bluuebunny/crossref_metadata_2025 huggingface dataset:
Burden of Infectious Disease in a State of India: A Comparative Analysis
Authors: Persai Divya
Published: May 2015

The presentation will throw light on the status of disease survelliance in infectious disease in a state of India in comparision to the entire country. This study is first to document case rates at a state-level in India and recognise the contribution of the IDSP system for epidemiological considerations.
The Relationship between Organizational Wisdom and Knowledge Management, Competitive Intelligence and Business Intelligence
Authors: Pourdjam A Mohammad , Ali-Siadat Seyed , Rajaeepour Saeed
Published: May 2015

After the strategic management period in the past decades, signs of forming a new approach are seen with a focus on the wisdom of organizations management. This study was conducted with the purpose of examining the relationship of organizational wisdom and the components of strategic intelligence among employees of the Iranian University of Applied Science and Technology in 2014. The method of this study is descriptive correlation from the cross-sectional survey type and as far as the purpose is concerned, it is in the group of research and development. The target population is the influential employees in organization decision-making including 591 participants and the sample size was estimated to be 236 people and the stratified random sampling used was sensitive to the groups' size. To collect data, a researcher-made questionnaire with 108 items was used with 5-point Likert scale that enjoyed content and construct validity. The Cronbach's coefficient was calculated to be 0.93. The collected data was analyzed using the statistical methods of correlation coefficient determination and stepwise regressions. The findings showed that statistically organizational wisdom and strategic intelligence are significantly related with the regression coefficient of 0.67 within the research model (p<0.01), and the components of knowledge management explains 43%, competitive intelligence 32%, and business intelligence 37% of the variation of organizational wisdom; thus, increasing the strategic intelligence in organizations is mutually related with enhancing organizational wisdom.
The Effective Mechanisms in Monitoring and Management of E-Government
Authors: Alguliyev Rasim , Yusifov Farhad
Published: May 2015

In paper main principles of formation and management of e-government areanalyzed. Web analytics application issue is investigated as the possibility to increase the effectiveness of e-government management indicators. Web analytics isanalyzed as effective feedback mechanism in monitoring and management of e-government. Some recommendations on how to design e-government programs were made.
Organizational Behavior of Terrorist Groups
Authors: Jung Jeyong , Lee Julak
Published: May 2015

Terror attacks have been typically performed by group members, which implies that perpetrators were not independent actors, but acted violently as being part of a larger group.  In addition, the execution of terrorist attacks is not only facilitated by macro-level factors but also as the tools to increase payoffs, survival, and maintenance at the group level. As links between disgruntled individuals and society, organizational behavior elements are something that needs to be examined. In this paper, several organizational behavior theories to compare were applied and contrast between terrorist groups and normal organizations under the categories of mobilizations, decision-making, and leadership.
Leadership and nurses’ satisfaction with supervision
Authors: Melo Rosa C.C.P. , Neves Diogo S.
Published: May 2015

Objective: The main objectives of this study were to evaluate the performance of leadership roles and the nurses’ satisfaction with supervision and to examine the relationship between the performance of leadership roles and nurse satisfaction.Methods: A quantitative, descriptive, correlational and transversal study was conducted, with a sample made up of 79 nurses practicing in two public health institutions in the district of Coimbra in Portugal. Data collected included demographic characteristics, eight leadership roles and five levels of supervision satisfaction. The Munson’s Supervision Satisfaction Scale and the Quinn’s Leadership Scale were used. The instruments adaptation and validation study revealed adequate psychometric properties being considered as valid instruments for the quantitative study pursuance.Results: The results indicate an acknowledgement of all roles of leadership, having a tendency towards the roles of producer (4.73) and director (4.64) indicating leadership centered on the rational goals model, revealing a greater concern with efficiency and productivity. The role of innovator was the one least perceived (4.16). Most nurses (83.50%) were satisfied with the supervision. The relationships between all the leadership roles and nurse satisfaction were positive, with the roles of facilitator (r = .842; p < .001) and mentor (r = .871; p < .001) with the strongest correlation.Conclusions: The investigation revealed that the leader who plays all roles of leadership raises the level of supervision satisfaction of the nurses he/she leads. A poor performance of the facilitator role suggests the need for head nurses to acquire leadership skills which help them manage interpersonal conflicts and promote cohesion and teamwork within the current context of health care restructuring and decreased nurse staffing levels.
The Arab Spring and its influence on European Union Policy
Authors: Araźna Marzena
Published: May 2015

The scale of incidents related to Arab Awaking and the consequences of movement in MENA
region surprised the European Union and international community. However, the report
of the Arab Human Development Report predicted in 2009 � that the Arab world will face
security challenges associated with growing population, which can lead to internal tensions
between different communities. The Arab Spring has contributed to the creation of new
political, economic and social realities which forced EU to take necessary action to adapt
to this situation. Significant efforts were taken according to financial support which was
delivered in increased budgets of European Neighborhood Policy projects, The European
Investment Bank (EIB), the European Bank for Reconstruction and Development (EBRD).
Due to the fact of immigration from region increases anxiety on the South of EU. In order
to prevent illegal border crossing EU established Joint Operation Hermes 2011 � to resolve
problem. However the Tunisami consequences are still considered as a threat to European
Union security.
In Vitro Differentiation of Human Neural Progenitor Cells Into Striatal GABAergic Neurons
Authors: Lin Lin , Yuan Juan , Sander Bjoern , Golas Monika M.
Published: May 2015

Huntington's disease (HD) results from a CAG repeat expansion in the gene encoding the huntingtin protein. This inherited disorder is characterized by progressive neurodegeneration. In particular, HD progression involves the loss of striatal projection neurons. The limited availability of reliable sources of human striatal projection neurons currently hampers our understanding of HD mechanisms and hinders the development of novel HD treatments. In this paper, we described two- and three-step methods for differentiating human neural progenitor cells toward striatal projection neurons. In the two-step differentiation protocol, 90%, 54%, and 6% of MAP2-positive cells were immunopositive for GABA, calbindin (CALB1), and DARPP-32/PPP1R1B, respectively. In the three-step differentiation protocol, 96%, 84%, and 21% of MAP2-positive cells were immunopositive for GABA, calbindin, and DARPP-32/PPP1R1B, respectively. In line with a striatal projection neuron phenotype, cells differentiated with our protocols displayed significantly increased expression of MAP2, CALB1, DARPP-32/PPP1R1B, ARPP21, and CTIP2. Application of glutamate receptor agonists induced calcium influx; accordingly, the cells also expressed various ionotropic glutamate receptor subunits. Differentiated cells also released GABA on stimulation. We suggest that our three-step differentiation protocol presents a reliable and simplified method for the generation of striatal projection neurons, yielding a critical resource for neuronal physiology and neurodegenerative disorder studies.

Significance

The earliest changes in the neurodegenerative disorder Huntington's disease affect a specific type of brain neurons, the so-called medium spiny neurons of the striatum. In this study, two protocols were developed for the differentiation of neural progenitor cells into striatal medium spiny neurons, and the differentiated neurons were extensively characterized. The data indicate that the three-step differentiation protocol presents a reliable and simplified method for the generation of striatal medium spiny neurons. The generated striatal medium spiny neurons could represent a critical resource for the study of neurodegenerative disorders, a model system for drug discovery, and a step toward cell-based regeneration therapies.
Megestrol Acetate Increases the Proliferation, Migration, and Adipogenic Differentiation of Adipose-Derived Stem Cells via Glucocorticoid Receptor
Authors: Sung Jong-Hyuk , An Hyo-Sun , Jeong Jin-Hyun , Shin Soyoung , Song Seung Yong
Published: May 2015

Because adipose-derived stem cells (ASCs) are usually expanded to acquire large numbers of cells for therapeutic applications, it is important to increase the production yield and regenerative potential during expansion. Therefore, a tremendous need exists for alternative ASC stimuli during cultivation to increase the proliferation and adipogenic differentiation of ASCs. The present study primarily investigated the involvement of megestrol acetate (MA), a progesterone analog, in the stimulation of ASCs, and identifies the target receptors underlying stimulation. Mitogenic and adipogenic effects of MA were investigated in vitro, and pharmacological inhibition and small interfering (si) RNA techniques were used to identify the molecular mechanisms involved in the MA-induced stimulation of ASCs. MA significantly increased the proliferation, migration, and adipogenic differentiation of ASCs in a dose-dependent manner. Glucocorticoid receptor (GR) is highly expressed compared with other nuclear receptors in ASCs, and this receptor is phosphorylated after MA treatment. MA also upregulated genes downstream of GR in ASCs, including ANGPTL4, DUSP1, ERRF11, FKBP5, GLUL, and TSC22D3. RU486, a pharmacological inhibitor of GR, and transfection of siGR significantly attenuated MA-induced proliferation, migration, and adipogenic differentiation of ASCs. Although the adipogenic differentiation potential of MA was inferior to that of dexamethasone, MA had mitogenic effects in ASCs. Collectively, these results indicate that MA increases the proliferation, migration, and adipogenic differentiation of ASCs via GR phosphorylation.

Significance

Magestrol acetate (MA) increases the proliferation, migration, and adipogenic differentiation of adipose-derived stem cells (ASCs) via glucocorticoid receptor phosphorylation. Therefore, MA can be applied to increase the production yield during expansion and can be used to facilitate adipogenic differentiation of ASCs.
Seismic interferometry and stationary phase at caustics
Authors: Snieder Roel , Sens‐Schönfelder Christoph
Published: May 2015

Waves that propagate between two receivers can be extracted by cross correlating noise recorded at these receivers if the noise is generated by sources on a closed surface surrounding the receivers. This concept is called seismic interferometry. Of all these noise sources, those for whom the travel time difference for propagation to the two receivers is in the stationary phase zone, give the dominant contribution. In this paper we analyze the stationary phase properties when one receiver is at a caustic for waves leaving the other receiver. A simple model for a waveguide and a general treatment of caustics show that, at a caustic, the curvature of the travel time difference at the stationary phase zone vanishes. As a result the stationary phase region is considerably wider at a caustic than at other points, and it is more likely that noise sources are present in the stationary phase region. This explains why it is easier to extract waves from seismic interferometry when the receivers are at caustics such as antipodal receivers on the Earth.
Potential of ambient seismic noise techniques to monitor the St. Gallen geothermal site (Switzerland)
Authors: Obermann A. , Kraft T. , Larose E. , Wiemer S.
Published: May 2015

The failures of two recent deep geothermal energy projects in Switzerland (Basel, 2006; St. Gallen, 2013) have again highlighted that one of the key challenges for the successful development and operation of deep underground heat exchangers is to control the risk of inducing potentially hazardous seismic events. In St. Gallen, after an injection test and two acid injections that were accompanied by a small number of micro‐earthquakes (ML<0.2), operators were surprised by an uncontrolled gas release from the formation (gas kick). The “killing” procedures that had to be initiated following standard drilling procedures led to a ML3.5 earthquake. With ambient seismic noise cross correlations from nine stations, we observe a significant loss of waveform coherence that we can horizontally and vertically constrain to the injection location of the fluid. The loss of waveform coherence starts with the onset of the fluid injections 4 days prior to the gas kick. We interpret the loss of coherence as a local perturbation of the medium. We show how ambient seismic noise analysis can be used to assess the aseismic response of the subsurface to geomechanical well operations and how this method could have helped to recognize the unexpected reservoir dynamics at an earlier stage than the microseismic response alone, allowed.
Synthesis and structural characterization of ferrous trioctahedral smectites: Implications for clay mineral genesis and detectability on Mars
Authors: Chemtob Steven M. , Nickerson Ryan D. , Morris Richard V. , Agresti David G. , Catalano Jeffrey G.
Published: May 2015

Widespread detections of phyllosilicates in Noachian terrains on Mars imply a history of near‐surface fluid‐rock interaction. Ferrous trioctahedral smectites are thermodynamically predicted products of basalt weathering on early Mars, but to date only Fe3+‐bearing dioctahedral smectites have been identified from orbital observations. In general, the physicochemical properties of ferrous smectites are poorly studied because they are susceptible to air oxidation. In this study, eight Fe2+‐bearing smectites were synthesized from Fe2+‐Mg‐Al silicate gels at 200°C under anoxic conditions. Samples were characterized by inductively coupled plasma optical emission spectrometry, powder X‐ray diffraction, Fe K‐edge X‐ray absorption spectroscopy (XAS), Mössbauer spectroscopy, and visible/near‐infrared (VNIR) reflectance spectroscopy. The range of redox states was Fe3+/ΣFe = 0 to 0.06 ± 0.01 as determined by both XAS and, for short integration times, Mössbauer. The smectites have 060 distances (d(060)) between 1.53 and 1.56 Å, indicating a trioctahedral structure. d(060) and XAS‐derived interatomic Fe‐(Fe,Mg,Al) distance scaled with Fe content. Smectite VNIR spectra feature OH/H2O absorption bands at 1.4 and 1.9 µm, (Fe2+,Mg,Al)3‐OH stretching bands near 1.4 µm, and Fe2+Fe2+Fe2+‐OH, MgMgMg‐OH, AlAl(Mg,Fe2+)‐OH, and AlAl‐OH combination bands at 2.36 µm, 2.32 µm 2.25 µm, and 2.20 µm, respectively. The spectra for ferrous saponites are distinct from those for dioctahedral ferric smectites, permitting their differentiation from orbital observations. X‐ray diffraction patterns for synthetic high‐Mg ferrosaponite and high‐Mg ferrian saponite are both consistent with the Sheepbed saponite detected by the chemistry and mineralogy (CheMin) instrument at Gale Crater, Mars, suggesting that anoxic basalt alteration was a viable pathway for clay mineral formation on early Mars.
Separating physical and biological controls on long‐term evapotranspiration fluctuations in a tropical deciduous forest subjected to monsoonal rainfall
Authors: Igarashi Yasunori , Katul Gabriel G. , Kumagai Tomo'omi , Yoshifuji Natsuko , Sato Takanori , Tanaka Nobuaki , Tanaka Katsunori , Fujinami Hatsuki , Suzuki Masakazu , Tantasirin Chatchai
Published: May 2015

Evapotranspiration (ET), especially in the mainland of the Indochina Peninsula, can impact and is impacted by the Asian monsoonal (AM) system, thereby prompting interest in its long‐term variability. To separate the physical and biological factors controlling ET variability in a tropical deciduous forest under the AM influence, 7 year eddy covariance and ancillary measurements were collected and analyzed. The 7 year mean rainfall (Pr) and ET along with their standard deviations were 1335 ± 256 and 977 ± 108 mm (about 73% of Pr), respectively, suggesting close coupling between these two hydrologic fluxes. However, other physical and biological drivers decouple seasonal and annual variations of ET from Pr. To explore them, a big‐leaf model complemented by perturbation analysis was employed. The big‐leaf model agreed well with the measured ET at daily to multiyear time scales, lending confidence in its ability to separate biological and physical controls on ET. Using this formulation, both first‐order and second‐order Taylor series expansions of the total ET derivatives were applied to the big‐leaf model and compared with measured changes in ET (dET). Higher‐order and joint terms in the second‐order expansion were necessary for matching measured and analyzed dET. Vapor pressure deficit (D) was the primary external physical controlling driver of ET. Leaf area index (LAI) and bulk stomatal conductance (gs) were shown to be the main significant biological drivers of the transpiration component of ET. It can be surmised that rainfall variability controls long‐term ET through physical (mainly D) and biological (mainly LAI and gs) factors in this ecosystem.
The interplay between transport and reaction rates as controls on nitrate attenuation in permeable, streambed sediments
Authors: Lansdown K. , Heppell C. M. , Trimmer M. , Binley A. , Heathwaite A. L. , Byrne P. , Zhang H.
Published: May 2015

Anthropogenic nitrogen fixation and subsequent use of this nitrogen as fertilizer have greatly disturbed the global nitrogen cycle. Rivers are recognized hot spots of nitrogen removal in the landscape as interaction between surface water and sediments creates heterogeneous redox environments conducive for nitrogen transformations. Our understanding of riverbed nitrogen dynamics to date comes mainly from shallow sediments or hyporheic exchange flow pathways with comparatively little attention paid to groundwater‐fed, gaining reaches. We have used 15N techniques to quantify in situ rates of nitrate removal to 1 m depth within a groundwater‐fed riverbed where subsurface hydrology ranged from strong upwelling to predominantly horizontal water fluxes. We combine these rates with detailed hydrologic measurements to investigate the interplay between biogeochemical activity and water transport in controlling nitrogen attenuation along upwelling flow pathways. Nitrate attenuation occurred via denitrification rather than dissimilatory nitrate reduction to ammonium or anammox (range = 12 to >17,000 nmol 15N L−1 h−1). Overall, nitrate removal within the upwelling groundwater was controlled by water flux rather than reaction rate (i.e., Damköhler numbers <1) with the exception of two hot spots of biogeochemical activity. Deep sediments were as important a nitrate sink as shallow sediments with fast rates of denitrification and short water residence time close to the riverbed surface balanced by slower rates of denitrification and water flux at depth. Within this permeable riverbed >80% of nitrate removal occurs within sediments not exposed to hyporheic exchange flows under base flow conditions, illustrating the importance of deep sediments as nitrate sinks in upwelling systems.
Detecting soil moisture impacts on convective initiation in Europe
Authors: Taylor Christopher M.
Published: May 2015

Feedbacks between soil moisture and precipitation are important for understanding hydroclimatic variability in many regions. However, much uncertainty remains about how land surface fluxes influence the initiation of deep convection locally. While some studies consider only atmospheric and soil profiles, in a one‐dimensional sense, others have argued that horizontal variability in fluxes plays an important role in convective triggering, via mesoscale circulations. This paper presents the first comprehensive observational analysis over Europe linking convective initiation to soil moisture, based on satellite observations of cloud top and land surface temperature, and soil moisture. The results show that convective initiations are favored on the downwind side of dry surfaces, close to wetter areas. The signal is clearest following dry periods and under light winds, consistent with forcing by a mesoscale circulation. Overall, the detected signal in Europe is weaker than in previous Sahelian analysis, but key spatial characteristics are essentially the same.
Microwave remote sensing of short‐term droughts during crop growing seasons
Authors: Yuan Xing , Ma Zhuguo , Pan Ming , Shi Chunxiang
Published: May 2015

Severe short‐term (monthly to seasonal) droughts frequently occurred over China in recent years, with devastating impacts on crop production. This study assesses the capability of microwave remote sensing in detecting soil moisture (agricultural) droughts over China and in providing early warnings. The 22 year (1992–2013) European Space Agency satellite soil moisture retrievals are compared against the in situ observations at 312 stations in China, the global soil moisture reanalysis, and the observed rainfall deficit. Both the reanalysis and remote sensing products can only detect less than 60% of drought months at in situ station scale, but they capture the interannual variations of short‐term drought area at river basin scales quite well. As compared with reanalysis, the passive and merged microwave products have better drought detection over sparsely vegetated regions in northwestern China and the active microwave product with better vegetation penetration works the best in eastern China.
A physical explanation for the development of redox microzones in hyporheic flow
Authors: Briggs Martin A. , Day‐Lewis Frederick D. , Zarnetske Jay P. , Harvey Judson W.
Published: May 2015

Recent observations reveal a paradox of anaerobic respiration occurring in seemingly oxic‐saturated sediments. Here we demonstrate a residence time‐based explanation for this paradox. Specifically, we show how microzones favorable to anaerobic respiration processes (e.g., denitrification, metal reduction, and methanogenesis) can develop in the embedded less mobile porosity of bulk‐oxic hyporheic zones. Anoxic microzones develop when transport time from the streambed to the pore center exceeds a characteristic uptake time of oxygen. A two‐dimensional pore‐network model was used to quantify how anoxic microzones develop across a range of hyporheic flow and oxygen uptake conditions. Two types of microzones develop: flow invariant and flow dependent. The former is stable across variable hydrologic conditions, whereas the formation and extent of the latter are sensitive to flow rate and orientation. Therefore, pore‐scale residence time heterogeneity, which can now be evaluated in situ, offers a simple explanation for anaerobic signals occurring in oxic pore waters.
Cascadia subducting plate fluids channelled to fore‐arc mantle corner: ETS and silica deposition
Authors: Hyndman R. D. , McCrory P. A. , Wech A. , Kao H. , Ague J.
Published: May 2015

In this study we first summarize the constraints that on the Cascadia subduction thrust, there is a 70 km gap downdip between the megathrust seismogenic zone and the Episodic Tremor and Slip (ETS) that lies further landward; there is not a continuous transition from unstable to conditionally stable sliding. Seismic rupture occurs mainly offshore for this hot subduction zone. ETS lies onshore. We then suggest what does control the downdip position of ETS. We conclude that fluids from dehydration of the downgoing plate, focused to rise above the fore‐arc mantle corner, are responsible for ETS. There is a remarkable correspondence between the position of ETS and this corner along the whole margin. Hydrated mineral assemblages in the subducting oceanic crust and uppermost mantle are dehydrated with downdip increasing temperature, and seismic tomography data indicate that these fluids have strongly serpentinized the overlying fore‐arc mantle. Laboratory data show that such fore‐arc mantle serpentinite has low permeability and likely blocks vertical expulsion and restricts flow updip within the underlying permeable oceanic crust and subduction shear zone. At the fore‐arc mantle corner these fluids are released upward into the more permeable overlying fore‐arc crust. An indication of this fluid flux comes from low Poisson's Ratios (and Vp/Vs) found above the corner that may be explained by a concentration of quartz which has exceptionally low Poisson's Ratio. The rising fluids should be silica saturated and precipitate quartz with decreasing temperature and pressure as they rise above the corner.
Measuring and modeling the lifetime of nitrous oxide including its variability
Authors: Prather Michael J. , Hsu Juno , DeLuca Nicole M. , Jackman Charles H. , Oman Luke D. , Douglass Anne R. , Fleming Eric L. , Strahan Susan E. , Steenrod Stephen D. , Søvde O. Amund , Isaksen Ivar S. A. , Froidevaux Lucien , Funke Bernd
Published: May 2015

The lifetime of nitrous oxide, the third‐most‐important human‐emitted greenhouse gas, is based to date primarily on model studies or scaling to other gases. This work calculates a semiempirical lifetime based on Microwave Limb Sounder satellite measurements of stratospheric profiles of nitrous oxide, ozone, and temperature; laboratory cross‐section data for ozone and molecular oxygen plus kinetics for O(1D); the observed solar spectrum; and a simple radiative transfer model. The result is 116 ± 9 years. The observed monthly‐to‐biennial variations in lifetime and tropical abundance are well matched by four independent chemistry‐transport models driven by reanalysis meteorological fields for the period of observation (2005–2010), but all these models overestimate the lifetime due to lower abundances in the critical loss region near 32 km in the tropics. These models plus a chemistry‐climate model agree on the nitrous oxide feedback factor on its own lifetime of 0.94 ± 0.01, giving N2O perturbations an effective residence time of 109 years. Combining this new empirical lifetime with model estimates of residence time and preindustrial lifetime (123 years) adjusts our best estimates of the human‐natural balance of emissions today and improves the accuracy of projected nitrous oxide increases over this century.
Isotope‐based Fluvial Organic Carbon (ISOFLOC) Model: Model formulation, sensitivity, and evaluation
Authors: Ford William I. , Fox James F.
Published: May 2015

Watershed‐scale carbon budgets remain poorly understood, in part due to inadequate simulation tools to assess in‐stream carbon fate and transport. A new numerical model termed ISOtope‐based FLuvial Organic Carbon (ISOFLOC) is formulated to simulate the fluvial organic carbon budget in watersheds where hydrologic, sediment transport, and biogeochemical processes are coupled to control benthic and transported carbon composition and flux. One ISOFLOC innovation is the formulation of new stable carbon isotope model subroutines that include isotope fractionation processes in order to estimate carbon isotope source, fate, and transport. A second innovation is the coupling of transfers between carbon pools, including algal particulate organic carbon, fine particulate and dissolved organic carbon, and particulate and dissolved inorganic carbon, to simulate the carbon cycle in a comprehensive manner beyond that of existing watershed water quality models. ISOFLOC was tested and verified in a low‐gradient, agriculturally impacted stream. Results of a global sensitivity analysis suggested the isotope response variable had unique sensitivity to the coupled interaction between fluvial shear resistance of algal biomass and the concentration of dissolved inorganic carbon. Model calibration and validation suggested good agreement at event, seasonal, and annual timescales. Multiobjective uncertainty analysis suggested inclusion of the carbon stable isotope routine reduced uncertainty by 80% for algal particulate organic carbon flux estimates.
Lymphatic System
Authors: Washington Elizabeth A , Mahakapuge Thilini AN , Scheerlinck Jean‐Pierre Y , Kimpton Wayne G
Published: May 2015

The lymphatic system consists of a network of vessels lined with endothelial cells and interconnected lymph nodes, distributed throughout most of the body. It functions as a tissue drainage system, controlling the volume of blood and extracellular fluid and preventing tissue oedema. The lymphatic system collects tissue fluids and cells from most organs and tissues, transports it as lymph via a combination of intrinsic and extrinsic lymphatic pumps, ultimately returning these cells to blood. Dendritic cells patrol the tissues detecting danger signals and bringing foreign antigens back to the lymph nodes via afferent lymphatics where adaptive immune responses are induced. Thus, the lymphatic system integrates the immune system and widely dispersed organs and tissues, allowing for their protection from infections. It also plays a role in the turnover of macromolecules, which make up the extracellular matrix, fat absorption from the gut and immune function.

Key Concepts

The lymphatic system comprises a network of vessels lined by endothelial cells.

Lymphatic vessels drain nearly all tissues and organs in the body and interconnect lymph nodes.

Afferent lymphatics transport lymph from the tissues to lymph nodes, whereas efferent lymphatics transport lymph away from lymph nodes.

Lymphatics are essential for returning proteins, fluids and cells to blood, absorbing fat from the gut and are involved in the homeostasis of interstitial macromolecules.

The lymphatic system is a key regulator of extracellular fluid volume and is involved in preventing oedema.

The lymphatics play a central role in integrating the immune system, carrying lymphocytes, professional antigen‐presenting cells and antigens from the tissues to the lymph nodes.

Lymphatic endothelial cells function as professional antigen‐presenting cells, communicate directly with lymphocytes and antigen‐presenting cells to control cell traffic.
Influenza Epidemics
Authors: Neumann Gabriele , Kawaoka Yoshihiro
Published: May 2015

Influenza viruses can cause epidemics or pandemics (worldwide epidemics), during which acute febrile respiratory disease spreads rapidly among all age groups, accompanied by excess hospitalisation and death. Here, we describe the recorded influenza virus pandemics, including the most recent pandemic that was caused in 2009 by a novel virus of the H1N1 subtype. Influenza virus replication and adaptation to new hosts account for much of the evolutionary success of these viruses. We review the viral proteins that are known to affect host range and pathogenicity (i.e. the haemagglutinin protein HA, the neuraminidase protein NA, the polymerase protein PB2, the nonstructural protein NS1 and the PB1‐F2 protein). We also discuss the clinical features of influenza virus infections, influenza virus immunology and influenza virus control, including antiviral treatment and vaccination.

Key Concepts

Influenza A viruses cause annual epidemics that result from point mutations in the surface glycoprotein(s) HA (and NA) (antigenic drift).

At random intervals, influenza pandemics are caused by viruses that introduce HA proteins into the human population against which most humans lack immunity.

Influenza A viruses evolve through reassortment and point mutations.

Aquatic birds are the natural reservoir of influenza A viruses.

Influenza A viruses can be transmitted among species, despite host range restriction factors.

The HA protein is the major protective antigen and an important determinant of host range and pathogenicity.

The PB2, NS1 and PB1‐F2 proteins are also important determinants of pathogenicity.

Avian H5N1 and H7N9 viruses sporadically infect humans and cause severe respiratory infections with high case fatality rates; currently, these viruses do not transmit efficiently among humans.

For human influenza viruses, inactivated and live attenuated vaccines are available.

Three classes of antiviral compounds (ion channel, neuraminidase and polymerase inhibitors) exist: resistance to ion channel inhibitors is now widespread among circulating H1N1 and H3N2 influenza viruses; most human influenza viruses, as well as most avian H5N1 and H7N9 viruses, are sensitive to neuraminidase inhibitors, although viruses with resistance to neuraminidase inhibitors have been reported. Resistance to the recently approved polymerase inhibitor has not been reported yet.
Salmonella
Genomes in the Context of Lifestyle
Authors: Klemm Elizabeth J , Wong Vanessa K , Dougan Gordon
Published: May 2015

The
Enterobacteriaceae
encompass a large family of Gram‐negative gastrointestinal resident bacteria, including the
Salmonella enterica
species. Members of this family have persisted for millions of years, although there is diversity in terms of host range and disease phenotype. The core genome shared between all
Enterobacteriaceae
includes genes essential for colonising the host intestine, whereas the accessory genome that is specific to certain subspecies and serovars reflects the diversity in lifestyle. This is especially well illustrated in
S. enterica
, which has over 2,000 different serovars with a wide range of lifestyles, comprising generalists and host‐adapted serovars. Changes to the genome content drive this diversity and this frequently occurs via horizontal gene transfer, bacteriophage and transposon acquisition, plasmid movement and genome degradation. Many specific examples illustrate these evolutionary adaptations in
Salmonella
.

Key Concepts

Whole genome sequencing and comparative genomics have revealed a conserved ‘core genome’ common to enteric bacteria.

Horizontal gene transfer, bacteriophages and plasmid acquisition generates a repertoire of ‘accessory genome’ features that provides diversification.

Presence of certain
Salmonella
Pathogenicity Islands (SPIs) differentiates
Salmonella
from other
Enterobacteriaceae
and differentiates
S
.
bongori
from
S
.
enterica
: all
Salmonella
spp. have SPI‐1, implicated in host cell invasion, while only
S
.
enterica
has SPI‐2, which is required for survival within the host cell.

S
.
enterica
is an old and complex species with over 2000 serovars that differ in terms of host range and disease phenotype.

S
. Typhi is an example of a host‐adapted serovar that causes severe invasive disease and is restricted to humans.

Host adaptation in
S
. Typhi is driven by genome degradation, the loss of genes not required for the systemic lifestyle in human hosts and gene acquisition, including the genes encoding the Vi capsule and typhoid toxin.
Influence of impeller type on hydrodynamics and gas‐liquid mass‐transfer in stirred airlift bioreactor
Authors: de Jesus Sérgio S. , Moreira Neto João , Santana Aline , Maciel Filho Rubens
Published: May 2015

The influence of impeller type in a mechanically stirred airlift bioreactor was analyzed in relation to the non‐Newtonian viscous fluids. The agitation was carried out through a marine impeller (axial impeller) and a paddle impeller (radial impeller) located along with the gas sparger in the region comprised by the riser. The bioreactor was sparged with air under different velocities (0.036–0.060 m s−1). Carboxymethylcellulose 1.94% and xanthan 1.80% were used as a fluid model. The gas holdup and volumetric mass‐transfer coefficient increased in up to five and three times, respectively, when compared to a conventional airlift bioreactor; however, better results were obtained when the straight paddle impeller type was used. The results suggest that the studied bioreactor can be used successfully in viscous fluid, and it can be more efficient than conventional airlift bioreactors. The results obtained suggest the use of radial impellers. © 2015 American Institute of Chemical Engineers AIChE J, 61: 3159–3171, 2015
Depression and cognitive impairment following recovery from thrombotic thrombocytopenic purpura
Authors: Han Bowie , Page Evaren E. , Stewart Lauren M. , Deford Cassandra C. , Scott James G. , Schwartz Lauren H. , Perdue Jedidiah J. , Terrell Deirdra R. , Vesely Sara K. , George James N.
Published: May 2015

After recovery from an acute episode of acquired thrombotic thrombocytopenic purpura (TTP), patients often describe problems with memory, concentration, and endurance. We have previously reported the occurrence of depression and cognitive impairment in these patients. In this study, we describe the frequency, severity, and clinical course of depression and cognitive impairment. Fifty‐two (85%) out of 61 eligible Oklahoma Registry patients who had recovered from TTP, documented by ADAMTS13 activity <10%, have had at least one (median, four) evaluation for depression over 11 years using the Beck Depression Inventory‐II; 31 (59%) patients screened positive for depression at least once; in 15 (29%), the results suggested severe depression at least once. Nine of these 15 patients had a psychiatric interview, the definitive diagnostic evaluation; the diagnosis of major depressive disorder was established in eight (89%) patients. In 2014, cognitive ability was evaluated in 33 patients by the Montreal Cognitive Assessment and the Repeatable Battery for Assessment of Neuropsychological Status (RBANS). Both tests detected significant cognitive impairment in the patients as a group. Fifteen out of the 33 patients had been evaluated by extensive cognitive tests in 2006. The 2014 RBANS results were significantly worse than the 2006 results for the overall score and two out of the five RBANS domains (immediate and delayed memory). Neither depression nor cognitive impairment was significantly associated with the occurrence of relapses or ADAMTS13 activity <10% during remission. These observations emphasize the importance of screening evaluations for depression and cognitive impairment after recovery from acquired TTP. Am. J. Hematol. 90:709–714, 2015. © 2015 Wiley Periodicals, Inc.
Copy number variants including RAS pathway genes—How much RASopathy is in the phenotype?
Authors: Lissewski Christina , Kant Sarina G. , Stark Zornitza , Schanze Ina , Zenker Martin
Published: May 2015

The RASopathies comprise a group of clinically overlapping developmental syndromes the common pathogenetic basis of which is dysregulated signal flow through the RAS‐MAPK pathway. Mutations in several components or modifiers of the pathway have been identified in Noonan syndrome and related disorders. Over the past years copy number variants (CNVs) encompassing RAS pathway genes (PTPN11, RAF1, MEK2, or SHOC2) have been reported in children with developmental syndromes. These observations raised speculations that the associated phenotypes represent RASopathies, implying that the increased or reduced expression of the respective RAS pathway component and a consecutive dysregulation of RAS pathway signalling is responsible for the clinical picture. Herein, we present two individuals and three of their relatives harboring duplications of either 3p25.2 including the RAF1 locus or 19p13.3 including the MEK2 locus. Duplication carriers exhibited variable clinical phenotypes including non‐specific facial dysmorphism, short stature, and learning difficulties. A careful review of the literature supported the impression that phenotypes associated with CNVs including RAS pathway genes commonly share non‐specific symptoms with RASopathies, while the characteristic “gestalt” is lacking. Considering the known molecular pathogenesis of RASopathies, it is questionable that a modest increase in the expression of a functionally normal signaling component can mimic the effects of a qualitatively abnormal (hyperactive) mutant protein. We thus argue that current empirical and biological evidence is still insufficient to allow the conclusion that an altered copy number of a RAS pathway component is indeed the mechanism that is critical for the phenotype associated with CNVs including RASopathy genes. © 2015 Wiley Periodicals, Inc.
The fetal brain transcriptome and neonatal behavioral phenotype in the Ts1Cje mouse model of Down syndrome
Authors: Guedj Faycal , Pennings Jeroen L. A. , Ferres Millie A. , Graham Leah C. , Wick Heather C. , Miczek Klaus A. , Slonim Donna K. , Bianchi Diana W.
Published: May 2015

Human fetuses with Down syndrome demonstrate abnormal brain growth and reduced neurogenesis. Despite the prenatal onset of the phenotype, most therapeutic trials have been conducted in adults. Here, we present evidence for fetal brain molecular and neonatal behavioral alterations in the Ts1Cje mouse model of Down syndrome. Embryonic day 15.5 brain hemisphere RNA from Ts1Cje embryos (n = 5) and wild type littermates (n = 5) was processed and hybridized to mouse gene 1.0 ST arrays. Bioinformatic analyses were implemented to identify differential gene and pathway regulation during Ts1Cje fetal brain development. In separate experiments, the Fox scale, ultrasonic vocalization and homing tests were used to investigate behavioral deficits in Ts1Cje pups (n = 29) versus WT littermates (n = 64) at postnatal days 3–21. Ts1Cje fetal brains displayed more differentially regulated genes (n = 71) than adult (n = 31) when compared to their age‐matched euploid brains. Ts1Cje embryonic brains showed up‐regulation of cell cycle markers and down‐regulation of the solute‐carrier amino acid transporters. Several cellular processes were dysregulated at both stages, including apoptosis, inflammation, Jak/Stat signaling, G‐protein signaling, and oxidoreductase activity. In addition, early behavioral deficits in surface righting, cliff aversion, negative geotaxis, forelimb grasp, ultrasonic vocalization, and the homing tests were observed. The Ts1Cje mouse model exhibits abnormal gene expression during fetal brain development, and significant neonatal behavioral deficits in the pre‐weaning period. In combination with human studies, this suggests that the Down syndrome phenotype manifests prenatally and provides a rationale for prenatal therapy to improve perinatal brain development and postnatal neurocognition. © 2015 Wiley Periodicals, Inc.
Congenital contractural arachnodactyly complicated with aortic dilatation and dissection: Case report and review of literature
Authors: Takeda Norifumi , Morita Hiroyuki , Fujita Daishi , Inuzuka Ryo , Taniguchi Yuki , Imai Yasushi , Hirata Yasunobu , Komuro Issei
Published: May 2015

Congenital contractural arachnodactyly (CCA) is a connective tissue disease caused by mutations of the FBN2, which encodes fibrillin‐2. CCA patients have a marfanoid habitus; however, aortic dilatation and/or dissection as observed in Marfan syndrome have been rarely documented. Here, we report on a Japanese familial case of CCA resulting from a FBN2 splicing mutation (IVS32+5g→a), which leads to exon 32 being skipped, and the patients developed aortic dilatation and type A dissection. Although CCA patients have been believed to have favorable prognoses, repetitive aortic imaging studies must be performed in some patients to detect possible aortic disease early, and genetic testing of FBN2 might be useful to identify such high‐risk patients. © 2015 Wiley Periodicals, Inc.
Sudomotor innervation in transthyretin amyloid neuropathy: Pathology and functional correlates
Authors: Chao Chi‐Chao , Huang Cho‐Min , Chiang Hao‐Hua , Luo Kai‐Ren , Kan Hung‐Wei , Yang Naomi Chu‐Chiao , Chiang Hao , Lin Whei‐Min , Lai Shu‐Mei , Lee Ming‐Jen , Shun Chia‐Tung , Hsieh Sung‐Tsang
Published: May 2015

Objective

Autonomic neuropathy is a major component of familial amyloid polyneuropathy (FAP) due to mutated transthyretin, with sudomotor failure as a common manifestation. This study aimed to investigate the pathology and clinical significance of sudomotor denervation.

Methods

Skin biopsies were performed on the distal leg of FAP patients with a follow‐up duration of 3.8 ± 1.6 years. Sudomotor innervation was stained with 2 markers: protein gene product 9.5 (PGP 9.5), a general neuronal marker, and vasoactive intestinal peptide (VIP), a sudomotor nerve functional marker, followed by quantitation according to sweat gland innervation index (SGII) for PGP 9.5 (SGIIPGP 9.5) and VIP (SGIIVIP).

Results

There were 28 patients (25 men) with Ala97Ser transthyretin and late onset (59.9 ± 6.0 years) disabling neuropathy. Autonomic symptoms were present in 22 patients (78.6%) at the time of skin biopsy. The SGIIPGP 9.5 and SGIIVIP of FAP patients were significantly lower than those of age‐ and gender‐matched controls. The reduction of SGIIVIP was more severe than that of SGIIPGP 9.5 (p = 0.002). Patients with orthostatic hypotension or absent sympathetic skin response at palms were associated with lower SGIIPGP 9.5 (p = 0.019 and 0.002, respectively). SGIIPGP 9.5 was negatively correlated with the disability grade at the time of skin biopsy (p = 0.004), and was positively correlated with the interval from the time of skin biopsy to the time of wheelchair usage (p = 0.029).

Interpretation

This study documented the pathological evidence of sudomotor denervation in FAP. SGIIPGP 9.5 was functionally correlated with autonomic symptoms, autonomic tests, ambulation status, and progression of disability. Ann Neurol 2015;78:272℃283
Effect of pioglitazone medication on the incidence of dementia
Authors: Heneka Michael T. , Fink Anne , Doblhammer Gabriele
Published: May 2015

Objective

Peroxisome proliferator activated receptor γ–activating drugs show various salutary effects in preclinical models of neurodegenerative disease. The decade‐long clinical usage of these drugs as antidiabetics now allows for evaluation of patient‐oriented data sources.

Methods

Using observational data from 2004–2010, we analyzed the association of pioglitazone and incidence of dementia in a prospective cohort study of 145,928 subjects aged ≥60 years who, at baseline, were free of dementia and insulin‐dependent diabetes mellitus. We distinguished between nondiabetics, diabetics without pioglitazone, diabetics with prescriptions of <8 calendar quarters of pioglitazone, and diabetics with ≥8 quarters. Cox proportional hazard models explored the relative risk (RR) of dementia incidence dependent on pioglitazone use adjusted for sex, age, use of rosiglitazone or metformin, and cardiovascular comorbidities.

Results

Long‐term use of pioglitazone was associated with a lower dementia incidence. Relative to nondiabetics, the cumulative long‐term use of pioglitazone reduced the dementia risk by 47% (RR = 0.53, p = 0.029). If diabetes patients used pioglitazone <8 quarters, the dementia risk was comparable to those of nondiabetics (RR = 1.16, p = 0.317), and diabetes patients without a pioglitazone treatment had a 23% increase in dementia risk (RR = 1.23, p < 0.001). We did not find evidence for age effects, nor for selection into pioglitazone treatment due to obesity.

Interpretation

These findings indicate that pioglitazone treatment is associated with a reduced dementia risk in initially non–insulin‐dependent diabetes mellitus patients. Prospective clinical trials are needed to evaluate a possible neuroprotective effect in these patients in an ageing population. Ann Neurol 2015;78:284–294