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The development of cisplatin resistance is one of the major causes of mammary cancer treatment failure, and is associated with changes in Sox4 gene expression. To investigate the characteristic changes that occur in canine mammary gland tumor (CMGT) cells following the development of acquired cisplatin resistance, along with the relationship between these changes and the Sox4 gene. We constructed cisplatin-resistant cell line, CHMpCIS, from the cell line CHMp, which was isolated from the primary lesion of a malignant CMGT. The biological characteristics of these cells were examined by Western blot analysis, Transwell assays, and mammosphere formation assays. Compared to CHMp cells, CHMpCIS cells exhibited elevated cisplatin resistance, apoptotic escape ability, enhanced epithelial-mesenchymal transition (EMT) and cancer stem cell (CSC) features, in addition to over-activation of the Wnt/β-catenin signaling pathway and increased Sox4 protein. In CMGT cases, CMGT tissues (CMGTT) expressed higher levels of Sox4 protein and mRNA compared to adjacent tissues (CAMGTT). We found that these changes were inhibited by silencing of Sox4 expression in CHMpCIS cells. Furthermore, activation of the Wnt/β-catenin signaling pathway increased Sox4 expression levels through a positive feedback loop. These results suggested that CHMpCIS cells circumvented the damage caused by cisplatin through altering the expression of the Sox4 gene and activating the Wnt/β-catenin pathway, thereby changing the cellular biological characteristics. • A cisplatin-resistant cell line was developed for canine mammary gland tumors. • The cell line underwent a series of alterations in its biological properties. • Sox4 gene silencing reversed altered biological properties of the cell line. • Sox4 protein and mRNA expression were increased in canine mammary gland tumor tissues. [ABSTRACT FROM AUTHOR]

This article presents the formation of composite microstructures by combining two established concepts: centrifugal slip casting and the utilization of a magnetic field to control the distribution of magnetic particles. The integration of these methodologies offers the potential to create zones within the composite with distinct hardness values. The study introduces a novel method for fabricating ceramic-metal composites, with a key focus on determining the feasibility of manipulating the location of the metallic phase using a magnetic field. Through this innovative approach, the research aims to produce composite hollow cylinders with a gradient distribution of metallic particles. The relative density of the composites was 97 %. The hardness values for the samples range from 970 HV to 2700 HV, displaying variability based on the metallic phase content within the material. The compressive strength for Al 2 O 3 -Ni samples was equal to 128.92 MPa. The Al 2 O 3 grains in zone III after the sintering process have an average size of 1.27 ± 0.68 µm. The Al 2 O 3 -Ni composites indicate a smaller heat capacity of the material compared to pure Al 2 O 3 samples. • Gradient composite obtained by centrifugal slip casting with a magnetic field. • FGM composites. • Mechanical properties of Al2O3-Ni. [ABSTRACT FROM AUTHOR]

Progestin resistance is a critical factor that prevents patients with endometrial cancer (EC) from receiving conservative therapy. However, the etiology remains elusive. Cancer stem cells (CSCs) may be a contributing factor to progestin resistance in EC. These cells share similar stemness properties with embryonic stem cells that have a multipotent but differential naïve phenotype. Embryonic stem cells are programed to self-renew, to differentiate and to show plasticity toward a normal cellular phenotype in their defined microenvironment. However, whether this microenvironment may promote CSC differentiation toward a better responsive phenotype and reverse progestin resistance has not yet been clarified. In the current study, we found that progestin resistance of endometrial CSCs can be improved or reversed by using in vitro fertilization (IVF)-generated embryonic sac-derived fluid containing the embryonic microenvironment. Furthermore, suppression or reversal of progestin resistance was mediated by placental alkaline phosphatase (ALPP), a factor secreted into the embryonic microenvironment by IVF-generated blastocysts. ALPP significantly reversed progestin resistance by facilitating endometrial CSC differentiation through downregulating the stemness genes NANOG, OCT4 and SOX2. We further showed that the downregulation of NANOG, OCT4 and SOX2 by ALPP was carried out by TET1/2-mediated epigenetic modulation of the promoter regions of these genes. Such changes at the molecular level initiated endometrial CSC differentiation and promoted a better responsive endometrial cancer phenotype. In fact, their response to progestin treatment was similar to that of well-differentiated endometrioid carcinoma cells without CSCs. ALPP could be a novel target in the process to overcome progestin resistance, and such findings may provide a new approach for the conservative treatment of endometrial cancer. [ABSTRACT FROM AUTHOR]

Background& Purpose: Pandemics such as COVID-19 can lead to severe shortages in healthcare resources, requiring the development of evidence-based Crisis Standard of Care (CSC) protocols. A protocol that limits the resuscitation of out-of-hospital cardiac arrests (OHCA) to events that are more likely to result in a positive outcome can lower hospital burdens and reduce emergency medical services resources and infection risk, although it would come at the cost of lives lost that could otherwise be saved. Our primary objective was to evaluate candidate OHCA CSC protocols involving known predictors of survival and identify the protocol that results in the smallest resource burden, as measured by the number of hospitalizations required per favorable OHCA outcome achieved. Our secondary objective was to describe the effects of the CSC protocols in terms of health outcomes and other measures of resource burden.Methods: We conducted a retrospective cohort study of adult patients in the Cardiac Arrest Registry to Enhance Survival (CARES) database. Non-traumatic OHCA events from 2018 were included (n = 79,533). Candidate CSC protocols involving combinations of known predictors of good survival for OHCA were applied to the existing dataset to measure the resulting numbers of resuscitation attempts, transportations to hospital, hospital admissions, and favorable neurological outcomes. These outcomes were also assessed under Standard Care, defined as no CSC protocol applied to the data.Results: The CSC protocol with the smallest number of hospitalizations per survivor with a favorable neurological outcome was that an OHCA resuscitation should only be attempted if the arrest was witnessed by emergency medical services or the first monitored rhythm was shockable (number of hospitalizations: 2.26 [95% CI: 2.21-2.31] vs. 3.46 [95% CI: 3.39-3.53] under Standard Care). This rule resulted in significant reductions in resource utilization (46.1% of hospitalizations and 29.2% of resuscitation attempts compared to Standard Care) while still preserving 70.5% of the favorable neurological outcomes under Standard Care. For every favorable neurological outcome lost under this CSC protocol, 6.3 hospital beds were made free that could be used to treat other patients.Conclusion: In a pandemic scenario, pre-hospital CSC protocols that might not otherwise be considered have the potential to greatly improve overall survival, and this study provides an evidence-based approach towards selecting such a protocol. As this study was performed using data generated before the COVID-19 pandemic, future studies incorporating pandemic-era data will further help develop evidence-based CSC protocols. [ABSTRACT FROM AUTHOR]

• After 1 and 6 weeks, half dose photodynamic therapy reduces SRF and CMT in chronic CSC. • Choroidal thickness and CVI at 6 weeks after PDT laser will reduce in chronic CSC. • larger laser treated area has no impact on final outcome of CSC patients after PDT. Central serous chorioretinopathy (CSC) is characterized by focal serous detachment of the retina, primarily affecting the macula. Photodynamic therapy (PDT) is the best choice for treatment of chronic and recurrent patients. In this study we aim to evaluate the early effects of the half dose protocol (3 mg/m2 verteporfine) of PDT laser treatment on the micro vasculature of choroid. Among thirty-one patients (62 eyes), twenty eyes were in the control group and forty-two eyes received PDT laser treatment. Vision log MAR, CMT (central macular thickness), SRF (sub retinal fluid), BCT (baseline choroidal thickness), CVI (choroidal vascular index), and laser treated area were compared between two groups. Results show that no strong correlation was detected between the impact of laser treatment and resolution of SRF in the first week in the fovea. The mean best corrected visual acuity (BCVA) of the patients significantly increased from 20/63 at the beginning of the study, according to the Snellen chart, to 20/49 in the first week and 20/38 in the sixth week. PDT can significantly reduce SRF and CMT in 6 weeks compared to the control group. Although there was initially a small, non-statistically significant increase in choroidal thickness and CVI after 1 week, a dramatic decrease occurs after 6 weeks. Therefore, after 6 weeks of PDT laser, all the indicators such as SRF, CMT, choroidal thickness, and CVI significantly reduced. PDT laser can significantly reduce SRF and CMT at 1 and 6 weeks and choroidal thickness and CVI at 6 weeks in chronic CSC patients. Also, a larger laser treated area has no impact on the final outcome. Therefore, it seems that the mechanism of PDT in CSC disease is the recovery of choriocapillaris circulation. [ABSTRACT FROM AUTHOR]

Abstract As a result of the global decarbonisation policy, the increased penetration of RES (Renewable Energy Sources) into the electrical power system is introducing some serious technical challenges, one of the most serious being to maintain voltage profiles within acceptable/allowable limits. The unpredictable generation of a considerable share of the renewable energy can result in voltage deviations that system-network operators are not able to control effectively. At the present stage of the technology, the power electronic converters that are applied for most of the RES are used as a kind of adapter that ensures optimal RES operation and transmits the active power to the grid. But each of these converters, together with an energy source (or sink), inherently also exhibits the characteristics of a FACTS device. As a result, there should be no hindrance to applying the theories for enhanced EPS (Electric Power System) stability limits, developed for FACTS devices, also for RES converters. Many of the problems that are caused in an EPS by the large share of RES could be solved by the RES itself, also at the system level, if properly controlled and IT connected to each other and to the system operator. In this context, the present paper reviews the impact of FACTS devices on the voltage stability with methods based on the calculation of PV curves. An analytical, in-depth approach can clearly demonstrate the theoretical feasibility of FACTS devices for voltage-stability enhancement. The paper presents such an approach for CSC, SSSC, SVC and STATCOM, based on an analytical calculation of the area between the PV curves and the voltage margins in a PV diagram. The basic contribution of the paper is a theoretical explanation of the suitability of various FACTS devices for maintaining an optimal voltage profile, taking into account any variation of a device parameter. Highlights • Growth of renewable energy sources can significantly influence voltage stability. • Influence of FACTS devices on voltage stability in electric power system is shown. • A new idea named PV area criteria for voltage stability is presented. • PV area criterion estimates suitability of FACTS for voltage-stability enhancement. [ABSTRACT FROM AUTHOR]

Early studies indicated that the androgen receptor (AR) might play key roles to impact hepatocellular carcinoma (HCC) progression at different stages. Its linkage to hypoxia, a condition that occurs frequently during the HCC progression, however, remains unclear. Here we found that AR/miR-520f-3p/SOX9 signaling is involved in altering HCC cells sensitivity to the Sorafenib therapy under hypoxia via increasing the cancer stem cells (CSC) population. Mechanism dissection revealed that AR might alter the miR-520f-3p/SOX9 signaling through transcriptional regulation via binding to the androgen-response-elements (AREs) on the promoter region of miR-520f, which could then suppress SOX9 mRNA translation via targeting its 3' untranslated region (3'UTR). The in vivo mouse model with orthotopic xenografts of HCC cells also validated the in vitro data, and a human HCC sample survey confirmed the positive linkage of AR/miR-520f-3p/SOX9 signaling to the CSC population during HCC progression. Together, these preclinical findings suggest that hypoxia may increase the HCC CSC population via altering the AR/miR-520f-3p/SOX9 signaling, and targeting this newly identified signaling with the small molecule, miR-520f-3p, may help in the development of the novel therapy to better suppress the HCC progression. [ABSTRACT FROM AUTHOR]

Abstract Osteosarcoma is the most common malignant bone tumor in childhood and adolescence; however, the mechanism of this malignancy remains uncertain. Transducin (beta)-like 1 × -linked receptor 1 (TBL1XR1) plays an important role in controlling the transcriptional switch between gene activation and gene repression. However, the clinical significance and the precise biological function of TBL1XR1 in osteosarcoma remain unclear. In the present study, we revealed that TBL1XR1 is markedly upregulated in osteosarcoma cell lines and tissues, at both the mRNA and protein levels. Overexpression of TBL1XR1 dramatically enhanced, whereas inhibition of TBL1XR1 reduced, the cancer stem cell (CSC)-like phenotype and tumorigenicity of osteosarcoma cells, both in vitro and in vivo. Importantly, TBL1XR1 enhanced the tumorigenicity of osteosarcoma cells via activating STAT3 signaling and TBL1XR1 expression correlated significantly with STAT3 phosphorylation in osteosarcoma. Taken together, our results provide new evidence that TBL1XR1 overexpression induces CSCs-like phenotypes and tumorigenic capability of osteosarcoma and might represent a novel therapeutic target for its treatment. [ABSTRACT FROM AUTHOR]

Abstract Cancer stem cells (CSCs) comprise the subpopulation of tumor bulk and acquire resistant to conventional therapies and are considered as the primary tumor initiator cells. Nowadays, the tumor heterogeneity originated from CSCs, and its progenitors are accepted as a mortifying drawback in front of the cancer therapies. However, escalating knowledge gained from studies investigating the biology of CSCs will open up new frames for targeted therapies and decrease the chance of recurrence of the disease. In this review, the general understanding of CSCs and current studies were discussed briefly. Considering the latest data collected from studies of CSCs, defining the tumor heterogeneity and tumor microenvironment comprehensively will be very important to step up the cancer research. [ABSTRACT FROM AUTHOR]

High-performance fiber-reinforced cement composite (HPFRCC), an advanced construction material, has superior material properties than normal concrete. As concrete constitutive models, such as the Karagozian & Case (K&C) and continuous surface cap (CSC) models, are utilized in various numerical analyses of HPFRCC structures under static and dynamic loadings, here, calibration methods for these two constitutive models are suggested to describe the material behaviors of HPFRCC more precisely based on uniaxial and triaxial test data. Multi-element analysis of laboratory material tests is performed on the calibrated models with four different element sizes not only to examine their reliability but also to investigate their mesh-size dependency. Moreover, the differences in the performance of these models are analyzed in terms of their theoretical background, and numerical simulations are performed on the HPFRCC structures subjected to a low-velocity impact as well as near-field blast tests. By comparing the numerical and experimental results, the CSC model is found to exhibit strength for simulating crack distribution at low strain rates, whereas the K&C model shows reasonable predictions of the failure behavior of HPFRCC structures at high strain rates. [ABSTRACT FROM AUTHOR]

Many types of detectors, such as cathode strip chambers, provide a possibility to reconstruct track positions by induced strip charges. There are two main types of algebraic methods for this purpose: center of gravity methods and little-known differential methods. In the differential methods, the coordinate is calculated by a ratio whose numerator and denominator are linear combinations of differences of strip charges. Instead of strip charges, one can also use increasing functions of strip charges. Only special cases of these methods have appeared in the literature. A consistent description of these methods is not yet presented. The center of gravity methods can also be improved. The comparative performance of the general differential methods and the center of gravity methods is unknown. This paper fills this gap. Many new generalized formulas for both types of methods are derived. Their performance is studied with a simplified simulation of a detector. [ABSTRACT FROM AUTHOR]

As Comprehensive Stroke Centers (CSCs) strive to improve neuro-intervention (NIR) times, process improvements are put in place to streamline workflows. Our prior publication (VISIION) demonstrated improvements in key performance indicators (KPIs). The purpose VISIION-S was to analyze whether those results were sustainable. Consecutive Direct Arriving LVO (DALVO) and telemedicine transfer LVO (BEMI) stroke NIR cases were assessed, including subgroups of DALVO-OnHours, DALVO-OffHours, BEMI-OnHours, and BEMI-OffHours. We analyzed times for the original 6 months pre (6/10/20-1/15/21) and compared them to a 17 month post-implementation period (1/16/21- 6/25/22) to evaluate for sustainability. Mann-Whitney U was utilized. 150 NIR cases were analyzed pre (n = 47) v. post (n = 103) implementation (DALVO-OnHours 7 v. 20, DALVO-OffHours 10 v. 25, BEMI-OnHours 13 v. 20, BEMI-OffHours 17 v. 38). For Door-to-groin (DTG), improvement was noted for DALVO-OffHours 39%(157 min,96 min;p < 0.001), DALVO-ALL 25%(127 min,95 min;p = 0.006), BEMI-OffHours 46%(45 min,25 min;p = 0.023), and BEMI-ALL 40%(42 min,25 min;p = 0.005). Activation-to-groin (ATG), door-to-device (DTD), and door-to-recanalization (DTR) also showed statistical improvements. For DALVO-OffHours, there were reductions in door to CT (DTC) 80%(26 min,5 min;p < 0.001), ATG 32%(90 min,61 min;p = 0.036), DTG 39%(157 min,96 min;p < 0.001), DTD 31%(178 min,123 min;p = 0.002), and DTR 32%(197 min,135 min;p = 0.003). We noted sustainability over a 17 month period with sustained reduction in KPIs for even more NIR time interval comparisons. In the greatest opportunity subgroup (DALVO-OffHours), we noted a reduction in all 5 time interval metrics. Our sustainability finding is important to show that process improvements continued even after the immediate period, adding credibility to the results. Models such as this could be useful for other centers striving to optimize workflow and improve times. [ABSTRACT FROM AUTHOR]

Metastasis, the dissemination of cancer cells from primary tumors, represents a major hurdle in the treatment of cancer. The epithelial-mesenchymal transition (EMT) has been studied in normal mammalian development for decades, and it has been proposed as a critical mechanism during cancer progression and metastasis. EMT is tightly regulated by several internal and external cues that orchestrate the shifting from an epithelial-like phenotype into a mesenchymal phenotype, relying on a delicate balance between these two stages to promote metastatic development. EMT is thought to be induced in a subset of metastatic cancer stem cells (MCSCs), bestowing this population with the ability to spread throughout the body and contributing to therapy resistance. The EMT pathway is of increasing interest as a novel therapeutic avenue in the treatment of cancer, and could be targeted to prevent tumor cell dissemination in early stage patients or to eradicate existing metastatic cells in advanced stages. In this review, we describe the sequence of events and defining mechanisms that take place during EMT, and how these interactions drive cancer cell progression into metastasis. We summarize clinical interventions focused on targeting various aspects of EMT and their contribution to preventing cancer dissemination. [ABSTRACT FROM AUTHOR]

• CD24 and CSC: Few previous studies have summarized the relationship between CD24 and corresponding cancer stem cells. This review summarizes the reported CD24-related tumor stem cells so far. • CD24 and tumor progression: CD24, as a kind of innate immune checkpoints, not only can be mediated tumor cell immune escape, also can promote the proliferation and metastasis of tumor cells, this paper summarizes the current related studies of CD24 promote tumor progression, indicate its potential as a cancer related molecules, provides a theoretical basis for future targeted therapies. • CD24 is involved in drug resistance of tumor cells: Chemotherapy resistance is a common problem in tumor treatment. Studies have found that CD24 may promote tumor drug resistance after chemotherapy. This paper summarizes the post chemotherapy drug resistance of tumors related to CD24 for the first time. The CD24 protein is a heat-stable protein with a small core that undergoes extensive glycosylation. It is expressed on the surface of various normal cells, including lymphocytes, epithelial cells, and inflammatory cells. CD24 exerts its function by binding to different ligands. Numerous studies have demonstrated the close association of CD24 with tumor occurrence and progression. CD24 not only facilitates tumor cell proliferation, metastasis, and immune evasion but also plays a role in tumor initiation, thus, serving as a marker on the surface of cancer stem cells (CSCs). Additionally, CD24 induces drug resistance in various tumor cells following chemotherapy. To counteract the tumor-promoting effects of CD24, several treatment strategies targeting CD24 have been explored, such as the use of CD24 monoclonal antibodies (mAb) alone, the combination of CD24 and chemotoxic drugs, or the combination of these drugs with other targeted immunotherapeutic techniques. Regardless of the approach, targeting CD24 has demonstrated significant anti-tumor effects. Therefore, the present study focuses on anti-tumor therapy and provides a comprehensive review of the structure and fundamental physiological function of CD24 and its impact on tumor development, and suggests that targeting CD24 may represent an effective strategy for treating malignant tumors. [ABSTRACT FROM AUTHOR]

Background Three NPXY motifs and one FERM domain in CCM1 makes it a versatile scaffold protein for tethering the signaling components together within the CCM signaling complex (CSC). The cellular role of CCM1 protein remains inadequately expounded. Both phosphotyrosine binding (PTB) and pleckstrin homology (PH) domains were recognized as structurally related but functionally distinct domains. Methods By utilizing molecular cloning, protein binding assays and RT-qPCR to identify novel cellular partners of CCM1 and its cellular expression patterns; by screening candidate PTB/PH proteins and subsequently structurally simulation in combining with current X-ray crystallography and NMR data to defined the essential structure of PTB/PH domain for NPXY-binding and the relationship among PTB, PH and FERM domain(s). Results We identified a group of 28 novel cellular partners of CCM1, all of which contain either PTB or PH domain(s), and developed a novel classification system for these PTB/PH proteins based on their relationship with different NPXY motifs of CCM1. Our results demonstrated that CCM1 has a wide spectrum of binding to different PTB/PH proteins and perpetuates their specificity to interact with certain PTB/PH domains through selective combination of three NPXY motifs. We also demonstrated that CCM1 can be assembled into oligomers through intermolecular interaction between its F3 lobe in FERM domain and one of the three NPXY motifs. Despite being embedded in FERM domain as F3 lobe, F3 module acts as a fully functional PH domain to interact with NPXY motif. The most salient feature of the study was that both PTB and PH domains are structurally and functionally comparable, suggesting that PTB domain is likely evolved from PH domain with polymorphic structural additions at its N-terminus. Conclusions A new β1A-strand of the PTB domain was discovered and new minimum structural requirement of PTB/PH domain for NPXY motif-binding was determined. Based on our data, a novel theory of structure, function and relationship of PTB, PH and FERM domains has been proposed, which extends the importance of the NPXY-PTB/PH interaction on the CSC signaling and/or other cell receptors with great potential pointing to new therapeutic strategies. General significance The study provides new insight into the structural characteristics of PTB/PH domains, essential structural elements of PTB/PH domain required for NPXY motif-binding, and function and relationship among PTB, PH and FERM domains. [ABSTRACT FROM AUTHOR]

Tumorigenesis and tumor progression relies on the dialectics between tumor cells, the extracellular matrix and its remodelling enzymes, neighbouring cells and soluble cues. The host immune response is crucial in eliminating or promoting tumor growth and the reciprocal coevolution of tumor and immune cells, during disease progression and in response to therapy, shapes tumor fate by activating innate and adaptive mechanisms. The phenotypic plasticity is a common feature of epithelial and immune cells and epithelial-mesenchymal transition (EMT) is a dynamic process, governed by microenvironmental stimuli, critical in tumor cell shaping, increased tumor cell heterogeneity and stemness. In this review we will outline how the dysregulation of microenvironmental signaling is crucial in determining tumor plasticity and EMT, arguing how therapy resistance hinges on these dynamics. [ABSTRACT FROM AUTHOR]

The thermal performance of a novel concentric tube absorber for a conical solar collector (CSC) under forced convection was investigated by numerical and experimental analyses. In this system, the CSC assembly is mounted on dual axis tracking platform that can accurately track the sun position to get maximum concentrated solar radiation over the entire circumference of the absorber. Due to conical-shape reflector, the non-uniformity of the solar flux distribution along the absorber length is high; therefore, the non-uniform concentrated solar flux was applied to the absorber surface as boundary condition in Fluent software. To evaluate the heat transfer characteristics and performance of the system, heat loss and gain factors were derived from the novel concentric tube absorber while varying the flow rate. The concentric tube absorber of the CSC system was developed and analyzed with different operational parameters. The double-tube design provides the uniformly distributed flow and temperature symmetricity along the absorber length. The predicted results of the CSC system were in good agreement with the measured results. [ABSTRACT FROM AUTHOR]

• The proposed method can effectively eliminate the effect of desorption and pyrolysis, and the CO 2 /CO ratio produced from oxidation is about 3. • The active sites generated from coal pyrolysis strongly affect the concentrations of gas at the beginning of oxidation, but they barely influence the CO 2 /CO ratio. • The intermediates product by the oxidation of methylene linked to multiple benzene rings are the same precursor to produce CO and CO 2 , which cause the CO 2 /CO ratio is 3. The CO 2 /CO ratio produced by the reaction of active groups in coal with oxygen can truly reflect the state of coal spontaneous combustion. However, there are various paths for coal to produce CO and CO 2 , including oxidation, pyrolysis, and desorption. Gas production from coal desorption and pyrolysis influences CO and CO 2 produced from oxidation, especially pyrolysis manifests as the production of gas and active sites. For this reason, a method that can exclude the interference of gas production from desorption and pyrolysis is designed, and based on this method, the variation of CO 2 /CO ratio of coal under different pathways is studied. The active sites generated from coal pyrolysis was also investigated using pyrolytic coal, and the intrinsic causes of CO 2 /CO ratio variation were studied based on microanalysis and model compounds. The experimental results show that the proposed method can effectively eliminate the effect of desorption and pyrolysis, and the CO 2 /CO ratio produced from oxidation is about 3. The active sites generated from coal pyrolysis strongly affect the concentrations of CO and CO 2 at the beginning of oxidation, but they barely influence their ratio which is always about 3. The intermediates product by the oxidation of methylene linked to multiple benzene rings are the same precursor to produce CO and CO 2 , which are the main cause of a CO 2 /CO ratio of 3. The gradual involvement of different active groups in the reaction considerably affects the ratio of CO 2 /CO produced by oxidation path. Therefore, the low-temperature oxidation to produce CO and CO 2 can be divided into three stages, which provides theoretical support for predicting the state of coal spontaneous combustion based on the change law of CO 2 /CO ratio. [ABSTRACT FROM AUTHOR]

• HLB value of surfactant affects the promoting effect on hydrate formation. • Tween80 and AEO-9 improve the scatter of the induction time of hydrate formation and hydrate production. • The chain length affects the promoting effect of Tween series and AEO series surfactants on hydrate formation. • AEO-9 is conducive to increase hydrate production and cool storage in hydrate. Some surfactants have been observed to enhance hydrate formation kinetics, but other surfactants have no influence on improving hydrate formation. We used some anionic surfactants (MES, AOT, sodium oleate, potassium oleate) and nonionic surfactants (Tween series and AEO series)) with different HLB value to study the influence mechanism of hydrate formation in this study. The influence of surfactants on nucleation time, cool storage in hydrates and cycling stability of cyclopentene hydrate formation under quiescent conditions are studied. Anionic surfactants cannot promote cyclopentene hydrate formation in this work. While Tween80 and AEO-9 with HLB in the range of 14 ∼ 15 can effectively promote cyclopentene hydrate formation. But when the HLB values of Tween series or AEO series increase or decrease, they cannot promote cyclopentene hydrate formation. The hydrate nucleation time is the shortest and the cool storage of cyclopentene hydrates is the largest when the concentrations of Tween80 and AEO-9 are 1.0 wt% and 2.5 wt%, respectively. Adding proper amount of Tween80 or AEO-9 also can decrease the dispersion of hydrate nucleation and improve the hydrate formation/dissociation cycle stability. [ABSTRACT FROM AUTHOR]

Despite the strong association of the insulin/insulin-like growth factor (IGF) signaling (IIS) pathway with tumor initiation, recurrence, and metastasis, the mechanism by which this pathway regulates cancer progression is not well understood. Here, we report that IIS supports breast cancer stem cell (CSC) self-renewal in an IRS2-phosphatidylinositol 3-kinase (PI3K)-dependent manner that involves the activation and stabilization of MYC. IRS2-PI3K signaling enhances MYC expression through the inhibition of GSK3β activity and suppression of MYC phosphorylation on threonine 58, thus reducing proteasome-mediated degradation of MYC and sustaining active pS62-MYC function. A stable T58A-Myc mutant rescues CSC function in Irs2 −/− cells, supporting the role of this MYC stabilization in IRS2-dependent CSC regulation. These findings establish a mechanistic connection between the IIS pathway and MYC and highlight a role for IRS2-dependent signaling in breast cancer progression. [Display omitted] • Insulin/IGF signaling (IIS) supports breast cancer stem cell (CSC) self-renewal • IIS regulates stemness in an IRS2- and PI3K-dependent manner • IRS2/PI3K signaling activates and stabilizes MYC to enhance CSC function Lee et al. show that the insulin/IGF signaling pathway regulates breast cancer stem cell (CSC) function in an IRS2- and PI3K-dependent manner. This regulation involves the activation and stabilization of MYC, as shown by the ability of a stable T58A-MYC mutant to restore CSC function in IRS2 −/− cells. [ABSTRACT FROM AUTHOR]

Gemcitabine, the standard chemotherapy drug for advanced pancreatic cancer, has shown limited benefits because of profound chemoresistance. However, the mechanism involved remains unclear. Cancer stem cells exhibit great tumorigenicity and are closely correlated with drug resistance and tumor relapse. In this study, we demonstrated that certain doses of gemcitabine increased the ratios of CD24+ and CD133+ cells and the expression of stemness-associated genes such as Bmi1, Nanog, and Sox2. The enhancement of stemness after gemcitabine treatment was accompanied by increased cell migration, chemoresistance, and tumorigenesis. Moreover, we found that gemcitabine promoted the binding of phosphorylated STAT3 to the promoter of Bmi1, Nanog, and Sox2 genes. Furthermore, inhibition of STAT3 partially reversed gemcitabine-induced sphere formation, migration, chemoresistance, and tumor relapse. We also demonstrated that the activation of STAT3 and gemcitabine-enhanced stemness was NADPH oxidase (Nox)-generated, ROS-dependent, and NF-κB partially mediated the process. Together, our results suggest a pivotal role of pancreatic cancer stem cells in developing chemoresistance toward gemcitabine treatment through the Nox/ROS/NF-κB/STAT3 signaling pathway. These findings will provide new insight for identifying potential targets that can be used to sensitize pancreatic cancer cells to chemotherapy. [ABSTRACT FROM AUTHOR]

Paternal smoking is associated with infertility, birth defects and childhood cancers. Our earlier studies using cigarette smoke condensate (CSC) demonstrated several deleterious changes in male germ cells. Here, we hypothesize that chronic paternal exposure to CSC causes molecular and phenotypic changes in the sire and the offspring, respectively. In this mouse study, CSC caused DNA damage and cytotoxicity in testes via accumulation of benzo(a)pyrene (B[a]P) and cotinine. Decreased expression of growth arrest and DNA damage inducible alpha ( Gadd45a), aryl hydrocarbon receptor ( Ahr ), and cyclin-dependent kinase inhibitor 1A ( P21 ) was seen in CSC exposed testes. Apoptotic germ cell death was detected by induction of Fas, FasL, and activated caspase-3. The CSC-exposed males displayed reduction in sperm motility and fertilizing ability and sired pups with reduced body weight and crown-rump length, and smaller litter size with higher numbers of resorption. This model of CSC exposure demonstrates testicular toxicity and developmental defects in the offspring. [ABSTRACT FROM AUTHOR]

The study of cancer stem cells (CSCs) has shown that tumors are driven by a subpopulation of self-renewing CSCs that retain the capacity to engender the various differentiated cell populations that form tumors. The characterization of CSCs has indicated that CSCs are remarkably resistant to conventional radio- and chemo-therapy. Clinically, the remaining populations of CSC are responsible for metastasis and recurrence in patients with cancer, which can lead to the disease becoming chronic and incurable. Therefore, the elimination of CSCs is an important goal of cancer treatments. Furthermore, CSCs are subject to strong regulation by the surrounding microenvironment, which also impacts tumor responses. In this review, we discuss the mechanisms by which pathways that are defective in CSCs influence ultimately therapeutic and clinical outcomes. [ABSTRACT FROM AUTHOR]

Cancer stem-like cells (CSCs) are resistant to chemotherapy and highly tumorigenic, which contributes to tumor occurrence and post-treatment relapse. We developed a novel C60 fullerene-silica nanoparticle system surface-decorated with hyaluronan (HA) to target the variant CD44 overexpressed on breast CSCs. Furthermore, doxorubicin hydrochloride (DOX) and indocyanine green (ICG) can be encapsulated in the nanoparticles with ultrahigh encapsulation efficiency (>90%) and loading content (e.g., 48.5% at a drug-to-nanoparticle feeding ratio of 1:1, compared to the commonly used drug-to-nanoparticle feeding ratio of 1:20 with a drug loading content of less than 5%). As a result, the DOX and ICG-laden nanoparticles can be used as a single nanoplatform to achieve combined chemo, photodynamic, and photothermal therapy under near infrared laser irradiation for effective destruction of the breast CSCs both in vitro and in vivo , with no evident systemic toxicity. Moreover, we found the nanoparticles with a higher drug loading content (e.g., 48.5 versus 4.6%) also have significantly higher antitumor efficacy, given the same total drug dose. These results demonstrate the great potential of the multifunctional hybrid nanoparticle system for augmenting cancer therapy by eliminating the CSCs. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma progression is thought to be driven by cancer stem cells (CSCs). No clinical trial has, as yet, shown convincing long-term disease free survival results for the majority of patients in HCC. So it is important to discover new anti-cancer agents. In our study, we chose sophocarpine, which is derived from the foxtail-like sophora herb, for its efficacy to inhibit HCC including CSCs and potential mechanism study. Our results show that sophocarpine could not only reduce HCC cell viability, eliminate HCC and reverse hepatoma cells malignant phenotype, but also reduce the ratio of CSCs and inhibit the sphere formation of CSCs in vitro. In vivo, sophocarpine significantly displayed antitumor effects in subcutaneous xenograft HCC models and orthotopic transplantation tumor models. Further studies showed that sophocarpine could exert anti-tumor effects partly via downregulating the activity of the cancer stem cell related pathways and inhibiting EMT induced by TGF-β. [ABSTRACT FROM AUTHOR]

This era is called as ICT era which comprises the ICT Mediated Agriculture Extension in Rural as well as Urban areas to disseminate the ethics of information by Decision Support System (DSS), Management Information System(MIS) and Expert System(ES) by impregnating the User Interface and Knowledge Management System. So, E-Agriculture, therefore describes an emerging field focused on the enhancement of agricultural and rural development through improved information and communication process. The main Objective is to provide an Interface to farmers and consumers and to facilitate linking up of agriculture produce marketing cooperative.ITCs,E-chaupal,IT-Kiosks,Eid-party agriline,Gyandoot Project,Warana weired Village,Information Village Project of MSSRF(MS Swaminathan Research Foundation),I-kisan project of Nagarjun group of companies,Kisan Call Center(KCC),Bhoomi Project,Village Knowledge Center etc. are the recent development in e-governance mediated agriculture in India.It add value to the lives of Farmers and End-users in a Sustainable way through Knowledge Management Portals, e-kiosks, Common Service centers in grass root level [ABSTRACT FROM AUTHOR]

According to the cancer stem-like cell (CSC) hypothesis, neoplastic clones are maintained by a small fraction of cells with stem cell properties. Also, melanoma resistance to chemo- and radiotherapy is thought to be attributed to melanoma stem-like cells (MSCs). Caffeic acid phenethyl ester (CAPE) is a bioactive molecule, whose antitumor activity is approved in different tumor types. CAPE induced both apoptosis and E2F1 expression in CD133 − , but not in CD133 + melanoma subpopulations. The resistance of CD133 + melanoma subpopulation is attributed to the enhanced drug efflux mediated by ATP-binding cassette sub-family B member 5 (ABCB5), since the knockdown of ABCB5 was found to sensitize CD133 + cells to CAPE. CAPE-induced apoptosis is mediated by E2F1 as evidenced by the abrogation of apoptosis induced in response to the knockdown of E2F1. The functional analysis of E2F1 in CD133 + melanoma subpopulation demonstrated the ability of E2F1 gene transfer to trigger apoptosis of CD133 + cells and to enhance the activation of apoptosis signal-regulating kinase (ASK1), c-Jun N-terminal kinase and p38, and the DNA-binding activities of the transcription factors AP-1 and p53. Also, the induction of E2F1 expression was found to enhance the expression of the pro-apoptotic proteins Bax, Noxa and Puma, and to suppress the anti-apoptotic protein Mcl-1. Using specific pharmacological inhibitors we could demonstrate that E2F1 overcomes the chemo-resistance of MSCs/CD133 + cells by a mechanism mediated by both mitochondrial dysregulation and ER-stress-dependent pathways. In conclusion, our data addresses the mechanisms of CAPE/E2F1-induced apoptosis of chemo-resistant CD133 + melanoma subpopulation. [ABSTRACT FROM AUTHOR]

Serial controllable FACTS devices, such as a Controllable Series Compensator (CSC) and a Static Synchronous Series Compensator (SSSC), can have a significant impact on the voltage stability of an electric power system. This paper presents a mathematical derivation for the voltage dependency of a CSC and a SSSC in a single-load infinitive-bus model. The comparison of the impact of a CSC and a SSSC on the voltage stability in a five-bus system confirmed the new analytical equations. According to theoretical considerations, from the point of view of voltage controllability, each device has its own advantages, but in the case of low voltages or low loads a SSSC is superior to a CSC. [ABSTRACT FROM AUTHOR]

We previously showed that the Arf1-mediated lipolysis pathway sustains stem cells and cancer stem cells (CSCs); its ablation resulted in necrosis of stem cells and CSCs, which further triggers a systemic antitumor immune response. Here we show that knocking down Arf1 in intestinal stem cells (ISCs) causes metabolic stress, which promotes the expression and translocation of ISC-produced damage-associated molecular patterns (DAMPs; Pretaporter [Prtp] and calreticulin [Calr]). DAMPs regulate macroglobulin complement-related (Mcr) expression and secretion. The secreted Mcr influences the expression and localization of enterocyte (EC)-produced Draper (Drpr) and LRP1 receptors (pattern recognition receptors [PRRs]) to activate autophagy in ECs for ATP production. The secreted ATP possibly feeds back to kill ISCs by activating inflammasome-like pyroptosis. We identify an evolutionarily conserved pathway that sustains stem cells and CSCs, and its ablation results in an immunogenic cascade that promotes death of stem cells and CSCs as well as antitumor immunity. [Display omitted] • Knocking down Arf1 results in stem cell death through a sterile immunity-like pathway • Knocking down Arf1 in intestinal stem cells induces expression of Prtp and Calr • Prtp and Calr induce expression of Drpr and LRP1 in ECs via Mcr to produce ATP • ATP kills ISCs by activating inflammasome-like pyroptosis Aggarwal et al. show that disruption of Arf1-mediated lipolysis results in stem cell death through a sterile immunity-like pathway in adult Drosophila. They identify an evolutionarily conserved pathway that specifically sustains stem cells and cancer stem cells (CSCs), and its ablation results in an immunogenic cascade that promotes death of stem cells and CSCs as well as antitumor immunity. [ABSTRACT FROM AUTHOR]

CD44 is a hyaluronan binding cell surface signal transducing receptor that influences motility, cell survival and proliferation as well as the formation of tumor microenvironment. CD44 contains two variable regions encoded by variable exons. Alternative splicing, which is often deregulated in cancer, can produce various isoforms of CD44 with properties that may have different tissue specific effects and therefore even diverse effects on cancer progression. This review summarizes and puts together all major regulators of alternative splicing of CD44 in cancer that have been documented so far and that have an experimentally proved effect on CD44 isoform switching. It is important to better understand the mechanisms of alternative splicing of CD44, where all the variability of CD44 originates, to be able to explain the isoform switching and occurrence of variant isoforms of CD44 (CD44v) in cancer. [ABSTRACT FROM AUTHOR]

E-District Portal is one of the popular Information and Communication Technology (ICT) initiatives of Government of India to manage district administration in more effective way in place of manual system in West Bengal with the others state of India. Author(s) main objective is to explore different important factors in pilot district of West Bengal those are directly involved with the common citizen's satisfaction and contributing to citizen's behavioral change towards acceptance of e-District project, which could be a lesson learn to take more corrective action to roll out e-District services in future. A well set up questionnaires have been developed over the different related observables and conducted survey among the common citizen's randomly to get their feedback. In this study, quantitative methodology has been adopted to analyze the various observables. The Principal Component method and VARIMAX rotation options of Factor Analysis has been utilized to reduce the set of observables in order to identify key factors. The Kaiser-Meyer-Olkin (KMO) value also has been measured to check the adequacy of the collected dataset for factor analysis. [ABSTRACT FROM AUTHOR]

Background: Treating acute ischemic stroke (AIS) within 4.5 hours and door-to-needle time of less than 60 minutes may optimize recovery. It is unknown if onset to Primary Stroke Center (PSC) time goals affect outcome. The purpose of this study was to examine effects of symptom onset to PSC time goals on outcome. Methods: Analysis included prospectively collected data from the University of California San Diego Specialized Program of Treatment Research in Acute Stroke. All AIS patients treated with intravenous recombinant tissue plasminogen activator were included if treated within 270 minutes, and 90-day modified Rankin Scale (mRS) score was known. Primary outcome of the 90-day mRS was analyzed using multivariable logistic regression. Good outcome was defined as a 90-day mRS score of 0-2. Variables assessed were time from onset to arrival, stroke code, neurologic exam, imaging, laboratories, treatment decision, and treatment (by quartiles). Results: Two hundred ninety-one patients were included (49.8% female, mean age 70.6 ± 16.1, median National Institutes of Health Stroke Scale 10, SD = 8.5). Good outcome occurred in 45% of patients. Significant baseline differences included HTN (P ≤ .001), A fib (P ≤ .001), prestroke mRS (P < .001), and Hispanic ethnicity (P = .011). Comparing good with poor outcome groups: mean onset to arrival was 70.6 min versus 62.5 min (P = .129) and mean onset to treatment was 140.1 min versus 134.9 min (P = .118). Controlling for prespecified covariates, no PSC time goals were significant predictors of the 90-day outcome. Conclusions: In our Comprehensive Stroke Center (CSC), onset to PSC time goals were not significant predictors of the 90-day outcome. Expedited care processes in CSC may compensate for differences in outcome. These results should be validated in a larger cohort and in PSCs versus CSCs. [Copyright &y& Elsevier]

Abstract: Three-dimensional (3D) tissue culture platforms that are capable of mimicking in vivo microenvironments to replicate physiological conditions are vital tools in a wide range of cellular and clinical studies. Here, learning from the nature of cilia in lungs – clearing mucus and pathogens from the airway – we develop a 3D culture approach via flexible and kinetic copolymer-based chains (nano-cilia) for diminishing cell-to-substrate adhesion. Multicellular spheroids or colonies were tested for 3–7 days in a microenvironment consisting of generated cells with properties of putative cancer stem cells (CSCs). The dynamic and reversible regulation of epithelial–mesenchymal transition (EMT) was examined in spheroids passaged and cultured in copolymer-coated dishes. The expression of CSC markers, including CD44, CD133, and ABCG2, and hypoxia signature, HIF-1α, was significantly upregulated compared to that without the nano-cilia. In addition, these spheroids exhibited chemotherapeutic resistance in vitro and acquired enhanced metastatic propensity, as verified from microfluidic chemotaxis assay designed to replicate in vivo-like metastasis. The biomimetic nano-cilia approach and microfluidic device may offer new opportunities to establish a rapid and cost-effective platform for the study of anti-cancer therapeutics and CSCs. [Copyright &y& Elsevier]

Abstract: Muscle-invasive bladder cancer is associated with a high frequency of metastasis, and fewer therapies substantially prolong survival. Silibinin, a nontoxic natural flavonoid, has been shown to exhibit pleiotropic anticancer effects in many cancer types, including bladder cancer. Our and other previous studies have demonstrated that silibinin induced apoptosis and inhibited proliferation of bladder cancer cells, whether silibinin could suppress bladder cancer metastasis has not been elucidated. In the present study, we utilized a novel highly metastatic T24-L cell model, and found that silibinin treatment not only resulted in the suppression of cell migration and invasion in vitro, but also decreased bladder cancer lung metastasis and prolonged animal survival in vivo. Mechanistically, silibinin could inhibit glycogen synthase kinase-3β (GSK3β) phosphorylation, β-catenin nuclear translocation and transactivation, and ZEB1 gene transcription that subsequently regulated the expression of cytokeratins, vimentin and matrix metalloproteinase-2 (MMP2) to reverse epithelial–mesenchymal transition (EMT). On the other hand, silibinin inhibited ZEB1 expression and then suppressed the properties of cancer stem cells (CSCs), which were evidenced as decreased spheroid colony formation, side population, and the expression of stem cell factor CD44. Overall, this study reveals a novel mechanism for silibinin targeting bladder cancer metastasis, in which inactivation of β-catenin/ZEB1 signaling by silibinin leads to dual-block of EMT and stemness. [Copyright &y& Elsevier]

• Half-dose photodynamic therapy (HD-PDT) has been widely used for central serous chorioretinopathy (CSC) with good anatomical results, however, long-term functional outcomes after this treatment remain uncertain. • Our multimodal longitudinal analysis of CSC patients after HD-PDT shows that the visual acuity and central macular thickness significant improvement persist in the long run. • However, this sustained improvement is not paired by a sustained improvement in macular sensitivity and electrical response, which seems to decline after the first 12 to 24 months. • This long-term functional deterioration might result from the disease itself and not directly from the treatment. Half-dose photodynamic therapy (HD-PDT) has been widely used for central serous chorioretinopathy (CSC) with good anatomical results. However, long-term functional outcomes after this treatment remain uncertain. This study aimed a longitudinal multimodal macular assessment, correlating functional and anatomical outcomes. This is a retrospective study performed in a tertiary referral center including 111 eyes from 95 CSC patients. Data on best corrected visual acuity (BCVA), central macular thickness (CMT), central retinal sensitivity (CRS) using microperimetry (MP) and multifocal electroretinography (mfERG) at baseline and 3, 6, 12, 18, 24, 36, 48 and 60 months after treatment were registered. A correlation analysis was performed. Mean follow-up was 34.5 ± 26.3 months. A significant improvement in BCVA and CMT was registered in all the visits. CRS significantly improved until 24 months (p < 0.001 at 12 months, p < 0.05 at 24 months), worsening afterwards. The mfERG amplitude of N1 and P1 waves significantly improved in the first 12 months, aggravating afterwards. The implicit time improved until 24 months, deteriorating after 48 months. This long-term decline was also described in some inactive untreated fellow eyes A multimodal longitudinal analysis of CSC patients after HD-PDT shows that, after the first 12 to 24 months, the significant sustained improvement in BCVA and CMT is not paired by a sustained improvement in macular sensitivity or electrical response. This long-term functional deterioration might result from the disease itself and not directly from the treatment. [ABSTRACT FROM AUTHOR]

Abstract: Hypoxia is one of the fundamental biological phenomena that are intricately associated with the development and aggressiveness of a variety of solid tumors. Hypoxia-inducible factors (HIF) function as a master transcription factor, which regulates hypoxia responsive genes and has been recognized to play critical roles in tumor invasion, metastasis, and chemo-radiation resistance, and contributes to increased cell proliferation, survival, angiogenesis and metastasis. Therefore, tumor hypoxia with deregulated expression of HIF and its biological consequence lead to poor prognosis of patients diagnosed with solid tumors, resulting in higher mortality, suggesting that understanding of the molecular relationship of hypoxia with other cellular features of tumor aggressiveness would be invaluable for developing newer targeted therapy for solid tumors. It has been well recognized that cancer stem cells (CSCs) and epithelial-to-mesenchymal transition (EMT) phenotypic cells are associated with therapeutic resistance and contribute to aggressive tumor growth, invasion, metastasis and believed to be the cause of tumor recurrence. Interestingly, hypoxia and HIF signaling pathway are known to play an important role in the regulation and sustenance of CSCs and EMT phenotype. However, the molecular relationship between HIF signaling pathway with the biology of CSCs and EMT remains unclear although NF-κB, PI3K/Akt/mTOR, Notch, Wnt/β-catenin, and Hedgehog signaling pathways have been recognized as important regulators of CSCs and EMT. In this article, we will discuss the state of our knowledge on the role of HIF-hypoxia signaling pathway and its kinship with CSCs and EMT within the tumor microenvironment. We will also discuss the potential role of hypoxia-induced microRNAs (miRNAs) in tumor development and aggressiveness, and finally discuss the potential effects of nutraceuticals on the biology of CSCs and EMT in the context of tumor hypoxia. [Copyright &y& Elsevier]

Abstract: Cigarette smoke contains numerous compounds that cause oxidative stress and alter gene expression in many tissues, and cigarette smoking is correlated with male infertility. To identify mechanisms by which this occurs, we evaluated expression of antioxidant genes in mouse spermatocytes in response to cigarette smoke condensate (CSC). CSC exposure led to oxidative stress and dose-dependent up-regulation of Hsp90aa1, Ahr, Arnt, Sod1, Sod2, and Cyp1a1 expression in a mouse spermatocyte cell line. An antagonist of the aryl hydrocarbon receptor (AHR) abrogated several CSC-mediated changes in mRNA and protein levels. Consistent with these results, spermatocytes isolated by laser-capture microdissection from CSC-treated mice showed increased expression of several antioxidant genes. In vivo exposure to CSC was genotoxic to spermatocytes, resulting in apoptosis and disruptions to the seminiferous tubules. Our in vivo and in vitro data indicate that CSC-mediated damage to murine spermatocytes is AHR-dependent and is mediated by oxidative stress. [Copyright &y& Elsevier]

Summary: Although chronic psychosocial stress is often accompanied by changes in basal hypothalamo-pituitary-adrenal (HPA) axis activity, it is vital for a chronically-stressed organism to mount adequate glucocorticoid (GC) responses when exposed to acute challenges. The main aim of the present study was to test whether this is true or not for the chronic subordinate colony housing (CSC, 19 days) paradigm, an established and clinically relevant mouse model of chronic psychosocial stress. As shown previously, CSC mice are characterized by unaffected morning and decreased evening plasma corticosterone (CORT) levels despite enlarged adrenals, suggesting a maladaptive breakdown of adrenal functioning. Plasma CORT levels, determined by repeated blood sampling via jugular vein catheters, as well as relative right adrenal CORT content were increased in CSC compared with single-housed control (SHC) mice in response to acute elevated platform (EPF, 5min) exposure. However, in vitro stimulation of adrenal explants with physiological and pharmacological doses of ACTH revealed an attenuated responsiveness of both the left and right adrenal glands following CSC, despite mRNA and/or protein expression of melanocortin 2 receptor (Mc2r), Mc2r accessory protein (MRAP), and key enzymes of steroidogenesis were not down-regulated. Taken together, we show that chronic psychosocial stressor exposure impairs in vitro ACTH responsiveness of both the left and right adrenal glands, whereas it increases adrenal responsiveness to an acute heterotypic stressor in vivo. This suggests that an additional factor present during acute stressor exposure in vivo rescues left and right adrenal ACTH sensitivity, or itself acts as CORT secretagogue in chronically stressed CSC mice. [Copyright &y& Elsevier]

Abstract: Constrained groove pressing (CGP) process is one of the favorable severe plastic deformation methods to fabricate ultra-fine grain sheet materials. In this paper, commercial pure aluminum sheet was subjected to CGP process using conventional and covered sheet casing (CSC) methods. Three dies with different groove lengths and angles (t =1mm and θ =45°; t =1.8mm and θ =45°; t =1mm and θ =53°) were designed and manufactured. Mechanical properties including strength, elongation to failure and hardness are obtained and discussed. The influences of these two methods and die groove angle on specimen strain behavior and required force value are analyzed by the finite element method in plain strain condition. The results show that the CSC method leads to better hardness distribution, uniform strain dispersal and finer surface quality as compared to conventional method. Moreover, the new method is a good candidate for substituting the conventional CGP process. [Copyright &y& Elsevier]

Summary: Chronic stress, in particular chronic psychosocial stress, is a risk factor in the aetiology of various psychopathologies including anxiety- and depression-related disorders. Therefore, recent studies have focussed on the development of social-stress paradigms, which are believed to be more relevant to the human situation than non-social-stress paradigms. The majority of these paradigms have been reported to increase both anxiety- and depression-related behaviour in rats or mice. However, in order to dissect the mechanisms underlying anxiety or depression, animal models are needed, which specifically induce one, or the other, phenotype. Here, we study both short- (1d after stressor termination) and long-term (4d or 7d after stressor termination) behavioural and physiological consequences of two well-validated chronic psychosocial stress models: social-defeat/overcrowding (SD/OC) and chronic subordinate colony housing (CSC). We demonstrate that SD/OC and CSC result in different physiological alterations: SD/OC more strongly affecting body-weight development, whereas CSC more strongly affects adrenal and pituitary morphology. Both stressors were shown to flatten circadian locomotor activity immediately after stress termination, which normalized 7d later in SD/OC group but reversed to hyperactivity during the dark phase in the CSC group. Importantly, neither stress paradigm resulted in an increase in depression-related behaviour as assessed using the forced swim test, tail suspension test and saccharin preference test at any time-point. However, both stress paradigms lead to an anxiogenic phenotype; albeit with different temporal profiles and not towards a novel con-specific (social anxiety). CSC exposure elevates anxiety-related behaviour immediately after stressor termination, which lasts for at least 1wk. In contrast, the anxiogenic phenotype only develops 1wk after SD/OC termination. In conclusion, both models are unique for uncovering the molecular underpinnings of anxiety-related behaviour without conflicting depression-based alterations. [ABSTRACT FROM AUTHOR]

Abstract: l-DOPA remains the gold-standard treatment for Parkinson''s disease (PD). However, the emergence of l-DOPA-induced dyskinesia (LID) and motor fluctuations represents a major clinical problem in PD. The selective localization of adenosine A2A receptors to the basal ganglia and specifically to the indirect output pathway appear to be crucial both in the pathogenesis of PD and in the development of LID. In this study, we investigated the effects of a 3-week treatment with l-DOPA (50mg/kg/day+benserazide 12.5mg/kg/day, twice daily, i.p.) alone or combined with adenosine A2A receptor antagonist 8-(3-Chlorostyryl)caffeine (CSC) (5mg/kg/day, twice daily), on the rotational motor response duration, abnormal involuntary movements (AIM) and the associated striatal expression of adenosine A2A receptor in rats with a nigrostriatal lesion. CSC treatment ameliorated the shortening of the rotational motor response duration, partly attenuated dyskinesia and reduced striatal expression of adenosine A2A receptor induced by l-DOPA. Electron microscopy technique results showed that the postsynapse density depth was much thicker, synapse cleft width was narrower and the ratio of perforated synapses significantly increased in the l-DOPA-treated rats, while systemic coadministration of CSC with l-DOPA attenuated the overactivity of corticostriatal synaptic ultrastructure and function induced by l-DOPA. In conclusion, CSC by means of its dual action as A2A receptor antagonist and MAO-B inhibitor ameliorated the changed behavior, expression of adenosine A2A receptor and postsynaptic effects, observed in the 6-OHDA-lesioned rats, pointing out to its potential benefit for the treatment of LID. [Copyright &y& Elsevier]

Abstract: This note contains a description of the muon system constructed for the Compact Muon Solenoid experiment at LHC. A description of all three different subdetectors composing the spectrometer (Drift Tube Chambers, Cathode Strip Chambers and Resistive Plate Chambers), their construction and commissioning will be reviewed, together with some results obtained in different campaigns of cosmic data taking. [Copyright &y& Elsevier]

Abstract: In this study, the cytoprotective effects of caffeine (CAF) and 8-(3-chlorostyryl)-caffeine (CSC), A2A receptor antagonists, were tested against 6-OHDA-induced cytotoxicity, in rat mesencephalic cells. Both drugs significantly increased the number of viable cells, after their exposure to 6-OHDA, as measured by the MTT assay. While nitrite levels in the cells were drastically increased by 6-OHDA, their concentrations were brought toward normality after CAF or CSC, indicating that both drugs block 6-OHDA-induced oxidative stress which leads to free radicals generation. A complete blockade of 6-OHDA-induced lipid peroxidation, considered as a major source of DNA damage, was observed after cells treatment with CAF or CSC. 6-OHDA decreased the number of normal cells while increasing the number of apoptotic cells. In the CAF plus 6-OHDA group, a significant recover in the number of viable cells and a decrease in the number of apoptotic cells were seen, as compared to the group treated with 6-OHDA alone. A similar effect was observed after cells exposure to CSC in the presence of 6-OHDA. Unexpectedly, while a significant lower number of activated microglia was observed after cells exposure to CAF plus 6-OHDA, this was not the case after cells exposure to CSC under the same conditions. While CAF lowered the percentage of reactive astrocytes increased by 6-OHDA, CSC presented no effect. The effects of these drugs were also examined on the releases of myeloperoxidase (MPO), an inflammatory marker, and lactate dehydrogenase (LDH), a marker for cytotoxicity, in human neutrophils, in vitro. CSC and CAF (0.1, 1 and 10μg/ml) produced inhibitions of the MPO release from PMA-stimulated cells, ranging from 45 to 83%. In addition, CSC and CAF (5, 50 and 100μg/ml) did not show any cytotoxicity in the range of concentrations used, as determined by the LDH assay. All together, our results showed a strong neuroptrotection afforded by caffeine or CSC, on rat mesencephalic cells exposed to 6-OHDA. Furthermore, CSC and caffeine actions, inhibiting MPO as well as LDH releases, would contribute to their possible benefit in the treatment of neurodegenerative diseases, including DP. These effects are partially due to the ability of these A2A antagonists to decrease the cells free radicals production and oxidative stress, that are major components of 6-OHDA-induced cytotoxicity. [Copyright &y& Elsevier]

Antimicrobial surfaces are currently being studied as an aid to reduce transmission of pathogens leading to healthcare-associated infections (HAIs). Among the most harmful and costly pathogens that cause HAIs is meticillin-resistant Staphylococcus aureus (MRSA). Currently available and previously investigated antimicrobial surface technologies that are effective against MRSA (e.g. copper alloy surfaces) take 30min to several hours to achieve significant reduction. This article presents a new antimicrobial surface technology made of compressed sodium chloride that reduces MRSA 20-30 times faster than copper alloy surfaces. [ABSTRACT FROM AUTHOR]

Abstract: Several carbon–silica composite materials have been synthesized from MCM-41 and furfuryl alcohol and characterized via X-ray diffraction, nitrogen adsorption, and thermal gravimetric analysis. The materials are completely nanoporous, have high surface areas, and pore size distributions centered near 12Å. In order to determine the sensitivity of the resulting carbon to synthesis conditions, materials were prepared using different furfuryl alcohol solvents and were polymerized and carbonized at either atmospheric pressure, 5atm, or under vacuum. As a control, silica gel was impregnated with furfuryl alcohol, which was polymerized and carbonized. The surface areas of the materials are affected by both solvent selection and the pressure at which carbonization takes place. The results are consistent with work done by others, which document furfuryl alcohol spontaneously generating nanoporosity when carbonized. The high surface area and narrow pore size distribution of these materials provides evidence that carbon–silica composites may be suitable candidates for novel separations. [Copyright &y& Elsevier]

One of the hallmarks of a cancer cell is the ability for indefinite proliferation leading to the immortalization of the cell. Activation of several signaling pathways leads to the immortalization of cancer cells via the reactivation of enzyme telomerase (hTERT). hTERT is active in germ cells, stem cells and also cancer cells. An earlier report from our lab suggests that SMAR1, a tumor suppressor protein, is significantly downregulated in the higher grades of colorectal cancers. Our study identifies SMAR1 as a transcriptional repressor of hTERT. We find that SMAR1 interacts with HDAC1/mSin3a co-repressor complex at the hTERT promoter and brings about HDAC1-mediated transcriptional repression of the promoter. Most solid tumors including colorectal cancer reactivate hTERT expression as it confers several advantages to the cancer cells like increased proliferation and angiogenesis. One of these non-canonical functions of hTERT is inducing the pool of cancer stem cell population. We find that in the CD133HighCD44High cancer stem cells population, SMAR1 expression is highly diminished leading to elevated hTERT expression. We also find that knockdown of SMAR1 promotes total CD133+CD44+ population and impart enhanced sphere-forming ability to the colorectal cancer cells. SMAR1 also inhibits invasion and metastasis in colorectal cancer cell lines via repression of hTERT. Our study provides evidence that downregulation of SMAR1 causes activation of hTERT leading to an increase in the cancer stem cell phenotype in colorectal cancer cells. [ABSTRACT FROM AUTHOR]

Abstract: Environmental and occupational toxicants may induce pulmonary inflammation. Chronic inflammation has been linked to several human diseases and also to initiation and promotion of cancer. Generation of reactive oxygen/nitrogen species (ROS/RNS), secretion of cytokines, chemokines and pro-angiogenic factors are believed to play a role. Interleukin IL-1β, encoded by the IL1B gene, is a key cytokine produced and secreted by many cell types after activation by biological or chemical agents. Several polymorphisms in the IL1B gene have been identified, and some are associated with increased risk for lung cancer. Especially, the IL1B −31T/C polymorphism has received attention. We have investigated the effect of the lung carcinogens cigarette-smoke condensate (CSC) and benzo[a]pyrene (B[a]P) on the promoters of the IL1B gene varying only at the site of the −31T/C polymorphism. The promoter fragments containing either C or T were cloned in luciferase reporter vectors and transfected into human lung epithelial NCI-H2009 cells. The results show that treatment of the transfected cells with CSC or B[a]P induced the promoter significantly above the control level. Interestingly, the promoter with the wild-type allele T in position −31 showed the stronger induction when compared with the promoter with variant allele C in this position. Bioinformatics and DNA-protein analysis indicated the presence of a novel transcription-factor binding site and the formation of protein complexes at the C promoter. [Copyright &y& Elsevier]

Abstract: In this note, we propose an algorithm for fast and efficient track segment reconstruction in Cathode Strip Chambers used by the Compact Muon Solenoid experiment for muon detection in the forward direction. The algorithm is designed to be CPU-efficient and is targeted for High Level Trigger (HLT, online reconstructed events pre-selection) purposes. The segment finding efficiency and the spatial resolution attainable with the proposed algorithm as well as the required CPU time are benchmarked using the Cosmics Muon data and found to surpass the HLT requirements. [Copyright &y& Elsevier]

Abstract: The present work showed the effects of 8-(-3-chlorostyryl)-caffeine (CSC), an A2A receptors antagonist and MAO B inhibitor, on behavior and biochemical alterations in 6-OHDA-lesioned rats. Male Wistar rats (280 g) were injected with CSC (1 and 5 mg/kg, i.p.) alone or combined with l-DOPA (50 mg/kg+benserazide 12.5 mg/kg), starting 6 days after the striatal 6-OHDA lesions, and once daily for the next 7 days. Fourteen days after the 6-OHDA lesion (and 24 h after CSC or vehicle), the number of net body rotations/h (after the apomorphine challenge) was recorded and, at the next day, animals were sacrificed. The ipsilateral striatum was used for HPLC measurements of monoamines and amino acids or for determination of nitrite contents and lipid peroxidation. Results showed that the increase in body rotation, induced by the 6-OHDA lesion, after the apomorphine challenge, was significantly and dose-dependently reversed by CSC. Furthermore, the decreased striatal levels of DA and metabolites, in the 6-OHDA-lesioned rats, were reversed after CSC treatment, and these effects were potentiated after the combination with l-DOPA. Similar results were observed with NE, 5-HT and 5-HIAA. While glutamate and GABA were increased in the 6-OHDA-lesioned group, CSC alone or mainly combined with l-DOPA reversed these alterations. In addition, the CSC treatment of 6-OHDA-lesioned rats reversed the increased nitrite formation and lipid peroxidation induced by 6-OHDA. In conclusion, CSC by means of its dual action as A2A antagonist and MAO-B inhibitor reversed behavior and biochemical alterations, observed in the 6-OHDA-lesioned rats, pointing out to its potential benefit for the treatment of PD. [Copyright &y& Elsevier]

Abstract: Compact Muon Solenoid (CMS) is one of the detectors designed to study very high-energy proton–proton interactions at the Large Hadron Collider (LHC) starting from 2007. Muons produced from these collisions will provide clean signatures for many of the interesting processes to be studied at the LHC. CMS has put great emphasis on developing a highly efficient muon system. The system has been designed to identify, reconstruct and measure muons with high efficiency and accuracy. Three different detectors have been chosen: Drift Tubes (DT), Cathode Strips Chambers (CSC) and resistive plate chambers (RPC). In this paper, we will describe the main features of each of these detectors and the system. [Copyright &y& Elsevier]