Miracle-dz/UniFAR-FTUs huggingface dataset:
Evidence of Three‐Dimensional Scroll Waves with Ribbon‐Shaped Filament as a Mechanism of Ventricular Tachycardia in the Isolated Rabbit Heart

Scroll Waves in the Heart. Introduction: Rotating vortices have been observed in excitable media of different nature. Vortices may sustain life or kill in different species, by underlining morphogenesis in Dictiostelium discoideum during starvation, or arrhythmias during sudden cardiac death in mammals. Investigation of vortices in the heart has been limited by two‐dimensional experimental techniques. In contrast, three‐dimensional (3D) Belousov‐Zhabotinsky excitable medium and mathematical models have been shown to sustain scroll‐shaped waves. The heart is a 3D structure; therefore, scroll waves may underlie cardiac arrhythmias.
Dynamic Entrepreneurial and Managerial Role in the Front End Loading (FEL) Phase for Sensing and Seizing Emerging Technologies

Emerging technologies in the current era is characterised by the increasing network of digital devices and connectivity. Businesses around the world are challenged to keep up with these changes and to sustain their businesses at the same time. This poses challenges for the firm’s management team to identify the benefits of an emerging technology to the firm, when to adopt an emerging technology and or when to ignore it. In response to some of these challenges, business management teams are constantly in search of sustainable and flexible models that can easily adapt to technological evolution in their business environments. These models are used to plan on how to create, deliver and capture value from the emerging technology. This response approach requires that the firm’s strategy model is agile and resonant while the corresponding business model for value creation and capture is adaptable. This paper adapts the concept of the stage-gate methodology to analyse the robust planning activities in the early stages of sensing, seizing and transformation of an internet-enabled emerging technology from a firm’s external business environment. The main focus of this paper is on the ‘front-end loading’ phase of the process which basically incorporates strategic sensing activities of an emerging technological opportunity. The phase also includes business model adaptation activities that enable the firm to seize and transform the sensed opportunity. This phase is analysed to establish how firms can take advantage of their dynamic managerial and entrepreneurial capabilities to sense, seize and transform these technological opportunities into technologically-enabled value propositions. Some theoretical propositions are made on what business firms can do with their dynamic entrepreneurial and managerial capabilities to enable them sense and seize emerging technologies and areas of further research are also identified.
Evaluation of TNF-α and IL-1 Blockade in Collagen-Induced Arthritis and Comparison with Combined Anti-TNF-α/Anti-CD4 Therapy1

We have evaluated the effects of anti-TNF-α, anti-IL-1, and combined anti-TNF-α/anti-CD4 therapy in collagen-induced arthritis. Blockade of TNF-α or IL-1 before disease onset delayed, but did not prevent, the induction of arthritis. When treatment was initiated after onset of arthritis, anti-TNF-α, anti-IL-1β, and anti-IL-1R (which blocks IL-1α and IL-1β) were all found to be effective in reducing the severity of arthritis, with anti-IL-1R and anti-IL-1β showing greater efficacy than anti-TNF-α. Anti-IL-1β was equally as effective as anti-IL-1R, indicating that IL-1β plays a more prominent role than IL-1α in collagen-induced arthritis. An additive effect was observed between anti-TNF-α and anti-IL-1R in the prevention of joint erosion and in normalization of the levels of serum amyloid P. Combined anti-TNF-α/anti-CD4 therapy also caused normalization of serum amyloid P levels. The therapeutic effect of anti-TNF-α plus anti-CD4 was comparable to that of anti-TNF-α plus anti-IL-1R, suggesting that combined anti-TNF-α/anti-CD4 therapy prevents both TNF-α- and IL-1-mediated pathology. Anti-TNF-α treatment reduced IL-1β expression in the joint and, conversely, anti-IL-1β treatment reduced TNF-α expression. Combined anti-TNF-α/anti-CD4 treatment almost completely blocked the expression of IL-1β, thereby confirming the ability of this form of combination therapy to prevent IL-1β-mediated pathology.
CBL mutations in myeloproliferative neoplasms are also found in the gene’s proline-rich domain and in patients with the V617FJAK2

Background Despite the discovery of the p.V617F in JAK2, the molecular pathogenesis of some chronic myeloproliferative neoplasms remains unclear. Although very rare, different studies have identified CBL (Cas-Br-Murine ecotropic retroviral transforming sequence) mutations in V617FJAK2-negative patients, mainly located in the RING finger domain. In order to determine the frequency of CBL mutations in these diseases, we studied different regions of all CBL family genes (CBL, CBLB and CBLC) in a selected group of patients with myeloproliferative neoplasms. We also included V617FJAK2-positive patients to check whether mutations in CBL and JAK2 are mutually exclusive events. Design and Methods Using denaturing high performance liquid chromatography, we screened for mutations in CBL, CBLB and CBLC in a group of 172 V617FJAK2-negative and 232 V617FJAK2-positive patients with myeloproliferative neoplasms not selected for loss of heterozygosity. The effect on cell proliferation of the mutations detected was analyzed on a 32D(FLT3) cell model. Results An initial screening of all coding exons of CBL, CBLB and CBLC in 44 V617FJAK2-negative samples revealed two new CBL mutations (p.C416W in the RING finger domain and p.A678V in the proline-rich domain). Analyses performed on 128 additional V617FJAK2-negative and 232 V617FJAK2-positive samples detected three CBL changes (p.T402HfsX29, p.P417R and p.S675C in two cases) in four V617FJAK2-positive patients. None of these mutations was found in 200 control samples. Cell proliferation assays showed that all of the mutations promoted hypersensitivity to interleukin-3 in 32D(FLT3) cells. Conclusions Although mutations described to date have been found in the RING finger domain and in the linker region of CBL, we found a similar frequency of mutations in the proline-rich domain. In addition, we found CBL mutations in both V617FJAK2-positive (4/232; 1.7%) and negative (2/172; 1.2%) patients and all of them promoted hypersensitivity to interleukin-3.
Molecular Scaffold Analysis of Natural Products Databases in the Public Domain

Natural products represent important sources of bioactive compounds in drug discovery efforts. In this work, we compiled five natural products databases available in the public domain and performed a comprehensive chemoinformatic analysis focused on the content and diversity of the scaffolds with an overview of the diversity based on molecular fingerprints. The natural products databases were compared with each other and with a set of molecules obtained from in‐house combinatorial libraries, and with a general screening commercial library. It was found that publicly available natural products databases have different scaffold diversity. In contrast to the common concept that larger libraries have the largest scaffold diversity, the largest natural products collection analyzed in this work was not the most diverse. The general screening library showed, overall, the highest scaffold diversity. However, considering the most frequent scaffolds, the general reference library was the least diverse. In general, natural products databases in the public domain showed low molecule overlap. In addition to benzene and acyclic compounds, flavones, coumarins, and flavanones were identified as the most frequent molecular scaffolds across the different natural products collections. The results of this work have direct implications in the computational and experimental screening of natural product databases for drug discovery.
Semantics derived automatically from language corpora contain human-like biases

Machines learn what people know implicitly AlphaGo has demonstrated that a machine can learn how to do things that people spend many years of concentrated study learning, and it can rapidly learn how to do them better than any human can. Caliskan et al. now show that machines can learn word associations from written texts and that these associations mirror those learned by humans, as measured by the Implicit Association Test (IAT) (see the Perspective by Greenwald). Why does this matter? Because the IAT has predictive value in uncovering the association between concepts, such as pleasantness and flowers or unpleasantness and insects. It can also tease out attitudes and beliefs—for example, associations between female names and family or male names and career. Such biases may not be expressed explicitly, yet they can prove influential in behavior. Science, this issue p. 183; see also p. 133 Computers can learn which words go together more or less often and can thus mimic human performance on a test of implicit bias. Machine learning is a means to derive artificial intelligence by discovering patterns in existing data. Here, we show that applying machine learning to ordinary human language results in human-like semantic biases. We replicated a spectrum of known biases, as measured by the Implicit Association Test, using a widely used, purely statistical machine-learning model trained on a standard corpus of text from the World Wide Web. Our results indicate that text corpora contain recoverable and accurate imprints of our historic biases, whether morally neutral as toward insects or flowers, problematic as toward race or gender, or even simply veridical, reflecting the status quo distribution of gender with respect to careers or first names. Our methods hold promise for identifying and addressing sources of bias in culture, including technology.
Supra-Agonist Peptides Enhance the Reactivation of Memory CTL Responses1

Single amino acid substitutions at TCR contacts may transform a natural peptide Ag in CTL ligands with partial agonist, antagonist, or null activity. We obtained peptide variants by changing nonanchor amino acid residues involved in MHC class I binding. These peptides were derived from a subdominant HLA-A2-presented, latent membrane protein 2-derived epitope expressed in EBV-infected cells and in EBV-associated tumors. We found that small structural changes produced ligands with vastly different activities. In particular, the variants that associated more stably to HLA-A2/molecules did not activate any CTL function, behaving as null ligands. Interestingly, T cell stimulations performed with the combination of null ligands and the natural epitope produced significantly higher specific CTL reactivation than reactivation of CTLs induced by the wild-type epitope alone. In addition, these particular variants activated memory CTL responses in the presence of concentrations of natural epitope that per se did not induce T cell responses. We show here that null ligands increased ZAP-70 tyrosine kinase activation induced by the natural epitope. Our results demonstrate for the first time that particular peptide variants, apparently behaving as null ligands, interact with the TCR, showing a supra-agonist activity. These variant peptides did not affect the effector T cell functions activated by the natural epitope. Supra-agonist peptides represent the counterpart of antagonists and may have important applications in the development of therapeutic peptides.
Reovirus Binding to Cell Surface Sialic Acid Potentiates Virus-Induced Apoptosis

ABSTRACT Reovirus induces apoptosis in cultured cells and in vivo. Genetic studies indicate that the efficiency with which reovirus strains induce apoptosis is determined by the viral S1 gene, which encodes attachment protein ς1. However, the biochemical properties of ς1 that influence apoptosis induction are unknown. To determine whether the capacity of ς1 to bind cell surface sialic acid determines the magnitude of the apoptotic response, we used isogenic reovirus mutants that differ in the capacity to engage sialic acid. We found that T3SA+, a virus capable of binding sialic acid, induces high levels of apoptosis in both HeLa cells and L cells. In contrast, non-sialic-acid-binding strain T3SA− induces little or no apoptosis in these cell types. Differences in the capacity of T3SA− and T3SA+ to induce apoptosis are not due to differences in viral protein synthesis or production of viral progeny. Removal of cell surface sialic acid with neuraminidase abolishes the capacity of T3SA+ to induce apoptosis. Similarly, incubation of T3SA+ with sialyllactose, a trisaccharide comprised of lactose and sialic acid, blocks apoptosis. These findings demonstrate that reovirus binding to cell surface sialic acid is a critical requirement for the efficient induction of apoptosis and suggest that virus receptor utilization plays an important role in regulating cell death.
Predictors of Unprotected Sex with Non-cohabitating Primary Partners among Sheltered and Low-income Housed Women in Los Angeles County

This study investigated associations of substance use, relationship abuse and HIV self-protective behavior with unprotected sex among 290 impoverished women with a non-cohabitating primary partner. Unprotected sex was associated with having a physically or psychologically abusive partner among low-income housed women, and having an abusive partner who also drank to intoxication among women living in shelters. Indicators of HIV self-protective behavior were associated with less frequent unprotected sex among sheltered women, even after accounting for abuse and substance use within the relationship. Results suggest the need for HIV-prevention interventions to address the problems of partner substance use and relationship abuse.
A homolog of FBP2/KSRP binds to localized mRNAs in Xenopus oocytes

A Xenopus oocyte expression library was screened for proteins that bind to the 340-nucleotide localization element of Vg1 mRNA. Four different isolates encoded a Xenopus homolog of the human transcription factor, FUSE-binding protein 2 (FBP2). This protein has been independently identified as the splicing regulatory factor KSRP. The only significant difference between the Xenopus protein, designated VgRBP71, and KSRP is the absence of a 58 amino acid segment near the N-terminal of the former. In vivo binding assays show that VgRBP71 is associated with mRNAs localized to either the vegetal or animal hemispheres, but was not found with control mRNAs. Unlike other factors that bind to the localization element of Vg1 mRNA, VgRBP71 does not accumulate at the vegetal cortex with the mRNA; rather, it is present in the nucleus and throughout the cytoplasm at all stages of oogenesis. Cytoplasmic VgRBP71 appears to be most concentrated at the cell cortex. VgRBP71 interacts with Prrp, another protein that binds to the Vg1 localization element; this association does not require the presence of Vg1 mRNA.
Temperature-sensitive RNA polymerase II mutations in Chinese hamster ovary cells.

Mutant Chinese hamster ovary cell lines temperature-sensitive (TS) for growth and containing TS mutations in RNA polymerase II (nucleosidetriphosphate:RNA nucleotidyltransferase, EC 2.7.7.6) have been isolated. Wild-type cells were treated with the mutagen N-methyl-N'-nitro-N-nitrosoguanidine and a population of cells possessing mutations in RNA polymerase II was initially selected by isolating alpha-amanitin-resistant clones at 34 degrees . Of 168 such alpha-amanitin-resistant isolates screened for temperature sensitivity, nine were TS for growth at 39.5 degrees . By examining the behavior of the alpha-amanitin resistance of these TS cell lines in somatic cell hybrids, the TS mutation in a number of them was shown to be in RNA polymerase II. Hybrid cells obtained by the fusion of the TS and alpha-amanitin-resistant cells with cells possessing alpha-amanitin-sensitive polymerase II grew at both 34 degrees and 39.5 degrees ; the TS mutations were recessive. At 34 degrees all the hybrids were alpha-amanitin-resistant and possessed a mixture of alpha-amanitin-resistant and sensitive polymerase II. At 39.5 degrees the alpha-amanitin-resistant polymerase II activities in hybrids of four of the TS cell lines were lost; these four lines were alpha-amanitin-sensitive and possessed only alpha-amanitin-sensitive polymerase II. Temperature-insensitive revertants of two of these mutants were isolated. Reversion of the TS phenotype for mutants TsAma(R)-1 and TsAma(R)-8 was accompanied by an alteration in the level of alpha-amanitin resistance of the RNA polymerase II activities in the revertant cells. Together these data provide convincing evidence that TS mutations in RNA polymerase II can be coselected with alpha-amanitin resistance.
The application of principal component analysis to quantify technique in sports

Analyzing an athlete's “technique,” sport scientists often focus on preselected variables that quantify important aspects of movement. In contrast, coaches and practitioners typically describe movements in terms of basic postures and movement components using subjective and qualitative features. A challenge for sport scientists is finding an appropriate quantitative methodology that incorporates the holistic perspective of human observers. Using alpine ski racing as an example, this study explores principal component analysis (PCA) as a mathematical method to decompose a complex movement pattern into its main movement components. Ski racing movements were recorded by determining the three‐dimensional coordinates of 26 points on each skier which were subsequently interpreted as a 78‐dimensional posture vector at each time point. PCA was then used to determine the mean posture and principal movements (PMk) carried out by the athletes. The first four PMk contained 95.5 ± 0.5% of the variance in the posture vectors which quantified changes in body inclination, vertical or fore‐aft movement of the trunk, and distance between skis. In summary, calculating PMk offered a data‐driven, quantitative, and objective method of analyzing human movement that is similar to how human observers such as coaches or ski instructors would describe the movement.
Differential flatness based control of supercapacitor substation for DC grid system

This paper presents a new control approach for dc-link stabilization in weak networks that use supercapacitors (SC) as the energy storage substation. A 4-phase parallel converter with interleaved switching technique is presented as a 2-quadrant SC converter, and a reduced-order mathematical model of the system is described for power plant control. Using a nonlinear control approach based on the flatness property, we propose a straightforward solution to dynamic and stabilization problems in the power electronics systems of networks, which is the key contribution described in this paper. To validate the proposed method, a hardware system is modeled using digital estimation with a DS1104 dSPACE controller platform. We analyze a prototype small-scale network that uses a 700 W six-pulse rectifier as a dc main generator and a 100 F, 32 V SC bank as an energy storage substation. Finally, the utility of the control algorithm is validated using experimental results measured during load cycles.
Intravoxel incoherent motion and diffusion-tensor imaging in renal tissue under hydration and furosemide flow challenges.

PURPOSE To assess the reproducibility and the distribution of intravoxel incoherent motion (IVIM) and diffusion-tensor (DT) imaging parameters in healthy renal cortex and medulla at baseline and after hydration or furosemide challenges. MATERIALS AND METHODS Using an institutional review board-approved HIPAA-compliant protocol with written informed consent, IVIM and DT imaging were performed at 3 T in 10 volunteers before and after water loading or furosemide administration. IVIM (apparent diffusion coefficient [ADC], tissue diffusivity [D(t)], perfusion fraction [f(p)], pseudodiffusivity [D(p)]) and DT (mean diffusivity [MD], fractional anisotropy [FA], eigenvalues [λ(i)]) imaging parameters and urine output from serial bladder volumes were calculated. (a)Reproducibility was quantified with coefficient of variation, intraclass correlation coefficient, and Bland-Altman limits of agreement; (b) contrast and challenge response were quantified with analysis of variance; and (c) Pearson correlations were quantified with urine output. RESULTS Good reproducibility was found for ADC, D(t), MD, FA, and λ(i) (average coefficient of variation, 3.7% [cortex] and 5.0% [medulla]), and moderate reproducibility was found for D(p), f(p), and f(p) · D(p) (average coefficient of variation, 18.7% [cortex] and 25.9% [medulla]). Baseline cortical diffusivities significantly exceeded medullary values except D(p), for which medullary values significantly exceeded cortical values, and λ(1,) which showed no contrast. ADC, D(t), MD, and λ(i) increased significantly for both challenges. Medullary diffusivity increases were dominated by transverse diffusion (1.72 ± 0.09 [baseline] to 1.79 ± 0.10 [hydration] μm(2)/msec, P = . 0059; or 1.86 ± 0.07 [furosemide] μm(2)/msec, P = . 0094). Urine output correlated with cortical ADC with furosemide (r = 0.7, P = .034) and with medullary λ(1) (r = 0.83, P = .0418), λ(2) (r = 0.85, P = .0301), and MD (r = 0.82, P = .045) with hydration. CONCLUSION Diffusion MR metrics are sensitive to flow changes in kidney induced by diuretic challenges. The results of this study suggest that vascular flow, tubular dilation, water reabsorption, and intratubular flow all play important roles in diffusion-weighted imaging contrast.
Pressure dependence of the electronic density of states and Tc in superconducting Rb3C60.

The functional dependence of the superconducting transition temperature {ital T}{sub {ital c}} on the electronic density of states {ital N}({ital E}{sub {ital f}}) was determined for Rb{sub 3}C{sub 60} by measuring the magnetic susceptibility under hydrostatic pressure to {approximately} 1 GPa in a commercial SQUID magnetometer. Both {ital T}{sub {ital c}} and {ital N}({ital E}{sub {ital f}}) decrease under pressure at the rates {minus}31{percent}/GPa and {minus}14.5{percent}/GPa, respectively, but lie above the corresponding values for K{sub 3}C{sub 60} at the same lattice parameter. The present results are consistent with weak-coupling BCS theory with characteristic energy {ital E}{sub char}/{ital k}{sub {ital B}}{approx_equal} 320{endash}810 K. {copyright} {ital 1996 The American Physical Society. }
Genome organization of Sp beta c2 bacteriophage carrying the thyP3 gene

Thymine auxotrophs of Bacillus subtilis strains lysogenic for temperate bacteriophage SP beta c2 were transformed to prototrophy by DNA from related phage phi 3T. During transformation, the phi 3T-encoded thymidylate synthetase gene, thyP3, became integrated into the extreme right end of the SP beta c2 prophage near the bacterial citK gene. Upon heat induction, the transformed B. subtilis cells released SP beta c2T phages that could lysogenize thymine auxotrophs and convert them to prototrophy. Comparison of restriction endonuclease fragments of DNAs from SP beta c2 and SP beta c2T phages revealed that the latter contained a large region of deletion and substitution near the center of the chromosome. This region included the phage attachment site on the SP beta c2 genome.