Photochemistry, mixing and diurnal cycles in the upper ocean

The interplay between ocean photochemistry and surface boundary-layer physics is explored in a range of analytical and numerical process models. For simple systems, key attributes of the photochemical distribution—diurnal cycle, surface concentration, and the bulk concentration difference across the “mixed layer”—can be expressed in terms of a small number of physical (vertical diffusivity) and photochemical (turnover timescale and production depth scale) scaling factors. A coupled, 1-D photochemical/physical model is used to examine the more general case with finite mixing rates, variable photochemical production and evolving boundary layer depth. Finite boundary layer mixing rates act to increase both the diurnal cycle and mean concentration at the surface. The diurnal cycle and mean surface concentration are further amplified by coupling between photochemistry and diurnal physics. The daily heating/cooling cycle of the upper ocean can lead to a significant reduction in mixing and boundary-layer depth during the day when photochemical production is at a maximum. Accounting for these effects results in additional surface trapping of photochemically produced species and significant enhancements of the surface diurnal cycle and daily mean. The implications of our model results for field data interpretation and global air-sea flux calculations are also discussed

Structure and Function of Histone H3 Lysine 9 Methyltransferases and Demethylases

Histone lysine methylation is a dynamic chromatin modification that plays key regulatory roles in gene expression and other genomic functions. Methylation of Lys9 in histone H3 (H3K9) is a prominent modification that has been implicated in diverse processes, including transcriptional silencing, heterochromatin formation, and DNA methylation. In this review, we summarize recent advances in understanding the structure and substrate specificity of the H3K9-specific methyltransferases G9A and GLP and explore current efforts to develop inhibitors of these enzymes. In addition, we discuss the structure and specificity of the recently discovered PHF8 family of histone demethylases that target H3K9 as well as other methylation sites in histones H3 and H4. Finally, we conclude by comparing the H3K9 binding modes displayed by these enzymes and examine the relevance of these studies to their biological functions and to structure-based inhibitor design.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/79431/1/254_ftp.pd

Buyer Perceptions of Supply Disruption Risk: A Behavioral View and Empirical Assessment

As supply chains become more complex, firms face increasing risks of supply disruptions. The process through which buyers make decisions in the face of these risks, however, has not been explored. Despite research highlighting the importance of behavioral approaches to risk, there is limited research that applies these views of risk in the supply chain literature. This paper addresses this gap by drawing on behavioral risk theory to investigate the causal relationships amongst situation, representations of risk, and decision-making within the purchasing domain. We operationalize and explore the relationship between three representations of supply disruption risk: magnitude of supply disruption, probability of supply disruption, and overall supply disruption risk. Additionally, we draw on exchange theories to identify product and market factors that impact buyers’ perceptions of the probability and magnitude of supply disruption. Finally, we look at how representations of risk affect the decision to seek alternative sources of supply. We test our model using data collected from 223 purchasing managers and buyers of direct materials. Our results show that both the probability and the magnitude of supply disruption are important to buyers’ overall perceptions of supply disruption risk. We also find that product and market situational factors impact perceptions of risk, but they are best understood through their impact on perceptions of probability and magnitude. Finally, we find that decisions are based on assessments of overall risk. These findings provide insight into the decision-making process and show that all three representations of risk are necessary for fully understanding risky decision-making with respect to supply disruptions

Making Sense Of Supply Disruption Risk Research: A Conceptual Framework Grounded In Enactment Theory

The rich stream of supply disruption risk (SDR) literature incorporates several different theories and constructs across studies, but lacks a unifying decision-making framework. We review 79 SDR studies and advance a comprehensive framework, grounded in enactment theory, which integrates the disparate elements of SDR research and offers new insights into the SDR decision-making process. Enactment theory posits a three-stage, closed-loop process, consisting of enactment, selection and retention, through which individuals process and make sense of equivocal environments. We suggest that this sense-making process also underlies SDR decision-making, and provides the theoretical underpinnings for the environmental, organizational and individual factors that affect the formation of buyers\u27 perceptions of SDR and the actions they take to mitigate such risks. In accordance with our conceptual framework, we develop seven propositions that advance the social and psychological factors that drive the idiosyncratic nature of SDR decision-making

Elucidating the Role of Injury-Induced Electric Fields (EFs) in Regulating the Astrocytic Response to Injury in the Mammalian Central Nervous System

Injury to the vertebrate central nervous system (CNS) induces astrocytes to change their morphology, to increase their rate of proliferation, and to display directional migration to the injury site, all to facilitate repair. These astrocytic responses to injury occur in a clear temporal sequence and, by their intensity and duration, can have both beneficial and detrimental effects on the repair of damaged CNS tissue. Studies on highly regenerative tissues in non-mammalian vertebrates have demonstrated that the intensity of direct-current extracellular electric fields (EFs) at the injury site, which are 50–100 fold greater than in uninjured tissue, represent a potent signal to drive tissue repair. In contrast, a 10-fold EF increase has been measured in many injured mammalian tissues where limited regeneration occurs. As the astrocytic response to CNS injury is crucial to the reparative outcome, we exposed purified rat cortical astrocytes to EF intensities associated with intact and injured mammalian tissues, as well as to those EF intensities measured in regenerating non-mammalian vertebrate tissues, to determine whether EFs may contribute to the astrocytic injury response. Astrocytes exposed to EF intensities associated with uninjured tissue showed little change in their cellular behavior. However, astrocytes exposed to EF intensities associated with injured tissue showed a dramatic increase in migration and proliferation. At EF intensities associated with regenerating non-mammalian vertebrate tissues, these cellular responses were even more robust and included morphological changes consistent with a regenerative phenotype. These findings suggest that endogenous EFs may be a crucial signal for regulating the astrocytic response to injury and that their manipulation may be a novel target for facilitating CNS repair

Frequent side chain methyl carbon‐oxygen hydrogen bonding in proteins revealed by computational and stereochemical analysis of neutron structures

The propensity of backbone Cα atoms to engage in carbon‐oxygen (CH···O) hydrogen bonding is well‐appreciated in protein structure, but side chain CH···O hydrogen bonding remains largely uncharacterized. The extent to which side chain methyl groups in proteins participate in CH···O hydrogen bonding is examined through a survey of neutron crystal structures, quantum chemistry calculations, and molecular dynamics simulations. Using these approaches, methyl groups were observed to form stabilizing CH···O hydrogen bonds within protein structure that are maintained through protein dynamics and participate in correlated motion. Collectively, these findings illustrate that side chain methyl CH···O hydrogen bonding contributes to the energetics of protein structure and folding. Proteins 2015; 83:403–410. © 2014 Wiley Periodicals, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/110709/1/prot24724-sup-0001-suppinfo01.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/110709/2/prot24724.pd

Simulator evaluation of system identification with on-line control law update for the controls and astrophysics experiment in space

A procedure for optimizing the performance of large flexible spacecraft that require active vibration suppression to achieve required performance is presented. The procedure is to conduct on-orbit testing and system identification followed by a control system design. It is applied via simulation to a spacecraft configuration currently being considered for flight test by NASA - the Controls, Astrophysics, and Structures Experiment in Space (CASES). The system simulator is based on a NASTRAN finite element structural model. A finite number of modes is used to represent the structural dynamics. The system simulator also includes models of the electronics, actuators, sensors, the digital controller, and the internal and external disturbances. Nonlinearities caused by quantization are included in the study to examine tolerance of the procedure to modelling errors. Disturbance and sensor noise is modelled as a Gaussian process. For system identification, the system is excited using sinusoidal inputs at the resonant frequencies of the structure using each actuator. Mode shapes, frequencies, and damping ratios are identified from the unforced response sensor data after each excitation. Then, the excitation data is used to identify the actuator influence coefficients. The results of the individual parameter identification analyses are assembled into an aggregate system model. The control design is accomplished based only on the identified model using multi-input/output linear quadratic Gaussian theory. Its performance is evaluated based on time-to-damp as compared with the uncontrolled structure

Genomic Assessment of Blood-Derived Circulating Tumor DNA in Patients With Colorectal Cancers: Correlation With Tissue Sequencing, Therapeutic Response, and Survival.

PurposeGenomic alterations in blood-derived circulating tumor DNA (ctDNA) from patients with colorectal cancers were correlated with clinical outcomes.Patients and methodsNext-generation sequencing of ctDNA (54- to 73-gene panel) was performed in 94 patients with colorectal cancer.ResultsMost patients (96%) had metastatic or recurrent disease at the time of blood draw. The median number of nonsynonymous alterations per patient was three (range, zero to 30). The most frequently aberrant genes were TP53 (52.1% of patients), KRAS (34%), and APC (28.7%). Concordance between tissue and blood next-generation sequencing ranged from 63.2% (APC) to 85.5% (BRAF). Altogether, 74 patients (79%) had one or more nonsynonymous alterations, 69 (73%) had one or more potentially actionable alterations, and 61 (65%) had an alteration actionable by a drug approved by the US Food and Drug Administration (on or off label). Lung metastases correlated with improved survival from diagnosis in univariable analysis. ctDNA of 5% or more from blood tests as well as EGFR and ERBB2 (HER2) nonsynonymous alterations correlated with worse survival (but only ERBB2 remained significant in multivariable analysis). No two patients had identical molecular portfolios. Overall, 65% versus 31% of patients treated with matched (n = 17) versus unmatched therapy (n = 18) after ctDNA testing achieved stable disease for 6 months or more, partial response, or complete response (P = .045); progression-free survival, 6.1 versus 2.3 months (P = .08); and survival not reached versus 9.4 months (P = .146; all by multivariable analysis).ConclusionPatients with colorectal cancer have heterogeneous ctDNA profiles, and most harbor potentially actionable ctDNA alterations. Matched therapy yielded higher rates of stable disease for 6 months or more, partial response, or complete response. ctDNA assessment may have clinical utility and merits further investigation

Sealing in Turbomachinery

Clearance control is of paramount importance to turbomachinery designers and is required to meet today's aggressive power output, efficiency, and operational life goals. Excessive clearances lead to losses in cycle efficiency, flow instabilities, and hot gas ingestion into disk cavities. Insufficient clearances limit coolant flows and cause interface rubbing, overheating downstream components and damaging interfaces, thus limiting component life. Designers have put renewed attention on clearance control, as it is often the most cost effective method to enhance system performance. Advanced concepts and proper material selection continue to play important roles in maintaining interface clearances to enable the system to meet design goals. This work presents an overview of turbomachinery sealing to control clearances. Areas covered include: characteristics of gas and steam turbine sealing applications and environments, benefits of sealing, types of standard static and dynamics seals, advanced seal designs, as well as life and limitations issues