bluuebunny/crossref_metadata_2025 huggingface dataset:
The Need to be Rid of the Idea of General Customary Law
Authors: Carty Anthony
Published: November 2018

B.S. Chimni's study of customary international law (CIL) is a review of its role both as a supporter of the existing global capitalist order and as a potential instrument to challenge that order in favor of a postmodern deliberative reasoning as the shaper of a new CIL. It has been my view, since the The Decay of International Law? in 1986, that general customary international law is not an intelligible concept and not actually used in practice to demonstrate empirically the existence of any rule of law. I follow Hans Morgenthau, who wrote in 1940 in the American Journal of International Law that the manner in which the International Court of Justice (ICJ) uses this concept is to decide what it likes and call it customary law. I reiterated this view in my review of the ICJ in the first edition of my Philosophy of International Law in 2007. While Chimni quotes my writings on general custom frequently and very positively in his article, this is always to support a progressive customary law and never to do what I would propose, which is to make a complete break with CIL in favor of an independent approach to the problems it is supposed to answer.
Merchant’s Road Toward the Utopia in Heliodorus’Aethiopica
Authors: Sanchez Hernandez Juan Pablo
Published: November 2018

Heliodorus’Aethiopicanarrates the adventurous journey of a couple through Egypt to the kingdom of Meroe in Ethiopia where they get married. To increase the plausibility of this story Heliodorus uses his knowledge of Rome’s trade activities in the East and he even introduces some characters involved in trade ventures in those regions (e.g. Nausicles) at crucial moments of its development. On the other hand, Heliodorus’ references to luxurious products of Eastern and African origin, as well as to exotic animals or tribes, are recurring elements (orleitmotifs) that are consciously interspersed throughout the novel. Those references not only serve to unify a carefully planned plot and guide the reader to an intended conclusion, but also to map the idealised Ethiopia and its neighboring subjected regions (inhabited by some fantastic tribes), where the protagonists will eventually live.
The Knowledge Level of Dentists in Turkey About Their Potential Role on the Disaster Victims Identification (DVI) Team
Authors: Yasar Zehtiye Fusun , Durukan Elif , Buken Erhan
Published: November 2018

Objective

Although dentists are valuable assets in identification teams during disaster events, forensic dentistry is not used effectively in the identification studies conducted in Turkey, and the importance of dental data is ignored. The aim of this study was to determine the level of knowledge of dentists regarding their duties and responsibilities during major disasters.

Methods

This descriptive study was conducted between December 2015 and June 2016. Registered dentists (n=20.280) of the Turkish Dental Association were invited to complete the organization’s online survey. A total of 539 dentists participated in the volunteer workshop. Data were analyzed using SPSS, version 22.0 (IBM Corp, Armonk, NY). The chi-square analysis was used to evaluate the knowledge level of dentists by group regarding disaster victim identification (DVI) – the process and procedure of recovering and identifying victims of major disasters (eg, earthquake, terrorist attack).

Results

The dentists included in the study consisted of 320 (59.4%) females and 219 (40.6%) males with a mean age of 37.4±12.6 years. The number of specialists and general dentists were 249 (45.6%) and 297 (54.4%), respectively; 249 (69.71%) dentists who had knowledge about forensic dentistry stated that they received this information during their formal training. The percentage of dentists who were aware of the existence of an organization of a disaster response operation in Turkey was 74.2%, but only 20.5% (n=110) had knowledge about DVI. We found that 92.9% (n=104) of these dentists believed that dentists should be included in the team for the identification of disaster victims. On the other hand, only half (52.3%) of the dentists with knowledge of DVI wanted to work on the identification teams. The majority (99.1%) considered DNA analysis to be the safest method for identification.

Conclusion

Our findings show that, although dentists know about the identification process, they do not have enough relevant knowledge. (Disaster Med Public Health Preparedness.2019;13:533-538)
The ontological security of special relationships: the case of Germany’s relations with Israel
Authors: Oppermann Kai , Hansel Mischa
Published: November 2018

This article suggests studying special relationships in international politics from an ontological security perspective. It argues that conceptualising the partners to special relationships as ontological security seekers provides a promising theoretical angle to address gaps in our understanding of three important dimensions of such relations: their emergence and stability; the processes and practices of maintaining them; and the power relations within special relations. The article illustrates its theoretical argument in a case study on the German-Israeli relationship. The close partnership between the two countries that has developed since the Holocaust ranks as one of the most remarkable examples of special relationships in the international arena. We argue that foregrounding the ontological security that the special relationship provides, in particular for Germany, sheds important new light on how German-Israeli relations have developed. Specifically, we hold that Germany’s ontological security needs were already an important driver in establishing the relationship and have been a key stabiliser of it ever since; that the ontological security perspective can make sense of three interrelated practices of maintaining the ‘specialness’ of the relationship; and that the asymmetries between the ontological security needs of the two partners help account for Israel’s political leverage in the relationship.
Is the efficacy of antibiotic prophylaxis for surgical procedures decreasing? Systematic review and meta-analysis of randomized control trials
Authors: Gandra Sumanth , Trett Anna , Alvarez-Uria Gerardo , Solomkin Joseph S. , Laxminarayan Ramanan
Published: November 2018

Objective

Rising antibiotic resistance could reduce the effectiveness of antibiotics in preventing postoperative infections. We investigated trends in the efficacy of antibiotic prophylaxis regimens for 3 commonly performed surgical procedures—appendectomy, cesarean section, and colorectal surgery—and 1 invasive diagnostic procedure, transrectal prostate biopsy (TRPB).

Design

Systematic review and meta-analysis.

Methods

We searched PubMed and Cochrane databases (through October 31, 2017) for randomized control trials (RCTs) that measured the efficacy of antibiotic prophylaxis for 4 index procedures in preventing postoperative infections (surgical site infections [SSIs] following the 3 surgical procedures and a combination of urinary tract infections [UTIs] and sepsis following TRPB).

Results

Of 399 RCTs, 74 studies (9 appendectomy, 11 cesarean section, 39 colorectal surgery, and 15 TRPB) were included. Multilevel logistic regression models with random intercepts for each study showed no statistically significant increase in SSIs over time for appendectomy (adjusted odds ratio [aOR] per year, 1.03; 95% confidence interval [CI], 0.92–1.16; P=.57), cesarean section (aOR per year, 1.01; 95% CI, 0.96–1.05; P=.80), and TRPB (aOR per year, 0.95; 95% CI, 0.77–1.18; P=.67). However, there was a significant increase in SSIs proportion following colorectal surgery (aOR per year, 1.049; 95% CI, 1.03–1.07; P<.001).

Conclusion

The efficacy of antibiotic prophylaxis agents in preventing SSIs following colorectal surgery has declined. Small number of RCTs and low infections rates limited our ability to assess true effect for simple appendectomy, cesarean section, or TRPB.
Effects of distributed roughness on crossflow instability through generalized resonance mechanisms
Authors: He Jiyang , Butler Adam , Wu Xuesong
Published: November 2018

Experiments have shown that micron-sized distributed surface roughness can significantly promote transition in a three-dimensional boundary layer dominated by crossflow instability. This sensitive effect has not yet been fully explained physically and mathematically. Past studies focused on surface roughness exciting crossflow vortices and/or changing the local stability characteristics. The present paper seeks possible additional mechanisms by investigating the effects of distributed surface roughness on crossflow instability through resonant interactions with eigenmodes. A key observation is that the perturbation induced by roughness with specific wavenumbers can interact with two eigenmodes (travelling and stationary vortices) through triadic resonance, or interact with one eigenmode (stationary vortices) through Bragg scattering. Unlike the usual triadic resonance of neutral, or nearly neutral, eigenmodes, the present triadic resonance can take place among modes with $O(1)$ growth rates, provided that these are equal; unlike the usual Bragg scattering involving neutral waves, crossflow stationary vortices can also be unstable. For these amplifying waves, the generalized triadic resonance and Bragg scattering are put forward, and the resulting corrections to the growth rates are derived by a multiple-scale method. The analysis is extended to the case where up to four crossflow vortices interact with each other in the presence of suitable roughness components. The numerical results for Falkner–Skan–Cooke boundary layers show that roughness with a small height (a few percent of the local boundary-layer thickness) can change growth rates substantially (by a more-or-less $O(1)$ amount). This sensitive effect is attributed to two facts: (i) the resonant nature of the triadic interaction and Bragg scattering, which makes the correction to the growth rate proportional to the roughness height, and (ii) the wavenumbers of the roughness component required for the resonance are close to those of the neutral stationary crossflow modes, as a result of which a small roughness can generate a large response. Another important effect of roughness is that its presence renders the participating eigenmodes, which are otherwise independent, fully coupled. Our theoretical results suggest that micron-sized distributed surface roughness influences significantly both the amplification and spectral composition of crossflow vortices.
PARITY RESULTS FOR PARTITIONS WHEREIN EACH PART APPEARS AN ODD NUMBER OF TIMES
Authors: HIRSCHHORN MICHAEL D. , SELLERS JAMES A.
Published: November 2018

We consider the function $f(n)$ that enumerates partitions of weight $n$ wherein each part appears an odd number of times. Chern [‘Unlimited parity alternating partitions’, Quaest. Math. (to appear)] noted that such partitions can be placed in one-to-one correspondence with the partitions of $n$ which he calls unlimited parity alternating partitions with smallest part odd. Our goal is to study the parity of $f(n)$ in detail. In particular, we prove a characterisation of $f(2n)$ modulo 2 which implies that there are infinitely many Ramanujan-like congruences modulo 2 satisfied by the function $f.$ The proof techniques are elementary and involve classical generating function dissection tools.
Efficacy of a written prayer technique on the anxiety of mothers of children with cancer
Authors: Ahmadi Maryam , Zaree Khdije , Kazemnejad Leily Anoushirvan , Sadat Hoseini Akram Sadat
Published: November 2018

Objective

To investigate the effect of a written prayer technique on the anxiety of mothers of children with cancer.

Method

This clinical trial recruited 90 mothers of children with cancer admitted to the Medical Centre of Tehran. Using a convenience sampling method, we randomly assigned the participants to two groups: control (n = 45) and intervention (n = 45). Data were collected through the Spielberger's anxiety scale and a demographic questionnaire. Maternal anxiety was measured before the intervention, immediately after the three-day intervention, and five weeks after the intervention. We used a writing technique in the intervention and control groups for 20 minutes over three consecutive days. In the intervention group, participants wrote down their sincere desires and wishes that they demanded from God without any worry or stress. The control group spent 20 minutes writing their normal daily schedules; for example, feeding their children or changing their children's clothes. During the three consecutive days of intervention, we asked both groups not to worry about grammar or spelling errors. Finally, the data were analyzed using descriptive and analytical statistical methods.

Result

A statistically significant difference was observed between the two groups (intervention and control mean, 34.9 ± 9.9 and 47.9 ± 16.2, respectively) relative to anxiety after the intervention (p < 0.001). After five weeks, the intervention group continued to exhibit significantly reduced anxiety compared with the control group (intervention and control mean, 34.7 ± 9.6 and 48.5 ± 16.4; p < 0.001).

Significance of results

The written prayer technique appears to be an effective, efficient, cost-effective, and practical method for reducing anxiety in mothers of children with cancer.
Electron Phase‐Space Holes in Three Dimensions: Multispacecraft Observations by Magnetospheric Multiscale
Authors: Holmes J. C. , Ergun R. E. , Newman D. L. , Ahmadi N. , Andersson L. , Le Contel O. , Torbert R. B. , Giles B. L. , Strangeway R. J. , Burch J. L.
Published: November 2018

Electron phase‐space holes are kinetic plasma structures commonly observed in space plasmas on Debye length scales. Near the Earth's duskside flank at 10 Earth radii, a series of 32 electron holes (EHs) are detected within a 1‐s window on all four Magnetospheric Multiscale spacecraft. The spacecraft separation of <7 km is similar to the expected EH size in this region. Length, width, amplitude, and relative positions are determined for individual EHs using a cylindrically symmetric model fit to Magnetospheric Multiscale E field measurements. The model shows good agreement with observed E fields far from the EH center. Deviations in E⊥ from the model are present near the center, indicating observed EHs have complex, sometimes irregular, internal structure. Perturbation magnetic fields δB modeled assuming an E × B0 electron current reproduce the measured parallel perturbation in most cases, although there is a systematic variation due to geometric and finite gyroradius effects. Many EHs in this event have large amplitude for their size, reaching the theoretical lower limit in length parallel to the background magnetic field, which requires the electron phase‐space density to approach 0 in the center. It is possible that EHs of this type have recently formed, eventually weakening or becoming longer over time. This study provides the most detailed measurements of EHs to date. Their derived properties are largely in agreement with expectations from previous research. It remains unclear whether the few notable differences are due to rapid time evolution or are specific to the local environment.
Quasi‐6‐Day Wave Effects on the Equatorial Ionization Anomaly Over a Solar Cycle
Authors: Yamazaki Yosuke
Published: November 2018

The quasi‐6‐day wave (Q6DW) has recently been recognized as an important source of ionospheric variability. This study shows how the response of the equatorial ionosphere to the Q6DW changes over a solar cycle. Global maps of total electron content (TEC) from Global Positioning System data are used to quantify Q6DW effects on the equatorial ionization anomaly during 2004–2017. The results are compared with the Q6DW amplitude in the lower thermosphere as derived from the geopotential height measurements by the Aura satellite. A nearly one‐to‐one correspondence is found between Q6DW activities in the ionosphere and lower thermosphere, indicating robust vertical coupling. The absolute amplitude of the Q6DW in low‐latitude TEC varies with the solar activity index F10.7 and can reach 8 TEC unit (=1016 el/m2) near the crests of the equatorial ionization anomaly during solar maximum. On the other hand, the relative amplitude is unaffected by solar activity, with its annual maximum value being ∼10% for both solar minimum and solar maximum. These results establish the persistent influence of the Q6DW on the equatorial ionosphere under different solar activity conditions.
Neogene Paleomagnetic Study of the Western Baicheng Depression: Implications for the Intensified Deformation of Tian Shan Since the Latest Miocene
Authors: Zhang Zhiliang , Sun Jimin , Lü Lixing , Wang Weitao , Li Yousheng
Published: November 2018

The fold‐and‐thrust belts in the southern forelands of Tian Shan were tectonically deformed as a result of intracontinental deformation in response to the India‐Asia collision; therefore, they are essential for understanding tectonic evolution and basinward propagation of the Tian Shan Range. Although the reactivation of Tian Shan has long been studied, when and how this deformation was initiated and propagated are still controversial. In this study, we present new paleomagnetic results, anisotropy of magnetic susceptibility, tectonic rotations, and interpretations of subsurface seismic images on the Kalayuergun Structural Belt, western Baicheng Depression. Our new results suggest that the deformation of the Kalayuergun Structural Belt initiated at ~5.3 Ma and became young southeasterly, indicating that the deformation reached to the study area in the latest Miocene and propagated basinward progressively since then. The clockwise rotations, about half amounts of which must have been occurred at around ~5.3 Ma, can be linked to the activity of the Kalayuergun dextral strike‐slip fault on the western end of the anticline. Combined with previous results around Tian Shan, we suggest that the long range has been subjected to an episode of intensified tectonic deformation since the latest Miocene, which was caused by the accelerated northward motion of the Tarim Block and Pamir in response to the India‐Asia collision.
Closing the Gap Between the Coral Sea and the Equator: Direct Observations of the North Australian Western Boundary Currents
Authors: Ridgway Ken R. , Benthuysen Jessica A. , Steinberg Craig
Published: November 2018

Boundary currents along northeastern Australia provide source waters for the East Australian Current and redistribute water to the equator within the Gulf of Papua Current (GPC). These currents are formed following the bifurcation of two Coral Sea westward jets, the North Vanuatu Jet (NVJ) and the North Caledonian Jet. While the existence of the boundary currents has been inferred from limited geostrophic sections, gridded climatological analyses, and modeling studies, no direct measurements have been collected. This study synthesizes current and water property measurements from a 7‐year record at Lizard Island and multiple Seaglider deployments between 2010 and 2014. Both repeat glider transects at 14.5 and 18°S and deployments spanning latitudes between 18 and 11°S are included. Cross‐track velocities of these currents show their vertical structure, seasonal changes, and the spatial translation of the bifurcation latitude. The NVJ bifurcation varies seasonally about a mean latitude between 14.4 and 14.7°S. It has a peak northward extent in summer, when the East Australian Current and GPC exhibit maximum and minimum transports, respectively. The deeper GPC originates from the North Caledonian Jet south of 18°S and varies seasonally by 4 Sv. When the westward flow of the NVJ reaches the boundary, the GPC's northward transport grows by ~13 Sv. The salinity signature of the glider data confirms that up to 6 Sv of this influx is sourced from the base of the NVJ. The observed seasonal cycle of current strength and changes in along boundary transport are consistent with the results from an ocean general circulation model.
Rainfall Thresholds for Flow Generation in Desert Ephemeral Streams
Authors: Kampf Stephanie K. , Faulconer Joshua , Shaw Jeremy R. , Lefsky Michael , Wagenbrenner Joseph W. , Cooper David J.
Published: November 2018

Rainfall thresholds for streamflow generation are commonly mentioned in the literature, but studies rarely include methods for quantifying and comparing thresholds. This paper quantifies thresholds in ephemeral streams and evaluates how they are affected by rainfall and watershed properties. The study sites are in southern Arizona, USA; one is hyperarid and the other is semiarid. At both sites rainfall and streamflow were monitored in watersheds ranging from 10−3 to 102 km2. Streams flowed an average of 0–5 times per year in hyperarid watersheds and 3–11 times per year in semiarid watersheds. Although hyperarid sites had fewer flow events, their flow frequency (fraction of rain events causing flow) was higher than in semiarid sites for small (<1 km2) watersheds. At both locations flow frequency decreased with drainage area, but the decrease was steeper in hyperarid watersheds. Watershed mean 60‐min intensity thresholds ranged from 3–13 mm/hr in hyperarid watersheds and 7–16 mm/hr in semiarid watersheds. Higher runoff thresholds and lower flow frequencies in small semiarid watersheds likely relate to greater ground cover and soil development compared to the desert pavement and bedrock surfaces in hyperarid sites. The choice of rain data strongly influenced threshold values; single rain gauges were only adequate for threshold prediction in <1‐km2 watersheds, and incomplete rainfall data led to increases in thresholds with drainage area. We recommend using mean rainfall intensity over the drainage area for threshold analysis because this reduces apparent scale dependence in thresholds caused by incomplete rainfall information.
Participation of xCT in melanoma cell proliferation in vitro and tumorigenesis in vivo
Authors: Shin Seung-Shick , Jeong Byeong-Seon , Wall Brian A. , Li Jiadong , Shan Naing Lin , Wen Yu , Goydos James S. , Chen Suzie
Published: November 2018

Our research group demonstrated that riluzole, an inhibitor of glutamatergic signaling reduced melanoma cell proliferation in vitro and tumor progression in vivo. The underlying mechanisms of riluzole are largely unknown. Microarray analyses on two human melanoma cell lines revealed that riluzole stimulates expression of the cystine-glutamate amino acid antiporter, xCT (SLC7A11). Western immunoblot analysis from cultured human melanoma or normal melanocytic cells showed that xCT was significantly overexpressed in most melanomas, but not normal cells. Studies using human tumor biopsy samples demonstrated that overexpression of xCT was correlated with cancer stage and progression. To further investigate if xCT is involved in melanoma cell growth, we derived several stable clones through transfection of exogenous xCT to melanoma cells that originally showed very low expression of xCT. The elevated xCT expression promoted cell proliferation in vitro and inversely, these melanoma clones showed a dose-dependent decrease in cell proliferation in response to riluzole treatment. Xenograft studies showed that these clones formed very aggressive tumors at a higher rate compared to vector controls. Conversely, treatment of xenograft-bearing animals with riluzole down-regulated xCT expression suggesting that xCT is a molecular target of riluzole. Furthermore, protein lysates from tumor biopsies of patients that participated in a riluzole monotherapy phase II clinical trial showed a reduction in xCT levels in post-treatment specimens from patients with stable disease. Taken together, our results show that xCT may be utilized as a marker to monitor patients undergoing riluzole-based chemotherapies.
Fragmented Care is Prevalent Among Inflammatory Bowel Disease Readmissions and is Associated With Worse Outcomes
Authors: Cohen-Mekelburg Shirley , Rosenblatt Russell , Gold Stephanie , Shen Nicole , Fortune Brett , Waljee Akbar K. , Saini Sameer , Scherl Ellen , Burakoff Robert , Unruh Mark
Published: November 2018

OBJECTIVES:

Inflammatory bowel disease (IBD) is a complex chronic disease that often requires a multispeciality approach; thus, IBD patients are prone to care fragmentation. We aim to determine the prevalence of fragmentation among hospitalized IBD patients and identify associated predictors and visit-level outcomes.

METHODS:

The State Inpatient Databases for New York and Florida were used to identify 90-day readmissions among IBD inpatients from 2009 to 2013. The prevalence of fragmentation, defined as a readmission to a non-index hospital, was reported. Characteristics associated with fragmented care were identified using multivariable logistic regression. Multivariable models were utilized to determine the association between fragmentation and outcomes (in-hospital mortality, readmission length of stay, and inpatient colonoscopy).

RESULTS:

Among IBD inpatients, 25,241 and 29,033 90-day readmission visits were identified, in New York and Florida, respectively. The prevalence of fragmentation was 26.4% in New York and 32.5% in Florida. Younger age, a non-emergent admission type, public payer or uninsured status, mood disorder, and substance abuse were associated with fragmented care, while female gender and a primary diagnosis of an IBD-related complication had an inverse association. Fragmented inpatient care is associated with a higher likelihood of in-hospital death, higher rates of inpatient colonoscopy, and a longer readmission length of stay.

CONCLUSIONS:

Over one in four IBD inpatient readmissions are fragmented. Disparities and differences in fragmentation exist and contribute to poor patient outcomes. Additional efforts targeting fragmentation should be made to better coordinate IBD management, reduce healthcare gaps, and promote high-value care.
Knockdown of KIAA1199 attenuates growth and metastasis of hepatocellular carcinoma
Authors: Liu Jingmei , Han Ping , Gong Jin , Wang Yunwu , Chen Bingxin , Liao Jiazhi , Tian Dean
Published: November 2018

Accumulating evidence indicates that KIAA1199 plays a vital role in tumor progression. However, the role of KIAA1199 in hepatocellular carcinoma (HCC) still remains unknown. In this study, we found that KIAA1199 was upregulated in human HCC tissues and in highly metastatic HCC cell lines. Furthermore, the expression of KIAA1199 was significantly correlated with tumor size and metastasis in HCC. Knockdown of KIAA1199 inhibited cell proliferation and migration in vitro, and suppressed tumorigenicity and lung metastasis in vivo. In addition, silencing of KIAA1199 induced G1 phase arrest by reducing cyclinD1 expression. Moreover, KIAA1199 knockdown induced apoptosis by activating endoplasmic reticulum (ER) stress, which was based on the upregulation of ER stress markers, activating transcription factor 4 (ATF4) and CAAT/enhancer-binding protein homologous protein (CHOP). In conclusion, our data demonstrated that KIAA1199 knockdown inhibited the growth and metastasis of HCC.
In situ synthesis of supported metal nanocatalysts through heterogeneous doping
Authors: Kwak No Woo , Jeong Seung Jin , Seo Han Gil , Lee Siwon , Kim YeonJu , Kim Jun Kyu , Byeon Pilgyu , Chung Sung-Yoon , Jung WooChul
Published: November 2018

Supported metal nanoparticles hold great promise for many fields, including catalysis and renewable energy. Here we report a novel methodology for the in situ growth of architecturally tailored, regenerative metal nanocatalysts that is applicable to a wide range of materials. The main idea underlying this strategy is to selectively diffuse catalytically active metals along the grain boundaries of host oxides and then to reduce the diffused metallic species to form nanoclusters. As a case study, we choose ceria and zirconia, the most recognized oxide supports, and spontaneously form various metal particles on their surface with controlled size and distribution. Metal atoms move back and forth between the interior (as cations) and the exterior (as clusters) of the host oxide lattice as the reductive and oxidative atmospheres repeat, even at temperatures below 700 °C. Furthermore, they exhibit excellent sintering/coking resistance and reactivity toward chemical/electrochemical reactions, demonstrating potential to be used in various applications.
Barren plateaus in quantum neural network training landscapes
Authors: McClean Jarrod R. , Boixo Sergio , Smelyanskiy Vadim N. , Babbush Ryan , Neven Hartmut
Published: November 2018

Many experimental proposals for noisy intermediate scale quantum devices involve training a parameterized quantum circuit with a classical optimization loop. Such hybrid quantum-classical algorithms are popular for applications in quantum simulation, optimization, and machine learning. Due to its simplicity and hardware efficiency, random circuits are often proposed as initial guesses for exploring the space of quantum states. We show that the exponential dimension of Hilbert space and the gradient estimation complexity make this choice unsuitable for hybrid quantum-classical algorithms run on more than a few qubits. Specifically, we show that for a wide class of reasonable parameterized quantum circuits, the probability that the gradient along any reasonable direction is non-zero to some fixed precision is exponentially small as a function of the number of qubits. We argue that this is related to the 2-design characteristic of random circuits, and that solutions to this problem must be studied.
Endothelial cell rearrangements during vascular patterning require PI3-kinase-mediated inhibition of actomyosin contractility
Authors: Angulo-Urarte Ana , Casado Pedro , Castillo Sandra D. , Kobialka Piotr , Kotini Maria Paraskevi , Figueiredo Ana M. , Castel Pau , Rajeeve Vinothini , Milà-Guasch Maria , Millan Jaime , Wiesner Cora , Serra Helena , Muixi Laia , Casanovas Oriol , Viñals Francesc , Affolter Markus , Gerhardt Holger , Huveneers Stephan , Belting Heinz-Georg , Cutillas Pedro R. , Graupera Mariona
Published: November 2018

Angiogenesis is a dynamic process relying on endothelial cell rearrangements within vascular tubes, yet the underlying mechanisms and functional relevance are poorly understood. Here we show that PI3Kα regulates endothelial cell rearrangements using a combination of a PI3Kα-selective inhibitor and endothelial-specific genetic deletion to abrogate PI3Kα activity during vessel development. Quantitative phosphoproteomics together with detailed cell biology analyses in vivo and in vitro reveal that PI3K signalling prevents NUAK1-dependent phosphorylation of the myosin phosphatase targeting-1 (MYPT1) protein, thereby allowing myosin light chain phosphatase (MLCP) activity and ultimately downregulating actomyosin contractility. Decreased PI3K activity enhances actomyosin contractility and impairs junctional remodelling and stabilization. This leads to overstretched endothelial cells that fail to anastomose properly and form aberrant superimposed layers within the vasculature. Our findings define the PI3K/NUAK1/MYPT1/MLCP axis as a critical pathway to regulate actomyosin contractility in endothelial cells, supporting vascular patterning and expansion through the control of cell rearrangement.
Water assisted biomimetic synergistic process and its application in water-jet rewritable paper
Authors: Xi Guan , Sheng Lan , Du Jiahui , Zhang Jinyan , Li Minjie , Wang Hongze , Ma Yufei , Zhang Sean Xiao-An
Published: November 2018

The colour of water-jet rewritable paper (WJRP) is difficult to be expanded via single hydrochromic molecule, especially black. Here, inspired by the amazing phenomenon of bound-water in cells enabling various biological transformations via facilitating synergistic inter-/intra-molecular proton transfer, we present a simple strategy toward WJRP based on binary systems containing less-sensitive acidochromic dyes and mild proton donors (or developers). With such a binary system containing commercial black dye as the colouring agent, benzyl 4-hydroxybenzoate as the developer, and biomimetic bound-water as proton-transferring medium, we successfully achieve the long-awaited black WJRP. Printed images on such WJRP have excellent performances and long retaining time (>1 month). In addition, the robustness, durability and reversibility of WJRP could be increased distinctly by using polyethylene terephthalate as substrate. This strategy significantly expands hydrochromic colours to entire visible range in an eco-friendly way, which opens an avenue of smart materials for practical needs and industrialization.
Warming assessment of the bottom-up Paris Agreement emissions pledges
Authors: Robiou du Pont Yann , Meinshausen Malte
Published: November 2018

Under the bottom-up architecture of the Paris Agreement, countries pledge Nationally Determined Contributions (NDCs). Current NDCs individually align, at best, with divergent concepts of equity and are collectively inconsistent with the Paris Agreement. We show that the global 2030-emissions of NDCs match the sum of each country adopting the least-stringent of five effort-sharing allocations of a well-below 2 °C-scenario. Extending such a self-interested bottom-up aggregation of equity might lead to a median 2100-warming of 2.3 °C. Tightening the warming goal of each country’s effort-sharing approach to aspirational levels of 1.1 °C and 1.3 °C could achieve the 1.5 °C and well-below 2 °C-thresholds, respectively. This new hybrid allocation reconciles the bottom-up nature of the Paris Agreement with its top-down warming thresholds and provides a temperature metric to assess NDCs. When taken as benchmark by other countries, the NDCs of India, the EU, the USA and China lead to 2.6 °C, 3.2 °C, 4 °C and over 5.1 °C warmings, respectively.
Coherent multidimensional spectroscopy of dilute gas-phase nanosystems
Authors: Bruder Lukas , Bangert Ulrich , Binz Marcel , Uhl Daniel , Vexiau Romain , Bouloufa-Maafa Nadia , Dulieu Olivier , Stienkemeier Frank
Published: November 2018

Two-dimensional electronic spectroscopy (2DES) is one of the most powerful spectroscopic techniques with unique sensitivity to couplings, coherence properties and real-time dynamics of a quantum system. While successfully applied to a variety of condensed phase samples, high precision experiments on isolated systems in the gas phase have been so far precluded by insufficient sensitivity. However, such experiments are essential for a precise understanding of fundamental mechanisms and to avoid misinterpretations. Here, we solve this issue by extending 2DES to isolated nanosystems in the gas phase prepared by helium nanodroplet isolation in a molecular beam-type experiment. This approach uniquely provides high flexibility in synthesizing tailored, quantum state-selected model systems of single and many-body character. In a model study of weakly-bound Rb2 and Rb3 molecules we demonstrate the method’s unique capacity to elucidate interactions and dynamics in tailored quantum systems, thereby also bridging the gap to experiments in ultracold quantum science.
Author Correction: Pathogen-derived HLA-E bound epitopes reveal broad primary anchor pocket tolerability and conformationally malleable peptide binding
Authors: Walters Lucy C. , Harlos Karl , Brackenridge Simon , Rozbesky Daniel , Barrett Jordan R. , Jain Vitul , Walter Thomas S. , O’Callaghan Chris A. , Borrow Persephone , Toebes Mireille , Hansen Scott G. , Sacha Jonah B. , Abdulhaqq Shaheed , Greene Justin M. , Früh Klaus , Marshall Emily , Picker Louis J. , Jones E. Yvonne , McMichael Andrew J. , Gillespie Geraldine M.
Published: November 2018

The original version of this Article contained an error in the spelling of the author Jonah B Sacha, which was incorrectly given as Jonah Sacha. These errors have now been corrected in both the PDF and HTML versions of the Article.
Microbiota-driven interleukin-17-producing cells and eosinophils synergize to accelerate multiple myeloma progression
Authors: Calcinotto Arianna , Brevi Arianna , Chesi Marta , Ferrarese Roberto , Garcia Perez Laura , Grioni Matteo , Kumar Shaji , Garbitt Victoria M. , Sharik Meaghen E. , Henderson Kimberly J. , Tonon Giovanni , Tomura Michio , Miwa Yoshihiro , Esplugues Enric , Flavell Richard A. , Huber Samuel , Canducci Filippo , Rajkumar Vincent S. , Bergsagel P. Leif , Bellone Matteo
Published: November 2018

The gut microbiota has been causally linked to cancer, yet how intestinal microbes influence progression of extramucosal tumors is poorly understood. Here we provide evidence implying thatPrevotella heparinolyticapromotes the differentiation of Th17 cells colonizing the gut and migrating to the bone marrow (BM) of transgenic Vk*MYC mice, where they favor progression of multiple myeloma (MM). Lack of IL-17 in Vk*MYC mice, or disturbance of their microbiome delayed MM appearance. Similarly, in smoldering MM patients, higher levels of BM IL-17 predicted faster disease progression. IL-17 induced STAT3 phosphorylation in murine plasma cells, and activated eosinophils. Treatment of Vk*MYC mice with antibodies blocking IL-17, IL-17RA, and IL-5 reduced BM accumulation of Th17 cells and eosinophils and delayed disease progression. Thus, in Vk*MYC mice, commensal bacteria appear to unleash a paracrine signaling network between adaptive and innate immunity that accelerates progression to MM, and can be targeted by already available therapies.
Glucose metabolism induced by Bmp signaling is essential for murine skeletal development
Authors: Lee Seung-Yon , Abel E. Dale , Long Fanxin
Published: November 2018

Much of the mammalian skeleton originates from a cartilage template eventually replaced by bone via endochondral ossification. Despite much knowledge about growth factors and nuclear proteins in skeletal development, little is understood about the role of metabolic regulation. Here we report that genetic deletion of the glucose transporter Glut1 (Slc2a1), either before or after the onset of chondrogenesis in the limb, severely impairs chondrocyte proliferation and hypertrophy, resulting in dramatic shortening of the limbs. The cartilage defects are reminiscent to those caused by deficiency in Bmp signaling. Importantly, deletion of Bmpr1a in chondrocytes markedly reduces Glut1 levels in vivo, whereas recombinant BMP2 increases Glut1 mRNA and protein levels, boosting glucose metabolism in primary chondrocytes. Biochemical studies identify a Bmp-mTORC1-Hif1a signaling cascade resulting in upregulation of Glut1 in chondrocytes. The results therefore uncover a hitherto unknown connection between Bmp signaling and glucose metabolism in the regulation of cartilage development.
RET rearrangements are actionable alterations in breast cancer
Authors: Paratala Bhavna S. , Chung Jon H. , Williams Casey B. , Yilmazel Bahar , Petrosky Whitney , Williams Kirstin , Schrock Alexa B. , Gay Laurie M. , Lee Ellen , Dolfi Sonia C. , Pham Kien , Lin Stephanie , Yao Ming , Kulkarni Atul , DiClemente Frances , Liu Chen , Rodriguez-Rodriguez Lorna , Ganesan Shridar , Ross Jeffrey S. , Ali Siraj M. , Leyland-Jones Brian , Hirshfield Kim M.
Published: November 2018

Fusions involving the oncogenic gene RET have been observed in thyroid and lung cancers. Here we report RET gene alterations, including amplification, missense mutations, known fusions, novel fusions, and rearrangements in breast cancer. Their frequency, oncogenic potential, and actionability in breast cancer are described. Two out of eight RET fusions (NCOA4-RET and a novel RASGEF1A-RET fusion) and RET amplification were functionally characterized and shown to activate RET kinase and drive signaling through MAPK and PI3K pathways. These fusions and RET amplification can induce transformation of non-tumorigenic cells, support xenograft tumor formation, and render sensitivity to RET inhibition. An index case of metastatic breast cancer progressing on HER2-targeted therapy was found to have the NCOA4-RET fusion. Subsequent treatment with the RET inhibitor cabozantinib led to a rapid clinical and radiographic response. RET alterations, identified by genomic profiling, are promising therapeutic targets and are present in a subset of breast cancers.
Reward regulation in plant–frugivore networks requires only weak cues
Authors: Albrecht Jörg , Hagge Jonas , Schabo Dana G. , Schaefer H. Martin , Farwig Nina
Published: November 2018

Theory assumes that fair trade among mutualists requires highly reliable communication. In plant–animal mutualisms the reliability of cues that indicate reward quality is often low. Therefore, it is controversial whether communication allows animal mutualists to regulate their reward intake. Here we show that even loose relationships between fruit brightness and nutritional rewards (r2 = 0.11–0.35) allow birds to regulate their nutrient intake across distinct European plant–frugivore networks. Resident, over-wintering generalist frugivores that interact with diverse plant species select bright, lipid-rich fruits, whereas migratory birds select dark, sugar- and antioxidant-rich fruits. Both nutritional strategies are consistent with previous physiological experiments suggesting that over-wintering generalists aim to maximize their energy intake, whereas migrants aim to enhance the build-up of body fat, their immune response and oxidative status during migration. Our results suggest that animal mutualists require only weak cues to regulate their reward intake according to specific nutritional strategies.
Dna2 processes behind the fork long ssDNA flaps generated by Pif1 and replication-dependent strand displacement
Authors: Rossi Silvia Emma , Foiani Marco , Giannattasio Michele
Published: November 2018

Dna2 is a DNA helicase-endonuclease mediating DSB resection and Okazaki fragment processing. Dna2 ablation is lethal and rescued by inactivation of Pif1, a helicase assisting Okazaki fragment maturation, Pol32, a DNA polymerase δ subunit, and Rad9, a DNA damage response (DDR) factor. Dna2 counteracts fork reversal and promotes fork restart. Here we show that Dna2 depletion generates lethal DNA structures activating the DDR. While PIF1 deletion rescues the lethality of Dna2 depletion, RAD9 ablation relieves the first cell cycle arrest causing genotoxicity after few cell divisions. Slow fork speed attenuates DDR in Dna2 deprived cells. Electron microscopy shows that Dna2-ablated cells accumulate long ssDNA flaps behind the forks through Pif1 and fork speed. We suggest that Dna2 offsets the strand displacement activity mediated by the lagging strand polymerase and Pif1, processing long ssDNA flaps to prevent DDR activation. We propose that this Dna2 function has been hijacked by Break Induced Replication in DSB processing.
NUAK2 is a critical YAP target in liver cancer
Authors: Yuan Wei-Chien , Pepe-Mooney Brian , Galli Giorgio G. , Dill Michael T. , Huang Hai-Tsang , Hao Mingfeng , Wang Yumeng , Liang Han , Calogero Raffaele A. , Camargo Fernando D.
Published: November 2018

The Hippo-YAP signaling pathway is a critical regulator of proliferation, apoptosis, and cell fate. The main downstream effector of this pathway, YAP, has been shown to be misregulated in human cancer and has emerged as an attractive target for therapeutics. A significant insufficiency in our understanding of the pathway is the identity of transcriptional targets of YAP that drive its potent growth phenotypes. Here, using liver cancer as a model, we identify NUAK2 as an essential mediator of YAP-driven hepatomegaly and tumorigenesis in vivo. By evaluating several human cancer cell lines we determine that NUAK2 is selectively required for YAP-driven growth. Mechanistically, we found that NUAK2 participates in a feedback loop to maximize YAP activity via promotion of actin polymerization and myosin activity. Additionally, pharmacological inactivation of NUAK2 suppresses YAP-dependent cancer cell proliferation and liver overgrowth. Importantly, our work here identifies a specific, potent, and actionable target for YAP-driven malignancies.
Author Correction: Predictive Value of Serum Gamma-glutamyltranspeptidase for Future Cardiometabolic Dysregulation in Adolescents- a 10-year longitudinal study
Authors: Lin Chien-Ming , Hsieh Chang-Hsun , Lee Chien-Hsing , Pei Dee , Lin Jiunn-Diann , Wu Chung-Ze , Liang Yao-Jen , Hung Yi-Jen , Chen Yen-Lin
Published: November 2018

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.
Safranal induces DNA double-strand breakage and ER-stress-mediated cell death in hepatocellular carcinoma cells
Authors: Al-Hrout Ala’a , Chaiboonchoe Amphun , Khraiwesh Basel , Murali Chandraprabha , Baig Badriya , El-Awady Raafat , Tarazi Hamadeh , Alzahmi Amnah , Nelson David R. , Greish Yaser E. , Ramadan Wafaa , Salehi-Ashtiani Kourosh , Amin Amr
Published: November 2018

Poor prognoses remain the most challenging aspect of hepatocellular carcinoma (HCC) therapy. Consequently, alternative therapeutics are essential to control HCC. This study investigated the anticancer effects of safranal against HCC using in vitro, in silico, and network analyses. Cell cycle and immunoblot analyses of key regulators of cell cycle, DNA damage repair and apoptosis demonstrated unique safranal-mediated cell cycle arrest at G2/M phase at 6 and 12 h, and at S-phase at 24 h, and a pronounced effect on DNA damage machinery. Safranal also showed pro-apoptotic effect through activation of both intrinsic and extrinsic initiator caspases; indicating ER stress-mediated apoptosis. Gene set enrichment analysis provided consistent findings where UPR is among the top terms of up-regulated genes in response to safranal treatment. Thus, proteins involved in ER stress were regulated through safranal treatment to induce UPR in HepG2 cells.
Construction and characterization of a Saccharomyces cerevisiae strain able to grow on glucosamine as sole carbon and nitrogen source
Authors: Flores Carmen-Lisset , Gancedo Carlos
Published: November 2018

Saccharomyces cerevisiae can transport and phosphorylate glucosamine, but cannot grow on this amino sugar. While an enzyme catalyzing the reaction from glucosamine-6-phosphate to fructose-6-phosphate, necessary for glucosamine catabolism, is present in yeasts using N-acetylglucosamine as carbon source, a sequence homology search suggested that such an enzyme is absent from Saccharomyces cerevisiae. The gene YlNAG1 encoding glucosamine-6-phosphate deaminase from Yarrowia lipolytica was introduced into S. cerevisiae and growth in glucosamine tested. The constructed strain grew in glucosamine as only carbon and nitrogen source. Growth on the amino sugar required respiration and caused an important ammonium excretion. Strains overexpressing YlNAG1 and one of the S. cerevisiae glucose transporters HXT1, 2, 3, 4, 6 or 7 grew in glucosamine. The amino sugar caused catabolite repression of different enzymes to a lower extent than that produced by glucose. The availability of a strain of S. cerevisiae able to grow on glucosamine opens new possibilities to investigate or manipulate pathways related with glucosamine metabolism in a well-studied organism.
Simultaneous Blood Flow Measurement and Dermoscopy of Skin Lesions Using Dual-Mode Dermascope
Authors: White Sean M. , Valdebran Manuel , Kelly Kristen M. , Choi Bernard
Published: November 2018

Dermascopes are commonly utilized for the qualitative visual inspection of skin lesions. While automated image processing techniques and varied illumination strategies have been used to aid in structural analysis of lesions, robust quantification of functional information is largely unknown. To address this knowledge gap, we have developed a compact, handheld dermascope that enables real-time blood flow measurements of skin during conventional visual inspection. In-vitro characterization demonstrated that the dermascope is capable of quantifying changes in flow across a physiologically relevant range even when used in a handheld manner with clinic lighting and dermascope LEDs on. In a small pilot clinical study, we demonstrated the dermascope’s ability to detect flow differences between two distinct lesion types.