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https://www.readbyqxmd.com/read/28941377/guiding-principles-of-value-creation-through-collaborative-innovation-in-pharmaceutical-research
#1
Liang Schweizer, Jeff He
Open innovation has become the main trend in pharmaceutical research. Potential obstacles and pitfalls of collaborations often lead to missed opportunities and/or poorly executed partnerships. This paper aims to provide a framework that facilitates the execution of successful collaborations. We start by mapping out three checkpoints onto early-stage collaborative partnerships: inception, ignition and implementation. Different value types and value drivers are then laid out for each stage of the partnership...
September 20, 2017: Drug Discovery Today
https://www.readbyqxmd.com/read/28939533/comparative-mapping-of-on-targets-and-off-targets-for-the-discovery-of-anti-trypanosomatid-folate-pathway-inhibitors
#2
Joanna Panecka-Hofman, Ina Pöhner, Francesca Spyrakis, Talia Zeppelin, Flavio Di Pisa, Lucia Dello Iacono, Alessio Bonucci, Antonio Quotadamo, Alberto Venturelli, Stefano Mangani, Maria Paola Costi, Rebecca C Wade
BACKGROUND: Multi-target approaches are necessary to properly analyze or modify the function of a biochemical pathway or a protein family. An example of such a problem is the repurposing of the known human anti-cancer drugs, antifolates, as selective anti-parasitic agents. This requires considering a set of experimentally validated protein targets in the folate pathway of major pathogenic trypanosomatid parasites and humans: (i) the primary parasite on-targets: pteridine reductase 1 (PTR1) (absent in humans) and bifunctional dihydrofolate reductase-thymidylate synthase (DHFR-TS), (ii) the primary off-targets: human DHFR and TS, and (iii) the secondary on-target: human folate receptor β, a folate/antifolate transporter...
September 20, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28938621/effect-of-earlier-proteinuria-on-graft-functions-after-one-year-living-donor-renal-transplantation
#3
Zaiyou Dai, Luxi Ye, Dajin Chen, Xing Zhang, Meifang Wang, Rending Wang, Jianyong Wu, Jianghua Chen
BACKGROUND: Proteinuria is an indicator of subsequent renal function decline in most nephropathies and early proteinuria has been assumed to be a risk factor of poor kidney transplant outcomes. However, there is no information about the effect of earlier-proteinuria at the first week on short-term graft function after living donor renal transplantation. METHODS: Retrospective cohort study of 439 living donor kidney transplants to analyze the effect of early proteinuria at 7-day post-transplantation on short-term prognosis of living donor renal transplantation...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28938400/il-1%C3%AE-inhibits-connexin-43-and-disrupts-decidualization-of-human-endometrial-stromal-cells-through-erk1-2-and-p38-map-kinase
#4
Jie Yu, Sarah L Berga, Wei Zou, D Grace Yook, Joshua C Pan, Aurora Arroyo Andrade, Lijuan Zhao, Neil Sidell, Indrani C Bagchi, Milan K Bagchi, Robert N Taylor
Inflammation can interfere with endometrial receptivity. We examined how IL-1β affects expression of the uterine gap junction protein, Cx43, which is known to be critical for embryonic implantation. We used an in vitro model of human endometrial stromal cells (ESC), Western blotting and a combination of validated, selective kinase inhibitors to evaluate five canonical IL-1β signaling pathways. Cx43 and two other markers of ESC differentiation (prolactin and VEGF) were inhibited predominantly via IL-1β-activated ERK1/2 and p38 MAP kinase cascades...
September 11, 2017: Endocrinology
https://www.readbyqxmd.com/read/28938337/pulse-pressure-is-associated-with-plasma-amyloid-%C3%AE-transport-dysfunction
#5
Yu Jiang, Suhang Shang, Pei Li, Chen Chen, Liangjun Dang, Jin Wang, Kang Huo, Meiying Deng, Jingyi Wang, Qiumin Qu
OBJECTIVE: Increased pulse pressure (PP) has been implicated in the development and progression of Alzheimer's disease in middle-aged and elderly adults. Considering the close relationship between peripheral amyloid-β clearance and brain amyloid-β deposition, we investigated the potential association between PP and plasma amyloid-β transport function. METHODS: In this cross-sectional study, a total of 1118 participants underwent a health assessment and quantification of plasma amyloid-β and amyloid-β transporter expression...
September 21, 2017: Journal of Hypertension
https://www.readbyqxmd.com/read/28938276/anesthesia-with-dexmedetomidine-and-low-dose-isoflurane-increases-solute-transport-via-the-glymphatic-pathway-in-rat-brain-when-compared-with-high-dose-isoflurane
#6
Helene Benveniste, Hedok Lee, Fengfei Ding, Qian Sun, Ehab Al-Bizri, Rany Makaryus, Stephen Probst, Maiken Nedergaard, Elliot A Stein, Hanbing Lu
BACKGROUND: The glymphatic pathway transports cerebrospinal fluid through the brain, thereby facilitating waste removal. A unique aspect of this pathway is that its function depends on the state of consciousness of the brain and is associated with norepinephrine activity. A current view is that all anesthetics will increase glymphatic transport by inducing unconsciousness. This view implies that the effect of anesthetics on glymphatic transport should be independent of their mechanism of action, as long as they induce unconsciousness...
September 22, 2017: Anesthesiology
https://www.readbyqxmd.com/read/28938219/age-dependent-effects-of-acute-methylphenidate-on-amygdala-reactivity-in-stimulant-treatment-naive-patients-with-attention-deficit-hyperactivity-disorder
#7
Marco A Bottelier, Anouk Schrantee, Bart Ferguson, Hyke G H Tamminga, Cheima Bouziane, J J Sandra Kooij, Michiel B de Ruiter, Liesbeth Reneman
In the present study, we investigate whether methylphenidate (MPH) affects emotional processing and whether this effect is modulated by age. We measured amygdala reactivity with functional Magnetic Resonance Imaging (fMRI) during processing of angry and fearful facial expressions in male stimulant treatment-naive patients with ADHD (N = 35 boys; N = 46 men) and 23 healthy control subjects (N = 11 boys; N = 12 men). In ADHD patients, we also measured amygdala reactivity 90min after an acute oral challenge with MPH (0...
September 12, 2017: Psychiatry Research
https://www.readbyqxmd.com/read/28938075/the-human-plasma-proteome-draft-of-2017-building-on-the-human-plasma-peptideatlas-from-mass-spectrometry-and-complementary-assays
#8
Jochen M Schwenk, Gilbert S Omenn, Zhi Sun, David S Campbell, Mark S Baker, Christopher M Overall, Ruedi Aebersold, Robert L Moritz, Eric W Deutsch
Human blood plasma provides a highly accessible window to the proteome of any individual in health and disease. Since its inception in 2002, the Human Proteome Organization's Human Plasma Proteome Project (HPPP) has been promoting advances in the study and understanding of the full protein complement of human plasma and on determining the abundance and modifications of its components. In 2017, we review the history of the HPPP and the advances of human plasma proteomics in general, including several recent achievements...
September 22, 2017: Journal of Proteome Research
https://www.readbyqxmd.com/read/28938074/native-electron-capture-dissociation-maps-to-iron-binding-channels-in-horse-spleen-ferritin
#9
Owen S Skinner, Michael O McAnally, Richard P Van Duyne, George C Schatz, Kathrin Breuker, Philip D Compton, Neil L Kelleher
Native electron capture dissociation (NECD) is a process during which proteins undergo fragmentation similar to that from radical dissociation methods, but without the addition of exogenous electrons. However, after three initial reports of NECD from the cytochrome c dimer complex, no further evidence of the effect has been published. Here, we report NECD behavior from horse spleen ferritin, a ~490 kDa protein complex ~20-fold larger than the previously studied cytochrome c dimer. Application of front-end infrared excitation (FIRE) in conjunction with low- and high-m/z quadrupole isolation and collisionally activated dissociation (CAD) provides new insights into the NECD mechanism...
September 22, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/28938073/transfer-learning-from-markov-models-leads-to-efficient-sampling-of-related-systems
#10
Mohammad Muneeb Sultan, Vijay S Pande
We recently showed that the time-structure based independent component analysis method from Markov state model literature provided a set of variationally optimal slow collective variables for Metadynamics (tICA-Metadynamics). In this paper, we extend the methodology towards efficient sampling of related mutants by borrowing ideas from transfer learning methods in machine learning. Our method explicitly assumes that a similar set of slow modes and metastable states are found in both the wild type (base line) and its mutants...
September 22, 2017: Journal of Physical Chemistry. B
https://www.readbyqxmd.com/read/28938053/persistent-hotspots-of-lymphatic-filariasis-microfilaraemia-despite-14-years-of-mass-drug-administration-in-ghana
#11
Nana-Kwadwo Biritwum, Paul Yikpotey, Benjamin K Marfo, Samuel Odoom, Ernest O Mensah, Odame Asiedu, Bright Alomatu, Edward T Hervie, Abednego Yeboah, Serge Ade, Sven G Hinderaker, Anthony Reid, Kudakwashe C Takarinda, Benjamin Koudou, Joseph B Koroma
Background: Among the 216 districts in Ghana, 98 were declared endemic for lymphatic filariasis in 1999 after mapping. Pursuing the goal of elimination, WHO recommends annual treatment using mass drugs administration (MDA) for at least 5 years. MDA was started in the country in 2001 and reached national coverage in 2006. By 2014, 69 districts had 'stopped-MDA' (after passing the transmission assessment survey) while 29 others remained with persistent microfilaraemia (mf) prevalence (≥1%) despite more than 11 years of MDA and were classified as 'hotspots'...
December 1, 2016: Transactions of the Royal Society of Tropical Medicine and Hygiene
https://www.readbyqxmd.com/read/28938018/genome-wide-identification-of-bacterial-plant-colonization-genes
#12
Benjamin J Cole, Meghan E Feltcher, Robert J Waters, Kelly M Wetmore, Tatiana S Mucyn, Elizabeth M Ryan, Gaoyan Wang, Sabah Ul-Hasan, Meredith McDonald, Yasuo Yoshikuni, Rex R Malmstrom, Adam M Deutschbauer, Jeffery L Dangl, Axel Visel
Diverse soil-resident bacteria can contribute to plant growth and health, but the molecular mechanisms enabling them to effectively colonize their plant hosts remain poorly understood. We used randomly barcoded transposon mutagenesis sequencing (RB-TnSeq) in Pseudomonas simiae, a model root-colonizing bacterium, to establish a genome-wide map of bacterial genes required for colonization of the Arabidopsis thaliana root system. We identified 115 genes (2% of all P. simiae genes) with functions that are required for maximal competitive colonization of the root system...
September 22, 2017: PLoS Biology
https://www.readbyqxmd.com/read/28938013/spatial-distribution-of-cutaneous-leishmaniasis-in-the-state-of-paran%C3%A3-brazil
#13
Helen Aline Melo, Diogo Francisco Rossoni, Ueslei Teodoro
The geographic distribution of cutaneous leishmaniasis (CL) makes it a disease of major clinical importance in Brazil, where it is endemic in the state of Paraná. The objective of this study was to analyze the spatial distribution of CL in Paraná between 2001 and 2015, based on data from the Sistema de Informação de Agravos de Notificação (Information System for Notifiable Diseases) regarding autochthonous CL cases. Spatial autocorrelation was performed using Moran's Global Index and the Local Indicator of Spatial Association (LISA)...
2017: PloS One
https://www.readbyqxmd.com/read/28938012/f-map-a-bayesian-approach-to-infer-the-gene-regulatory-network-using-external-hints
#14
Maryam Shahdoust, Hamid Pezeshk, Hossein Mahjub, Mehdi Sadeghi
The Common topological features of related species gene regulatory networks suggest reconstruction of the network of one species by using the further information from gene expressions profile of related species. We present an algorithm to reconstruct the gene regulatory network named; F-MAP, which applies the knowledge about gene interactions from related species. Our algorithm sets a Bayesian framework to estimate the precision matrix of one species microarray gene expressions dataset to infer the Gaussian Graphical model of the network...
2017: PloS One
https://www.readbyqxmd.com/read/28937987/combination-of-minimum-enclosing-balls-classifier-with-svm-in-coal-rock-recognition
#15
QingJun Song, HaiYan Jiang, Qinghui Song, XieGuang Zhao, Xiaoxuan Wu
Top-coal caving technology is a productive and efficient method in modern mechanized coal mining, the study of coal-rock recognition is key to realizing automation in comprehensive mechanized coal mining. In this paper we propose a new discriminant analysis framework for coal-rock recognition. In the framework, a data acquisition model with vibration and acoustic signals is designed and the caving dataset with 10 feature variables and three classes is got. And the perfect combination of feature variables can be automatically decided by using the multi-class F-score (MF-Score) feature selection...
2017: PloS One
https://www.readbyqxmd.com/read/28937943/multiomics-analysis-of-tumor-microenvironment-reveals-gata2-and-mirna-124-3p-as-potential-novel-biomarkers-in-ovarian-cancer
#16
Esra Gov, Medi Kori, Kazim Yalcin Arga
Ovarian cancer is a common and, yet, one of the most deadly human cancers due to its insidious onset and the current lack of robust early diagnostic tests. Tumors are complex tissues comprised of not only malignant cells but also genetically stable stromal cells. Understanding the molecular mechanisms behind epithelial-stromal crosstalk in ovarian cancer is a great challenge in particular. In the present study, we performed comparative analyses of transcriptome data from laser microdissected epithelial, stromal, and ovarian tumor tissues, and identified common and tissue-specific reporter biomolecules-genes, receptors, membrane proteins, transcription factors (TFs), microRNAs (miRNAs), and metabolites-by integration of transcriptome data with genome-scale biomolecular networks...
September 22, 2017: Omics: a Journal of Integrative Biology
https://www.readbyqxmd.com/read/28937853/assessment-of-microvascular-invasion-of-hepatocellular-carcinoma-with-diffusion-kurtosis-imaging
#17
Wen-Tao Wang, Li Yang, Zhao-Xia Yang, Xin-Xing Hu, Ying Ding, Xu Yan, Cai-Xia Fu, Robert Grimm, Meng-Su Zeng, Sheng-Xiang Rao
Purpose To evaluate the potential role of diffusion kurtosis imaging and conventional magnetic resonance (MR) imaging findings including standard monoexponential model of diffusion-weighted imaging and morphologic features for preoperative prediction of microvascular invasion (MVI) of hepatocellular carcinoma (HCC). Materials and Methods Institutional review board approval and written informed consent were obtained. Between September 2015 and November 2016, 84 patients (median age, 54 years; range, 29-79 years) with 92 histopathologically confirmed HCCs (40 MVI-positive lesions and 52 MVI-negative lesions) were analyzed...
September 22, 2017: Radiology
https://www.readbyqxmd.com/read/28937670/feshbach-resonances-in-the-exit-channel-of-the-f%C3%A2-%C3%A2-ch3oh%C3%A2-%C3%A2-%C3%A2-hf%C3%A2-%C3%A2-ch3o-reaction-observed-using-transition-state-spectroscopy
#18
Marissa L Weichman, Jessalyn A DeVine, Mark C Babin, Jun Li, Lifen Guo, Jianyi Ma, Hua Guo, Daniel M Neumark
The transition state governs how chemical bonds form and cleave during a chemical reaction and its direct characterization is a long-standing challenge in physical chemistry. Transition state spectroscopy experiments based on negative-ion photodetachment provide a direct probe of the vibrational structure and metastable resonances that are characteristic of the reactive surface. Dynamical resonances are extremely sensitive to the topography of the reactive surface and provide an exceptional point of comparison with theory...
October 2017: Nature Chemistry
https://www.readbyqxmd.com/read/28937659/assessing-the-allocation-of-special-elderly-nursing-homes-in-tokyo-japan
#19
Ninglong You, Zhenjiang Shen, Tatsuya Nishino
Social welfare and public health departments require reliable assessments to enhance the rationality of phased construction of special elderly nursing homes (SENHs). This paper aims to assess the allocation of SENHs based on a beds-needed index for SENHs (BNIS). This may help departments determine the priority for approving locations of SENHs more accurately with a limited budget. Traditional assessments in Tokyo use the sphere of welfare, ward, and sphere of daily life as spatial units for estimating beds-to-elderly population ratios...
September 22, 2017: International Journal of Environmental Research and Public Health
https://www.readbyqxmd.com/read/28937588/robust-dehaze-algorithm-for-degraded-image-of-cmos-image-sensors
#20
Chen Qu, Du-Yan Bi, Ping Sui, Ai-Nong Chao, Yun-Fei Wang
The CMOS (Complementary Metal-Oxide-Semiconductor) is a new type of solid image sensor device widely used in object tracking, object recognition, intelligent navigation fields, and so on. However, images captured by outdoor CMOS sensor devices are usually affected by suspended atmospheric particles (such as haze), causing a reduction in image contrast, color distortion problems, and so on. In view of this, we propose a novel dehazing approach based on a local consistent Markov random field (MRF) framework. The neighboring clique in traditional MRF is extended to the non-neighboring clique, which is defined on local consistent blocks based on two clues, where both the atmospheric light and transmission map satisfy the character of local consistency...
September 22, 2017: Sensors
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