bluuebunny/crossref_metadata_2025 huggingface dataset:
A hybrid approach for head and neck cancer using online image guidance and offline adaptive radiotherapy planning
Authors: Srivastava Roopam , Sharma P.K. , Das K.J. Maria , Manjhi Jayanand
Published: February 2019

Background

This is a prospective study to evaluate the dosimetric benefits of treatment plan adaptation for patients who had undergone repeat computed tomography (ReCT)and re-planning due to treatment-induced anatomical changes during radiotherapy.

Materials and Methods

This study involved five head and neck cancer patients who had their treatment plan modified, based on weekly thrice imaging protocol. Impact of mid-course imaging was assessed in patients using ReCT and cone beam computed tomography (CBCT)-based dose verification. Patients were imaged, apart from their initial CT, during the course of their radiation therapy with a ReCT and on board imager CBCT (Varian Medical Systems Inc., Palo Alto, CA, USA). Each CBCT/CT series was rigidly registered to the initial CT in the treatment planning system Eclipse (Varian Medical Systems Inc.) using bony landmarks. The structures were copied to the current CBCT/CT series and, where needed, manually edited slicewise. The dose distribution from the treatment plan was viewed as of the current anatomy by applying the treatment plan the CBCT/CT series, and studying the corresponding dose–volume histograms for organs at risk doses.

Results

The reduction of parotid volumes due to weight loss was observed in all patients, which means an increase in predicted mean doses of parotid when initial CT plan was re-calculated on ReCT and CBCT (Table 1). This explains the necessity of adaptive planning. The predicted mean dose of parotid glands was increased and constraints to spinal cord and skin were exceeded, so re-planning was performed.

Conclusions

The CBCT is a useful tool to view anatomic changes in patients and get an estimate of their impact on dose distribution. Re-planning based on imaging in head and neck patients during the course of radiotherapy is mandatory to reduce side effects.
Cover crop species affect mycorrhizae-mediated nutrient uptake and pest resistance in maize
Authors: Murrell Ebony G. , Ray Swayamjit , Lemmon Mary E. , Luthe Dawn S. , Kaye Jason P.
Published: February 2019

Arbuscular mycorrhizal fungi (AMF) can increase plant nutrient uptake and chemical defense production, both of which can improve plants’ ability to resist insect herbivory. Cover crops—non-commercial species planted in between cash crops in a crop rotation—can naturally alter both soil nutrients and AMF. We tested whether different cover crop species alter AMF colonization, plant nutrient status and plant–insect interactions in a subsequent maize crop. Cover crop species were either non-mycorrhizal, non-leguminous (canola, forage radish), mycorrhizal non-leguminous (cereal rye, oats), mycorrhizal leguminous (clover, pea) or absent (fallow). We measured the cascading consequences of cover crop treatment on maize root AMF colonization, maize growth and performance of an herbivorous insect (European corn borer) feeding on the maize. Maize AMF colonization was greater in plots previously planted with mycorrhizal (rye, oats) than non-mycorrhizal (canola, radish) cover crops or no cover crop (fallow). AMF colonization was linked to increased plant phosphorous and nitrogen, and maize growth increased with low plant N:P. Induced jasmonic acid pathway plant defenses increased with increasing maize growth and AMF colonization. European corn borer survivorship decreased with lower plant N:P, and insect development rate decreased with increased induced plant defenses. Our data describe a cascade in which cover crop species selection can increase or decrease mycorrhizal colonization of subsequent maize crop roots, which in turn impacts phosphorus uptake and may affect herbivory resistance in the maize. These results suggest that farmers could select cover crop species to manage nutrient uptake and pest resistance, in order to amend or limit fertilizer and pesticide use.
Is competition among cooperative banks a negative sum game?
Authors: Coccorese Paolo , Ferri Giovanni
Published: February 2019

Does ‘inner competition’ – rivalry among network members – worsen performance in a network of cooperative banks? By weakening the functionality of the network, inner competition might, in fact, endanger network-dependent scale economies. Testing our hypothesis on Italy's network of mutual cooperative banks (Banche di Credito Cooperativo – BCCs), we find a worsening of performance of both incumbents and (even more) aggressors when BCCs compete among themselves. However, the worsening is mild when BCCs compete with comparable non-mutual banks external to the BCC network. We conclude that inner competition among cooperative banks is a negative sum game and, thus, limiting it would be desirable to preserve the stability of cooperative banking networks.
“A Circuit Tour of the Globe”: “Hiawatha” and the Double-Stake of Imperial Pop
Authors: SCHENKER FREDERICK J.
Published: February 2019

Between 1903 and 1904, the two-step “Hiawatha” spread rapidly throughout much of the colonial world. The travels of “Hiawatha” reveal both what Stuart Hall calls the “double-stake” of popular culture as well as what Amy Kaplan describes as the “anarchic” nature of empire: through its circulation and repeated hearings, “Hiawatha” became both a kind of colonizing force and also a medium that disturbed ideas about racial hierarchies and nationhood that served to justify colonial rule. By charting the global movement of “Hiawatha,” I show how the song became both a colonial force and also a medium for expressions that challenged imperial logic. The tune exhibited imperial tendencies: it saturated soundscapes and, as part of an emerging form of new musical commodities, coaxed listeners into recognizing their shifting status from auditors to consumers. Through its Native American subject matter, the song also helped to perpetuate ideas of evolutionary racial science that served to justify the violence of imperialism. The very qualities that made “Hiawatha” a colonizing song, though, especially its repetitious ubiquity, also increased the complexity of its meaning as it circuited the globe, leading some listeners to hear an accumulation of meanings that seemed to exceed the forms of US imperial pop.
Selling “The Things Money Can't Buy”: Piano Advertising in the Mid-Twentieth Century
Authors: COVEY PAUL MICHAEL
Published: February 2019

This study explores piano advertising strategies after 1940 by examining ads printed inEtude, the Music Magazinebetween then and 1957, when it discontinued publication. Aware of the emerging US consumer culture, piano companies experimented throughout this period with more aggressive marketing techniques than they had previously used. BecauseEtude’s intended audience included musicians and enthusiasts of every skill and experience level, it was approached accordingly by advertisers. Thus, we can trace in its pages the development of methodologies that, owing to an increasingly sophisticated understanding of the contemporary range of consumers and their interests, came to target distinct and different market segments. Examination of strategies aimed at the respective groups illuminates an important chapter in the development of twentieth-century advertising while highlighting the piano's special status among consumer products and its cultural associations. Analysis of the industry's strategies in dealing with the mid-twentieth-century US economy reveals contemporary understandings of such associations and their effect on the implications of piano acquisition.
Size for gestational age at birth according to offspring sex and gestational weight gain in underweight women
Authors: Kasuga Y. , Shigemi D. , Tamagawa M. , Suzuki T. , Kim S.-H. , Higuchi T. , Yasunaga H. , Nakada S.
Published: February 2019

Although maternal pre-pregnancy body mass index (BMI) and gestational weight gain (GWG) are related to fetal growth, there is a paucity of data regarding how offspring sex affects the relationship between maternal BMI in underweight mothers (pre-pregnancy BMI <18.5 kg/m2) and size for gestational age at birth. The aim of this study was to investigate the effect of offspring sex on the relationships among maternal pre-pregnancy BMI, GWG and size for gestational age at birth in Japanese underweight mothers. Records of women with full-term pregnancies who underwent perinatal care at Kawasaki Municipal Hospital (Kawasaki, Japan) between January 2013 and December 2017 were retrospectively reviewed. The study cohort included underweight (n=566) and normal-weight women (18.5 kg/m2⩽pre-pregnancy BMI<25 kg/m2; n=2671). The incidence of small for gestational age (SGA) births in the underweight group was significantly higher than that in the normal-weight group (P<0.01). Additionally, SGA incidence in the underweight group was significantly higher than that in the normal-weight group (P<0.01) in female, but not male (P=0.30) neonates. In the women with female neonates, pre-pregnancy underweight was associated with a significantly increased probability of SGA (odds ratio [OR]: 1.80; P<0.01), but inadequate GWG was not (OR: 1.38; P=0.11). In contrast, in women with male neonates, inadequate GWG was associated with a significantly increased probability of SGA (OR: 1.53; P=0.03), but not with pre-pregnancy underweight (OR: 1.30; P=0.10). In conclusion, the present results suggest that pre-pregnancy underweight is associated with SGA in female offspring but not in male offspring.
Recurrence and mortality 1 year after hospital admission for non-fatal self-harm: a nationwide population-based study
Authors: Vuagnat A. , Jollant F. , Abbar M. , Hawton K. , Quantin C.
Published: February 2019

Aims

A large number of people present each day at hospitals for non-fatal deliberate self-harm (DSH). Examination of the short-term risk of non-fatal recurrence and mortality at the national level is of major importance for both individual medical decision-making and global organisation of care.

Methods

Following the almost exhaustive linkage (96%) of two national registries in France covering 45 million inhabitants (i.e. 70% of the whole population), information about hospitalisation for DSH in 2008–2009 and vital status at 1 year was obtained. Individuals who died during the index hospital stay were excluded from analyses.

Results

Over 2 years, 136,451 individuals were hospitalised in medicine or surgery for DSH. The sample comprised 62.8% women, median age 38 in both genders, with two peaks at 16 and 44 years in women, and one peak at 37 years in men. The method used for DSH was drug overdose in 82.1% of cases. Admission to an intensive care unit occurred in 12.9%. Following index hospitalisation, 71.3% returned home and 23.7% were transferred to a psychiatric inpatient care unit. DSH recurrence during the following year occurred in 12.4% of the sample, within the first 6 months in 75.2%, and only once in 74.6%. At 1 year, 2.6% of the sample had died. The overall standardised mortality ratio was 7.5 but reached more than 20 in young adults. The causes were natural causes (35.7%), suicide (34.4%), unspecified cause (17.5%) and accident (12.4%). Most (62.9%) deaths by suicide occurred within the first 6 months following index DSH. Violent means (i.e. not drug overdose) were used in 70% of suicide cases. Concordance between means used for index DSH and for suicide was low (30% overall), except for drug overdose. Main suicide risk factors were older age, being male, use of a violent means at index DSH, index admission to an intensive care unit, a transfer to another medical department or to a psychiatric inpatient unit, and recurrence of DSH. However, these factors had low positive predictive values individually (below 2%).

Conclusions

Non-fatal DSH represent frequent events with a significant risk of short-term recurrence and death from various causes. The first 6 months following hospital discharge appear to be a critical period. Specific short-term aftercare programs targeting all people with a DSH episode have to be developed, along other suicide prevention strategies.
Buddhist Monuments Across the Bay of Bengal: Cultural Routes and Maritime Networks
Authors: Ray Himanshu Prabha
Published: February 2019

Religious architecture, often called ‘monuments’ within the current understanding of ancient shrines, are prominent features of the landscape in South and Southeast Asia. Many of these sites are admired for their artistic and aesthetic appeal and are centres of tourism and travel. This paper traces the historical trajectory of three contemporary monuments of Buddhist affiliation across the Bay of Bengal, namely Nalanda in north India, Borobudur in Central Java, and Nakhon Pathom in Central Thailand to address both their distinctiveness and their interconnectedness. The paper also focuses on the extent to which these shrines reflect the religious theories that prevailed between the sixth and the thirteenth centuries AD and are currently known to us through religious texts. It is not often appreciated that ‘collections’ of religious texts, as well as the ‘discovery’ of monuments were mediated through the priorities and practices of European and Western scholars from the eighteenth and nineteenth centuries. The history of the study of Buddhism shows that it centred on religious texts and philosophical doctrines produced by a small group of monastic elites, with little attention paid to the more difficult questions of the contexts underlying textual production and circulation. This paper suggests that it is important to factor in the colonization of South and Southeast Asia into any discussion on the understanding of religions and monuments, as well as current interest in these monuments, which are also World Heritage Sites and associated with present interests in maritime heritage.
Demonstrating the Use of a Class of Min‐Max Smoothers for D Region Event Detection in Narrow Band VLF Phase
Authors: Lotz S. I. , Clilverd M.
Published: February 2019

This paper describes the use of a class of nonlinear smoothers for the identification of interesting phenomena in narrow band very low frequency (VLF) transmission phase caused by perturbation events in the D region of the ionosphere. The LULU smoothers, named for their smoothing of upward (L) and downward (U) peaks in a signal, usually used for image processing tasks, are described, and examples are shown where these operators are used to automatically isolate and identify features in the phase of narrow band transmissions received at high and high‐middle latitudes (Antarctica and Marion Island, respectively). Identification of solar flare events, electromagnetic ion cyclotron wave precipitation, and substorm injection events are demonstrated, showing the potential for this technique to be used for space weather monitoring.
Association between serum and adipose tissue resistin with dysglycemia in South Asian women
Authors: Wijetunge Sulochana , Ratnayake R. M. C. J. , Kotakadeniya H. M. S. R. B. , Rosairo Shanthini , Albracht-Schulte Kembra , Ramalingam Latha , Moustaid-Moussa Naima , Kalupahana Nishan Sudheera
Published: February 2019

Background/Objectives

Mechanisms of obesity-associated insulin resistance and dysglycemia in South Asians remain relatively unknown. The objective of this study was to detect subcutaneous (SAT) vs. visceral (VAT) adipose tissue characteristics and adipocytokines associated with obesity, insulin resistance, and dysglycemia in South Asian women.

Subjects/Methods

This was a hospital-based cross-sectional study conducted in Sri Lanka. Subjects comprised of 58 adult women who underwent routine abdominal surgeries. SAT and VAT were obtained from anterior abdominal wall and omentum, respectively. Measures of adiposity, serum insulin and glucose, SAT and VAT crown-like structures (CLS), macrophages, resistin by immunohistochemistry, mean adipocyte area (MAA), and serum adipocytokines were examined.

Results

The homeostatic model assessment for insulin resistance (HOMA-IR) score significantly correlated with age and waist circumference (WC), but not with body mass index (BMI). Although the number of CLS positively correlated with BMI, there were no significant differences between the number of CLS in women with normal fasting glucose (NFG) vs. those with impaired fasting glucose (IFG), indicating that adipose tissue macrophage infiltration is unlikely to be related to dysglycemia. In contrast, serum resistin level was on average 60% higher in women with IFG compared to ones with NFG (p < 0.05). Serum resistin levels correlated with age (r = 0.36, p < 0.05) and WC (r = 0.27, p < 0.05). There were no associations in serum levels of other adipocytokines with IFG. Adipose immunohistochemistry showed that women with IFG had a higher percentage of resistin positive adipocytes in SAT compared to ones with NFG. MAA of VAT, but not SAT, correlated with both BMI and WC.

Conclusions

Resistin may be an important adipokine linking central adiposity and insulin resistance in South Asian women. Both systemic and adipose tissue resistin are linked to dysglycemia in these individuals and may be a potential biomarker for diabetes in this population.
Author Correction: Child sexual offenders show prenatal and epigenetic alterations of the androgen system
Authors: Kruger Tillmann H. C. , Sinke Christopher , Kneer Jonas , Tenbergen Gilian , Khan Abdul Qayyum , Burkert Alexandra , Müller-Engling Linda , Engler Harald , Gerwinn Hannah , von Wurmb-Schwark Nicole , Pohl Alexander , Weiß Simone , Amelung Till , Mohnke Sebastian , Massau Claudia , Kärgel Christian , Walter Martin , Schiltz Kolja , Beier Klaus M. , Ponseti Jorge , Schiffer Boris , Walter Henrik , Jahn Kirsten , Frieling Helge
Published: February 2019

The affiliations. Originally, Kolja Schilz was named last in the affiliations, implying that he is the senior author. This has been corrected; Kolja Schilz is now mentioned after Martin Walter in both the html and PDF versions of the article.
H19 potentiates let-7 family expression through reducing PTBP1 binding to their precursors in cholestasis
Authors: Zhang Li , Yang Zhihong , Huang Wendong , Wu Jianguo
Published: February 2019

Cholestasis induces the hepatic long non-coding RNA H19, which promotes the progression of cholestatic liver fibrosis. However, microRNAs that are dysregulated by H19 during cholestasis remain elusive. Using miRNA-sequencing analysis followed by qPCR validation, we identified marked upregulation of eight members of the let-7 family in cholestatic livers by bile duct ligation (BDL) and H19 overexpression. In particular, the expression of let-7a-1/7d/7f-1 was highly induced in H19-BDL livers but decreased in H19KO-BDL livers. Interestingly, H19 decreased the nuclear let-7 precursors as well as the primary transcripts of let-7a-1/7d/7f-1 levels in BDL mouse livers. Bioinformatics, RNA pull-down, and RNA immunoprecipitation (RIP) assays revealed that the crucial RNA-binding protein polypyrimidine tract-binding protein 1 (PTBP1), an H19 interaction partner, interacted with the precursors of let-7a-1 and let-7d and suppressed their maturation. Both PTBP1 and let-7 expression was differentially regulated by different bile acid species in hepatocyte and cholangiocyte cells. Further, H19 negatively regulated PTBP1’s mRNA and protein levels but did not affect its subcellular distribution in BDL mouse livers. Moreover, we found that H19 restrained but PTBP1 facilitated the bioavailability of let-7 miRNAs to their targets. Taken together, this study revealed for the first time that H19 promoted let-7 expression by decreasing PTBP1’s expression level and its binding to the let-7 precursors in cholestasis.
The apocarotenoid metabolite zaxinone regulates growth and strigolactone biosynthesis in rice
Authors: Wang Jian You , Haider Imran , Jamil Muhammad , Fiorilli Valentina , Saito Yoshimoto , Mi Jianing , Baz Lina , Kountche Boubacar A. , Jia Kun-Peng , Guo Xiujie , Balakrishna Aparna , Ntui Valentine O. , Reinke Beate , Volpe Veronica , Gojobori Takashi , Blilou Ikram , Lanfranco Luisa , Bonfante Paola , Al-Babili Salim
Published: February 2019

Carotenoid cleavage dioxygenases (CCDs) form hormones and signaling molecules. Here we show that a member of an overlooked plant CCD subfamily from rice, that we name Zaxinone Synthase (ZAS), can produce zaxinone, a novel apocarotenoid metabolite in vitro. Loss-of-function mutants (zas) contain less zaxinone, exhibit retarded growth and showed elevated levels of strigolactones (SLs), a hormone that determines plant architecture, mediates mycorrhization and facilitates infestation by root parasitic weeds, such as Striga spp. Application of zaxinone can rescue zas phenotypes, decrease SL content and release and promote root growth in wild-type seedlings. In conclusion, we show that zaxinone is a key regulator of rice development and biotic interactions and has potential for increasing crop growth and combating Striga, a severe threat to global food security.
Strain engineering in perovskite solar cells and its impacts on carrier dynamics
Authors: Zhu Cheng , Niu Xiuxiu , Fu Yuhao , Li Nengxu , Hu Chen , Chen Yihua , He Xin , Na Guangren , Liu Pengfei , Zai Huachao , Ge Yang , Lu Yue , Ke Xiaoxing , Bai Yang , Yang Shihe , Chen Pengwan , Li Yujing , Sui Manling , Zhang Lijun , Zhou Huanping , Chen Qi
Published: February 2019

The mixed halide perovskites have emerged as outstanding light absorbers for efficient solar cells. Unfortunately, it reveals inhomogeneity in these polycrystalline films due to composition separation, which leads to local lattice mismatches and emergent residual strains consequently. Thus far, the understanding of these residual strains and their effects on photovoltaic device performance is absent. Herein we study the evolution of residual strain over the films by depth-dependent grazing incident X-ray diffraction measurements. We identify the gradient distribution of in-plane strain component perpendicular to the substrate. Moreover, we reveal its impacts on the carrier dynamics over corresponding solar cells, which is stemmed from the strain induced energy bands bending of the perovskite absorber as indicated by first-principles calculations. Eventually, we modulate the status of residual strains in a controllable manner, which leads to enhanced PCEs up to 20.7% (certified) in devices via rational strain engineering.
Differential organization of tonic and chronic B cell antigen receptors in the plasma membrane
Authors: Gomes de Castro Maria Angela , Wildhagen Hanna , Sograte-Idrissi Shama , Hitzing Christoffer , Binder Mascha , Trepel Martin , Engels Niklas , Opazo Felipe
Published: February 2019

Stimulation of the B cell antigen receptor (BCR) triggers signaling pathways that promote the differentiation of B cells into plasma cells. Despite the pivotal function of BCR in B cell activation, the organization of the BCR on the surface of resting and antigen-activated B cells remains unclear. Here we show, using STED super-resolution microscopy, that IgM-containing BCRs exist predominantly as monomers and dimers in the plasma membrane of resting B cells, but form higher oligomeric clusters upon stimulation. By contrast, a chronic lymphocytic leukemia-derived BCR forms dimers and oligomers in the absence of a stimulus, but a single amino acid exchange reverts its organization to monomers in unstimulated B cells. Our super-resolution microscopy approach for quantitatively analyzing cell surface proteins may thus help reveal the nanoscale organization of immunoreceptors in various cell types.
Long non-coding RNAs discriminate the stages and gene regulatory states of human humoral immune response
Authors: Agirre Xabier , Meydan Cem , Jiang Yanwen , Garate Leire , Doane Ashley S. , Li Zhuoning , Verma Akanksha , Paiva Bruno , Martín-Subero José I. , Elemento Olivier , Mason Christopher E. , Prosper Felipe , Melnick Ari
Published: February 2019

lncRNAs make up a majority of the human transcriptome and have key regulatory functions. Here we perform unbiased de novo annotation of transcripts expressed during the human humoral immune response to find 30% of the human genome transcribed during this process, yet 58% of these transcripts manifest striking differential expression, indicating an lncRNA phylogenetic relationship among cell types that is more robust than that of coding genes. We provide an atlas of lncRNAs in naive and GC B-cells that indicates their partition into ten functionally categories based on chromatin features, DNase hypersensitivity and transcription factor localization, defining lncRNAs classes such as enhancer-RNAs (eRNA), bivalent-lncRNAs, and CTCF-associated, among others. Specifically, eRNAs are transcribed in 8.6% of regular enhancers and 36.5% of super enhancers, and are associated with coding genes that participate in critical immune regulatory pathways, while plasma cells have uniquely high levels of circular-RNAs accounted for by and reflecting the combinatorial clonal state of the Immunoglobulin loci.
Carbonate formation in salt dome cap rocks by microbial anaerobic oxidation of methane
Authors: Caesar K. H. , Kyle J. R. , Lyons T. W. , Tripati A. , Loyd S. J.
Published: February 2019

Major hydrocarbon accumulations occur in traps associated with salt domes. Whereas some of these hydrocarbons remain to be extracted for economic use, significant amounts have degraded in the subsurface, yielding mineral precipitates as byproducts. Salt domes of the Gulf of Mexico Basin typically exhibit extensive deposits of carbonate that form as cap rock atop salt structures. Despite previous efforts to model cap rock formation, the details of subsurface reactions (including the role of microorganisms) remain largely unknown. Here we show that cap rock mineral precipitation occurred via closed-system sulfate reduction, as indicated by new sulfur isotope data. 13C-depleted carbonate carbon isotope compositions and low clumped isotope-derived carbonate formation temperatures indicate that microbial, sulfate-dependent, anaerobic oxidation of methane (AOM) contributed to carbonate formation. These findings suggest that AOM serves as an unrecognized methane sink that reduces methane emissions in salt dome settings perhaps associated with an extensive, deep subsurface biosphere.
Self-trapped state enabled filterless narrowband photodetections in 2D layered perovskite single crystals
Authors: Li Junze , Wang Jun , Ma Jiaqi , Shen Hongzhi , Li Lu , Duan Xiangfeng , Li Dehui
Published: February 2019

Filterless narrowband photodetectors can realize color discrimination without filter or bulk spectrometer, thus greatly reducing the system volume and cost for many imaging applications. Charge collection narrowing has been demonstrated to be a successful approach to achieve filterless narrowband photodetections; nevertheless, it sacrifices the sensitivity of the photodetectors. Here we show a highly tunable narrowband photodetector based on two-dimensional perovskite single crystals with high external quantum efficiency (200%), ultralow dark current (10−12 A), and high on–off ratio (103). The spectral response of the narrowband photodetectors can be continuously tuned from red to blue with all full-width at half-maximum < 60 nm and especially < 20 nm in blue wavelength range. The excellent performance can be ascribed to self-trapped states within bandgap and extremely low electrical conductivity in the out-of-plane direction. Our findings open the exciting potential of 2D perovskites for next-generation optoelectronics.
Giant thermoelectric power factor in ultrathin FeSe superconductor
Authors: Shimizu Sunao , Shiogai Junichi , Takemori Nayuta , Sakai Shiro , Ikeda Hiroaki , Arita Ryotaro , Nojima Tsutomu , Tsukazaki Atsushi , Iwasa Yoshihiro
Published: February 2019

The thermoelectric effect is attracting a renewed interest as a concept for energy harvesting technologies. Nanomaterials have been considered a key to realize efficient thermoelectric conversions owing to the low dimensional charge and phonon transports. In this regard, recently emerging two-dimensional materials could be promising candidates with novel thermoelectric functionalities. Here we report that FeSe ultrathin films, a high-Tc superconductor (Tc; superconducting transition temperature), exhibit superior thermoelectric responses. With decreasing thickness d, the electrical conductivity increases accompanying the emergence of high-Tc superconductivity; unexpectedly, the Seebeck coefficient α shows a concomitant increase as a result of the appearance of two-dimensional natures. When d is reduced down to ~1 nm, the thermoelectric power factor at 50 K and room temperature reach unprecedented values as high as 13,000 and 260 μW cm−1 K−2, respectively. The large thermoelectric effect in high Tc superconductors indicates the high potential of two-dimensional layered materials towards multi-functionalization.
Divergent roles of FT-like 9 in flowering transition under different day lengths in Brachypodium distachyon
Authors: Qin Zhengrui , Bai Yuxue , Muhammad Sajid , Wu Xia , Deng Pingchuan , Wu Jiajie , An Hailong , Wu Liang
Published: February 2019

Timing of reproductive transition is precisely modulated by environmental cues in flowering plants. Facultative long-day plants, including Arabidopsis and temperate grasses, trigger rapid flowering in long-day conditions (LDs) and delay flowering under short-day conditions (SDs). Here, we characterize a SD-induced FLOWERING LOCUS T ortholog, FT-like 9 (FTL9), that promotes flowering in SDs but inhibits flowering in LDs in Brachypodium distachyon. Mechanistically, like photoperiod-inductive FT1, FTL9 can interact with FD1 to form a flowering activation complex (FAC), but the floral initiation efficiency of FTL9-FAC is much lower than that of FT1-FAC, thereby resulting in a positive role for FTL9 in promoting floral transition when FT1 is not expressed, but a dominant-negative role when FT1 accumulates significantly. We also find that CONSTANS 1 (CO1) can suppress FTL9 in addition to stimulate FT1 to enhance accelerated flowering under LDs. Our findings on the antagonistic functions of FTL9 under different day-length environments will contribute to understanding the multifaceted roles of FT in fine-tune modulation of photoperiodic flowering in plants.
PD-1 blockade potentiates HIV latency reversal ex vivo in CD4+ T cells from ART-suppressed individuals
Authors: Fromentin Rémi , DaFonseca Sandrina , Costiniuk Cecilia T. , El-Far Mohamed , Procopio Francesco Andrea , Hecht Frederick M. , Hoh Rebecca , Deeks Steven G. , Hazuda Daria J. , Lewin Sharon R. , Routy Jean-Pierre , Sékaly Rafick-Pierre , Chomont Nicolas
Published: February 2019

HIV persists in latently infected CD4+ T cells during antiretroviral therapy (ART). Immune checkpoint molecules, including PD-1, are preferentially expressed at the surface of persistently infected cells. However, whether PD-1 plays a functional role in HIV latency and reservoir persistence remains unknown. Using CD4+ T cells from HIV-infected individuals, we show that the engagement of PD-1 inhibits viral production at the transcriptional level and abrogates T-cell receptor (TCR)-induced HIV reactivation in latently infected cells. Conversely, PD-1 blockade with the monoclonal antibody pembrolizumab enhances HIV production in combination with the latency reversing agent bryostatin without increasing T cell activation. Our results suggest that the administration of immune checkpoint blockers to HIV-infected individuals on ART may facilitate latency disruption.
Adenosine deaminase-1 delineates human follicular helper T cell function and is altered with HIV
Authors: Tardif Virginie , Muir Roshell , Cubas Rafael , Chakhtoura Marita , Wilkinson Peter , Metcalf Talibah , Herro Rana , Haddad Elias K.
Published: February 2019

Follicular helper T cells (Tfh) play critical roles instructing, and initiating T-cell dependent antibody responses. The underlying mechanisms that enhance their function is therefore critical for vaccine development. Here we apply gene array analysis identifying adenosine deaminase (ADA) as a key molecule that delineates a human Tfh helper program in proliferating circulating Tfh (cTfh) cells and Germinal Centers Tfh (GC-Tfh). ADA-1 expression and enzymatic activity are increased in efficient cTfh2-17/GC-Tfh cells. Exogenous ADA-1 enhances less efficient cTfh1 and pro-follicular Tfh PD-1+ CXCR5+ cells to provide B cell help, while pharmacological inhibition of ADA-1 activity impedes cTfh2-17/GC-Tfh function and diminished antibody response. Mechanistically, ADA-1 controls the Tfh program by influencing IL6/IL-2 production, controlling CD26 extracellular expression and could balance signals through adenosine receptors. Interestingly, dysfunctional Tfh from HIV infected-individual fail to regulate the ADA pathway. Thus, ADA-1 regulates human Tfh and represents a potential target for development of vaccine strategy.
Active learning in materials science with emphasis on adaptive sampling using uncertainties for targeted design
Authors: Lookman Turab , Balachandran Prasanna V. , Xue Dezhen , Yuan Ruihao
Published: February 2019

One of the main challenges in materials discovery is efficiently exploring the vast search space for targeted properties as approaches that rely on trial-and-error are impractical. We review how methods from the information sciences enable us to accelerate the search and discovery of new materials. In particular, active learning allows us to effectively navigate the search space iteratively to identify promising candidates for guiding experiments and computations. The approach relies on the use of uncertainties and making predictions from a surrogate model together with a utility function that prioritizes the decision making process on unexplored data. We discuss several utility functions and demonstrate their use in materials science applications, impacting both experimental and computational research. We summarize by indicating generalizations to multiple properties and multifidelity data, and identify challenges, future directions and opportunities in the emerging field of materials informatics.
Enhancing hydrogen evolution on the basal plane of transition metal dichacolgenide van der Waals heterostructures
Authors: Ling Faling , Kang Wei , Jing Huirong , Zeng Wen , Chen Yankun , Liu Xiaoqing , Zhang Yixin , Qi Lin , Fang Liang , Zhou Miao
Published: February 2019

Recent years have seen a surge in the use of low-dimensional transition metal dichacolgenides, such as MoS2, as catalysts for the electrochemical hydrogen evolution reaction. In particular, sulfur vacancies in MoS2 can activate the inert basal plane, but that requires an unrealistically high defect concentration (~9%) to achieve optimal activity. In this work, we demonstrate by first-principles calculations that assembling van der Waals heterostructures can enhance the catalytic activity of MoS2 with low concentrations of sulfur vacancies. We integrate MoS2 with various two-dimensional nanostructures, including graphene, h-BN, phosphorene, transition metal dichacolgenides, MXenes, and their derivatives, aiming to fine-tune the free energy of atomic hydrogen adsorption. Remarkably, an optimal free energy can be achieved for a low sulfur vacancy concentration of ~2.5% in the MoS2/MXene-OH heterostructure, as well as high porosity and tunability. These results demonstrate the potential of combining two-dimensional van der Waals assembly with defect engineering for efficient hydrogen production.
Low Frequency ALK Hotspots Mutations In Neuroblastoma Tumours Detected By Ultra-deep Sequencing: Implications For ALK Inhibitor Treatment
Authors: Javanmardi Niloufar , Fransson Susanne , Djos Anna , Sjöberg Rose-Marie , Nilsson Staffan , Truvé Katarina , Kogner Per , Martinsson Tommy
Published: February 2019

The ALK tyrosine kinase receptor is oncogenically activated in neuroblastoma. Whereas numerous ALK fusion genes have been reported in different malignancies, in neuroblastoma ALK is mainly activated through point mutations. Three hotspot residues (F1174, F1245, and R1275) account for 85% of mutant ALK seen in neuroblastoma. In a cohort of 105 Swedish neuroblastoma cases of all stages, these hotspot regions were re-sequenced (>5000X). ALK mutations were detected in 16 of 105 patients (range of variant allele fraction: 2.7–60%). Mutations at the F1174 and F1245 hotspot were observed in eleven and three cases respectively. ALK mutations were also detected at the I1171 and L1240 codons in one tumor each. No mutations were detected at R1275. Sanger sequencing could confirm ALK status for all mutated samples with variant allele fraction above 15%. Four of the samples with subclonal ALK mutation fraction below this would have gone undetected relying on Sanger sequencing only. No distinct mutation spectrum in relation to neuroblastoma tumours genomic subtypes could be detected although there was a paucity of ALK mutations among 11q-deleted tumors. As ALK mutations status opens up an excellent opportunity for application of small molecule inhibitors targeting ALK, early and sensitive detection of ALK alterations is clinically important considering its potential role in tumour progression.
Defects, Lithium Mobility and Tetravalent Dopants in the Li3NbO4 Cathode Material
Authors: Kuganathan Navaratnarajah , Kordatos Apostolos , Kelaidis Nikolaos , Chroneos Alexander
Published: February 2019

The defect processes of oxides such as self-diffusion impact their performance in electrochemical devices such as batteries and solid oxide fuel cells. The performance of lithium ion batteries can be improved by increasing the Li-ion diffusion. In that respect Li3NbO4 is identified as a positive electrode material for rechargeable lithium ion batteries. Here, we employ static atomistic scale simulations to examine the defect properties, doping behaviour and lithium ion migration paths in Li3NbO4. The present calculations show a correct reproduction of experimentally observed crystal structure of Li3NbO4. The Li-Nb anti-site defect is found to be the dominant intrinsic defect process suggesting that a small concentration of Li on Nb sites and Nb on Li sites is present. Vacancy assisted long range lithium diffusion paths were examined and our calculations reveal that the lowest activation energy (1.13 eV) migration path is two dimensional forming a zig-zag shape. Subvalent doping by Ge on the Nb site is thermodynamically favourable process and a potential strategy to incorporate extra Li in the form of Li interstitial in Li3NbO4. The results presented herein can motivate further experimental work for the development of Li3NbO4 based batteries.
Molecular modelling evaluation of exon 18 His845_Asn848delinsPro PDGFRα mutation in a metastatic GIST patient responding to imatinib
Authors: Nannini Margherita , Tarantino Giuseppe , Indio Valentina , Ravegnini Gloria , Astolfi Annalisa , Urbini Milena , De Leo Antonio , Santini Donatella , Ceccarelli Claudio , Gruppioni Elisa , Altimari Annalisa , Castellucci Paolo , Fanti Stefano , Di Scioscio Valerio , Saponara Maristella , Gatto Lidia , Pession Andrea , Martelli Pier Luigi , Casadio Rita , Pantaleo Maria Abbondanza
Published: February 2019

Platelet-Derived Growth Factor Receptor Alpha (PDGFRA) mutations occur in approximately 5–7% of gastrointestinal stromal tumours (GIST). Over half of all PDGFRA mutations are represented by the substitution at position 842 in the A-loop of an aspartic acid (D) with a valine (V), recognized as D842V, conferring primary resistance to imatinib in vitro and in clinical observations due to the conformation of the kinase domain, which negatively affects imatinib binding. The lack of interaction between imatinib and the D842V PDGFRA mutated model has been established and widely confirmed in vivo. However, for the other PDGFRA mutations, the correlation between pre-clinical and clinical data is still unclear. An in silico evaluation of the p.His845_Asn848delinsPro mutation involving exon 18 of PDGFRA in a metastatic GIST patient responding to first-line imatinib has been provided. Docking analyses were performed, and the ligand-receptor interactions were evaluated with the jCE algorithm for structural alignment. The docking simulation and structural superimposition analysis show that PDGFRA p.His845_Asn848delinsPro stabilizes the imatinib binding site with the residues that are conserved in KIT. The in vivo evidence that PDGFRA p.His845_Asn848delinsPro is sensitive to imatinib was confirmed by the molecular modelling, which may represent a reliable tool for the prediction of clinical outcomes and treatment selection in GIST, especially for rare mutations.
Lambda bacteriophage nanoparticles displaying GP2, a HER2/neu derived peptide, induce prophylactic and therapeutic activities against TUBO tumor model in mice
Authors: Razazan Atefeh , Nicastro Jessica , Slavcev Roderick , Barati Nastaran , Arab Atefeh , Mosaffa Fatemeh , Jaafari Mahmoud Reza , Behravan Javad
Published: February 2019

Generating a protective and long-lasting immune response is the primary goal in the expanding field of immunotherapeutic research. In current study we designed an immunogenic bacteriophage- based vaccine to induce a cytotoxic T lymphocyte activity against a mice tumor model over-expressing HER2/neu. Bacteriophage λ displaying a HER2/neu derived peptide GP2 was constructed and used as an anti-cancer vaccine in a BALB/c mouse xenograft tumor model. The results of our study indicated that phage nanoparticles displaying GP2 as a fused peptide to the gpD phage capsid protein induced a robust CTL response. Furthermore, the chimeric phage nanoparticles protected mice against HER2/neu-positive tumor challenge in both prophylactic and therapeutic settings. In conclusion, we propose that λ phage nanoparticles decorated with GP2 peptide merit further investigation for the development of peptide-based vaccines against HER2/neu overexpressing tumors.
The effect of Robertsonian translocations on the intranuclear positioning of NORs (nucleolar organizing regions) in human sperm cells
Authors: Wiland Ewa , Olszewska Marta , Huleyuk Nataliya , Chernykh Vyacheslav B. , Kurpisz Maciej
Published: February 2019

Only a few studies have described sperm chromosome intranuclear positioning changes in men with reproductive failure and an incorrect somatic karyotype. We studied the influence of Robertsonian translocations on the acrocentric chromosome positioning in human sperm cells. The basis of the analysis was the localization of NORs (nucleolar organizing regions) in sperm nuclei from three Robertsonian translocation carriers, namely, rob(13;22), rob(13;15) and rob(13;14), with a known meiotic segregation pattern. All three carriers presented with a similar percentage of genetically normal sperm cells (i.e., approximately 40%). To visualize NORs, we performed 2D-FISH with directly labelled probes. We used the linear and radial topologies of the nucleus to analyse the NORs distribution. We found an affected positioning of NORs in each case of the Robertsonian translocations. Moreover, the NORs tended to group, most often in two clusters. Both in Robertsonian carriers and control sperm cells, NORs mostly colocalized in the medial areas of the nuclei. In the case of the Roberstonian carriers, NORs were mostly concentrated in the peripheral part of the medial area, in contrast to control sperm cells in which the distribution was more dispersed towards the internal area.
Extracellular and intracellular small-molecule galectin-3 inhibitors
Authors: Stegmayr John , Zetterberg Fredrik , Carlsson Michael C. , Huang Xiaoli , Sharma Gunjan , Kahl-Knutson Barbro , Schambye Hans , Nilsson Ulf J. , Oredsson Stina , Leffler Hakon
Published: February 2019

Galectin-3 is a carbohydrate binding protein which has important roles in cancer and immunity. Potent galectin-3 inhibitors have been synthesized, for experimental purposes and potential clinical use. As galectin-3 is implicated in both intra- and extracellular activities, permeability of galectin-3 inhibitors is an important parameter determining biological effects. We compared the cellular uptake of galectin-3 inhibitors and their potency in the intracellular or extracellular space. The inhibitors differed in their polar surface area (PSA), but had similar affinities for galectin-3. Using a well-established permeability assay, we confirmed that the uptake was significantly higher for the inhibitor with the lowest PSA, as expected. To analyze intracellular activity of the inhibitors, we developed a novel assay based on galectin-3 accumulation around damaged intracellular vesicles. The results show striking differences between the inhibitors intracellular potency, correlating with their PSAs. To test extracellular activity of the inhibitors, we analyzed their potency to block binding of galectin-3 to cell surfaces. All inhibitors were equally able to block galectin-3 binding to cells and this was proportional to their affinity for galectin-3. These inhibitors may serve as useful tools in exploring biological roles of galectin-3 and may further our understanding of intracellular versus extracellular roles of galectin-3.
Long-term effects of different planting patterns on greenhouse soil micromorphological features in the North China Plain
Authors: Liu Zhe , Han Jichang , Sun Zenghui , Chen Tianqing , Hou Yin , Lei Na , Dong Qiguang , He Jing , Lu Yizhong
Published: February 2019

Soil structure represents a basis for soil water retention and fertiliser availability. Here, we performed a micromorphological analysis of thin soil sections to evaluate the effects of 10 years of organic planting (OPP), pollution-free planting (PFP), and conventional planting (CPP) on greenhouse soil structure in the North China Plain. We also analysed soil bulk density, soil organic matter (SOM), and wet aggregate stability. The CPP soil microstructure included weakly separated angular block or plate forms and weak development of soil pores (fissured or simply accumulated pores) with the highest bulk density (1.33 g cm−3) and lowest SOM (26.76 g kg−1). Unlike CPP, the OPP soil microstructure was characterised by highly separated granular and aggregated structures and an abundance of plant and animal remains. OPP was associated with the highest total porosity (55.4%), lowest bulk density (1.17 g cm−3), and highest SOM (54.81 g kg−1) in the soil surface layer. OPP also improved the ventilation pore content (proportion of pores >0.1 mm, 44.09%). OPP aggregates showed different hierarchies of crumb microstructure and higher mean weight diameter and geometric mean diameter values than did CPP. These results confirm the benefits of long-term OPP for soil structure and quality in the greenhouse.