gebhart/patrepeval huggingface dataset:
The Hidden Component of Size in Two-Dimensional Fragment Descriptors:  Side Effects on Sampling in Bioactive Libraries (1999)

We have carried out a number of sampling experiments in libraries of bioactive compounds to illustrate how size biases introduced by two-dimensional (2D) fragment distance functions may provide misleading information about the diversity of compound subsets. The number of different biological targets covered by a given subset is used as a measure of bioactive diversity, and it is considered to be the relevant property with which 2D diversity should correlate. Since the nature of the size biases depends on the way in which 2D distance is computed, we investigated three different methods of calculating distance. Use of 1-Tanimoto as a dissimilarity measure leads to the spurious conclusion that collections of structurally small compounds are inherently more diverse than other collections which may cover a broader range of sizes and more biological targets. XOR or squared Euclidean distance, by contrast, shows a preference for subsets of structurally larger compounds, but this does not appear to have as many adverse consequences in terms of target coverage. A simple product of 1-Tanimoto and XOR tends to equalize the opposing size effects of the two component distance functions and leads to a relatively unbiased means of comparing structures. Results here suggest that careful consideration should be given to the way in which chemical structures are compared whenever 2D fragment descriptors are used.
Abstract B39: Identifying molecular signatures of tumor dormancy as a basis for the rational design of precision nanomedicines (2016)

Abstract Tumor progression is dependent on a number of sequential steps, including initial tumor-vascular interactions and recruitment of blood vessels (i.e., the “angiogenic switch”), as well as an established interaction of tumor cells with their surrounding microenvironment and its different immune, endothelial and connective cellular and extra-cellular components. Failure of a microscopic tumor, either primary, recurrent or metastatic, to complete one or more of these early stages may lead to delayed clinical manifestation of the cancer (i.e., tumor dormancy). Micrometastasis, dormant tumors, and residual tumor cells - referred to as minimal residual disease, contribute to the occurrence of relapse, and constitute fundamental clinical manifestations of tumor dormancy that together are responsible for the vast majority of cancer deaths. However, although the tumor dormancy phenomenon has critical implications for early detection and treatment of cancer, it is one of the most neglected areas in cancer research and the associated biological mechanisms are still mostly unknown. We have created several models of patient-derived xenografts mimicking pairs of dormant vs fast-growing, primary vs metastatic and drug-sensitive vs resistant cancers. We investigated the molecular and cellular changes in tumor-host interactions that govern tumor progression. Those led to the discovery of novel targets and provided important tools for cancer theranostics (therapy and diagnostics). Based on the acquired knowledge, we designed a new strategy to improve treatment outcomes of patients with bone neoplasms, glioblastoma, brain metastases, melanoma, breast and prostate cancers. We have identified molecular signatures which following their selective delivery into target cells, can potentially induce a dormant-like phenotype. This goal was achieved by utilizing polymeric nanomedicines and guidance by high resolution, intravital non-invasive imaging techniques. A better understanding of tumor dormancy and the availability of relevant markers will most likely change the way we diagnose and treat the disease using novel combined theranostic nanomedicines. Citation Format: Galia Tiram, Shiran Ferber, Ronit Satchi-Fainaro. Identifying molecular signatures of tumor dormancy as a basis for the rational design of precision nanomedicines. [abstract]. In: Proceedings of the AACR Special Conference: Function of Tumor Microenvironment in Cancer Progression; 2016 Jan 7–10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2016;76(15 Suppl):Abstract nr B39.
Comparative study of resolution limits for double patterning and EUV processes for the 32nm contact hole case (2010)

Currently, EUV and double patterning (DP) are competing technologies for the 22nm hp node. The goal of this paper is to perform a case study and explore resolution limits on a 32nm contact hole array. In order to investigate the resolution limit for a DP process quantitatively, considering the substrate topography structure is crucial. We applied wafertopography/ lithography simulation to study the relevant effects in detail. To perform a comparative study between ArF DP and EUV lithography we first analyzed the resolution limit for DP process. We investigated the performance of a LDLD and a LFLE (litho-freeze-litho-etch) process by decreasing pitch until the resolution limit was reached. The possible minimum x- pitch (with y-parallel line, first mask) is 85nm, the minimum y-pitch generated for the second litho step with x-parallel lines is 90nm. This x-y anisotropic phenomenon is caused by the second litho step, where oblique incident light propagating through space regions contributes to total image. The bulk image distribution is sensitive to the material in the spacer region, therefore further process optimization is possible by tuning material properties. Alternatively the fabrication of 32nm size contact holes with EUV lithography was simulated. Pattern shift due to shadowing, aberrations and flare effects have been considered. A pitch of 64nm (1:1) can be realized at low flare levels, but corrections for shadowing and flare are essential. Based on this quantification the gap of possible minimum pitch between DP and EUV are discussed. Furthermore relation between DP topography effect and SMO are discussed.
Intrinsic Instabilities in Homogeneously Broadened Lasers (1983)

Experimental observation has shown that it is no simple matter to make a homogeneously broadened laser operate in a single longitudinal mode. However, elementary theoretical treatments of homogeneously broadening predict that such lasers can operate in only a single mode, because all of the atoms constituting the gain medium experience identical degrees of saturation.
A methylation-mediator complex in hormone signaling (2004)

The recruitment of coactivators by nuclear hormone receptors (NRs) promotes transcription by subverting chromatin-mediated repression. Although the histone methylation enzyme CARM1 and an ATP-remodeling complex have been individually implicated in nuclear receptor-dependent transcription, neither a functional nor mechanistic linkage between these systems has been identified. In the process of purifying endogenous CARM1-interacting proteins, we identified an associated complex, nucleosomal methylation activator complex (NUMAC), which includes at least eight components of SWI/SNF, including the ATPase BRG1. In the NUMAC complex, the methylase, CARM1, acquires the ability to covalently modify nucleosomal histones, and the directed nucleosome versus free core histone methylation-specificity change is increased dramatically. Reciprocally, CARM1 stimulates the ATPase activity of BRG1, a key component in nucleosome remodeling. In vivo, CARM1 and BRG1 coassemble on an estrogen receptor (ER)-target gene to cooperatively activate ER-dependent transcription. This association of ATP-remodeling factors with HMT CARM1 defines a new component of regulation in the nuclear hormone-signaling pathway.
Easy-plane spin Hall nano-oscillators as spiking neurons for neuromorphic computing (2022)

Ferromagnetic nanoconstrictions can serve as integrate-and-fire neurons, communicating via spin-wave pulses analogous to neural spikes. The nanoconstriction geometry leads to easy-plane oscillators which manifest phase dynamics analogous to damped driven oscillators. The authors propose a sample geometry where nanoconstrictions undergo phase slips and produce pulses of spin-wave signals when triggered by a small spin torque. They show with the help of macrospin modeling and micromagnetic simulations that these spin-wave pulses can excite other nanoconstriction neurons and that they possess the basic fan-in and fan-out capability required for neuromorphic systems.
Systèmes de détention et concept de mesure des émissions d'ammoniac en cas d'aération naturelle (2011)

The relevant housing systems and a suitable measuring concept have to be defined in order to improve the data base for ammonia emissions (NH&lt;sub&gt;3&lt;/sub&gt;) from cattle farming. Statistics and an expert survey show that the proportion of loose housing facilities and outdoor exercise areas in Switzerland increased from 5 % in 1990 to around 40 % in 2010. Experts identified the most common situation in dairy cattle loose housing as a naturally ventilated single-building stable with cubicles, solid floors and an outdoor exercise yard alongside. The design of a measuring concept to quantify emissions should represent emissions from naturally ventilated stables and outdoor exercise areas without influencing livestock activity or the stable climate. The tracer ratio method is established for measurements in naturally ventilated stables. This enables real-time measurements under practical conditions. To derive emission factors, measurements on several commercial farms are required. The great climatic variation in outdoor climate housing systems over the course of the year can be recorded by means of measurements spread systematically throughout the year. Measurements were taken over 24 hour periods as well as high temporal resolution map daily patterns and short-term events. The interpretation of these emission data requires to record relevant accompanying parameters with information on the animals, feeding, housing and traffic area soiling as well as on management and climate.
Unplanned admissions for patients with myeloma in the UK: Low frequency but high costs (2019)

MM is associated with a significant number of hospital admissions and NHS costs. The majority of the hospital admissions are elective, but the highest burden in terms of costs relates to unplanned admissions, with numbers increasing over time.
Fra-1/AP-1 Impairs Inflammatory Responses and Chondrogenesis in Fracture Healing (2009)

Inflammation inevitably follows injury of various tissues, including bone. Transgenic overexpression of Fra-1, a component of the transcription factor activator protein-1 (AP-1), in various tissues progressively and globally enhances bone formation, but little is known about the possible effects of Fra-1/AP-1 on fracture healing. We created a transverse fracture of the mouse tibial diaphysis and examined fracture healing radiologically, histologically, and immunologically. Strikingly, fracture union was delayed even though the bone formation rate in callus was higher in Fra-1 transgenic (Tg) mice. In these mice, chondrogenesis around the fracture site was impaired, resulting in accumulation of fibrous tissue, which interferes with the formation of a bony bridge across the callus. Curiously, immediately after fracture, induction of the inflammatory mediators TNF-alpha, interleukin (IL)-6, and Cox-2 was significantly suppressed in Fra-1 Tg mice followed, by the reduced expression of Sox-9 and BMP-2. Because serum prostaglandin E(2) (PGE(2)) levels were dramatically low in these mice, we administered PGE(2) to the fracture site using a slow-release carrier. The accumulation of fibrous tissue in Fra-1 Tg mice was significantly reduced by PGE(2) administration, and chondrogenesis near the fracture site was partially restored. These data suggest that the Fra-1-containing transcription factor AP-1 inhibits fracture-induced endochondral ossification and bony bridge formation presumably through suppression of inflammation-induced chondrogenesis.
Context life cycle management in smart space environments (2009)

Life cycle management plays an essential role in context-aware systems, it needs to aware surrounding contexts and adapt to changing contexts in highly dynamic environments. Consequently, context management is different from traditional approaches due to the characteristics of contextual information are dynamic, transient, and fallible. Understanding the life cycle of a context is the key issue to maintain consistent contextual information. Accordingly, we propose an ontology-based model for representing, deducing, and managing consistent contextual information. In addition, an agent-based architecture supports the process of context life cycle management.
The Sublingual Microcirculation Throughout Neonatal and Pediatric Extracorporeal Membrane Oxygenation Treatment: Is It Altered by Systemic Extracorporeal Support? (2019)

<b>Background:</b> Extracorporeal membrane oxygenation (ECMO) treatment alleviates systemic cardiorespiratory failure. However, it is unclear whether ECMO also improves microcirculatory function, as the microcirculation can be disturbed despite normal systemic hemodynamics. We therefore aimed to study the sublingual microcirculation (SMC) throughout neonatal and pediatric ECMO treatment. We hypothesized that the SMC improves after starting ECMO, that the SMC differs between venovenous (VV) and venoarterial (VA) ECMO, and that insufficient recovery of microcirculatory disturbances during ECMO predicts mortality. <b>Methods:</b> This single-center prospective longitudinal observational study included 34 consecutive children (April 2016-September 2018). The SMC was assessed daily with a handheld vital microscope (integrated with incident dark field illumination) before, during, and after ECMO. Validated parameters of vessel density, perfusion, and flow quality were assessed for all vessels (diameter <100 μm) and small vessels (<20 μm). Linear mixed models and logistic regression models were built to assess changes over time and identify significant covariates. Using ROC curves, the predictive values of microcirculatory parameters were assessed for mortality on ECMO and overall mortality. <b>Results:</b> The study population comprised 34 patients (median age 0.27 years, 16 neonates, 16 females). Twelve patients were treated with VV and 22 with VA ECMO. Twelve patients died during ECMO (stopped due to futility) and 3 died after ECMO but before discharge. Microcirculatory parameters did not change significantly before, during or after ECMO. Except between microcirculatory flow index (MFI) and mean arterial pressure (MAP), no significant associations were found between microcirculatory parameters and global systemic hemodynamics. The probability of an undisturbed MFI (>2.6) increased with higher MAP (OR: 1.050, 95%CI: 1.008-1.094). Microcirculatory parameters did not significantly differ between VV and VA ECMO or between survivors and non-survivors. None of the microcirculatory parameters could predict mortality on ECMO or overall mortality. <b>Conclusion:</b> In this heterogeneous study population, we were not able to demonstrate an effect of ECMO on the sublingual microcirculation. Microcirculatory parameters did not change throughout ECMO treatment and did not differ between VV and VA ECMO or between survivors and non-survivors. Future research should focus on determining which neonatal and pediatric ECMO patients would benefit from microcirculatory monitoring and how.
Tunable Thermal Transport across Interfaces via Phonon Engineering (2019)

The influence of He ion radiation on GaAs thermal conductivity was investigated using TDTR and the PGM. We found that damage in the shallow defect only regions of the radiation profile scattering phonons with a frequency to the fourth dependence due to randomly distributed Frankel pairs. Damage near the end of range however, scatters phonons with a second order frequency dependence due to the cascading defects caused by the rapid radiation energy loss at the end of range resulting in defect clusters. Using the PGM and experimental thermal conductivity trends it was then possible to estimate the defect recombination rate and size of defect clusters. The methodology developed here results in a powerful tool for interrogating radiation damage in semiconductors.
Gene for yeast glutamine tRNA synthetase encodes a large amino-terminal extension and provides a strong confirmation of the signature sequence for a group of the aminoacyl-tRNA synthetases. (1987)

The gene for the yeast Saccharomyces cerevisiae glutamine tRNA synthetase is shown here to encode a protein of 809 amino acids. This contrasts with the 551 amino acids of the Escherichia coli glutamine tRNA synthetase. The yeast GLN4 transcripts have 5' termini that start approximately 25 nucleotides in front of the long open reading frame. Much of the extra size of the yeast enzyme is due to a large amino-terminal extension. At codon 225, the yeast enzyme aligns with the amino terminus of the E. coli protein. From this point on, the two sequences have an average of 40% identity, with a few small gaps for alignment, until their respective carboxyl termini. At codon 254 of the yeast and codon 30 of the E. coli enzyme, however, there starts an exact 15-amino acid match between the two proteins. This match encompasses and is partially the same as a short sequence which is a signature sequence for the amino acid group of the bacterial aminoacyl-tRNA synthetases which are specific for different amino acids. This is the strongest sequence match found between any yeast cytoplasmic or mitochondrial aminoacyl-tRNA synthetase with its bacterial homologue. This region of the structure is associated with a nucleotide fold. The result provides strong validation of the signature sequence, especially for sequences where the homology relationships are less dramatic than in this example. Because the 224-amino acid extension of the yeast enzyme does not align with any part of the E. coli enzyme, we propose that it is not associated directly with the catalytic function of the enzyme. Its possible function is investigated in the accompanying paper.
Supplementary Figures S1-S9 from Autoantibody Landscape in Patients with Advanced Prostate Cancer (2023)

&lt;p&gt;Supplementary Figures S1-S9&lt;/p&gt;
Real-time communications in a computer-controlled workcell (1991)

A computer-integrated manufacturing (CIM) system is composed of several workcells, each of which contains robots, numerical-control machines, sensors, and a transport mechanism. The author considers a communication subsystem that is designed to support real-time control and coordination of devices in each CIM cell. The concept of a poll number is proposed to control the access to the intracell bus. The bus access mechanism with the poll number is intended to minimize the probability of real-time messages missing their deadlines. Use of a poll number provides not only for decentralized control of the intracell bus, but also a high degree of flexibility in scheduling messages. The performance of the bus access mechanism with a poll number is analyzed and compared with that of a token bus which is widely used in CIM systems such as MAP (Manufacturing Automation Protocol) networks. The probability of a real-time message missing its deadline in a token bus is found to be much higher than that of the proposed mechanism.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Gene‐Gene Interaction Between <i>FGF20</i> and <i>MAOB</i> in Parkinson Disease (2008)

The fibroblast growth factor 20 (FGF20) and monoamine oxidase B (MAOB) genes are associated with Parkinson Disease (PD) risk and both are in the dopamine bio-pathway. Therefore, we investigated the joint effect between polymorphisms in the FGF20 and MAOB genes for evidence of interaction contributing to PD risk. Fourteen polymorphisms (eight for FGF20, six for MAOB) were genotyped in 736 families and analyzed using conditional logistic regression (CLR). Significant two-locus interactions were found in females between the polymorphisms rs1721100 of FGF20 and rs1799836 of MAOB, and between the polymorphisms rs1721082 of FGF20 and rs1799836 of MAOB. The risk alleles for each SNP identified from CLR, rs1721100 C, rs1721082 T and rs1799836 A, are consistent with previous reports. Using indicator variables for the SNP genotypes, rs1721100 GC with rs1799836 AA showed significant interaction (P = 0.021), compared with the reference group rs1721100 GG with rs1799836 GG. Using an allele-dose model for the risk alleles, rs1721100 and rs1799836 showed significant interaction (P = 0.019). We found similar interaction results between rs1721082 and rs1799836. In conclusion, variants in FGF20 and MAOB show evidence of statistical interactions, which emphasizes the importance of considering them jointly in genetic analysis of PD and illustrates potential patterns of biological interaction contributing to PD risk.
A Coiled‐Coil Domain Containing 50 Splice Variant Is Modulated by Serine/Arginine‐Rich Splicing Factor 3 and Promotes Hepatocellular Carcinoma in Mice by the Ras Signaling Pathway (2018)

Deregulation of alternative splicing contributes to the malignant progression of cancer. Little is known about the significant alternative splicing events in hepatocellular carcinoma (HCC). High-throughput sequencing revealed that coiled-coil domain containing 50 (CCDC50) pre-mRNA is aberrantly spliced in 50% of our HCC cases. A BaseScope assay was performed to examine the expression of CCDC50S (a truncated oncogenic splice variant) in HCC tissues. Compared with benign liver tumors and several other types of solid tumors, CCDC50S mRNA was up-regulated in HCC, with a diagnostic potential (sensitivity, 0.711; specificity, 0.793). High expression of CCDC50S mRNA in HCC was significantly correlated with poor tumor differentiation, advanced tumor node metastasis (TNM) stage, and unfavorable prognosis. Overexpression of CCDC50S exerted tumorigenic activities that promoted HCC growth and metastasis by activation of Ras/forkhead box protein O4 (Foxo4) signaling. Either suppression of mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK) phosphorylation or overexpression of Foxo4 markedly attenuated CCDC50S-mediated phenotypes. Furthermore, serine- and arginine-rich splicing factor 3 (SRSF3) directly bound to CCDC50S mRNA to maintain its stability in the cytoplasm. The cytosolic retention of SRSF3 was mediated by the interaction of hepatitis B virus-encoded X protein (HBx) and 14-3-3β. Ectopic HBx expression induced expression of cytosolic SRSF3 and CCDC50S. Conclusion: Our study provided compelling evidence that up-regulation of CCDC50S was modulated by HBx/SRSF3/14-3-3β complex and enhanced oncogenic progression of HCC through the Ras/Foxo4 signaling pathway. These data suggest that CCDC50S may serve as a diagnostic and prognostic biomarker and probably a promising therapeutic target in HCC.
Photoenolization Reactions in Organic Synthesis. A Direct Synthesis of 4-Deoxyaklavinone (1991)

The 11-deoxyanthracycline skeleton of 4-deoxyaklavinone was constructed starting from 3,6-dimethoxy-2-methylbenzaldehyde and diallyl 2-pentenedioate by a regioselective intermolecular photoenolization reaction and a Pd(0)-mediated dealkoxycarbonylation-aromatization reaction.