bluuebunny/crossref_metadata_2025_split huggingface dataset:
Kinematic Synthesis of Minimally Actuated Multi-Loop Planar Linkages With Second Order Motion Constraints for Object Grasping
Authors: Soh Gim Song , Robson Nina 
Published: March 2014

In this paper, we consider the dimensional synthesis of one degree-of-freedom multi-loop planar linkages such that they do not violate normal direction and second order curvature constraints imposed by contact with objects. Our goal is in developing minimally actuated multi-loop mechanical devices for human-robot interaction, that is, devices whose tasks will happen in a human environment.
Currently no systematic method exists for the kinematic synthesis of robotic fingers that incorporate multi-loop kinematic structure with second order task constraints, related to curvature. We show how to use these contact and curvature effects to formulate the synthesis equations for the design of a planar one-degree-of-freedom six-bar linkage. An example for the design of a finger that maintains a specified contact with an object, for an anthropomorphic task, is presented at the end of the paper.
It is important to note, that the theoretical foundation presented in this paper, assists in solving some of the open problems of this field, providing preliminary results on the synthesis of kinematic chains with multi-loop topology and the use of novel task specifications that incorporate curvature constraints with future applications in grasping and object manipulation.
Modeling and incorporating cardiac‐induced lung tissue motion in a breathing motion model
Authors: White Benjamin M. , Santhanam Anand , Thomas David , Min Yugang , Lamb James M. , Neylon Jack , Jani Shyam , Gaudio Sergio , Srinivasan Subashini , Ennis Daniel , Low Daniel A. 
Published: March 2014

Purpose:The purpose of this work is to develop a cardiac‐induced lung motion model to be integrated into an existing breathing motion model.Methods:The authors’ proposed cardiac‐induced lung motion model represents the lung tissueˈs specific response to the subjectˈs cardiac cycle. The model is mathematically defined as a product of a converging polynomial functionh of the cardiac phase (c) and the maximum displacement of each voxel () among all the cardiac phases. The function h(c) was estimated from cardiac‐gated MR imaging of ten healthy volunteers using an Akaike Information Criteria optimization algorithm. For each volunteer, a total of 24 short‐axis and 18 radial planar views were acquired on a 1.5 T MR scanner during a series of 12–15 s breath‐hold maneuvers. Each view contained 30 temporal frames of equal time‐duration beginning with the end‐diastolic cardiac phase. The frames in each of the planar views were resampled to create a set of three‐dimensional (3D) anatomical volumes representing thoracic anatomy at different cardiac phases. A 3D multiresolution optical flow deformable image registration algorithm was used to quantify the difference in tissue position between the end‐diastolic cardiac phase and the remaining cardiac phases. To account for image noise, voxel displacements whose maximum values were less than 0.3 mm, were excluded. In addition, the blood vessels were segmented and excluded in order to eliminate registration artifacts caused by blood‐flow.Results:The average cardiac‐induced lung motions for displacements greater than 0.3 mm were found to be 0.86 ± 0.74 and 0.97 ± 0.93 mm in the left and right lungs, respectively. The average model residual error for the ten healthy volunteers was found to be 0.29 ± 0.08 mm in the left lung and 0.38 ± 0.14 mm in the right lung for tissue displacements greater than 0.3 mm. The relative error decreased with increasing cardiac‐induced lung tissue motion. While the relative error was > 60% for submillimeter cardiac‐induced lung tissue motion, the relative error decreased to < 5% for cardiac‐induced lung tissue motion that exceeded 10 mm in displacement.Conclusions:The authors’ studies implied that modeling and including cardiac‐induced lung motion would improve breathing motion model accuracy for tissues with cardiac‐induced motion greater than 0.3 mm.
Immune Responses to Vi Capsular Polysaccharide Typhoid Vaccine in Children 2 to 16 Years Old in Karachi, Pakistan, and Kolkata, India
Authors: Ochiai R. Leon , Khan M. Imran , Soofi Sajid B. , Sur Dipika , Kanungo Suman , You Young Ae , Habib M. Atif , Sahito Shah Muhammad , Manna Byomkesh , Dutta Shanta , Acosta Camilo J. , Ali Mohammad , Bhattacharya Sujit K. , Bhutta Zulfiqar A. , Clemens John D. 
Published: March 2014

ABSTRACTThe geometric mean concentration (GMC) and the proportion maintaining a protective level (150 enzyme-linked immunosorbent assay (ELISA) units [ELU]/ml) 2 years following a single dose of 25 μg of injectable Vi capsular polysaccharide typhoid vaccine was measured against that of the control hepatitis A vaccine in children 2 to 16 years old in cluster randomized trials in Karachi and Kolkata. The GMC for the Vi group (1,428 ELU/ml) was statistically significantly different from the GMC of the control hepatitis A vaccine group (86 ELU/ml) after 6 weeks. A total of 117 children (95.1%) in the Vi group and 9 (7.5%) in the hepatitis A group showed a 4-fold rise in Vi IgG antibody concentrations at 6 weeks (P< 0.01). Protective antibody levels remained significantly different between the two groups at 2 years (38% in the Vi vaccine groups and 6% in the hepatitis A group [P< 0.01]). A very small proportion of younger children (2 to 5 years old) maintained protective Vi IgG antibody levels at 2 years, a result that was not statistically significantly different compared to that for the hepatitis A group (38.1% versus 10.5%). The GMCs of the Vi IgG antibody after 2 years were 133 ELU/ml for children 2 to <5 years old and 349 ELU/ml for children 5 to 16 years old. In conclusion, Vi capsular polysaccharide typhoid vaccine is immunogenic in children in settings of South Asia where typhoid is highly endemic. The antibody levels in children who received this vaccine remained higher than those in children who received the control vaccine but were significantly reduced at 2 years of follow-up.
Major Variation in MICs of Tigecycline in Gram-Negative Bacilli as a Function of Testing Method
Authors: Marchaim Dror , Pogue Jason M. , Tzuman Oran , Hayakawa Kayoko , Lephart Paul R. , Salimnia Hossein , Painter Theresa , Zervos Marcus J. , Johnson Laura E. , Perri Mary Beth , Hartman Pamela , Thyagarajan Rama V. , Major Sharon , Goodell Melanie , Fakih Mohamad G. , Washer Laraine L. , Newton Duane W. , Malani Anurag N. , Wholehan Jason M. , Mody Lona , Kaye Keith S. 
Published: March 2014

ABSTRACT

Tigecycline is one of the few remaining therapeutic options for extensively drug-resistant (XDR) Gram-negative bacilli (GNB). MICs of tigecycline to
Acinetobacter baumannii
have been reported to be elevated when determined by the Etest compared to determinations by the broth microdilution (BMD) method. The study aim was to compare the susceptibility of GNB to tigecycline by four different testing methods. GNB were collected from six health care systems (25 hospitals) in southeast Michigan from January 2010 to September 2011. Tigecycline MICs among
A. baumannii
, carbapenem-resistant
Enterobacteriaceae
(CRE), extended-spectrum β-lactamase (ESBL)-producing
Enterobacteriaceae
, and susceptible
Enterobacteriaceae
isolates were determined by Etest, BMD, Vitek-2, and MicroScan. Nonsusceptibility was categorized as a tigecycline MIC of ≥4 μg/ml for both
A. baumannii
and
Enterobacteriaceae
. The study included 4,427 isolates: 2,065 ESBL-producing
Enterobacteriaceae
, 1,105
A. baumannii
, 888 susceptible
Enterobacteriaceae
, and 369 CRE isolates. Tigecycline nonsusceptibility among
A. baumannii
isolates was significantly more common as determined by Etest compared to that determined by BMD (odds ratio [OR], 10.3;
P
< 0.001), MicroScan (OR, 12.4;
P
< 0.001), or Vitek-2 (OR, 9.4;
P
< 0.001). These differences were not evident with the other pathogens. Tigecycline MICs varied greatly according to the
in vitro
testing methods among
A. baumannii
isolates. Etest should probably not be used by laboratories for tigecycline MIC testing of
A. baumannii
isolates, since MICs are significantly elevated with Etest compared to those determined by the three other methods.
Travel-Related Carbapenemase-Producing Gram-Negative Bacteria in Alberta, Canada: the First 3 Years
Authors: Peirano Gisele , Ahmed-Bentley Jasmine , Fuller Jeff , Rubin Joseph E. , Pitout Johann D. D. 
Published: March 2014

ABSTRACT

We describe here the characteristics of Alberta, Canada, patients with infections or colonizations with carbapenemase-producing Gram-negative bacteria during 2010 to 2013 that were linked to recent travel outside Canada. Antimicrobial susceptibility was determined by broth microdilution, and isolates were characterized using PCR, sequencing, and multilocus sequencing typing. A broth mating study was used to assess the transferability of resistance plasmids, which were subsequently characterized. All the patients (
n
= 12) included in our study had contact with a health care system while abroad. Most of the patients presented with urinary tract infections (UTIs) and were admitted to hospitals within weeks after their return to Alberta. Secondary spread occurred in 1 case, resulting in the death of another patient. The carbapenemase-producing bacteria (
n
= 17) consisted of
Escherichia coli
(sequence type 101 [ST101], ST365, ST405, and ST410) with NDM-1,
Klebsiella pneumoniae
(ST15, ST16, ST147, ST258, ST340, ST512, and ST972) with NDM-1, OXA-181, KPC-2, and KPC-3,
Acinetobacter baumannii
with OXA-23,
Providencia rettgeri
with NDM-1,
Enterobacter cloacae
with KPC-2, and
Citrobacter freundii
with NDM-1. The
bla
NDM-1
gene was associated with various narrow- (i.e., IncF) and broad- (i.e., IncA/C and IncL/M) host-range plasmids with different addiction factors. Our results show that NDM-producing
K. pneumoniae
, belonging to a variety of sequence types with different plasmid scaffolds, are regularly imported from India into Alberta. Clinical microbiology laboratories should remain vigilant in detecting bacteria with carbapenemases.
Evidence for Subclinical Influenza A(H1N1)pdm09 Virus Infection among Dogs in Guangdong Province, China
Authors: Su Shuo , Chen Jidang , Jia Kun , Khan Salah Uddin , He Shuyi , Fu Xinliang , Hong Malin , Sun Lingshuang , Qi Wenbao , Gray Gregory C. , Li Shoujun 
Published: March 2014

ABSTRACT
During 2012, we identified sampled dogs with elevated levels of antibodies (≥1:40) against A(H1N1)pdm09 virus by using a hemagglutination inhibition (HI) assay (seroprevalence, 24.7%) and a microneutralization (MN) assay (seroprevalence, 10.8%). These high seroprevalences of A(H1N1)pdm09 among dogs without clinical signs of influenza support the premise that dogs may play a role in the human influenza ecology in China.
Performance of the EUCAST Disk Diffusion Method, the CLSI Agar Screen Method, and the Vitek 2 Automated Antimicrobial Susceptibility Testing System for Detection of Clinical Isolates of Enterococci with Low- and Medium-Level VanB-Type Vancomycin Resistance: a Multicenter Study
Authors: Hegstad Kristin , Giske Christian G. , Haldorsen Bjørg , Matuschek Erika , Schønning Kristian , Leegaard Truls M. , Kahlmeter Gunnar , Sundsfjord Arnfinn 
Published: March 2014

ABSTRACT

Different antimicrobial susceptibility testing methods to detect low-level vancomycin resistance in enterococci were evaluated in a Scandinavian multicenter study (
n
= 28). A phenotypically and genotypically well-characterized diverse collection of
Enterococcus faecalis
(
n
= 12) and
Enterococcus faecium
(
n
= 18) strains with and without nonsusceptibility to vancomycin was examined blindly in Danish (
n
= 5), Norwegian (
n
= 13), and Swedish (
n
= 10) laboratories using the EUCAST disk diffusion method (
n
= 28) and the CLSI agar screen (
n
= 18) or the Vitek 2 system (bioMérieux) (
n
= 5). The EUCAST disk diffusion method (very major error [VME] rate, 7.0%; sensitivity, 0.93; major error [ME] rate, 2.4%; specificity, 0.98) and CLSI agar screen (VME rate, 6.6%; sensitivity, 0.93; ME rate, 5.6%; specificity, 0.94) performed significantly better (
P
= 0.02) than the Vitek 2 system (VME rate, 13%; sensitivity, 0.87; ME rate, 0%; specificity, 1). The performance of the EUCAST disk diffusion method was challenged by differences in vancomycin inhibition zone sizes as well as the experience of the personnel in interpreting fuzzy zone edges as an indication of vancomycin resistance. Laboratories using Oxoid agar (
P
< 0.0001) or Merck Mueller-Hinton (MH) agar (
P
= 0.027) for the disk diffusion assay performed significantly better than did laboratories using BBL MH II medium. Laboratories using Difco brain heart infusion (BHI) agar for the CLSI agar screen performed significantly better (
P
= 0.017) than did those using Oxoid BHI agar. In conclusion, both the EUCAST disk diffusion and CLSI agar screening methods performed acceptably (sensitivity, 0.93; specificity, 0.94 to 0.98) in the detection of VanB-type vancomycin-resistant enterococci with low-level resistance. Importantly, use of the CLSI agar screen requires careful monitoring of the vancomycin concentration in the plates. Moreover, disk diffusion methodology requires that personnel be trained in interpreting zone edges.
Crystal Structure of the Herpesvirus Inner Tegument Protein UL37 Supports Its Essential Role in Control of Viral Trafficking
Authors: Pitts Jared D. , Klabis Jenifer , Richards Alexsia L. , Smith Gregory A. , Heldwein Ekaterina E. 
Published: March 2014

ABSTRACT
In cells infected with herpesviruses, two capsid-associated, or inner tegument, proteins, UL37 and UL36, control cytosolic trafficking of capsids by as yet poorly understood mechanisms. Here, we report the crystal structure of the N-terminal half of UL37 from pseudorabies virus, an alphaherpesvirus closely related to herpes simplex viruses and varicella-zoster virus. The structure—the first for any alphaherpesvirus inner tegument protein—reveals an elongated molecule of a complex architecture rich in helical bundles. To explore the function of the UL37 N terminus, we used the three-dimensional framework provided by the structure in combination with evolutionary trace analysis to pinpoint several surface-exposed regions of potential functional importance and test their importance using mutagenesis. This approach identified a novel functional region important for cell-cell spread. These results suggest a novel role for UL37 in intracellular virus trafficking that promotes spread of viral infection, a finding that expands the repertoire of UL37 functions. Supporting this, the N terminus of UL37 shares structural similarity with cellular multisubunit tethering complexes (MTCs), which control vesicular trafficking in eukaryotic cells by tethering transport vesicles to their destination membranes. Our results suggest that UL37 could be the first viral MTC mimic and provide a structural rationale for the importance of UL37 for viral trafficking. We propose that herpesviruses may have co-opted the MTC functionality of UL37 to bring capsids to cytoplasmic budding destinations and further on to cell junctions for spread to nearby cells.

IMPORTANCE
To move within an infected cell, viruses encode genes for proteins that interact with host trafficking machinery. In cells infected with herpesviruses, two capsid-associated proteins control the cytosolic movement of capsids by as yet poorly understood mechanisms. Here, we report the crystal structure for the N-terminal half of one of these proteins, UL37. Structure-based mutagenesis revealed a novel function for UL37 in virus trafficking to cell junctions for cell-cell spread. The unexpected structural similarity to components of cellular multisubunit tethering complexes, which control vesicular traffic, suggests that UL37 could be the first viral MTC mimic and provides a structural basis for the importance of UL37 for virus trafficking.
Herpes Simplex Virus 1 Protein UL37 Interacts with Viral Glycoprotein gK and Membrane Protein UL20 and Functions in Cytoplasmic Virion Envelopment
Authors: Jambunathan Nithya , Chouljenko Dmitry , Desai Prashant , Charles Anu-Susan , Subramanian Ramesh , Chouljenko Vladimir N. , Kousoulas Konstantin G. 
Published: March 2014

ABSTRACT
We have shown that glycoprotein K (gK) and its interacting partner, the UL20 protein, play crucial roles in virion envelopment. Specifically, virions lacking either gK or UL20 fail to acquire an envelope, thus causing accumulation of capsids in the cytoplasm of infected cells. The herpes simplex virus 1 (HSV-1) UL37 protein has also been implicated in cytoplasmic virion envelopment. To further investigate the role of UL37 in virion envelopment, the recombinant virus DC480 was constructed by insertion of a 12-amino-acid protein C (protC) epitope tag within the UL37 amino acid sequence immediately after amino acid 480. The DC480 mutant virus expressed full-size UL37 as detected by the anti-protC antibody in Western immunoblots, accumulated unenveloped capsids in the cytoplasm of infected cells, and produced very small plaques on African green monkey kidney (Vero) cells that were similar in size to those produced by the UL20-null and UL37-null viruses. The DC480 virus replicated nearly 4 log less efficiently than the parental wild-type virus when grown on Vero cells. However, DC480 mutant virus titers increased nearly 20-fold when the virus was grown on FRT cells engineered to express the UL20 gene in comparison to the titers on Vero cells, while the UL37-null virus replicated approximately 20-fold less efficiently than the DC480 virus on FRT cells. Coimmunoprecipitation experiments and proximity ligation assays showed that gK and UL20 interact with the UL37 protein in infected cells. Collectively, these results indicate that UL37 interacts with the gK-UL20 protein complex to facilitate cytoplasmic virion envelopment.

IMPORTANCE
Herpes simplex viruses acquire their final envelopes by budding into cytoplasmic membranes derived from the
trans
-Golgi network (TGN). The tegument proteins UL36 and UL37 are known to be transported to the TGN sites of virus envelopment and to function in virion envelopment, since mutants lacking UL37 accumulate capsids in the cytoplasm that are unable to bud into TGN membranes. Viral glycoprotein K (gK) also functions in cytoplasmic envelopment, in a protein complex with the membrane-associated protein UL20 (UL20mp). This work shows for the first time that the UL37 protein functionally interacts with gK and UL20 to facilitate cytoplasmic virion envelopment. This work may lead to the design of specific drugs that can interrupt UL37 interactions with the gK-UL20 protein complex, providing new ways to combat herpesviral infections.
Inhibition of Dengue Virus Replication by a Class of Small-Molecule Compounds That Antagonize Dopamine Receptor D4 and Downstream Mitogen-Activated Protein Kinase Signaling
Authors: Smith Jessica L. , Stein David A. , Shum David , Fischer Matthew A. , Radu Constantin , Bhinder Bhavneet , Djaballah Hakim , Nelson Jay A. , Früh Klaus , Hirsch Alec J. 
Published: March 2014

ABSTRACT
Dengue viruses (DENV) are endemic pathogens of tropical and subtropical regions that cause significant morbidity and mortality worldwide. To date, no vaccines or antiviral therapeutics have been approved for combating DENV-associated disease. In this paper, we describe a class of tricyclic small-molecule compounds—dihydrodibenzothiepines (DHBTs), identified through high-throughput screening—with potent inhibitory activity against DENV serotype 2. SKI-417616, a highly active representative of this class, displayed activity against all four serotypes of DENV, as well as against a related flavivirus, West Nile virus (WNV), and an alphavirus, Sindbis virus (SINV). This compound was characterized to determine its mechanism of antiviral activity. Investigation of the stage of the viral life cycle affected revealed that an early event in the life cycle is inhibited. Due to the structural similarity of the DHBTs to known antagonists of the dopamine and serotonin receptors, we explored the roles of two of these receptors, serotonin receptor 2A (5HTR2A) and the D4 dopamine receptor (DRD4), in DENV infection. Antagonism of DRD4 and subsequent downstream phosphorylation of epidermal growth factor receptor (EGFR)-related kinase (ERK) were found to impact DENV infection negatively, and blockade of signaling through this network was confirmed as the mechanism of anti-DENV activity for this class of compounds.

IMPORTANCE
The dengue viruses are mosquito-borne, reemerging human pathogens that are the etiological agents of a spectrum of febrile diseases. Currently, there are no approved therapeutic treatments for dengue-associated disease, nor is there a vaccine. This study identifies a small molecule, SKI-417616, with potent anti-dengue virus activity. Further analysis revealed that SKI-417616 acts through antagonism of the host cell dopamine D4 receptor and subsequent repression of the ERK phosphorylation pathway. These results suggest that SKI-417616, or other compounds targeting the same cellular pathways, may have therapeutic potential for the treatment of dengue virus infections.
Comparison of Varicella-Zoster Virus RNA Sequences in Human Neurons and Fibroblasts
Authors: Baird Nicholas L. , Bowlin Jacqueline L. , Cohrs Randall J. , Gilden Don , Jones Kenneth L. 
Published: March 2014

ABSTRACT

Varicella-zoster virus (VZV) infection causes varicella, after which the virus becomes latent in ganglionic neurons. In tissue culture, VZV-infected human neurons remain viable at 2 weeks, whereas fibroblasts develop cytopathology. Next-generation RNA sequencing was used to compare VZV transcriptomes in neurons and fibroblasts and identified only 12 differentially transcribed genes of the 70 annotated VZV open reading frames (ORFs), suggesting that defective virus transcription does not account for the lack of cell death in VZV-infected neurons
in vitro
.
Host MicroRNA Regulation of Human Cytomegalovirus Immediate Early Protein Translation Promotes Viral Latency
Authors: O'Connor Christine M. , Vanicek Jiri , Murphy Eain A. 
Published: March 2014

ABSTRACTReactivation of human cytomegalovirus (HCMV) is a significant cause of disease and death in immunocompromised patients, underscoring the need to understand how latency is controlled. Here we demonstrate that HCMV has evolved to utilize cellular microRNAs (miRNAs) in cells that promote latency to regulate expression of a viral protein critical for viral reactivation. Our data reveal that hsa-miR-200 miRNA family members target theUL122(immediate early protein 2) 3′ untranslated region, resulting in repression of this viral protein. Utilizing recombinant viruses that mutate the miRNA-binding site compared to the sequence of the wild-type virus results in lytic rather than latent infections inex vivoinfections of primary CD34+cells. Cells permissive for lytic replication demonstrate low levels of these miRNAs. We propose that cellular miRNA regulation of HCMV is critical for maintenance of viral latency.IMPORTANCEHuman cytomegalovirus (HCMV) is a herpesvirus that infects a majority of the population. Once acquired, individuals harbor the virus for life, where the virus remains, for the most part, in a quiet or latent state. Under weakened immune conditions, the virus can reactivate, which can cause severe disease and often death. We have found that members of a family of small RNAs, termed microRNAs, encoded by human myeloid progenitor cells are capable of repressing a key viral protein, thus enabling the virus to ensure a quiet/latent state. As these progenitor cells mature further down the myeloid lineage toward cells that support active viral replication, the levels of these microRNAs decrease. Together, our data suggest that host cell microRNA regulation of HCMV is important for the quiet/latent state of this pathogen.