317 research outputs found

    Rapid laser-induced photochemical conversion of sol–gel precursors to In2O3 layers and their application in thin-film transistors

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    We report the development of indium oxide (In2O3) transistors via a single step laser-induced photochemical conversion process of a sol–gel metal oxide precursor. Through careful optimization of the laser annealing conditions we demonstrated successful conversion of the precursor to In2O3 and its subsequent implementation in n-channel transistors with electron mobility up to 13 cm2 V−1 s−1. Importantly, the process does not require thermal annealing making it compatible with temperature sensitive materials such as plastic. On the other hand, the spatial conversion/densification of the sol–gel layer eliminates additional process steps associated with semiconductor patterning and hence significantly reduces fabrication complexity and cost. Our work demonstrates unambiguously that laser-induced photochemical conversion of sol–gel metal oxide precursors can be rapid and suitable for the manufacturing of large-area electronics

    End-to-end learning of multiple sequence alignments with differentiable Smith-Waterman

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    Abstract Motivation Multiple Sequence Alignments (MSAs) of homologous sequences contain information on structural and functional constraints and their evolutionary histories. Despite their importance for many downstream tasks, such as structure prediction, MSA generation is often treated as a separate pre-processing step, without any guidance from the application it will be used for. Results Here, we implement a smooth and differentiable version of the Smith-Waterman pairwise alignment algorithm that enables jointly learning an MSA and a downstream machine learning system in an end-to-end fashion. To demonstrate its utility, we introduce SMURF (Smooth Markov Unaligned Random Field), a new method that jointly learns an alignment and the parameters of a Markov Random Field for unsupervised contact prediction. We find that SMURF learns MSAs that mildly improve contact prediction on a diverse set of protein and RNA families. As a proof of concept, we demonstrate that by connecting our differentiable alignment module to AlphaFold2 and maximizing predicted confidence, we can learn MSAs that improve structure predictions over the initial MSAs. Interestingly, the alignments that improve AlphaFold predictions are self-inconsistent and can be viewed as adversarial. This work highlights the potential of differentiable dynamic programming to improve neural network pipelines that rely on an alignment and the potential dangers of optimizing predictions of protein sequences with methods that are not fully understood. Availability Our code and examples are available at: https://github.com/spetti/SMURF. Supplementary information Supplementary data are available at Bioinformatics online. </jats:sec

    Good Clinical Laboratory Practices Improved Proficiency Testing Performance at Clinical Trials Centers in Ghana and Burkina Faso

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    BACKGROUND: The recent drive towards accreditation of clinical laboratories in Africa by the World Health Organization-Regional Office for Africa (WHO-AFRO) and the U.S Government is a historic step to strengthen health systems, provide better results for patients and an improved quality of results for clinical trials. Enrollment in approved proficiency testing (PT) programs and maintenance of satisfactory performance is vital in the process of accreditation. Passing proficiency testing surveys has posed a great challenge to many laboratories across sub-Saharan Africa. Our study was aimed at identifying the causes of unsatisfactory PT results in clinical research laboratories conducting or planning to conduct malaria vaccine trials sponsored by the National Institutes of Health (NIH). METHODOLOGY: PT reports for 2009 and 2010 from the College of American Pathologists (CAP) for the laboratories were reviewed as part of the process. Errors accounting for unsatisfactory results were classified into clerical, methodological, technical, problem with PT materials, and random errors. A training program on good clinical laboratory practices (GCLP) was developed for each center to address areas for improvement. RESULTS: The major cause of PT failure in the four centers was methodological. The application of GCLP improved the success rate in the PT surveys from 58% in 2009 to 88% in 2010. It also decreased the error rate on PT by 35%. CONCLUSION: A previous report from the CAP- PT participating laboratories indicated that the major causes of error were clerical. These types of errors were predominantly made in laboratories in the US, with much more experience in quality control, and varied significantly from what we found. In our centers in sub-Saharan Africa, methodological errors, and not clerical errors, accounted for the vast majority of errors. A process was started for continuous improvement which has decreased methodological errors by 35%, but more improvement is needed

    High Cryptococcal Antigen Titers in Blood Are Predictive of Subclinical Cryptococcal Meningitis Among Human Immunodeficiency Virus-Infected Patients

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    Background High mortality rates among asymptomatic cryptococcal antigen (CrAg)–positive patients identified through CrAg screening, despite preemptive fluconazole treatment, may be due to undiagnosed cryptococcal meningitis. Methods Symptoms were reviewed in CrAg-positive patients identified by screening 19233 individuals with human immunodeficiency virus infection and CD4 cell counts <100/µL at 17 clinics and 3 hospitals in Johannesburg from September 2012 until September 2015, and at 2 hospitals until June 2016. Cerebrospinal fluid samples from 90 of 254 asymptomatic patients (35%) and 78 of 173 (45%) with headache only were analyzed for cryptococcal meningitis, considered present if Cryptococcus was identified by means of India ink microscopy, culture, or CrAg test. CrAg titers were determined with stored blood samples from 62 of these patients. The associations between blood CrAg titer, concurrent cryptococcal meningitis, and mortality rate were assessed. Results Cryptococcal meningitis was confirmed in 34% (95% confidence interval, 25%–43%; 31 of 90) of asymptomatic CrAg-positive patients and 90% (81%–96%; 70 of 78) with headache only. Blood CrAg titer was significantly associated with concurrent cryptococcal meningitis in asymptomatic patients (P 160 (sensitivity, 88.2%; specificity, 82.1%); the odds ratio for concurrent cryptococcal meningitis was 34.5 (95% confidence interval, 8.3–143.1; P < .001). Conclusions About a third of asymptomatic CrAg-positive patients have concurrent cryptococcal meningitis. More effective clinical assessment strategies and antifungal regimens are required for CrAg-positive patients, including investigation for cryptococcal meningitis irrespective of symptoms. Where it is not possible to perform lumbar punctures in all CrAg-positive patients, blood CrAg titers should be used to target those most at risk of cryptococcal meningitis
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