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The combined value of any product design method depends on the design benefits and costs of use, determining the need to put the method into practice. In this study, a virtual reality design system was constructed to support the widely adopted user interview method for the usability improvement design of an existing product, using an industrial remote control as example. The combined value of the method was verified to be superior to the use of user interviews alone, in terms of the number and importance of usability questions mined by users, the level of styling of improved design solutions guided by usability questions, and the willingness of designers to use the method. It provides a useful reference for the promotion of immersive technology in the field of product design and the search for new focus points.

The essential factors that affect the interfacial mass transfer rate of crown ether–ionic liquid systems are studied by examining the physicochemical properties of mixtures of ionic liquids with benzo-15-crown-5. In the present work, the 1-alkyl-3-methylimidazolium bis((trifluoromethyl)sulfonyl)imides ionic liquids ([C2MIm][NTf2], [C3MIm][NTf2], [C4MIm][NTf2], and [C5MIm][NTf2]) are adopted as the solvent and benzo-15-crown-5 is used as the solute. A series of binary mixtures of the ionic liquid and benzo-15-crown-5, with different molar fractions of ionic liquids, is formulated by the weight method. The viscosity and density are determined for four binary mixtures of ionic liquid and benzo-15-crown-5 at atmospheric pressure in a temperature range of 298.15 to 343.15 K. The values obtained for viscosity and density are fitted with empirical equations, and the energy barrier, a-constant, and the isobaric thermal expansion coefficient are all calculated. Interactions between the ionic liquid and the solute benzo-15-crown-5 are analyzed, and the above properties are discussed by comparison with systems in which different solutes are present in the same ionic liquid. It is found that interactions between the ionic liquid and benzo-15-crown-5 in the mixtures are more intense than in mixed systems composed of ionic liquids and other solutes.

Upregulation of Rho-associated protein kinase 2 (ROCK2) hallmarks the progression of neurodegenerative diseases. However, the molecular mechanisms underlying the regulation of ROCK2 expression are not clear and thus addressed in the current study. We generated a subacute model of Parkinson's disease in mice with a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) method. The MPTP model was validated by impaired rotational behavior of the mice upon apomorphine exposure, astrocytic activation, and reduction in tyrosine-hydroxylase-positive neurons in the mouse striatum. Moreover, MPTP induced increases in ROCK2 protein but not in ROCK2 mRNA. Further analysis showed that MPTP inhibited the expression of microRNA-291 (miR-291), which suppressed ROCK2 mRNA via 3'-UTR-binding in neuronal cells to increase ROCK2 protein. Intracranial injection of miR-291 four days before MPTP alleviated the impaired rotational behavior of the mice upon apomorphine exposure, MPTP-induced astrocytic activation, and the reduction in tyrosine-hydroxylase-positive neurons in the mouse striatum. Together, these data suggest that miR-291 has a protective role in neurodegeneration, likely through regulation of ROCK2.

This study aim to identify the clinical risk factors of and to develop a radiomics-based predictive model for early postoperative seizure.We retrospectively assessed 322 operative patients with meningioma who met the inclusion criteria from January 2014 to December 2016 at The First Affiliated Hospital of Wenzhou Medical University. Univariate and multivariate analyses were performed to determine the predictive value of clinical variables. Magnetic resonance imaging (MRI) was performed to obtain the radiomic score (Rscore) for early postoperative seizure. Radiological features were evaluated using the AK software. The minimal redundancy (mRMR) and least absolute shrinkage and selection operator (LASSO) methods were used to assess for radiomic features, and the Rscore was obtained based on radiomic characteristics using a specific formula.In total, 260 patients who met the inclusion criteria were finally enrolled in this study. Among them, 20 experienced early postoperative seizure. Logistic regression analysis showed that Rscore was associated with a significantly high risk of seizure (p0.000). Receiver operating characteristic (ROC) curve analysis revealed that the area under the ROC curve of the Rscore was 0.92 (95% confidence interval: 0.853-0.987). The model had a high accuracy for predicting early postoperative seizure.The Rscore was found to be associated with a high risk of early postoperative seizures. Thus, a higher Rscore (-1.644) can identify high-risk patients requiring intensive care.

This paper summarizes the overview of the language policy in Bangladesh, using Cooper’s language planning theory, based on educational planning, ontology planning and status planning.The research shows that the multi-ethnic cultural furnace promotes the government of Bangladesh, but English has penetrated in all areas of society, the language policy in Bangladesh still ignores minority languages, but the formulation and formulation of language policy in Bangladesh, Can provide some reference for our country.

The Smart Grid is a fundamental breakthrough that will change the current electricity grid significantly. The conventional power grid is a centralized network whereas smart grid is decentralized smart network compromising power network with communication network that will facilitate two way power flows. Therefore, the design of the underlying Information and Communication Technology infrastructure is a critical challenge in this area. For the attainment of a more distributed power generation and storage system, novel communication technologies should be integrated with the power grid. In SG, the development and growth of wireless technologies can be proven as more advantageous. The best option for communicating between far nodes, infrastructure, and intelligent meters is cellular communication technology. With the emergence of the fifth generation (5G) network, mobile cellular networks are evolving to take a strong stance in attempts to achieve large-scale capacity, connectivity and processing. Both the mobile technology of today and the emerging new age of cellular network are deemed useful for the smart grid. The future cellular networks exhibit relevant services in the smart grid for critical and timely applications. Existence and future cellular networks and their vision for smart grid are presented in this article. The central point of this article is to demonstrate the future cellular network in comparison to other wireless communication technologies and new webs in a SG to effectively bring the energy of internet into the future. Benefits and challenges of emerging cellular networks for smart grid are also presented.

To date, the management of dopamine agonist (DA)-resistant prolactinomas remains a major clinical problem. Previously, we determined that miRNA-93 expression increases in DA-resistant prolactinomas; however, the role of miRNA-93 in the DA resistance remains largely unexplored. Hence, this study aimed to investigate the susceptibility of tumor cells to cabergoline (CAB) and the autophagy changes in MMQ and GH3 cells after miRNA-93 overexpression or inhibition. We used bioinformatics to identify the potential target of miRNA-93. Subsequently, we analyzed the correlation between miRNA-93 and autophagy-related 7 (ATG7) using protein expression analysis and luciferase assays. Furthermore, the change in the effect of miRNA-93 was measured after ATG7 overexpression. miRNA-93 expression was elevated in DA-resistant prolactinomas, whereas the expression of its identified target, ATG7, was downregulated. miRNA-93 overexpression suppressed the cytotoxic effect of CAB in MMQ and GH3 cells. In contrast, miRNA-93 downregulation enhanced CAB efficiency and promoted cell autophagy, eventually resulting in apoptosis. These results were further confirmed in in vivo xenograft models in nude mice. ATG7 overexpression could reverse the inhibitory effect of miRNA-93 on CAB treatment. Taken together, our results suggest that miRNA-93 mediates CAB resistance via autophagy downregulation by targeting ATG7 and serves as a promising therapeutic target for prolactinoma.

The splicing factor SPF45 (RBM17) is a well-known component of the spliceosome that is involved in alternative splicing. RBM17 is frequently overexpressed in many tumors and plays a crucial role in cancer progression and drug resistance. However, the role of RBM17 in the development of glioma has not been thoroughly elucidated to date. In the present study, we found that RBM17 was overexpressed in glioma and that a high level of expression of RBM17 was closely associated with a poor prognosis in glioma patients. We investigated the effect of RBM17 on apoptosis, cell growth and cell cycle indexes and the activation of apoptosis signaling by shRNA in human U87 and U251 glioma cells. The downregulated expression of RBM17 mRNA was accompanied by the induction of cell cycle arrest, and apoptosis, reduced cell proliferation in the two cell lines, and reduced cell survival, as measured by the increased activation of caspase-3, caspase-9, and PARP (poly ADP-ribose polymerase). Furthermore, in subcutaneous U87 cell xenograft tumors in nude mice, intradermal administration of an shRNA targeting RBM17 significantly downregulated RBM17 expression in vivo and was accompanied by the suppressed growth of glioma. To the best of our knowledge, our results are the first to confirm that RBM17 functions in promoting cell proliferation, affecting the cell cycle, and inducing apoptosis in human glioma cells both in vitro and in vivo. These results indicate that RBM17 may be a therapeutic target in the clinical management of glioma.

Although tumor stem-like cells (TSLCs) have been studied in a range of malignant tumors, evidence for the presence of these cells in pituitary adenomas needs further exploration. Here, we identified a small subset of sphere-forming cells possess tumor stem-like cell properties in rat prolactinoma MMQ cells, which resist to dopamine agonist treatment. Comparing to MMQ cells, sphere-forming cells showed higher cell viability after dopamine agonist (DA) treatment. Furthermore, the cells showed lower expression of prolactin (PRL) and dopamine 2 receptor (D2R). On the contrary, the daughter tumor cells differentiated from these cells restored the sensitivity to DA and showed high expression of PRL and D2R. The lower D2R expression and DA resistance might be due to DNA hypermethylation of D2R promoter. Our study demonstrates that the sphere-forming cells isolated from MMQ cells possess the trait of TSLCs and resist to DA treatment, which offers the opportunity to further investigate the mechanisms underlying tumor recurrence based on TSLCs.

BACKGROUND Neural stem cells are reported to exist in the hippocampus of adult mammals and are important sources of neurons for repair. The Notch1 signaling pathway is considered as one of the important regulators of neural stem cells, but its role in adult brains is unclear. We aimed to describe the role of Notch1 signaling in the adult rat hippocampus after traumatic brain injury. MATERIAL AND METHODS The model rats were randomly divided into 4 groups as follows: sham, sham-TBI, sham-Ad-TBI, and NICD-Ad-TBI. We used adenovirus-mediated gene transfection to upregulate endogenous NICD in vivo. Firstly, a TBI rat model was constructed with lateral fluid percussion. Then, the hippocampus was collected to detect the expression of Notch1 markers and stem cell markers (DCX) by Western blot analysis, immunohistochemistry, and immunofluorescence. The prognosis after TBI treatment was evaluated by the Morris Water Maze test. RESULTS First, we found the expression of NICD in vivo was significantly increased by adenovirus-mediated gene transfection as assessed by Notch1 immunofluorescence and Western blot analysis. Second, enhancing NICD stimulated the regeneration of neural stem cells in the DG of the adult rat brain following traumatic brain injury, as evaluated by DCX and NeuN double-staining. Furthermore, Notch1 signaling activation can promote behavioral improvement after traumatic brain injury, including spatial learning and memory capacity. CONCLUSIONS Our findings suggest that targeted regulation of Notch1 signaling may have a useful effect on stem cell transformation. Notch1 signaling may have a potential brain-protection effect, which may result from neurogenesis.

Surgical treatment for cerebral amyloid angiopathy (CAA)-related intracerebral hemorrhage (ICH) is controversial. A subset of CAA-related ICH with associated subdural hemorrhage (SDH) has been reported. This study aimed to evaluate clinical results and surgical outcomes of this type of ICH with associated SDH.Study participants included 98 patients with CAA-related ICH who met Boston criteria. Patients were divided into an SDH group and a control (no SDH) group. Clinical and neuroimaging features and surgical outcomes of the 2 groups were compared.Lobular shape of hematoma was found significantly more often in the SDH group (65.7% [23/35]) compared with the control group (25.4% [16/63]; P0.001). Subarachnoid hemorrhage was found significantly more often in the SDH group (34.3% [12/35]) compared with the control group (7.9% [5/63]; P = 0.001). The rate of postoperative hemorrhage was significantly higher in the SDH group (61.5% [8/13]) than in the control group (16.2% [6/37]; P = 0.006). The frequency of occurrence of postoperative hemorrhage was significantly higher in the SDH group (13/13) than in the control group (6/37; P = 0.017). A good surgical outcome occurred in none (0/12) of the patients in the SDH group, whereas a good surgical outcome occurred in 51.9% (14/27) of patients in the control group (P = 0.006).Patients with CAA-related ICH with associated SDH more frequently have postoperative hemorrhage and have a worse surgical outcome. These findings are useful in choosing therapeutic methods and preoperative planning of surgical strategy.

BACKGROUND Dopamine agonists (DAs) are the first-line treatment for prolactinomas. DAs primarily target the dopamine D2 receptor (D2R). Tumor stem-like cells (TSLCs) are associated with the tolerance to radiotherapy and chemotherapy. TSLCs have also been identified in pituitary adenomas. We aimed to characterize the expression pattern of stem cell markers and D2R in human and rat prolactinomas. MATERIAL AND METHODS Human prolactinoma specimens (n=14) were obtained from patients with surgical resection. The xenograft model of rat prolactinomas was generated by endermically injecting MMQ cells, HE and PRL were confirmed by immunohistochemical staining of tumor sections, and the expression of serum PRL was measured by ELISA. The expression of stem cell markers (CD133, Nestin, Oct4, and Sox2) and D2R in prolactinomas was detected by immunofluorescence. The proportion of CD133-expressing cells after DA treatment was evaluated by flow cytometry in vitro. RESULTS We found that a small subpopulation of cells expressing stem cell markers existed both in human and rat prolactinomas. Furthermore, the CD133-expressing cells showed negative D2R expression. Conversely, the D2R-expressing cells showed negative CD133 expression. The proportion of CD133-expressing cells in surviving tumor cells was significantly increased after DA treatment. CONCLUSIONS Our results confirmed the existence of cells expressing stem cell markers in human and rat prolactinomas. Additionally, the CD133-expressing cells might resist DA therapy due to the lack of D2R expression.

Heat shock protein 47 (HSP47) is a 47 kDa collagen binding protein that has a close relationship with the development and progression of tumours. However, little is known concerning the expression profile of HSP47 in laryngeal squamous cell carcinoma (LSCC) patients and there is still insufficient data concerning the underlying mechanisms. The aim of the present study was to explore the expression of HSP47 in LSCC and provide an overview of its association with tumourigenicity and clinical prognosis. The expression of HSP47 in LSCC and adjacent non-cancerous laryngeal tissues was assessed via western blotting and immunohistochemical studies. The prognostic significance of HSP47 expression was analysed using a Kaplan-Meier survival curve. To investigate the influence of HSP47 on the viability, invasion and apoptosis of a LSCC cell line, we performed an in vitro analysis with plasmid vectors and small interfering RNA (siRNA). Our results showed that HSP47 protein expression in the LSCC tissues was markedly decreased compared to that noted in the adjacent non-cancerous tissues, and low expression of HSP47 was correlated with poor prognosis in LSCC patients. Upregulation of HSP47 via plasmid vectors inhibited the proliferation, reduced the invasive ability, increased the sensitivity to cisplatin chemotherapy, promoted apoptosis, and induced the G1 phase arrest of LSCC cells in vitro. The expression of apoptosis-regulating proteins was also altered when HSP47 was upregulated, involving increased expression of cleaved caspase-7/-8/-9, PARP, and Bax and decreased expression of Bcl-2. Our present data suggest that HSP47 is an important prognostic factor and an attractive therapeutic target in LSCC due to its influence on the biological behaviour of LSCC cells.

Cluster of differentiation 164 (CD164), a sialomucin, has been demonstrated to be involved in the regulation of proliferation, apoptosis, adhesion and differentiation in multiple cancers. CD164 is regarded to be a potential promotor of tumor growth. However, the involvement of CD164 in human glioma proliferation and apoptosis remains unknown. The aim of the present study was to investigate the expression and oncogenic function of CD164 in normal human astrocytes (NHA) and glioma cells in vitro and in vivo. The results of the present study demonstrated that CD164 mRNA and protein levels were significantly increased in human glioma cell lines and tissue samples. CD164 overexpression promoted the proliferation of NHA in vitro, and its tumorigenic effect was confirmed in a murine xenograft model. Knockdown of CD164 inhibited cell proliferation and promoted apoptosis of the U87 human glioma cell line in vitro and in vivo. In addition, knockdown of CD164 was demonstrated to upregulate the Bax/Bcl2 ratio and phosphatase and tensin homolog (PTEN) expression, reduce protein kinase B (AKT) phosphorylation and promote the expression of p53 in U87 cells. The results suggest that CD164 expression may have affected the proliferation and apoptosis of human glioma cells via the PTEN/phosphoinositide 3-kinase/AKT pathway, and may therefore present a potential target for the diagnosis and treatment of glioma.

Lyme borreliosis is a tick-borne disease caused by the Borrelia burgdorferisensu lato complex. Bio-Rad Laboratories has developed a fully automated multiplex bead-based assay for the detection of IgM and IgG antibodies to B. burgdorferi. The BioPlex 2200 Lyme Total assay exhibits an improved rate of seropositivity in patients with early Lyme infection. Asymptomatic subjects from endemic and nonendemic origins demonstrated a seroreactivity rate of approximately 4% that was similar to other commercial assays evaluated in this study. Coupled to this result was the observation that the Lyme Total assay retained a high first-tier specificity of 96% while demonstrating a relatively high sensitivity of 91% among a well-characterized CDC Premarketing Lyme serum panel. The Lyme Total assay also performs well under a modified two-tier algorithm (sensitivity, 84.4 to 88.9%; specificity, 98.4 to 99.5%). Furthermore, the new assay is able to readily detect early Lyme infection in patient samples from outside North America.

The occurrence of an inherent or acquired resistance to temozolomide (TMZ) is a major burden for patients suffering from glioma. Recently, studies have demonstrated that microRNAs play an important role in the regulation of tumor properties in cancers. However, whether miR‐497 contributes to glioma resistance to chemotherapy is not fully understood. In this study, we showed that the expression of miR‐497 was markedly up‐regulated in TMZ‐resistant glioma cells; high miR‐497 expression level was associated with TMZ‐resistant phenotype of glioma cells. The down‐regulation of miR‐497 in glioma cells enhanced the apoptosis‐induction and growth inhibition effects of TMZ both in vitro and in vivo, whereas promotion of miR‐497 increased the chemosensitization of glioma cells to TMZ. The increased level of miR‐497 in TMZ‐resistant glioma cells was concurrent with the up‐regulation of insulin‐like growth factor 1 receptor (IGF1R)/insulin receptor substrate 1 (IRS1) pathway‐related proteins, that is, IGF1R, IRS1, mammalian target of rapamycin (mTOR), and Bcl‐2. In addition, the knockdown of mTOR and Bcl‐2 reduced the tolerance of glioma cells to TMZ. Our results demonstrated that overexpression of miR‐497 is significantly correlated with TMZ resistance in glioma cells by regulating the IGF1R/IRS1 pathway. Therefore, miR‐497 may be used as a new target for treatment of chemotherapy‐resistant glioma.

Energy efficiency is one of the most important issues for High Performance Computing (HPC) today. Heterogeneous HPC platform with some energy-efficient customizable cores (as application-specific accelerators) is believed as one of the promising solutions to meet ever-increasing computing needs and to overcome power density limitations. In this paper, we focus on using customizable processor cores to optimize the typical stencil computations — the kernel of many high-performance applications. We develop a series of effective software/hardware co-optimization strategies to exploit the instruction-level and memory-computation parallelism, as well as to decrease the energy consumption. These optimizations include loop tiling, prefetching, cache customization, Single Instruction Multiple Data (SIMD), and Direct Memory Access (DMA), as well as necessary ISA extensions. Detailed tests of power-efficiency are given to evaluate the effect of all these optimizations comprehensively. The results are impressive: the combination of these optimizations has improved the application performance by 341% while the energy consumption has been decreased by 35%; a preliminary comparison with X86, GPU, and FPGA platforms also showed that the design could achieve an order of magnitude higher performance efficiency. We believe this work can help understand sources of inefficiency in general-purpose chips and can be used as a beginning to customize an energy efficient CMP for further improvement.

Stroke is the second most common cause of death worldwide, and thus, it imposes great financial burdens on both individuals and society. Mesenchymal stem cell (MSC) therapy is a promising approach for ischemic brain injury. However, MSC treatment potential is progressively reduced with age, limiting their therapeutic efficacy for brain repair post‑stroke. C1q and tumor necrosis factor‑related protein 9 (CTRP9) is a novel cytoprotective cytokine with antioxidant effects, which is highly expressed in brain tissue. The present study tested the hypothesis that CTRP9 might act as an antisenescence factor to promote the rejuvenation of aged MSCs. MSCs were isolated from the bone marrow of young (8‑weeks‑old) and aged (18‑months‑old) male C57BL/6 mice. Cell proliferation was measured by Cell Counting Kit‑8 assay and cell viability was determined by MTT assay. Gene expression levels of interleukin (IL)‑6 and IL‑10 were evaluated with reverse transcription‑quantitative polymerase chain reaction, and secretion of vascular endothelial growth factor, basic fibroblast growth factor, hepatocyte growth factor, and insulin‑like growth factor were measured by ELISA. The expression levels of proteins in the peroxisome proliferator‑activated receptor γcoactivator (PGC)‑1α/AMP‑activated protein kinase (AMPK) signaling pathway were investigated with western blotting. Oxidative stress was evaluated by detecting mitochondrial membrane potential, reactive oxygen species, superoxide dismutase activity and malondialdehyde. MSCs isolated from aged mice exhibited reduced proliferation and viability, and impaired immunoregulatory and paracrine abilities, compared with MSCs from younger mice. CTRP9 had a significant antisenescence effect in aged MSCs by activating PGC‑1α/AMPK signaling and decreasing the oxidative response. Silencing either PGC‑1α or AMPK abolished the above effects of CTRP9. These results suggest that CTRP9 may have a critical role in cellular senescence by facilitating stem cell rejuvenation, and may therefore have the potential to enhance the efficacy of stem cell therapy.

In a community cloud, multiple user groups dynamically share a massive number of data blocks. The authors present a new associative data sharing method that uses virtual disks in the MeePo cloud, a research storage cloud built at Tsinghua University. Innovations in the MeePo cloud design include big data metering, associative data sharing, data block prefetching, privileged access control (PAC), and privacy preservation. These features are improved or extended from competing features implemented in DropBox, CloudViews, and MySpace. The reported results support the effectiveness of the MeePo cloud.

// Sushil Kumar 1 , Bin Lu 2,3 , Updesh Dixit 1 , Sajjad Hossain 4 , Yongzhang Liu 2 , Jing Li 5 , Peter Hornbeck 5 , Weiming Zheng 6 , Adam G. Sowalsky 7 , Leszek Kotula 4 and Raymond B. Birge 1 1 Department of Microbiology, Biochemistry and Molecular Genetics, Cancer Center, Rutgers New Jersey Medical School, Newark, New Jersey, USA 2 Institute of Biophysics, School of Life Sciences, Wenzhou Medical University, Wenzhou, China 3 Attardi Institute of Mitochondrial Biomedicine, School of Life Sciences, Wenzhou Medical University, Wenzhou, China 4 Departments of Urology and Biochemistry and Molecular Biology, SUNY Upstate Medical University, New York, NY, USA 5 Cell Signaling Technology, Danvers, MA, USA 6 Department of Neurosurgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China 7 Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA Correspondence to: Raymond B. Birge, email: // Leszek Kotula, email: // Keywords : non-canonical Crk signaling, Abi1, glioblastoma multiformae, cell invasion Received : September 22, 2015 Accepted : September 29, 2015 Published : October 12, 2015 Abstract Crk is the prototypical member of a class of Src homology 2 (SH2) and Src homology 3 (SH3) domain-containing adaptor proteins that positively regulate cell motility via the activation of Rac1 and, in certain tumor types such as GBM, can promote cell invasion and metastasis by mechanisms that are not well understood. Here we demonstrate that Crk, via its phosphorylation at Tyr251, promotes invasive behavior of tumor cells, is a prominent feature in GBM, and correlating with aggressive glioma grade IV staging and overall poor survival outcomes. At the molecular level, Tyr251 phosphorylation of Crk is negatively regulated by Abi1, which competes for Crk binding to Abl and attenuates Abl transactivation. Together, these results show that Crk and Abi1 have reciprocal biological effects and act as a molecular rheostat to control Abl activation and cell invasion. Finally, these data suggest that Crk Tyr251 phosphorylation regulate invasive cell phenotypes and may serve as a biomarker for aggressive GBM.

Hormonal regulation of pituitary gonadotropin gene expression has been attributed to gonadotropin-releasing hormone (GnRH)-mediated stimulation of immediate early gene expression and gonadal steroid interactions with their respective nuclear receptors. A number of orphan nuclear receptors including steroidogenic factor 1, liver receptor homologue 1, dosage-sensitive sex reversal, adrenal hypoplasia critical region, on chromosome X, gene 1, and chicken ovalbumin upstream promoter-transcription factors I/II as well as the GATA family members, GATA2 and GATA4, have also been implicated in transcriptional regulation of the gonadotropin genes. We hypothesized that hormonally mediated changes in these latter transcription factors may provide an additional mechanism for mediating hormonal effects beyond the more classically appreciated pathways. In these studies, we demonstrate significant regulation of orphan nuclear receptor and GATA messenger RNA levels by GnRH, dihydrotestosterone, estradiol, and progesterone in both cultured primary pituitary cells and gonadotrope-derived cell line, LβT2. These results advance our understanding of the complex mechanisms by which GnRH and steroid hormones achieve precise regulation of anterior pituitary function.

The continued emergence of antibiotic resistant bacteria in recent years is of great concern. The search for new classes of antibacterial agents has expanded to non-traditional sources such as shellfish. An antibacterial subunit of hemoglobin (Hb-I) was purified from the mantle of Arca inflata by phosphate extraction and ion exchange chromatography. A novel antibacterial peptide, AI-hemocidin 2, derived from Hb-I, was discovered using bioinformatics analysis. It displayed antibacterial activity across a broad spectrum of microorganisms, including several Gram-positive and Gram-negative bacteria, with minimal inhibitory concentration (MIC) values ranging from 37.5 to 300 μg/mL, and it exhibited minimal hemolytic or cytotoxic activities. The antibacterial activity of AI-hemocidin 2 was thermostable (25–100 °C) and pH resistant (pH 3–10). The cellular integrity was determined by flow cytometry. AI-hemocidin 2 was capable of permeating the cellular membrane. Changes in the cell morphology were observed with a scanning electron microscope. Circular dichroism spectra suggested that AI-hemocidin 2 formed an α-helix structure in the membrane mimetic environment. The results indicated that the anti-bacterial mechanism for AI-hemocidin 2 occurred through disrupting the cell membrane. AI-hemocidin 2 might be a potential candidate for tackling antibiotic resistant bacteria.

Pituitary adenylate cyclase-activating polypeptide (PACAP) and its receptors are expressed in the hypothalamus, the gonadotrope cells of the anterior pituitary gland, and the gonads, forming an autocrine–paracrine system in these tissues. Within the pituitary, PACAP functions either alone or synergistically with gonadotropin-releasing hormone (GnRH) to stimulate gonadotropin gene expression and secretion. Our goal was to define the hormonal regulation of pituitary PACAP and PACAP receptor (PAC1) gene expression by dihydrotestosterone (DHT), estradiol, and progesterone alone or in conjunction with GnRH. Treatment of adult male rat pituitary cell cultures with DHT or progesterone augmented GnRH-mediated increase in PACAP messenger RNA (mRNA) levels, but neither had an effect when present alone. Conversely, estradiol treatment blunted PACAP gene expression but did not alter GnRH effects on PACAP expression. Expression of PACAP receptor mRNA was decreased by GnRH treatment, minimally increased by DHT treatment, but not altered by the addition of estradiol or progesterone. DHT and GnRH together blunted PACAP receptor gene expression. Taken together, these results suggest that the activity of the intrapituitary PACAP-PAC1 system is regulated via the complex interaction of gonadal steroids and hypothalamic GnRH.

Up-regulation of Notch4 was observed in the endothelial cells in the arteriovenous malformations (AVMs) in mice. However, whether Notch4 is also involved in brain AVMs in humans remains unclear. Here, we performed immunohistochemistry on normal brain vascular tissue and surgically resected brain AVMs and found that Notch4 was up-regulated in the subset of abnormal vessels of the brain AVM nidus, compared with control brain vascular tissue. Two-photon confocal images show that Notch4 was expressed not only in the endothelial but also in the smooth muscle cells of the vascular wall in brain AVMs. Western blotting shows that Notch4 was activated in brain AVMs, but not in middle cerebral artery of normal human brain, which was confirmed by immunostaining. Our findings suggest a possible contribution of Notch4 signalling to the development of brain AVMs in human.

As the CMP (Chip-Multiprocessor) scale increases' moving data to computation becomes more and more expensive in terms of latency and energy consumption. Conversely, the scheme of moving computation to data has potential to improve efficiency, especially for the irregular applications that contain graph computing, hash map or matrix multiplication. This paper proposed a near-data processing scheme for the large scale CMPs with hardware message passing support, which we called in-place computation scheme. In the in-place computation scheme, an application's critical irregular data is partitioned into on-chip memory-slices and each slice is managed by an adjacent core, as any other core intends to operate such data, it sends a message to the data owner to process it, rather than fetching the data back for computation by itself. In the paper, we described the programming model, hardware/software requirements and optimization strategies of the in-place computation scheme in details. Simulations show that, compared with conventional implementations, it can improve the performance and energy-efficiency significantly in most cases, due to following factors: 1) It greatly reduces data movements and synchronizations, 2) It decreases core-pipeline stalls and improves efficiency of memory-accesses.

Glioma is a malignant tumor that affects all kinds of people all over the world. It demonstrates remarkable infiltrative and invasive features. The high expression of interleukin-13 receptor subunit alpha-2 (IL-13Rα2) reportedly plays a pivotal role in some cancers. However, whether IL-13Rα2 contributes to glioma remains unknown. This study demonstrates that IL-13Rα2 is significantly up-regulated in human glioma tissue samples. It is also associated with late stages of disease progression and diminished survival in glioma patients. Gain- and loss-of-function studies demonstrate that IL-13Rα2 promotes the growth, migration, and invasion of glioma cells. In addition, mechanistic investigations show that IL-13Rα2 activates Scr, phosphatidylinositol 3 kinase (PI3K), Akt, and mTOR. Also, restraining Scr in glioma cells attenuates the activation of Scr/PI3K/Akt/mTOR pathway by IL-13Rα2, whereas the silencing of Scr markedly rescues the pro-invasive effect of IL-13Rα2. In conclusion, our results suggest that the high expression of IL-13Rα2 is significantly associated with the growth and metastasis of human glioma cells via the Scr/PI3K/Akt/mTOR pathway, while IL-13Rα2 may be a potential therapeutic target for glioma treatment.

Pituitary apoplexy is a rare disease caused by a sudden hemorrhage into or infarction of the pituitary gland. Its optimal management remains controversial. The aim of this study was to compare the outcomes of surgical and non-surgical treatments for pituitary apoplexy.A systematic literature search was performed of MedLine, EmBase, the Cochrane Library, and the Web of Science for articles published between January 1992 and September 2014. Studies of the outcomes in consecutive patients that compared surgical intervention with non-surgical treatment for pituitary apoplexy were included.Six studies met the inclusion criteria. As compared to the non-surgically treated patients, surgically treated patients had a significantly higher rate of recovery of ocular palsy and visual field (both P0.05). However, there was no significant difference in the recovery of visual acuity and pituitary function (P0.05) between the two groups.The findings of our study suggest that surgical intervention should be advocated for pituitary apoplexy patients with visual field defects and ocular palsy.

Communication patterns of parallel applications are important to optimize application performance and design better communication subsystems. Communication patterns can be extracted from communication traces. However, existing approaches to generate communication traces need to execute the entire parallel applications on full-scale systems that are time consuming and expensive. We propose a novel technique, called Fact, which can perform FAst Communication Traces collection for large-scale parallel applications on small-scale systems. Our idea is to reduce the original program to obtain a program slice through static analysis, and to execute the program slice to acquire the communication traces. Our idea is based on an observation that most computation and message contents in parallel applications are not relevant to their spatial and volume communication attributes, and therefore can be removed for the purpose of communication trace collection. We have implemented Fact and evaluated it with NPB programs and Sweep3D. The results show that Fact can reduce resource consumptions by two orders of magnitude in most cases.

Normal sexual development and reproductive function depend on precise temporal and quantitative expression of the pituitary gonadotropins, LH and FSH. LHβ-subunit gene expression is achieved by transcription factors acting at highly conserved and closely spaced cis-elements in the proximal 200 base pairs of the promoter. We now demonstrate that LHβ promoter activity is further regulated by the orphan nuclear receptors, chicken ovalbumin upstream promoter-transcription factors (COUP-TFI and COUP-TFII). These data establish that COUP-TFs are expressed in primary pituitary gonadotropes and two gonadotrope-derived cell lines. COUP-TFs bind to two promoter regions in the LHβ gene which overlap but are distinct from two previously defined cis-elements for another orphan nuclear receptor, steroidogenic factor-1 (SF-1). Transient transfection studies demonstrated that COUP-TFs stimulate LHβ gene promoter activity in the absence of SF-1, but blunt SF-1-mediated stimulation of gene expression in a reporter construct containing both SF-1 cis-elements (GSEs). Evaluation of constructs containing mutations or truncations in the GSEs revealed a complex pattern of activation and inhibition by COUP-TF on this promoter, suggesting multiple mechanisms by which this factor modulates LHβ gene expression. To our knowledge, these data are the first to demonstrate COUP-TF expression and function in pituitary gonadotropes.