bluuebunny/crossref_metadata_2025 huggingface dataset:
Bone Disease in Multiple Myeloma: Pathophysiology and Management
Authors: Hameed Abdul , Brady Jennifer J. , Dowling Paul , Clynes Martin , O'Gorman Peter
Published: August 2014

Myeloma bone disease (MBD) is a devastating complication of multiple myeloma (MM). More than 80% of MM patients suffer from destructive bony lesions, leading to pain, fractures, mobility issues, and neurological deficits. MBD is not only a main cause of disability and morbidity in MM patients but also increases the cost of management. Bone destruction and lack of bone formation are main factors in the development of MBD. Some novel factors are found to be involved in the pathogenesis of MBD, eg, receptor activator of nuclear factor kappa-B ligand (RANKL), osteoprotegerin (OPG) system (RANKL/OPG), Wingless (Wnt), dickkopf-1 (Wnt/DKK1) pathway. The addition of novel agents in the treatment of MM, use of bisphosphonates and other supportive modalities such as radiotherapy, vertebroplasty/kyphoplasty, and surgical interventions, all have significant roles in the treatment of MBD. This review provides an overview on the pathophysiology and management of MBD.
Preliminary Study on Tubuloglomerular Dysfunction and Evidence of Renal Inflammation in Patients with Visceral Leishmaniasis
Authors: Oliveira Michelle J. C. , Silva Junior Geraldo B. , Sampaio Aline M. , Montenegro Bárbara L. , Alves Marília P. , Henn Guilherme A. L. , Rocha Hermano A. L. , Meneses Gdayllon C. , Martins Alice M. C. , Daher Elizabeth F.
Published: August 2014

Visceral leishmaniasis (VL) is a re-emerging zoonosis of worldwide distribution. Monocyte chemotactic protein-1 (MCP-1) and malondialdehyde (MDA) are inflammation biomarkers that have never been investigated in VL. The aim of this study is to investigate the association between renal abnormalities and inflammation biomarkers in VL. This study is a preliminary prospective study with 16 VL adult patients evaluated before treatment compared with a group of 13 healthy volunteers and 5 VL patients evaluated after treatment. Urinary concentration and acidification tests were performed. MCP-1 and MDA were quantified in urine. Urinary concentration deficit was found in all VL patients before (100%) and four VL patients after (80%) treatment. Urinary acidification deficit was found in nine cases before (56.2%) and two cases after (40%) treatment. Urinary MCP-1 (374 ± 359 versus 42 ± 29 pg/mg creatinine, P = 0.002) as well as urinary MDA (5.4 ± 2.6 versus 2.0 ± 0.8 μmol/mL) showed significant differences between VL patients and controls. These data show that VL patients present urinary concentration and acidification deficit, which can persist even after specific treatment. Urinary MCP-1 and MDA are elevated in patients with VL, which suggests renal inflammation and incipient renal damage.
Profile of Catfish (Clarias sp) Oocyte Exposed by Laserpuncture
Authors: Hariani Dyah , A. P. W Marhendra , Am Aulanni , E Suprayitno
Published: August 2014

Anexposure of low-powered laserpuncture at reproductive acupoint of catfish brood stock is known stimulate oocyte maturation. However, the profile of oocyte resulted from laserpuncture exposure has not been known. The present study aimed to identify the profile of catfish (Clarias sp.) oocyte in post-exposure laserpuncture. A total of 48 catfishes with ages of 8-9 months was grouped into two, i.e. fishes were exposed with laserpuncture and without exposure to laserpuncture (control) with 3 replications. Laserpuncture exposure was conducted once a week until the brood stock matured. Profile of oocyte such as, the GSI value, egg diameter, total of oocytes and the gonad maturity stage were examined. The results showed that laserpuncture exposure at the catfish reproductive acupoint could trigger the oocyte development without reducing quality of the oocyte indicated by the increase of gonadosomatic index (GSI), oocyte diameter, total of oocytes and gonad maturity stage similar to control. Moreover, laserpuncture exposure accelerated the gonad maturation, three weeks faster than control.
Eco-Diversity of Edible Insects of Nigeria and Its Impact on Food Security
Authors: Temitope Adeoye Olubusola , Job Oyelowo Oyetayo , Abiodun Adebisi-Fagbohungbe Tola , Dare Akinyemi Olukayode
Published: August 2014

Inspite of the strong aversion shown to Entomophagy (consumption of edible insects) due to civilization, insects have played an important part in the history of human nutrition in Africa, Australia, Asia and the Americas. Hundreds of species have been used as human food. Globally, about 14 insect orders contain one or more species of edible insects. Africa is one of the leading continents that consume insects as food. In Africa, insects form part of the traditional diets of millions of people and are also used as feed for their farm animals. Nowadays, Entomophagy is a major entomological research interest with focus on its future prospect for food and feed security. Nigeria, the focus of this study is very rich in forest edible insects due to its marked ecological and climatic diversity. Some of the popular edible insects are grasshoppers, caterpillars, beetle grubs and adults, winged termites, bee, wasp and ant brood as well as winged ants, cicadas, and a variety of aquatic insects. Despite their importance as food, biodiversity and conservation efforts have focused mainly on other groups of animals, ignoring the vast world of insects. Therefore, there is a compelling need to collect data on the diversity and conservation of edible insects in Africa, and to make this information available to all interested parties. This study provides information on the list and distribution of these edible insects in Nigeria, their harvesting, processing and preservation techniques, their seasonality, nutritional value and the potential for expanding the market.
Intra-Arterial Immunoselected CD34+ Stem Cells for Acute Ischemic Stroke
Authors: Banerjee Soma , Bentley Paul , Hamady Mohammad , Marley Stephen , Davis John , Shlebak Abdul , Nicholls Joanna , Williamson Deborah A. , Jensen Steen L. , Gordon Myrtle , Habib Nagy , Chataway Jeremy
Published: August 2014

Treatment with CD34+ hematopoietic stem/progenitor cells has been shown to improve functional recovery in nonhuman models of ischemic stroke via promotion of angiogenesis and neurogenesis. We aimed to determine the safety and feasibility of treatment with CD34+ cells delivered intra-arterially in patients with acute ischemic stroke. This was the first study in human subjects. We performed a prospective, nonrandomized, open-label, phase I study of autologous, immunoselected CD34+ stem/progenitor cell therapy in patients presenting within 7 days of onset with severe anterior circulation ischemic stroke (National Institutes of Health Stroke Scale [NIHSS] score ≥8). CD34+ cells were collected from the bone marrow of the subjects before being delivered by catheter angiography into the ipsilesional middle cerebral artery. Eighty-two patients with severe anterior circulation ischemic stroke were screened, of whom five proceeded to treatment. The common reasons for exclusion were age >80 years (n = 19); medical instability (n = 17), and significant carotid stenosis (n = 13). The procedure was well tolerated in all patients, and no significant treatment-related adverse effects occurred. All patients showed improvements in clinical functional scores (Modified Rankin Score and NIHSS score) and reductions in lesion volume during a 6-month follow-up period. Autologous CD34+ selected stem/progenitor cell therapy delivered intra-arterially into the infarct territory can be achieved safely in patients with acute ischemic stroke. Future studies that address eligibility criteria, dosage, delivery site, and timing and that use surrogate imaging markers of outcome are desirable before larger scale clinical trials.
Enhanced Genetic Modification of Adult Growth Factor Mobilized Peripheral Blood Hematopoietic Stem and Progenitor Cells With Rapamycin
Authors: Li Lijing , Torres-Coronado Mónica , Gu Angel , Rao Anitha , Gardner Agnes M. , Epps Elizabeth W. , Gonzalez Nancy , Tran Chy-Anh , Wu Xiwei , Wang Jin-Hui , DiGiusto David L.
Published: August 2014

Genetic modification of adult human hematopoietic stem and progenitor cells (HSPCs) with lentiviral vectors leads to long-term gene expression in the progeny of the HSPCs and has been used to successfully treat several monogenic diseases. In some cases, the gene-modified cells have a selective growth advantage over nonmodified cells and eventually are the dominant engrafted population. However, in disease indications for which the gene-modified cells do not have a selective advantage, optimizing transduction of HSPC is paramount to successful stem cell-based gene therapy. We demonstrate here that transduction of adult CD34+ HSPCs with lentiviral vectors in the presence of rapamycin, a widely used mTORC1 inhibitor, results in an approximately threefold increase in stable gene marking with minimal effects on HSPC growth and differentiation. Using this approach, we have demonstrated that we can enhance the frequency of gene-modified HSPCs that give rise to clonogenic progeny in vitro without excessive increases in the number of vector copies per cell or changes in integration pattern. The genetic marking of HSPCs and expression of transgenes is durable, and transplantation of gene-modified HSPCs into immunodeficient mice results in high levels of gene marking of the lymphoid and myeloid progeny in vivo. The prior safe clinical history of rapamycin in other applications supports the use of this compound to generate gene-modified autologous HSPCs for our HIV gene therapy clinical trials.
Neural Precursor Cell Transplantation Enhances Functional Recovery and Reduces Astrogliosis in Bilateral Compressive/Contusive Cervical Spinal Cord Injury
Authors: Wilcox Jared T. , Satkunendrarajah Kajana , Zuccato Jeffrey A. , Nassiri Farshad , Fehlings Michael G.
Published: August 2014

Spinal cord injury has a significant societal and personal impact. Although the majority of injuries involve the cervical spinal cord, few studies of cell transplantation have used clinically relevant models of cervical spinal cord injury, limiting translation into clinical trials. Given this knowledge gap, we sought to examine the effects of neural stem/precursor cell (NPC) transplants in a rodent model of bilateral cervical contusion-compression spinal cord injury. Bilateral C6-level clip contusion-compression injuries were performed in rats, which were then blindly randomized at 2 weeks after injury into groups receiving adult brain-derived NPCs, vehicle, or sham operation. Long-term survival of NPCs was evident at 10 weeks after transplant. Cell grafts were localized rostrocaudally surrounding the lesion, throughout white and gray matter. Graft-derived cells were found within regions of gliotic scar and motor tracts and deposited myelin around endogenous axons. The majority of NPCs developed an oligodendroglial phenotype with greater neuronal profiles in rostral grafts. Following NPC transplantation, white matter was significantly increased compared with control. Astrogliosis and glial scar deposition, measured by GFAP-positive and chondroitin sulfate proteoglycan-positive volume, was significantly reduced. Forelimb grip strength, fine motor control during locomotion, and axonal conduction (by in vivo electrophysiology) was greater in cell-treated animals compared with vehicle controls. Transplantation of NPCs in the bilaterally injured cervical spinal cord results in significantly improved spinal cord tissue and forelimb function, warranting further study in preclinical cervical models to improve this treatment paradigm for clinical translation.
El ingenio como clave de éxito en el actual sector de la comunicación corporativa
Authors: Llorente Barroso Carmen
Published: August 2014

Reseña del libro “How to get your message across: Últimas tendencias creativas y procesos de innovación en campañas de comunicación”
¿Hacia dónde caminan nuestros museos? Futuros pasos para el siglo XXI
Authors: Torres David Ruiz
Published: August 2014

Los espacios expositivos en la actualidad sufren una mudanza que afecta a su concepción, aportando nuevos enfoques de lo que considerábamos como museo, así como en su discurso expositivo convencional. Esto mismo es lo que María Luisa Bellido Gant ha tenido en cuenta a la hora de editar este libro, que recoge los contenidos más punteros a nivel internacional en lo que a éstos ámbitos se refiere. Esta razón constituye uno de los firmes pilares que llevan a prestar especial atención al lector cuyo interés en obtener una visión reciente y aproximada a las nuevas tendencias museológicas, obliga a no obviar este compendio.
Creating Utopia through Real Struggle: A Case Study of the Rialto Community Housing Campaign
Authors: Hearne Rory
Published: August 2014

The article examines the potential of a symbiotic strategy to transform capitalism in a more socialist direction through a case study of a community campaign to address substandard housing conditions resulting from neoliberal property-based regeneration policies and austerity. The case study contrasts the empowerment of disadvantaged groups with dominant partnership approaches to achieving social justice in Ireland. It concludes that while such human rights approaches offer the potential to achieve improvements in people's living conditions, their prospect for symbiotic transformation is limited, unless they link to wider social and political forces challenging structural inequalities, including class and gender.
Transforming Capitalism through Real Utopias
Authors: Wright Erik Olin
Published: August 2014

This paper explores a broad framework for thinking sociologically about emancipatory alternatives to dominant institutions and social structures, especially capitalism. The framework is grounded in two foundational propositions: (1) Many forms of human suffering and many deficits in human flourishing are the result of existing institutions and social structures. (2) Transforming existing institutions and social structures in the right way has the potential to substantially reduce human suffering and expand the possibilities for human flourishing. An emancipatory social science responding to these propositions faces four broad tasks: specifying the moral principles for judging social institutions; using these moral principles as the standards for diagnosis and critique of existing institutions; developing an account of viable alternatives in response to the critique; and proposing a theory of transformation for realizing those alternatives. The idea of “real utopias” is one way of thinking about alternatives and transformation.
The Transformative Capacity of the Commons and Commoning
Authors: Ryan Anne B.
Published: August 2014

This paper treats the commons and commoning as transformative practices, since they involve democratic self-organisation for the collective management of resources. Commoning is also treated as an expression of social power and the paper considers the relationship of commoning to Wright's transformative logics of symbiotic and interstitial strategies. The role of the state and its capacity to support and promote commoning in interstitial and symbiotic forms is also considered.
Saving Jobs, Promoting Democracy: Worker Co-Operatives
Authors: Nolan Stephen , Massebiaux Eleonore Perrin , Gorman Tomas
Published: August 2014

The article examines transformative alternatives that may offer pathways to a more participative, sustainable and equitable social order. It focuses on one form of alternative, worker-owned co-operatives, and argues this existing form of democratic and economic relations has already proven capacity to generate more equitable socio-economic outcomes and residual social capital. The worker-owned model islocated within an ideological framework that focuses on the inherent democratising principles of their praxis that can in the right circumstances underpin firm strategic foundations for radical social change. It examines the development of worker-owned co-ops in Ireland north and south and the obstacles that need to be overcome to make these a more feasible and common form of economic ownership. Reflecting on the current debate in Ireland it argues such co-ops cannot work effectively without a secure legal framework governing their status and softer supports including entrepreneurship development, leadership training, market research, accessing loan finance and grant aid, inter-cooperative networking and federation building. The article poses workers' co-operatives as sites of political struggle and consciousness, expressed in co-operatives' core values including sovereignty of labour, the subordinate nature of capital, democracy, inter-cooperation and sustainability, and in tangible democratic experiences and transformative praxis.
Dynamic Control of High-speed Train Following Operation
Authors: Pan Deng , Zheng Yingping
Published: August 2014

Both safety and efficiency should be considered in high-speed train following control. The real-time calculation of dynamic safety following distance is used by the following train to understand the quality of its own following behavior. A new velocity difference control law can help the following train to adjust its own behavior from a safe and efficient steady-following state to another one if the actual following distance is greater than the safe following distance. Meanwhile, the stopping control law would work for collision avoidance when the actual following distance is less than the safe following distance. The simulation shows that the dynamic control of actual inter-train distance can be well accomplished by the behavioral adjustment of the following train, and verifies the effectiveness and feasibility of our presented methods for train following control.
A NEW PASSENGER ORIENTED PERFORMANCE MEASUREMENT FRAMEWORK FOR PUBLIC RAIL TRANSPORTATION SYSTEMS
Authors: KESTEN Ali Sercan , Öğüt Kemal Selçuk
Published: August 2014

This paper presents a practical approach for monitoring public transportation systems' performance by focusing on customer evaluations. Within the framework of the developed method, 22 indicators are aggregated for 6 different measures, which are time, cost, accessibility and transfer, comfort, safety – security and quality of service respectively. Passenger Oriented Performance IndeX (POPIX) has been developed and applied to the Istanbul Metro, Light Rail and Tram systems. The goal of this research is to propose a new customer oriented performance index for transportation systems, enabling a reliable and objective base for monitoring system performance by setting performance goals and identifying priorities. Meanwhile, the proposed methodology also allows for the investigation of the performance changes of a particular transportation system and for performance comparison of different systems directly from the customer point of view. The data of the index is attained by the Customer Satisfaction Survey of Istanbul Public Railways' 2005, 2006 and 2007. The POPIX methodology has been defined and the corresponding POPIX scores are calculated for the systems investigated. Furthermore, the % POPIX concept has been developed for the comparison of different systems. Lastly, the shifted POPIX concept has been proposed for more reliable comparison between different years. The framework has been implemented to the public railway systems and individual index scores are calculated for each indicator, measure and overall system. The measures of cost, accessibility and transfer and comfort have lower index scores. Metro index scores are superior in comparison to the Tram and Light Rail for all the years analyzed.
STANDARDISATION OF PLOTTING COURSES AND SELECTING TURN POINTS IN MARITIME NAVIGATION
Authors: Lušić Zvonimir , Kos Serđo , Galić Stipe
Published: August 2014

Today's methods of plotting courses and selecting sailing routes and turn points in maritime navigation are still largely based on subjective assessment of the master or the officer in charge. This results in a great variety of course distribution and, accordingly, in various ship movements. Modern electronic aids, in particular ECDIS (Electronic Chart Display and Information System) can significantly facilitate maritime voyage planning, course plotting, selection of turning points, etc. In addition to displaying electronic charts, the specific feature of these systems is that they facilitate route planning, supervision of ship movements, data recording, database search, alarm setting, etc. However, these systems do not yet provide automatic selection of courses on user's request in a standardised form. Therefore, in most cases, the routes and turn points are selected empirically or because they have been previously defined and used. This paper shows the drawbacks of the existing methods of selecting routes and plotting courses in maritime navigation and gives recommendations how to improve them.
Thermal electron acceleration by localized bursts of electric field in the radiation belts
Authors: Artemyev A. V. , Agapitov O. V. , Mozer F. , Krasnoselskikh V.
Published: August 2014

In this paper we investigate the resonant interaction of thermal ∼10–100 eV electrons with a burst of electrostatic field that results in electron acceleration to kilovolt energies. This single burst contains a large parallel electric field of one sign and a much smaller, longer‐lasting parallel field of the opposite sign. The Van Allen Probe spacecraft often observes clusters of spatially localized bursts in the Earth's outer radiation belts. These structures propagate mostly away from the geomagnetic equator and share properties of soliton‐like nonlinear electron acoustic waves: a velocity of propagation is about the thermal velocity of cold electrons (∼3000–10,000 km/s), and a spatial scale of electric field localization along the field lines is about the Debye radius of hot electrons (∼5–30 km). We model the nonlinear resonant interaction of these electric field structures and cold background electrons.
Heliosheath magnetic field and plasma observed by Voyager 2 during 2011
Authors: Burlaga L. F. , Ness N. F. , Richardson J. D.
Published: August 2014

We discuss magnetic field and plasma observations from Voyager 2 (V2) during 2011, when V2 was beginning to see the effects of increasing solar activity following the solar minimum in 2009. The magnetic field strength (B) profile showed large amplitude fluctuations that can be resolved into a linear increase ofBwith time and a sinusoidal variation of the period of 86.2 ± 0.8 days. Voyager 2 was in a unipolar region in which the magnetic polarity was directed away from the Sun along the Parker spiral 96% of the time, indicating that V2 was poleward of the heliospheric current sheet throughout most of 2011. The distribution ofBwas lognormal, but a Gaussian distribution was observed when the linear variation ofBwas subtracted from the data. The distribution of daily increments ofBwas aq‐Gaussian distribution withq = 1.1 ± 0.1, which is less intermittent than normally observed in the heliosheath. However, the distribution of hourly increments ofBwas aq‐Gaussian distribution withq = 1.5 ± 0.03. The density, temperature, and velocity increased linearly from the beginning of 2011 to approximately day 254. The magnetic and thermal pressure tended to increase throughout the year, but the magnetic pressure dominated most of the time. The counting rate of >70 MeV/nucleon particles increased rapidly during the first 250 days, but it leveled out during the rest of the year whenBwas stronger. The empirical CR‐Brelationship describes this behavior.
Formation of fine sediment deposit from a flash flood river in the Mediterranean Sea
Authors: Grifoll Manel , Gracia Vicenç , Aretxabaleta Alfredo , Guillén Jorge , Espino Manuel , Warner John C.
Published: August 2014

We identify the mechanisms controlling fine deposits on the inner‐shelf in front of the Besòs River, in the northwestern Mediterranean Sea. This river is characterized by a flash flood regime discharging large amounts of water (more than 20 times the mean water discharge) and sediment in very short periods lasting from hours to few days. Numerical model output was compared with bottom sediment observations and used to characterize the multiple spatial and temporal scales involved in offshore sediment deposit formation. A high‐resolution (50 m grid size) coupled hydrodynamic‐wave‐sediment transport model was applied to the initial stages of the sediment dispersal after a storm‐related flood event. After the flood, sediment accumulation was predominantly confined to an area near the coastline as a result of preferential deposition during the final stage of the storm. Subsequent reworking occurred due to wave‐induced bottom shear stress that resuspended fine materials, with seaward flow exporting them toward the midshelf. Wave characteristics, sediment availability, and shelf circulation determined the transport after the reworking and the final sediment deposition location. One year simulations of the regional area revealed a prevalent southwestward average flow with increased intensity downstream. The circulation pattern was consistent with the observed fine deposit depocenter being shifted southward from the river mouth. At the southern edge, bathymetry controlled the fine deposition by inducing near‐bottom flow convergence enhancing bottom shear stress. According to the short‐term and long‐term analyses, a seasonal pattern in the fine deposit formation is expected.
Hierarchical Composite Electrodes of Nickel Oxide Nanoflake 3D Graphene for High‐Performance Pseudocapacitors
Authors: Wang Chundong , Xu Junling , Yuen Muk‐Fung , Zhang Jie , Li Yangyang , Chen Xianfeng , Zhang Wenjun
Published: August 2014

NiO nanoflakes are created with a simple hydrothermal method on 3D (three‐dimensional) graphene scaffolds grown on Ni foams by microwave plasma enhanced chemical vapor deposition (MPCVD). Such as‐grown NiO‐3D graphene hierarchical composites are then applied as monolithic electrodes for a pseudo‐supercapacitor application without needing binders or metal‐based current collectors. Electrochemical measurements impart that the hierarchical NiO‐3D graphene composite delivers a high specific capacitance of ≈1829 F g−1 at a current density of 3 A g−1 (the theoretical capacitance of NiO is 2584 F g−1). Furthermore, a full‐cell is realized with an energy density of 138 Wh kg−1 at a power density of 5.25 kW kg−1, which is much superior to commercial ones as well as reported devices in asymmetric capacitors of NiO. More attractively, this asymmetric supercapacitor exhibits capacitance retention of 85% after 5000 cycles relative to the initial value of the 1st cycle.
Microflotronics: A Flexible, Transparent, Pressure‐Sensitive Microfluidic Film
Authors: Li Ruya , Nie Baoqing , Digiglio Philip , Pan Tingrui
Published: August 2014

There is an increasing demand for sensitive, flexible, and low‐cost pressure sensing solutions for health monitoring, wearable sensing, robotic and prosthetic applications. Here, the first flexible and pressure‐sensitive microfluidic film is reported, referred to as a microflotronic, with high transparency and seamless integratability with the state‐of‐the‐art microelectronics. The microflotronic film represents the initial effort to utilize a continuous microfluidic layer as the sensing elements for large‐area dynamic pressure mapping applications, and meanwhile an ultrahigh sensitivity of 0.45 kPa−1 has been achieved in a compact, flexible, and transparent packaging. The response time of the device is in the millisecond range, which is at least an order of magnitude faster than that of its conventional flexible solid‐state counterparts. In addition, the fabrication process of the device is fully compatible with the industrial‐scale manufacturing of capacitive touchscreen devices and liquid‐crystal displays. The overall device packaging can be as thin as 200 μm with an optical transparency greater than 80%. Several practical applications were successfully demonstrated, including surface topology mapping and dynamic blood pressure monitoring. The microflotronic devices offer an alternative approach to the solid‐state pressure sensors, by offering an unprecedented sensitivity and ultrafast response time in a completely transparent, flexible and adaptive platform.
Primary myelofibrosis: 2014 update on diagnosis, risk‐stratification, and management
Authors: Tefferi Ayalew
Published: August 2014

Disease overview: Primary myelofibrosis (PMF) is a myeloproliferative neoplasm characterized by stem cell‐derived clonal myeloproliferation, abnormal cytokine expression, bone marrow fibrosis, anemia, splenomegaly, extramedullary hematopoiesis (EMH), constitutional symptoms, cachexia, leukemic progression, and shortened survival.Diagnosis: Diagnosis is based on bone marrow morphology. The presence ofJAK2,CALR, orMPLmutation is supportive but not essential for diagnosis; approximately 90% of patients carry one of these mutations and 10% are “triple‐negative.” None of these mutations are specific to PMF and are also seen in essential thrombocythemia (ET). Prefibrotic PMF mimics ET in its presentation and the distinction, enabled by careful bone marrow morphological examination, is prognostically relevant. Differential diagnosis also includes chronic myeloid leukemia, myelodysplastic syndromes, chronic myelomonocytic leukemia, and acute myeloid leukemia.Risk Stratification: The Dynamic International Prognostic Scoring System‐plus (DIPSS‐plus) uses eight predictors of inferior survival: age >65 years, hemoglobin <10 g/dL, leukocytes >25 × 109/L, circulating blasts ≥1%, constitutional symptoms, red cell transfusion dependency, platelet count <100 × 109/L, and unfavorable karyotype (i.e., complex karyotype or sole or two abnormalities that include +8, −7/7q−, i(17q), inv(3), −5/5q−, 12p−, or 11q23 rearrangement). The presence of 0, 1, “2 or 3,” and ≥4 adverse factors defines low, intermediate‐1, intermediate‐2, and high‐risk disease with median survivals of approximately 15.4, 6.5, 2.9, and 1.3 years, respectively. High risk disease is also defined byCALR−/ASXL1+mutational status.Risk‐Adapted Therapy: Observation alone is adequate for asymptomatic low/intermediate‐1 risk disease, especially withCALR+/ASXL1−mutational status. Stem cell transplant is considered for DIPSS‐plus high risk disease or any risk disease withCALR−/ASXL1+mutational status. Investigational drug therapy is reasonable for symptomatic intermediate‐1 or intermediate‐2 risk disease. Splenectomy is considered for drug‐refractory splenomegaly. Involved field radiotherapy is most useful for post‐splenectomy hepatomegaly, non‐hepatosplenic EMH, PMF‐associated pulmonary hypertension, and extremity bone pain. Am. J. Hematol. 89:916–925, 2014. © 2014 Wiley Periodicals, Inc.
Y‐chromosome analysis in a Northwest Iberian population: Unraveling the impact of Northern African lineages
Authors: Alvarez Luis , Ciria Estela , Marques Sofia L. , Santos Cristina , Aluja Maria Pilar
Published: August 2014

Objectives

To provide new clues about the genetic origin, composition and structure of the population of the Spanish province of Zamora, with an emphasis on the genetic impact of the period of Islamic rule in the Iberian Peninsula.

Methods

Polymorphisms in the paternally inherited Y‐chromosome, Single Nucleotide Polymorphisms and Short Tandem Repeats, were analyzed in 235 unrelated males born in six different regions in the Zamora province.

Results

A relatively homogenous Y‐chromosome haplogroup composition was observed in the Zamora province. Haplogroups R1b1‐P25 and I‐M170, widespread in European populations, accounted for 64.9% of the total sample. Moreover, all of the observed African lineages, accounting for 10.2% of the total variability, belonged to haplogroups having Northwest African origin (E1b1b1b‐M81, E1b1b1a‐β‐M78, and J1‐M267).

Conclusions

No differences between regions or sub‐structure due to geographical boundaries were detected. The specific Northwest African male lineages observed contrast with the mitochondrial DNA data, where the majority of African lineages were found to be sub‐Saharan. This work made it possible to study the impact of recent historical events in the male gene pool in the province of Zamora in Spain. Am. J. Hum. Biol. 26:740–746, 2014. © 2014 Wiley Periodicals, Inc.
Fluxionally Chiral DMAP Catalysts: Kinetic Resolution of Axially Chiral Biaryl Compounds
Authors: Ma Gaoyuan , Deng Jun , Sibi Mukund P.
Published: August 2014

Can organocatalysts that incorporate fluxional groups provide enhanced selectivity in asymmetric transformations? To address this issue, we have designed chiral 4‐dimethylaminopyridine (DMAP) catalysts with fluxional chirality. These catalysts were found to be efficient in promoting the acylative kinetic resolution of secondary alcohols and axially chiral biaryl compounds with selectivity factors of up to 37 and 51, respectively.
N‐Heterocyclic Carbene, High Oxidation State Molybdenum Alkylidene Complexes: Functional‐Group‐Tolerant Cationic Metathesis Catalysts
Authors: Buchmeiser Michael R. , Sen Suman , Unold Jörg , Frey Wolfgang
Published: August 2014

We synthesized the first N‐heterocyclic carbene (NHC) complexes of Schrock’s molybdenum imido alkylidene bis(triflate) complexes. Unlike existing bis(triflate) complexes, the novel 16‐electron complexes represent metathesis active, functional‐group‐tolerant catalysts. Single‐crystal X‐ray structures of two representatives of this novel class of Schrock catalysts are presented and reactivity is discussed in view of their structural peculiarities. In the presence of monomer (substrate), these catalysts form cationic species and can be employed in ring‐closing metathesis (RCM), ring‐opening metathesis polymerization (ROMP), as well as in the cyclopolymerization of α,ω‐diynes. Monomers containing functional groups, which are not tolerated by the existing variations of Schrock’s catalyst, e.g., sec‐amine, hydroxy, and carboxylic acid moieties, can be used. These catalysts therefore hold great promise in both organic and polymer chemistry, where they allow for the use of protic monomers.
Phenotypic differences may limit the potential for habitat restoration involving species translocation: a case study of shape ecophenotypes in different populations of Modiolus modiolus (Mollusca: Bivalvia)
Authors: Fariñas‐Franco Jose M. , Sanderson William G. , Roberts Dai
Published: August 2014

Modiolus modiolus reefs have disappeared from most of their historical distribution range in Strangford Lough (Northern Ireland) while remnant populations are highly fragmented.

This study investigated morphological differences in Strangford Lough and Irish Sea M. modiolus with an aim to provide sound scientific advice to managers involved in shellfish reef restoration programmes including translocation.

By characterizing shape ecophenotypes within target and source areas it is possible to select morphologically similar source stocks to increase survival and self sustainability of the restored population.

Linear and geometric shell shape analyses identified significant differences among M. modiolus populations from the Irish Sea and Strangford Lough. Three different phenotypes within the Strangford Lough metapopulation were identified. It is hypothesized that substrate type, tidal current strength and population thinning caused by mobile fishing gear influenced such morphological differences.

This investigation confirmed, for the first time, phenotypic variability in M. modiolus which could affect future supplementation programmes aiming to restore degraded populations.

Copyright © 2014 John Wiley & Sons, Ltd.
Cell Biology of Sarcomeric Protein Engineering: Disease Modeling and Therapeutic Potential
Authors: Thompson Brian R. , Metzger Joseph M.
Published: August 2014

The cardiac sarcomere is the functional unit for myocyte contraction. Ordered arrays of sarcomeric proteins, held in stoichiometric balance with each other, respond to calcium to coordinate contraction and relaxation of the heart. Altered sarcomeric structure–function underlies the primary basis of disease in multiple acquired and inherited heart disease states. Hypertrophic and restrictive cardiomyopathies are caused by inherited mutations in sarcomeric genes and result in altered contractility. Ischemia‐mediated acidosis directly alters sarcomere function resulting in decreased contractility. In this review, we highlight the use of acute genetic engineering of adult cardiac myocytes through stoichiometric replacement of sarcomeric proteins in these disease states with particular focus on cardiac troponin I. Stoichiometric replacement of disease causing mutations has been instrumental in defining the molecular mechanisms of hypertrophic and restrictive cardiomyopathy in a cellular context. In addition, taking advantage of stoichiometric replacement through gene therapy is discussed, highlighting the ischemia‐resistant histidine‐button, A164H cTnI. Stoichiometric replacement of sarcomeric proteins offers a potential gene therapy avenue to replace mutant proteins, alter sarcomeric responses to pathophysiologic insults, or neutralize altered sarcomeric function in disease. Anat Rec, 297:1663–1669, 2014. © 2014 Wiley Periodicals, Inc.
Structural Implications of β‐Cardiac Myosin Heavy Chain Mutations in Human Disease
Authors: Colegrave Melanie , Peckham Michelle
Published: August 2014

Over 500 disease‐causing point mutations have been found in the human β‐cardiac myosin heavy chain, many quite recently with modern sequencing techniques. This review shows that clusters of these mutations occur at critical points in the sequence and investigates whether the many studies on these mutants reveal information about the function of this protein. Anat Rec, 297:1670–1680, 2014. © 2014 Wiley Periodicals, Inc.
Finding the Sweet Spot: Assembly and Glycosylation of the Dystrophin‐Associated Glycoprotein Complex
Authors: Townsend Dewayne
Published: August 2014

The dystrophin‐associated glycoprotein complex (DGC) is a collection of glycoproteins that are essential for the normal function of striated muscle and many other tissues. Recent genetic studies have implicated the components of this complex in over a dozen forms of muscular dystrophy. Furthermore, disruption of the DGC has been implicated in many forms of acquired disease. This review aims to summarize the current state of knowledge regarding the processing and assembly of dystrophin‐associated proteins with a focus primarily on the dystroglycan heterodimer and the sarcoglycan complex. These proteins form the transmembrane portion of the DGC and undergo a complex multi‐step processing with proteolytic cleavage, differential assembly, and both N‐ and O‐glycosylation. The enzymes responsible for this processing and a model describing the sequence and subcellular localization of these events are discussed. Anat Rec, 297:1694–1705, 2014. © 2014 Wiley Periodicals, Inc.
Translational Control of Tropomyosin Expression in Vertebrate Hearts
Authors: Dube Dipak K. , Mclean Matthew D. , Dube Syamalima , Poiesz Bernard J.
Published: August 2014

The tropomyosin (TM) gene family produces a set of related TM proteins with important functions in striated and smooth muscle, and nonmuscle cells. In vertebrate striated muscle, the thin filament consists largely of actin, TM, the troponin (Tn) complex (Tn‐I, Tn‐C and Tn‐T), and tropomodulin (Tmod) and is responsible for mediating Ca2+ control of muscle contraction and relaxation. There are four known genes (designated as TPM1, TPM2, TPM3, and TPM4) for TM in vertebrates. The four TM genes generate a multitude of tissue‐ and developmental‐specific isoforms through the use of different promoters, alternative mRNA splicing, different 3′‐end mRNA processing and tissue‐specific translational control. In this review, we have focused mainly on the regulation of TM expression in striated muscles, primarily in vertebrate hearts with special emphasis on translational control using mouse and Mexican axolotl animal models. Anat Rec, 297:1585–1595, 2014. © 2014 Wiley Periodicals, Inc.
Getting Folded: Chaperone Proteins in Muscle Development, Maintenance and Disease
Authors: Smith Daniel A. , Carland Carmen R. , Guo Yiming , Bernstein Sanford I.
Published: August 2014

Chaperone proteins are critical for protein folding and stability, and hence are necessary for normal cellular organization and function. Recent studies have begun to interrogate the role of this specialized class of proteins in muscle biology. During development, chaperone‐mediated folding of client proteins enables their integration into nascent functional sarcomeres. In addition to assisting with muscle differentiation, chaperones play a key role in the maintenance of muscle tissues. Furthermore, disruption of the chaperone network can result in neuromuscular disease. In this review, we discuss how chaperones are involved in myofibrillogenesis, sarcomere maintenance, and muscle disorders. We also consider the possibilities of therapeutically targeting chaperones to treat muscle disease. Anat Rec, 297:1637–1649, 2014. © 2014 Wiley Periodicals, Inc.
The Role of Mechanotransduction on Vascular Smooth Muscle Myocytes Cytoskeleton and Contractile Function
Authors: Ye George J.C. , Nesmith Alexander P. , Parker Kevin Kit
Published: August 2014

Smooth muscle (SM) exhibits a highly organized structural hierarchy that extends over multiple spatial scales to perform a wide range of functions at the cellular, tissue, and organ levels. Early efforts primarily focused on understanding vascular SM (VSM) function through biochemical signaling. However, accumulating evidence suggests that mechanotransduction, the process through which cells convert mechanical stimuli into biochemical cues, is requisite for regulating contractility. Cytoskeletal proteins that comprise the extracellular, intercellular, and intracellular domains are mechanosensitive and can remodel their structure and function in response to external mechanical cues. Pathological stimuli such as malignant hypertension can act through the same mechanotransductive pathways to induce maladaptive remodeling, leading to changes in cellular shape and loss of contractile function. In both health and disease, the cytoskeletal architecture integrates the mechanical stimuli and mediates structural and functional remodeling in the VSM. Anat Rec, 297:1758–1769, 2014. © 2014 Wiley Periodicals, Inc.
A Titan but not Necessarily a Ruler: Assessing the Role of Titin During Thick Filament Patterning and Assembly
Authors: Myhre J. Layne , Pilgrim David
Published: August 2014

The sarcomeres of striated muscle are among the most elaborate and dynamic eukaryotic cellular protein machinery, and the mechanisms by which these semicrystalline filament networks are initially patterned and assembled remain contentious. In addition to the acto‐myosin filaments that provide motor function, the sarcomere contains titin filaments, comprised of individual molecules of the giant Ig‐ and fibronectin domain‐rich protein titin. Titin is the largest known protein, containing many structurally distinct domains with a variety of proposed functions, including sarcomere stabilization, the prevention of over‐stretching, and returning to resting length after contraction. One molecule of titin, which binds to both the Z‐disk and the M‐line, spans a half‐sarcomere, and is proposed to serve as a “molecular ruler” that dictates the spacing of sarcomeres. The semirigid rod‐like A‐band region of titin has also been proposed to act as a scaffold for thick filament formation during muscle development, but despite decades of research, this hypothesis has not been rigorously tested. Recent studies in zebrafish have brought into question the necessity for the A‐band region of titin during the early stages of sarcomere patterning. In this review, we give an overview of the many different roles of titin in the development and function of striated muscle, and address the validity of the “molecular ruler” model of myofibrillogenesis in light of the current literature. Anat Rec, 297:1604–1614, 2014. © 2014 Wiley Periodicals, Inc.
Electrical conduction behavior of organic light‐emitting diodes using fluorinated self‐assembled monolayer with molybdenum oxide‐doped hole transporting layer
Authors: Park Sang‐Geon , Mori Tatsuo
Published: August 2014

The electrical conductivity behavior of a fluorinated self‐assembled monolayer (FSAM) of a molybdenum oxide (MoOx)‐doped α‐naphthyl diamine derivative (α‐NPD) in organic light‐emitting diodes (OLEDs) was investigated. The current density of the MoOx‐doped α‐NPD/FSAM device was proportional to its voltage owing to smooth carrier injection through the FSAM and the high carrier density of its bulk. The temperature‐dependent characteristics of this device were investigated. The current density–voltage characteristics at different temperatures were almost the same owing to its very low activation energy. The activation energy of the device was estimated to be 1.056 × 10−2 [eV] and was very low due to the inelastic electron tunneling of FSAM molecules. Copyright © 2014 John Wiley & Sons, Ltd.
Reactions of rac‐(ebthi)M(η2‐Me3SiC2SiMe3) (M=Ti, Zr) with Aryl Nitriles
Authors: Becker Lisanne , Arndt Perdita , Spannenberg Anke , Rosenthal Uwe
Published: August 2014

The reactions of the Group 4 metallocene alkyne complexes rac‐(ebthi)M(η2‐Me3SiC2SiMe3) (1 a: M=Ti, 1 b: M=Zr; rac‐(ebthi)=rac‐1,2‐ethylene‐1,1′‐bis(η5‐tetrahydroindenyl)) with PhCN were investigated. For 1 a, an unusual nitrile–nitrile coupling to 1‐titana‐2,5‐diazacyclopenta‐2,4‐diene (2) at ambient temperature was observed. At higher temperature, the CC coupling of two nitriles resulted in the formation of a dinuclear complex with a four‐membered diimine bridge (3). The reaction of 1 b with PhCN afforded dinuclear compound 4 and 2,4,6‐triphenyltriazine. Additionally, the reactivity of 1 b towards other nitriles was investigated.
Versatile Iridicycle Catalysts for Highly Efficient and Chemoselective Transfer Hydrogenation of Carbonyl Compounds in Water
Authors: Talwar Dinesh , Wu Xiaofeng , Saidi Ourida , Salguero Noemí Poyatos , Xiao Jianliang
Published: August 2014

Cyclometalated iridium complexes are shown to be highly efficient and chemoselective catalysts for the transfer hydrogenation of a wide range of carbonyl groups with formic acid in water. Examples include α‐substituted ketones (α‐ether, α‐halo, α‐hydroxy, α‐amino, α‐nitrile or α‐ester), α‐keto esters, β‐keto esters and α,β‐unsaturated aldehydes. The reduction was carried out at substrate/catalyst ratios of up to 50 000 at pH 4.5 and required no organic solvent. The protocol provides a practical, easy and efficient way for the synthesis of β‐functionalised secondary alcohols, such as β‐hydroxyethers, β‐hydroxyamines and β‐hydroxyhalo compounds, which are valuable intermediates in pharmaceutical, fine chemical, perfume and agrochemical synthesis.
Template‐Free Synthesis and Mechanistic Study of Porous Three‐Dimensional Hierarchical Uranium‐Containing and Uranium Oxide Microspheres
Authors: Wang Lin , Zhao Ran , Wang Cong‐zhi , Yuan Li‐yong , Gu Zhan‐jun , Xiao Cheng‐liang , Wang Shu‐ao , Wang Xin‐wei , Zhao Yu‐liang , Chai Zhi‐fang , Shi Wei‐qun
Published: August 2014

A novel type of uranium‐containing microspheres with an urchin‐like hierarchical nano/microstructure has been successfully synthesized by a facile template‐free hydrothermal method with uranyl nitrate hexahydrate, urea, and glycerol as the uranium source, precipitating agent, and shape‐controlling agent, respectively. The as‐synthesized microspheres were usually a few micrometers in size and porous inside, and their shells were composed of nanoscale rod‐shaped crystals. The growth mechanism of the hydrothermal reaction was studied, revealing that temperature, ratios of reactants, solution pH, and reaction time were all critical for the growth. The mechanism study also revealed that an intermediate compound of 3 UO3⋅NH3⋅5 H2O was first formed and then gradually converted into the final hydrothermal product. These uranium‐containing microspheres were excellent precursors to synthesize porous uranium oxide microspheres. With a suitable calcination temperature, very uniform microspheres of uranium oxides (UO2+x, U3O8, and UO3) were successfully synthesized.