Mechanism insight into MnO for CO activation and O removal processes on Co(0001) surface: a DFT and kMC study

3588 Background: Gene fusions involving R-spondin ( RSPO) family members have been shown to drive Wnt-dependent tumor initiation in colorectal cancer (CRC). Therapies targeting Wnt pathway are being actively investigated for tumors harboring RSPO2/3 fusions. Here we set out to characterize the molecular features of CRC with and without RSPO fusions to gain insight into potential rationale combination therapy strategies. Methods: Tumor DNA sequencing of 592 genes (NextSeq, Illumina), RNA sequencing of 53 gene fusions (ArcherDx FusionPlex) and immunohistochemistry for PD-L1 on tumor cells (SP142) were tested on CRC tumors at Caris Life Sciences, Phoenix, AZ. Molecular profiles of RSPO2/3 positive (pos) were compared with negative (neg) tumors, Fisher-Exact was used for comparative analysis. Results: A total of 1356 CRC samples were analyzed. RSPO3 and RSPO2 fusions were detected in 42 (3.1%) and 4 (0.3%) samples, respectively, including 5 fusion events not previously reported (e.g., IFNGR1-RSPO3). A female predominance was seen in RSPO fusion pos vs. neg tumors (71.7% vs 45.0%, p < 0.001); no association with age or tumor sidedness was seen. RSPO2/3 fusions were mutually exclusive of MSI-high (0 vs. 5%), ERBB2 alterations (0 vs. 1% mutation, 4% amplification) and other Wnt pathway activation drivers including APC (2 vs. 75%), CTNNB1 (0 vs. 1.4%) and RNF43 (0 vs. 5.3%) mutations. Significantly higher BRAF (26 vs. 7%), RAF1 (4.5 vs. 0.4%) and SMAD4 (30 vs. 11%) mutation rates were seen in RSPO pos vs. neg tumors (p < 0.05). A universal co-activation of MAPK pathway ( KRAS, NRAS or BRAF) was seen with RSPO fusions. There was a significantly elevated PD-L1 expression in RSPO3 pos tumors (14%) compared to RSPO neg (6%, p = 0.04) and APC-mutated (5%, p = 0.02) tumors that are MSS. Conclusions: This is the largest series of CRC cases harboring an RSPO rearrangement reported to date. Comprehensive molecular analyses asserted the unique molecular landscape associated with RSPO fusions in CRC and suggested potential combinatorial approach to target Wnt/MAPK pathway. The immune modulatory effects specific to RSPO2/3 fusion revealed by PD-L1 expression suggest co-targeting Wnt pathway with PD1/PDL1 inhibitors in RSPO pos tumors.

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Occurrence and enrichment of ‘bacterial sherpas’: climb to sustainability in wastewater treatment

Water Science & Technology ◽

10.2166/wst.2015.364 ◽

2015 ◽

Vol 72 (9) ◽

pp. 1481-1487

Author(s):

M. Arnaldos ◽

K. R. Pagilla

Keyword(s):

Wastewater Treatment ◽

Wastewater Treatment Plants ◽

Initial Response ◽

Biological Processes ◽

Sufficient Time ◽

Treatment Stage ◽

Removal Processes ◽

Biological Nitrogen ◽

Insight Into ◽

Low Do

The paper presents research on hemoglobin (Hb)-expressing bacteria in biological wastewater treatment systems. The outcome(s) will greatly reduce the aeration needs of wastewater treatment plants (WWTPs) and provide insight into emerging biological nitrogen removal processes using low dissolved oxygen (DO) conditions. In anthropogenic terms, the bacteria that express Hb could be considered as ‘bacterial sherpas’ that can function under low DO conditions. Hitherto, this functionality of bacteria has not been realized due to the initial response of the aerobic treatment stage: namely, morphology change by bacteria to filamentous forms to overcome oxygen mass transfer limitations causing bulking/foaming and nitrification inhibition. There is evidence, however, of the potential expression of Hb proteins by activated sludge (AS) bacteria. First, bacteria known to possess genes coding Hb proteins have been isolated from AS systems. Secondly, there is evidence that WWTPs are able to operate their biological processes at low DO without sludge bulking or incomplete nitrification. Our research has focused on nitrifying systems and has shown that this is due to prolonged operation at low DO conditions (0.1 mg O2/L), which allows sufficient time for bacterial acclimation. Additionally, it has been shown that enhanced Hb expression is linked to acclimation to low DO conditions.

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Residual Stresses and Workpiece Deformation Due to Polishing and Plating of Computer Hard Disk Substrates

Journal of Manufacturing Science and Engineering ◽

10.1115/1.2830572 ◽

1999 ◽

Vol 121 (1) ◽

pp. 32-40 ◽

Cited By ~ 3

Author(s):

B. E. Klamecki

Keyword(s):

Residual Stress ◽

Plastic Deformation ◽

Residual Stresses ◽

Processing Conditions ◽

Bending Moments ◽

Stress Distributions ◽

Material Deformation ◽

Removal Processes ◽

Insight Into ◽

Shape Data

Residual stress distributions due to plating and polishing were determined for nickel-phosphorus plated aluminum alloy disks. Knowledge of these stresses provides insight into the material deformation and removal processes, information as to the effects of processing conditions on residual stress magnitude and can also serve as a basis for development of models of material deformation and removal in polishing. Measured disk shape data was fitted to an analytical solution for plate displacement due to bending moments, and residual stresses were calculated. Plating and polishing residual stresses were separated. Polishing residual stress is compressive indicating differential plastic deformation between the surface and interior regions of the workpiece. Residual stresses produced in polishing operations in which process motions were constrained so that polishing was unidirectional were measured. The results show large differences between amounts of deformation in the polishing direction and the direction perpendicular to it.

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Co-Activation of ANP and BNP in Human CAD: Insight into Non-Hemodynamic Release Mechanisms

Journal of Cardiac Failure ◽

10.1016/j.cardfail.2005.06.120 ◽

2005 ◽

Vol 11 (6) ◽

pp. S122

Keyword(s):

Release Mechanisms ◽

Co Activation ◽

Insight Into

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Mechanistic insight into CO activation, methanation and C-C bond formation from coverage dependent CO hydrogenation on Fe(110)

Surface Science ◽

10.1016/j.susc.2019.121456 ◽

2019 ◽

Vol 689 ◽

pp. 121456 ◽

Cited By ~ 1

Author(s):

Teng Li ◽

Xiaodong Wen ◽

Yong-Wang Li ◽

Haijun Jiao

Keyword(s):

Co Hydrogenation ◽

Bond Formation ◽

Mechanistic Insight ◽

Co Activation ◽

Insight Into

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Calibration problems in hydrogen luminosities

Symposium - International Astronomical Union ◽

10.1017/s0074180900053626 ◽

1966 ◽

Vol 24 ◽

pp. 322-330

Author(s):

A. Beer

Keyword(s):

Galactic Structure ◽

B Stars ◽

Insight Into

The investigations which I should like to summarize in this paper concern recent photo-electric luminosity determinations of O and B stars. Their final aim has been the derivation of new stellar distances, and some insight into certain patterns of galactic structure.

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Stochasting modeling of planetary ring systems

International Astronomical Union Colloquium ◽

10.1017/s025292110010154x ◽

1984 ◽

Vol 75 ◽

pp. 461-469 ◽

Cited By ~ 1

Author(s):

Robert W. Hart

Keyword(s):

Maximum Entropy ◽

Ring System ◽

The Sun ◽

Ultimate State ◽

Interparticle Interactions ◽

Ring Systems ◽

First Order ◽

Planetary Ring ◽

Insight Into

ABSTRACTThis paper models maximum entropy configurations of idealized gravitational ring systems. Such configurations are of interest because systems generally evolve toward an ultimate state of maximum randomness. For simplicity, attention is confined to ultimate states for which interparticle interactions are no longer of first order importance. The planets, in their orbits about the sun, are one example of such a ring system. The extent to which the present approximation yields insight into ring systems such as Saturn's is explored briefly.

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