gebhart/patrepeval huggingface dataset:
Kinetics of hole nucleation in biomembrane rupture (2011)

The core component of a biological membrane is a fluid-lipid bilayer held together by interfacial-hydrophobic and van der Waals interactions, which are balanced for the most part by acyl chain entropy confinement. If biomembranes are subjected to persistent tensions, an unstable (nanoscale) hole will emerge at some time to cause rupture. Because of the large energy required to create a hole, thermal activation appears to be requisite for initiating a hole and the activation energy is expected to depend significantly on mechanical tension. Although models exist for the kinetic process of hole nucleation in tense membranes, studies of membrane survival have failed to cover the ranges of tension and lifetime needed to critically examine nucleation theory. Hence, rupturing giant (~20 μm) membrane vesicles ultra-slowly to ultra-quickly with slow to fast ramps of tension, we demonstrate a method to directly quantify kinetic rates at which unstable holes form in fluid membranes, at the same time providing a range of kinetic rates from < 0.01 s(-1) to > 100 s(-1). Measuring lifetimes of many hundreds of vesicles, each tensed by precision control of micropipet suction, we have determined the rates of failure for vesicles made from several synthetic phospholipids plus 1:1 mixtures of phospho- and sphingo-lipids with cholesterol, all of which represent prominent constituents of eukaryotic cell membranes. Plotted on a logarithmic scale, the failure rates for vesicles are found to rise dramatically with increase of tension. Converting the experimental profiles of kinetic rates into changes of activation energy versus tension, we show that the results closely match expressions for thermal activation derived from a combination of meso-scale theory and molecular-scale simulations of hole formation. Moreover, we demonstrate a generic approach to transform analytical fits of activation energies obtained from rupture experiments into energy landscapes characterizing the process hole nucleation along the reaction coordinate defined by hole size.
Pressure-sensitive adhesion in the blends of poly(N-vinyl pyrrolidone) and poly(ethylene glycol) of disparate chain lengths (2002)

Adhesive behavior in blends of high molecular weight poly(N-vinyl pyrrolidone (PVP) with a short-chain, liquid poly(ethylene glycol) (PEG) has been studied using a 180° peel test as a function of PVP-PEG composition and water vapor sorption. Hydrophilic pressure-sensitive adhesives are keenly needed in various fields of contemporary industry and medicine, and the PVP-PEG blends, pressure-sensitive adhesion has been established to appear within a narrow composition range, in the vicinity of 36 wt% PEG, and it is affected by the blend hydration. Both plasticizers, PEG and water, behave as tackifiers (enhancers of adhesion) in the blends with glassy PVP. However, PEP alone is shown to account for the occurrence of adhesion, and the tackifying effect of PEG is appreciably stronger than that of sorbed water. Blend hydration enhances adhesion for the systems that exhibit an apparently adhesive type of debonding from a standard substrate (at PEG content less than 36 wt%), but the same amounts of sorbed water are also capable of depressign adhesion in the PEG-overloaded blends, where a cohesive mechanism of adhesive joint failure is typical. The PVP-PEG blend with 36% PEG couples both the adhesive and cohesive mechanisms of bond rupture (i.e., the fibrillation of adhesive polymer under debonding force and predominantly adhesive locus of failure). Blend hydration effect on adhesion has been found to be reversible. The micromechanics of adhesive joint failure for PVP-PEG hydrogels involves the fibrillation of adhesive polymer, followed by fibrils stretching and fracturing as their elongation attains 1000-1500%. Peel force to rupture the adhesive bond of PVP-PEG blends increases with increasing size of the tensile deformation zone, increasing cohesive strength of the material, and increasing tensile compliance of the material, obeying the well-known Kaelble equation, derived originally for conventional rubbery pressure-sensitive adhesives. The major deformation mode upon peeling the PVP-PEG adhesive from a standard substrate is extension, and direct correlations have been established between the composition behaviour of peel strength and that of the total work of viscoelastic strain to break the PVP-PEG films under uniaxial drawing. As a result of strong interfacial interaction with the PET backing film, the PVP-PEG adhesive has a heterogeneous two-layer structure, where different layers demonstrate dissimilar adhesive characteristics.
Predictive perceptual compression for real time video communication (2004)

Approximately 2 degrees in our 140 degree vision span has sharp vision. Many researchers have been fascinated by the idea of eye-tracking integrated perceptual compression of an image or video, yet any practical system has yet to emerge. The unique challenge presented by real time perceptual video streaming is how to handle the fast nature of the human eye and provide its integration with computationally intensive video transcoding scheme. The delay introduced by video transmission in the network presents a difficulty. This delay creates a problem when we try to use information about eye movements for perceptual encoding. In this paper we discuss a new approach to the eye-tracker based video compression. Rather than relying on the point of gaze, this novel scheme tracks a vicinity of interest and offers a prediction mechanism for eye movements. The described system compensates the interim eye movements between the sampling and actual coding. The proposed scheme can be applied to a large variety of today's video compression standards. We have developed an eye gaze-aware MPEG-2 transcoder that can perceptually re-encode a live video stream in real time. The experiments we have conducted illustrate the substantial impact this integrated prediction method has on perceptual video compression and bit-rate reduction.
Unbiased Reconstruction of a Mammalian Transcriptional Network Mediating Pathogen Responses (2009)

Models of mammalian regulatory networks controlling gene expression have been inferred from genomic data but have largely not been validated. We present an unbiased strategy to systematically perturb candidate regulators and monitor cellular transcriptional responses. We applied this approach to derive regulatory networks that control the transcriptional response of mouse primary dendritic cells to pathogens. Our approach revealed the regulatory functions of 125 transcription factors, chromatin modifiers, and RNA binding proteins, which enabled the construction of a network model consisting of 24 core regulators and 76 fine-tuners that help to explain how pathogen-sensing pathways achieve specificity. This study establishes a broadly applicable, comprehensive, and unbiased approach to reveal the wiring and functions of a regulatory network controlling a major transcriptional response in primary mammalian cells.
Combined image-processing algorithms for improved optical coherence tomography of prostate nerves (2010)

Cavernous nerves course along the surface of the prostate gland and are responsible for erectile function. These nerves are at risk of injury during surgical removal of a cancerous prostate gland. In this work, a combination of segmentation, denoising, and edge detection algorithms are applied to time-domain optical coherence tomography (OCT) images of rat prostate to improve identification of cavernous nerves. First, OCT images of the prostate are segmented to differentiate the cavernous nerves from the prostate gland. Then, a locally adaptive denoising algorithm using a dual-tree complex wavelet transform is applied to reduce speckle noise. Finally, edge detection is used to provide deeper imaging of the prostate gland. Combined application of these three algorithms results in improved signal-to-noise ratio, imaging depth, and automatic identification of the cavernous nerves, which may be of direct benefit for use in laparoscopic and robotic nerve-sparing prostate cancer surgery.
Disruption of thymocyte development and lymphomagenesis induced by SV4O T-antigen (1990)

The lck gene encodes a membrane-associated protein tyrosine kinase that is expressed specifically in lymphoid cells, especially thymocytes. Structural analysis of the murine and human lck genes previously identified conserved 5' flanking sequences that were proposed to represent transcriptional regulatory elements. Here we demonstrate that a murine lck promoter construct containing these sequences directs the expression of the SV40 T-antigen gene in lymphoid cells. Remarkably, expression of SV40 T-antigen in transgenic animals dramatically disturbs thymic development, resulting in preferential loss of CD4+CD8+ thymocytes. In contrast, immature cells lacking both CD4 and CD8 markers are present in near-normal numbers. Thus SV40 T-antigen expression appears partially to arrest thymopoiesis. Mice bearing the lck-SV40 transgene develop readily explantable thymic tumors at 12-18 weeks of age. Fluorocytometric analyses of lck-SV40 tumor cells reveal that immature thymocytes are frequently immortalized. The lck-SV40 mouse may therefore provide materials for the in vitro investigation of thymocyte differentiation.
Plasmid-directed synthesis of hepatitis B surface antigen in monkey cells. (1983)

We introduced the gene encoding the hepatitis B virus surface antigen (HBsAg) into simian virus 40 (SV40)-based plasmids capable of autonomously replicating in both Escherichia coli and permissive monkey cells. After introduction into monkey cells by transfection, these plasmids directed the synthesis of high levels of HBsAg, as determined by immunofluorescence, radioimmunoassays, and identification by sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the polypeptides comprising the antigen. Expression was dependent upon the presence of an SV40 promoter, with both the early and late promoters able to effectively initiate transcription. Using expression of HBsAg to assay promoter function, we demonstrated that an intact copy of the SV40 72-base pair repeat, which constitutes an essential element of the SV40 early promoter during the lytic SV40 cycle and which can enhance the transcriptional activity of heterologous promoters, was not required for HBsAg expression, suggesting that the hepatitis genome contains an enhancer element capable of complementing that provided by the 72-base pair repeat element of SV40. The antigen appears to be glycosylated after synthesis in transfected cells and is apparently secreted, as evidenced by the localization of [35S]cysteine-labeled antigen to the medium of transfected cultures. Using constructions in which the first ATG sequence appearing in HBsAg mRNA was that corresponding to the gene encoding the mature form of the antigen, we demonstrated that these post-translational events could occur without the involvement of a putative precursor peptide suggested by the DNA sequence of the viral genome. In view of the inability of hepatitis B virus to propagate in vitro, this strategy offers a convenient approach for further characterizing the biosynthesis of this antigen and may provide a means to identify additional polypeptides encoded by this virus.
Immunochemical localization of the epitope for a monoclonal antibody that neutralizes human platelet-derived growth factor mitogenic activity. (1989)

A monoclonal antibody (mAb), sis 1, generated against human c-sis-encoded platelet-derived growth factor (PDGF) BB, was shown by enzyme-linked immunosorbent assay and Western blot (immunoblot) analysis to recognize human PDGF BB and human platelet PDGF AB but not the human PDGF AA. This monoclonal antibody potently inhibited PDGF receptor-binding and mitogenic activities of both human PDGF BB and PDGF AB but had no effect on PDGF AA. Finally, we demonstrated that an immunoaffinity-purified anti-c-sis peptide antibody (anti-V4) which also blocked binding of PDGF BB to its cognate receptor and competed with mAb sis 1 for binding to PDGF BB. All of these results suggest that mAb sis 1 recognizes an epitope of the c-sis gene product, PDGF BB, that spatially overlaps the V4 surface domain of PDGF BB, immunochemically localizing a region of PDGF BB critical for PDGF receptor binding and activation.
Upconversion Emission Enhancement in Yb3+/Er3+-Codoped Y2O3 Nanocrystals by Tridoping with Li+ Ions (2008)

We demonstrate that tridoping with Li+ ions enhances the visible green and red upconversion (UC) emissions in Er3+/Yb3+-codoped Y2O3 nanocrystals by up to half of the bulk counterpart, i.e., about 2 orders of magnitude higher than previous results. X-ray diffraction and decay time investigations give evidence that tridoping with Li+ ions can tailor the local crystal field of the Y2O3 host lattice. Theoretical calculations illustrate well that a significant UC intensity enhancement arises from the synthesized tailoring effect induced by the Li+ ions, which increase lifetimes in the intermediate 4I11/2 (Er) and 2F5/2 (Yb) states, increase optically active sites in the Y2O3 host lattice, and dissociate the Yb3+ and Er3+ ion clusters in the nanocrytals. The general theoretical description of the visible UC radiations shows that the Yb3+ ion sensitization and the tailoring effect induced by the Li+ ions are two independent enhancement mechanisms, which is expected to lead to an increasing number of photonic and biomedical applications in the future.
THE METABOLISM OF ANTHRACENE DERIVATIVES AND ORGANIC ACIDS IN SELECTEDALOESPECIES (1968)

Die saisonbedingten Veränderungen der Anthrachinone und organischen Säuren in Aloe–Arten werden beschrieben.
Molecular Characterization of Two Types of Resistance in Sunflower to Plasmopara halstedii, the Causal Agent of Downy Mildew (2011)

Depending on host-pathotype combination, two types of sunflower-Plasmopara halstedii incompatibility reactions have previously been identified. Type I resistance can restrict the growth of the pathogen in the basal region of the hypocotyls, whereas type II cannot, thus allowing the pathogen to reach the cotyledons. In type II resistance, a large portion of the hypocotyls is invaded by the pathogen and, subsequently, a hypersensitive reaction (HR) is activated over a long portion of the hypocotyls. Thus, the HR in type II resistance coincides with a higher induction of hsr203j sunflower homologue in comparison with type I resistance, where the HR is activated only in the basal part of hypocotyls. Although the pathogen was not detected in cotyledons of type I resistant plants, semiquantitative polymerase chain reaction confirmed the early abundant growth of the pathogen in cotyledons of susceptible plants by 6 days postinfection (dpi). This was in contrast to scarce growth of the pathogen in cotyledons of type II-resistant plants at a later time point (12 dpi). This suggests that pathogen growth differs according to the host-pathogen combination. To get more information about sunflower downy mildew resistance genes, the full-length cDNAs of RGC151 and RGC203, which segregated with the PlARG gene (resistance type I) and Pl14 gene (resistance type II), were cloned and sequenced. Sequence analyses revealed that RGC151 belongs to the Toll/interleukin-1 receptor (TIR) nucleotide-binding site leucine-rich repeat (NBS-LRR) class whereas RGC203 belongs to class coiled-coil (CC)-NBS-LRR. This study suggests that type II resistance may be controlled by CC-NBS-LRR gene transcripts which are enhanced upon infection by P. halstedii, rather than by the TIR-NBS-LRR genes that might control type I resistance.
A Triphenylamine-Containing Donor−Acceptor Molecule for Stable, Reversible, Ultrahigh Density Data Storage (2007)

A triphenylamine-containing donor−acceptor molecule was designed and synthesized. Its thin film showed excellent bistable electronic switching behavior with a high ON/OFF current ratio. With this molecule, stable, reliable, and reversible ultrahigh density data storage was demonstrated using STM.
Integrin cytoplasmic domains mediate inside-out signal transduction (1994)

We analyzed the binding of fibronectin to integrin alpha 5 beta 1 in various cells; in some cells fibronectin bound with low affinity (e.g., K562 cells) whereas in others (e.g., CHO), it bound with high affinity (Kd approximately 100 nM) in an energy-dependent manner. We constructed chimeras of the extracellular and transmembrane domains of alpha IIb beta 3 joined to the cytoplasmic domains of alpha 5 beta 1. The affinity state of these chimeras was assessed by binding of fibrinogen or the monoclonal antibody, PAC1. The cytoplasmic domains of alpha 5 beta 1 conferred an energy-dependent high affinity state on alpha IIb beta 3 in CHO but not K562 cells. Three additional alpha cytoplasmic domains (alpha 2, alpha 6A, alpha 6B) conferred PAC1 binding in CHO cells, while three others (alpha M, alpha L, alpha v) did not. In the high affinity alpha chimeras, cotransfection with a truncated (beta 3 delta 724) or mutated (beta 3(S752-->P)) beta 3 subunit abolished high affinity binding. Thus, both cytoplasmic domains are required for energy-dependent, cell type-specific affinity modulation. In addition, mutations that disrupted a highly conserved alpha subunit GFFKR motif, resulted in high affinity binding of ligands to alpha IIb beta 3. In contrast to the chimeras, the high affinity state of these mutants was independent of cellular metabolism, cell type, and the bulk of the beta subunit cytoplasmic domain. Thus, integrin cytoplasmic domains mediate inside-out signaling. Furthermore, the highly conserved GFFKR motif of the alpha subunit cytoplasmic domain maintains the default low affinity state.
Essential fatty acids and their metabolites could function as endogenous HMG-CoA reductase and ACE enzyme inhibitors, anti-arrhythmic, anti-hypertensive, anti-atherosclerotic, anti-inflammatory, cytoprotective, and cardioprotective molecules (2008)

Lowering plasma low density lipoprotein-cholesterol (LDL-C), blood pressure, homocysteine, and preventing platelet aggregation using a combination of a statin, three blood pressure lowering drugs such as a thiazide, a beta blocker, and an angiotensin converting enzyme (ACE) inhibitor each at half standard dose; folic acid; and aspirin-called as polypill- was estimated to reduce cardiovascular events by approximately 80%. Essential fatty acids (EFAs) and their long-chain metabolites: gamma-linolenic acid (GLA), dihomo-GLA (DGLA), arachidonic acid, eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) and other products such as prostaglandins E1 (PGE1), prostacyclin (PGI2), PGI3, lipoxins (LXs), resolvins, protectins including neuroprotectin D1 (NPD1) prevent platelet aggregation, lower blood pressure, have anti-arrhythmic action, reduce LDL-C, ameliorate the adverse actions of homocysteine, show anti-inflammatory actions, activate telomerase, and have cytoprotective properties. Thus, EFAs and their metabolites show all the classic actions expected of the "polypill". Unlike the proposed "polypill", EFAs are endogenous molecules present in almost all tissues, have no significant or few side effects, can be taken orally for long periods of time even by pregnant women, lactating mothers, and infants, children, and adults; and have been known to reduce the incidence cardiovascular diseases including stroke. In addition, various EFAs and their long-chain metabolites not only enhance nitric oxide generation but also react with nitric oxide to yield their respective nitroalkene derivatives that produce vascular relaxation, inhibit neutrophil degranulation and superoxide formation, inhibit platelet activation, and possess PPAR-gamma ligand activity and release NO, thus prevent platelet aggregation, thrombus formation, atherosclerosis, and cardiovascular diseases. Based on these evidences, I propose that a rational combination of omega-3 and omega-6 fatty acids and the co-factors that are necessary for their appropriate action/metabolism is as beneficial as that of the combined use of a statin, thiazide, a beta blocker, and an angiotensin converting enzyme (ACE) inhibitor, folic acid, and aspirin. Furthermore, appropriate combination of omega-3 and omega-6 fatty acids may even show additional benefits in the form of protection from depression, schizophrenia, Alzheimer's disease, and enhances cognitive function; and serve as endogenous anti-inflammatory molecules; and could be administered from childhood for life long.
Successful Treatment of Severe Tardive Dyskinesia with Valbenazine, Including a Patient’s Perspective (2017)

BACKGROUND Tardive dyskinesia (TD) is a chronic involuntary movement disorder frequently induced by dopamine receptor blockers, particularly first-generation antipsychotics. Until recently, management of TD was restricted to lowering the dose of the current medication, switching to another medication, or using off-label treatments with insufficient evidence of efficacy. Valbenazine, a vesicular monoamine transporter-2 (VMAT2) inhibitor, became the first drug to be approved by the FDA specifically for the treatment of TD. CASE REPORT We describe the case of a 49-year-old African-American woman who was diagnosed with bipolar disorder at the age of 34 and treated with lithium carbonate (900 mg daily) and citalopram (10 mg daily). She also received low doses of second-generation antipsychotics for weeks at a time, but these were always discontinued due to severe sedation. Over a decade later, at the age of 45, she experienced rapid onset of severe TD symptoms. She enrolled in a phase III double-blind clinical trial and received valbenazine 80 mg, with encouraging results. CONCLUSIONS Once-daily dosing of valbenazine (80 mg) was effective and safe over a long period, even in this atypical case of severe and rapid-onset TD.
Structural Assessment and Catalytic Consequences of the Oxygen Coordination Environment in Grafted Ti−Calixarenes (2007)

Calixarene-Ti complexes were grafted onto SiO2 (0.18-0.24 Ti nm-2) to form isolated and accessible Ti centers persistently coordinated to multidentate calixarene ligands. Grafted Ti-tert-butylcalix[4]arenes gave Ti K-edge absorption spectra with pre-edge features at 4968.6-4968.9 eV, independently of Ti surface density and of their use in epoxidation catalysis. The structure and reactivity of grafted Ti-calix[4]arenes were weakly dependent on thermal treatment below 573 K, and the relative epoxidation rates of trans- and cis-alkenes showed that calixarene ligands did not restrict access to Ti centers more than corresponding calcined Ti-SiO2 materials. For all materials, 13C NMR and UV-visible spectroscopies confirmed the presence of Ti-O-Si connectivity and identical ligand-to-metal transitions. Grafted Ti-homooxacalix[3]arene complexes, however, gave weaker pre-edge features at higher energies ( approximately 4969.5 eV), consistent with greater Ti 3d occupancy and coordination numbers greater than four, and 20-fold lower cyclohexene epoxidation rate constants (per Ti) than on calix[4]arene-based materials. These different rates and near-edge spectra result from aldehyde formation caused by unimolecular cleavage of ether linkages in homooxacalix[3]arene ligands during grafting, leading to higher coordination and electron density at Ti centers. Materials based on tert-butylcalix[4]arene and homooxacalix[3]arenes led to similar epoxidation rates and near-edge spectra after calcination, consistent with the conversion of both materials to isolated Ti centers with identical structure. These materials provide a systematic approach for relating oxidation reactivity to Ti 3d occupancy, a descriptor of Lewis acid strength, and Ti coordination, because they provide Ti centers with varying electron density and coordination, but maintain accessible active centers with uniform structure and unrestricted access to reactants.