Miracle-dz/UniFAR-FTUs huggingface dataset:
A phase II study of the MDR inhibitor biricodar (INCEL, VX-710) and paclitaxel in women with advanced ovarian cancer refractory to paclitaxel therapy.

PURPOSE Incel (biricodar, VX-710) restores drug sensitivity to P-glycoprotein (MDR1) and multidrug-resistance-associated protein (MRP1) expressing cells. This phase II study evaluated the safety/tolerability, pharmacokinetics, and efficacy of VX-710 plus paclitaxel in women with advanced ovarian cancer refractory to prior paclitaxel therapy. EXPERIMENTAL DESIGN Eligible patients had paclitaxel-refractory disease defined as progressive disease after a minimum of two cycles of paclitaxel (weekly or 3-week schedule) or relapsed disease within 4 months of prior paclitaxel therapy. Patients received 80 mg/m(2) paclitaxel over 3 h starting 4 h after initiation of a 24-h continuous intravenous infusion of 120 mg/m(2)/h VX-710. Cycles were repeated every 3 weeks. RESULTS Fifty patients received treatment and 45 were evaluable for response. VX-710 + paclitaxel therapy was generally well tolerated. Myelosuppression was the principal toxicity, with a median Cycle 1 nadir absolute neutrophil count of 0.27 x 10(9) cells/L and a 47% overall incidence of Grade 4 neutropenia. Mild to moderate peripheral neuritis or neuropathy was the primary nonhematologic toxicity, affecting 62% of patients. Other nonhematologic toxicities were generally mild to moderate and reversible. Paclitaxel area under the concentration-versus-time curve (AUC) (16 +/- 5.3 microg x h/mL) during the first treatment cycle was comparable to standard 175 mg/m(2) paclitaxel administered over 3 h. Of the 3 patients who achieved partial responses, 2 had progressed during prior paclitaxel therapy. Twelve patients maintained stable disease and 14/45 (31%) of patients had CA-125 reductions of 50-90% for up to 24 weeks. The median time-to-disease progression was 10 weeks for the intent-to-treat population and 20.7 weeks for the CA-125 responders. CONCLUSIONS The results suggest that VX-710 with paclitaxel has modest activity in paclitaxel-resistant ovarian cancer. Further research is warranted in less heavily treated patients.
Loneliness and depression in independent living retirement communities: risk and resilience factors

Socio-emotional selectivity theory posits that as individuals age, they desire less social stimulation and novelty, and tend to select close, reliable relationships to meet their emotional needs. Residence in congregate facilities affords social exposure, yet does not guarantee access to close relationships, so that loneliness may be a result. Further, the gerontology literature has suggested that loneliness in late life may be a risk factor for serious mental health concerns such as depression. This article examined data on loneliness and depressive symptoms from older adults aged 60–98, residing in two age-segregated independent living facilities. Overlap between those scoring in the depressed range on the Geriatric Depression Scale and those scoring more than one standard deviation above the mean on the UCLA Loneliness Scale was less than 50%, although zero-order correlation of the two continuous scores was moderately high. Potential risk and resilience factors were regressed on the continuous scores of the two scales in separate hierarchical multiple regression analyses. Depression was predicted by being older, number of chronic health conditions, grieving a recent loss, fewer neighbor visitors, less participation in organized social activities and less church attendance. Grieving a recent loss, receiving fewer visits from friends, and having a less extensive social network predicted loneliness. In addition, loneliness scores explained about 8% of the unique variance in depression scores, suggesting it is an independent risk factor for depressive symptoms. Loneliness scores were seen to be more widely dispersed in these respondents, with less variance explained by the available predictors. Suggestions are made for addressing loneliness in older adults as a means of preventing more serious mental health consequences.
A Low-Power and Area-Efficient 14-bit SAR ADC with Hybrid CDAC for Array Sensors

This paper proposes a low-power and area efficient 14-bit Successive Approximation Register (SAR) analog-to-digital converter (ADC) for array sensors. A hybrid capacitor digital-to-analog converter (CDAC), which consist of a 10-bit split CDAC and a 5-bit serial CDAC, is utilized to increase the area efficiency. The total required number of unit capacitors are only 52. A foreground digital calibration is employed to compensate the linearity error caused by the capacitor mismatch and bridge parasitic capacitor. The HSPICE post-layout simulation results show that the peak DNL and INL of the proposed ADC are enhanced from 1.27/-1 LSB and 17.29/-16.24 LSB to 0.74/-0.49 LSB and 1.27/-0.54 LSB, respectively. And ENOB is improved from 9.82bit to 13.65 bit at 48.14-KHz input after calibration. With a power consumption of 59 µW, the FOM is 45.42 fJ/step. The CDAC occupies an active area of 15 × 800 µm2 and the area efficiency ADC core is only 0.934 µm2/code.
LPI Radar detection: SNR performances for a dual channel Cross-Correlation based ESM Receiver

Detection of Low Probability of Intercept (LPI) Radar signal is an important issue for an Electronic Support Measure (ESM) Receiver. In the present work a LPI Radar signal is assumed to be phase modulated by a code. The ESM Receiver does not have any knowledge of the modulating code and carrier frequency of the LPI Radar signal, it can only make general assumptions about the occupied bandwidth. The lack of knowledge of the modulating code strongly constrains the maximum obtainable Signal to Noise Ratio (SNR) by a typical ESM Receiver. This paper presents a Receiver architecture which allows an improvement of the achievable SNR: the proposed architecture combines in an optimized way a Uniform Filter Bank with the Cross-Correlation technique: the idea is to use coherent processing on both channels of a Dual Receiver and then integrate the cross product in order to recover all the energy of the LPI signal. However, since the same signal received is used to demodulate itself, nonlinear effects arise and the resultant SNR has to be elaborated. Theoretical SNR performances, derived for a generic case, will be compared with simulations carried out with realistic phase modulated LPI signals. Measurements done on new generation Elettronica SpA (ELT) Digital Receiver based ESM shall be finally compared with both theoretical and simulation results.
Successful use of cuffed central venous hemodialysis catheters inserted percutaneously.

Although endogenous fistulae and grafts are preferred for permanent hemodialysis access, central venous catheters are often required for varying intervals when creating permanent access is not feasible. The prospective experience with 118 catheters in over a 3.5-yr period is reported; 93 (79%) were placed by percutaneous techniques, and 25 (21%) were placed by operative techniques. Seventy seven catheters (65%) were placed in the subclavian vein, 36 (31%) were placed in the internal jugular vein (usually right side), and 5 (4%) were placed in the femoral vein. Early postplacement complications were infrequent. Catheter function at last local follow-up ranged from several days to nearly 2 yr, averaging approximately 3 mo, even though many patients returned to their referring centers with a functioning catheter after only a short follow-up. Actuarial survival for percutaneously placed catheters was approximately 60% at 6 mo and 30% at 12 mo. Catheter failure occurred in 36% of cases, equally divided between malfunction (thrombosis refractory to fibrinolysis, extrusion, kinking, or related event) and infection with septicemia requiring removal. Such failure was not more frequent after percutaneous placement than after operative placement. Failure due to mechanical malfunction, but not that due to infection, tended to be less frequent among catheters placed in the internal jugular vein than among catheters placed in the subclavian vein. Finally, infection with septicemia involved 22% of all catheters and occurred at an average cumulated rate of approximately one infection per patient-year. Coagulase-positive staphylococcus was the most common organism isolated. (ABSTRACT TRUNCATED AT 250 WORDS)
Work-life transitions for young, coastal adults: a qualitative follow-up study

The transition from education to the world of work has changed significantly for most young people in recent years. Social and economic changes have impacted the process, particularly for youth in small communities. Much career development research has identified the needs of urban youth; however, the needs of young people living in rural areas have largely been omitted. This qualitative study illuminated the work-life transitions of nine adults from a small, coastal community on northern Vancouver Island. Elicited through semi-structured interviews, a variety of living and work pathways were identified. Participants described supportive families, community involvement, passions for their surrounding environment, and positive future outlooks; in addition to struggling with frequent moving, economic hardship, and changes in employment and career aspirations. The results have important implications for research and policy regarding education and work planning.
Mercaptide formed between the residue Cys70 and Hg2+ or Co2+ behaves as a functional positively charged side chain operative in the Arg70-->Cys mutant of the metal-tetracycline/H+ antiporter of Escherichia coli.

The bacterial tetracycline/H+ antiporter (TetA) mediates active efflux of a chelation complex of tetracycline with a divalent cation such as Mg2+, Co2+, or Mn2+ [Yamaguchi, A. , Udagawa, T. , & Sawai, T. (1990a) J. Biol. Chem. 265, 4809-4813]. The positive charge of Arg70 in the antiporter is important for the transport function [Yamaguchi, A. , Someya, Y. , & Sawai, T. (1992c) J. Biol. Chem. 267, 19155-19162]. Out of six site-directed mutants of Arg70, only the Lys70 mutant retained moderate transport activity, whereas the Ser70, Ala70, Trp70, Leu70, and Asp70 mutants had no or extremely low transport activity. In this study, we constructed the Cys70 mutant and found that the Cys70 mutant showed, unexpectedly, a significant activity comparable to that of the Lys70 mutant in the presence of Co2+ ions, whereas it showed very low activity as well as the Ala70 mutant in the presence of Mg2+ or Mn2+ ions. Hg2+, which is known to be a cysteine specific modifier but has no ability to form a complex with tetracycline, caused a dramatic increase in the Vmax value of Co(2+)-dependent tetracycline transport mediated by the Cys70 mutant without affecting the k(m) value, whereas activities of the wild-type and the Lys70 and Ala70 mutants were not affected by Hg2+, Hg2+ alone without Co2+ could not support the transport activity at all, because Hg2+ does not form a chelation complex with tetracycline. These observations suggest that a mercaptide formed between the SH group of Cys70 and Hg2+ or Co2+ works as a positively charged side chain like that of Arg or Lys. When the SH group of the Cys70 mutant was masked with modification by sulfhydryl reagents, the residual activity was no longer affected by Hg2+. Inversely, when the Cys70 mutant was preincubated with Hg2+, it was protected from the inactivation by sulfhydryl reagents. These observations also confirm the mercaptide formation between the Cys70 and a divalent cation as a functional side chain.
Corrosion inhibition of iron in 0.5 mol L-1 H2SO4 by halide ions

The inhibition effect of halide ions such as iodide, bromide and chloride ions on the corrosion of iron in 0.5 mol L-1 H2SO4 and the adsorption behaviour of these ions on the electrode surface have been studied by polarization and impedance methods. It has been found that the inhibition of nearly 90% has been observed for iodide ions at 2.5 ´ 10-3 mol L-1, for bromide ions at 10 ´ 10-3 mol L-1 and 80% for chloride ions at 2.5 ´ 10-3 mol L-1. The inhibition effect is increased with increase of halide ions concentration in the case of I- and Br- ions, whereas it has decreased in the case of Cl- ion at concentrations higher than 5 ´ 10-3 mol L-1. The double layer capacitance values have decreased considerably in the presence of halide ions which indicate that these anions are adsorbed on iron at the corrosion potential.
Boon Or Bane? Reassessing the Productivity of Foreign Direct Investment

We assess the effects of foreign and domestic capital on economic growth using the latest data and better models of economic growth than those previously used. We explicitly consider the role of human capital in the process of economic development. We find no evidence that foreign direct investment harms the economic prospects of developing countries. The flow of foreign capital from 1980 to 1991 spurred growth in gross domestic product per capita, while the level of foreign stock, or “foreign penetration,” had no discernible effect. Indeed, new foreign investment was more productive dollar for dollar than was capital from domestic sources. Previous suggestions that foreign investment flows are less beneficial than domestic ones were based on a misinterpretation. Moreover, foreign direct investment stimulates investment from domestic sources. Consequently, developing countries have no reason to eschew foreign capital, as dependency theorists urge.
Genetic variation at the CELF1 (CUGBP, elav‐like family member 1 gene) locus is genome‐wide associated with Alzheimer's disease and obesity

Deviations from normal body weight are observed prior to and after the onset of Alzheimer's disease (AD). Midlife obesity confers increased AD risk in later life, whereas late‐life obesity is associated with decreased AD risk. The role of underweight and weight loss for AD risk is controversial. Based on the hypothesis of shared genetic variants for both obesity and AD, we analyzed the variants identified for AD or obesity from genome‐wide association meta‐analyses of the GERAD (AD, cases = 6,688, controls = 13,685) and GIANT (body mass index [BMI] as measure of obesity, n = 123,865) consortia. Our cross‐disorder analysis of genome‐wide significant 39 obesity SNPs and 23 AD SNPs in these two large data sets revealed that: (1) The AD SNP rs10838725 (pAD = 1.1 × 10−08) at the locus CELF1 is also genome‐wide significant for obesity (pBMI = 7.35 × 10−09). (2) Four additional AD risk SNPs were nominally associated with obesity (rs17125944 at FERMT2, pBMI = 4.03 × 10−05, pBMI corr = 2.50 × 10−03; rs3851179 at PICALM; pBMI = 0.002, rs2075650 at TOMM40/APOE, pBMI = 0.024, rs3865444 at CD33, pBMI = 0.024). (3) SNPs at two of the obesity risk loci (rs4836133 downstream of ZNF608; pAD = 0.002 and at rs713586 downstream of RBJ/DNAJC27; pAD = 0.018) were nominally associated with AD risk. Additionally, among the SNPs used for confirmation in both studies the AD risk allele of rs1858973, with an AD association just below genome‐wide significance (pAD = 7.20 × 10−07), was also associated with obesity (SNP at IQCK/GPRC5B; pBMI = 5.21 × 10−06; pcorr = 3.24 × 10−04). Our first GWAS based cross‐disorder analysis for AD and obesity suggests that rs10838725 at the locus CELF1 might be relevant for both disorders. © 2014 Wiley Periodicals, Inc.
Molecular mechanisms mediating pathological plasticity in Huntington's disease and Alzheimer's disease

Neurodegenerative diseases such as Huntington's disease and Alzheimer's disease, although very different in etiology, share common degenerative processes. These include neuronal dysfunction, decreased neural connectivity, and disruption of cellular plasticity. Understanding the molecular mechanisms underlying the neural plasticity deficits in these devastating conditions may lead the way toward new therapeutic targets, both disease‐specific and more generalized, which can ameliorate degenerative cognitive deficits. Furthermore, investigations of ‘pathological plasticity’ in these diseases lend insight into normal brain function. This review will present evidence for altered plasticity in Huntington's and Alzheimer's diseases, relate these findings to symptomatology, and review possible causes and commonalities.
Qualitative Assessment of Pertussis Diagnostics in United States Laboratories

Background: United States national surveillance data show that the use of culture for pertussis diagnostics has sharply declined, whereas polymerase chain reaction (PCR) is now the most common testing method. PCR testing for pertussis is rapid and sensitive, but the lack of standardization and variable specificity is concerning. Methods: A web-based survey containing 12 questions was sent to public health, commercial and hospital-based US laboratories performing clinical diagnostics to determine the pertussis diagnostics used. An extensive real-time PCR (RT-PCR) questionnaire accompanied a proficiency panel assessing the types of extraction methods, RT-PCR methods and current quality control in place at the laboratories. The proficiency panel of 12 specimens containing Bordetella pertussis at various concentrations and negative controls was created to detect cross-contamination and assess the lower limit of detection. Results: One hundred twenty-three (35%) of 355 respondents from the web-based survey performed diagnostic tests for the presence of B. pertussis. Eighty-three (71%) labs reported performing culture, whereas 67 (54%) labs used PCR. All 41 laboratories that consented to participate in the proficiency exercise used the IS481 RT-PCR target; however, a variety of extraction and RT-PCR methods were employed. The laboratories correctly identified 92% of the B. pertussis specimens, and 5% of the laboratories (1.8% of the panel specimens) reported at least 1 false-positive. Conclusions: The small percentage of false-positives suggests that adequate procedures are in place to prevent cross-contamination. Differing extraction and PCR methods as well as variable analytic sensitivity emphasize the necessity for an external well-defined quality control program and interlaboratory pertussis PCR harmonization.
International Financial Spillovers to Emerging Market Economies: How Important are Economic Fundamentals?

We assess the importance of economic fundamentals in the transmission of international shocks to financial markets in various emerging market economies (EMEs). Our analysis covers the so-called taper-tantrum episode of 2013 and six earlier episodes of severe EME-wide financial stress since the mid-1990s. Cross-country regressions lead us to the following results: (1) EMEs with relatively better economic fundamentals suffered less deterioration in financial markets during the 2013 taper-tantrum episode. (2) Differentiation among EMEs set in quite early and persisted throughout this episode. (3) Controlling for economic fundamentals, we also find that, during the taper tantrum, financial conditions deteriorated more in those EMEs that had earlier experienced larger private capital inflows and greater exchange rate appreciation. (4) For earlier episodes, we find little evidence of investor differentiation across EMEs being explained by differences in their relative vulnerabilities during EME crises of the 1990s and early 2000s. (5) That said, differentiation across EMEs based on fundamentals does not appear to be unique to the 2013 episode. Differences in economic fundamentals played a role in explaining the heterogeneous EME financial market responses during the global financial crisis of 2008, and the role of fundamentals appeared to progressively increase through the European crisis in 2011 and subsequently the 2013 taper tantrum.
Selective Channel Inversion Precoding for the Downlink of MIMO Wireless Systems

In this paper a novel channel inversion (CI) precoding scheme is introduced for the downlink of multiple input multiple output (MIMO) systems. The proposed technique outperforms conventional CI by exploiting some of the consequential inter-channel interference (ICI). It achieves this by applying partial channel inversion such that the constructive part of ICI is preserved and exploited while the destructive part is eliminated by means of CI precoding. By doing so, the effective signal to interference-plus-noise ratio (SINR) delivered to the mobile unit (MU) receivers is enhanced, without the need to invest in additional transmitted signal power at the MIMO base station (BS). The trade-off to this achievement is a minor increase in the complexity of the BS processing. The presented theoretical analysis and simulations show that due to the SINR enhancement, significant performance gains are offered by the proposed MIMO precoding technique compared to its conventional counterpart.
Tax Ethics and Taxpayer Attitudes: A Survey

Politically and economically, few matters are as important as the taxes people pay to their government. Justice Holmes once described taxes as a mark of the privilege of citizenship in a civilized society, but for most of us it is an unwelcomed burden to be endured. Remote and intangible governmental benefits, vast as they may be, are less likely to be appreciated than the immediate benefits individuals receive for their money in the private market. The issue of the tyranny of taxation without representation provided a significant momentum for the political movement which led to the Declaration of Independence and subsequent formation of the union. The revoluntionaries of the day, with diverse regional, economic, and political backgrounds, were united in their opposition to the new taxes which the British Parliament attempted to impose on the colonies. Two hundred years of population growth accompanied by industrialization, urbanization, and wars have produced crushing tax burdens at a time when the nation and its people are suffering from both high unemployment and high inflation. Randy Hamilton, past president of the American Society for Public Administration, warned the Society's members that as the nation's tax burden approaches 35 per cent of the Gross National Product, the United States should anticipate the same sort of massive taxpayer revolt now being experienced in certain European countries. ' The complexities of the tax laws, which leave even the better educated taxpayer confused and bewildered, have added insult to injury. Economists have long been exploring various economic aspects of taxation, including tolerable and maximum levels of taxation; its effects on price stability, economic growth, and unemployment; and the distribution of tax burdens among various groups of taxpayers. This study, on the other hand, is an attempt to explore the tax attitudes of the people who pay taxes to government-directly or indirectly, knowingly or, in some cases, unknowingly. Abstract economic analyses are undoubtedly important to an understanding of tax systems, but of equal importance in a democratic system is the taxpayer's perception, evaluation and compliance with the tax laws.