Sampling and Analytical Strategies for Biomarker Discovery Using Mass Spectrometry

There is an often unspoken truth behind the course of scientific investigation that involves not what is necessarily academically worthy of study, but rather what is scientifically worthy in the eyes of funding agencies. The perception of worthy research is, as cost is driven in the simplest sense in economics, often driven by demand. Presently, the demand for novel diagnostic and therapeutic protein biomarkers that possess high sensitivity and specificity is placing major impact on the field of proteomics. The focal discovery technology that is being relied on is mass spectrometry (MS), whereas the challenge of biomarker discovery often lies not in the application of MS but in the underlying proteome sampling and bioinformatic processing strategies. Although biomarker discovery research has been historically technology-driven, it is clear from the meager success in generating validated biomarkers that increasing attention must be placed at the pre-analytic stage, such as sample retrieval and preparation. As diseases vary, so do the combinations of sampling and sample analyses necessary to discover novel biomarkers. In this review, we highlight different strategies used toward biomarker discovery and discuss them in terms of their reliance on technology and methodology

Is Modeling of Freshman Engineering Success Different from Modeling of Non‐Engineering Success?

The engineering community has recognized the need for a higher retention rate in freshman engineering. If we are to increase the freshman retention rate, we need to better understand the characteristics of academic success for engineering students. One approach is to compare academic performance of engineering students to that of non‐engineering students. This study explores the differences in predicting academic success (defined as the first year GPA) for freshman engineering students compared to three non‐engineering student sectors (Pre‐Med, STEM, and non‐STEM disciplines) within a university. Academic success is predicted with pre‐college variables from the UCLA/CIRP survey using factor analysis and regression analysis. Except for the factor related to the high school GPA and rank, the predictors for each student sector were discipline specific. Predictors unique to the engineering sector included the factors related to quantitative skills (ACT Math and Science test scores and placement test scores) and confidence in quantitative skills.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/95487/1/j.2168-9830.2008.tb00993.x.pd

PCN10 ARE FURTHER STUDIES OF BREAST CANCER TUMOR MARKERS TO DETECT RECURRENCE WORTHWHILE? A VALUE OF RESEARCH ANALYSIS

Cuello, Ramon (escultor)Primer pla de l'obra. Davant de la casa on vivia l'escultor a Sants hi havia hagut una fonda on paraven les diligències que unien l'interior de Catalunya amb el port de Barcelona. De metall, mesura 2,58 x 0,80 x 0,80 metres

Proteostatic Control of Telomerase Function through TRiC-Mediated Folding of TCAB1

SummaryTelomere maintenance by telomerase is impaired in the stem cell disease dyskeratosis congenita and during human aging. Telomerase depends upon a complex pathway for enzyme assembly, localization in Cajal bodies, and association with telomeres. Here, we identify the chaperonin CCT/TRiC as a critical regulator of telomerase trafficking using a high-content genome-wide siRNA screen in human cells for factors required for Cajal body localization. We find that TRiC is required for folding the telomerase cofactor TCAB1, which controls trafficking of telomerase and small Cajal body RNAs (scaRNAs). Depletion of TRiC causes loss of TCAB1 protein, mislocalization of telomerase and scaRNAs to nucleoli, and failure of telomere elongation. DC patient-derived mutations in TCAB1 impair folding by TRiC, disrupting telomerase function and leading to severe disease. Our findings establish a critical role for TRiC-mediated protein folding in the telomerase pathway and link proteostasis, telomere maintenance, and human disease

Integrating value of research into NCI Clinical Trials Cooperative Group research review and prioritization: A pilot study

BackgroundThe Institute of Medicine has called for approaches to help maximize the return on investments (ROI) in cancer clinical trials. Value of Research (VOR) is a health economics technique that estimates ROI and can inform research prioritization. Our objective was to evaluate the impact of using VOR analyses on the clinical trial proposal review process within the SWOG cancer clinical trials consortium.MethodsWe used a previously developed minimal modeling approach to calculate VOR estimates for 9 phase II/III SWOG proposals between February 2015 and December 2016. Estimates were presented to executive committee (EC) members (N = 12) who determine which studies are sent to the National Cancer Institute for funding consideration. EC members scored proposals from 1 (best) to 5 based on scientific merit and potential impact before and after receiving VOR estimates. EC members were surveyed to assess research priorities, proposal evaluation process satisfaction, and the VOR process.ResultsValue of Research estimates ranged from −$2.1B to$16.46B per proposal. Following review of VOR results, the EC changed their score for eight of nine proposals. Proposal rankings were different in pre‐ vs postscores (P value: 0.03). Respondents had mixed views of the ultimate utility of VOR for their decisions with most supporting (42%) or neutral (41%) to the idea of adding VOR to the evaluation process.ConclusionsThe findings from this pilot study indicate use of VOR analyses may be a useful adjunct to inform proposal reviews within NCI Cooperative Clinical Trials groups.The Instiztute of Medicine has called for approaches to help maximize the return on investments in cancer clinical trials. The findings from this pilot study indicate use of value of research analyses may be a useful adjunct to inform proposal reviews within NCI Cooperative Clinical Trials groups.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/146484/1/cam41657.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/146484/2/cam41657_am.pd

Thermo-fluid dynamics modelling of steam electrolysis in fully-assembled tubular high-temperature proton-conducting cells

Electrolysis based on renewable energies offers a promising carbon-free solution for hydrogen generation and storage. The recent developments of proton ceramic electrolysis cells operating at intermediate temperatures bear promise of superior energy efficiency compared to oxide ion conducting electrolytes. Here, a proton ceramic Single Engineering Unit (SEU) design is optimized for steam electrolysis using a computational fluid dynamics (CFD) model implemented in a COMSOL Multiphysics software. The SEU is an all-in-one tubular cell arrangement that constitutes the smallest electrolysis unit and enables efficient, adaptable pressurized hydrogen generation. The parametrical modelling study is conducted for two adiabatic operation scenarios with distinct steam conversion rates and tested for multiple key parameters, namely internal and external chamber pressures and inlet stream temperature. The modelling results show that low steam conversions enable operation at higher current densities and that the thermoneutral voltage for a fixed steam conversion is highly sensitive to the process conditions and operation modes. The increment of the pressure of the generated hydrogen implies a reduced production rate at thermoneutral voltage, although it can be compensated with an enhanced steam pressure or a reduced inlet temperature. Additionally, the introduction of a porous medium as the SEU current collector in the steam chamber enhances heat transport within this chamber. The area specific resistance of the system determines the current density, enforcing an adaption of the area of the electrolyser to satisfy the target hydrogen production and energy efficiency. The resulting proposed SEU design and adapted operational parameters allow effective delivery of pressurized dry hydrogen for a wide range of conditions and applications.publishedVersio

Moral emotions and moral disengagement: concurrent and longitudinal associations with aggressive behavior among early adolescents

The complex temporal associations among moral disengagement, moral emotions, and aggressive behavior were investigated within a short-term four-wave longitudinal study in a sample of early adolescents (at T1: N = 245; Mage= 12.16 years; SD = 0.85). Moral disengagement and aggressive behavior were investigated by validated self-report scales. Shame and guilt were assessed in response to six-story vignettes. A series of four-wave longitudinal mediation analyses were conducted to test several theoretically meaningful models. Mediation models revealed positive reciprocal longitudinal effects between aggressive behavior and moral disengagement. Aggressive behavior negatively predicted moral emotions, and moral disengagement was negatively associated with moral emotions over time. When testing competing models including all three variables in one model, no theoretical meaningful mediation process emerged: Instead, high moral disengagement predicted lower moral emotions but higher aggressive behavior over time. Results are discussed regarding their practical importance for prevention and intervention programs

Strong polarization-induced reduction of addition energies in single-molecule nanojunctions

We address polarization-induced renormalization of molecular levels in solid-state based single-molecule transistors and focus on an organic conjugate molecule where a surprisingly large reduction of the addition energy has been observed. We have developed a scheme that combines a self-consistent solution of a quantum chemical calculation with a realistic description of the screening environment. Our results indeed show a large reduction, and we explain this to be a consequence of both (a) a reduction of the electrostatic molecular charging energy and (b) polarization induced level shifts of the HOMO and LUMO levels. Finally, we calculate the charge stability diagram and explain at a qualitative level general features observed experimentally.Comment: 9 pages, 5 figure