bluuebunny/crossref_metadata_2025 huggingface dataset:
A Bound on Expected Stock Returns
Authors: Kadan Ohad , Tang Xiaoxiao
Published: July 2019

We present a sufficient condition under which the prices of options written on a particular stock can be aggregated to calculate a lower bound on the expected returns of that stock. The sufficient condition imposes a restriction on a combination of the stock’s systematic and idiosyncratic risk. The lower bound is forward-looking and can be calculated on a high-frequency basis. We estimate the bound empirically and study its cross-sectional properties. We find that the bound increases with beta and book-to-market ratio and decreases with size and momentum. The bound provides an economically meaningful signal about future stock returns. (JEL G11, G12)

Authors have furnished an Internet Appendix, which is available on the Oxford University Press Web site next to the link to the final published paper online.
OCCUPATIONAL RADIATION EXPOSURE DOSE OF THE EYE IN DEPARTMENT OF CARDIAC ARRHYTHMIA PHYSICIAN
Authors: Kato Mamoru , Chida Koichi , Ishida Takato , Sasaki Fumiaki , Toyoshima Hideto , Oosaka Hajime , Terata Ken , Abe Yoshihisa , Kinoshita Toshibumi
Published: July 2019

Interventional radiology (IR) procedures tend to be complex, which delivers high radiation exposure to patient. In the present study, we measured the radiation exposure dose [Hp(3)] in the eye using a direct eye dosemeter placed next to the physician’s eye during procedures. Physicians wore a direct eye dosemeter just lateral to eyes and an additional direct eye dosemeter outside the radiation protective eyeglasses close to their eyes. Additionally, a neck glass badge was worn at the neck. Although we found a positive correlation between the left neck glass badge dose [Hp(0.07)] and the left eye lens dose [Hp(3)], the value of R2 of the regression equation were 0.62 and 0.71 (outside and inside). We thought that the exact eye lens dose might not be estimated from the neck glass badge. In conclusion, a correct evaluation of the lens dose [Hp(3)] using the direct eye dosemeter is recommended for tachyarrhythmia physicians.
Youth Sexual Development: A Primer for Social Workers
Authors: Brandon-Friedman Richard A
Published: July 2019

Sexuality and sexual expression are core aspects of most clients’ lives, yet most schools of social work fail to cover sexual development, leaving social workers uninformed about this essential area of human development. This is particularly the case when the sexual development of youths is concerned, as youth sexuality is often considered too controversial to explore. Considering a positive approach to youth sexuality that seeks to enhance youths’ sexual development and promote their achievement of full sexual and reproductive rights, this article seeks to provide social workers with a resource they can use to enhance their understanding of youth sexual development and its applicability to social work practice. The two main theoretical orientations used to understand sexual identity development are covered as well as the research support for each. Following the explanation of theory is a discussion of how the two theoretical orientations can be integrated to form a more expansive base for the understanding of sexual identity development. A final section provides guidance on how an advanced understanding of youthful sexual identity development can enhance social work practice at the micro, mezzo, and macro levels.
Seroprevalence of Zika virus in selected regions in Kenya
Authors: Kisuya Bramuel , Masika Moses M , Bahizire Esto , Oyugi Julius O
Published: July 2019

Background

The Zika virus pandemic in South America in 2015–2016 and the association of Zika virus infection with neurological complications such as microcephaly in newborns distressed the global community. There is limited data on the prevalence of Zika virus in Kenya despite evidence of its circulation in East Africa. This study aimed at assessing the seroprevalence of Zika virus in selected areas in Kenya.

Methods

Healthy adult human sera originally collected from Nairobi, Eldoret and Kisumu from 2009 to 2014 and archived at the University of Nairobi laboratories were examined for Zika virus antibodies. An IgG-based ELISA was used to screen 577 sera. Any serum tested positive by ELISA was confirmed for Zika virus infection by plaque reduction neutralization test (PRNT).

Results

The seroprevalence of Zika virus in the study population was about 0.2 % (1/577) as confirmed by PRNT. Additionally, three sera that were false positive by ELISA for Zika virus were confirmed as positive for dengue virus by PRNT.

Conclusion

There was evidence of low previous exposure to Zika virus in the study population. Of the three regions in Kenya where sera for this study were obtained, only Kisumu County had one case of previous exposure to Zika virus.
Impact of Unilateral versus Bilateral Breast Reconstruction on Procedure Choices and Outcomes
Authors: Taylor Erin M. , Wilkins Edwin G. , Pusic Andrea L. , Qi Ji , Kim Hyungjin Myra , Hamill Jennifer B. , Guldbrandsen Gretchen E. , Chun Yoon S.
Published: July 2019

Background:

In choosing between implant-based and autologous breast reconstruction, surgeons and patients must weigh relative risks and benefits. However, differences in outcomes across procedure types may vary between unilateral versus bilateral reconstructions. Procedure-related differences in complications and patient-reported outcomes were evaluated for unilateral and bilateral reconstruction.

Methods:

Complications and patient-reported outcomes (BREAST-Q and Patient-Reported Outcomes measurement Information System surveys) were assessed at 2 years for patients undergoing autologous or implant-based reconstructions. Stratified regression models compared outcomes between autologous and implant-based reconstructions, separately for unilateral and bilateral cohorts.

Results:

Among 2125 patients, 917 underwent unilateral (600 implant and 317 autologous) and 1208 underwent bilateral (994 implant and 214 autologous) reconstructions. Complication rates were significantly higher in the autologous versus implant-based group for both unilateral (overall: OR, 2.50, p < 0.001; major: OR, 2.19, p = 0.001) and bilateral (overall: OR, 2.13, p < 0.001; major: OR, 1.69, p = 0.014) cohorts. In unilateral reconstruction, the autologous group demonstrated significantly better patient-reported outcomes versus implant-based group in satisfaction with breast (mean difference, 9.85; p < 0.001), psychosocial well-being (mean difference, 4.84; p = 0.006), and sexual well-being (mean difference, 11.42; p < 0.001). In bilateral reconstruction, the autologous group demonstrated significantly higher patient-reported outcomes only for satisfaction with breast (mean difference, 5.13; p = 0.001).

Conclusions:

Although autologous reconstruction is associated with significantly better patient-reported outcomes compared to implant-based techniques in unilateral reconstruction, procedure choice has far less impact in bilateral reconstruction. Autologous procedures have higher complications rates in both unilateral and bilateral settings.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, III.
Autogenous Fat Grafting to the Breast and Gluteal Regions: Safety Profile Including Risks and Complications
Authors: Chopan Mustafa , White Jared A. , Sayadi Lohrasb R. , Buchanan Patrick J. , Katz Adam J.
Published: July 2019

Given the widespread utility and therapeutic potential of autogenous fat grafting, plastic surgeons should be familiar with its safety profile and associated adverse events. This article provides a critical review of the literature and delineates risk factors associated with various complications when grafting to the breast and gluteal regions. The majority of adverse events are related to fat necrosis and require minimal diagnostic or therapeutic intervention. Larger graft volumes, as in cosmetic augmentation, are associated with higher incidences of fatty necrosis. The oncologic safety of fat grafting is supported by multiple clinical studies with thousands of breast cancer patients, albeit predominantly retrospective in nature. Although less frequent, serious complications include fat emboli during gluteal augmentation. Identification of associated risk factors and implementation of proper surgical techniques may minimize the occurrence of life-threatening complications.
Platelet-Rich Plasma and Platelet-Rich Fibrin Enhance the Outcomes of Fat Grafting: A Comparative Study
Authors: Xiong Shaoheng , Qiu Lihong , Su Yinjun , Zheng Hui , Yi Chenggang
Published: July 2019

Background:

Autologous fat grafting is an efficient procedure in plastic surgery. However, its long-term tissue absorption is variable and technique-dependent. Platelet-rich plasma positively affects fat-grafting outcomes but still has shortcomings, and platelet-rich fibrin has been reported to have efficacy in fat transplantation. Here, we compared the effects of platelet-rich fibrin and platelet-rich plasma in fat grafting using histologic analysis.

Methods:

Twenty rabbits were divided randomly into two groups. In each group, the groin region fat pads were cut into 1-mm3 granules. Platelet-rich fibrin–treated or platelet-rich plasma–treated fat granules were transplanted into one ear, whereas the contralateral ear was transplanted with normal saline–treated fat granules. Histologic characteristics and capillary density of grafted tissue were analyzed 12 weeks after fat grafting.

Results:

The grafted fat in the platelet-rich fibrin–treated group showed higher tissue retention than that in the control group [weight retention, 19.57 percent (interquartile range, 13.87 to 29.93 percent) versus 9.04 percent (interquartile range, 6.16 to 16.80 percent), p < 0.05; and volume retention, 18.00 percent (interquartile range, 10.50 to 26.50 percent) versus 8.00 percent (interquartile range, 5.75 to 13.25 percent), p < 0.05] and higher neovascularized capillary density than that in the platelet-rich plasma–treated and control groups. The platelet-rich plasma–treated group showed higher vessel density without superior tissue retention compared with the control group.

Conclusion:

Platelet-rich fibrin increased tissue retention, quality, and vascularization of grafted fat compared with the control group and showed effects similar to those of platelet-rich plasma on tissue retention and histologic graft improvement.
Digital Image Speckle Correlation to Optimize Botulinum Toxin Type A Injection: A Prospective, Randomized, Crossover Trial
Authors: Verma Richa , Klein Gabriel , Xu Yan , Rafailovich Miriam , Gilbert Fernandez Juan Jose , Khan Sami U. , Bui Duc T. , Dagum Alexander B.
Published: July 2019

Background:

Historically, physicians have relied on their subjective measures when determining the site and dosages for botulinum toxin type A injections. Digital image speckle correlation is a technology that tracks pore movement from rest to maximal exertion, allowing for the determination of the optimal sites of injection. In this prospective, randomized, crossover trial, the efficacy of using digital image speckle correlation was compared to physician assessment in choosing botulinum toxin type A injection sites.

Methods:

Ten female patients were analyzed in this blinded crossover study. Subjects were randomized to either injections based on digital image speckle correlation analysis or injections based on the 2004 facial aesthetics consensus recommendations. All patients received 20 U of botulinum toxin type A in the glabellar region and were crossed over and reinjected after 6 months. Follow-up was completed with the Facial Line Outcomes 11-item survey and repeated imaging with digital image speckle correlation, to measure patient satisfaction and degree of paralysis, respectively. Statistical comparison was completed by means of matched sample t test.

Results:

On average, the digital image speckle correlation analysis provided 4.8 injection sites, whereas the practitioner chose five injections sites. Patients receiving digital image–directed injections had higher rates of satisfaction on the Facial Line Outcomes instrument (p = 0.0003) and a larger degree of paralysis (p = 0.003). Furthermore, muscle function returned to normal later in patients injected with digital image speckle correlation (17.9 weeks versus 20 weeks; p = 0.03).

Conclusions:

This study demonstrates the benefits of using digital image speckle correlation in determining optimal botulinum toxin type A injection location. Digital analysis allows practitioners to better treat facial rhytides by eliminating subjective decisions regarding dose and site of injection.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, II.
The Pushback Pharyngeal Flap: An 18-Year Experience
Authors: Rochlin Danielle H. , Mittermiller Paul A. , Sheckter Clifford C. , Menard Robert M.
Published: July 2019

Background:

The pharyngeal flap is one of the oldest and most popular techniques for correction of velopharyngeal insufficiency. The authors describe a large series using a technique that combines a pharyngeal flap with a palate pushback to avoid common causes of operative failure while restoring the velopharyngeal mechanism.

Methods:

A retrospective cohort study was performed of patients who underwent a pushback pharyngeal flap by a single surgeon from 2000 to 2017. All patients had a preoperative nasoendoscopy diagnostic of velopharyngeal insufficiency. Operative technique involved elevation of the hard palate mucosa through a retroalveolar incision, passage of the flap through the nasopharyngeal mucosa opening, and inset with sutures through the hard palate mucosa.

Results:

There were 40 patients with a median age of 9.7 years. Preoperative closure patterns were predominately coronal (85.7 percent), with poor posterior wall motion and an average gap size of 27.5 mm2. Postoperative complications included flap dehiscence (n = 1), transient dysphagia (n = 2), obstructive sleep apnea (n = 4), and a palatal fistula and/or persistent velopharyngeal insufficiency that required further surgery (n = 6). At an average of 2.5 years postoperatively, 91.7 percent of patients achieved adequate velopharyngeal function, with significant improvements in the majority of speech metrics (p < 0.001).

Conclusions:

The pushback pharyngeal flap is a safe and effective technique for treatment of velopharyngeal insufficiency. Advantages include high, secure inset with prevention of palatal scar contracture and shortening.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, IV.
Racial Disparities in Cleft Palate Repair
Authors: Wu Robin T. , Peck Connor J. , Shultz Blake N. , Travieso Roberto , Steinbacher Derek M.
Published: July 2019

Background:

Various factors can influence outcomes in cleft palate care. This study sought to determine the impact of race on admissions, hospital costs, and short-term complications in cleft palate repair.

Methods:

Cleft palate operations were identified in the Kids’ Inpatient Database data, from 2000 to 2009. Data were combed for demographics, perioperatives, complications, and hospital characteristics. Bivariate and multivariate analyses were performed between races in total, primary, and revision cohorts.

Results:

There were 3464 white, 1428 Hispanic, 413 black, 398 Asian/Pacific-Islander, and 470 patients of other races captured. Black patients experienced more emergent admissions (p = 0.005) and increased length of stay (p = 0.029). Hospital charges were highest for black and Hispanic patients and lowest for white patients (p = 0.019). Black patients had more total complications than non-black patients (p = 0.039), including higher rates of postoperative fistula (p = 0.020) and nonspecific complications among revision repairs (p = 0.003). Asian/Pacific Islander in the primary cohort experienced higher rates of accidental puncture (p = 0.031) and fistula (p < 0.001). Other patients had the highest rates of wound disruption (p = 0.013). After controlling for race, diagnosis, Charlson Comorbidity Index score, region, elective/nonelective, payer, and income quartile, length of stay (p < 0.001) and age (p < 0.001) were associated with increases in both total complications and costs.

Conclusions:

Race may play a significant role in cleft palate repair, as white patients had fewer complications, shorter length of stay, and lower costs following repair. Delayed age at treatment may predispose patients to adverse sequelae in minority populations, in terms of influencing length of stay and costs.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Risk, II.
Hair-bearing human skin generated entirely from pluripotent stem cells
Authors: Lee Jiyoon , Rabbani Cyrus , Gao Hongyu , Steinhart Matthew , Woodruff Benjamin M. , Pflum Zachary , Kim Alexander , Heller Stefan , Liu Yunlong , Shipchandler Taha Z. , Koehler Karl R.
Published: July 2019

The skin is important for regulating bodily fluid retention and temperature, guarding against external stresses, and mediating touch and pain sensation. The skin is also susceptible to damage from burns, diseases, or genetic defects, which affect nearly one billion people worldwide1,2. For the advancement of skin regenerative therapies, it remains challenging to construct new skin with hair follicles and nerves in tissue cultures and in bioengineered skin grafts3–8. Here, we report an organoid culture system that generates complex skin from human pluripotent stem cells. We use step-wise modulation of the TGFβ and FGF signalling pathways to co-induce cranial epithelial cells and neural crest cells within a spherical cell aggregate. During 4-5 months incubation, we observe the emergence of a cyst-like skin organoid composed of stratified epidermis, fat-rich dermis, and pigmented hair follicles equipped with sebaceous glands. A network of sensory neurons and Schwann cells form nerve-like bundles that target Merkel cells in organoid hair follicles, mimicking human touch circuitry. Single-cell RNA sequencing and direct comparison to foetal specimens suggest that skin organoids are equivalent to human facial skin in the second-trimester of development. Moreover, we show that skin organoids produce planar hair-bearing skin when grafted on nude mice. Together, our results demonstrate the self-assembly of nearly complete skin tissue in vitro that can be used to reconstitute skin in vivo. We anticipate that our skin organoid model will be foundational to future studies of human skin development, disease modelling, or reconstructive surgery.
Restructuring of amygdala subregion apportion across adolescence
Authors: Campbell Claire E. , Mezher Adam F. , Eckel Sandrah P. , Tyszka J. Michael , Pauli Wolfgang M. , Nagel Bonnie J. , Herting Megan M.
Published: July 2019

Total amygdala volumes develop in association with sex and puberty, and postmortem studies find neuronal numbers increase in a nuclei specific fashion across development. Thus, amygdala subregions and composition may evolve with age. Our goal was to examine if amygdala subregion absolute volumes and/or relative proportion varies as a function of age, sex, or puberty in a large sample of typically developing adolescents (N=408, 43% female, 10-17 years). Utilizing the in vivo CIT168 atlas, we quantified 9 subregions and implemented Generalized Additive Mixed Models to capture potential non-linear associations with age and pubertal status between sexes. Only males showed significant age associations with the basolateral ventral and paralaminar subdivision (BLVPL), central nucleus (CEN), and amygdala transition area (ATA). Again, only males showed relative differences in the proportion of the BLVPL, CEN, ATA, along with lateral (LA) and amygdalostriatal transition area (ASTA), with age. Using a best-fit modeling approach, age, and not puberty, was found to drive these associations. The results suggest that amygdala subregions show unique developmental patterns with age in males across adolescence. Future research is warranted to determine if our findings may contribute to sex differences in mental health that emerge across adolescence.
Targeted phosphoproteomics of the Ras signaling network reveal regulatory mechanisms mediated by oncogenic KRAS
Authors: Urisman Anatoly , Yuan Tina L. , Trinidad Marena , Morris John H. , Afghani Shervin , Oses-Prieto Juan A. , Ritchie Cayde D. , Zahari Muhammad S. , Benes Cyril H. , Burlingame Alma L. , McCormick Frank
Published: July 2019

Background

KRAS mutations are present in up to 30% of lung adenocarcinoma cases and are associated with poor survival. No effective targeted therapy against KRAS is currently available, and novel strategies to counteract oncogenic KRAS signaling are needed.

Results

We used targeted proteomics to monitor abundance and site-specific phosphorylation in a network of over 150 upstream and downstream effectors of KRAS signaling in H358 cells (KRAS G12C). We compared patterns of protein regulation following sustained signaling blockade in the RAS/ERK module at two different levels, KRAS and MEK. Network-based analysis demonstrated complex non-linear patterns of regulation with wide-spread crosstalk among diverse subnetworks. Among 85 most regulated proteins in the network, only 12 proteins showed concordant regulation in response to signaling blockade at both KRAS and MEK levels, while the remainder were either specifically regulated in response to KRAS knockdown or MEK inhibition or showed orthogonal regulation in both conditions. Dephosphorylation of DNA methyltransferase 1 (DNMT1) at S714 was identified among the changes unique to KRAS knockdown, and here we elucidate the role of this phosphorylation in KRAS-dependent transcriptional silencing of tumor suppressor genes.

Conclusions

Network-based analysis of the Ras signaling has shown complex non-linear patterns of regulation with wide-spread crosstalk among diverse subnetworks. Our work illustrates a targeted proteomics approach to functional interrogation of complex signaling networks focused on identification of readily testable hypotheses. These methods are widely applicable to diverse questions in tumor biology and other signaling paradigms.
Improving root characterisation for genomic prediction in cassava
Authors: Yonis Bilan Omar , del Carpio Dunia Pino , Wolfe Marnin , Jannink Jean-Luc , Kulakow Peter , Rabbi Ismail
Published: July 2019

Cassava is widely cultivated due to its high drought tolerance and high carbohydrate-containing storage roots. The lack of uniformity and irregular shape of storage roots within and between genotypes poses significant constraints on harvesting and post-harvest processing. Routine assessment of storage root size and shape in breeding plots relies on visual scores.

Here, we phenotyped the Genetic gain and offspring (C1) populations from the International Institute of Tropical Agriculture (IITA) breeding program for root shape and size-related traits using image analysis of storage root photographs taken in the field.

In our study, using univariate genome-wide association analysis, we detected for most shape and size related traits, significant QTL regions located on chromosomes 1 and 12. The QTL region on chromosome 12 has been previously associated, using IITA breeding populations, to cassava mosaic disease (CMD) resistance.

Because the uniformity in size and shape of cassava roots is an important breeding goal, we calculated the standard deviation of individual root measurements per clone. The use of standard deviation measurements allowed the identification of new significant QTL for Perimeter, Feret and Aspect Ratio on chromosomes 6, 9 and 16. Using genomic prediction cross validation, the accuracies of root size and shape-related traits were lower than those previously reported for dry matter content (DM) and cassava mosaic virus resistance (CMD). Predictive accuracies of the mean values of root size and shape image-extracted traits were mostly higher than yield trait prediction accuracies in the C1 population. This study aimed to evaluate the feasibility of the image phenotyping protocol and to assess the use of genome-wide analyses for size and shape image-extracted traits. The methodology described here and the results obtained in this study are promising and open up the opportunity to apply high-throughput methods in cassava.
Z-scores unite >70 pairwise indices of ecological similarity and association for binary data
Authors: Keil Petr
Published: July 2019

Pairwise ecological resemblance, which includes compositional similarity between sites (beta diversity), or associations between species (co-occurrence), can be measured by >70 indices. Classical examples for presence-absence data are Jaccard index or C-score. These can be expressed using contingency table matching components a, b, c and d - the joint presences, presences at only one site/species, and joint absences. Using simulations of point patterns for two species with known magnitude of association, I demonstrate that most of the indices describe this simulated association almost identically, as long as they are calculated as a Z-score, i.e. as deviation of the index from a null expectation. Further, I show that Z-scores estimated resemblance better than raw forms of the indices, particularly in the face of confounding effects of spatial scale and conspecific aggregation. Finally, I show that any single of the matching components, when expressed as Z-score, can be used as an index that performs as good as the classical indices; this also includes joint absences. All this simplifies selection of the “right” resemblance index, it underscores the advantage of expressing resemblance as deviation from a null expectation, and it revives the potential of joint absences as a meaningful ecological quantity.
Sample delivery using capillary and delivery medium for serial crystallography
Authors: Nam Ki Hyun
Published: July 2019

Serial crystallography (SX) is an innovative technology in structural biology that enables the visualization of molecular dynamics of macromolecules at room temperature. SX experiments always require a considerable amount of effort to deliver a crystal sample to the X-ray interaction point continuously and reliably. Here, a sample delivery method using a capillary and a delivery medium is introduced. The crystals embedded in the delivery medium can pass through the capillary tube, which is aligned with the X-ray beam, at very low flow rates without requiring elaborate delivery techniques and drastically reducing sample consumption. This simple but highly efficient sample delivery method can allow researchers to deliver crystals precisely to X-rays in SX experiments.
European common frog (Rana temporaria) recolonised Switzerland from multiple glacial refugia in northern Italy via trans- and circum-Alpine routes
Authors: Jansen van Rensburg A , Robin M , Phillips B C , Van Buskirk J
Published: July 2019

The high mountain ranges of western Europe have had a profound effect on the recolonisation of Europe from glacial refugia. The Alps present a particularly interesting case, because they present an absolute barrier to dispersal to most lineages, obstructing recolonisation from multiple refugia in the Italian Alps. Here we investigate the effect of the European Alps on the the phylogeographic history ofRana temporariaacross its range in Switzerland. Based on partialcytochrome bandCOX1sequences we find two mitochondrial lineages that occur roughly north and south of the alpine ridge bisecting Switzerland, with contact zones between them in the east and west. The northern haplogroup falls within the previously identified common western European haplogroup, while the southern haplogroup is unique to Switzerland. We find that the lineages diverged ~110 kya, approximately the onset of the last glacial maximum, indicative of origins in separate refugia. Phylogenetic analyses suggest that the lineages originate from two refugia in northern Italy, and colonised Switzerland via trans- and curcum-alpine routes. Our results show that the European Alps is a semi-permeable barrier to dispersal forR. temporaria, and have contributed to the complex recolonisation history of Switzerland.
Methods for Copy Number Aberration Detection from Single-cell DNA Sequencing Data
Authors: Fan Xian , Edrisi Mohammadamin , Navin Nicholas , Nakhleh Luay
Published: July 2019

Single-cell DNA sequencing technologies are enabling the study of mutations and their evolutionary trajectories in cancer. Somatic copy number aberrations (CNAs) have been implicated in the development and progression of various types of cancer. A wide array of methods for CNA detection has been either developed specifically for or adapted to single-cell DNA sequencing data. Understanding the strengths and limitations that are unique to each of these methods is very important for obtaining accurate copy number profiles from single-cell DNA sequencing data. Here we review the major steps that are followed by these methods when analyzing such data, and then review the strengths and limitations of the methods individually. In terms of segmenting the genome into regions of different copy numbers, we categorize the methods into three groups, select a representative method from each group that has been commonly used in this context, and benchmark them on simulated as well as real datasets. While single-cell DNA sequencing is very promising for elucidating and understanding CNAs, even the best existing method does not exceed 80% accuracy. New methods that significantly improve upon the accuracy of these three methods are needed. Furthermore, with the large datasets being generated, the methods must be computationally efficient.
Revisiting the landscape of evolutionary breakpoints across human genome using multi-way comparison
Authors: Vitae Golrokh , Remita Amine M. , Diallo Abdoulaye Baniré
Published: July 2019

Genome rearrangement is one of the major forces driving the processes of the evolution and disease development. The chromosomal position affected by these rearrangements are called breakpoints. The breakpoints occurring during the evolution of species are known to be non randomly distributed. Detecting their landscape and mapping them to genomic features constitute an important features in both comparative and functional genomics. Several studies have attempted to provide such mapping based on pairwise comparison of genes as conservation anchors. With the availability of more accurate multi-way alignments, we design an approach to identify synteny blocks and evolutionary breakpoints based on UCSC 45-way conservation sequence alignments with 12 selected species. The multi-way designed approach with the mild flexibility of presence of selected species, helped to have a better determination of human lineage-specific evolutionary breakpoints. We identified 261,391 human lineage-specific evolutionary breakpoints across the genome and 2,564 dense regions enriched with biological processes involved in adaptive traits such asresponse to DNA damage stimulus, cellular response to stressandmetabolic process. Moreover, we found 230 regions refractory to evolutionary breakpoints that carry genes associated with crucial developmental process such asorgan morphogenesis, skeletal system development, chordate embryonic development, nerve developmentandregulation of biological process. This initial map of the human genome will help to gain better insight into several studies including developmental studies and cancer rearrangement processes.
Partial absence of PD-1 expression by tumor-specific CD8+T cells in EBV-driven lymphoepithelioma-like carcinoma: a case report
Authors: Simoni Yannick , Becht Etienne , Li Shamin , Loh Chiew Yee , Yeong Joe Poh Sheng , Lim Tony Kiat Hon , Takano Angela , Tan Daniel S.W. , Newell Evan W.
Published: July 2019

Lymphoepithelioma-like carcinoma (LELC) is an uncommon lung cancer, typically observed in young, non-smoking Asian populations. LELC is associated with Epstein-Barr virus (EBV) infection of lung tumor cells of epithelial origin, suggesting a carcinogenic role of EBV as observed in nasopharyngeal carcinoma (NPC). Here, we studied the antigen specificity and phenotype of CD8+tumor infiltrating lymphocytes (TILs) in one LELC patient positive for EBV infection in lung tumor cells. Using MHC class I tetramers, we detected two populations of EBV-specific CD8+TILs, which can be considered as tumor-specific CD8+T cells, in the tumor of this patient. Transcriptomic analyses of these two populations reveal their distinct exhausted profiles and polyclonal TCR repertoire. High dimensional analyses at single cell level using mass cytometry showed showed that populations of tumor specific CD8+TILs are phenotypically heterogeneous, although they consistently express CD39. Unexpectedly, although the LELC tumor cells expressed abundant PD-L1, these tumor-specific CD8+TILs mostly did not express PD-1, suggesting that anti-PD1/PD-L1 immunotherapy may not be an appropriate strategy for disinhibiting EBV-specific cells for the treatment of LELC patients. These results might also help to explain low rates of checkpoint blockade immunotherapy response for NPC, despite the antigenicity of EBV for both tumor types.
The language network is recruited but not required for non-verbal event semantics
Authors: Ivanova Anna A. , Mineroff Zachary , Zimmerer Vitor , Kanwisher Nancy , Varley Rosemary , Fedorenko Evelina
Published: July 2019

The ability to combine individual meanings into complex representations of the world is often associated with language. Yet people also construct combinatorial event-level representations from non-linguistic input, e.g. from visual scenes. Here, we test whether the language network in the human brain is involved in and necessary for semantic processing of nonverbal events. In Experiment 1, we scanned participants with fMRI while they performed a semantic plausibility judgment task vs. a difficult perceptual control task on sentences and line drawings that describe/depict simple agent-patient interactions. We found that the language network responded robustly during the semantic task but not during the perceptual control task. This effect was observed for both sentences and pictures (although the response to sentences was stronger). Thus, language regions in healthy adults are engaged during a semantic task performed on pictorial depictions of events. But is this engagement necessary? In Experiment 2, we tested two individuals with global aphasia, who have sustained massive damage to perisylvian language areas and display severe language difficulties, against a group of age-matched control participants. Individuals with aphasia were severely impaired on a task of matching sentences and pictures. However, they performed close to controls in assessing the plausibility of pictorial depictions of agent-patient interactions. Overall, our results indicate that the left fronto-temporal language network is recruited but not necessary for semantic processing of nonverbal events.
Behavioral responses of the invasive flyPhilornis downsito stimuli from bacteria and yeast in the laboratory and the field in the Galapagos Islands
Authors: Yuval Boaz , Lahuatte Paola , Polpass Arul J. , Causton Charlotte , Jurkevitch Edouard , Kouloussis Nikolaus , Ben-Yosef Michael
Published: July 2019

Philornis downsi(Diptera: Muscidae) is a nest parasitic fly that has invaded the Galapagos archipelago and exerts an onerous burden on populations of endemic land birds. As part of an ongoing effort to develop tools for the integrated management of this fly, our objective was to determine its long and short-range responses to bacterial and yeast cues associated with adultP. downsi. We hypothesized that the bacterial and yeast communities will elicit attraction at distance through volatiles, and appetitive responses upon contact. Accordingly, we amplified bacteria from guts of adult field-caught individuals and bird feces, and yeasts from fermenting papaya juice (a known attractant ofP. downsi), on selective growth media, and assayed the response of flies to these microbes or their exudates. In the field, we baited traps with bacteria or yeast and monitored adult fly attraction. In the laboratory, we used the Proboscis Extension Response (PER) to determine the sensitivity of males and females to tarsal contact with bacteria or yeast. Long range trapping efforts yielded two female flies over 112 trap nights (one in extracts from bird faeces and one in extracts from gut bacteria from adult flies). In the laboratory, tarsal contact with bacterial stimuli from gut bacteria from adult flies elicited significantly more responses than did yeast stimuli. We discuss the significance of these findings in context with other studies in the field and identify targets for future work.
Co-evolutionary analysis accurately predicts details of interactions between the Integrator complex subunits
Authors: Fongang Bernard , Zhu Yingjie , Wagner Eric J. , Kudlicki Andrzej , Rowicka Maga
Published: July 2019

Solving the structure of large, multi-subunit complexes is difficult despite recent advances in cryoEM, due to remaining challenges to express and purify complex subunits. Computational approaches that predict protein-protein interactions, including Direct Coupling Analysis (DCA), represent an attractive alternative to dissect interactions within protein complexes. However, due to high computational complexity and high false positive rate they are applicable only to small proteins. Here, we present a modified DCA to predict residues and domains involved in interactions of large proteins. To reduce false positive levels and increase accuracy of prediction, we use local Gaussian averaging and predicted secondary structure elements. As a proof-of-concept, we apply our method to two Integrator subunits, INTS9 and INTS11, which form a heterodimeric structure previously solved by crystallography. We accurately predict the domains of INTS9/11 interaction. We then apply this approach to predict the interaction domains of two complexes whose structure is currently unknown: 1) The heterodimer formed by the Cleavage and Polyadenylation Specificity Factor 100-kD (CPSF100) and 73-kD (CPSF73); 2) The heterotrimer formed by INTS4/9/11. Our predictions of interactions within these two complexes are supported by experimental data, demonstrating that our modified DCA is a useful method for predicting interactions and can easily be applied to other complexes.
Compensatory mechanisms affect sensorimotor integration during ongoing vocal-motor acts in marmoset monkeys
Authors: Pomberger Thomas , Löschner Julia , Hage Steffen R.
Published: July 2019

In vertebrates, any transmission of vocal signals faces the challenge of acoustic interferences such as heavy rain, wind, animal, or urban sounds. Consequently, several mechanisms and strategies have evolved to optimize the signal-to-noise ratio. Examples to increase detectability are the Lombard effect, an involuntary rise in call amplitude in response to masking ambient noise, which is often associated with several other vocal changes such as call frequency and duration, as well as the animals’ capability of limiting calling to periods where noise perturbation is absent. Previous studies revealed rapid vocal flexibility and various audio-vocal integration mechanisms in marmoset monkeys. Using acoustic perturbation triggered by vocal behavior, we investigated whether marmoset monkeys are capable of exhibiting changes in call structure when perturbing noise starts after call onset or whether such effects only occur if noise perturbation starts prior to call onset. We show that marmoset monkeys are capable of rapidly modulating call amplitude and frequency in response to such perturbing noise bursts. Vocalizations swiftly increased call frequency after noise onset indicating a rapid effect of perturbing noise on vocal motor pattern production. Call amplitudes were also affected. Interestingly, however, the marmosets did not exhibit the Lombard effect as previously reported but decreased their call intensity in response to perturbing noise. Our findings indicate that marmosets possess a general avoidance strategy to call in the presences of ambient noise and suggest that these animals are capable of counteracting a previously thought involuntary audio-vocal mechanism, the Lombard effect, presumably via cognitive control processes.
G protein-coupled potassium channels implicated in mouse and cellular models of GNB1 Encephalopathy
Authors: Colombo Sophie , Petri Sabrina , Shalomov Boris , Reddy Haritha P. , Tabak Galit , Dhindsa Ryan S. , Gelfman Sahar , Teng Sasa , Krizay Daniel , Rafikian Elizabeth E. , Bera Amal K. , Yang Mu , Boland Michael J. , Peng Yueqing , Frankel Wayne N. , Dascal Nathan , Goldstein David B.
Published: July 2019

De novo mutations in GNB1, encoding the Gβ1 subunit of G proteins, cause a neurodevelopmental disorder with global developmental delay and epilepsy. Mice carrying a pathogenic mutation, K78R, recapitulate aspects of the disorder, including developmental delay and frequent spike-wave discharges (SWD). Cultured mutant cortical neurons display aberrant bursting activity on multi-electrode arrays. Strikingly, the antiepileptic drug ethosuximide (ETX) restores normal neuronal network behavior in vitro and suppresses SWD in vivo. In contrast, while valproic acid suppresses SWD, it does not restore normal network behavior, suggesting that ETX has mechanistic specificity for the effects of aberrant Gβ1 signaling. Consistent with this, we show that K78R is a gain-of-function of G protein-coupled potassium channel (GIRK) activation that is potently inhibited by ETX. This work suggests that altered Gβ1 signaling causes disease in part through effects on GIRK channels, illustrates the utility of cultured neuronal networks in pharmacological screening, and establishes effective pre-clinical models for GNB1 Encephalopathy.
Two CoII coordination polymers of biphenyl-2,2′,5,5′-tetracarboxylic acid with flexible N-donor ligands: syntheses, structures and magnetic properties
Authors: Su Feng , Zhou Cheng-Yong , Wu Lin-Tao , Wu Xi , Su Jing , Han Chun , Wang Zhi-Jun
Published: July 2019

Two CoII-based coordination polymers, namely poly[(μ4-biphenyl-2,2′,5,5′-tetracarboxylato){μ2-1,3-bis[(1H-imidazol-1-yl)methyl]benzene}dicobalt(II)], [Co2(C16H6O8)(C14H14N4)2]
n
or [Co2(o,m-bpta)(1,3-bimb)2]
n
(I), and poly[[aqua(μ4-biphenyl-2,2′,5,5′-tetracarboxylato){1,4-bis[(1H-imidazol-1-yl)methyl]benzene}dicobalt(II)] dihydrate], {[Co2(C16H6O8)(C14H14N4)2(H2O)2]·4H2O}
n
or {[Co2(o,m-bpta)(1,4-bimb)2(H2O)2]·4H2O}
n
(II), were synthesized from a mixture of biphenyl-2,2′,5,5′-tetracarboxylic acid, i.e. [H4(o,m-bpta)], CoCl2·6H2O and N-donor ligands under solvothermal conditions. The complexes were characterized by IR spectroscopy, elemental analysis, single-crystal X-ray diffraction and powder X-ray diffraction analysis. The bridging (o,m-bpta)4− ligands combine with CoII ions in different μ4-coordination modes, leading to the formation of one-dimensional chains. The central CoII atoms display tetrahedral [CoN2O2] and octahedral [CoN2O4] geometries in I and II, respectively. The bis[(1H-imidazol-1-yl)methyl]benzene (bimb) ligands adopt trans or cis conformations to connect CoII ions, thus forming two three-dimensional (3D) networks. Complex I shows a (2,4)-connected 3D network with left- and right-handed helical chains constructed by (o,m-bpta)4− ligands. Complex II is a (4,4)-connected 3D novel network with ribbon-like chains formed by (o,m-bpta)4− linkers. Magnetic studies indicate an orbital contribution to the magnetic moment of I and II due to the longer Co...Co distances. An attempt has been made to fit the χM
T results to the magnetic formulae for mononuclear CoII complexes, the fitting indicating the presence of weak antiferromagnetic interactions between the CoII ions.
Impact of mission requirements on the design of low observable UCAV configurations
Authors: Sepulveda Palacios Eduardo , Smith Howard
Published: July 2019

Purpose

The purpose of this paper is to characterise the effects of mission and performance parameters on the design space of low observable subsonic unmanned combat aerial vehicles (UCAVs) operating in typical Hi-Lo-Hi ground strike missions.

Design/methodology/approach

Conceptual design methodologies appropriate to low observable, tailless UCAVs have been integrated into a multidisciplinary aircraft design environment, GENUS, developed at Cranfield University’s aircraft design group. A basic Hi-Lo-Hi mission is designed and a baseline configuration is established through the GENUS framework. Subsequently, an evolutionary optimiser and a robust gradient-based optimiser are used to obtain convergent design solutions for various leading edge sweep angles, mission ranges, cruise Mach numbers and other operational constraints.

Findings

The results indicate that performance constraints, specifically in the form of specific excess power (SEP), have a large influence on the overall sizing of subsonic tailless UCAVs. This requirement drives the engine sizing, which represents a considerable proportion of the empty and gross mass of the vehicle. Cruise Mach number studies show that no significant advantages exist for operating at low speeds while maintaining performance requirements consistent with combat missions. There is a drastic increase in the vehicle’s mass and thrust requirements for flight speeds above Mach 0.8, with low sweep configurations showing a more pronounced effect. Increases in the range are not overly dependent on the leading edge sweep angle. Top-level radar cross section (RCS) results also favour configurations with higher leading edge sweep angles, especially from the nose-on aspect. Finally, research and development costs are shown to be directly linked to engine size.

Originality/value

This research shows the use of an integrated aircraft design environment that incorporates aerodynamics, performance, packaging and low observability aspects into the optimisation loop. Through this methodology, this study supports the efforts towards characterising and establishing alternate visions of the future of aerial warfare through the use of low cost, survivable unmanned platforms in network-centric cooperative tasks.
Experience economy in ethnic cuisine: a case of Chengdu cuisine
Authors: Lai Ivan K.W. , Lu Dong , Liu Yide
Published: July 2019

Purpose

The concept of experience economy states that customers seek experiences whether from products and services. Tourism is at the forefront of the experience economy because tourists are looking for staged experience encompassing the four realms (entertainment, educational, esthetic and escapism). The purpose of this paper is to empirically explore the effects of the experience economy on tourists’ word-of-mouth (WOM) in Chengdu cuisine through satisfaction and memory.

Design/methodology/approach

In total, 397 valid data were collected from the tourists who have experienced the ethnic cuisine in Chengdu. A partial least-square structural equation modeling technique was used to examine the research model.

Findings

The empirical results indicated that esthetic is the antecedent of the other three realms of experience economy; esthetic, educational and entertainment experiences influence satisfaction; four realms of experience economy influence memory; and satisfaction and memory ultimately influence WOM.

Practical implications

The findings of this study provide practical implications for operators of ethnic restaurants in designing their restaurants and menus, travel agencies in planning the tour itinerary and governments in using ethnic cuisine for destination marketing.

Originality/value

This study is a pioneer in studying the experience economy in the ethnic cuisine. It has identified the relationships between four dimensions of experience economy of ethnic cuisine, tourist satisfaction, memory and WOM toward ethnic cuisine in a tourist destination. It has also integrated the senses of Chinese cuisine (“sight,” “smell” and “taste”) into the measures of esthetic experience for studying experience economy in ethnic cuisine.