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Sibling Rivalry among Paralogs Promotes Evolution of the Human Brain

Geneticists have long sought to identify the genetic changes that made us human, but pinpointing the functionally relevant changes has been challenging. Two papers in this issue suggest that partial duplication of SRGAP2, producing an incomplete protein that antagonizes the original, contributed to human brain evolution

Analysis of network-wide transit passenger flows based on principal component analysis

<p>Transit networks are complex systems in which the passenger flow dynamics are difficult to capture and understand. While there is a growing ability to monitor and record travelers' behavior in the past decade, knowledge on network-wide passenger flows, which are essentially high-dimensional multivariate data, is still limited. This paper describes how Principal Component Analysis (PCA) can be leveraged to develop insight into such multivariate time series transformed from raw individual tapping records of smart card data. With a one-month data set of the Shenzhen metro system used in this study, it is shown that a great amount of variance contained in the original data can be effectively retained in lower-dimensional sub-spaces composed of top few Principal Components (PCs). Features of such low dimensionality, PCs and temporal stability of the flow structure are further examined in detail. The results and analysis provided in this paper make a contribution to the understanding of transit flow dynamics and can benefit multiple important applications for transit systems, such as passenger flow modeling and short-term prediction.</p

Complete Solving for Explicit Evaluation of Gauss Sums in the Index 2 Case

Let $p$ be a prime number, $q=p^f$ for some positive integer $f$, $N$ be a positive integer such that $\gcd(N,p)=1$, and let \k be a primitive multiplicative character of order $N$ over finite field \fq. This paper studies the problem of explicit evaluation of Gauss sums in "\textsl{index 2 case}" (i.e. f=\f{\p(N)}{2}=[\zn:\pp], where \p(\cd) is Euler function). Firstly, the classification of the Gauss sums in index 2 case is presented. Then, the explicit evaluation of Gauss sums G(\k^\la) (1\laN-1) in index 2 case with order $N$ being general even integer (i.e. N=2^{r}\cd N_0 where $r,N_0$ are positive integers and $N_03$ is odd.) is obtained. Thus, the problem of explicit evaluation of Gauss sums in index 2 case is completely solved

Succinct Representation of Codes with Applications to Testing

Motivated by questions in property testing, we search for linear error-correcting codes that have the "single local orbit" property: i.e., they are specified by a single local constraint and its translations under the symmetry group of the code. We show that the dual of every "sparse" binary code whose coordinates are indexed by elements of F_{2^n} for prime n, and whose symmetry group includes the group of non-singular affine transformations of F_{2^n} has the single local orbit property. (A code is said to be "sparse" if it contains polynomially many codewords in its block length.) In particular this class includes the dual-BCH codes for whose duals (i.e., for BCH codes) simple bases were not known. Our result gives the first short (O(n)-bit, as opposed to the natural exp(n)-bit) description of a low-weight basis for BCH codes. The interest in the "single local orbit" property comes from the recent result of Kaufman and Sudan (STOC 2008) that shows that the duals of codes that have the single local orbit property under the affine symmetry group are locally testable. When combined with our main result, this shows that all sparse affine-invariant codes over the coordinates F_{2^n} for prime n are locally testable. If, in addition to n being prime, if 2^n-1 is also prime (i.e., 2^n-1 is a Mersenne prime), then we get that every sparse cyclic code also has the single local orbit. In particular this implies that BCH codes of Mersenne prime length are generated by a single low-weight codeword and its cyclic shifts

Novel structurally related compounds reactivate latent HIV-1 in a bcl-2-transduced primary CD4+ T cell model without inducing global T cell activation

Background: The latent reservoir of HIV-1 in resting memory CD4+ T cells is a major barrier to curing HIV-1 infection. Eradication strategies involve reactivation of this latent reservoir; however, agents that reactivate latent HIV-1 through non-specific T cell activation are toxic. Methods: Using latently infected Bcl-2-transduced primary CD4+ T cells, we screened the MicroSource Spectrum library for compounds that reactivate latent HIV-1 without global T cell activation. Based on the structures of the initial hits, we assembled 50 derivatives from commercial sources and mostly by synthesis. The doseresponse relationships of these derivatives were established in a primary cell model. Activities were confirmed with another model of latency (J-Lat). Cellular toxicity and cytokine secretion were tested using freshly isolated human CD4+ T cells. Results: We identified two classes of quinolines that reactivate latent HIV-1. Class I compounds are the Mannich adducts of 5-chloroquinolin-8-ol. Class II compounds are quinolin-8-yl carbamates. Most EC 50 values were in the 0.5 -10 mM range. HIV-1 reactivation ranged from 25% to 70% for anti-CD3+ anti-CD28 co-stimulation. All quinolin-8-ol derivatives that reactivate latent HIV-1 follow Lipinski&apos;s Rule of Five, and most follow the stricter rule of three for leads. After 48 h of treatment, none of the analogues induced detectable cytokine secretion in primary resting CD4+ T cells. Conclusions: We discovered a group of quinolin-8-ol derivatives that can induce latent HIV-1 in a primary cell model without causing global T cell activation. This work expands the number of latency-reversing agents and provides new possible scaffolds for further drug development research

Achieving a cure for HIV infection: do we have reasons to be optimistic?

The introduction of highly active antiretroviral therapy (HAART) in 1996 has transformed a lethal disease to a chronic pathology with a dramatic decrease in mortality and morbidity of AIDS-related symptoms in infected patients. However, HAART has not allowed the cure of HIV infection, the main obstacle to HIV eradication being the existence of quiescent reservoirs. Several other problems have been encountered with HAART (such as side effects, adherence to medication, emergence of resistance and cost of treatment), and these motivate the search for new ways to treat these patients. Recent advances hold promise for the ultimate cure of HIV infection, which is the topic of this review. Besides these new strategies aiming to eliminate the virus, efforts must be made to improve current HAART. We believe that the cure of HIV infection will not be attained in the short term and that a strategy based on purging the reservoirs has to be associated with an aggressive HAART strategy

Inhibition of Histone Deacetylase Activity in Human Endometrial Stromal Cells Promotes Extracellular Matrix Remodelling and Limits Embryo Invasion

Invasion of the trophoblast into the maternal decidua is regulated by both the trophoectoderm and the endometrial stroma, and entails the action of tissue remodeling enzymes. Trophoblast invasion requires the action of metalloproteinases (MMPs) to degrade extracellular matrix (ECM) proteins and in turn, decidual cells express tissue inhibitors of MMPs (TIMPs). The balance between these promoting and restraining factors is a key event for the successful outcome of pregnancy. Gene expression is post-transcriptionally regulated by histone deacetylases (HDACs) that unpacks condensed chromatin activating gene expression. In this study we analyze the effect of histone acetylation on the expression of tissue remodeling enzymes and activity of human endometrial stromal cells (hESCs) related to trophoblast invasion control. Treatment of hESCs with the HDAC inhibitor trichostatin A (TSA) increased the expression of TIMP-1 and TIMP-3 while decreased MMP-2, MMP-9 and uPA and have an inhibitory effect on trophoblast invasion. Moreover, histone acetylation is detected at the promoters of TIMP-1 and TIMP-3 genes in TSA-treated. In addition, in an in vitro decidualized hESCs model, the increase of TIMP-1 and TIMP-3 expression is associated with histone acetylation at the promoters of these genes. Our results demonstrate that histone acetylation disrupt the balance of ECM modulators provoking a restrain of trophoblast invasion. These findings are important as an epigenetic mechanism that can be used to control trophoblast invasion