The identification of initial hits is a crucial stage in the drug discovery process. Although many projects adopt high-throughput screening of small-molecule libraries at this stage, there is ...significant potential for screening libraries of macromolecules created using chemical biology approaches. Not only can the production of the library be directly interfaced with a cell-based assay, but these libraries also require significantly fewer resources to generate and maintain. In this context, cyclic peptides are increasingly viewed as ideal scaffolds and have proven capability against challenging targets such as protein-protein interactions. Here we discuss a range of methods used for the creation of cyclic peptide libraries and detail examples of their successful implementation.
This article empirically demonstrates the use of fine resolution satellite-based aerosol optical depth (AOD) to develop time and space resolved estimates of ambient particulate matter (PM) ≤2.5 μm ...and ≤10 μm in aerodynamic diameters (PM
2.5
and PM
10
, respectively). AOD was computed at three different spatial resolutions, i.e., 2 km (means 2 km × 2 km area at nadir), 5 km, and 10 km, by using the data from MODerate Resolution Imaging Spectroradiometer (MODIS), aboard the Terra and Aqua satellites. Multiresolution AOD from MODIS (AOD
MODIS
) was compared with the in situ measurements of AOD by NASA's AErosol RObotic NETwork (AERONET) sunphotometer (AOD
AERONET
) at Bondville, IL, to demonstrate the advantages of the fine resolution AOD
MODIS
over the 10-km AOD
MODIS
, especially for air quality prediction. An instrumental regression that corrects AOD
MODIS
for meteorological conditions was used for developing a PM predictive model.
The 2-km AOD
MODIS
aggregated within 0.025° and 15-min intervals shows the best association with the in situ measurements of AOD
AERONET
. The 2-km AOD
MODIS
seems more promising to estimate time and space resolved estimates of ambient PM than the 10-km AOD
MODIS
, because of better location precision and a significantly greater number of data points across geographic space and time. Utilizing the collocated AOD
MODIS
and PM data in Cleveland, OH, a regression model was developed for predicting PM for all AOD
MODIS
data points. Our analysis suggests that the slope of the 2-km AOD
MODIS
(instrumented on meteorological conditions) is close to unity with the PM monitored on the ground. These results should be interpreted with caution, because the slope of AOD
MODIS
ranges from 0.52 to 1.72 in the site-specific models. In the cross validation of the overall model, the root mean square error (RMSE) of PM
10
was smaller (2.04 μg/m
3
in overall model) than that of PM
2.5
(2.5 μg/m
3
). The predicted PM in the AOD
MODIS
data (∼2.34 million data points) was utilized to develop a systematic grid of daily PM at 5-km spatial resolution with the aid of spatiotemporal Kriging.
Standardization of tumor assessment lays the foundation for validation of grading systems, permits reproducibility of oncologic studies among investigators, and increases confidence in the ...significance of study results. Currently, there is minimal methodological standardization for assessing tumors in veterinary medicine, with few attempts to validate published protocols and grading schemes. The current article attempts to address these shortcomings by providing standard guidelines for tumor assessment parameters and protocols for evaluating specific tumor types. More detailed information is available in the Supplemental Files, the intention of which is 2-fold: publication as part of this commentary, but more importantly, these will be available as “living documents” on a website (www.vetcancerprotocols.org), which will be updated as new information is presented in the peer-reviewed literature. Our hope is that veterinary pathologists will agree that this initiative is needed, and will contribute to and utilize this information for routine diagnostic work and oncologic studies. Journal editors and reviewers can utilize checklists to ensure publications include sufficient detail and standardized methods of tumor assessment. To maintain the relevance of the guidelines and protocols, it is critical that the information is periodically updated and revised as new studies are published and validated with the intent of providing a repository of this information. Our hope is that this initiative (a continuation of efforts published in this journal in 2011) will facilitate collaboration and reproducibility between pathologists and institutions, increase case numbers, and strengthen clinical research findings, thus ensuring continued progress in veterinary oncologic pathology and improving patient care.
Scientific and public interest relating to golf and health has increased recently. Players, potential players, the golf industry and facilities, and decision makers will benefit from a better ...understanding of how to realise potential health benefits and minimise health issues related to golf. We outline an International Consensus on Golf and Health. A systematic literature review informed the development of a survey. Utilising modified Delphi methods, an expert panel of 25 persons including public health and golf industry leaders, took part in serial surveys providing feedback on suggested items, and proposing new items. Predefined criteria for agreement determined whether each item was included within each survey round and in the final consensus. The working group identified 79 scientifically supportable statement items from literature review and discussions. Twenty-five experts (100%) completed all three rounds of surveys, rating each item, and suggesting modifications and/or new items for inclusion in subsequent surveys. After three rounds, 83 items achieved consensus with each with >75% agreement and <10% disagreement. These items are included in the final International Consensus on Golf and Health. The final consensus presented here can inform scientific knowledge, and action plans for (1) golfers and potential golfers, (2) golf facilities and the golf industry, and (3) policy and decision makers external to golf. These outputs, if widely adopted, will contribute to an improved understanding of golf and health, and aid these groups in making evidence-informed decisions to improve health and well-being.
Present GaN technology consists primarily of heteroepitaxial, lateral high electron mobility transistors; however, high-power devices would be much more efficiently manufactured with a vertical ...geometry due to better blocking voltage scaling. This technology has yet to be realized due to the inconsistency of GaN wafer properties. These inconsistencies can be detected with several long-range, non-destructive techniques including Raman spectroscopy, optical profilometry, and photoluminescence mapping. In particular, Raman spectroscopy is an effective tool for determining the carrier concentration of GaN substrates and whether the wafers are uniform or inhomogeneous. In this work, vertical
p
-
i
-
n
GaN diodes are fabricated using both uniform and inhomogeneous wafers determined by using the
A
1
Raman peak position to monitor carrier concentration. The inhomogeneous samples have regular patterns of varying conductivity as a result of electron-donating defects brought about by changes in crystal stress. By avoiding these defects, we have found that diode performance improves by increasing the +/− 10 V rectification ratio by up to a factor of 5X and reducing the 200 V reverse bias leakage current by several orders of magnitude. Using the higher quality substrates with uniform electron carrier concentrations can improve the rectification ratio by another order of magnitude.
Economic Growth and the Rise of Forests Foster, Andrew D.; Rosenzweig, Mark R.
The Quarterly journal of economics,
05/2003, Letnik:
118, Številka:
2
Journal Article
Recenzirano
Odprti dostop
Although forests have diminished globally over the past 400 years, forest cover has increased in some areas, including India in the last two decades. Aggregate time-series evidence on forest growth ...rates and income growth across countries and within India and a newly assembled data set that combines national household survey data, census data, and satellite images of land use in rural India at the village level over a 29-year period are used to explore the hypothesis that increases in the demand for forest products associated with income and population growth lead to forest growth. The evidence is consistent with this hypothesis, which also shows that neither the expansion of agricultural productivity nor rising wages in India increased local forest cover.
Diamonds containing the negatively charged nitrogen-vacancy centre are a promising system for room-temperature magnetometry. The combination of nano- and micro-diamond particles with optical fibres ...provides an option for deploying nitrogen-vacancy magnetometers in harsh and challenging environments. Here we numerically explore the coupling efficiency from nitrogen-vacancy centres within a diamond doped at the core/clad interface across a range of commercially available fibre types so as to inform the design process for a diamond in fibre magnetometers. We determine coupling efficiencies from nitrogen-vacancy centres to the guided modes of a step-index fibre and predict the optically detected magnetic resonance (ODMR) generated by a ensemble of four nitrogen-vacancy centres in this hybrid fibre system. Our results show that the coupling efficiency is enhanced with a high refractive index difference between the fibre core and cladding and depends on the radial position of the nitrogen-vacancy centres in the fibre core. Our ODMR simulations show that due to the preferential coupling of the nitrogen-vacancy emission to the fibre guided modes, certain magnetometry features such as ODMR contrast can be enhanced and lead to improved sensitivity in such diamond-fibre systems, relative to conventional diamond only ensemble geometries.
Large-language models (LLMs) such as GPT-4 caught the interest of many scientists. Recent studies suggested that these models could be useful in chemistry and materials science. To explore these ...possibilities, we organized a hackathon. This article chronicles the projects built as part of this hackathon. Participants employed LLMs for various applications, including predicting properties of molecules and materials, designing novel interfaces for tools, extracting knowledge from unstructured data, and developing new educational applications. The diverse topics and the fact that working prototypes could be generated in less than two days highlight that LLMs will profoundly impact the future of our fields. The rich collection of ideas and projects also indicates that the applications of LLMs are not limited to materials science and chemistry but offer potential benefits to a wide range of scientific disciplines.
We report the findings of a hackathon focused on exploring the diverse applications of large language models in molecular and materials science.
Studies of clinical populations that combine MRI data generated at multiple sites are increasingly common. The Canadian Biomarker Integration Network in Depression (CAN-BIND; www.canbind.ca) is a ...national depression research program that includes multimodal neuroimaging collected at several sites across Canada. The purpose of the current paper is to provide detailed information on the imaging protocols used in a number of CAN-BIND studies. The CAN-BIND program implemented a series of platform-specific MRI protocols, including a suite of prescribed structural and functional MRI sequences supported by real-time monitoring for adherence and quality control. The imaging data are retained in an established informatics and databasing platform. Approximately 1300 participants are being recruited, including almost 1000 with depression. These include participants treated with antidepressant medications, transcranial magnetic stimulation, cognitive behavioural therapy and cognitive remediation therapy. Our ability to analyze the large number of imaging variables available may be limited by the sample size of the substudies. The CAN-BIND program includes a multimodal imaging database supported by extensive clinical, demographic, neuropsychological and biological data from people with major depression. It is a resource for Canadian investigators who are interested in understanding whether aspects of neuroimaging — alone or in combination with other variables — can predict the outcomes of various treatment modalities.
In the presence of imperfect information, voluntary certification can provide an important complement to mandatory inspections as a basis for environmental regulation in low income countries. Using ...data from Mexico's Clean Industry Program, we show that patterns of compliance and certification by sector are consistent with a model in which selection into the voluntary program permits more efficient targeting of regulator effort. As expected given the informational role played by certification in the model, we also find evidence, for a sample of publicly traded firms, of positive stock price deviations linked to the announcement of certification. PUBLICATION ABSTRACT
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