Design of linear and nonlinear control systems via state variable feedback, with applications in nuclear reactor control

Linear and nonlinear control systems via state variable feedback with applications in nuclear reactor contro

Selective Modulation Interferometric Spectrometer (SIMS) Technique Applied to Background Suppression

A method of using the SIMS (the Selective Modulation Interferometric Spectrometer) to measure the difference between the spectral content of two optical beams is given. The differ - encing is done optically; that is, the modulated detector signal is directly proportional to the difference between the two spectra being compared. This optical differencing minimizes the dynamic -range requirements of the electronics and requires only a simple modification of the basic cyclic SIMS spectrometer. This technique can be used to suppress background radiation for the enhancement of target detection and tracking. Laboratory measurements demonstrating the application of this technique are reported

Tunable Optical Filter Using an Interferometer for Selective Modulation

Using the selective modulation interferometric spectrometer (SIMS) as a tunable filter is proposed. This tunable filter can have a large optical throughput and a resolving power on the order of a few thousand. A basic explanation of the operation of this filter is given with an emphasis on the similarities and differences between it and a Fourier spectrometer. Several equations that have been found to be particularly useful in designing, operating, and calibrating this filter are presented. The construction and operation of a tunable filter prototype are reported

Protein Design with Guided Discrete Diffusion

A popular approach to protein design is to combine a generative model with a discriminative model for conditional sampling. The generative model samples plausible sequences while the discriminative model guides a search for sequences with high fitness. Given its broad success in conditional sampling, classifier-guided diffusion modeling is a promising foundation for protein design, leading many to develop guided diffusion models for structure with inverse folding to recover sequences. In this work, we propose diffusioN Optimized Sampling (NOS), a guidance method for discrete diffusion models that follows gradients in the hidden states of the denoising network. NOS makes it possible to perform design directly in sequence space, circumventing significant limitations of structure-based methods, including scarce data and challenging inverse design. Moreover, we use NOS to generalize LaMBO, a Bayesian optimization procedure for sequence design that facilitates multiple objectives and edit-based constraints. The resulting method, LaMBO-2, enables discrete diffusions and stronger performance with limited edits through a novel application of saliency maps. We apply LaMBO-2 to a real-world protein design task, optimizing antibodies for higher expression yield and binding affinity to several therapeutic targets under locality and developability constraints, attaining a 99% expression rate and 40% binding rate in exploratory in vitro experiments

MYOD1 involvement in myopathy

[Excerpt] Introduction Myogenic Differentiation 1 (MYOD1) encodes a transcription factor that plays an important role in myogenic determination into mature skeletal muscle [1]. The first loss-of-function mutation of MYOD1 in humans was described in three siblings with perinatal lethal fetal akinesia [2].[...]We thank the individual and family. Funding was provided by The Fonds de recherche du Québec - Santé (FRQS) and Canadian Institutes of Health Research (CIHR) to P.M.C., Fundação para a Ciência e Tecnologia (FCT) with the fellowship SFRH/BD/84650/2010 to F.L. and Groupe Pasteur Mutualité Foundation (GPM Foundation) to M.M.info:eu-repo/semantics/publishedVersio

The impact of socially-accountable, community-engaged medical education on graduates in the Central Philippines: implications for the global rural medical workforce

Introduction: Developing and retaining a high quality medical workforce, especially within low-resource countries has been a world-wide challenge exacerbated by a lack of medical schools, the maldistribution of doctors towards urban practice, health system inequities, and training doctors in tertiary centers rather than in rural communities. Aim: To describe the impact of socially-accountable health professional education on graduates; specifically: their motivation towards community-based service, preparation for addressing local priority health issues, career choices, and practice location. Methods: Cross-sectional survey of graduates from two medical schools in the Philippines: the University of Manila-School of Health Sciences (SHS-Palo) and a medical school with a more conventional curriculum. Results: SHS-Palo graduates had significantly (p < 0.05) more positive attitudes to community service. SHS-Palo graduates were also more likely to work in rural and remote areas (p < 0.001) either at district or provincial hospitals (p = 0.032) or in rural government health services (p < 0.001) as Municipal or Public Health Officers (p < 0.001). Graduates also stayed longer in both their first medical position (p = 0.028) and their current position (p < 0.001). Conclusions: SHS-Palo medical graduates fulfilled a key aim of their socially-accountable institution to develop a health professional workforce willing and able, and have a commitment to work in underserved rural communties

The MRN complex is transcriptionally regulated by MYCN during neural cell proliferation to control replication stress

The MRE11/RAD50/NBS1 (MRN) complex is a major sensor of DNA double strand breaks, whose role in controlling faithful DNA replication and preventing replication stress is also emerging. Inactivation of the MRN complex invariably leads to developmental and/or degenerative neuronal defects, the pathogenesis of which still remains poorly understood. In particular, NBS1 gene mutations are associated with microcephaly and strongly impaired cerebellar development, both in humans and in the mouse model. These phenotypes strikingly overlap those induced by inactivation of MYCN, an essential promoter of the expansion of neuronal stem and progenitor cells, suggesting that MYCN and the MRN complex might be connected on a unique pathway essential for the safe expansion of neuronal cells. Here, we show that MYCN transcriptionally controls the expression of each component of the MRN complex. By genetic and pharmacological inhibition of the MRN complex in a MYCN overexpression model and in the more physiological context of the Hedgehog-dependent expansion of primary cerebellar granule progenitor cells, we also show that the MRN complex is required for MYCN-dependent proliferation. Indeed, its inhibition resulted in DNA damage, activation of a DNA damage response, and cell death in a MYCN- and replication-dependent manner. Our data indicate the MRN complex is essential to restrain MYCN-induced replication stress during neural cell proliferation and support the hypothesis that replication-born DNA damage is responsible for the neuronal defects associated with MRN dysfunctions.Cell Death and Differentiation advance online publication, 12 June 2015; doi:10.1038/cdd.2015.81

Optimal strategy to identify incidence of diagnostic of diabetes using administrative data

<p>Abstract</p> <p>Background</p> <p>Accurate estimates of incidence and prevalence of the disease is a vital step toward appropriate interventions for chronic disease like diabetes. A growing body of scientific literature is now available on producing accurate information from administrative data. Advantages of use of administrative data to determine disease incidence include feasibility, accessibility and low cost, but straightforward use of administrative data can produce biased information on incident cases of chronic disease like diabetes. The present study aimed to compare criteria for the selection of diabetes incident cases in a medical administrative database.</p> <p>Methods</p> <p>An exhaustive retrospective cohort of diabetes cases was constructed for 2002 using the Canadian National Diabetes Surveillance System case definition (one hospitalization or two physician claims with a diagnosis of diabetes over a 2-year period) with the Quebec health service database. To identify previous occurrence of diabetes in the database, a five-year observation period was evaluated using retrograde survival function and kappa agreement. The use of NDSS case definition to identify incident cases was compared to a single occurrence of an ICD-9 code 250 in the records using the McNemar test.</p> <p>Results</p> <p>Retrograde survival function showed that the probability of being a true incident case after a 5-year diabetes-free observation period was almost constant and near 0.14. Agreement between 10 years (maximum period) and 5 years and more diabetes-free observation periods were excellent (kappa > 0.9). Respectively 41,261 and 37,473 incident cases were identified using a 5-year diabetes-free observation period with NDSS definition and using a single ICD-9 code 250.</p> <p>Conclusion</p> <p>A 5-year diabetes-free observation period was a conservative time to identify incident cases in an administrative database using one ICD-9 code 250 record.</p