gebhart/patrepeval huggingface dataset:
Temperature-Activated Nucleic Acid Nanostructures (2013)

DNA and poly(N-isopropylacrylamide) are co-assembled onto gold nanoparticles. The DNA sequences can be reversibly exposed or hidden from the polymer surface in response to temperature cues, thereby translating the temperature trigger to the on-off switching of the surface chemistry and function. When exposed by heating (∼30 °C), the DNA rapidly hybridizes to complementary strands, and chain-end biotin groups become readily accessible, while at lower temperatures these activities are largely blocked.
High-throughput Approaches to Uncover Synergistic Drug Combinations in Leukemia (2022)

ABSTRACT We report a comprehensive drug synergy study in acute myeloid leukemia (AML). In this work, we investigate 11 cell lines spanning both MLL-rearranged and non-rearranged subtypes. The work comprises a resource for the community, with many synergistic drug combinations that could not have been predicted a priori , and open source code for automation and analyses. We base our definitions of drug synergy on the Chou-Talalay method, which is useful for visualizations of synergy experiments in isobolograms, and median-effects plots, among other representations. Our key findings include drug synergies affecting the chromatin state, specifically in the context of regulation of the modification state of histone H3 lysine-27. We report open source high throughput methodology such that multidimensional drug screening can be accomplished with equipment that is accessible to most laboratories. This study will enable preclinical investigation of new drug combinations in a lethal blood cancer, with data analysis and automation workflows freely available to the community. Abstract Figure
Design and Evaluation of Dengue NS3 Protease Peptide Inhibitors (2012)

Viruses are a major threat to humans due to their unique adaptability, evolvability and capability to control their hosts as parasites and genetic elements. HIV/AIDS is the third largest cause of death by infectious diseases in the world, and drug resistance due to the viral mutations is still the leading cause of treatment failure. The flaviviruses, such as Dengue virus (DEN) and Japanese encephalitis virus (JEV), represent other major cause of morbidity and mortality, and the areas where these viruses are endemic are spreading rapidly. No curative therapy for any flavivirus could be made available as yet.The first part of this thesis focuses on the HIV-1 drug resistance caused by mutations in a major HIV drug target, the HIV-1 reverse transcriptase (RT) as a response to the largest class of clinically used anti-retrovirals, the NRTIs. A robust proteochemometric model was created to analyse the complex mutation patterns in RT drug resistance. The model identified more than ten frequently-occurring mutations, each conferring at least two-fold decrease in susceptibility for one or several NRTIs. Using our prediction server (hivdrc.org), the model can be applied to propose optimum combination therapy for patients harbouring mutated HIV variants.The second part of the thesis encompasses studies on a promising drug target, the NS2B(H)-NS3pro, in two flaviviruses, namely the dengue virus (DEN) and Japanese encephalitis virus (JEV). Functional determinants of DEN NS2B(H)-NS3pro were identified by site-directed mutagenesis. Further, peptide inhibitors were designed using proteochemometrics (PCM) and statistical molecular design (SMD), synthesized and assayed on DEN proteases, which resulted in some novel peptides with low micromolar or sub-micromolar inhibitor activity. The very poorly characterised JEV NS2B(H)-NS3pro was cloned, purified and the kinetic parameters of this attractive drug target were determined for a series of model substrates and inhibitor. The results identified the role in target-ligand interaction of different residues on specific positions in the target (NS2B(H)-NS3pro) and ligands (substrates/inhibitors).Overall, the findings in this thesis contribute to rational antiviral drug discovery and therapy.
Pulse buildup in passively mode-locked monolithic quantum-well semiconductor lasers (1993)

The buildup of pulses in a passively mode-locked monolithic semiconductor laser is investigated experimentally and theoretically. A simple model, based on competition between the fundamental and higher order mode-locking ‘‘supermodes,’’ gives a time constant for the buildup in good agreement with the experimental values, which are on the order of 3.5 ns. The theory shows that to minimize the pulse buildup time, the photon life time and the width of the gain spectrum should be minimized, and the gain and the gain modulation, should be maximized.
Lycian Erimñnuha (2019)

AbstractThe article takes a closer look at the Lycian name Erimñnuha. The analysis of this name is the basis for the study of several other Lycian names, all containing the element Mñnu-.
Local structural deformation in[Zn(1−propyltetrazole)6](BF4)2and[Fe(1−propyltetrazole)6](BF4)2crystals observed by positron-annihilation spectroscopy (1998)

The two-dimensional angular correlation spectra of 2\ensuremath{\gamma} annihilation radiation (2D-ACAR) from single crystals of ${[\mathrm{Zn}(1\ensuremath{-}\mathrm{p}\mathrm{r}\mathrm{o}\mathrm{p}\mathrm{y}\mathrm{l}\mathrm{t}\mathrm{e}\mathrm{t}\mathrm{r}\mathrm{a}\mathrm{z}\mathrm{o}\mathrm{l}\mathrm{e})}_{6}{](\mathrm{B}\mathrm{F}}_{4}{)}_{2}$ at 30, 150, and 290 K and ${[\mathrm{Fe}(1\ensuremath{-}\mathrm{p}\mathrm{r}\mathrm{o}\mathrm{p}\mathrm{y}\mathrm{l}\mathrm{t}\mathrm{e}\mathrm{t}\mathrm{r}\mathrm{a}\mathrm{z}\mathrm{o}\mathrm{l}\mathrm{e})}_{6}{](\mathrm{B}\mathrm{F}}_{4}{)}_{2}$ at 150 and 290 K have been measured. A structural deformation in ${[\mathrm{Zn}(1\ensuremath{-}\mathrm{p}\mathrm{r}\mathrm{o}\mathrm{p}\mathrm{y}\mathrm{l}\mathrm{t}\mathrm{e}\mathrm{t}\mathrm{r}\mathrm{a}\mathrm{z}\mathrm{o}\mathrm{l}\mathrm{e})}_{6}{](\mathrm{B}\mathrm{F}}_{4}{)}_{2}$ has been observed through the change of the momentum distribution of the positronium. The similarity of the anisotropies of the 2D-ACAR spectra for ${[\mathrm{Zn}(1\ensuremath{-}\mathrm{p}\mathrm{r}\mathrm{o}\mathrm{p}\mathrm{y}\mathrm{l}\mathrm{t}\mathrm{e}\mathrm{t}\mathrm{r}\mathrm{a}\mathrm{z}\mathrm{o}\mathrm{l}\mathrm{e})}_{6}{](\mathrm{B}\mathrm{F}}_{4}{)}_{2}$ and ${[\mathrm{Fe}(1\ensuremath{-}\mathrm{p}\mathrm{r}\mathrm{o}\mathrm{p}\mathrm{y}\mathrm{l}\mathrm{t}\mathrm{e}\mathrm{t}\mathrm{r}\mathrm{a}\mathrm{z}\mathrm{o}\mathrm{l}\mathrm{e})}_{6}{](\mathrm{B}\mathrm{F}}_{4}{)}_{2}$ in the rhombohedral structure indicates that a similar structural deformation also takes place in ${[\mathrm{Fe}(1\ensuremath{-}\mathrm{p}\mathrm{r}\mathrm{o}\mathrm{p}\mathrm{y}\mathrm{l}\mathrm{t}\mathrm{e}\mathrm{t}\mathrm{r}\mathrm{a}\mathrm{z}\mathrm{o}\mathrm{l}\mathrm{e})}_{6}{](\mathrm{B}\mathrm{F}}_{4}{)}_{2}.$ This deformation can be the trigger of the spin-crossover transition.
<title>3D display with focused light array</title> (1996)

The performance of an electro-holographic display has been limited by space and spatial bandwidth of spatial light modulators. This paper presents a new type 3D display using numerous small-size light sources. The concept of the display is based on the electro- holographic display using acousto-optic devices. Each light source is aligned on a circle at narrow intervals, and its output beam is focused on the center of the circle. Its focal point or the image of its focal point is scanned by the mechanical X-Y scanner, and each light's intensity is modulated by each parallax image of the viewing angle. This display can produce big-and-natural 3D images with high resolution and high refresh-rate.
Trial Watch (2014)

Toll-like receptors (TLRs) are an evolutionarily conserved group of enzymatically inactive, single membrane-spanning proteins that recognize a wide panel of exogenous and endogenous danger signals. Besides constituting a crucial component of the innate immune response to bacterial and viral pathogens, TLRs appear to play a major role in anticancer immunosurveillance. In line with this notion, several natural and synthetic TLR ligands have been intensively investigated for their ability to boost tumor-targeting immune responses elicited by a variety of immunotherapeutic and chemotherapeutic interventions. Three of these agents are currently approved by the US Food and Drug Administration (FDA) or equivalent regulatory agencies for use in cancer patients: the so-called bacillus Calmette-Guérin, monophosphoryl lipid A, and imiquimod. However, the number of clinical trials testing the therapeutic potential of both FDA-approved and experimental TLR agonists in cancer patients is stably decreasing, suggesting that drug developers and oncologists are refocusing their interest on alternative immunostimulatory agents. Here, we summarize recent findings on the use of TLR agonists in cancer patients and discuss how the clinical evaluation of FDA-approved and experimental TLR ligands has evolved since the publication of our first Trial Watch dealing with this topic.
Change in cervical length after prophylactic cerclage (1999)

Prophylactic cerclage results in measurable increases in cervical length, which might contribute to the success of the procedure. Further study is needed to determine whether the degree of cervical lengthening after cerclage predicts term delivery.
Reversible Soft-Contact Lamination and Delamination for Non-Invasive Fabrication and Characterization of Bulk-Heterojunction and Bilayer Organic Solar Cells (2010)

Soft-contact lamination (ScL) provides a means to non-invasively establish electrical contact in organic solar cells. In contrast to the typical bottom-up fabrication approaches wherein active components are deposited sequentially in a layer-by-layer fashion, ScL allows individual functional layers to be separately deposited and optimized before these isolated components are brought together to complete the devices. Lamination and delamination of top electrodes to and from the active layer, respectively, are reversible and thus enables the characterization of the once-buried active layer after device processing and testing. ScL also enables the fabrication and characterization of bilayer organic solar cells comprising electron donors and electron acceptors that have comparable solubilities, the fabrication of which would not have been possible with the standard bottom-up approaches.
Scaling rules for flow focusing devices: From standard to large FFDs for cell encapsulation in alginates (2009)

Flow focusing devices (FFDs), with dimensions smaller than 100 mum have recently been used for cell encapsulation. However, encapsulation of larger clusters of cells, like islets of Langerhans, is of considerable interest. Producing larger capsules requires larger FFDs. We focus here on the geometrical scaling-up between a small FFD (50 mum) and a larger one (100 mum, 200 mum, 1 mm). We determine the driving pressure conditions to obtain the droplet regime at any size of the FFD. A similar behavior of the device is experimentally obtained by a scaling of the dimensions by a ratio lambda and a scaling of the driving pressures by the ratio 1/lambda.
Diphenylacetylene‐Linked Peptide Strands Induce Bidirectional β‐Sheet Formation (2014)

Abstract In the search for synthetic mimics of protein secondary structures relevant to the mediation of protein–protein interactions, we have synthesized a series of tetrasubstituted diphenylacetylenes that display β‐sheet structures in two directions. Extensive X‐ray crystallographic and NMR solution phase studies are consistent with these proteomimetics adopting sheet structures, displaying both hydrophobic and hydrophilic amino acid side chains.
Risk Factors for Myocardial Injury in Patients with Coronavirus Disease 2019 in China (2020)

Abstract Aims In patients with coronavirus disease 2019 (COVID-19), the involvement of the cardiovascular system significantly relates to poor prognosis. However, the risk factors for acute myocardial injury have not been sufficiently studied. Thus, we aimed to determine the characteristics of myocardial injury and define the association between routine blood markers and cardiac troponin I, in order to perform a predictive model. Methods and results This retrospective cohort study included patients with confirmed COVID-19 from Wuhan Tongji Hospital (Wuhan, China). Data were compared between those with and without myocardial injury. Kaplan–Meier analysis and Cox regression models were used to describe the association between myocardial injury and poor prognosis. Simple correlation analyses were used to find factors associated with high-sensitivity cardiac troponin I levels. Univariate and multivariate logistic regression methods were used to explore the risk factors associated with myocardial injury. The area under the receiver operating characteristic curve was used to determine the predictive value of the model. Of 353 patients included in the study, 79 presented myocardial injury. Patients with myocardial injury had higher levels of inflammation markers, poorer liver and kidney function, and more complications compared with patients without myocardial injury. High-sensitivity cardiac troponin I levels were significantly associated with neutrophil/lymphocyte ratio, creatinine, d-dimer, lactate dehydrogenase, and inflammatory cytokines and negatively associated with oxygen saturation. It was significantly associated with poor prognosis after adjusting for age, sex, and complications. Multivariate regression showed that myocardial injury was associated with a high neutrophil/lymphocyte ratio (odds ratio 2.30, 95% CI 1.11–4.75, per standard deviation increase, P = 0.02), creatinine (3.58, 1.35–8.06, P = 0.01), and lactate dehydrogenase (3.39, 1.42–8.06, P = 0.01) levels. Using a predictive model, the area under the receiver operating characteristic curve was 0.92 (0.88–0.96). Conclusions In patients with COVID-19, neutrophil/lymphocyte ratio, creatinine, and lactate dehydrogenase are blood markers that could help identify patients with a high risk of myocardial injury at an early stage.
Abdominal Aortic Calcification is an Independent Predictor of Cardiovascular Events in Peritoneal Dialysis Patients (2012)

Abdominal aortic calcification (AAC) is reported as a predictor for cardiovascular events in general population and in hemodialysis patients. At present, there are no AAC data in peritoneal dialysis. The purpose of this study was to evaluate the prognostic role of AAC score on cardiovascular events in peritoneal dialysis patients. Seventy-four peritoneal dialysis patients were enrolled. AAC was measured on baseline lateral abdomen radiographs by the semi-quantitative method as described by Kauppila. The other cardiovascular risk factors were obtained from patient history and blood examination. The Kaplan-Meier method was used to evaluate freedom from cardiovascular events, and differences were assessed with the log-rank statistic. Multivariate Cox regression models addressed time to cardiovascular events. The median period of follow-up was 30.5months (IQR 19.4-32.7). During follow-up, there were 29 cardiovascular events (39.2%). In univariable analysis, patient's age (HR=1.050; P=0.001), urine output (HR=0.999; P=0.02), and AAC stratified by tertiles (overall P-value<0.001) were significantly associated with cardiovascular events. In multivariable regression analysis, AAC score stratified by tertiles was the only independent predictor for cardiovascular events (overall P-value<0.001). To our knowledge, we have shown for the first time that AAC score is an independent predictor of cardiovascular events in peritoneal dialysis patients. Risk stratification by assessment of AAC score may provide important information for the management of cardiovascular disease in peritoneal dialysis patients without any additional expense, because these patients have several abdominal X-ray scans to evaluate the catheter position.
Layer-by-Layer Self-Assembled Pyrrole-Based Donor−Acceptor Chromophores as Electro-Optic Materials (2003)

The synthesis of the heterocycle-based diethanolaminomethyl-functionalized derivative 1-(pyridin-4-yl)-2-[(N-methylpyrrol-2-yl)-5-methylenediethanolamine]ethene (2) from (1-pyridin-4-yl)-2-(N-methyl-pyrrol-2-yl)ethene (1) and their methylpyridinium dyes 1-(N-methylpyridinio)-2-[(N-methylpyrrol-2-yl)-5-methylenediethanolamine]ethene iodide (3) and 1-(N-methylpyridinio)-2-[(N-methylpyrrol-2-yl)-5-methylenediethanolamine]ethene iodide (4) is described. NLO-active chromophore monolayers SA-1 and SA-2 were obtained by reaction of p-iodomethylphenyldiiodochlorosilane (5)-functionalized substrates and dye precursors 1 and 2, respectively. A χ(2) value of ∼120 pm/V is observed for SA-2. The new diethanolaminomethyl-functionalized chromophore 2 is also a suitable building block for the layer-by-layer formation of intrinsically acentric, highly transparent nonlinear optical/electro-optic multilayers (SAS = self-assembled superlattice). The organic SAS films are characterized by a combination of physicochemical methods including synchrotron specular X-ray reflectivity, angle-dependent polarized second-harmonic generation, optical (absorption and photoluminescence) spectroscopy, X-ray photospectroscopy, atomic force microscopy, and advancing contact angle measurements.
Pharmacologic Targeting of TFIIH Suppresses KRAS-Mutant Pancreatic Ductal Adenocarcinoma and Synergizes with TRAIL (2022)

Pancreatic ductal adenocarcinoma (PDAC) typically presents as metastatic disease at diagnosis and remains refractory to treatment. Next-generation sequencing efforts have described the genomic landscape, classified molecular subtypes, and confirmed frequent alterations in major driver genes, with coexistent alterations in KRAS and TP53 correlating with the highest metastatic burden and poorest outcomes. However, translating this information to guide therapy remains a challenge. By integrating genomic analysis with an arrayed RNAi druggable genome screen and drug profiling of a KRAS/TP53 mutant PDAC cell line derived from a patient-derived xenograft (PDCL), we identified numerous targetable vulnerabilities that reveal both known and novel functional aspects of pancreatic cancer biology. A dependence on the general transcription and DNA repair factor TFIIH complex, particularly the XPB subunit and the CAK complex (CDK7/CyclinH/MAT1), was identified and further validated utilizing a panel of genomically subtyped KRAS mutant PDCLs. TFIIH function was inhibited with a covalent inhibitor of CDK7/12/13 (THZ1), a CDK7/CDK9 kinase inhibitor (SNS-032), and a covalent inhibitor of XPB (triptolide), which led to disruption of the protein stability of the RNA polymerase II subunit RPB1. Loss of RPB1 following TFIIH inhibition led to downregulation of key transcriptional effectors of KRAS-mutant signaling and negative regulators of apoptosis, including MCL1, XIAP, and CFLAR, initiating caspase-8 dependent apoptosis. All three drugs exhibited synergy in combination with a multivalent TRAIL, effectively reinforcing mitochondrial-mediated apoptosis. These findings present a novel combination therapy, with direct translational implications for current clinical trials on metastatic pancreatic cancer patients. Significance: This study utilizes functional genetic and pharmacological profiling of KRAS-mutant pancreatic adenocarcinoma to identify therapeutic strategies and finds that TFIIH inhibition synergizes with TRAIL to induce apoptosis in KRAS-driven pancreatic cancer.
Prohormone brain natriuretic peptide (proBNP), BNP and N-terminal-proBNP circulating levels in chronic hemodialysis patients. Correlation with ventricular function, fluid removal and effect of hemodiafiltration (2008)

Despite their elimination, BNP, NT-proBNP and proBNP could be potential markers of left ventricular remodeling in chronic renal failure patients on hemodialysis. According to these results, their cut-off values, however, need to be re-evaluated.
Abstract A138: Evaluation of neonatal Fc receptor (FcRn) expression and function in tumor cell lines and their potential effect on IgG disposition in solid tumors. (2011)

Abstract The human neonatal Fc receptor, hFcRn, is a trafficking receptor for human IgG expressed by various cell types such as vascular endothelial cells, antigen presenting cells, and colorectal, mammary, and pulmonary epithelial cells. Binding of FcRn by monomeric IgG occurs in a pH-restricted manner and, depending on the interacting cell type, can lead to IgG recycling or transcytosis. The recycling pathway is predominant in the vascular endothelium and it traffics IgG away from lysosomal degradation; transcytotic IgG transport, on the other hand, has been more commonly observed in intestinal, breast, and lung epithelium. We hypothesize that solid tumors originating from FcRn-expressing epithelia maintain FcRn expression and that functional expression of FcRn in tumors may affect IgG subcellular trafficking, metabolism, and overall tumor disposition. In the investigations presented herein, we provide quantitative evidence of robust FcRn expression by colorectal and breast tumor cell lines as examined by Flow-Assisted Cell Sorting (FACS) and Western Blotting. Furthermore, we show by Fluorescence Microscopy in selected cell lines that FcRn is localized in both early and recycling endosomes and that its localization in recycling endosomes supports its function in these cells, which is also shown by FACS to be predominantly that of a recycling receptor. To evaluate our hypothesis in vivo, we have developed and characterized an hFcRn mouse tumor model in which hFcRn expression is conditional on doxycycline dosing. Briefly, hFcRn-transduced HM7 colorectal tumor cells (HM7-hFcRn+) implanted into athymic nude mice were evaluated as a function of growth kinetics, vascular volume, and hFcRn expression for up to 14 days following cell inoculation. We show by immunohistochemical staining and FACS substantial hFcRn expression in HM7-FcRn+ tumors relative to parental HM7 tumors during the course of study. Tumor growth and tumor vascular volumes were similar to the parental model as shown by caliper measurements and indirect (99m)Tc red blood cell labeling, respectively, suggesting that this model is appropriate for our purpose. These results provide evidence of hFcRn expression in colorectal and breast cancer cell lines commonly used in xenograft studies and suggest that such expression may lead to IgG recycling in these cell types. Furthermore, we have developed a mouse tumor model that will allow us to determine whether the recycling function of hFcRn observed in vitro translates to an in vivo setting and its effect on IgG tumor distribution, metabolism, and ultimately, anti-tumor efficacy. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2011 Nov 12-16; San Francisco, CA. Philadelphia (PA): AACR; Mol Cancer Ther 2011;10(11 Suppl):Abstract nr A138.
The Multidisciplinary Heart Team in Cardiovascular Medicine (2023)

Cardiovascular multidisciplinary heart teams (MDHTs) have evolved significantly over the past decade. These teams play a central role in the treatment of a wide array of cardiovascular diseases affecting interventional cardiology, cardiac surgery, interventional imaging, advanced heart failure, adult congenital heart disease, cardio-oncology, and cardio-obstetrics. To meet the specific needs of both patients and heart programs, the composition and function of cardiovascular MDHTs have had to adapt and evolve. Although lessons have been learned from multidisciplinary cancer care, best practices for the operation of cardiovascular MDHTs have yet to be defined, and the evidence base supporting their effectiveness is limited. This expert panel review discusses the history and evolution of cardiovascular MDHTs, their composition and role in treating patients across a broad spectrum of disciplines, basic tenets for successful operation, and the future challenges facing them.