bluuebunny/crossref_metadata_2025 huggingface dataset:
The Fundamental Aspects of TEMOM Model for Particle Coagulation due to Brownian Motion—Part II: In the Continuum Regime
Authors: Qing He , Mingliang Xie
Published: December 2013

The fundamental aspects of the Taylor-series expansion method of moment (TEMOM) model proposed to model the aerosol population balance equation due to Brownian coagulation in the continuum regime is shown in this study, such as the choice of the expansion pointu, the relationship between asymptotic behavior and analytical solution, and the error of the high-order moment equations. All these analyses will contribute to the buildup of the theoretical system of the TEMOM model.
Autosomal Dominant Pseudohypoaldosteronism Type 1 in an Infant with Salt Wasting Crisis Associated with Urinary Tract Infection and Obstructive Uropathy
Authors: Bowden Sasigarn A. , Cozzi Corin , Hickey Scott E. , Thrush Devon Lamb , Astbury Caroline , Nuthakki Sushma
Published: December 2013

Type 1 pseudohypoaldosteronism (PHA1) is a salt wasting syndrome caused by renal resistance to aldosterone. Primary renal PHA1 or autosomal dominant PHA1 is caused by mutations in mineralocorticoids receptor gene (NR3C2), while secondary PHA1 is frequently associated with urinary tract infection (UTI) and/or urinary tract malformations (UTM). We report a 14-day-old male infant presenting with severe hyperkalemia, hyponatremic dehydration, metabolic acidosis, and markedly elevated serum aldosterone level, initially thought to have secondary PHA1 due to the associated UTI and posterior urethral valves. His serum aldosterone remained elevated at 5 months of age, despite resolution of salt wasting symptoms. Chromosomal microarray analysis revealed a deletion of exons 3–5 inNR3C2in the patient and his asymptomatic mother who also had elevated serum aldosterone level, confirming that he had primary or autosomal dominant PHA1. Our case raises the possibility that some patients with secondary PHA1 attributed to UTI and/or UTM may instead have primary autosomal dominant PHA1, for which genetic testing should be considered to identify the cause, determine future recurrence risk, and possibly prevent the life-threatening salt wasting in a subsequent family member. Future clinical research is needed to investigate the potential overlapping between secondary PHA1 and primary autosomal dominant PHA1.
Synthesis, Electrochemical, Spectroscopic, Antimicrobial, and Superoxide Dismutase Activity of Nickel (II) Complexes with Bidentate Schiff Bases
Authors: Patel R. N. , Rawat S. P. , Choudhary Mukesh
Published: December 2013

Five new nickel (II) complexes, namely, [Ni(L1)2](ClO4)2(1); [Ni(L2)2](ClO4)2(2); [Ni(L3)2](ClO4)2(3); [Ni(L4)2](ClO4)2(4); [Ni(L5)2](ClO4)2(5), where L1 = benzoylhydrazide; L2 = N-[(1)-1-(2-methylphenyl)ethylidene]benzohydrazide; L3=N-[(1)-1-(4-methylphenyl)ethylidene]benzohydrazide; L4=N-[(1)-1-(2-methoxyphenyl)ethylidene]benzohydrazide; L5 = N-[(1)-1-(4-methoxy-phenyl)ethylidene]benzohydrazide, have been synthesized and characterized by various physicochemical and spectroscopic techniques. The synthesized complexes are stable powders, insoluble in common organic solvents such as ethanol, benzene, carbon tetrachloride, chloroform, and diethyl ether, and are nonelectrolytes. The magnetic and spectroscopic data indicate a distorted square planar geometry for all complexes. The superoxide dismutase activity of these complexes has been measured and discussed. Antibacterial and antifungal properties of these complexes were also tested.
Antioxidant Potential of a Polyherbal Antimalarial as an Indicator of Its Therapeutic Value
Authors: Arrey Tarkang Protus , Nwachiban Atchan Achille Parfait , Kuiate Jules-Roger , Okalebo Faith Apoelot , Guantai Anastasia Nkatha , Agbor Gabriel Agbor
Published: December 2013

Nefangis a polyherbal product composed ofMangifera indica(bark and leaf),Psidium guajava, Carica papaya, Cymbopogon citratus, Citrus sinensis, and Ocimum gratissimum(leaves), used for the treatment of malaria. Compounds with antioxidant activity are believed to modulate plasmodial infection. Antioxidant activity of the constituent aqueous plants extracts,in vitro, was evaluated using the 2,2-diphenyl-1-picrylhydrazyl (DPPH), total phenolic content (TPC), and ferric reducing antioxidant power (FRAP) methods and,in vivo,Nefang(100 and 500 mg kg−1) activity was evaluated in carbon tetrachloride-induced oxidative stressed Wistar rats. Superoxide dismutase, catalase activities, and lipid peroxidation by the malondialdehyde and total proteins assays were carried out.P. guajava, M. indicaleaf, and bark extracts had the highest antioxidant properties in all three assays, with no statistically significant difference. Rats treated with the carbon tetrachloride had a statistically significant decrease in levels of triglycerides, superoxide dismutase, and catalase (P<0.05) and increase in malondialdehyde activity, total protein levels, and liver and renal function markers, whereas rats treated withNefangshowed increased levels in the former and dose-dependent decrease towards normal levels in the later. These results reveal the constituent plants ofNefangthat contribute to itsin vivoantioxidant potential. This activity is a good indication of the therapeutic potential ofNefang.
A Heuristic Algorithm for Solving Triangle Packing Problem
Authors: Wang Ruimin , Luo Yuqiang , Dong Jianqiang , Liu Shuai , Qi Xiaozhuo
Published: December 2013

The research on the triangle packing problem has important theoretic significance, which has broad application prospects in material processing, network resource optimization, and so forth. Generally speaking, the orientation of the triangle should be limited in advance, since the triangle packing problem is NP-hard and has continuous properties. For example, the polygon is not allowed to rotate; then, the approximate solution can be obtained by optimization method. This paper studies the triangle packing problem by a new kind of method. Such concepts as angle region, corner-occupying action, corner-occupying strategy, and edge-conjoining strategy are presented in this paper. In addition, an edge-conjoining and corner-occupying algorithm is designed, which is to obtain an approximate solution. It is demonstrated that the proposed algorithm is highly efficient, and by the time complexity analysis and the analogue experiment result is found.
Asymptotic Behavior of Solutions to a Vector Integral Equation with Deviating Arguments
Authors: González Cristóbal , Jiménez-Melado Antonio
Published: December 2013

In this paper, we propose the study of an integral equation, with deviating arguments, of the typey(t)=ω(t)-∫0∞‍f(t,s,y(γ1(s)),…,y(γN(s)))ds,t≥0,in the context of Banach spaces, with the intention of giving sufficient conditions that ensure the existence of solutions with the same asymptotic behavior at∞asω(t). A similar equation, but requiring a little less restrictive hypotheses, isy(t)=ω(t)-∫0∞‍q(t,s)F(s,y(γ1(s)),…,y(γN(s)))ds,t≥0.In the case ofq(t,s)=(t-s)+, its solutions with asymptotic behavior given byω(t)yield solutions of the second order nonlinear abstract differential equationy''(t)-ω''(t)+F(t,y(γ1(t)),…,y(γN(t)))=0,with the same asymptotic behavior at∞asω(t).
Cysteine Catabolism: A Novel Metabolic Pathway Contributing to Glioblastoma Growth
Authors: Prabhu Antony , Sarcar Bhaswati , Kahali Soumen , Yuan Zhigang , Johnson Joseph J. , Adam Klaus-Peter , Kensicki Elizabeth , Chinnaiyan Prakash
Published: December 2013

The relevance of cysteine metabolism in cancer has gained considerable interest in recent years, largely focusing on its role in generating the antioxidant glutathione. Through metabolomic profiling using a combination of high-throughput liquid and gas chromatography–based mass spectrometry on a total of 69 patient-derived glioma specimens, this report documents the discovery of a parallel pathway involving cysteine catabolism that results in the accumulation of cysteine sulfinic acid (CSA) in glioblastoma. These studies identified CSA to rank as one of the top metabolites differentiating glioblastoma from low-grade glioma. There was strong intratumoral concordance of CSA levels with expression of its biosynthetic enzyme cysteine dioxygenase 1 (CDO1). Studies designed to determine the biologic consequence of this metabolic pathway identified its capacity to inhibit oxidative phosphorylation in glioblastoma cells, which was determined by decreased cellular respiration, decreased ATP production, and increased mitochondrial membrane potential following pathway activation. CSA-induced attenuation of oxidative phosphorylation was attributed to inhibition of the regulatory enzyme pyruvate dehydrogenase. Studies performed in vivo abrogating the CDO1/CSA axis using a lentiviral-mediated short hairpin RNA approach resulted in significant tumor growth inhibition in a glioblastoma mouse model, supporting the potential for this metabolic pathway to serve as a therapeutic target. Collectively, we identified a novel, targetable metabolic pathway involving cysteine catabolism contributing to the growth of aggressive high-grade gliomas. These findings serve as a framework for future investigations designed to more comprehensively determine the clinical application of this metabolic pathway and its contributory role in tumorigenesis. Cancer Res; 74(3); 787–96. ©2013 AACR.
EGFRvIII mCAR-Modified T-Cell Therapy Cures Mice with Established Intracerebral Glioma and Generates Host Immunity against Tumor-Antigen Loss
Authors: Sampson John H. , Choi Bryan D. , Sanchez-Perez Luis , Suryadevara Carter M. , Snyder David J. , Flores Catherine T. , Schmittling Robert J. , Nair Smita K. , Reap Elizabeth A. , Norberg Pamela K. , Herndon James E. , Kuan Chien-Tsun , Morgan Richard A. , Rosenberg Steven A. , Johnson Laura A.
Published: December 2013

Purpose: Chimeric antigen receptor (CAR) transduced T cells represent a promising immune therapy that has been shown to successfully treat cancers in mice and humans. However, CARs targeting antigens expressed in both tumors and normal tissues have led to significant toxicity. Preclinical studies have been limited by the use of xenograft models that do not adequately recapitulate the immune system of a clinically relevant host. A constitutively activated mutant of the naturally occurring epidermal growth factor receptor (EGFRvIII) is antigenically identical in both human and mouse glioma, but is also completely absent from any normal tissues.

Experimental Design: We developed a third-generation, EGFRvIII-specific murine CAR (mCAR), and performed tests to determine its efficacy in a fully immunocompetent mouse model of malignant glioma.

Results: At elevated doses, infusion with EGFRvIII mCAR T cells led to cures in all mice with brain tumors. In addition, antitumor efficacy was found to be dependent on lymphodepletive host conditioning. Selective blockade with EGFRvIII soluble peptide significantly abrogated the activity of EGFRvIII mCAR T cells in vitro and in vivo, and may offer a novel strategy to enhance the safety profile for CAR-based therapy. Finally, mCAR-treated, cured mice were resistant to rechallenge with EGFRvIIINEG tumors, suggesting generation of host immunity against additional tumor antigens.

Conclusion: All together, these data support that third-generation, EGFRvIII-specific mCARs are effective against gliomas in the brain and highlight the importance of syngeneic, immunocompetent models in the preclinical evaluation of tumor immunotherapies. Clin Cancer Res; 20(4); 972–84. ©2013 AACR.
Cellular Uptake of Imatinib into Leukemic Cells Is Independent of Human Organic Cation Transporter 1 (OCT1)
Authors: Nies Anne T. , Schaeffeler Elke , van der Kuip Heiko , Cascorbi Ingolf , Bruhn Oliver , Kneba Michael , Pott Christiane , Hofmann Ute , Volk Christopher , Hu Shuiying , Baker Sharyn D. , Sparreboom Alex , Ruth Peter , Koepsell Hermann , Schwab Matthias
Published: December 2013

Purpose: In addition to mutated BCR-ABL1 kinase, the organic cation transporter 1 (OCT1, encoded by SLC22A1) has been considered to contribute to imatinib resistance in patients with chronic myeloid leukemia (CML). As data are conflicting as to whether OCT1 transports imatinib and may serve as a clinical biomarker, we used a combination of different approaches including animal experiments to elucidate comprehensively the impact of OCT1 on cellular imatinib uptake.

Experimental Design: Transport of imatinib was studied using OCT1-expressing Xenopus oocytes, mammalian cell lines (HEK293, MDCK, V79) stably expressing OCT1, human leukemic cells, and Oct1-knockout mice. OCT1 mRNA and protein expression were analyzed in leukemic cells from patients with imatinib-naïve CML as well as in cell lines.

Results: Transport and inhibition studies showed that overexpression of functional OCT1 protein in Xenopus oocytes or mammalian cell lines did not lead to an increased cellular accumulation of imatinib. The CML cell lines (K562, Meg-01, LAMA84) and leukemic cells from patients expressed neither OCT1 mRNA nor protein as demonstrated by immunoblotting and immunofluorescence microscopy, yet they showed a considerable imatinib uptake. Oct1 deficiency in mice had no influence on plasma and hepatic imatinib concentrations.

Conclusions: These data clearly demonstrate that cellular uptake of imatinib is independent of OCT1, and therefore OCT1 is apparently not a valid biomarker for imatinib resistance. Clin Cancer Res; 20(4); 985–94. ©2013 AACR.
Misalignment of a Novel Single-Piece Acrylic Intraocular Lens in the First Three Months after Surgery
Authors: Chen Yen-An , Hirnschall Nino , Maedel Sophie , Findl Oliver
Published: December 2013

Purpose: To evaluate the misalignment of a new single-piece microincisional hydrophobic acrylic intraocular lens (IOL) in emmetropic, myopic and hyperopic eyes within the first 3 months after surgery. Setting: Vienna Institute for Research in Ocular Surgery, Karl Landsteiner Institute, Hanusch Hospital, Department of Ophthalmology, Vienna, Austria. Methods: Patients with age-related cataract were included in this prospective study. Each patient received a single-piece microincisional hydrophobic acrylic IOL (AF-1 NY-60, Hoya) in the study eye. Subgroups of emmetropic, myopic and hyperopic eyes were defined according to IOL power calculation. Anterior chamber depth (ACD) measurements were performed with an AC-Master. Tilt and decentration of the IOL were measured with a Purkinje meter. Follow-up assessments were performed 1 h, 3 weeks and 3 months after surgery. Results: Forty-two eyes of 42 patients (21 emmetropic, 10 myopic and 11 hyperopic eyes) were included. The mean ACD 1 h, 3 weeks and 3 months after surgery was 4.597 ± 0.533, 4.483 ± 0.347 and 4.438 ± 0.398 mm, respectively. Differences in ACD between follow-ups and between subgroups were not statistically significant (both p > 0.05). On average, 3 months after surgery IOLs were tilted 0.81 ± 2.86° nasally and 0.70 ± 3.13° inferiorly and decentered 0.06 ± 0.24 mm nasally and 0.15 ± 0.29 mm superiorly. Differences in tilt and decentration were not statistically significant (both p > 0.05). We observed 1 case of severe capsular fibrosis. Conclusions: The single-piece microincisional hydrophobic acrylic IOL showed good axial stability and only little, clinically not relevant tilt and decentration in the first 3 months after surgery.
Fungal Keratitis - Improving Diagnostics by Confocal Microscopy
Authors: Nielsen Esben , Heegaard Steffen , Prause Jan Ulrik , Ivarsen Anders , Mortensen Klaus Leth , Hjortdal Jesper
Published: December 2013

Purpose: Introducing a simple image grading system to support the interpretation of in vivo confocal microscopy (IVCM) images in filamentous fungal keratitis. Setting: Clinical and confocal studies took place at the Department of Ophthalmology, Aarhus University Hospital, Denmark. Histopathological analysis was performed at the Eye Pathology Institute, Department of Neuroscience and Pharmacology, University of Copenhagen, Denmark. Methods: A recent series of consecutive patients with filamentous fungal keratitis is presented to demonstrate the results from in-house IVCM. Based upon our experience with IVCM and previously published images, we composed a grading system for interpreting IVCM images of filamentous fungal keratitis. Results: A recent case series of filamentous fungal keratitis from 2011 to 2012 was examined. There were 3 male and 3 female patients. Mean age was 44.5 years (range 12-69), 6 out of 17 (35%) cultures were positive and a total of 6/7 (86%) IVCM scans were positive. Three different categories of IVCM results for the grading of diagnostic certainty were formed. Conclusion: IVCM is a valuable tool for diagnosing filamentous fungal keratitis. In order to improve the reliability of IVCM, we suggest implementing a simple and clinically applicable grading system for aiding the interpretation of IVCM images of filamentous fungal keratitis.
Identification of CalDAG-GEFI as an intracellular target for the vicinal dithiol binding agent phenylarsine oxide in human platelets
Authors: Kuo Chih-Yun , Wang Hui-Chun , Kung Po-Hsiung , Lu Chi-Yu , Liao Chieh-Yu , Wu Ming-Tsang , Wu Chin-Chung
Published: December 2013

CalDAG-GEFI, a guanine nucleotide exchange factor activating Rap1, is known to play a key role in Ca2+-dependent glycoprotein (GP)IIb/IIIa activation and platelet aggregation. Although inhibition of CalDAG-GEFI could be a potential strategy for antiplatelet therapy, no inhibitor of this protein has been identified. In the present study, phenylarsine oxide (PAO), a vicinal dithiol blocker, potently prevented Rap1 activation in thrombin-stimulated human platelets without significantly inhibiting intracellular Ca2+ mobilisation and protein kinase C activation. PAO also prevented the Ca2+ ionophore-induced Rap1 activation and platelet aggregation, which are dependent on CalDAG-GEFI. In the biotin-streptavidin pull-down assay, CalDAG-GEFI was efficiently pull-downed by streptavidin beads from the lysates of biotin-conjugated PAO-treated platelets, suggesting that PAO binds to intracellular CalDAG-GEFI with high affinity. The above effects of PAO were reversed by a vicinal dithiol compound 2,3-dimercaptopropanol. In addition, CalDAG-GEFI formed disulfide-linked oligomers in platelets treated with the thiol-oxidant diamide, indicating that CalDAG-GEFI contains redox-sensitive thiols. In a purified recombinant protein system, PAO directly inhibited CalDAG-GEFI-stimulated GTP binding to Rap1. Using CalDAG-GEFI and Rap1-overexpressed human embryonic kidney 293T cells, we further confirmed that PAO abolished Ca2+-mediated Rap1 activation. Taken together, these results have demonstrated that CalDAG-GEFI is one of the targets of action of PAO, and propose an important role of vicinal cysteines for the functions of CalDAG-GEFI.
Benign FGB (148Lys→Asn, and 448Arg→Lys), and novel causative γ211Tyr→His mutation distinguished by time of flight mass spectrometry in a family with hypofibrinogenaemia
Authors: Mangos Hilda , Faed James M. , Brennan Stephen O.
Published: December 2013

We describe a novel procedure for the direct analysis of plasma fibrinogen by HPLC time of flight (TOF) mass spectrometry and apply it to the investigation of a family with hypofibrinogenaemia. Electrospray TOF analysis provided much higher resolution than was possible with our previous quadrupole analyser and revealed three different mass changes within the fibrinogen Bβ and γ chains of the family. It also demonstrated the actual hypofibrinogenaemia phenotype was caused by an aberrant _ chain (-23 Da) which was expressed at a diminished ratio of 0.2:1 relative to γA and co-inherited with a second coequally expressed Bβ variant (BβM /BβA, 1:1). Co-segregation was confirmed by gene analysis that showed the affected father and son had a very rare Bβ148Lys→Arg mutation (-14 Da) inherited together with a unique new γ211Tyr→His mutation (-26 Da). This latter causative substitution occurs at a site that is absolutely conserved across all fibrinogen chains and preserved across all species. TOF analysis also identified a variant B_ chain (54,186 Da) that was coequally expressed with normal Bβ chains (54,213 Da) in the unaffected mother.
A new species of Oxytropis (Fabaceae: Papilionoideae) from India
Authors: Chaudhary Lal Babu , Bajpai Omesh , Behera Soumit Kumar , Sahu Nayan
Published: December 2013

A new species Oxytropis sanjappae is described and illustrated from the Himalaya in India. The new species is widely scattered from Losar to Kaza in Lahul-Spiti region of Himachal Pradesh State. The relationship of the species has been discussed with O. cachemiriana and O. tatarica. The new species differs in having hairs very dense, silky and white, stems generally absent or quite reduced, racemes capitate, globose-ovoid or oblong, many-flowered, dense and elongating in infruitescence, calyx teeth distinctly longer than tube, corolla light purplish pink and almost equal to calyx, wing petals obtuse at apex, mucro of the keel petal ca. 1 mm long and pods comparatively larger in size. A taxonomic key to the all 18 species of the genus occurring in India including new ones has been provided for the first time. In addition, the ecological studies related with the frequency, density, basal cover and importance value index (IVI) have also been carried out to know the conservation status of the species in the Himalaya.
Acanthoplesiops cappuccino, a new species of acanthoclinine fish from the Red Sea (Teleostei: Plesiopidae)
Authors: GILL ANTHONY C. , BOGORODSKY SERGEY V. , MAL AHMAD O.
Published: December 2013

Acanthoplesiops cappuccino is described from the 16.4 mm SL holotype collected from Jeddah, Saudi Arabia, Red Sea. The following combination of characters distinguishes it from congeners: dorsal-fin rays XVIII,4; anal-fin rays VII,4; pectoral-fin rays 18; caudal fin not connected to last rays of dorsal and anal fins by membrane; and caudal peduncle with a pale yellowish brown bar, which extends broadly on to caudal fin. An underwater photo of the anaesthetised holotype is provided, as well as one of the freshly dead holotype and only known specimen of the similar species A. naka. Tables summarizing diagnostic characters of the six known species of Acanthoplesiops are included. n�Uhd�_u�_k congeners by possessing both rostral and maxillary barbels; having the last simple dorsal-fin ray weak and smooth; the lateral line complete, with 40–42+1 pored scales; ½7–½8/1/3½ scales in transverse line from dorsal-fin origin to pelvic-fin origin; 4½ scales between lateral line and anal-fin origin. Hypselobarbus kolus is considered a synonym of H. curmuca, which is redescribed: it is distinguished from all congeners by possessing maxillary barbels only; the last simple dorsal-fin ray weak and smooth; 41–43+1 lateral-line scales; 9–10/1/4½–5 scales in transverse line between origins of dorsal and pelvic fins; and 5½–6 scales between lateral line and anal-fin origin.
The salmon, the lungfish (or the coelacanth) and the cow: a revival?
Authors: BOCKMANN FLÁVIO A. , DE CARVALHO MARCELO R. , DE CARVALHO MURILO
Published: December 2013

In the late 1970s, intense and sometimes acrimonious discussions between the recently established phylogeneticists/cladists and the proponents of the long-standing ‘gradistic’ school of systematics transcended specialized periodicals to reach a significantly wider audience through the journal Nature (Halstead, 1978, 1981; Gardiner et al., 1979; Halstead et al., 1979). As is well known, cladistis ‘won’ the debate by showing convincingly that mere similarity or ‘adaptive levels’ were not decisive measures to establish kinship. The essay ‘The salmon, the lungfish and the cow: a reply’ by Gardiner et al. (1979) epitomized that debate, deliberating to a wider audience the foundations of the cladistic paradigm, advocating that shared derived characters (homologies) support a sister-group relationship between the lungfish and cow exclusive of the salmon (see also Rosen et al., 1981; Forey et al., 1991).
Change in the Odds of Warm Years and Seasons Due to Anthropogenic Influence on the Climate
Authors: Christidis Nikolaos , Stott Peter A.
Published: December 2013

The new Hadley Centre system for attribution of weather and climate extremes provides assessments of how human influence on the climate may lead to a change in the frequency of such events. Two different types of ensembles of simulations are generated with an atmospheric model to represent the actual climate and what the climate would have been in the absence of human influence. Estimates of the event frequency with and without the anthropogenic effect are then obtained. Three experiments conducted so far with the new system are analyzed in this study to examine how anthropogenic forcings change the odds of warm years, summers, or winters in a number of regions where the model reliably reproduces the frequency of warm events. In all cases warm events become more likely because of human influence, but estimates of the likelihood may vary considerably from year to year depending on the ocean temperature. While simulations of the actual climate use prescribed observational data of sea surface temperature and sea ice, simulations of the nonanthropogenic world also rely on coupled atmosphere–ocean models to provide boundary conditions, and this is found to introduce a major uncertainty in attribution assessments. Improved boundary conditions constructed with observational data are introduced in order to minimize this uncertainty. In more than half of the 10 cases considered here anthropogenic influence results in warm events being 3 times more likely and extreme events 5 times more likely during September 2011–August 2012, as an experiment with the new boundary conditions indicates.
Mantle cell lymphoma in cyclin D1 transgenic mice with Bim-deficient B cells
Authors: Katz Samuel G. , LaBelle James L. , Meng Hailong , Valeriano Regina P. , Fisher Jill K. , Sun Heather , Rodig Scott J. , Kleinstein Steven H. , Walensky Loren D.
Published: December 2013

Key Points

Immune stimulation of cyclin D1 transgenic mice bearing Bim-deficient B cells induces an MCL phenotype. The induced lymphoma of EμCycD1CD19CREBimfl/fl mice highlights the collaborative roles of Bim deletion and cyclin D1 expression in MCL.
A meta-analysis of genome-wide association studies identifies ORM1 as a novel gene controlling thrombin generation potential
Authors: Rocanin-Arjo Ares , Cohen William , Carcaillon Laure , Frère Corinne , Saut Noémie , Letenneur Luc , Alhenc-Gelas Martine , Dupuy Anne-Marie , Bertrand Marion , Alessi Marie-Christine , Germain Marine , Wild Philipp S. , Zeller Tanja , Cambien Francois , Goodall Alison H. , Amouyel Philippe , Scarabin Pierre-Yves , Trégouët David-Alexandre , Morange Pierre-Emmanuel ,   and the CardioGenics Consortium
Published: December 2013

Key Points

Genetic variations at the ORM1 locus and concentrations of the encoded protein associate with thrombin generation. These findings may guide the development of novel antithrombotic treatments.
Promoter methylation of Wnt-antagonists in polypoid and nonpolypoid colorectal adenomas
Authors: Voorham Quirinus JM , Janssen Jerry , Tijssen Marianne , Snellenberg Suzanne , Mongera Sandra , van Grieken Nicole CT , Grabsch Heike , Kliment Martin , Rembacken Bjorn J , Mulder Chris JJ , van Engeland Manon , Meijer Gerrit A , Steenbergen Renske DM , Carvalho Beatriz
Published: December 2013

Background

Nonpolypoid adenomas are a subgroup of colorectal adenomas that have been associated with a more aggressive clinical behaviour compared to their polypoid counterparts. A substantial proportion of nonpolypoid and polypoid adenomas lack APC mutations, APC methylation or chromosomal loss of the APC locus on chromosome 5q, suggesting the involvement of other Wnt-pathway genes. The present study investigated promoter methylation of several Wnt-pathway antagonists in both nonpolypoid and polypoid adenomas.

Methods

Quantitative methylation-specific PCR (qMSP) was used to evaluate methylation of four Wnt-antagonists, SFRP2, WIF-1, DKK3 and SOX17 in 18 normal colorectal mucosa samples, 9 colorectal cancer cell lines, 18 carcinomas, 44 nonpolypoid and 44 polypoid adenomas. Results were integrated with previously obtained data on APC mutation, methylation and chromosome 5q status from the same samples.

Results

Increased methylation of all genes was found in the majority of cell lines, adenomas and carcinomas compared to normal controls. WIF-1 and DKK3 showed a significantly lower level of methylation in nonpolypoid compared to polypoid adenomas (p < 0.01). Combining both adenoma types, a positive trend between APC mutation and both WIF-1 and DKK3 methylation was observed (p < 0.05).

Conclusions

Methylation of Wnt-pathway antagonists represents an additional mechanism of constitutive Wnt-pathway activation in colorectal adenomas. Current results further substantiate the existence of partially alternative Wnt-pathway disruption mechanisms in nonpolypoid compared to polypoid adenomas, in line with previous observations.
Monocyte depletion increases local proliferation of macrophage subsets after skeletal muscle injury
Authors: Côté Claude H , Bouchard Patrice , van Rooijen Nico , Marsolais David , Duchesne Elise
Published: December 2013

Background

Sequential accumulation of M1 and M2 macrophages is critical for skeletal muscle recovery after an acute injury. While M1 accumulation is believed to rely on monocyte infiltration, the mechanisms of M2 accumulation remain controversial, but could involve an infiltrating precursor. Yet, strong depletion of monocytes only partially impairs skeletal muscle healing, supporting the existence of alternative mechanisms to palliate the loss of infiltrating macrophage progenitors. The aims of this study are thus to investigate if proliferation occurs in macrophage subsets within injured skeletal muscles; and to determine if monocyte depletion leads to increased proliferation of macrophages after injury.

Methods

Injury was induced by bupivacaine injection in the tibialis anterior muscle of rats. Blood monocytes were depleted by daily intravenous injections of liposome-encapsulated clodronate, starting 24 h prior to injury. In separate experiments, irradiation of hind limb was also performed to prevent resident cell proliferation. Upon euthanasia, blood and muscles were collected for flow cytometric analyses of macrophage/monocyte subsets.

Results

Clodronate induced a 80%-90% depletion of monocyte but only led to 57% and 41% decrease of M1 and M2 macrophage accumulation, respectively, 2 d following injury. Conversely, the number of M1 macrophages in monocyte-depleted rats was 2.4-fold higher than in non-depleted rats 4 d after injury. This was associated with a 16-fold increase in the number of proliferative M1 macrophages, which was reduced by 46% in irradiated animals. Proliferation of M2 macrophages was increased tenfold by clodronate treatment 4 d post injury. The accumulation of M2 macrophages was partially impaired by irradiation, regardless of monocyte depletion.

Conclusions

M1 and M2 subsets proliferate after skeletal muscle injury and their proliferation is enhanced under condition of monocyte depletion. Our study supports the conclusion that both infiltrating and resident precursors could contribute to M1 or M2 macrophage accumulation in muscle injury.
The effect of prosthetic feedback on the strategies and synergies used by vestibular loss subjects to control stance
Authors: Honegger Flurin , Hillebrandt Imke MA , van den Elzen Nadja GA , Tang Kok-Sing , Allum John HJ
Published: December 2013

Background

This study investigated changes in stance movement strategies and muscle synergies when bilateral peripheral vestibular loss (BVL) subjects are provided feedback of pelvis sway angle.

Methods

Six BVL (all male) and 7 age-matched male healthy control (HC) subjects performed 3 stance tasks: standing feet hip width apart, eyes closed, on a firm and foam surface, and eyes open on foam. Pelvis and upper trunk movements were recorded in the roll and pitch planes. Surface EMG was recorded from pairs of antagonistic muscles at the lower leg, trunk and upper arm. Subjects were first assessed without feedback. Then, they received training with vibrotactile, auditory, and fall-warning visual feedback during stance tasks before being reassessed with feedback.

Results

Feedback reduced pelvis sway angle displacements to values of HCs for all tasks. Movement strategies were reduced in amplitude but not otherwise changed by feedback. These strategies were not different from those of HCs before or after use of feedback. Low frequency motion was in-phase and high frequency motion anti-phasic. Feedback reduced amplitudes of EMG, activity ratios (synergies) of antagonistic muscle pairs and slightly reduced baseline muscle activity.

Conclusions

This is the first study demonstrating how vestibular loss subjects achieve a reduction of sway during stance with prosthetic feedback. Unchanged movement strategies with reduced amplitudes are achieved with improved antagonistic muscle synergies. This study suggests that both body movement and muscle measures could be explored when choosing feedback variables, feedback location, and patient groups for prosthetic devices which reduce sway of those with a tendency to fall.
Kinetic and isotherm studies of adsorption and biosorption processes in the removal of phenolic compounds from aqueous solutions: comparative study
Authors: Gholizadeh Abdolmajid , Kermani Majid , Gholami Mitra , Farzadkia Mehdi
Published: December 2013

The phenolic compounds are known by their carcinogenicity and high toxicity as well as creating unpleasant taste and odor in water resources. The present study develops a cost-effective technology for the treatment of water contaminated with phenolic compounds, including Phenol (Ph), 2-chlorophenol (2-CP), and 4-chlorophenol (4-CP). So, two sorbents, rice bran ash (RBA) and biomass of brown algae, Cystoseiraindica, were used and results were compared with the commercially granular activated carbon (GAC). The phenolic compounds were determined using a high performance liquid chromatography (HPLC) under batch equilibrium conditions. The effects of contact time, pH, initial adsorbate concentration, and adsorbent dosages on the removal efficiency were studied. The adsorption data were simulated by isotherm and kinetic models. Results indicated that RBA and GAC had the lowest efficiency for the removal of 2-CP, while the order of removal efficiency for C. indica biomass was as follows: 2-CP > 4-CP > phenol. The efficiency of GAC was higher than those of other adsorbents for all of the phenolic compounds. Furthermore, the adsorption capacity of RBA was found to be higher than that of C. indica biomass. The optimal initial pH for the removal of phenol, 2-CP and 4-CP was determined to be 5, 7, and 7 for RBA, GAC, and algal biomass, respectively. Kinetic studies suggested that the pseudo-second order best fitted the kinetic data.
Integrative analyses of gene expression and DNA methylation profiles in breast cancer cell line models of tamoxifen-resistance indicate a potential role of cells with stem-like properties
Authors: Lin Xue , Li Jian , Yin Guangliang , Zhao Qian , Elias Daniel , Lykkesfeldt Anne E , Stenvang Jan , Brünner Nils , Wang Jun , Yang Huanming , Bolund Lars , Ditzel Henrik J
Published: December 2013

Introduction

Development of resistance to tamoxifen is an important clinical issue in the treatment of breast cancer. Tamoxifen resistance may be the result of acquisition of epigenetic regulation within breast cancer cells, such as DNA methylation, resulting in changed mRNA expression of genes pivotal for estrogen-dependent growth. Alternatively, tamoxifen resistance may be due to selection of pre-existing resistant cells, or a combination of the two mechanisms.

Methods

To evaluate the contribution of these possible tamoxifen resistance mechanisms, we applied modified DNA methylation-specific digital karyotyping (MMSDK) and digital gene expression (DGE) in combination with massive parallel sequencing to analyze a well-established tamoxifen-resistant cell line model (TAMR), consisting of 4 resistant and one parental cell line. Another tamoxifen-resistant cell line model system (LCC1/LCC2) was used to validate the DNA methylation and gene expression results.

Results

Significant differences were observed in global gene expression and DNA methylation profiles between the parental tamoxifen-sensitive cell line and the 4 tamoxifen-resistant TAMR sublines. The 4 TAMR cell lines exhibited higher methylation levels as well as an inverse relationship between gene expression and DNA methylation in the promoter regions. A panel of genes, including NRIP1, HECA and FIS1, exhibited lower gene expression in resistant vs. parental cells and concurrent increased promoter CGI methylation in resistant vs. parental cell lines. A major part of the methylation, gene expression, and pathway alterations observed in the TAMR model were also present in the LCC1/LCC2 cell line model. More importantly, high expression of SOX2 and alterations of other SOX and E2F gene family members, as well as RB-related pocket protein genes in TAMR highlighted stem cell-associated pathways as being central in the resistant cells and imply that cancer-initiating cells/cancer stem-like cells may be involved in tamoxifen resistance in this model.

Conclusion

Our data highlight the likelihood that resistant cells emerge from cancer-initiating cells/cancer stem-like cells and imply that these cells may gain further advantage in growth via epigenetic mechanisms. Illuminating the expression and DNA methylation features of putative cancer-initiating cells/cancer stem cells may suggest novel strategies to overcome tamoxifen resistance.
Postsynaptic glutamate receptors regulate local BMP signaling at theDrosophilaneuromuscular junction
Authors: Sulkowski Mikolaj , Kim Young-Jun , Serpe Mihaela
Published: December 2013

Effective communication between pre- and postsynaptic compartments is required for proper synapse development and function. At the Drosophila neuromuscular junction (NMJ), a retrograde BMP signal functions to promote synapse growth, stability and homeostasis and coordinates the growth of synaptic structures. Retrograde BMP signaling triggers accumulation of the pathway effector pMad in motoneuron nuclei and at synaptic termini. Nuclear pMad, in conjunction with transcription factors, modulates the expression of target genes and instructs synaptic growth; a role for synaptic pMad remains to be determined. Here, we report that pMad signals are selectively lost at NMJ synapses with reduced postsynaptic sensitivities. Despite this loss of synaptic pMad, nuclear pMad persisted in motoneuron nuclei, and expression of BMP target genes was unaffected, indicating a specific impairment in pMad production/maintenance at synaptic termini. During development, synaptic pMad accumulation followed the arrival and clustering of ionotropic glutamate receptors (iGluRs) at NMJ synapses. Synaptic pMad was lost at NMJ synapses developing at suboptimal levels of iGluRs and Neto, an auxiliary subunit required for functional iGluRs. Genetic manipulations of non-essential iGluR subunits revealed that synaptic pMad signals specifically correlated with the postsynaptic type-A glutamate receptors. Altering type-A receptor activities via protein kinase A (PKA) revealed that synaptic pMad depends on the activity and not the net levels of postsynaptic type-A receptors. Thus, synaptic pMad functions as a local sensor for NMJ synapse activity and has the potential to coordinate synaptic activity with a BMP retrograde signal required for synapse growth and homeostasis.
Medical Home Characteristics and Asthma Control: A Prospective, Observational
Cohort Study Protocol
Authors: Sills Marion R. , Kwan Bethany M. , Yawn Barbara P. , Sauer Brian C. , Fairclough Diane L. , Federico Monica J. , Juarez-Colunga Elizabeth , Schilling Lisa M.
Published: December 2013

Background: This paper describes the methods for an observational comparative
effectiveness research study designed to test the association between practice-level
medical home characteristics and asthma control in children and adults receiving care in
safety-net primary care practices.Methods: This is a prospective, longitudinal cohort
study, utilizing survey methodologies and secondary analysis of existing structured
clinical, administrative, and claims data. The Scalable Architecture for Federated
Translational Inquiries Network (SAFTINet) is a safety net-oriented, primary care
practice-based research network, with federated databases containing electronic health
record (EHR) and Medicaid claims data. Data from approximately 20,000 patients from 50
practices in four healthcare organizations will be included. Practice-level medical home
characteristics will be correlated with patient-level asthma outcomes, controlling for
potential confounding variables, using a clustered design. Linear and non-linear mixed
models will be used for analysis. Study inception was July 1, 2012. A causal graph
theory approach was used to guide covariate selection to control for bias and
confounding.Discussion: Strengths of this design include a priori specification of
hypotheses and methods, a large sample of patients with asthma cared for in safety-net
practices, the study of real-world variations in the implementation of the medical home
concept, and the innovative use of a combination of claims data, patient-reported data,
clinical data from EHRs, and practice-level surveys. We address limitations in causal
inference using theory, design and analysis.
New Analytical Methods for a Learning Healthcare System: A Message from the Guest
Editor
Authors: Stoto Michael A.
Published: December 2013

Whether one reads Computerworld or Institute of Medicine issue briefs, it’s clear
that most now accept the idea that existing electronic clinical data (ECD) and other
health records can be used to manage and improve the processes, outcomes, and the
quality of health care. Indeed the increasing popularity of the term “learning
healthcare system” signals the broad acceptance of the idea that routinely collected
clinical data can – indeed should – be used to advance knowledge and support continuous
learning. But despite what the big data enthusiasts say, none of this is easy without
the appropriate analytical methods.This commentary introduces the seven papers in eGEMs’
second special issue, which are the result of invitations to researchers who have
participated in EDM Forum activities as well as an open call for paper in early summer
2013. These papers offer a beginning snapshot of the ways innovative thinkers across the
country are developing methodology to advance the national dialogue on the use of ECD to
conduct CER, support QI, and generally to improve outcomes in a learning healthcare
system.
Granulometric structure, zeta potential and differential scanning calorimetry of native starch powders from Dioscorea spp
Authors: K. Gbassi Gildas , N. Amin Christophe , G. Atheba Patrick , Trokourey Albert , Yolou Seri , Ake Michele
Published: December 2013

Starch powders from two cultivars of Dioscorea rotundata (DR) were analysed on the physicochemical aspect. Granulometric structure, zeta potential and differential scanning calorimetry of starch powders showed the following properties. Various shapes with predominance of granule ranging from 10 to 40 Î¼m were noted. The zeta potential of DR went from positive values to negative values as the pH was increasing from 2 to 8. From pH 2 to 4, the zeta potential was positive. A significant difference was obtained between each value (p > 0.05). The zeta potential took a negative value from pH 5 and above. The results of thermal analysis show that starches start swelling at 68.9ï‚±1.5 ï‚°C. Enthalpy of gelatinization was about 15 J.g-1.
On Mixed Convection Stagnation Point Flow of Second Grade Fluid with Convective Boundary Condition and Thermal Radiation
Authors: Hayat T.
Published: December 2013

This work focuses on the mixed convection stagnation point flow subject to the convective boundary conditions. Mathematical formulation involves the constitutive equations of thermodynamic second grade fluid. Analysis has been performed when thermal radiation effect is present. Nonlinear flow analysis is computed for the homotopic solutions in the series forms. Behaviors of different arising physical parameters are examined. Numerical values of local Nusselt number are given and analyzed.
Rapid effects of Kikyo-to on sore throat pain associated with acute upper respiratory tract infection
Authors: Ishimaru Naoto , Maeno Takami , Suzuki Masatsune , Maeno Tetsuhiro
Published: December 2013

Background: Kikyo-to is used empirically for relieving sore throat pain associated with acute upper respiratory tract infection (URTI) in Japan. However, few studies have demonstrated its clinical effect. This study was conducted to investigate the efficacy of Kikyo-to on sore throat pain associated with acute URTI. Methods: Patients with sore throat pain who were diagnosed with URTI in General Medicine Department Office, Tsukuba Medical Center Hospital from January to March 2012 were enrolled. Patients received 2.5 g of Kikyo-to diluted in a cup of hot water. The primary outcome was the change in sore throat score on the visual analog scale (VAS) 10 min after Kikyo-to administration. Secondary outcomes were change in sore throat score on VAS after 30 min and impact of sore throat pain on daily life (none, mild, moderate, and severe) after 10 and 30min. Results: Forty patients were eligible. Mean VAS score was 48.2±18.2 before treatment and reduced significantly to 35.4±18.1 after 10 min and 30.7±19.3 after 30 min (p<0.001 in both periods). The proportion of patients with moderate or more impact of sore throat pain on daily life was 67.5% and was reduced significantly to 37.5% after 10 min and 30% after 30 min (p<0.001 in both periods). The patients reported no side effects. Conclusions: Kikyo-to relieves sore throat pain associated with acute URTI.
Laser interstitial thermal therapy as a novel treatment modality for brain tumors in the thalamus and basal ganglia
Authors: Schroeder Jason L. , Missios Symeon , Barnett Gene H. , Mohammadi Alireza Mohammad
Published: December 2013

Introduction:

Deep-seated hemispheric brain tumors pose unique challenges for surgical treatment. These tumors are often considered inoperable and when surgery is undertaken significant, serious, morbidity and even mortality may complicate the outcome. Laser interstitial thermal therapy (LITT) is a minimally invasive alternative to traditional open surgery that affects tumor cell death by producing a zone of thermal tissue damage that can be monitored and controlled with the aid of real-time magnetic resonance thermography.

Subjects and methods:

A retrospective review of six patients treated with LITT at the Cleveland Clinic between 5/2011 and 8/2013 was performed. We evaluated clinical patient data and pre-, intra-, and post-operative magnetic resonance imaging (MRI) data for correlation.

Results:

Six patients were treated with a total of eight separate LITT procedures for their thalamic (n=5) or basal ganglia (n=1) tumors. All tumors were histologically malignant and five were primary tumors. Pre- and post-operative neurological deficits were recorded. The two patients that underwent multiple procedures were retreated for different reasons – one due to insufficient coverage and the other due to tumor recurrence. Sustained post-operative neurological deficits were observed after three procedures and one patient died within 2 days of surgery from a thalamic hemorrhage.

Conclusions:

LITT is a minimally invasive surgical treatment that can lead to successful ablation of tumors of the thalamus or basal ganglia. However, this treatment has the potential for neurological morbidity or even mortality and as such further studies are needed to evaluate the true risk vs. reward potential for LITT with regard to treating deep-seated tumors.