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https://www.readbyqxmd.com/read/28230005/current-mechanism-of-acquired-resistance-to-epidermal-growth-factor-receptor-tyrosine-kinase-inhibitors-and-updated-therapy-strategies-in-human-nonsmall-cell-lung-cancer
#1
REVIEW
Kaixian Zhang, Qianqian Yuan
Lung cancer continues to be a major health problem and the most common cancer-related mortality worldwide with about 80%-85% patients suffering from nonsmall cell lung cancer (NSCLC). More than 80% of NSCLC cases are often diagnosed as advanced stage and harbor epidermal growth factor receptor (EGFR) activating mutation. Although great success in initial response to EGFR-tyrosine kinase inhibitors (EGFR-TKIs) are found in EGFR-mutant NSCLC patients, acquired resistance usually occurs on the continuous treatment...
December 2016: Journal of Cancer Research and Therapeutics
https://www.readbyqxmd.com/read/28229535/enrichment-and-viability-inhibition-of-circulating-tumor-cells-on-a-dual-acid-responsive-composite-nanofiber-film
#2
Wenqian Wang, Yaya Cheng, Yansheng Li, Hao Zhou, Li-Ping Xu, Yongqiang Wen, Liang Zhao, Xueji Zhang
The formation and metastatic colonization of circulating tumor cells (CTCs) are responsible for the vast majority of cancer-related deaths. Over the last decade, drug delivery system (DDS) has been rapidly developed with nanotechnology arising, however, most of the reported tumor-targeting DDSs were just able to deliver drugs to the solid tumor cells but not CTCs. In here, a novel drug delivery system was constructed with composite nanofiber film to inhibit the viability of circulating tumor cells (CTCs). In this system, gold nanoparticles (Au NPs) were functionalized with doxorubicin (DOX) through an acid-responsive cleavable linker to get the Au-DOX NPs...
February 23, 2017: ChemMedChem
https://www.readbyqxmd.com/read/28228527/activation-mechanism-of-the-g-protein-coupled-sweet-receptor-heterodimer-with-sweeteners-and-allosteric-agonists
#3
Soo-Kyung Kim, Yalu Chen, Ravinder Abrol, William A Goddard, Brian Guthrie
The sweet taste in humans is mediated by the TAS1R2/TAS1R3 G protein-coupled receptor (GPCR), which belongs to the class C family that also includes the metabotropic glutamate and γ-aminobutyric acid receptors. We report here the predicted 3D structure of the full-length TAS1R2/TAS1R3 heterodimer, including the Venus Flytrap Domains (VFDs) [in the closed-open (co) active conformation], the cysteine-rich domains (CRDs), and the transmembrane domains (TMDs) at the TM56/TM56 interface. We observe that binding of agonists to VFD2 of TAS1R2 leads to major conformational changes to form a TM6/TM6 interface between TMDs of TAS1R2 and TAS1R3, which is consistent with the activation process observed biophysically on the metabotropic glutamate receptor 2 homodimer...
February 22, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28224003/darwinism-for-the-genomic-age-connecting-mutation-to-diversification
#4
Xia Hua, Lindell Bromham
A growing body of evidence suggests that rates of diversification of biological lineages are correlated with differences in genome-wide mutation rate. Given that most research into differential patterns of diversification rate have focused on species traits or ecological parameters, a connection to the biochemical processes of genome change is an unexpected observation. While the empirical evidence for a significant association between mutation rate and diversification rate is mounting, there has been less effort in explaining the factors that mediate this connection between genetic change and species richness...
2017: Frontiers in Genetics
https://www.readbyqxmd.com/read/28221803/effects-of-thickness-on-the-metal-insulator-transition-in-free-standing-vanadium-dioxide-nanocrystals
#5
Mustafa M Fadlelmula, Engin C Sürmeli, Mehdi Ramezani, T Serkan Kasırga
Controlling solid state phase transitions via external stimuli offers rich physics along with possibilities of unparalleled applications in electronics and optics. The well-known metal-insulator transition (MIT) in vanadium dioxide (VO2) is one instance of such phase transitions emerging from strong electronic correlations. Inducing the MIT using electric field has been investigated extensively for the applications in electrical and ultrafast optical switching. However, as the Thomas-Fermi screening length is very short, for considerable alteration in the material's properties with electric field induced MIT, crystals below 10 nm are needed...
February 23, 2017: Nano Letters
https://www.readbyqxmd.com/read/28218747/mhc-i-peptides-get-out-of-the-groove-and-enable-a-novel-mechanism-of-hiv-1-escape
#6
Phillip Pymm, Patricia T Illing, Sri H Ramarathinam, Geraldine M O'Connor, Victoria A Hughes, Corinne Hitchen, David A Price, Bosco K Ho, Daniel W McVicar, Andrew G Brooks, Anthony W Purcell, Jamie Rossjohn, Julian P Vivian
Major histocompatibility complex class I (MHC-I) molecules play a crucial role in immunity by capturing peptides for presentation to T cells and natural killer (NK) cells. The peptide termini are tethered within the MHC-I antigen-binding groove, but it is unknown whether other presentation modes occur. Here we show that 20% of the HLA-B*57:01 peptide repertoire comprises N-terminally extended sets characterized by a common motif at position 1 (P1) to P2. Structures of HLA-B*57:01 presenting N-terminally extended peptides, including the immunodominant HIV-1 Gag epitope TW10 (TSTLQEQIGW), showed that the N terminus protrudes from the peptide-binding groove...
February 20, 2017: Nature Structural & Molecular Biology
https://www.readbyqxmd.com/read/28211814/are-major-dementias-triggered-by-poor-blood-flow-to-the-brain-theoretical-considerations
#7
Jack C de la Torre
There is growing evidence that chronic brain hypoperfusion plays a central role in the development of Alzheimer's disease (AD) long before dyscognitive symptoms or amyloid-β accumulation in the brain appear. This commentary proposes that dementia with Lewy bodies (DLB), frontotemporal dementia (FTD), and Creutzfeldt-Jakob disease (CJD) may also develop from chronic brain hypoperfusion following a similar but not identical neurometabolic breakdown as AD. The argument to support this conclusion is that chronic brain hypoperfusion, which is found at the early stages of the three dementias reviewed here, will reduce oxygen delivery and lower oxidative phosphorylation promoting a steady decline in the synthesis of the cell energy fuel adenosine triphosphate (ATP)...
February 15, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28193177/anopheline-salivary-protein-genes-and-gene-families-an-evolutionary-overview-after-the-whole-genome-sequence-of-sixteen-anopheles-species
#8
Bruno Arcà, Fabrizio Lombardo, Claudio J Struchiner, José M C Ribeiro
BACKGROUND: Mosquito saliva is a complex cocktail whose pharmacological properties play an essential role in blood feeding by counteracting host physiological response to tissue injury. Moreover, vector borne pathogens are transmitted to vertebrates and exposed to their immune system in the context of mosquito saliva which, in virtue of its immunomodulatory properties, can modify the local environment at the feeding site and eventually affect pathogen transmission. In addition, the host antibody response to salivary proteins may be used to assess human exposure to mosquito vectors...
February 13, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28192287/improved-image-quality-using-monolithic-scintillator-detectors-with-dual-sided-readout-in-a-whole-body-tof-pet-ring-a-simulation-study
#9
Valerio Tabacchini, Suleman Surti, Giacomo Borghi, Joel S Karp, Dennis R Schaart
We have recently built and characterized the performance of a monolithic scintillator detector based on a 32 mm  ×  32 mm  ×  22 mm LYSO:Ce crystal read out by digital silicon photomultiplier (dSiPM) arrays coupled to the crystal front and back surfaces in a dual-sided readout (DSR) configuration. The detector spatial resolution appeared to be markedly better than that of a detector consisting of the same crystal with conventional back-sided readout (BSR). Here, we aim to evaluate the influence of this difference in the detector spatial response on the quality of reconstructed images, so as to quantify the potential benefit of the DSR approach for high-resolution, whole-body time-of-flight (TOF) positron emission tomography (PET) applications...
February 13, 2017: Physics in Medicine and Biology
https://www.readbyqxmd.com/read/28190683/there-and-back-again-two-views-on-the-protein-folding-puzzle
#10
REVIEW
Alexei V Finkelstein, Azat J Badretdin, Oxana V Galzitskaya, Dmitry N Ivankov, Natalya S Bogatyreva, Sergiy O Garbuzynskiy
The ability of protein chains to spontaneously form their spatial structures is a long-standing puzzle in molecular biology. Experimentally measured folding times of single-domain globular proteins range from microseconds to hours: the difference (10-11 orders of magnitude) is the same as that between the life span of a mosquito and the age of the universe. This review describes physical theories of rates of overcoming the free-energy barrier separating the natively folded (N) and unfolded (U) states of protein chains in both directions: "U-to-N" and "N-to-U"...
January 27, 2017: Physics of Life Reviews
https://www.readbyqxmd.com/read/28182804/medical-and-economic-burden-of-heparin-induced-thrombocytopenia-a-retrospective-nationwide-inpatient-sample-nis-study
#11
Ranjan Pathak, Vijaya Raj Bhatt, Paras Karmacharya, Madan Raj Aryal, Anthony A Donato
In recent years, US hospitals have switched from use of unfractionated heparin to use of low-molecular-weight heparin, which is associated with lower risk of heparin-induced thrombocytopenia (HIT). In the study reported here, we retrospectively searched the Nationwide Inpatient Sample (NIS) for patients who were at least 18 years old and received a diagnosis of HIT between 2009 and 2011. Our goal was to get an updated perspective on the incidence and economic impact of HIT. We calculated the incidence of HIT overall and in subgroups of patients who underwent cardiac, vascular, or orthopedic surgery...
February 2017: Journal of Hospital Medicine: An Official Publication of the Society of Hospital Medicine
https://www.readbyqxmd.com/read/28177297/enhanced-performance-of-zno-microballoon-arrays-for-triboelectric-nanogenerator
#12
Weili Deng, Binbin Zhang, Long Jin, Yueqi Chen, Wenjun Chu, Haitao Zhang, Minhao Zhu, Weiqing Yang
In recent years, triboelectric nanogenerator (TENG), harvesting energy from the environment as sustainable power source as a kind of new technology, has attracted great attention. Presently, many reports focused on the effect of the surface modification on the performance of electrical output of TENG. In this work, we have fabricated a vertically-grown ZnO microballoon (ZnOMB) arrays on top of pyramid-featured PDMS patterned film, contacted with the PTFE film to construct TENG. The electrical output performances of the designed TENG were presented under the external forces with different frequencies...
February 8, 2017: Nanotechnology
https://www.readbyqxmd.com/read/28169336/on-our-rapidly-shrinking-capacity-to-comply-with-the-planetary-boundaries-on-climate-change
#13
Jean-Denis Mathias, John M Anderies, Marco A Janssen
The planetary boundary framework constitutes an opportunity for decision makers to define climate policy through the lens of adaptive governance. Here, we use the DICE model to analyze the set of adaptive climate policies that comply with the two planetary boundaries related to climate change: (1) staying below a CO2 concentration of 550 ppm until 2100 and (2) returning to 350 ppm in 2100. Our results enable decision makers to assess the following milestones: (1) a minimum of 33% reduction of CO2 emissions by 2055 in order to stay below 550 ppm by 2100 (this milestone goes up to 46% in the case of delayed policies); and (2) carbon neutrality and the effective implementation of innovative geoengineering technologies (10% negative emissions) before 2060 in order to return to 350 ppm in 2100, under the assumption of getting out of the baseline scenario without delay...
February 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28157556/self-taught-convolutional-neural-networks-for-short-text-clustering
#14
Jiaming Xu, Bo Xu, Peng Wang, Suncong Zheng, Guanhua Tian, Jun Zhao, Bo Xu
Short text clustering is a challenging problem due to its sparseness of text representation. Here we propose a flexible Self-Taught Convolutional neural network framework for Short Text Clustering (dubbed STC(2)), which can flexibly and successfully incorporate more useful semantic features and learn non-biased deep text representation in an unsupervised manner. In our framework, the original raw text features are firstly embedded into compact binary codes by using one existing unsupervised dimensionality reduction method...
January 12, 2017: Neural Networks: the Official Journal of the International Neural Network Society
https://www.readbyqxmd.com/read/28155723/locexpress-a-web-server-for-efficiently-estimating-expression-of-novel-transcripts
#15
Mei Hou, Feng Tian, Shuai Jiang, Lei Kong, Dechang Yang, Ge Gao
BACKGROUND: The temporal and spatial-specific expression pattern of a transcript in multiple tissues and cell types can indicate key clues about its function. While several gene atlas available online as pre-computed databases for known gene models, it's still challenging to get expression profile for previously uncharacterized (i.e. novel) transcripts efficiently. RESULTS: Here we developed LocExpress, a web server for efficiently estimating expression of novel transcripts across multiple tissues and cell types in human (20 normal tissues/cells types and 14 cell lines) as well as in mouse (24 normal tissues/cell types and nine cell lines)...
December 22, 2016: BMC Genomics
https://www.readbyqxmd.com/read/28151952/genomic-footprints-of-selective-sweeps-from-metabolic-resistance-to-pyrethroids-in-african-malaria-vectors-are-driven-by-scale-up-of-insecticide-based-vector-control
#16
Kayla G Barnes, Gareth D Weedall, Miranda Ndula, Helen Irving, Themba Mzihalowa, Janet Hemingway, Charles S Wondji
Insecticide resistance in mosquito populations threatens recent successes in malaria prevention. Elucidating patterns of genetic structure in malaria vectors to predict the speed and direction of the spread of resistance is essential to get ahead of the 'resistance curve' and to avert a public health catastrophe. Here, applying a combination of microsatellite analysis, whole genome sequencing and targeted sequencing of a resistance locus, we elucidated the continent-wide population structure of a major African malaria vector, Anopheles funestus...
February 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28150692/ultrahigh-charpy-impact-toughness-450j-achieved-in-high-strength-ferrite-martensite-laminated-steels
#17
Wenquan Cao, Mingda Zhang, Chongxiang Huang, Shuyang Xiao, Han Dong, Yuqing Weng
Strength and toughness are a couple of paradox as similar as strength-ductility trade-off in homogenous materials, body-centered-cubic steels in particular. Here we report a simple way to get ultrahigh toughness without sacrificing strength. By simple alloying design and hot rolling the 5Mn3Al steels in ferrite/austenite dual phase temperature region, we obtain a series of ferrite/martensite laminated steels that show up-to 400-450J Charpy V-notch impact energy combined with a tensile strength as high as 1...
February 2, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28141719/-more-than-meets-the-eye-when-the-neonatal-course-may-impact-several-years-out
#18
Fadiyla Dopwell, John Maypole, Bharati Sinha, Heidi Currier, William DeBassio, Marilyn Augustyn
Nadia is a 7-year-old girl who you have followed since her discharge from the Neonatal Intensive Care Unit (NICU). Her parents are here today for an urgent visit with behavioral concerns, such as inattention, hyperactivity, and aggression.Nadia is a former 40-weeker born through vacuum-assisted vaginal delivery at 9 pounds 7 ounces. Her delivery was complicated with shoulder dystocia, which resulted in resuscitation. Her Apgar scores were 1, 3, and 4 at 1, 5, and 10 minutes, respectively. After intubation and stabilization on mechanical ventilation, Nadia was transferred to the NICU...
February 2017: Journal of Developmental and Behavioral Pediatrics: JDBP
https://www.readbyqxmd.com/read/28137451/intermittent-intake-of-rapid-cocaine-injections-promotes-robust-psychomotor-sensitization-increased-incentive-motivation-for-the-drug-and-mglu2-3-receptor-dysregulation
#19
Florence Allain, David C S Roberts, Daniel Lévesque, Anne-Noël Samaha
The choice between smoking, injecting or swallowing a drug influences the risk of addiction, as this determines both how much drug gets into the brain and how fast. Most animal studies on addiction focus on how much drug it takes to produce pathological drug use. How fast drugs get to the brain is generally ignored. A few studies have examined the influence of the speed of drug onset, but speed varied along with cumulative intake. Here we held average cumulative intake constant and determined whether variation in the speed of cocaine onset alone predicts outcome...
January 27, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28137253/the-integration-of-weighted-human-gene-association-networks-based-on-link-prediction
#20
Jian Yang, Tinghong Yang, Duzhi Wu, Limei Lin, Fan Yang, Jing Zhao
BACKGROUND: Physical and functional interplays between genes or proteins have important biological meaning for cellular functions. Some efforts have been made to construct weighted gene association meta-networks by integrating multiple biological resources, where the weight indicates the confidence of the interaction. However, it is found that these existing human gene association networks share only quite limited overlapped interactions, suggesting their incompleteness and noise. RESULTS: Here we proposed a workflow to construct a weighted human gene association network using information of six existing networks, including two weighted specific PPI networks and four gene association meta-networks...
January 31, 2017: BMC Systems Biology
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