bluuebunny/crossref_metadata_2025 huggingface dataset:
Familial Congenital Methemoglobinemia in Pomeranian Dogs Caused by a Missense Variant in the NADH‐Cytochrome B5 Reductase Gene
Authors: Shino H. , Otsuka‐Yamasaki Y. , Sato T. , Ooi K. , Inanami O. , Sato R. , Yamasaki M.
Published: January 2018

Background

In veterinary medicine, congenital methemoglobinemia associated with nicotinamide adenine dinucleotide (NADH)‐cytochrome b5 reductase (b5R) deficiency is rare. It has been reported in several breeds of dogs, but little information is available about its etiology.

Objectives

To analyze the NADH‐cytochrome b5 reductase gene, CYB5R3, in a Pomeranian dog family with methemoglobinemia suspected to be caused by congenital b5R deficiency.

Animals

Three Pomeranian dogs from a family with methemoglobinemia were analyzed. Five healthy beagles and 5 nonrelated Pomeranian dogs without methemoglobinemia were used as controls.

Methods

Methemoglobin concentration, b5R activity, and reduced glutathione (GSH) concentration were measured, and a turbidity index was used to evaluate Heinz body formation. The CYB5R3 genes of the affected dog and healthy dogs were analyzed by direct sequencing.

Results

Methemoglobin concentrations in erythrocytes of the affected dogs were remarkably higher than those of the control dogs. The b5R activity of the affected dogs was notably lower than that of the control dogs. DNA sequencing indicated that this Pomeranian family carried a CYB5R3 gene missense variant (ATC→CTC at codon 194) that resulted in the replacement of isoleucine (Ile) by leucine (Leu).

Conclusions and Clinical Importance

This dog family had familial congenital methemoglobinemia caused by b5R deficiency, which resulted from a nonsynonymous variant in the CYB5R3 gene. This variation (c.580A>C) led to an amino acid substitution (p.Ile194Leu), and Ile194 was located in the proximal region of the NADH‐binding motif. Our data suggested that this variant in the canine CYB5R3 gene would affect function of the b5R in erythrocytes.
Serum Cytokine Profiling in Cats with Acute Idiopathic Cystitis
Authors: Parys M. , Yuzbasiyan‐Gurkan V. , Kruger J.M.
Published: January 2018

Background

Feline idiopathic cystitis (FIC) is a common lower urinary tract disorder of domestic cats that resembles interstitial cystitis/painful bladder syndrome (IC/PBS) in humans. Diagnosis ofFICis based on clinical signs and exclusion of other disorders because of a lack of specific pathologic findings or other objective biomarkers. Cytokines are potential noninvasive biomarkers to define the presence, severity, and progression of disease, and response to treatment.

Objectives

The objective of this pilot study was to determine concentrations of selected cytokines in serum from healthy cats and cats with acuteFIC.

Animals

Serum samples from 13 healthy cats and from 12 cats with nonobstructive acuteFICwere utilized.

Methods

Multiplex analysis of 19 cytokines (CCL2,CCL5,CXCL1,CXCL12,CXCL8, Flt3L,GM‐CSF,IFN‐γ,IL‐12 (p40),IL‐13,IL‐18,IL‐1β,IL‐2,IL‐4,IL‐6,PDGF‐BB,SCF,sFas, andTNF‐α) was performed with a commercially available feline‐specific multiplex bead‐based assay.

Results

Mean serum concentrations ofIL‐12 (p40;P< 0.0001),CXCL12 (P= 0.002),IL‐18 (P= 0.032), and Flt3L (P= 0.0024) were significantly increased inFICcats compared to healthy cats.GM‐CSF,IL‐1b,IL‐2, andPDGF‐BBwere undetectable or detected in an insufficient number of cats to allow meaningful comparisons.

Conclusions and Clinical Importance

We have identified increased serum concentrations of pro‐inflammatory cytokines and chemokinesCXCL12,IL‐12,IL‐18, and Flt3L inFIC‐affected cats. These findings suggest potential candidates for noninvasive biomarkers for diagnosis, staging, and therapeutic outcome monitoring of affected cats and provide additional insight into the etiopathogenesis ofFIC.
Indeterminacy and fundamental reduced form representations of DSGE models
Authors: Sorge Marco Maria
Published: January 2018

Dynamic stochastic general equilibrium (DSGE) models are known to exhibit indeterminacy—that is, equilibrium nonuniqueness—under realistic parameterizations. This paper studies how the potential for indeterminacy impacts on the possibility of recovering a DSGE model's structural shocks via empirical vector autoregressions (VARs), which in turn requires the model's reduced form representation to be fundamental. By means of a simple example, we first establish that indeterminacy is neither necessary nor sufficient for (non)fundamental representations to arise. We then investigate the relationship between indeterminacy and nonfundamentalness in the context of a general class of linearized DSGE models, which nests the New Keynesian framework as a special case. It is shown that an indeterminate equilibrium model may generically admit a fundamental moving average representation, even when its determinate counterpart always involves nonfundamentalness. As a main implication, checking for existence of a VAR representation of a DSGE model's equilibria cannot be regarded as an indirect test for the indeterminacy hypothesis.
Understanding the determinants of adolescent nutrition in Bangladesh
Authors: Leroy Jef L. , Ruel Marie , Sununtnasuk Celeste , Ahmed Akhter
Published: January 2018

Evidence on the nutritional status and diets of adolescents in low‐ and middle‐income countries is scant. We characterized the nutritional status (body mass index Z‐scores (BMIZs)) and nutrient intakes of adolescent boys and girls in rural areas in Bangladesh using the 2011–2012 BIHS data, used regression models to identify the socioeconomic determinants of these outcomes, and household fixed effects models to assess whether the gap between boys and girls changed with women's education and empowerment and household wealth. The adolescents’ BMIZ and adequacy of their nutrient intakes were suboptimal. Gender differences varied by outcome and were not systematically in favor of boys. Household wealth was associated with higher BMIZ and probability of adequate energy and micronutrient intakes. Women's education and empowerment were mostly not associated with the study outcomes and did not modify gender differences. There is an urgent need to invest in improving the diets of adolescent boys and girls in Bangladesh. The limited role of women's education and empowerment in improving adolescent nutrition suggests that resources may be too constrained. It may also reflect deeply rooted beliefs about adolescent nutrition and differences between boys and girls that would need to be addressed to improve their nutrition.
Acetylcholine receptor antibody–mediated animal models of myasthenia gravis and the role of complement
Authors: Kusner Linda L. , Sengupta Manjistha , Kaminski Henry J.
Published: January 2018

Because of the failure of many promising therapeutics identified in preclinical evaluation, funding sources have established guidelines for increased rigor in animal evaluations. The myasthenia gravis (MG) community of scientists has developed guidelines for preclinical assessment for potential MG treatments. Here, we provide a focused summary of these recommendations and the role of complement in disease development in experimental models of MG.
Dedifferentiated Fat (DFAT) cells: A cell source for oral and maxillofacial tissue engineering
Authors: Kishimoto N , Honda Y , Momota Y , Tran SD
Published: January 2018

Tissue engineering is a promising method for the regeneration of oral and maxillofacial tissues. Proper selection of a cell source is important for the desired application. This review describes the discovery and usefulness of dedifferentiated fat (DFAT) cells as a cell source for tissue engineering. Dedifferentiated Fat cells are a highly homogeneous cell population (high purity), highly proliferative, and possess a multilineage potential for differentiation into various cell types under proper in vitro inducing conditions and in vivo. Moreover, DFAT cells have a higher differentiation capability of becoming osteoblasts, chondrocytes, and adipocytes than do bone marrow‐derived mesenchymal stem cells and/or adipose tissue‐derived stem cells. The usefulness of DFAT cells in vivo for periodontal tissue, bone, peripheral nerve, muscle, cartilage, and fat tissue regeneration was reported. Dedifferentiated Fat cells obtained from the human buccal fat pad (BFP) are a minimally invasive procedure with limited esthetic complications for patients. The BFP is a convenient and accessible anatomical site to harvest DFAT cells for dentists and oral surgeons, and thus is a promising cell source for oral and maxillofacial tissue engineering.
Pediatric patient with end‐stage kidney disease secondary to Eagle‐Barrett syndrome and metastatic unresectable hepatoblastoma treated successfully with chemotherapy and liver‐kidney transplant
Authors: Ortiz Daniel , Harden Avis , Corrales‐Medina Fernando F. , Saigal Gaurav , Tekin Akin , Garcia Jennifer
Published: January 2018

HBL is the most common malignant liver neoplasm in children. The etiology of HBL is largely unknown but there are certain syndromes, such as Beckwith‐Wiedemann syndrome, that have been clearly associated with an increased incidence of this malignancy. EBS, also known as prune belly syndrome, is a congenital anomaly characterized by lax abdominal musculature, bilateral cryptorchidism requiring, in some cases, hemodialysis due to significant kidney and urinary tract dysfunctions. Despite an improvement on the survival rates of patients with advanced‐stage HBL, the presence of concomitant end‐stage renal disease that occurs in patients with EBS constitutes a therapeutic challenge for the clinician not only due to the use of nephrotoxic chemotherapy but also due to the potential need for multi‐organ transplant. We report case of a 2‐year‐old male patient with EBS diagnosed with stage IV, metastatic HBL successfully treated with multi‐agent chemotherapy while on dialysis whom then underwent a simultaneous liver‐kidney transplant followed by adjuvant chemotherapy. Ultimately, the patient achieved cancer remission with normalization of his renal function. Our report emphasizes that patients with HBL in the setting of EBS will not only require careful kidney function monitoring while receiving chemotherapy, but they might also need to undergo multi‐organ transplantation in order to achieve adequate cancer control and also normalization of their kidney function. Awareness of this unusual association calls for further investigation to potentially establish a genetic association between these two disease processes.
Effects of iron and vitamin B12 deficiencies on peripheral blood colony‐forming unit capacity
Authors: Zabun Merve M. , Köksal Yasin , Çelik Bülent , Özgüner Meltem , Özbek Namık Y.
Published: January 2018

Iron and vitamin B12 deficiencies are two of the most common diseases in the childhood group. Deficiencies of iron and vitamin B12 affect many systems in the body. In this study, to discover the effects of iron and vitamin B12 deficiencies on the hematopoietic stem cells, we studied CFU assay from peripheral blood. One hundred and two children were included in our study and were evaluated in five categories: iron deficiency, iron deficiency anemia, vitamin B12 deficiency, iron and vitamin B12 deficiency, and controls. As a result of statistical analysis, no significant difference was detected between five groups in terms of CFU assays. The results of our study suggest that, in emergent situations, stem cell samples can be collected before treatment with B12 or iron which are common deficiencies in donors of hematopoietic stem cell transplantation. We conclude that we could reach more accurate results by designing a study which contains more patients and includes in vivo results.
Morphology, morphometry and chromatin distribution in llama sperm nuclei
Authors: Giuliano S , Cisale H , Ferrari MR
Published: January 2018

Contents

The objectives of this study were as follows: (i) to describe and evaluate the frequencies of different morphologies of llama sperm nuclei, (ii) to determine morphometric values of nuclear parameters, (iii) to describe and estimate the frequencies of different classes of chromatin distribution and (iv) to measure haploidDNAcontent and analyse its nuclear distribution. The study was performed using ejaculates collected from seven males, and sperm nuclei were stained with the Feulgen reaction. Normal morphology ranged from 78.36% to 93.92%, and abnormalities included short, small, large, pyriform, narrow, micro and round nuclei. Important differences in nuclei considered normal were found between some males. The following average values were obtained for each sperm nuclear morphometric parameter analysed: area 11.64 μm2, perimeter 13.16 μm, length 5.12 μm, width 2.81 μm, ellipticity 1.85 and form 0.83. Differences between males were significant for all the parameters (p < .01). Light microscope observations and cytophotometric determinations allowed discriminating between three classes of chromatin distribution: homogeneous, diffuse and showing a clear band. Significant differences between males were found for the frequencies of the three classes (p < .01). Cluster analysis methods were used to estimate the resemblance between males according to the characteristics of their sperm nuclei. A great intermale variability was found for morphological, morphometric and chromatin distribution data. These parameters would have low dependence between them.
Exceptional Laguerre Polynomials
Authors: Bonneux Niels , Kuijlaars Arno B.J.
Published: January 2018

The aim of this paper is to present the construction of exceptional Laguerre polynomials in a systematic way and to provide new asymptotic results on the location of the zeros. To describe the exceptional Laguerre polynomials, we associate them with two partitions. We find that the use of partitions is an elegant way to express these polynomials and we restate some of their known properties in terms of partitions. We discuss the asymptotic behavior of the regular zeros and the exceptional zeros of exceptional Laguerre polynomials as the degree tends to infinity.
How can genetics help understand the relationship between cognitive dysfunction and schizophrenia?
Authors: Smeland Olav B. , Andreassen Ole A.
Published: January 2018

Despite the consistent finding that cognitive dysfunction is a core characteristic of schizophrenia (SCZ), little is known about the underlying pathophysiology. Recent progress in human genetics, driven by large genome‐wide association studies (GWAS), has provided new data about the genetic architecture of complex human traits, including cognition and SCZ. Novel analytical tools have provided unprecedented opportunities to leverage the large amount of information from GWAS. Here we review the latest findings related to genetic architecture and risk genes of SCZ and cognitive functions, and recent findings of overlapping genetic factors. The recent GWAS of SCZ implicate over 100 risk gene loci, each with a small effect. A similar genetic architecture seems to be present in cognitive domains, suggesting that these phenotypes are highly polygenic. Further, GWAS have revealed more than 20 gene loci associated with cognitive traits, including intelligence, general cognition (g‐factor), reaction time and verbal‐numerical reasoning. Several gene loci have been implicated in educational attainment, a proxy measure of cognitive function. Recently, overlapping gene loci were found between education and SCZ, and between SCZ and cognitive traits, suggesting common genetic risk between SCZ and cognitive dysfunction. Mathematical modeling of GWAS of cognition and SCZ indicate that only a fraction of the heritability is identified. The evidence suggests a polygenic architecture for SCZ and cognitive functions, and a large degree of shared genetic risk. This indicates novel molecular genetic mechanisms and strengthens the notion that SCZ is more likely a part of the normal distribution and not a separate entity.
Cognitive control in the prefrontal cortex: A central or distributed executive?
Authors: Nyberg Lars
Published: January 2018

Cognitive control is the foundation for attaining goals by flexible adaptation of action to changing environmental demands. It has been hypothesized to be critically dependent upon the prefrontal cortex (PFC). In this mini‐review, evidence for domain‐general versus domain‐specific cognitive control is examined, with a particular focus on attention and memory. The reviewed studies examined different levels of cognitive control in relation to performance and patterns of brain activity, and a few included direct comparisons of cognitive‐control modulations across cognitive domains. Within domains, increased demands on cognitive control consistently translated into increased PFC activity, but limited overlap in recruited PFC regions was observed between domains. It is concluded that the PFC supports multiple cognitive‐control systems that collectively may be conceived of as a distributed executive.
The right‐side perceptual bias in aging determined in a laboratory setting and during a virtual driving task
Authors: Hämäläinen Heikki , Rashid Izullah Faramosh , Koivisto Mika , Takio Fiia , Luimula Mika
Published: January 2018

Spatial perceptual rightward bias which was originally described in Dichotic Listening studies seems to be a general phenomenon. This bias is age dependent, being evident in children with developing executive functions, and emerging again at older age as a function of aging and the declining executive functions. In the two studies presented here we compared the performance of young and elderly adults in spatial divided attention tasks with auditory and visual stimuli when the stimulus detection performance was measured in separate sessions in a laboratory setting (Study I), to performance when the same types of stimuli were mixed with a task in which the subject's primary objective was to drive a car in a virtual environment (virtual reality; Study II). The aim was to see if the perceptual bias could be detected and also to look at how it would differ in these two situations. 90 right‐handed subjects (50 young and 40 elderly) participated in Study I and 84 subjects (64 young and 20 elderly) participated in Study II. Study I showed the rightward bias to be more evident in the elderly subjects in both modalities and in more demanding tasks. Study II revealed that in the triple task the spatial perceptual bias was evident in both modalities for the elderly participants when the conditions were more demanding. An interesting finding concerning the right‐side perceptual bias was the simultaneous occurrence of left‐side driving errors, i.e. crossing the lane border to the left especially by the elderly. Both of these biases may reflect the asymmetries of the attention‐related neuronal networks.
Lack of ACTPK1, an STY kinase, enhances ammonium uptake and use, and promotes growth of rice seedlings under sufficient external ammonium
Authors: Beier Marcel P. , Obara Mitsuhiro , Taniai Akiko , Sawa Yuki , Ishizawa Jin , Yoshida Haruki , Tomita Narumi , Yamanaka Tsuyoshi , Ishizuka Yawara , Kudo Syuko , Yoshinari Akira , Takeuchi Shiho , Kojima Soichi , Yamaya Tomoyuki , Hayakawa Toshihiko
Published: January 2018

Ammonium influx into plant roots via the high‐affinity transport system (HATS) is down‐modulated under elevated external ammonium, preventing ammonium toxicity. In ammonium‐fed Arabidopsis, ammonium transporter 1 (AMT1) trimers responsible for HATS activity are allosterically inactivated in a dose‐dependent manner via phosphorylation of the conserved threonine at the carboxyl‐tail by the calcineurin B‐like protein 1‐calcineurin B‐like protein‐interacting protein kinase 23 complex and other yet unidentified protein kinases. Using transcriptome and reverse genetics in ammonium‐preferring rice, we revealed the role of the serine/threonine/tyrosine protein kinase gene OsACTPK1 in down‐modulation of HATS under sufficient ammonium. In wild‐type roots, ACTPK1 mRNA and protein accumulated dose‐dependently under sufficient ammonium. To determine the function of ACTPK1, two independent mutants lacking ACTPK1 were produced by retrotransposon Tos17 insertion. Compared with segregants lacking insertions, the two mutants showed decreased root growth and increased shoot growth under 1 mm ammonium due to enhanced ammonium acquisition, via aberrantly high HATS activity, and use. Furthermore, introduction of OsACTPK1 cDNA fused to the synthetic green fluorescence protein under its own promoter complemented growth and the HATS influx, and suggested plasma membrane localization. Root cellular expression of OsACTPK1 also overlapped with that of ammonium‐induced OsAMT1;1 and OsAMT1;2. Meanwhile, threonine‐phosphorylated AMT1 levels were substantially decreased in roots of ACTPK1‐deficient mutants grown under sufficient ammonium. Bimolecular fluorescence complementation assay further confirmed interaction between ACTPK1 and AMT1;2 at the cell plasma membrane. Overall, these findings suggest that ACTPK1 directly phosphorylates and inactivates AMT1;2 in rice seedling roots under sufficient ammonium.
Mobilizing to Advance Creative Projects: NewCar’s Prototype Parts Purchasing Activity
Authors: Obstfeld David
Published: January 2018

This chapter illustrates the BKAP model through an extended ethnographic case to show how network and knowledge processes interact to produce project-based innovation. An ethnographic case study in the same automotive setting found in Chapter 4 illustrates the emergence of creative projects launched in pursuit of innovation. Specifically, this chapter depicts how an automobile manufacturer’s prototype parts purchasing routine contrasts with two creative projects undertaken to redesign it. The chapter elaborates how trajectory strategy, consisting of the trajectory projection and scheme, and trajectory management, consisting of knowledge articulation, brokerage activity, and an additional category emerging from the author’s field data—contingency management—impact the two projects’ adoption. To lay the groundwork for how the two creative projects emerged, the author describes the “cowboy culture” presented in the Introduction, a culture imprinted within NewCar that gave rise to behaviors through which creative projects were pursued.
Culture and Commerce
Authors: Khaire Mukti
Published: January 2018

This book describes how commercial ventures in creative industries have cultural impact. Since royal patronage of arts ended, firms in the creative industries, working within the market mechanism, have been responsible for the production and distribution of the cultural goods—art, books, films, fashion, and music—that enrich our lives. This book counters the popular perception that this marriage of art and business is a necessary evil, proposing instead that entrepreneurs who introduce radically new cultural works to the market must bring about a change in society’s beliefs about what is appropriate and valuable to encourage consumption of these goods. In so doing, these pioneer entrepreneurs change minds, not just lives; the seeds of cultural change are embedded in the world of commerce. Building on theories of value construction and cultural production, integrated with field research on pioneer firms (like Chanel and the Sundance Institute) and new market categories (like modern art and high fashion in India), the author develops conceptual frameworks that explain the structure and functioning of creative industries. Through a systematic exposition of the roles and functions of the players in this space—creators, producers, and intermediaries—the book proposes a new way to understand the relationship among markets, entrepreneurship, and culture. Khaire also discusses challenges inherent in being entrepreneurial in the creative industries, paying special attention to the implications of digitalization and globalization, and suggests prescriptive directions for individuals and firms wishing to balance pecuniary motivations with cultural convictions in this rapidly changing world.
The Business of Culture
Authors: Khaire Mukti
Published: January 2018

The worlds of business and culture are seen as unrelated, even opposing. This chapter describes why and how the two are related. Creators, producers, and intermediaries constitute a value chain in markets formed at the intersection of commerce (where producers, with goods for sale, reside), commentary (discourse generated by intermediaries as well as producers that contributes to construction of value of goods), culture (beliefs about value, influenced by the commentary), and consumption (acquiring goods aligned with cultural norms and therefore valued). Markets for symbolic and new products require higher levels of commentary than those for utilitarian and well-understood products, given the greater need to assess and construct the value of these products. Pioneer entrepreneurs create markets for new cultural goods by first establishing them as appropriate and valuable to induce their consumption. This requires changing conventions of appropriateness and value, which in turn can effect cultural change.
An Independent President or Administrator?
Authors: Belco Michelle , Rottinghaus Brandon
Published: January 2018

Chapter 6 explores the unilateral actions of the president’s dual roles after legislation (bills) is on Congress’s agenda. At this stage, presidents can bargain with Congress over the formulation of legislation. Independent presidents use unilateral orders to preempt the lengthy legislative process and administrators do so to issue unilateral orders to support legislation. Presidents are clearly interested in issuing unilateral orders that work to their advantage whether it is to prevent legislation from progressing or to facilitate legislative progress when it is otherwise slowed by collective action problems in Congress. Presidents are more likely to use unilateral orders to preempt legislation when the issue is on their agenda, there is greater friction between the branches, Congress is internally divided, and presidents have greater discretion to act.
The Youth Magazine in Early Colonial Korea
Authors: Zur Dafna
Published: January 2018

This chapter outlines the social, political, and economic conditions that enabled the emergence of a print culture for young readers in colonial Korea. It historicizes this emergence globally and locally, against the backdrop of discourses on the role of youth that circulated among intellectuals and educators in Korea, Japan, and China. With the emergence of the modern political subject, youth came to embody the nation’s aspirations. The figure of the child that emerged a decade later contrasted with this early configuration of the political, non-adult youth. This chapter sets the stage for the book's argument: that children were celebrated as privileged protagonists of the future because, like youth, they were intellectually and emotionally unburdened by the past and ideally situated to build a modern nation. But unlike youth, the new children possessed a child-heart conducive to the colonial project of engineering a new, affectively privileged modern subject.
Liberating the Child-Heart
Authors: Zur Dafna
Published: January 2018

This chapter turns to children’s literature at its most significant watershed moment: the liberation of Korea from its thirty-five-year colonization. In the five years between 1945 and the Korean War in 1950, the Korean peninsula experienced the euphoria of liberation, the arrival of the United State Military Government in Korea, the hardening of ideological positions, and the ensuing mass migration up and down the peninsula, as well as the official establishment of two separate and mutually intolerant regimes. Children’s literature provides a fascinating counterpoint to these historical shifts by showcasing powerful nationalist tendencies that set the tone for a new beginning, while simultaneously presenting strong undercurrents remaining from the colonial past. Most significantly, this chapter looks at the much-celebrated and freshly liberated child-heart and questions the extent of liberation in light of a newly forged relationship between Korea’s new young citizens and their liberated land.
Epilogue
Authors: Zur Dafna
Published: January 2018

The dropping of atomic bombs in Hiroshima and Nagasaki and the devastation of the Korean War signaled the period known globally as the “loss of innocence.” The Epilogue hints at some of the implications of the language of science and technology and its penetration into the fiction of the postwar Koreas. The genre of science fiction, found only in children’s literary magazines in this period, put into practice a variety of contested theories of education, of the relationship between science and art, and of the role of fiction in both describing and prescribing better futures. Ultimately, the postwar era demonstrates the break between the long-sustained bond between child and nature, and by extension a recalibration of the relationship between humans, culture, and the natural world.
New Vehicles to Drive the Collaborative Model
Authors: Monk Ashby , Sharma Rajiv , Sinclair Duncan L.
Published: January 2018

Chapter 4 presents actual case study examples of the vehicles that have been set up and represent the collaborative model. Whereas earlier chapters provided the theoretical explanation and validation for the collaborative model, Chapter 4 provides detailed explanations of eight investor-led co-investment platforms, joint ventures, and platform companies. The vehicles illustrated represent innovative ways for institutional investors to pool capital together to invest around the world into long-term assets such as infrastructure, agriculture, and real estate. The case studies are designed to outline how they came about and what the challenges were in their setup. The chapter is supplemented with a database that identifies over a hundred collaborative investment vehicles that have been set up mostly in the last few years. This chapter will help provide key lessons on strategy, governance, and structural issues as more of these vehicles are setup in the future.
Lamb wave propagation in monocrystalline silicon wafers
Authors: Fromme Paul , Pizzolato Marco , Robyr Jean-Luc , Masserey Bernard
Published: January 2018

Monocrystalline silicon wafers are widely used in the photovoltaic industry for solar panels with high conversion efficiency. Guided ultrasonic waves offer the potential to efficiently detect micro-cracks in the thin wafers. Previous studies of ultrasonic wave propagation in silicon focused on effects of material anisotropy on bulk ultrasonic waves, but the dependence of the wave propagation characteristics on the material anisotropy is not well understood for Lamb waves. The phase slowness and beam skewing of the two fundamental Lamb wave modes A0 and S0 were investigated. Experimental measurements using contact wedge transducer excitation and laser measurement were conducted. Good agreement was found between the theoretically calculated angular dependency of the phase slowness and measurements for different propagation directions relative to the crystal orientation. Significant wave skew and beam widening was observed experimentally due to the anisotropy, especially for the S0 mode. Explicit finite element simulations were conducted to visualize and quantify the guided wave beam skew. Good agreement was found for the A0 mode, but a systematic discrepancy was observed for the S0 mode. These effects need to be considered for the non-destructive testing of wafers using guided waves.
Unraveling the Metabolic Routes of Retapamulin: Insights into Drug Development of Pleuromutilins
Authors: Sun Feifei , Zhang Huiyan , Gonzales Gerard Bryan , Zhou Jinhui , Li Yi , Zhang Jinzhen , Jin Yue , Wang Zhanhui , Li Yanshen , Cao Xingyuan , Zhang Suxia , Yang Shupeng
Published: January 2018

Retapamulin, a semisynthetic pleuromutilin derivative, is exclusively used for the topical short-term medication of impetigo and staphylococcal infections. In the present study, we report that retapamulin is adequately and rapidly metabolized
in vitro
via various metabolic pathways, such as hydroxylation, including mono-, di-, and trihydroxylation, and demethylation. Like tiamulin and valnemulin, the major metabolic routes of retapamulin were hydroxylation at the 2β and 8α positions of the mutilin moiety. Moreover,
in vivo
metabolism concurred with the results of the
in vitro
assays. Additionally, we observed significant interspecies differences in the metabolism of retapamulin. Until now, modifying the side chain was the mainstream method for new drug discovery of the pleuromutilins. This approach, however, could not resolve the low bioavailability and short efficacy of the drugs. Considering the rapid metabolism of the pleuromutilins mediated by cytochrome P450 enzymes, we propose that blocking the active metabolic site (C-2 and C-8 motif) or administering the drug in combination with cytochrome P450 enzyme inhibitors is a promising pathway in the development of novel pleuromutilin drugs with slow metabolism and long efficacy.
Production of Ophthalmic Acid Using Engineered Escherichia coli
Authors: Ito Tomokazu , Tokoro Maiko , Hori Ran , Hemmi Hisashi , Yoshimura Tohru
Published: January 2018

Ophthalmic acid (OA;
l
-γ-glutamyl-
l
-2-aminobutyryl-glycine) is an analog of glutathione (GSH;
l
-γ-glutamyl-
l
-cysteinyl-glycine) in which the cysteine moiety is replaced by
l
-2-aminobutyrate. OA is a useful peptide for the pharmaceutical and/or food industries. Herein, we report a method for the production of OA using engineered
Escherichia coli
cells.
yggS
-deficient
E. coli
, which lacks the highly conserved pyridoxal 5′-phosphate-binding protein YggS and naturally accumulates OA, was selected as the starting strain. To increase the production of OA, we overexpressed the OA biosynthetic enzymes glutamate-cysteine ligase (GshA) and glutathione synthase (GshB), desensitized the product inhibition of GshA, and eliminated the OA catabolic enzyme γ-glutamyltranspeptidase. The production of OA was further enhanced by the deletion of
miaA
and
ridA
with the aim of increasing the availability of ATP and attenuating the unwanted degradation of amino acids, respectively. The final strain developed in this study successfully produced 277 μmol/liter of OA in 24 h without the formation of by-products in a minimal synthetic medium containing 1 mM each glutamate, 2-aminobutyrate, and glycine.

IMPORTANCE
Ophthalmic acid (OA) is a peptide that has the potential for use in the pharmaceutical and/or food industries. An efficient method for the production of OA would allow us to expand our knowledge about its physiological functions and enable the industrial/pharmaceutical application of this compound. We demonstrated the production of OA using
Escherichia coli
cells in which OA biosynthetic enzymes and degradation enymes were engineered. We also showed that unique approaches, including the use of a Δ
yggS
mutant as a starting strain, the establishment of an S495F mutation in GshA, and the deletion of
ridA
or
miaA
, facilitated the efficient production of OA in
E. coli
.
Efficacy of T2 Magnetic Resonance Assay in Monitoring Candidemia after Initiation of Antifungal Therapy: the Serial Therapeutic and Antifungal Monitoring Protocol (STAMP) Trial
Authors: Mylonakis Eleftherios , Zacharioudakis Ioannis M. , Clancy Cornelius J. , Nguyen M. Hong , Pappas Peter G.
Published: January 2018

The performance of blood culture for monitoring candidemia clearance is hampered by its low sensitivity, especially during antifungal therapy. The T2 magnetic resonance (T2MR) assay combines magnetic resonance with nanotechnology to identify whole
Candida
species cells. A multicenter clinical trial studied the performance of T2MR in monitoring candidemia clearance compared to blood culture. Adults with a blood culture positive for yeast were enrolled and had blood cultures and T2MR testing performed on prespecified days. Thirty-one patients completed the trial. Thirteen of the 31 patients (41.9%) had at least one positive surveillance T2MR and/or blood culture result. All positive blood cultures (7/7 [100%]) had an accompanying positive T2MR result with concordance in the identified
Candida
sp., while only 7/23 (30.4%) T2MR results had an accompanying positive blood culture. There was one case of discordance in species identification between T2MR and the preenrollment blood culture with evidence to support deep-seated infection by the
Candida
spp. detected by the T2MR assay. Based on the log rank test, there was a statistically significant improvement in posttreatment surveillance using the T2MR assay compared to blood culture (
P
= 0.004). Limitations of the study include the small sample size and lack of outcome data. In conclusion, the T2MR assay significantly outperformed blood cultures for monitoring the clearance of candidemia in patients receiving antifungal therapy and may be useful in determining adequate source control, timing for deescalation, and optimal duration of treatment. However, further studies are needed to determine the viability of
Candida
species cells detected by the T2MR assay and correlate the results with patient outcomes. (This study is registered at ClinicalTrials.gov under registration number NCT02163889.)
Human Papillomavirus 16 E7 Stabilizes APOBEC3A Protein by Inhibiting Cullin 2-Dependent Protein Degradation
Authors: Westrich Joseph A. , Warren Cody J. , Klausner Michael J. , Guo Kejun , Liu Chang-Wei , Santiago Mario L. , Pyeon Dohun
Published: January 2018

APOBEC3 (A3) mutation signatures have been observed in a variety of human cancer genomes, including those of cervical and head and neck cancers caused by human papillomavirus (HPV) infection. However, the driving forces that promote off-target A3 activity remain mostly unclear. Here, we report a mechanism for the dramatic increase of A3A protein levels in HPV-positive keratinocytes. We show that expression of the viral protein E7 from high-risk HPVs, but not E7 from low-risk HPVs, significantly prolongs the cellular half-life of A3A protein in human keratinocytes and HPV-positive cancer cell lines. We have mapped several residues within the cullin 2 (CUL2) binding motif of HPV16 E7 as being important for mediating A3A protein stabilization. Furthermore, we provide direct evidence that both A3A and HPV16 E7 interact with CUL2, suggesting that the E7-CUL2 complex formed during HPV infection may regulate A3A protein levels in the cell. Using an
in vitro
cytidine deaminase assay, we show that E7-stabilized A3A remains catalytically active. Taken together, our findings suggest that the HPV oncoprotein E7 dysregulates endogenous A3A protein levels and thus provides novel mechanistic insight into cellular triggers of A3 mutations in HPV-positive cancers.

IMPORTANCE
Human papillomavirus (HPV) is causally associated with over 5% of all human malignancies. Several recent studies have shown that a subset of cancers, including HPV-positive head and neck and cervical cancers, have distinct mutational signatures potentially caused by members of the APOBEC3 cytidine deaminase family. However, the mechanism that induces APOBEC3 activity in cancer cells is poorly understood. Here, we report that the HPV oncoprotein E7 stabilizes the APOBEC3A (A3A) protein in human keratinocytes by inhibiting ubiquitin-dependent protein degradation in a cullin-dependent manner. Interestingly, the HPV E7-stabilized A3A protein maintains its deaminase activity. These findings provide a new insight into cancer mutagenesis enhanced by virus-induced A3A protein stabilization.
Combined fit to the cross-sections of e+e−→ π+π−ψ(3686) and e+e−→ Λc+Λc−
Authors: Zhang Jielei , Yuan Limin
Published: January 2018

The cross-sections of [Formula: see text] and [Formula: see text] have been measured by Belle experiment. A resonance [Formula: see text] is observed in [Formula: see text] decay mode, while another resonance [Formula: see text] is observed in [Formula: see text] decay mode. The two resonances [Formula: see text] and [Formula: see text]’s parameters are consistent with each other, so a combined fit is performed to the two cross-sections assuming [Formula: see text] and [Formula: see text] are same resonance. [Formula: see text]’s parameters are determined to be [Formula: see text], [Formula: see text], where the first uncertainties are statistical and the second systematic. The ratio [Formula: see text] is also obtained and it indicates that [Formula: see text]’s main decay modes may be [Formula: see text]. We determine the lower limit of its leptonic decay width of around 40 eV, which can be compared with the theoretical expectations of different models.
Probabilistic Linguistic Analytic Hierarchy Process and Its Application on the Performance Assessment of Xiongan New Area
Authors: Xie Wanying , Xu Zeshui , Ren Zhiliang , Wang Hai
Published: January 2018

Analytic Hierarchy Process (AHP) is one of the most favorable decision tools for dealing with complex decision-making problems. Probabilistic linguistic term set (PLTS) is an up-to-date tool to deal with uncertain information in the decision-making process. In this paper, we extend the AHP to the probabilistic linguistic environment for perfecting the modeling ability of AHP in various decision-making problems. In order to apply the PLTSs to the AHP properly, we first redefine the probabilistic linguistic comparison matrix (PLCM) and propose a new consistency index. Then, we propose a new approach to check and improve the consistency of the PLCMs. After that, we aggregate the individual PLCMs into the collective PLCM and derive the priorities of the collective PLCM. Finally, we combine the priorities with the decision matrix to complete the ranking of alternatives, and a case concerning the performance assessments of three new areas is given and the comparative analysis about the results is performed to demonstrate the feasibility of the proposed method.
Clustered Hyperbolic Categories
Authors: Saleh Ibrahim
Published: January 2018

We introduce a class of categories, called clustered hyperbolic categories, which are constructed from a categorized version of preseeds called categorical preseeds using categorical mutations that are a “functorial” edition of preseed mutations. Every Weyl preseed p gives rise to a categorical preseed [Formula: see text] which generates a clustered hyperbolic category; this is formed by copies of categories each one of which is equivalent to the category of representations of the Weyl cluster algebra [Formula: see text]. A “categorical realization” of Weyl cluster algebra is provided in the sense of defining a map Fp from any clustered hyperbolic category induced from p to the Weyl cluster algebra [Formula: see text], where the image of Fp generates [Formula: see text].
Optimizing the Magnetic Dipole-Field Source for Magnetically Guided Cochlear-Implant Electrode-Array Insertions
Authors: Leon Lisandro , Warren Frank M. , Abbott Jake J.
Published: January 2018

Magnetic guidance of cochlear-implant electrode arrays during insertion has been demonstrated in vitro to reduce insertion forces, which is believed to be correlated to a reduction in trauma. In those prior studies, the magnetic dipole-field source (MDS) was configured to travel on a path that would be coincident with the cochlea’s modiolar axis, which was an unnecessary constraint that was useful to demonstrate feasibility. In this paper, we determine the optimal configuration (size and location) of a spherical-permanent-magnet MDS needed to accomplish guided insertions with a 100[Formula: see text]mT field strength required at the cochlea, and we provide a methodology to perform such an optimization more generally. Based on computed-tomography scans of 30 human subjects, the MDS should be lateral-to and slightly anterior-to the cochlea with an approximate radius (mean and standard deviation across subjects) of 64[Formula: see text]mm and 4.5[Formula: see text]mm, respectively. We compare these results to the modiolar configuration and find that the volume of the MDS can be reduced by a factor of five with a 43% reduction in its radius by moving it to the optimal location. We conservatively estimate that the magnetic forces generated by the optimal configuration are two orders of magnitude below the threshold needed to puncture the basilar membrane. Although subject-specific optimal configurations are computed in this paper, a one-size-fits-all version with a radius of approximately 75[Formula: see text]mm is more robust to registration error and likely more practical. Finally, we explain how to translate the results obtained to an electromagnetic MDS.
Fault-Tolerant Approximate BFS Structures
Authors: Parter Merav , Peleg David
Published: January 2018

A
fault-tolerant
structure for a network is required to continue functioning following the failure of some of the network’s edges or vertices. This article addresses the problem of designing a
fault-tolerant
(α , β) approximate BFS structure (or FT-ABFS structure for short), namely, a subgraph
H
of the network
G
such that subsequent to the failure of some subset
F
of edges or vertices, the surviving part of
H
(namely,
H \ F
) still contains an
approximate
BFS spanning tree for (the surviving part of)
G
, satisfying dist(
s,v,H \ F
) ≤
α
ċ dist(
s,v,G \ F
)+
β
for every
v
isin
V
.

Our first result is an algorithm that given an
n
-vertex unweighted undirected graph
G
and a source
s
constructs a
multiplicative
(3,0) FT-ABFS structure rooted at
s
resilient to a failure of a
single
edge with at most 4
n
edges (improving by an
O
(log
n
) factor on the near-tight result of Baswana and Khanna (2010) for the special case of edge failures). This was recently improved to 2n edges by Bilò et al. (2014). Next, we consider the multiple edge faults case, for a constant integer
f
>1, we prove that there exists a (polynomial-time constructible) (3
f
,
f
log
n
) FT-ABFS structure with
O
(
f
n
) edges that is resilient against
f
faults. We also show the existence of a (3
f
+1,0) FT-ABFS structure with
O
(
f
log
f
n
ċ
n
) edges.

We then consider
additive
(1,
β
) FT-ABFS structures and demonstrate an interesting dichotomy between multiplicative and additive spanners. In contrast to the linear size of (
α
,0) FT-ABFS structures, we show that for every
n
, there exist
δ
, ε >0, and
n
-vertex graphs
G
with a source
s
for which any (1,
n
δ
) FT-ABFS structure rooted at
s
has Ω (
n
7/6
−ε) edges. For the case of additive stretch 3, we show that (1,3) FT-ABFS structures admit a lower bound of Ω (
n
5/4
) edges.
Exploiting Content Spatial Distribution to Improve Detection of Intrusions
Authors: Angiulli Fabrizio , Argento Luciano , Furfaro Angelo
Published: January 2018

We present PCkAD, a novel semisupervised anomaly-based IDS (Intrusion Detection System) technique, detecting application-level content-based attacks. Its peculiarity is to learn legitimate payloads by splitting packets into chunks and determining the within-packet distribution of n-grams. This strategy is resistant to evasion techniques as blending. We prove that finding the right legitimate content is NP-hard in the presence of chunks. Moreover, it improves the false-positive rate for a given detection rate with respect to the case where the spatial information is not considered. Comparison with well-known IDSs using n-grams highlights that PCkAD achieves state-of-the-art performances.