bluuebunny/crossref_metadata_2025 huggingface dataset:
Synthetic Antimicrobial Peptides Exhibit Two Different Binding Mechanisms to the Lipopolysaccharides Isolated from Pseudomonas aeruginosa and Klebsiella pneumoniae
Authors: Chai Hanbo , Allen William E. , Hicks Rickey P.
Published: December 2014

Circular dichroism and 1H NMR were used to investigate the interactions of a
series of synthetic antimicrobial peptides (AMPs) with lipopolysaccharides (LPS) isolated from
Pseudomonas aeruginosa and Klebsiella pneumoniae. Previous CD studies with AMPs
containing only three Tic-Oic dipeptide units do not exhibit helical characteristics upon
interacting with small unilamellar vesicles (SUVs) consisting of LPS. Increasing the number of
Tic-Oic dipeptide units to six resulted in five analogues with CD spectra that exhibited helical
characteristics on binding to LPS SUVs. Spectroscopic and in vitro inhibitory data suggest that
there are two possible helical conformations resulting from two different AMP-LPS binding
mechanisms. Mechanism one involves a helical binding conformation where the AMP binds
LPS very strongly and is not efficiently transported across the LPS bilayer resulting in the loss of
inhibitory activity. Mechanism two involves a helical binding conformation where the AMP
binds LPS very loosely and is efficiently transported across the LPS bilayer resulting in an
increase in inhibitory activity. Mechanism three involves a nonhelical binding conformation
where the AMP binds LPS very loosely and is efficiently transported across the LPS bilayer
resulting in an increase in inhibitory activity.
Influence ofDPYDGenetic Polymorphisms on 5-Fluorouracil Toxicities in Patients with Colorectal Cancer: A Meta-Analysis
Authors: Li Qiang , Liu Ying , Zhang Hong-Mei , Huang Yin-Peng , Wang Tian-Yi , Li Dong-Sheng , Sun Hong-Zhi
Published: December 2014

Our meta-analysis aggregated existing results from relevant studies to comprehensively investigate the correlations between genetic polymorphisms in dihydropyrimidine dehydrogenase (DPYD) gene and 5-fluorouracil (5-FU) toxicities in patients with colorectal cancer (CRC). The MEDLINE (1966∼2013), the Cochrane Library Database (Issue 12, 2013), EMBASE (1980∼2013), CINAHL (1982∼2013), Web of Science (1945∼2013), and the Chinese Biomedical Database (CBM) (1982∼2013) were searched without language restrictions. Meta-analyses were conducted with the use of STATA software (Version 12.0, Stata Corporation, College Station, TX, USA). Seven clinical cohort studies with a total of 946 CRC patients met our inclusion criteria, and NOS scores of each of the included studies were ≥5. Our findings showed thatDPYDgenetic polymorphisms were significantly correlated with high incidences of 5-FU-related toxicity in CRC patients. SNP-stratified analysis indicated that there were remarkable connections of IVS14+1G>A, 464T>A, and 2194G>A polymorphisms with the incidence of marrow suppression in CRC patients receiving 5-FU chemotherapy. Furthermore, we found that IVS14+1G>A, 496A>G, and 2194G>A polymorphisms were correlated with the incidence of gastrointestinal reaction. Ethnicity-stratified analysis also revealed thatDPYDgenetic polymorphisms might contribute to the development of marrow suppression and gastrointestinal reaction among Asians, but not among Caucasians. The present meta-analysis suggests thatDPYDgenetic polymorphisms may be correlated with the incidence of 5-FU-related toxicity in CRC patients.
Treatment Efficiency by means of a Nonthermal Plasma Combined with Heterogeneous Catalysis of Odoriferous Volatile Organic Compounds Emissions from the Thermal Drying of Landfill Leachates
Authors: Almarcha Daniel , Almarcha Manuel , Jimenez-Coloma Elena , Vidal Laura , Puigcercós Montserrat , Barrutiabengoa Iban
Published: December 2014

The objective of the present work was to assess the odoriferous volatile organic compounds depuration efficiency of an experimental nonthermal plasma coupled to a catalytic system used for odor abatement of real emissions from a leachate thermal drying plant installed in an urban solid waste landfill. VOC screening was performed by means of HRGC-MS analysis of samples taken at the inlet and at the outlet of the nonthermal plasma system. Odor concentration by means of dynamic olfactometry, total organic carbon, mercaptans, NH3, and H2S were also determined in order to assess the performance of the system throughout several days. Three plasma frequencies (100, 150, and 200 Hz) and two catalyst temperatures (150°C and 50°C) were also tested. Under conditions of maximum capacity of the treatment system, the results show VOC depuration efficiencies around 69%, with average depuration efficiencies between 44 and 95% depending on the chemical family of the substance. Compounds belonging to the following families have been detected in the samples: organic acids, alcohols, ketones, aldehydes, pyrazines, and reduced sulphur compounds, among others. Average total organic carbon removal efficiency was 88%, while NH3and H2S removal efficiencies were 88% and 87%, respectively, and odor concentration abatement was 78%.
Quercetin Protects against Obesity-Induced Skeletal Muscle Inflammation and Atrophy
Authors: Le Ngoc Hoan , Kim Chu-Sook , Park Taesun , Park Jung Han Yoon , Sung Mi-Kyung , Lee Dong Gun , Hong Sun-Myung , Choe Suck-Young , Goto Tsuyoshi , Kawada Teruo , Yu Rina
Published: December 2014

Skeletal muscle inflammation and atrophy are closely associated with metabolic impairment such as insulin resistance. Quercetin, a natural polyphenol flavonoid, is known to elicit anti-inflammatory and antioxidant activities. In this study, we investigated its effect on obesity-induced skeletal muscle inflammation and atrophy in mice. Male C57BL/6 mice were fed a regular diet, a high-fat diet (HFD), and an HFD supplemented with quercetin for nine weeks. Quercetin reduced levels of inflammatory cytokines and macrophage accumulation in the skeletal muscle of the HFD-fed obese mice. It also reduced transcript and protein levels of the specific atrophic factors, Atrogin-1 and MuRF1, in the skeletal muscle of the HFD-fed obese mice, and protected against the reduction of muscle mass and muscle fiber size. In vitro, quercetin markedly diminished transcript levels of inflammatory receptors and activation of their signaling molecules (ERK, p38 MAPK, and NF-κB) in cocultured myotubes/macrophages, and this was accompanied by reduced expression of the atrophic factors. Together, these findings suggest that quercetin reduces obesity-induced skeletal muscle atrophy by inhibiting inflammatory receptors and their signaling pathway. Quercetin may be useful for preventing obesity-induced muscle inflammation and sarcopenia.
Resection of a Catecholamine-Elaborating Retroperitoneal Paraganglioma Invading the Inferior Vena Cava
Authors: Mannina E. M. , Xiong Z. , Self R. , Kandil E.
Published: December 2014

Paragangliomas are rare tumors originating outside of the adrenal medulla which can be associated with catecholamine secretion or mass effect, one of which typically leads to their discovery. The differences between these tumors and traditional intra-adrenal pheochromocytomas are a subject of recent investigations. Standard of care therapy is medical management and surgical resection of the tumor. When tumors are biochemically active, medical optimization of the autonomic nervous system is a critical component to a safe, definitive resection. Tumors arising in the retroperitoneum present technical challenges for the surgeon as they are often large and difficult to access, making an oncologic resection much more difficult. Lastly, these tumors are mostly benign and rarely invade adjacent structures—an operative finding not always predicted by preoperative imaging—which, if present, adds significant complexity and risk to the resection. A case illustrating these challenges in the management of a biochemically active retroperitoneal paraganglioma invading the inferior vena cava follows.
Clinical Outcome of Patients with Complete Pathological Response to Neoadjuvant Chemoradiotherapy for Locally Advanced Rectal Cancers: The Indian Scenario
Authors: Sinukumar Snita , Patil Prachi , Engineer Reena , Desouza Ashwin , Saklani Avanish
Published: December 2014

Introduction. Neoadjuvant chemoradiotherapy and total mesorectal excision are considered the standard treatment for locally advanced rectal cancer. Various studies have reported pathological downstaging and a complete pathological response rate of 15%–27% following neoadjuvant chemoradiotherapy which has translated into improved survival. We endeavour to determine the clinical outcome of patients attaining a complete pathological tumor response following neoadjuvant chemoradiotherapy in the Indian setting where most of our patient population is younger and presents with aggressive tumor biology.Materials and Methods. Clinicopathological and treatment details were recorded for 64 patients achieving pathological complete response from 2010 to 2013. Disease-free survival (DFS), overall survival (OS), and locoregional and systemic recurrence rates were evaluated for these patients.Results. After a median follow-up of 30.5 months (range 11–59 months), the 3-year overall survival (OS) was 94.6% and the 3-year disease-free survival (DFS) was 88.5%. The locoregional and systemic recurrence rates were 4.7% and 3.1%, respectively.Conclusion. In the Indian subcontinent, despite younger patients with aggressive tumor biology, outcome in complete responders is good.
The Quality Assessment of Stored Red Blood Cells Probed Using Atomic-Force Microscopy
Authors: Lamzin I. M. , Khayrullin R. M.
Published: December 2014

At the moment the suitability of stored red blood cells (sRBC) for transfusion is checked by routine methods such as haemoglobin estimation and the level of haemolysis. These methods cannot characterize directly the quality of the membranes of sRBC. The aim of this work is to assess the quality of sRBC based on such criteria as the membrane’s stiffness and the size and the form of sRBC. Materials and Methods. We have investigated 5 series of dry cytosmears of the sRBC which had been kept in blood bank in a period from 1 to 35 days. After AFM imaging, in every specimen, 5 RBC were chosen at random; the diameter, the height, and the stiffness were measured on each of them. Results. The present study shows high increase of the mean values of YM and height of RBC after 35 days of storage and decrease of the mean values of their diameter. Conclusion. Statistically significant high increase of the mean values of YM indicates the decrease of the elasticity of the cells in the course of storing of the RBC. This parameter along with the morphological characteristics can be used as criterion for assessment of applicability of the sRBC for blood transfusion.
Stenting as a Rescue Treatment of a Pulmonary Artery False Aneurysm Caused by Swan-Ganz Catheterization
Authors: Keymel Stefanie , Merx Marc W. , Zeus Tobias , Kelm Malte , Steiner Stephan
Published: December 2014

Pulmonary vascular injury is a rare but life-threatening complication of Swan-Ganz catheterization. We report an 82-year old patient who underwent right heart catheterization by a balloon-tipped catheter because of suspected pulmonary hypertension. After deflation of the catheter in the wedge position, hemoptoe appeared associated with acute respiratory insufficiency requiring respiratory support by intubation and mechanical ventilation. Pulmonary angiography showed the formation of a false aneurysm of a segment artery of the left lower lobe. Immediate interventional therapy was performed by the implantation of two coated coronary stent grafts into the injured pulmonary artery thereby excluding the false aneurysm. Bleeding was stopped by this interventional approach while antegrade blood flow was maintained. Long term follow-up after 3 months showed an effective treatment with a completely thrombotic false aneurysm. However, despite oral anticoagulation and dual antiplatelet therapy, graft patency could not be achieved after 3 months. In summary, implantation of coated stents is a feasible and safe approach for the acute and long term treatment of potentially life-threatening condition of a pulmonary artery false aneurysm while treatment to achieve long term patency of the affected vessel still remains an issue to be resolved.
PGC1α−1 Nucleosome Position and Splice Variant Expression and Cardiovascular Disease Risk in Overweight and Obese Individuals
Authors: Henagan Tara M. , Stewart Laura K. , Forney Laura A. , Sparks Lauren M. , Johannsen Neil , Church Timothy S.
Published: December 2014

PGC1α, a transcriptional coactivator, interacts with PPARs and others to regulate skeletal muscle metabolism.PGC1αundergoes splicing to produce several mRNA variants, with theNTPGC1αvariant having a similar biological function to the full lengthPGC1α(FLPGC1α). CVD is associated with obesity and T2D and a lower percentage of type 1 oxidative fibers and impaired mitochondrial function in skeletal muscle, characteristics determined byPGC1αexpression.PGC1αexpression is epigenetically regulated in skeletal muscle to determine mitochondrial adaptations, and epigenetic modifications may regulate mRNA splicing. We report in this paper that skeletal musclePGC1α  −1 nucleosome (−1N) position is associated with splice variantNTPGC1αbut notFLPGC1αexpression. Division of participants based on the −1N position revealed that those individuals with a −1N phased further upstream from the transcriptional start site (UP) expressed lower levels ofNTPGC1αthan those with the −1N more proximal to TSS (DN). UP showed an increase in body fat percentage and serum total and LDL cholesterol. These findings suggest that the −1N may be a potential epigenetic regulator ofNTPGC1αsplice variant expression, and −1N position andNTPGC1αvariant expression in skeletal muscle are linked to CVD risk. This trial is registered with clinicaltrials.gov, identifierNCT00458133.
Inferior Mean of Measures on Curves and Subspaces
Authors: Movshovich Yevgenya
Published: December 2014

We obtain new sharp upper bounds of the inferior mean for positive harmonic functions defined by finite boundary measures that lie on curves or subspaces of the boundary of the half-space.
rre37Overexpression Alters Gene Expression Related to the Tricarboxylic Acid Cycle and Pyruvate Metabolism inSynechocystissp. PCC 6803
Authors: Iijima Hiroko , Watanabe Atsuko , Takanobu Junko , Hirai Masami Yokota , Osanai Takashi
Published: December 2014

The tricarboxylic acid (TCA) cycle and pyruvate metabolism of cyanobacteria are unique and important from the perspectives of biology and biotechnology research. Rre37, a response regulator induced by nitrogen depletion, activates gene expression related to sugar catabolism. Our previous microarray analysis has suggested that Rre37 controls the transcription of genes involved in sugar catabolism, pyruvate metabolism, and the TCA cycle. In this study, quantitative real-time PCR was used to measure the transcript levels of 12 TCA cycle genes and 13 pyruvate metabolism genes. The transcripts of 6 genes (acnB,icd,ppc,pyk1,me, andpta) increased after 4 h of nitrogen depletion in the wild-type GT strain but the induction was abolished byrre37overexpression. The repression of gene expression offumC, ddh, andackAcaused by nitrogen depletion was abolished byrre37overexpression. The expression ofmewas differently affected byrre37overexpression, compared to the other 24 genes. These results indicate that Rre37 differently controls the genes of the TCA cycle and pyruvate metabolism, implying the key reaction of the primary in this unicellular cyanobacterium.
The Cost of Prolonged Hospitalization due to Postthyroidectomy Hypocalcemia: A Case-Control Study
Authors: Zahedi Niaki Navid , Singh Harmeet , Moubayed Sami P. , Leboeuf Rebecca , Tabet Jean-Claude , Christopoulos Apostolos , Ayad Tareck , Olivier Marie-Jo , Guertin Louis , Bissada Eric
Published: December 2014

The aim of this study is to evaluate the additional costs associated with calcium monitoring and treatment as well as evaluate the incidence and predictors of postthyroidectomy hypocalcemia. Methods. This case-control study involved thyroidectomy and completion thyroidectomy patients operated on between January 2012 and August 2013. Cases were defined as requiring calcitriol supplementation, and controls did not require supplementation. Patient (age, sex), nodule (cytology, pathology), surgical data (neck dissection, parathyroid identification, and reimplantation), and hospital stay (days hospitalized in total and after drain removal) were compared. Comparisons were made using t-tests and chi-square tests with an alpha of 0.05. The estimated cost associated with the extended stay was then compared with the cost of supplementation. Results. A total of 191 patients were evaluated (61 cases and 130 controls). Predictors of hypocalcemia include female age, neck dissection, and parathyroid reimplantation. Hypocalcemic patients were hospitalized for a longer period of time after drain removal (2.5 versus 0.8 days, P<0.001), and hospitalization costs after neck drain removal were higher in this group as well (8,367.32$ versus 2,534.32$, P<0.001). Conclusion. Postoperative hypocalcemia incurs significant additional health care costs at both the local and health care system levels.
Determination of Provenance and Tectonic Settings of Niger Delta Clastic Facies Using Well-Y, Onshore Delta State, Nigeria
Authors: Oni S. O. , Olatunji A. S. , Ehinola O. A.
Published: December 2014

Provenance analysis serves to reconstruct the predepositional history of a sediment/sedimentary rock. This paper focuses on the reconstruction of the provenance and tectonic settings of the Niger delta clastic facies using geochemical approach. The main types of geochemical tests include major, trace, and rare earth element (REE) tests. Twenty-one samples of shales and sandstones units were purposely collected from a depth between 1160 and 11,480 m, grinded, pulverized, and sieved with a <75 μm. About 5 g was packed and sent to Acme analytical Laboratory Ltd., Vancouver, Canada. The analyses were carried out by both induced coupled plasma-mass spectrometry (ICP-MS) and induced coupled plasma-emission spectrometry (ICP-ES). Bulk-rock geochemistry of major oxides, trace elements, and rare earth elements was utilized for the provenance and tectonic setting determination. Based on the discrimination diagram for major oxides, the probable provenance of the south eastern Delta clastic sediments was mainly of the active continental margins. The bivariate plots of La versus Th, La/Y versus Sc/Cr, and Ti/Zr versus La/Sc and the trivariate plots of La-Th-Sc, Th-Sc-Zr/10, and Th-Co-Zr/10 are all plotted on the fields of active continental margin sediments which is consistent with the known actively opening of a failed arm of triple junction. The trace elements and REE analysis indicates that they are virtually Fe-rich, lithic/quartz arkosic sandstones. The normalizing factors used for the REE are Wakita chondrite. Their rare earth elements (REE) pattern displays high light REE/heavy REE (LREE/HREE) ratio, flat HREE, and a significant negative Eu anomaly which correlate well with the UCC and PAAS average composition. The source area may have contained felsic igneous rocks.
Influence of TiO2Nanoparticles on Growth and Phenolic Compounds Production in Photosynthetic Microorganisms
Authors: Comotto Mattia , Casazza Alessandro Alberto , Aliakbarian Bahar , Caratto Valentina , Ferretti Maurizio , Perego Patrizia
Published: December 2014

The influence of titanium dioxide nanoparticles (pure anatase and 15% N doped anatase) on the growth ofChlorella vulgaris,Haematococcus pluvialis, andArthrospira platensiswas investigated. Results showed that pure anatase can lead to a significant growth inhibition ofC. vulgarisandA. platensis(17.0 and 74.1%, resp.), while forH. pluvialisthe nanoparticles do not cause a significant inhibition. Since in these stress conditions photosynthetic microorganisms can produce antioxidant compounds in order to prevent cell damages, we evaluated the polyphenols content either inside the cells or released in the medium. Although results did not show a significant difference inC. vulgaris, the phenolic concentrations of two other microorganisms were statistically affected by the presence of titanium dioxide. In particular, 15% N doped anatase resulted in a higher production of extracellular antioxidant compounds, reaching the concentration of 65.2 and68.0 mg gDB-1forH. pluvialisandA. platensis, respectively.
In and Ga Codoped ZnO Film as a Front Electrode for Thin Film Silicon Solar Cells
Authors: Pham Duy Phong , Nguyen Huu Truong , Phan Bach Thang , Cao Thi My Dung , Hoang Van Dung , Dao Vinh Ai , Yi Junsin , Tran Cao Vinh
Published: December 2014

Doped ZnO thin films have attracted much attention in the research community as front-contact transparent conducting electrodes in thin film silicon solar cells. The prerequisite in both low resistivity and high transmittance in visible and near-infrared region for hydrogenated microcrystalline or amorphous/microcrystalline tandem thin film silicon solar cells has promoted further improvements of this material. In this work, we propose the combination of major Ga and minor In impurities codoped in ZnO film (IGZO) to improve the film optoelectronic properties. A wide range of Ga and In contents in sputtering targets was explored to find optimum optical and electrical properties of deposited films. The results show that an appropriate combination of In and Ga atoms in ZnO material, followed by in-air thermal annealing process, can enhance the crystallization, conductivity, and transmittance of IGZO thin films, which can be well used as front-contact electrodes in thin film silicon solar cells.
Meningocele in a Congolese Female with Beckwith-Wiedemann Phenotype
Authors: Mbuyi-Musanzayi Sébastien , Lubala Kasole Toni , Lumaka Aimé , Kayembe Kitenge Tony , Kabamba Ngombe Leon , Kalenga Muenze Prosper , Lukusa Tshilobo Prosper , Tshilombo Katombe François , Banza Lubaba Nkulu Célestin , Devriendt Koenraad
Published: December 2014

Beckwith-Wiedemann syndrome (BWS) is a rare congenital syndrome characterized by an overgrowth, macroglossia, exomphalos, and predisposition to embryonal tumors. Central nervous abnormalities associated with BWS are rare. We describe a one-day-old Congolese female who presented meningocele associated with BWS phenotype.
Lag Times between Lymphoproliferative Disorder and Clinical Diagnosis of Chronic Lymphocytic Leukemia: A Prospective Analysis Using Plasma Soluble CD23
Authors: Kaaks Rudolf , Sookthai Disorn , Łuczyńska Anna , Oakes Christopher C. , Becker Susen , Johnson Theron , Johansson Annsofie , Melin Beatrice , Sjöberg Klas , Trichopoulos Dimitrios , Trichopoulou Antonia , Lagiou Pagona , Mattiello Amalia , Tumino Rosario , Masala Giovanna , Agnoli Claudia , Boeing Heiner , Aleksandrova Krasimira , Brennan Paul , Franceschi Silvia , Roulland Sandrine , Casabonne Delphine , de Sanjose Silvia , Sánchez María-José , Huerta José María , Ardanaz Eva , Sala Nuria , Overvad Kim , Tjønneland Anne , Halkjær Jytte , Weiderpass Elisabete , Bueno-de-Mesquita H. B(as). , Vermeulen Roel , Peeters Petra H. , Vineis Paolo , Kelly Rachel S. , Khaw Kay-Tee , Travis Ruth C. , Key Timothy J. , Riboli Elio , Nieters Alexandra
Published: December 2014

Background: Chronic lymphocytic leukemia (CLL) is a chronic disease that often progresses slowly from a precursor stage, monoclonal B-cell lymphocytosis (MBL), and that can remain undiagnosed for a long time.

Methods: Within the European Prospective Investigation into Cancer cohort, we measured prediagnostic plasma sCD23 for 179 individuals who eventually were diagnosed with CLL and an equal number of matched control subjects who remained free of cancer.

Results: In a very large proportion of CLL patients' plasma sCD23 was clearly elevated 7 or more years before diagnosis. Considering sCD23 as a disease predictor, the area under the ROC curve (AUROC) was 0.95 [95% confidence interval (CI), 0.90–1.00] for CLL diagnosed within 0.1 to 2.7 years after blood measurement, 0.90 (95% CI, 0.86–0.95) for diagnosis within 2.8 to 7.3 years, and 0.76 (95% CI, 0.65–0.86) for CLL diagnosed between 7.4 and 12.5 years. Even at a 7.4-year and longer time interval, elevated plasma sCD23 could predict a later clinical diagnosis of CLL with 100% specificity at >45% sensitivity.

Conclusions: Our findings provide unique documentation for the very long latency times during which measurable B-cell lymphoproliferative disorder exists before the clinical manifestation of CLL.

Impact: Our findings have relevance for the interpretation of prospective epidemiologic studies on the causes of CLL in terms of reverse causation bias. The lag times indicate a time frame within which an early detection of CLL would be theoretically possible. Cancer Epidemiol Biomarkers Prev; 24(3); 538–45. ©2014 AACR.
Targeting the Metabolic Plasticity of Multiple Myeloma with FDA-Approved Ritonavir and Metformin
Authors: Dalva-Aydemir Sevim , Bajpai Richa , Martinez Maylyn , Adekola Kehinde U.A. , Kandela Irawati , Wei Changyong , Singhal Seema , Koblinski Jennifer E. , Raje Noopur S. , Rosen Steven T. , Shanmugam Mala
Published: December 2014

Purpose: We have previously demonstrated that ritonavir targeting of glycolysis is growth inhibitory and cytotoxic in a subset of multiple myeloma cells. In this study, our objective was to investigate the metabolic basis of resistance to ritonavir and to determine the utility of cotreatment with the mitochondrial complex I inhibitor metformin to target compensatory metabolism.

Experimental Design: We determined combination indices for ritonavir and metformin, impact on myeloma cell lines, patient samples, and myeloma xenograft growth. Additional evaluation in breast, melanoma, and ovarian cancer cell lines was also performed. Signaling connected to suppression of the prosurvival BCL-2 family member MCL-1 was evaluated in multiple myeloma cell lines and tumor lysates. Reliance on oxidative metabolism was determined by evaluation of oxygen consumption, and dependence on glutamine was assessed by estimation of viability upon metabolite withdrawal in the context of specific metabolic perturbations.

Results: Ritonavir-treated multiple myeloma cells exhibited increased reliance on glutamine metabolism. Ritonavir sensitized multiple myeloma cells to metformin, effectively eliciting cytotoxicity both in vitro and in an in vivo xenograft model of multiple myeloma and in breast, ovarian, and melanoma cancer cell lines. Ritonavir and metformin effectively suppressed AKT and mTORC1 phosphorylation and prosurvival BCL-2 family member MCL-1 expression in multiple myeloma cell lines in vitro and in vivo.

Conclusions: FDA-approved ritonavir and metformin effectively target multiple myeloma cell metabolism to elicit cytotoxicity in multiple myeloma. Our studies warrant further investigation into repurposing ritonavir and metformin to target the metabolic plasticity of myeloma to more broadly target myeloma heterogeneity and prevent the reemergence of chemoresistant aggressive multiple myeloma. Clin Cancer Res; 21(5); 1161–71. ©2014 AACR.
The hidden minority? Dilemmas around the status of the russophone Ukrainians in contemporary Ukraine
Authors: Koziura Karolina
Published: January 2015

The hidden minority? Dilemmas around the status of the russophone Ukrainians in contemporary UkraineUkraine, as one of the states which became independent in 1991, can be perceived as an example of the typical transition of Soviet Socialist Republics into democratic states centered on the issue of nationalizing policies and processes. However, there are also differences which make this country a very interesting case study for investigation. Mainly, Russians here form the biggest national group concentrated in the East and South of the country. The persistence and reuse of the “myth of two Ukraines” led to the widespread conclusion that Ukraine is a country which is divided between Ukrainophone West and Russophone East. This article is focuses on the third group, which is somehow hidden in the mainstream linguistic debates, namely the Russian-speaking citizens of Ukraine who define themselves as ethnic Ukrainians. Based on the examples of Donbas and Crimean regions, it tries to define whether one can perceive them as a national minority.
Demograficzne aspekty samostanowienia narodu na przykładzie współczesnej Walii
Authors: Libor Grzegorz
Published: January 2015

Demographic aspects of self-determination of nation on the example of modern WalesDemographic problems and their consequences have been analyzed in many different ways, from different points of view. Their conditions and mutual relations have been taken into account as well, even though the interest in population problems in capitalist societies results from the fairly prosaic reasons. Dealing with them means increasing costs. Under certain conditions, however, non-economic benefits can, or at least should, become more important than economic losses. The case of Wales seems to confirm this thesis. The basis for a prosperous and strong nation is its proper demographic condition invaluable from the perspective of competing with other nation – in this case with English one. The purpose of this article is to present the demographic situation of Wales, identify the most important of its demographic problems, as well as the actions taken by the Welsh Government in this regard. Demograficzne aspekty samostanowienia narodu na przykładzie współczesnej WaliiProblemy demograficzne i ich konsekwencje analizowane były do tej pory na wiele różnych sposobów i przy uwzględnieniu różnych punktów widzenia. Badano ich wzajemne relacje i uwarunkowania, mimo iż zainteresowanie problemami demograficznymi w społeczeństwach kapitalistycznych wynikało i nadal wynika z dość prozaicznych powodów. Radzenie sobie z nimi wymaga bowiem ponoszenia coraz to większych kosztów. W określonych warunkach jednak pozaekonomiczne korzyści mogą, a przynajmniej powinny, stać się ważniejsze od gospodarczych strat. Przypadek tytułowej Walii zdaje się potwierdzać tą tezę. Podstawą dobrze prosperującego i silnego narodu jest jego odpowiednia kondycja demograficzna, bezcenna z perspektywy rywalizacji z innym narodem. Celem artykułu jest zaprezentowanie sytuacji demograficznej Walii, zidentyfikowanie najważniejszych jej problemów demograficznych, a także wskazanie działań podejmowanych przez rząd walijski w tym zakresie.
Czesi we Wrocławiu podczas Euro 2012. Przyczynek do analizy polsko-czeskich relacji społecznych
Authors: Dębicki Marcin
Published: January 2015

Czechs in Wrocław during Euro 2012. A contribution to the analysis of the Polish-Czech social relationsThe aim of the article is to analyse the Polish-Czech relations on a social platform, seen through the prism of the football event—Euro 2012. The text opens with a glance at a broader context of these relations generated by mutual stereotypes and the media coverage of certain peculiarities of both national cultures. Then it goes on to giving quite detailed a record of the atmosphere created by the Polish and Czechs fans during the tournament, which was written into the conception of pop nationalism. The whole picture is enriched with an attempt to refer the situation observed in Wrocław to the attitudes Poles generally have to Czechs, expressed by means of statistical data as well as features of character traditionally ascribed to this nation in Poland. Czesi we Wrocławiu podczas Euro 2012. Przyczynek do analizy polsko-czeskich relacji społecznychCelem artykułu jest przeprowadzenie analizy relacji polsko-czeskich na płaszczyźnie społecznej, widzianych przez pryzmat wydarzenia piłkarskiego – Euro 2012. Tekst otwiera spojrzenie na szerszy kontekst owych relacji, tworzony przez wzajemne stereotypy oraz przekazy medialne dotyczące niektórych osobliwości obu kultur narodowych. Następnie przedstawiono dosyć szczegółowy zapis atmosfery stworzonej przez polskich i czeskich kibiców podczas rzeczonego turnieju, co zostało wpisane w pojęcie banalnego nacjonalizmu. Cały obraz jest wzbogacony o próbę odniesienia sytuacji zaobserwowanej we Wrocławiu do postaw, jakie Polacy, ogólnie rzecz biorąc, posiadają wobec Czechów. Nastawienia te wyrażono za pomocą danych statystycznych, jak również cech charakteru tradycyjnie przypisywanych temu narodowi w Polsce.
The Impact of ENSO on the South Atlantic Subtropical Dipole Mode
Authors: Rodrigues Regina R. , Campos Edmo J. D. , Haarsma Reindert
Published: January 2015

The impact of El Niño–Southern Oscillation (ENSO) on the South Atlantic subtropical dipole mode (SASD) is investigated using both observations and model simulations. The SASD is the dominant mode of coupled ocean–atmosphere variability in the South Atlantic. This study focuses on austral summer, when both ENSO and SASD peak. It is shown that negative SASD events are associated with central Pacific El Niño events by triggering the Pacific–South American wave train (PSA). The latter resembles the third leading mode of atmospheric variability in the Southern Hemisphere (PSA2) and causes a weakening and meridional shift of the South Atlantic subtropical high, which then generates the negative SASD events. On the other hand, a strengthening of the South Atlantic subtropical high related to central La Niña teleconnections causes positive SASD events. The results herein show that the PSA2, triggered by central Pacific ENSO events, connects the tropical Pacific to the Atlantic. This connection is absent from eastern Pacific ENSO events, which appear to initiate the second leading mode of atmospheric variability in the Southern Hemisphere (PSA1). It is for this reason that previous studies have found weak correlations between ENSO and SASD. These findings can improve the climate prediction of southeastern South America and southern Africa since these regions are affected by sea surface temperature anomalies of both the Pacific and Atlantic Oceans.
Double-Diffusive Interleaving: Properties of the Steady-State Solution
Authors: Li Yuehua , McDougall Trevor J.
Published: January 2015

Double-diffusive interleaving is examined as it progresses from a linear instability toward finite amplitude. When the basic stratification is in the “finger” sense, the initial series of finger interfaces is unstable and one grows in strength at the expense of the others. At an intermediate stage of its development, the interleaving motions pass through a stage when every second interface in the vertical is stable to double diffusion. At a later time this interface turns into a “diffusive” double-diffusive interface. This study takes the fluxes of heat and salt across both the finger and diffusive interfaces to be given by the laboratory flux laws, and the authors ask whether a steady state is possible. It is found that the fluxes across the diffusive interfaces must be many times stronger relative to the corresponding fluxes across the finger interfaces than is indicated from existing flux expressions derived from laboratory experiments. The total effect of the interleaving motion on the vertical fluxes of heat and of salt are calculated for the steady-state solutions. It is found that both the fluxes of heat and salt are upgradient, corresponding to a negative vertical diffusion coefficient for all heat, salt, and density. For moderate to large Prandtl numbers, these negative effective diapycnal diffusivities of heat and salt are approximately equal so that the interleaving process acts to counteract some of the usual turbulent diapycnal diffusivity due to breaking internal waves.
Experimental identification of flow properties of a S355 structural steel for hot deformation processes
Authors: Schmicker David , Paczulla Stefan , Nitzschke Steffen , Groschopp Sven , Naumenko Konstantin , Jüttner Sven , Strackeljan Jens
Published: December 2014

A major issue in modeling the dynamics of hot deformation processes is the proper definition of the constitutive law and, therewith, the identification of material parameters. Popular approaches in relating the stress and strain rate values are equations for the power-law and the power-law breakdown regimes. The material parameters of these two models are basically described by a temperature-dependent absolute value, for example, a flow stress, and a strain rate sensitivity being often referred to as power-law exponent or ductility of the material. The current contribution addresses the experimental identification of these two parameters of a S355 structural steel by an innovative testing program on a Gleeble 3500 testing environment. This allows the identification of the hot deformation parameters for a range of temperatures by only one test with varying temperatures. Furthermore, an extrapolation technique is proposed to capture higher strain rate regimes, as occurring in hot deformation processes. A specific application of the material data on basis of a simulated friction welding process demonstrates the scope of the acquired material parameters and concludes the findings of this article.
Football in Arabic literature in diaspora: Global influences and local manifestations
Authors: Awad Yousef
Published: December 2014

This paper explores how Arab writers in diaspora present football in their literary works. Through an examination of Rabih Alameddine’s I, the Divine, Laila Lalami’s Secret Son and Leila Aboulela’s Lyrics Alley, the paper highlights the way in which Arab novelists in diaspora draw on the game’s international popularity to supplement and clarify the themes that these novels explore. Specifically, this paper investigates how the three novels portray the relationship between the individual and the nation and it suggests that these novels may be read within a context of a growing Arab involvement in international football over the past few years, including recent investments by state members of the Gulf Cooperation Council in European football, the emergence of international football superstars of Arab descent, the direct and indirect influences of football on recent socioeconomic and political transformations in Arab countries, including the Arab Spring, and FIFA’s controversial decision to stage the 2022 FIFA World Cup in Qatar. Thanks to their position between cultures, these writers render football as a site on which socioeconomic, political and cultural discourses converge. By depicting the quotidian experiences of culturally and ethnically varied characters, the novels offer divergent perspectives on the game’s entanglement with global and local influences and football emerges as a central issue around which the above writers construct some of the most important episodes in the three novels. In this way the three novels demonstrate that the game’s international popularity makes it intricately linked with the daily experiences of the characters they depict.
Evolutionary Spirituality
Authors: Hubbard Barbara Marx
Published: January 2015

Like the great visionaries of the past, many human beings around the globe today are experiencing a spiritual awakening. In response to the unprecedented threats and changes in our environment, an evolutionary spirituality is emerging that offers a new perspective on the nature of the universe and of human life. Instead of accepting a mechanistic and materially limiting definition of existence, growing numbers of individuals are coming to perceive consciousness as the prime moving force throughout the cosmos and to view themselves as active agents in an ongoing process of universal co-creation.
The Future Evolution of Consciousness
Authors: Lombardo Thomas
Published: January 2015

Human consciousness is an evolutionary phenomenon embedded within an evolutionary universe. Future consciousness is an evolution of evolution, bringing the evolutionary process under purposeful control. Through future consciousness, we are guiding our own self-evolution. “Flourishing in the flow of evolution” is a realistic and dynamic model for identifying psychological well-being and our preferable future evolution. Wisdom facilitates flourishing and is the highest expression of future consciousness. Wisdom serves as the guiding light for both our individual future development and our collective evolution. Education should serve the ongoing development of wisdom. Science fiction provides an arena for imagining and thinking about the possibilities of the future. Science fiction reflects flexible, diverse, and holistic future consciousness expressed in a narrative and mythic form. A key challenge to science fiction is to envision what future conscious minds will be like.
The Brink of Disaster . . . or The Brink of Maturity?
Authors: Sahtouris Elisabet
Published: January 2015

Humanity faces a perfect storm of crises yet persists in distortion of evidence and outright denial. To account for this, the author argues that the foundations of science, theories based on them, and the adoption of Darwinian competition by economists have blinded us to an evolutionary mandate to shift from our youthful, competitive global economy into mature cooperation toward a truly wise society that integrates our economy into Earth’s ecology as an ecosophy. Nature shows the way, and once we see the mature side of evolution, we can recognize the promising signs of our own human evolution.
An investigation of biomarkers derived from legacy microarray data for their utility in the RNA-seq era
Authors: Su Zhenqiang , Fang Hong , Hong Huixiao , Shi Leming , Zhang Wenqian , Zhang Wenwei , Zhang Yanyan , Dong Zirui , Lancashire Lee J , Bessarabova Marina , Yang Xi , Ning Baitang , Gong Binsheng , Meehan Joe , Xu Joshua , Ge Weigong , Perkins Roger , Fischer Matthias , Tong Weida
Published: December 2014

Background

Gene expression microarray has been the primary biomarker platform ubiquitously applied in biomedical research, resulting in enormous data, predictive models, and biomarkers accrued. Recently, RNA-seq has looked likely to replace microarrays, but there will be a period where both technologies co-exist. This raises two important questions: Can microarray-based models and biomarkers be directly applied to RNA-seq data? Can future RNA-seq-based predictive models and biomarkers be applied to microarray data to leverage past investment?

Results

We systematically evaluated the transferability of predictive models and signature genes between microarray and RNA-seq using two large clinical data sets. The complexity of cross-platform sequence correspondence was considered in the analysis and examined using three human and two rat data sets, and three levels of mapping complexity were revealed. Three algorithms representing different modeling complexity were applied to the three levels of mappings for each of the eight binary endpoints and Cox regression was used to model survival times with expression data. In total, 240,096 predictive models were examined.

Conclusions

Signature genes of predictive models are reciprocally transferable between microarray and RNA-seq data for model development, and microarray-based models can accurately predict RNA-seq-profiled samples; while RNA-seq-based models are less accurate in predicting microarray-profiled samples and are affected both by the choice of modeling algorithm and the gene mapping complexity. The results suggest continued usefulness of legacy microarray data and established microarray biomarkers and predictive models in the forthcoming RNA-seq era.
Systematic evaluation of connectivity map for disease indications
Authors: Cheng Jie , Yang Lun , Kumar Vinod , Agarwal Pankaj
Published: December 2014

Background

Connectivity map data and associated methodologies have become a valuable tool in understanding drug mechanism of action (MOA) and discovering new indications for drugs. One of the key ideas of connectivity map (CMAP) is to measure the connectivity between disease gene expression signatures and compound-induced gene expression profiles. Despite multiple impressive anecdotal validations, only a few systematic evaluations have assessed the accuracy of this aspect of CMAP, and most of these utilize drug-to-drug matching to transfer indications across the two drugs.

Methods

To assess CMAP methodologies in a more direct setting, namely the power of classifying known drug-disease relationships, we evaluated three CMAP-based methods on their prediction performance against a curated dataset of 890 true drug-indication pairs. The disease signatures were generated using Gene Logic BioExpress™ system and the compound profiles were derived from the Connectivity Map database (CMAP, build 02, http://www.broadinstitute.org/CMAP/).

Results

The similarity scoring algorithm called eXtreme Sum (XSum) performs better than the standard Kolmogorov-Smirnov (KS) statistic in terms of the area under curve and can achieve a four-fold enrichment at 0.01 false positive rate level, with AUC = 2.2E-4, P value = 0.0035.

Conclusion

Connectivity map can significantly enrich true positive drug-indication pairs given an effective matching algorithm.
Joint inversion of seismic refraction and resistivity data using layered models — Applications to groundwater investigation
Authors: Juhojuntti Niklas , Kamm Jochen
Published: January 2015

We developed a method for joint inversion of seismic refraction and resistivity data, using sharp-boundary models with few layers (typically three). We demonstrated the usefulness of the approach via examples from near-surface case studies involving shallow groundwater exploration and geotechnical investigations, although it should also be applicable to other types of layered environments, e.g., sedimentary basins. In our model parameterization, the layer boundaries were common for the resistivity and velocity distributions. Within the layers, only lateral variations in the material parameters (resistivity and velocity) were allowed, and we assumed no correlation between these. The inversion was performed using a nonlinear least-squares algorithm, using lateral smoothing to the layer boundaries and to the materialparameters. Depending on the subsurface conditions, the smoothing can be applied either to the depth of the layer boundaries or to the layer thicknesses. The forward responses and Jacobian for refraction seismics were calculated through ray tracing. The resistivity computations were performed with finite differences and a cell-to-layer transform for the Fréchet derivatives. Our method performed well in synthetic tests, and in the case studies, the layer boundaries were in good agreement with in situ tests and seismic reflection data, although minimum-structure inversion generally has a better data fit due to more freedom to introduce model heterogeneity. We further found that our joint inversion approach can provide more accurate thickness estimates for seismic hidden layers.