Miracle-dz/UniFAR-FTUs huggingface dataset:
Statistics of VIX Futures and Their Applications to Trading Volatility Exchange-Traded Products

We study the dynamics of VIX futures and ETNs/ETFs. We find that contrary to classical commodities, VIX and VIX futures exhibit large volatility and skewness, consistent with the absence of cash-and-carry arbitrage. The constant-maturity futures (CMF) term-structure can be modeled as a stationary stochastic process in which the most likely state is a contango with VIX ≈ 12% and a long-term futures price V∞ ≈ 20%. We analyze the behavior of ETFs and ETNs based on constant-maturity rolling futures strategies, such as VXX, XIV and VXZ, assuming stationarity and through a multi-factor model calibrated to historical data. We find that buy-and-hold strategies consisting of shorting ETNs that roll long futures, or buying ETNs that roll short futures, will produce theoretically-sure profits if it is assumed that CMFs are stationary and ergodic (see Proposition 3.1). To quantify further, we estimate a 2-factor lognormal model with mean-reverting factors to VIX and CMF historical data from 2011 to 2016. The results confirm the profitability of buy-and-hold strategies, but also indicate that the latter have modest Sharpe ratios, of the order of SR = 0.5 or less, and high variability over 1-year horizon simulations. This is due to the surges in VIX and CMF backwardations which are experienced sporadically, but also inevitably, in the volatility futures market.
Structural and functional characterization of the PNKP–XRCC4–LigIV DNA repair complex

Abstract Non-homologous end joining (NHEJ) repairs DNA double strand breaks in non-cycling eukaryotic cells. NHEJ relies on polynucleotide kinase/phosphatase (PNKP), which generates 5΄-phosphate/3΄-hydroxyl DNA termini that are critical for ligation by the NHEJ DNA ligase, LigIV. PNKP and LigIV require the NHEJ scaffolding protein, XRCC4. The PNKP FHA domain binds to the CK2-phosphorylated XRCC4 C-terminal tail, while LigIV uses its tandem BRCT repeats to bind the XRCC4 coiled-coil. Yet, the assembled PNKP-XRCC4–LigIV complex remains uncharacterized. Here, we report purification and characterization of a recombinant PNKP–XRCC4–LigIV complex. We show that the stable binding of PNKP in this complex requires XRCC4 phosphorylation and that only one PNKP protomer binds per XRCC4 dimer. Small angle X-ray scattering (SAXS) reveals a flexible multi-state complex that suggests that both the PNKP FHA and catalytic domains contact the XRCC4 coiled-coil and LigIV BRCT repeats. Hydrogen-deuterium exchange indicates protection of a surface on the PNKP phosphatase domain that may contact XRCC4–LigIV. A mutation on this surface (E326K) causes the hereditary neuro-developmental disorder, MCSZ. This mutation impairs PNKP recruitment to damaged DNA in human cells and provides a possible disease mechanism. Together, this work unveils multipoint contacts between PNKP and XRCC4–LigIV that regulate PNKP recruitment and activity within NHEJ.
Gene therapy with tumor-specific promoter mediated suicide gene plus interleukin-12 gene enhanced tumor inhibition and prolonged host survival in a murine model of Lewis lung carcinoma.

e13086 Background: Gene therapy is a promising therapeutic approach for cancer. Targeted expression of desired therapeutic proteins within the tumor is the best approach to reduce toxicity and improve survival. This study was to establish a more effective and less toxic gene therapy of cancer. METHODS Combined gene therapy strategy with recombinant adenovirus expressing horseradish peroxidase (HRP) mediated by human telomerase reverse transcriptase (hTERT) promoter (AdhTERTHRP) and murine interleukin-12 (mIL-12) under the control of Cytomegalovirus (CMV) promoter (AdCMVmIL-12) was developed and evaluated against Lewis lung carcinoma (LLC) both in vivo and in vitro. The mechanism of action and systemic toxicities were also investigated. RESULTS HRP and mIL-12 proteins were detected in LLC cells and subcutaneous tumors. The combination of AdhTERTHRP/IAA treatment and AdCMVmIL-12 resulted in significant tumor growth inhibition and survival improvement compared with AdhTERTHRP/IAA alone (mean tumor volume, 427.4 ± 48.7 mm3 vs 581.9 ± 46.9 mm3, p = 0.005 on day 15; median overall survival (OS), 51 d vs 33 d) or AdCMVmIL-12 alone (mean tumor volume, 362.2 ± 33.8 mm3 vs 494.4 ± 70.2 mm3, p = 0.046 on day 12; median OS, 51 d vs 36 d). The expressed mIL-12 in tumor in combination group stimulated more CD4+ T helper cells and CD8+ cytotoxic T cells, compared with either AdCMVmIL-12 alone (1.3-fold increase for CD4+ T cells and 1.2-fold increase for CD8+ T cells, P<0.01) or AdhTERTHRP alone (2.1-fold increase for CD4+ T cells and 2.2-fold increase for CD8+ T cells, P <0.01). The apoptotic cells in combination group were significantly increased compared with AdCMVmIL-12 alone group (2.8-fold increase, P<0.01) or AdhTERTHRP alone group (1.6-fold increase, P<0.01). No significant systematic toxicities were observed. CONCLUSIONS Combination gene therapy with AdhTERTHRP/IAA and AdCMVmIL-12 could significantly inhibit tumor growth and improve host survival in LLC model, without significant systemic adverse effects.
Effects of a lifestyle intervention on adiposity and fitness in overweight or low fit preschoolers (Ballabeina)

Overweight (OW) and low fit children represent cardiovascular high‐risk groups. A multidimensional school‐based lifestyle intervention performed in 652 preschoolers reduced skinfold thickness and waist circumference, and improved fitness, but did not affect BMI. The objective of this study is to examine whether the intervention was equally effective in OW (≥90th national percentile) and/or low fit (lowest sex‐ and age‐adjusted quartile of aerobic fitness) children compared to their normal weight and normal fit counterparts.
Patients undergoing lymphadenectomy for stage III melanomas of known or unknown primary site do not differ in outcome

The outcome of patients with palpable melanoma metastases in lymph nodes in the presence (metastatic melanoma of known primary site, MKP) or absence (metastatic melanoma of unknown primary site, MUP) of an identifiable primary tumour remains controversial. Some of the previous studies contained large case series that included historical patients. We aimed to compare outcomes of those with MUPs versus MKPs with palpable lymph node invasion, after staging with modern imaging technology. Aprospective study of patients from a single tertiary institution who were undergoing lymph node dissection for palpable metastatic melanoma between 2000 and 2011 was conducted. All patients were ascertained by computerised tomography scanning and most diagnosed after 2004 had positron emission tomography scanning also. Clinicopathological details about the primary melanoma and lymph node dissections were gathered. Factors associated with recurrence and melanoma‐specific mortality in those with MKP and with MUP were assessed using univariate and multivariate analyses. Out of 485 patients studied, 82 had MUP and 403 had MKP. Patients were followed up for a median of 17.4 and 19.0 months, for MKP and MUP, respectively. Five‐year adjusted melanoma‐specific survival was 58% for MUPs versus 49% for MKPs and was not significantly different between the two groups (adjusted Cox proportional Hazard ratio = 0.88 95% confidence interval [0.58, 1.33] p = 0.54). Previously established prognostic factors such as number of positive nodes and extracapsular extension were confirmed in both sets of patients. We conclude that among melanoma patients presenting with clinically detectable nodes, when accurately staged, those without an identifiable primary lesion have similar outcomes to patients with MKP.
Role for nsP2 Proteins in the Cessation of Alphavirus Minus-Strand Synthesis by Host Cells

ABSTRACT In order to establish nonlytic persistent infections (PI) of BHK cells, replicons derived from Sindbis (SIN) and Semliki Forest (SFV) viruses have mutations in nsP2. Five different nsP2 PI replicons were compared to wild-type (wt) SIN, SFV, and wt nsPs SIN replicons. Replicon PI BHK21 cells had viral RNA synthesis rates that were less than 5% of those of the wt virus and ∼10% or less of those of SIN wt replicon-infected cells, and, in contrast to wt virus and replicons containing wt nsP2, all showed a phenotype of continuous minus-strand synthesis and of unstable, mature replication/transcription complexes (RC+) that are active in plus-strand synthesis. Minus-strand synthesis and incorporation of [3H]uridine into replicative intermediates differed among PI replicons, depending on the location of the mutation in nsP2. Minus-strand synthesis by PI cells appeared normal; it was dependent on continuous P123 and P1234 polyprotein synthesis and ceased when protein synthesis was inhibited. The failure by the PI replicons to shut off minus-strand synthesis was not due to some defect in the PI cells but rather was due to the loss of some function in the mutated nsP2. This was demonstrated by showing that superinfection of PI cells with wt SFV triggered the shutdown of minus-strand synthesis, which we believe is a host response to infection with alphaviruses. Together, the results indicate alphavirus nsP2 functions to engage the host response to infection and activate a switch from the early-to-late phase. The loss of this function leads to continuous viral minus-strand synthesis and the production of unstable RC+.
Multi-band carrier-less amplitude and phase modulation for VLC: An overview

The rapid development of solid-state lighting technologies has been the stimulus for visible light communications (VLC) to be the focus of enormous interest over the last decade. The key feature of simultaneous data transmission and illumination using white light-emitting diodes (LEDs) makes VLC a potential candidate for future power efficient communication networks that aim to meet the ever-increasing demands for high-speed internet services. Researchers, motivated by the success of VLC technology, have developed a number of techniques and methods to support communication systems with both high transmission speeds and spectral efficiency. Here, we provide an overview of the multi-band carrier-less amplitude and phase (m-CAP) modulation technique enabling highly spectrally efficient VLC links in bandlimited environments.
Treatment of malignant hypercalcaemia

Hypercalcaemia is a common paraneoplastic syndrome caused by the production by tumours of several factors which affect bone resorption and/or tubular calcium reabsorption. Antihypercalcaemic therapy in cancer patients involves rehydration manoeuvres, as well as the use of a variety of available drugs which inhibit bone resorption, namely plicamycin, calcitonin, bisphosphonates and gallium nitrate. While plicamycin is currently out of use because of its considerable toxicity, bisphosphonates have become the standard therapy in hypercalcaemia of malignancy (HM). These compounds are potent inhibitors of bone resorption but they do not affect tubular calcium reabsorption, which limits their efficacy in humoral HM (HHM) cases. In these patients, gallium nitrate should be the therapy of choice. Among the available bisphosphonates, pamidronate administered in a single infusion of 90 mg, normalises serum calcium levels in > 90% of HM patients. A recently introduced bisphosphonate, zoledronate, is likely to replace pamidronate as a first-line therapy in these patients. The effectiveness of calcitonin in HM treatment is limited, although it seems to be useful at the outset in cases with severe symptomatic hypercalcaemia. Future treatment options of HM are likely to include new bone resorption inhibitors, for example, naturally-occurring osteoprotegerin, or alternate approaches aimed at reducing the tumour production of parathyroid hormone-related protein with noncalcaemic analogues of calcitriol or ras-isoprenylation inhibitors. The development of putative therapeutic agents targeted to inhibit distal calcium reabsorption should be valuable in the management of HHM cases.
Overexpression of Histone Deacetylase 1 Confers Resistance to Sodium Butyrate–Mediated Apoptosis in Melanoma Cells through a p53-Mediated Pathway

Melanoma cells typically express wild-type p53, yet they are notoriously resistant to DNA-damaging agents. Here, we show that sodium butyrate (NaB), a histone deacetylase (HDAC) inhibitor, induced apoptosis in human melanoma cells in a dose- and time-dependent manner. Apoptosis was associated with HDAC1-dependent induction of Bax and acetylation of p53. Down-regulation of HDAC1 by an antisense vector sensitized the cells to NaB-induced apoptosis, whereas its overexpression conferred resistance to this agent. Increased HDAC1 levels and activity impaired NaB-mediated activation of Bax promoter and Bax protein levels. Finally, using p53-null melanoma cell line and RNA interference in cells expressing wild-type p53 protein, we show that Bax induction and NaB-mediated apoptosis is p53 dependent.
Evaluation of the Gen-Probe Chlamydia trachomatis transcription-mediated amplification assay with urine specimens from women

We evaluated the Gen-Probe Chlamydia trachomatis transcription-mediated amplification (TMA) assay with urine specimens for the detection of C. trachomatis infections in women. The novel test, based on the isothermal amplification of chlamydial RNA, was compared with the Roche Amplicor PCR with urine and cell culture with endocervical specimens. First-catch urine and endocervical swab specimens were collected from a total of 561 patients, of whom 70 (12.3%) were confirmed to have chlamydial infection. The diagnostic sensitivity and specificity of TMA with urine were 91.4 and 99.6%, respectively, and those of Amplicor PCR were 97.1 and 99.8%, respectively. By repeated analysis of the specimens with discrepant results, the sensitivity of TMA could be increased to 99%, indicating that some methodological improvements in the assay are still to be expected. The sensitivity of PCR could be increased to 100% by the elimination of DNA polymerase inhibitors in a repeated analysis. The sensitivity and specificity of cell culture with cervical specimens were 85.7 and 100%, respectively. The results indicate that TMA with urine specimens from women is a sensitive and specific assay for the detection of C. trachomatis, providing a new noninvasive technique for the screening of chlamydial infections in women.
There and back again – estimating equivalence scales with measurement error

ABSTRACT Using income satisfaction data from the German Socio-Economic Panel, we find large differences in the equivalence weight of a partner when it is being estimated by direct and reverse regressions. We argue that neither of the two models will produce consistent estimates when there is stochastic error in satisfaction and measurement error in incomes. We propose a correction of mismeasured incomes using a constructed alternative income measure. The corrected results are relatively close to those obtained from direct regression. We do not find evidence that previous studies, using the direct regression method, severely suffer from measurement error in incomes.
The adoption of sustainable agricultural practices by smallholder farmers in Ethiopian highlands: An integrative approach

Abstract The adoption of Sustainable Agricultural Practices (SAPs) remains high on the policy and research agenda in most of sub-Saharan Africa. This paper adopts an integrative approach to investigate how psycho-social and socioeconomic factors influence the uptake of SAPs by smallholder farmers in Ethiopian Highlands. The study applies the Theory of Planned Behavior theoretical framework, as well as the Ordered Probit model and Partial Least Squares Structural Equation Modeling (PLS-SEM) to model farmers' adoption decisions. The results show that socioeconomic factors such as access to agricultural loans and off-farm income, household labor availability and livestock ownership increase the probability of adopting two or more SAPs. The results further show that farmers' intentions and personal norms significantly influence the number of SAPs adopted at farm-level. These results imply that efforts to promote the widespread adoption of SAPs by smallholder farmers should focus on enhancing farmers' access to agricultural loans and off-farm income, through increased integration into the non-farm rural economy and addressing liquidity constraints through affordable rural financing schemes. The adoption of SAPs can further be enhanced by raising farmers' general awareness and knowledge to change their perceptions and attitudes towards sustainable farming practices.
Phraseology in Teaching and Learning Spanish as a Foreign Language in the USA

The aim of this study is to analyze the acquisition of phraseological units at the elementary, secondary, and university levels in order to develop a better understanding of the linguistic competence o f American students in learning Spanish as a foreign language in Utah. Aft er discussing the importance of phraseology as a fundamental part of the linguis tic content in the L2 classroom, we analyze the most frequent phraseological u nits in L2 Spanish manuals and how students in the different academic contexts where able to identify their meaning in contextualized and non-contextualized se ttings. The results showed the importance of context in the identification of these phraseological units with a significantly higher percentage of accuracy in th e contextualized setting. The study also addresses the important role that idioma tic expressions can play in teaching phraseology and culture thus enriching the sociolinguistic competence with diatopic variation as a core of phraseology.
Incidence and predictive factors of first episode of spontaneous bacterial peritonitis in cirrhosis with ascites: Relevance of ascitic fluid protein concentration

To investigate the long‐term probability of the appearance of the first episode of spontaneous bacterial peritonitis in cirrhosis with ascites and to identify predictors of this complication, we closely followed throughout their illness 127 patients consecutively admitted to our unit for the treatment of an episode of ascites without prior spontaneous bacterial peritonitis (follow‐up period: 21 ± 22 mo). Thirteen patients (10%) had the first spontaneous bacterial peritonitis episode during follow‐up. The appearance probability of this complication is 11% at 1 yr and 15% at 3 yr. Thirty‐three variables obtained at admission (including clinical data, standard liver and kidney function test results, ascitic fluid protein concentrations and hemodynamic parameters) were analyzed in relation to their value in predicting spontaneous bacterial peritonitis development. In univariate analysis (Kaplan‐Meier curves) five variables reached statistical significance (p < 0.05) as predictive factors for the development of the first spontaneous bacterial peritonitis episode. These five variables were poor nutritional status, increased serum bilirubin levels, increased serum AST levels, decreased prothrombin activity and reduced total protein concentration in ascitic fluid. When these five variables were introduced in a multivariate analysis, only the ascitic fluid protein concentration was found to correlate independently with spontaneous bacterial peritonitis development (p = 0.002). The probability of first spontaneous bacterial peritonitis after 3 yr of follow‐up was 24% and 4% in patients with ascitic fluid protein content lower than 1 gm/dl and greater than or equal to 1 gm/dl, respectively. We concluded that the most important predictor of the development of the first spontaneous bacterial peritonitis episode in cirrhosis with ascites is the total protein concentration in ascitic fluid. (HEPATOLOGY 1992;16:724–727.)
Aromatase inhibitors in post-menopausal metastatic breast carcinoma

To summarise the advances in the hormonal treatment of post-menopausal metastatic breast cancer, this paper reviews the published literature regarding the randomised trials comparing aromatase inhibitors (AIs) versus tamoxifen as a first-line therapeutic choice, or AIs versus megestrole acetate (MEG) as a second-line option. The pooled analysis of these authors on AI versus MEG as a second-line option for post-menopausal metastatic breast cancer suggested that AIs do not add any significant benefit over MEG in terms of overall response rate (ORR) and time to progression. According to the Cochrane Database, use of an AI as a second-line therapy versus any other endocrine therapy (mostly MEG) has shown a significant benefit in terms of overall survival, but not for progression-free survival, clinical benefit (CB) or ORR. Concerning the authors’ comparisons between AIs versus tamoxifen as a first-line endocrine option in post-menopausal women with metastatic breast carcinoma, AIs seem to be superior to tamoxifen, with a significant benefit in terms of ORR, CB and time to progression being observed in favour of AIs over tamoxifen with fixed effects estimates. According to the Cochrane Database, there was an advantage to the use of AIs over tamoxifen in terms of progression-free survival and CB, but not for overall survival or ORR. With regards to toxicity, AIs show similar levels of hot flushes and arthralgia, increased risks of nausea, diarrhoea and vomiting, but a decreased risk of vaginal bleeding and thromboembolic events compared with other endocrine therapies. Weight gain, dyspnoea and peripheral oedema seem to be more frequent with MEG. At present, there is no proved overall survival difference in patients who are treated first with an AI and then with tamoxifen compared with the opposite sequence. In the metastatic setting, results are limited and are based on retrospective analyses.
Texture perception through direct and indirect touch: An analysis of perceptual space for tactile textures in two modes of exploration

Considerable information about the texture of objects can be perceived remotely through a probe. It is not clear, however, how texture perception with a probe compares with texture perception with the bare finger. Here we investigate the perception of a variety of textured surfaces encountered daily (e.g., corduroy, paper, and rubber) using the two scanning modes—direct touch through the finger and indirect touch through a probe held in the hand—in two tasks. In the first task, subjects rated the overall pair-wise dissimilarity of the textures. In the second task, subjects rated each texture along three continua, namely, perceived roughness, hardness, and stickiness of the surfaces, shown previously as the primary dimensions of texture perception in direct touch. From the dissimilarity judgment experiment, we found that the texture percept is similar though not identical in the two scanning modes. From the adjective rating experiments, we found that while roughness ratings are similar, hardness and stickiness ratings tend to differ between scanning conditions. These differences between the two modes of scanning are apparent in perceptual space for tactile textures based on multidimensional scaling (MDS) analysis. Finally, we demonstrate that three physical quantities, vibratory power, compliance, and friction carry roughness, hardness, and stickiness information, predicting perceived dissimilarity of texture pairs with indirect touch. Given that different types of texture information are processed by separate groups of neurons across direct and indirect touch, we propose that the neural mechanisms underlying texture perception differ between scanning modes.