bluuebunny/crossref_metadata_2025 huggingface dataset:
Predictive Value of Molecular Drug Resistance Testing of Mycobacterium tuberculosis Isolates in Valle del Cauca, Colombia
Authors: Ferro Beatriz E. , García Pamela K. , Nieto Luisa Maria , van Soolingen Dick
Published: May 2013

Previous evaluations of the molecular GenoType tests have promoted their use to detect resistance to first- and second-line antituberculosis drugs in different geographical regions. However, there are known geographic variations in the mutations associated with drug resistance in
Mycobacterium tuberculosis
, and especially in South America, there is a paucity of information regarding the frequencies and types of mutations associated with resistance to first- and second-line antituberculosis drugs. We therefore evaluated the performance of the GenoType kits in this region by testing 228
M. tuberculosis
isolates in Colombia, including 134 resistant and 94 pansusceptible strains. Overall, the sensitivity and specificity of the GenoType MTBDR
plus
test ranged from 92 to 96% and 97 to 100%, respectively; the agreement index was optimal (Cohen's kappa, >0.8). The sensitivity of the GenoType MTBDR
sl
test ranged from 84 to 100% and the specificity from 88 to 100%. The most common mutations were
katG
S315T1,
rpoB
S531L,
embB
M306V,
gyrA
D94G, and
rrs
A1401G. Our results reflect the utility of the GenoType tests in Colombia; however, as some discordance still exists between the conventional and molecular approaches in resistance testing, we adhere to the recommendation that the GenoType tests serve as early guides for therapy, followed by phenotypic drug susceptibility testing for all cases.
Clustering of Tuberculosis Cases Based on Variable-Number Tandem-Repeat Typing in Relation to the Population Structure of Mycobacterium tuberculosis in the Netherlands
Authors: Sloot Rosa , Borgdorff Martien W. , de Beer Jessica L. , van Ingen Jakko , Supply Philip , van Soolingen Dick
Published: May 2013

The population structure of 3,776
Mycobacterium tuberculosis
isolates was determined using variable-number tandem-repeat (VNTR) typing. The degree of clonality was so high that a more relaxed definition of clustering cannot be applied. Among recent immigrants with non-Euro-American isolates, transmission is overestimated if based on identical VNTR patterns.
Ward-Specific Rates of Nasal Cocolonization with Methicillin-Susceptible and -Resistant Staphylococcus spp. and Potential Impact on Molecular Methicillin-Resistant Staphylococcus aureus Screening Tests
Authors: Trouillet-Assant Sophie , Rasigade Jean-Philippe , Lustig Sebastien , Lhoste Yannick , Valour Florent , Guerin Claude , Aubrun Frederic , Tigaud Sylvestre , Laurent Frederic
Published: May 2013

We report that the rates of nasal cocolonization with methicillin-susceptible
Staphylococcus aureus
and methicillin-resistant coagulase-negative staphylococci can vary widely between patients admitted to different wards within a single hospital. Such cocolonization can greatly influence the performance of molecular methicillin-resistant
S. aureus
(MRSA) screening tests depending on the methods used and targets selected.
Rapid Molecular Detection of Macrolide Resistance in the Mycobacterium avium Complex: Are We There Yet?
Authors: Christianson Sara , Grierson William , Wolfe Joyce , Sharma Meenu K.
Published: May 2013

Macrolides are an important tool in the treatment of
Mycobacterium avium
complex infections. Here, we evaluate the use of 23S rRNA gene sequencing for the rapid detection of macrolide resistance. Routine sequencing of the 23S rRNA gene is highly specific for macrolide resistance but lacks in sensitivity.
Multicenter Study Evaluating the Vitek MS System for Identification of Medically Important Yeasts
Authors: Westblade Lars F. , Jennemann Rebecca , Branda John A. , Bythrow Maureen , Ferraro Mary Jane , Garner Omai B. , Ginocchio Christine C. , Lewinski Michael A. , Manji Ryhana , Mochon A. Brian , Procop Gary W. , Richter Sandra S. , Rychert Jenna A. , Sercia Linda , Burnham Carey-Ann D.
Published: May 2013

The optimal management of fungal infections is correlated with timely organism identification. Matrix-assisted laser desorption ionization–time of flight (MALDI-TOF) mass spectrometry (MS) is revolutionizing the identification of yeasts isolated from clinical specimens. We present a multicenter study assessing the performance of the Vitek MS system (bioMérieux) in identifying medically important yeasts. A collection of 852 isolates was tested, including 20
Candida
species (626 isolates, including 58
C. albicans
, 62
C. glabrata
, and 53
C. krusei
isolates), 35
Cryptococcus neoformans
isolates, and 191 other clinically relevant yeast isolates; in total, 31 different species were evaluated. Isolates were directly applied to a target plate, followed by a formic acid overlay. Mass spectra were acquired using the Vitek MS system and were analyzed using the Vitek MS v2.0 database. The gold standard for identification was sequence analysis of the D2 region of the 26S rRNA gene. In total, 823 isolates (96.6%) were identified to the genus level and 819 isolates (96.1%) were identified to the species level. Twenty-four isolates (2.8%) were not identified, and five isolates (0.6%) were misidentified. Misidentified isolates included one isolate of
C. albicans
(
n
= 58) identified as
Candida dubliniensis
, one isolate of
Candida parapsilosis
(
n
= 73) identified as
Candida pelliculosa
, and three isolates of
Geotrichum klebahnii
(
n
= 6) identified as
Geotrichum candidum
. The identification of clinically relevant yeasts using MS is superior to the phenotypic identification systems currently employed in clinical microbiology laboratories.
Identification of
bla
OXA-51-like
,
bla
OXA-58
,
bla
DIM-1
, and
bla
VIM
Carbapenemase Genes in Hospital Enterobacteriaceae Isolates from Sierra Leone
Authors: Leski Tomasz A. , Bangura Umaru , Jimmy David H. , Ansumana Rashid , Lizewski Stephen E. , Li Robert W. , Stenger David A. , Taitt Chris R. , Vora Gary J.
Published: May 2013

We describe the results of a molecular epidemiological survey of 15 carbapenemase-encoding genes from a recent collection of clinical isolates from Mercy Hospital in Bo, Sierra Leone. The most salient findings revealed that (i) 60% of the isolates harbored multiple carbapenemase genes; (ii) the
bla
DIM-1
gene, which has previously only been reported in The Netherlands, is also circulating in this environment; and (iii)
bla
OXA-51-like
and
bla
OXA-58
genes, which were thought to reside exclusively in
Acinetobacter
species, can also be found in members of the
Enterobacteriaceae
.
Asymptomatic Carriage of Sequence Type 398,
spa
Type t571 Methicillin-Susceptible Staphylococcus aureus in an Urban Jail: a Newly Emerging, Transmissible Pathogenic Strain
Authors: David Michael Z. , Siegel Jane , Lowy Franklin D. , Zychowski Diana , Taylor Alexis , Lee Caroline J. , Boyle-Vavra Susan , Daum Robert S.
Published: May 2013

Sequence type 398 (ST398)
Staphylococcus aureus
, frequently carried by livestock, has caused severe human infections and often carries transmissible antibiotic resistance genes. Among methicillin-susceptible
S. aureus
isolates colonizing Dallas County Jail detainees, 13.2% were ST398,
spa
type t571, and were genetically similar to human colonization isolates from New York, Chicago, and the Dominican Republic.
The CD225 Domain of IFITM3 Is Required for both IFITM Protein Association and Inhibition of Influenza A Virus and Dengue Virus Replication
Authors: John Sinu P. , Chin Christopher R. , Perreira Jill M. , Feeley Eric M. , Aker Aaron M. , Savidis George , Smith Sarah E. , Elia Andrew E. H. , Everitt Aaron R. , Vora Mehul , Pertel Thomas , Elledge Stephen J. , Kellam Paul , Brass Abraham L.
Published: May 2013

The interferon-induced transmembrane protein 3 (IFITM3) gene is an interferon-stimulated gene that inhibits the replication of multiple pathogenic viruses
in vitro
and
in vivo
. IFITM3 is a member of a large protein superfamily, whose members share a functionally undefined area of high amino acid conservation, the CD225 domain. We performed mutational analyses of IFITM3 and identified multiple residues within the CD225 domain, consisting of the first intramembrane domain (intramembrane domain 1 [IM1]) and a conserved intracellular loop (CIL), that are required for restriction of both influenza A virus (IAV) and dengue virus (DENV) infection
in vitro
. Two phenylalanines within IM1 (F75 and F78) also mediate a physical association between IFITM proteins, and the loss of this interaction decreases IFITM3-mediated restriction. By extension, similar IM1-mediated associations may contribute to the functions of additional members of the CD225 domain family. IFITM3's distal N-terminal domain is also needed for full antiviral activity, including a tyrosine (Y20), whose alteration results in mislocalization of a portion of IFITM3 to the cell periphery and surface. Comparative analyses demonstrate that similar molecular determinants are needed for IFITM3's restriction of both IAV and DENV. However, a portion of the CIL including Y99 and R87 is preferentially needed for inhibition of the orthomyxovirus. Several IFITM3 proteins engineered with rare single-nucleotide polymorphisms demonstrated reduced expression or mislocalization, and these events were associated with enhanced viral replication
in vitro
, suggesting that possessing such alleles may impact an individual's risk for viral infection. On the basis of this and other data, we propose a model for IFITM3-mediated restriction.
Contribution of Follicular Dendritic Cells to Persistent HIV Viremia
Authors: Zhang Jingshan , Perelson Alan S.
Published: May 2013

HIV-1 infections cannot be completely eradicated by drug therapy, as the virus persists in reservoirs. Low-level plasma viremia has been detected in patients treated for over 7 years, but the cellular compartments that support this low-level viremia have not been identified. The decay of HIV-1 during treatment appears to occur in four phases, with the 3rd and 4th phases occurring when the virus is below the limit of detection of conventional assays. Here, we focus on the 3rd phase of decay, which has been estimated to have a half-life of 39 months. We show that follicular dendritic cells (FDC), which have been identified as an HIV reservoir, can be the main source of the low-level viremia detected during the 3rd phase of decay and contribute to viremia at even longer times. Our calculations show that the kinetics of leakage of virus from FDC is consistent with three types of available clinical data.
NS3 of Bluetongue Virus Interferes with the Induction of Type I Interferon
Authors: Chauveau Emilie , Doceul Virginie , Lara Estelle , Breard Emmanuel , Sailleau Corinne , Vidalain Pierre-Olivier , Meurs Eliane F. , Dabo Stéphanie , Schwartz-Cornil Isabelle , Zientara Stéphan , Vitour Damien
Published: May 2013

Upon infection with Bluetongue virus (BTV), an arthropod-borne virus, type I interferon (IFN-I) is producedin vivoandin vitro. IFN-I is essential for the establishment of an antiviral cellular response, and most if not all viruses have elaborated strategies to counteract its action. In this study, we assessed the ability of BTV to interfere with IFN-I synthesis and identified the nonstructural viral protein NS3 as an antagonist of the IFN-I system.
Comparison of the Levels of Infectious Virus in Respirable Aerosols Exhaled by Ferrets Infected with Influenza Viruses Exhibiting Diverse Transmissibility Phenotypes
Authors: Gustin Kortney M. , Katz Jacqueline M. , Tumpey Terrence M. , Maines Taronna R.
Published: May 2013

Influenza viruses pose a major public health burden to communities around the world by causing respiratory infections that can be highly contagious and spread rapidly through the population. Despite extensive research on influenza viruses, the modes of transmission occurring most often among humans are not entirely clear. Contributing to this knowledge gap is the lack of an understanding of the levels of infectious virus present in respirable aerosols exhaled from infected hosts. Here, we used the ferret model to evaluate aerosol shedding patterns and measure the amount of infectious virus present in exhaled respirable aerosols. By comparing these parameters among a panel of human and avian influenza viruses exhibiting diverse respiratory droplet transmission efficiencies, we are able to report that ferrets infected by highly transmissible influenza viruses exhale a greater number of aerosol particles and more infectious virus within respirable aerosols than ferrets infected by influenza viruses that do not readily transmit. Our findings improve our understanding of the ferret transmission model and provide support for the potential for influenza virus aerosol transmission.
Unusual solid mass in the popliteal fossa
Authors: Smurthwaite Katharine Anne , Barnard Edward
Published: May 2013

We present a clinical case image of a 20-year-old man with a lump behind his knee. A radiograph taken in the emergency department demonstrated the classical appearance of an osteochondroma. Osteochondroma is the commonest skeletal neoplasm. Surgical excision results in symptom resolution in over 90% of patients.
Symptomatic lobar intracerebral haemorrhage preceded by transient focal neurological episodes
Authors: Hurford Robert , Charidimou Andreas , Werring David
Published: May 2013

We report the case of a symptomatic intracerebral haemorrhage (ICH) in an elderly woman, secondary to cerebral amyloid angiopathy (CAA), and present the relevant imaging. A few months before, our patient experienced multiple, stereotyped, brief episodes of spreading paraesthesias, which were considered to be transient ischaemic attacks (TIAs) and treated with antithrombotic agents. In this case report, we explore CAA, a highly prevalent but under-recognised form of small vessel cerebrovascular disease and common cause of ICH. We then briefly discuss the clinical significance of transient focal neurological episodes in the context of CAA, as potential warning signs of future ICH. An important clinical message is that misdiagnosis of CAA-related focal neurological symptoms as TIAs (and prescribing antithrombotic drugs) could lead to potentially avoidable ICH. We also provide the current evidence base for the acute and secondary prevention treatment of patients with lobar ICH attributed to CAA, and discuss the prognosis.
Giant aneurysm in a left coronary artery fistula: diagnostic cardiovascular imaging and treatment considerations
Authors: Frestad Daria , Helqvist Steffen , Helvind Morten , Kofoed Klaus
Published: May 2013

Congenital coronary artery fistula complicated with giant coronary artery aneurysm is a very rare condition. In this case report, we present a 65-year-old woman, referred to us with a continuous heart murmur, occasional atypical chest pain and few episodes of fainting. A giant aneurysm and a coronary–pulmonary fistula were diagnosed using multiple cardiovascular imaging modalities to provide a sufficient anatomical picture. The patient was considered at high risk of sudden death from aneurysm rupture and received surgical treatment. Subsequent histopathological examination revealed a true aneurysm with severe wall calcifications, ulcerations and large areas with marked thinning of the wall. The postoperative course was uneventful.
Nitrofurantoin: cause of DRESS syndrome
Authors: Leão Rodrigo Nazário , Barreto Paulo , Leão Ricardo R , Ribeiro José Vaz
Published: May 2013

Urinary tract infections (UTIs) are a common pathological entity among elderly patients. The widespread use of antibiotics for uncomplicated UTIs has gained many opponents mainly due to the increasing drug resistance observed. Nitrofurantoin is a commonly used antibacterial drug because it has low side effects and a good antiurinary bacterial profile. However, in this paper, we present a case of a nitrofurantoin-induced DRESS (drug reaction/rash with eosinophilia and systemic symptoms) syndrome in a 77-year-old woman. During UTI treatment, the patient developed an acute skin rash which spread all over the body and a considerable decrease in urine volume. At the emergency department, we found her developing eosinophilic pneumonia, anaemia and renal impairment that we relate to nitrofurantoin administration. To our knowledge, this is the second published case report which evokes nitrofurantoin as a possible cause of DRESS syndrome.
Unwanted baggage
Authors: Leitz Nicolas , Leitz Zarqa , Schaller Martin
Published: May 2013

An elderly woman with a rapidly progressing lower leg ulcer presented with features of systemic inflammatory response syndrome (SIRS). The ulcer had occurred after hitting her leg against a piece of luggage. The causative pathogen in our case was byCorynebacterium ulcerans, demonstrated in bacterial cultures and by PCR. Disease progression was stopped only by Linezolid intravenous. after several other antibiotics failed to help. Diphtheria is known to most physicians as a respiratory disease caused byCorynebacterium diphtheriawhich is occurring in the developed world infrequently because of widespread use of immunisation programmes. However, cutaneous infection with diphtheria is increasingly being diagnosed.
Concurrent caecal and transverse colonic tuberculosis masquerating synchronous colonic carcinoma
Authors: Demetriou George A , Nair Manojkumar S , Navaratnam Romi
Published: May 2013

We present a 46-year-old Somalian woman, who attended our hospital, with 1 week history of worsening epigastric pain and vomiting, worse after eating on a background of 3 months history of four stones loss of weight, malaise and decreased appetite. CT scan of the abdomen revealed an annular 10 cm long mass of the right transverse colon with a second mass of the caecum raising concerns of a synchronous colonic cancer. She underwent an extended right hemi-colectomy due to the development of obstruction from the transverse colon lesion. The histology revealed caseating, transmural granulomatous inflammation consistent with tuberculosis. She had an uneventful recovery and was discharged on the tenth postoperative day on antituberculosis (anti-TB) medications. She reports complete resolution of her symptoms 4 months after discharge.
Critical upper airway obstruction in sporadic angioedema responding to C1-esterase inhibitor
Authors: O'Keefe Andrew W , McCusker Christine , Ben-Shoshan Moshe
Published: May 2013

We describe a case of recurrent oropharyngeal angioedema in a 16-year-old boy with a history of sickle cell disease and thrombocytopenia and with no family history of angioedema. Emergency treatment of angioedema with C1-esterase inhibitor (C1-INH) provided immediate relief, avoiding the placement of a surgical airway. Further evaluation has shown C1-INH to be normal in quantity and function, with normal complement studies during acute attacks. Genetic testing revealed no abnormality in the factor XII gene. Our case exemplifies that even in cases of sporadic angioedema, treatment with C1-INH may be an effective and life-saving management strategy.
An efficient method for correction of anterior crossbite without using bite plates
Authors: Bhardwaj Preeti , Verma Santosh Kumar , Rastogi Khushboo , Bhushan Rajarshi
Published: May 2013

In cases of anterior crossbite we need to disocclude the bite so as to initiate unrestricted pathway for the teeth to come into the arch. Various techniques have been advocated for this purpose but most of them are either costly, time consuming or not very effective. So, by the use of simple bondable Begg bracket and elastics we devised a method to disocclude the bite and help in correction of anterior crossbite. It is easy, economical, efficient and less time consuming.
Polymorphous low-grade adenocarcinoma of maxillary alveolus metastasising to the abdomen: the role of immunomarkers in diagnosis
Authors: Thennavan Aatish , Rao Lakshmi , Radhakrishnan Raghu
Published: May 2013

Polymorphous low-grade adenocarcinoma (PLGA) originating mostly in the minor salivary glands of the posterior hard and soft palate is characterised by its indolent growth and a slower rate of metastasis. Seldom does the PLGA present an aggressive behaviour and demonstrate distant metastasis, as in the present case where a 73-year-old female patient with a swelling in the maxillary alveolus was diagnosed as PLGA exhibiting high-grade transformation, subsequently metastasizing to the abdomen and lungs. The importance of immunomarkers, c-kit and ki-67 in deciphering the clinical behaviour of this PLGA is highlighted. Distant metastasis to the abdomen has not yet been reported; hence, this case of PLGA emphasises the importance of immunohistochemistry in assessing its aggressiveness and understanding a novel aspect of its pathogenesis.
Assessment of the range of variation ofNγfrom 60 estimation methods for footings on sand
Authors: Diaz-Segura Edgar Giovanny
Published: May 2013

The range of variation of the bearing capacity factor, Nγ, was assessed using 60 estimation methods for rough footings on sand subjected to static vertical loading. The influence on the Nγvalues of the use of correlations for the estimation of the friction angle, [Formula: see text], derived from in situ tests was also assessed. The analysis shows a marked dependency on the methods used to determine Nγ, showing differences for the same [Formula: see text] values of up to 267% between estimated values. Uncertainty in the estimation of [Formula: see text], due to the use of correlations with in situ tests, leads to a range of variation for Nγhigher than that seen using the 60 estimation methods. Finally, given the regular use of the in situ standard penetration test (SPT) on sands, and based on a series of analyses using finite elements, a simplified method in terms of the SPT N-values is proposed for estimation of Nγin footings on sands.
Seismic assessment and upgrade of Type 2 construction steel moment-resisting frames built in Canada between the 1960s and 1980s using passive supplemental damping
Authors: Kyriakopoulos Nikolas , Christopoulos Constantin
Published: May 2013

The seismic performance of a typical 1960s Type 2 construction steel moment-resisting frame hospital structure designed only for lateral wind loads was investigated. The structure was found to have a soft first storey and displayed large P–Δ sensitivities. An experimental program determined that the connections had considerable inherent ductility and were stable up to 2.0% interstorey drift, despite not having been designed for a ductile cyclic response. The structure was numerically modelled using advanced strength degradation considerations. A nonlinear time-history analysis was conducted using Montreal and Vancouver ground motions and the structure’s performance was found to be inadequate under the considered design hazard levels. Retrofits were proposed for the two orthogonal frames using a performance-based approach and supplemental damping, rather than local interventions to increase the ductility of these connections, and the performance of the final retrofit designs were investigated numerically to confirm that the desired performance levels were achieved.
Predominance of ammonia-oxidizing archaea andnirK-gene-bearing denitrifiers among ammonia-oxidizing and denitrifying populations in sediments of a large urban eutrophic lake (Lake Donghu)
Authors: Hou Jie , Cao Xiuyun , Song Chunlei , Zhou Yiyong
Published: May 2013

The coupled nitrification–denitrification process plays a pivotal role in cycling and removal of nitrogen in aquatic ecosystems. In the present study, the communities of ammonia oxidizers and denitrifiers in the sediments of 2 basins (Guozhenghu Basin and Tuanhu Basin) of a large urban eutrophic lake (Lake Donghu) were determined using the ammonia monooxygenase subunit A (amoA) gene and the nitrite reductase gene. At all sites of this study, the archaeal amoA gene predominated over the bacterial amoA gene, whereas the functional gene for denitrification nirK gene far outnumbered the nirS gene. Spatially, compared with the Tuanhu Basin, the Guozhenghu Basin showed a significantly greater abundance of the archaeal amoA gene but less abundance of the nirK and nirS genes, while there was no significant difference of bacterial amoA gene copy numbers between the 2 basins. Unlike the archaeal amoA gene, the nirK gene showed a significant difference in community structure between the 2 basins. Archaeal amoA diversity was limited to the water–sediment cluster of Crenarchaeota, in sharp contrast with nirK for which 22 distinct operational taxonomic units were found. Accumulation of organic substances were found to be positively related to nirK and nirS gene copy numbers but negatively related to archaeal amoA gene copy numbers, whereas the abundance of the bacterial amoA gene was related to ammonia concentration.
ANALYSIS OF MASS MODIFICATIONS OF THE VECTOR AND AXIAL VECTOR HEAVY MESONS IN THE NUCLEAR MATTER WITH THE QCD SUM RULES
Authors: WANG ZHI-GANG
Published: May 2013

In this paper, we calculate the mass modifications of the vector and axial vector mesons D*, B*, D1 and B1 in the nuclear matter with the QCD sum rules, and obtain the mass-shifts δMD* = -71 MeV , δMB* = -380 MeV , δMD1 = 72 MeV , δMB1 = 264 MeV , and the scattering lengths aD* = -1.07 fm , aB* = -7.17 fm , aD1 = 1.15 fm and aB1 = 5.03 fm for the D*N, B*N, D1N and B1N interactions, respectively.
CASIMIR TORQUE ON TWO ROTATING PLATES
Authors: CHEN XIANG
Published: May 2013

We investigate the torque on two rotating particles and two rotating plates due to the thermal fluctuation and vacuum fluctuation. A general formula has been developed including the temperature difference on each plate and vacuum, and the different angular velocity on each plate. We show that the Casimir torque in absorbing material occurs whenever there is a difference in temperature or a relative angular velocity between the plates and the vacuum.
THE CONJUGACY PROBLEM IN HYPERBOLIC GROUPS FOR FINITE LISTS OF GROUP ELEMENTS
Authors: BUCKLEY D. J. , HOLT DEREK F.
Published: May 2013

Let G be a word-hyperbolic group with given finite generating set, for which various standard structures and constants have been pre-computed. An (non-practical) algorithm is described that, given as input two lists A and B, each composed of m words in the generators and their inverses, determines whether or not the lists are conjugate in G, and returns a conjugating element, should one exist. The algorithm runs in time O(mμ), where μ is an upper bound on the length of elements in the two lists. Similarly, an algorithm is outlined that computes generators of the centralizer of A, with the same bound on running time.
Entropy-Enthalpy Compensation: Role and Ramifications in Biomolecular Ligand Recognition and Design
Authors: Chodera John D. , Mobley David L.
Published: May 2013

Recent calorimetric studies of interactions between small molecules and biomolecular targets have generated renewed interest in the phenomenon of entropy-enthalpy compensation. In these studies, entropic and enthalpic contributions to binding are observed to vary substantially and in an opposing manner as the ligand or protein is modified, whereas the binding free energy varies little. In severe examples, engineered enthalpic gains can lead to completely compensating entropic penalties, frustrating ligand design. Here, we examine the evidence for compensation, as well as its potential origins, prevalence, severity, and ramifications for ligand engineering. We find the evidence for severe compensation to be weak in light of the large magnitude of and correlation between errors in experimental measurements of entropic and enthalpic contributions to binding, though a limited form of compensation may be common. Given the difficulty of predicting or measuring entropic and enthalpic changes to useful precision, or using this information in design, we recommend ligand engineering efforts instead focus on computational and experimental methodologies to directly assess changes in binding free energy.
Evolution in Microbes
Authors: Kussell Edo
Published: May 2013

This review presents a broad survey of experimental microbial evolution, covering diverse topics including trade-offs, epistasis, fluctuating conditions, spatial dynamics, cooperation, aging, and stochastic switching. Emphasis is placed on examples that highlight key conceptual points or address theoretical predictions. Experimental evolution is discussed from two points of view. First, population trajectories are described as adaptive walks on a fitness landscape, whose genetic structure can be probed by experiments. Second, populations are viewed from a physiological perspective, and their nongenetic heterogeneity is examined. Bringing together these two viewpoints remains a major challenge for the future.
Common Folds and Transport Mechanisms of Secondary Active Transporters
Authors: Shi Yigong
Published: May 2013

Secondary active transporters exploit the electrochemical potential of solutes to shuttle specific substrate molecules across biological membranes, usually against their concentration gradient. Transporters of different functional families with little sequence similarity have repeatedly been found to exhibit similar folds, exemplified by the MFS, LeuT, and NhaA folds. Observations of multiple conformational states of the same transporter, represented by the LeuT superfamily members Mhp1, AdiC, vSGLT, and LeuT, led to proposals that structural changes are associated with substrate binding and transport. Despite recent biochemical and structural advances, our understanding of substrate recognition and energy coupling is rather preliminary. This review focuses on the common folds and shared transport mechanisms of secondary active transporters. Available structural information generally supports the alternating access model for substrate transport, with variations and extensions made by emerging structural, biochemical, and computational evidence.
IQGAP1 links PDGF receptor-β signal to focal adhesions involved in vascular smooth muscle cell migration: role in neointimal formation after vascular injury
Authors: Kohno Takashi , Urao Norifumi , Ashino Takashi , Sudhahar Varadarajan , Inomata Hyoe , Yamaoka-Tojo Minako , McKinney Ronald D. , Fukai Tohru , Ushio-Fukai Masuko
Published: May 2013

Platelet-derived growth factor (PDGF) stimulates vascular smooth muscle cell (VSMC) migration and neointimal formation in response to injury. We previously identified IQ-domain GTPase-activating protein 1 (IQGAP1) as a novel VEGF receptor 2 binding scaffold protein involved in endothelial migration. However, its role in VSMC migration and neointimal formation in vivo is unknown. Here we show that PDGF stimulation rapidly promotes IQGAP1 association with PDGF receptor-β (PDGFR) as well as IQGAP1 tyrosine phosphorylation in cultured VSMC. Overexpression or knockdown of IQGAP1 enhances or inhibits PDGFR autophosphorylation (p-PDGFR), respectively. Immunofluorescence and cell fractionation analysis reveals that PDGF-induced p-PDGFR localized in focal adhesions (FAs), but not caveolae/lipid rafts, is inhibited by IQGAP1 knockdown with siRNA. PDGF stimulation promotes IQGAP1 association with PDGFR/FA signaling protein complex. Functionally, IQGAP1 siRNA inhibits PDGF-induced FA formation as well as VSMC migration induced by PDGF. In vivo, IQGAP1 expression is markedly increased at neointimal VSMC in wire-injured femoral arteries. Mice lacking IQGAP1 exhibit impaired neointimal formation in response to vascular injury. In summary, IQGAP1, through interaction with PDGFR and FA signaling proteins, promotes activation of PDGFR in FAs as well as FA formation, which may contribute to VSMC migration and neointimal formation after injury. Our findings provide insight into IQGAP1 as a potential therapeutic target for vascular migration-related diseases.
Matrix metalloproteinase 9 is a distal-less 3 target-gene in placental trophoblast cells
Authors: Clark Patricia A. , Xie Jianjun , Li Sha , Zhang Xuesen , Coonrod Scott , Roberson Mark S.
Published: May 2013

Matrix metalloproteinases (MMPs) are enzymes that regulate extracellular matrix composition and contribute to cell migration. Microarray studies in mouse placenta suggested that MMP-9 transcript abundance was dependent on distal-less 3 (Dlx3), a placental-specific transcriptional regulator; however, it was not clear if this was a direct or indirect effect. Here we investigate mechanism(s) for Dlx3-dependent MMP-9 gene transcription and gelatinase activity in placental trophoblasts. Initial studies confirmed that MMP-9 activity was reduced in placental explants from Dlx3−/− mice and that murine MMP-9 promoter activity was induced by Dlx3 overexpression. Two binding sites within a murine MMP-9 promoter fragment bound Dlx3, and mutations in both elements reduced basal MMP-9-luciferase reporter activity and abolished regulation by Dlx3. Chromatin immunoprecipitation studies in JEG3 cells confirmed Dlx3 binding to the endogenous human MMP-9 promoter at three distinct sites and knockdown of human Dlx3 resulted in reduced endogenous MMP-9 transcripts and secreted activity. These studies provide novel evidence that Dlx3 is involved directly in the transcriptional regulation of mouse and human MMP-9 gene expression in placental trophoblasts.
Mitochondrial ROS in the prohypertensive immune response
Authors: Nazarewicz Rafal R. , Dikalov Sergey I.
Published: May 2013

In the past decade, it has become clear that reactive oxygen species (ROS) and inflammation play an important role in the development of hypertension. Scavenging of mitochondrial superoxide and blocking either IL-17 or tumor necrosis factor-α (TNF-α) attenuates hypertension. T-cells, critical for development of hypertension, once activated intensively produce cytokines, proliferate, and differentiate. Thus T-cell activation leads to expanded energy demand. To fulfill these needs, T-cells through tightly regulated mechanisms, supported by mitochondrial ROS (mtROS), alter their metabolic phenotype. In this review we summarize data and show evidence supporting new concept that mtROS directly contributes to prohypertensive response of immune cells.
Reactive oxygen species and IRF1 stimulate IFNα production by proximal tubules during ischemic AKI
Authors: Winterberg Pamela D. , Wang Yanxia , Lin Keng-Mean , Hartono John R. , Nagami Glenn T. , Zhou Xin J. , Shelton John M. , Richardson James A. , Lu Christopher Y.
Published: May 2013

We previously reported that expression of the transcription factor interferon regulatory factor 1 (IRF1) is an early, critical maladaptive signal expressed by renal tubules during murine ischemic acute kidney injury (AKI). We now show that IRF1 mediates signals from reactive oxygen species (ROS) generated during ischemic AKI and that these signals ultimately result in production of α-subtypes of type I interferons (IFNαs). We found that genetic knockout of the common type I IFN receptor (IFNARI−/−) improved kidney function and histology during AKI. There are major differences in the spatial-temporal production of the two major IFN subtypes, IFNβ and IFNαs: IFNβ expression peaks at 4 h, earlier than IFNαs, and continues at the same level at 24 h; expression of IFNαs also increases at 4 h but continues to increase through 24 h. The magnitude of the increase in IFNαs relative to baseline is much greater than that of IFNβ. We show by immunohistology and study of isolated cells that IFNβ is produced by renal leukocytes and IFNαs are produced by renal tubules. IRF1, IFNαs, and IFNARI were found on the same renal tubules during ischemic AKI. Furthermore, we found that ROS induced IFNα expression by renal tubules in vitro. This expression was inhibited by small interfering RNA knockdown of IRF1. Overexpression of IRF1 resulted in the production of IFNαs. Furthermore, we found that IFNα stimulated production of maladaptive proinflammatory CXCL2 by renal tubular cells. Altogether our data support the following autocrine pathway in renal tubular cells: ROS > IRF1 > IFNα > IFNARI > CXCL2.
Visual receptive field properties of cells in the optic tectum of the archer fish
Authors: Ben-Tov Mor , Kopilevich Ivgeny , Donchin Opher , Ben-Shahar Ohad , Giladi Chen , Segev Ronen
Published: May 2013

The archer fish is well known for its extreme visual behavior in shooting water jets at prey hanging on vegetation above water. This fish is a promising model in the study of visual system function because it can be trained to respond to artificial targets and thus to provide valuable psychophysical data. Although much behavioral data have indeed been collected over the past two decades, little is known about the functional organization of the main visual area supporting this visual behavior, namely, the fish optic tectum. In this article we focus on a fundamental aspect of this functional organization and provide a detailed analysis of receptive field properties of cells in the archer fish optic tectum. Using extracellular measurements to record activities of single cells, we first measure their retinotectal mapping. We then determine their receptive field properties such as size, selectivity for stimulus direction and orientation, tuning for spatial frequency, and tuning for temporal frequency. Finally, on the basis of all these measurements, we demonstrate that optic tectum cells can be classified into three categories: orientation-tuned cells, direction-tuned cells, and direction-agnostic cells. Our results provide an essential basis for future investigations of information processing in the archer fish visual system.
Lie-Algebraic Approach for Pricing Zero-Coupon Bonds in Single-Factor Interest Rate Models
Authors: Lo C. F.
Published: May 2013

The Lie-algebraic approach has been applied to solve the bond pricing problem in single-factor interest rate models. Four of the popular single-factor models, namely, the Vasicek model, Cox-Ingersoll-Ross model, double square-root model, and Ahn-Gao model, are investigated. By exploiting the dynamical symmetry of their bond pricing equations, analytical closed-form pricing formulae can be derived in a straightfoward manner. Time-varying model parameters could also be incorporated into the derivation of the bond price formulae, and this has the added advantage of allowing yield curves to be fitted. Furthermore, the Lie-algebraic approach can be easily extended to formulate new analytically tractable single-factor interest rate models.
MMP1, MMP9, and COX2 Expressions in Promonocytes Are Induced by Breast Cancer Cells and Correlate with Collagen Degradation, Transformation-Like Morphological Changes in MCF-10A Acini, and Tumor Aggressiveness
Authors: Chimal-Ramírez G. K. , Espinoza-Sánchez N. A. , Utrera-Barillas D. , Benítez-Bribiesca L. , Velázquez J. R. , Arriaga-Pizano L. A. , Monroy-García A. , Reyes-Maldonado E. , Domínguez-López M. L. , Piña-Sánchez Patricia , Fuentes-Pananá E. M.
Published: May 2013

Tumor-associated immune cells often lack immune effector activities, and instead they present protumoral functions. To understand how tumors promote this immunological switch, invasive and noninvasive breast cancer cell (BRC) lines were cocultured with a promonocytic cell line in a Matrigel-based 3D system. We hypothesized that if communication exists between tumor and immune cells, coculturing would result in augmented expression of genes associated with tumor malignancy. Upregulation of proteasesMMP1andMMP9and inflammatoryCOX2genes was found likely in response to soluble factors. Interestingly, changes were more apparent in promonocytes and correlated with the aggressiveness of the BRC line. Increased gene expression was confirmed by collagen degradation assays and immunocytochemistry of prostaglandin 2, a product of COX2 activity. Untransformed MCF-10A cells were then used as a sensor of soluble factors with transformation-like capabilities, finding that acini formed in the presence of supernatants of the highly aggressive BRC/promonocyte cocultures often exhibited total loss of the normal architecture. These data support that tumor cells can modify immune cell gene expression and tumor aggressiveness may importantly reside in this capacity. Modeling interactions in the tumor stroma will allow the identification of genes useful as cancer prognostic markers and therapy targets.
High-Dose Barium Impaction Therapy Is Useful for the Initial Hemostasis and for Preventing the Recurrence of Colonic Diverticular Bleeding Unresponsive to Endoscopic Clipping
Authors: Niikura Ryota , Nagata Naoyoshi , Yamano Kazuyoshi , Shimbo Takuro , Uemura Naomi
Published: May 2013

Most cases of colonic diverticular bleeding stop spontaneously, but some patients experience massive bleeding that requires emergency treatment. Endoscopy can be useful when the bleeding source is identified. However, bleeding sometimes recurs within a short period despite the successful endoscopic treatment. Under such conditions, more invasive therapy such as interventional angiography or surgery is required and can prolong hospitalization and involve frequent blood transfusions. We report the case of a 68-year-old woman who presented with massive hematochezia. The patient was in hemorrhagic shock and required 16 units of blood transfusion to recover to general condition. We performed multidetector row computed tomography, but it showed no sites of bleeding. We conducted colonoscopy and identified the source of bleeding as colonic diverticula. We treated the bleeding with endoscopic hemoclips and achieved hemostasis, but bleeding recurred the next day. Four units of blood transfusion were required. We tried high-dose barium impaction therapy to avoid further blood transfusion and surgery. No complications or recurrent bleeding was observed for an 18-month period. Therapeutic barium enema is an option for colonic diverticular bleeding unresponsive to endoscopic clipping and may be effective for preventing recurrent bleeding.
Geometrical and Spectral Properties of the Orthogonal Projections of the Identity
Authors: González Luis , Suárez Antonio , García Dolores
Published: May 2013

We analyze the best approximation (in the Frobenius sense) to the identity matrix in an arbitrary matrix subspace ( nonsingular, being any fixed subspace of ). Some new geometrical and spectral properties of the orthogonal projection are derived. In particular, new inequalities for the trace and for the eigenvalues of matrix are presented for the special case that is symmetric and positive definite.
Bilateral Nipple Leiomyoma
Authors: Deveci Ugur , Kapakli Mahmut Sertan , Altintoprak Fatih , Cayırcı Mine , Manukyan Manuk Norayk , Kebudi Abut
Published: May 2013

Cutaneous leiomyomas are benign smooth muscle neoplasms of the skin. They arise from vascular, arrector pili, genital, and areolar smooth muscles. The most common localizations of cutaneous leiomyomas are the extensor surfaces of the extremities and the trunk. To our knowledge, only few cases of one-sided nipple leiomyomas have been reported, but two-sided nipple leiomyomas have not been presented. For the first time, here, we report a bilateral nipple leiomyoma.
Decrease in Hospitalizations for Pneumonia in Children under Five Years of Age in an Indian Reservation in Panama after the Introduction of the Heptavalent Pneumococcal Conjugate Vaccine (PCV7)
Authors: Nieto Guevara Javier , Daza Carlos , Smith Rebecca
Published: May 2013

This study quantifies the impact of Heptavalent-Pneumococcal Conjugate Vaccine (PCV7) in Panama on indigenous children younger than 5 years old, based on clinical pneumonia cases. This study demonstrates a significant 41.2% reduction in hospitalizations and 38.6% reduction in referrals for pneumonia following the introduction of PCV7. Burden of disease from pneumonia appears reduced in the ≤12-month- and 13-to-24-month-old groups.
The Studies of Chlorogenic Acid Antitumor Mechanism by Gene Chip Detection: The Immune Pathway Gene Expression
Authors: Kang Tian Yi , Yang Hua Rong , Zhang Jie , Li Dan , Lin Jie , Wang Li , Xu XiaoPing
Published: May 2013

Persistently increasing incident of cancer in human beings has served to emphasize the importance of studies on mechanism of antitumor substances. Chlorogenic acid (CA), extracted from folium cortex eucommiae, has been confirmed to have lots of biological activities encompassing inhibition of tumor. However, the anticancer mechanism of CA remains unclear. Here, we have utilized a whole mouse genome oligo microarray (4*44K) to analyze gene expression level of female BALB/c mice (implanted with EMT-6 sarcoma cells) after treatment with low, medium, and high-dose CA (5 mg/kg, 10 mg/kg, and 20 mg/kg), docetaxel, interferon, and normal saline separately at 6 time points (3rd, 6th, 9th, 12th, 15th, and 18th days after administration). Differentially expressed genes screened out by time-series analysis, GO analysis, and pathway analysis, and four immune-related genes were selected for further confirmation using RT-qPCR. The results demonstrated that CA is able to change gene expression and that the responsive genes (CaN, NFATC2, NFATC2ip, and NFATC3) involved in immune pathways had been significantly upregulated by CA. Expression of immune factors such as IL-2R and IFN-γcan be improved by CA to promote activation and proliferation of T cells, macrophages, and NK cells, thus enhancing their surveillance and killing abilities, further suppressing the growth rate of tumor cells.
Influence of Sodium Dodecyl Sulfonate on the Formation of ZnO Nanorods from ε‐Zn(OH)2
Authors: Wang Jing , Liu Chengxiang , Xiang Lan
Published: May 2013

The influence of sodium dodecyl sulfonate (SDSN) on the formation of ZnO nanorods from ε‐Zn(OH)2 was investigated in this paper. The ε‐Zn(OH)2 precursor was prepared at room temperature using ZnSO4 and NaOH as the reactants and then converted to ZnO nanorods after aging at 80°C in NaOH solution containing a minor amount of sodium dodecyl sulfonate (SDSN). The experimental results and the molecular simulation revealed that the influence of SDSN on the formation of ZnO from ε‐Zn(OH)2 should be attributed to the adsorption of SDSN on ε‐Zn(OH)2 surfaces, which inhibited the dissolution of ε‐Zn(OH)2 in NaOH solution, leading to the formation of the ZnO nanorods with a diameter of 50–200 nm, a length of 3.0–15.0 μm, and an aspect ratio of 30–100.
Development of Solar Electricity Supply System in India: An Overview
Authors: Gupta Sandeep Kumar , Anand Raghubir Singh
Published: May 2013

Solar electricity supply system has grown at very rapid pace in India during the last few years. A total of 1047.84 MW of grid connected photovoltaic projects and 160.8 MW of off-grid systems have been commissioned under different policy mechanisms between January 2010 and November 2012. It is observed that solar capacity development has achieved a greater height under state policies (689.81 MW) than others. A study is made in this paper of various national and state level schemes, incentives, packages, instruments, and different mechanisms to promote solar photovoltaics and its effectiveness.