Manifold Elastic Net: A Unified Framework for Sparse Dimension Reduction

It is difficult to find the optimal sparse solution of a manifold learning based dimensionality reduction algorithm. The lasso or the elastic net penalized manifold learning based dimensionality reduction is not directly a lasso penalized least square problem and thus the least angle regression (LARS) (Efron et al. \cite{LARS}), one of the most popular algorithms in sparse learning, cannot be applied. Therefore, most current approaches take indirect ways or have strict settings, which can be inconvenient for applications. In this paper, we proposed the manifold elastic net or MEN for short. MEN incorporates the merits of both the manifold learning based dimensionality reduction and the sparse learning based dimensionality reduction. By using a series of equivalent transformations, we show MEN is equivalent to the lasso penalized least square problem and thus LARS is adopted to obtain the optimal sparse solution of MEN. In particular, MEN has the following advantages for subsequent classification: 1) the local geometry of samples is well preserved for low dimensional data representation, 2) both the margin maximization and the classification error minimization are considered for sparse projection calculation, 3) the projection matrix of MEN improves the parsimony in computation, 4) the elastic net penalty reduces the over-fitting problem, and 5) the projection matrix of MEN can be interpreted psychologically and physiologically. Experimental evidence on face recognition over various popular datasets suggests that MEN is superior to top level dimensionality reduction algorithms.Comment: 33 pages, 12 figure

Multiple hybridization events between Drosophila simulans and Drosophila mauritiana are supported by mtDNA introgression

The study of speciation has advanced considerably in the last decades because of the increased application of molecular tools. In particular, the quantification of gene flow between recently diverged species could be addressed. Drosophila simulans and Drosophila mauritiana diverged, probably allopatrically, from a common ancestor approximately 250 000 years ago. However, these species share one mitochondrial DNA (mtDNA) haplotype indicative of a recent episode of introgression. To study the extent of gene flow between these species, we took advantage of a large sample of D. mauritiana and employed a range of different markers, i.e. nuclear and mitochondrial sequences, and microsatellites. This allowed us to detect two new mtDNA haplotypes (MAU3 and MAU4). These haplotypes diverged quite recently from haplotypes of the siII group present in cosmopolitan populations of D. simulans. The mean divergence time of the most diverged haplotype (MAU4) is approximately 127 000 years, which is more than 100 000 years before the assumed speciation time. Interestingly, we also found some evidence for gene flow at the nuclear level because an excess of putatively neutral loci shows significantly reduced differentiation between D. simulans and D. mauritiana. Our results suggest that these species are exchanging genes more frequently than previously thought

A [4Fe-4S]-Fe(CO)(CN)-L-cysteine intermediate is the first organometallic precursor in [FeFe] hydrogenase H-cluster bioassembly.

Biosynthesis of the [FeFe] hydrogenase active site (the 'H-cluster') requires the interplay of multiple proteins and small molecules. Among them, the radical S-adenosylmethionine enzyme HydG, a tyrosine lyase, has been proposed to generate a complex that contains an Fe(CO)2(CN) moiety that is eventually incorporated into the H-cluster. Here we describe the characterization of an intermediate in the HydG reaction: a [4Fe-4S][(Cys)Fe(CO)(CN)] species, 'Complex A', in which a CO, a CN- and a cysteine (Cys) molecule bind to the unique 'dangler' Fe site of the auxiliary [5Fe-4S] cluster of HydG. The identification of this intermediate-the first organometallic precursor to the H-cluster-validates the previously hypothesized HydG reaction cycle and provides a basis for elucidating the biosynthetic origin of other moieties of the H-cluster

A False Start in the Race Against Doping in Sport: Concerns With Cycling’s Biological Passport

Professional cycling has suffered from a number of doping scandals. The sport’s governing bodies have responded by implementing an aggressive new antidoping program known as the biological passport. Cycling’s biological passport marks a departure from traditional antidoping efforts, which have focused on directly detecting prohibited substances in a cyclist’s system. Instead, the biological passport tracks biological variables in a cyclist’s blood and urine over time, monitoring for fluctuations that are thought to indirectly reveal the effects of doping. Although this method of indirect detection is promising, it also raises serious legal and scientific concerns. Since its introduction, the cycling community has debated the reliability of indirect biological-passport evidence and the clarity, consistency, and transparency of its use in proving doping violations. Such uncertainty undermines the legitimacy of finding cyclists guilty of doping based on this indirect evidence alone. Antidoping authorities should address these important concerns before continuing to pursue doping sanctions against cyclists solely on the basis of their biological passports

Epidemiologic application of verbal autopsy to investigate the high occurrence of cancer along Huai River Basin, China

<p>Abstract</p> <p>Background</p> <p>In 2004, the media repeatedly reported water pollution and "cancer villages" along the Huai River in China. Due to the lack of death records for more than 30 years, a retrospective survey of causes of death using verbal autopsy was carried out to investigate cancer rates in this area.</p> <p>Methods</p> <p>An epidemiologic study was designed to compare numbers of deaths and causes of death between the study areas with water pollution and the control areas without water pollution in S County and Y District in 2005. The study areas were selected based on the distribution of the Huai River and its tributaries. Verbal autopsy was used to assist cause of death (COD) diagnoses and to verify mortality rates. The standard mortality rates (SMRs) of cancer in the study area were compared with those in the control areas. In order to verify the difference between mortality rates due to cancers in the study and the control areas, patients who reported having cancer in the survey received a second diagnosis by national and provincial oncologists with pathological and laboratory examinations. Comparisons were made to determine if differential cancer prevalence rates in the study and control areas were similar to the difference in mortality due to cancer in these study and control areas. Mortality rates of cancers in study and control areas were also compared with national statistics for the rural population of China.</p> <p>Results</p> <p>Over five years, 3,301 deaths were identified, including 1,158 cancer deaths. The annual average SMRs of cancer in the study areas of S County and Y District were 277.8/100,000 and 223.6/100,000, respectively, which is three to four times higher than those in the control areas. In addition, a total of 626 cases of cancer in the study and control areas were confirmed. The prevalence rates of cancer were 545/100,000 and 128.1/100,000 per year in the study and control areas in S County, respectively, and 440.9/100,000 and 200/100,000 per year in the study and control areas in Y District, respectively. The mortality and prevalence rates of digestive cancers were higher in the study areas than the control areas. In 2000, the SMR for cancer in rural areas nationwide was 120.9/100,000, and in study areas in S County and Y District, the excess rates of deaths were 184/100,000 and 138.8/100,000, respectively.</p> <p>Conclusions</p> <p>The death rates of digestive cancers were much higher in the study areas of S County and Y District. The patterns for between-area differences in prevalence and mortality rates of cancer were similar. Verbal autopsy is shown to be a useful tool in retrospective mortality surveys in low-resource areas with limited access to health care.</p

The influence of the accessory genome on bacterial pathogen evolution

Bacterial pathogens exhibit significant variation in their genomic content of virulence factors. This reflects the abundance of strategies pathogens evolved to infect host organisms by suppressing host immunity. Molecular arms-races have been a strong driving force for the evolution of pathogenicity, with pathogens often encoding overlapping or redundant functions, such as type III protein secretion effectors and hosts encoding ever more sophisticated immune systems. The pathogens’ frequent exposure to other microbes, either in their host or in the environment, provides opportunities for the acquisition or interchange of mobile genetic elements. These DNA elements accessorise the core genome and can play major roles in shaping genome structure and altering the complement of virulence factors. Here, we review the different mobile genetic elements focusing on the more recent discoveries and highlighting their role in shaping bacterial pathogen evolution

Empirical Evidence for Son-Killing X Chromosomes and the Operation of SA-Zygotic Drive

Diploid organisms have two copies of all genes, but only one is carried by each haploid gamete and diploid offspring. This causes a fundamental genetic conflict over transmission rate between alternative alleles. Single genes, or gene clusters, only rarely code for the complex phenotypes needed to give them a transmission advantage (drive phenotype). However, all genes on a male's X and Y chromosomes co-segregate, allowing different sex-linked genes to code for different parts of the drive phenotype. Correspondingly, the well-characterized phenomenon of male gametic drive, occurring during haploid gametogenesis, is especially common on sex chromosomes. The new theory of sexually antagonistic zygotic drive of the sex chromosomes (SA-zygotic drive) extends the logic of gametic drive into the diploid phase of the lifecycle, whenever there is competition among siblings or harmful sib-sib mating. The X and Y are predicted to gain a transmission advantage by harming offspring of the sex that does not carry them.Here we analyzed a mutant X-chromosome in Drosophila simulans that produced an excess of daughters when transmitted from males. We developed a series of tests to differentiate between gametic and SA-zygotic drive, and provide multiple lines of evidence that SA-zygotic drive is responsible for the sex ratio bias. Driving sires produce about 50% more surviving daughters than sons.Sex-ratio distortion due to genetic conflict has evolved via gametic drive and maternally transmitted endosymbionts. Our data indicate that sex chromosomes can also drive by harming the non-carrier sex of offspring

Apolipoprotein M Gene (APOM) Polymorphism Modifies Metabolic and Disease Traits in Type 2 Diabetes

This study aimed at substantiating the associations of the apolipoproein M gene (APOM) with type 2 diabetes (T2D) as well as with metabolic traits in Hong Kong Chinese. In addition, APOM gene function was further characterized to elucidate its activity in cholesterol metabolism. Seventeen APOM SNPs documented in the NCBI database were genotyped. Five SNPs were confirmed in our study cohort of 1234 T2D and 606 control participants. Three of the five SNPs rs707921(C+1871A), rs707922(G+1837T) and rs805264(G+203A) were in linkage disequilibrium (LD). We chose rs707922 to tag this LD region for down stream association analyses and characterized the function of this SNP at molecular level. No association between APOM and T2D susceptibility was detected in our Hong Kong Chinese cohort. Interestingly, the C allele of rs805297 was significantly associated with T2D duration of longer than 10 years (OR = 1.245, p = 0.015). The rs707922 TT genotype was significantly associated with elevated plasma total- and LDL- cholesterol levels (p = 0.006 and p = 0.009, respectively) in T2D patients. Molecular analyses of rs707922 lead to the discoveries of a novel transcript APOM5 as well as the cryptic nature of exon 5 of the gene. Ectopic expression of APOM5 transcript confirmed rs707922 allele-dependent activity of the transcript in modifying cholesterol homeostasis in vitro. In conclusion, the results here did not support APOM as a T2D susceptibility gene in Hong Kong Chinese. However, in T2D patients, a subset of APOM SNPs was associated with disease duration and metabolic traits. Further molecular analysis proved the functional activity of rs707922 in APOM expression and in regulation of cellular cholesterol content

A Simple and Sensitive Method for Measuring Tumor-Specific T Cell Cytotoxicity

A simple and sensitive method to quantitatively measure the cytolytic effect of tumor-specific T killer cells is highly desirable for basic and clinical studies. Chromium (51Cr) release assay has been the “gold standard” for quantifying cytolytic activities of cytotoxic T lymphocytes (CTLs) against target cells and this method is still being used in many laboratories. However, a major drawback of this method is the use of radioactive materials, which is inconvenient to handle because of environmental safety concerns and expensive due to the short half-life of the isotope. Consequently, several nonradioactive methods have been reported recently. Here we report a new method that we recently developed for quantifying antigen-specific cytolytic activity of CTLs. This method fully exploits the high sensitivity and the relative simplicity of luciferase quantitative assay. We initially expected the released luciferase in the supernatant to be the adequate source for monitoring cell death. However, to our total surprise, incubation of these killer T cells with the tumor cell targets did not result in significant release of luciferase in the culture medium. Instead, we found that the remaining luciferase inside the cells could accurately reflect the overall cell viability