Miracle-dz/UniFAR-FTUs huggingface dataset:
Survival superiority of females with melanoma.

We read with interest the article by Stidham et al 1 in which they claim to have demonstrated a female superiority in survival from melanoma, particularly because they had previously failed to do so. 2 The Sydney Melanoma Unit has had a continuing interest in this question for many years but this article failed to convince us of such a superiority for three important reasons. First, no attempt was made to group patients according to pathologic stage of disease at first presentation—the factor that is indisputably the most dominant predictor of survival from melanoma. Data from several major melanoma centers worldwide (including Duke University Medical Center in Durham, NC) show a preponderance of women first presenting with stage I and II disease (AJCC/UICC pathologic pTNM system) and a preponderance of men first presenting with stage III disease. 2 Because women have less advanced disease at first presentation, this obviously bestows
Molecular analysis of genes encoding outer surface protein C (OspC) of Borrelia burgdorferi sensu lato: relationship to ospA genotype and evidence of lateral gene exchange of ospC

It has been shown by analysis with monoclonal and polyclonal antibodies that outer surface protein C (OspC) of Borrelia burgdorferi sensu lato is highly heterogeneous. To determine if the heterogeneity has a genetic basis, the genes of 18 different B. burgdorferi sensu lato strains have been amplified by PCR, cloned, and sequenced. The ospC genes could be amplified from all strains tested, even from two strains which did not express OspC in detectable amounts. Among the 18 strains, 16 significantly different types of ospC sequences have been found. The sequence identities of the deduced amino acid sequences of different ospC genotypes range between 62 and 80% (determined without the leader peptide). The sequences range between 62 and 80% (determined without the leader peptide). The sequences correspond to one of the 13 OspC types distinguishable by analysis with monoclonal antibodies (B. Wilske, S. Jauris-Heipke, R. Lobentanzer, I. Pradel, V. Preac-Mursic, D. Roessler, E. Soutschek, and R. C. Johnson, J. Clin. Microbiol. 33:103-109, 1995) or represent additional types. Two completely new types were found, and OspC type 8 (which was found in Borrelia afzelii and Borrelia garinii) could be divided into two groups with different sequences but the same antibody pattern. Thus, strains belonging to different species or OspA serotypes were always significantly different in their ospC sequences. This was also confirmed by ospA sequence analysis. Interestingly, some strains of the same OspA serotype or genotype were very heterogeneous with respect to OspC, while others had nearly identical OspC proteins. Such groups of strains were found among B. burgdorferi sensu stricto, B. afzelii, and B. garinii strains. Cluster analysis of 5'-terminal and 3'-terminal stretches of ospC suggested recent intragenic recombination events in the ospC gene at least one B. afzelii strain. In addition, other recombination events between ancestors of strains belonging to the same or different species were evidenced by this type of analysis.
Genetic Selection for Context-Dependent Stochastic Phenotypes: Sp1 and TATA Mutations Increase Phenotypic Noise in HIV-1 Gene Expression

The sequence of a promoter within a genome does not uniquely determine gene expression levels and their variability; rather, promoter sequence can additionally interact with its location in the genome, or genomic context, to shape eukaryotic gene expression. Retroviruses, such as human immunodeficiency virus-1 (HIV), integrate their genomes into those of their host and thereby provide a biomedically-relevant model system to quantitatively explore the relationship between promoter sequence, genomic context, and noise-driven variability on viral gene expression. Using an in vitro model of the HIV Tat-mediated positive-feedback loop, we previously demonstrated that fluctuations in viral Tat-transactivating protein levels generate integration-site-dependent, stochastically-driven phenotypes, in which infected cells randomly ‘switch’ between high and low expressing states in a manner that may be related to viral latency. Here we extended this model and designed a forward genetic screen to systematically identify genetic elements in the HIV LTR promoter that modulate the fraction of genomic integrations that specify ‘Switching’ phenotypes. Our screen identified mutations in core promoter regions, including Sp1 and TATA transcription factor binding sites, which increased the Switching fraction several fold. By integrating single-cell experiments with computational modeling, we further investigated the mechanism of Switching-fraction enhancement for a selected Sp1 mutation. Our experimental observations demonstrated that the Sp1 mutation both impaired Tat-transactivated expression and also altered basal expression in the absence of Tat. Computational analysis demonstrated that the observed change in basal expression could contribute significantly to the observed increase in viral integrations that specify a Switching phenotype, provided that the selected mutation affected Tat-mediated noise amplification differentially across genomic contexts. Our study thus demonstrates a methodology to identify and characterize promoter elements that affect the distribution of stochastic phenotypes over genomic contexts, and advances our understanding of how promoter mutations may control the frequency of latent HIV infection.
Cross-sectional comparison of quality of life and illness intrusiveness in patients who are treated with nocturnal home hemodialysis versus peritoneal dialysis.

BACKGROUND AND OBJECTIVES Nocturnal home hemodialysis provides excellent biochemical and metabolic control of uremia; however, extensive training is necessary and technical barriers exist for intensive home hemodialysis compared with the relative simplicity of peritoneal dialysis. It was hypothesized that nocturnal home hemodialysis is associated with improved quality of life but higher illness intrusiveness compared with peritoneal dialysis. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS All home dialysis patients at the University Health Network were approached to complete the Kidney Disease Quality of Life-Short Form, Beck Depression Inventory, and Illness Intrusiveness Survey during February to June 2006. RESULTS Sixty-nine percent of all eligible patients completed the survey. Of the three domains derived from the Kidney Disease Quality of Life-Short Form, there was no difference in the kidney disease component summary, physical component summary, and the mental component summary between the two groups. There was a trend toward better sexual function in the nocturnal home hemodialysis group; however, nocturnal home hemodialysis patients experienced less social support than the peritoneal dialysis group. There was no difference between the nocturnal home hemodialysis and peritoneal dialysis patients with respect to the Beck Depression Index. Total illness intrusiveness score was similar between the nocturnal home hemodialysis and peritoneal dialysis patients. CONCLUSIONS This study suggests that nocturnal home hemodialysis is not perceived as a more intrusive treatment and demonstrates that patients who are on peritoneal dialysis have similar perceived symptomatic control of their kidney disease.
The Wiener Index of simply generated random trees

Asymptotics are obtained for the mean, variance, and higher moments as well as for the distribution of the Wiener index of a random tree from a simply generated family (or, equivalently, a critical Galton–Watson tree). We also establish a joint asymptotic distribution of the Wiener index and the internal path length, as well as asymptotics for the covariance and other mixed moments. The limit laws are described using functionals of a Brownian excursion. The methods include both Aldous' theory of the continuum random tree and analysis of generating functions. © 2003 Wiley Periodicals, Inc. Random Struct. Alg. , 22: 337–358, 2003
The mechanics of walking in children.

The work done at each step, during level walking at a constant average speed, to lift the centre of mass of the body, to accelerate it forward, and to increase the sum of both gravitational potential and kinetic energies, has been measured at various speeds on children of 2‐12 years of age, with the same technique used previously for adults (Cavagna, 1975; Cavagna, Thys & Zamboni, 1976). The pendulum‐like transfer between potential and kinetic energies (Cavagna et al. 1976) reaches a maximum at the speed at which the weight‐specific work to move the centre of mass a given distance is at a minimum ('optimal’ speed). This speed is about 2 X 8 km/hr at 2 years of age and increases progressively with age up to 5 km/hr at 12 years of age and in adults. The speed freely chosen during steady walking at the different ages is similar to this ‘optimal’ speed. At the ‘optimal’ speed, the time of single contact (time of swing) is in good agreement with that predicted, for the same stature, by a ballistic walking model assuming a minimum of muscular work (Mochon & McMahon, 1980). Above the ‘optimal’ speed, the recovery of mechanical energy through the potential‐kinetic energy transfer decreases. This decrease is greater the younger the subject. A reduction of this recovery implies a greater amount of work to be supplied by muscles: at 4 X 5 km/hr the weight‐specific muscular power necessary to move the centre of mass is 2 X 3 times greater in a 2‐year‐old child than in an adult.
Estimation of Saliva Cotinine Cut-Off Points for Active and Passive Smoking during Pregnancy—Polish Mother and Child Cohort (REPRO_PL)

A reliable assessment of smoking status has significant public health implications and is essential for research purposes. The aim of this study was to determine optimal saliva cotinine cut-off values for smoking during pregnancy. The analyses were based on data from 1771 women from the Polish Mother and Child Cohort. Saliva cotinine concentrations were assessed by high performance liquid chromatography coupled with tandem mass spectrometry (HPLC-ESI + MS/MS). The saliva cotinine cut-off value for active smoking was established at 10 ng/mL (sensitivity 96%, specificity 95%) and for passive smoking at 1.5 ng/mL (sensitivity 63%, specificity 71%). About 5% of the self-reported non-smoking women were classified as smokers based on the cotinine cut-off value. Significantly more younger, single, and less educated self-reported non-smokers had a cotinine concentration higher than 10 ng/mL compared to those who were older, married, and who had a university degree. Close to 30% of the non-smokers who indicated that smoking was not allowed in their home could be classified as exposed to passive smoking based on the cut-off value. The study suggests that self-reported smoking status is a valid measure of active smoking, whereas in the case of passive smoking, a combination of questionnaire data and biomarker verification may be required.
Flywheel: Google's Data Compression Proxy for the Mobile Web

Mobile devices are increasingly the dominant Internet access technology. Nevertheless, high costs, data caps, and throttling are a source of widespread frustration, and a significant barrier to adoption in emerging markets. This paper presents Flywheel, an HTTP proxy service that extends the life of mobile data plans by compressing responses in-flight between origin servers and client browsers. Flywheel is integrated with the Chrome web browser and reduces the size of proxied web pages by 50% for a median user. We report measurement results from millions of users as well as experience gained during three years of operating and evolving the production service at Google.
The age prospective memory paradox within the same sample in time-based and event-based tasks

ABSTRACT The present research investigated the age prospective memory (PM) paradox by testing the performance of the same participants on laboratory and naturalistic PM tasks. Younger, middle-aged, and older adults performed three tasks (time-based, event-based with focal cue, and event-based with nonfocal cue); first in the laboratory, then in the context of their everyday lives. Additionally, the social importance of PM tasks was manipulated in the laboratory. As expected, age-dependent declines on the laboratory tasks were reversed in the naturalistic tasks. Middle-aged adults performed as well as younger adults in the laboratory and as well as the elderly outside of the laboratory. When the social importance of laboratory tasks was stressed, the performance of younger adults fell. In addition, older adults showed higher self-reported commitment to the naturalistic tasks than both younger and middle-aged adults. Findings are discussed in the context of possible explanations for the age PM paradox.
Adaptive terrain-based memetic algorithms

The Terrain-Based Memetic Algorithm (TBMA) is a diffusion MA in which the local search (LS) behavior depends on the topological distribution of memetic material over a grid (terrain). In TBMA, the spreading of meme values -- such as LS step sizes -- emulates cultural differences which often arise in sparse populations. In this paper, adaptive capabilities of TBMAs are investigated by meme diffusion: individuals are allowed to move in the terrain and/or to affect their environment, by either following more effective memes or by transmitting successful meme values to nearby cells. In this regard, four TBMA versions are proposed and evaluated on three image vector quantizer design instances. The TBMAs are compared with K-Means and a Cellular MA. The results strongly indicate that utilizing dynamically adaptive meme evolution produces the best solutions using fewer fitness evaluations for this application.
On the numerical solution of the Burgers's equation

In this paper, we consider the linear heat equation arisen from the Burgers's equation using the Hopf–Cole transformation. Discretization of this equation with respect to the space variable results in a linear system of ordinary differential equations. The solution of this system involves in computing exp(α A)y for some vector y, where A is a large special tridiagonal matrix and α is a positive real number. We give an explicit expression for computing exp(α A)y. Finally, some numerical experiments are given to show the efficiency of the method.
Specificity and Mechanism of Tetracycline Resistance in a Multiple Drug Resistant Strain of Escherichia coli

Izaki, Kazuo (University of Tokyo, Tokyo, Japan), Kan Kiuchi, and Kei Arima. Specificity and mechanism of tetracycline resistance in a multiple drug resistant strain of Escherichia coli. J. Bacteriol. 91:628–633. 1966. —A decrease in the uptake of tetracycline occurred concurrently with a rise in the level of resistance of a multiple drug resistant strain of Escherichia coli grown in the presence of tetracycline. Although the strain was also resistant to streptomycin and chloramphenicol, growth in the presence of these two antibiotics did not influence the uptake of tetracycline. The induction of resistance, or decreased uptake of tetracycline, was dependent on growth of the organism in the presence of the drug. Decreased uptake of tetracycline could not be induced in a sensitive strain of the same organism under conditions suitable for induction of the resistant strain. The decrease in accumulating power of the resistant organism cultured in the presence of tetracycline does not appear to be due to selection of a resistant strain from cultures containing both resistant and sensitive strains.
Ultrasound Guidance of Central Vein Catheterization

The multiple indications for central venous catheters (CVCs) include parenteral nutrition, intravascular depletion, access for vasoactive medications, hemodynamic monitoring, cardiopulmonary arrest, difficult peripheral intravenous (IV) access and long-term IV access for medications, such as antibiotics. While these catheters can be life saving, they are also associated with significant risks. These risks increase in association with several characteristics, including patient anatomy (eg, morbid obesity, cachexia, or local scarring from surgery or radiation treatment), patient setting (eg, patients receiving mechanical ventilation or during emergencies such as cardiac arrest) and co-morbidities (eg, bullous emphysema or coagulopathy). CVCs are placed by clinicians whose training and experience may vary greatly. The procedure takes place in a variety of hospital settings including intensive care units, emergency departments, operating rooms, preand post-anesthesia care units, hemodialysis units, cardiac catheterization units and other inpatient settings. Outpatient placement of CVCs has also become commonplace, occurring in hemodialysis centers and oncology centers providing outpatient chemotherapy. Percutaneous insertions of CVCs are usually performed by “blind” techniques that rely on anatomic landmarks – ie, palpable or visible structures with known relationships to the desired vein. For example, the infraclavicular approach to the subclavian vein requires correct localization of the clavicle reference site, suprasternal notch and sternocleidomastoid-clavicular triangle landmarks, proper positioning of the patient and operator and correct venipuncture point depth, direction and insertion angle. Analogously, the various approaches to the internal jugular vein require thorough knowledge of this vein’s course in relation to the sternocleidomastoid muscle and carotid artery. Newer technologies, such as portable ultrasound (US) devices, provide bedside imaging of the central veins during catheter placement. The advantages associated with US guided CVC placement include detection of anatomic variations and exact vessel location, avoidance of central veins with pre-existing thrombosis that may prevent successful CVC placement, and guidance of both guidewire and catheter placement after initial needle insertion. This review assesses the impact of real-time ultrasound guidance on improving the safety of CVC insertions.
TCP Hybla: a TCP enhancement for heterogeneous networks

In heterogeneous networks, TCP connections that incorporate a terrestrial or satellite radio link are greatly disadvantaged with respect to entirely wired connections, because of their longer round trip times (RTTs). To cope with this problem, a new TCP proposal, the TCP Hybla, is presented and discussed in the paper. It stems from an analytical evaluation of the congestion window dynamics in the TCP standard versions (Tahoe, Reno, NewReno), which suggests the necessary modifications to remove the performance dependence on RTT. TCP Hybla performance is firstly evaluated in the case of an ideal channel, with good correlation between analytical and simulation data. Then, more realistic situations, which require the adoption of a benchmark network topology and a careful ns‐2 simulation set‐up, are examined. In particular, TCP Hybla performance is compared with that achievable by TCP standard in the presence of congestion and link losses, either separately or jointly considered. In all the examined cases, the superiority of TCP Hybla is evident, as it greatly reduces the severe penalization suffered by wireless, and especially satellite, TCP connections. Finally, it is worth noting that TCP Hybla does not infringe the end to end semantics of TCP and is compatible with other promising enhancements. Copyright © 2004 John Wiley & Sons, Ltd.
A novel flux-reversal hybrid magnet memory machine

This paper proposes a novel flux-reversal hybrid magnet memory machine (FR-HMMM), which is geometrically characterized by consequent-pole hybrid magnets mounted on the stator poles. The low-coercive-force (LCF) permanent magnets (PMs) are alternately placed between the adjacent stator slots, while the rare-earth NdFeB PMs are located on the center of stator pole. Due to the consequent pole configuration, this new topology has the advantages of reduced flux leakage and equivalent active air-gap length, as well as increased torque density compared to the conventional FR counterparts. Meanwhile, this new machine benefits from excellent flux regulation capability with negligible excitation loss since the LCF magnets can be freely magnetized or demagnetized via a current pulse supplied by dc coils wound on the LCF PMs. In addition, the existence of iron pole on the stator surface minimizes the armature demagnetization risk. The machine topology and operating principle are introduced based on the conventional FR structure. Afterwards, the simplified magnetic circuits are developed to unveil the operating principle and optimize the PM hybrid ratio. The design optimization of the proposed machine having various stator/rotor pole numbers is performed. The electromagnetic characteristics of the optimized model are compared with those of the conventional PM counterpart, which confirm the advantages of the proposed design.
Eliminating tyrosine sequence variants in CHO cell lines producing recombinant monoclonal antibodies

Amino acid sequence variants are defined as unintended amino acid sequence changes that contribute to product variation with potential impact to product safety, immunogenicity, and efficacy. Therefore, it is important to understand the propensity for sequence variant (SV) formation during the production of recombinant proteins for therapeutic use. During the development of clinical therapeutic products, several monoclonal antibodies (mAbs) produced from Chinese Hamster Ovary (CHO) cells exhibited SVs at low levels (≤3%) in multiple locations throughout the mAbs. In these examples, the cell culture process depleted tyrosine, and the tyrosine residues in the recombinant mAbs were replaced with phenylalanine or histidine. In this work, it is demonstrated that tyrosine supplementation eliminated the tyrosine SVs, while early tyrosine starvation significantly increased the SV level in all mAbs tested. Additionally, it was determined that phenylalanine is the amino acid preferentially misincorporated in the absence of tyrosine over histidine, with no other amino acid misincorporated in the absence of tyrosine, phenylalanine, and histidine. The data support that the tyrosine SVs are due to mistranslation and not DNA mutation, most likely due to tRNATyr mischarging due to the structural similarities between tyrosine and phenylalanine. Biotechnol. Bioeng. 2013; 110: 1087–1097. © 2012 Wiley Periodicals, Inc.
On the effective depth of viral sequence data

Abstract Genome sequence data are of great value in describing evolutionary processes in viral populations. However, in such studies, the extent to which data accurately describes the viral population is a matter of importance. Multiple factors may influence the accuracy of a dataset, including the quantity and nature of the sample collected, and the subsequent steps in viral processing. To investigate this phenomenon, we sequenced replica datasets spanning a range of viruses, and in which the point at which samples were split was different in each case, from a dataset in which independent samples were collected from a single patient to another in which all processing steps up to sequencing were applied to a single sample before splitting the sample and sequencing each replicate. We conclude that neither a high read depth nor a high template number in a sample guarantee the precision of a dataset. Measures of consistency calculated from within a single biological sample may also be insufficient; distortion of the composition of a population by the experimental procedure or genuine within-host diversity between samples may each affect the results. Where it is possible, data from replicate samples should be collected to validate the consistency of short-read sequence data.