Miracle-dz/UniFAR-FTUs huggingface dataset:
Oncolytic Virotherapy: The Cancer Cell Side

Simple Summary Oncolytic viruses (OVs) are a promising immunotherapy that specifically target and kill cancer cells and stimulate anti-tumor immunity. While different OVs are endowed with distinct features, which enhance their specificity towards tumor cells; attributes of the cancer cell also critically contribute to this specificity. Such features comprise defects in innate immunity, including antiviral responses, and the metabolic reprogramming of the malignant cell. The tumorigenic features which support OV replication can be intrinsic to the transformation process (e.g., a direct consequence of the activity of a given oncogene), or acquired in the course of tumor immunoediting—the selection process applied by antitumor immunity. Oncogene-induced epigenetic silencing plays an important role in negative regulation of immunostimulatory antiviral responses in the cancer cells. Reversal of such silencing may also provide a strong immunostimulant in the form of viral mimicry by activation of endogenous retroelements. Here we review features of the cancer cell that support viral replication, tumor immunoediting and the connection between oncogenic signaling, DNA methylation and viral oncolysis. As such, this review concentrates on the malignant cell, while detailed description of different OVs can be found in the accompanied reviews of this issue. Abstract Cell autonomous immunity genes mediate the multiple stages of anti-viral defenses, including recognition of invading pathogens, inhibition of viral replication, reprogramming of cellular metabolism, programmed-cell-death, paracrine induction of antiviral state, and activation of immunostimulatory inflammation. In tumor development and/or immunotherapy settings, selective pressure applied by the immune system results in tumor immunoediting, a reduction in the immunostimulatory potential of the cancer cell. This editing process comprises the reduced expression and/or function of cell autonomous immunity genes, allowing for immune-evasion of the tumor while concomitantly attenuating anti-viral defenses. Combined with the oncogene-enhanced anabolic nature of cancer-cell metabolism, this attenuation of antiviral defenses contributes to viral replication and to the selectivity of oncolytic viruses (OVs) towards malignant cells. Here, we review the manners by which oncogene-mediated transformation and tumor immunoediting combine to alter the intracellular milieu of tumor cells, for the benefit of OV replication. We also explore the functional connection between oncogenic signaling and epigenetic silencing, and the way by which restriction of such silencing results in immune activation. Together, the picture that emerges is one in which OVs and epigenetic modifiers are part of a growing therapeutic toolbox that employs activation of anti-tumor immunity for cancer therapy.
Reaching performance scale for stroke – Test‐retest reliability, measurement error, concurrent and discriminant validity

Post‐stroke upper limb motor improvement can be better quantified by describing movement patterns characterizing movement quality and use of compensations. Movement patterns can be described using both kinematic and clinical outcomes. One clinical outcome that assesses movement quality and compensations used for reaching a Close (18 points) and Far target (18 points) is the Reaching Performance Scale for Stroke (RPSS).
The role of sedimentary organic matter in bacterial sulfate reduction: The G model tested1

Laboratory study of the bacterial decomposition of Long Island Sound plankton in oxygenated seawater over a period of 2 years shows that the organic material undergoes decomposition via first-order kinetics and can be divided into two decomposable fractions, of considerably different reactivity, and a nonmetabolizable fraction. This planktonic material, after undergoing varying degrees of oxic degradation, was added in the laboratory to anoxic sediment taken from a depth of 1 m at the NWC site of Long Island Sound and the rate of bacterial sulfate reduction in the sediment measured by the ? S radiotracer technique. The stimulated rate of sulfate reduction was in direct proportion to the amount of planktonic carbon added. This provides direct confirmation of the first-order decomposition, or C; model, for marine sediments and proves that the in situ rate of sulfate reduction is organic-matter limited. Slower sulfate reduction rates resulted when oxically degraded plankton rather than fresh plankton was added, and the results confirm the presence of the same two fractions of organic matter deduced from the oxic degradation studies. Near-surface Long Island Sound sediment, which already contains abundant readily decomposable organic matter, was also subjected to anoxic decomposition by bacterial sulfate reduction. The decrease in sulfate reduction rate with time parallels decreases in the amount of organic matter, and these results also indicate the presence of two fractions of organic carbon of distinctly different reactivity. From plots of the log of reduction rate vs. time two first-order rate constants were obtained that agree well with those derived from the plankton addition experiment. Together, the two experiments confirm the use of a simple multi-first-order rate law for organic matter decomposition in marine sediments.
Towards Zero Zinc Oxide: Feeding Strategies to Manage Post-Weaning Diarrhea in Piglets

Simple Summary Zinc oxide (ZnO) supplementation at pharmacological doses in post-weaning piglets is a consolidated practice that allows efficient control of post-weaning diarrhea (PWD), a condition exacerbated by Escherichia coli F4 (K88) infections. Far from being completely elucidated, the multifactorial ZnO mechanism of action is in all likelihood exerted at the gastrointestinal level. However, increasing environmental concerns are arising from prolonged ZnO use. This article reviews the utilization of ZnO in piglets, the biological rationale behind its powerful activity, and the emerging threats that are leading towards a significant reduction in its use. Finally, a wide analysis of the strengths and weaknesses of innovative alternative strategies to manage PWD at the nutritional level is given. Abstract Zinc oxide (ZnO) at pharmacological doses is extensively employed in the pig industry as an effective tool to manage post-weaning diarrhea (PWD), a condition that causes huge economic losses because of its impact on the most pivotal phase of a piglet’s production cycle. In a multifactorial way, ZnO exerts a variety of positive effects along the entire gastrointestinal tract by targeting intestinal architecture, digestive secretions, antioxidant systems, and immune cells. ZnO also has a moderate antibacterial effect against Escherichia coli F4 (K88), the main causative agent of PWD. However, the environmental impact of ZnO and new emerging threats are posing serious questions to the sustainability of its extensive utilization. To work towards a future free from pharmacological ZnO, novel nutritional approaches are necessary, and many strategies have been investigated. This review article provides a comprehensive framework for ZnO utilization and its broad mode of action. Moreover, all the risks related to pharmacological ZnO levels are presented; we focus on European institutions’ decisions subsequently. The identification of a novel, complete solution against PWD should be accompanied by the adoption of holistic strategies, thereby combining good management practices to feeding approaches capable of mitigating Escherichia coli F4 (K88) infections and/or lowering ZnO utilization. Promising results can be obtained by adjusting diet composition or employing organic acids, natural identical compounds, polyphenol-rich extracts, prebiotics, and probiotics.
An Outline of Multi-Sensor Fusion Methods for Mobile Agents Indoor Navigation

Indoor autonomous navigation refers to the perception and exploration abilities of mobile agents in unknown indoor environments with the help of various sensors. It is the basic and one of the most important functions of mobile agents. In spite of the high performance of the single-sensor navigation method, multi-sensor fusion methods still potentially improve the perception and navigation abilities of mobile agents. This work summarizes the multi-sensor fusion methods for mobile agents’ navigation by: (1) analyzing and comparing the advantages and disadvantages of a single sensor in the task of navigation; (2) introducing the mainstream technologies of multi-sensor fusion methods, including various combinations of sensors and several widely recognized multi-modal sensor datasets. Finally, we discuss the possible technique trends of multi-sensor fusion methods, especially its technique challenges in practical navigation environments.
Effects of trapped charges on Hg-Schottky capacitance–voltage measurements of n-type epitaxial silicon wafers

The effects of surface charge in the oxide layer for Hg-Schottky capacitance–voltage (C–V) measurements have been discussed in detail. The accumulation of majority carriers at the Si surface has been identified as a major factor controlling the stability and accuracy of the Hg-Schottky C–V measurement. For n-type wafers, the fixed oxide charge in Si oxide layer induces electron accumulation at the oxide/Si interface. This electron accumulation cannot be dissipated until a depleting voltage as high as −5.0 V is applied depending on the preparation of the oxide layer. It has been found that introducing Cu during the growth of the oxide layer can produce a deep trap level in the oxide. Pre-electrical-field stress at 5 MV/cm for 5 s can fill these traps and eliminate electron accumulation, resulting in a stable and accurate C–V measurement. Our results on p-type wafers show that the fixed oxide charge in the oxide layer can establish a surface depletion condition and produce a stable and accurate C–V measurement. With these experimental results, we propose that Si oxide layer can improve the stability and accuracy of the Hg-Schottky C–V measurement for both n- and p-type wafers. For n-type wafers, pre-electrical stress and a Si oxide layer with deep electron trap level are necessary; for p-type wafers, only the fixed oxide charge is needed.
Palmitic acid–rich oils with and without interesterification lower postprandial lipemia and increase atherogenic lipoproteins compared with a MUFA-rich oil: A randomized controlled trial

ABSTRACT Background Interesterified (IE) fats are widely used in place of trans fats; however, little is known about their metabolism. Objectives To test the impact of a commonly consumed IE compared with a non-IE equivalent fat on in vivo postprandial and in vitro lipid metabolism, compared with a reference oil [rapeseed oil (RO)]. Methods A double-blinded, 3-phase crossover, randomized controlled trial was performed in healthy adults (n = 20) aged 45–75 y. Postprandial plasma triacylglycerol and lipoprotein responses (including stable isotope tracing) to a test meal (50 g fat) were evaluated over 8 h. The test fats were IE 80:20 palm stearin/palm kernel fat, an identical non-IE fat, and RO (control). In vitro, mechanisms of digestion were explored using a dynamic gastric model (DGM). Results Plasma triacylglycerol 8-h incremental area under the curves were lower following non-IE compared with RO [–1.7 mmol/L⋅h (95% CI: –3.3, –0.0)], but there were no differences between IE and RO or IE and non-IE. LDL particles were smaller following IE and non-IE compared with RO (P = 0.005). Extra extra large, extra large, and large VLDL particle concentrations were higher following IE and non-IE compared with RO at 6–8 h (P < 0.05). No differences in the appearance of [13C]palmitic acid in plasma triacylglycerol were observed between IE and non-IE fats. DGM revealed differences in phase separation of the IE and non-IE meals and delayed release of SFAs compared with RO. Conclusions Interesterification did not modify fat digestion, postprandial lipemia, or lipid metabolism measured by stable isotope and DGM analysis. Despite the lower lipemia following the SFA-rich fats, increased proatherogenic large triacylglycerol-rich lipoprotein remnant and small LDL particles following the SFA-rich fats relative to RO adds a new postprandial dimension to the mechanistic evidence linking SFAs to cardiovascular disease risk.
Culture, Thinking Styles and Investment Decision

Past research suggests that people with different thinking styles show different cognitive processes. Accordingly, we test how thinking style and advice jointly affect investment decision. We conduct three experiments with 530 participants. In Study 1, coin, card and stamp investors who had high levels of holistic thinking and made decisions on their own obtained the lowest returns. In Study 2, participants who used analytic thinking to make decisions on their own in the Balloon Analog Risk Task (BART) earned the most. In Study 3, Westerners who made decisions on their own using analytic thinking had the highest incomes, while Easterners using holistic thinking and listening to others also had positive returns. The results support the framing effect in investment decisions, and the two simulation paradigms are presented for future studies and to confirm the impacts of thinking styles.
Efficient Inverted Index Compression Algorithm Characterized by Faster Decompression Compared with the Golomb-Rice Algorithm

This article deals with compression of binary sequences with a given number of ones, which can also be considered as a list of indexes of a given length. The first part of the article shows that the entropy H of random n-element binary sequences with exactly k elements equal one satisfies the inequalities klog2(0.48·n/k)<H<klog2(2.72·n/k). Based on this result, we propose a simple coding using fixed length words. Its main application is the compression of random binary sequences with a large disproportion between the number of zeros and the number of ones. Importantly, the proposed solution allows for a much faster decompression compared with the Golomb-Rice coding with a relatively small decrease in the efficiency of compression. The proposed algorithm can be particularly useful for database applications for which the speed of decompression is much more important than the degree of index list compression.
An effective pair potential for heavy water

The properties of heavy water are of interest in different disciplines. The simulation of such a substance, particularly in comparison with ordinary water, requires an appropriate interaction potential that allows the simulations of large systems. The potential presented in this work is an efective three-point charge potential type based on the well-known simple point charges/extended model and is named simple point charges/heavy water (SPC/HW). Molecular dynamics simulation done with the SPC/HW potential shows a good agreement with the experimental values for several properties.
Synthesis and characterization of a shock-synthesized cubic B-C-N solid solution of composition BC2.5N

A cubic BC2.5N solid solution (c-BC2.5N) was synthesized in 18% yield by shock-compression of a hexagonal BC2.5N compound. c-BC2.5N was confirmed to have a diamond structure without a long range order of atomic arrangement. The material is a polycrystal composed of microcrystals of 5–20 nm in size. All constituent atoms are teterahedrally coordinated, giving C—C, C—B, C—N, and B—N bonds, and are homogeneously distributed on the lattice planes rather than showing a full short range order of atomic arrangement.
Decoding of Ankle Joint Movements in Stroke Patients Using Surface Electromyography

Stroke is a cerebrovascular disease (CVD), which results in hemiplegia, paralysis, or death. Conventionally, a stroke patient requires prolonged sessions with physical therapists for the recovery of motor function. Various home-based rehabilitative devices are also available for upper limbs and require minimal or no assistance from a physiotherapist. However, there is no clinically proven device available for functional recovery of a lower limb. In this study, we explored the potential use of surface electromyography (sEMG) as a controlling mechanism for the development of a home-based lower limb rehabilitative device for stroke patients. In this experiment, three channels of sEMG were used to record data from 11 stroke patients while performing ankle joint movements. The movements were then decoded from the sEMG data and their correlation with the level of motor impairment was investigated. The impairment level was quantified using the Fugl-Meyer Assessment (FMA) scale. During the analysis, Hudgins time-domain features were extracted and classified using linear discriminant analysis (LDA) and artificial neural network (ANN). On average, 63.86% ± 4.3% and 67.1% ± 7.9% of the movements were accurately classified in an offline analysis by LDA and ANN, respectively. We found that in both classifiers, some motions outperformed others (p < 0.001 for LDA and p = 0.014 for ANN). The Spearman correlation (ρ) was calculated between the FMA scores and classification accuracies. The results indicate that there is a moderately positive correlation (ρ = 0.75 for LDA and ρ = 0.55 for ANN) between the two of them. The findings of this study suggest that a home-based EMG system can be developed to provide customized therapy for the improvement of functional lower limb motion in stroke patients.
Maturation of Mitochondrially Targeted Prx V Involves a Second Cleavage by Mitochondrial Intermediate Peptidase That Is Sensitive to Inhibition by H2O2

Prx V mRNA contains two in-frame AUG codons, producing a long (L-Prx V) and short form of Prx V (S-Prx V), and mouse L-Prx V is expressed as a precursor protein containing a 49-amino acid N-terminal mitochondria targeting sequence. Here, we show that the N-terminal 41-residue sequence of L-Prx V is cleaved by mitochondrial processing peptidase (MPP) in the mitochondrial matrix to produce an intermediate Prx V (I-Prx V) with a destabilizing phenylalanine at its N-terminus, and further, that the next 8-residue sequence is cleaved by mitochondrial intermediate peptidase (MIP) to convert I-Prx V to a stabilized mature form that is identical to S-Prx V. Further, we show that when mitochondrial H2O2 levels are increased in HeLa cells using rotenone, in several mouse tissues by deleting Prx III, and in the adrenal gland by deleting Srx or by exposing mice to immobilized stress, I-Prx V accumulates transiently and mature S-Prx V levels decrease in mitochondria over time. These findings support the view that MIP is inhibited by H2O2, resulting in the accumulation and subsequent degradation of I-Prx V, identifying a role for redox mediated regulation of Prx V proteolytic maturation and expression in mitochondria.
Phase 1 study of telisotuzumab vedotin in Japanese patients with advanced solid tumors

Telisotuzumab vedotin (formerly ABBV‐399) is an antibody‐drug conjugate targeting c‐Met–overexpressing tumor cells, irrespective of MET gene amplification status. Safety, pharmacokinetics, and preliminary efficacy of telisotuzumab vedotin were evaluated outside of Japan. This phase 1 open‐label study evaluated the safety, tolerability, pharmacokinetics, and preliminary antitumor activity of telisotuzumab vedotin in Japanese patients with advanced solid tumors. Telisotuzumab vedotin was administered intravenously at either 2.4 mg/kg (n = 3) or 2.7 mg/kg (n = 6) every 3 weeks, following a 3 + 3 design. Maximum tolerated dose was not reached on the basis of the study design; no dose‐limiting toxicity events were observed. The most common treatment‐emergent adverse events related to telisotuzumab vedotin were peripheral sensory neuropathy (44%), and nausea, decreased appetite, and decreased white blood cell count (33% each). Most frequent grade ≥3 treatment‐emergent adverse events, irrespective of relationship to telisotuzumab vedotin, were decreased neutrophil count and hypoalbuminemia, reported in two patients (22%) each. Systemic exposure of telisotuzumab vedotin at both dose levels was approximately dose proportional. Pharmacokinetic profile in Japanese patients was similar to that previously reported in non‐Japanese patients. Two (22%) patients achieved a partial response, six (67%) had stable disease, one (11%) had progressive disease. Overall disease control rate was 89% (eight of nine patients; 95% confidence interval: 51.8%–99.7%]). Median progression‐free survival was 7.1 months (95% confidence interval: 1.2–10.4). In conclusion, telisotuzumab vedotin demonstrated a manageable safety profile, with antitumor activity in Japanese patients with advanced solid tumors; the recommended phase 2 dose was confirmed as 2.7 mg/kg every 3 weeks.
Pharmacological Activation of p53 during Human Monocyte to Macrophage Differentiation Attenuates Their Pro-Inflammatory Activation by TLR4, TLR7 and TLR8 Agonists

Simple Summary Pharmacological activation of tumor suppressor p53 is a promising therapeutic strategy for a range of hematologic and solid cancers. Whether p53 activation augments or suppresses anti-tumor innate immunity is less understood. Here we show that treatment of differentiating human macrophages with a p53 activator idasanutlin suppresses their inflammatory responses to activators of toll-like receptors (TLR) -4 and -7/8. This is accompanied by reduced expression of TLR7, TLR8, as well as TLR4 co-receptor CD14. These data help evaluating the possibilities of combining p53-targeting and immunostimulatory anti-cancer therapies. Abstract The transcription factor p53 has well-recognized roles in regulating cell cycle, DNA damage repair, cell death, and metabolism. It is an important tumor suppressor and pharmacological activation of p53 by interrupting its interaction with the ubiquitin E3 ligase mouse double minute 2 homolog (MDM2) is actively explored for anti-tumor therapies. In immune cells, p53 modulates inflammatory responses, but the impact of p53 on macrophages remains incompletely understood. In this study, we used the MDM2 antagonist idasanutlin (RG7388) to investigate the responses of primary human macrophages to pharmacological p53 activation. Idasanutlin induced a robust p53-dependent transcriptional signature in macrophages, including several pro-apoptotic genes. However, idasanutlin did not generally sensitize macrophages to apoptosis, except for an enhanced response to a Fas-stimulating antibody. In fully differentiated macrophages, idasanutlin did not affect pro-inflammatory gene expression induced by toll-like receptor 4 (TLR4), TLR3, and TLR7/8 agonists, but inhibited interleukin-4-induced macrophage polarization. However, when present during monocyte to macrophage differentiation, idasanutlin attenuated inflammatory responses towards activation of TLR4 and TLR7/8 by low doses of lipopolysaccharide or resiquimod (R848). This was accompanied by a reduced expression of CD14, TLR7, and TLR8 in macrophages differentiated in the presence of idasanutlin. Our data suggest anti-inflammatory effects of pharmacological p53 activation in differentiating human macrophages.
A comparative study on cost and life‐cycle analysis for 100 MW very large‐scale PV (VLS‐PV) systems in deserts using m‐Si, a‐Si, CdTe, and CIS modules

This paper is a study of comparisons between five types of 100 MW Very Large‐Scale Photovoltaic Power Generation (VLS‐PV) Systems, from economic and environmental viewpoints. The authors designed VLS‐PV systems using typical PV modules of multi‐crystalline silicon (12·8% efficiency), high efficiency multi‐crystalline silicon (15·8%), amorphous silicon (6·9%), cadmium tellurium (9·0%), and copper indium selenium (11·0%), and evaluated them by Life‐Cycle Analysis (LCA). Cost, energy requirement, and CO2 emissions were calculated. In addition, the authors evaluated generation cost, energy payback time (EPT), and CO2 emission rates. As a result, it was found that the EPT is 1·5–2·5 years and the CO2 emission rate is 9–16 g‐C/kWh. The generation cost was 11–12 US Cent/kWh on using 2 USD/W PV modules, and 19–20 US Cent/kWh on using 4 USD/W PV module price. Copyright © 2007 John Wiley & Sons, Ltd.