gebhart/patrepeval huggingface dataset:
IKKβ is required for the formation of the NLRP3 inflammasome (2021)

The rapid formation and activation of the NLRP3 inflammasome is induced by co-stimulation with LPS and nigericin. It requires the LPS-stimulated activation of IKKβ, which exerts its effects independently of de novo gene transcription, protein translation and other protein kinases activated by IKKβ. IKKβ is not required for the nigericin-induced dispersion of the trans-Golgi network (TGN), but to bring NLRP3 in proximity with TGN38. The nigericin-induced dispersion of the Golgi is enhanced by co-stimulation with LPS, and this enhancement is IKKβ-dependent. Prolonged stimulation with LPS to increase the expression of NLRP3, followed by stimulation with nigericin, produced larger TGN38-positive puncta, and the ensuing activation of the NLRP3 inflammasome was also suppressed by IKKβ inhibitors added prior to stimulation with nigericin. IKKβ therefore has a key role in recruiting NLRP3 to the dispersed TGN, leading to the formation and activation of the NLRP3 inflammasome.
Supplemental Figure Legends from PanIN Neuroendocrine Cells Promote Tumorigenesis via Neuronal Cross-talk (2023)

&lt;p&gt;Contains the figure legends for supplemental Figures S1-S8, Table S1 and Videos V1 and V2.&lt;/p&gt;
A Light-Modulated Sequence-Specific DNA-Binding Peptide (2000)

Gripping compounds! A homodimer is formed by linking two monomers of b-ZIP protein basic regions through a photoresponsive azobenzene unit. By simple irradiation at appropriate wavelenghths, this dimer can be switched between isomers which have moderate (trans) and high (cis) sequence-specific affinity for gripping the major groove of DNA (see scheme). BR=basic region, ds=double-stranded.
Experimental optical tomography (1984)

Computed optical tomography reconstructs a 2-D planar cross-sectional map of the absorption from line integrals of the absorption along a large number of rays traversing the image field. It offers accurate and absolute spatially resolved absorption measurements with good time resolution. Tomography does not require access outside the plane of interest and remains quantitative even in optically thick systems.
Evidence fortheInvolvement ofa Cytoplasmic Factor intheAging oftheYeastSaccharomyces cerevisiae (1989)

their generation times reverted tothat characteristic oftheir own age.Recovery fromthemother cell effect was also observed whenthedaughters were left attached totheir mothers. Theresults suggest that senescence, as manifested bytheincrease ingeneration time, isa phenotypically dominant feature inyeast cells andthatitis determined bya diffusible cytoplasmic factor(s) thatundergoes turnover. Thisfactor(s) appeared tobe transmitted bya cell notonlytoitsdaughter, butalsoindirectly toits granddaughter. Inseparate studies, it wasdetermined that theinduced deposition ofchitin, themajor component ofthebudscar,intheyeast cell wall hadno appreciable effect on life span.We raise thepossibility thatthecytoplasmic factor(s) that appearsto mediate thesenescent isamajor determinant ofyeast life span.Thisfactor(s) may betheproduct ofage-specific geneexpression. Thebudding yeastSaccharomyces cerevisiae possessesa limited life span(6). Yeastcells produce a finite numberof daughters during their life spans,which areelaborated onthe surface ofmothercells as buds.Thenumberofbuds produced bythemother, one during eachcell division cycle, isthemetric ofthelife span.Chronological agedoesnotplay a role(9). Yeastaging can bedescribed bytheGompertz equation (15). Morphological andphysiological changes accompany theaging process.Theseinclude anincrease incell size (6), anincrease ingeneration time onetothree divisions before cell death (6), andadecrease intheability tomate(8). Individual cells display awiderangeoflife spans.Themean andthemaximumlife spansfora given yeaststrain are characteristic forthat strain, butthey varyfromonestrain to another (4,6-9). Asyeastcells age,theyaccumulate bud scarsontheir surface duetobudabscission. Thesebudscars aretheproduct ofthedeposition ofthepolysaccharide chitin inthecell wall. Ithasbeensuggested that theaccumulation ofbudscarson theyeastcellsurface may result inits senescence(4,6). Yeastcells appeartobeanexcellent experimental system forthestudy ofaging. Besides easeofcultivation, yeastcells possesstheadvantage thattheyarewellsuited togenetic manipulation, bothclassical andmolecular (19). Inaddition, life spanstudies canbereadily carried outon individual cells andpedigrees can beconstructed, duetotheasymmetric modeofcell division. However, nothing isknownabout the molecular determinants oflife span inyeasts.Before attempting a genetic andmolecular dissection oftheaging process,itisimportant toexamine thenatureofthedeterminants oflife spaninthese organisms. Inthiscommunication, evidence ispresented thatthe senescent phenotype prevails inyeastcells andthatitis determined bya diffusible cytoplasmic factor(s) thatundergoesturnover. We alsoadddatatothebodyofevidence
An 80-Gbps Distributed Driver with Two-Tap Feedforward Equalization in 45-nm CMOS SOI (2022)

This paper presents an integrated differential, distributed Mach-Zehnder modulator (MZM) driver with two-tap feedforward equalization (FFE). The driver consists of two-stack, pseudo-differential FET stages capable of voltage swings exceeding the V <inf xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">DD</inf> (1V). The measured chip produces error-free (BER $\lt 10^{-11})$ NRZ transmission up to 64 Gbps with 0.3 UI sampling margin and four-level pulse amplitude modulation (PAM-4) transmission up to 80 Gbps (40 Gbaud). The total power consumption of the driver is 310 mW for an energy efficiency of 4.8 pJ/bit for NRZ and 3.9 pJ/bit for PAM-4.
A 56.4-to-63.4GHz spurious-free all-digital fractional-N PLL in 65nm CMOS (2013)

Frequency synthesis at mm-Waves is still dominated by analog PLLs, although all-digital PLLs (ADPLLs) [1] have been widely explored below 10GHz. The major obstacle has been the poor quality of digitally controlled oscillators (DCO) as MOS varactor Q-factor drops to <;10 at 60GHz. A mm-Wave digital transmitter (TX) based on a 60GHz fractional-N ADPLL with two-point FM is proposed here. The TX features extensive reconfigurability and permits the highest degree of integration of RF and baseband circuitry for low-cost, high-volume applications. To simplify the TX architecture, the synthesizer is capable of FM, hence a time-to-digital converter (TDC) is preferred over bang-bang phase detection. With the aid of autonomous calibrations of DCO and TDC gain, wideband two-point FM is achieved.
Computational strategies for object recognition (1992)

This article reviews the available methods for automated identification of objects in digital images. The techniques are classified into groups according to the nature of the computational strategy used. Four classes are proposed: (1) the simplest strategies, which work on data appropriate for feature vector classification, (2) methods that match models to symbolic data structures for situations involving reliable data and complex models, (3) approaches that fit models to the photometry and are appropriate for noisy data and simple models, and (4) combinations of these strategies, which must be adopted in complex situations. Representative examples of various methods are summarized, and the classes of strategies with respect to their appropriateness for particular applications.
Multi-Domain Solutions for the Deployment of Private 5G Networks (2021)

Private 5G networks have become a popular choice of various vertical industries to build dedicated and secure wireless networks in industry environments to deploy their services with enhanced service flexibility and device connectivity to foster industry digitalization. This article proposes multiple multi-domain solutions to deploy private 5G networks for vertical industries across their local premises and interconnecting them with the public networks. Such scenarios open up a new market segment for various stakeholders, and break the current operators' business and service provisioning models. This, in turn, demands new interactions among the different stakeholders across their administrative domains. To this aim, three distinct levels of multi-domain solutions for deploying vertical's 5G private networks are proposed in this work, which can support interactions at different layers among various stakeholders, allowing for distinct levels of service exposure and control. Building on a set of industry verticals (comprising Industry 4.0, Transportation and Energy), different deployment models are analyzed and the proposed multi-domain solutions are applied. These solutions are implemented and validated through two proof-of-concept prototypes integrating a 5G private network platform (5Growth platform) with public ones. These solutions are being implemented in three vertical pilots conducted with real industry verticals. The obtained results demonstrated the feasibility of the proposed multi-domain solutions applied at the three layers of the system enabling various levels of interactions among the different stakeholders. The achieved end-to-end service instantiation time across multiple domains is in the range of minutes, where the delay impact caused by the resultant multi-domain interactions is considerably low. The proposed multi-domain approaches offer generic solutions and standard interfaces to support the different private network deployment models.
High-speed and low-latency front-haul system for heterogeneous wireless networks using seamless fiber-millimeter-wave (2015)

We propose a novel high-capacity and low-latency front-haul system for small cells-based heterogeneous wireless networks. We experimentally demonstrate a proof-of-concept seamless convergence of radio-over-fiber (RoF) and millimeter-wave (MMW) system at 90 GHz for high-speed wireless signal transmission. Simultaneous transmission and demodulation of standard-compliant very-high-throughput WLAN IEEE 802.11ac and high-speed LTE-A signals over the system are successfully confirmed for the downlink direction. Satisfactory transmission performance over the converged 10-km RoF and a 5-m 90-GHz wireless link is achieved. The measured root-mean-square error vector magnitude is much better than the requirement defined by the standards.
Chloroperoxidase‐catalyzed enantioselective oxidations in hydrophobic organic media (2001)

Chloroperoxidase from Caldariomyces fumago, a peroxidase that performs P450-like chemistry, was immobilized via covalent attachment into polyurethane foam as well as conjugated with a surfactant or polymer via colyophilization. The resulting preparations catalyzed enantio- and regioselective oxidations in hydrophobic organic media with tert-butyl hydroperoxide as the oxidant. Dried PUR-foam immobilized CPO mediated the selective oxidation of indole to 2-oxindole (regioselectivity: 99%) in water-saturated isooctane or 1-octanol. Thioanisole was converted into the corresponding (R)-sulfoxide (ee > 99%) in isooctane medium. The complexes of CPO with sodium octadecylsulphate or ethyl cellulose mediated the oxidation of thioanisole in water-immiscible organic media with variable enantioselectivity due to radical side-reactions. In the presence of α-tocopherol, acting as radical scavenger, the (R)-sulfoxide was formed with ee > 90%. The effect of the water activity on the catalytic activity of the complexes was investigated. The CPO complexes likewise mediated the regioselctive oxidation of indole into 2-oxindole in water-saturated isooctane or 1-octanol and its kinetics were investigated. The reaction suffered from substrate inhibition when carried out in isooctane. © 2001 John Wiley & Sons, Inc. Biotechnol Bioeng 72: 523–529, 2001.
BREATH ETHANE AND PLASMA CYTOKINE LEVELS IN HEMODIALYSIS PATIENTS (2002)

Long-term hemodialysis is associated with increased levels of ethane in the breath (a marker for oxidant stress) and elevated plasma cytokines (a marker for inflammation). Oxidant stress and inflammation may arise from common biological processes. To address this hypothesis, we measured breath ethane, and several different plasma cytokines and acute phase markers, including interleukin 6 (IL-b), α-1 acid glycoprotein (AAG), C reactive protein (UP) and myeloperoxidase (MPO), in 12 patients seen at monthly intervals (from 3–6 consecutive time points). Breath ethane was measured by GC. Plasma proteins were measured by nephelometry or ELISA. Serial changes in each parameter were compared by an adaptation of the sign test, a non-parametric procedure. Employing the sign test, changes in ethane were not related to changes in protein markers of inflammation. We also examined for a correlation between ethane and AAG, using a cross-correlation. Although the significance test would not be appropriate, this test yielded a positive association between ethane and AAG. This latter finding is consistent with the observation from other investigations that ethane and AAG both change relatively slowly over time in individual patients (over a interval of 30 days or longer), unlike CRP and IL-6 which fluctuate over intervals of a few days or even hours.
Blood glucose forecasting in patients with insulin dependent diabetes mellitus with the Universal Process Modeling Algorithm (1992)

Acute and chronic complications in patients with IDDM result from insufficiently controlled blood glucose. In order to assist insulin therapy we applied the Universal Process Modeling Algorithm (UPMA) to forecast blood glucose in patients with IDDM. Two diabetic patients (one stable and one unstable) documented blood glucose, therapy, physical activity and diets with an electronic diary (handyDOC™) over 12 months each. That data of the preceeding month were used to predict blood glucose changes in the consecutive month. Predictions of the short-term blood glucose fluctuations were significantly correlated with the observed blood glucose changes, correlation coefficients ranged from 0.45 to 0.73 (p<0.01) in either patient. Extremes of blood glucose changes (i.e. hypo- and hyperglycemias) were identified correctly in the majority (>70%) of the events. In contrast, neither of two diabetologists was able to produce a reliable prediction of future blood glucose changes (0.05 < r < 0.12; p>0.l).
CompressPoints: An Evaluation Methodology for Compressed Memory Systems (2018)

Current memory technology has hit a wall trying to scale to meet the increasing demands of modern client and datacenter systems. Data compression is a promising solution to this problem. Several compressed memory systems have been proposed in the past years [1], [2], [3], [4]. Unfortunately, a reasonable methodology to evaluate these systems is missing. In this paper, we identify the challenges for evaluating main memory compression. We propose an effective methodology to evaluate a compressed memory system by proposing mechanisms to: (i) incorporate correct virtual address translation, (ii) choose a region in the application that is representative of the compression ratio, in addition to regular metrics like IPC and cache hit rates, and (iii) choose a representative region for multi-core workloads, bringing down the correlation error from 12.8 to 3.8 percent.
Synergistic Growth of Giant Wormlike Micelles in Ternary Mixed Surfactant Solutions: Effect of Octanoic Acid (2016)

The synergistic growth of giant wormlike micelles in ternary mixed solutions composed of an anionic surfactant (sodium laurylethersulfate, SLES), a zwitterionic surfactant (cocamidopropyl betaine, CAPB), and octanoic acid (HC8) is studied. Rheological data and their analysis in terms of Cole-Cole plots and micellar characteristic times are presented, and the micellar structures behind the observed rheological behavior are revealed by cryo-TEM micrographs. The surfactant composition is fixed near the maximal micelle size of the binary SLES + CAPB system, whereas the concentration of HC8 is varied. At a given HC8 concentration, the viscosity of the ternary micellar solutions exhibits a very high and sharp peak. Polarized-light optical microscopy indicates that all investigated solutions are isotropic rather than liquid-crystalline. The cryo-TEM imaging shows complex phase behavior: wormlike micelles to the left of the peak, giant entangled wormlike micelles at the peak, and long wormlike micelles coexisting with multiconnected micellar aggregates to the right of the peak. The formation of multiconnected micelles leads to a drop in viscosity at the higher concentrations. The results contribute to a better understanding of the structure-rheology relations in micellar surfactant solutions and could be useful for controlling the properties of formulations in personal-care and house-hold detergency.
Adaptive language acquisition using incremental learning (1993)

An incremental approach to solving an algebraic formulation of the language acquisition problem is presented. This problem consists of solving a system of linear equations, where each equation represents a sentence/action pair and each variable denotes a word/action association. The algebraic model for language acquisition has been shown to provide advantages over the relative frequency estimate models when dealing with small-sample statistics. Two incremental methods are investigated to solve the system of linear equations. The incremental methods provide a regularized solution that is shown experimentally to be advantageous over the pseudo-inverse solution for classifying test data. In addition, the methods are more efficient with respect to computational and memory requirements.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
G‐Quadruplexes as Therapeutic Targets in Cancer (2013)

This chapter contains sections titled: Introduction Quadruplex Fundamentals Genomic Quadruplexes Quadruplexes in Human Telomeres Quadruplexes as Anticancer Targets – Evidence fromIn Vivo Studies Native Quadruplex Structures Quadruplex–Small-Molecule Structures Developing Superior Quadruplex-Binding Ligands Conclusions
Abstract IA16: Chemical inhibition of bromodomains (2012)

Abstract In cancer, epigenetic proteins are among the most promising and intently pursued targets in drug discovery. This relates to the growing appreciation that cancer growth pathways are centrally influenced by proteins which modify chromatin. Already, inhibitors of DNA methyltransferases and histone deacetylases have demonstrated substantial clinical efficacy leading to regulatory approval for use in hematologic malignancies. These events have triggered intense competition to develop inhibitors of chromatin modifying enzymes, or so-called epigenetic “writers” and “erasers.” Perhaps owing to perceptions regarding the feasibility of targeting protein:protein interactions, small-molecule inhibitors of chromatin-binding modules or epigenetic “readers” have not been described. Recently, we reported the first potent, small-molecule inhibitor of human bromodomains, JQ1, which exhibits selectivity for the BET family of bromodomain-containing transcriptional co-activators. Of broad relevance to cancer, we will present research demonstrating that c-Myc expression is critically dependent on BRD4 function and localization to discrete upstream regulatory regions. Exposure of cancer cells to JQ1 prompts immediate downregulation of c-Myc expression leading to suppression of a transcriptional program associated with proliferation, survival and metabolic adaptation. In translational models of Myc-dependent hematologic malignancies, the efficacy of JQ1 treatment establishes a mechanistic rationale for the leveraged clinical development of drug-like JQ1 derivatives. Toward this objective, we have completed chemical optimization of novel, drug-like inhibitors of BET bromodomains as reagents capable of supporting human clinical investigation. This research has established the feasibility of inhibiting epigenetic reader proteins with efficient, cell-permeable, small molecules. In support of an open-innovation model of chemical biology, we have created a chemical probe allowing the broad study of chromatin biology, which has already been provided to more than 250 academic, governmental and industrial laboratories worldwide. Together, we have rapidly identified mechanism-based opportunities for clinical translation in cancer, inflammation, and metabolic diseases. Citation Format: James E. Bradner. Chemical inhibition of bromodomains [abstract]. In: Proceedings of the AACR Special Conference on Chemical Systems Biology: Assembling and Interrogating Computational Models of the Cancer Cell by Chemical Perturbations; 2012 Jun 27-30; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2012;72(13 Suppl):Abstract nr IA16.
Metabolic and immune markers for precise monitoring of COVID-19 severity and treatment (2021)

Abstract Deep understanding of the SARS-CoV-2 effects on host molecular pathways is paramount for the discovery of early biomarkers of outcome of coronavirus disease 2019 (COVID-19) and the identification of novel therapeutic targets. In that light, we generated metabolomic data from COVID-19 patient blood using high-throughput targeted nuclear magnetic resonance (NMR) spectroscopy and high-dimensional flow cytometry. We find considerable changes in serum metabolome composition of COVID-19 patients associated with disease severity, and response to tocilizumab treatment. We built a clinically annotated, biologically-interpretable space for precise time-resolved disease monitoring and characterize the temporal dynamics of metabolomic change along the clinical course of COVID-19 patients and in response to therapy. Finally, we leverage joint immuno-metabolic measurements to provide a novel approach for patient stratification and early prediction of severe disease. Our results show that high-dimensional metabolomic and joint immune-metabolic readouts provide rich information content for elucidation of the host’s response to infection and empower discovery of novel metabolic-driven therapies, as well as precise and efficient clinical action.