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DNA-encoded library technology grants access to nearly infinite opportunities to explore the chemical structure space for drug discovery. Successful navigation depends on the design and synthesis of libraries with appropriate physicochemical properties (PCPs) and structural diversity while aligning with practical considerations. To this end, we analyze combinatorial library design constraints including the number of chemistry cycles, bond construction strategies, and building block (BB) class selection in pursuit of ideal library designs. We compare two-cycle library designs (amino acid + carboxylic acid, primary amine + carboxylic acid) in the context of PCPs and chemical space coverage, given different BB selection strategies and constraints. We find that broad availability of amines and acids is essential for enabling the widest exploration of chemical space. Surprisingly, cost is not a driving factor, and virtually, the same chemical space can be explored with budget BBs.

This report seeks to inform the potential for motor systems to support decarbonization by estimating their potential energy, electricity cost, and CO2 emissions reduction potential from adoption of proven energy efficiency actions and advanced technologies. This is the third and final report in a series of reports disseminating the findings of the U.S. Department of Energy’s (DOE’s) Motor System Market Assessment (MSMA). The MSMA and this report focus on polyphase motor systems greater than or equal to 1 horsepower (hp) in the industrial and commercial sectors. In the U.S. Industrial and Commercial Motor System Market Assessment Report Volume 1: Characteristics of the Installed Base (Volume 1 report), it was determined that these motor systems consume more than 1,000 terawatt-hours (TWh) annually. This equates to 29% of the U.S. electric grid load and results in 765 million metric tons (MMT) of CO2 emissions and $166 billion in electricity costs. This report finds that substantial reductions to these energy, cost, and emissions impacts are possible, with three areas of significant opportunity being (1) improved load matching, (2) replacing older inefficient motors with more efficient motors, and (3) improving the condition of fluid (e.g., air, water, compressed air) distribution systems.

Mouse knockouts facilitate the study ofgene functions. Often, multiple abnormal phenotypes are induced when a gene is inactivated. The International Mouse Phenotyping Consortium (IMPC) has generated thousands of mouse knockouts and catalogued their phenotype data. We have acquired metabolomics data from 220 plasma samples from 30 unique mouse gene knockouts and corresponding wildtype mice from the IMPC. To acquire comprehensive metabolomics data, we have used liquid chromatography (LC) combined with mass spectrometry (MS) for detecting polar and lipophilic compounds in an untargeted approach. We have also used targeted methods to measure bile acids, steroids and oxylipins. In addition, we have used gas chromatography GC-TOFMS for measuring primary metabolites. The metabolomics dataset reports 832 unique structurally identified metabolites from 124 chemical classes as determined by ChemRICH software. The GCMS and LCMS raw data files, intermediate and finalized data matrices, R-Scripts, annotation databases, and extracted ion chromatograms are provided in this data descriptor. The dataset can be used for subsequent studies to link genetic variants with molecular mechanisms and phenotypes.

Background: Current estimates of dementia and Alzheimer's disease incidence and prevalence are required to understand the health needs of the elderly. Objective: We used two Australia cohort studies, administrative datasets, and data linkage techniques to estimate dementia rates in Australia. Methods: The study used Australian Longitudinal Study on Women's Health and the Health in Men Cohort Study. Records of dementia were obtained from linked sources and incidence and prevalence estimates were produced. Capture-recapture methods were used to estimate numbers of dementia cases not identified through data linkage. Results: There were 3399 (28.5%) men with dementia identified from any source and 3767 (34.8%) women. Rates of dementia incidence and prevalence were similar between sexes but were raised in men once estimates of unidentified cases were included. Conclusions: Cohort studies and linked administrative data can be used together to produce current estimates of dementia prevalence and incidence comparable to other population estimates. [ABSTRACT FROM AUTHOR]

Visceral hypersensitivity, a hallmark of disorders of the gut‐brain axis, is associated with exposure to early‐life stress (ELS). Activation of neuronal β3‐adrenoceptors (AR) has been shown to alter central and peripheral levels of tryptophan and reduce visceral hypersensitivity. In this study, we aimed to determine the potential of a β3‐AR agonist in reducing ELS‐induced visceral hypersensitivity and possible underlying mechanisms. Here, ELS was induced using the maternal separation (MS) model, where Sprague Dawley rat pups were separated from their mother in early life (postnatal day 2–12). Visceral hypersensitivity was confirmed in adult offspring using colorectal distension (CRD). CL‐316243, a β3‐AR agonist, was administered to determine anti‐nociceptive effects against CRD. Distension‐induced enteric neuronal activation as well as colonic secretomotor function were assessed. Tryptophan metabolism was determined both centrally and peripherally. For the first time, we showed that CL‐316243 significantly ameliorated MS‐induced visceral hypersensitivity. Furthermore, MS altered plasma tryptophan metabolism and colonic adrenergic tone, while CL‐316243 reduced both central and peripheral levels of tryptophan and affected secretomotor activity in the presence of tetrodotoxin. This study supports the beneficial role of CL‐316243 in reducing ELS‐induced visceral hypersensitivity, and suggests that targeting the β3‐AR can significantly influence gut‐brain axis activity through modulation of enteric neuronal activation, tryptophan metabolism, and colonic secretomotor activity which may synergistically contribute to offsetting the effects of ELS. [ABSTRACT FROM AUTHOR]

Distributions of the natural radionuclide 210Po and its grandparent 210Pb along the GP15 Pacific Meridional Transect provide information on scavenging rates of reactive chemical species throughout the water column and fluxes of particulate organic carbon (POC) from the primary production zone (PPZ). 210Pb is in excess of its grandparent 226Ra in the upper 400–700 m due to the atmospheric flux of 210Pb. Mid‐water 210Pb/226Ra activity ratios are close to radioactive equilibrium (1.0) north of ∼20°N, indicating slow scavenging, but deficiencies at stations near and south of the equator suggest more rapid scavenging associated with a "particle veil" located at the equator and hydrothermal processes at the East Pacific Rise. Scavenging of 210Pb and 210Po is evident in the bottom 500–1,000 m at most stations due to enhanced removal in the nepheloid layer. Deficits in the PPZ of 210Po (relative to 210Pb) and 210Pb (relative to 226Ra decay and the 210Pb atmospheric flux), together with POC concentrations and particulate 210Po and 210Pb activities, are used to calculate export fluxes of POC from the PPZ. 210Po‐derived POC fluxes on large (>51 μm) particles range from 15.5 ± 1.3 mmol C/m2/d to 1.5 ± 0.2 mmol C/m2/d and are highest in the Subarctic North Pacific; 210Pb‐derived fluxes range from 6.7 ± 1.8 mmol C/m2/d to 0.2 ± 0.1 mmol C/m2/d. Both 210Po‐ and 210Pb‐derived POC fluxes are greater than those calculated using the 234Th proxy, possibly due to different integration times of the radionuclides, considering their different radioactive mean‐lives and scavenging mean residence times. Key Points: 210Po and 210Pb distributions along 152°W yield scavenging rates and fluxes of particulate organic carbon (POC) from the water columnResidence times of 210Pb with respect to scavenging in the primary production zone (PPZ) are 0.8 to 15 y. Values for 210Po are 0.2–0.5 yExport of POC from the PPZ ranges from 15.5 to 1.5 mmol C/m2/d using 210Po and 6.7 to 0.2 mmol C/m2/d using 210Pb [ABSTRACT FROM AUTHOR]

The New Haven Local Section of the American Chemical Society held a virtual version of its annual Student Research Symposium prompted by the COVID-19 pandemic. A combination of YouTube, Google Drive, Open Broadcaster Software, and Zoom was utilized to hold the symposium which included juried oral and poster presentations. While our aim was to preserve as much of the in-person experience as possible despite the crisis, we found some very encouraging advantages to the virtual format as we designed it. These included reduced presenter fatigue, more substantive one-on-one interactions between student and senior researchers, expanded accessibility for students, faculty, and the general public, and the virtual symposium being a fraction of the cost of an in-person symposium. The details of this experience and advice for its application in the wider educational community are reported.

Purpose Methods Results Conclusion Level of Evidence This study aimed to compare the range of motion (ROM), surgical outcomes, and patient‐reported outcome measures (PROMs) following anterior cruciate ligament (ACL) reconstruction outcomes in patients 60 years or older at the time of surgery to 40‐ to 59‐year‐old patients.In this retrospective cohort study from 2015 to 2022, a 3:1 propensity match was performed to match late adulthood patients (≥60 years old) undergoing ACL reconstruction with middle adulthood (40–59 years old) ACL reconstruction patients. Patients were matched based on sex, ACL graft utilized and concomitant procedures performed during ACL reconstruction. Statistical analysis compared demographics, preoperative injury management, surgical outcomes, PROMs, and minimal clinical important difference (MCID) and substantial clinical benefit (SCB) achievement rates for all ACL reconstruction patients included.Twenty late adulthood and 60 middle adulthood patients who underwent ACL reconstruction were included in the final cohort. Patients who were 60 years or older experienced no difference in reoperation rate (n.s.), incidence of retears (n.s.) or ROM (n.s.) at 1 year post‐operatively. There were also no differences in International Knee Documentation Committee (ΔIKDC) (31.3 ± 19.1 vs. 34.2 ± 18.2, n.s.) or ΔPCS‐12 (12.4 ± 9.8 vs. 12.9 ± 10.8, n.s.) scores at 1 year post‐operatively. Furthermore, the younger and older patient cohorts demonstrated similar rates of achieving the MCID (80.0% vs. 83.3%, n.s.) and SCB (50.0% vs. 61.7%, n.s.) scores for IKDC.Patients 60 years or older and 40‐ to 59‐year‐old patients demonstrated similar outcomes after undergoing ACL reconstruction with allograft. This study concludes that ACL reconstruction in late adulthood can still be a successful treatment option and should allow surgeons to feel more comfortable when performing indicated surgical intervention for older patients who experience an ACL tear.Level III, Therapeutic III, retrospective cohort study. [ABSTRACT FROM AUTHOR]