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Based on the consecutive synoptic magnetic maps, we devise a new method to calculate the solar differential rotation coefficients. This method is very easy to implement and has a high accuracy. Firstly, based on the two-term or three-term differential rotation formula, we simulate a synoptic map CR |$_{n}$| evolves one Carrington Rotation (CR) time only under the effect of the differential rotation, and thereby a stretched synoptic map CR |$_{n*}$| is obtained. Then, through searching the maximum covariance between the maps CR |$_{n*}$| and CR |$_{n+1}$| by the grid search method, the rotation coefficients can be determined. Based on the synoptic maps of CRs 1625 to 2278 (during the years 1975–2023), the two-term coefficients A and B for latitude region between |$\pm 40^{\circ }$| are calculated. The rotation coefficient B shows an obvious 11-yr period. From the time series of B , we find that the Sun usually rotates more differentially in the rising phases of the sunspot cycles than in the falling phases. Moreover, the strong magnetic field corresponds to an increasing of B (note that B has a negative sign) or decreasing of differential. The evolutionary trend of B also indicates that there are several years until the maximum value of B will be reached in solar cycle 25, and the coefficient B will be still in the rising phase in the few coming years. The two-term rotation coefficients for the two hemispheres are also calculated separately, and in the studied time-scale, the largest N–S asymmetry of the rotation rate appeared in October 2007. [ABSTRACT FROM AUTHOR]

Therapy-related leukemia carries a poor prognosis, and leukemia after chemotherapy is a growing risk in clinic, whose mechanism is still not well understood. Ikaros transcription factor is an important regulator in hematopoietic cells development and differentiation. In the absence of Ikaros, lymphoid cell differentiation is blocked at an extremely early stage, and myeloid cell differentiation is also significantly affected. In this work, we showed that chemotherapeutic drug etoposide reduced the protein levels of several isoforms of Ikaros including IK1, IK2 and IK4, but not IK6 or IK7, by accelerating protein degradation, in leukemic cells. To investigate the molecular mechanism of Ikaros degradation induced by etoposide, immunoprecipitation coupled with LC-MS/MS analysis was conducted to identify changes in protein interaction with Ikaros before and after etoposide treatment, which uncovered KCTD5 protein. Our further study demonstrates that KCTD5 is the key stabilizing factor of Ikaros and chemotherapeutic drug etoposide induces Ikaros protein degradation through decreasing the interaction of Ikaros with KCTD5. These results suggest that etoposide may induce leukemic transformation by downregulating Ikaros via KCTD5, and our work may provide insights to attenuate the negative impact of chemotherapy on hematopoiesis. [ABSTRACT FROM AUTHOR]

Temporary works are necessary to ensure the construction and operation of railways. These works are characterized by their large scale, numerous locations, and long construction periods. However, suitable land resources for such purposes are extremely limited in mountainous railway areas. Additionally, the selection of sites for these works often overlaps with areas affected by debris flow, leading to high potential risks from geological disasters. Taking the Jinjia Gully watershed as an example, this paper explores a method for assessing debris flow risks in single gullies, including the zoning of debris flow danger areas, vulnerability analysis, and risk assessment. Based on the data obtained from field surveys, they utilize ArcGIS and the Analytic Hierarchy Process (AHP), combined with numerical simulations and indoor experiments, to establish a quantitative risk assessment method for large-scale temporary works. The results indicate that (1) the area of debris flow hazard zones decreases with increasing rainfall frequency, and (2) the vulnerability assessment model can not only reflect the types of individual work, structural materials, and construction quality but also the shielding effect of building clusters. In the direction of flow, the shielding effect range of buildings on debris flow accumulation fans is approximately 37.5 times the size of the buildings. In the direction of extension, when the angle between current and rear buildings exceeds 0.674 radians, the shielding effect can be neglected. (3) At a rainfall frequency of p = 5%, more than 80% of large-scale temporary works are in extremely low or low-risk zones, indicating that the study area is at a low risk level. [ABSTRACT FROM AUTHOR]

Background: MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine), original found in synthetic heroin, causes Parkinson's disease (PD) in human through its metabolite MPP+ by inhibiting complex I of mitochondrial respiratory chain in dopaminergic neurons. This study explored whether yeast internal NADH-quinone oxidoreductase (NDI1) has therapeutic effects in MPTP- induced PD models by functionally compensating for the impaired complex I. MPP+-treated SH-SY5Y cells and MPTP-treated mice were used as the PD cell culture and mouse models respectively. The recombinant NDI1 lentivirus was transduced into SH-SY5Y cells, or the recombinant NDI1 adeno-associated virus (rAAV5-NDI1) was injected into substantia nigra pars compacta (SNpc) of mice. Results: The study in vitro showed NDI1 prevented MPP+-induced change in cell morphology and decreased cell viability, mitochondrial coupling efficiency, complex I-dependent oxygen consumption, and mitochondria-derived ATP. The study in vivo revealed that rAAV-NDI1 injection significantly improved the motor ability and exploration behavior of MPTP-induced PD mice. Accordingly, NDI1 notably improved dopaminergic neuron survival, reduced the inflammatory response, and significantly increased the dopamine content in striatum and complex I activity in substantia nigra. Conclusions: NDI1 compensates for the defective complex I in MPP+/MPTP-induced models, and vastly alleviates MPTP-induced toxic effect on dopaminergic neurons. Our study may provide a basis for gene therapy of sporadic PD with defective complex I caused by MPTP-like substance. [ABSTRACT FROM AUTHOR]

Acute myeloid leukemia (AML) is a hematologic malignant disease largely affecting older adults with poor outcomes. Lack of effective targeted treatment is a major challenge in managing the disease in the clinic. Scaffolding adaptor Gab2 is amplified in a subset of AML. However, the causative role of Gab2 in AML remains to be explored. In this study, it was found that Gab2 was expressed at high levels in AML patient samples and AML cell lines. Experiments by knocking down Gab2 expression using shRNA showed that Gab2 promoted AML cell growth and migration in vitro and in vivo. Further studies using Gab2 mutants and pharmacological inhibitors revealed that Gab2 increased CREB phosphorylation via the SHP‐2/Erk signaling pathway. CREB phosphorylation contributed to Gab2‐induced cell migration by increasing MMP2 and MMP9 expression. This research indicates that high Gab2 expression promotes AML progression through the SHP2‐Erk‐CREB signaling pathway. CREB suppression may help treat AML with high Gab2 expression. [ABSTRACT FROM AUTHOR]

The scaffolding adapter GAB2 maps to a region (11q13-14) commonly amplified in human breast cancer, and is overexpressed in breast cancer cell lines and primary tumors, but its functional role in mammary carcinogenesis has remained unexplored. We found that overexpression of GAB2 (Grb2-associated binding protein 2) increases proliferation of MCF10A mammary cells in three-dimensional culture. Coexpression of GAB2 with antiapoptotic oncogenes causes lumenal filling, whereas coexpression with Neu (also known as ErbB2 and HER2) results in an invasive phenotype. These effects of GAB2 are mediated by hyperactivation of the Shp2-Erk pathway. Furthermore, overexpression of Gab2 potentiates, whereas deficiency of Gab2 ameliorates, Neu-evoked breast carcinogenesis in mice. Finally, GAB2 is amplified in some GAB2-overexpressing human breast tumors. Our data suggest that GAB2 may be a key gene within an 11q13 amplicon in human breast cancer and propose a role for overexpression of GAB2 in mammary carcinogenesis. Agents that target GAB2 or GAB2-dependent pathways may be useful for treating breast tumors that overexpress GAB2 or HER2 or both., Author(s): Mohamed Bentires-Alj (corresponding author) [1, 2]; Susana G Gil [1]; Richard Chan [1]; Zhigang C Wang [3]; Yongping Wang [1]; Naoko Imanaka [1]; Lyndsay N Harris [4]; Andrea Richardson [...]

Src homology-2 (SH2) domain-containing phosphatases (Shps) are a small, highly conserved subfamily of protein-tyrosine phosphatases, members of which are present in both vertebrates and invertebrates. The mechanism of regulation of Shps by ligand binding is now well understood. Much is also known about the normal signaling pathways regulated by each Shp and the consequences of Shp deficiency. Recent studies have identified mutations in human Shp2 as the cause of the inherited disorder Noonan syndrome. Shp2 mutations might also contribute to the pathogenesis of some leukemias. In addition, Shp2 might be a key virulence determinant for the important human pathogen Helicobacter pylori. Despite these efforts, however, the key targets of each Shp have remained elusive. Identifying these substrates remains a major challenge for future research.

Abstract Background Human immunodeficiency virus (HIV) infected patients are at increased risk for the development of pulmonary arterial hypertension (PAH). Recent reports have demonstrated that HIV associated viral proteins induce reactive oxygen species (ROS) with resultant endothelial cell dysfunction and related vascular injury. In this study, we explored the impact of HIV protein induced oxidative stress on production of hypoxia inducible factor (HIF)-1α and platelet-derived growth factor (PDGF), critical mediators implicated in the pathogenesis of HIV-PAH. Methods The lungs from 4-5 months old HIV-1 transgenic (Tg) rats were assessed for the presence of pulmonary vascular remodeling and HIF-1α/PDGF-BB expression in comparison with wild type controls. Human primary pulmonary arterial endothelial cells (HPAEC) were treated with HIV-associated proteins in the presence or absence of pretreatment with antioxidants, for 24 hrs followed by estimation of ROS levels and western blot analysis of HIF-1α or PDGF-BB. Results HIV-Tg rats, a model with marked viral protein induced vascular oxidative stress in the absence of active HIV-1 replication demonstrated significant medial thickening of pulmonary vessels and increased right ventricular mass compared to wild-type controls, with increased expression of HIF-1α and PDGF-BB in HIV-Tg rats. The up-regulation of both HIF-1α and PDGF-B chain mRNA in each HIV-Tg rat was directly correlated with an increase in right ventricular/left ventricular+septum ratio. Supporting our in-vivo findings, HPAECs treated with HIV-proteins: Tat and gp120, demonstrated increased ROS and parallel increase of PDGF-BB expression with the maximum induction observed on treatment with R5 type gp-120CM. Pre-treatment of endothelial cells with antioxidants or transfection of cells with HIF-1α small interfering RNA resulted in abrogation of gp-120CM mediated induction of PDGF-BB, therefore, confirming that ROS generation and activation of HIF-1α plays critical role in gp120 mediated up-regulation of PDGF-BB. Conclusion In summary, these findings indicate that viral protein induced oxidative stress results in HIF-1α dependent up-regulation of PDGF-BB and suggests the possible involvement of this pathway in the development of HIV-PAH.

Field measurements at the Qingtu Lake Observation Array site were performed to explore the features of large scale structures relevant to very large scale motions (VLSMs) and large scale motions (LSMs) in the atmospheric surface layer during dust weather events. The three velocity components, PM10 concentrations (particles with size less than 10 μm), and sand saltation fluxes at different heights were measured synchronously. By comparing with the results in clean-air flows, the influences of sand particles on the VLSMs were investigated. The present results indicate that the streamwise turbulent kinetic energy across all scales is enhanced in the sand-laden flows. However, the energy enhancement of small-scale motions is more pronounced than that of large scale structures, resulting in a decreased energy fraction of the large scale structures in the sand-laden flows. The inclination angles of the large scale structures are found to increase with sand concentration, owing to the decreased velocity gradient. The streamwise length scale of large scale structures and the size of the most energetic turbulent structures are found to be unchanged in the sand-laden flows relative to those in the clean-air flows. This is the study on the particle-laden wall turbulence at the largest Reynolds number to date, and the results demonstrate that the dispersed tiny particles in very dilute particle–gas flows can affect the turbulence even for the large scale structures. [ABSTRACT FROM AUTHOR]

Cholesterol is a risk factor for breast cancer. However, it is still unclear whether the cholesterol biosynthesis pathway plays any significant role in breast carcinogenesis. 24‐Dehydrocholesterol reductase (DHCR24) is a key enzyme in the cholesterol synthesis pathway. Although DHCR24 is reported to have different functions in different cancers, it is not clear whether DHCR24 is involved in breast cancer. In this study, we found that DHCR24 expression was higher in breast cancer especially in luminal and HER2 positive breast cancer tissues compared with normal breast. Changes in DHCR24 expression altered cellular cholesterol content without affecting the adherent growth of breast cancer cells. However, DHCR24 knockdown reduced whereas DHCR24 overexpression enhanced breast cancer stem‐like cell populations such as mammosphere and aldehyde dehydrogenase positive cell numbers. In addition, DHCR24 overexpression increased the expression of the Hedgehog pathway‐regulated genes. Treating DHCR24 overexpressing breast cancer cell lines with the Hedgehog pathway inhibitor GANT61 blocked DHCR24‐induced mammosphere growth and increased mRNA levels of the Hedgehog regulated genes. Furthermore, expression of a constitutively activated mutant of Smoothened, a key hedgehog signal transducer, rescued the decreases in mammosphere growth and Hedgehog regulated gene expression induced by knockdown of DHCR24. These results indicate that DHCR24 promotes the growth of breast cancer stem‐like cells in part through enhancing the Hedgehog signaling pathway. Our data suggest that cholesterol contribute to breast carcinogenesis by enhancing Hedgehog signaling and cancer stem‐like cell populations. Enzymes including DHCR24 involved in cholesterol biosynthesis should be considered as potential treatment targets for breast cancer. [ABSTRACT FROM AUTHOR]

Chimeric Antigen Receptor (CAR)-T cells have great efficacy against CD19+ leukemia but little success for solid tumors. This study explored the effectiveness of third generation anti-HER2 CAR-T cells alone or in combination with anti-PD1 antibody on breast tumor cells expressing HER2 in vitro and in immune competent mouse model. The PDL1-positive mouse mammary tumor cell line 4T1 engineered to express luciferase and human HER2 was used as the target cell line (4T1-Luc-HER2). Anti-HER2 CAR-T cells were generated by transducing mouse spleen T cells with recombinant lentiviruses. ELISA analysis showed that IL-2 and IFN-γ secretion was increased in CAR-T cells co-cultured with the target cells, and the secretion of these two cytokines was increased further with the addition of anti-PD1 antibody. Lactate dehydrogenase assay revealed that CAR-T cells displayed a potent cytotoxicity against the target cells, and the addition of anti-PD1 antibody further enhanced the cytotoxicity. At the effector: target ratio of 16:1, cytotoxicity was 39.8% with CAR-T cells alone, and increased to 49.5% with the addition of anti-PD1 antibody. In immune competent syngeneic mouse model, CAR-T cells were found to be present in tumor stroma, inhibited tumor growth and increased tumor apoptosis significantly. Addition of anti-PD1 antibody further enhanced these anti-tumor activities. Twenty-one days after treatment, tumor weight was reduced by 50.0% and 73.3% in CAR-T group and CAR-T plus anti-PD1 group compared with blank T group. Our results indicate that anti-PD1 antibody can greatly increase the efficacy of anti-HER2 CAR-T against HER2-positive solid tumors. [ABSTRACT FROM AUTHOR]

As a subtype of acute myeloid leukemia (AML), acute promyelocytic leukemia (APL) is characterized by a chromosomal translocation, most of which result in the production of a PML‐RAR alpha fusion protein. Although the overall survival rate of APL patients has improved dramatically due to all‐trans retinoic acid (ATRA) treatment, ATRA‐resistance remains a clinical challenge in the management of APL. Therefore, alternative agents should be considered for ATRA‐resistant APL patients. Here, we report that antimalaria drug primaquine phosphate (PRQ) exhibits an anti‐leukemia effect on both ATRA‐sensitive cell line NB4 and ATRA‐resistant APL cell lines, NB4‐LR2, NB4‐LR1, and NB4‐MR2. Moreover, PRQ significantly inhibited primary colony formation of untreated or relapsed APL patients. Further study showed that PRQ could induce the apoptosis of APL cells by inhibiting NF‐κB signaling pathway. The in vivo study showed that PRQ significantly inhibited NB4‐LR2 xenograft tumors growth. These results suggest that PRQ is a potential therapeutic agent for ATRA‐resistant APL patients. [ABSTRACT FROM AUTHOR]

Abstract: Background: The production of anti‐Her2 chimeric antigen receptor (CAR) T cells needs to be optimized to make it a reliable therapy. Methods: Three types of lentiviral vectors expressing anti‐Her2 CAR together with packaging plasmids were co‐transfected into 293 T‐17 cells. The vector with the best packaging efficiency was selected, and the packaging cell culture system and packaging plasmid system were optimized. Centrifugation speed was optimized for the concentration of lentivirus stock. The various purification methods used included membrane filtration, centrifugation with a sucrose cushion and the novelly‐designed instantaneous high‐speed centrifugation. The recombinant lentiviruses were transduced into human peripheral T cells with an optimized multiplicity of infection (MOI). CAR expression levels by three vectors and the efficacy of CAR‐T cells were compared. Results: When co‐transfected, packaging cells in suspension were better than the commonly used adherent culture condition, with the packaging system psPAX2/pMD2.G being better than pCMV‐dR8.91/pVSV‐G. The optimal centrifugation speed for concentration was 20 000 g, rather than the generally used ultra‐speed. Importantly, adding instantaneous centrifugation for purification significantly increased human peripheral T cell viability (from 13.25% to 62.80%), which is a technical breakthrough for CAR‐T cell preparation. The best MOI value for transducing human peripheral T cells was 40. pLVX‐EF1a‐CAR‐IRES‐ZsGreen1 expressed the highest level of CAR in human peripheral T cells and the cytotoxicity of CAR‐T cells reached 63.56%. Conclusions: We optimized the preparation of recombinant lentivirus that can express third‐generation anti‐Her2 CAR in T cells, which should lay the foundation for improving the efficacy of CAR‐T cells with respect to killing target cells. [ABSTRACT FROM AUTHOR]

The purpose of this study was to evaluate the properties of resistant starch (RS) from Chinese chestnut ( Castanea mollissima), which was prepared by autoclaving treatment and pullulanase hydrolysis. Scanning electron microscopy (SEM) revealed that the chestnut resistant starch (CRS) granules had a cohesive structure, an irregular shape, and diameters ranging from 6.0 to 7.2 µm. The enzymatic and retrogradation processes increased the yield of RS, and also decreased its swelling power, water solubility, and viscosity. An increase in transparency was also observed. The percent syneresis of the two starches increased steadily over time. X-ray diffraction (XRD) analyses revealed that autoclaving and pullulanase hydrolysis converted C-type native starch into a B-type pattern and increased the crystallinity. In addition, differential scanning calorimetry (DSC) results indicated a reduction in gelatinization temperature and enthalpy compared with native starch. The thermal properties of RS increased due to the retrogradation and recrystallization ( p < .05). Practical applications Chinese chestnut ( Castanea mollissima) is an important nut crop with high nutrition and planted in China widely. High water content in fresh chestnut leads to mildew attack easily, which will affect the chestnut market value and trade business. Therefore, it has great significance and practical demand to develop the deep processing technology and diversify its products. The resistant starch has been implemented as an ingredient for its resistant digestion properties for making flour food and functional food. However, the research and application of resistant starch from Chinese chestnut ( Castanea mollissima) has been rarely seen. This study investigated the structural and physicochemical properties of chestnut resistant starch and provided a reference for the application of chestnut resistant starch in the food processing industries. For example, an increase in transparency and syneresis suggested chestnut resistant starch could be potentially used as a functional ingredient in jelly, beverages, and other food products, but not be possible for use in the frozen food industry. [ABSTRACT FROM AUTHOR]

Besides its well-known function in allergic response, mast cell, one of the key immune cells present in tumor microenvironment, plays important roles in cancer progression. However, the functional role of mast cells in breast cancer development and metastasis is not well understood. To test the involvement of mast cells in breast cancer, we examined the effects of loss of mast cells on mammary tumor development by crossing the well-known mast cell deficient mouse strain sash (KitW-sh/W-sh) with the mammary tumor transgenic mouse strain MMTV-Polyoma Middle T antigen (Py MT). Although mammary tumor onset was not affected in the absence of mast cells, mammary growth and metastasis were reduced in Py MT/KitW-sh/W-sh mice compared with Py MT/wild-type mice ( WT). Histological and immunofluorescent analyses showed that tumors from Py MT/KitW-sh/W-sh mice showed largely differentiated morphology with reduced angiogenesis compared with MMTV-Py MT/ WT mice. Our results suggest that mast cells may promote breast cancer growth and metastasis. Agents that can block mast cells growth are potential new therapies to treat metastatic breast cancer. [ABSTRACT FROM AUTHOR]

Pairings on elliptic curves are currently of great interest due to their applications in a number of cryptographic protocols such as identity-based encryption, group signatures, short signatures, and the tripartite Diffie-Hellman. Miller's algorithm is the most commonly used method of computing Tate pairing. Denominator elimination can improve Miller's algorithm when the embedding degree has the form 2i3j. However, if the embedding degree does not have the above form, how can the speed of Miller's algorithm be increased? In this article, the authors modified Miller's algorithm over Huff curves. It is about 20.38% faster than the original algorithm. [ABSTRACT FROM PUBLISHER]

The genomes of different human beings are similar. There are only a relatively small number of genetic differences between people. The genetic differences between people are very worthy of study. Researchers have proposed the fixation index FST measurement to find the single nucleotide polymorphisms (SNPs) which can reflect human population differences. However, most SNPs have interactions and they work together, which leads to the differences among human populations. The number of all possible m-locus combinations chosen from n SNPs grows exponentially. Most methods concern on 2-locus interactions. In this paper, we propose a novel method to find a new coordinate system under which the energy distributions of different populations are quite different. We select out candidate SNPs from n SNPs by using the information of the axes in the coordinate system. The number of candidate SNPs is small, thus SNP-SNP interactions can be searched efficiently. The method can also find interactions of more than two loci. These interactions should be able to reflect the evolution of human populations from another way. The numbers of SNP-SNP interactions are regarded as the differences between pairwise populations and a hierarchical clustering algorithm is used to construct the evolutionary tree. In the experiments, we apply the method to SNP data of four chromosomes separately and the trees constructed on these four chromosomes are highly consistent. Furthermore, the trees are also consistent with previous studies, which indicates that evolutionary information is well mined. The method provides a new insight to analyze the human population differences. [ABSTRACT FROM PUBLISHER]

Both dietary fat and carbohydrates (Carbs) may play important roles in the development of insulin resistance. The main goal of this study was to further define the roles for fat and dietary carbs in insulin resistance. C57BL/6 mice were fed normal chow diet (CD) or HFD containing 0.1–25.5% carbs for 5 weeks, followed by evaluations of calorie consumption, body weight and fat gains, insulin sensitivity, intratissue insulin signaling, ectopic fat, and oxidative stress in liver and skeletal muscle. The role of hepatic gluconeogenesis in the HFD-induced insulin resistance was determined in mice. The role of fat in insulin resistance was also examined in cultured cells. HFD with little carbs (0.1%) induced severe insulin resistance. Addition of 5% carbs to HFD dramatically elevated insulin resistance and 10% carbs in HFD was sufficient to induce a maximal level of insulin resistance. HFD with little carbs induced ectopic fat accumulation and oxidative stress in liver and skeletal muscle and addition of carbs to HFD dramatically enhanced ectopic fat and oxidative stress. HFD increased hepatic expression of key gluconeogenic genes and the increase was most dramatic by HFD with little carbs, and inhibition of hepatic gluconeogenesis prevented the HFD-induced insulin resistance. In cultured cells, development of insulin resistance induced by a pathological level of insulin was prevented in the absence of fat. Together, fat is essential for development of insulin resistance and dietary carb is not necessary for HFD-induced insulin resistance due to the presence of hepatic gluconeogenesis but a very small amount of it can promote HFD-induced insulin resistance to a maximal level. [ABSTRACT FROM AUTHOR]

Highlights: [•] We examined the level of miR-490-3p in A549 lung cancer cells compared with normal bronchial epithelial cell line. [•] We are the first to show the function of miR-490-3p in A549 lung cancer cells. [•] We demonstrate CCND1 may be one of the targets of miR-490-3p. [Copyright &y& Elsevier]

Background: Human immunodeficiency virus (HIV) infected patients are at increased risk for the development of pulmonary arterial hypertension (PAH). Recent reports have demonstrated that HIV associated viral proteins induce reactive oxygen species (ROS) with resultant endothelial cell dysfunction and related vascular injury. In this study, we explored the impact of HIV protein induced oxidative stress on production of hypoxia inducible factor (HIF)-1α and platelet-derived growth factor (PDGF), critical mediators implicated in the pathogenesis of HIV-PAH.Methods: The lungs from 4-5 months old HIV-1 transgenic (Tg) rats were assessed for the presence of pulmonary vascular remodeling and HIF-1α/PDGF-BB expression in comparison with wild type controls. Human primary pulmonary arterial endothelial cells (HPAEC) were treated with HIV-associated proteins in the presence or absence of pretreatment with antioxidants, for 24 hrs followed by estimation of ROS levels and western blot analysis of HIF-1α or PDGF-BB.Results: HIV-Tg rats, a model with marked viral protein induced vascular oxidative stress in the absence of active HIV-1 replication demonstrated significant medial thickening of pulmonary vessels and increased right ventricular mass compared to wild-type controls, with increased expression of HIF-1α and PDGF-BB in HIV-Tg rats. The up-regulation of both HIF-1α and PDGF-B chain mRNA in each HIV-Tg rat was directly correlated with an increase in right ventricular/left ventricular+septum ratio. Supporting our in-vivo findings, HPAECs treated with HIV-proteins: Tat and gp120, demonstrated increased ROS and parallel increase of PDGF-BB expression with the maximum induction observed on treatment with R5 type gp-120CM. Pre-treatment of endothelial cells with antioxidants or transfection of cells with HIF-1α small interfering RNA resulted in abrogation of gp-120CM mediated induction of PDGF-BB, therefore, confirming that ROS generation and activation of HIF-1α plays critical role in gp120 mediated up-regulation of PDGF-BB.Conclusion: In summary, these findings indicate that viral protein induced oxidative stress results in HIF-1α dependent up-regulation of PDGF-BB and suggests the possible involvement of this pathway in the development of HIV-PAH. [ABSTRACT FROM AUTHOR]

Scalar multiplication nP is the core operation of elliptic curve public-key cryptosystems. Double bases representation of n is proposed to speed up scalar multiplication. Avanzi et al. presented a recoding algorithm for Koblitz curves which works in all cases with optimal constants [1]. However, their algorithm may be expensive to implement because it requires many divisions in [τ]. In this paper, we show that divisions in [τ] can be replaced by divisions in . Our improved version of the algorithm runs in about 33% of the time of the Avanzi et al. algorithm on the Koblitz curve K-163, with larger improvements as the size of the curve increases. [ABSTRACT FROM AUTHOR]

Abstract: Let denote the “Euler polynomial” if and if . Set to be the number of prime factors (counting multiplicity) of the positive integer n. The Ono invariant of is defined to be except when in which case is defined to be 1. Finally, let denote the class number of K. In 2002 J. Cohen and J. Sonn conjectured that and is a prime. They verified that the conjecture is true for . Moreover, they proved that the conjecture holds for assuming the extended Riemann Hypothesis. In this paper, we show that the conjecture holds for by the aid of computer. And using a result of Bach, we also proved that the conjecture holds for assuming the extended Riemann Hypothesis. In conclusion, we proved the conjecture is true assuming the extended Riemann Hypothesis. [Copyright &y& Elsevier]

Tyrosine phosphorylation plays an important role in controlling cellular growth, differentiation and function. Abnormal regulation of tyrosine phosphorylation can result in human diseases such as cancer. A major challenge of signal transduction research is to determine how the initial activation of protein-tyrosine kinases (PTKs) by extracellular stimuli triggers multiple downstream signaling cascades, which ultimately elicit diverse cellular responses. Recent studies reveal that members of the Gab/Dos subfamily of scaffolding adaptor proteins (hereafter, ‘Gab proteins’) play a crucial role in transmitting key signals that control cell growth, differentiation and function from multiple receptors. Here, we review the structure, mechanism of action and function of these interesting molecules in normal biology and disease. [Copyright &y& Elsevier]