bluuebunny/crossref_metadata_2025_split huggingface dataset:
Highly Acidic C-Terminal Region of Cytomegalovirus pUL96 Determines Its Functions during Virus Maturation Independently of a Direct pp150 Interaction
Authors: Brechtel Teal M. , Mocarski Edward S. , Tandon Ritesh 
Published: February 2014

ABSTRACT

Tegument proteins pp150 and pUL96 function at a late step in cytomegalovirus (CMV) maturation. Here, we show that pp150 interacts directly with pUL96; however, the N-terminal region of pp150 and the C-terminal region of pUL96, which are critical for these proteins to function, are not required for this interaction. Moreover, the largely dispensable C-terminal region of pp150 is critical for pp150-pUL96 interaction. To further study the role of pUL96, several point and clustered mutations were engineered into the CMV Towne bacterial artificial chromosome (Towne-BAC) genome, replacing the conserved negatively charged C-terminal residues of pUL96. Although individual point mutations (E
122
A, D
124
A, and D
125
A) reduced virus growth slightly, the clustered mutations of
122
EVDDAV
127
significantly reduced virus growth, produced small syncytial plaque phenotypes, and impacted a late stage of virus maturation. When the UL96 C-terminal alanine conversion mutant (B6-BAC) virus was serially passaged in cell culture, it gained a plaque size comparable to that of Towne-BAC, displayed an altered restriction fragment length pattern, and replicated with increased growth kinetics. Whole-genome sequencing of this passaged virus (UL96P10) and the similarly passaged Towne-BAC virus revealed major differences only in the RNA4.9 and UL96 regions. When one of the mutations in the UL96 coding region was engineered into the B6-BAC virus, it significantly increased the plaque size and rescued the virus growth rate. Thus, accumulation of compensatory mutations only in UL96 in this revertant and the specific involvement of functionally dispensable regions of pp150 in the pUL96-pp150 interaction point toward a role for pUL96 in virus maturation that does not depend upon pp150.

IMPORTANCE
Human cytomegalovirus causes significant medical problems in newborns, as well as in people with low immunity. In this study, we investigated the functions of two essential virus proteins, pp150 and pUL96, and determined the impact of their mutual interaction on virus replication. These studies provide valuable information that is critical for the development of targeted antiviral therapies.
Effect of a 12-Month Exercise Intervention on Serum Biomarkers of Angiogenesis in Postmenopausal Women: A Randomized Controlled Trial
Authors: Duggan Catherine , Xiao Liren , Wang Ching-Yun , McTiernan Anne 
Published: February 2014

AbstractBackground: Increased physical activity is associated with decreased risk of several types of cancer, but underlying mechanisms are poorly understood. Angiogenesis, in which new blood vessels are formed, is common to adipose tissue formation/remodeling and tumor vascularization.Methods: We examined effects of a 12-month 45 minutes/day, 5 days/week moderate-intensity aerobic exercise intervention on four serum markers of angiogenesis in 173 sedentary, overweight, postmenopausal women, 50 to 75 years, randomized to intervention versus stretching control. Circulating levels of positive regulators of angiogenesis [VEGF, osteopontin (OPN), plasminogen activator inhibitor-1 (PAI-1)], and the negative regulator pigment epithelium-derived factor (PEDF), were measured by immunoassay at baseline and 12 months. Changes were compared using generalized estimating equations, adjusting for baseline levels of analytes and body mass index (BMI).Results: VEGF, OPN, or PAI-1 levels did not differ by intervention arm. Participants randomized to exercise significantly reduced PEDF (−3.7%) versus controls (+3.0%; P = 0.009). Reductions in fat mass were significantly associated with reductions in PAI-1 (Ptrend = 0.03; Ptrend = 0.02) and PEDF (Ptrend = 0.002; Ptrend = 0.01) compared with controls, or to those who gained any fat mass respectively. There was a significant association between decreases in VO2max, and increased reductions in PEDF (Ptrend = 0.03), compared with participants who increased their level of fitness.Conclusions: Fat loss reduces circulating PAI-1 and PEDF. Changes in VO2max are associated with alterations in PEDF, but these associations are complex.Impact: Unexpected reductions in PEDF with decreasing fat mass, and with decreasing VO2max, warrant further study, including examining the effects of different types and intensities of exercise; and role of dietary weight-loss with and without exercise. Cancer Epidemiol Biomarkers Prev; 23(4); 648–57. ©2014 AACR.
Temozolomide Does Not Impair Gene Therapy-Mediated Antitumor Immunity in Syngeneic Brain Tumor Models
Authors: Candolfi Marianela , Yagiz Kader , Wibowo Mia , Ahlzadeh Gabrielle E. , Puntel Mariana , Ghiasi Homayon , Kamran Neha , Paran Christopher , Lowenstein Pedro R. , Castro Maria G. 
Published: February 2014

Abstract
Purpose: Glioblastoma multiforme is the most common primary brain cancer in adults. Chemotherapy with temozolomide (TMZ) significantly prolongs the survival of patients with glioblastoma multiforme. However, the three-year survival is still approximately 5%. Herein, we combined intratumoral administration of an adenoviral vector expressing Flt3L (Ad-Flt3L) with systemic temozolomide to assess its impact on therapeutic efficacy.
Experimental Design: Wild-type or immunodeficient mice bearing intracranial glioblastoma multiforme or metastatic melanoma were treated with an intratumoral injection of Ad-Flt3L alone or in combination with the conditionally cytotoxic enzyme thymidine kinase (Ad-TK), followed by systemic administration of ganciclovir and temozolomide. We monitored survival and measured the tumor-infiltrating immune cells.
Results: Although treatment with temozolomide alone led to a small improvement in median survival, when used in combination with gene therapy-mediated immunotherapy, it significantly increased the survival of tumor-bearing mice. The antitumor effect was further enhanced by concomitant intratumoral administration of Ad-TK, leading to 50% to 70% long-term survival in all tumor models. Although temozolomide reduced the content of T cells in the tumor, this did not affect the therapeutic efficacy. The antitumor effect of Ad-Flt3L+Ad-TK+TMZ required an intact immune system because the treatment failed when administered to knock out mice that lacked lymphocytes or dendritic cells.
Conclusions: Our results challenge the notion that chemotherapy leads to a state of immune-suppression which impairs the ability of the immune system to mount an effective antitumor response. Our work indicates that temozolomide does not inhibit antitumor immunity and supports its clinical implementation in combination with immune-mediated therapies. Clin Cancer Res; 20(6); 1555–65. ©2014 AACR.
Distinct associations of complement C3a and its precursor C3 with atherosclerosis and cardiovascular disease
Authors: van Greevenbroek Marleen M. , Arts Ilja C. , van der Kallen Carla J. , Geijselaers Stefan L. , Feskens Edith J. , Jansen Eugene H. , Schalkwijk Casper G. , Stehouwer Coen D. , Hertle Elisabeth 
Published: February 2014

SummaryComplement C3 is a novel risk factor for cardiovascular disease (CVD), but the underlying mechanism is currently unknown. We determined the associations of the anaphylatoxin C3a, the activation product of C3, and of C3 itself with estimates of atherosclerosis and CVD. We studied associations of C3a and C3 with carotid intima-media thickness (cIMT), ankle-arm blood pressure index (AAIx) and CVD in cross-sectional analyses among 545 participants of the Cohort on Diabetes and Atherosclerosis Maastricht (CODAM) study (62% men, 59.4 ± 6.9 years) and examined effect modification by smoking. We conducted linear and logistic regression analyses with adjustments for age, sex, glucose metabolism status, lipids, adiposity, renal function, blood pressure, pack-years smoked, physical activity, use of medication and investigated mediation by inflammation. C3a was independently associated with cIMT (β=0.032 mm, [95% confidence interval: 0.004; 0.060]) and AAIx (β=−0.022, [−0.043; −0.001]), but C3 was not. Effect modification by smoking was only observed for CVD (Psmoking*C3a=0.008, Psmoking*C3=0.018), therefore these associations were stratified for smoking behaviour. Both C3a (odds ratio [OR] =2.96, [1.15; 7.62]) and C3 (OR =1.98, [1.21; 3.22]) were independently associated with CVD in heavy smokers. The association of C3 with CVD was independent of C3a. Low-grade inflammation did partially explain the association of C3a with AAIx, but not the other observed associations. This suggests that C3a and C3 have distinct roles in pathways leading to CVD. C3a may promote atherosclerosis and additionally advance CVD in heavy smokers. Conversely, C3 may be associated with CVD in heavy smokers via pathways other than atherosclerosis.
The Dispersion of Silver Iodide Particles from Ground-Based Generators over Complex Terrain. Part II: WRF Large-Eddy Simulations versus Observations
Authors: Xue Lulin , Chu Xia , Rasmussen Roy , Breed Daniel , Boe Bruce , Geerts Bart 
Published: February 2014

AbstractA numerical modeling study has been conducted to explore the ability of the Weather Research and Forecasting (WRF) model-based large-eddy simulation (LES) with 100-m grid spacing to reproduce silver iodide (AgI) particle dispersion by comparing the model results with measurements made on 16 February 2011 over the Medicine Bow Mountains in Wyoming. Xue et al.'s recently developed AgI cloud-seeding parameterization was applied in this study to simulate AgI release from ground-based generators. Qualitative and quantitative comparisons between the LES results and observed AgI concentrations were conducted. Analyses of turbulent kinetic energy (TKE) features within the planetary boundary layer (PBL) and comparisons between the 100-m LES and simulations with 500-m grid spacing were performed as well. The results showed the following: 1) Despite the moist bias close to the ground and above 4 km AGL, the LES with 100-m grid spacing captured the essential environmental conditions except for a slightly more stable PBL relative to the observed soundings. 2) Wind shear is the dominant TKE production mechanism in wintertime PBL over complex terrain and generates a PBL of about 1000-m depth. The terrain-induced turbulent eddies are primarily responsible for the vertical dispersion of AgI particles. 3) The LES-simulated AgI plumes were shallow and narrow, in agreement with observations. The LES overestimated AgI concentrations close to the ground, which is consistent with the higher static stability in the model than is observed. 4) Non-LES simulations using PBL schemes had difficulty in capturing the shear-dominant turbulent PBL structure over complex terrain in wintertime. Therefore, LES of wintertime orographic clouds with grid spacing close to 500 m or finer are recommended.
Aircraft Evaluation of Ground-Based Raman Lidar Water Vapor Turbulence Profiles in Convective Mixed Layers
Authors: Turner D. D. , Ferrare R. A. , Wulfmeyer V. , Scarino A. J. 
Published: February 2014

AbstractHigh temporal and vertical resolution water vapor measurements by Raman and differential absorption lidar systems have been used to characterize the turbulent fluctuations in the water vapor mixing ratio field in convective mixed layers. Since daytime Raman lidar measurements are inherently noisy (due to solar background and weak signal strengths), the analysis approach needs to quantify and remove the contribution of the instrument noise in order to derive the desired atmospheric water vapor mixing ratio variance and skewness profiles. This is done using the approach outlined by Lenschow et al.; however, an intercomparison with in situ observations was not performed.Water vapor measurements were made by a diode laser hygrometer flown on a Twin Otter aircraft during the Routine Atmospheric Radiation Measurement (ARM) Program Aerial Facility Clouds with Low Optical Water Depths Optical Radiative Observations (RACORO) field campaign over the ARM Southern Great Plains (SGP) site in 2009. Two days with Twin Otter flights were identified where the convective mixed layer was quasi stationary, and hence the 10-s, 75-m data from the SGP Raman lidar could be analyzed to provide profiles of water vapor mixing ratio variance and skewness. Airborne water vapor observations measured during level flight legs were compared to the Raman lidar data, demonstrating good agreement in both variance and skewness. The results also illustrate the challenges of comparing a point sensor making measurements over time to a moving platform making similar measurements horizontally.
An analysis of potential applications of wide-scale solar energy in Hong Kong
Authors: Li Danny HW , Chong Ben LP , Chan Wilco WH , Lam Joseph C 
Published: February 2014

Renewable energy plays a crucial role in replacing major part of fossil fuels to generate sustainable, inexhaustible, clean, and safe energy. In Hong Kong, solar energy has been identified suitable for wide-scale applications. Photovoltaic (PV) and solar water heating (SWH) facilities are the two promising solar-based conversion technologies. Electricity and hot water generations via solar energy means fossil fuel saved together with the likely pollutants and greenhouse gases reductions. However, there are a number of barriers including high initial cost and large installation space required. This paper studies the cost, energy, and environmental issues when PV and SWH systems are widely used in Hong Kong. The energy expenditures in the forms of electricity, gas, and hot water, and the global solar radiation in Hong Kong were analyzed. The total required land areas, the financial implications, and the environmental benefits for such solar energy applications were estimated and reported. Practical application: Solar energy plays an important role in replacing fossil fuels to generate electricity without emitting pollutants and requiring no fuel. This paper analyzes the energy, financial, and environmental aspects for solar thermal and solar electric installations. The findings in this study provide the information when active solar energy systems are widely applied in Hong Kong.
Classification tree analysis of the factors influencing injury-related disability caused by the Wenchuan earthquake
Authors: Liu Xiang , Liu Yuan-Yuan , Liu Si-Huan , Zhang Xiang-Rong , Du Lei , Huang Wen-Xia 
Published: February 2014

Objective To identify the factors that influenced the risk of injury-related disability caused by the Wenchuan earthquake. Methods A chi-squared automatic interaction detection (CHAID) classification tree analysis was used to retrospectively analyse clinical data from patients who underwent surgical treatment for earthquake-related injuries in the first 5 days after the earthquake. The CHAID classification tree explored the relationships between the development of disability and potential influencing factors including sex, age, time interval between injury and treatment, wound type, preoperative and postoperative haemoglobin levels, and operation time. Results A total of 334 patients underwent surgery; of these, 113 (33.8%) were discharged with varying degrees of permanent disability. The CHAID classification tree showed that children (≤17 years old), a long time interval between injury and treatment, an open wound and a low preoperative haemoglobin level were significant risk factors for disability. Conclusion The results of this study can help to stratify patients according to their medical needs and to help allocate the available resources efficiently to ensure the best outcomes for injured patients during future earthquakes.
The Prevalence of Rotator Cuff Tears
Authors: Liem Dennis , Buschmann Vera Elisa , Schmidt Carolin , Gosheger Georg , Vogler Tim , Schulte Tobias L. , Balke Maurice 
Published: February 2014

Background: Rotator cuff tears are a common cause of pain and disability of the shoulder. Information on the prevalence and identification of potential risk factors could help in early detection of rotator cuff tears and improve treatment outcome. Hypothesis: Patients treated for a symptomatic rotator cuff tear on one side have a higher prevalence of rotator cuff tears and decreased shoulder function on the contralateral side compared with an age- and sex-matched group of healthy individuals. Study Design: Case control study; Level of evidence, 3. Methods: One group consisted of 55 patients who had been arthroscopically treated on one shoulder for rotator cuff tear (tear group). In this group, the nonoperated contralateral shoulder was examined. For comparison, the matching shoulder in a control group consisting of 55 subjectively healthy individuals matched by age (±1 year) and sex to the tear group was included. Diagnosis of a rotator cuff tear was made by ultrasound. Outcomes were measured using the Constant score. Results: The prevalence of supraspinatus tears was significantly higher ( P < .0001) in the tear group (67.3%) compared with the control group (11.0%). The Constant score for the activities of daily living subscale, however, was significantly lower (18.4) in the tear group compared with the control group (19.9; P = .012). No other subcategory score nor the overall score showed a significant difference. There was a significantly higher tear prevalence in the tear group of patients aged between 50 and 59 years ( P < .001) and 60 and 69 years ( P = .004). No tear was diagnosed in the control group in individuals younger than 60 years. Conclusion: Patients treated for partial and full-thickness rotator cuff tears have a significantly higher risk of having a tear on the contralateral side and have noticeable deficits in their shoulder function regarding activities of daily living even if the tear is otherwise asymptomatic.
Focal Laser Photocoagulation and Photodynamic Therapy for Lupus Choroidopathy
Authors: Cho HY , Nasir HH , Sobrin L 
Published: February 2014

Purpose To describe the results of photodynamic therapy (PDT) and/or focal laser photocoagulation in the treatment of serous retinal detachments secondary to lupus choroidopathy. Methods The medical records of three patients with serous detachments secondary to lupus choroidopathy who were treated with PDT and/or focal laser photocoagulation were reviewed. Concomitant systemic medical therapy as well as visual acuity and optical coherence tomography (OCT) outcomes were recorded. Results All patients received systemic immunosuppressive therapy and had control of their extraocular manifestations prior to PDT and/or laser photocoagulation. One patient received only focal laser photocoagulation and had complete resolution of the subretinal fluid on OCT. The two other patients received a combination of PDT and focal laser treatment. One had improvement in vision and resolution of subretinal fluid on OCT. The second patient, who had longstanding lupus choroidopathy and associated subretinal fluid and macular edema, had only a significant decrease in fluid on OCT but no vision improvement. Conclusion In conjunction with control of systemic disease, PDT and/or focal laser photocoagulation can be successful in resolving subretinal fluid secondary to lupus choroidopathy.
Pancreatitis Quality of Life Instrument: Development of a new instrument
Authors: Wassef Wahid , Bova Carol , Barton Bruce , Hartigan Celia 
Published: February 2014

Objectives: The goal of this project was to develop the first disease-specific instrument for the evaluation of quality of life in chronic pancreatitis. Methods: Focus groups and interview sessions were conducted, with chronic pancreatitis patients, to identify items felt to impact quality of life which were subsequently formatted into a paper-and-pencil instrument. This instrument was used to conduct an online survey by an expert panel of pancreatologists to evaluate its content validity. Finally, the modified instrument was presented to patients during precognitive testing interviews to evaluate its clarity and appropriateness. Results: In total, 10 patients were enrolled in the focus groups and interview sessions where they identified 50 items. Once redundant items were removed, the 40 remaining items were made into a paper-and-pencil instrument referred to as the Pancreatitis Quality of Life Instrument. Through the processes of content validation and precognitive testing, the number of items in the instrument was reduced to 24. Conclusions: This marks the development of the first disease-specific instrument to evaluate quality of life in chronic pancreatitis. It includes unique features not found in generic instruments (economic factors, stigma, and spiritual factors). Although this marks a giant step forward, psychometric evaluation is still needed prior to its clinical use.
Outcomes of Total Knee Arthroplasty in Relation to Preoperative Patient-Reported and Radiographic Measures
Authors: Kahn Timothy L. , Soheili Aydin , Schwarzkopf Ran 
Published: February 2014

Introduction: Total knee arthroplasty (TKA) is the preferred surgical treatment for end-stage osteoarthritis. However, substantial numbers of patients still experience poor outcomes. Consequently, it is important to identify which patient characteristics are predictive of outcomes in order to guide clinical decisions. Our hypothesis is that preoperative patient-reported outcome measures and radiographic measures may help to predict TKA outcomes. Methods: Using cohort data from the Osteoarthritis Initiative, we studied 172 patients who underwent TKA. For each patient, we compiled pre- and postoperative Western Ontario and McMaster University Arthritis Index (WOMAC) scores. Radiographs were measured for knee joint angles, femorotibial angles, anatomical lateral distal femoral angles, and anatomical medial proximal tibial angles; Kellgren and Lawrence (KL) grades were assigned to each compartment of the knee. All studied measurements were compared to WOMAC outcomes. Results: Preoperative WOMAC disability, pain, and total scores were positively associated with postoperative WOMAC total scores ( P = .010, P = .010, and P = .009, respectively) and were associated with improvement in WOMAC total scores ( P < .001, P < .001, and P < .001, respectively). For radiographic measurements, preoperative joint angles were positively associated with improvements in postoperative WOMAC total scores ( P = .044). Combined KL grades (medial and lateral compartments) were negatively correlated with postoperative WOMAC disability and pain scores ( P = .045 and P = .044) and were positively correlated with improvements in WOMAC total scores ( P = .001). Conclusions: All preoperative WOMAC scores demonstrated positive associations with postoperative WOMAC scores, while among the preoperative radiographic measurements only combined KL grades and joint angles showed any correlation with postoperative WOMAC scores. Higher preoperative KL grades and joint angles were associated with better (lower) postoperative WOMAC scores, demonstrating an inverse correlation.
Crystal structure of histidine-rich glycoprotein N2 domain reveals redox activity at an interdomain disulfide bridge: implications for angiogenic regulation
Authors: Kassaar Omar , McMahon Stephen A. , Thompson Rory , Botting Catherine H. , Naismith James H. , Stewart Alan J. 
Published: February 2014

Key PointsThe x-ray crystal structure of the N2 domain from HRG at 1.93 Å resolution is presented. The structure reveals an S-glutathionyl adduct at Cys185, which has implications for angiogenic regulation.