gebhart/patrepeval huggingface dataset:
Host Defense Peptides as Templates for Antifungal Drug Development (2020)

Current treatment for invasive fungal diseases is limited to three classes of antifungal drugs: azoles, polyenes, and echinocandins. The most recently introduced antifungal class, the echinocandins, was first approved nearly 30 years ago. The limited antifungal drug portfolio is rapidly losing its clinical utility due to the inexorable rise in the incidence of invasive fungal infections and the emergence of multidrug resistant (MDR) fungal pathogens. New antifungal therapeutic agents and novel approaches are desperately needed. Here, we detail attempts to exploit the antifungal and immunoregulatory properties of host defense peptides (HDPs) in the design and evaluation of new antifungal therapeutics and discuss historical limitations and recent advances in this quest.
Tyrosine Kinase Inhibitors. 13. Structure−Activity Relationships for Soluble 7-Substituted 4-[(3-Bromophenyl)amino]pyrido[4,3-d]pyrimidines Designed as Inhibitors of the Tyrosine Kinase Activity of the Epidermal Growth Factor Receptor (1997)

The general class of 4-(phenylamino)quinazolines are potent (some members with IC50 values << 1 nM) and selective inhibitors of the tyrosine kinase activity of the epidermal growth factor receptor (EGFR), via competitive binding at the ATP site of the enzyme, but many of the early analogues had poor aqueous solubility (<< 1 mM). A series of 7-substituted 4-[(3-bromophenyl)-amino]pyrido[4,3-d]pyrimidines, together with selected (3-methylphenyl)amino analogues, were prepared by reaction of the analogous 7-fluoro derivatives with appropriate amine nucleophiles in 2-BuOH or aqueous 1-PrOH. All of the compounds were evaluated for their ability to inhibit the tyrosine-phosphorylating action of EGF-stimulated full-length EGFR enzyme. Selected analogues were also evaluated for their inhibition of autophosphorylation of the EGF receptor in A431 human epidermoid carcinoma cells in culture and against A431 tumor xenografts in mice. Analogues bearing a wide variety of polyol, cationic, and anionic solubilizing substituents retained activity, but the most effective in terms of both increased aqueous solubility (> 40 mM) and retention of overall inhibitory activity (IC50's of 0.5-10 nM against isolated enzyme and 8-40 nM for inhibition of EGFR autophosphorylation in A431 cells) were weakly basic amine derivatives. These results are broadly consistent with a proposed model for the binding of these compounds to EGFR, in which the 6- and 7-positions of the pyridopyrimidine ring are in a largely hydrophobic binding region of considerable steric freedom, at the entrance of the adenine binding cleft. The most active cationic analogues have a weakly basic side chain where the amine moiety is three or more carbon atoms away from the nucleus. Two of the compounds (bearing weakly basic morpholinopropyl and strongly basic (dimethylamino)butyl solubilizing groups) produced in vivo tumor growth delays of 13-21 days against advanced stage A431 epidermoid xenografts in nude mice, when administered i.p. twice per day on days 7-21 posttumor implant. Treated tumors did not increase in size during therapy and resumed growth at the termination of therapy, indicating an apparent cytostatic effect for these compounds under these treatment conditions. The data suggest that continuous long-term therapy with these compounds may result in substantial tumor growth inhibition.
Selectivity of Hydroxamate- and Difluoromethyloxadiazole-Based Inhibitors of Histone Deacetylase 6 In Vitro and in Cells (2023)

Histone deacetylase 6 (HDAC6) is a unique member of the HDAC family of enzymes due to its complex domain organization and cytosolic localization. Experimental data point toward the therapeutic use of HDAC6-selective inhibitors (HDAC6is) for use in both neurological and psychiatric disorders. In this article, we provide side-by-side comparisons of hydroxamate-based HDAC6is frequently used in the field and a novel HDAC6 inhibitor containing the difluoromethyl-1,3,4-oxadiazole function as an alternative zinc-binding group (compound <b>7</b>). In vitro isotype selectivity screening uncovered HDAC10 as a primary off-target for the hydroxamate-based HDAC6is, while compound <b>7</b> features exquisite 10,000-fold selectivity over all other HDAC isoforms. Complementary cell-based assays using tubulin acetylation as a surrogate readout revealed approximately 100-fold lower apparent potency for all compounds. Finally, the limited selectivity of a number of these HDAC6is is shown to be linked to cytotoxicity in RPMI-8226 cells. Our results clearly show that off-target effects of HDAC6is must be considered before attributing observed physiological readouts solely to HDAC6 inhibition. Moreover, given their unparalleled specificity, the oxadiazole-based inhibitors would best be employed either as research tools in further probing HDAC6 biology or as leads in the development of truly HDAC6-specific compounds in the treatment of human disease states.
X-ray Damage to CF 3 CO 2 -Terminated Organic Monolayers on Si/Au: Principal Effect of Electrons (1991)

The relative importance of x-rays alone and of x-ray-generated primary and secondary electrons in damaging organic materials was explored by use of self-assembled monolayers (SAMs) on multilayer thin-film supports. The substrates were prepared by the deposit of thin films of silicon (0, 50, 100, and 200 angstroms) on thick layers of gold (2000 angstroms). These systems were supported on chromium-primed silicon wafers. Trifluoroacetoxy-terminated SAMs were assembled on these substrates, and the samples were irradiated with common fluxes of monochromatic aluminum K(alpha) x-rays. The fluxes and energy distributions of the electrons generated by interactions of the x-rays with the various substrates, however, differed. The substrates that emitted a lower flux of electrons exhibited a slower loss of fluorine from the SAMs. This observation indicated that the electrons-and not the x-rays themselves-were largely responsible for the damage to the organic monolayer.
UTILE-Gen: Automated Image Analysis in Nanoscience Using Synthetic Dataset Generator and Deep Learning (2023)

This work presents the development and implementation of a deep learning-based workflow for autonomous image analysis in nanoscience. A versatile, agnostic, and configurable tool was developed to generate instance-segmented imaging datasets of nanoparticles. The synthetic generator tool employs domain randomization to expand the image/mask pairs dataset for training supervised deep learning models. The approach eliminates tedious manual annotation and allows training of high-performance models for microscopy image analysis based on convolutional neural networks. We demonstrate how the expanded training set can significantly improve the performance of the classification and instance segmentation models for a variety of nanoparticle shapes, ranging from spherical-, cubic-, to rod-shaped nanoparticles. Finally, the trained models were deployed in a cloud-based analytics platform for the autonomous particle analysis of microscopy images.
The Temporal Order of Genetic and Pathway Alterations in Tumorigenesis (2011)

Cancer evolves through the accumulation of mutations, but the order in which mutations occur is poorly understood. Inference of a temporal ordering on the level of genes is challenging because clinically and histologically identical tumors often have few mutated genes in common. This heterogeneity may at least in part be due to mutations in different genes having similar phenotypic effects by acting in the same functional pathway. We estimate the constraints on the order in which alterations accumulate during cancer progression from cross-sectional mutation data using a probabilistic graphical model termed Hidden Conjunctive Bayesian Network (H-CBN). The possible orders are analyzed on the level of genes and, after mapping genes to functional pathways, also on the pathway level. We find stronger evidence for pathway order constraints than for gene order constraints, indicating that temporal ordering results from selective pressure acting at the pathway level. The accumulation of changes in core pathways differs among cancer types, yet a common feature is that progression appears to begin with mutations in genes that regulate apoptosis pathways and to conclude with mutations in genes involved in invasion pathways. H-CBN models provide a quantitative and intuitive model of tumorigenesis showing that the genetic events can be linked to the phenotypic progression on the level of pathways.
Enhanced inter-cell interference coordination in co-channel multi-layer LTE-advanced networks (2013)

Different technical solutions and innovations are enabling the move from macro-only scenarios towards heterogeneous networks with a mixture of different base station types. In this article we focus on multi-layer LTE-Advanced networks, and especially address aspects related to interference management. The network controlled time-domain enhanced inter-cell interference coordination (eICIC) concept is outlined by explaining the benefits and characteristics of this solution. The benefits of using advanced terminal device receiver architectures with interference suppression capabilities are motivated. Extensive system level performance results are presented with bursty traffic to demonstrate the eICIC concepts ability to dynamically adapt according to the traffic conditions.
Infusing Knowledge into the Textual Entailment Task Using Graph Convolutional Networks (2020)

Textual entailment is a fundamental task in natural language processing. Most approaches for solving this problem use only the textual content present in training data. A few approaches have shown that information from external knowledge sources like knowledge graphs (KGs) can add value, in addition to the textual content, by providing background knowledge that may be critical for a task. However, the proposed models do not fully exploit the information in the usually large and noisy KGs, and it is not clear how it can be effectively encoded to be useful for entailment. We present an approach that complements text-based entailment models with information from KGs by (1) using Personalized PageRank to generate contextual subgraphs with reduced noise and (2) encoding these subgraphs using graph convolutional networks to capture the structural and semantic information in KGs. We evaluate our approach on multiple textual entailment datasets and show that the use of external knowledge helps the model to be robust and improves prediction accuracy. This is particularly evident in the challenging BreakingNLI dataset, where we see an absolute improvement of 5-20% over multiple text-based entailment models.
Depth image based rendering with advanced texture synthesis (2010)

In free viewpoint television or 3D video, depth image based rendering (DIBR) is used to generate virtual views based on a textured image and its associated depth information. In doing so, image regions which are occluded in the original view may become visible in the virtual image. One of the main challenges in DIBR is to extrapolate known textures into the disoccluded area without inserting subjective annoyance. In this paper, a new hole filling approach for DIBR using texture synthesis is presented. Initially, the depth map in the virtual view is filled at disoccluded locations. Then, in the textured image, holes of limited spatial extent are closed by solving Laplace equations. Larger disoccluded regions are initialized via median filtering and subsequently refined by patch-based texture synthesis. Experimental results show that the proposed approach provides improved rendering results in comparison to the latest MPEG view synthesis reference software (VSRS) version 3.6.
A18848 MITOCHONDRIAL DYSFUNCTION – IMPLICATION AND IMPORTANCE IN CARDIAC HYPERTROPHY (2018)

Objectives: The objective of this study was to understand involvement, significance and prevention of mitochondrial dysfunction in cardiac hypertrophic condition. Methods: To induce cardiac hypertrophy in vitro, h9c2 (2–1) cardiomyocytes were treated with phenylephrine (PE) for 24 h in the absence or presence of PPAR alpha agonist, fenofibrate. Cellular hypertrophy, expression of the fatty acid β-oxidation and mitochondrial genes, mitochondrial trans-membrane potential, dynamicity, production of cellular and mitochondrial calcium level and reactive oxygen species (ROS), mitochondrial activity, biogenesis were examined. Results: Cardiac hypertrophy and remodeling of the mitochondria were prevented by PPAR alpha agonist, fenofibrate which also corrected deranged fatty acid oxidation genes in hypertrophic cardiomyocytes. Decrease in mitochondrial trans-membrane potential and dynamicity in PE-treated cardiomyocytes were also blocked by fenofibrate. Increase in reactive oxygen species (ROS) and calcium level in hypertrophic condition both at cellular and mitochondrial level was ameliorated by fenofibrate. Furthermore, PE induced impairment of mitochondrial activity and ATP generation were partially checked when cells were co-treated with fenofibrate. Expression of some miRNAs which were found to be putative regulators of mitochondrial marker gene, voltage dependent anion channel (VDAC), were altered in hypertrophic cardiomyocytes which were restored when the cells were co-treated with fenofibrate. Conclusion: Overall, the results demonstrate that PPAR alpha signaling is critically involved in mitochondrial dysfunction in hypertrophic cardiomyocytes in which miRNAs might play a significant role.
Optimal bovine pericardial tissue selection sites. II. Cartographic analysis (1998)

In Part I of this work we used small-angle light scattering (SALS) to quantify the fiber architecture of 20 bovine pericardial sacs, along with corresponding tissue-thickness measurements, to determine optimal material selection sites. In order to determine the anatomic consistency of these sites, the fiber architecture and thickness data from all 20 sacs were averaged together using a cartographic analysis method that took advantage of the geometry of the prolate spheroid mold used to process the sacs. Optimal selection sites were determined based on a local criteria where all fiber preferred directions within a 2.54-cm circular area were within +/- 10 degrees. The largest contiguous area (LCA) for the entire BP sac was 20.54 cm2, located in the vicinity of the left ventricle of the heart. The LCA tissue thicknesses were also relatively uniform, further supporting the use of these areas. However, even within these optimal areas there was a +/- 20 degrees standard deviation in local fiber preferred directions, resulting in at best a 40 degrees spread in local preferred directions. The observed structural variability may be due to regionally heterogeneous physiologic loadings induced by the ligamentous attachments. These attachments may alter the regional fiber preferred orientation to support local mechanical loadings. Overall, given the inherent structural variability of the BP sac, we conclude that use of anatomic location alone will not consistently guarantee the selection of tissue specimens with a highly homogeneous and predictable fibrous structure. It is thus suggested that a direct fiber measurement presorting method be employed when selecting BP specimens for bioprosthetic applications where tissue structural homogeneity and uniformity is critical.
Effect of Head-Restraint Rigidity on Whiplash Injury Risk (2004)

&lt;div class="htmlview paragraph"&gt;The present study investigated the effects of the structural stiffness of the head restraint and its attachment rigidity on the biomechanical responses and related injury measures of the neck in a rear impact vehicular collision. A series of simulated rear impacts were conducted using a mid-sized male test dummy seated in a modified late-model front passenger seat on a deceleration crash sled with a FMVSS 202 pulse. Preliminary results demonstrated that a more rigid head restraint in its design and attachment produced lesser values in most biomechanical injury measures such as neck shear force, neck extension bending moment, tension-extension neck injury criterion (Nij), shear-moment neck injury criterion (Nkm), and head-torso relative extension angular displacement. This is true for a wide range of seatback recliner stiffness. This suggests that a more rigid head restraint may have a protective advantage over a more pliant one for the neck in a rear impact. The result of this study underscores the need for dynamic testing to completely evaluate the performance of head restraint system.&lt;/div&gt;
A phosphoinositide hub connects CLE peptide signaling and polar auxin efflux regulation (2023)

Auxin efflux through plasma-membrane-integral PIN-FORMED (PIN) carriers is essential for plant tissue organization and tightly regulated. For instance, a molecular rheostat critically controls PIN-mediated auxin transport in developing protophloem sieve elements of Arabidopsis roots. Plasma-membrane-association of the rheostat proteins, BREVIS RADIX (BRX) and PROTEIN KINASE ASSOCIATED WITH BRX (PAX), is reinforced by interaction with PHOSPHATIDYLINOSITOL-4-PHOSPHATE-5-KINASE (PIP5K). Genetic evidence suggests that BRX dampens autocrine signaling of CLAVATA3/EMBRYO SURROUNDING REGION-RELATED 45 (CLE45) peptide via its receptor BARELY ANY MERISTEM 3 (BAM3). How excess CLE45-BAM3 signaling interferes with protophloem development and whether it does so directly or indirectly remains unclear. Here we show that rheostat polarity is independent of PIN polarity, but interdependent with PIP5K. Catalytically inactive PIP5K confers rheostat polarity without reinforcing its localization, revealing a possible PIP5K scaffolding function. Moreover, PIP5K and PAX cooperatively control local PIN abundance. We further find that CLE45-BAM3 signaling branches via RLCK-VII/PBS1-LIKE (PBL) cytoplasmic kinases to destabilize rheostat localization. Our data thus reveal antagonism between CLE45-BAM3-PBL signaling and PIP5K that converges on auxin efflux regulation through dynamic control of PAX polarity. Because second-site bam3 mutation suppresses root as well as shoot phenotypes of pip5k mutants, CLE peptide signaling likely modulates phosphoinositide-dependent processes in various developmental contexts.
PI3K/AKT/mTOR inhibition in combination with doxorubicin is an effective therapy for leiomyosarcoma (2016)

In summary, this study supports further investigation into the use of PI3K and mTOR inhibitors alone and in combination with standard treatment in leiomyosarcoma patients.
Bioinspired Stimuli‐Responsive and Antifreeze‐Secreting Anti‐Icing Coatings (2015)

The detrimental impacts of icing on transportation and power industries are well‐known. Inspired by natural systems that secrete a functional liquid in response to stimuli, this work introduces an anti‐icing coating that responds to surface icing by releasing antifreeze liquid. It consists of an outer porous superhydrophobic epidermis and a wick‐like underlying dermis that is infused with antifreeze liquid. The functionality of the new coating is validated through condensation frosting, simulated freezing fog, and freezing rain experiments. In the tested conditions, the introduced anti‐icing skin delays onset of frost, rime, and glaze accumulation at least ten times longer than anti‐icing superhydrophobic and lubricant impregnated surfaces. Furthermore, the coating delays onset of glaze formation ten times longer than surfaces flooded with a thin film of antifreeze. In each of the icing scenarios, the fundamental mechanisms responsible for antifreeze release and their relation to required antifreeze replenishment rates are described.
RNAs Containing Carbocyclic Ribonucleotides (2021)

Toward the goal of evaluation of carbocyclic ribonucleoside-containing oligonucleotide therapeutics, we developed convenient, scalable syntheses of all four carbocyclic ribonucleotide phosphoramidites and the uridine solid-support building block. Crystallographic analysis confirmed configuration and stereochemistry of these building blocks. Duplexes with carbocyclic RNA (car-RNA) modifications in one strand were less thermodynamically stable than duplexes with unmodified RNA. However, circular dichroism spectroscopy indicated that global conformations of the duplexes containing car-RNAs were similar to those in the unmodified duplexes.
ChemInform Abstract: Synthetic Studies on Quassinoids: Total Synthesis and Biological Evaluation of (+)‐Des‐D‐chaparrinone. (1999)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Big Thinking: The Power of Nanoscience (LBNL Science at the Theater) (2011)

Science at the Theater, June 6th, 2011: Berkeley Lab scientists reveal how nanoscience will bring us cleaner energy, faster computers, and improved medicine. Alex Weber-Bargioni: How can we see things at the nanoscale? Alex is pioneering new methods that provide unprecedented insight into nanoscale materials and molecular interactions. The goal is to create rules for building nanoscale materials. Babak Sanii: Nature is an expert at making nanoscale devices such as proteins. Babak is developing ways to see these biological widgets, which could help scientists develop synthetic devices that mimic the best that nature has to offer. Ting Xu: How are we going to make nanoscale devices? A future in which materials and devices are able to assemble themselves may not be that far down the road. Ting is finding ways to induce a wide range of nanoscopic building blocks to assemble into complex structures. Delia Milliron: The dividends of nanoscience could reshape the way we live, from smart windows and solar cells to artificial photosynthesis and improved medical diagnosis. Delia is at the forefront of converting fundamental research into nanotechnology. Moderated by Jim DeYoreo, interim director of the Molecular Foundry, a facility located at Berkeley Lab where scientists from around the world address the myriad challenges in nanoscience.
Non‐peptide fibrinogen receptor antagonists. 21. The synthesis of [3H]L-738,167 (1998)

The synthesis of [3H]L-738,167, an orally active fibrogen receptor antagonist, is described. A precursor containing the 2-bromotolyl moiety was synthesized, and a reductive debromination reaction using tritium gas and Pearlman's catalyst gave the desired product with a final specific activity of 21 Ci/mmol. © 1998 John Wiley & Sons, Ltd.
Physiological effects of ocean acidification on animal calcifiers (2016)

Abstract This chapter reviews the current state of knowledge about the diversity in physiological responses (including energy metabolism, acid–base balance, and biomineralization) to ocean acidification (OA) in four major taxonomic groups of marine calcifiers—corals, molluscs, crustaceans, and echinoderms. The interactive effects between acidification and other commonly occurring environmental factors, such as temperature, salinity, hypoxia, and trace metals, on the physiology of these animal calcifiers is reviewed. Assessment of the inter-phylum and inter-species variability in response of OA (either alone or in combination with other stressors) is critical in identifying most vulnerable ecosystems as a focus for conservation efforts, reducing the impact of other stressors such as pollution, and aquaculture efforts to improve resilience of existing stocks of economically important marine organisms.