bluuebunny/crossref_metadata_2025 huggingface dataset:
Shot peening in a novel centrifugal air blast reactor
Authors: Ranaware P. G. , Rathod M. J.
Published: July 2016

A novel reactor to synthesise a thick nanocrystalline (NC) layer on metallic surface by shot peening is presented. In this cylindrical reactor, air enters inside the reactor tangentially and propels shots on specimen surface for peening. The air then leaves the reactor after multiple rotations. Air vortex and very high turbulence inside the reactor dissipate the heat generated during shot peening and thus avoids dynamic recovery. Experiments were conducted on samples of austenitic stainless steel with different shot velocities. Characterisation of shot peened surfaces showed that thick layers with NC/nano-twinned structure were developed under all peening conditions used in the experiments. Microstrain in the lattice, dislocation density and volume fraction of strain-induced martensite observed to increase with rise in shot velocity. Consistent reduction in grain size and enhancement in dislocation density with increase in strain, indicate that no dynamic recovery occurred during the shot peening process in the reactor.
Breuil 𝒪-windows and 𝜋-divisible 𝒪-modules
Authors: Cheng Chuangxun
Published: July 2016

Let

p
>
2

p>2

be a prime number. Let

O

\mathcal {O}

be the ring of integers of a finite extension of

Q

p

\mathbb {Q}_p

and let

π
\pi

be a uniformizer of

O

\mathcal {O}

. We prove that, for any complete Noetherian regular local

O

\mathcal {O}

-algebra

R
R

with perfect residue field of characteristic

p
p

, the category of Breuil

O

\mathcal {O}

-windows over

R
R

is equivalent to the category of

π
\pi

-divisible

O

\mathcal {O}

-modules over

R
R

. We also prove that the category of Breuil

O

\mathcal {O}

-modules over

R
R

is equivalent to the category of commutative finite flat

O

\mathcal {O}

-group schemes over

R
R

which are kernels of isogenies of

π
\pi

-divisible

O

\mathcal {O}

-modules. As an application of these equivalences, we then prove a boundedness result on Barsotti-Tate groups and deduce some corollaries. The results generalize some earlier results of Zink, Vasiu-Zink, and Lau.
Homogeneous solutions to the 3D Euler system
Authors: Shvydkoy Roman
Published: July 2016

We study stationary homogeneous solutions to the 3D Euler equation. The problem is motivated by recent exclusions of self-similar blowup for Euler and its relation to the Onsager conjecture and intermittency. We reveal several new classes of solutions and prove rigidity properties in specific categories of genuinely 3D solutions. In particular, irrotational solutions are characterized by vanishing of the Bernoulli function, and tangential flows are necessarily 2D axisymmetric pure rotations. In several cases solutions are excluded altogether. The arguments reveal geodesic features of the Euler flow on the sphere. We further show that in the case when homogeneity corresponds to the Onsager-critical state, the anomalous energy flux at the singularity vanishes, which is suggestive of absence of extreme00-dimensional intermittencies in dissipative flows.
S2 from Equine infectious anemia virus is an infectivity factor which counteracts the retroviral inhibitors SERINC5 and SERINC3
Authors: Chande Ajit , Cuccurullo Cristiana , Rosa Annachiara , Ziglio Serena , Carpenter Susan , Pizzato Massimo
Published: July 2016

The lentivirus equine infectious anemia virus (EIAV) encodes S2, a pathogenic determinant important for virus replication and disease progression in horses. No molecular function has yet been linked to this accessory protein. We now report that S2 can replace the activity of Nef on HIV-1 infectivity, being required to antagonize the inhibitory activity of SERINC proteins on Nef-defective HIV-1. Similar to Nef, S2 excludes SERINC5 from virus particles and requires an ExxxLL motif predicted to recruit the clathrin adaptor AP2. Accordingly, a functional endocytic machinery is essential for S2-mediated infectivity enhancement, which is impaired by inhibitors of clathrin-mediated endocytosis. In addition to retargeting SERINC5 to a late endosomal compartment, S2 promotes the host factor degradation. Emphasizing the similarity with Nef, we show that S2 is myristoylated and, compatible with a crucial role of the post-translational modification, its N-terminal glycine is required for the anti-SERINC5 activity.

EIAV-derived vectors devoid of S2 are less susceptible than HIV-1 to the inhibitory effect of both human and equine SERINC5. We then identified the envelope glycoprotein of EIAV as a determinant which also modulates retrovirus susceptibility to SERINC5, indicating a bi-modular ability of the equine lentivirus to counteract the host factor.

S2 shares no sequence homology with other retroviral factors known to counteract SERINC5. Adding to primate lentivirus Nef and gammaretrovirus glycoGag, the accessory protein from EIAV makes another example of a retroviral virulence determinant which independently evolved SERINC5-antagonizing activity. SERINC5 therefore plays a critical role for the interaction of the host with diverse retrovirus pathogens.

Significance Statement

SERINC5 and SERINC3 are recently discovered cellular inhibitors of retroviruses, which are incorporated into virus particles and impair their ability to propagate the infection to target cells. Only two groups of viruses (represented by HIV-1 and MLV) have so far been identified to have evolved the ability of counteracting SERINC inhibition. We now discovered that Equine infectious anemia virus, which causes a debilitating disease in horses, also acquired the ability to protect the virus particle from inhibition by SERINC5 and SERINC3, using its small protein S2. The evidence that three different retroviruses have independently evolved the ability to elude inhibition bySERINC5 and SERINC3 indicates that these cellular factors play a fundamental role against various retrovirus pathogens.
Structure of Topologically Associating Domains and gene regulation embedded in the 5C data revealed by a polymer model and stochastic simulations
Authors: Shukron O. , Holcman D.
Published: July 2016

Chromatin organization is probed by chromosomal capture data, from which the encounter probability (EP) between genomic sites is represented in a large matrix. However, this matrix is obtained by averaging the EP over cell population, where diagonal blocks called TADs, contains hidden information about sub-chromatin organization. Our aim here is to elucidate the relationship between TADs structure and gene regulation. For this end, we reconstruct the chromatin dynamics from the EP matrix using polymer model and explore the transient properties, constrained by the statistics of the data. To construct the polymer, we use the EP decay in two steps: first, to account for TADs, we introduce random connectors inside a restricted region defining the TADs. Second, we account for long-range frequent specific genomic interactions in the polymer architecture. Finally, stochastic simulations show that only a small number of randomly placed connectors are required to reproduce the EP of TADs, and allow us to compute the mean first time and the conditional encounter probability of three key genomic sites to meet. These encounter times reveal how chromatin can self-regulate. The present polymer construction is generic and can be used to study steady-state and transient properties of chromatin constrained on 5C data.
Dispersal: a central and independent trait in life history
Authors: Bonte Dries , Dahirel Maxime
Published: July 2016

The study of trade-offs among major life history components (age at maturity, lifespan and reproduction) allowed the development of a quantitative framework to understand how environmental variation shapes patterns of biodiversity among and within species.

Because every environment is inherently spatially structured, and in most cases temporally variable, individuals need to move within and among habitats to maximize fitness. Dispersal is often assumed to be tightly integrated into life histories through genetic correlations with other vital traits. This assumption is particularly strong within the context of a fast-slow continuum of life-history variation. Such a framework is to date used to explain many aspects of population and community dynamics. Evidence for a consistent and context-independent integration of dispersal in life histories is, however, weak. We therefore advocate the explicit integration of dispersal into life history theory as a principal axis of variation influencing fitness, that is free to evolve, independently of other life history traits.

We synthesize theoretical and empirical evidence on the central role of dispersal and its evolutionary dynamics on the spatial distribution of ecological strategies and its impact on population spread, invasions and coexistence. By applying an optimality framework we show that the inclusion of dispersal as an independent dimension of life histories might substantially change our view on evolutionary trajectories in spatially structured environments.

Because changes in the spatial configuration of habitats affect the costs of movement and dispersal, adaptations to reduce these costs will increase phenotypic divergence among and within populations. We outline how this phenotypic heterogeneity is anticipated to further impact population and community dynamics.
Nkx2.1 regulates the proliferation and cell fate of telencephalic astrocytes during embryonic development
Authors: Minocha Shilpi , Valloton Delphine , Arsenijevic Yvan , Cardinaux Jean-René , Dreier Guidi Raffaella , Hornung Jean-Pierre , Lebrand Cécile
Published: July 2016

The homeodomain transcription factor Nkx2.1 controls cell differentiation of telencephalic GABAergic interneurons and oligodendrocytes. Here, we show that Nkx2.1 additionally regulates astrogliogenesis of the telencephalon from embryonic day (E) 14.5 to E16.5. Our work aims to identify the different mechanisms by which Nkx2.1 controls telencephalic astrogliogenesis. InNkx2.1-/-, a drastic loss of astrocytes is observed which is not related to cell death.In vivoanalysis using BrdU incorporation reveals that Nkx2.1 affects the proliferation of ventral neural stem cells that generate early astrocytes.In vitroneurosphere assays show that Nkx2.1 additionally affects the differentiation step of Nkx2.1-derived astrocytes. Chromatin immunoprecipitation andin vitroco-transfection studies of a Nkx2.1-expressing plasmid indicate that Nkx2.1 binds to the promoter of astroglial differentiation gene GFAP, and regulates its expression. Hence, Nkx2.1 controls astroglial production spatiotemporally in embryos by regulating stem cell division and specification of the contributing Nkx2.1+precursors.
Crystal structures of 2-[(4,6-diaminopyrimidin-2-yl)sulfanyl]-N-(3-nitrophenyl)acetamide monohydrate andN-(2-chlorophenyl)-2-[(4,6-diaminopyrimidin-2-yl)sulfanyl]acetamide
Authors: Subasri S. , Timiri Ajay Kumar , Barji Nayan Sinha , Jayaprakash Venkatesan , Vijayan Viswanathan , Velmurugan Devadasan
Published: July 2016

The title compounds, C12H12N6O3S·H2O, (I), and C12H12ClN5OS, (II), are 2-[(4,6-diaminopyrimidin-2-yl)sulfanyl]acetamides. Compound (I) crystallized as a monohydrate. In both compounds, the molecules have a folded conformation, with the pyrimidine ring being inclined to the benzene ring by 56.18 (6)° in (I) and by 67.84 (6)° in (II). In both molecules, there is an intramolecular N—H...N hydrogen bond stabilizing the folded conformation. In (I), there is also a C—H...O intramolecular short contact, and in (II) an intramolecular N—H...Cl hydrogen bond is present. In the crystal of (I), molecules are linked by a series of N—H...O, O—H...O and O—H...N hydrogen bonds, forming undulating sheets parallel to the (100). The sheets are linkedviaan N—H...Owaterhydrogen bond, forming a three-dimensional network. In the crystal of (II), molecules are linked by a series of N—H...O, N—H...N and C—H...O hydrogen bonds, forming slabs parallel to (001).
Crystal structure of bis[2,5-bis(pyridin-2-yl)-1,3,4-thiadiazole-κ2N2,N3]bis(thiocyanato-κS)copper(II)
Authors: Laachir Abdelhakim , Bentiss Fouad , Guesmi Salaheddine , Saadi Mohamed , El Ammari Lahcen
Published: July 2016

The mononuclear title complex, [Cu(SCN)2(C12H8N4S)2], was obtained by the reaction of 2,5-bis(pyridin-2-yl)-1,3,4-thiadiazole and potassium thiocyanate with copper(II) chloride dihydrate. The copper cation lies on an inversion centre and displays an elongated octahedral coordination geometry. The equatorial positions are occupied by the N atoms of two 2,5-bis(pyridin-2-yl)-1,3,4-thiadiazole ligands, whereas the axial positions are occupied by the S atoms of two thiocyanate anions. The thiadiazole and the pyridyl rings linked to the metal are approximately coplanar, with a maximum deviation from the mean plane of 0.190 (2) Å. The cohesion of the crystal structure is ensured by weak C—H...N hydrogen bonds and π–π interactions between parallel pyridyl rings of neighbouring molecules [centroid-to-centroid distance = 3.663 (2) Å], leading to a three-dimensional network.
Identifying the Interdependence Between Monetary Policy and Financial Stress: Evidence from China
Authors: Li Rong , Tian Xiaohui
Published: July 2016

We estimate the interdependence between Chinese monetary policy and financial stress using structural vector autoregression. To solve the simultaneity problem, we employ a strategy including both short‐run and long‐run restrictions that maintains the qualitative properties of monetary policy shocks derived from the literature. This method is applied to Chinese monthly data, together with a newly constructed index of financial stress in this paper. Our findings suggest there exists strong interdependence between monetary policy and financial stress. The financial stress index increases immediately by 0.4 of its standard deviation after a monetary policy shock that raises the M2 growth rate by 1 percentage point. An increase of financial stress by one standard deviation leads to a decline in the M2 growth rate by 2 percentage points.
Subterranean termite (Blattodea: Termitoidae) pests in metropolitan Brisbane, Australia, 1997–2006: patterns and implications
Authors: Peters Brenton C , Perkins Lynda E , Cochrane Gary H , Zalucki Myron P
Published: July 2016

The distribution and abundance of subterranean termites in Brisbane, Australia, has not previously been investigated, despite the sub‐tropical climate being favourable for these xylophagous insects which often cause damage to the built environment. Data on the incidence of termite infestations, including taxonomic identity, locality and site of infestation within premises were collected by a large commercial pest management company in metropolitan Brisbane during a ten‐year period (1997 – 2006). General Linear Models based on a negative binomial distribution were used to examine the influence of the climatic variables of rainfall and Southern Oscillation Index (SOI), and the demographic variables of premise density and socioeconomic status, on the number of termite infestations found. Two genera of termites dominated: Schedorhinotermes, which was the most abundant both indoors and outdoors, and Coptotermes. That Schedorhinotermes spp. were the major xylophagous subterranean termites recorded is unique in Australian capital cities where Coptotermes spp. usually dominate. The patterns of abundance and distribution of both genera are discussed with respect to their differing biology. SOI, premise density per ha and household income all significantly explained the variation in termite abundance reported across metropolitan Brisbane over the 10 year study. Our results shows the potential for using SOI as a predictor of termite activity. Further study is needed to more accurately correlate the key drivers of termite activity with the incidence of termite infestations in premises.
Rhinovirus‐specific antibody responses in preschool children with acute wheeze reflect severity of respiratory symptoms
Authors: Stenberg‐Hammar K. , Niespodziana K. , Söderhäll C. , James A. , Cabauatan C.R. , Konradsen J. R. , Melén E. , van Hage M. , Valenta R. , Hedlin G.
Published: July 2016

Background

Some children with rhinovirus (RV) infections wheeze, but it is unknown whether this is due to more virulent strains of virus or differences in host immune responses. The aim of this study was to investigate the RV species‐specific antibody responses measured at a follow‐up visit in preschool children in relation to reported time with respiratory symptoms and the presence of different RV species during an acute episode of wheeze.

Method

Nasopharyngeal swabs and blood samples were taken among 120 preschool children (<4 years of age) at an acute episode of wheeze and at a follow‐up visit (median 11 weeks later). Nested PCR was used to detect different RV strains, and serum levels of IgG1 against purified recombinant VP1 proteins from representatives of the three RV species (RV‐A, RV‐B, and RV‐C) were measured by ELISA.

Results

Rhinovirus was detected in 74% (n = 80/108) of the children at the acute visit, and RV‐C was the most common subtype (n = 59/80, 74%). An increase in RV‐specific IgG1 was seen in 61% (n = 73) of the children at follow‐up, most frequently against RV‐A (n = 61/73, 86%) irrespective of the RV strains detected by PCR. Increases in RV‐specific IgG1 against RV‐A or against RV‐A and RV‐C were significantly associated with more respiratory symptoms (p = 0.03, p = 0.007).

Conclusion

Antibody response to recombinant RV VP1 proteins was associated with longer time with respiratory symptoms.
HBsAg kinetics in chronic hepatitis D during interferon therapy: on‐treatment prediction of response
Authors: Niro G. A. , Smedile A. , Fontana R. , Olivero A. , Ciancio A. , Valvano M. R. , Pittaluga F. , Coppola N. , Wedemeyer H. , Zachou K. , Marrone A. , Fasano M. , Lotti G. , Andreone P. , Iacobellis A. , Andriulli A. , Rizzetto M.
Published: July 2016

Background

Therapy of chronic hepatitis D with Interferon is successful when testing for HDV‐RNA turns negative. This end‐point is disputed.

Aim

To assess the role of serum hepatitis B surface antigen (HBsAg) in the clearance of HDV‐RNA in pegylated interferon (Peg‐IFN)‐treated chronic hepatitis D (CHD).

Methods

Sixty‐two patients with CHD, treated with Peg‐IFN, were considered. The patients belonged to three groups: 14 patients cleared the HBsAg and HDV‐RNA (responders, R), 12 cleared the HDV‐RNA remaining positive for HBsAg (partial responders, PR) and 36 cleared neither the HBsAg nor the HDV‐RNA (nonresponders, NR).

Results

In responders, at baseline the median value (mv) of HBsAg and HDV‐RNA was 1187 and 188 663 IU/mL. By month 6 of therapy, HBsAg declined to less than 1000 IU/mL and HDV‐RNA was undetectable in 12 patients. In NR, the pre‐therapy median value of HBsAg and HDV viremia was 6577 and 676 319 IU/mL. There was no significant reduction of antigen at month 6; after a decline, HDV‐RNA rebounded to baseline levels. In PR, the median value of baseline HBsAg was 7031 IU/mL; it declined at month 6 in the majority. HDV‐RNA progressively declined from an initial median value of 171 405 IU/mL. HBsAg <1000 IU/mL at month 6 discriminated responders and PR from NR (P < 0.001). By ROC curve, the threshold of 0.105 log reduction of HBsAg associated with 1.610 log reduction of HDV‐RNA from baseline to month 6 predicted the clearance of this marker.

Conclusions

A reduction of serum HBsAg is mandatory for the definitive clearance of the HDV‐RNA. Quantitative HBsAg may predict the long‐term response to Peg‐IFN therapy and provide a guide to prolong or stop treatment.
Effect of long‐term adherence to clopidogrel on the VASP‐PRI after elective coronary stent implantation: a randomized controlled study
Authors: Forni Ogna Valentina , Menetrey Isabelle , Muller Olivier , Tousset Eric , Guihard Linda , Fontana Pierre , Eeckhout Eric , Eap Chin B. , Vrijens Bernard , Burnier Michel , Wuerzner Grégoire
Published: July 2016

Aims

The biological response to clopidogrel is highly variable and a poor responsiveness is associated with major adverse cardiac events. Adherence to therapy is a major cause of poor responsiveness but its impact on long‐term platelet inhibition is unknown. The objective of the present study was to evaluate the effect of different programmes monitoring adherence to clopidogrel on platelet reactivity.

Methods

The study took the form of a monocentric, parallel group, randomized controlled trial. Adults treated with clopidogrel 75 mg after elective coronary stenting were randomized into one of three groups: (i) a standard of care group; (ii) a standard of care + adherence electronic monitoring group, in which drug intake was recorded but kept blinded until the study end; or (iii) an integrated care group, with regular feedback on recorded adherence. Clopidogrel response was assessed with the vasodilator‐stimulated phosphoprotein–platelet reactivity index (VASP‐PRI) at randomization, 3 months and 6 months.

Results

A total of 123 adults were enrolled and randomized. Baseline VASP‐PRI was highly variable, with a mean of 48 ± 18.8%. No difference between groups in VASP‐PRI was found at 6 months (P = 0.761), despite better adherence to clopidogrel in the integrated care group. However, adherence (P = 0.035) and baseline VASP‐PRI (P = 0.015) were associated with VASP‐PRI at 3 months and 6 months. The association between adherence and VASP‐PRI was lost in patients with baseline VASP‐PRI > 50%. Diabetes, CYP2C19*2 carrier status and body mass index were significant predictors of VASP‐PRI.

Conclusions

The platelet response to clopidogrel during chronic therapy remained highly variable, despite high adherence. Different adherence monitoring programmes did not affect VASP‐PRI at 6 months. Poor adherence is associated with lower VASP‐PRI only in initial good responders to clopidogrel.
Dual institution experience of nodal marginal zone lymphoma reveals excellent long‐term outcomes in the rituximab era
Authors: Starr Adam G. , Caimi Paolo F. , Fu PingFu , Massoud Mira R. , Meyerson Howard , Hsi Eric D. , Mansur David B. , Cherian Sheen , Cooper Brenda W. , De Lima Marcos J. G. , Lazarus Hillard M. , Gerson Stanton L. , Jagadeesh Deepa , Smith Mitchell R. , Dean Robert M. , Pohlman Brad L. , Hill Brian T. , William Basem M.
Published: July 2016

Nodal marginal zone lymphoma (NMZL) is a rare non‐Hodgkin lymphoma that arises from mature B‐cells. We delineate outcomes, prognostic factors and treatment trends among a large cohort of patients withNMZLin the rituximab era. We identified 56 such patients treated at our institutions. The majority presented with advanced stage disease (78·6%). Over a median follow‐up of 38·2 months, median progression‐free survival (PFS) was 42·4 months and median overall survival (OS) was not reached. Kaplan–Meier estimates ofOSat 120 months after diagnosis was 71·9%. High‐risk follicular lymphoma international prognostic index (FLIPI) was associated with inferiorPFS. Age >60 years and elevated serum lactate dehydrogenase (LDH) were associated with inferiorOS. Transformation to diffuse large B‐cell lymphoma occurred in 7 patients, 6 of who presented with advanced disease.OSwas comparable to our previously reported extranodalMZLcohort.FLIPIscore predicted for inferiorPFSandOSwhen both cohorts were analysed together (n = 267). In summary, outcomes inNMZLare favourable with a large majority of patients surviving at 120 months. High riskFLIPI, age >60 years, and elevated serumLDHwere associated with inferior outcomes.
A phase II trial of bendamustine in combination with rituximab in older patients with previously untreated diffuse large B‐cell lymphoma
Authors: Park Steven I. , Grover Natalie S. , Olajide Oludamilola , Asch Adam S. , Wall James G. , Richards Kristy L. , Sobol Anna L. , Deal Allison M. , Ivanova Anastasia , Foster Matthew C. , Muss Hyman B. , Shea Thomas C.
Published: July 2016

Bendamustine in combination with rituximab (BR) has been associated with high response rates and acceptable toxicity in older patients with relapsed/refractory diffuse large B‐cell lymphoma (DLBCL). Evaluation of BR is warranted in the front‐line setting for DLBCL patients not eligible for anthracyclines or for the elderly. In this phase II study, we enrolled DLBCL patients aged ≥65 years who were poor candidates for R‐CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) to determine the efficacy and safety of BR in previously untreated stage II–IV DLBCL. Twenty‐three patients were enrolled with a median age of 80 years. 52% of patients presented with poor functional status (Eastern Cooperative Oncology Group performance score of ≥2). The overall response rate was 78% with 12 complete responses (52%). At a median follow up of 29 months, the median overall survival was 10·2 months and the median progression‐free survival was 5·4 months. The most common grade 3/4 adverse events were haematological. Combination therapy with BR demonstrates high response rates as front‐line therapy in frail older patients with DLBCL, but survival rates were low. BR should be used with caution in future clinical trials involving older DLBCL patients with poor functional status.
Endocytosis of exogenous factor V by ex‐vivo differentiated megakaryocytes from patients with severe parahaemophilia
Authors: Radu Claudia M. , Spiezia Luca , Bulato Cristiana , Gavasso Sabrina , Campello Elena , Sartorello Francesca , Castoldi Elisabetta , Simioni Paolo
Published: July 2016

Although human megakaryocytes can synthesize factor V (FV), platelet FV derives largely from endocytosis of plasma FV. Recently, it has been shown that plasma transfusions can replenish the platelet FV pool in parahaemophilic patients. Here we corroborate this finding by showing FV endocytosis by ex vivo differentiated megakaryocytes derived from patients with inherited parahaemophilia. Mononuclear stem cells isolated from peripheral blood of healthy subjects and of three patients with severe parahaemophilia were cultured in the presence of thrombopoietin and interleukin‐3 and differentiated into CD41‐positive polynucleated megakaryocytes. Exogenous purified FV was added to the culture medium to evaluate FV endocytosis. Immunofluorescence staining revealed abundant FV expression in megakaryocytes derived from healthy donors, but no FV expression in those derived from patients with severe parahaemophilia. However, after the addition of purified FV to the culture medium, megakaryocytes from parahaemophilia patients became positive upon FV immunostaining, suggesting endocytosis of exogenous FV. Endocytosed FV retained factor Xa‐co‐factor activity as assessed by a prothrombin time‐based functional test in megakaryocyte lysates. Addition of exogenous FV to culture medium can restore the FV content of megakaryocytes derived from patients with severe FV defects. This rescue mechanism can have important clinical implications in the management of parahaemophilia patients.
Recombinant IL‐7/HGFβ hybrid cytokine separates acute graft‐versus‐host‐disease from graft‐versus‐tumour activity by altering donor T cell trafficking
Authors: Hu Rong , Liu Yalan , Song Yinhong , Su Min , Lu Xiuling , Rood Debra , Lai Laijun
Published: July 2016

Given that donor T cells from a transplant contribute both the desired graft‐versus‐tumour (GVT) effect and detrimental graft‐versus‐host disease (GVHD), strategies to separate GVHD and GVT activity are a major clinical goal. We have previously demonstrated that in vivo administration of a recombinant (r)IL‐7/HGFβ hybrid cytokine, consisting of interleukin‐7 (IL‐7, IL7) and the β‐chain of hepatocyte growth factor (HGFβ), significantly inhibits the growth of cancer cells in murine tumour models. The antit‐umour effect of rIL‐7/HGFβ is related to a marked infiltration T cells in the tumour tissues. We have also shown that GVHD was not induced in rIL‐7/HGFβ‐treated T cell‐depleted allogeneic haematopoietic stem cell transplantation (HSCT) recipients. We show here that, in T cell‐replete allogeneic HSCT murine models, rIL‐7/HGFβ attenuated acute GVHD (aGVHD), while promoting GVT activity. This was related to an alteration of donor T cell trafficking, with an increased infiltration of donor T cells into tumour tissues and the lympho‐haematopoietic system but decreased number of the T cells in the GVHD target organs. Therefore, rIL‐7/HGFβ may offer a new tool to alleviate aGVHD while prompting GVT, and to study the molecular regulation of T cell trafficking.
Application of an NGS‐based 28‐gene panel in myeloproliferative neoplasms reveals distinct mutation patterns in essential thrombocythaemia, primary myelofibrosis and polycythaemia vera
Authors: Delic Sabit , Rose Dominic , Kern Wolfgang , Nadarajah Niroshan , Haferlach Claudia , Haferlach Torsten , Meggendorfer Manja
Published: July 2016

Molecular routine diagnostics for BCR‐ABL1‐negative myeloproliferative neoplasms (MPN) currently focusses on mutations in JAK2, CALR and MPL. In recent years, recurrent mutations in MPNs have been identified in several other genes. We here present the validation of a next generation sequencing (NGS)‐based 28‐gene panel and its use in MPN. We analysed the mutation status of 28 genes in 100 MPN patients [40 essential thrombocythaemia (ET), 30 primary myelofibrosis (PMF), 30 polycythaemia vera (PV)] and found two or more mutated genes in 53 patients. Moreover, significantly more mutated splicing genes (SF3B1, SRSF2 and U2AF1) were present in PMF (0·60 mutated genes/patient) compared to ET (0·15) while no mutations in splicing genes were found in PV. Additionally, chromatin modification genes (ASXL1 and EZH2) were frequently mutated in PMF patients (0·50) and, to a significantly lesser extent, in ET (0·13) and PV (0·07). Contrarily, DNA methylation genes (DNMT3A, IDH1, IDH2 and TET2) were mutated most often in PV (0·5) and less frequently in ET (0·23) and PMF (0·20), but without reaching statistical significance. Our results demonstrate the feasibility and utility of NGS‐based panel diagnostics for MPN. With 53% of the patients bearing two or more mutated genes, their prognostic relevance needs further studies.
Randomized controlled study of the efficacy and safety of continuous saline bladder irrigation after transurethral resection for the treatment of non‐muscle‐invasive bladder cancer
Authors: Onishi Takehisa , Sugino Yusuke , Shibahara Takuji , Masui Satoru , Yabana Tadashi , Sasaki Takeshi
Published: July 2016

Objective

To evaluate the efficacy and safety of continuous saline bladder irrigation (CSBI) after transurethral resection of bladder tumour (TURBT) in patients with low‐ to intermediate‐risk non‐muscle invasive bladder cancer (NMIBC).

Patients and Methods

In this prospective randomized study, 250 patients with primary low‐ to intermediate‐risk tumours were enrolled. Patients were randomly allocated to receive CSBI (2 000 mL/h for the first 1 h, then 1 000 mL/h for 2 h, followed by 500 mL/h for 15 h) or a single immediate instillation of mitomycin C (MMC) after TURBT. The primary endpoint was recurrence‐free survival, and secondary endpoints were progression‐free survival and adverse events.

Results

A total of 227 patients (114 in the CSBI group and 113 in MMC group) remained for analysis after exclusion criteria had been applied. The median follow‐up period was 37 months. No significant differences in patient characteristics were observed between the groups. The 5‐year recurrence‐free rates for CSBI and MMC were 62.6% (95% confidence interval [CI] 0.49–0.73) and 70.4% (95% CI 0.59–0.78), respectively. Kaplan–Meier analysis of recurrence‐free survival did not show any significant differences between the groups (log‐rank test P = 0.53). Furthermore, there were no significant differences between the groups in terms of tumour progression rate and the median time to first recurrence. The incidence of adverse events was significantly lower in the CSBI group.

Conclusions

The results show that CSBI after TURBT may be a treatment option for patients with low‐ to intermediate‐risk NMIBC in terms of its prophylactic effect and safety.
Sunbird hovering behavior is determined by both the forager and resource plant
Authors: Padyšáková Eliška , Janeček Štěpán
Published: July 2016

The long‐standing paradigm that pollination systems adapted to hovering birds evolved only in the New World was recently challenged by the discovery of hovering pollination by Old World specialized passerine pollinators. This raises the possibility that hovering pollination may evolve more easily than previously believed, given sufficient selective pressure on plant traits, on nectarivory, or both. We observed foraging behavior by the sunbird Cyanomitra oritis at flowers of the native Old World plant Impatiens sakeriana. We measured the length of pedicels and peduncles (PedPed length), which can make the flowers difficult to reach while the bird perches on the stem, and determined if it influenced sunbird hovering or perching at a flower. Detailed analyses of video recordings showed that sunbirds only hovered at flowers with a long PedPed, whereas they employed both foraging modes when an adequate perch was available. A hovering sunbird could deplete nectar in a shorter time than a perching one. The frequency of visits was not greater at flowers with longer PedPed or with more open I. sakeriana flowers in the vicinity. Our study provides evidence that sunbird behavior does not follow simple energetic models, and that some sunbird pollination systems in the Old World resemble highly specialized hummingbird systems in the New World much more than expected, especially the overall adaptation of the system to bird hovering.
Clinical outcome of norovirus infection in renal transplant patients
Authors: Brakemeier Susanne , Taxeidi Styliani I. , Dürr Michael , Hofmann Jörg , Schmidt Danilo , Bachmann Friederike , Gaedeke Jens , Budde Klemens
Published: July 2016

Transplant patients are at increased risk for developing severe norovirus (NoV) infections with secondary complications such as rejection episodes and acute transplant failure.

This single‐center retrospective study included all kidney transplant patients tested positive for NoV RNA between January 2007 and December 2011. Data were compared to a control group of 528 kidney transplant patients without NoV infection.

Sixty‐five kidney transplant patients were recorded NoV RNA positive. Of these, 26 patients (40%) presented with acute transplant failure (AKI). In 43 patients (66.2%), dose reduction in immunosuppression was performed, and of 22 patients receiving tacrolimus, four patients (18.2%) showed toxic trough levels above 15 ng/mL at time of diagnosis. In three patients (4.6%), indicated therapeutic procedures had to be postponed due to prolonged severe diarrhea. Ten patients (15.4%) developed chronic NoV infection. One‐year patient and graft survival in NoV patients and controls was 92.3% and 96.4%, respectively (n.s.).

Compared to controls, eGFR was already significantly lower before NoV infection and loss of eGFR relative to baseline over 12 and 36 months was significantly higher in NoV‐infected patients. In particular, patients initially presenting with AKI experienced a long‐term loss of transplant function. Risk factors for NoV infection were immunosuppression containing steroids and antirejection therapy.
Lung transplantation following death by drowning: a review of the current literature
Authors: Pasupneti Shravani , Patel Kapil , Mooney Joshua J. , Chhatwani Laveena , Dhillon Gundeep , Weill David
Published: July 2016

While multiple donor characteristics have been cited as ideal for lung transplantation, there are minimal widely accepted exclusion criteria. One criterion that many centers view with hesitation is death by drowning. However, recent literature suggests such donors may result in acceptable outcomes following transplantation. This review highlights a case of a patient who underwent a successful bilateral lung transplant from a donor following a drowning event. A review of the current literature is presented, concluding with a new proposed set of favorable donor criteria following death by drowning.
The occurrence of Tubakia dryina in Poland – new hosts and ITS variation
Authors: Boroń P. , Grad B.
Published: July 2016

This study describes a preliminary investigation of the occurrence of Tubakia dryina in Poland, based on fungal isolations from symptomless leaves and from necrotic areas of leaf blades of Quercus robur, Fagus sylvatica and Tilia cordata. Occurrence of T. dryina on leaves of the two latter species is reported for the first time. Frequency of incidence on different hosts varied between tree species, with the highest rate on oaks and the lowest on linden. The results also suggest the ubiquitous occurrence of T. dryina on oaks in Poland. This situation is in contrast to previous observations showing much lower frequency of this fungus in the past. A preliminary, ITS‐based, analysis of genetic diversity among Polish isolates of T. dryina revealed the presence of two distinct haplotypes, both of which are widespread in Poland and occur on the same trees in most locations. No further genetic diversity was observed within either detected lineages using ITS analyses.
Rapid diagnosis of pathogenic Phytophthora species in soil by real‐time PCR
Authors: Nowakowska J. A. , Malewski T. , Tereba A. , Oszako T.
Published: July 2016

Real‐time PCR assays based on the TaqMan system and using ITS sequences were developed for the identification of Phytophthora species, including P. cactorum, P. megasperma, P. plurivora, P. pseudosyringae and P. quercina, all of which are currently causing significant damage to roots of forest trees in both managed stands and natural ecosystems. Total genomic DNA was extracted from mycelia of aforementioned Phytophthora isolates. Species‐specific primers for P. cactorum, P. megasperma, P. plurivora, P. pseudosyringae and P. quercina were designed based on ITS sequences of rDNA. The amplification efficiency of target DNA varied from 93.1% (P. pseudosyringae) to 106.8% (P. quercina). The limit of the detection was calculated as 100 – 1,000 fg DNA, depending on the Phytophthora species. In mixed soil samples, all Phytophthora species were detected for Ct values shifted by 0.7 – 2.1 cycles. Based on these real‐time PCR assays we were able to identify the five Phytophthora species. These techniques will be of value in the identification of these pathogens, which may cause up to 80 – 90% fine root loss in oak stands.
Constipation: an emerging risk factor for Parkinson's disease?
Authors: Stirpe P. , Hoffman M. , Badiali D. , Colosimo C.
Published: July 2016

Constipation is the most prominent and disabling manifestation of lower gastrointestinal (GI) dysfunction in Parkinson's disease (PD). The prevalence of constipation in PD patients ranges from 24.6% to 63%; this variability is due to the different criteria used to define constipation and to the type of population enrolled in the studies. In addition, constipation may play an active role in the pathophysiological changes that underlie motor fluctuations in advanced PD through its negative effects on absorption of levodopa. Several clinical studies now consistently suggest that constipation may precede the first occurrence of classical motor features in PD. Studies in vivo, using biopsies of the GI tract and more recently functional imaging investigations, showed the presence of α‐synuclein (α‐SYN) aggregates and neurotransmitter alterations in enteric tissues. All these findings support the Braak proposed model for the pathophysiology of α‐SYN aggregates in PD, with early pathological involvement of the enteric nervous system and dorsal motor nucleus of the vagus. Therefore, constipation could have the potential sensitivity to be used as a clinical biomarker of the prodromal phase of the disease. The use of colonic biopsies to look at α‐SYN pathology, once confirmed by larger prospective studies, might eventually represent a feasible, albeit partially invasive, new diagnostic biomarker for PD.
Navigating Critical Theory and Postmodernism: Social Justice and Therapist Power in Family Therapy
Authors: D'Arrigo‐Patrick Justine , Hoff Chris , Knudson‐Martin Carmen , Tuttle Amy
Published: July 2016

The family therapy field encourages commitment to diversity and social justice, but offers varying ideas about how to attentively consider these issues. Critical informed models advocate activism, whereas postmodern informed models encourage multiple perspectives. It is often not clear how activism and an emphasis on multiple perspectives connect, engendering the sense that critical and postmodern practices may be disparate. To understand how therapists negotiate these perspectives in practice, this qualitative grounded theory analysis drew on interviews with 11 therapists, each known for their work from both critical and postmodern perspectives. We found that these therapists generally engage in a set of shared constructionist practices while also demonstrating two distinct forms of activism: activism through countering and activism through collaborating. Ultimately, decisions made about how to navigate critical and postmodern influences were connected to how therapists viewed ethics and the ways they were comfortable using their therapeutic power. The findings illustrate practice strategies through which therapists apply each approach.
Systematic review of the Kihon Checklist: Is it a reliable assessment of frailty?
Authors: Sewo Sampaio Priscila Yukari , Sampaio Ricardo Aurélio Carvalho , Yamada Minoru , Arai Hidenori
Published: July 2016

Aim

To investigate whether the Kihon Checklist (KCL) can predict frailty and disability.

Methods

The studies analyzed for the present review were retrieved by searching electronic databases and other sources using the keywords “Kihon Checklist” and “Basic Checklist.” The articles were restricted to those written in English and published in health sciences journals from the year 2006 until the end of April 2015. To be included in the full analysis, the study had to be primary research and use the KCL as a dependent or independent variable.

Results

A total of 62 articles were identified in the initial search, and after screening, 13 articles were included in this review. The KCL was found to be closely correlated with validated assessments of frailty phenotypes. The complete version of the KCL and specific domains have been used as research outcomes to verify frailty in cross‐sectional and longitudinal studies. KCL domains were applied to evaluate different outcomes, such as depressive mood, functional disability and instrumental activities of daily living limitations.

Conclusions

The KCL is a reliable tool for predicting general frailty and frailty aspects in older adults. The KCL was shown to be adequate for cross‐cultural studies and to be suitable for addressing frailty demands among elderly in multiple cohorts. The KCL is a short questionnaire, which makes its administration by health promoters easy; thus, it has been used to evaluate the effectiveness of frailty interventions. We strongly recommend use of the KCL in community and clinical practice to assess frailty status. Geriatr Gerontol Int 2016; 16: 893‐902.
Identification and functional characterisation of bioactive peptides in rice bran albumin hydrolysates
Authors: Uraipong Chatchaporn , Zhao Jian
Published: July 2016

The potential heath‐benefitting bioactivities of rice bran albumin hydrolysates were investigated. The antioxidant and α‐glucosidase‐ and angiotensin‐converting enzyme (ACE)‐inhibitory activities of the crude hydrolysates and their fractions were determined. The fractions with the highest bioactivities were analysed by liquid chromatography–tandem mass spectrometry/mass spectrometry to identify the active peptide sequences. Hydrolysates produced by commercial proteases Alcalase and Protamax exhibited the highest α‐glucosidase‐ and ACE‐inhibitory activities, resulting in 43.1 ± 2.1% and 54.4 ± 5.1% inhibition of the enzymes, respectively. Inhibitory activities against both enzymes were highest in the MW<3‐kDa fractions that were eluted under alkaline conditions. A number of peptide sequences were identified in the fractions, which contained several sequences with reported α‐glucosidase‐ or ACE‐inhibitory activities. This is the first time that such activities are reported for rice bran albumin hydrolysate, and it demonstrated that the hydrolysates may be developed into nutraceuticals useful in managing diabetics and hypertension.
Increased expression of TACI on NOD B cells results in germinal centre reaction anomalies, enhanced plasma cell differentiation and immunoglobulin production
Authors: Banday Viqar S. , Thyagarajan Radha , Sundström Mia , Lejon Kristina
Published: July 2016

B cells have an important pathogenic role in the development of type 1 diabetes in the non‐obese diabetic (NOD) mouse. We have previously reported that NOD mice display an increased percentage of TACIhigh‐expressing B cells compared with C57BL/6 mice and this trait is linked to chromosomes 1 and 8. In this paper the genetic association of the transmembrane activator, calcium modulator and cyclophilin ligand interactor (TACI) trait was confirmed using double congenic NOD.B6C1/Idd22 mice. TACI ligation by a proliferation‐inducing ligand (APRIL) has been shown to influence plasma cell differentiation, immunoglobulin production and isotype switch. Hence, the functional consequence of the up‐regulation of TACI on NOD B cells was analysed both in vitro and in vivo. NOD B cells stimulated with APRIL showed an enhanced plasma cell differentiation and class switch to IgG and IgA compared with B cells from C57BL/6 mice. Moreover, flow cytometry analyses revealed that germinal centre B cells in NOD failed to down‐regulate TACI. Availability of the TACI ligand B‐cell activating factor (BAFF) has been shown to be a limiting factor in the germinal centre reaction. In line with this, upon immunization with 4‐hydroxy‐3‐nitrophenylacetyl hapten‐conjugated hen egg lysozyme, NOD mice produced higher titres of low‐affinity antibodies compared with C57BL/6 mice. This observation was supported by the detection of increased levels of BAFF in NOD germinal centres after immunization compared with C57BL/6 by immunofluorescence. Our results support the hypothesis that increased TACI expression on NOD B cells contributes to the pathogenesis of type 1 diabetes in the NOD mouse.
Statistical Scale Space Methods
Authors: Holmström Lasse , Pasanen Leena
Published: July 2016

The goal of statistical scale space analysis is to extract scale‐dependent features from noisy data. The data could be for example an observed time series or digital image in which case features in either different temporal or spatial scales would be sought. Since the 1990s, a number of statistical approaches to scale space analysis have been developed, most of them using smoothing to capture scales in the data, but other interpretations of scale have also been proposed. We review the various statistical scale space methods proposed and mention some of their applications.