Miracle-dz/UniFAR-FTUs huggingface dataset:
PD‐1 Blockade with Cemiplimab in Advanced Cutaneous Squamous‐Cell Carcinoma

Background No systemic therapies have been approved for the treatment of advanced cutaneous squamous‐cell carcinoma. This cancer may be responsive to immune therapy, because the mutation burden of the tumor is high and the disease risk is strongly associated with immunosuppression. In the dose‐escalation portion of the phase 1 study of cemiplimab, a deep and durable response was observed in a patient with metastatic cutaneous squamous‐cell carcinoma. Methods We report the results of the phase 1 study of cemiplimab for expansion cohorts of patients with locally advanced or metastatic cutaneous squamous‐cell carcinoma, as well as the results of the pivotal phase 2 study for a cohort of patients with metastatic disease (metastatic‐disease cohort). In both studies, the patients received an intravenous dose of cemiplimab (3 mg per kilogram of body weight) every 2 weeks and were assessed for a response every 8 weeks. In the phase 2 study, the primary end point was the response rate, as assessed by independent central review. Results In the expansion cohorts of the phase 1 study, a response to cemiplimab was observed in 13 of 26 patients (50%; 95% confidence interval [CI], 30 to 70). In the metastatic‐disease cohort of the phase 2 study, a response was observed in 28 of 59 patients (47%; 95% CI, 34 to 61). The median follow‐up was 7.9 months in the metastatic‐disease cohort of the phase 2 study. Among the 28 patients who had a response, the duration of response exceeded 6 months in 57%, and 82% continued to have a response and to receive cemiplimab at the time of data cutoff. Adverse events that occurred in at least 15% of the patients in the metastatic‐disease cohort of the phase 2 study were diarrhea, fatigue, nausea, constipation, and rash; 7% of the patients discontinued treatment because of an adverse event. Conclusions Among patients with advanced cutaneous squamous‐cell carcinoma, cemiplimab induced a response in approximately half the patients and was associated with adverse events that usually occur with immune checkpoint inhibitors. (Funded by Regeneron Pharmaceuticals and Sanofi; ClinicalTrials.gov numbers, NCT02383212 and NCT02760498.)
A Soft-Switching Bidirectional DC–DC Converter for the Battery Super-Capacitor Hybrid Energy Storage System

For the battery super-capacitor hybrid energy storage system (BSHESS) applied to the electric vehicle (EV) or the hybrid electric vehicle (HEV), the bidirectional dc–dc converter (BDC) is the key component to control the energy flow between the battery and the super-capacitor. To reduce the internal energy loss of the BSHESS, the efficient BDC with soft-switching characteristics is the best choice. In this paper, through analyzing several existing soft-switching BDCs, a new coupled inductor based soft-switching BDC is proposed. This BDC has a simple structure with no auxiliary switch and can provide soft-switching conditions for both switches without additional control signals. In order to prove the feasibility of the proposed BDC, experimental results, which have been obtained from an experimental prototype, are presented. Experimental results show that soft-switching conditions of both switches of the proposed BDC are achieved.
Constraint Force Equation Methodology for Modeling Multi-Body Stage Separation Dynamics

This paper discusses a generalized approach to the multi-body separation problems in a launch vehicle staging environment based on constraint force methodology and its implementation into the Program to Optimize Simulated Trajectories II (POST2), a widely used trajectory design and optimization tool. This development facilitates the inclusion of stage separation analysis into POST2 for seamless end-to-end simulations of launch vehicle trajectories, thus simplifying the overall implementation and providing a range of modeling and optimization capabilities that are standard features in POST2. Analysis and results are presented for two test cases that validate the constraint force equation methodology in a stand-alone mode and its implementation in POST2.
Pharmacokinetics and Pharmacodynamics of Curcumin in regulating anti‐inflammatory and epigenetic gene expression

Chronic inflammation is a key driver of cancer development. Nitrite levels, which are regulated by inducible nitric oxide synthase (iNOS), play a critical role in inflammation. While the anti‐oxidant and anti‐inflammatory effects of curcumin, a natural product present in the roots of Curcuma longa have been studied widely, the acute pharmacokinetics (PK) and pharmacodynamics (PD) of curcumin in suppressing pro‐inflammatory markers and epigenetic modulators remain unclear. This study evaluated the PK and PD of curcumin‐induced suppression of lipopolysaccharide (LPS)‐mediated inflammation in rat lymphocytes. LPS was administered intravenously either alone or with curcumin to female Sprague–Dawley rats. Plasma samples were analysed for curcumin concentration and mRNA expression was quantified in lymphocytes. The relative gene expression of several inflammatory and epigenetic modulators was analysed. To investigate the relationship between curcumin concentration and iNOS, TNF‐α, and IL‐6 gene expression, PK/PD modeling using Jusko's indirect response model (IDR) integrating transit compartments (TC) describing the delayed response was conducted. The concentration–time profile of curcumin exhibited a bi‐exponential decline, which was well described by a two‐compartmental pharmacokinetic model. Importantly the results demonstrate that LPS induced gene expression of pro‐inflammatory markers in lymphocytes, with peak expression at approximately 3 h and curcumin suppressed the gene expression in animals administered with LPS. These effects were well captured using the IDR model and an IDR model with the transit compartments. In summary, the PK/PD modeling approach could potentially provide a robust quantitative framework for evaluating the acute anti‐inflammatory and epigenetic effects of curcumin in future clinical trials.
Predicting New Zealand riverine fish reference assemblages

Biomonitoring is a common method to monitor environmental change in river ecosystems, a key advantage of biomonitoring over snap-shot physicochemical monitoring is that it provides a more stable, long-term insight into change that is also effects-based. In New Zealand, the main biomonitoring method is a macroinvertebrate sensitivity scoring index, with little established methods available for biomonitoring of fish. This study models the contemporary distribution of common freshwater fish and then uses those models to predict freshwater fish assemblages for each river reach under reference conditions. Comparison of current fish assemblages with those predicted in reference conditions (as observed/expected (O/E) ratios) may provide a suitable option for freshwater fish biomonitoring. Most of the fish communities throughout the central North Island and lower reaches show substantial deviation from the modelled reference community. Most of this deviation is explained by nutrient enrichment, followed by downstream barriers (i.e. dams) and loss of riparian vegetation. The presence of modelled introduced species had relatively little impact on the presence of the modelled native fish. The maps of O/E fish assemblage may provide a rapid way to identify potential restoration sites.
Histology and ultrastructure of the gut of the black mollie (poecilia spp.), a hybrid teleost

A light and electron microscopic (TEM and SEM) study of the gut of the black mollie (Poecilia spp.) shows that the gut is a relatively undifferentiated muscular tube lined with a simple columnar epithelium. The mucosa and underlying lamina propria are formed into folds. The apices of the folds form obtuse angles at the cranial end and more acute ones caudally. The mucosal epithelium is a simple columnar sheet with PAS‐positive goblet cells interspersed throughout. The enterocytes are covered apically with uniform microvilli in most of the tract, and the plasma membrane deeply infolded basally. Mitochondria are located in the basal folds. A continuous basal lamina separates the epithelial mucosa from the underlying lamina propria. Enterocytes have a PAS‐positive Golgi apparatus in the supranuclear region. The enterocytes of the cranial and middle thirds of the gut are morphologically indistinguishable, but those in the caudal third display shorter and sparser microvilli. There is no evidence of pinocytotic activity in the enterocytes of the cranial two thirds of the gut tube, but some apical pinocytotic vesicles are seen in the cells in the caudal third. The tunica muscularis consists of two layers of smooth muscle, inner circular and outer longitudinal. We observe lateral separation of enterocytes from each other deep to the junctional complexes in the caudal and midgut regions. The gut of the mollie lacks some of the specialized cell types commonly found in other fishes. It cannot create an acidic gastric environment; overall control of digestive activity, osmolarity, and ionic balance presumably rest in the structural relationships between epithelial cells and between the epithelium and its supporting tissues. Regional specialization of cells and of the gut as a whole may confer digestive function equivalent to that found in more complicated systems.
Efficient trajectory reshaping in a dynamic environment

A general trajectory planner for optimal control problems is presented and applied to a robot system. The approach is based on timed elastic bands and nonlinear model predictive control. By exploiting the sparsity in the underlying optimization problems the computational effort can be significantly reduced, resulting in a real-time capable planner. In addition, a localization based switching strategy is employed to enforce convergence and stability. The planning procedure is illustrated in a robotics application using a realistic SCARA type robot.
Therapeutic Values of Human Urinary Kallidinogenase on Cerebrovascular Diseases

The term “tissue kallikrein” is used to describe a group of serine proteases shared considerable sequence homology and colocalize in the same chromosomal locus 19q13. 2–q13.4. It has been widely discovered in various tissues and has been proved to be involved in kinds of pathophysiological processes, such as inhibiting oxidative stress, inflammation, apoptosis, fibrosis and promoting angiogenesis, and neurogenesis. Human Urinary Kallidinogenase (HUK) extracted from human urine is a member of tissue kallikrein which could convert kininogen to kinin and hence improve the plasma kinin level. Medical value of HUK has been widely investigated in China, especially on acute ischemic stroke. In this review, we will summarize the therapeutic values of Human Urinary Kallidinogenase on acute ischemic stroke and its potential mechanisms.
Competitive Interactions Between Incompatible Mutants of the Social Bacterium Myxococcus xanthus DK1622

Due to the high similarity in their requirements for space and food, close bacterial relatives may be each other's strongest competitors. Close bacterial relatives often form visible boundaries to separate their swarming colonies, a phenomenon termed colony-merger incompatibility. While bacterial species are known to have many incompatible strains, it is largely unclear which traits lead to multiple incompatibilities and the interactions between multiple incompatible siblings. To investigate the competitive interactions of closely related incompatible strains, we mutated Myxococcus xanthus DK1622, a predatory bacterium with complex social behavior. From 3392 random transposon mutations, we obtained 11 self-identification (SI) deficient mutants that formed unmerged colony boundaries with the ancestral strain. The mutations were at nine loci with unknown functions and formed nine independent SI mutants. Compared with their ancestral strain, most of the SI mutants showed reduced growth, swarming and development abilities, but some remained unchanged from their monocultures. When pairwise mixed with their ancestral strain for co-cultivation, these mutants exhibited improved, reduced or unchanged competitive abilities compared with the ancestral strain. The sporulation efficiencies were affected by the DK1622 partner, ranging from almost complete inhibition to 360% stimulation. The differences in competitive growth between the SI mutants and DK1622 were highly correlated with the differences in their sporulation efficiencies. However, the competitive efficiencies of the mutants in mixture were inconsistent with their growth or sporulation abilities in monocultures. We propose that the colony-merger incompatibility in M. xanthus is associated with multiple independent genetic loci, and the incompatible strains hold competitive interaction abilities, which probably determine the complex relationships between multiple incompatible M. xanthus strains and their co-existence strategies.
Lagrange Coded Computing: Optimal Design for Resiliency, Security and Privacy

We consider a scenario involving computations over a massive dataset stored distributedly across multiple workers, which is at the core of distributed learning algorithms. We propose Lagrange Coded Computing (LCC), a new framework to simultaneously provide (1) resiliency against stragglers that may prolong computations; (2) security against Byzantine (or malicious) workers that deliberately modify the computation for their benefit; and (3) (information-theoretic) privacy of the dataset amidst possible collusion of workers. LCC, which leverages the well-known Lagrange polynomial to create computation redundancy in a novel coded form across workers, can be applied to any computation scenario in which the function of interest is an arbitrary multivariate polynomial of the input dataset, hence covering many computations of interest in machine learning. LCC significantly generalizes prior works to go beyond linear computations. It also enables secure and private computing in distributed settings, improving the computation and communication efficiency of the state-of-the-art. Furthermore, we prove the optimality of LCC by showing that it achieves the optimal tradeoff between resiliency, security, and privacy, i.e., in terms of tolerating the maximum number of stragglers and adversaries, and providing data privacy against the maximum number of colluding workers. Finally, we show via experiments on Amazon EC2 that LCC speeds up the conventional uncoded implementation of distributed least-squares linear regression by up to $13.43\times$, and also achieves a $2.36\times$-$12.65\times$ speedup over the state-of-the-art straggler mitigation strategies.
Policy-based network slicing management for future mobile communications

Innovative technologies, such as Software-Defined Networking (SDN) and Network Functions Virtualization (NFV), are enabling the possibility of managing network infrastructures and their services for enhancing network flexibility, efficient resource control, and cost-efficiency. How to combine these technologies requires taking into account the requirements established by the scenarios being executed, which can change at any time due to their dynamism. Network Slicing appeared to this end. This new technique tailors the needs of a particular scenario whose requirements are extremely heterogeneous and complex. By using Network Slicing, SDN/NFV-enabled environments can be strengthened to manage network resources and services depending on those requirements. Nevertheless, Network Slicing approaches lack management mechanisms that consider the heterogeneity and dynamism provided by scenarios based on future mobile networks. This article presents a formal definition of the Network Slicing information model, where all elements interacting with the Network Slices life cycle are formally represented. Another important contribution is a mobility-aware architecture that combines NFV/SDN techniques and introduces innovative components responsible for managing and orchestrating the Network Slices. Finally, a systematic comparison is made between the existing architectures and the proposed one.
Developmental Pathways Are Blueprints for Designing Successful Crops

Genes controlling plant development have been studied in multiple plant systems. This has provided deep insights into conserved genetic pathways controlling core developmental processes including meristem identity, phase transitions, determinacy, stem elongation, and branching. These pathways control plant growth patterns and are fundamentally important to crop biology and agriculture. This review describes the conserved pathways that control plant development, using Arabidopsis as a model. Historical examples of how plant development has been altered through selection to improve crop performance are then presented. These examples, drawn from diverse crops, show how the genetic pathways controlling development have been modified to increase yield or tailor growth patterns to suit local growing environments or specialized crop management practices. Strategies to apply current progress in genomics and developmental biology to future crop improvement are then discussed within the broader context of emerging trends in plant breeding. The ways that knowledge of developmental processes and understanding of gene function can contribute to crop improvement, beyond what can be achieved by selection alone, are emphasized. These include using genome re-sequencing, mutagenesis, and gene editing to identify or generate novel variation in developmental genes. The expanding scope for comparative genomics, the possibility to engineer new developmental traits and new approaches to resolve gene–gene or gene–environment interactions are also discussed. Finally, opportunities to integrate fundamental research and crop breeding are highlighted.
Taschenbuch der Physik

Unverzichtbare Kenntnisse der Physik! Schnellen Zugriff auf die erforderlichen Informationen Prufungen und wertvolle Unterstutzung bei der Losung von Aufgaben und Ubungen. Das Buch enthalt: Grundkenntnisse der 5 Abteilungen der Physik: Mechanik, Schwingungen und Wellen, Elektrizitat und Magnetismus, Thermodynamik, Quantenphysik; Anhang mit: eine Darstellung der Messfehler, die Rechnung Vektor, der Elemente von Zahnstein und eine Liste der SI-Einheiten; Tische aus massivem Grund und physikalischen Eigenschaften von Materialien; einheitliche Darstellung von physikalischen Konzepte und Designs - fur jeden physikalischen Grose werden in pragnanter Weise bei all den Eigenschaften, Methoden der Messung, wichtige Gesetze bezogenen Grose, Materialkonstanten, SI-Einheiten, Abmessungen, Transformations und Anwendungsbeispiele; leserfreundlichen Layout des Buches; eine umfassende Index; Logos, um Ihnen schnell die benotigten Informationen. = Niezastapione zrodlo wiedzy z zakresu fizyki! Szybki dostep do informacji wymaganych na egzaminach i cenna pomoc przy rozwiazywaniu zadan i cwiczen. Ksiazka zawiera: podstawowe wiadomosci z 5 dzialow fizyki: mechanika, drgania i fale, elektrycznosc i magnetyzm, termodynamika, fizyka kwantowa; dodatek zawierajacy: rachunek bledow pomiarowych, rachunek wektorowy, elementy rachunku rozniczkowego i calkowego oraz zestawienie jednostek SI; tabele stalych podstawowych i wlasciwosci fizycznych materialow; jednolite przedstawienie pojec i wzorow fizycznych - dla kazdej wielkosci fizycznej podano w zwiezly sposob wszystkie wlasciwosci, metody pomiaru, wazne prawa, wielkosci pokrewne, stale materialowe, jednostki SI, wymiary, przeksztalcenia i przyklady zastosowan; przyjazny dla czytelnika uklad ksiazki; obszerny skorowidz; znaki graficzne, ulatwiajace szybkie wyszukiwanie potrzebnych informacji.
Microwave Class-E Power Amplifiers: A Brief Review of Essential Concepts in High-Frequency Class-E PAs and Related Circuits

Since Nathan Sokal's invention of the class-E power amplifier (PA), the vast majority of class-E results have been reported at kilohertz and millihertz frequencies, but the concept is increasingly applied in the ultrahigh-frequency (UHF) [1]-[13], microwave [14]-[20], and even millimeter-wave range [21]. The goal of this article is to briefly review some interesting concepts concerning high-frequency class-E PAs and related circuits. (The article on page 26 of this issue, "A History of Switching-Mode Class-E Techniques" by Andrei Grebennikov and Frederick H. Raab, provides a historical overview of class-E amplifier development.)
Bending impact on the performance of a flexible Li4Ti5O12-based all-solid-state thin-film battery

Abstract The growing demand of flexible electronic devices is increasing the requirements of their power sources. The effect of bending in thin-film batteries is still not well understood. Here, we successfully developed a high active area flexible all-solid-state battery as a model system that consists of thin-film layers of Li4Ti5O12, LiPON, and Lithium deposited on a novel flexible ceramic substrate. A systematic study on the bending state and performance of the battery is presented. The battery withstands bending radii of at least 14 mm achieving 70% of the theoretical capacity. Here, we reveal that convex bending has a positive effect on battery capacity showing an average increase of 5.5%, whereas concave bending decreases the capacity by 4% in contrast with recent studies. We show that the change in capacity upon bending may well be associated to the Li-ion diffusion kinetic change through the electrode when different external forces are applied. Finally, an encapsulation scheme is presented allowing sufficient bending of the device and operation for at least 500 cycles in air. The results are meant to improve the understanding of the phenomena present in thin-film batteries while undergoing bending rather than showing improvements in battery performance and lifetime.
Pharmacokinetics of Praziquantel in Schistosoma mansoni- and Schistosoma haematobium-Infected School- and Preschool-Aged Children

There is a growing consensus to include preschool-aged children in preventive chemotherapy programs with praziquantel to improve schistosomiasis control. However, pharmacokinetic data, crucial to establish a safe and effective dose for this age group, are sparse. ABSTRACT There is a growing consensus to include preschool-aged children in preventive chemotherapy programs with praziquantel to improve schistosomiasis control. However, pharmacokinetic data, crucial to establish a safe and effective dose for this age group, are sparse. The objective of this study was to establish and compare the pharmacokinetic parameters of praziquantel in preschool- and school-aged children with schistosomiasis. Two pharmacokinetic trials in school- and preschool-aged children infected with Schistosoma mansoni or S. haematobium were conducted in Côte d'Ivoire. Dried blood spot samples were taken from 492 children at 10 time points following a single oral dose of 20, 40, or 60 mg/kg of body weight of praziquantel and analyzed using liquid chromatography-mass spectrometry. Noncompartmental analysis (NCA) was performed to obtain the pharmacokinetic parameters of R-praziquantel (RPZQ), S-praziquantel (SPZQ), and R-trans-4-hydroxy-praziquantel. No significant differences in pharmacokinetic parameters between species-specific infections were observed. While pharmacokinetic parameters differed significantly between age groups for S. mansoni, this trend was not observed with S. haematobium. Neither the area under the curve (AUC) nor the maximal blood concentration (Cmax) presented clear dose proportionality for R- and SPZQ. Logistic regression indicated a relationship between the RPZQ AUC and Cmax and the probability of cure. Praziquantel is subject to complex metabolic processes following erratic absorption. While the results of NCA are a very informative base for a better understanding of the drug, a more targeted approach in the form of population modeling is needed to quantify the factors influencing metabolic processes and draw conclusions.