Incorporating currencies, payment methods, and protocols that computers use to talk to each other, digital currencies are poised to grow in use and importance. The Handbook of Digital Currency gives ...readers a way to learn about subjects outside their specialties and provides authoritative background and tools for those whose primary source of information is journal articles. Taking a cross-country perspective, its comprehensive view of the field includes history, technicality, IT, finance, economics, legal, tax and regulatory environment. For those who come from different backgrounds with different questions in mind, The Handbook of Digital Currency is an essential starting point. * Discusses all major strategies and tactics associated with digital currencies, their uses, and their regulations * Presents future scenarios for the growth of digital currencies * Written for regulators, crime prevention units, tax authorities, entrepreneurs, micro-financiers, micro-payment businesses, cryptography experts, software developers, venture capitalists, hedge fund managers, hardware manufacturers, credit card providers, money changers, remittance service providers, exchanges, and academics * Winner of the 2015 "Outstanding Business Reference Source" by the Reference and User Services Association (RUSA)
Clear cell renal cell carcinoma (ccRCC), the most common form of kidney cancer, is characterized by elevated glycogen levels and fat deposition. These consistent metabolic alterations are associated ...with normoxic stabilization of hypoxia-inducible factors (HIFs) secondary to von Hippel-Lindau (VHL) mutations that occur in over 90% of ccRCC tumours. However, kidney-specific VHL deletion in mice fails to elicit ccRCC-specific metabolic phenotypes and tumour formation, suggesting that additional mechanisms are essential. Recent large-scale sequencing analyses revealed the loss of several chromatin remodelling enzymes in a subset of ccRCC (these included polybromo-1, SET domain containing 2 and BRCA1-associated protein-1, among others), indicating that epigenetic perturbations are probably important contributors to the natural history of this disease. Here we used an integrative approach comprising pan-metabolomic profiling and metabolic gene set analysis and determined that the gluconeogenic enzyme fructose-1,6-bisphosphatase 1 (FBP1) is uniformly depleted in over six hundred ccRCC tumours examined. Notably, the human FBP1 locus resides on chromosome 9q22, the loss of which is associated with poor prognosis for ccRCC patients. Our data further indicate that FBP1 inhibits ccRCC progression through two distinct mechanisms. First, FBP1 antagonizes glycolytic flux in renal tubular epithelial cells, the presumptive ccRCC cell of origin, thereby inhibiting a potential Warburg effect. Second, in pVHL (the protein encoded by the VHL gene)-deficient ccRCC cells, FBP1 restrains cell proliferation, glycolysis and the pentose phosphate pathway in a catalytic-activity-independent manner, by inhibiting nuclear HIF function via direct interaction with the HIF inhibitory domain. This unique dual function of the FBP1 protein explains its ubiquitous loss in ccRCC, distinguishing FBP1 from previously identified tumour suppressors that are not consistently mutated in all tumours.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, KISLJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
This paper empirically assesses the wage effects of the Job Corps program, one of the largest federally funded job training programs in the U.S. Even with the aid of a randomized experiment, the ...impact of a training program on wages is difficult to study because of sample selection, a pervasive problem in applied microeconometric research. Wage rates are only observed for those who are employed, and employment status itself may be affected by the training program. This paper develops an intuitive trimming procedure for bounding average treatment effects in the presence of sample selection. In contrast to existing methods, the procedure requires neither exclusion restrictions nor a bounded support for the outcome of interest. Identification results, estimators, and their asymptotic distribution are presented. The bounds suggest that the program raised wages, consistent with the notion that the Job Corps raises earnings by increasing human capital, rather than solely through encouraging work. The estimator is generally applicable to typical treatment evaluation problems in which there is nonrandom sample selection/attrition.
This paper provides an introduction and "user guide" to Regression Discontinuity (RD) designs for empirical researchers. It presents the basic theory behind the research design, details when RD is ...likely to be valid or invalid given economic incentives, explains why it is considered a "quasi-experimental" design, and summarizes different ways (with their advantages and disadvantages) of estimating RD designs and the limitations of interpreting these estimates. Concepts are discussed using examples drawn from the growing body of empirical research using RD.
G-quadruplex (G4) sequences are abundant in untranslated regions (UTRs) of human messenger RNAs, but their functional importance remains unclear. By integrating multiple sources of genetic and ...genomic data, we show that putative G-quadruplex forming sequences (pG4) in 5' and 3' UTRs are selectively constrained, and enriched for cis-eQTLs and RNA-binding protein (RBP) interactions. Using over 15,000 whole-genome sequences, we find that negative selection acting on central guanines of UTR pG4s is comparable to that of missense variation in protein-coding sequences. At multiple GWAS-implicated SNPs within pG4 UTR sequences, we find robust allelic imbalance in gene expression across diverse tissue contexts in GTEx, suggesting that variants affecting G-quadruplex formation within UTRs may also contribute to phenotypic variation. Our results establish UTR G4s as important cis-regulatory elements and point to a link between disruption of UTR pG4 and disease.
IMPORTANCE The effect of serious injuries, such as hip fracture and head injury, on mortality and function is comparable to that of cardiovascular events. Concerns have been raised about the risk of ...fall injuries in older adults taking antihypertensive medications. The low risk of fall injuries reported in clinical trials of healthy older adults may not reflect the risk in older adults with multiple chronic conditions. OBJECTIVE To determine whether antihypertensive medication use was associated with experiencing a serious fall injury in a nationally representative sample of older adults. DESIGN, PARTICIPANTS, AND SETTING Competing risk analysis as performed with propensity score adjustment and matching in the nationally representative Medicare Current Beneficiary Survey cohort during a 3-year follow-up through 2009. Participants included 4961 community-living adults older than 70 years with hypertension. EXPOSURES Antihypertensive medication intensity based on the standardized daily dose for each antihypertensive medication class that participants used. MAIN OUTCOMES AND MEASURES Serious fall injuries, including hip and other major fractures, traumatic brain injuries, and joint dislocations, ascertained through Centers for Medicare & Medicaid Services claims. RESULTS Of the 4961 participants, 14.1% received no antihypertensive medications; 54.6% were in the moderate-intensity and 31.3% in the high-intensity antihypertensive groups. During follow-up, 446 participants (9.0%) experienced serious fall injuries, and 837 (16.9%) died. The adjusted hazard ratios for serious fall injury were 1.40 (95% CI, 1.03-1.90) in the moderate-intensity and 1.28 (95% CI, 0.91-1.80) in the high-intensity antihypertensive groups compared with nonusers. Although the difference in adjusted hazard ratios across the groups did not reach statistical significance, results were similar in the propensity score–matched subcohort. Among 503 participants with a previous fall injury, the adjusted hazard ratios were 2.17 (95% CI, 0.98-4.80) for the moderate-intensity and 2.31 (95% CI, 1.01-5.29) for the high-intensity antihypertensive groups. CONCLUSIONS AND RELEVANCE Antihypertensive medications were associated with an increased risk of serious fall injuries, particularly among those with previous fall injuries. The potential harms vs benefits of antihypertensive medications should be weighed in deciding to continue treatment with antihypertensive medications in older adults with multiple chronic conditions.
The emergence of COVID-19 in South Korea, and the public and private sector response to it, serves as a valuable case study for countries facing similar outbreaks. This article focuses on how Korean ...health officials implemented drive-through and walk-through diagnostic testing, and extensive movement and contact tracing, to identify and inform exposed members of the public. Mobile applications from both government agencies and private developers played an important role in guiding people to testing centers, communicating movement trajectories of confirmed cases on digital maps, and tracking the health and movements of travelers and others at risk of exposure. This case study illustrates the importance of rapid adaptation of transportation infrastructure and location-based information technology to respond to public health crises, and how governments can learn from experimentation and past experience to accelerate these responses.
We study the issue of polarization in society through a model of opinion formation. We say an opinion formation process is polarizing if it results in increased divergence of opinions. Empirical ...studies have shown that homophily, i.e., greater interaction between like-minded individuals, results in polarization. However, we show that DeGroot’s well-known model of opinion formation based on repeated averaging can never be polarizing, even if individuals are arbitrarily homophilous. We generalize DeGroot’s model to account for a phenomenon well known in social psychology as biased assimilation: When presented with mixed or inconclusive evidence on a complex issue, individuals draw undue support for their initial position, thereby arriving at a more extreme opinion. We show that in a simple model of homophilous networks, our biased opinion formation process results in polarization if individuals are sufficiently biased. In other words, homophily alone, without biased assimilation, is not sufficient to polarize society. Quite interestingly, biased assimilation also provides a framework to analyze the polarizing effect of Internet-based recommender systems that show us personalized content.
Throughout the 5000-year history of China, more than 300 epidemics were recorded. Traditional Chinese herbal medicine (TCM) has been used effectively to combat each of these epidemics’ infections, ...and saved many lives. To date, there are hundreds of herbal TCM formulae developed for the purpose of prevention and treatment during epidemic infections. When COVID-19 ravaged the Wuhan district in China in early January 2020, without a deep understanding about the nature of COVID-19, patients admitted to the TCM Hospital in Wuhan were immediately treated with TCM and reported later with >90% efficacy.
We conducted conduct a systematic survey of various TCM herbal preparations used in Wuhan and to review their efficacy, according to the published clinical data; and, secondly, to find the most popular herbs used in these preparations and look into the opportunity of future research in the isolation and identification of bioactive natural products for fighting COVID-19.
Although bioactive natural products in these herbal preparations may have direct antiviral activities, TCM employed for fighting epidemic infections was primarily based on the TCM theory of restoring the balance of the human immune system, thereby defeating the viral infection indirectly. In addition, certain TCM teachings relevant to the meridian system deserve better attention. For instance, many TCM herbal preparations target the lung meridian, which connects the lung and large intestine. This interconnection between the lung, including the upper respiratory system, and the intestine, may explain why certain TCM formulae showed excellent relief of lung congestion and diarrhea, two characteristics of COVID-19 infection.
There is good reason for us to learn from ancient wisdom and accumulated clinical experience, in combination with cutting edge science and technologies, to fight with the devastating COVID-19 pandemic now and emerging new coronaviruses in the future.
We consider nonparametric identification and estimation in a nonseparable model where a continuous regressor of interest is a known, deterministic, but kinked function of an observed assignment ...variable. We characterize a broad class of models in which a sharp "Regression Kink Design" (RKD or RK Design) identifies a readily interpretable treatment-on-the-treated parameter (Florens, Heckman, Meghir, and Vytlaèil (2008)). We also introduce a "fuzzy regression kink design" generalization that allows for omitted variables in the assignment rule, noncompliance, and certain types of measurement errors in the observed values of the assignment variable and the policy variable. Our identifying assumptions give rise to testable restrictions on the distributions of the assignment variable and predetermined covariates around the kink point, similar to the restrictions delivered by Lee (2008) for the regression discontinuity design. Using a kink in the unemployment benefit formula, we apply a fuzzy RKD to empirically estimate the effect of benefit rates on unemployment durations in Austria.