bluuebunny/crossref_metadata_2025 huggingface dataset:
A New Approach to the Rigid Finite Element Method in Modeling Spatial Slender Systems
Authors: Adamiec-Wójcik Iwona , Drąg Łukasz , Wojciech Stanisław
Published: May 2017

The static and dynamic analysis of slender systems, which in this paper comprise lines and flexible links of manipulators, requires large deformations to be taken into consideration. This paper presents a modification of the rigid finite element method which enables modeling of such systems to include bending, torsional and longitudinal flexibility. In the formulation used, the elements into which the link is divided have seven DOFs. These describe the position of a chosen point, the extension of the element, and its orientation by means of the Euler angles Z[Formula: see text]Y[Formula: see text]X[Formula: see text]. Elements are connected by means of geometrical constraint equations. A compact algorithm for formulating and integrating the equations of motion is given. Models and programs are verified by comparing the results to those obtained by analytical solution and those from the finite element method. Finally, they are used to solve a benchmark problem encountered in nonlinear dynamic analysis of multibody systems.
Accurate Task-Space Tracking for Humanoids with Modeling Errors Using Iterative Learning Control
Authors: Bhounsule Pranav A. , Yamane Katsu
Published: May 2017

Precise task-space tracking with manipulator-type systems requires an accurate kinematic model. In contrast to traditional manipulators, sometimes it is difficult to obtain an accurate kinematic model of humanoid robots due to complex structure and link flexibility. Also, prolonged use of the robot will lead to some parts wearing out or being replaced with a slightly different alignment, thus throwing off the initial calibration. Therefore, there is a need to develop a control algorithm that can compensate for the modeling errors and quickly retune itself, if needed, taking into account the controller bandwidth limitations and high dimensionality of the system. In this paper, we develop an iterative learning control algorithm that can work with existing inverse kinematics solvers to refine the joint-level control commands to enable precise tracking in the task space. We demonstrate the efficacy of the algorithm on a theme-park-type humanoid doing a drawing task, serving drink in a glass, and serving a drink placed on a tray without spilling. The iterative learning control algorithm is able to reduce the tracking error by at least two orders of magnitude in less than 20 trials.
An effective zinc phthalocyanine derivative against multidrug-resistant bacterial infection
Authors: Wang Dong , Zhang Yuxiang , Yan Shufeng , Chen Zihan , Deng Yicai , Xu Peng , Chen Jincan , Liu Wenzhen , Hu Ping , Huang Mingdong , Chen Zhuo
Published: May 2017

Bacterial skin and soft tissue infections are abundant worldwide. The rise in the incidence of multidrug-resistant (MDR) bacterial infections has made the need for alternative means of treatment more pressing. We herein report a zinc phthalocyanine derivative, pentalysine [Formula: see text]-carbonylphthalocyanine zinc (ZnPc-(Lys)[Formula: see text] and its strong capability of killing nosocomial MDR bacteria, including MDR-Escherichia coli and MDR-Acinetobacter baumannii. In vitro studies, we observed that ZnPc-(Lys)5 in micromolar concentrations killed above MDR bacteria in 6~6.5 log10 orders with only 5-min illumination of red light at a dosage of 12.75 J/cm[Formula: see text]. Further in vivo studies on a mouse infection model demonstrated that ZnPc-(Lys)5 efficiently inhibited the MDR bacterial growth after one-time photodynamic antibacterial therapy and, interestingly, significantly accelerated the wound healing. Putting together, our findings establish ZnPc-(Lys)5 as a potent antimicrobial candidate for the clinical test on localized infection.
A BIVALENT INACTIVATED VACCINE OF VIRAL NERVOUS NECROSIS VIRUS AND GROUPER IRIDOVIRUS APPLIED TO GROUPER BROODFISH (EPINEPHELUS COIOIDES) REDUCES THE RISK OF VERTICAL TRANSMISSION
Authors: Huang Sue-Min , Cheng Jin-Hua , Tu Chien , Chen Tzyy-Ing , Lin Chun-Ta , Chang Shao-Kuang
Published: May 2017

Forty-one broodfish of orange-spotted groupers (Epinephelus coioides) were selected to evaluate the effectiveness of a viral nervous necrosis virus (VNNV) and grouper iridovirus (GIV) inactivated bivalent vaccine in grouper broodfish. Real-time quantitative PCR analysis showed that a detection rate of 10.5% (2/19) was found in egg specimens of VNNV and GIV, which carried approximately 1780 copies of GIV viral DNA in the egg specimens from broodfish before vaccination. This confirmed the vertical transmission route of GIV in broodfish. A significant increase of the anti-VNNV serum antibody titer was more than 50% in the high titer level (1:1810 to 1:5120) and 45% in the moderate titer level (1:452 to 1:1280), which were higher than those of the anti-GIV display, with 50% (10/20) in a titer of 1:57 to 1:320 and 40% (8/20) in a titer of 1:452 to 1:1280 one month after the vaccination. This result showed that the VNNV is a highly antigenic virus and can effectively induce neutralizing antibodies better than GIV. In addition, the VNNV and GIV viral copy numbers were 97.1 and 1780 copies per [Formula: see text]g host egg DNA from the broodfish before vaccination, respectively. One month after the vaccination, the viral genomes of VNNV and GIV were undetectable in egg specimens. The results show that immunization can induce the production of specific protective neutralizing antibodies, and the infective antigens can thereby be eliminated by the immunity.

The results demonstrate that the specific antibodies of GIV and VNNV induced by vaccination can reduce the risk of vertical transmission of VNNV and GIV in grouper broodfish.
How Active Mechanics and Regulatory Biochemistry Combine to Form Patterns in Development
Authors: Gross Peter , Kumar K. Vijay , Grill Stephan W.
Published: May 2017

The development of organisms starting from their zygotic state involves a tight integration of the myriad biochemical signaling interactions with the mechanical forces that eventually pattern and shape the resulting embryo. In the past decade, it has become increasingly evident that several important developmental processes involve mechanical forces in an essential manner. In this review, we highlight the multifaceted role of mechanics in pattern formation, from protein and cell sorting to the generation of tissue shape. We then review the ways in which the active cellular cytoskeleton self-organizes to form dynamic patterns. Finally, we focus on mechanochemical feedback, where signaling proteins can establish patterns via coupling to the activity of the cytoskeleton. Throughout the review, we focus on the generic physical principles of the establishment of active mechanochemical patterns and point toward future directions in studying how the principles of mechanics and chemistry combine to drive morphogenetic pattern formation.
Soft Matter in Lipid–Protein Interactions
Authors: Brown Michael F.
Published: May 2017

Membrane lipids and cellular water (soft matter) are becoming increasingly recognized as key determinants of protein structure and function. Their influences can be ascribed to modulation of the bilayer properties or to specific binding and allosteric regulation of protein activity. In this review, we first consider hydrophobic matching of the intramembranous proteolipid boundary to explain the conformational changes and oligomeric states of proteins within the bilayer. Alternatively, membranes can be viewed as complex fluids, whose properties are linked to key biological functions. Critical behavior and nonideal mixing of the lipids have been proposed to explain how raft-like microstructures involving cholesterol affect membrane protein activity. Furthermore, the persistence length for lipid–protein interactions suggests the curvature force field of the membrane comes into play. A flexible surface model describes how curvature and hydrophobic forces lead to the emergence of new protein functional states within the membrane lipid bilayer.
Integration of Bacterial Small RNAs in Regulatory Networks
Authors: Nitzan Mor , Rehani Rotem , Margalit Hanah
Published: May 2017

Small RNAs (sRNAs) are central regulators of gene expression in bacteria, controlling target genes posttranscriptionally by base pairing with their mRNAs. sRNAs are involved in many cellular processes and have unique regulatory characteristics. In this review, we discuss the properties of regulation by sRNAs and how it differs from and combines with transcriptional regulation. We describe the global characteristics of the sRNA–target networks in bacteria using graph-theoretic approaches and review the local integration of sRNAs in mixed regulatory circuits, including feed-forward loops and their combinations, feedback loops, and circuits made of an sRNA and another regulator, both derived from the same transcript. Finally, we discuss the competition effects in posttranscriptional regulatory networks that may arise over shared targets, shared regulators, and shared resources and how they may lead to signal propagation across the network.
The NLRP3 inflammasome contributes to sarcopenia and lower muscle glycolytic potential in old mice
Authors: McBride Marin Jane , Foley Kevin P. , D’Souza Donna M. , Li Yujin E. , Lau Trevor C. , Hawke Thomas J. , Schertzer Jonathan D.
Published: May 2017

The mechanisms underpinning decreased skeletal muscle strength and slowing of movement during aging are ill-defined. “Inflammaging,” increased inflammation with advancing age, may contribute to aspects of sarcopenia, but little is known about the participatory immune components. We discovered that aging was associated with increased caspase-1 activity in mouse skeletal muscle. We hypothesized that the caspase-1-containing NLRP3 inflammasome contributes to sarcopenia in mice. Male C57BL/6J wild-type (WT) and NLRP3−/− mice were aged to 10 (adult) and 24 mo (old). NLRP3−/− mice were protected from decreased muscle mass (relative to body mass) and decreased size of type IIB and IIA myofibers, which occurred between 10 and 24 mo of age in WT mice. Old NLRP3−/− mice also had increased relative muscle strength and endurance and were protected from age-related increases in the number of myopathic fibers. We found no evidence of age-related or NLRP3-dependent changes in markers of systemic inflammation. Increased caspase-1 activity was associated with GAPDH proteolysis and reduced GAPDH enzymatic activity in skeletal muscles from old WT mice. Aging did not alter caspase-1 activity, GAPDH proteolysis, or GAPDH activity in skeletal muscles of NLRP3−/− mice. Our results show that the NLRP3 inflammasome participates in age-related loss of muscle glycolytic potential. Deletion of NLRP3 mitigates both the decline in glycolytic myofiber size and the reduced activity of glycolytic enzymes in muscle during aging. We propose that the etiology of sarcopenia involves direct communication between immune responses and metabolic flux in skeletal muscle.
The Effect of a Synthetic Heparan Sulfate on the Healing of Colonic Anastomoses
Authors: Nerstrøm Malene , Krarup Peter-Martin , Jorgensen Lars Nannestad , Ågren Magnus S.
Published: May 2017

Background. The mimetic compound OTR4120 may replace endogenous-degraded heparan sulfates that normally maintain the bioactivity of growth factors that are important for tissue repair. Herein, we investigated the effect of OTR4120 on the healing of normal colonic anastomoses. Methods. We evaluated the following two treatment groups of male Sprague Dawley rats (220–256 g): control-treated colonic anastomoses (n=25) and OTR4120-treated colonic anastomoses (n=25). We resected 10 mm of the left colon and then applied either saline alone (control) or OTR4120 (100 μg/mL) in saline to the colonic ends before an end-to-end single-layer anastomosis was constructed and again on the anastomosis before the abdomen and skin were closed. Results. On postoperative day 3, the anastomotic breaking strengths were 1.47 ± 0.32 N (mean ± SD) in the control group and 1.52 ± 0.27 N in the OTR4120-treated animals (P=0.622). We also found that the hydroxyproline concentration (indicator of collagen) in the anastomotic wounds did not differ (P=0.571) between the two groups. Conclusions. Our data demonstrate that a single local application of OTR4120 intraoperatively did not increase the biomechanical strength of colonic anastomoses at the critical postoperative day 3 when the anastomoses are the weakest.
The CEDAR Study: A Longitudinal Study of the Clinical Effects of Conventional DMARDs and Biologic DMARDs in Australian Rheumatology Practice
Authors: Roberts Lynden , Tymms Kathleen , de Jager Julien , Littlejohn Geoffrey , Griffiths Hedley , Nicholls Dave , Bird Paul , Young Jennifer , Hill Julie , Zochling Jane
Published: May 2017

Objectives. To observe the choices of conventional disease modifying antirheumatic drugs (cDMARDs) and biologic DMARDs (bDMARDs) in the management of rheumatoid arthritis (RA) in Australian routine clinical practice, to assess treatment survival and determine the effect of cDMARDs/bDMARDs on disease activity. Methods. Routinely collected, deidentified clinical data was sourced from 20 Australian rheumatology practices. RA patients aged ≥18 years, who had received cDMARDs/bDMARDs and a recorded subsequent visit, were included. A linear mixed model was used to determine the change over time and the percentage reduction in disease activity was summarized. Results. 12,526 RA patients were included: 72% females, mean age 62 years. cDMARDs and bDMARDs were used in 92% and 30% of patients, respectively. The most commonly prescribed cDMARD was methotrexate (76% patients); median time to stopping treatment was 337 months [95% CI: 279–ND]. Etanercept was the most commonly prescribed bDMARD (12% patients); median time to stopping treatment was 79 months [95% CI: 57–93]. Of 5,341 patients with a first change in medication (cDMARD or bDMARD), 87% had therapy escalation and 13% deescalation. Reduction in DAS28-ESR, 6-month post-DMARDs initiation ranged from 3%, adalimumab, to 14%, leflunomide and tocilizumab. Conclusions. In this large Australian cohort of unselected community RA patients, the choices of cDMARDs/bDMARDs are aligned with current international guidelines.
Postmenopausal Iron Overload Exacerbated Bone Loss by Promoting the Degradation of Type I Collagen
Authors: Cheng Qian , Zhang Xiaofei , Jiang Jun , Zhao Guoyang , Wang Yin , Xu Youjia , Xu Ximing , Ma Haile
Published: May 2017

117 postmenopausal women were divided into Normal, Bone loss (BL), and Osteoporosis group. Compared with Normal group (120.96 ± 43.18 μg/L), the serum ferritin (Fer) in BL (223.37 ± 130.27 μg/L) and Osteoporosis group (307.50 ± 161.48 μg/L) was significantly increased (p < 0.05). Fer level was negatively correlated with BMD (p < 0.01). TRACP levels in Osteoporosis group (4.37 ± 1.69 U/L) were significantly higher than Normal group (4.10 ± 1.60 U/L, p < 0.05). ALP levels in Osteoporosis group (112.06 ± 62.05 U/L) were significantly upregulated compared with Normal group (80.22 ± 14.94 U/L, p < 0.05). β-CTX and PINP were the degradation products of type I collagen. β-CTX levels in Osteoporosis group (667.90 ± 316.55 ng/L) were significantly increased compared with Normal group (406.06 ± 112.12 ng/L, p < 0.05). PINP levels in Osteoporosis group (78.03 ± 37.31 μg/L) were significantly higher than Normal group (37.60 ± 13.17 μg/L, p < 0.01). More importantly, there was a positive correlation between serum Fer and PINP (p < 0.01). Serum Fer showed a positive correlation of serum β-CTX (p < 0.01). The overloaded iron improved the degradation of type I collagen.
Significant Remote Sensing Vegetation Indices: A Review of Developments and Applications
Authors: Xue Jinru , Su Baofeng
Published: May 2017

Vegetation Indices (VIs) obtained from remote sensing based canopies are quite simple and effective algorithms for quantitative and qualitative evaluations of vegetation cover, vigor, and growth dynamics, among other applications. These indices have been widely implemented within RS applications using different airborne and satellite platforms with recent advances using Unmanned Aerial Vehicles (UAV). Up to date, there is no unified mathematical expression that defines all VIs due to the complexity of different light spectra combinations, instrumentation, platforms, and resolutions used. Therefore, customized algorithms have been developed and tested against a variety of applications according to specific mathematical expressions that combine visible light radiation, mainly green spectra region, from vegetation, and nonvisible spectra to obtain proxy quantifications of the vegetation surface. In the real-world applications, optimization VIs are usually tailored to the specific application requirements coupled with appropriate validation tools and methodologies in the ground. The present study introduces the spectral characteristics of vegetation and summarizes the development of VIs and the advantages and disadvantages from different indices developed. This paper reviews more than 100 VIs, discussing their specific applicability and representativeness according to the vegetation of interest, environment, and implementation precision. Predictably, research, and development of VIs, which are based on hyperspectral and UAV platforms, would have a wide applicability in different areas.
Decay of the 3D Quasilinear Hyperbolic Equations with Nonlinear Damping
Authors: Qiu Hongjun , Zhang Yinghui
Published: May 2017

We investigate the 3D quasilinear hyperbolic equations with nonlinear damping which describes the propagation of heat wave for rigid solids at very low temperature, below about 20 K. The global existence and uniqueness of strong solutions are obtained when the initial data is near its equilibrium in the sense of H3-norm. Furthermore, if, additionally, Lp-norm (1≤p<6/5) of the initial perturbation is finite, we also prove the optimal Lp-L2 decay rates for such a solution without the additional technical assumptions for the nonlinear damping f(v) given by Li and Saxton.
Homonymous Superior Quadrantanopia due to Erdheim-Chester Disease with Asymptomatic Pituitary Involvement
Authors: Amer Roaa Ridha , Qubaiban Sara Mohammed , Bakhsh Eman Abdulkarim
Published: May 2017

Polyostotic sclerosing histiocytosis, also known as Erdheim-Chester disease (ECD), is a rare form of non-Langerhans histiocytosis. ECD has wide clinical spectrums which mainly affect skeletal, neurological, dermatological, retroperitoneal, cardiac, and pulmonary manifestations. Here we describe a case of ECD in a 45-year-old female who presented initially with bilateral knee pain and homonymous superior quadrantanopia progressed to ophthalmoplegia and complete visual loss of the left eye over a period of one year. Plain X-ray of both knees showed bilateral patchy sclerosis of the distal femur and upper parts of the tibiae. Initial brain magnetic resonance imaging (MRI) showed bilateral enhancing masses in the temporal lobes anterior to the temporal horns, thickening of the pituitary stalk, partially empty sella, and involvement of the left cavernous sinus one year later. Our case is a peculiar case of ECD initially presented with unilateral homonymous superior quadrantanopia due to involvement of the visual apparatus in the mesial temporal lobe which progressed to unilateral ophthalmoplegia and total visual loss secondary to involvement of the cavernous sinus. Thus, the diagnosis of ECD should be kept in mind in the presence of bilateral bone sclerotic lesions.
Numerical Simulations of the Lunar Penetrating Radar and Investigations of the Geological Structures of the Lunar Regolith Layer at the Chang’E 3 Landing Site
Authors: Ding Chunyu , Su Yan , Xing Shuguo , Dai Shun , Xiao Yuan , Feng Jianqing , Liu Danqing , Li Chunlai
Published: May 2017

In the process of lunar exploration, and specifically when studying lunar surface structure and thickness, the established lunar regolith model is usually a uniform and ideal structural model, which is not well-suited to describe the real structure of the lunar regolith layer. The present study aims to explain the geological structural information contained in the channel 2 LPR (lunar penetrating radar) data. In this paper, the random medium theory and Apollo drilling core data are used to construct a modeling method based on discrete heterogeneous random media, and the simulation data are processed and collected by the electromagnetic numerical method FDTD (finite-difference time domain). When comparing the LPR data with the simulated data, the heterogeneous random medium model is more consistent with the actual distribution of the media in the lunar regolith layer. It is indicated that the interior structure of the lunar regolith layer at the landing site is not a pure lunar regolith medium but rather a regolith-rock mixture, with rocks of different sizes and shapes. Finally, several reasons are given to explain the formation of the geological structures of the lunar regolith layer at the Chang’E 3 landing site, as well as the possible geological stratification structure.
Influence of Dietary Supplementation with Prebiotic, Oregano Extract, and Vitamin E on Fatty Acid Profile and Oxidative Status of Rabbit Meat
Authors: Mattioli Simona , Cardinali Raffaella , Balzano Michele , Pacetti Deborah , Castellini Cesare , Dal Bosco Alessandro , Frega Natale Giuseppe
Published: May 2017

The effect of dietary supplementation with vitamin E, oregano, and prebiotic on fatty acids and oxidative profiles of rabbit meat (loin and hind leg) was evaluated. New Zealand white rabbits weaned at 30 days of age were fed with one of six diets until 80 days of age: standard diet includingω3 polyunsaturated fatty and conjugated linolenic acids sources (S) and five diets adding vitamin E (150 ppm, E), oregano water extract (2 g/kg feed diet, O), prebiotic (THEPAX® 1.5 g/kg feed diet, T), vitamin E plus prebiotic (TE), and oregano water extract plus prebiotic (TO), respectively. The lipid oxidative status (TBARS) showed lower values with respect to S, mainly when vitamin E was administered. In particular, all the experimental diets decreased TBARS values with respect to the control group in the loin, but no effect was found in the hind leg. In all feed samples, the amounts of fatty acid classes increased in the following order: polyunsaturated fatty acids > monounsaturated fatty acid > saturated fatty acid. The dietary supplementations did not affect the fatty acid composition of meat. The experimented diets compared to the control were not able to provide a selective increase of bioactive fatty acid in meat samples; however, the six nutritional strategies led to highly nutritional rabbit meat with an interesting value of theω6/ω3 ratio.
The Learning Preferences among Nursing Students in the King Saud University in Saudi Arabia: A Cross-Sectional Survey
Authors: Alharbi Homood A. , Almutairi Adel F. , Alhelih Eyad M. , Alshehry Abdualrahman S.
Published: May 2017

Objective.The present study aimed to identify the most common learning preferences among the nursing students in Saudi Arabia and to investigate the associations of certain demographic variables with the learning preferences.Methods.All the undergraduate nursing students in the nursing college were requested to participate in this descriptive cross-sectional study. An Arabic version of the Felder-Silverman learning style model (FSLSM) questionnaire was used to examine the learning preferences among undergraduate nursing students.Results.A total of 56 (43%) completed questionnaires were included in the final analysis. Results of the present study indicate that the most common learning preferences among the nursing students were visual (67.9%), followed by active (50%) and sequential (37.5%) learning preferences. The verbal style was the least common learning preference (3.6%) among the nursing students. There was no association between gender and learning preferences (p>.05).Conclusion.The present study concluded that the visual, active, and sequential styles are the commonest learning preferences among the nursing students. The nursing educators should emphasize the use of this information in their teaching methods to improve learning skills among the nursing students.
Hepatoprotective Effect of Polyphenol‐Enriched Fraction from Folium Microcos on Oxidative Stress and Apoptosis in Acetaminophen‐Induced Liver Injury in Mice
Authors: Wu Hongtan , Zhang Gang , Huang Lisen , Pang Haiyue , Zhang Na , Chen Yupei , Wang Gueyhorng
Published: May 2017

Folium Microcos (FM), the leaves of Microcos paniculata L., shows various biological functions including antioxidant activity and α‐glucosidase inhibitory effect. However, its therapeutic potential in acute liver injury is still unknown. This study investigated the hepatoprotective effect and underlying mechanisms of the polyphenol‐enriched fraction (FMF) from Folium Microcos. FMF exhibited strong free radical scavenging activities and prevented HepG2/Hepa1–6 cells from hydrogen peroxide‐ (H2O2‐) induced ROS production and apoptosis in vitro. Antioxidant activity and cytoprotective effects were further verified by alleviating APAP‐induced hepatotoxicity in mice. Western blot analysis revealed that FMF pretreatment significantly abrogated APAP‐mediated phosphorylation of MAPKs, activation of proapoptotic protein caspase‐3/9 and Bax, and restored expression of antiapoptotic protein Bcl2. APAP‐intoxicated mice pretreated with FMF showed increased nuclear accumulation of nuclear factor erythroid 2‐related factor (Nrf2) and elevated hepatic expression of its target genes, NAD(P)H:quinine oxidoreductase 1 (NQO1) and hemeoxygenase‐1(HO‐1). HPLC analysis revealed the four predominantly phenolic compounds present in FMF: narcissin, isorhamnetin‐3‐O‐β‐D‐glucoside, isovitexin, and vitexin. Consequently, these findings indicate that FMF possesses a hepatoprotective effect against APAP‐induced hepatotoxicity mainly through dual modification of ROS/MAPKs/apoptosis axis and Nrf2‐mediated antioxidant response, which may be attributed to the strong antioxidant activity of phenolic components.
Clinical Phenotype in a Toddler with a Novel Heterozygous Mutation of the Vitamin D Receptor
Authors: Brar Preneet Cheema , Dingle Elena , Pappas John , Raisingani Manish
Published: May 2017

We present the clinical phenotype of a toddler who presented with vitamin D-resistant rickets, with one of the highest initial levels of alkaline phosphatase and parathyroid hormone (PTH) levels reported in the literature. The toddler had novel compound heterozygous mutations in the ligand-binding site of the vitamin D receptor and had an excellent response to calcitriol (1,25(OH)2D).
Penetration Effect: Exotic Behavior of a Wave in Anisotropic Media
Authors: Vytovtov K. , Pischin O.
Published: May 2017

Plane harmonic wave propagation along an interface between vacuum and a semi-infinite uniaxial anisotropic medium is considered. It is shown that there is a bulk wave within an anisotropic medium in this case. It is also proved for the first time that a reflected wave must propagate perpendicularly to an interface. Moreover, a reflected wave is absent in the case of ordinary wave propagation.
Antiphospholipid Syndrome: Multiple Manifestations in a Single Patient—A High Suspicion Is Still Needed
Authors: Ibrahim Uroosa , Kedia Shiksha , Garcia Gwenalyn , Atallah Jean Paul
Published: May 2017

Antiphospholipid Syndrome (APS) is an autoimmune disorder with clinical and laboratory features of vascular thrombosis, pregnancy loss, and persistent antiphospholipid antibodies (aPLs). The pathophysiology is thought to involve the activation of endothelial cells, monocytes, platelets, and complement by aPLs. Disease can range from asymptomatic to rapidly fatal catastrophic APS. We present a case of a 34-year-old male referred for pancytopenia and splenomegaly. On examination, he had decreased sensation and 4/5 power in the left upper extremity. A lacy, purplish rash was noted on the trunk and upper extremity. MRI of brain showed acute/subacute lacunar infarctions. Laboratory studies revealed an elevated lactate dehydrogenase level, bilirubin and ferritin, decreased haptoglobin, and positive Coombs test. Antinuclear antibody test was negative and antiphospholipid antibody panel revealed positivity for anti-cardiolipin IgG and IgM, antiphosphatidylserine IgG, and anti-β2-glycoprotein IgG. The patient was diagnosed with primary APS. Pancytopenia is relatively rare in primary APS and is more often seen in secondary APS. Our patient demonstrated involvement of multiple organ systems as well as livedo reticularis and autoimmune-related findings such as Raynaud phenomenon and Coombs positive hemolytic anemia. We discuss the various clinical and laboratory findings in patients with APS that aid in diagnosis, as well as important management considerations.
Refractory Lactic Acidosis in Small Cell Carcinoma of the Lung
Authors: Oh Daniel J. , Dinerman Ellen , Matthews Andrew H. , Aron Abraham W. , Berg Katherine M.
Published: May 2017

Background. Elevated lactate levels in critically ill patients are most often thought to be indicative of relative tissue hypoxia or type A lactic acidosis. Shock, severe anemia, and thromboembolic events can all cause elevated lactate due to tissue hypoperfusion, as well as the mitochondrial dysfunction thought to occur in sepsis and other critically ill states. Malignancy can also lead to elevation in lactate, a phenomenon described as type B lactic acidosis, which is much less commonly encountered in the critically ill. Case Presentation. We present the case of a 73-year-old Caucasian woman with type 2 diabetes and hypertension who presented with abdominal pain, nausea, vomiting, nonbloody diarrhea, and weight loss over five weeks and was found to have unexplained refractory lactic acidosis despite fluids and antibiotics. She was later diagnosed with small cell carcinoma of the lung. Conclusions. In this case report, we describe a critically ill patient whose elevated lactate was incorrectly attributed to her acute illness, when in truth it was an indicator of an underlying, as yet undiagnosed, malignancy. We believe this case is instructive to the critical care clinician as a reminder of the importance of considering malignancy on the differential diagnosis of a patient presenting with elevated lactate out of proportion to their critical illness.
Effect of Biochar Application on Growth of Garden Pea (Pisum sativumL.) in Acidic Soils of Bule Woreda Gedeo Zone Southern Ethiopia
Authors: Berihun Tariku , Tolosa Shiferaw , Tadele Muluken , Kebede Firew
Published: May 2017

The aim of this experiment was to study the effect of types and rates of biochar on growth, yield, and yield component of garden pea at Bule wereda, Southern Ethiopia. The treatments consist of two types of biochar (corncobs andLantana camara) and four rates of biochar (0, 6, 12, and 18 t ha−1). The experiment was laid out as a randomized complete block design in a factorial arrangement with three replications. Soil samples were collected at a depth of 0–30 cm and germination parameter and phonology of garden pea were recorded. The result showed that soil bulk density, porosity, pH, and exchangeable acidity were significantly (P<0.001) affected by biochar application. The result also showed that maximum germination percentage of garden pea seeds (95.23%) was recorded at 18 t ha−1ofLantanabiochar. The shoot length was significantly (P<0.05) affected at 15 days and 30 days of biochar application. Moreover, fresh shoot weight and dry root biomass, number of seeds per pod, and grain yield of garden pea were significantly affected (P<0.05). Of the substrate and application rate applied,Lantana camara12 t ha−1andLantana camara18 t ha−1significantly increased yield of garden pea. Thus, further studies on effect of different biochars and their specific role are suggested to increase crop production.
IVIG Associated Aseptic Meningitis in a Renal Transplant Patient
Authors: Wanigasekera Tamara , Grainger Rachel J. , Sexton Donal J. , Magee Colm
Published: May 2017

The management of antibody-mediated rejection in renal transplant recipients involves plasmapheresis with IVIG. Aseptic meningitis is a rare adverse effect of IVIG therapy and is a diagnosis of exclusion. We report a case of a renal transplant patient who developed IVIG associated aseptic meningitis in the context of management of antibody-mediated rejection, four years after transplantation.
Comparing the Expression of Genes Related to Serotonin (5-HT) in C57BL/6J Mice and Humans Based on Data Available at the Allen Mouse Brain Atlas and Allen Human Brain Atlas
Authors: Acevedo-Triana C. A. , León L. A. , Cardenas F. P.
Published: May 2017

Brain atlases are tools based on comprehensive studies used to locate biological characteristics (structures, connections, proteins, and gene expression) in different regions of the brain. These atlases have been disseminated to the point where tools have been created to store, manage, and share the information they contain. This study used the data published by the Allen Mouse Brain Atlas (2004) for mice (C57BL/6J) and Allen Human Brain Atlas (2010) for humans (6 donors) to compare the expression of serotonin-related genes. Genes of interest were searched for manually in each case (in situ hybridization for mice and microarrays for humans), normalized expression data (z-scores) were extracted, and the results were graphed. Despite the differences in methodology, quantification, and subjects used in the process, a high degree of similarity was found between expression data. Here we compare expression in a way that allows the use of translational research methods to infer and validate knowledge. This type of study allows part of the relationship between structures and functions to be identified, by examining expression patterns and comparing levels of expression in different states, anatomical correlations, and phenotypes between different species. The study concludes by discussing the importance of knowing, managing, and disseminating comprehensive, open-access studies in neuroscience.
Evaluation of the Loading, Unloading, and Permanent Deformation of Newly Available Epoxy Resin Coated Ni-Ti Wires Using Self-Ligating Brackets
Authors: Garro-Piña Hazel , Jiménez-Cervantes María Cristina , Ondarza-Rovira Ricardo , Justus Roberto , García-López Salvador
Published: May 2017

Aim. The purpose of this study was to evaluate the load and unload deflection and permanent deformation of round 0.016′′ and rectangular 0.016′′×0.022′′ regular and coated Ni-Ti wires. Materials and Methods. Ni-Ti archwires produced by two manufacturers were evaluated. Both regular and coated round and rectangular Ni-Ti wire segments (n=15) from each group were submitted to a three-point bending test. Both types of wires were evaluated for permanent deformation at the end of a recovery cycle. Results. The coated round 0.016′′ Ni-Ti wires produced a significantly lower force in loading (p<0.01) and unloading (p<0.01) than regular wires of the same manufacturer and size. There was no significant difference in permanent deformation between coated and regular round Ni-Ti wires from the same company. For rectangular 0.016×0.022′′ Ni-Ti wires, there was a significant difference in the loading evaluation, but the unloading test presented no significant differences. The permanent deformation of the rectangular wires revealed no significant difference between them. Conclusion. The addition of an esthetic coating to these new Ni-Ti wires produced changes in their mechanical properties, manifested as a reduction in the applied force, which should be considered in clinical management.
Impact of B-Scan Averaging on Spectralis Optical Coherence Tomography Image Quality before and after Cataract Surgery
Authors: Podkowinski Dominika , Sharian Varnousfaderani Ehsan , Simader Christian , Bogunovic Hrvoje , Philip Ana-Maria , Gerendas Bianca S. , Schmidt-Erfurth Ursula , Waldstein Sebastian M.
Published: May 2017

Background and Objective. To determine optimal image averaging settings for Spectralis optical coherence tomography (OCT) in patients with and without cataract. Study Design/Material and Methods. In a prospective study, the eyes were imaged before and after cataract surgery using seven different image averaging settings. Image quality was quantitatively evaluated using signal-to-noise ratio, distinction between retinal layer image intensity distributions, and retinal layer segmentation performance. Measures were compared pre- and postoperatively across different degrees of averaging. Results. 13 eyes of 13 patients were included and 1092 layer boundaries analyzed. Preoperatively, increasing image averaging led to a logarithmic growth in all image quality measures up to 96 frames. Postoperatively, increasing averaging beyond 16 images resulted in a plateau without further benefits to image quality. Averaging 16 frames postoperatively provided comparable image quality to 96 frames preoperatively. Conclusion. In patients with clear media, averaging 16 images provided optimal signal quality. A further increase in averaging was only beneficial in the eyes with senile cataract. However, prolonged acquisition time and possible loss of details have to be taken into account.
A Universal High‐Performance Correlation Analysis Detection Model and Algorithm for Network Intrusion Detection System
Authors: Zhu Hongliang , Liu Wenhan , Sun Maohua , Xin Yang
Published: May 2017

In big data era, the single detection techniques have already not met the demand of complex network attacks and advanced persistent threats, but there is no uniform standard to make different correlation analysis detection be performed efficiently and accurately. In this paper, we put forward a universal correlation analysis detection model and algorithm by introducing state transition diagram. Based on analyzing and comparing the current correlation detection modes, we formalize the correlation patterns and propose a framework according to data packet timing and behavior qualities and then design a new universal algorithm to implement the method. Finally, experiment, which sets up a lightweight intrusion detection system using KDD1999 dataset, shows that the correlation detection model and algorithm can improve the performance and guarantee high detection rates.
NADPH Oxidases: Insights into Selected Functions and Mechanisms of Action in Cancer and Stem Cells
Authors: Skonieczna Magdalena , Hejmo Tomasz , Poterala-Hejmo Aleksandra , Cieslar-Pobuda Artur , Buldak Rafal J.
Published: May 2017

NADPH oxidases (NOX) are reactive oxygen species‐ (ROS‐) generating enzymes regulating numerous redox‐dependent signaling pathways. NOX are important regulators of cell differentiation, growth, and proliferation and of mechanisms, important for a wide range of processes from embryonic development, through tissue regeneration to the development and spread of cancer. In this review, we discuss the roles of NOX and NOX‐derived ROS in the functioning of stem cells and cancer stem cells and in selected aspects of cancer cell physiology. Understanding the functions and complex activities of NOX is important for the application of stem cells in tissue engineering, regenerative medicine, and development of new therapies toward invasive forms of cancers.
Chimeric PD-1:28 Receptor Upgrades Low-Avidity T cells and Restores Effector Function of Tumor-Infiltrating Lymphocytes for Adoptive Cell Therapy
Authors: Schlenker Ramona , Olguín-Contreras Luis Felipe , Leisegang Matthias , Schnappinger Julia , Disovic Anja , Rühland Svenja , Nelson Peter J. , Leonhardt Heinrich , Harz Hartmann , Wilde Susanne , Schendel Dolores J. , Uckert Wolfgang , Willimsky Gerald , Noessner Elfriede
Published: May 2017

Inherent intermediate- to low-affinity T-cell receptors (TCR) that develop during the natural course of immune responses may not allow sufficient activation for tumor elimination, making the majority of T cells suboptimal for adoptive T-cell therapy (ATT). TCR affinity enhancement has been implemented to provide stronger T-cell activity but carries the risk of creating undesired cross-reactivity leading to potential serious adverse effects in clinical application. We demonstrate here that engineering of low-avidity T cells recognizing a naturally processed and presented tumor-associated antigen with a chimeric PD-1:28 receptor increases effector function to levels seen with high-avidity T cells of identical specificity. Upgrading the function of low-avidity T cells without changing the TCR affinity will allow a large arsenal of low-avidity T cells previously thought to be therapeutically inefficient to be considered for ATT. PD-1:28 engineering reinstated Th1 function in tumor-infiltrating lymphocytes that had been functionally disabled in the human renal cell carcinoma environment without unleashing undesired Th2 cytokines or IL10. Involved mechanisms may be correlated to restoration of ERK and AKT signaling pathways. In mouse tumor models of ATT, PD-1:28 engineering enabled low-avidity T cells to proliferate stronger and prevented PD-L1 upregulation and Th2 polarization in the tumor milieu. Engineered T cells combined with checkpoint blockade secreted significantly more IFNγ compared with T cells without PD-1:28, suggesting a beneficial combination with checkpoint blockade therapy or other therapeutic strategies. Altogether, the supportive effects of PD-1:28 engineering on T-cell function make it an attractive tool for ATT. Cancer Res; 77(13); 3577–90. ©2017 AACR.
Detecting the Presence and Progression of Premalignant Lung Lesions via Airway Gene Expression
Authors: Beane Jennifer , Mazzilli Sarah A. , Tassinari Anna M. , Liu Gang , Zhang Xiaohui , Liu Hanqiao , Buncio Anne Dy , Dhillon Samjot S. , Platero Suso J. , Lenburg Marc E. , Reid Mary E. , Lam Stephen , Spira Avrum E.
Published: May 2017

Purpose: Lung cancer is the leading cause of cancer-related death in the United States. The molecular events preceding the onset of disease are poorly understood, and no effective tools exist to identify smokers with premalignant lesions (PMLs) that will progress to invasive cancer. Prior work identified molecular alterations in the smoke-exposed airway field of injury associated with lung cancer. Here, we focus on an earlier stage in the disease process leveraging the airway field of injury to study PMLs and its utility in lung cancer chemoprevention.

Experimental Design: Bronchial epithelial cells from normal appearing bronchial mucosa were profiled by mRNA-Seq from subjects with (n = 50) and without (n = 25) PMLs. Using surrogate variable and gene set enrichment analysis, we identified genes, pathways, and lung cancer–related gene sets differentially expressed between subjects with and without PMLs. A computational pipeline was developed to build and test a chemoprevention-relevant biomarker.

Results: We identified 280 genes in the airway field associated with the presence of PMLs. Among the upregulated genes, oxidative phosphorylation was strongly enriched, and IHC and bioenergetics studies confirmed pathway findings in PMLs. The relationship between PMLs and squamous cell carcinomas (SCC) was also confirmed using published lung cancer datasets. The biomarker performed well predicting the presence of PMLs (AUC = 0.92, n = 17), and changes in the biomarker score associated with progression/stability versus regression of PMLs (AUC = 0.75, n = 51).

Conclusions: Transcriptomic alterations in the airway field of smokers with PMLs reflect metabolic and early lung SCC alterations and may be leveraged to stratify smokers at high risk for PML progression and monitor outcome in chemoprevention trials. Clin Cancer Res; 23(17); 5091–100. ©2017 AACR.
miR-196b-5p Regulates Colorectal Cancer Cell Migration and Metastases through Interaction with HOXB7 and GALNT5
Authors: Stiegelbauer Verena , Vychytilova-Faltejskova Petra , Karbiener Michael , Pehserl Anna-Maria , Reicher Andreas , Resel Margit , Heitzer Ellen , Ivan Cristina , Bullock Marc , Ling Hui , Deutsch Alexander , Wulf-Goldenberg Annika , Adiprasito Jan Basri , Stoeger Herbert , Haybaeck Johannes , Svoboda Marek , Stotz Michael , Hoefler Gerald , Slaby Ondrej , Calin George Adrian , Gerger Armin , Pichler Martin
Published: May 2017

Purpose: miR-196b-5p has been previously implicated in malignant transformation; however, its role in colorectal cancer has not been fully explored. In this study, we examine the clinical and biological relevance of miR-196b-5p, and the molecular pathways regulated by miR-196b-5p in colorectal cancer.

Experimental Design: miR-196b-5p expression was quantitated by qRT-PCR in 2 independent cohorts composed of 292 patients with colorectal cancer in total, to explore its biomarker potential. Transient and stable gain- and loss-of-function experiments were conducted in a panel of colorectal cancer cell lines and mice, to evaluate the impact of miR-196b-5p on proliferation, chemosensitivity, migration/invasion, and metastases formation in vitro and in vivo. The molecular pathways influenced by miR-196b-5p were characterized using whole transcriptome profiling, in silico target prediction tools, luciferase interaction assays, and phenocopy/rescue gene knockdown experiments.

Results: Low miR-196b-5p expression was significantly associated with metastases and poor outcomes in 2 independent colorectal cancer patient cohorts (P < 0.05, log-rank test). miR-196b-5p inhibition led to significantly increased colorectal cancer cell migration/invasion and metastases formation in mice, whereas ectopic overexpression showed the opposite phenotype. Molecular profiling and target confirmation identified an interaction between miR-196b-5p and HOXB7 and GALNT5, which in turn regulated colorectal cancer cell migration.

Conclusions: The association of low levels of miR-196b-5p and poor prognosis in patients with colorectal cancer can be explained by its influence on cancer cell migration and metastases formation. miR-196b-5p has an impact on colorectal cancer progression pathways through direct interaction with genes involved in cancer cell migration. Clin Cancer Res; 23(17); 5255–66. ©2017 AACR.
Late-Onset Inflammatory Bowel Disease-Like Syndrome after Ipilimumab Therapy: A Case Report
Authors: Akel Reem , Anouti Bilal , Tfayli Arafat
Published: May 2017

Background: Antitumor immunotherapy has become a major player in cancer therapy. Ipilimumab is a humanized monoclonal antibody against the cytotoxic T lymphocyte-associated antigen 4 (CTLA-4), an important downregulator of T-cell activation. Ipilimumab has demonstrated tumor regression and improvement in overall survival in patients with metastatic melanoma. Unfortunately, immune activation induced by this drug has been associated with several immune-mediated adverse effects, namely diarrhea and colitis. Case Presentation: We report the case of a 71-year-old male patient diagnosed with BRAF wild-type metastatic melanoma treated with three cycles of ipilimumab, after which he developed grade 3 enteritis. The patient improved on treatment with steroids, and ipilimumab was permanently discontinued at this point. Three years later, the patient’s diarrhea returned and colonoscopy revealed active chronic colitis with ulceration resembling inflammatory bowel disease. He was started on Asacol (mesalamine). The patient did not report extraintestinal symptoms typically associated with inflammatory bowel disease, nor did he have a personal or family history of bowel disorders. Moreover, his presentation was not typical of inflammatory bowel disease in the elderly. Conclusion: Our findings suggest a link between ipilimumab-induced grade 3 enteritis and late-onset inflammatory bowel disease-like syndrome. To our knowledge, the case is the first in the literature to report late-onset inflammatory bowel disease-like syndrome years after discontinuation of ipilimumab treatment.