bluuebunny/crossref_metadata_2025 huggingface dataset:
Characterization of a Novel Composite Staphylococcal Cassette Chromosome
mec
in Methicillin-Resistant Staphylococcus pseudintermedius from Thailand
Authors: Chanchaithong Pattrarat , Prapasarakul Nuvee , Perreten Vincent , Schwendener Sybille
Published: December 2015

A novel staphylococcal cassette chromosome
mec
(SCC
mec
) composite island (SCC
mec
AI16
-SCC
czr
AI16
-CI) was identified in
Staphylococcus pseudintermedius
. Four integration site sequences for SCC subdivided the 60,734-bp island into 41,232-bp SCC
mec
AI16
, 19,400-bp SCC
czr
AI16
, and 102-bp SCC-like
AI16
elements. SCC
mec
AI16
represents a new combination of
ccrA1B3
genes with a class A
mec
complex. SCC
czr
AI16
contains
ccrA1B6
and genes related to restriction modification and heavy metal resistance. SCC
mec
AI16
-SCC
czr
AI16
-CI was found in methicillin-resistant
S. pseudintermedius
sequence type 112 (ST112) and ST111 isolated from dogs and veterinarians in Thailand.
Clinical Candidate VT-1161's Antiparasitic Effect
In Vitro
, Activity in a Murine Model of Chagas Disease, and Structural Characterization in Complex with the Target Enzyme CYP51 from Trypanosoma cruzi
Authors: Hoekstra William J. , Hargrove Tatiana Y. , Wawrzak Zdzislaw , da Gama Jaen Batista Denise , da Silva Cristiane F. , Nefertiti Aline S. G. , Rachakonda Girish , Schotzinger Robert J. , Villalta Fernando , Soeiro Maria de Nazaré C. , Lepesheva Galina I.
Published: December 2015

A novel antifungal drug candidate, the 1-tetrazole-based agent VT-1161 [(
R
)-2-(2,4-difluorophenyl)-1,1-difluoro-3-(1
H
-tetrazol-1-yl)-1-{5-[4-(2,2,2-trifluoroethoxy)phenyl]pyridin-2-yl}propan-2-ol], which is currently in two phase 2b antifungal clinical trials, was found to be a tight-binding ligand (apparent dissociation constant [

K
d

], 24 nM) and a potent inhibitor of cytochrome P450 sterol 14α-demethylase (CYP51) from the protozoan pathogen
Trypanosoma cruzi
. Moreover, VT-1161 revealed a high level of antiparasitic activity against amastigotes of the Tulahuen strain of
T. cruzi
in cellular experiments (50% effective concentration, 2.5 nM) and was active
in vivo
, causing >99.8% suppression of peak parasitemia in a mouse model of infection with the naturally drug-resistant Y strain of the parasite. The data strongly support the potential utility of VT-1161 in the treatment of Chagas disease. The structural characterization of
T. cruzi
CYP51 in complex with VT-1161 provides insights into the molecular basis for the compound's inhibitory potency and paves the way for the further rational development of this novel, tetrazole-based inhibitory chemotype both for antiprotozoan chemotherapy and for antifungal chemotherapy.
The Asp20-to-Asn Substitution in the Response Regulator AdeR Leads to Enhanced Efflux Activity of AdeB in Acinetobacter baumannii
Authors: Nowak Jennifer , Schneiders Thamarai , Seifert Harald , Higgins Paul G.
Published: December 2015

Overexpression of the resistance-nodulation-cell division-type efflux pump AdeABC is often associated with multidrug resistance in
Acinetobacter baumannii
and has been linked to mutations in the genes encoding the AdeRS two-component system. In a previous study, we reported that the Asp20→Asn amino acid substitution in the response regulator AdeR is associated with
adeB
overexpression and reduced susceptibility to the antimicrobials levofloxacin, tigecycline, and trimethoprim-sulfamethoxazole. To further characterize the effect of the Asp20→Asn substitution on antimicrobial susceptibility, the expression of the efflux genes
adeB
,
adeJ
, and
adeG
, and substrate accumulation, four plasmid constructs [containing
adeR
(
Asp20
)
S
,
adeR
(
Asn20
)
S
,
adeR
(
Asp20
)
SABC
, and
adeR
(
Asn20
)
SABC
] were introduced into the
adeRSABC
-deficient
A. baumannii
isolate NIPH 60. Neither
adeRS
construct induced changes in antimicrobial susceptibility or substrate accumulation from that for the vector-only control. The
adeR
(
Asp20
)
SABC
transformant showed reduced susceptibility to 6 antimicrobials and accumulated 12% less ethidium than the control, whereas the Asn20 variant showed reduced susceptibility to 6 of 8 antimicrobial classes tested, and its ethidium accumulation was only 72% of that observed for the vector-only construct.
adeB
expression was 7-fold higher in the
adeR
(
Asn20
)
SABC
transformant than in its Asp20 variant. No changes in
adeG
or
adeJ
expression or in acriflavine or rhodamine 6G accumulation were detected. The antimicrobial susceptibility data suggest that AdeRS does not regulate any resistance determinants other than AdeABC. Furthermore, the characterization of the Asp20→Asn20 substitution proves that the reduced antimicrobial susceptibility previously associated with this substitution was indeed caused by enhanced efflux activity of AdeB.
International Evaluation of MIC Distributions and Epidemiological Cutoff Value (ECV) Definitions for Fusarium Species Identified by Molecular Methods for the CLSI Broth Microdilution Method
Authors: Espinel-Ingroff A. , Colombo A. L. , Cordoba S. , Dufresne P. J. , Fuller J. , Ghannoum M. , Gonzalez G. M. , Guarro J. , Kidd S. E. , Meis J. F. , Melhem T. M. S. C. , Pelaez T. , Pfaller M. A. , Szeszs M. W. , Takahaschi J. P. , Tortorano A. M. , Wiederhold N. P. , Turnidge J.
Published: December 2015

The CLSI epidemiological cutoff values (ECVs) of antifungal agents are available for various
Candida
spp.,
Aspergillus
spp., and the Mucorales. However, those categorical endpoints have not been established for
Fusarium
spp., mostly due to the difficulties associated with collecting sufficient CLSI MICs for clinical isolates identified according to the currently recommended molecular DNA-PCR-based identification methodologies. CLSI MIC distributions were established for 53
Fusarium dimerum
species complex (SC), 10
F. fujikuroi
, 82
F. proliferatum
, 20
F. incarnatum-F. equiseti
SC, 226
F. oxysporum
SC, 608
F. solani
SC, and 151
F. verticillioides
isolates originating in 17 laboratories (in Argentina, Australia, Brazil, Canada, Europe, Mexico, and the United States). According to the CLSI guidelines for ECV setting, ECVs encompassing ≥97.5% of pooled statistically modeled MIC distributions were as follows: for amphotericin B, 4 μg/ml (
F. verticillioides
) and 8 μg/ml (
F. oxysporum
SC and
F. solani
SC); for posaconazole, 2 μg/ml (
F. verticillioides
), 8 μg/ml (
F. oxysporum
SC), and 32 μg/ml (
F. solani
SC); for voriconazole, 4 μg/ml (
F. verticillioides
), 16 μg/ml (
F. oxysporum
SC), and 32 μg/ml (
F. solani
SC); and for itraconazole, 32 μg/ml (
F. oxysporum
SC and
F. solani
SC). Insufficient data precluded ECV definition for the other species. Although these ECVs could aid in detecting non-wild-type isolates with reduced susceptibility to the agents evaluated, the relationship between molecular mechanisms of resistance (gene mutations) and MICs still needs to be investigated for
Fusarium
spp.
Clofazimine Prevents the Regrowth of Mycobacterium abscessus and Mycobacterium avium Type Strains Exposed to Amikacin and Clarithromycin
Authors: Ferro Beatriz E. , Meletiadis Joseph , Wattenberg Melanie , de Jong Arjan , van Soolingen Dick , Mouton Johan W. , van Ingen Jakko
Published: December 2015

Multidrug therapy is a standard practice when treating infections by nontuberculous mycobacteria (NTM), but few treatment options exist. We conducted this study to define the drug-drug interaction between clofazimine and both amikacin and clarithromycin and its contribution to NTM treatment.
Mycobacterium abscessus
and
Mycobacterium avium
type strains were used. Time-kill assays for clofazimine alone and combined with amikacin or clarithromycin were performed at concentrations of 0.25× to 2× MIC. Pharmacodynamic interactions were assessed by response surface model of Bliss independence (RSBI) and isobolographic analysis of Loewe additivity (ISLA), calculating the percentage of statistically significant Bliss interactions and interaction indices (I), respectively. Monte Carlo simulations with predicted human lung concentrations were used to calculate target attainment rates for combination and monotherapy regimens. Clofazimine alone was bacteriostatic for both NTM. Clofazimine-amikacin was synergistic against
M. abscessus
(I = 0.41; 95% confidence interval [CI], 0.29 to 0.55) and
M. avium
(I = 0.027; 95% CI, 0.007 to 0.048). Based on RSBI analysis, synergistic interactions of 28.4 to 29.0% and 23.2 to 56.7% were observed at 1× to 2× MIC and 0.25× to 2× MIC for
M. abscessus
and
M. avium
, respectively. Clofazimine-clarithromycin was also synergistic against
M. abscessus
(I = 0.53; 95% CI, 0.35 to 0.72) and
M. avium
(I = 0.16; 95% CI, 0.04 to 0.35), RSBI analysis showed 23.5% and 23.3 to 53.3% at 2× MIC and 0.25× to 0.5× MIC for
M. abscessus
and
M. avium
, respectively. Clofazimine prevented the regrowth observed with amikacin or clarithromycin alone. Target attainment rates of combination regimens were >60% higher than those of monotherapy regimens for
M. abscessus
and
M. avium
. The combination of clofazimine with amikacin or clarithromycin was synergistic
in vitro
. This suggests a potential role for clofazimine in treatment regimens that warrants further evaluation.
Molecular Characterization by Using Next-Generation Sequencing of Plasmids Containing
bla
NDM-7
in Enterobacteriaceae from Calgary, Canada
Authors: Chen L. , Peirano G. , Lynch T. , Chavda K. D. , Gregson D. B. , Church D. L. , Conly J. , Kreiswirth B. N. , Pitout J. D.
Published: December 2015

Enterobacteriaceae
with
bla
NDM-7
are relatively uncommon and had previously been described in Europe, India, the United States, and Japan. This study describes the characteristics of
Enterobacteriaceae
(
Klebsiella pneumoniae
[
n
= 2],
Escherichia coli
[
n
= 2],
Serratia marcescens
[
n
= 1], and
Enterobacter hormaechei
[
n
= 1] isolates) with
bla
NDM-7
obtained from 4 patients from Calgary, Canada, from 2013 to 2014. The 46,161-bp IncX3 plasmids with
bla
NDM-7
are highly similar to other
bla
NDM
-harboring IncX3 plasmids and, interestingly, showed identical structures within the different isolates. This finding may indicate horizontal transmission within our health region, or it may indicate contact with individuals from areas of endemicity within the hospital setting. Patients infected or colonized with bacteria containing
bla
NDM-7
IncX3 plasmids generate infection control challenges. Epidemiological and molecular studies are required to better understand the dynamics of transmission, the risk factors, and the reservoirs for bacteria harboring
bla
NDM-7
. To the best of our knowledge, this is the first report of
S. marcescens
and
E. hormaechei
with
bla
NDM-7
.
HexR Controls Glucose-Responsive Genes and Central Carbon Metabolism in Neisseria meningitidis
Authors: Antunes Ana , Golfieri Giacomo , Ferlicca Francesca , Giuliani Marzia M. , Scarlato Vincenzo , Delany Isabel
Published: December 2015

Neisseria meningitidis
, an exclusively human pathogen and the leading cause of bacterial meningitis, must adapt to different host niches during human infection.
N. meningitidis
can utilize a restricted range of carbon sources, including lactate, glucose, and pyruvate, whose concentrations vary in host niches. Microarray analysis of
N. meningitidis
grown in a chemically defined medium in the presence or absence of glucose allowed us to identify genes regulated by carbon source availability. Most such genes are implicated in energy metabolism and transport, and some are implicated in virulence. In particular, genes involved in glucose catabolism were upregulated, whereas genes involved in the tricarboxylic acid cycle were downregulated. Several genes encoding surface-exposed proteins, including the MafA adhesins and
Neisseria
surface protein A, were upregulated in the presence of glucose. Our microarray analysis led to the identification of a glucose-responsive
hexR
-like transcriptional regulator that controls genes of the central carbon metabolism of
N. meningitidis
in response to glucose. We characterized the HexR regulon and showed that the
hexR
gene is accountable for some of the glucose-responsive regulation;
in vitro
assays with the purified protein showed that HexR binds to the promoters of the central metabolic operons of the bacterium. Based on DNA sequence alignment of the target sites, we propose a 17-bp pseudopalindromic consensus HexR binding motif. Furthermore,
N. meningitidis
strains lacking
hexR
expression were deficient in establishing successful bacteremia in an infant rat model of infection, indicating the importance of this regulator for the survival of this pathogen
in vivo
.

IMPORTANCE
Neisseria meningitidis
grows on a limited range of nutrients during infection. We analyzed the gene expression of
N. meningitidis
in response to glucose, the main energy source available in human blood, and we found that glucose regulates many genes implicated in energy metabolism and nutrient transport, as well as some implicated in virulence. We identified and characterized a transcriptional regulator (HexR) that controls metabolic genes of
N. meningitidis
in response to glucose. We generated a mutant lacking HexR and found that the mutant was impaired in causing systemic infection in animal models. Since
N. meningitidis
lacks known bacterial regulators of energy metabolism, our findings suggest that HexR plays a major role in its biology by regulating metabolism in response to environmental signals.
Inactivation of Cell Division Protein FtsZ by SulA Makes Lon Indispensable for the Viability of a ppGpp
0
Strain of Escherichia coli
Authors: Nazir Aanisa , Harinarayanan Rajendran
Published: December 2015

The modified nucleotides (p)ppGpp play an important role in bacterial physiology. While the accumulation of the nucleotides is vital for adaptation to various kinds of stress, changes in the basal level modulates growth rate and vice versa. Studying the phenotypes unique to the strain lacking (p)ppGpp (ppGpp
0
) under overtly unstressed growth conditions may be useful to understand functions regulated by basal levels of (p)ppGpp and its physiological significance. In this study, we show that the ppGpp
0
strain, unlike the wild type, requires the Lon protease for cell division and viability in LB. Our results indicate the decrease in FtsZ concentration in the ppGpp
0
strain makes cell division vulnerable to SulA inhibition. We did not find evidence for SOS induction contributing to the cell division defect in the ppGpp
0
Δ
lon
strain. Based on the results, we propose that basal levels of (p)ppGpp are required to sustain normal cell division in
Escherichia coli
during growth in rich medium and that the basal SulA level set by Lon protease is important for insulating cell division against a decrease in FtsZ concentration and conditions that can increase the susceptibility of FtsZ to SulA.

IMPORTANCE
The physiology of the stringent response has been the subject of investigation for more than 4 decades, with the majority of the work carried out using the bacterial model organism
Escherichia coli
. These studies have revealed that the accumulation of (p)ppGpp, the effector of the stringent response, is associated with growth retardation and changes in gene expression that vary with the intracellular concentration of (p)ppGpp. By studying a synthetic lethal phenotype, we have uncovered a function modulated by the basal levels of (p)ppGpp and studied its physiological significance. Our results show that (p)ppGpp and Lon protease contribute to the robustness of the cell division machinery in
E. coli
during growth in rich medium.
Proteome Profiling of the Rhodobacter capsulatus Molybdenum Response Reveals a Role of IscN in Nitrogen Fixation by Fe-Nitrogenase
Authors: Hoffmann Marie-Christine , Wagner Eva , Langklotz Sina , Pfänder Yvonne , Hött Sina , Bandow Julia E. , Masepohl Bernd
Published: December 2015

Rhodobacter capsulatus
is capable of synthesizing two nitrogenases, a molybdenum-dependent nitrogenase and an alternative Mo-free iron-only nitrogenase, enabling this diazotroph to grow with molecular dinitrogen (N
2
) as the sole nitrogen source. Here, the Mo responses of the wild type and of a mutant lacking ModABC, the high-affinity molybdate transporter, were examined by proteome profiling, Western analysis, epitope tagging, and
lacZ
reporter fusions. Many Mo-controlled proteins identified in this study have documented or presumed roles in nitrogen fixation, demonstrating the relevance of Mo control in this highly ATP-demanding process. The levels of Mo-nitrogenase, NifHDK, and the Mo storage protein, Mop, increased with increasing Mo concentrations. In contrast, Fe-nitrogenase, AnfHDGK, and ModABC, the Mo transporter, were expressed only under Mo-limiting conditions. IscN was identified as a novel Mo-repressed protein. Mo control of Mop, AnfHDGK, and ModABC corresponded to transcriptional regulation of their genes by the Mo-responsive regulators MopA and MopB. Mo control of NifHDK and IscN appeared to be more complex, involving different posttranscriptional mechanisms. In line with the simultaneous control of IscN and Fe-nitrogenase by Mo, IscN was found to be important for Fe-nitrogenase-dependent diazotrophic growth. The possible role of IscN as an A-type carrier providing Fe-nitrogenase with Fe-S clusters is discussed.

IMPORTANCE
Biological nitrogen fixation is a central process in the global nitrogen cycle by which the abundant but chemically inert dinitrogen (N
2
) is reduced to ammonia (NH
3
), a bioavailable form of nitrogen. Nitrogen reduction is catalyzed by nitrogenases found in diazotrophic bacteria and archaea but not in eukaryotes. All diazotrophs synthesize molybdenum-dependent nitrogenases. In addition, some diazotrophs, including
Rhodobacter capsulatus
, possess catalytically less efficient alternative Mo-free nitrogenases, whose expression is repressed by Mo. Despite the importance of Mo in biological nitrogen fixation, this is the first study analyzing the proteome-wide Mo response in a diazotroph. IscN was recognized as a novel member of the molybdoproteome in
R. capsulatus
. It was dispensable for Mo-nitrogenase activity but supported diazotrophic growth under Mo-limiting conditions.
Disulfide-Bond-Forming Pathways in Gram-Positive Bacteria
Authors: Reardon-Robinson Melissa E. , Ton-That Hung
Published: December 2015

Disulfide bonds are important for the stability and function of many secreted proteins. In Gram-negative bacteria, these linkages are catalyzed by thiol-disulfide oxidoreductases (Dsb) in the periplasm. Protein oxidation has been well studied in these organisms, but it has not fully been explored in Gram-positive bacteria, which lack traditional periplasmic compartments. Recent bioinformatics analyses have suggested that the high-GC-content bacteria (i.e., actinobacteria) rely on disulfide-bond-forming pathways. In support of this, Dsb-like proteins have been identified inMycobacterium tuberculosis, but their functions are not known.Actinomyces orisandCorynebacterium diphtheriaehave recently emerged as models to study disulfide bond formation in actinobacteria. In both organisms, disulfide bonds are catalyzed by the membrane-bound oxidoreductase MdbA. Remarkably, unlike known Dsb proteins, MdbA is important for pathogenesis and growth, which makes it a potential target for new antibacterial drugs. This review will discuss disulfide-bond-forming pathways in bacteria, with a special focus on Gram-positive bacteria.
Erythema migrans associated with partial Horner's syndrome
Authors: Verma Isha , Agrawal Abhinav
Published: December 2015

Lyme disease is a tick-borne illness caused mainly by three species of spirochaeteBorrelia—B. burgdorferi,B. afzeliiandB. garinii. It has three stages of presentation—early localised, early-disseminated and late Lyme. Erythema migrans is the most common manifestation of Lyme disease, and is usually seen 7–14 days after the tick bite. Patients seldom remember the tick bite. Patients may often present with neurological manifestations indicating neuroborreliosis. These manifestations range from a simple nerve palsy to severe complications such as papilloedema, myelitis or meningitis. We present a case of a 37-year-old woman who presented with partial Horner's syndrome, which was associated with erythema migrans, and other signs of Lyme disease.
Effect of pool confinement on pressures around a block impacted by plunging aerated jets
Authors: Duarte Rafael , Schleiss Anton J. , Pinheiro António
Published: December 2015

The erosion caused by jets issued from hydraulic structures progressively develops a confined scour-hole on the riverbed. A realistic scour assessment must consider both the influence of the air entrained when the jet plunges into the pool and the flow patterns induced by bottom geometry. This experimental study systematically analyzes the combined influence of jet aeration and pool confinement on the dynamic pressures affecting the water–rock interface and inside 3D fissures around a block. The results show that confinement reduces mean pressures and pressure fluctuations when the pool is relatively deep, but almost no influence is found when the pool is shallow, while air entrainment has an opposite effect. Three mechanisms are identified, two of them depend on the pool depth. Furthermore, when a block is mobile, pressures are attenuated inside the surrounding joints. The consequent block vibrations and the presence of air reduce pressure waves celerity inside the fissures.
On the study of the Higgs properties at a muon collider
Authors: Greco Mario
Published: December 2015

The discovery of the Higgs particle at 125 GeV is demanding a detailed knowledge of the properties of this fundamental component of the Standard Model. To that aim various proposals of electron and muon colliders have been put forward for precision studies of the partial widths of the various decay channels. It is shown that in the case of a Higgs factory through a muon collider, sizeable radiative effects — of order of 50% — must be carefully taken into account for a precise measurement of the leptonic and total widths of the Higgs particle. Similar effects do not apply in the case of Higgs production in electron–positron colliders.
The relation of spatial and tensor product of Arveson systems — the random set point of view
Authors: Liebscher Volkmar
Published: December 2015

We characterise the embedding of the spatial product of two Arveson systems into their tensor product using the random set technique. An important implication is that the spatial tensor product does not depend on the choice of the reference units, i.e. it is an intrinsic construction. There is a continuous range of examples coming from the zero sets of Bessel processes where the two products do not coincide. The lattice of all subsystems of the tensor product is analysed in different cases. As a by-product, the Arveson systems coming from Bessel zeros prove to be primitive in the sense of Ref. 12.
Virtual Testing of Large Composite Structures: A Multiple Length/Time-Scale Framework
Authors: Gigliotti Luigi , Pinho Silvestre T.
Published: December 2015

This paper illustrates a multiple length/time-scale framework for the virtual testing of large composite structures. Such framework hinges upon a Mesh Superposition Technique (MST) for the coupling between areas of the structure modelled at different length-scales and upon an efficient solid-to-shell numerical homogenization which exploits the internal symmetries of Unit Cells (UCs). Using this framework, it is possible to minimize the areas of the structure modelled at the lowest- (and computationally demanding) scales and the computational cost required to calculate the homogenised to be used in the higher-scales subdomains of multiscale FE models, as well as to simulate the mechanical response of different parts of the structure using different solvers, depending on where they are expected to provide the most computationally efficient solution. The relevance and key-aspects of the multiple length/time-scale framework are demonstrated through the analysis of a real-sized aeronautical composite component.
Biological Soft Robotics
Authors: Feinberg Adam W.
Published: December 2015

In nature, nanometer-scale molecular motors are used to generate force within cells for diverse processes from transcription and transport to muscle contraction. This adaptability and scalability across wide temporal, spatial, and force regimes have spurred the development of biological soft robotic systems that seek to mimic and extend these capabilities. This review describes how molecular motors are hierarchically organized into larger-scale structures in order to provide a basic understanding of how these systems work in nature and the complexity and functionality we hope to replicate in biological soft robotics. These span the subcellular scale to macroscale, and this article focuses on the integration of biological components with synthetic materials, coupled with bioinspired robotic design. Key examples include nanoscale molecular motor-powered actuators, microscale bacteria-controlled devices, and macroscale muscle-powered robots that grasp, walk, and swim. Finally, the current challenges and future opportunities in the field are addressed.
Synergizing Engineering and Biology to Treat and Model Skeletal Muscle Injury and Disease
Authors: Bursac Nenad , Juhas Mark , Rando Thomas A.
Published: December 2015

Although skeletal muscle is one of the most regenerative organs in our body, various genetic defects, alterations in extrinsic signaling, or substantial tissue damage can impair muscle function and the capacity for self-repair. The diversity and complexity of muscle disorders have attracted much interest from both cell biologists and, more recently, bioengineers, leading to concentrated efforts to better understand muscle pathology and develop more efficient therapies. This review describes the biological underpinnings of muscle development, repair, and disease, and discusses recent bioengineering efforts to design and control myomimetic environments, both to study muscle biology and function and to aid in the development of new drug, cell, and gene therapies for muscle disorders. The synergy between engineering-aided biological discovery and biology-inspired engineering solutions will be the path forward for translating laboratory results into clinical practice.
Consumption-Based Asset Pricing, Part 2: Habit Formation, Conditional Risks, Long-Run Risks, and Rare Disasters
Authors: Breeden Douglas T. , Litzenberger Robert H. , Jia Tingyan
Published: December 2015

Following Part 1 of this article, which reviews late-1970s to 1990s classic derivations and tests of the consumption capital asset pricing model, here in Part 2 we review more recent developments, some of which are based on utility functions with non-time-separable preferences. Important second-generation consumption-based asset pricing advances are also reviewed, including models with habit formation and long-run risk. These models give large cyclical changes in relative risk aversion and risk premiums as well as lagged impacts of aggregate consumption changes on risk premiums. We review asset pricing with rare disasters and models focused on consumer spending on durables and real estate, as well as the fraction of spending financed by labor income. The second-generation models discussed have more free parameters and fit the empirical data better than did the first-generation consumption-based asset pricing models.
Hedge Funds: A Dynamic Industry in Transition
Authors: Getmansky Mila , Lee Peter A. , Lo Andrew W.
Published: December 2015

The hedge-fund industry has grown rapidly over the past two decades, offering investors unique investment opportunities that often reflect more complex risk exposures than those of traditional investments. In this article, we present a selective review of the recent academic literature on hedge funds as well as updated empirical results for this industry. Our review is written from several distinct perspectives: the investor's, the portfolio manager's, the regulator's, and the academic's. Each of these perspectives offers a different set of insights into the financial system, and the combination provides surprisingly rich implications for the Efficient Markets Hypothesis, investment management, systemic risk, financial regulation, and other aspects of financial theory and practice.
The Value and Risk of Human Capital
Authors: Benzoni Luca , Chyruk Olena
Published: December 2015

Human capital embodies the knowledge, skills, health, and values that contribute to making people productive. These qualities, however, are hard to measure, and quantitative studies of human capital are typically based on the valuation of the lifetime income that a person generates in the labor market. This article surveys the theoretical and empirical literature that models a worker's life-cycle earnings and identifies appropriate discount rates to translate those cash flows into a certainty equivalent of wealth. We begin with an overview of a stylized model of human capital valuation with exogenous labor income. We then discuss extensions to this framework that study the underlying economic sources of labor income shocks, the choices that people make during their lives (such as about work, leisure, retirement, and investment in education), and the implications of these factors for human capital valuation and risk.
The Role of Risk Management in Corporate Governance
Authors: Ellul Andrew
Published: December 2015

Failures of banks' governance and risk management functions have been identified as key causes of the 2007–2008 financial crisis. This article reviews the empirical literature that investigates the relationship between governance structures and risk management functions as well as their impact on banks' risk taking and performance. I first discuss risk management's responsibilities and relevance for a value-maximizing bank. The business nature of financial institutions and their funding structure, together with explicit and implicit government guarantees, set them apart from nonfinancial firms. I argue that conventional governance structures alone may be unable to restrain risk taking in banks and thus the presence of a strong and independent risk management function becomes necessary to monitor and control enterprise-wide risk exposures. Recent evidence shows that a strong risk management function, compatible with the appropriate business model and culture, can restrain tail risk exposures at financial institutions and promote long-term value maximization.
Recent Advances in Research on Hedge Fund Activism: Value Creation and Identification
Authors: Brav Alon , Jiang Wei , Kim Hyunseob
Published: December 2015

Hedge fund activism emerged as a major force of corporate governance in the 2000s. By the mid-2000s, there were between 150 and 200 activist hedge funds in action each year, advocating for changes in 200–300 publicly listed companies in the United States. In this article, we review the evolution and major characteristics of hedge fund activism, as well as the short- and long-term impacts of the performance and governance of targeted companies. Though most of the analyses here are based on a comprehensive sample of over 2,000 activism events in the United States from 1994 to 2011, hand-collected by the authors from regulatory filings and news searches, this article covers all major studies on the topic, including those on markets outside of the United States.
Financing Innovation
Authors: Kerr William R. , Nanda Ramana
Published: December 2015

We review the recent literature on the financing of innovation, inclusive of large companies and new start-ups. This research strand has been very active over the past five years, generating important new findings, questioning some long-held beliefs, and creating its own puzzles. Our review outlines the growing body of work that documents a role for debt financing related to innovation. We highlight the new literature on learning and experimentation across multistage innovation projects and how this impacts optimal financing design. We further highlight the strong interaction between financing choices for innovation and changing external conditions, especially reduced experimentation costs.
Disaster Risk and Its Implications for Asset Pricing
Authors: Tsai Jerry , Wachter Jessica A.
Published: December 2015

After lying dormant for more than two decades, the rare disaster framework has emerged as a leading contender to explain facts about the aggregate market, interest rates, and financial derivatives. In this article, we survey recent models of disaster risk that provide explanations for the equity premium puzzle, the volatility puzzle, return predictability, and other features of the aggregate stock market. We show how these models can also explain violations of the expectations hypothesis in bond pricing as well as the implied volatility skew in option pricing. We review both modeling techniques and results and consider both endowment and production economies. We show that these models provide a parsimonious and unifying framework for understanding puzzles in asset pricing.
Peer-to-Peer Crowdfunding: Information and the Potential for Disruption in Consumer Lending
Authors: Morse Adair
Published: December 2015

Can peer-to-peer lending (P2P) disintermediate and mitigate information frictions in lending so that choices and outcomes for at least some borrowers and investors are improved? I offer a framing of issues and survey the nascent literature on P2P. On the investor side, P2P disintermediates an asset class of consumer loans, and investors may be able to capture rents associated with the removal of a layer of financial intermediation. Risk and portfolio choice questions linger prior to any inference. On the borrower side, evidence suggests that proximate knowledge (direct or inferred) unearths soft information. Thus, P2P may be able to offer pricing and/or access benefits to potential borrowers. Early research suggests that the future of consumer lending will involve more big data and reintermediation of underwriting by all types of financial institutions. I ask many more questions than current research can answer, hoping to motivate future research.
Trend Analysis of Malaria Occurrence in Wolaita Zone, Southern Ethiopia: Retrospective Cross-Sectional Study
Authors: Legesse Deresse , Haji Yusuf , Abreha Solomon
Published: December 2015

Background. Malaria is a major public health problem in Ethiopia. The trend of malaria occurrence remains unknown in the study area. This study is aimed at determining the last five years’ trend of malaria occurrence from 2008/09 to 2012/13 in Wolaita Zone, Southern Ethiopia. Methods. A health facility-based retrospective study was conducted in Wolaita Zone from March to August, 2014. Five years’ laboratory confirmed malaria record review was made from six health centers. Result. A total of 105,755 laboratory confirmed malaria cases were reported, with total slide positivity rate of 33.27% and mean annual occurrence of 21,151 cases. Malaria occurred with a fluctuating trend in the study area, with its peak occurring at the year 2011/12. Overall, no remarkable decline in the total laboratory confirmed malaria was observed in the last five years. P. falciparum was the predominantly reported species, accounting for 75,929 (71.80%) of cases. The highest slide positivity rate was observed in the age group of 5–14 years (40.5%) followed by 1–4 years (35.5%). Two malaria peak seasons occurred: one from September to December and the other from April to June. Conclusion. No remarkable decline in laboratory confirmed malaria in the last five years was observed.
Acute Myocarditis in a Patient with Newly Diagnosed Granulomatosis with Polyangiitis
Authors: Munch Anne , Sundbøll Jens , Høyer Søren , Pareek Manan
Published: December 2015

A 22-year-old woman recently diagnosed with granulomatosis with polyangiitis (GPA) was admitted to the department of cardiology due to chest pain and shortness of breath. The ECG showed widespread mild PR-segment depression, upwardly convex ST-segment elevation, and T-wave inversion. The troponin T level was elevated at 550 ng/L. Transthoracic echocardiography showed basal inferoseptal thinning and hypokinesis, mild pericardial effusion, and an overall preserved left ventricular ejection fraction of 55%. Global longitudinal strain, however, was clearly reduced. Cardiac magnetic resonance imaging (MRI) showed findings consistent with myocarditis but the etiology of the apical hypokinesis could not be determined with certainty and may well have been due to a myocardial infarction, a notion supported by a coronary angiogram displaying slow flow in the territory of the left anterior descending artery. Finally, an endomyocardial biopsy confirmed the diagnosis of myocarditis. The cardiac symptoms subsided upon treatment with high-dose prednisolone and rituximab.
The Significance of Asthma Follow-Up Consultations for Adherence to Asthma Medication, Asthma Medication Beliefs, and Asthma Control
Authors: Axelsson Malin , Ekerljung Linda , Lundbäck Bo
Published: December 2015

Objective. The aim was to investigate adherence to asthma medication treatment, medication beliefs, and asthma control in relation to asthma follow-up consultations in asthmatics in the general population. A further aim was to describe associations between adherence, medication beliefs, and asthma control.Method. In the population-based West Sweden Asthma Study, data allowing calculation of adherence for 4.5 years based on pharmacy records were obtained from 165 adult asthmatics. Additional data were collected through questionnaires and structured interviews.Results. The mean adherence value for filled prescriptions for regular asthma medication was 68% (median 55.3%) but varied over the year under study. Adherence to combination inhalers with corticosteroids and long-acting beta2agonists was higher than adherence to single inhalers with corticosteroids only. More than one-third of participants reported not having seen an asthma nurse or physician for several years. Regular asthma follow-up consultations were associated with both higher adherence and the belief that asthma medication was necessary but were not associated with asthma control.Conclusions. Adherence to asthma medication treatment was low and varied over the year under study. The current study suggests that quality improvements in asthma care are needed if adherence to asthma medication is to be improved.
Computer Simulation and Analysis on Flow Characteristics and Distribution Patterns of Polymethylmethacrylate in Lumbar Vertebral Body and Vertebral Pedicle
Authors: Liu Da , Liu Xu-li , Zhang Bo , Liao Dong-fa , Li Zhi-qiang , Zhou Jiang-jun , Kang Xia , Zheng Wei , Lei Wei
Published: December 2015

This study was designed to analyze the flow and distribution of polymethylmethacrylate (PMMA) in vertebral body through computer simulation. Cadaveric lumbar vertebrae were scanned through electron beam tomography (EBT). The data was imported into Mimics software to build computational model. Vertebral body center and junction of pedicle and vertebral body were chosen as injection points. Silicone oil with viscosity of 100,000 cSt matching with PMMA bone cement was chosen for injection. The flow and distribution of silicone oil were analyzed using Fluent software. In vertebral body, silicone oil formed a circle-like shape centered by injection point on transverse and longitudinal sections, finally forming a sphere-like shape as a whole. Silicone oil diffused along lateral and posterior walls forming a circle-like shape on transverse section centered by injection point in pedicle, eventually forming a sphere-like shape as a whole. This study demonstrated that silicone oil flowed and diffused into a circle-like shape centered by injection point and finally formed a sphere-like shape as a whole in both vertebral body and pedicle. The flow and distribution of silicon oil in computational model could simulate PMMA distribution in vertebral body. It may provide theoretical evidence to reduce PMMA leakage risk during percutaneous vertebroplasty.
Identification of Extended-Spectrumβ-LactamasesEscherichia coliStrains Isolated from Market Garden Products and Irrigation Water in Benin
Authors: Moussé Wassiyath , Sina Haziz , Baba-Moussa Farid , Noumavo Pacôme A. , Agbodjato Nadège A. , Adjanohoun Adolphe , Baba-Moussa Lamine
Published: December 2015

The present study aimed at biochemical and molecular characterization ofEscherichia colistrains isolated from horticultural products and irrigation water of Cotonou. The samples were collected from 12 market gardeners of 4 different sites. Rapid’E. colimedium was used for identification ofE. colistrains and the antimicrobial susceptibility was performed by the agar disk diffusion method. Theβ-lactamases production was sought by the liquid acidimetric method. The genes coding forβ-lactamases and toxins were identified by PCR method. The results revealed that about 34.95% of the analyzed samples were contaminated byE. coli. Cabbages were the most contaminated byE. coli(28.26%) in dry season. All isolated strains were resistant to amoxicillin. The penicillinase producingE. colicarriedblaTEM(67.50%),blaSHV(10%), andblaCTX-M(22.50%) genes. The study revealed that the resistance genes such as SLTI (35.71%), SLTII (35.71%), ETEC (7.15%), and VTEC (21.43%) were carried. Openly to the found results and considering the importance of horticultural products in Beninese food habits, it is important to put several strategies aiming at a sanitary security by surveillance and sensitization of all the actors on the risks of some practices.
Bufalin Inhibits HCT116 Colon Cancer Cells and Its Orthotopic Xenograft Tumor in Mice Model through Genes Related to Apoptotic and PTEN/AKT Pathways
Authors: Wang Jie , Chen Chao , Wang Shiying , Zhang Yong , Yin Peihao , Gao Zhongxiang , Xu Jie , Feng Dianxu , Zuo Qinsong , Zhao Ronghua , Chen Teng
Published: December 2015

Aims. To investigate the anticolorectal cancer (CRC) effects of Bufalin, a bioactive polyhydroxysteroid from Venenum Bufonis, using HCT116 human CRC cell and an established orthotopic xenograft model in mice, and to explore the mechanisms of action.Material and Methods. Cultured HCT116 cells or BALB/c mice with orthotopic tumor were treated by Bufalin (positive control: 5-FU). Cell proliferation, apoptosis, and cycling were determined by MTT, Annexin V/PI staining, and flow cytometry, respectively. In mice, tumor inhibition rate and animal survival were calculated. The expressions of PTEN/phosphate-PTEN, AKT/phosphate-AKT, Bad, Bcl-xl, Bax, or Caspase-3 in cells and/or tumors were determined by Western blot or immunohistochemical staining.Results. Bufalin significantly inhibited cell proliferation and induced cell apoptosis and cycle arrest in a dose/time-dependent manner. In the animal model, Bufalin treatment resulted in significant inhibition of tumor growth and prolonged survival. In the Bufalin-treated cultured cells and/or xenograft tumors, the expressions of PTEN, Bad, Bax, and Caspase-3 were significantly increased, while p-AKT and Bcl-xL significantly decreased.Conclusions. Our results indicate that Bufalin inhibit cell proliferation and orthotopic tumor growth by inducing cell apoptosis through the intrinsic apoptotic pathway, which is of pivotal significance in the identification of an anticancer drug that may synergize with Bufalin.
HCBLS: A Hierarchical Cluster-Based Location Service in Urban Environment
Authors: Aissaoui Raik , Dhraief Amine , Belghith Abdelfettah , Menouar Hamid , Mathkour Hassan , Filali Fethi , Abu-Dayya Adnan
Published: December 2015

Vehicle location information is central to many location-based services and applications in VANETs. Tracking vehicles positions and maintaining an accurate up-to-date view of the entire network are not easy due to the high mobility of vehicles and consequently rapid topology changes. The design of a scalable, accurate, and efficient location service is still a very challenging issue. In this paper, we propose a lightweight hierarchical cluster-based location service in city environments (HCBLS). HCBLS integrates a logical clustering based on the city digital map and consequently does not involve extra signaling overhead. An advanced location update aggregation at different levels of the assumed hierarchy is adopted to maintain up-to-date and accurate location information. Simulation results show that HCBLS achieves much better performances than the Efficient Map-Based Location Service (EMBLS) and any regular (non-cluster-based) updating scheme. HCBLS increases the success rate by around 10%, improves the overview of the network by more than 30%, lowers the location update and query costs by more than 7 times, lowers the message delivery latency by around 3 times, and presents around 4 times better localization accuracy.
A Unified Approach to Nonlinear Dynamic Inversion Control with Parameter Determination by Eigenvalue Assignment
Authors: Wang Yu-Chi , Sheu Donglong , Lin Chin-E
Published: December 2015

This paper presents a unified approach to nonlinear dynamic inversion control algorithm with the parameters for desired dynamics determined by using an eigenvalue assignment method, which may be applied in a very straightforward and convenient way. By using this method, it is not necessary to transform the nonlinear equations into linear equations by feedback linearization before beginning control designs. The applications of this method are not limited to affine nonlinear control systems or limited to minimum phase problems if the eigenvalues of error dynamics are carefully assigned so that the desired dynamics is stable. The control design by using this method is shown to be robust to modeling uncertainties. To validate the theory, the design of a UAV control system is presented as an example. Numerical simulations show the performance of the design to be quite remarkable.
Fabrication of Surface Level Cu/SiCp Nanocomposites by Friction Stir Processing Route
Authors: Srinivasan Cartigueyen , Karunanithi Mahadevan
Published: December 2015

Friction stir processing (FSP) technique has been successfully employed as low energy consumption route to prepare copper based surface level nanocomposites reinforced with nanosized silicon carbide particles (SiCp). The effect of FSP parameters such as tool rotational speed, processing speed, and tool tilt angle on microstructure and microhardness was investigated. Single pass FSP was performed based on Box-Behnken design at three factors in three levels. A cluster of blind holes 2 mm in diameter and 3 mm in depth was used as particulate deposition technique in order to reduce the agglomeration problem during composite fabrication. K-type thermocouples were used to measure temperature histories during FSP. The results suggest that the heat generation during FSP plays a significant role in deciding the microstructure and microhardness of the surface composites. Microstructural observations revealed a uniform dispersion of nanosized SiCp without any agglomeration problem and well bonded with copper matrix at different process parameter combinations. X-ray diffraction study shows that no intermetallic compound was produced after processing. The microhardness of nanocomposites was remarkably enhanced and about 95% more than that of copper matrix.
Cervical Spinal Meningeal Melanocytoma Presenting as Intracranial Superficial Siderosis
Authors: Srirama Jayamma Savitha , Sud Seema , Buxi TBS , Madan VS , Goyal Ashish , Dhawan Shashi
Published: December 2015

Meningeal melanocytoma is a rare pigmented tumor of the leptomeningeal melanocytes. This rare entity results in diagnostic difficulty in imaging unless clinical and histopathology correlation is performed. In this case report, we describe a case of meningeal melanocytoma of the cervical region presenting with superficial siderosis. Extensive neuroradiological examination is necessary to locate the source of the bleeding in such patients. Usually, the patient will be cured by the complete surgical excision of the lesion.