bluuebunny/crossref_metadata_2025_split huggingface dataset:
Regulation of PCGEM1 by p54/nrb in prostate cancer
Authors: Ho Tsui-Ting , Huang Jianguo , Zhou Nanjiang , Zhang Ziqiang , Koirala Pratirodh , Zhou Xinchun , Wu Fangting , Ding Xianfeng , Mo Yin-Yuan 
Published: September 2016

AbstractPCGEM1 is a long non-coding RNA (lncRNA) that is often upregulated in prostate cancer. However, little is known how PCGEM1 is regulated. In the present study, we show transcriptional regulation of PCGEM1 in response to androgen deprivation by p54/nrb. While ectopic expression of p54/nrb increases, suppression of p54/nrb by RNAi or knockout (KO) reduces PCGEM1. Moreover, rescue experiments indicate that re-expression of p54/nrb in KO cells restores the ability to induce PCGEM1, leading to upregulation of the androgen receptor splice variant AR3 which has been shown to play a role in castration resistance. Finally, 3,3′-Diindolylmethane (DIM), a known chemoprevention agent, is capable of suppressing PCGEM1 expression by preventing the interaction of p54/nrb with the PCGEM1 promoter. In particular, DIM reduces tumor growth by suppression of PCGEM1 and promoting apoptosis in the castrated xenograft mouse model. Together, these results demonstrate a novel mechanism of p54/nrb-mediated expression of PCGEM1 and AR3, contributing to castration resistance in prostate cancer.
Structure-based discovery of two antiviral inhibitors targeting the NS3 helicase of Japanese encephalitis virus
Authors: Fang Jin’e , Li Huan , Kong Dexin , Cao Shengbo , Peng Guiqing , Zhou Rui , Chen Huanchun , Song Yunfeng 
Published: September 2016

AbstractJapanese encephalitis virus (JEV) is a flavivirus that threatens more than half of the world’s population. Vaccination can prevent the disease, but no specific antiviral drug is yet available for clinical therapy and the death rate caused by JEV can reach as high as 60%. The C-terminus of non-structural protein 3 (NS3) of flavivirus encodes helicase and has been identified as a potential drug target. In this study, high throughput molecular docking was employed to identify candidate JEV NS3 helicase inhibitors in a commercial library containing 250,000 compounds. Forty-one compounds were then tested for their ability to inhibit NS3 activity. Two compounds inhibited unwinding activity strongly but had no effect on the ATPase activity of the protein. Western blots, IFA and plaque reduction assays demonstrated that both compounds inhibited the virus in cell culture. The EC50s of the two compounds were 25.67 and 23.50 μM, respectively. Using simulated docking, the two compounds were shown to bind and block the NS3 RNA unwinding channel, consistent with the results of the enzyme inhibition tests. The atoms participating in intramolecular interaction were identified to facilitate future compound optimization.
A novel technique based on in vitro oocyte injection to improve CRISPR/Cas9 gene editing in zebrafish
Authors: Xie Shao-Lin , Bian Wan-Ping , Wang Chao , Junaid Muhammad , Zou Ji-Xing , Pei De-Sheng 
Published: September 2016

AbstractContemporary improvements in the type II clustered regularly interspaced short palindromic repeats/CRISPR-associated protein 9 (CRISPR/Cas9) system offer a convenient way for genome editing in zebrafish. However, the low efficiencies of genome editing and germline transmission require a time-intensive and laborious screening work. Here, we reported a method based on in vitro oocyte storage by injecting oocytes in advance and incubating them in oocyte storage medium to significantly improve the efficiencies of genome editing and germline transmission by in vitro fertilization (IVF) in zebrafish. Compared to conventional methods, the prior micro-injection of zebrafish oocytes improved the efficiency of genome editing, especially for the sgRNAs with low targeting efficiency. Due to high throughputs, simplicity and flexible design, this novel strategy will provide an efficient alternative to increase the speed of generating heritable mutants in zebrafish by using CRISPR/Cas9 system.
Predictive controller design for a high‐frequency injection sensorless synchronous reluctance drive system
Authors: Liu Tian‐Hua , Haslim Hade Saputra , Tseng Shao‐Kai 
Published: September 2016

This study proposes implementation of a predictive controller for a sensorless synchronous reluctance drive system. First, high‐frequency voltage is injected in the α‐axis. Then by measuring the α–β axis high‐frequency currents, the rotor position of the SynRM can be estimated. After that, a predictive speed controller is implemented to improve transient responses, load disturbance responses, and tracking responses. To demonstrate its viability, a proposed 560 W sensorless drive system is implemented by using a TMS‐320F‐28335 DSP made by Texas Instruments and some circuits. Experimental results clearly indicate that the proposed high‐frequency α‐axis voltage injection method with a predictive speed‐loop controller offers superior responses including faster transient responses, better load disturbance responses, and better tracking responses than a high‐frequency d–q axis voltage injection method with a PI speed‐loop controller.
Infrapatellar Fat Pad Excision during Total Knee Arthroplasty Did Not Alter the Patellar Tendon Length: A 5-Year Follow-Up Study
Authors: Dedeoğlu Süleyman , Çakar Murat , Çabuk Haluk , Bayraktar Tahsin , Gürbüz Hakan , İmren Yunus 
Published: September 2016

AbstractPartial or total resection of the infrapatellar fat pad (IPFP) helps surgeon improve access to lateral tibial plateau for better placement of the knee prosthesis. We aimed to investigate the effect of IPFP excision on clinical and radiologic outcomes including patellar tendon length (PTL), range of motion, and functional scores after total knee arthroplasty (TKA) at 5-year follow-up. We retrospectively evaluated postoperative first X-rays (day 0) and postoperative final 5-year control views of 228 knees in patients with primary osteoarthritis who underwent TKA between September 2006 and December 2009 in our hospital. Exclusion criteria were patients who had lateral release, patellar resurfacing, septic or aseptic loosening, fracture around the replaced knee, any other prior knee surgery, or any systemic inflammatory disease. IPFP was completely resected in all knees to enhance surgical exposure and patellar mobilization. Radiologic evaluation of PTL was performed in early postoperative and 5-year control X-rays comparatively. The mean early postoperative PTL was 47.4 ± 6 (range: 35–72), the mean final postoperative PTL was 47 ± 6.3 (range: 33–68) (p = 0.1). The average preoperative flexion was 115 ± 11 degrees, whereas it was 111 ± 4 degrees, postoperatively (p = 0.73). Both the clinical and functional outcome scores improved in all patients. IPFP excision during TKA did not alter PTL at 5-year follow-up. A focus on other surgical and/or host-related factors may help clarify contradictory patellar tendon shortening reported in the literature.
Relationship between Widening and Position of the Tunnels and Clinical Results of Anterior Cruciate Ligament Reconstruction to Knee Osteoarthritis: 30 Patients at a Minimum Follow-Up of 10 Years
Authors: Ayala-Mejias Juan , Garcia-Gonzalez Benjamin , Alcocer-Perez-España Luis , Berjano Pedro , Villafañe Jorge 
Published: September 2016

AbstractTo evaluate the relationship between tunnel position and widening and long-term clinical results in anterior cruciate ligament (ACL) reconstruction, a retrospective cohort of 30 patients undergoing ACL reconstruction with double semitendinous plus double gracilis (SAC technique) with longer than 10-year follow-up was selected. CT scans in the first 3 months and at final follow-up was evaluated. Position, angle, and widening of tunnels including Nebelung criteria were recorded in all CT scans. Physical, KT-1000, and clinical evaluation were performed at final follow-up. Outcomes and knee arthritis severity were evaluated at final follow-up. Mean follow-up was 11.2 ± 1.2. At final follow-up, 85 and 57% of tibial and femoral tunnels, respectively, developed some degree of enlargement. Frontal tibial angle (mean) was 72°, sagittal tibial angle 63°, frontal femoral angle 47°, sagittal femoral angle 20°, and tunnels divergence angle 36°. Preoperatively, KT-1000 30L and Lachman test scores were 5.52 and 5.79 respectively. In the last follow-up, 30L and manual Lachman test scores were 0.97 and 1.13, respectively (p < 0.001). In IKDC scale, pivot shift and Jerk tests showed 83 and 84% grade A results, respectively (p < 0.0001). In Fairbank scale, 23% worsened one grade and 27% worsened more than one grade (p < 0.005). Tibial tunnels widened more than femoral tunnels and further dilatation was found between intermediate and final follow-up. Higher incidence of tibial tunnel widening was observed in patients with tunnel verticalization. Tibial tunnel dilation was associated with long-term degenerative changes but not with final knee instability.
Witnessing entanglement without entanglement witness operators
Authors: Pezzè Luca , Li Yan , Li Weidong , Smerzi Augusto 
Published: September 2016

Significance
The experimental detection and theoretical characterization of entanglement in many-body systems is a mostly unsolved problem. Here we relate entanglement to the statistical speed measuring how quickly nearby states become distinguishable under the action of an arbitrary many-body Hamiltonian. The method is remarkably simple: We witness multipartite entanglement, just elaborating on published experimental data with ions and photons. The unveiled connection between the statistical speed and entanglement provides a unifying framework that can shed new light on quantum information science and quantum critical phenomena.
Tunable allosteric library of caspase-3 identifies coupling between conserved water molecules and conformational selection
Authors: Maciag Joseph J. , Mackenzie Sarah H. , Tucker Matthew B. , Schipper Joshua L. , Swartz Paul , Clark A. Clay 
Published: September 2016

Significance
The interconversion of states in the caspase-3 native ensemble is affected by binding of ligands that either stabilize or destabilize active-site loops. It is not clear how the ensemble is regulated in cells, aside from modulating levels of endogenous caspase inhibitors. We describe a library of caspase-3 variants with activities that vary by more than four orders of magnitude and show that removal of conserved water molecules may provide a strategy to design novel allosteric inhibitors that globally destabilize the active conformation within the ensemble. Our results suggest that posttranslational modifications fine-tune caspase activity by disrupting conserved water networks, and our database provides an approach to examine caspase signaling in cells by modifying caspase-3 activity while simultaneously maintaining endogenous enzyme levels.
Mutant PFN1 causes ALS phenotypes and progressive motor neuron degeneration in mice by a gain of toxicity
Authors: Yang Chunxing , Danielson Eric W. , Qiao Tao , Metterville Jake , Brown Robert H. , Landers John E. , Xu Zuoshang 
Published: September 2016

Significance
ALS is an incurable neurodegenerative disease caused by loss of motor neurons leading to paralysis and death. To understand the disease mechanism and develop therapeutics, mammalian models that phenocopy human disease are crucial. For more than two decades, transgenic animals expressing mutant copper zinc superoxide dismutase (SOD1) gene represented the only model that faithfully reproduced the human disease. Despite recent identification of new causal genes, construction of another mammalian model with progressive loss of motor neurons and concomitant clinical phenotypes has proven difficult. In this study, we have generated a transgenic mouse model by expressing mutant profilin 1. These mice replicate key features of human ALS and thus provide an in vivo system for study of disease mechanisms and development of therapeutics.
Suppression of NF-κB activity via nanoparticle-based siRNA delivery alters early cartilage responses to injury
Authors: Yan Huimin , Duan Xin , Pan Hua , Holguin Nilsson , Rai Muhammad Farooq , Akk Antonina , Springer Luke E. , Wickline Samuel A. , Sandell Linda J. , Pham Christine T. N. 
Published: September 2016

Significance
Osteoarthritis is a common debilitating joint disease that affects millions in the United States and for which there are few therapeutic options. Critical barriers to the successful development of osteoarthritis treatment include limited understanding of the pathways governing early cartilage degradation and ineffective delivery of therapeutic agents to the resident chondrocytes in the avascular cartilage. Using a peptidic nanoparticle carrying siRNA that specifically suppresses NF-κB, we show that early antiinflammatory intervention reduces chondrocyte death caused by joint injury, a known predisposing factor for osteoarthritis. The peptidic nanoparticle deeply penetrates human cartilage to deliver its therapeutic cargo to the chondrocytes, demonstrating its ability to permeate the dense cartilage matrix. This approach promises to overcome the barriers to effectively treat osteoarthritis.
Repression of p63 and induction of EMT by mutant Ras in mammary epithelial cells
Authors: Yoh Kathryn E. , Regunath Kausik , Guzman Asja , Lee Seung-Min , Pfister Neil T. , Akanni Olutosin , Kaufman Laura J. , Prives Carol , Prywes Ron 
Published: September 2016

SignificanceThe oncogenes Harvey Rat Sarcoma Virus GTPase (H-RAS) and phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) are well known for altering cell growth and morphology. We show here that they are also able to modify the differentiation state of mammary epithelial cells by inducing an epithelial-to-mesenchymal transition (EMT). This transition leads to greater invasiveness, a hallmark of the progression of tumors toward metastasis. Expression of p63, a protein required for the development of mammary epithelial cells, is strongly repressed by these oncogenes. In turn, loss of p63, which occurs at the transcriptional level, causes a shift in microRNAs and transcription factors that control EMT. Targeting specific genes within this Ras-to-EMT axis may be useful as a therapy to block breast cancer progression.
Innovation network
Authors: Acemoglu Daron , Akcigit Ufuk , Kerr William R. 
Published: September 2016

Significance
We describe the strength and importance of the innovation network that links patenting technology fields together. We quantify that technological advances spill out of individual fields and enrich the work of neighboring technologies, but these spillovers are also localized and not universal. Thus, innovation advances in one part of the network can significantly impact nearby disciplines but rarely those very far away. We verify the strength and stable importance of the innovation network by showing how past innovations can predict future innovations in other fields over 10-y horizons. This better understanding of how scientific progress occurs and how inventions build upon themselves is an important input to our depictions of the cumulative process of innovation and its economic growth consequences.
State aggregation for fast likelihood computations in molecular evolution
Authors: Davydov Iakov I , Robinson-Rechavi Marc , Salamin Nicolas 
Published: September 2016

Abstract

Motivation
Codon models are widely used to identify the signature of selection at the molecular level and to test for changes in selective pressure during the evolution of genes encoding proteins. The large size of the state space of the Markov processes used to model codon evolution makes it difficult to use these models with large biological datasets. We propose here to use state aggregation to reduce the state space of codon models and, thus, improve the computational performance of likelihood estimation on these models.

Results
We show that this heuristic speeds up the computations of the M0 and branch-site models up to 6.8 times. We also show through simulations that state aggregation does not introduce a detectable bias. We analyzed a real dataset and show that aggregation provides highly correlated predictions compared to the full likelihood computations. Finally, state aggregation is a very general approach and can be applied to any continuous-time Markov process-based model with large state space, such as amino acid and coevolution models. We therefore discuss different ways to apply state aggregation to Markov models used in phylogenetics.

Availability and Implementation
The heuristic is implemented in the godon package (https://bitbucket.org/Davydov/godon) and in a version of FastCodeML (https://gitlab.isb-sib.ch/phylo/fastcodeml).

Supplementary information
Supplementary data are available at Bioinformatics online.
Measuring Appropriate Antimicrobial Use: Attempts at Opening the Black Box
Authors: Spivak Emily S. , Cosgrove Sara E. , Srinivasan Arjun 
Published: September 2016

AbstractIndiscriminate antimicrobial use has plagued medicine since antibiotics were first introduced into clinical practice &gt;70 years ago. Infectious diseases physicians and public health officials have advocated for preservation of these life-saving drugs for many years. With rising burden of antimicrobial-resistant organisms and Clostridium difficile infections, halting unnecessary antimicrobial use has become one of the largest public health concerns of our time. Inappropriate antimicrobial use has been quantified in various settings using numerous definitions; however, no established reference standard exists. With mounting national efforts to improve antimicrobial use, a consensus definition and standard method of measuring appropriate antimicrobial use is imperative. We review existing literature on systematic approaches to define and measure appropriate antimicrobial use, and describe a collaborative effort at developing standardized audit tools for assessing the quality of antimicrobial prescribing.
Evaluating total uncertainty for biomass- and abundance-at-age estimates from eastern Bering Sea walleye pollock acoustic-trawl surveys
Authors: Woillez Mathieu , Walline Paul D. , Ianelli James N. , Dorn Martin W. , Wilson Christopher D. , Punt Andre E. 
Published: September 2016

Abstract
A comprehensive evaluation of the uncertainty of acoustic-trawl survey estimates is needed to appropriately include them in stock assessments. However, this evaluation is not straightforward because various data types (acoustic backscatter, length, weight, and age composition) are combined to produce estimates of abundance- and biomass-at-age. Uncertainties associated with each data type and those from functional relationships among variables need to be evaluated and combined. Uncertainty due to spatial sampling is evaluated using geostatistical conditional (co-) simulations. Multiple realizations of acoustic backscatter were produced using transformed Gaussian simulations with a Gibbs sampler to handle zeros. Multiple realizations of length frequency distributions were produced using transformed multivariate Gaussian co-simulations derived from quantiles of the empirical length distributions. Uncertainty due to errors in functional relationships was evaluated using bootstrap for the target strength-at-length and the weight-at-length relationships and for age–length keys. The contribution of each of these major sources of uncertainty was assessed for acoustic-trawl surveys of walleye pollock in the eastern Bering Sea in 2006–2010. This simulation framework allows a general computation for estimating abundance- and biomass-at-age variance–covariance matrices. Such estimates suggest that the covariance structure assumed in fitting stock assessment models differs substantially from what careful analysis of survey data actually indicate.
A retrospective comparison of outcome and toxicity of preoperative image-guided intensity-modulated radiotherapy versus conventional pelvic radiotherapy for locally advanced rectal carcinoma
Authors: Huang Chun-Ming , Huang Ming-Yii , Tsai Hsiang-Lin , Huang Ching-Wen , Ma Cheng-Jen , Lin Chih-Hung , Huang Chih-Jen , Wang Jaw-Yuan 
Published: September 2016

Abstract
The aim of the study was to compare clinical outcomes and toxicity between 3D conformal radiotherapy (3DCRT) and image-guided intensity-modulated radiotherapy (IG-IMRT) administered through helical tomotherapy in locally advanced rectal cancer (LARC) patients receiving preoperative chemoradiotherapy. We reviewed 144 patients with Stage II–III rectal cancer receiving preoperative fluoropyrimidine-based chemoradiotherapy followed by radical resection. Tumor responses following chemoradiotherapy were evaluated using the Dworak tumor regression grade (TRG). Of the 144 patients, 45 received IG-IMRT and 99 received 3DCRT. A significant reduction in Grade 3 or 4 acute gastrointestinal toxicity (IG-IMRT, 6.7%; 3DCRT, 15.1%; P = 0.039) was observed by IG-IMRT. The pathologic complete response (pCR) rate did not differ between the IG-IMRT and the 3DCRT group (17.8% vs 15.1%, P = 0.52). Patients in the IG-IMRT group had the trend of favorable tumor regressions (TRG 3 or 4) compared with those in the 3DCRT group (66.7% vs 43.5%, P = 0.071). The median follow-up was 53 months (range, 18–95 months) in the 3DCRT group and 43 months (range, 17–69 months) in the IG-IMRT group. Four-year overall, disease-free, and local failure–free survival rates of the IG-IMRT and 3DCRT groups were 81.6% and 67.9% (P = 0.12), 53.8% and 51.8% (P = 0.51), and 88% and 75.1% (P = 0.031), respectively. LARC patients treated with preoperative IG-IMRT achieved lower acute gastrointestinal adverse effects and a higher local control rate than those treated with 3DCRT, but there was no prominent difference in distant metastasis rate and overall survival between two treatment modalities.
Gram-Positive Diplococci in a Cerebrospinal Fluid Gram Stain
Authors: Collins Jennifer P. , Westblade Lars F. , Anderson Evan J. 
Published: September 2016

Abstract
A 5-month-old girl presented with meningitis after receiving amoxicillin for bilateral otitis media. The cerebrospinal fluid (CSF) Gram stain suggested Streptococcus pneumoniae: Gram-positive diplococci with a surrounding clear area indicative of a bacterial capsule. Her CSF and blood cultures grew penicillin-resistant S pneumoniae serotype 35B. This serotype is not included in the 13-valent pneumococcal conjugate vaccine (PCV-13) and has been identified as a cause of invasive pneumococcal disease in the post-PCV-13 era.
Gravitational waves from an SMBH binary in M 87
Authors: Yonemaru Naoyuki , Kumamoto Hiroki , Kuroyanagi Sachiko , Takahashi Keitaro , Silk Joseph 
Published: September 2016

Abstract
We study gravitational-wave (GW) emission from a hypothetical supermassive black-hole (SMBH) binary at the center of M 87. The existence of an SMBH other than that usually identified with the central active galactic nucleus (AGN) is a possible explanation for the observed displacement [∼O(1) pc] between the AGN and the galactic centroid, and it is reasonable to assume considering the evolution of SMBHs through galaxy mergers. Because the period of the binary and the resulting GWs is much longer than the observational time-span, we calculate the variation of the GW amplitude, rather than the amplitude itself. We investigate its dependence on the orbital elements and the second BH mass, taking the observational constraints into account. The frequency of the GWs is too low to be detected with the conventional pulsar timing array and we propose a new method for detecting such low-frequency GWs with the distribution function of pulsar spin-down rates. Although the GWs from an SMBH binary that explains the observed displacement are extremely hard to detect even by the new method, GWs are still useful for probing the M 87 center.