bluuebunny/crossref_metadata_2025_split huggingface dataset:
Codon bias imposes a targetable limitation on KRAS-driven therapeutic resistance
Authors: Ali Moiez , Kaltenbrun Erin , Anderson Gray R. , Stephens Sarah Jo , Arena Sabrina , Bardelli Alberto , Counter Christopher M. , Wood Kris C. 
Published: June 2017

AbstractKRAS mutations drive resistance to targeted therapies, including EGFR inhibitors in colorectal cancer (CRC). Through genetic screens, we unexpectedly find that mutant HRAS, which is rarely found in CRC, is a stronger driver of resistance than mutant KRAS. This difference is ascribed to common codon bias in HRAS, which leads to much higher protein expression, and implies that the inherent poor expression of KRAS due to rare codons must be surmounted during drug resistance. In agreement, we demonstrate that primary resistance to cetuximab is dependent upon both KRAS mutational status and protein expression level, and acquired resistance is often associated with KRASQ61 mutations that function even when protein expression is low. Finally, cancer cells upregulate translation to facilitate KRASG12-driven acquired resistance, resulting in hypersensitivity to translational inhibitors. These findings demonstrate that codon bias plays a critical role in KRAS-driven resistance and provide a rationale for targeting translation to overcome resistance.
Cross-orientation suppression in visual area V2
Authors: Rowekamp Ryan J. , Sharpee Tatyana O. 
Published: June 2017

AbstractObject recognition relies on a series of transformations among which only the first cortical stage is relatively well understood. Already at the second stage, the visual area V2, the complexity of the transformation precludes a clear understanding of what specifically this area computes. Previous work has found multiple types of V2 neurons, with neurons of each type selective for multi-edge features. Here we analyse responses of V2 neurons to natural stimuli and find three organizing principles. First, the relevant edges for V2 neurons can be grouped into quadrature pairs, indicating invariance to local translation. Second, the excitatory edges have nearby suppressive edges with orthogonal orientations. Third, the resulting multi-edge patterns are repeated in space to form textures or texture boundaries. The cross-orientation suppression increases the sparseness of responses to natural images based on these complex forms of feature selectivity while allowing for multiple scales of position invariance.
Vector assembly of colloids on monolayer substrates
Authors: Jiang Lingxiang , Yang Shenyu , Tsang Boyce , Tu Mei , Granick Steve 
Published: June 2017

AbstractThe key to spontaneous and directed assembly is to encode the desired assembly information to building blocks in a programmable and efficient way. In computer graphics, raster graphics encodes images on a single-pixel level, conferring fine details at the expense of large file sizes, whereas vector graphics encrypts shape information into vectors that allow small file sizes and operational transformations. Here, we adapt this raster/vector concept to a 2D colloidal system and realize ‘vector assembly’ by manipulating particles on a colloidal monolayer substrate with optical tweezers. In contrast to raster assembly that assigns optical tweezers to each particle, vector assembly requires a minimal number of optical tweezers that allow operations like chain elongation and shortening. This vector approach enables simple uniform particles to form a vast collection of colloidal arenes and colloidenes, the spontaneous dissociation of which is achieved with precision and stage-by-stage complexity by simply removing the optical tweezers.
Formation and electronic properties of palladium hydrides and palladium-rhodium dihydride alloys under pressure
Authors: Yang Xiao , Li Huijian , Ahuja Rajeev , Kang Taewon , Luo Wei 
Published: June 2017

AbstractWe present the formation possibility for Pd-hydrides and Pd-Rh hydrides system by density functional theory (DFT) in high pressure upto 50 GPa. Calculation confirmed that PdH2in face-centered cubic (fcc) structure is not stable under compression that will decomposition to fcc-PdH and H2. But it can be formed under high pressure while the palladium is involved in the reaction. We also indicate a probably reason why PdH2can not be synthesised in experiment due to PdH is most favourite to be formed in Pd and H2environment from ambient to higher pressure. With Rh doped, the Pd-Rh dihydrides are stabilized in fcc structure for 25% and 75% doping and in tetragonal structure for 50% doping, and can be formed from Pd, Rh and H2at high pressure. The electronic structural study on fcc type PdxRh1−xH2indicates the electronic and structural transition from metallic to semi-metallic as Pd increased from x = 0 to 1.
The early metabolomic response of adipose tissue during acute cold exposure in mice
Authors: Lu Xiyuan , Solmonson Ashley , Lodi Alessia , Nowinski Sara M. , Sentandreu Enrique , Riley Christopher L. , Mills Edward M. , Tiziani Stefano 
Published: June 2017

AbstractTo maintain core body temperature in cold conditions, mammals activate a complex multi-organ metabolic response for heat production. White adipose tissue (WAT) primarily functions as an energy reservoir, while brown adipose tissue (BAT) is activated during cold exposure to generate heat from nutrients. Both BAT and WAT undergo specific metabolic changes during acute cold exposure. Here, we use an untargeted metabolomics approach to characterize the initial metabolic response to cold exposure in multiple adipose tissue depots in mice. Results demonstrate dramatically distinct metabolic responses during cold exposure in BAT and WAT. Amino acids, nucleotide pathways, and metabolites involved in redox regulation were greatly affected 4 hours post-exposure in BAT, while no polar metabolites were observed to significantly change in WAT depots up to 6 hours post exposure. Lipid metabolism was activated early (2 hours) in both BAT and the subcutaneous WAT depots, with the most striking change being observed in the modulation of diglyceride and monoglyceride levels in BAT. Overall, these data provide a timeline of global thermogenic metabolism in adipose depots during acute cold exposure. We have highlighted differences in visceral and subcutaneous WAT thermogenic metabolism and demonstrate the distinct metabolism of BAT during cold exposure.
Thermal and structural studies of carbon coated Mo2C synthesized via in-situ single step reduction-carburization
Authors: Mir Rameez Ahmad , Sharma Piyush , Pandey Om Prakash 
Published: June 2017

AbstractCarbon coated nano molybdenum carbide (Mo2C) has been synthesized at 800 °C through single step reduction route using molybdenum trioxide (MoO3) as a precursor, polypropylene (P.P) as a carbon source and magnesium (Mg) as a catalyst in an autoclave. The synthesized samples were characterized by X-ray diffraction (XRD), thermal analysis techniques (TG/DTA/DTG), field emission scanning electron microscopy (FESEM) and transmission electron microscopy (TEM). Williamson- Hall (W-H) analysis has been done to estimate various parameters like strain, stress and strain energy density. Multi-stage kinetic analysis of the product phase has been studied to establish the nature of the thermal decomposition. Coats-Redfern method applied to determine the mechanism involved in the decomposition of the product phase shows that initial and final stage follow F1 mechanism whereas middle stage follow F3 mechanism. The activation energy (Ea) and pre-exponential factor (A) has also been determined. The morphological studies shows that the particles have partially spherical/faceted shape, with carbon coated having wide particle size distribution. The surface chemistry and surface area analysis were studied by X-ray photoelectron spectroscopy (XPS) and Brunauer-Emmet-Teller (BET), respectively. The formation mechanism of carbon coated Mo2C nano particles has been predicted based on the XRD, TG/DTA & DTG and microstructural results.
Reconstruction of pathway modification induced by nicotinamide using multi-omic network analyses in triple negative breast cancer
Authors: Kim Ji Young , Lee Hyebin , Woo Jongmin , Yue Wang , Kim Kwangsoo , Choi Seongmin , Jang Ja-June , Kim Youngsoo , Park In Ae , Han Dohyun , Ryu Han Suk 
Published: June 2017

AbstractTriple negative breast cancer (TNBC) is characterized by an aggressive biological behavior in the absence of a specific target agent. Nicotinamide has recently been proven to be a novel therapeutic agent for skin tumors in an ONTRAC trial. We performed combinatory transcriptomic and in-depth proteomic analyses to characterize the network of molecular interactions in TNBC cells treated with nicotinamide. The multi-omic profiles revealed that nicotinamide drives significant functional alterations related to major cellular pathways, including the cell cycle, DNA replication, apoptosis and DNA damage repair. We further elaborated the global interaction networks of molecular events via nicotinamide-inducible expression changes at the mRNA and functional protein levels. This approach indicated that nicotinamide treatment rewires interaction networks toward dysfunction in DNA damage repair and away from a pro-growth state in TNBC. To our knowledge, the high-resolution network interactions identified in the present study provide the first evidence to comprehensively support the hypothesis of nicotinamide as a novel therapeutic agent in TNBC.
Bacteriocin Gene-Trait matching across the complete Lactobacillus Pan-genome
Authors: Collins Fergus W. J. , O’Connor Paula M. , O’Sullivan Orla , Gómez-Sala Beatriz , Rea Mary C. , Hill Colin , Ross R. Paul 
Published: June 2017

AbstractLactobacilli constitute a large genus of Gram-positive lactic acid bacteria which have widespread roles ranging from gut commensals to starters in fermented foods. A combination of in silico and laboratory-based screening allowed us to determine the overall bacteriocin producing potential of representative strains of each species of the genus. The genomes of 175 lactobacilli and 38 associated species were screened for the presence of antimicrobial producing genes and combined with screening for antimicrobial activity against a range of indicators. There also appears to be a link between the strains’ environment and bacteriocin production, with those from the animal and human microbiota encoding over twice as many bacteriocins as those from other sources. Five novel bacteriocins were identified belonging to differing bacteriocin classes, including two-peptide bacteriocins (muricidin and acidocin X) and circular bacteriocins (paracyclicin). In addition, there was a clear clustering of helveticin type bacteriolysins in the Lactobacillus acidophilus group of species. This combined in silico and in vitro approach to screening has demonstrated the true diversity and complexity of bacteriocins across the genus. It also highlights their biological importance in terms of communication and competition between closely related strains in diverse complex microbial environments.
Programmable Deployment of Tensegrity Structures by Stimulus-Responsive Polymers
Authors: Liu Ke , Wu Jiangtao , Paulino Glaucio H. , Qi H. Jerry 
Published: June 2017

AbstractTensegrity structures with detached struts are naturally suitable for deployable applications, both in terrestrial and outer-space structures, as well as morphing devices. Composed of discontinuous struts and continuous cables, such systems are only structurally stable when self-stress is induced; otherwise, they lose the original geometrical configuration (while keeping the topology) and thus can be tightly packed. We exploit this feature by using stimulus responsive polymers to introduce a paradigm for creating actively deployable 3D structures with complex shapes. The shape-change of 3D printed smart materials adds an active dimension to the configurational space of some structural components. Then we achieve dramatic global volume expansion by amplifying component-wise deformations to global configurational change via the inherent deployability of tensegrity. Through modular design, we can generate active tensegrities that are relatively stiff yet resilient with various complexities. Such unique properties enable structural systems that can achieve gigantic shape change, making them ideal as a platform for super light-weight structures, shape-changing soft robots, morphing antenna and RF devices, and biomedical devices.
Genome-wide analysis suggests a differential microRNA signature associated with normal and diabetic human corneal limbus
Authors: Kulkarni Mangesh , Leszczynska Aleksandra , Wei Gabbie , Winkler Michael A. , Tang Jie , Funari Vincent A. , Deng Nan , Liu Zhenqiu , Punj Vasu , Deng Sophie X. , Ljubimov Alexander V. , Saghizadeh Mehrnoosh 
Published: June 2017

AbstractSmall non-coding RNAs, in particular microRNAs (miRNAs), regulate fine-tuning of gene expression and can impact a wide range of biological processes. However, their roles in normal and diseased limbal epithelial stem cells (LESC) remain unknown. Using deep sequencing analysis, we investigated miRNA expression profiles in central and limbal regions of normal and diabetic human corneas. We identified differentially expressed miRNAs in limbus vs. central cornea in normal and diabetic (DM) corneas including both type 1 (T1DM/IDDM) and type 2 (T2DM/NIDDM) diabetes. Some miRNAs such as miR-10b that was upregulated in limbus vs. central cornea and in diabetic vs. normal limbus also showed significant increase in T1DM vs. T2DM limbus. Overexpression of miR-10b increased Ki-67 staining in human organ-cultured corneas and proliferation rate in cultured corneal epithelial cells. MiR-10b transfected human organ-cultured corneas showed downregulation of PAX6 and DKK1 and upregulation of keratin 17 protein expression levels. In summary, we report for the first time differential miRNA signatures of T1DM and T2DM corneal limbus harboring LESC and show that miR-10b could be involved in the LESC maintenance and/or their early differentiation. Furthermore, miR-10b upregulation may be an important mechanism of corneal diabetic alterations especially in the T1DM patients.
Understanding ‘saturation’ of radar signals over forests
Authors: Joshi Neha , Mitchard Edward T. A. , Brolly Matthew , Schumacher Johannes , Fernández-Landa Alfredo , Johannsen Vivian Kvist , Marchamalo Miguel , Fensholt Rasmus 
Published: June 2017

AbstractThere is an urgent need to quantify anthropogenic influence on forest carbon stocks. Using satellite-based radar imagery for such purposes has been challenged by the apparent loss of signal sensitivity to changes in forest aboveground volume (AGV) above a certain ‘saturation’ point. The causes of saturation are debated and often inadequately addressed, posing a major limitation to mapping AGV with the latest radar satellites. Using ground- and lidar-measurements across La Rioja province (Spain) and Denmark, we investigate how various properties of forest structure (average stem height, size and number density; proportion of canopy and understory cover) simultaneously influence radar backscatter. It is found that increases in backscatter due to changes in some properties (e.g. increasing stem sizes) are often compensated by equal magnitude decreases caused by other properties (e.g. decreasing stem numbers and increasing heights), contributing to the apparent saturation of the AGV-backscatter trend. Thus, knowledge of the impact of management practices and disturbances on forest structure may allow the use of radar imagery for forest biomass estimates beyond commonly reported saturation points.
Intravascular forward-looking ultrasound transducers for microbubble-mediated sonothrombolysis
Authors: Kim Jinwook , Lindsey Brooks D. , Chang Wei-Yi , Dai Xuming , Stavas Joseph M. , Dayton Paul A. , Jiang Xiaoning 
Published: June 2017

AbstractEffective removal or dissolution of large blood clots remains a challenge in clinical treatment of acute thrombo-occlusive diseases. Here we report the development of an intravascular microbubble-mediated sonothrombolysis device for improving thrombolytic rate and thus minimizing the required dose of thrombolytic drugs. We hypothesize that a sub-megahertz, forward-looking ultrasound transducer with an integrated microbubble injection tube is more advantageous for efficient thrombolysis by enhancing cavitation-induced microstreaming than the conventional high-frequency, side-looking, catheter-mounted transducers. We developed custom miniaturized transducers and demonstrated that these transducers are able to generate sufficient pressure to induce cavitation of lipid-shelled microbubble contrast agents. Our technology demonstrates a thrombolysis rate of 0.7 ± 0.15 percent mass loss/min in vitro without any use of thrombolytic drugs.
Autotransporter domain-dependent enzymatic analysis of a novel extremely thermostable carboxylesterase with high biodegradability towards pyrethroid pesticides
Authors: Cai Xianghai , Wang Wei , Lin Lin , He Dannong , Huang Gang , Shen Yaling , Wei Wei , Wei Dongzhi 
Published: June 2017

AbstractThe EstPS1 gene, which encodes a novel carboxylesterase of Pseudomonas synxantha PS1 isolated from oil well-produced water, was cloned and sequenced. EstPS1 has an open reading frame of 1923 bp and encodes the 640-amino acid carboxylesterase (EstPS1), which contains an autotransporter (AT) domain (357–640 amino acids). Homology analysis revealed that EstPS1 shared the highest identity (88%) with EstA from Pseudomonas fluorescens A506 (NCBI database) and belonged to the carboxylesterase family (EC 3.1.1.1). The optimum pH and temperature of recombinant EstPS1 were found to be 8.0 and 60 °C, respectively. EstPS1 showed high thermostability, and the half-lives (T1/2 thermal inactivation) at 60, 70, 80, 90, and 100 °C were 14 h, 2 h, 31 min, 10 min, and 1 min, respectively. To understand the role of the AT domain in carboxylesterase, AT domain-truncated carboxylesterase (EstPS1ΔAT) was generated. EstPS1ΔAT showed a clearly decreased secretion rate, owing to the AT domain strongly improved secretory expression in the heterogeneous system. EstPS1 degraded various pyrethroid pesticides, and hydrolysis efficiencies were dependent on the pyrethroid molecular structure. EstPS1 degraded all the tested pyrethroid pesticides and hydrolysed the p-nitrophenyl esters of medium-short-chain fatty acids, indicating that EstPS1 is an esterase with broad specificity.
Nomogram model to predict postoperative infection after mandibular osteoradionecrosis surgery
Authors: Liu Zhonglong , Dai Tianguo , Wang Zhonghe , Zhang Zhiyuan , Qiu Weiliu , He Yue 
Published: June 2017

AbstractOsteoradionecrosis of the mandible (ORNM) is one of the most dreaded complications of radiotherapy. The poor healing capacity of soft tissue after radiation may lead to surgical failure. The current study was designed to identify prognostic factors for postoperative infection (PPI) and propose corresponding prophylaxis and intervention protocols. A retrospective study was conducted concerning ORNM patients from 2000 to 2015. A risk-stratification score and nomogram model were established to predict the risk of PPI. A total of 257 patients were analyzed, and the total incidence of PPI was 23.3% (60/257). In multiple logistic regression analysis, radiation dose$$\geqslant $$⩾80 Gy (versus <80 Gy, OR = 2.044, P = 0.035, 95% CI: 1.05–3.979), bilateral ORNM (versus unilateral, OR = 4.120, P = 0.006, 95% CI: 1.501–11.307), skin fistula (versus none, OR = 3.078, P = 0.040, 95% CI: 1.05–9.023), and implant utilization (versus none, OR = 2.115, P = 0.020, 95% CI: 1.125–3.976) were significantly associated with PPI. The susceptibility to PPI in patients with risk-stratification scores of 14–22 was 2.833 times that of patients with scores of 7–13, and 7.585 times that of cases defined as scores of 0–6. The discrimination capability of the nomogram model was estimated using a ROC curve with an AUC of 0.708, revealing potentially useful predictive abilities. In conclusion, current risk-stratification scores and nomogram models effectively predicted the risk of PPI in ORNM patients.
Identification and characterization of a rich population of CD34+ mesenchymal stem/stromal cells in human parotid, sublingual and submandibular glands
Authors: Togarrati Padma Priya , Sasaki Robson T. , Abdel-Mohsen Mohamed , Dinglasan Nuntana , Deng Xutao , Desai Shivani , Emmerson Elaine , Yee Elizabeth , Ryan William R. , da Silva Marcelo C. P. , Knox Sarah M. , Pillai Satish K. , Muench Marcus O. 
Published: June 2017

AbstractMesenchymal stem/stromal cells (MSCs) play crucial roles in maintaining tissue homeostasis during physiological turnovers and injuries. Very little is known about the phenotype, distribution and molecular nature of MSCs in freshly isolated human salivary glands (SGs) as most reports have focused on the analysis of cultured MSCs. Our results demonstrate that the cell adhesion molecule CD34 was widely expressed by the MSCs of human major SGs, namely parotid (PAG), sublingual (SLG) and submandibular (SMG) glands. Further, gene expression analysis of CD34+ cells derived from fetal SMGs showed significant upregulation of genes involved in cellular adhesion, proliferation, branching, extracellular matrix remodeling and organ development. Moreover, CD34+ SMG cells exhibited elevated expression of genes encoding extracellular matrix, basement membrane proteins, and members of ERK, FGF and PDGF signaling pathways, which play key roles in glandular development, branching and homeostasis. In vitro CD34+ cell derived SG-MSCs revealed multilineage differentiation potential. Intraglandular transplantation of cultured MSCs in immunodeficient mice led to their engraftment in the injected and uninjected contralateral and ipsilateral glands. Engrafted cells could be localized to the stroma surrounding acini and ducts. In summary, our data show that CD34+ derived SG-MSCs could be a promising cell source for adoptive cell-based SG therapies, and bioengineering of artificial SGs.
Secreted IgM deficiency leads to increased BCR signaling that results in abnormal splenic B cell development
Authors: Tsiantoulas Dimitrios , Kiss Mate , Bartolini-Gritti Barbara , Bergthaler Andreas , Mallat Ziad , Jumaa Hassan , Binder Christoph J. 
Published: June 2017

AbstractMice lacking secreted IgM (sIgM−/−) antibodies display abnormal splenic B cell development, which results in increased marginal zone and decreased follicular B cell numbers. However, the mechanism by which sIgM exhibit this effect is unknown. Here, we demonstrate that B cells insIgM−/−mice display increased B cell receptor (BCR) signaling as judged by increased levels of phosphorylated Bruton’s tyrosine kinase (pBtk), phosphorylated Spleen tyrosine kinase (pSyk), and nuclear receptor Nur77. Low dosage treatment with the pBtk inhibitor Ibrutinib reversed the altered B cell development in the spleen ofsIgM−/−mice, suggesting that sIgM regulate splenic B cell differentiation by decreasing BCR signaling. Mechanistically, we show that B cells, which express BCRs specific to hen egg lysozyme (HEL) display diminished responsiveness to HEL stimulation in presence of soluble anti-HEL IgM antibodies. Our data identify sIgM as negative regulators of BCR signaling and suggest that they can act as decoy receptors for self-antigens that are recognized by membrane bound BCRs.