bluuebunny/crossref_metadata_2025 huggingface dataset:
Changing US extreme temperature statistics
Authors: Finkel J. M. , Katz J. I.
Published: May 2017

ABSTRACT

The rise in global mean temperature is an incomplete description of warming. For many purposes, including agriculture and human life, temperature extremes may be more important than temperature means and changes in local extremes may be more important than mean global changes. We define a non‐parametric statistic to describe extreme temperature behaviour by quantifying the frequency of local daily all‐time highs and lows, normalized by their frequency in the null hypothesis of no climate change. We average this metric over 1218 weather stations in the 48 contiguous United States. In the period 1893–2014 there were statistically significantly fewer all‐time record lows than would be found in the null hypothesis of unchanging climate. Record highs, by contrast, do not statistically significantly differ from the null hypothesis. The metric is evaluated by Monte Carlo simulation for stationary and warming temperature distributions, permitting description of the statistics of historic temperature records by equivalent warming rates.
Modulating the oxidative environment during mesenchymal stem cells chondrogenesis with serum increases collagen accumulation in agarose culture
Authors: Tangtrongsup Suwimol , Kisiday John D.
Published: May 2017

Chondrogenesis of mesenchymal stem cells (MSCs) is induced in culture conditions that have been associated with oxidative stress, although the extent to which the oxidative environment affects differentiation and extracellular matrix (ECM) accumulation is not known. The objectives of this study were to evaluate the oxidative environment during MSCs chondrogenesis in conventional serum‐free medium, and the effect of serum‐supplementation on intracellular reactive oxygen species (ROS) and chondrogenesis. Young adult equine MSCs were seeded into agarose and cultured in chondrogenic medium, with or without 5% fetal bovine serum (FBS), for up to 15 days. Samples were evaluated for intracellular ROS, the antioxidant glutathione, ECM and gene expression measures of chondrogenesis, and carbonylation as an indicator of oxidative damage. Intracellular ROS increased with time in culture, and was lower in medium supplemented with FBS. Glutathione decreased ∼12‐fold during early chondrogenesis (p < 0.0001), and was not affected by FBS (p = 0.25). After 15 days of culture, FBS supplementation increased hydroxyproline accumulation ∼80% (p = 0.0002); otherwise, measures of chondrogenesis were largely unaffected. Protein carbonylation in chondrogenic MSCs cultures was not significantly different between serum‐free and FBS cultures (p = 0.72). Supplementation with adult equine serum increased hydroxyproline accumulation by 45% over serum‐free culture (p = 0.0006). In conclusion, this study characterized changes in the oxidative environment during MSC chondrogenesis, and suggested that lowering ROS may be an effective approach to increase collagen accumulation. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:506–514, 2018.
Raman spectroscopy and theoretic study of hyperpolarizability effect in diiodobutenyl‐bis‐thioquinolinium triiodide at low temperature
Authors: Yushina I. D. , Batalov V. I. , Bartashevich E. V. , Davydov A. O. , Zelenovskiy P. S. , Masunov A. E.
Published: May 2017

Various structural features, such as proton disorder or noncovalent interactions, determine the existence of switchable nonlinear optical properties under varying external conditions. Thus, for the single crystal of diiodobutenyl‐bis‐thioquinolinium triiodide with the bridge hydrogen atom, previously characterized under ambient conditions by C2/c symmetry, we have measured Raman spectra in the temperature range from 298 K down to 113 K. Variations in low‐wavenumber region of Raman spectra at temperatures below 153 K have been attributed to the change of the bridge hydrogen atom position in the [NHN]+ fragment, thus lowering the crystal symmetry from C2/c to Cc. Quantum chemical calculations in the solid state for noncentrosymmetric Cc structure predict high hyperpolarizability and second‐order electric susceptibilities, comparable to those of modern nonlinear optical materials. This indicates the emergence of nonlinear optical properties in the low‐temperature phase of the studied crystal. Copyright © 2017 John Wiley & Sons, Ltd.
Time‐resolved Raman spectroscopy of polystyrene under laser driven shock compression
Authors: Rastogi Vinay , Chaurasia S. , Rao Usha , Sijoy C. D. , Mishra V. , Kumar Manmohan , Chaturvedi S. , Deo M. N.
Published: May 2017

The microscopic and dynamic response of the atactic polystyrene molecules under shock compression at laser power density of 4.9 GW/cm2 was studied using time‐resolved Raman spectroscopy. The shock pressure estimated in the polystyrene sample was 2 GPa, and the temporal and wavenumber resolutions in these experiments were 3 ns and 3 cm−1, respectively. The shocked polystyrene showed a blue shift of 5 and 7 cm−1 for the 1004 cm−1 (C―C―C ring bending mode ν12) and 1606 cm−1 (C―C ring stretching mode
. , respectively. The changes in ν12 and
modes are observed with respect to shock wave propagation. It is observed that the intensities of the Raman peaks decrease and the FWHM of the modes increase due to formation of additional new peaks with delay. The reason behind this indicates the mechanical processes associated with the uniaxial nature of the shock compression. The shock velocity inside the polystyrene was calculated as 2.9±0.12 km/s using the evolution of intensity ratio of peaks with time. This is in good agreement with the shock velocity (3.0 km/s) deduced from the 2D simulations, performed using three temperature radiation hydrodynamic code, THRD. Copyright © 2017 John Wiley & Sons, Ltd.
Skin reactions after photodynamic therapy are unaffected by 839 nm photobiomodulation therapy: A randomized, double‐blind, placebo‐controlled, clinical trial
Authors: Bay Christiane , Vissing Anne‐Cathrine , Thaysen‐Petersen Daniel , Lerche Catharina Margrethe , Togsverd‐Bo Katrine , Heydenreich Jakob , Haedersdal Merete
Published: May 2017

Background and Objective

Photodynamic therapy (PDT) is associated with erythema and edema. Photobiomodulation (PBM) therapy may stimulate the skin recovery process. We investigated the potential of PBM to reduce PDT‐induced skin reactions.

Study Design and Methods

Healthy volunteers (n = 20) were randomized to receive left‐ or right side PBM (near‐infrared 839/595 nm) or placebo‐PBM (595 nm) on their buttocks. Corresponding test areas were exposed to standardized PDT reactions, using ablative fractional laser‐assisted PDT (AFXL‐PDT) with methyl‐aminolevulinate (MAL) incubated for 30, 90, and 180 minutes before red‐light illumination. Each buttock received PBM and placebo‐PBM for five consecutive days, starting one day before PDT interventions. Follow‐up visits were performed 4 and 11 days after PDT. Outcome measure included blinded, observer‐assessed skin reactions, substantiated by objectively measured erythema and pigment percentages and skin temperatures.

Results

PDT interventions induced a standardized range of erythema and edema in all subjects. Skin reactions were clinically unaffected by PBM throughout the active treatment period and at all subsequent follow‐up visits (PBM vs. placebo‐PBM, P = 1.000). Clinical results were supported by similar erythema intensities and skin temperatures in PBM and placebo‐PBM treated skin: median erythema 28.1% versus 30.3% (AFXL‐PDT with 30 minutes MAL‐incubation), 36.1% versus 35.2% (90 minutes MAL‐incubation) and 39.4% versus 40.9% (180 minutes MAL‐incubation) (Day 4, P > 0.05). No differences in clinical hyperpigmentation or pigment percentages were observed between corresponding test areas in any subject on the final 11‐day follow‐up.

Conclusion

Under the current study conditions, PDT‐induced skin reactions were unaffected by PBM. Lasers Surg. Med. 49:810–818, 2017. © 2017 Wiley Periodicals, Inc.
Long‐term polarisation and immersion for copper corrosion in high‐level nuclear waste environment
Authors: Kong D. C. , Dong C. F. , Ni X. Q. , Xu A. N. , He C. , Xiao K. , Li X. G.
Published: May 2017

Long‐term polarisation and immersion for copper corrosion were investigated in chloride‐containing sulphide solutions. Results showed that no active state exists for copper in sulphide‐containing solutions, whereas a typical active‐to‐passive transition exists in the second passivation region, indicating a hydroxyl activation effect on copper. After the sulphide passive film broke down, the pitting area was re‐passivated by hydroxide ions; however, if the chloride and sulphide concentrations were both high, then there was no second passivation and the copper would dissolve rapidly. The corrosion resistance and the film thickness both increased with increasing immersion time and an average corrosion rate of 51.2 µm/year was obtained in aerobic solution, which was much higher than in bentonite or under deoxygenated conditions. Moreover, several local corrosion pits appeared after 1‐year immersion and this would occur at the beginning of storage.
Fast computation of full density matrix of multispin systems for spatially localizedin vivomagnetic resonance spectroscopy
Authors: Zhang Yan , An Li , Shen Jun
Published: May 2017

Purpose

Numerical simulations of three‐dimensionally localizedMRSspectra have been very time consuming for multispin systems because the current state‐of‐the‐art method requires computation of a large ensemble of spins pixel‐by‐pixel in three dimensional space. This paper describes a highly accelerated technique for computing spatially localizedMRSspectra using the full solution to the Liouville–von Neumann equation.

Methods

The time evolution of spatially localized multispin density matrix as the full solution to the Liouville–von Neumann equation was analyzed. A new technique based on one dimensional spatial projection of the full density matrix was proposed. This method was implemented using a computer program written in Java language.

Results

TheMRSspectra calculated using the new method were found to be identical to conventional three‐dimensional simulation for the same digitization of the voxel while the new method reduced computation time by orders of magnitude and led to not only improved speed but also accuracy. Applications of the new method to phantom studies of multispin systems and quantification ofin vivoMRSspectra of brain were demonstrated.

Conclusion

The dramatically enhanced computational efficiency makes accurate simulation of localizedMRSspectra highly accessible for calculating basis sets for spectral quantification and for optimizing pulse sequences.
Measurement of glycine in healthy and tumorous brain by triple‐refocusing MRS at 3 T in vivo
Authors: Tiwari Vivek , An Zhongxu , Ganji Sandeep K. , Baxter Jeannie , Patel Toral R. , Pan Edward , Mickey Bruce E. , Maher Elizabeth A. , Pinho Marco C. , Choi Changho
Published: May 2017

Glycine (Gly) has been implicated in several neurological disorders, including malignant brain tumors. The precise measurement of Gly is challenging largely as a result of the spectral overlap with myo‐inositol (mI). We report a new triple‐refocusing sequence for the reliable co‐detection of Gly and mI at 3 T and for the evaluation of Gly in healthy and tumorous brain. The sequence parameters were optimized with density‐matrix simulations and phantom validation. With a total TE of 134 ms, the sequence gave complete suppression of the mI signal between 3.5 and 3.6 ppm and, consequently, well‐defined Gly (3.55 ppm) and mI (3.64 ppm) peaks. In vivo 1H magnetic resonance spectroscopy (MRS) data were acquired from the gray matter (GM)‐dominant medial occipital and white matter (WM)‐dominant left parietal regions in six healthy subjects, and analyzed with LCModel using in‐house‐calculated basis spectra. Tissue segmentation was performed to obtain the GM and WM contents within the MRS voxels. Metabolites were quantified with reference to GM‐rich medial occipital total creatine at 8 mM. The Gly and mI concentrations were estimated to be 0.63 ± 0.05 and 8.6 ± 0.6 mM for the medial occipital and 0.34 ± 0.05 and 5.3 ± 0.8 mM for the left parietal regions, respectively. From linear regression of the metabolite estimates versus fractional GM content, the concentration ratios between pure GM and pure WM were estimated to be 2.6 and 2.1 for Gly and mI, respectively. Clinical application of the optimized sequence was performed in four subjects with brain tumor. The Gly levels in tumors were higher than those of healthy brain. Gly elevation was more extensive in a post‐contrast enhancing region than in a non‐enhancing region. The data indicate that the optimized triple‐refocusing sequence may provide reliable co‐detection of Gly and mI, and alterations of Gly in brain tumors can be precisely evaluated.
Dental Scratches and Handedness in East Asian Early Pleistocene Hominins
Authors: Xing S. , O'Hara M. , Guatelli‐Steinberg D. , Ge J. , Liu W.
Published: May 2017

The current study aims to characterise dental scratches found on an East Asian hominin upper left central incisor (I1) and lower left lateral incisor (I2) from the Early Pleistocene (Meipu site, Yunxian County), and infer the preference for handedness of these two individuals by quantifying the orientation of dental scratches. The labial surfaces of these two teeth were observed and imaged using light microscopes and/or scanning electron microscope under different magnifications (5–70×). The angle, width and length of each dental scratch was measured and analysed. The dental scratches described and quantified on the labial enamel surface of Meipu I1 and I2 fit the description of cutmarks caused by ‘stuff and cut’ behaviour. Most scratches are oriented in the right oblique direction, averaging 47.11 degrees in I1 and 44.60 degrees in I2. This result indicates preference for the right hand as the dominant one in holding a tool during ‘stuff and cut’ behaviours. This is the earliest reported ‘stuff and cut’ behaviour and inferred right‐handedness in East Asia. It fills a temporal gap between the earliest known example in the African Early Pleistocene (~1.8 Ma) and the next known instance in the European Middle Pleistocene. This is also the first time the ‘stuff and cut’ behaviour and right‐handedness has been reported in a hominin assigned to Homo erectus sensu lato. Copyright © 2017 John Wiley & Sons, Ltd.
Lack of transgene and glyphosate effects on yield, and mineral and amino acid content of glyphosate‐resistant soybean
Authors: Duke Stephen O , Rimando Agnes M , Reddy Krishna N , Cizdziel James V , Bellaloui Nacer , Shaw David R , Williams Martin M , Maul Jude E
Published: May 2017

BACKGROUND

There has been controversy as to whether the glyphosate resistance gene and/or glyphosate applied to glyphosate‐resistant (GR) soybean affect the content of cationic minerals (especially Mg, Mn and Fe), yield and amino acid content of GR soybean. A two‐year field study (2013 and 2014) examined these questions at sites in Mississippi, USA.

RESULTS

There were no effects of glyphosate, the GR transgene or field crop history (for a field with both no history of glyphosate use versus one with a long history of glyphosate use) on grain yield. Furthermore, these factors had no consistent effects on measured mineral (Al, As, Ba, Cd, Ca, Co, Cr, Cs, Cu, Fe, Ga, K, Li, Mg, Mn, Ni, Pb, Rb, Se, Sr, Tl, U, V, Zn) content of leaves or harvested seed. Effects on minerals were small and inconsistent between years, treatments and mineral, and appeared to be random false positives. No notable effects on free or protein amino acids of the seed were measured, although glyphosate and its degradation product, aminomethylphosphonic acid (AMPA), were found in the seed in concentrations consistent with previous studies.

CONCLUSIONS

Neither glyphosate nor the GR transgene affect the content of the minerals measured in leaves and seed, harvested seed amino acid composition, or yield of GR soybean. Furthermore, soils with a legacy of GR crops have no effects on these parameters in soybean. © 2017 Society of Chemical Industry
Robotic longitudinal pancreaticojejunostomy for chronic pancreatitis: Comparison of clinical outcomes and cost to the open approach
Authors: Kirks Russell C. , Lorimer Patrick D. , Fruscione Michael , Cochran Allyson , Baker Erin H. , Iannitti David A. , Vrochides Dionisios , Martinie John B.
Published: May 2017

Background

This study compares clinical and cost outcomes of robot‐assisted laparoscopic (RAL) and open longitudinal pancreaticojejunostomy (LPJ) for chronic pancreatitis.

Methods

Clinical and cost data were retrospectively compared between open and RAL LPJ performed at a single center from 2008–2015.

Results

Twenty‐six patients underwent LPJ: 19 open and 7 RAL. Two robot‐assisted cases converted to open were included in the open group for analysis. Patients undergoing RAL LPJ had less intraoperative blood loss, a shorter surgical length of stay, and lower medication costs. Operation supply cost was higher in the RAL group. No difference in hospitalization cost was found.

Conclusions

Versus the open approach, RAL LPJ performed for chronic pancreatitis shortens hospitalization and reduces medication costs; hospitalization costs are equivalent. A higher operative cost for RAL LPJ is mitigated by a shorter hospitalization. Decreased morbidity and healthcare resource economy support use of the robotic approach for LPJ when appropriate.
Methods for studying the metabolic basis of Drosophila development
Authors: Li Hongde , Tennessen Jason M.
Published: May 2017

The field of metabolic research has experienced an unexpected renaissance. While this renewed interest in metabolism largely originated in response to the global increase in diabetes and obesity, studies of metabolic regulation now represent the frontier of many biomedical fields. This trend is especially apparent in developmental biology, where metabolism influences processes ranging from stem cell differentiation and tissue growth to sexual maturation and reproduction. In this regard, the fruit fly Drosophila melanogaster has emerged as a powerful tool for dissecting conserved mechanisms that underlie developmental metabolism, often with a level of detail that is simply not possible in other animals. Here we describe why the fly is an ideal system for exploring the relationship between metabolism and development, and outline a basic experimental strategy for conducting these studies. WIREs Dev Biol 2017, 6:e280. doi: 10.1002/wdev.280

This article is categorized under:

Technologies > Analysis of Cell, Tissue, and Animal Phenotypes
Two-point correlation in wall turbulence according to the attached-eddy hypothesis
Authors: Mouri Hideaki
Published: May 2017

For the constant-stress layer of wall turbulence, two-point correlations of velocity fluctuations are studied theoretically by using the attached-eddy hypothesis, i.e. a phenomenological model of a random superposition of energy-containing eddies that are attached to the wall. While previous studies had invoked additional assumptions, we focus on the minimum assumptions of the hypothesis to derive the most general forms of the correlation functions. They would allow us to use or assess the hypothesis without any effect of those additional assumptions. We also study the energy spectra and the two-point correlations of the rate of momentum transfer and of the rate of energy dissipation.
Polities and nomads: the emergence of the Silk Road exchange in the Tarim Basin region during late prehistory (2000–400 bce)
Authors: Høisæter Tomas Larsen
Published: May 2017

The Silk Road trade network was arguably the most important network of global exchange and interaction prior to the fifteenth century. On the question of how and when it developed, scholars have focused mainly on the role of either the empires dominating the two ends of the trade network or the nomadic empires on the Eurasian steppe. The sedentary people of Central Asia have, however, mostly been neglected. This article traces the development of the city-states of the Tarim Basin in eastern Central Asia, from c. 2000 bce to 400 bce. It argues that the development of the city-states of the Tarim Basin is closely linked to the rise of the ancient Silk Road and that the interaction between the Tarim polities, the nomads of the Eurasian steppe and the Han Empire was the central dynamic in the creation of the ancient Silk Road network in eastern Central Asia.
Litigating Federalism: An Empirical Analysis of Decisions of the Belgian Constitutional Court
Authors: Dalla Pellegrina Lucia , De Mot Jef , Faure Michael , Garoupa Nuno
Published: May 2017

Belgian Constitutional Court – Conflicts between regions, communities and the central government – Allocation of competences – Decisions with high political content – Degree of political alignment between the parties in litigation and judicial behaviour at the Court – Empirical testing – All decisions of the Belgian Constitutional Court, 1985-2012 – Alignment between the alleged political preferences of the judges and the political affiliation of the Petitioner increases the rate of success of the latter
Translating Christianity and Buddhism: Catholic Missionaries in Eighteenth- and Nineteenth-Century Burma
Authors: Finch Andrew J.
Published: May 2017

Catholic mission in Burma during the eighteenth and nineteenth centuries provides evidence for the importance of translation as an element of both Christian evangelism and apologetic. In Burma missionaries were faced by a varied linguistic environment, which became more complex over time. An effective mission required Burmese and the two Karen dialects. Additionally, missionaries were pastors to existing Portuguese Christian communities. British expansion during the nineteenth century added English and Tamil to these pastoral languages. English also became a language of education, Christian debate and mediation. Those wishing to understand Buddhism through its canonical texts had to acquire, or borrow from Buddhist monks, expertise in Pali. This translation and interpretation of Buddhist texts became a tool for both evangelization and Christian defence. In this latter role, the manner in which Buddhist terms were translated or employed became significant within wider European debates concerning the relationship of Christianity to Buddhism.
Innovation ja, aber wie?
Authors: Vaucher Fabian
Published: May 2017

Zusammenfassung. Die regulatorischen Rahmenbedingungen, ein kompetitives Umfeld, aber auch die Zunahme an chronisch kranken Patienten und neue Bedürfnisse der Bevölkerung führen dazu, dass sich die fast 1800 Apotheken in der Schweiz in einem äusserst dynamischen Umfeld bewegen. Innovation ist in diesem Transformationsprozess der Motor auf dem Weg in die Zukunft. Längst sind zu den klassischen Funktionen weitere Aufgaben hinzugekommen, die die Apotheke zur ersten Anlaufstelle bei gesundheitlichen Problemen machen. Der Bundesrat hat in seinem Bericht zur Neupositionierung der Apotheken in der Grundversorgung angekündigt, die pharmazeutischen Kompetenzen von Apothekerinnen und Apothekern noch stärker nutzen zu wollen, insbesondere zur Qualitätssteigerung in der Arzneimitteltherapie.
Gute Lebens- und Sterbensqualität – Versorgung und Versorgungslücken von Palliative Care in der Schweiz
Authors: Krones Tanja , Monteverde Settimio
Published: May 2017

Zusammenfassung. Der medizinische Fortschritt erforderte eine grundlegenden Neubesinnung über das Verhältnis von Medizin und Tod. Paradigmatisch vollzogen wurde diese erstmals durch das Wirken der Krankenschwester, Sozialarbeiterin und Ärztin Cicely Saunders, die das Zulassen und das Gestalten des letzten Lebensabschnitts als genuinen Auftrag der Medizin verstand, klinisch konsequent umsetzte und erforschte. Durch die WHO-Definition der Palliative Care wurde die globale, kultur- und systemübergreifende Bedeutung des Themas ins Bewusstsein gerufen. Bald schon konnte die Forschung die Wirksamkeit von Palliative Care auf die Lebensqualität unheilbar kranker und sterbender Menschen belegen. Aber auch Faktoren wie die Belastung pflegender Angehöriger oder der wirksame Einsatz von Gesundheitsressourcen können durch Palliative Care positiv beeinflusst werden. Auch in der Schweiz hat sich Palliative Care in den Versorgungsstrukturen des Gesundheitswesens gut etabliert, was dem Zusammenwirken verschiedener Akteure aus der Ebene der Gesundheitspolitik, der Patientenversorgung und der privaten Initiative zu verdanken ist. Trotzdem belegt die Schweiz in der Quality of Death Studie des „Economist“ weltweit keinen der vorderen Plätze, wofür gemäss Studie gerade auch Finanzierungslücken in der Palliative Care verantwortlich gemacht werden. Dieser Beitrag zeigt, wie schwierig es ist, Palliative Care als Teil einer flächendeckenden Gesundheitsversorgung zu verstehen und umzusetzen. Auch die mit Palliative Care verbundene finanzielle Belastung für Einzelne und Haushalte ist dabei nicht ausser Acht zu lassen. Aufbauend auf bisherigen Bemühungen sind weitere Schritte in Richtung flächendeckender Implementierung nötig, die dem Motto „The palliative care team follows the patient“ („engl. „Das Palliative Care Team folgt dem Patienten“) folgen und problematische implizite Steuerungseffekte aufgrund bestehender Finanzierungslücken aufdecken. Als Möglichkeit einer solchen integrierten, patientenzentrierten Palliative Care Versorgung wird das Konzept des Advance Care Planning ausgeführt.
Waldenstrom macroglobulinemia cells devoid of BTKC481S or CXCR4WHIM-like mutations acquire resistance to ibrutinib through upregulation of Bcl-2 and AKT resulting in vulnerability towards venetoclax or MK2206 treatment
Authors: Paulus A , Akhtar S , Yousaf H , Manna A , Paulus S M , Bashir Y , Caulfield T R , Kuranz-Blake M , Chitta K , Wang X , Asmann Y , Hudec R , Springer W , Ailawadhi S , Chanan-Khan A
Published: May 2017

Although ibrutinib is highly effective in Waldenstrom macroglobulinemia (WM), no complete remissions in WM patients treated with ibrutinib have been reported to date. Moreover, ibrutinib-resistant disease is being steadily reported and is associated with dismal clinical outcome (overall survival of 2.9–3.1 months). To understand mechanisms of ibrutinib resistance in WM, we established ibrutinib-resistant in vitro models using validated WM cell lines. Characterization of these models revealed the absence of BTKC481S and CXCR4WHIM-like mutations. BTK-mediated signaling was found to be highly attenuated accompanied by a shift in PI3K/AKT and apoptosis regulation-associated genes/proteins. Cytotoxicity studies using the AKT inhibitor, MK2206±ibrutinib, and the Bcl-2-specific inhibitor, venetoclax±ibrutinib, demonstrated synergistic loss of cell viability when either MK22016 or venetoclax were used in combination with ibrutinib. Our findings demonstrate that induction of ibrutinib resistance in WM cells can arise independent of BTKC481S and CXCR4WHIM-like mutations and sustained pressure from ibrutinib appears to activate compensatory AKT signaling as well as reshuffling of Bcl-2 family proteins for maintenance of cell survival. Combination treatment demonstrated greater (and synergistic) antitumor effect and provides rationale for development of therapeutic strategies encompassing venetoclax+ibrutinib or PI3K/AKT inhibitors+ibrutinib in ibrutinib-resistant WM.
Transcriptomic and microRNAomic profiling reveals multi-faceted mechanisms to cope with phosphate stress in a dinoflagellate
Authors: Shi Xinguo , Lin Xin , Li Ling , Li Meizhen , Palenik Brian , Lin Senjie
Published: May 2017

Although gene regulation can occur at both transcriptional and epigenetic (microRNA) levels, combined transcriptomic and microRNAomic responses to environmental stress are still largely unexplored for marine plankton. Here, we conducted transcriptome and microRNAome sequencing for Prorocentrum donghaiense to understand the molecular mechanisms by which this dinoflagellate copes with phosphorus (P) deficiency. Under P-depleted conditions, G1/S specific cyclin gene was markedly downregulated, consistent with growth inhibition, and genes related to dissolved organic phosphorus (DOP) hydrolysis, carbon fixation, nitrate assimilation, glycolysis, and cellular motility were upregulated. The elevated expression of ATP-generating genes (for example, rhodopsin) and ATP-consuming genes suggests some metabolic reconfiguration towards accelerated ATP recycling under P deficiency. MicroRNAome sequencing revealed 17 microRNAs, potentially regulating 3268 protein-coding genes. Functional enrichment analysis of these microRNA-targeted genes predicted decreases in sulfatide (sulfolipid) catabolism under P deficiency. Strikingly, we detected a significant increase in sulfolipid sulfatide content (but not in sulphoquinovosyldiacylglycerol content) and its biosynthesis gene expression, indicating a different sulfolipid-substituting-phospholipid mechanism in this dinoflagellate than other phytoplankters studied previously. Taken together, our integrative transcriptomic and microRNAomic analyses show that enhanced DOP utilization, accelerated ATP cycling and repressed sulfolipid degradation constitute a comprehensive strategy to cope with P deficiency in a model dinoflagellate.
Scalable focused ion beam creation of nearly lifetime-limited single quantum emitters in diamond nanostructures
Authors: Schröder Tim , Trusheim Matthew E. , Walsh Michael , Li Luozhou , Zheng Jiabao , Schukraft Marco , Sipahigil Alp , Evans Ruffin E. , Sukachev Denis D. , Nguyen Christian T. , Pacheco Jose L. , Camacho Ryan M. , Bielejec Edward S. , Lukin Mikhail D. , Englund Dirk
Published: May 2017

The controlled creation of defect centre—nanocavity systems is one of the outstanding challenges for efficiently interfacing spin quantum memories with photons for photon-based entanglement operations in a quantum network. Here we demonstrate direct, maskless creation of atom-like single silicon vacancy (SiV) centres in diamond nanostructures via focused ion beam implantation with ∼32 nm lateral precision and <50 nm positioning accuracy relative to a nanocavity. We determine the Si+ ion to SiV centre conversion yield to be ∼2.5% and observe a 10-fold conversion yield increase by additional electron irradiation. Low-temperature spectroscopy reveals inhomogeneously broadened ensemble emission linewidths of ∼51 GHz and close to lifetime-limited single-emitter transition linewidths down to 126±13 MHz corresponding to ∼1.4 times the natural linewidth. This method for the targeted generation of nearly transform-limited quantum emitters should facilitate the development of scalable solid-state quantum information processors.
Finding multiple reaction pathways via global optimization of action
Authors: Lee Juyong , Lee In-Ho , Joung InSuk , Lee Jooyoung , Brooks Bernard R.
Published: May 2017

Global searching for reaction pathways is a long-standing challenge in computational chemistry and biology. Most existing approaches perform only local searches due to computational complexity. Here we present a computational approach, Action-CSA, to find multiple diverse reaction pathways connecting fixed initial and final states through global optimization of the Onsager–Machlup action using the conformational space annealing (CSA) method. Action-CSA successfully overcomes large energy barriers via crossovers and mutations of pathways and finds all possible pathways of small systems without initial guesses on pathways. The rank order and the transition time distribution of multiple pathways are in good agreement with those of long Langevin dynamics simulations. The lowest action folding pathway of FSD-1 is consistent with recent experiments. The results show that Action-CSA is an efficient and robust computational approach to study the multiple pathways of complex reactions and large-scale conformational changes.
Highly indistinguishable and strongly entangled photons from symmetric GaAs quantum dots
Authors: Huber Daniel , Reindl Marcus , Huo Yongheng , Huang Huiying , Wildmann Johannes S. , Schmidt Oliver G. , Rastelli Armando , Trotta Rinaldo
Published: May 2017

The development of scalable sources of non-classical light is fundamental to unlocking the technological potential of quantum photonics. Semiconductor quantum dots are emerging as near-optimal sources of indistinguishable single photons. However, their performance as sources of entangled-photon pairs are still modest compared to parametric down converters. Photons emitted from conventional Stranski–Krastanov InGaAs quantum dots have shown non-optimal levels of entanglement and indistinguishability. For quantum networks, both criteria must be met simultaneously. Here, we show that this is possible with a system that has received limited attention so far: GaAs quantum dots. They can emit triggered polarization-entangled photons with high purity (g(2)(0) = 0.002±0.002), high indistinguishability (0.93±0.07 for 2 ns pulse separation) and high entanglement fidelity (0.94±0.01). Our results show that GaAs might be the material of choice for quantum-dot entanglement sources in future quantum technologies.
Ultrafast coherence transfer in DNA-templated silver nanoclusters
Authors: Thyrhaug Erling , Bogh Sidsel Ammitzbøll , Carro-Temboury Miguel R , Madsen Charlotte Stahl , Vosch Tom , Zigmantas Donatas
Published: May 2017

DNA-templated silver nanoclusters of a few tens of atoms or less have come into prominence over the last several years due to very strong absorption and efficient emission. Applications in microscopy and sensing have already been realized, however little is known about the excited-state structure and dynamics in these clusters. Here we report on a multidimensional spectroscopy investigation of the energy-level structure and the early-time relaxation cascade, which eventually results in the population of an emitting state. We find that the ultrafast intramolecular relaxation is strongly coupled to a specific vibrational mode, resulting in the concerted transfer of population and coherence between excited states on a sub-100 fs timescale.
Whole genome sequencing and imputation in isolated populations identify genetic associations with medically-relevant complex traits
Authors: Southam Lorraine , Gilly Arthur , Süveges Dániel , Farmaki Aliki-Eleni , Schwartzentruber Jeremy , Tachmazidou Ioanna , Matchan Angela , Rayner Nigel W. , Tsafantakis Emmanouil , Karaleftheri Maria , Xue Yali , Dedoussis George , Zeggini Eleftheria
Published: May 2017

Next-generation association studies can be empowered by sequence-based imputation and by studying founder populations. Here we report ∼9.5 million variants from whole-genome sequencing (WGS) of a Cretan-isolated population, and show enrichment of rare and low-frequency variants with predicted functional consequences. We use a WGS-based imputation approach utilizing 10,422 reference haplotypes to perform genome-wide association analyses and observe 17 genome-wide significant, independent signals, including replicating evidence for association at eight novel low-frequency variant signals. Two novel cardiometabolic associations are at lead variants unique to the founder population sequences: chr16:70790626 (high-density lipoprotein levels beta −1.71 (SE 0.25), P=1.57 × 10−11, effect allele frequency (EAF) 0.006); and rs145556679 (triglycerides levels beta −1.13 (SE 0.17), P=2.53 × 10−11, EAF 0.013). Our findings add empirical support to the contribution of low-frequency variants in complex traits, demonstrate the advantage of including population-specific sequences in imputation panels and exemplify the power gains afforded by population isolates.
Astragaloside IV alleviates heart failure via activating PPARα to switch glycolysis to fatty acid β-oxidation
Authors: Dong Zhiwei , Zhao Pei , Xu Ming , Zhang Chen , Guo Wei , Chen Huihua , Tian Jing , Wei Hongchang , lu Rong , Cao Tongtong
Published: May 2017

In heart failure (HF), energy metabolism pathway in cardiac muscle changes from fatty acid β-oxidation to glycolysis. However, the exact mechanism is unknown. Sarcoendoplasmic reticulum Ca2+α ATPase (SERCA) expression is downregulated and mitochondrial function is reduced in HF, perhaps partly due to a substantially reduced energy supply for excitation–contraction coupling resulting from a lower fatty acid β-oxidation rate. We investigated whether Astragaloside IV can activate peroxisome proliferator-activated receptor alpha (PPARα) to stimulate fatty acid β-oxidation and increase cardiac energy production, improving mitochondrial function and the efficiency of SERCA in HF. In pressure overload-induced HF mice and isolated hypertrophic myocardial cells, fatty acid β-oxidation and heart function were substantially strengthened following Astragaloside IV treatment, as demonstrated by the increased expression of PPARα and SERCA2a. In vitro, Astragaloside IV regulated energy metabolism by increasing ATP production and enhancing mitochondrial function, attributable to increased oxygen consumption and slightly increased mitochondrial Ca2+ uptake. In HF, Astragaloside IV switched glycolysis to fatty acid β-oxidation, as confirmed by reduced anaerobic glycolysis and an increased oxygen consumption ratio. These results suggest that Astragaloside IV can stimulate fatty acid β-oxidation and improve mitochondrial function, which may present a novel cardioprotective treatment that inhibits the progress of HF.
Hsp70 facilitates trans-membrane transport of bacterial ADP-ribosylating toxins into the cytosol of mammalian cells
Authors: Ernst Katharina , Schmid Johannes , Beck Matthias , Hägele Marlen , Hohwieler Meike , Hauff Patricia , Ückert Anna Katharina , Anastasia Anna , Fauler Michael , Jank Thomas , Aktories Klaus , Popoff Michel R. , Schiene-Fischer Cordelia , Kleger Alexander , Müller Martin , Frick Manfred , Barth Holger
Published: May 2017

Binary enterotoxins Clostridium (C.) botulinum C2 toxin, C. perfringens iota toxin and C. difficile toxin CDT are composed of a transport (B) and a separate non-linked enzyme (A) component. Their B-components mediate endocytic uptake into mammalian cells and subsequently transport of the A-components from acidic endosomes into the cytosol, where the latter ADP-ribosylate G-actin resulting in cell rounding and cell death causing clinical symptoms. Protein folding enzymes, including Hsp90 and peptidyl-prolyl cis/trans isomerases facilitate transport of the A-components across endosomal membranes. Here, we identified Hsp70 as a novel host cell factor specifically interacting with A-components of C2, iota and CDT toxins to facilitate their transport into the cell cytosol. Pharmacological Hsp70-inhibition specifically prevented pH-dependent trans-membrane transport of A-components into the cytosol thereby protecting living cells and stem cell-derived human miniguts from intoxication. Thus, Hsp70-inhibition might lead to development of novel therapeutic strategies to treat diseases associated with bacterial ADP-ribosylating toxins.
Synchrotron phase-contrast microtomography of coprolites generates novel palaeobiological data
Authors: Qvarnström Martin , Niedźwiedzki Grzegorz , Tafforeau Paul , Žigaitė Živil , Ahlberg Per E.
Published: May 2017

Coprolites (fossil faeces) reveal clues to ancient trophic relations, and contain inclusions representing organisms that are rarely preserved elsewhere. However, much information is lost by classical techniques of investigation, which cannot find and image the inclusions in an adequate manner. We demonstrate that propagation phase-contrast synchrotron microtomography (PPC-SRμCT) permits high-quality virtual 3D-reconstruction of coprolite inclusions, exemplified by two coprolites from the Upper Triassic locality Krasiejów, Poland; one of the coprolites contains delicate beetle remains, and the other one a partly articulated fish and fragments of bivalves.
Monocyclic β-lactams loaded on hydroxyapatite: new biomaterials with enhanced antibacterial activity against resistant strains
Authors: Giacomini Daria , Torricelli Paola , Gentilomi Giovanna Angela , Boanini Elisa , Gazzano Massimo , Bonvicini Francesca , Benetti Emanuele , Soldati Roberto , Martelli Giulia , Rubini Katia , Bigi Adriana
Published: May 2017

The development of biomaterials able to act against a wide range of bacteria, including antibiotic resistant bacteria, is of great importance since bacterial colonization is one of the main causes of implant failure. In this work, we explored the possibility to functionalize hydroxyapatite (HA) nanocrystals with some monocyclic N-thio-substituted β-lactams. To this aim, a series of non-polar azetidinones have been synthesized and characterized. The amount of azetidinones loaded on HA could be properly controlled on changing the polarity of the loading solution and it can reach values up to 17 wt%. Data on cumulative release in aqueous solution show different trends which can be related to the lipophilicity of the molecules and can be modulated by suitable groups on the azetidinone. The examined β-lactams-HA composites display good antibacterial activity against reference Gram-positive and Gram-negative bacteria. However, the results of citotoxicity and antibacterial tests indicate that HA loaded with 4-acetoxy-1-(methylthio)-azetidin-2-one displays the best performance. In fact, this material strongly inhibited the bacterial growth of both methicillin resistant and methicillin susceptible clinical isolates of S. aureus from surgical bone biopsies, showing to be a very good candidate as a new functional biomaterial with enhanced antibacterial activity.
Artificial enamel induced by phase transformation of amorphous nanoparticles
Authors: Onuma Kazuo , Iijima Mayumi
Published: May 2017

Human tooth enamel has tightly packed c-axis-oriented hydroxyapatite (HAP: Ca10(PO4)6(OH)2) nanorods with high elastic modulus. Fabrication of an enamel architecture in vitro supports the repair of teeth using HAP; however, existing methods require complex and laborious steps to form an enamel-like structure. Here we present a very simple and effective technique for forming artificial enamel in near-physiological solution using a substrate composed of amorphous calcium phosphate (ACP) nanoparticles. Without any functionalized modification of the substrate surface, faint dissolution and successive phase transformation automatically induce formation of an intermediate layer of low-crystalline HAP nanoparticles, on which highly oriented HAP nanorods grow by geometrical selection. We also show that an enamel structure forms on a substrate of amorphous calcium carbonate when the surface nanoparticles react so as to form an intermediate layer similar to that in ACP. Our results demonstrate that there is a wide range of substrate choices for nanorod array formation. Contrary to current understanding, a stable surface designed in nanoscale is not essential for the growth of arranged guest crystals. Reactive amorphous nanoparticles and their transformation efficiently induce a nanorod array structure.
Injectable in situ cross-linking chitosan-hyaluronic acid based hydrogels for abdominal tissue regeneration
Authors: Deng Youming , Ren Jianan , Chen Guopu , Li Guanwei , Wu Xiuwen , Wang Gefei , Gu Guosheng , Li Jieshou
Published: May 2017

Abdominal wall defect caused by open abdomen (OA) or abdominal trauma is a serious issue since it induces several clinical problems. Although a variety of prosthetic materials are commonly employed, complications occur including host soft tissue response, fistula formation and chronic patient discomfort. Recently, abundant natural polymers have been used for injectable hydrogel synthesis in tissue regeneration. In this study, we produced the chitosan - hyaluronic acid (CS/HA) hydrogel and investigated its effects on abdominal tissue regeneration. The physical and biological properties of the hydrogel were demonstrated to be suitable for application in abdominal wounds. In a rat model simulating open abdomen and large abdominal wall defect, rapid cellular response, sufficient ECM deposition and marked neovascularization were found after the application of the hydrogel, compared to the control group and fibrin gel group. Further, the possible mechanism of these findings was studied. Cytokines involved in angiogenesis and cellular response were increased and the skew toward M2 macrophages credited with the functions of anti-inflammation and tissue repair was showed in CS/HA hydrogel group. These findings suggested that CS/HA hydrogel could prevent the complications and was promising for abdominal tissue regeneration.
A new method to reduce the number of time delays in a network
Authors: Wagemakers Alexandre , Sanjuán Miguel A. F.
Published: May 2017

Time delays may cause dramatic changes to the dynamics of interacting oscillators. Coupled networks of interacting dynamical systems can have unexpected behaviours when the signal between the vertices are time delayed. It has been shown for a very general class of systems that the time delays can be rearranged as long as the total time delay over the constitutive loops of the network is conserved. This fact allows to reduce the number of time delays of the problem without loss of information. There is a theoretical lower bound for this number that can be numerically improved if the time delays are commensurable. Here we propose a formulation of the problem and a numerical method to even further reduce the number of time delays in a network.
RNAseq analysis reveals pathways and candidate genes associated with salinity tolerance in a spaceflight-induced wheat mutant
Authors: Xiong Hongchun , Guo Huijun , Xie Yongdun , Zhao Linshu , Gu Jiayu , Zhao Shirong , Li Junhui , Liu Luxiang
Published: May 2017

Salinity stress has become an increasing threat to food security worldwide and elucidation of the mechanism for salinity tolerance is of great significance. Induced mutation, especially spaceflight mutagenesis, is one important method for crop breeding. In this study, we show that a spaceflight-induced wheat mutant, named salinity tolerance 1 (st1), is a salinity-tolerant line. We report the characteristics of transcriptomic sequence variation induced by spaceflight, and show that mutations in genes associated with sodium ion transport may directly contribute to salinity tolerance in st1. Furthermore, GO and KEGG enrichment analysis of differentially expressed genes (DEGs) between salinity-treated st1 and wild type suggested that the homeostasis of oxidation-reduction process is important for salt tolerance in st1. Through KEGG pathway analysis, “Butanoate metabolism” was identified as a new pathway for salinity responses. Additionally, key genes for salinity tolerance, such as genes encoding arginine decarboxylase, polyamine oxidase, hormones-related, were not only salt-induced in st1 but also showed higher expression in salt-treated st1 compared with salt-treated WT, indicating that these genes may play important roles in salinity tolerance in st1. This study presents valuable genetic resources for studies on transcriptome variation caused by induced mutation and the identification of salt tolerance genes in crops.