gebhart/patrepeval huggingface dataset:
Significant durable response with fianlimab (anti-LAG-3) and cemiplimab (anti-PD-1) in advanced melanoma: Post adjuvant PD-1 analysis. (2023)

9501 Background: Previous reports have demonstrated that treatment (Tx) with anti-LAG-3 Ab fianlimab + anti-PD-1 Ab cemiplimab had a 63.8% ORR across two separate cohorts of advanced PD-(L)1 naïve metastatic melanoma (Mel) patients (pts). The benefit the fianlimab + cemiplimab combination in pts exposed to prior anti-PD-1 Tx as adjuvant (adj) Tx is unknown. Here we present phase 1 safety and clinical activity data from pts with advanced Mel including those who received prior adj systemic Tx. Methods: Three separate expansion cohorts of adult pts with unresectable or metastatic Mel (excluding uveal Mel) who were anti–PD-(L)1 Tx-naïve for advanced disease were enrolled. All pts received fianlimab 1600 mg + cemiplimab 350 mg IV Q3W for 12 months (mos) (optional additional 12 mos if clinically indicated). Study enrollment closed in June 2022. Tumor measurements were performed every 6 weeks (wks) for 24 wks, then every 9 wks. Results: 98 pts were enrolled and treated with fianlimab + cemiplimab as of 01 Nov 2022 data cutoff. Median age was 68.0 years, 60.2% were male, and 89.8% were White. 2.0% of pts had received prior metastatic Tx (not anti–PD-(L)1) and 23.5% had received prior systemic Tx for Mel in the adj/neo-adj setting (disease-free interval &gt; 6 mos), including 13.3% treated with an anti-PD-1 (nivolumab or pembrolizumab). Median follow up was 12.6 mos and median treatment duration was 32.9 wks. Grade ≥3 treatment-emergent adverse events (TEAEs), serious TEAEs, and immune-related AEs (irAEs) occurred in 43.9%, 32.7%, and 65.3% of pts, respectively. 16.3% of pts discontinued Tx due to a TEAE. Rates of irAEs were similar to anticipated rates for PD-1 monotherapy with the exception of adrenal insufficiency (AI) with 12.2% (all grades) and 4.1% (grade ≥3). RECIST 1.1-based investigator-assessed overall ORR was 61.2% (12 complete responses; 48 partial responses), with median DOR (mDOR) not reached [NR] (95% CI: 22.6– not estimated [NE]). KM estimation of median PFS (mPFS) was 15.3 (95% CI: 9.4–NE) mos. In pts with any prior adj Tx, ORR, mDOR, and mPFS was 60.9% (14/23), NR, and 13.3 mos, respectively. In pts with prior anti-PD-1 adj Tx, ORR, mDOR, and mPFS was 61.5% (8/13), NR, and 11.8 mos, respectively. Data from subgroup and correlative biomarker analyses, PK and immunogenicity will be included in the presentation. Conclusions: Fianlimab + cemiplimab in advanced Mel pts showed high clinical activity that compares favorably with other approved combinations of immune checkpoint inhibitors in the same clinical setting. This is the first indication that dual LAG-3 blockade can produce high level of activity with significant ORR in pts with advanced Mel post adj anti-PD-1 Tx. The safety profile of fianlimab + cemiplimab is similar to anti-PD-1 monotherapy with the exception of AI. A phase 3 trial (NCT05352672) of fianlimab + cemiplimab in Tx-naïve advanced Mel pts is ongoing. Clinical trial information: NCT03005782 .
Experimental and Simulation Study of the Effects of Heavy-ion Irradiation on HfO2-based RRAM Cells (2017)

HfO <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sub> -based resistive RAMs have been irradiated with high-linear energy transfer heavy ions and subjected to an extensive characterization, showing that the cells are immune from upsets. No relevant changes were observed in the irradiated cells on resistance distribution and programming voltages. The irradiation experiment has been performed without any applied bias (retention mode). Reasons for the observed hardness are discussed using physics-based simulations. Moreover, simulations put in evidence that the cell might be sensitive if it is struck during a read operation, since the applied read voltage prevents the instantaneous recombination of the generated defects due to the Coulomb interaction between oxygen ions and vacancies.
Neural Networks-Based Equalizers for Coherent Optical Transmission: Caveats and Pitfalls (2022)

This paper performs a detailed, multi-faceted analysis of key challenges and common design caveats related to the development of efficient neural networks (NN) based nonlinear channel equalizers in coherent optical communication systems. The goal of this study is to guide researchers and engineers working in this field. We start by clarifying the metrics used to evaluate the equalizers’ performance, relating them to the loss functions employed in the training of the NN equalizers. The relationships between the channel propagation model’s accuracy and the performance of the equalizers are addressed and quantified. Next, we assess the impact of the order of the pseudo-random bit sequence used to generate the – numerical and experimental – data as well as of the DAC memory limitations on the operation of the NN equalizers both during the training and validation phases. Finally, we examine the critical issues of overfitting limitations, the difference between using classification instead of regression, and batch-size-related peculiarities. We conclude by providing analytical expressions for the equalizers’ complexity evaluation in the digital signal processing (DSP) terms and relate the metrics to the processing latency.
The role of renal hypoperfusion in development of renal microcirculatory dysfunction in endotoxemic rats: reply to Ji et al. (2011)

Dear Editor,

We would like to thank Ji et al. [1] for their comments regarding our recently published study [2]. The authors raised two very interesting and relevant points of concern.

First, they point out that we might have missed the initial peak in TNF-α expression shortly after LPS infusion and therefore cannot conclude that neither immediate nor late fluid could prevent systemic inflammatory activation. However, although we may have missed the peak expression, we could still detect increased TNF-α levels at the end of our protocol group which evidently indicates that neither immediate nor late fluid resuscitation could completely prevent systemic inflammatory activation. Furthermore, plasma TNF-α may not accurately reflect TNF-α kinetics in tissue. For instance, Detmer et al. [3] found that TNF-α increased until 360 min after LPS exposure in smooth muscle cells. The kinetics of TNF-α release may also been modified by interaction of TNF-α with other cytokines. Andersson et al. [4] found a reciprocal functional relationship between cytokines with HMG-1 extending and amplifying the secretion of TNF-α. Thus, if anything, the point raised by Ji et al. does not preclude our conclusion. Nonetheless, we must acknowledge that the main aim of our study was not to investigate the whole picture of the LPS-induced cytokine response spectrum, but to investigate the role of LPS-induced hypotension and renal hypoperfusion in the development of renal microcirculatory dysfunction and systemic and renal inflammatory activation. The method we used fits this goal.

Second, Ji et al. raised concerns regarding the relatively small sample size. This might be a valid point here. However, although we can not exclude a lack of power, we believe that increasing the sample size would not show a different result with respect to the very similar TNF-α plasma levels in the immediately and delayed resuscitated groups. The authors also pointed out that there was a clerical error in the abstract of the article. For this we would like to apologize.

Finally, the authors state that the data presented in our study should be interpreted with some caution. Of course, as should the data presented in every study. Furthermore, the authors state that more research is needed. Again, we agree. Although we could explore the role of renal hypoperfusion in the development of renal microcirculatory failure, application of immediate fluid resuscitation is clinically impossible. Hence, future research could focus on developing therapeutic strategies protecting the renal microcirculation in endotoxemia, hemorrhage, ischemia/reperfusion injury, and other scenarios in which the kidney might suffer from hypoperfusion and inflammation.
Generation of Recombination Activating Gene-1-Deficient Neonatal Piglets: A Model of T and B Cell Deficient Severe Combined Immune Deficiency (2014)

Although severe combined immune deficiency (SCID) is a very important research model for mice and SCID mice are widely used, there are only few reports describing the SCID pig models. Therefore, additional research in this area is needed. In this study, we describe the generation of Recombination activating gene-1 (Rag-1)-deficient neonatal piglets in Duroc breed using somatic cell nuclear transfer (SCNT) with gene targeting and analysis using fluorescence-activated cell sorting (FACS) and histology. We constructed porcine Rag-1 gene targeting vectors for the Exon 2 region and obtained heterozygous/homozygous Rag-1 knockout cell colonies using SCNT. We generated two Rag-1-deficient neonatal piglets and compared them with wild-type neonatal piglets. FACS analysis showed that Rag-1 disruption causes a lack of Immunoglobulin M-positive B cells and CD3-positive T cells in peripheral blood mononuclear cells. Consistent with FACS analysis, histological analysis revealed structural defects and an absence of mature lymphocytes in the spleen, mesenteric lymph node (MLNs), and thymus in Rag-1-deficient piglets. These results confirm that Rag-1 is necessary for the generation of lymphocytes in pigs, and Rag-1-deficient piglets exhibit a T and B cell deficient SCID (T-B-SCID) phenotype similar to that of rodents and humans. The T-B-SCID pigs with Rag-1 deficiency generated in this study could be a suitably versatile model for laboratory, translational, and biomedical research, including the development of a humanized model and assessment of pluripotent stem cells.
Evidence for dimeric and tetrameric water clusters in HZSM-5 (1997)

Temperature-programmed desorption shows that water desorbs from HZSM-5 (Si/Al = 13) · nH2O in a two-step process. The amount of water evolved at each step corresponds to about two H2O per acidic proton, indicating that the tetrameric cluster formed at full loading consists of a strongly bound pair and a weakly bound pair of water molecules. Quantum mechanical studies using cluster models of aluminosilicate systems indicate that the desorption energies for the first and second water molecules of a dimer adsorbed at the acid site are 9.7 and 12.6 kcal/mol, respectively. These values are within the energy resolution of the TPD experiment and are consistent with both water molecules from the dimer seeming to desorb simultaneously. Evidence for a tetramer is consistent with earlier findings on dealuminated mordenites.
Exploring the excited-state charge transfer fluorescence profile of 7-hydroxycoumarin and 2-methylimidazole – a combined X-ray diffraction and theoretical approach (2022)

This study investigated the effect of 2-methylimidazole (2-MIM) addition on the fluorescence of ethyl-7-hydroxy-2-oxo-2<i>H</i>-chromene-3-carboxylate using low-cost density functional theory (DFT) and Time-Dependent DFT calculations on single crystal X-ray geometries of ethyl-7-hydroxy-2-oxo-2<i>H</i>-chromene-3-carboxylate hydrate (1), 2-MIM (2), and the 1 : 1 co-crystal of (1) and (2), (3). At low concentrations (1 : 1-1 : 10) of 2-MIM, the fluorophore shows a decrease in the fluorescence intensity, but at higher concentrations (above 1 : 10) the fluorescence excitation maximum shifted from 354 nm to 405 nm, with a significant emission intensity increase. The changed excitation and emission profile at high concentrations is due to the deprotonation of the coumarin's phenolic group, which was confirmed by the increased shielding of the aromatic protons in the titration <sup>1</sup>H NMR spectra. The experimental fluorescence data between the 1 : 1 and 1 : 10 ratios agreed with the theoretical fluorescence data, with a redshift and decreased intensity when comparing (1) and (3). The data indicated that combining the fluorophore with 2-MIM increased levels of vibronic coupling between 2-MIM and the fluorophore decreasing de-excitation efficiency. These increased vibronic changes were due to charge transfer between the fluorophore and 2-MIM in (3). The subtle movement of the proton, H(5) toward N(2') (0.07 Å) caused a significant decrease in fluorescence due to electron density distribution (EDD) changes. This was identified by comparison of the EDD in the excited (S<sub>1</sub>) and ground (S<sub>0</sub>) states plotted as an isosurface of EDD difference. For the higher concentrations, an alternative excitation pathway was explored by modifying the crystal geometry of (3) based on <sup>1</sup>H NMR spectroscopy data to resemble excitoplexes. Theses excitoplex geometries reflected the fluorescence profile of the fluorophore with high concentrations of 2-MIM; there were dramatic changes in the theoretical fluorescence pathway, which was 100% vibronic coupling compared to 15.31% in the free fluorophore. At this concentration, the de-excitation pathway causes remodelling of the lactone ring <i>via</i> stretching/breaking the CO bond in the S<sub>1</sub> causing increased fluorescence by movement of the transition dipole moment. These results reflect previous studies, but the methods used are less experimentally and computationally expensive. This study is among the first to explain charge transfer fluorescence using crystalline geometries. This study will be of interest to the fields of crystal engineering and fluorescence spectroscopy.
Correlation of Raman spectra of zeolites with framework architecture (1991)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTCorrelation of Raman spectra of zeolites with framework architecturePrabir K. Dutta, K. Mohana Rao, and Jong Yul ParkCite this: J. Phys. Chem. 1991, 95, 17, 6654–6656Publication Date (Print):August 1, 1991Publication History Published online1 May 2002Published inissue 1 August 1991https://pubs.acs.org/doi/10.1021/j100170a050https://doi.org/10.1021/j100170a050research-articleACS PublicationsRequest reuse permissionsArticle Views1227Altmetric-Citations136LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access options Get e-Alerts
Simulation of Model Predictive Controller Based Oscillatory Water Pumping System for Residential Applications (2019)

The utilization of renewable energy sources has been rising from the last few years due to their enormous advantages. This paper presents the design of bladeless wind turbine utilizing the principles of the wind. It involves design of model predictive controller based maximum power point tracking system which tracks the voltage, current and power of the bladeless wind turbine. This paper also involves the design of water pumping system with the utilization of single phase induction motor and so the design of single phase inverter has been proposed. It presents the battery management system which continuously monitors the charging and discharging states of the battery based up on the power requirement. The entire system was designed and the results have been analyzed using MATLAB Simulink.
Autumn warming and carbon balance of a boreal Scots pine forest in Southern Finland (2009)

Abstract. We analyzed the dynamics of carbon balance components: gross primary production (GPP) and total ecosystem respiration (TER), of a boreal Scots pine forest in Southern Finland. Our aim was to study how these dynamics are related to different environmental conditions and how they affect the inter-annual variation in the carbon balance in autumn (September–December). We used standard micrometeorological data and CO2 exchange measurements collected by the eddy covariance (EC) technique over 11 years. The intra-annual relationships between the carbon balance components and the environmental factors were studied by the correlation analysis. Two models, a stand photosynthesis model and a generic dynamic vegetation model (ORCHIDEE), were also applied in the analysis. EC data revealed that increasing autumn temperature significantly enhances TER: the temperature sensitivity was 9.5 gC m−2 °C−1 for the period September–October (early autumn when high radiation levels still occur) and 3.8 gC m−2 °C−1 for November–December (late autumn with suppressed radiation level). The cumulative GPP was practically independent of the temperature in early autumn. In late autumn, air temperature could explain part of the variation in GPP but the temperature sensitivity was very weak, less than 1 g C m−2 °C−1. The stand photosynthesis model predicted that under a predescribed 3–6°C temperature increase, the temperature sensitivity of 4–5 gC m−2 °C−1 in GPP may appear in early autumn. The TER and GPP sensitivities, produced by the ORCHIDEE model, were similar to observed ones when the site level ½ h time step was applied, but the results calculated by using daily meteorological forcing, interpolated to ½ h time step, were biased stemming from the nonlinear relationship between the processes and the environmental factors.
Progress on Phase Separation Microfluidics (2014)

High power density GaN HEMT technology can increase the capability of defense electronics systems with the reduction of CSWaP. However, thermal limitations have currently limited the inherent capabilities of this technology where transistor-level power densities that exceed 10 kW/cm2 are electrically feasible. This paper introduces the concept of an evaporative microcooling device utilizing some of the current two-phase vapor separation technologies currently being developed for water and dielectric liquids.
Overexpression of alpha synuclein disrupts APP and Endolysosomal axonal trafficking in a mouse model of synucleinopathy (2023)

Mutations or triplication of the alpha synuclein (ASYN) gene contribute to synucleinopathies including Parkinson's disease (PD), Dementia with Lewy bodies (DLB) and multiple system atrophy (MSA). Recent evidence suggests that ASYN also plays an important role in amyloid-induced neurotoxicity, although the mechanism(s) remains unknown. One hypothesis is that accumulation of ASYN alters endolysosomal pathways to impact axonal trafficking and processing of the amyloid precursor protein (APP). To define an axonal function for ASYN, we used a transgenic mouse model of synucleinopathy that expresses a GFP-human ASYN (GFP-hASYN) transgene and an ASYN knockout (ASYN<sup>-/-</sup>) mouse model. Our results demonstrate that expression of GFP-hASYN in primary neurons derived from a transgenic mouse impaired axonal trafficking and processing of APP. In addition, axonal transport of BACE1, Rab5, Rab7, lysosomes and mitochondria were also reduced in these neurons. Interestingly, axonal transport of these organelles was also affected in ASYN<sup>-/-</sup> neurons, suggesting that ASYN plays an important role in maintaining normal axonal transport function. Therefore, selective impairment of trafficking and processing of APP by ASYN may act as a potential mechanism to induce pathological features of Alzheimer's disease (AD) in PD patients.
Effect of Alternating Layers of Anionic and Cationic Polyelectrolyte Complexes on Colorant Fixing and Liquid&#xA0;Absorption (2014)

Inkjet ink colorants usually require different substrate modification depending on the colorant chemistry, solvent composition, and ink formulation. In this work, the authors investigated a novel concept based on alternating layers of anionic and cationic polyelectrolytes on a paper surface and the impact on ink colorant fixing and liquid absorption. The effect of nanoparticles in polyelectrolyte layers was investigated in order to clarify the changes in absorption rates. The alternating layering of micron-thin layers of cationic and anionic polyelectrolytes subjected to interim drying showed that the spreading and absorption of nanosize pigmented water-based ink were sensitive to the charge characteristics of the polyelectrolyte multilayer and also to the presence of nanopigments that enhanced the absorption speed and capacity. The interlayer polyelectrolyte complexing resulted not only in different ink-trapping fixing effects, but also in varying uniformity in ink spreading and absorption.
Pre-transplant achievement of negativity in minimal residual disease and French–American–British L1 morphology predict superior outcome after allogeneic transplant for Philadelphia chromosome positive acute lymphoblastic leukemia: an analysis of Southeast Asian patients (2014)

To better understand predictive factors and improve the clinical outcome of allogeneic transplant for patients with Philadelphia positive acute lymphoblastic leukemia, we analyzed 67 Southeast Asian patients transplanted in our institutions. Multivariate analysis showed that disease status before transplant, year of transplant and, interestingly, French-American-British (FAB) subtype had a significant impact on overall survival (OS) and non-relapse mortality. Patients who were minimal residual disease (MRD) negative at transplant had a 3-year OS of 73% compared to those who were MRD positive (45%) and refractory (0%). The 3-year cumulative incidence of relapse was 18% and 36% for the MRD negative and positive groups, respectively. FAB L1 subtype had a significantly superior 3-year OS of 63% vs. 29% for L2 subtype. Pre-transplant use of a tyrosine kinase inhibitor significantly improved outcomes in univariate but not multivariate analysis, as it served to induce more patients into MRD negativity, which was the factor that directly improved transplant outcome.
Single and multi-pixel modulators for infrared beams using active metamaterials. (2009)

Abstract not provided.
ChemInform Abstract: Catalytic Z‐Selective Cross‐Metathesis in Complex Molecule Synthesis: A Convergent Stereoselective Route to Disorazole C1. (2015)

Abstract The diastereo‐ and enantioselective preparation of the macrocyclic natural product (IV) with anticancer and antifungal activities is described which comprises the title reaction as a key step.
Analytic descriptions of parabolic X-ray mirrors (2022)

On X-ray beamlines and telescopes, glancing-incidence mirrors with parabolic profiles are used to collimate, focus, and collect light. Here, analytic descriptions for paraboloidal, plane-parabolic, and parabolic cylindrical mirrors in several congruent geometries that are commonly used in fabrication, metrology, and modeling are provided. The exact expressions are derived directly from Fermat's principle, without coordinate transformations, in several mirror-centered coordinate systems, including one with the surface tangent to the central point of intersection. Coefficients for a sixth-order polynomial series approximation are calculated for that coordinate system.