bluuebunny/crossref_metadata_2025 huggingface dataset:
Characterization of Complexes Synthesized Using Schiff Base Ligands and Their Screening for Toxicity Two Fungal and One Bacterial Species on Rice Pathogens
Authors: Mangamamba T. , Ganorkar M. C. , Swarnabala G.
Published: September 2014

Coordination complexes with metal ions Cu(II), Ni(II), Co(II), Fe(III), Mn(II), Cr(III), and VO(II) with six ligands formed by condensation products using azides and aldehydes or ketones are characterized. Both the ligands and the complexes synthesized are characterized by C, H, N, Cl and metal analyses, IR, UV-Vis, TGA, and magnetic susceptibility for tentative structure proposal. Several of them are screened for their toxicity (i.e., physiological activity) against fungal speciesRhizoctonia solaniandAcrocylindrium oryzaeand a bacterium,Xanthomonas oryzaeon rice pathogens. The study shows that the observed physiological activity is enhanced for the metal complexes as compared to the simple metal salts or ligands, except in the case of L3 or HAEP ligand, where the free –OH and –NH2groups on the ligand seemed to have inhibited the activity. It is also observed that the order of activity has a dependence on the increased atomic weight of the metal ion in use. In some cases, especially the VO(II) complexes, they are found to be better than the standards in use, both for the fungicides and for the bactericide.
Password-Only Authenticated Three-Party Key Exchange Proven Secure against Insider Dictionary Attacks
Authors: Nam Junghyun , Choo Kim-Kwang Raymond , Paik Juryon , Won Dongho
Published: September 2014

While a number of protocols for password-only authenticated key exchange (PAKE) in the 3-party setting have been proposed, it still remains a challenging task to prove the security of a 3-party PAKE protocol against insider dictionary attacks. To the best of our knowledge, there is no 3-party PAKE protocol that carries a formal proof, or even definition, of security against insider dictionary attacks. In this paper, we present the first 3-party PAKE protocol proven secure against both online and offline dictionary attacks as well as insider and outsider dictionary attacks. Our construct can be viewed as a protocol compiler that transforms any 2-party PAKE protocol into a 3-party PAKE protocol with 2 additional rounds of communication. We also present a simple and intuitive approach of formally modelling dictionary attacks in the password-only 3-party setting, which significantly reduces the complexity of proving the security of 3-party PAKE protocols against dictionary attacks. In addition, we investigate the security of the well-known 3-party PAKE protocol, called GPAKE, due to Abdalla et al. (2005, 2006), and demonstrate that the security of GPAKE against online dictionary attacks depends heavily on the composition of its two building blocks, namely a 2-party PAKE protocol and a 3-party key distribution protocol.
Chondroitin Sulfate Proteoglycans in the Nervous System: Inhibitors to Repair
Authors: Siebert Justin R. , Conta Steencken Amanda , Osterhout Donna J.
Published: September 2014

Chondroitin sulfate proteoglycans (CSPGs) are widely expressed in the normal central nervous system, serving as guidance cues during development and modulating synaptic connections in the adult. With injury or disease, an increase in CSPG expression is commonly observed close to lesioned areas. However, these CSPG deposits form a substantial barrier to regeneration and are largely responsible for the inability to repair damage in the brain and spinal cord. This review discusses the role of CSPGs as inhibitors, the role of inflammation in stimulating CSPG expression near site of injury, and therapeutic strategies for overcoming the inhibitory effects of CSPGs and creating an environment conducive to nerve regeneration.
Obesity Related Alterations in Plasma Cytokines and Metabolic Hormones in Chimpanzees
Authors: Nehete Pramod , Magden Elizabeth R. , Nehete Bharti , Hanley Patrick W. , Abee Christian R.
Published: September 2014

Obesity is characterized by chronic low-grade inflammation and serves as a major risk factor for hypertension, coronary artery disease, dyslipidemias, and type-2 diabetes. The purpose of this study was to examine changes in metabolic hormones, inflammatory cytokines, and immune function, in lean, overweight, and obese chimpanzees in a controlled environment. We observed increased plasma circulating levels of proinflammatory TH-1 cytokines, Interferon gamma, interleukin-6, interleukin-12p40, tumor necrosis factor, soluble CD40 ligand, and Interleukin-1βand anti-inflammatory TH-2 cytokines, Interleukin-4, Interleukin-RA, Interleukin-10, and Interleukin-13 in overweight and obese chimpanzees. We also observed increased levels of metabolic hormones glucagon-like-peptide-1, glucagon, connecting peptide, insulin, pancreatic peptide YY3–36, and leptin in the plasma of overweight and obese chimpanzees. Chemokine, eotaxin, fractalkine, and monocyte chemoattractant protein-1 were higher in lean compared to obese chimpanzees, while chemokine ligand 8 increased in plasma of obese chimpanzees. We also observed an obesity-related effect on immune function as demonstrated by lower mitogen induced proliferation, and natural killer activity and higher production of IFN-γby PBMC in Elispot assay, These findings suggest that lean, overweight, and obese chimpanzees share circulating inflammatory cytokines and metabolic hormone levels with humans and that chimpanzees can serve as a useful animal model for human studies.
Electrical Switching in Thin Film Structures Based on Molybdenum Oxides
Authors: Pergament A. L. , Malinenko V. P. , Aleshina L. A. , Kazakova E. L. , Kuldin N. A.
Published: September 2014

We report on the experimental study of electrical instabilities in thin film structures on the basis of molybdenum oxides. Thin films of molybdenum oxide are obtained by thermal vacuum evaporation and anodic oxidation. The results of X-ray structural analysis, investigation of optical and electrical properties, are presented. It is shown that the initial vacuum-deposited oxide represents amorphous MoO3. In the MOM (metal-oxide-metal) structures with Mo oxide films obtained by the two methods, the effect of electrical switching with an S-shaped current-voltage characteristic is found. We put forward a hypothesis according to which the switching mechanism is associated with the development of electrical instability caused by the insulator-to-metal transition in Mo8O23. The switching channel, comprising this lower valence oxide, emerges in the initial film during the process of electrical forming of the MOM structure. The obtained results indicate the possibility of application of these structures in oxide micro- and nanoelectronics as electronic switches and other electronic devices.
Effects of Tumor Microenvironment Heterogeneity on Nanoparticle Disposition and Efficacy in Breast Cancer Tumor Models
Authors: Song Gina , Darr David B. , Santos Charlene M. , Ross Mark , Valdivia Alain , Jordan Jamie L. , Midkiff Bentley R. , Cohen Stephanie , Nikolaishvili-Feinberg Nana , Miller C. Ryan , Tarrant Teresa K. , Rogers Arlin B. , Dudley Andrew C. , Perou Charles M. , Zamboni William C.
Published: September 2014

Purpose: Tumor cells are surrounded by a complex microenvironment. The purpose of our study was to evaluate the role of heterogeneity of the tumor microenvironment in the variability of nanoparticle (NP) delivery and efficacy.

Experimental Designs: C3(1)-T-Antigen genetically engineered mouse model (C3-TAg) and T11/TP53Null orthotopic syngeneic murine transplant model (T11) representing human breast tumor subtypes basal-like and claudin-low, respectively, were evaluated. For the pharmacokinetic studies, non-liposomal doxorubicin (NL-doxo) or polyethylene glycol tagged (PEGylated) liposomal doxorubicin (PLD) was administered at 6 mg/kg i.v. x1. Area under the concentration versus time curve (AUC) of doxorubicin was calculated. Macrophages, collagen, and the amount of vasculature were assessed by IHC. Chemokines and cytokines were measured by multiplex immunochemistry. NL-doxo or PLD was administered at 6 mg/kg i.v. weekly x6 in efficacy studies. Analyses of intermediary tumor response and overall survival were performed.

Results: Plasma AUC of NL-doxo and PLD encapsulated and released doxorubicin was similar between two models. However, tumor sum total AUC of PLD was 2-fold greater in C3-TAg compared with T11 (P < 0.05). T11 tumors showed significantly higher expression of CC chemokine ligand (CCL) 2 and VEGF-a, greater vascular quantity, and decreased expression of VEGF-c compared with C3-TAg (P < 0.05). PLD was more efficacious compared with NL-doxo in both models.

Conclusion: The tumor microenvironment and/or tumor cell features of breast cancer affected NP tumor delivery and efficacy, but not the small-molecule drug. Our findings reveal the role of the tumor microenvironment in variability of NP delivery and therapeutic outcomes. Clin Cancer Res; 20(23); 6083–95. ©2014 AACR.
LY2875358, a Neutralizing and Internalizing Anti-MET Bivalent Antibody, Inhibits HGF-Dependent and HGF-Independent MET Activation and Tumor Growth
Authors: Liu Ling , Zeng Wei , Wortinger Mark A. , Yan S. Betty , Cornwell Paul , Peek Victoria L. , Stephens Jennifer R. , Tetreault Jonathan W. , Xia Jinqi , Manro Jason R. , Credille Kelly M. , Ballard Darryl W. , Brown-Augsburger Patricia , Wacheck Volker , Chow Chi-Kin , Huang Lihua , Wang Yong , Denning Irene , Davies Julian , Tang Ying , Vaillancourt Peter , Lu Jirong
Published: September 2014

Purpose: MET, the receptor for hepatocyte growth factor (HGF), has been implicated in driving tumor proliferation and metastasis. High MET expression is correlated with poor prognosis in multiple cancers. Activation of MET can be induced either by HGF-independent mechanisms such as gene amplification, specific genetic mutations, and transcriptional upregulation or by HGF-dependent autocrine or paracrine mechanisms.

Experimental Design/Results: Here, we report on LY2875358, a novel humanized bivalent anti-MET antibody that has high neutralization and internalization activities, resulting in inhibition of both HGF-dependent and HGF-independent MET pathway activation and tumor growth. In contrast to other bivalent MET antibodies, LY2875358 exhibits no functional agonist activity and does not stimulate biologic activities such as cell proliferation, scattering, invasion, tubulogenesis, or apoptosis protection in various HGF-responsive cells and no evidence of inducing proliferation in vivo in a monkey toxicity study. LY2875358 blocks HGF binding to MET and HGF-induced MET phosphorylation and cell proliferation. In contrast to the humanized one-armed 5D5 anti-MET antibody, LY2875358 induces internalization and degradation of MET that inhibits cell proliferation and tumor growth in models where MET is constitutively activated. Moreover, LY2875358 has potent antitumor activity in both HGF-dependent and HGF-independent (MET-amplified) xenograft tumor models. Together, these findings indicate that the mechanism of action of LY2875358 is different from that of the one-armed MET antibody.

Conclusions: LY2875358 may provide a promising therapeutic strategy for patients whose tumors are driven by both HGF-dependent and HGF-independent MET activation. LY2875358 is currently being investigated in multiple clinical studies. Clin Cancer Res; 20(23); 6059–70. ©2014 AACR.
A Synthetic Lethal Screen Reveals Enhanced Sensitivity to ATR Inhibitor Treatment in Mantle Cell Lymphoma with ATM Loss-of-Function
Authors: Menezes Daniel L. , Holt Jenny , Tang Yan , Feng Jiajia , Barsanti Paul , Pan Yue , Ghoddusi Majid , Zhang Wei , Thomas George , Holash Jocelyn , Lees Emma , Taricani Lorena
Published: September 2014

Mechanisms to maintain genomic integrity are essential for cells to remain viable. Not surprisingly, disruption of key DNA damage response pathway factors, such as ataxia telangiectasia-mutated (ATM)/ataxia telangiectasia and RAD3-related (ATR) results in loss of genomic integrity. Here, a synthetic lethal siRNA-screening approach not only confirmed ATM but identified additional replication checkpoint proteins, when ablated, enhanced ATR inhibitor (ATRi) response in a high-content γ-H2AX assay. Cancers with inactivating ATM mutations exhibit impaired DNA double-stranded break (DSB) repair and rely on compensatory repair pathways for survival. Therefore, impairing ATR activity may selectively sensitize cancer cells to killing. ATR inhibition in an ATM-deficient context results in phosphorylation of DNA-dependent protein kinase catalytic subunits (DNA-PKcs) and leads to induction of γ-H2AX. Using both in vitro and in vivo models, ATR inhibition enhanced efficacy in ATM loss-of-function mantle cell lymphoma (MCL) compared with ATM wild-type cancer cells. In summary, single-agent ATR inhibitors have therapeutic utility in the treatment of cancers, like MCL, in which ATM function has been lost.

Implications: These data suggest that single-agent ATR inhibitors have therapeutic utility and that ATR uses a complex and coordinated set of proteins to maintain genomic stability that could be further exploited. Mol Cancer Res; 13(1); 120–9. ©2014 AACR.
Neuronavigation Using Three-Dimensional Proton Magnetic Resonance Spectroscopy Data
Authors: Kanberoglu Berkay , Moore Nina Z. , Frakes David , Karam Lina J. , Debbins Josef P. , Preul Mark C.
Published: September 2014

Background: Applications in clinical medicine can benefit from fusion of spectroscopy data with anatomical imagery. For example, new 3-dimensional (3D) spectroscopy techniques allow for improved correlation of metabolite profiles with specific regions of interest in anatomical tumor images, which can be useful in characterizing and treating heterogeneous tumors that appear structurally homogeneous. Objectives: We sought to develop a clinical workflow and uniquely capable custom software tool to integrate advanced 3-tesla 3D proton magnetic resonance spectroscopic imaging (1H-MRSI) into industry standard image-guided neuronavigation systems, especially for use in brain tumor surgery. Methods:1H-MRSI spectra from preoperative scanning on 15 patients with recurrent or newly diagnosed meningiomas were processed and analyzed, and specific voxels were selected based on their chemical contents. 3D neuronavigation overlays were then generated and applied to anatomical image data in the operating room. The proposed 3D methods fully account for scanner calibration and comprise tools that we have now made publicly available. Results: The new methods were quantitatively validated through a phantom study and applied successfully to mitigate biopsy uncertainty in a clinical study of meningiomas. Conclusions: The proposed methods improve upon the current state of the art in neuronavigation through the use of detailed 3D 1H-MRSI data. Specifically, 3D MRSI-based overlays provide comprehensive, quantitative visual cues and location information during neurosurgery, enabling a progressive new form of online spectroscopy-guided neuronavigation.
Cellular and Axonal Constituents of Neocortical Molecular Layer Heterotopia
Authors: Ramos Raddy L. , Siu Nga Yan , Brunken William J. , Yee Kathleen T. , Gabel Lisa A. , Van Dine Sarah E. , Hoplight Blair J.
Published: September 2014

Human neocortical molecular layer heterotopia consist of aggregations of hundreds of neurons and glia in the molecular layer (layer I) and are indicative of neuronal migration defect. Despite having been associated with dyslexia, epilepsy, cobblestone lissencephaly, polymicrogyria, and Fukuyama muscular dystrophy, a complete understanding of the cellular and axonal constituents of molecular layer heterotopia is lacking. Using a mouse model, we identify diverse excitatory and inhibitory neurons as well as glia in heterotopia based on molecular profiles. Using immunocytochemistry, we identify diverse afferents in heterotopia from subcortical neuromodulatory centers. Finally, we document intracortical projections to/from heterotopia. These data are relevant toward understanding how heterotopia affect brain function in diverse neurodevelopmental disorders.
Smooth Muscle-Depressant Activity of AP-18, a Putative TRPA1 Antagonist in the Guinea Pig Intestine
Authors: Bartho Lorand , Sándor Zsolt , Kelemen Dezsö , Papp Robert , Benko Rita
Published: September 2014

AP-18, a putative antagonist at TRPA1 receptor/ion channel, caused smooth muscle relaxation at 10-100 µmol/l. It inhibited cholinergic twitch responses evoked by electrical field stimulation of cholinergic nerves as well as contractions in response to acetylcholine and histamine in the guinea pig small intestine. AP-18 (30 µmol/l) blocked spontaneous contractions of longitudinal strips of human jejunum. It is concluded that AP-18 may have limited value in studying TRPA1-mediated responses in smooth muscles and should probably be used with care in other preparations because of possible nonspecific effects.
Adherence and Patients' Attitudes to Oral Anticancer Drugs: A Prospective Series of 201 Patients Focusing on Targeted Therapies
Authors: Barthélémy Philippe , Asmane-De la Porte Irène , Meyer Nicolas , Duclos Brigitte , Serra Sebastian , Dourthe Louis-Marie , Amé Shanti , Litique Valère , Giron Cathy , Goldbarg Veronica , Fornecker Luc , Quoix Elisabeth , Kurtz Jean-Emmanuel
Published: September 2014

Objectives: Patient adherence is a challenge in oncology and hematology practice. Hormone therapy data in breast cancer suggest insufficient adherence and poor persistence. Limited data are available for targeted therapies (TT) including tyrosine kinase and mammalian target of rapamycin inhibitors. Methods: We performed a prospective survey using a 15-item questionnaire in patients with solid tumors and hematologic malignancies receiving oral anticancer therapy. Treatment duration, setting (adjuvant vs. metastatic), cancer type, age, and comedication were recorded. Results: 201 patients (median age 65.5 years) participated, 102 with TT and 99 with hormone therapy or chemotherapy (HC). The median time of drug intake was 11.0 months. Written information was more frequently given to TT patients (68.6 vs. 23.2%, p < 0.0001). TT and HC patients showed equal adherence to therapy (72.5 vs. 69.6%, p = n.s.) despite TT patients experiencing more side effects (p < 0.0001) and taking more concomitant oral medication (p = 0.0042). Forgotten doses were the leading cause of nonadherence in HC patients (83%, as compared to 54% in the TT group), whereas dose reduction by the patient was higher in the TT group (32 vs. 17%). Conclusions: Despite advances in providing information to patients leading to better adherence among TT patients, efforts towards better patient education are warranted including dedicated staff for monitoring outpatient anticancer oral therapy.
Testicular Metastasis of Prostate Cancer: A Case Report
Authors: Kusaka Ayumu , Koie Takuya , Yamamoto Hayato , Hamano Itsuto , Yoneyama Takahiro , Hashimoto Yasuhiro , Ohyama Chikara , Tobisawa Yuki , Yoneyama Tohru
Published: September 2014

The incidence of secondary neoplasms of the testis during autopsies is approximately 2.5%. Although most secondary testicular metastases are due to prostate cancer, only a few patients with prostate cancer have clinically manifested testicular metastasis. We report the case of a prostate cancer patient with testicular metastasis who was diagnosed after the presence of a palpable mass in the right testis. A 56-year-old Japanese male presented to our hospital with an elevated serum prostate-specific antigen (PSA) level of 137 ng/ml. He was diagnosed with stage IV (T3N1M1b) prostate cancer and received androgen deprivation therapy, followed by various hormonal manipulations. His serum PSA level was undetectable for 1 year. No distant metastases were detected during imaging examinations. He received radiation therapy; however, his serum PSA level increased gradually. Four months later, he presented with right testicular swelling. Computed tomography revealed a heterogenous mass in the right testis and a right high inguinal orchiectomy was performed. Histopathological analysis showed that the right testis was infiltrated with metastatic adenocarcinoma with a Gleason score of 8. This is a rare case of right testicular metastasis in a patient with prostate cancer. Testicular metastasis of prostate cancer can be aggressive and metastasize.
Hypoxia- or PDGF-BB-dependent paxillin tyrosine phosphorylation in pulmonary hypertension is reversed by HIF-1α depletion or imatinib treatment
Authors: Veith Christine , Zakrzewicz Dariusz , Dahal Bhola Kumar , Bálint Zoltán , Murmann Kirsten , Wygrecka Malgorzata , Seeger Werner , Schermuly Ralph Theo , Kwapiszewska Grazyna , Weissmann Norbert
Published: September 2014

Chronic exposure to hypoxia induces a pronounced remodelling of the pulmonary vasculature leading to pulmonary hypertension (PH). The remodelling process also entails increased proliferation and decreased apoptosis of pulmonary arterial smooth muscle cells (PASMC), processes regulated by the cytoskeletal protein paxillin. In this study, we aimed to examine the molecular mechanisms leading to deregulation of paxillin in PH. We detected a time-dependent increase in paxillin tyrosine 31 (Y31) and 118 (Y118) phosphorylation following hypoxic exposure (1 % O2) or platelet-derived growth factor (PDGF)-BB stimulation of primary human PASMC. In addition, both, hypoxia- and PDGF-BB increased the nuclear localisation of phospho-paxillin Y31 as indicated by immunofluorescence staining in human PASMC. Elevated paxillin tyrosine phosphorylation in human PASMC was attenuated by hypoxia-inducible factor (HIF)-1α depletion or by treatment with the PDGF-BB receptor antagonist, imatinib. Moreover, we observed elevated paxillin Y31 and Y118 phosphorylation in the pulmonary vasculature of chronic hypoxic mice (21 days, 10 % O2) which was reversible by imatinib-treatment. PDGF-BB-dependent PASMC proliferation was regulated via the paxillin-Erk1/2-cyclin D1 pathway. In conclusion, we suggest paxillin up-regulation and phosphorylation as an important mechanism of vascular remodelling underlying pulmonary hypertension.

Note: Parts of the doctoral thesis of Christine Veith are integrated into this report.
The relevance of coagulation in cardiovascular disease: what do the biomarkers tell us?
Authors: Rumley Ann , Lowe Gordon
Published: September 2014

Several haemostatic factors have been associated with incident arterial cardiovascular disease in prospective studies and meta-analyses. Plasma fibrinogen shows a strong and consistent association with risk; however, this may reflect its inflammatory marker status, and causality remains to be proven. The common haemostatic gene polymorphisms for factor II, factor V and the von Willebrand factor: Factor VIII (non-O blood group) show significant associations with coronary heart disease (CHD) risk, consistent with potential causality. Increased D-dimer and t-PA antigen levels are associated with CHD risk, suggesting roles for coagulation activation and endothelial disturbance. There is little evidence for associations with CVD with other haemostatic factors.
Dietary omega-3 alpha-linolenic acid does not prevent venous thrombosis in mice
Authors: Stivala Simona , Savarese Gianluigi , Camici Giovanni G. , Lüscher Thomas F. , Wagner Denisa , Reiner Martin , Martinod Kimberly , Beer Jürg
Published: September 2014

Venous thromboembolism (VTE) is a leading cause of cardiovascular death. Omega-3 fatty acids (n-3 FA) exhibit protective effects against cardiovascular disease. Others and our group have reported that the plant-derived n-3 FA alpha-linolenic acid (ALA) displays antiinflammatory, anticoagulant and antiplatelet effects, thereby reducing atherosclerosis and arterial thrombosis in mice fed a high ALA diet. Since procoagulant factors such as tissue factor and fibrin as well as platelets and leukocytes are crucially involved in the development of VTE, we investigated possible protective effects of dietary ALA on venous thrombus formation in a mouse model of stenosis- and furthermore, in a mouse model of endothelial injury-induced venous thrombosis. Four week old C57BL/6 mice underwent four weeks of high (7.3g%) or low ALA (0.03g%) treatment before being exposed to inferior vena cava (IVC) stenosis for 48 hours or laser injury of the endothelium of the internal jugular vein (IJV). Thrombus generation frequency, thrombus size and composition (IVC stenosis group) and time to thrombus formation (endothelial injury group) were assessed. In addition, plasma glycocalicin, a marker of platelet activation, platelet P-selectin and activated integrin expression as well as plasma thrombin generation was determined, but did not reveal any significant differences between he groups. Despite its protective properties against arterial thrombus formation, dietary ALA did not protect against venous thrombosis neither in the IVC stenosis nor the endothelial injury model, further indicating that the biological processes involved in arterial and venous thrombosis are different.
Antithrombin up-regulates AMP-activated protein kinase signalling during myocardial ischaemia/reperfusion injury
Authors: Ma Yina , Wang Jinli , Gao Junjie , Yang Hui , Wang Yanqing , Manithody Chandrashekhara , Li Ji , Rezaie Alireza R.
Published: September 2014

Antithrombin (AT) is a protein of the serpin superfamily involved in regulation of the proteolytic activity of the serine proteases of the coagulation system. AT is known to exhibit anti-inflammatory and cardioprotective properties when it binds to heparan sulfate proteo - glycans (HSPGs) on vascular cells. AMP-activated protein kinase (AMPK) plays an important cardioprotective role during myocardial ischaemia and reperfusion (I/R). To determine whether the cardioprotective signaling function of AT is mediated through the AMPK pathway, we evaluated the cardioprotective activities of wild-type AT and its two derivatives, one having high affinity and the other no affinity for heparin, in an acute I/R injury model in C57BL/6J mice in which the left anterior descending coronary artery was occluded. The serpin derivatives were given 5 minutes before reperfusion. The results showed that AT-WT can activate AMPK in both in vivo and ex vivo conditions. Blocking AMPK activity abolished the cardioprotective function of AT against I/R injury. The AT derivative having high affinity for heparin was more effective in activating AMPK and in limiting infraction, but the derivative lacking affinity for heparin was inactive in eliciting AMPK-dependent cardioprotective activity. Activation of AMPK by AT inhibited the inflammatory c-Jun N-terminal protein kinase (JNK) pathway during I/R. Further studies revealed that the AMPK activity induced by AT also modulates cardiac substrate metabolism by increasing glucose oxidation but inhibiting fatty acid oxidation during I/R. These results suggest that AT binds to HSPGs on heart tissues to invoke a cardioprotective function by triggering cardiac AMPK activation, thereby attenuating JNK inflammatory signalling pathways and modulating substrate metabolism during I/R.
Loss of cysteine 584 impairs the storage and release, but not the synthesis of von Willebrand factor
Authors: Daidone Viviana , Barbon Giovanni , Pontara Elena , Cattini Grazia , Gallinaro Lisa , Zampese Enrico , Pizzo Paola , Casonato Alessandra
Published: September 2014

Cysteines play a key part in von Willebrand factor (VWF) dimerisation and polymerisation, and their loss may severely affect VWF structure and function. We report on three patients with type 3 von Willebrand disease carrying the new c.1751G>T missense mutation that induces the substitution of cysteine 584 by phenylalanine (C584F), and the deletion of seven nucleotides in exon 7 (c.729_735del), producing a premature stop codon at position 454 (E244Lfs*211). VWF was almost undetectable in the patients’ plasma and platelets, while a single, poorly represented, oligomer emerged on plasma VWF multimer analysis. No post-DDAVP increase in VWF and factor VIII was observed. Expressing human recombinant C584F-VWF in HEK293T cells showed that C584F-VWF was synthesised and multimerised but not secreted – apart from the first oligomer, which was slightly represented in the conditioned medium, with a pattern similar to the patients’ plasma VWF. The in vitro expression of the E244Lfs*211–VWF revealed a defective synthesis of the mutated VWF, with a behavior typical of loss of function mutations. Cellular trafficking, investigated in HEK293 cells, indicated a normal C584F-VWF content in the endoplasmic reticulum and Golgi apparatus, confirming the synthesis and multimerisation of C584F-VWF. No pseudo-Weibel Palade bodies were demonstrable, however, suggesting that C584F mutation impairs the storage of C584F-VWF. These findings point to cysteine 584 having a role in the release of VWF and its targeting to pseudo-Weibel Palade bodies in vitro, as well as in its storage and release by endothelial cells in vivo.
Cytoprotective-selective activated protein C therapy for ischaemic stroke
Authors: Zlokovic Berislav , Griffin John , Mosnier Laurent
Published: September 2014

Despite years of research and efforts to translate stroke research to clinical therapy, ischaemic stroke remains a major cause of death, disability, and diminished quality of life. Primary and secondary preventive measures combined with improved quality of care have made significant progress. However, no novel drug for ischaemic stroke therapy has been approved in the past decade. Numerous studies have shown beneficial effects of activated protein C (APC) in rodent stroke models. In addition to its natural anticoagulant functions, APC conveys multiple direct cytoprotective effects on many different cell types that involve multiple receptors including protease activated receptor (PAR) 1, PAR3, and the endothelial protein C receptor (EPCR). Application of molecular engineered APC variants with altered selectivity profiles to rodent stroke models demonstrated that the beneficial effects of APC primarily require its cytoprotective activities but not its anticoagulant activities. Extensive basic, preclinical, and clinical research provided a compelling rationale based on strong evidence for translation of APC therapy that has led to the clinical development of the cytoprotectiveselective APC variant, 3K3A-APC, for ischaemic stroke. Recent identification of non-canonical PAR1 and PAR3 activation by APC that give rise to novel tethered-ligands capable of inducing biased cytoprotective signalling as opposed to the canonical signalling provides a mechanistic explanation for how APC-mediated PAR activation can selectively induce cytoprotective signalling pathways. Collectively, these paradigm-shifting discoveries provide detailed insights into the receptor targets and the molecular mechanisms for neuroprotection by cytoprotective-selective 3K3A-APC, which is currently a biologic drug in clinical trials for ischaemic stroke.
Records of chimaeroid fishes (Holocephali: Chimaeriformes) from the Pacific coast of Costa Rica, with the description of a new species of Chimera (Chimaeridae) from the eastern Pacific Ocean
Authors: ANGULO ARTURO , LÓPEZ MYRNA I. , BUSSING WILLIAM A. , MURASE ATSUNOBU
Published: September 2014

A new species of Chimaera Linnaeus 1758 is described from three specimens collected from off the Pacific coasts of Costa Rica and Peru. Chimaera orientalis n. sp., the first species of the genus described from the eastern Pacific Ocean, is distinguished from its other congeners by a combination of coloration and morphology. Additionally, new records of occurrence for another four species of chimaeroid fishes (Harriotta raleighana (Goode & Bean 1895), Rhinochimaera africana Compagno, Stehmann & Ebert 1990, Hydrolagus colliei Lay & Bennett 1839, and H. macrophthalmus de Buen 1959) previously unknown for the continental shelf of the Pacific coast of Costa Rica and Central America are reported. A key to the eastern Pacific species of the order Chimaeriformes is also presented.
Extension of the TAMSAT Satellite-Based Rainfall Monitoring over Africa and from 1983 to Present
Authors: Tarnavsky Elena , Grimes David , Maidment Ross , Black Emily , Allan Richard P. , Stringer Marc , Chadwick Robin , Kayitakire Francois
Published: September 2014

Tropical Applications of Meteorology Using Satellite Data and Ground-Based Observations (TAMSAT) rainfall monitoring products have been extended to provide spatially contiguous rainfall estimates across Africa. This has been achieved through a new, climatology-based calibration, which varies in both space and time. As a result, cumulative estimates of rainfall are now issued at the end of each 10-day period (dekad) at 4-km spatial resolution with pan-African coverage. The utility of the products for decision making is improved by the routine provision of validation reports, for which the 10-day (dekadal) TAMSAT rainfall estimates are compared with independent gauge observations. This paper describes the methodology by which the TAMSAT method has been applied to generate the pan-African rainfall monitoring products. It is demonstrated through comparison with gauge measurements that the method provides skillful estimates, although with a systematic dry bias. This study illustrates TAMSAT’s value as a complementary method of estimating rainfall through examples of successful operational application.
Developing Social Justice Competencies
Authors: Flores Michelle P. , De La Rue Lisa , Neville Helen A. , Santiago Sammy , ben Rakemayahu Kemuyah , Garite Robert , Spankey  , Brawn Michael , Valgoi Maria , Brooks James , Lee Eun Sul , Ginsburg Rebecca
Published: September 2014

The social science and education fields are increasingly looking to non-traditional pedagogical methods as a way to increase students’ awareness of social justice issues. Critical inquiry projects, human rights education, and service learning models are some of the theoretically grounded approaches that advocate for novel ways of increasing social justice awareness in education. In this article, we propose a model of social justice consultation training activities that build on key principles of social justice work, core components of social justice competencies, and the American Psychological Association Guidelines on Multicultural Education, Training, Research, Practice, and Organizational Change for Psychologists. We present the Climate Initiative case study to illustrate consultation training activities designed to promote social justice competencies. The Climate Initiative was a collaborative project between class members in a multicultural issues in counseling course and a social justice–oriented prison education program. We have included a summary of self-reflection experiences and evaluations of the process by counseling psychology trainees and students. Future recommendations for utilizing the consultation approach as a non-traditional teaching method are also provided.
A Longitudinal Study of the Impact of Home Vacancy on Robbery and Burglary Rates During the U.S. Housing Crisis, 2005-2009
Authors: Jones Roderick W. , Pridemore William Alex
Published: September 2014

The growing empirical literature on the effects on crime of the recent housing crisis in the United States provides inconsistent results for a direct effect. Furthermore, no longitudinal studies examine the association between home vacancy and crime during the U.S. housing crisis. To address this question, we used a sample of 126 major metropolitan statistical areas (MSAs) within the United States for the period 2005-2009 and estimated random and fixed effects models. Results indicated that increasing rates of home vacancy during the housing crisis were significantly associated with burglary rates within and between MSAs but had no association with robbery rates after controlling for other important crime covariates. We discuss the theoretical and methodological implications of these findings.
Shirazi scholars and the political culture of the sixteenth-century Indo-Persian world
Authors: Anooshahr Ali
Published: September 2014

This article studies the career of Fath Allah Shirazi who matriculated in Shiraz with some of the most prominent scholars of the age, and subsequently moved to India as his specific network lost political power in Safavid Iran during the reign of Shah Tahmasp. Fath Allah found employment at the Bijapur Sultanate and finally went to Mughal India and contributed to a number of administrative, intellectual and ‘ideological’ movements at the Mughal court. Shirazi’s career is significant as it sheds light on the significance (and dangers) of personal networks that facilitated the political prospects of the elites in the Indo-Persian world. It also demonstrates the importance of the Deccan in elite circulations between Iran and Mughal India in this period. Finally, it shows how such individuals had to constantly modify their learning in order to meet the varying needs of the centres of patronage in which they served.
Book Review: David Arnold, Everyday Technology: Machines and the Making of India’s Modernity
Authors: Roy Tirthankar
Published: September 2014

DAVID ARNOLD, Everyday Technology: Machines and the Making of India’s Modernity, Chicago: The University of Chicago Press, 2013, pp. 223.
Book Review: Irfan Habib and Faiz Habib, Atlas of Ancient Indian History
Authors: Subbarayalu Y.
Published: September 2014

IRFAN HABIB AND FAIZ HABIB, Atlas of Ancient Indian History, New Delhi: Oxford University Press, 2013, pp. 133, 13 maps.
Book Review: Tanvir Anjum, Chishti Sufis in the Sultanate of Delhi 1190–1400: From Restrained Indifference to Calculated Defiance
Authors: Banerjee Sushmita
Published: September 2014

TANVIR ANJUM, Chishti Sufis in the Sultanate of Delhi 1190–1400: From Restrained Indifference to Calculated Defiance, Karachi: Oxford University Press, 2011, pp. 434.
The Ethnic Army and the State
Authors: Harkness Kristen A.
Published: September 2014

Military coups have posed a persistent threat to political stability in Africa, undermining democratization efforts, igniting insurgencies, and leading to years of devastating military governance. Initial cross-national studies found little consistent evidence linking ethnicity to coups, leading recent formal and statistical work on coup risk and coup-proofing to largely ignore ethnic politics. This article, however, argues that in two important contexts of African political development—decolonization and democratization—ethnic politics are critical to understanding the occurrence of coups. Both case study evidence and statistical analysis of original data on African military history and ethnic politics reveal that practices of ethnic manipulation within security institutions have driven coup attempts. When leaders attempt to build ethnic armies, or dismantle those created by their predecessors, they provoke violent resistance from military officers.
Fascist Educational Policy from 1922 to 1943: A Contribution to the Current Debate on Political Religions
Authors: Tarquini Alessandra
Published: September 2014

This article contributes to the current debate on political religions presenting a case study: fascist educational policy from 1922 to 1943. The article is organized into four different parts: after a discussion of the major and most recent approaches to the concept of political religion, the second part examines some aspects of the educational policies of the 1920s; and in the third the main educational policies of the 1930s and the early 1940s, Giovanni Gentile’s role and Giuseppe Bottai’s contribution. Believing that fascism’s scholastic policies were determined by a political religion, based on the stated identity of politics and culture, the last part proposes an approach to the study of political religions and, more broadly, of the culture of totalitarian regimes.
A ‘Brutalizing’ War? The USA after the First World War
Authors: Keene Jennifer
Published: September 2014

Were US citizens brutalized by the First World War? Mobilization unified the nation, forcing both the willing and unwilling to take a stand in regards to the war and war-induced changes within American society. The spike in the use of violence to achieve political goals during the postwar period coincided with the return of veterans from the battlefield, but veterans did not instigate this period of violence. Rather than brutalization through combat, the ‘radicalizing’ effect of the war stemmed from how the mobilization process politicized both civilians and soldiers. The effects of war-related politicization resonated into the postwar period in both violent ways (giving the appearance of brutalization) and non-violent ways. Widespread violence in 1919, however, was only one variant of the more general radicalization and politicization US society underwent during the First World War. The non-violent trajectories that developed more fully in the early 1920s were less visible but equally important legacies of wartime mobilization. Over time, politicized veterans within the civil rights movement and veterans organizations quickly opted for nonviolent over violent forms of political expression. The USA thus joined the ranks of the other victor nations where successful veteran reintegration into existing social, economic, and political structures helped to mitigate war-associated violence. The state's embrace of veterans' demands for benefits ultimately gave most returned servicemen a stake in maintaining rather than challenging the existing political system. This did not mean that the effects of wartime politicization evaporated. Instead the two key social justice movements of the twentieth century, the fight for racial equality and the equitable distribution of income, benefited from the injection of politicized veterans into these respective causes.
An Analysis of Evaluative Comments in Teachers’ Online Discussions of Representations of Practice
Authors: Chieu Vu Minh , Kosko Karl W. , Herbst Patricio G.
Published: September 2014

It has been common to use video records of instruction in teacher professional development, but participants have rarely been encouraged to evaluate teachers and students’ actions in those records, allegedly because evaluation deters from the development of a professional discourse. In this study, we inspected teachers’ online discussions of animations of classroom episodes realized with cartoon characters, looking at the difference in the content of conversation turns when members made evaluative comments and when they did not make evaluative comments. We were interested in finding out whether making evaluative comments correlated with participants’ reflection on their professional practice and proposal of alternative teaching actions; for that purpose we used systemic functional linguistics (SFL) to develop a coding scheme that attended to evaluation, alternatives, and reflection in forum discussions. We found statistically significant evidence that the more the participants actively evaluated the teaching in the animations, the more they proposed alternative teaching actions and reflected on instructional practice. We relate these findings to the notion of social presence in online discussions.
The role of awareness in Internet non-use
Authors: Ting Carol
Published: September 2014

Despite the transformational impacts of the Internet on society and commerce, surveys have shown a sizable portion of non-Internet users reporting that they have no need for the Internet. Literature often explains Internet non-use as a result of lack of skills and/or informed decision to reject the Internet. This paper raises an alternative explanation: nonusers may report no need for the Internet because they are not fully aware of the Internet’s information and transaction benefits. Our survey data from rural Guangdong, China suggest that nonusers are comparatively under-informed about the Internet’s utilitarian benefits (such as aiding work and learning). Alternative explanations for the reported lack of need for the Internet are examined and policy implications are also discussed.
Hyper-precarious lives
Authors: Lewis Hannah , Dwyer Peter , Hodkinson Stuart , Waite Louise
Published: September 2014

This paper unpacks the contested inter-connections between neoliberal work and welfare regimes, asylum and immigration controls, and the exploitation of migrant workers. The concept of precarity is explored as a way of understanding intensifying and insecure post-Fordist work in late capitalism. Migrants are centrally implicated in highly precarious work experiences at the bottom end of labour markets in Global North countries, including becoming trapped in forced labour. Building on existing research on the working experiences of migrants in the Global North, the main part of the article considers three questions. First, what is precarity and how does the concept relate to working lives? Second, how might we understand the causes of extreme forms of migrant labour exploitation in precarious lifeworlds? Third, how can we adequately theorize these particular experiences using the conceptual tools of forced labour, slavery, unfreedom and precarity? We use the concept of ‘hyper-precarity’ alongside notions of a ‘continuum of unfreedom’ as a way of furthering human geographical inquiry into the intersections between various terrains of social action and conceptual debate concerning migrants’ precarious working experiences.
Developing a common framework for integrated solid waste management advances in Managua, Nicaragua
Authors: Olley Jane E , IJgosse Jeroen , Rudin Victoria , Alabaster Graham
Published: September 2014

This article describes the municipal solid waste management system in Managua, Nicaragua. It updates an initial profile developed by the authors for the 2010 UN-HABITAT publication Solid Waste Management in the World’s Cities and applies the methodology developed in that publication. In recent years, the municipality of Managua has been the beneficiary of a range of international cooperation projects aimed at improving municipal solid waste management in the city. The article describes how these technical assistance and infrastructure investments have changed the municipal solid waste management panorama in the city and analyses the sustainability of these changes. The article concludes that by working closely with the municipal government, the UN-HABITAT project Strengthening Capacities for Solid Waste Management in Managua was able to unite these separate efforts and situate them within a strategic framework to guide the evolution of the municipal solid waste management system in the forthcoming years. The creation of this multi-stakeholder platform allowed for the implementation of joint activities and ensured coherence in the products generated by the different projects. This approach could be replicated in other cities and in other sectors with similar effect. Developing a long term vision was essential for the advancement of municipal solid waste management in the city. Nevertheless, plan implementation may still be undermined by the pressures of the short term municipal administrative government, which emphasize operational over strategic investment.
Assessing Self-Regulated Strategies for School Writing
Authors: Malpique Anabela Abreu , Margarida Veiga Simão Ana
Published: September 2014

This study reports on the construction of a questionnaire to assess ninth-grade students’ use of self-regulated strategies for school writing tasks. Exploratory and confirmatory factorial analyses were conducted to validate the factor structure of the instrument. The initial factor analytic stage ( n = 296) revealed a 13-factor scale, accounting for 61.35% of the variance. Cross-cultural validation was carried out involving Portuguese and Brazilian students ( n = 732). Multi-group analyses of invariance were performed on the two samples. Results support a theoretically driven second-order model assessing 12 self-regulated strategies for writing. Full configural and metric invariance were established, suggesting that the 34-item measure may be robust to assess the model under investigation across cultures. Findings suggest that the instrument can be a valid theory-based assessment tool to help researchers and practitioners examine how students in transition to high school initiate and control their school writing tasks.