Miracle-dz/UniFAR-FTUs huggingface dataset:
Intracellular redox imbalance and extracellular amino acid metabolic abnormality contribute to arsenic‐induced developmental retardation in mouse preimplantation embryos

Inorganic arsenic, an environmental contaminant, is known to cause cancer, developmental retardation, and many other serious diseases. Previous researches have shown that arsenic exerts its toxicity partially through generating reactive oxygen species (ROS). However, it is still not well understood how ROS links arsenic exposure to developmental retardation of preimplantation embryo. Here we demonstrate that high‐level arsenite induces severe redox imbalance by decreasing the levels of glutathione and increasing the levels of ROS through the oxidative stress adaptor p66Shc, which induces apoptosis by activating the cytochrome c‐caspase. In addition, low‐level arsenite seriously perturbs the metabolism of extracellular amino acid, especially that of the cytotoxic and antioxidative amino acids in preimplantation embryos, may also be the reason for developmental delay. Furthermore, An antioxidant, N‐acetyl‐L‐cysteine, improves the development of arsenite‐exposed embryos by reducing intracellular ROS and adjusting amino acid metabolism, suggesting that increasing the intracellular antioxidant level may have preventive or therapeutic effects on arsenic‐induced embryonic toxicity. In conclusion, we suggest that p66Shc‐linked redox imbalance and abnormal extracellular amino acid metabolism mediate arsenite‐induced embryonic retardation. J. Cell. Physiol. 222: 444–455, 2010. © 2009 Wiley‐Liss, Inc.
The effects of HIV protease inhibitors atazanavir and lopinavir/ritonavir on insulin sensitivity in HIV-seronegative healthy adults

Background: Therapy with some HIV protease inhibitors (PI) contributes to insulin resistance and type 2 diabetes mellitus, by inhibition of insulin-sensitive glucose transporters. Atazanavir (ATV) is a new PI with substantially less in vitro effect on glucose transport than observed with other PI, including lopinavir (LPV) or ritonavir (RTV). Methods: Randomized, double-blind, crossover study of the effect of 5 days of administering ATV, lopinavir/ritonavir (LPV/r) or placebo on insulin-stimulated glucose disposal in 30 healthy HIV-negative subjects. Each subject was studied on two of three possible treatments with a wash-out period between treatments. Results: The mean insulin-stimulated glucose disposal (mg/min per kg body weight) per unit insulin (μU/ml) (M/I) was 9.88, 9.80 and 7.52 for placebo, ATV and LPV/r, respectively (SEM, 0.84 for all). There was no significant difference between ATV and placebo. The M/I for LPV/r was 23% lower than that for ATV (P = 0.010) and 24% lower than that for placebo (P = 0.008). The mean glycogen storage rates were 3.85, 4.00 and 2.54 mg/min per kg for placebo, ATV and LPV/r, respectively (SEM, 0.39 for all). There was no significant difference between ATV and placebo. The glycogen storage rate for LPV/r was 36% lower than ATV (P = 0.003) and 34% lower than placebo (P = 0.006). Conclusions: ATV given to healthy subjects for 5 days did not affect insulin sensitivity, while LPV/r induced insulin resistance. This observation is consistent with differential in vitro effects of these PI on glucose transport. Further data are needed to assess clinical implications for body composition.
Inapproximability of Minimum Vertex Cover on k-Uniform k-Partite Hypergraphs

We study the problem of computing the minimum vertex cover on $k$-uniform $k$-partite hypergraphs when the $k$-partition is given. On bipartite graphs (k=2), the minimum vertex cover can be computed in polynomial time. For $k \ge 3,$ this problem is known to be NP-hard. For general $k$, the problem was studied by Lovasz, who gave a $\frac{k}{2}$-approximation based on the standard LP relaxation. Subsequent work by Aharoni, Holzman, and Krivelevich showed a tight integrality gap of $(\frac{k}{2} - o(1))$ for the LP relaxation. We further investigate the inapproximability of minimum vertex cover on $k$-uniform $k$-partite hypergraphs and present the following results (here $\varepsilon > 0$ is an arbitrarily small constant): NP-hardness of obtaining an approximation factor of $(\frac{k}{4} - \varepsilon)$ for even $k$ and $(\frac{k}{4} - \frac{1}{4k} - \varepsilon)$ for odd $k$, NP-hardness of obtaining a nearly optimal approximation factor of $(\frac{k}{2}-1+\frac{1}{2k}-\varepsilon)$, and an optimal uniqu.
Neuroblastoma amplified sequence gene is associated with a novel short stature syndrome characterised by optic nerve atrophy and Pelger–Huët anomaly

Background Hereditary short stature syndromes are clinically and genetically heterogeneous disorders and the cause have not been fully identified. Yakuts are a population isolated in Asia; they live in the far east of the Russian Federation and have a high prevalence of hereditary short stature syndrome including 3-M syndrome. A novel short stature syndrome in Yakuts is reported here, which is characterised by autosomal recessive inheritance, severe postnatal growth retardation, facial dysmorphism with senile face, small hands and feet, normal intelligence, Pelger-Huët anomaly of leucocytes, and optic atrophy with loss of visual acuity and colour vision. This new syndrome is designated as short stature with optic atrophy and Pelger-Huët anomaly (SOPH) syndrome. Aims To identify a causative gene for SOPH syndrome. Methods Genomewide homozygosity mapping was conducted in 33 patients in 30 families. Results The disease locus was mapped to the 1.1 Mb region on chromosome 2p24.3, including the neuroblastoma amplified sequence (NBAS) gene. Subsequently, 33 of 34 patients were identified with SOPH syndrome and had a 5741G/A nucleotide substitution (resulting in the amino acid substitution R1914H) in the NBAS gene in the homozygous state. None of the 203 normal Yakuts individuals had this substitution in the homozygous state. Immunohistochemical analysis revealed that the NBAS protein is well expressed in retinal ganglion cells, epidermal skin cells, and leucocyte cytoplasm in controls as well as a patient with SOPH syndrome. Conclusion These findings suggest that function of NBAS may associate with the pathogenesis of short stature syndrome as well as optic atrophy and Pelger-Huët anomaly.
Child Anxiety Disorders: A Family-Based Treatment Manual for Practitioners

Ranging from mild and transient to severe and intractable, high levels of anxiety in children can lead to avoiding school, not participating in class, shying away from peer groups, worrying persistently, or even experiencing phobias and acute separation anxiety from parents. Despite the prevalence, effective, evidence-based therapeutic strategies for helping children overcome anxiety have been lacking, leaving psychologists, school counselors, and other child mental health professionals to rely on more generalized CBT and individual therapy approaches that don't necessarily target the problems at issue. In Child Anxiety Disorders, Wood and McLeod present a clinically-proven treatment protocol based on a collaborative, family-based intervention approach-one that has seen remission rates of 80% in children. Incorporating family therapy strategies and targeted CBT techniques, the authors lay out session-by-session guidelines for implementing the protocol, offering all those who work with and counsel children a hands-on toolkit to effectively resolve childhood anxiety, whether generalized or severe in nature. Preliminary chapters cover anxiety typologies, screening and assessment techniques, family and genetic influences, the nature of evidence-based practices, and other clinical considerations, such as pharmacotherapy. The second part of the book, the treatment manual, presents the 15-session protocol, including optional family therapy modules to strengthen family interactions, and worksheets and handouts to be used in and out of the therapy room.
MicroenvironmentNormalization of the Tumor Protective Type 1 Immunity and the Engineered to Express T-bet Promotes Intralesional Delivery of Dendritic Cells

T-bet(Tbx21),aT-boxtranscriptionfactor,hasbeenpreviouslyidentiﬁedasamasterregulatoroftype1Tcellpolarization. Wehavealso recently shown that the genetic engineering of human dendritic cells (DCs) to express human T-bet cDNAyields type 1-polarizing APCs invitro(1). Inthepresentstudy,murineCD11c + DCsweretransducedwitharecombinantadenovirusencodingfull-lengthmurineT-bets (DC.mTbets) and analyzed for their immunomodulatory functions in vitro and in vivo. Within the range of markers analyzed, DC. mTbets exhibited a control DC phenotype and were indistinguishable from control DCs in their ability to promote allogenic T cell proliferation in MLR in vitro. However, DC.mTbets were superior to control DCs in promoting Th1 and Tc1 responses in vitro via a mechanismrequiring DC–Tcell interaction orthecloseproximityofthesetwocelltypesand thatcanonlypartiallybeexplainedbythe action of DC-elaborated IL-12p70. When injected into day 7 s.c. CMS4 sarcoma lesions growing in syngenic BALB/c mice, DC.mTbets dramaticallyslowedtumorprogression(versuscontrolDCs)andextendedoverallsurvivalviaamechanismdependentonbothCD4 + and CD8 + Tcellsand,toalesserextent,asialoGM1 + NKcells.DC. mTbet-basedtherapyalsopromotedsuperiortumor-speciﬁcTc1responses inthespleensandtumor-draininglymphnodesoftreatedanimals,andwithinthetumormicroenvironmentitinhibitedtheaccumulation normalized translational DC.Tbets as a
Structural Biology and Crystallization Communications Structure of Recombinant Leishmania Donovani Pteridine Reductase Reveals a Disordered Active Site

Pteridine reductase (PTR1) is a potential target for drug development against parasitic Trypanosoma and Leishmania species, protozoa that are responsible for a range of serious diseases found in tropical and subtropical parts of the world. As part of a structure-based approach to inhibitor development, specifically targeting Leishmania species, well ordered crystals of L. donovani PTR1 were sought to support the characterization of complexes formed with inhibitors. An efficient system for recombinant protein production was prepared and the enzyme was purified and crystallized in an orthorhombic form with ammonium sulfate as the precipitant. Diffraction data were measured to 2.5 A ˚ resolution and the structure was solved by molecular replacement. However, a sulfate occupies a phosphate-binding site used by NADPH and occludes cofactor binding. The nicotinamide moiety is a critical component of the active site and without it this part of the structure is disordered. The crystal form obtained under these conditions is therefore unsuitable for the characterization of inhibitor complexes.
StatiX: making XML count

The availability of summary data for XML documents has many applications, from providing users with quick feedback about their queries, to cost-based storage design and query optimization. StatiX is a novel XML Schema-aware statistics framework that exploits the structure derived by regular expressions (which define elements in an XML Schema) to pinpoint places in the schema that are likely sources of structural skew. As we discuss below, this information can be used to build concise, yet accurate, statistical summaries for XML data. StatiX leverages standard XML technology for gathering statistics, notably XML Schema validators, and it uses histograms to summarize both the structure and values in an XML document. In this paper we describe the StatiX system. We develop algorithms that decompose schemas to obtain statistics at different granularities and discuss how statistics can be gathered as documents are validated. We also present an experimental evaluation which demonstrates the accuracy and scalability of our approach and show an application of these statistics to cost-based XML storage design.
Biohybrid surface preparation for protein/DNA microarray applications

The chemistry of slide substrates used in microarray technology is important, since it determines the spot morphology, signal intensity, low carry over and low evaporation rate. In this paper the experiments developed one substrate type - porous silicon as base for micro arrays with a gold layer film deposit on top. It was study two gold texture in order to find the best report between signal intensity and spot morphology. The experiments reveal that: (i) porous silicon substrate for both functionalization methods assure spots uniformity and a good relationship between signal intensity and solution concentration; (ii) it was observed bonds saturation for high concentrations for both types of samples.
Analysis of the HLA-restricted influenza-specific cytotoxic T lymphocyte response in transgenic mice carrying a chimeric human-mouse class I major histocompatibility complex

Transgenic murine lines have been constructed that express a chimeric class I molecule composed of the alpha 1 and alpha 2 domains of HLA- A2.1 and the alpha 3, transmembrane, and cytoplasmic domains of H-2Kb. Upon immunization with influenza virus, transgenic mice developed a strong A2.1Kb-restricted cytotoxic T lymphocyte (CTL) response specific for the same matrix protein epitope that serves as the dominant A2.1- restricted determinant in the equivalent human response. Fine specificity analysis of CTL clones using truncated peptides revealed strong similarity between the response repertoire of transgenic mice and that previously reported using influenza-specific A2.1-restricted CTL clones from humans. This suggests that even when considering T cell responses by different species, the alpha 1 and alpha 2 domains of the restriction element play a dominant role in determining the CTL specific repertoire. Thus, substituting the alpha 3 domain of A2.1 with a murine counterpart has permitted development of a transgenic strain that should serve as an excellent model system in studies of HLA- restricted responses.
Ube2g2–gp78-mediated HERP polyubiquitylation is involved in ER stress recovery

ABSTRACT A large number of studies have focused on how individual organisms respond to a stress condition, but little attention has been paid to the stress recovery process, such as the endoplasmic reticulum (ER) stress recovery. Homocysteine-induced ER protein (HERP) was originally identified as a chaperone-like protein that is strongly induced upon ER stress. Here we show that, after ER stress induction, HERP is rapidly degraded by Ube2g2–gp78-mediated ubiquitylation and proteasomal degradation. The polyubiquitylation of HERP in vitro depends on a physical interaction between the CUE domain of gp78 and the ubiquitin-like (UBL) domain of HERP, which is essential for HERP degradation in vivo during ER stress recovery. We further show that although HERP promotes cell survival under ER stress, high levels of HERP expression reduce cell viability under oxidative stress conditions, suggesting that HERP plays a dual role in cellular stress adaptation. Together, these results establish the ubiquitin–proteasome-mediated degradation of HERP as a novel mechanism that fine-tunes the stress tolerance capacity of the cell.
Antigen Receptor Proximal Signaling in Splenic B-2 Cell Subsets1

Splenic marginal zone (MZ) and follicular mantle (FO) B cells differ in their responses to stimuli in vitro and in vivo. We have previously shown that MZ cells exhibit greater calcium responses after ligation of membrane IgM (mIgM). We have now investigated the molecular mechanism underlying the difference in calcium responses following ligation of mIgM and studied the response to total B cell receptor ligation in these two subsets. We compared key cellular proteins involved in calcium signaling in MZ and FO cells. Tyrosine phosphorylation and activity of phospholipase C-γ2 and Syk protein tyrosine kinase were significantly higher in MZ cells than in FO cells after mIgM engagement, providing a likely explanation for our previous findings. Tyrosine phosphorylation of CD22 and expression of Src homology 2-containing inositol phosphatase and Src homology 2-containing protein tyrosine phosphatase-1 were also higher in the MZ cells. Expression and tyrosine phosphorylation of Btk, BLNK, Vav, or phosphatidylinositol 3-kinase were equivalent. In contrast, stimulation with anti-κ induced equivalent increases in calcium and activation of Syk in the two subsets. These signals were also equivalent in cells from IgM transgenic, JH knockout mice, which have equivalent levels of IgM in both subsets. With total spleen B cells, Btk was maximally phosphorylated at a lower concentration of anti-κ than Syk. Thus, calcium signaling in the subsets of mature B cells reflects the amount of Ig ligated more than the isotype or the subset and this correlates with the relative tyrosine phosphorylation of Syk.
Identification of a Specific Maleate Hydratase in the Direct Hydrolysis Route of the Gentisate Pathway

ABSTRACT In contrast to the well-characterized and more common maleylpyruvate isomerization route of the gentisate pathway, the direct hydrolysis route occurs rarely and remains unsolved. In Pseudomonas alcaligenes NCIMB 9867, two gene clusters, xln and hbz, were previously proposed to be involved in gentisate catabolism, and HbzF was characterized as a maleylpyruvate hydrolase converting maleylpyruvate to maleate and pyruvate. However, the complete degradation pathway of gentisate through direct hydrolysis has not been characterized. In this study, we obtained from the NCIMB culture collection a Pseudomonas alcaligenes spontaneous mutant strain that lacked the xln cluster and designated the mutant strain SponMu. The hbz cluster in strain SponMu was resequenced, revealing the correct location of the stop codon for hbzI and identifying a new gene, hbzG. HbzIJ was demonstrated to be a maleate hydratase consisting of large and small subunits, stoichiometrically converting maleate to enantiomerically pure d-malate. HbzG is a glutathione-dependent maleylpyruvate isomerase, indicating the possible presence of two alternative pathways of maleylpyruvate catabolism. However, the hbzF-disrupted mutant could still grow on gentisate, while disruption of hbzG prevented this ability, indicating that the direct hydrolysis route was not a complete pathway in strain SponMu. Subsequently, a d-malate dehydrogenase gene was introduced into the hbzG-disrupted mutant, and the engineered strain was able to grow on gentisate via the direct hydrolysis route. This fills a gap in our understanding of the direct hydrolysis route of the gentisate pathway and provides an explanation for the high yield of d-malate from maleate by this d-malate dehydrogenase-deficient natural mutant.
Temperature‐dependent modeling and performance analysis of coupled MLGNR interconnects

The temperature‐dependent circuit modeling and performance in terms of propagation delay, power dissipation, and crosstalk‐induced voltage waveform at the far end of victim line of multilayer graphene nanoribbon (MLGNR) interconnects have been analyzed at 22 nm technology node. A comparative performance analysis between MLGNR interconnects with resistance estimated using temperature‐dependent model and temperature‐independent model is examined. The results obtained are also compared with capacitively coupled interconnects of copper (Cu). The results show that as the temperature is varied from 300 K to 500 K, MLGNR has lower propagation delay and power dissipation as compared to Cu for 1 mm long interconnects. It is also observed that because of the dominance of both low resistance and ground capacitance compared to Cu, MLGNR has better crosstalk‐induced delay and voltage waveforms with rise in temperature at the far end of aggressor and victim line, respectively. Further, simulated results show an average relative improvement in propagation delay of 37.24% and corresponding improvement in power dissipation of approximately 19.59% by using a temperature‐dependent model in comparison to a temperature‐independent model of MLGNR resistance with interconnect lengths varying from 200 to 1000 μm. The reduction in the time duration of victim output pulse over these interconnect lengths also shows a significant improvement of approximately 35% by using temperature‐dependent model as against temperature‐independent model of MLGNR resistance.
Shower Light Beans Shower On Off Light On Off Door 1 Door 2 Door

Robotic manipulation is important for real, physical world applications. General Purpose manipulation with a robot (eg. delivering dishes, opening doors with a key, etc.) is demanding. It is hard because (1) objects are constrained in position and orientation, (2) many non-spatial constraints interact (or interfere) with each other, and (3) robots may have multidegree of freedoms (DOF). In this paper we solve the problem of general purpose robotic manipulation using a novel combination of motion planning and an action formalism (Situation Calculus). Our approach integrates motions of a robot with other actions (non-physical or external-to-robot) to achieve a goal while manipulating objects. It differs from previous, hierarchical approaches in that (a) it considers kinematic constraints in configuration space (CSpace) together with constraints over object manipulations; (b) it automatically generates high-level (logical) actions from a CSpace based motion planning algorithm; and (c) it decomposes a planning problem into small segments, thus reducing the complexity of planning.
Power System Stability enhancement by Single Network Adaptive Critic Stabilizers

This paper proposes a Single Network Adaptive Critic (SNAC) based Power System Stabilizer (PSS) for enhancing the small-signal stability of power systems over a wide range of operating conditions. SNAC uses only a single critic neural network instead of the action-critic dual network architecture of typical adaptive critic designs. SNAC eliminates the iterative training loops between the action and critic networks and greatly simplifies the training procedure. The performance of the proposed PSS has been tested on a Single Machine Infinite Bus test system for various system and loading conditions. The proposed stabilizer, which is relatively easier to synthesize, consistently outperformed stabilizers based on conventional lead-lag and linear quadratic regulator designs.
Automatic detection and correction of red-eye effect

In this paper, we address the problem of automatic red-eye detection and correction. A four step, novel approach is presented where the first step consists of face detection in the input image. In the second step the face image is converted to gray-scale image in such a way that facilitates the detection of iris pair and its corresponding radius values. In third and fourth steps iris pair is located, and the central points of irises and their corresponding radius values are utilized to desaturate the redness inside iris regions. The desaturation scheme is adaptive to the severity of redness. Images with different severity level and size of redness are used to test the robustness of the proposed scheme. We also compare our correction schemes with two existing automatic methods.
Chapter 15 : Cyanotoxins Workgroup Report

The Cyanotoxins Workgroup was charged with the identification and prioritization of research needs associated with: the identification of cyanotoxins; toxicokinetics and toxicodynamics of cyanotoxins; human susceptibility to the toxins; cyanobacterial genetics/omics and factors for inclusion in predictive models of toxin production; and risk reduction from an intentional or accidental release of cyanotoxins. Papers presented for the Cyanotoxins Session of the symposium on toxin types, toxicokinetics, and toxicodyamics (See Humpage this volume), cyanobacterial genetics of toxin production (See Neilan this volume), and parameters related to human risks from cyanobacterial exposure (See Love this volume) set the stage for Cyanotoxins Workgroup discussions. A consensus was achieved regarding the need to focus on the major identified classes of cyanotoxins. The group expressed the belief that the most significant toxic components of presently occurring harmful algal blooms have been identified, and the knowledge gaps for these most prevalent toxins are great enough to warrant the attention of most of our