Search

Dysphagia is a common symptom with significant impact on quality of life. Our diagnostic armamentarium was primarily limited to endoscopy and barium esophagram until the advent of manometric techniques in the 1970s, which provided the first reliable tool for assessment of esophageal motor function. Since that time, significant advances have been made over the last 3 decades in our understanding of various esophageal motility disorders due to improvement in diagnostics with high-resolution esophageal manometry. High-resolution esophageal manometry has improved the sensitivity for detecting achalasia and has also enhanced our understanding of spastic and hypomotility disorders of the esophageal body. In this review, we discuss the current approach to diagnosis and therapeutics of various esophageal motility disorders.

Abstract After the occurrence of a large earthquake, engineering seismologists are often requested to estimate strong ground motions at a site where strong motion data were not obtained. The goal of this study was to test the ability of a class of methods that uses Fourier phase characteristics for the post-earthquake ground motion estimation, making use of the precious opportunity provide by the ESG6 Blind Prediction Steps 2&3. It was also part of the goal of this study to test the performance of the effective stress analyses to account for soil nonlinearity. In addition to the dataset provided by the organizer of the blind prediction, the author used additional accelerometric data from a nearby JMA site. To simulate ground motions for an M5.9 earthquake at the target site “KUMA”, the Fourier amplitude spectrum was estimated from the spectral ratio between KUMA and the nearby JMA site. The Fourier phase spectrum was approximated by the spectrum of another event at KUMA. Comparison between the estimated and recorded ground motions after the blind prediction revealed that the estimated ground motions were fairly consistent with the observed ground motions, indicating the effectiveness of the method when the rupture process of the target event is simple and the soil nonlinearity at the target site is not significant. To simulate ground motions at KUMA for the M6.5 foreshock and the M7.3 mainshock of the 2016 Kumamoto earthquake sequence, the author conducted effective stress analyses using a program called “FLIP” to account for soil nonlinearity. Comparison between the estimated and recorded ground motions after the blind prediction indicated that the low-frequency components were overestimated and the high-frequency components were underestimated. The strong soil nonlinearity considered in the effective stress analyses was the main cause of the discrepancy. One explanation for this result could be that the nonlinear soil behavior at KUMA during the foreshock and the mainshock was not a strong one. Another explanation could be that the effect of soil nonlinearity was already included in the records at JMA and the effect of soil nonlinearity was double counted in the results submitted by the author. Graphical Abstract

After the occurrence of a large earthquake, engineering seismologists are often requested to estimate strong ground motions at a site where strong motion data were not obtained. The goal of this study was to test the ability of a class of methods that uses Fourier phase characteristics for the post-earthquake ground motion estimation, making use of the precious opportunity provide by the ESG6 Blind Prediction Steps 2&3. It was also part of the goal of this study to test the performance of the effective stress analyses to account for soil nonlinearity. In addition to the dataset provided by the organizer of the blind prediction, the author used additional accelerometric data from a nearby JMA site. To simulate ground motions for an M5.9 earthquake at the target site "KUMA", the Fourier amplitude spectrum was estimated from the spectral ratio between KUMA and the nearby JMA site. The Fourier phase spectrum was approximated by the spectrum of another event at KUMA. Comparison between the estimated and recorded ground motions after the blind prediction revealed that the estimated ground motions were fairly consistent with the observed ground motions, indicating the effectiveness of the method when the rupture process of the target event is simple and the soil nonlinearity at the target site is not significant. To simulate ground motions at KUMA for the M6.5 foreshock and the M7.3 mainshock of the 2016 Kumamoto earthquake sequence, the author conducted effective stress analyses using a program called "FLIP" to account for soil nonlinearity. Comparison between the estimated and recorded ground motions after the blind prediction indicated that the low-frequency components were overestimated and the high-frequency components were underestimated. The strong soil nonlinearity considered in the effective stress analyses was the main cause of the discrepancy. One explanation for this result could be that the nonlinear soil behavior at KUMA during the foreshock and the mainshock was not a strong one. Another explanation could be that the effect of soil nonlinearity was already included in the records at JMA and the effect of soil nonlinearity was double counted in the results submitted by the author. [ABSTRACT FROM AUTHOR]

With the advantages of high flexibility, strong adaptability, etc., the legged robot can help humans to complete numerous complicated tasks. In this paper, a kind of reconfigurable legged robot with a flexible waist was proposed. Compared with the common robots with a rigid trunk, the proposed robot can twist its waist flexibly. Through analysis, it is found that the flexible waist can improve the trunk workspace, foot endpoints' workspace and static stability margin of the robot, and further enhance the motion performance of the robot. Meanwhile, by imitating the creatures in nature, the motion gait planning of the robot was provided. Additionally, the proposed robot has excellent reconfigurable characteristics, and can flexibly transform among three forms to adapt to different working environments and accomplish different tasks. Further, after capsizing, the robot can complete the motion of turning over more easily. In this paper, the reconfiguration posture and the motion of turning over of the robot were planned in detail, and finally verified by ADAMS simulation. [ABSTRACT FROM AUTHOR]

The uncontrolled proliferation of malignant cells in growing tumors results in the generation of different stressors in the tumor microenvironment, such as nutrient shortage, hypoxia and acidosis, among others, that disrupt endoplasmic reticulum (ER) homeostasis and may lead to ER stress. As a response to ER stress, both normal and tumor cells launch a set of signaling pathways known as the unfolded protein response (UPR) to restore ER proteostasis and maintain cell viability and function. However, under sustained ER stress, an apoptotic cell death process can be induced and this has been the subject of different review articles, although the role of the TRAIL-R2/DR5-activated extrinsic pathway of apoptosis has not yet been thoroughly summarized. In this Review, we provide an updated overview of the molecular mechanisms regulating cell fate decisions in tumor cells undergoing ER stress and discuss the role of the tumor necrosis factor (TNF)-related apoptosis-inducing ligand receptor 2 (TRAIL-R2/DR5) in the final outcome of UPR signaling. Particularly, we focus on the mechanisms controlling cellular FLICE-like inhibitory protein (FLIP) levels in tumor cells undergoing ER stress, which may represent a potential target for therapeutic intervention in cancer. [ABSTRACT FROM AUTHOR]

Phytoplankton patterns have been observed widely in aquatic systems. Although pattern formation has been investigated based on many PDEs, discrete models on aquatic systems can provide more complex dynamics. A discrete toxic-phytoplankton–zooplankton model is studied in this paper, with the consideration of Allee effect and cross-diffusion. Focusing on Allee effect coefficient, flip and Neimark–Sacker bifurcation analyses are carried out. And focusing on cross-diffusion coefficient, Turing bifurcation analyses are carried out. Parameter conditions and bifurcation diagram of these bifurcations are obtained correspondingly. Numerical simulations are then performed which are consistent with results of theoretical analysis. Irregular patterns can be formed by flip bifurcation. Spirals can be formed by Neimark–Sacker bifurcation. Spots and stripes can be formed by Turing bifurcation. When Turing and flip, or Turing and Neimark–Sacker bifurcations both occur, special patterns can be obtained. [ABSTRACT FROM AUTHOR]

The ongoing co-circulation of multiple severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) strains necessitates advanced methods such as high-throughput multiplex pseudovirus systems for evaluating immune responses to different variants, crucial for developing updated vaccines and neutralizing antibodies (nAbs). We have developed a quadri-fluorescence (qFluo) pseudovirus platform by four fluorescent reporters with different spectra, allowing simultaneous measurement of the nAbs against four variants in a single test. qFluo shows high concordance with the classical single-reporter assay when testing monoclonal antibodies and human plasma. Utilizing qFluo, we assessed the immunogenicities of the spike of BA.5, BQ.1.1, XBB.1.5, and CH.1.1 in hamsters. An analysis of cross-neutralization against 51 variants demonstrated superior protective immunity from XBB.1.5, especially against prevalent strains such as "FLip" and JN.1, compared to BA.5. Our finding partially fills the knowledge gap concerning the immunogenic efficacy of the XBB.1.5 vaccine against current dominant variants, being instrumental in vaccine-strain decisions and insight into the evolutionary path of SARS-CoV-2., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Dysphagia is a common symptom with significant impact on quality of life. Our diagnostic armamentarium was primarily limited to endoscopy and barium esophagram until the advent of manometric techniques in the 1970s, which provided the first reliable tool for assessment of esophageal motor function. Since that time, significant advances have been made over the last 3 decades in our understanding of various esophageal motility disorders due to improvement in diagnostics with high-resolution esophageal manometry. High-resolution esophageal manometry has improved the sensitivity for detecting achalasia and has also enhanced our understanding of spastic and hypomotility disorders of the esophageal body. In this review, we discuss the current approach to diagnosis and therapeutics of various esophageal motility disorders. [ABSTRACT FROM AUTHOR]

Let X be a normal Q-factorial projective variety with at most log canonical singularities. We shall give a sufficient condition for the existence of at most finitely many KX-negative extremal rays R(C NE(X) of divisorial type. As an application, we show that for a nonisomorphic surjective endomorphism f:X - X of a normal projective Q-factorial terminal 3-fold X with (X) > 0, a suitable power fk (k > 0) of f descends to a nonisomorphic surjective endomorphism g:Xmin - Xmin of a minimal model Xmin of X. [ABSTRACT FROM AUTHOR]

In this article, we propose key recovery attack on two stream ciphers: Kreyvium and FLIP $_{530}(42,128,360)$ 530 (42 , 128 , 360) using Differential Fault Attack (DFA) technique. These two ciphers are being used in Fully Homomorphic Encryption (FHE) due to their low error growth during keystream generation. Kreyvium is an NFSR-based stream cipher and FLIP is a permutation-based stream cipher. We first show that the complete state of the Kreyvium can be recovered by injecting 3 faults and considering 450 many keystream bits. In case of FLIP, we show that if there is a 1-bit fault in the state of the cipher then from 9000 normal and faulty keystream bits the state (i.e., the secret key) of the cipher can be recovered. For single bit fault, one will require to solve a system of equations for each 530 possible fault locations to recover the correct key of FLIP. To the best of our knowledge, this is the first article which analyzes the security of these two FHE supported stream ciphers under DFA and it has been observed that DFA completely reveals the secret keys of these two ciphers with very minimal faults. [ABSTRACT FROM AUTHOR]

Previously, we proposed a new perspective of triptolide (TP)-associated hepatotoxicity: liver hypersensitivity upon lipopolysaccharide (LPS) stimulation. However, the mechanisms for TP/LPS-induced hepatotoxicity remained elusive. The present study aimed to clarify the role of LPS in TP/LPS-induced hepatotoxicity and the mechanism by which TP induces liver hypersensitivity upon LPS stimulation. TNF-α inhibitor, etanercept, was injected intraperitoneally into mice to investigate whether induction of TNF-α by LPS participated in the liver injury induced by TP/LPS co-treatment. Mice and hepatocytes pretreated with TP were stimulated with recombinant TNF-α to assess the function of TNF-α in TP/LPS co-treatment. Additionally, time-dependent NF-κB activation and NF-κB-mediated pro-survival signals were measured in vivo and in vitro. Finally, overexpression of cellular FLICE-inhibitory protein (FLIP), the most potent NF-κB-mediated pro-survival protein, was measured in vivo and in vitro to assess its function in TP/LPS-induced hepatotoxicity. Etanercept counteracted the toxic reactions induced by TP/LPS. TP-treatment sensitized mice and hepatocytes to TNF-α, revealing the role of TNF-α in TP/LPS-induced hepatotoxicity. Mechanistic studies revealed that TP inhibited NF-κB dependent pro-survival signals, especially FLIP, induced by LPS/TNF-α. Moreover, overexpression of FLIP alleviated TP/LPS-induced hepatotoxicity in vivo and TP/TNF-α-induced apoptosis in vitro. Mice and hepatocytes treated with TP were sensitive to TNF-α, which was released from LPS-stimulated immune cells. These and other results show that the TP-induced inhibition of NF-κB-dependent transcriptional activity and FLIP production are responsible for liver hypersensitivity.

Objectives: Inflammation is an important predisposing and progressive factor in chronic kidney disease (CKD). Heterogeneous nuclear ribonucleoprotein K (hnRNPK) is associated with many fundamental cellular processes, but in chronic inflammatory pathologies remains unclear. Methods: An in vitro peripheral inflammation model was established using lipopolysaccharide (LPS)-stimulated mouse RAW264.7 macrophages, followed by inflammasome activation by ATP treatment. Knockdown of hnRNPK by sihnRNPK and FLICE-like inhibitory protein (FLIP) by siFLIP transfection were achieved in Raw264.7 macrophages. ELISA was used to determine the expression of IL-1β, IL-18 and TNF-α. Real time PCR was applied to detect the mRNA levels of hnRNPK, NOD-like receptors family pyrin domain-containing 3 (NLRP3), FLIP, Caspase-1, IL-1β and IL-18. Western blot and immunofluorescence were performed to detect relevant protein expressions. Co-immunoprecipitation (Co-IP) was used to assess the interaction of hnRNPK with FLIP. Results: Results showed that LPS plus ATP activated NLRP3 inflammasome, which evidenced by the up-regulation of TNF-α, IL-1β and IL-18. Notably, hnRNPK and FLIP were significantly up-regulated in activated NLRP3 inflammasome of macrophages. HnRNPK or FLIP knockdown significantly suppressed the activation of NLRP3 inflammasome, as reflected by down-regulation of Caspase-1, IL-1β and IL-18. Importantly, hnRNPK could directly bind to FLIP in activated NLRP3 inflammasome. Discussion: Our findings suggest that hnRNPK could promote the activation of NLRP3 inflammasome by directly binding FLIP, which might provide potential new therapeutic targets for CKD.

With the advantages of high flexibility, strong adaptability, etc., the legged robot can help humans to complete numerous complicated tasks. In this paper, a kind of reconfigurable legged robot with a flexible waist was proposed. Compared with the common robots with a rigid trunk, the proposed robot can twist its waist flexibly. Through analysis, it is found that the flexible waist can improve the trunk workspace, foot endpoints’ workspace and static stability margin of the robot, and further enhance the motion performance of the robot. Meanwhile, by imitating the creatures in nature, the motion gait planning of the robot was provided. Additionally, the proposed robot has excellent reconfigurable characteristics, and can flexibly transform among three forms to adapt to different working environments and accomplish different tasks. Further, after capsizing, the robot can complete the motion of turning over more easily. In this paper, the reconfiguration posture and the motion of turning over of the robot were planned in detail, and finally verified by ADAMS simulation.

The uncontrolled proliferation of malignant cells in growing tumors results in the generation of different stressors in the tumor microenvironment, such as nutrient shortage, hypoxia and acidosis, among others, that disrupt endoplasmic reticulum (ER) homeostasis and may lead to ER stress. As a response to ER stress, both normal and tumor cells launch a set of signaling pathways known as the unfolded protein response (UPR) to restore ER proteostasis and maintain cell viability and function. However, under sustained ER stress, an apoptotic cell death process can be induced and this has been the subject of different review articles, although the role of the TRAIL-R2/DR5-activated extrinsic pathway of apoptosis has not yet been thoroughly summarized. In this Review, we provide an updated overview of the molecular mechanisms regulating cell fate decisions in tumor cells undergoing ER stress and discuss the role of the tumor necrosis factor (TNF)-related apoptosis-inducing ligand receptor 2 (TRAIL-R2/DR5) in the final outcome of UPR signaling. Particularly, we focus on the mechanisms controlling cellular FLICE-like inhibitory protein (FLIP) levels in tumor cells undergoing ER stress, which may represent a potential target for therapeutic intervention in cancer.

Background and Objectives: Apoptosis is essential for the survival and normal functioning of multicellular organisms, yet any interruption in this process could be detrimental. Increased production of reactive oxygen species and oxidative stress are key factors affecting apoptosis. Our objective was to determine the impact of exercise with and without vitamin D supplementation on expression of FLIP, Fas, and caspase 8 in lung of rats poisoned with H2O2. Methods: Forty-eight adult male rats were randomly divided into six groups: (C), (H), (HD), (HE), (HDE) and dimethyl sulfoxide. Groups H, HE, HD and HDE received 1 mmol/Kg intraperitoneal injection of H2O2. HE and HDE groups ran on treadmill for eight weeks. Expression of FLIP, Fas and caspase 8 was measured in lung tissues using RT-qPCR. Statistical analysis of data was carried out using SPSS 22 at significance level of 0.05. Results: Vitamin D supplementation caused a significant decrease in expression of Fas (P=0.014) and caspase 8 (P=0.016) compared to the control group. However, it significantly overexpressed FLIP in the lung tissues compared to the control group (P=0.005). Exercise with and without vitamin D supplementation had no significant effect on the expression of the apoptosis regulatory genes. Conclusion: Our results show that VD exerts protective effects on lung tissue by regulating apoptotic factors. Aerobic exercise alone and combined with VD has no significant effect on the apoptotic factors. These results indicate that VD supplementation can reduce lung injury under oxidative stress conditions.

In this paper, bifurcation analysis of a three-dimensional discrete game model is provided. Possible codimension-one (codim-1) and codimension-two (codim-2) bifurcations of this model and its iterations are investigated under variation of one and two parameters, respectively. For each bifurcation, normal form coefficients are calculated through reduction of the system to the associated center manifold. The bifurcations detected in this paper include transcritical, fold, flip (period-doubling), Neimark–Sacker, period-doubling Neimark–Sacker, resonance 1:2, resonance 1:3, resonance 1:4 and fold-flip bifurcations. Moreover, we depict bifurcation diagrams corresponding to each bifurcation with the aid of numerical continuation method. These bifurcation curves not only confirm our analytical results, but also reveal a richer dynamics of the model especially in the higher iterations. [ABSTRACT FROM AUTHOR]

Festivais literários fomentam uma política cultural cujos desdobramentos irão recair na significação do texto literário, tanto por meio dos dispositivos de afeto quanto pelas performances dos autores. Este artigo analisa o impacto desses eventos na cultura literária brasileira e propõe uma reflexão sobre as relações entre performance e literatura, contribuindo para ampliar o debate sobre a mediação literária. [ABSTRACT FROM AUTHOR]

Objectives: Inflammation is an important predisposing and progressive factor in chronic kidney disease (CKD). Heterogeneous nuclear ribonucleoprotein K (hnRNPK) is associated with many fundamental cellular processes, but in chronic inflammatory pathologies remains unclear. Methods: An in vitro peripheral inflammation model was established using lipopolysaccharide (LPS)-stimulated mouse RAW264.7 macrophages, followed by inflammasome activation by ATP treatment. Knockdown of hnRNPK by sihnRNPK and FLICE-like inhibitory protein (FLIP) by siFLIP transfection were achieved in Raw264.7 macrophages. ELISA was used to determine the expression of IL-1β, IL-18 and TNF-α. Real time PCR was applied to detect the mRNA levels of hnRNPK, NOD-like receptors family pyrin domain-containing 3 (NLRP3), FLIP, Caspase-1, IL-1β and IL-18. Western blot and immunofluorescence were performed to detect relevant protein expressions. Co-immunoprecipitation (Co-IP) was used to assess the interaction of hnRNPK with FLIP. Results: Results showed that LPS plus ATP activated NLRP3 inflammasome, which evidenced by the up-regulation of TNF-α, IL-1β and IL-18. Notably, hnRNPK and FLIP were significantly up-regulated in activated NLRP3 inflammasome of macrophages. HnRNPK or FLIP knockdown significantly suppressed the activation of NLRP3 inflammasome, as reflected by down-regulation of Caspase-1, IL-1β and IL-18. Importantly, hnRNPK could directly bind to FLIP in activated NLRP3 inflammasome. Discussion: Our findings suggest that hnRNPK could promote the activation of NLRP3 inflammasome by directly binding FLIP, which might provide potential new therapeutic targets for CKD. [ABSTRACT FROM AUTHOR]

In CHES 2017, Jean et al. presented a paper on “Bit-Sliding” in which the authors proposed lightweight constructions for SPN based block ciphers like AES, PRESENT and SKINNY. The main idea behind these constructions was to reduce the length of the datapath to 1 bit and to reformulate the linear layer for these ciphers so that they require fewer scan flip-flops (which have built-in multiplexer functionality and so larger in area as compared to a simple flip-flop). In this paper, we develop their idea even further in few separate directions. First, we prove that given an arbitrary linear transformation, it is always possible to construct the linear layer using merely 2 scan flip-flops. This points to an optimistic venue to follow to gain further GE reductions, yet the straightforward application of the techniques in our proof to PRESENT and GIFT leads to inefficient implementations of the linear layer, as reducing ourselves to 2 scan flip-flops setting requires thousands of clock cycles and leads to very high latency. Equipped with the well-established formalism on permutation groups, we explore whether we can reduce the number of clock cycles to a practical level, i.e. few hundreds, by adding few more pairs of scan flip flops. For PRESENT, we show that 4 (resp. 8, 12) scan flip-flops are sufficient to complete the permutation layer in 384 (resp. 256, 128) clock cycles. For GIFT, we show that 4 (resp. 8, 10) scan flip flops correspond to 320 (resp. 192, 128) clock cycles. Finally, in order to provide the best of the two worlds (i.e. circuit area and latency), we push our scan flip-flop choices even further to completely eliminate the latency incurred by the permutation layer, without compromising our stringent GE budget. We show that not only 12 scan flip flops are sufficient to execute PRESENT permutation in 64 clock cycles, but also the same scan flip flops can be used readily in a combined encryption decryption circuit. Our final design of PRESENT and GIFT beat the record of Jean et al. and Banik et al. in both latency and in circuit-size metric. We believe that the techniques presented in our work can also be used at choosing bit-sliding-friendly linear layer permutations for the future SPN-based designs.

Objective: Deviations in the apoptotic process have been demonstrated in prostate carcinogenesis. We aimed to evaluate especially the process of extrinsic apoptosis in the spectrum of neoplastic lesions of the prostate epithelium so as to reveal the variations in the apoptotic process. Material and Method: The study included 20 benign prostatic hyperplasia, 8 high-grade prostatic intraepithelial neoplasia and 82 prostatic carcinoma patients. Immunohistochemistry was performed on sections obtained from materials of suprapubic prostatectomy, tru-cut biopsy, transurethral resection and radical prostatectomy. While Fas and FasL were evaluated in glandular and stromal areas, DcR1 and FLIP were evaluated in only glandular areas. Intensity and extent of immunostaining for Fas and FasL antibodies were separately scored and both scores were summarized. The total score of ≥ 4 both for Fas and FasL, expressions of FLIP and DcR1determined in more than 5% of glandular areas were accepted as positive. Results: Glandular FasL positivity was observed in 63.8 and 20% of the cases with prostatic carcinoma and benign prostatic hyperplasia, respectively (p=0.001). The loss of stromal Fas expression in PCa was obvious (p

p53 is the most frequently mutated, well-studied tumor-suppressor gene, yet the molecular basis of the switch from p53-induced cellcycle arrest to apoptosis remains poorly understood. Using a combination of transcriptomics and functional genomics, we unexpectedly identified a nodal role for the caspase-8 paralog and only human pseudo-caspase, FLIP(L), in regulating this switch. Moreover, we identify FLIP(L) as a direct p53 transcriptional target gene that is rapidly up-regulated in response to Nutlin-3A, an MDM2 inhibitor that potently activates p53. Genetically or pharmacologically inhibiting expression of FLIP(L) using siRNA or entinostat (a clinically relevant class- I HDAC inhibitor) efficiently promoted apoptosis in colorectal cancer cells in response to Nutlin-3A, which otherwise predominantly induced cell-cycle arrest. Enhanced apoptosis was also observed when entinostat was combined with clinically relevant, p53-activating chemotherapy in vitro, and this translated into enhanced in vivo efficacy. Mechanistically, FLIP(L) inhibited p53-induced apoptosis by blocking activation of caspase-8 by the TRAIL-R2/DR5 death receptor; notably, this activation was not dependent on receptor engagement by its ligand, TRAIL. In the absence of caspase-8, another of its paralogs, caspase-10 (also transcriptionally up-regulated by p53), induced apoptosis in Nutlin-3A-treated, FLIP(L)-depleted cells, albeit to a lesser extent than in caspase-8-proficient cells. FLIP(L) depletion also modulated transcription of canonical p53 target genes, suppressing p53- induced expression of the cell-cycle regulator p21 and enhancing p53-induced up-regulation of proapoptotic PUMA. Thus, even in the absence of caspase-8/10, FLIP(L) silencing promoted p53-induced apoptosis by enhancing PUMA expression. Thus, we report unexpected, therapeutically relevant roles for FLIP(L) in determining cell fate following p53 activation. [ABSTRACT FROM AUTHOR]

• Determine and upsample a splash volume for induced splash dynamics. • Special particles to infer surface tension behavior on upsampled particles. • Sparse implicit linear wave formulation to couple our model with input particles. • Offer a trade-off between realistic and artistic splash effects. • Following pre-computation steps, allow interactive splash editing. Realistic and detailed liquid splashes require costly fine-scale discretization. We present an efficient post-processing approach for particle-based methods to locally improve the behavior of splashes on coarser liquids. Our method first computes a splash volume over time from the intersections between an identified upsampling volume and colliding volumes. We then upsample particles inside cells of the splash volume; these cells are pre-computed using a likelihood score based on criteria favoring emerging particles. In addition to the advection scheme, enhanced realism is achieved by applying a localized artificial pressure on upsampled particles in order to mimic surface tension in critical regions of splashes. Finally, we propagate waves using a novel implicit model that couples the impact of upsampled particles on the coarser liquid by updating the velocity field at these locations. Our implicit wave model can produce detailed swirls by solely applying velocity updates directly on the underlying particles from the coarse liquid, and prevents from using a high density of surface points. As a result, our approach can generate localized and parameterizable high-resolution splashes from solid-liquid and liquid-liquid interactions, and thus can simulate a wide range of unique and customizable splashes on top of an animated coarse liquid. [ABSTRACT FROM AUTHOR]

Previously, we proposed a new perspective of triptolide (TP)-associated hepatotoxicity: liver hypersensitivity upon lipopolysaccharide (LPS) stimulation. However, the mechanisms for TP/LPS-induced hepatotoxicity remained elusive. The present study aimed to clarify the role of LPS in TP/LPS-induced hepatotoxicity and the mechanism by which TP induces liver hypersensitivity upon LPS stimulation. TNF- α inhibitor, etanercept, was injected intraperitoneally into mice to investigate whether induction of TNF- α by LPS participated in the liver injury induced by TP/LPS co-treatment. Mice and hepatocytes pretreated with TP were stimulated with recombinant TNF- α to assess the function of TNF- α in TP/LPS co-treatment. Additionally, time-dependent NF- κ B activation and NF- κ B-mediated pro-survival signals were measured in vivo and in vitro. Finally, overexpression of cellular FLICE-inhibitory protein (FLIP), the most potent NF- κ B-mediated pro-survival protein, was measured in vivo and in vitro to assess its function in TP/LPS-induced hepatotoxicity. Etanercept counteracted the toxic reactions induced by TP/LPS. TP-treatment sensitized mice and hepatocytes to TNF- α , revealing the role of TNF- α in TP/LPS-induced hepatotoxicity. Mechanistic studies revealed that TP inhibited NF- κ B dependent pro-survival signals, especially FLIP, induced by LPS/TNF- α. Moreover, overexpression of FLIP alleviated TP/LPS-induced hepatotoxicity in vivo and TP/TNF- α -induced apoptosis in vitro. Mice and hepatocytes treated with TP were sensitive to TNF- α , which was released from LPS-stimulated immune cells. These and other results show that the TP-induced inhibition of NF- κ B-dependent transcriptional activity and FLIP production are responsible for liver hypersensitivity. Triptolide (TP) treatment increased the sensitivity of liver upon lipopolysaccharide (LPS), which participated in TP/LPS-induced hepatotoxicity through promoting the TNF- α release. Inactivation of NF- κ B and NF- κ B-mediated cellular FLICE-inhibitory protein expression by TP were responsible for this sensitization. It is necessary to pay attention to the hepatotoxicity of drugs that block TNF- α -TNF-R1 signaling. Image 1 [ABSTRACT FROM AUTHOR]

The long FLIP splice form FLIP(L) can act as both an inhibitor and promoter of caspase‐8 at death‐inducing signalling complexes (DISCs) formed by death receptors such as TRAIL‐R2 and related intracellular complexes such as the ripoptosome. Herein, we describe a revised DISC assembly model that explains how FLIP(L) can have these opposite effects by defining the stoichiometry (with respect to caspase‐8) at which it converts from being anti‐ to pro‐apoptotic at the DISC. We also show that in the complete absence of FLIP(L), procaspase‐8 activation at the TRAIL‐R2 DISC has significantly slower kinetics, although ultimately the extent of apoptosis is significantly greater. This revised model of DISC assembly also explains why FLIP's recruitment to the TRAIL‐R2 DISC is impaired in the absence of caspase‐8 despite showing that it can interact with the DISC adaptor protein FADD and why the short FLIP splice form FLIP(S) is the more potent inhibitor of DISC‐mediated apoptosis. Synopsis: A revised model of TRAIL‐R2 DISC assembly and stoichiometry can explain the ability of FLIP(L) to act as either an inhibitor or activator of apoptosis signalling in these complexes. The stoichiometry of the pseudo‐caspase FLIP(L) relative to caspase‐8 at the TRAIL‐R2 death‐inducing signalling complex (DISC) was re‐examined.When equistochiometric with capase‐8, FLIP(L) inhibits apoptosis at the TRAIL‐R2 DISC (caspase‐8:FLIP(L) ratio ≈ 1:1).Sub‐stoichiometric FLIP(L) (caspase‐8:FLIP(L) ratio > 1:1) accelerates caspase‐8 activation.The revised model of DISC assembly predicts that relatively small changes in FLIP(L)'s DISC recruitment can have profound effects on cell death signalling. [ABSTRACT FROM AUTHOR]

Boolean functions are usually studied under the assumption that each input bit is considered independent and identically distributed. However, in the case of some stream ciphers, a keystream bit is generated by using a nonlinear Boolean function with inputs from a restricted domain. At Eurocrypt 2016, one such stream cipher (FLIP) has been proposed, where a Boolean function on $n$ variables was exploited with inputs of weight $\frac {n}{2}$ only. Recently, Carlet et al. studied several properties of such functions and obtained certain bounds on linear approximations of direct sum in the restricted domain. In this paper, we observe that for a direct sum like $f=f_{1}+f_{2}$ , the inputs to each sub-function $f_{1}$ , $f_{2}$ do not follow a uniform distribution in the restricted domain. In this regard, we study the properties of the Boolean functions by considering a general probability distribution on the inputs. We further obtain several bounds related to the biases of direct sums. Finally, we obtain a lower bound on the bias of the nonlinear filter function of FLIP. Our results provide a general framework to study security parameters of ciphers over restricted domain. [ABSTRACT FROM AUTHOR]

The literal definition of dysphagia is “disturbed eating”. However, it is more accurately described in clinical practice as a sensation of food or liquid being stuck in the esophagus or chest. If this sensation is associated with pain, it is labeled odynophagia, and if it is associated with persistent obstruction and bolus retention, it is categorized as a food impaction. Through research and technological advances, we continue to expand our understanding of the etiologies and underlying pathophysiology relating to this complaint. However, for now, our clinical algorithms focus on endoscopy and manometry to break down dysphagia into three categories: obstructive dysphagia, esophageal motility disorders, and functional dysphagia. Here, we review some critical pitfalls in our current clinical diagnoses, new proposed underlying mechanisms of esophageal motor disorders, and developing technologies to aid in diagnosis and treatment.

Therapeutic targeting of the apoptotic pathways for the treatment of cancer is emerging as a valid and exciting approach in anti-cancer therapeutics. Accumulating evidence demonstrates that cancer cells are typically “addicted” to a small number of anti-apoptotic proteins for their survival, and direct targeting of these proteins could provide valuable approaches for directly killing cancer cells. Several approaches and agents are in clinical development targeting either the intrinsic mitochondrial apoptotic pathway or the extrinsic death receptor mediated pathways. In this review, we discuss the main apoptosis pathways and the key molecular targets which are the subject of several drug development approaches, the clinical development of these agents and the emerging resistance factors and combinatorial treatment approaches for this class of agents with existing and emerging novel targeted anti-cancer therapeutics.

We study the main cryptographic features of Boolean functions (balancedness, nonlinearity, algebraic immunity) when, for a given number n of variables, the input to these functions is restricted to some subset E of

Oral demonstration of knowledge is an effective learning and assessment strategy. It has been shown that generating explanations to oneself, or self-explaining, can improve student understanding of information. This can be achieved via student-generated videos. The quantitative effects of student-generated videos on learning and assessment in postsecondary education are unknown. To our knowledge, this is the first study to analyze the effects asynchronous student-generated videos have on student learning and assessment in a large-enrollment (∼400 students), undergraduate physiology course. Students were charged with making self-generated videos discussing major physiological concepts and uploading these videos to Flip for assessment. Flip is an online, social education platform for asynchronous video-based discussion. In the present study, we combined four semesters ( n = 1,100 students) of Flip data and analyzed the effects it had on student examination performance. Specifically, we first analyzed how students performed on exam questions corresponding to their Flip prompts in comparison to students not assigned those prompts [25/44 (57%) were statistically significantly different]. Second, we analyzed the association between Flip prompt score and performance on corresponding exam questions [39/44 (89%) were statistically significantly different]. Third, we analyzed the association between cumulative Flip score and performance on all corresponding, and noncorresponding exam questions. Finally, we analyzed the association between cumulative Flip score and averaged exam performance. There was a positive association ( r = 0.54). Taken together, our data suggest that asynchronous student-generated Flip videos can facilitate student learning and assessment in a large-enrollment, undergraduate physiology course. NEW & NOTEWORTHY Oral demonstration of knowledge is an effective learning and assessment strategy. Student-generated videos have been shown to improve learning and assessment in secondary education. To our knowledge, this is the first study to analyze the effects asynchronous student-generated Flip videos have on student learning and assessment in postsecondary education. The results of the present study suggest that asynchronous student-generated Flip videos can facilitate student learning and assessment in a large-enrollment (∼400 students), undergraduate physiology course.

At EUROCRYPT 2016, Méaux et al. introduced a new design strategy for symmetric ciphers for fully homomorphic encryption (FHE), which they dubbed filter permutators. Although less efficient than classical stream ciphers, when used in conjunction with an adequate FHE scheme, they allow constant and small noise growth when homomorphically evaluating decryption circuit. In this article, we present a security proof up to the birthday bound (with respect to the size of the IV and the size of the key space) for this new structure in the random oracle model and in the multi-user setting. In particular, this result justifies the theoretical soundness of filter permutators. We also provide a related-key attack against all instances of FLIP, a stream cipher based on this design. [ABSTRACT FROM AUTHOR]

Abstract We realize a family of generalized cluster algebras as Caldero–Chapoton algebras of quivers with relations. Each member of this family arises from an unpunctured polygon with one orbifold point of order 3, and is realized as a Caldero–Chapoton algebra of a quiver with relations naturally associated to any triangulation of the alluded polygon. The realization is done by defining for every arc j on the polygon with orbifold point a representation M (j) of the referred quiver with relations, and by proving that for every triangulation τ and every arc j ∈ τ , the product of the Caldero–Chapoton functions of M (j) and M (j ′) , where j ′ is the arc that replaces j when we flip j in τ , equals the corresponding exchange polynomial of Chekhov–Shapiro in the generalized cluster algebra. Furthermore, we show that there is a bijection between the set of generalized cluster variables and the isomorphism classes of E -rigid indecomposable decorated representations of Λ. [ABSTRACT FROM AUTHOR]

One of the classic hallmarks of cancer is disruption of cell death signalling. Inhibition of cell death promotes tumour growth and metastasis, causes resistance to chemo‐ and radiotherapies as well as targeted agents, and is frequently due to overexpression of antiapoptotic proteins rather than loss of pro‐apoptotic effectors. FLIP is a major apoptosis‐regulatory protein frequently overexpressed in solid and haematological cancers, in which its high expression is often correlated with poor prognosis. FLIP, which is expressed as long (FLIP(L)) and short (FLIP(S)) splice forms, achieves its cell death regulatory functions by binding to FADD, a critical adaptor protein which links FLIP to the apical caspase in the extrinsic apoptotic pathway, caspase‐8, in a number of cell death regulating complexes, such as the death‐inducing signalling complexes (DISCs) formed by death receptors. FLIP also plays a key role (together with caspase‐8) in regulating another form of cell death termed programmed necrosis or 'necroptosis', as well as in other key cellular processes that impact cell survival, including autophagy. In addition, FLIP impacts activation of the intrinsic mitochondrial‐mediated apoptotic pathway by regulating caspase‐8‐mediated activation of the pro‐apoptotic Bcl‐2 family member Bid. It has been demonstrated that FLIP can not only inhibit death receptor‐mediated apoptosis, but also cell death induced by a range of clinically relevant chemotherapeutic and targeted agents as well as ionizing radiation. More recently, key roles for FLIP in promoting the survival of immunosuppressive tumour‐promoting immune cells have been discovered. Thus, FLIP is of significant interest as an anticancer therapeutic target. In this article, we review FLIP's biology and potential ways of targeting this important tumour and immune cell death regulator. FLIP is a key regulator of apoptosis through its ability to regulate procaspase‐8 dimerization, processing and activation. In addition, FLIP is involved in other critical cellular processes such as autophagy and necroptosis. Here, we provide an up‐to‐date review on the function and regulation of FLIP and discuss strategies for therapeutic targeting of this important cell death regulator in cancer. [ABSTRACT FROM AUTHOR]

The functional luminal imaging probe (FLIP) has been used to measure the distensibility of the anal canal. We hypothesized that with increasing distension of the anal canal with FLIP there will be an increase in length of the anal sphincter muscle allowing measurement of the length-tension function of anal sphincter and puborectalis muscles (PRM). We studied 14 healthy nulliparous women. A custom-designed FLIP bag (30-mm diameter) was placed in the vagina and then in the anal canal, distended in 10-ml steps with volumes ranging from 30 to 90 ml. At each volume, subject performed maximal voluntary squeezes. Length-tension measurements were also made with a manometric probe system. Tension was calculated (pressure x radius) in Newtons per meter using a custom software program. Peak tensions at different FLIP volumes were compared with the manometric data. No change in the luminal CSA was noted at low fluid volumes; the sphincter muscles were able to fully collapse the FLIP bag within the anal canal/vagina even at rest. At larger volumes, with each squeeze there was an increase in the bag pressure and reduction in the cross-sectional area, which represents concentric contraction of the muscle. Both rest and squeeze tension increased with the increase in volume in the anal as well as vaginal canal indicating that the external anal sphincter and puborectalis muscles produce more tension when lengthened. FLIP device, which has been used to describe the distensibility of the anal canal can also provide information on the length-tension function of the anal sphincters and PRM. NEW & NOTEWORTHY The functional luminal imaging probe (FLIP) has been used to describe the distensibility of the anal canal. This report is the first to describe the use of the FLIP in the vaginal canal and the anal canal to provide information on the length-tension function of the anal sphincter and puborectalis muscles, which may provide clinicians with additional information regarding the active components of muscle contraction involved in the anal closure function. [ABSTRACT FROM AUTHOR]

The transverse asymmetry (sidedness) of phospholipids in plasma membrane bilayers is well characterized, distinctive, actively maintained and functionally important. In contrast, numerous studies using a variety of techniques have concluded that plasma membrane bilayer cholesterol is either mostly in the outer leaflet or the inner leaflet or is fairly evenly distributed. Sterols might simply partition according to their differing affinities for the asymmetrically disposed phospholipids, but some studies have proposed that it is actively transported to the outer leaflet. Other work suggests that the sterol is enriched in the inner leaflet, driven by either positive interactions with the phosphatidylethanolamine on that side or by its exclusion from the outer leaflet by the long chain sphingomyelin molecules therein. This uncertainty raises three questions: is plasma membrane cholesterol sidedness fixed in a given cell or cell type; is it generally the same among mammalian species; and does it serve specific physiological functions? This review grapples with these issues. [ABSTRACT FROM AUTHOR]

Open ocean measurements of the turbulent wind, directional wave field, and wave breaking are used to investigate the effect of waves on the wind stress, the momentum flux between atmosphere and ocean. Data were collected during the Surface Waves and Processes Program (SWAPP), which took place in February and March of 1990 from the research platform FLIP, situated in the North Pacific.Traditional formulations of the drag coefficient are reviewed and tested in swell dominated, open ocean conditions in Chapter II. General trends indicate that drag increases with increasing wind speed, inverse wave age, and wave height, but the existence of significant scatter shows that none provides a stable, accurate estimate of the wind stress. However, significant correlations of the drag coefficient with these parameters are seen during the onset of three wind events, when waves are being actively generated. Additionally, the rate of increase of the drag coefficient in each of these periods is most closely linked to the turning rate of the wind, indicating that temporal and directional effects must play an important role.The directional relationship between waves and the wind stress is investigated in Chapter III. Non-zero angles between the direction of the wind stress and the mean wind are measured. In general, the direction of the wind stress lies between the directions of the mean wind and that of the long period swell. Moreover, a significant trend between the variations of the wind stress and swell directions is found for higher wind speeds. Finally, a relation between the wind stress and wave directions can be noticed as a function of frequency, suggesting a close dynamical link.A possible connection between wave breaking and the wind stress is investigated in Chapter IV. From comparisons of data from 15 half hour periods, the directions of the whitecap motion and the wind stress are found to be generally co-linear. As well, the speed of whitecap motion is shown to correlate with the drag coefficient. These results suggest that information about wave breaking may be used to estimate both the magnitude and direction of the wind stress.

本研究以翻轉式概念構圖為教學策略，期望能提升學生的閱讀理解能力。研究對象為新北市某國小五年級學生，以立意取樣選取兩個班級作為實驗組及控制組，實驗組教師運用翻轉式概念構圖進行教學，控制組教師以傳統講述式進行大意教學。本研究採準實驗研究設計，歷時10週，共10堂課（400分鐘），研究結果發現，實驗組經由翻轉式概念構圖的教學，在「提取訊息」與「推論訊息」沒有顯著差異，但在「詮釋整合」與「比較評估」的能力明顯優於控制組，且實驗組之中的高學習成效學生經過實驗後，在「推論訊息」能力上與低學習成效學生沒有顯著差異，但在「提取訊息」、「詮釋整合」及「比較評估」的能力優於低學習成效的學生。因此，翻轉式概念構圖教學策略能有效提升學生的閱讀理解能力。 In this study, using fl ip concept mapping teaching strategy, hoping to enhance the students’ reading comprehension. The participants is fi fth-grade students in a mountainous area of New Taipei City. Select two classes as the experimental group and a control group, experimental group for teachers to use fl ip concept mapping teaching, control group for teachers to use traditional teaching. Quasi-experimental design, which lasted ten weeks a total of ten lessons. The conclusions as following below: 1. Through fl ip concept map teaching, the “extract information” and “inference messages” of reading comprehension in experimental group shows nosignificant difference, but better than control group in ability of “explain integration” and “comparative assessment”. 2. Through experiments, the higher learning effectiveness of experimental group students show no significant difference in “inference messages” with lower learning effectiveness students, but better than lower learning effectiveness students in ability of “extract information,” “explain integration” and “comparative assessment”.

Objective Gastric cancer is a major health issue worldwide. Using a therapeutic approach, with minor side-effects, is very essential for the treatment of the gastric cancer. Shiraia bambusicola is a parasitic fungus which is widely used in China for curing several diseases with little side-effects. However, the mechanisms are not well understood yet. The aim of this study was to further understand the pharmacological mechanisms of Shiraia bambusicola and investigate whether it can be used for curing gastric cancer. Materials and Methods In this experimental study, we mainly tested the effect of active components extracted from Shiraia bambusicola on BGC823, A549 and HepG2 cells. We used MTT assay to test cell viability. We also analyzed morphologic changes caused by apoptosis using Hoechst 33342 fluorescence staining, as well as cell cycle status and apoptosis ratio using flow-cytometer. In addition, protein expression level was tested by Western-blotting assay. Results BGC-823 cell proliferation was specifically inhibited by active components of Shiraia bambusicola. Meanwhile, these active components could induce BGC-823 cells apoptosis and retard the cell cycle in S/G2 phase. We also determined that two critical protein markers cleaved Poly(ADP-ribose) polymerase-1 (PARP-1) and FLICE-inhibitory protein (FLIP), involved in apoptosis process, were regulated by these active components. Conclusion These data shed light on the treatment of human gastric cancer and conclude that Shiraia bambusicola can be a good therapeutic candidate for treatment of this malignancy.