gebhart/patrepeval huggingface dataset:
Rivaroxaban e malattia renale cronica: evidenze dal presente e prospettive future (2019)

Cardiovascular diseases represent the main cause of comorbidly in chronic kidney disease (CKD) patients, with a 7% incidence in atrial fibrillation (AF) in end-stage renal disease (ESRD) patients. Until recently, prophylactic treatment of atrial fibrillation complications (such as thromboembolism) was mainly based on vitamin K antagonists (VKA) or heparin. In the last years, direct oral anticoagulants (DOACs) have been made available; however, their renal clearance limits their use on patients with severe renal impairment (eGFR &lt;15 mL/min). Among DOACs, Rivaroxaban, a factor X-activated (Xa) inhibitor, shows good renal profile and it can be used in CKD patients up to stage 4 as well as in ESRD patients (at the moment only in North America and Canada). (Cardionephrology)
Temporal mechanisms of multimodal binding (2009)

The simultaneity of signals from different senses-such as vision and audition-is a useful cue for determining whether those signals arose from one environmental source or from more than one. To understand better the sensory mechanisms for assessing simultaneity, we measured the discrimination thresholds for time intervals marked by auditory, visual or auditory-visual stimuli, as a function of the base interval. For all conditions, both unimodal and cross-modal, the thresholds followed a characteristic 'dipper function' in which the lowest thresholds occurred when discriminating against a non-zero interval. The base interval yielding the lowest threshold was roughly equal to the threshold for discriminating asynchronous from synchronous presentations. Those lowest thresholds occurred at approximately 5, 15 and 75 ms for auditory, visual and auditory-visual stimuli, respectively. Thus, the mechanisms mediating performance with cross-modal stimuli are considerably slower than the mechanisms mediating performance within a particular sense. We developed a simple model with temporal filters of different time constants and showed that the model produces discrimination functions similar to the ones we observed in humans. Both for processing within a single sense, and for processing across senses, temporal perception is affected by the properties of temporal filters, the outputs of which are used to estimate time offsets, correlations between signals, and more.
ISCOMATRIX Adjuvant Induces Efficient Cross-Presentation of Tumor Antigen by Dendritic Cells via Rapid Cytosolic Antigen Delivery and Processing via Tripeptidyl Peptidase II (2009)

Abstract Cancer vaccines aim to induce antitumor CTL responses, which require cross-presentation of tumor Ag to CTLs by dendritic cells (DCs). Adjuvants that facilitate cross-presentation of vaccine Ag are therefore key for inducing antitumor immunity. We previously reported that human DCs could not efficiently cross-present the full-length cancer/testis Ag NY-ESO-1 to CTL unless formulated as either an immune complex (NY-ESO-1/IC) or with ISCOMATRIX adjuvant. We now demonstrate that NY-ESO-1/ICs induce cross-presentation of HLA-A2- and HLA-Cw3-restricted epitopes via a proteasome-dependent pathway. In contrast, cross-presentation of NY-ESO-1/ISCOMATRIX vaccine was proteasome independent and required the cytosolic protease tripeptidyl peptidase II. Trafficking studies revealed that uptake of ICs and ISCOMATRIX vaccine by DCs occurred via endocytosis with delivery to lysosomes. Interestingly, ICs were retained in lysosomes, whereas ISCOMATRIX adjuvant induced rapid Ag translocation into the cytosol. Ag translocation was dependent on endosomal acidification and IL-4-driven differentiation of monocytes into DCs. This study demonstrates that Ag formulation determines Ag processing and supports a role for tripeptidyl peptidase II in cross-presentation of CTL epitopes restricted to diverse HLA alleles.
Skin PDT dose-depth estimation for radiometric comparison of lamp and daylight sources (Conference Presentation) (2023)

Skin-based photodynamic therapy (PDT) is used for the clinical treatment of actinic keratosis (AKs) and other skin lesions with continued expansion into the standard of care. Due to the spectral dependency of photosensitizer activation and skin optical fluence, there is a need for more accurate methods to estimate the delivered dose at depth from different PDT light sources and treatment regimens. Here, we present radiometric methods for calculating photosensitizer-effective fluence and dose at depth and determine differences between red-lamp, blue-lamp, and daylight-based PDT treatments.
Immune complexes increase nitric oxide production by interferon-γ-stimulated murine macrophage-like J774.16 cells (1995)

Murine macrophage-like J774.16 cells were tested for changes in nitric oxide production upon incubation with immune complexes. Cryptococcus neoformans capsular polysaccharide and polysaccharide-specific monoclonal antibodies were added to J774.16 cells in the presence and absence of recombinant murine interferon-gamma (IFN-gamma). The effect of immune complexes on nitrite synthesis was both concentration dependent and isotype dependent. In the presence of IFN-gamma, immune complexes of IgG1, IgG2, IgG2b, or IgG3 isotype increased nitrite levels, whereas complexes of IgM isotype did not. Immune complexes did not alter nitrite production by unstimulated macrophages. Antibody alone, antigen alone, and antigen with irrelevant IgG1 antibody did not augment nitrite formation, either in the presence or absence of IFN-gamma, indicating a requirement for Fc gamma R cross-linking. These results suggest that IgG isotypes may offer additional protection against pathogens by enhancing macrophage nitric oxide production.
Successes and frontiers in extreme UV patterning (2016)

Impressive progress in replacing 193nm immersion multi-patterning techniques has been made in the last few years, but there are several remaining challenges before the full scaling benefits can be realized.
Carbomethoxychlorocarbene:  Spectroscopy, Theory, Chemistry and Kinetics (2001)

Photolysis (254 nm) of methyl 8-chloro-3a,7a-methanoindan-8-carboxylate (5) in argon at 14 K produces carbomethoxychlorocarbene (6) as a persistent species. The IR and UV-vis spectra of the carbene were recorded and analyzed with the aid of density functional calculations (B3-LYP/6-31G). The IR spectrum of 6 is consistent with the carbene having a nonplanar singlet ground state, in agreement with the G3(MP2)//B3-LYP calculations of Scott and Radom (accompanying paper). Irradiation (300 nm) of 5 in solution produces indane in 97% yield. In cyclohexane, carbene 6 is trapped by insertion into a CH bond, whereas in 2,3-dimethylbutene it adds to the double bond to form a cyclopropane. Laser flash photolysis of 5 (308 nm, 17 ns, XeCl excimer) produces carbene 6 which reacts with pyridine to form an ylide (lambda(max) = 440 nm). It was possible to resolve the growth of the ylide in Freon-113 (CF(2)ClCFCl(2)) to measure the lifetime (tau = 114 ns, ambient temperature) of the carbene and the absolute rate constant of its reaction with pyridine (k(pyr) = 2 x 10(9) M(-)(1) s(-)(1)). A plot of log(1/tau) versus 1/T in CF(2)ClCFCl(2) is linear with Arrhenius parameters E(a) = 10.9 +/- 0.8 kJ/mol and A = 10(9.1)(+/-)(0.2) s(-)(1). In perfluorohexane, a less reactive solvent than Freon-113, E(a) = 23.4 +/- 1.7 kJ/mol, A = 10(10.6)(+/-)(0.) s(-)(1), and tau = 354 ns at 293 K. It is argued that the activation barrier to carbene disappearance in perfluorohexane represents the lower limit to the barrier to Wolff rearrangement of the carbene.
Characterization of Novel OmpA-Like Protein of Leptospira interrogans That Binds Extracellular Matrix Molecules and Plasminogen (2011)

Leptospira interrogans is the etiological agent of leptospirosis, a zoonotic disease of human and veterinary concern. The identification of novel proteins that mediate host-pathogen interactions is important for understanding the bacterial pathogenesis as well as to identify protective antigens that would help fight the disease. We describe in this work the cloning, expression, purification and characterization of three predicted leptospiral membrane proteins, LIC10258, LIC12880 (Lp30) and LIC12238. We have employed Escherichia coli BL21 (SI) strain as a host expression system. Recently, we have identified LIC12238 as a plasminogen (PLG)-binding receptor. We show now that Lp30 and rLIC10258 are also PLG-receptors of Leptospira, both exhibiting dose-dependent and saturating binding (K(D), 68.8±25.2 nM and 167.39±60.1 nM, for rLIC10258 and rLIC12880, respectively). In addition, LIC10258, which is a novel OmpA-like protein, binds laminin and plasma fibronectin ECM molecules and hence, it was named Lsa66 (Leptospiral surface adhesin of 66 kDa). Binding of Lsa66 to ECM components was determined to be specific, dose-dependent and saturable, with a K(D) of 55.4±15.9 nM to laminin and of 290.8±11.8 nM to plasma fibronectin. Binding of the recombinant proteins to PLG or ECM components was assessed by using antibodies against each of the recombinant proteins obtained in mice and confirmed by monoclonal anti-polyhistidine antibodies. Lsa66 caused partial inhibition on leptospiral adherence to immobilized ECM and PLG. Moreover, this adhesin and rLIC12238 are recognized by antibodies in serum samples of confirmed leptospirosis cases. Thus, Lsa66 is a novel OmpA-like protein with dual activity that may promote the attachment of Leptospira to host tissues and may contribute to the leptospiral invasion. To our knowledge, this is the first leptospiral protein with ECM and PLG binding properties reported to date.
Computer-aided choice of production means for assembly lines (1995)

info:eu-repo/semantics/published
Charge Disproportionation and Complex Magnetism in a PbMnO3 Perovskite Synthesized under High Pressure (2020)

Because of the possible crossover of Pb and 3d transition-metal (TM) redox levels, a charge transfer between Pb and TM leads to a continuous evolution from Pb2+Ti4+O3 to Pb4+Ni2+O3 in the perovskite family of PbTMO3 as verified by several reports. However, very little information is known about PbMnO3 in the PbTMO3 series. The perovskite PbMnO3 is the most difficult one to synthesize, although its geometric tolerance factor is close to 1. Here, we report a careful study of PbMnO3 synthesized under 15 GPa by a structural refinement and high-precision X-ray absorption spectroscopy (XAS) as well as a variety of measurements of physical properties. We can rationalize the physical properties of PbMnO3 based on a local bonding model and the valence states of Pb and Mn from XAS. Moreover, the complete study of PbMnO3 allows us to construct a more consistent picture of the valence evolution and the charge disproportionation for the entire family of PbTMO3 perovskites.
Inhibition of Glucosylceramide Synthase Does Not Reverse Drug Resistance in Cancer Cells (2004)

The multidrug-resistant cancer cell lines NCI/AdR(RES) and MES-SA/DX-5 have higher glycolipid levels and higher P-glycoprotein expression than the chemosensitive cell lines MCF7-wt and MES-SA. Inhibiting glycolipid biosynthesis by blocking glucosylceramide synthase has been proposed to reverse drug resistance in MDR cells by causing an increased accumulation of proapoptotic ceramide during treatment of cells with cytotoxic drugs. We treated both multidrug-resistant cell lines with the glucosylceramide synthase inhibitors PDMP (d-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol), C9DGJ (N-nonyl-deoxygalactonojirimycin) or C4DGJ (N-butyl-deoxygalactonojirimycin). PDMP achieved a significant reversal of drug resistance in agreement with previous reports. However, the N-alkylated iminosugars C9DGJ and C4DGJ, which are more selective glucosylceramide synthase inhibitors than PDMP, failed to cause any reversal of drug resistance despite depleting glycolipids to the same extent as PDMP. Our results suggest that (a) inhibition of glucosylceramide synthase does not reverse multidrug resistance and (b) the chemosensitization achieved by PDMP cannot be caused by inhibition of glucosylceramide synthase alone.
Kinetic mechanism and ATP‐binding site reactivity of p38γ MAP kinase (1999)

Activated p38gamma MAP kinase exhibited significant basal ATPase activity in the absence of a kinase substrate, and addition of a phosphoacceptor substrate increased k(cat)/K(m)20-fold. AMP-PCP was competitive with ATP binding and non-competitive with phosphoacceptor substrate binding. The nucleotide binding site affinity label 5'-(p-fluorosulfonylbenzoyl)adenosine (FSBA) bound stoichiometrically at Lys-56 in the ATP site of both unphosphorylated and activated p38gamma. AMP-PCP only protected the activated enzyme from FSBA inactivation, implying that AMP-PCP does not bind unphosphorylated p38gamma. Basal ATPase activities were also observed for activated p38alpha, ERK2 and JNK3 suggesting that the enzymatic mechanism may be similar for all classes of MAP kinases.
A Transfected Sialyltransferase That Is Elevated in Breast Cancer and Localizes to the medial/trans-Golgi Apparatus Inhibits the Development of core-2–based O-Glycans (1997)

The alpha2,3 sialyltransferase, alpha2,3 SAT (O), catalyzes the transfer of sialic acid to Galbeta1,3 N-acetyl-D-galactosamine (GalNAc) (core-1) in mucin type O-glycosylation, and thus terminates chain extension. A Core-2 branch can also be formed from core-1 by the core-2 beta1,6 N-acetyl-d-glucosamine transferase (beta1,6 GlcNAc T) that leads to chain extension. Increased levels of the alpha2,3 SAT (O) and decreased levels of the core-2 beta1,6 GlcNAc T are seen in breast cancer cells and correlate with differences in the structure of the O-glycans synthesized (Brockhausen et al., 1995; Lloyd et al., 1996). Since in mucin type O-glycosylation sugars are added individually and sequentially in the Golgi apparatus, the position of the transferases, as well as their activity, can determine the final structure of the O-glycans synthesized. A cDNA coding for the human alpha2,3 SAT (O) tagged with an immunoreactive epitope from the myc gene has been used to map the position of the glycosyltransferase in nontumorigenic (MTSV1-7) and malignant (T47D) breast epithelial cell lines. Transfectants were analyzed for expression of the enzyme at the level of message and protein, as well as for enzymic activity. In T47D cells, which do not express core-2 beta1,6 GlcNAc T, the increased activity of the sialyltransferase correlated with increased sialylation of core-1 O-glycans on the epithelial mucin MUC1. Furthermore, in MTSV1-7 cells, which do express core-2 beta1,6 GlcNAc T, an increase in sialylated core-1 structures is accompanied by a reduction in the ratio of GlcNAc: GalNAc in the O-glycans attached to MUC1, implying a decrease in branching. Using quantitative immunoelectron microscopy, the sialyltransferase was mapped to the medial- and trans-Golgi cisternae, with some being present in the TGN. The data represent the first fine mapping of a sialyltransferase specifically active in O-glycosylation and demonstrate that the structure of O-glycans synthesized by a cell can be manipulated by transfecting with recombinant glycosyltransferases.
On the Capacity of Memoryless Relay Networks (2006)

In a relay network, the signal processing at the relay significantly affects the capacity benefits of cooperation. In this work, we explore the optimal relay functionality for capacity maximization in a memoryless relay network, i.e. a network where, during each channel use, the signal transmitted by a relay depends only on the last received symbol at that relay. By relating some of the existing memoryless forwarding strategies to the fundamental signal processing operations of estimation and detection, we develop a new scheme that forwards the unconstrained minimum mean square error (MMSE) estimate obtained at the relay to the destination. For a single relay system, we derive the characterization of the optimal relay function and show that the relay function of EF (estimate and forward) satisfies the optimality condition. For the multiple relay case, we consider both parallel and serial relay networks and show that EF performs better than both AF (amplify and forward) and DF (demodulate and forward). For hybrid networks that contain both serial and parallel elements, and when robust performance is desired at all SNR, the advantage of EF over the best of AF and DF is found to be significant.
Data from Validation of a Plasma-Based Comprehensive Cancer Genotyping Assay Utilizing Orthogonal Tissue- and Plasma-Based Methodologies (2023)

&lt;div&gt;Abstract&lt;p&gt;&lt;b&gt;Purpose:&lt;/b&gt; To analytically and clinically validate a circulating cell-free tumor DNA sequencing test for comprehensive tumor genotyping and demonstrate its clinical feasibility.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Experimental Design:&lt;/b&gt; Analytic validation was conducted according to established principles and guidelines. Blood-to-blood clinical validation comprised blinded external comparison with clinical droplet digital PCR across 222 consecutive biomarker-positive clinical samples. Blood-to-tissue clinical validation comprised comparison of digital sequencing calls to those documented in the medical record of 543 consecutive lung cancer patients. Clinical experience was reported from 10,593 consecutive clinical samples.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Results:&lt;/b&gt; Digital sequencing technology enabled variant detection down to 0.02% to 0.04% allelic fraction/2.12 copies with ≤0.3%/2.24–2.76 copies 95% limits of detection while maintaining high specificity [prevalence-adjusted positive predictive values (PPV) &gt;98%]. Clinical validation using orthogonal plasma- and tissue-based clinical genotyping across &gt;750 patients demonstrated high accuracy and specificity [positive percent agreement (PPAs) and negative percent agreement (NPAs) &gt;99% and PPVs 92%–100%]. Clinical use in 10,593 advanced adult solid tumor patients demonstrated high feasibility (&gt;99.6% technical success rate) and clinical sensitivity (85.9%), with high potential actionability (16.7% with FDA-approved on-label treatment options; 72.0% with treatment or trial recommendations), particularly in non–small cell lung cancer, where 34.5% of patient samples comprised a directly targetable standard-of-care biomarker.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Conclusions:&lt;/b&gt; High concordance with orthogonal clinical plasma- and tissue-based genotyping methods supports the clinical accuracy of digital sequencing across all four types of targetable genomic alterations. Digital sequencing's clinical applicability is further supported by high rates of technical success and biomarker target discovery. &lt;i&gt;Clin Cancer Res; 24(15); 3539–49. ©2018 AACR&lt;/i&gt;.&lt;/p&gt;&lt;/div&gt;
Experimental emulation for OTFS waveform RF-impairments (2022)

Orthogonal time-frequency space (OTFS) waveform exceeds the challenges that face orthogonal frequency division multiplexing (OFDM) in the high-mobility environment with high time-frequency dispersive channels. Since practical pulse shaping design and RF-impairments effects have a direct impact on waveform behavior, this paper investigates experimental implementation for practical pulse shaping design and RF-impairments that affect OTFS waveform performance and compares them to OFDM waveform as a benchmark. Firstly, the doubly-dispersive channel effect is analyzed, then an experimental framework is established for investigating the RF-impairments include non-linearity, Carrier frequency offset, I/Q-imbalances, DC-offset, and phase noise are considered. The experiments were conducted in a real indoor wireless environment using software-defined radio (SDR)based on the Keysight EXG X-Serie devices. The experimental results validate the accuracy of the theoretical results.
Time-resolved transient absorption ultrasonic microscopy measurements of the ground state recovery time (2012)

We have recently developed Transient Absorption Ultrasonic Microscopy (TAUM) as an ultrahigh-resolution photoacoustic microscopy technique. The amplitude of the multiphoton pump-probe interaction is dependent on the interpulse delay between the pump and probe pulses. Measuring the interpulse delay dependent TAUM amplitude maps out the ground state recovery time of the chromophore. The ground state recovery time is a molecular signature that may be used to differentiate multiple chromophores, analogous to fluorescence lifetime. We have used TAUM to measure the ground state recovery time of Rhodamine 6G to be 3.65 ns, which matches well with known literature values. Whole blood is also investigated, with measured ground state recovery times of 3.74 ns for oxygenated blood and 7.9 ns for deoxygenated blood. The distinct difference in lifetimes for the oxidized and reduced forms suggests the feasibility of subcellular SO2 images maps in future iterations of TAUM.
A Structural Model for Binding of the Serine-Rich Repeat Adhesin GspB to Host Carbohydrate Receptors (2011)

GspB is a serine-rich repeat (SRR) adhesin of Streptococcus gordonii that mediates binding of this organism to human platelets via its interaction with sialyl-T antigen on the receptor GPIbα. This interaction appears to be a major virulence determinant in the pathogenesis of infective endocarditis. To address the mechanism by which GspB recognizes its carbohydrate ligand, we determined the high-resolution x-ray crystal structure of the GspB binding region (GspB(BR)), both alone and in complex with a disaccharide precursor to sialyl-T antigen. Analysis of the GspB(BR) structure revealed that it is comprised of three independently folded subdomains or modules: 1) an Ig-fold resembling a CnaA domain from prokaryotic pathogens; 2) a second Ig-fold resembling the binding region of mammalian Siglecs; 3) a subdomain of unique fold. The disaccharide was found to bind in a pocket within the Siglec subdomain, but at a site distinct from that observed in mammalian Siglecs. Confirming the biological relevance of this binding pocket, we produced three isogenic variants of S. gordonii, each containing a single point mutation of a residue lining this binding pocket. These variants have reduced binding to carbohydrates of GPIbα. Further examination of purified GspB(BR)-R484E showed reduced binding to sialyl-T antigen while S. gordonii harboring this mutation did not efficiently bind platelets and showed a significant reduction in virulence, as measured by an animal model of endocarditis. Analysis of other SRR proteins revealed that the predicted binding regions of these adhesins also had a modular organization, with those known to bind carbohydrate receptors having modules homologous to the Siglec and Unique subdomains of GspB(BR). This suggests that the binding specificity of the SRR family of adhesins is determined by the type and organization of discrete modules within the binding domains, which may affect the tropism of organisms for different tissues.
Life at the extreme: lessons from the genome (2012)

Extremophile plants thrive in places where most plant species cannot survive. Recent developments in high-throughput technologies and comparative genomics are shedding light on the evolutionary mechanisms leading to their adaptation.
Pyridoxamine: A novel treatment for schizophrenia with enhanced carbonyl stress (2017)

High-dose pyridoxamine add-on treatment was, in part, effective for a subpopulation of schizophrenia patients with enhanced carbonyl stress. Further randomized, placebo-controlled trials with careful monitoring will be required to validate the efficacy of high-dose pyridoxamine for these patients.