Analog VLSI circuit design of spike-timing-dependent synaptic plasticity

Thesis (M. Eng.)--Massachusetts Institute of Technology, Dept. of Electrical Engineering and Computer Science, 2008.Cataloged from PDF version of thesis.Includes bibliographical references (p. 61-63).Synaptic plasticity is the ability of a synaptic connection to change in strength and is believed to be the basis for learning and memory. Currently, two types of synaptic plasticity exist. First is the spike-timing-dependent-plasticity (STDP), a timing-based protocol that suggests that the efficacy of synaptic connections is modulated by the relative timing between presynaptic and postsynaptic stimuli. The second type is the Bienenstock-Cooper-Munro (BCM) learning rule, a classical ratebased protocol which states that the rate of presynaptic stimulation modulates the synaptic strength. Several theoretical models were developed to explain the two forms of plasticity but none of these models came close in identifying the biophysical mechanism of plasticity. Other studies focused instead on developing neuromorphic systems of synaptic plasticity. These systems used simple curve fitting methods that were able to reproduce some types of STDP but still failed to shed light on the biophysical basis of STDP. Furthermore, none of these neuromorphic systems were able to reproduce the various forms of STDP and relate them to the BCM rule. However, a recent discovery resulted in a new unified model that explains the general biophysical process governing synaptic plasticity using fundamental ideas regarding the biochemical reactions and kinetics within the synapse. This brilliant model considers all types of STDP and relates them to the BCM rule, giving us a fresh new approach to construct a unique system that overcomes all the challenges that existing neuromorphic systems faced. Here, we propose a novel analog verylarge- scale-integration (aVLSI) circuit that successfully and accurately captures the whole picture of synaptic plasticity based from the results of this latest unified model. Our circuit was tested for all types of STDP and for each of these tests, our design was able to reproduce the results predicted by the new-found model. Two inputs are required by the system, a glutamate signal that carries information about the presynaptic stimuli and a dendritic action potential signal that contains information about the postsynaptic stimuli. These two inputs give rise to changes in the excitatory postsynaptic current which represents the modifiable synaptic efficacy output. Finally, we also present several techniques and alternative circuit designs that will further improve the performance of our neuromorphic system.by Joshua Jen C. Monzon.M.Eng

MTBVAC vaccine is safe, immunogenic and confers protective efficacy against Mycobacterium tuberculosis in newborn mice

Development of novel more efficient preventive vaccines against tuberculosis (TB) is crucial to achieve TB eradication by 2050, one of the Millennium Development Goals (MDG) for the current century. MTBVAC is the first and only live attenuated vaccine based on a human isolate of Mycobacterium tuberculosis developed as BCG-replacement strategy in newborns that has entered first-in-human adult clinical trials. In this work, we characterize the safety, immunogenicity and protective efficacy of MTBVAC in a model of newborn C57/BL6 mice. Our data clearly indicate that MTBVAC is safe for newborn mice, and does not affect animal growth or organ development. In addition, MTBVAC-vaccinated mice at birth showed enhanced immunogenicity and better protection against M. tuberculosis challenge in comparison with BCG

Lean production management model under the change management approach to reduce order fulfillment times for Peruvian textile SMEs

Currently, small- and medium-sized enterprises face order fulfillment issues, thus generating reduced service levels. In addition, these companies are usually not aware of the importance of continuous improvement tools or of training staff as a mitigation strategy for this situation. Within this framework, the authors performed a literature review to compile production models through which downtimes could be reduced. The production model designed therefrom comprises Lean Manufacturing and work study tools within a Change Management approach. This design focuses on model implementation by small companies without requiring large investment, cutting-edge technology, or qualified personnel. Finally, an application case study was conducted in a small textile manufacturing company located at the Gamarra Fashion Center in Lima, Peru. The results that were reported revealed that late order fulfillment instances reduced by up to 18%, which had an impact on downtimes, unnecessary movements, and in-process inventory levels, thus increasing productivity by 85%

Guidance of sentinel lymph node biopsy decisions in patients with T1-T2 melanoma using gene expression profiling.

AIM: Can gene expression profiling be used to identify patients with T1-T2 melanoma at low risk for sentinel lymph node (SLN) positivity? PATIENTS & METHODS: Bioinformatics modeling determined a population in which a 31-gene expression profile test predicted \u3c5% SLN positivity. Multicenter, prospectively-tested (n = 1421) and retrospective (n = 690) cohorts were used for validation and outcomes, respectively. RESULTS: Patients 55-64 years and ≥65 years with a class 1A (low-risk) profile had SLN positivity rates of 4.9% and 1.6%. Class 2B (high-risk) patients had SLN positivity rates of 30.8% and 11.9%. Melanoma-specific survival was 99.3% for patients ≥55 years with class 1A, T1-T2 tumors and 55.0% for class 2B, SLN-positive, T1-T2 tumors. CONCLUSION: The 31-gene expression profile test identifies patients who could potentially avoid SLN biopsy

Ensembles from Ordered and Disordered Proteins Reveal Similar Structural Constraints during Evolution

The conformations accessible to proteins are determined by the inter-residue interactions between amino acid residues. During evolution, structural constraints that are required for protein function providing biologically relevant information can exist. Here, we studied the proportion of sites evolving under structural constraints in two very different types of ensembles, those coming from ordered and disordered proteins. Using a structurally constrained model of protein evolution, we found that both types of ensembles show comparable, near 40%, number of positions evolving under structural constraints. Among these sites, ~ 68% are in disordered regions and ~ 57% of them show long-range inter-residue contacts. Also, we found that disordered ensembles are redundant in reference to their structurally constrained evolutionary information and could be described on average with ~ 11 conformers. Despite the different complexity of the studied ensembles and proteins, the similar constraints reveal a comparable level of selective pressure to maintain their biological functions. These results highlight the importance of the evolutionary information to recover meaningful biological information to further characterize conformational ensembles.Fil: Marchetti, Julia. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Monzón, Alexander. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología; Argentina. Università di Padova; Italia. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Tosatto, Silvio C.E.. Università di Padova; ItaliaFil: Parisi, Gustavo Daniel. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Fornasari, Maria Silvina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Spin Injection in a Ballistic Two-Dimensional Electron Gas

We explore electrically injected, spin polarized transport in a ballistic two-dimensional electron gas. We augment the Buettiker-Landauer picture with a simple, but realistic model for spin-selective contacts to describe multimode reservoir-to-reservoir transport of ballistic spin 1/2 particles. Clear and unambiguous signatures of spin transport are established in this regime, for the simplest measurement configuration that demonstrates them directly. These new effects originate from spin precession of ballistic carriers; they exhibit strong dependence upon device geometry and vanish in the diffusive limit. Our results have important implications for prospective ``spin transistor'' devices.Comment: Submitted to Phys. Rev. Let

Critical assessment of protein intrinsic disorder prediction (CAID) - Results of round 2

Protein intrinsic disorder (ID) is a complex and context-dependent phenomenon that covers a continuum between fully disordered states and folded states with long dynamic regions. The lack of a ground truth that fits all ID flavors and the potential for order-to-disorder transitions depending on specific conditions makes ID prediction challenging. The CAID2 challenge aimed to evaluate the performance of different prediction methods across different benchmarks, leveraging the annotation provided by the DisProt database, which stores the coordinates of ID regions when there is experimental evidence in the literature. The CAID2 challenge demonstrated varying performance of different prediction methods across different benchmarks, highlighting the need for continued development of more versatile and efficient prediction software. Depending on the application, researchers may need to balance performance with execution time when selecting a predictor. Methods based on AlphaFold2 seem to be good ID predictors but they are better at detecting absence of order rather than ID regions as defined in DisProt. The CAID2 predictors can be freely used through the CAID Prediction Portal, and CAID has been integrated into OpenEBench, which will become the official platform for running future CAID challenges

CAID prediction portal: A comprehensive service for predicting intrinsic disorder and binding regions in proteins

Intrinsic disorder (ID) in proteins is well-established in structural biology, with increasing evidence for its involvement in essential biological processes. As measuring dynamic ID behavior experimentally on a large scale remains difficult, scores of published ID predictors have tried to fill this gap. Unfortunately, their heterogeneity makes it difficult to compare performance, confounding biologists wanting to make an informed choice. To address this issue, the Critical Assessment of protein Intrinsic Disorder (CAID) benchmarks predictors for ID and binding regions as a community blind-test in a standardized computing environment. Here we present the CAID Prediction Portal, a web server executing all CAID methods on user-defined sequences. The server generates standardized output and facilitates comparison between methods, producing a consensus prediction highlighting high-confidence ID regions. The website contains extensive documentation explaining the meaning of different CAID statistics and providing a brief description of all methods. Predictor output is visualized in an interactive feature viewer and made available for download in a single table, with the option to recover previous sessions via a private dashboard. The CAID Prediction Portal is a valuable resource for researchers interested in studying ID in proteins. The server is available at the URL: https://caid.idpcentral.org

The repetitive structure of DNA clamps: An overlooked protein tandem repeat

Structured tandem repeats proteins (STRPs) are a specific kind of tandem repeat proteins characterized by a modular and repetitive three-dimensional structure arrangement. The majority of STRPs adopt solenoid structures, but with the increasing availability of experimental structures and high-quality predicted structural models, more STRP folds can be characterized. Here, we describe “Box repeats”, an overlooked STRP fold present in the DNA sliding clamp processivity factors, which has eluded classification although structural data has been available since the late 1990s. Each Box repeat is a β⍺βββ module of about 60 residues, which forms a class V “beads-on-a-string” type STRP. The number of repeats present in processivity factors is organism dependent. Monomers of PCNA proteins in both Archaea and Eukarya have 4 repeats, while the monomers of bacterial beta-sliding clamps have 6 repeats. This new repeat fold has been added to the RepeatsDB database, which now provides structural annotation for 66 Box repeat proteins belonging to different organisms, including viruses