gebhart/patrepeval huggingface dataset:
Synthesis and Activity of a Novel Series of 3-Biarylquinuclidine Squalene Synthase Inhibitors (1996)

Quinuclidines with a 3-biaryl substituent are a new class of potent, orally active squalene synthase (SQS) inhibitors. Variants around these rigid structures indicate key structural requirements for cationic SQS inhibitors. Thus the lower in vitro potency found for quinuclidines bearing 3-substituents, which did not overlay the biphenyl group of 3-(biphenyl-4-yl)-3-hydroxyquinuclidine (2) (IC50 = 16 nM, rat microsomal SQS), implied a directional requirement for the 3-substituent. Similarly, the lower potency of the 3-terphenyl analogue 6 (IC50 = 370 nM) indicated size constraints for this substituent. In compounds with a linking group between the quinuclidine and biphenyl ring, linking groups of lower lipophilicity were less well tolerated (e.g., 17, CH2CH2, IC50 = 5 nM vs 19, NHCO, IC50 = 1.2 microM). Replacement of the distal phenyl ring of 2 with a more polar pyridine heterocycle caused a reduction in in vitro potency. In general, good in vivo activity in the rat was restricted to 3-hydroxy analogues, with the 3-[4-(pyrid-4-yl)phenyl] derivative 39 (IC50 = 161 nM) showing the best inhibition (following oral dosing) of cholesterol biosynthesis from mevalonate (ED50 = 2.7 mg/kg).
Prediction of the X‐ray absorption near edge structure of the new high‐density phase of SiO2 (2005)

Abstract The X‐ray absorption near edge structure (XANES) of the newly predicted high density phase of SiO 2 has been calculated using a state‐of‐the‐art supercell method including the core‐hole effect. It is shown that the spectra are unique and have little resemblance to those of low density α‐quartz and high density stishovite. It is demonstrated that the interpretation of XANES based purely on the coordination shell argument is oversimplified. Crystal symmetry and effects beyond the second nearest neighbour must be taken into consideration. (© 2005 WILEY‐VCH Verlag GmbH &amp; Co. KGaA, Weinheim)
De novo design of site-specific protein interactions with learned surface fingerprints (2022)

Abstract Physical interactions between proteins are essential for most biological processes governing life. However, the molecular determinants of such interactions have been challenging to understand, even as genomic, proteomic, and structural data grows. This knowledge gap has been a major obstacle for the comprehensive understanding of cellular protein-protein interaction (PPI) networks and for the de novo design of protein binders that are crucial for synthetic biology and translational applications. We exploit a geometric deep learning framework operating on protein surfaces that generates fingerprints to describe geometric and chemical features critical to drive PPIs. We hypothesized these fingerprints capture the key aspects of molecular recognition that represent a new paradigm in the computational design of novel protein interactions. As a proof-of-principle, we computationally designed several de novo protein binders to engage four protein targets: SARS-CoV-2 spike, PD-1, PD-L1, and CTLA-4. Several designs were experimentally optimized while others were purely generated in silico , reaching nanomolar affinity with structural and mutational characterization showing highly accurate predictions. Overall, our surface-centric approach captures the physical and chemical determinants of molecular recognition, enabling a novel approach for the de novo design of protein interactions and, more broadly, of artificial proteins with function.
New Biological Treatment Options in CSU (2021)

Chronic spontaneous urticaria (CSU) is a devastating disease and is associated with many co-morbidities and long-lasting suffering. Therefore, patients always look for a most efficient therapeutic approach to achieve a full remission. In many patients, CSU remain refractory to off-label doses of antihistamines and short courses of steroids, and therefore are treated with omalizumab. However, 15–20% of severe CSU patients will stay unresponsive to omalizumab and are defined as being of un-met needs. In this review we will shed light on the many new drugs which are assessed in ongoing clinical trials.
Protein kinases and adherens junction dynamics in the seminiferous epithelium of the rat testis (2004)

Earlier studies in multiple epithelia have shown that cell-cell actin-based adherens junction (AJ) dynamics are regulated, at least in part, by the interplay of kinases and phosphatases that determines the intracellular phosphoprotein content. Yet it is virtually unknown regarding the role of protein kinases in Sertoli-germ cell AJ dynamics in the seminiferous epithelium of the testis. To address this issue, an in vitro coculture system utilizing Sertoli and germ cells was used to study the regulation of several protein kinases, including c-Src (the cellular form of the v-src transforming gene of Rous Sarcoma virus, RSV), carboxyl-terminal Src kinase (Csk), and casein kinase 2 (CK2), during AJ assembly. Both Sertoli and germ cells were shown to express c-Src, Csk, and CK2 with a relative Sertoli:germ cell ratio of approximately 1:1, suggesting both cell types contributed equally to the pool of these kinases in the epithelium. c-Src and Csk were shown to be stage-specific proteins during the epithelial cycle, being highest at stages VII-VIII. Studies using immunoprecipitation have illustrated that these kinases were structurally associated with the N-cadherin/beta-catenin, but not the nectin/afadin, protein complex, implicating that the cadherin/catenin protein complex is their likely putative substrate. An induction in c-Src, Csk, and CK2 were detected during Sertoli-germ cell AJ assembly in vitro but not when Sertoli cells were cultured alone. When adult rats were treated with 1-(2,4-dichlorobenzyl)-indazole-3-carbohydrazide (AF-2364), a compound known to induce germ cell loss from the seminiferous epithelium, in particular elongating/elongate and round spermatids, by disrupting Sertoli-germ cell AJs, an induction of c-Src and Csk, but not CK2, was detected. Furthermore, a transient increase in the intrinsic kinase activities of c-Src, but not CK2, was also detected. This event was also associated with a loss of protein-protein association of N-cadherin and beta-catenin from the cadherin/catenin/c-Src/Csk/CK2 protein complex. Administration of PP1, a c-Src inhibitor, into adult rats via the jugular vein could induce the loss of spermatocytes and round spermatids, but not elongating/elongate spermatids, from the seminiferous epithelium. This result thus implicates the importance of c-Src in maintaining the integrity of AJs and possibly desmosome-like junctions between Sertoli cells and spermatocytes/round spermatids. In short, the data reported herein have shown that c-Src, Csk, and CK2 are novel protein kinases in AJ dynamics in the testis.
Enhancement of Mixing and Mass Transfer Performance with a Microstructure Minireactor for Controllable Preparation of CaCO3 Nanoparticles (2007)

CO2/Ca(OH)2 precipitation reaction was used to prepare CaCO3 nanoparticles in this work. As a fast reaction system, nice mixing and a fast mass transfer rate of CO2 are required to enhance supersaturation. To increase the mixing performance, a microstructure reactor, a membrane dispersion minireactor, which has microfiltration membranes as the dispersion media, was introduced and CaCO3 nanoparticles with average diameters ranging from 34.3 to 110 nm were prepared. Several operating conditions were investigated for the purpose of controlling the particle size. In addition, a deep analysis on the mass transfer flux density of CO2 was carried out and the particle size decreased with the increasing of the mass transfer flux density during the reaction. Compared with a membrane-free reactor, it was found that the mixing performance was significantly enhanced by the effect of the micropore membrane, and nanoparticles cannot be prepared without it.
High-Pressure Synthesis and Characterization of Ge-Doped Single Crystal Diamond (2016)

Here we report on successful synthesis of Ge-doped single crystal diamond at high-pressure high-temperature (HPHT) conditions of 7.0 GPa and 1500–1900 °C from an Mg–Ge–C system. The systematic study of diamond crystallization processes reveals that addition of Ge to the Mg–C system suppresses the intensity of diamond spontaneous nucleation enabling synthesis of relatively large (2–3 mm) diamond crystals via seeded growth. Temperature is found to be a key factor controlling diamond crystallization mechanisms, morphological characteristics, and optical properties of the crystals. It is established that the diamond growth rate depends almost exponentially on the temperature increasing from 3.3 μm/h at 1500 °C to 4.2 mm/h at 1900 °C. Spectroscopic characterization of the synthesized diamonds reveals the abundance of the 2.06 eV Ge–V centers in the photoluminescence spectra confirming successful doping of the diamonds with germanium. The feasibility of the Mg–Ge–C system for growing bulk low-strain diamond doped with isotopically enriched germanium is demonstrated. The isotopic shift of the zero-phonon lines of the 2.06 eV center and the newly observed 1.747 eV center is found, proving the involvement of germanium atoms in the structure of the corresponding defects.
Running exercise- and antidepressant-induced increases in growth and survival-associated signaling molecules are IGF-dependent (2007)

It is known that physical exercise increases hippocampal brain-derived neurotrophic factor (BDNF) mRNA and protein, as well as the expression of several pro-survival signaling proteins and that many of these effects depend on the uptake of peripheral insulin-like growth factor-1 (IGF-1) into the CNS. Because treatment with antidepressants has similar effects upon neurotrophin expression, we investigated whether antidepressant-induced BDNF changes also depend on IGF-1 uptake, as well as whether IGF-1 plays a role in the exercise/antidepressant-induced expression of molecules associated with plasticity/growth (GAP-43, SCG-10) and the intracellular activation of molecules associated with neuronal survival (Akt, ERK1/2). We evaluated the effects of a well known monoamine oxidase inhibitor, tranylcypromine, on BDNF mRNA and protein levels and phospho-Akt and phospho-ERK1/2 immunoreactivity, both with and without systemic blockade of IGF-1 uptake through the use of an antiserum raised against IGF-1. Anti-IGF-1 reversed the increase in BDNF mRNA and protein elicited by exercise as well as tranylcypromine. Exercise also significantly enhanced transcription of axon growth protein, GAP-43, an effect that was also evidenced to be IGF-1-dependent. The combination of exercise-plus-tranylcypromine also increased several cell survival signaling measures, but the BDNF changes associated with the combination treatment appeared to be independent of IGF-1 uptake. Together, these results indicate that the uptake of peripheral IGF-1 in the CNS is essential for antidepressant- as well as exercise-induced enhancement in hippocampal BDNF expression and thus, enhanced hippocampal neuronal survival and plasticity.
Expression Strategy of Densonucleosis Virus from the German Cockroach, Blattella germanica (2011)

Blattella germanica densovirus (BgDNV) is an autonomous parvovirus that infects the German cockroach. BgDNV possesses three mRNAs for NS proteins, two of which are splice variants of the unspliced transcript. The unspliced variant encodes open reading frame 5 (ORF5) (NS3), while NSspl1 encodes ORF3 (NS1) and ORF4 (NS2) and NSspl2 encodes the C-proximal half of NS1. BgDNV possesses three VP transcripts, one of which (VP) is unspliced, while the other two (VPspl1 and VPspl2) are generated by alternative splicing. The unspliced VP transcript contains both ORF1 and ORF2, while in VPspl1, ORF1 and ORF2 are joined in frame. The transcription of NS genes begins at an earlier stage of the virus life cycle than the transcription of VP genes. NS and VP transcripts overlap by 48 nucleotides (nt). BgDNV is characterized by two additional NS transcripts overlapping by more than 1,650 nt with VP-coding transcripts. Four different bands (97, 85, 80, and 57 kDa) corresponding to three BgDNV capsid proteins were detected on SDS-PAGE. Mass spectrometry analysis showed that the amino acid composition of the 85-kDa and 80-kDa proteins is the same. Moreover, both of these proteins are ubiquitinated. The BgDNV PLA(2) domain, which is critical for cellular uptake of the virus, is located in ORF2 and is present only in VP1. In contrast to all of the parvoviruses studied in this respect, VP2 has a unique N terminus that is not contained within VP1 and VP3. In situ recognition with NS1- and VP-specific antibodies revealed an uneven pattern of NS1 expression resembling a halo within the nuclear membrane.
A Comparison of Different Informative Vibrotactile Forward Collision Warnings: Does the Warning Need to Be Linked to the Collision Event? (2014)

Recent research demonstrates that auditory and vibrotactile forward collision warnings presenting a motion signal (e.g., looming or apparent motion across the body surface) can facilitate speeded braking reaction times (BRTs). The purpose of the present study was to expand on this work by directly comparing warning signals in which the motion conveyed was constant across all collision events with signals in which the speed of motion was dependent on the closing velocity (CV). Two experiments were conducted using a simulated car-following task and BRTs were measured. In Experiment 1, increasing intensity (looming) vibrotactile signals were presented from a single tactor attached to the driver's waist. When the increase in intensity was CV-linked, BRTs were significantly faster as compared to a no-warning condition, however, they were not significantly different from constant intensity and CV-independent looming warnings. In Experiment 2, a vertical array of three tactors was used to create motion either towards (upwards) or away (downwards) from the driver's head. When the warning signal presented upwards motion that was CV-linked, BRTs were significantly faster than all other warning types. Downwards warnings led to a significantly higher number of brake activations in false alarm situations as compared to upwards moving warnings. The effectiveness of dynamic tactile collision warnings would therefore appear to depend on both the link between the warning and collision event and on the directionality of the warning signal.
Alert: An Architecture for Transforming a Passive DBMS into an Active DBMS (1991)

Alert is an extension architecture designed for transforming a passive SQL DBMS into. an active DBMS. The salient features of the design of Alert are reusing, to the extent possible, the passive DBMS technology, and making minimal changes to the language and implementation of the passive DBMS. Alert provides a layered architecture that allows the semantics of a variety of production rule languages to be supported on top. Rules may be specified on userdefined as well as built-in operations. Both synchronous and asynchronous event, monit,oring are possible. This paper presents the design of Alert and its implementation in the Starburst extensible DBMS.
Single-Anchor Localizability in 5G Millimeter Wave Networks (2019)

Fifth generation networks utilizing millimeter wave frequencies enable single-anchor localization to be performed via a line-of-sight (LOS) path or, as recently suggested, via non-line-of-sight (NLOS) paths exclusively. Thus, for a single base station-mobile pair, under a Boolean model (random positions, sizes, and orientations) of reflectors, and considering first-order reflections (in addition to the LOS path), this letter analytically derives the probability that the mobile is able to obtain an unambiguous location estimate (i.e., the mobile's localizability). This analysis also reveals that localization, via NLOS signals exclusively, is a relatively small contributor to the mobile's overall localizability.
Tight function zonula occludens-3 regulates cyclin D1–dependent cell proliferation (2011)

Coordinated regulation of cell proliferation is vital for epithelial tissue homeostasis, and uncontrolled proliferation is a hallmark of carcinogenesis. A growing body of evidence indicates that epithelial tight junctions (TJs) play a role in these processes, although the mechanisms involved are poorly understood. In this study, we identify and characterize a novel plasma membrane pool of cyclin D1 with cell-cycle regulatory functions. We have determined that the zonula occludens (ZO) family of TJ plaque proteins sequesters cyclin D1 at TJs during mitosis, through an evolutionarily conserved class II PSD-95, Dlg, and ZO-1 (PDZ)-binding motif within cyclin D1. Disruption of the cyclin D1/ZO complex through mutagenesis or siRNA-mediated suppression of ZO-3 resulted in increased cyclin D1 proteolysis and G(0)/G(1) cell-cycle retention. This study highlights an important new role for ZO family TJ proteins in regulating epithelial cell proliferation through stabilization of cyclin D1 during mitosis.
Pilot-Tone Assisted Successive Interference Cancellation for Uplink Power- and Frequency-Division Multiplexing Passive Optical Network (2022)

Frequency division multiplexing (FDM) passive optical network (PON) is considered as a competitive solution for 5G-advanced and 6G mobile fronthaul (MFH) to support multiple radio units (RUs) with shared trunk fiber and distributed unit (DU). However, it is likely to cause uplink signal overlapping by laser wavelength drift, and guard bands should be reserved between FDM channels, which limits the spectral efficiency (SE). In this work, we propose to aggregate multiple uplink FDM channels using power division multiplexing and jointly adopt successive interference cancellation (SIC) at the receiver to improve the uplink SE. We first theoretically derive the SE of such power- and frequency-division multiplexing (PFDM) PON with both guard band and SIC together, and reveal that PFDM PON can achieve higher SE than the pure FDM PON with guard band only. Focusing on the case of two overlapped uplink signals, we propose a pilot-tone assisted SIC to improve the estimation accuracy of frequency offset and phase noise in heavily overlapped uplink signals. In the proof-of-concept experiments, compared to the orthogonal case without considering the guard band, 0.29 bit/s/Hz SE penalty due to the residual interference after SIC is observed when two uplink signals are completely overlapped. The results showed that, in the presence of laser drift, PFDM PON becomes more spectrally-efficient than FDM PON when the relative wavelength drift exceeds 20% of the signal bandwidth.
Efficacy of Humanized Mesenchymal Stem Cell Cultures for Bone Tissue Engineering: A Systematic Review with a Focus on Platelet Derivatives (2017)

Fetal bovine serum (FBS) is the most commonly used supplement for ex vivo expansion of human mesenchymal stem cells (hMSCs) for bone tissue engineering applications. However, from a clinical standpoint, it is important to substitute animal-derived products according to current good manufacturing practice (cGMP) guidelines. Humanized alternatives to FBS include three categories of products: human serum (HS), human platelet derivatives (HPDs)-including platelet lysate (PL) or platelet releasate (PR), produced by freeze/thawing or chemical activation of platelet concentrates, respectively, and chemically defined media (serum-free) (CDM). In this systematic literature review, the in vitro and in vivo osteogenic potential of hMSCs expanded in humanized (HS-, HPD-, or CDM-supplemented) media versus hMSCs expanded in FBS-supplemented media, was compared. In addition, PL and PR were compared in terms of their growth factor (GF)/cytokine-content and cell-culture efficacy. When using either 10-20% autologous or pooled HS, 3-10% pooled HPDs or CDM supplemented with GFs, in comparison with 10-20% FBS, a majority of studies reported similar or superior in vitro proliferation and osteogenic differentiation, and in vivo bone formation in ectopic or orthotopic rodent models. Moreover, a trend for higher GF content was observed in PL versus PR, although evidence for cell culture efficacy is limited. In summary, humanized supplements seem at least equally effective as FBS for hMSC expansion and osteogenic differentiation. Although pooled HPDs appear to be the most favorable supplement for large-scale hMSC expansion, further efforts are needed to standardize the preparation and composition of these products in compliance with cGMP standards.
Permeability alterations in unilamellar liposomes due to betaine‐type zwitterionic and anionic surfactant mixed systems (1993)

The alterations caused by betaine‐type zwitterionic and anionic surfactant mixed systems in the permeability of unilamellar liposomes have been investigated. The partition coefficient of these systems, at different molar fractions, between the aqueous phase and the lipid bilayer of liposomes has been determined. These surfactant mixed systems were formed by N ‐dodecyl‐ N,N ‐dimethylbetaine (C 12 ‐Bet) and sodium dodecyl sulfate (SDS) in the presence of 20 mM PIPES buffer and 110 mM Na 2 SO 4 , at pH 7.21. Unilamellar liposomes were prepared from egg phosphatidylcholine and phosphatidic acid (9:1 molar ratio). The release of the fluorescent agent 5‐(6)‐carboxyfluorescein induced by the systems has been studied at sub‐solubilizing concentrations. When the molar fraction of C 12 ‐Bet/SDS is about 0.4, the critical micelle concentration values of these systems exhibit a minimum, whereas their partition coefficient between the aqueous phase and lipid bilayer of lipid bilayers shows a maximum. There is a consistent correlation between the partition coefficient and the ability of the different systems of surfactants to modify the permeability of liposomes.
A Controlled Natural Language Interface for Semantic Media Wiki Using the Rabbit Language (2009)

Abstract—Despite their potential value as collaborative knowl-edge editing systems, semantic wikis present a number of usability challenges for human end users. In particular, there are several mismatches between the simple user interaction mechanisms of wikis (which are the key to the success of wikis) and the need for users to create, edit and understand structured knowledge content (e.g., in the form of RDF or OWL ontologies). In this paper, we present a Controlled Natural Language (CNL) approach to collaborative ontology development using Semantic MediaWiki (SMW). In order to support the expressivity required for OWL ontology development, we extended the representational substructure of the SMW system with an OWL meta model using a template-based mechanism. To improve usability, we provided a form-based guided input interface and implemented several CNL verbalizers (CNL text generation components). In particular, we developed verbalizers for the English and Chinese variants of the Rabbit CNL, as well as the Attempto Controlled English (ACE) CNL. The combination of semantic wiki systems and CNL editing interfaces may provide an effective mechanism for promoting the large-scale collaborative creation of semantically-enriched online content. I.
Religion in Colonial Civil Society (1996)

This paper has a fairly circumscribed project. It is a critical one. My concern is not directly with the matter of national identity or nationalism, but with a reflection on the narrative of modern Buddhist history in Sri Lanka, one that, to be sure, informs nationalism. Nor do I aim to introduce new and compelling evidence for 'what really happened' to Buddhism in the 19th century, but rather to inquire into some aspects of the way that story has generally been told, the rhetorical economy through which it has been constructed and to suggest—at least in outline—why and through what concepts it ought to be recast. Indeed, the task here is only to try to produce something of a revised conceptual terrain in which a different sort of history of the relation between Buddhism and modernity in Sri Lanka might usefully be written.