Miracle-dz/UniFAR-FTUs huggingface dataset:
Genome-Wide Association Study of Prognosis in Advanced Non–Small Cell Lung Cancer Patients Receiving Platinum-Based Chemotherapy

Purpose: Genetic variation may influence chemotherapy response and overall survival in cancer patients. Experimental design: We conducted a genome-wide scan in 535 advanced-stage non–small cell lung cancer (NSCLC) patients from two independent cohorts (307 from Nanjing and 228 from Beijing). A replication was carried out on an independent cohort of 340 patients from Southeastern China followed by a second validation on 409 patients from the Massachusetts General Hospital (Boston, MA). Results: Consistent associations with NSCLC survival were identified for five single-nucleotide polymorphisms (SNP) in Chinese populations with P values ranging from 3.63 × 10−5 to 4.19 × 10−7 in the additive genetic model. The minor allele of three SNPs (rs7629386 at 3p22.1, rs969088 at 5p14.1, and rs3850370 at 14q24.3) were associated with worse NSCLC survival while 2 (rs41997 at 7q31.31 and rs12000445 at 9p21.3) were associated with better NSCLC survival. In addition, rs7629386 at 3p22.1 (CTNNB1) and rs3850370 at 14q24.3 (SNW1-ALKBH1-NRXN3) were further replicated in the Caucasian population. Conclusion: In this three-stage genome-wide association studies, we identified five SNPs as markers for survival of advanced-stage NSCLC patients treated with first-line platinum-based chemotherapy in Chinese Han populations. Two of these SNPs, rs7629386 and rs3850370, could also be markers for survival among Caucasian patients. Clin Cancer Res; 18(19); 5507–14. ©2012 AACR.
Design of Digital Tri-mode Adaptive-Output Buck–Boost Power Converter for Power-Efficient Integrated Systems

An integrated buck-boost converter with a tri-mode digital control is presented. It employs an adaptive step-up/down voltage conversion to enable a wide range of output voltage. This is beneficial to the ever-increasing electronic systems that employ dynamic voltage scaling (DVS) techniques for power-efficient operations. Three control modes are employed in the converter to operate jointly and seamlessly for performance optimization during the periods of start-up, steady state, and dynamic voltage/load transient states. To avoid latch-up problem and minimize leakage current, an automatic substrate switching circuit (ASSC) is introduced. The design was fabricated in a 0.35-¿m digital CMOS N-well process, with a die area of 1.3 mm2. It precisely regulates an adaptively adjustable power output from 0.9 to 3.0 V. The maximum efficiency is 96.5%, which is measured at 0.9-V output and 45-mW load power. The efficiency remains above 50% over the entire 800-mW power range. The converter responds to a 45-mA load step transient change within 600 ns. The DVS tracking speed is 37 ¿s/V for a 1-V step-down change and is 150 ¿s/V for a 1-V step-up change. With a line regulation of 20.4 mV/V, the converter functions robustly when the input power source frequently varies between 1.6 and 3.3 V. The ASSC consumes only 88- ¿W static power.
ADAPTIVE DIVERGENCE IN DARWIN'S RACE: HOW COEVOLUTION CAN GENERATE TRAIT DIVERSITY IN A POLLINATION SYSTEM

Understanding how reciprocal selection shapes interacting species in Darwin's coevolutionary race is a captivating pursuit in evolutionary ecology. Coevolving traits can potentially display following three patterns: (1) geographical variation in matched traits, (2) bias in trait matching, and (3) bimodal distribution of a trait in certain populations. Based on the framework of adaptive dynamics, we present an evolutionary model for a coevolving pollination system involving the long‐proboscid fly (Moegistorhynchus longirostris) and the long‐tubed iris (Lapeirousia anceps). The model successfully demonstrates that Darwin's hypothesis can lead to all three patterns if costs are involved. Geographical variation in matched traits could be driven by geographical variation in environmental factors that affect the cost rate of trait escalation. Unequal benefits derived from the interaction by the fly and the flower could potentially cause the bias in trait matching of the system. Different cost rates to trait elongation incurred by the two species and weak assortative interactions in the coevolutionary race can drive divergent selection (i.e., an evolutionary branching) that leads to the bimodal distribution of traits. Overall, the model highlights the importance of assortative interactions and the balance of costs incurred by coevolving species as factors determining the eventual phenotypic outcome of coevolutionary interactions.
Time, frequency and information domain analysis of heart period and QT variability in asymptomatic long QT syndrome type 2 patients

This study was designed to characterize in time, frequency and information domains heart period (HP) and QT interval variabilities in asymptomatic (ASYMP) long QT syndrome type 2 (LQT2) subjects. HP, approximated as the temporal distance between two consecutive R-wave peaks, and QT, approximated as the temporal distance between the R-wave peak and the T-wave offset, were automatically derived from 24h Holter recordings in 10 ASYMP LQT2 patients and 13 healthy non mutation carriers (NMC) subjects. All analyses were carried out during DAY (from 2 to 6 PM) and NIGHT (from 12 to 4 AM). Mean, variance, spectral power and complexity indices at short, medium and long time scales were assessed over HP and QT beat-to-beat series. Circadian rhythmicity was evident in both NMC and ASYMP LQT2 but ASYMP LQT2 subjects were characterized by higher HP, QT interval and HP variability during both DAY and NIGHT. In addition, multiscale complexity analysis was able to differentiate the groups by showing a higher HP complexity and a lower QT complexity at long time scales in ASYMP LQT2 during DAY. ASYMP LQT2 exhibited a different autonomic control compared to NMC and such a differentiation could be protective and assure them a lower risk profile.
Antibiotic action of pyocyanin

Biologically produced pyocyanin was purified, and the nature of its antibacterial action was determined for several bacteria. The pigment was shown to be bactericidal for all susceptible organisms. The bactericidal effect was dependent upon pyocyanin concentration and resulted in decreases in viability ranging from 1 to 8 log viable cells ml-1. The gram-positive bacteria were more susceptible as a group to the antibiotic action than were the gram-negative bacteria. All apyocyanogenic pseudomonads tested were totally resistant to the pigment, suggesting that resistance may be a characteristic of the genus. Pseudomonas aeruginosa, the producer organism, was also essentially unaffected by high concentrations of pyocyanin. Facultative anaerobes were twofold or more times resistant to the action of the pigment under fermentative conditions; however, the antibiotic action did not require oxygen since denitrifying bacteria were more susceptible during anaerobic respiration than during aerobic respiration.
Measuring Rents from Public Employment: Regression Discontinuity Evidence from Kenya

Public employees in many developing economies earn much higher wages than similar private-sector workers. These wage premia may reflect an efficient return to effort or unobserved skills, or an inefficient rent causing labor misallocation. To distinguish these explanations, we exploit the Kenyan government's algorithm for hiring eighteen-thousand new teachers in 2010 in a regression discontinuity design. Fuzzy regression discontinuity estimates yield a civil-service wage premium of over 100% (not attributable to observed or unobserved skills), but no effect on motivation, suggesting rent-sharing as the most plausible explanation for the wage premium.
A four‐to‐one association between peptide motifs: four C‐terminal domains from cholinesterase assemble with one proline‐rich attachment domain (PRAD) in the secretory pathway

The major type of acetylcholinesterase in vertebrates (AChET) is characterized by the presence of a short C‐terminal domain of 40 residues, the ‘tryptophan amphiphilic tetramerization’ (WAT) domain. The presence of this domain is not necessary for catalytic activity but is responsible for hydrophobic interactions and for the capacity of AChET subunits to form quaternary associations with anchoring proteins, thereby conditioning their functional localization. In the collagen tail of asymmetric forms, we characterized a small conserved region that is sufficient for binding an AChET tetramer, the proline‐rich attachment domain (PRAD). We show that the WAT domain alone is sufficient for association with the PRAD, and that it can attach foreign proteins (alkaline phosphatase, GFP) to a PRAD‐containing construct with a glycophosphatidylinositol anchor (GPI), and thus anchor them to the cell surface. Furthermore, we show that isolated WAT domains, or proteins containing a WAT domain, can replace individual AChET subunits in PRAD‐linked tetramers. This suggests that the four WAT domains interact with the PRAD in a similar manner. These quaternary interactions can form without intercatenary disulfide bonds. The common catalytic domains of AChE are not necessary for tetrameric assembly, although they may contribute to the stability of the tetramer.
Pharmaceuticals in the environment--a human risk?

Pharmaceuticals in the environment and their potential toxic effects are emerging research areas, which is also reflected in the drug approval regulation. This far, focus has mainly been directed toward potential effects on nature and wildlife. In this paper, human risk as a consequence of exposure via the environment has been addressed and assessed. The synthetic estrogen 17alpha-ethinylestradiol (EE2), the antibiotic phenoxymethylpenicillin (Pen V), and the antineoplastic drug cyclophosphamide (CP) were chosen as modeling substances based on criteria of receptor specificity, elevated risk for human population groups for which the pharmaceuticals are not therapeutically intended, different modes of action, and prescription frequency. Attention has been focused on emissions from the use phase and subsequent diffuse release via the sewer systems. A reasonable worst-case environmental fate and human exposure were estimated using the software EUSES on worst-case emission quantities. The results indicate a negligible human risk connected to the environmental exposure for these substances. Danish conditions have been used as the modeling area, but the results are assumed to be valid for regions with similar drug consumption profiles.
Proteome profiling of human neutrophil granule subsets, secretory vesicles, and cell membrane: correlation with transcriptome profiling of neutrophil precursors

Neutrophils are indispensable in the innate immune defense against invading microorganisms. Neutrophils contain SVs and several subsets of granules that are essential for their function. Proteins present in neutrophil SVs and granules are synthesized during terminal granulopoiesis in the bone marrow. The heterogeneity of granules, as determined by marker proteins characteristic of each granule subset, is thought to result from differences in the biosynthetic windows of major classes of granule proteins, a process referred to as targeting by timing. Qualitative proteomic analysis of neutrophil granules, SVs, and plasma membrane has been performed before. Here, we performed subcellular fractionation on freshly isolated human neutrophils by nitrogen cavitation and density centrifugation on a four‐layer Percoll gradient. Granule subsets were pooled and subjected to SDS‐PAGE, and gel pieces were in‐gel‐digested with trypsin. The resulting peptides were analyzed using LTQ Orbitrap XL tandem MS. A total of 1292 unique proteins were identified and grouped, according to the neutrophil fraction, in which they displayed maximal expression. In addition to various known neutrophil proteins, several uncharacterized proteins were found, as well as proteins not described previously in neutrophils. To study the correlation between mRNA expression in neutrophil precursors and the localization of their cognate proteins, the distribution of 126 identified proteins was compared with their mRNA expression profiles. The neutrophil subcellular proteome profiles presented here may be used as a database in combination with the mRNA array database to predict and test the presence and localization of proteins in neutrophil granules and membranes.
Genetic mapping indicates that VP4 is the rotavirus cell attachment protein in vitro and in vivo

To identify the rotavirus protein which mediates attachment to cells in culture, viral reassortants between the simian rotavirus strain RRV and the murine strains EHP and EW or between the simian strain SA-11 and the human strain DS-1 were isolated. These parental strains differ in the requirement for sialic acid to bind and infect cells in culture. Infectivity and binding assays with the parental and reassortant rotaviruses indicate that gene 4 encodes the rotavirus protein which mediates attachment to cells in culture for both sialic acid-dependent and -independent strains. Using ligated intestinal segments of newborn mice and reassortants obtained between the murine strain EW and RRV, we developed an in vivo infectivity assay. In this system, the infectivity of EW was not affected by prior treatment of the enterocytes with neuraminidase, while neuraminidase treatment reduced the infectivity of a reassortant carrying gene 4 from RRV on an EW background more than 80% relative to the controls. Thus, VP4 appears to function as the cell attachment protein in vivo as well as in vitro.
Constrained Autoregressive (CAR) Model

In this paper, we propose a novel autoregressive (AR), constrained autoregressive (CAR) model for various signal modeling applications. CAR model is based on constraining one of the model parameters of the autoregressive model. This helps obtain a modified or desired AR spectrum for the signal. Constraining different AR parameters or changing the values of a particular parameter results in dissimilar AR spectrum for the signal. The value of this constrained parameter can be used for externally controlling the gain or improving the spectral resolution between two peaks in the spectrum. In this work, a0 parameter is constrained and different values are assigned for this coefficient. This changes the spectral gain. This CAR model is tested for applications such as pitch detection in a speech signal and detection of QRS complex in an electrocardiogram (ECG) signal. A higher gain CAR error filter improves the efficiency of the pitch detection algorithms or QRS complex detection.
Asymmetric trends in seasonal temperature variability in instrumental records from ten stations in Switzerland, Germany and the UK from 1864 to 2012

While the rise in global mean temperature over the past several decades is now widely acknowledged, the issue as to whether and to what extent temperature variability is changing continues to undergo debate. Here, variability refers to the spread of the temperature distribution. Much attention has been given to the effects that changes in mean temperature have on extremes, but these changes are accompanied by changes in variability, and it is actually the two together, in addition to all aspects of a changing climate pattern, that influence extremes. Since extremes have some of the largest impacts on society and ecology, changing temperature variability must be considered in tandem with a gradually increasing temperature mean. Previous studies of trends in temperature variability have produced conflicting results. Here we investigated ten long‐term instrumental records in Europe of minimum, mean and maximum temperatures, looking for trends in seasonal, annual and decadal measures of variability (standard deviation and various quantile ranges) as well as asymmetries in the trends of extreme versus mean temperatures via quantile regression. We found consistent and accelerating mean warming during 1864–2012. In the last 40 years (1973–2012) trends for Tmax were higher than for Tmin, reaching up to 0.8 °C per 10a in spring. On the other hand, variability trends were not as uniform: significant changes occurred in opposing directions depending on the season, as well as when comparing 1864–2012 trends to those of 1973–2012. Moreover, if variability changed, then it changed asymmetrically, that is only in the part above or below the median. Consequently, trends in the extreme high and low quantiles differed. Regional differences indicated that in winter, high‐alpine stations had increasing variability trends for Tmax especially at the upper tail compared to no changes or decreasing variability at low altitude stations. In contrast, summer variability increased at all stations studied.
Evaluation of triage decisions for intensive care admission.

OBJECTIVE To assess physician decision-making in triage for intensive care and how judgments impact on patient survival. DESIGN Prospective, descriptive study. SETTING General intensive care unit, university medical center. INTERVENTIONS All patients triaged for admission to a general intensive care unit were studied. Information was collected for the patient's age, diagnoses, surgical status, admission purpose, Acute Physiology and Chronic Health Evaluation (APACHE) II score, and mortality. The number of available beds at the time of triage and reasons for refused admission were obtained. MEASUREMENTS AND MAIN RESULTS Of 382 patients, 290 were admitted, 92 (24%) were refused admission, and 31 were admitted at a later time. Differences between admission diagnoses were found between patients admitted or not admitted (p < .001). Patients refused admission had higher APACHE II scores (15.6+/-1.5 admitted later and 15.8+/-1.4 never admitted) than did admitted patients (12.1+/-.4; p < .001). The frequency of admitting patients decreased when the intensive care unit was full (p < .001). Multivariate analysis revealed that triage to intensive care correlated with age, a full unit, surgical status, and diagnoses. Hospital mortality was lower in admitted (14%) than in refused patients (36% admitted later and 46% never admitted; p < .01) and in admitted patients with APACHE II scores of 11 to 20 (p = .02). The 28-day survival of patients was greater for admitted patients compared with patients never admitted (p = .01). CONCLUSIONS Physicians triage patients to intensive care based on the number of beds available, the admission diagnosis, severity of disease, age, and operative status. Admitting patients to intensive care is associated with a lower mortality rate, especially in patients with APACHE scores of 11 to 20.
LARGE ALPHABET CODING AND PREDICTION THROUGH POISSONIZATION AND TILTING

This paper introduces a convenient strategy for compression and prediction of sequences of independent, identically distributed random variables generated from a large alphabet of size m . In particular, the size of the sample is allowed to be variable. The employment of a Poisson model and tilting method simpliﬁes the implementation and analysis through independence. The resulting strategy is optimal within the class of distributions satisfying a moment condition, and is close to optimal for a smaller class – the class of distributions with an analogous condition on the counts. Moreover, the method can be used to code and predict sequences in a subset with the tail counts satisfying a given condition, and it can also be applied to envelope classes.
Truncating mutation of the DFNB59 gene causes cochlear hearing impairment and central vestibular dysfunction

We have identified a consanguineous family from Morocco segregating autosomal recessive congenital progressive hearing loss (ARNSHL) and retinal degeneration. Detailed clinical investigation of the six siblings revealed combined severe cone‐rod dystrophy (CORD) and severe/profound hearing impairment in two of them, while there is isolated CORD in three and nonsyndromic profound hearing loss in one. We therefore assumed a partial overlap of two nonsyndromic autosomal recessive conditions instead of a monogenic syndrome and performed genomewide linkage analysis. The disease loci were mapped to chromosome 2q31.1–2q32.1 for ARNSHL and to 2q13–2q14.1 for CORD, respectively. The retinal phenotype was shown to be due to homozygosity for a novel splice site mutation, c.2189+1G>T, in the retinitis pigmentosa gene MERTK. The ARNSHL interval comprised the DFNB59 locus. The DFNB59 gene has been identified recently, and two missense mutations (p.R183W and p.T54I) have been shown to cause auditory neuropathy in both humans and transgenic mice. Mutation screening in the DFNB59 gene in our family revealed homozygosity for a 1‐bp insertion in exon 2 (c.113_114insT), predicting a truncated protein of 47 amino acids, in all three hearing impaired subjects. This is the first description of biallelic putative loss‐of‐function of the DFNB59 gene. Detailed audiological investigation clearly indicated hair cell dysfunction and, in contrast to cases reported previously, excluded auditory neuropathy. We show that besides otoferlin (OTOF), DFNB59 is the second known gene in which mutations can result in these two distinct forms of hearing impairment. Moreover, all patients in our family with homozygosity for the DFNB59 mutation display central vestibular dysfunction. Hum Mutat 28(6), 571–577, 2007. © 2007 Wiley‐Liss, Inc.
Who Leads the Twitter Tango?

By reconsidering the complexities of the journalist–politician relationship, the study pursues the metaphor of tango introduced by Herbert J. Gans and analyses the online interplay in Twitter conversations between journalistic and political actors. Various types of conversations emerged through the quantitative analysis of the tweets, which ranged from seeking mutual affection, through monitoring–advocating connections and information sharing to unbridgeable advocacy. According to the interviewed journalistic and political actors, such tweets were shaped by their subjective considerations of boundaries in their Twitter repertoires as the principles of social media networking have not been institutionalized in either Slovenian newsrooms or parties. The results revealed that neither journalists nor politicians led the Twitter tango, but instead whether these actors engaged in Twitter conversations as either initiators or respondents. The identified boundary dynamics of the Twitter tango indicate that social media are a particular venue for the articulation of journalist–politician relationships, which in some cases are shaped by offline relations. The findings imply that in Slovenia contemporary journalism’s relation to politics is paradoxical because it is shaped by the liquidity of late-modern social communication and the compactness of an elite culture.
The Effects of Tomato Suspension Agreements on Market Price Dynamics and Farm Revenue

Since 1996 there have been several suspension agreements between the United States and Mexico that set reference prices for imported Mexican tomatoes. The 2013 suspension agreement raised the reference prices of Mexican tomatoes by 43%. This study conducts an econometric analysis to examine the effects of reference prices on the dynamics of tomato price and farm revenue. Findings indicate that the suspension agreements have resulted in significant adjustments in the U.S. and Mexican tomato prices, and that the two prices are now more interdependent under the 2013 agreement. Although the 2013 suspension agreement has boosted the prices of U.S. tomatoes, simulation analysis shows that the Mexican industry reaps most of the benefits from increased prices under the 2013 suspension agreement. The findings in this study could inform future trade negotiations.