gebhart/patrepeval huggingface dataset:
Zfp206 regulates ES cell gene expression and differentiation (2006)

Understanding transcriptional regulation in early developmental stages is fundamental to understanding mammalian development and embryonic stem (ES) cell properties. Expression surveys suggest that the putative SCAN-Zinc finger transcription factor Zfp206 is expressed specifically in ES cells [Zhang,W., Morris,Q.D., Chang,R., Shai,O., Bakowski,M.A., Mitsakakis,N., Mohammad,N., Robinson,M.D., Zirngibl,R., Somogyi,E. et al., (2004) J. Biol., 3, 21; Brandenberger,R., Wei,H., Zhang,S., Lei,S., Murage,J., Fisk,G.J., Li,Y., Xu,C., Fang,R., Guegler,K. et al., (2004) Nat. Biotechnol., 22, 707-716]. Here, we confirm this observation, and we show that ZFP206 expression decreases rapidly upon differentiation of cultured mouse ES cells, and during development of mouse embryos. We find that there are at least six isoforms of the ZFP206 transcript, the longest being predominant. Overexpression and depletion experiments show that Zfp206 promotes formation of undifferentiated ES cell clones, and positively regulates abundance of a very small set of transcripts whose expression is also specific to ES cells and the two- to four-cell stages of preimplantation embryos. This set includes members of the Zscan4, Thoc4, Tcstv1 and eIF-1A gene families, none of which have been functionally characterized in vivo but whose members include apparent transcription factors, RNA-binding proteins and translation factors. Together, these data indicate that Zfp206 is a regulator of ES cell differentiation that controls a set of genes expressed very early in development, most of which themselves appear to be regulators.
Do Open Source Developers Respond to Competition? The Case Study (2007)

This paper traces the history of TeX, the open source typesetting program. TeX was an early and very successful open source project that imposed its standards in a particularly competitive environment and inspired many advances in the typesetting industry. Developed over three decades, TeX came into competition with a variety of open source and proprietary alternatives. I argue from this case study that open source developers derive direct and indirect network externalities from the use of their software by others and must therefore consider non-developers' needs to make their software more attractive to a broader audience and more competitive with proprietary alternatives.
Interleukin-1 receptor antagonist circulates in experimental inflammation and in human disease (1992)

Interleukin-1 receptor antagonist (IL-1ra) is a 22-Kd protein that shares homology with IL-1 beta, binds to the IL-1 receptor, but has no known agonist properties. This inhibitor appears to be the first cytokine whose sole function is to block the actions of another cytokine. Exogenous IL-1ra administration has been shown to reduce mortality in experimental septic shock. We now report that IL-1ra is endogenously produced and circulates in experimental inflammation and in clinical disease. After experimental endotoxemia in human volunteers, IL-1ra concentrations increase from a baseline concentration of 460 +/- 200 pg mL-1 to 14,870 +/- 290 pg mL-1 at 3 hours (P less than .05). IL-1ra is also detectable in all plasma samples from critically ill patients with a mean concentration of 8,680 +/- 2,060 pg mL-1 (range 320 to 55,370 pgs mL-1). In nonhuman primates, Escherichia coli septic shock induces elevated plasma levels of IL-4ra (P less than .05). However, in animals that eventually succumb to septic shock, Il-1ra appears in quantities presumed inadequate to block the pathologic sequelae associated with high IL-1 beta levels. The findings suggest that IL-1ra may play a role in modulating the systemic host responses to a variety of nonlethal disease states by altering the balance between cytokines and their antagonists.
Aether (2010)

The shift to multi-core hardware brings new challenges to database systems, as the software parallelism determines performance. Even though database systems traditionally accommodate simultaneous requests, a multitude of synchronization barriers serialize execution. Write-ahead logging is a fundamental, omnipresent component in ARIES-style concurrency and recovery, and one of the most important yet-to-be addressed potential bottlenecks, especially in OLTP workloads making frequent small changes to data. In this paper, we identify four logging-related impediments to database system scalability. Each issue challenges different level in the software architecture: (a) the high volume of small-sized I/O requests may saturate the disk, (b) transactions hold locks while waiting for the log flush, (c) extensive context switching overwhelms the OS scheduler with threads executing log I/Os, and (d) contention appears as transactions serialize accesses to in-memory log data structures. We demonstrate these problems and address them with techniques that, when combined, comprise a holistic, scalable approach to logging. Our solution achieves a 20%-69% speedup over a modern database system when running log-intensive workloads, such as the TPC-B and TATP benchmarks. Moreover, it achieves log insert throughput over 1.8GB/s for small log records on a single socket server, an order of magnitude higher than the traditional way of accessing the log using a single mutex.
Strategies for UF/DF-Based Impurity Removal in the Post-conjugation Purification of Antibody–Drug Conjugates (2023)

Antibody–drug conjugates (ADCs) are increasingly prevalent as investigational and marketed treatments for a variety of cancers and other diseases. The structures of most ADCs comprise a small-molecule component (the drug-linker) chemically conjugated to a monoclonal antibody, and this hybrid construct presents a number of challenges for Chemistry, Manufacturing, and Controls (CMC) development. A Small Molecule Considerations for ADC Development Working Group (WG) has been established within the IQ Consortium to serve as a forum for biopharmaceutical industry companies to discuss development strategies for ADCs, with a focus on the drug-linker portion. The preceding paper from the WG presented results from a benchmarking survey of IQ member companies on a number of topics relating to drug-linker development. One of the key findings was that ultrafiltration/diafiltration (UF/DF) is used by all responding companies for purification of the ADC following the conjugation step and is a critical operation for control of small-molecule impurities in the ADC drug substance. UF/DF is well established in monoclonal antibody processing, but to date, there are relatively few literature reports detailing its application to ADCs. To help address this gap, this manuscript presents results and analysis from a more focused survey of IQ member companies on the application of UF/DF for post-conjugation purification of ADCs. Insight is provided into practical considerations such as common operating parameters, relative efficiency of removal of different types of impurities, technical challenges, and application of emerging technologies. In addition, recommendations are offered on where to start when developing a UF/DF process for a new ADC. The overall goals are to provide an overview of current industry practices for UF/DF purification of ADCs and to spur further communication and innovation in this area.
Direct Electronic Sensing of Biomolecular Activity and Signaling (2005)

[Instructions: Introduce the research area and project objectives. Discuss methods employed, field of impact, collaborations and notable results. Write for an audience of diverse NSE grantees and the wider scientific research community. (At a level roughly equivalent to that of a article in the journal Science.) Use text and figures as appropriate. It is important to include contact information, links, and important references at the end as shown below. ] The primary goal of this research program is to develop hybrid bioelectronic devices with singlemolecule sensitivity. Using an architecture based upon nanoscale conductors directly wired into circuits, these devices may provide new routes for both fundamental and applied nanoscience. The research team aims to fabricate and test biofunctional circuits, and then apply their use to explore enzymatic activity and biomolecular dynamics at the single molecule limit. Figure 1 below schematically depicts a hypothetical single-molecule sensor and captures the promise of different types of science which might be investigated. First, a biomolecule like calmodulin is covalently attached to a nanocircuit (Fig. 1a). Various dynamics of the biomolecule are then electronically monitored, as depicted in Figs. 1b-d. The UCI research team combines a range of interdisciplinary expertise in nanocircuit assembly and testing, the electronic behaviors of circuits in electrolytes, phage display of target and receptor proteins, and the biological interdependence of kinase proteins and their substrates.
Analysis of Telomeres and Telomerase (2003)

This unit describes techniques to analyze telomeric length and telomerase activity in human cells. Telomere length can be determined by a modification of Southern blotting in which the analysis of chromosome terminal restriction fragments (TRFs) provides the average lengths of all telomeres in a cell population. Telomerase activity can be measured in vitro by a sensitive and efficient polymerase chain reaction (PCR)-based detection method, also known as telomeric repeat amplification protocol (TRAP). These assays can be used to study the in vitro cellular effects of aging and cancer treatments on telomere biology and telomerase activity.
Catalytic Asymmetric Staudinger Reactions to Form β‐Lactams: An Unanticipated Dependence of Diastereoselectivity on the Choice of the Nitrogen Substituent. (2005)

Abstract For Abstract see ChemInform Abstract in Full Text.
Nanotechnology Based Materials and Devices for Health Care (2002)

This viewgraph presentation provides information on trends in NASA nanotechnology research and development, and future biotechnological applications for that nanotechnology. The presentation covers nanoelectronics, nanosensors, and nanomaterials, biomimetics, devices and materials for health care, carbon nanotubes, biosensors for astrobiology, solid-state nanopores for DNA sequencing, and protein nanotubes.
A multicenter phase II study of vaccines to prevent recurrence in patients with HER-2–positive breast cancer. (2023)

532 Background: Patients (pts) with early stage HER2-positive breast cancer are commonly treated with neoadjuvant HER2-targeted therapy. Pts who have residual invasive disease have a less favorable outcome and increased risk of recurrent disease than pts with a complete pathologic response (pCR). It also has been observed that pts who do not achieve a pCR have low or absent anti-HER-2 CD4 Th1 responses. We hypothesized that correcting anti-HER-2 CD4 Th1 response using vaccines will be safe, induce anti-tumor immunity in HER2-positive breast cancer and reduce the risk of recurrence. We conducted a multi-center, phase 2, randomized study to determine the safety, immunogenicity and recurrence free survival of two HER2 vaccines (multivalent anti-oncodriver DNA vaccine (WOKVAC) or HER-2-pulsed dendritic cell vaccine (DC1)). Methods: Pts with HER2-positive early breast cancer were eligible if they had residual invasive disease at surgery after receiving neoadjuvant chemotherapy plus HER2-targeted therapy. Patients were randomly assigned in a 1:1 ratio, with stratification according to residual cancer burden (RCB) (1+2 vs 3) to receive adjuvant HER2 vaccination with either DC1 or WOKVAC. For the initial vaccination phase, DC1 was delivered via US guided inguinal lymph node administration, weekly x 6 weeks and WOKVAC was given intradermally on weeks 1, 4, and 7. Booster vaccines were given at months 6, 9 and 12. The primary end point is to evaluate the safety and tolerability of each vaccine and assess immune response rate as measured by ELISPOT. Each treatment arm will be assessed separately. Secondary endpoints include recurrence-free survival. Exploratory analyses include the assessment of prognostic and predictive biomarkers including circulating tumor cells, serum HER2 levels, and other immune correlative biomarkers. Here we are reporting the initial safety results. Results: Total of 110 eligible pts (55 WOKVAC vs 55 DC1) were enrolled from 2/2018 to 12/2022 and received at least one dose of treatment and 38 pts pending completion of the booster phase. Most pts had clinical stage II/III 56/35 (82%) and 50% had positive node disease at diagnosis. 82% had hormone receptor positive disease. 37/38/8 patients had RCB 1/2/3. For patients without known RCB status, ypTNM was used to randomize (yp stage I/II/III = 13/13/1 pts). The most frequently observed treatment related adverse events (TRAE) were injection site pain/reaction (38%) and chills (34%), fever (25%) and fatigue (40%) for DC1 arm. For WOKVAC, the most common toxicities included injection site reaction (68%) and fatigue (37%). All of these were grade 1 and 2. Nine patients had events including new primary cancer (1), local recurrence (2), metastatic disease recurrence (6). Conclusions: Both DC1 and WOKVAC HER2 vaccines were well tolerated without significant toxicities. Updated results will be presented at the meeting including correlatives. Clinical trial information: NCT03384914 .
Calorimonas adulescens gen. nov., sp. nov., an anaerobic thermophilic bacterium utilizing methoxylated benzoates (2020)

A novel anaerobic, thermophilic bacterium (strain A05 MB<sup>T</sup>) was isolated from Daginsky thermal springs (Sakhalin, Russia) on 2-methoxybenzoate as a substrate. Cells of the strain were motile long rods, 3.0-5.0 µm in length and 0.5-0.6 µm in diameter. The temperature range for growth was 47-68 °C, with an optimum at 60 °C. The pH range for growth was 4.5-8.0, with an optimum at pH 5.5-6.0. Strain A05 MB<sup>T</sup> did not require NaCl for growth. The strain utilized methoxylated aromatic compounds (2-methoxybenzoate and 3,4-dimethoxybenzoate), a number of carbohydrates (glucose, fructose, mannose, trehalose, xylose, sucrose, galactose, ribose, maltose, raffinose, lactose, cellobiose and dextrin) and proteinaceous substrates (yeast extract, beef extract, peptone and tryptone). The end products of glucose fermentation were acetate, ethanol and CO<sub>2</sub>. The DNA G+C content of strain A05 MB<sup>T</sup> was 40.2 mol% (whole-genome analysis). 16S rRNA gene sequence analysis revealed that strain A05MB<sup>T</sup> belongs to the order <i>Thermoanaerobacterales</i> (phylum <i>Firmicutes</i>). The closest relative of strain A05 MB<sup>T</sup> was <i>Caloribacterium cisternae</i> (94.3 % 16S rRNA gene sequence similarity). Based on the phenotypic, genotypic and phylogenetic characteristics of the isolate, strain A05 MB<sup>T</sup> is considered to represent a novel species of a new genus, for which the name <i>Calorimonas adulescens</i> gen. nov., sp. nov. is proposed. The type strain of <i>Calorimonas adulescens</i> is A05 MB<sup>T</sup> (=KCTC 15839<sup>T</sup>=VKM B-3388<sup>T</sup>).
Spontaneous emission in microcavities with distributed mirrors (2002)

In order to exploit the full potential of surface emitting lasers (SELs), one must appreciate the severe limitations introduced by the distributed mirrors on the control of spontaneous emission. In this paper we summarize the large body of numerical techniques (as well as illustrative experimental examples) that have been used to calculate spontaneous emission properties, but primarily, we shall focus on the analytic models that have become available for the understanding of spontaneous emission in distributed mirror microcavities.
Metal-overlayer formation onC60for Ti, Cr, Au, La, and In: Dependence on metal-C60bonding (1993)

Photoelectron spectroscopy using x rays and synchrotron radiation was used to examine surface bonding and overlayer growth modes when the representative metals Ti, Cr, Au, La, and In were deposited onto thin films of pure ${\mathrm{C}}_{60}$. None of these metals intermixed with ${\mathrm{C}}_{60}$ or formed bulk metal-fulleride compounds. Instead, metallic clusters were produced when Au, Cr, and In atoms were condensed on ${\mathrm{C}}_{60}$. For Ti and La, the first layer formed as a monolayer but subsequent depositions produced clusters. The tendency to form a single layer for Ti and La reflects the hybridization of metal d and fullerene p orbitals, as with bulk carbides. In addition, limited amounts of metal carbide formation was evident for overlayers of Ti, La, and Cr due to some disruption of ${\mathrm{C}}_{60}$.
Abstract A2: Oncogenic and drug-sensitive ERBB2 mutations in glioblastoma (2009)

Abstract The Cancer Genome Atlas (TCGA) Consortium recently completed a multidimensional analysis of glioblastoma, characterizing somatic alterations across a large sample set, and identifying genetic lesions that likely contribute to tumor fitness (TCGA Network, Nature, 2008). However, functional experiments are required to determine whether significantly altered genes are in fact oncogenes or tumor suppressor genes in glioblastoma. We experimentally analyzed mutations in one of the significantly mutated genes, ERBB2. Unlike ERBB2 mutations in lung adenocarcinoma, ERBB2 mutations in glioblastoma are primarily located in the extracellular region, clustering around the domain that mediates receptor dimerization. We have determined that a subset of the reported mutations are gain-of-function and oncogenic, require kinase activity for oncogenic transformation, and are sensitive to specific small molecule kinase inhibitors. This discovery has therapeutic implications for glioblastoma patients who harbor somatic ERBB2 mutations. Citation Information: Cancer Res 2009;69(23 Suppl):A2.
EMILIN2 down‐modulates the Wnt signalling pathway and suppresses breast cancer cell growth and migration (2013)

EMILIN2 is an extracellular matrix (ECM) protein that exerts contradictory effects within the tumour microenvironment: it induces apoptosis in a number of tumour cells, but it also enhances tumour neo-angiogenesis. In this study, we describe a new mechanism by which EMILIN2 attenuates tumour cell viability. Based on sequence homology with the cysteine-rich domain (CRD) of the Frizzled receptors, we hypothesized that EMILIN2 could affect Wnt signalling activation and demonstrate direct interaction with the Wnt1 ligand. This physical binding leads to decreased LRP6 phosphorylation and to the down-modulation of β-catenin, TAZ and their target genes. As a consequence, EMILIN2 negatively affects the viability, migration and tumourigenic potential of MDA-MB-231 breast cancer cells in a number of two- and three-dimensional in vitro assays. EMILIN2 does not modulate Wnt signalling downstream of the Wnt-Frizzled interaction, since it does not affect the activation of the pathway following treatment with the GSK3 inhibitors LiCl and CHIR99021. The interaction with Wnt1 and the subsequent biological effects require the presence of the EMI domain, as there is no effect with a deletion mutant lacking this domain. Moreover, in vivo experiments show that the ectopic expression of EMILIN2, as well as treatment with the recombinant protein, significantly reduce tumour growth and dissemination of cancer cells in nude mice. Accordingly, the tumour samples are characterized by a significant down-regulation of the Wnt signalling pathway. Altogether, these findings provide further evidence of the complex regulations governed by EMILIN2 in the tumour microenvironment, and they identify a key extracellular regulator of the Wnt signalling pathway.
Preparation and Characterization of a Layered Molybdenum Trioxide with Poly(o-anisidine) Hybrid Thin Film and Its Aldehydic Gases Sensing Properties (2007)

Layered organic/inorganic hybrid thin film, which consist of MoO3 with poly(o-anisidine) (PoANIS), were investigated by X-ray diffraction (XRD) analysis, field-emission scanning electron microscopy...
F-59 New Advances in Elemental X-ray Imaging: the Chemical Fossil (2007)

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Secure Revocation Features in eKYC - Privacy Protection in Central Bank Digital Currency (2022)

Central bank digital currencies require the implementation of eKYC to verify whether a trading customer is eligible online. When an organization issues an ID proof of a customer for eKYC, that proof is usually achieved in practice by a hierarchy of issuers. However, the customer wants to disclose only part of the issuer's chain and documents to the trading partner due to privacy concerns. In this research, delegatable anonymous credential (DAC) and zero-knowledge range proof (ZKRP) allow customers to arbitrarily change parts of the delegation chain and message body to range proofs expressed in inequalities. That way, customers can protect the privacy they need with their own control. Zero-knowledge proof is applied to prove the inequality between two time stamps by the time stamp server (signature presentation, public key revocation, or non-revocation) without disclosing the signature content and stamped time. It makes it possible to prove that the registration information of the national ID card is valid or invalid while keeping the user's personal information anonymous. This research aims to contribute to the realization of a sustainable financial system based on self-sovereign identity management with privacy-enhanced PKI.
Técnicas de diseño optimizado para fuentes de alimentación de alta frecuencia (2011)

La potencia sin control no sirve de nada: hemos oido esta expresion tantas veces que ha pasado a formar parte del lenguaje de uso habitual. Cuando el contexto es la conversion de potencia, su simple significado se enriquece de tal manera con la ingenieria, los aspectos de diseno y la teoria matematica que no podria ser mas apropiado presentar un articulo que trate las recientes necesidades de unas tecnicas de control mas rapidas y robustas aplicadas a los convertidores conmutados de alta frecuencia. En este articulo no se hace un repaso detallado a un solo metodo de diseno para un convertidor de potencia conmutado, sino que se propone una panoramica de todos los aspectos principales y las metodologias mas comunes ya adoptadas, al tiempo que se mencionan tecnicas modernas y automaticas que pueden aplicarse para cumplir los nuevos requisitos de alta frecuencia.
Supplementary Figure and Table Legends from Sym004: A Novel Synergistic Anti–Epidermal Growth Factor Receptor Antibody Mixture with Superior Anticancer Efficacy (2023)

Supplementary Figure and Table Legends from Sym004: A Novel Synergistic Anti–Epidermal Growth Factor Receptor Antibody Mixture with Superior Anticancer Efficacy
The chemistry of the vitamin B3 metabolome (2018)

The functional cofactors derived from vitamin B3 are nicotinamide adenine dinucleotide (NAD<sup>+</sup>), its phosphorylated form, nicotinamide adenine dinucleotide phosphate (NADP<sup>+</sup>) and their reduced forms (NAD(P)H). These cofactors, together referred as the NAD(P)(H) pool, are intimately implicated in all essential bioenergetics, anabolic and catabolic pathways in all forms of life. This pool also contributes to post-translational protein modifications and second messenger generation. Since NAD<sup>+</sup> seats at the cross-road between cell metabolism and cell signaling, manipulation of NAD<sup>+</sup> bioavailability through vitamin B3 supplementation has become a valuable nutritional and therapeutic avenue. Yet, much remains unexplored regarding vitamin B3 metabolism. The present review highlights the chemical diversity of the vitamin B3-derived anabolites and catabolites of NAD<sup>+</sup> and offers a chemical perspective on the approaches adopted to identify, modulate and measure the contribution of various precursors to the NAD(P)(H) pool.