cell lung cancer (NSCLC). ALK fusions have gain of function properties while activating mutations in wild-type ALK can also occur within the tyrosine kinase domain. ALK rearrangements define a new molecular subtype of NSCLC that is exquisitely sensitive to ALK inhibition. Crizotinib, an orally available small molecule ATP-mimetic compound which was originally designed as a MET inhibitor, was recognized to have "off-target" anti-ALK activity and has been approved in the USA for the treatment of patients with ALK-positive NSCLC. Chromosomal rearrangements involving the ROS1 receptor tyrosine kinase have also been recently described in NSCLC, while crizotinib is currently under clinical trial in this molecular subset of NSCLC patients. The basic approaches of any computer aided drug design work in terms of structure and ligand based drug design. Details of each of these approaches should be covered with an emphasis on utilizing both in order to develop multi-targeted small-molecule kinase inhibitors. Such multi-targeted tyrosine kinase inhibitors can have antiproliferative activity against both ROS1and ALK rearranged NSCLC. Herein, we highlight the importance of targeting these proteins and the advances in optimizing more potent and selective ALK and ROS1 kinase inhibitors.
Monoclonal antibodies to carcinoembryonic antigen produced by somatic cell fusion. (1981)

Hybridoma cell lines secreting monoclonal antibodies to carcinoembryonic antigen (CEA) were generated by fusing mouse immune lymphocytes with the mouse myeloma variant cell line, NS-1. Antibody secreted by one cloned hybrid cell line could bind only a select portion of the CEA bound by the commercially available goat anti-CEA antiserum used in clinical assays. Radiolabeled CEA could be purified on a monoclonal antibody affinity column. Incorporation of this purified radiolabeled CEA in a double-antibody solid-phase assay with goat anti-CEA antiserum led to an approximately 2.5-fold increase in sensitivity of the assay. Genetically stable hybrid clones may be sources of virtually unlimited quantities of such antibodies which may have potential utility in improving the cancer specificity of clinical assays.
NMR determination of the fractal dimension in silica aerogels (1990)

$^{29}\mathrm{Si}$ nuclear relaxation experiments were performed in different forms of silica (alcogel, aerogel, amorphous, and crystallized) doped with paramagnetic impurities. Magic-angle spinning is used to quench the nuclear-spin diffusion. Under this condition, the saturation recovery of the $^{29}\mathrm{Si}$ magnetization follows a power law in a very large time range (up to 5 orders of magnitude). This nonexponential relaxation m(t)\ensuremath{\sim}${\mathit{t}}^{\mathrm{\ensuremath{\alpha}}}$ reflects the mass distribution in the sample: M(r)\ensuremath{\sim}${\mathit{r}}^{\mathit{D}}$ with \ensuremath{\alpha}=D/6. In aerogels, the measured fractal dimension D\ensuremath{\approxeq}2.2 is in agreement with that determined by small-angle x-ray scattering. In densified materials, a dimension D\ensuremath{\approxeq}3 is actually observed.
Fabrication of Elemental Copper by Intense Pulsed Light Processing of a Copper Nitrate Hydroxide Ink (2015)

Printed electronics and renewable energy technologies have shown a growing demand for scalable copper and copper precursor inks. An alternative copper precursor ink of copper nitrate hydroxide, Cu2(OH)3NO3, was aqueously synthesized under ambient conditions with copper nitrate and potassium hydroxide reagents. Films were deposited by screen-printing and subsequently processed with intense pulsed light. The Cu2(OH)3NO3 quickly transformed in less than 100 s using 40 (2 ms, 12.8 J cm(-2)) pulses into CuO. At higher energy densities, the sintering improved the bulk film quality. The direct formation of Cu from the Cu2(OH)3NO3 requires a reducing agent; therefore, fructose and glucose were added to the inks. Rather than oxidizing, the thermal decomposition of the sugars led to a reducing environment and direct conversion of the films into elemental copper. The chemical and physical transformations were studied with XRD, SEM, FTIR and UV-vis.
Nonproteolytic Incorporation of Protein Ligands into Human α2-Macroglobulin:  Implications for the Binding Mechanism of α2-Macroglobulin (1998)

alpha 2-Macroglobulin (alpha 2M) is a complex tetrameric protein of 718 kDa. In native alpha 2M, each of the four subunits contains a thiol ester between the side chains of Cys949 and Gln952. Cleavage of the thiol ester with small nucleophiles destabilizes the native conformation and causes a major conformational change in alpha 2M, which leads to exposure of receptor binding sites and a change in electrophoretic mobility. Recently it has been shown that nucleophilic cleavage of the four thiol esters in alpha 2M is a reversible process with energy requirements dependent on the nucleophile [Grøn, H., Thøgersen, I. B., Enghild, J. J., and Pizzo, S. V. (1996) Biochem. J. 318, 539-545]. The present study is a further investigation of the properties of alpha 2M with cleaved thiol esters and the potential for incorporation of protein ligands at the site of the thiol ester. The thiol ester in alpha 2M was cleaved by NH3. After removal of excess NH3, the alpha 2M derivative was incubated with excess protein ligand (hen egg lysozyme or bovine insulin) at 23, 37, or 50 degreesC, leading to covalent incorporation of the ligands in alpha 2M as analyzed by SDS-PAGE, gel filtration, and centrifugal microfiltration. Receptor binding studies and native pore-limit PAGE confirmed that the alpha 2M derivatives with ligand incorporated remained in the receptor-recognized, "fast" migrating conformation. This is the first demonstration of nonproteolytic, covalent incorporation of protein ligands into receptor-recognized alpha 2M.
2,3-Dihydro-6,7-dihydroxy-1H-isoindol-1-one-Based HIV-1 Integrase Inhibitors (2007)

The bis-salicylhydrazides class of HIV-1 integrase (IN) inhibitors has been postulated to function by metal chelation. However, members of this series exhibit potent inhibition only when Mn2+ is used as cofactor. The current study found that bis-aroylhydrazides could acquire inhibitory potency in Mg2+ using dihydroxybenzoyl substituents as both the right and left components of the hydrazide moiety. Employing a 2,3-dihydro-6,7-dihydroxy-1 H-isoindol-1-one ring system as a conformationally constrained 2,3-dihydroxybenzoyl equivalent provided good selectivity for IN-catalyzed strand transfer versus the 3'-processing reactions as well as antiviral efficacy in cells using HIV-1 based vectors.
Drug Efficacy at G Protein–Coupled Receptors (2002)

Efficacy has been defined in receptor pharmacology as a proportionality factor denoting the amount of physiological response a given ligand imparts to a biological system for a given amount of receptor occupancy. While first defined in terms of response, the concept can be expanded to a wide variety of G protein-coupled receptor (GPCR) behaviors, which includes pleiotropic interaction with multiple G proteins, internalization, oligomerization, desensitization, and interaction with membrane auxilliary proteins. Thus, there can be numerous types of efficacy, and different ligands can have a range of efficacies for different receptor behaviors. This review discusses the use of the efficacy concept in GPCR models based on the thermodynamic linkage theory and also in terms of the protein ensemble theory, in which macroaffinity of ligands for an ensemble of receptor microstates produces a new ligand-bound ensemble. The pharmacological characteristics of the ligand emerge from the intersection of the ligand-bound ensemble with the various ensembles defining pharmacological receptor behaviors. Receptor behaviors discussed are activation of G proteins; ability to be phosphorylated, desensitized, and internalized; formation of dimers and oligomers; and the interaction with auxiliary membrane and cytosolic proteins. The concepts of ligand-specific receptor conformation and conditional efficacy are also discussed in the context of ligand control of physiological response.