As the capability of mass spectrometry-based proteomics has matured, tens of thousands of peptides can be measured simultaneously, which has the benefit of offering a systems view of protein expression. However, a major challenge is that with an increase in throughput, protein quantification estimation from the native measured peptides has become a computational task. A limitation to existing computationally-driven protein quantification methods is that most ignore protein variation, such as alternate splicing of the RNA transcript and post-translational modifications or other possible proteoforms, which will affect a significant fraction of the proteome. The consequence of this assumption is that statistical inference at the protein level, and consequently downstream analyses, such as network and pathway modeling, have only limited power for biomarker discovery. Here, we describe a Bayesian model (BP-Quant) that uses statistically derived peptides signatures to identify peptides that are outside the dominant pattern, or the existence of multiple over-expressed patterns to improve relative protein abundance estimates. It is a research-driven approach that utilizes the objectives of the experiment, defined in the context of a standard statistical hypothesis, to identify a set of peptides exhibiting similar statistical behavior relating to a protein. This approach infers that changes in relative protein abundance can be used as a surrogate for changes in function, without necessarily taking into account the effect of differential post-translational modifications, processing, or splicing in altering protein function. We verify the approach using a dilution study from mouse plasma samples and demonstrate that BP-Quant achieves similar accuracy as the current state-of-the-art methods at proteoform identification with significantly better specificity. BP-Quant is available as a MatLab ® and R packages at https://github.com/PNNL-Comp-Mass-Spec/BP-Quant.

DNA polymerase from bacteriophage T7 undergoes large, substrate-induced conformational changes that are thought to account for high replication fidelity, but prior studies were adversely affected by mutations required to construct a Cys-lite variant needed for site-specific fluorescence labeling. Here we have optimized the direct incorporation of a fluorescent un-natural amino acid, (7-hydroxy-4-coumarin-yl)-ethylglycine, using orthogonal amber suppression machinery in Escherichia coli. MS methods verify that the unnatural amino acid is only incorporated at one position with minimal background. We show that the single fluorophore provides a signal to detect nucleotide-induced conformational changes through equilibrium and stopped-flow kinetic measurements of correct nucleotide binding and incorporation. Pre-steady-state chemical quench methods show that the kinetics and fidelity of DNA replication catalyzed by the labeled enzyme are largely unaffected by the unnatural amino acid. These advances enable rigorous analysis to establish the kinetic and mechanistic basis for high-fidelity DNA replication.

A new technique helps anesthesiologists track changes in states of consciousness

Idaho officials asked a U.S. Supreme Court justice to block an injunction that allows a group backing an education ballot initiative to collect electronic signatures because of COVID-19.

Global exchange of information on compliance with national, regional, and international fisheries laws and regulations governing sustainable fishing is now possible with the launch of the Global [...]

Carleton University will soon need to take 'significant measures' to balance its budget, according to a letter the Ottawa institution recently sent out to staff and students.

New product for intensive care units automates costly and time-consuming nursing work

Native-language assessments may more fully reflect what English-language learners know and can do academically after months away from school. But not all states offer them.

Idaho officials asked a U.S. Supreme Court justice to block an injunction that allows a group backing an education ballot initiative to collect electronic signatures because of COVID-19.

DOVER, DE (Jan. 30, 2023) –   The Delaware Division of Public Health (DPH) has been notified of multiple positive cases of COVID-19 that could be related to several in-person events last week in and around Legislative Hall. Out of an abundance of caution, DPH is offering recommendations to those planning to attend Joint Finance Committee hearings beginning […]

NEW CASTLE (July 12, 2023) – The Delaware Department of Health and Social Services (DHSS) announced today enhancements to the CostAware website, designed to help Delawareans understand how their health care dollars are spent by comparing the variation of average costs for different episodes of care and medical services based on actual medical claims in Delaware. […]

In our fast changing, increasingly digital world, building a strong customer relationship is the lynchpin to building a great business. The stakes are even higher now as global disruptions occur with alarming regularity—be it political unrest, economic meltdowns or a pandemic. A new, global study called Experience 2030: The Future [...]

4 tips for evolving your customer experience measurement was published on Customer Intelligence Blog.

Join this insightful on-demand webinar event "SI/PI Simulation and Measurement Correlation Forum" available through Signal Integrity Journal that features industry expert presentations ranging from chip to package to complex board designs.(read more)

Check here each week to keep up with the latest from John MacArthur's pulpit at Grace Community Church.

A new technique uses glowing molecules, laser light and microscopes to measure distances as minuscule as 0.1 nanometres – the width of a typical atom

Title: How to Use Ketone Strips to Measure Ketosis
Category: Health and Living
Created: 8/24/2022 12:00:00 AM
Last Editorial Review: 8/24/2022 12:00:00 AM

Simplified methods of acquisition and quantification would facilitate the use of synaptic density imaging in multicenter and longitudinal studies of Alzheimer disease (AD). We validated a simplified tissue-to-reference ratio method using SUV ratios (SUVRs) for estimating synaptic density with [¹¹C]UCB-J PET. Methods: Participants included 31 older adults with AD and 16 with normal cognition. The distribution volume ratio (DVR) using simplified reference tissue model 2 was compared with SUVR at short scan windows using a whole-cerebellum reference region. Results: Synaptic density was reduced in AD participants using DVR or SUVR. SUVR using later scan windows (60–90 or 70–90 min) was minimally biased, with the strongest correlation with DVR. Effect sizes using SUVR at these late time windows were minimally reduced compared with effect sizes with DVR. Conclusion: A simplified tissue-to-reference method may be useful for multicenter and longitudinal studies seeking to measure synaptic density in AD.

BACKGROUND AND PURPOSE:

Alterations of the basilar artery (BA) anatomy have been suggested as a possible MRA feature of Fabry disease (FD). Nonetheless, no information about their clinical or pathophysiologic correlates is available, limiting our comprehension of the real impact of vessel remodeling in FD.

Scotland was second out of 12 UK nations and regions on one key measure

While many states focused on issues like abortion and immigration throughout this election cycle, voters in California and Colorado approved tougher crime laws.

The Indian pharmaceutical industry is advocating for enhanced fire safety measures and improved insurance coverage for employees working in pharmaceutical facilities.

A research team at the University of California San Diego have developed a smartphone attachment that can provide information on changes in pupil size, which can be used to assess neurological phenomena, such as traumatic brain injury and Alzheimer’s disease. Such changes in pupil size have been difficult to characterize in the past in those […]

Nov 17, 2022

The speakers included Yale Law School professor Harold H. Koh ’75, and Patrick W. Pearsall, Director of the International Claims and Reparations Project at Columbia Law School. Koh and Pearsall discussed their experiences representing Ukraine in legal proceedings against Russia before the International Court of Justice.

Kamala Harris is blasting Donald Trump for vowing to protect women whether they “like it or not” at the same time he is calling for Republican Liz Cheney to be shot in the face. We get response from The Nation's abortion access correspondent Amy Littlefield and talk about 10 states with abortion rights on the ballot, including Arizona, Nevada, Florida, South Dakota and Missouri. Trump's remarks are a “succinct and clear definition of patriarchy,” says Littlefield. She argues the 2024 election will be decided in large part by white women and whether they will vote for abortion rights. Trump is “laying out the bargain that white patriarchy has offered for white women in this country,” says Littlefield. “He is saying, 'White women, we will protect you from Brown and Black men.'”

In a major piece for Mother Jones magazine on “Why Ballot Measures Are Democracy’s Last Line of Defense,” voting rights correspondent Ari Berman discusses abortion ballot measures in 10 states, important down-ballot races in Wisconsin and elsewhere, and the movement to abolish or reform the Electoral College.

On May 13, 2020, the Indian Government announced new tax relief measures and administrative concessions.

The French Government has presented to the Council of Ministers a third amendment to the Finance Bill for 2020, which provides additional support for businesses affected by the COVID-19 outbreak.

In two recent speeches, French Finance Minister Bruno Le Maire has outlined plans to extend COVID-19 supports for French businesses.

On May 21, 2020, the Italian Revenue Agency issued a summary of additional tax measures in Decree 34/2020, which are intended to further support taxpayers affected by the COVID-19 virus.

The number of dengue cases in Patna has been rising over the past few days, with 15 to 20 people admitted to hospitals daily. On Thursday, the city commemorated

On May 15, 2020, the United States House of Representatives approved the HEROES Act, which amends previous COVID-19-related stimulus legislation by changing loss carryback rules and providing further tax support for businesses and individuals.

The COVID (and) #8208;19 pandemic developed new patient care circumstances that may have grown nurses moral distress, including COVID (and) #8208;19 transmission

The Tamil Nadu government's health department has initiated increased surveillance measures in several villages of Coimbatore District to prevent the spread of the medlinkWest Nile Virus/medlink.

A cost-efficient digital assay developed measures the presence of HIV in single drop of blood. The findings of the study are published in i ACS Nano /i (!--ref1--).

A study on sustained mammal-to-mammal transmission of medlinkbird flu/medlink across various species reveals that global control measures are falling short.

Berlin ; Boston : De Gruyter, [2023]

Fisher, Lalena, author, illustrator

Cambridge, Mass. : National Bureau of Economic Research 2023