bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Computational Study of Fracture in the Calcaneus Under Variable Impact Conditions
Authors: Kantareddy Sai Nithin Reddy , Fielding Rebecca A. , Robinson Michael J. , Kraft Reuben H. 
Published: March 2016

This preliminary study aims to computationally model and study the fracture patterns in the human calcaneus during variable impact loading conditions. A finite element model of the foot and ankle is used to understand the effect of loading rates and orientation of the foot on fracture patterns. Simulations are carried out by applying varying impact velocities of steel plate to the foot & ankle model in accordance with data regarding underbody blasts. These impact velocities are applied to reach a peak in 1.5 ms. Fracture of bone is represented using the plastic kinematic constitutive model with element erosion method, where elements are removed from the simulation after an inelastic failure strain is exceeded. The simulations last for 5 ms to observe the extent of fracture in the calcaneus.
Following simulations, the resulting fracture patterns are compared to available images from experimental impact tests to qualitatively assess the simufutions. A mesh convergence study is performed to determine the level of refinement of mesh necessary to represent this problem. The mesh appears to converge at the refinement level of the medium coarse mesh. The effect of impact velocities on fracture is studied on unjlexed and flexed foot models. At lower velocities, fracture is observed in the form of a single continuous crack, and a pronounced branched type of network is observed at higher velocities. Finally, variation in fracture networks due to variability in strength of the bone is studied. For lower values of failure strain, significantly larger and branched networks of fracture are observed.
A Method to Design Custom-Fit Stent Graft for Abdominal Aortic Aneurism
Authors: Colombo Giorgio , Bartesaghi Simone , Pallares Eduardo 
Published: March 2016

Abdominal Aorta Aneurysm (AAA) affects aorta, especially above the iliac bifurcation where the Wall Shear Stress (WSS) is greater. Consequence may be fatal in case of breakage; a way to treat it is Endovascular Aneurysm Repair (EVAR) where a stent graft is placed inside the aorta without open surgery requirement. Because of the standards, stent graft can be chosen between several sizes: in some cases, this device cannot fit perfectly with the anatomy of the patient and this can lead to a not optimal behavior of the prosthesis and further complications.
This study present a method to design and test specific custom-fit stent graft able to better adapt to the patient artery improving the efficiency of the prosthesis and reducing the risk of the migration of the graft as well as the fabric torn. The design method is based on a 3D geometric model of the aorta, generated from CT scan data. Centrelines and geometric data for cross sections along the aorta are the inputs necessary to define the mesh of the stent. A custom algorithm is developed to size the stent in relation to the geometric data of the specific patient; when the frame of the prosthesis is defined, a CAD-based Loft Surface has used to define surfaces between the stent rings. For the bifurcation, again CAD-based Boundary Surfaces is used.
The described procedure has been also applied in a Augmented Virtual Reality simulation of the EVAR and, finally, it permits a CFD simulation to evaluate the behavior of the prosthesis inserted into the aorta.
Mechanical Properties of Additively Manufactured PEEK Components Using Fused Filament Fabrication
Authors: Rahman Kazi Moshiur , Letcher Todd , Reese Riley 
Published: March 2016

Polyether ether ketone (PEEK) is introduced as a material for the additive manufacturing process called fused filament fabrication (FFF), as opposed to selective laser sintering (SLS) manufacturing. FFF manufacturing has several advantages over SLS manufacturing, including lower initial machine purchases costs, ease of use (spool of filament material vs powder material), reduced risk of material contamination and/or degradation, and safety for the users of the equipment. PEEK is an excellent candidate for FFF due to its low moisture absorption as opposed to other common FFF materials, such as Acrylonitrile Butadiene Styrene (ABS).
PEEK has been processed into a filament and samples have been manufactured using several build orientations and extrusion paths. The samples were used to conduct tensile, compression, flexural, and impact testing to determine mechanical strength characteristics such as yield strength, modulus of elasticity, ultimate tensile strength and maximum elongation, etc. All tests were conducted at room temperature. A microscope analysis was also conducted to show features on the failures surfaces. The mechanical property results from this study are compared to other published results using traditional thermo-plastic manufacturing techniques, such injection molding.
Tensile testing was conducted at three raster orientations, 0°, 90° and alternating between 0° and 90°. Average ultimate tensile stresses were determined to be 73 MPa for 0° orientation, and 54 MPa for 90° orientation, with alternating 0°/90° orientations of 66.5 MPa. Compression testing was conducted at two raster orientations, 0° and alternating between 0° and 90°. Average ultimate strength for the single orientation direction was 80.9 MPa with the alternating orientations at 72.8 MPa. Flexural testing was conducted at three raster orientations, 0°, 90° and alternating between 0° and 90°. Ultimate flexural stress was determined to be 111.7 MPa for 0°, 79.7 MPa for 90°, and 95.3 MPa for orientations alternating between 0° and 90°. Finally, impact testing was conducted at three raster orientations, 0°, 90° and alternating between 0° and 90°. Average impact energy absorbed was determined to be 17.5 Nm in the 0° orientation, 1.4 Nm in the 90° orientation, and 0.7 Nm for the alternating 0° and 90° orientations.
Solving Koffee Karousel Design Problems: A Case Study in the Senior Mechanical Engineering Design Student Project
Authors: McCall Casey , Bzymek Zbigniew M. 
Published: March 2016

The University of Connecticut Department of Mechanical Engineering has developed an industry recognized Senior Design Capstone course. The course provides fourth-year students the opportunity for a “major design experience in which they apply the principles of engineering, basic sciences, and mathematics to model, analyze, design, and realize physical systems, components or processes, and it prepares students to work professionally” [1]. The course is taught by a class instructor and is supported by the faculty of the Mechanical Engineering department at UConn. In the 2013–2014 academic year there were over 40 projects in the course. This paper presents the issues and challenges that students faced when working on a project for Koffee Karousel’s coin-operated K-Cup vending machine. Work on the project began with the problem statement, and was followed by the generation of possible solutions (accepting the most promising ones) and finally, choosing the ideal solution. The subsequent steps involved preliminary and detailed design, structural analysis, creating a 3D CAD representation, generating drawings, and producing a prototype. The prototype was then tested to verify its capabilities. The example of switching from a coin-operated design, with its limited potential use, to an electronically operated solution is described in this paper. The objective of this senior design project was to implement a credit card reader onto the original Koffee Karousel design. To accomplish this goal, a redesign of the Koffee-Karousel’s coin mechanism was required. An electrical engineering team of four students worked independently on the credit card and display setup, while a mechanical team worked on a lever mechanism and gears activated by the validation of a credit card. The implementation of this new mechanism included designing a replacement face, a couple of brackets for electrical hardware, and several new parts, including an actuator and a mini-stepper motor. In addition, students designed the new cam that would interface with stepper motor. Some parts were accepted from the current design of the lever and ejector. The new design still allows the customer to choose which K-Cup flavor they want by hand by operating a rotating knob at the top of the carousel, but no longer requires the user to trigger the ejector mechanism manually. Students tested the new mechanism to ensure it was not only efficient, but also worked properly. The stresses on each individual part were calculated for the first design iteration to ensure the new design would not yield or fail over time due to fatigue.
The project and its challenges are described in this paper, as well as the students’ contributions to the design of the Karousel mechanisms, switching it from a purely mechanical to a mechatronik solution.
Clarithromycin Resistance Mechanisms of Epidemic β-Lactamase-Nonproducing Ampicillin-Resistant Haemophilus influenzae Strains in Japan
Authors: Seyama Shoji , Wajima Takeaki , Nakaminami Hidemasa , Noguchi Norihisa 
Published: March 2016

ABSTRACT

The aim of this study was to clarify the clarithromycin resistance mechanisms of β-lactamase-nonproducing ampicillin-resistant
Haemophilus influenzae
strains. In all clarithromycin-resistant strains, the transcript level of
acrB
was significantly elevated, and these strains had a frameshift mutation in
acrR
. Introduction of the
acrR
mutation into
H. influenzae
Rd generated a clarithromycin-resistant transformant with the same MIC as the donor strain. Our results indicate that the
acrR
mutation confers clarithromycin resistance by the increasing the transcription of
acrB
.
Effects of Efflux Pump Inhibitors on Colistin Resistance in Multidrug-Resistant Gram-Negative Bacteria
Authors: Ni Wentao , Li Yanjun , Guan Jie , Zhao Jin , Cui Junchang , Wang Rui , Liu Youning 
Published: March 2016

ABSTRACT

We tested the effects of various putative efflux pump inhibitors on colistin resistance in multidrug-resistant Gram-negative bacteria. Addition of 10 mg/liter cyanide 3-chlorophenylhydrazone (CCCP) to the test medium could significantly decrease the MICs of colistin-resistant strains. Time-kill assays showed CCCP could reverse colistin resistance and inhibit the regrowth of the resistant subpopulation, especially in
Acinetobacter baumannii
and
Stenotrophomonas maltophilia
. These results suggest colistin resistance in Gram-negative bacteria can be suppressed and reversed by CCCP.
Antitrypanosomal Activities and Mechanisms of Action of Novel Tetracyclic Iridoids from Morinda lucida Benth
Authors: Kwofie Kofi D. , Tung Nguyen Huu , Suzuki-Ohashi Mitsuko , Amoa-Bosompem Michael , Adegle Richard , Sakyiamah Maxwell M. , Ayertey Frederick , Owusu Kofi Baffour-Awuah , Tuffour Isaac , Atchoglo Philip , Frempong Kwadwo K. , Anyan William K. , Uto Takuhiro , Morinaga Osamu , Yamashita Taizo , Aboagye Frederic , Appiah Alfred A. , Appiah-Opong Regina , Nyarko Alexander K. , Yamaguchi Yasuchika , Edoh Dominic , Koram Kwadwo A. , Yamaoka Shoji , Boakye Daniel A. , Ohta Nobuo , Shoyama Yukihiro , Ayi Irene 
Published: March 2016

ABSTRACT

Trypanosoma brucei
parasites are kinetoplastid protozoa that devastate the health and economic well-being of millions of people in Africa through the disease human African trypanosomiasis (HAT). New chemotherapy has been eagerly awaited due to severe side effects and the drug resistance issues plaguing current drugs. Recently, there has been an emphasis on the use of medicinal plants worldwide.
Morinda lucida
Benth. is a popular medicinal plant widely distributed in Africa, and several research groups have reported on the antiprotozoal activities of this plant. In this study, we identified three novel tetracyclic iridoids, molucidin, ML-2-3, and ML-F52, from the CHCl
3
fraction of
M. lucida
leaves, which possess activity against the GUTat 3.1 strain of
T. brucei brucei
. The 50% inhibitory concentrations (IC
50
) of molucidin, ML-2-3, and ML-F52 were 1.27 μM, 3.75 μM, and 0.43 μM, respectively. ML-2-3 and ML-F52 suppressed the expression of paraflagellum rod protein subunit 2, PFR-2, and caused cell cycle alteration, which preceded apoptosis induction in the bloodstream form of
Trypanosoma
parasites. Novel tetracyclic iridoids may be promising lead compounds for the development of new chemotherapies for African trypanosomal infections in humans and animals.
In Vitro
and
In Vivo
Pharmacokinetics of Aminoalkylated Diarylpropanes NP085 and NP102
Authors: Gibhard Liezl , Pravin Kendrekar , Abay Efrem , Wilhelm Anke , Swart Kenneth , Lawrence Nina , Khoury Rosal , van der Westhuizen Jan , Smith Peter , Wiesner Lubbe 
Published: March 2016

ABSTRACT

Malaria remains a great burden on humanity. Although significant advances have been made in the prevention and treatment of malaria, malaria control is now hindered by an increasing tolerance of the parasite to one or more drugs within artemisinin combination therapies; therefore, an urgent need exists for development of novel and improved therapies. The University of the Free State Chemistry Department previously synthesized an antimalarial compound, NP046.
In vitro
studies illustrated an enhanced efficacy against
Plasmodium falciparum
. However, NP046 showed low bioavailability. Efforts to enhance the bioavailability of NP046 have resulted in the synthesis of a number of aminoalkylated diarylpropanes, including NP085 and NP102. Pharmacokinetic studies were conducted in C57BL/6 mice, with 15 mg/kg NP085 or NP102 administered orally and the 5 mg/kg NP085 or NP102 administered intravenously. Blood samples were collected by means of tail bleeding at predetermined time intervals. Drug concentrations were determined using a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method, and subsequently pharmacokinetic modeling was done for both compounds. NP085 and NP102 were incubated
in vitro
with human and mouse liver microsomes. Both compounds were also subjected to a parallel artificial membrane permeation assay.
In vitro
studies of NP085 and NP102 illustrated that both of the compounds are rapidly absorbed and undergo rapid hepatic metabolism. The maximum concentration of drug (
C
max
) obtained following oral administration of NP085 and NP102 was 0.2 ± 0.4 and 0.7 ± 0.3 μM, respectively; the elimination half-life of both compounds was 6.1 h. NP085 and NP102 showed bioavailability levels of 8% and 22%, respectively.
Overcoming Chloroquine Resistance in Malaria: Design, Synthesis, and Structure-Activity Relationships of Novel Hybrid Compounds
Authors: Boudhar Aicha , Ng Xiao Wei , Loh Chiew Yee , Chia Wan Ni , Tan Zhi Ming , Nosten Francois , Dymock Brian W. , Tan Kevin S. W. 
Published: March 2016

ABSTRACT

Resistance to antimalarial therapies, including artemisinin, has emerged as a significant challenge. Reversal of acquired resistance can be achieved using agents that resensitize resistant parasites to a previously efficacious therapy. Building on our initial work describing novel chemoreversal agents (CRAs) that resensitize resistant parasites to chloroquine (CQ), we herein report new hybrid single agents as an innovative strategy in the battle against resistant malaria. Synthetically linking a CRA scaffold to chloroquine produces hybrid compounds with restored potency toward a range of resistant malaria parasites. A preferred compound, compound 35, showed broad activity and good potency against seven strains resistant to chloroquine and artemisinin. Assessment of aqueous solubility, membrane permeability, and
in vitro
toxicity in a hepatocyte line and a cardiomyocyte line indicates that compound 35 has a good therapeutic window and favorable drug-like properties. This study provides initial support for CQ-CRA hybrid compounds as a potential treatment for resistant malaria.
In Vitro
and
In Vivo
Activities of OP0595, a New Diazabicyclooctane, against CTX-M-15-Positive Escherichia coli and KPC-Positive Klebsiella pneumoniae
Authors: Morinaka Akihiro , Tsutsumi Yuko , Yamada Keiko , Takayama Yoshihiro , Sakakibara Shiro , Takata Toshihiko , Abe Takao , Furuuchi Takeshi , Inamura Seiichi , Sakamaki Yoshiaki , Tsujii Nakako , Ida Takashi 
Published: March 2016

ABSTRACT

Gram-negative bacteria are evolving to produce β-lactamases of increasing diversity that challenge antimicrobial chemotherapy. OP0595 is a new diazabicyclooctane serine β-lactamase inhibitor which acts also as an antibiotic and as a β-lactamase-independent β-lactam “enhancer” against
Enterobacteriaceae
. Here we determined the optimal concentration of OP0595 in combination with piperacillin, cefepime, and meropenem, in addition to the antibacterial activity of OP0595 alone and in combination with cefepime, in
in vitro
time-kill studies and an
in vivo
infection model against five strains of CTX-M-15-positive
Escherichia coli
and five strains of KPC-positive
Klebsiella pneumoniae
. An OP0595 concentration of 4 μg/ml was found to be sufficient for an effective combination with all three β-lactam agents. In both
in vitro
time-kill studies and an
in vivo
model of infection, cefepime-OP0595 showed stronger efficacy than cefepime alone against all β-lactamase-positive strains tested, whereas OP0595 alone showed weaker or no efficacy. Taken together, these data indicate that combinational use of OP0595 and a β-lactam agent is important to exert the antimicrobial functions of OP0595.
Protective Effect of a Synbiotic against Multidrug-Resistant Acinetobacter baumannii in a Murine Infection Model
Authors: Asahara Takashi , Takahashi Akira , Yuki Norikatsu , Kaji Rumi , Takahashi Takuya , Nomoto Koji 
Published: March 2016

ABSTRACT

This study investigated the ability of the probiotic
Bifidobacterium breve
strain Yakult (BbY) to protect against infection, as well as the potentiation of BbY activity by the synbiotic combination of BbY and prebiotic galactooligosaccharides (GOS). The study employed a mouse model of lethal intestinal multidrug-resistant
Acinetobacter baumannii
(MDRAb) infection. The endogenous intestinal microbiota was disrupted by the administration of multiple antibiotics, causing the loss of endogenous
Bifidobacterium
. Oral infection of these mice with MDRAb resulted in marked growth of this organism. Additional treatment of the infected mice with a sublethal dose of 5-fluorouracil (5-FU) induced systemic invasion by MDRAb and subsequent animal death. The continuous oral administration of BbY increased the survival rate and inhibited the intestinal growth and invasion by MDRAb in the infection model. Disruptions of the intestinal environment and barrier function in the infected mice were attenuated by BbY. Protection against the MDRAb infection was markedly potentiated by a synbiotic combination of BbY and GOS, although GOS by itself did not provide protection. Negative correlations were observed between intestinal MDRAb and BbY counts or acetic acid levels; positive correlations were observed between acetic acid levels and intestinal epithelium expression of tight-junction-related genes. These results demonstrated that the probiotic and synbiotic markedly potentiated protection against fatal intestinal infection caused by a multidrug-resistant bacterium. Probiotics and synbiotics are presumed to provide protection by compensation for the disrupted indigenous populations, thereby maintaining the intestinal environments and barrier functions otherwise targeted during opportunistic infection by MDRAb.
Population Pharmacokinetics of Isavuconazole in Subjects with Mild or Moderate Hepatic Impairment
Authors: Desai Amit , Schmitt-Hoffmann Anne-Hortense , Mujais Salim , Townsend Robert 
Published: March 2016

ABSTRACT
Isavuconazole, administered as the prodrug isavuconazonium sulfate, was recently approved by the U.S. Food and Drug Administration and the European Medicines Agency for the treatment of adults with invasive aspergillosis and mucormycosis. The objective of this analysis was to develop a population pharmacokinetic model using NONMEM (version 7.2) for subjects with hepatic impairment, using intravenous and oral administration data from two hepatic studies, and to simulate concentration profiles to steady state, thus evaluating the need for dose adjustment. A two-compartment model with Weibull absorption function and first-order elimination process adequately described plasma isavuconazole concentrations. The population mean clearance in healthy subjects was 2.5 liters/h (5th and 95th percentiles: 2.0 and 3.1). The mean clearance values for subjects with mild and moderate hepatic impairment decreased approximately to 1.55 liters/h (5th and 95th percentiles: 1.3 and 1.8 liters/h) and 1.32 liters/h (5th and 95th percentiles: 1.05 and 1.35), respectively. Peripheral volume of distribution increased with body mass index. Simulations of mean concentration time profiles to steady state showed less than a 2-fold increase in mean trough concentrations for subjects with mild and moderate hepatic impairment compared with healthy subjects. After administration of the single dose, safety data for subjects with mild and moderate hepatic impairment were generally comparable to those for healthy subjects in both studies. Due to the <2-fold increase in trough concentrations and the established safety margin, dose adjustment appears to be unnecessary in subjects with mild or moderate hepatic impairment.
Intramacrophage Infection Reinforces the Virulence of Edwardsiella tarda
Authors: Zhang Lingzhi , Ni Chunshan , Xu Wenting , Dai Tongcheng , Yang Dahai , Wang Qiyao , Zhang Yuanxing , Liu Qin 
Published: March 2016

ABSTRACT

Edwardsiella tarda
is an important pathogenic bacterium that can replicate in macrophages. However, how the intramacrophage infection process affects the virulence of this bacterium is essentially unknown. Here, we show that
E. tarda
replicates and induces a caspase-1-dependent cell pyroptosis in a murine macrophage model. Via pyroptosis, intracellular
E. tarda
escapes to the extracellular milieu, forming a unique bacterial population. Being different from the bacteria cultured alone, this unique population possesses a reprogrammed transcriptional profile, particularly with upregulated type III secretion system (T3SS)/T6SS cluster genes. Subsequent studies revealed that the macrophage-released population gains enhanced infectivity for host epithelial cells and increases resistance to multiple host defenses and hence displays significantly promoted virulence
in vivo
. Further studies indicated that T3SS is essentially required for the macrophage infection process, while T6SS contributes to infection-induced bacterial virulence. Altogether, this work demonstrates that
E. tarda
can utilize macrophages as a niche for virulence priming and for spreading infection, suggesting a positive role for intramacrophage infection in bacterial pathogenesis.

IMPORTANCE
Many pathogens can replicate in macrophages, which is crucial for their pathogenesis. To survive in the macrophage cell, pathogens are likely to require fitness genes to counteract multiple host-killing mechanisms. Here,
Edwardsiella tarda
is proved to exit from macrophages during infection. This macrophage-released population displays a reprogrammed transcriptional profile with significantly upregulated type III secretion system (T3SS)/T6SS-related genes. Furthermore, both enhanced infectivity in epithelial cells and activated resistance to complex host defenses were conferred on this macrophage-primed population, which consequently promoted the full virulence of
E. tarda
in vivo
. Our work provides evidence that
E. tarda
can utilize macrophages as a niche for virulence priming and for spreading infection, highlighting the importance of the intramacrophage infection cycle for the pathogenesis of
E. tarda
.