Calibration-free and hardware-efficient neural spike detection for brain machine interfaces

Recent translational efforts in brain-machine interfaces (BMI) are demonstrating the potential to help people with neurological disorders. The current trend in BMI technology is to increase the number of recording channels to the thousands, resulting in the generation of vast amounts of raw data. This in turn places high bandwidth requirements for data transmission, which increases power consumption and thermal dissipation of implanted systems. On-implant compression and/or feature extraction are therefore becoming essential to limiting this increase in bandwidth, but add further power constraints – the power required for data reduction must remain less than the power saved through bandwidth reduction. Spike detection is a common feature extraction technique used for intracortical BMIs. In this paper, we develop a novel firing-rate-based spike detection algorithm that requires no external training and is hardware efficient and therefore ideally suited for real-time applications. Key performance and implementation metrics such as detection accuracy, adaptability in chronic deployment, power consumption, area utilization, and channel scalability are benchmarked against existing methods using various datasets. The algorithm is first validated using a reconfigurable hardware (FPGA) platform and then ported to a digital ASIC implementation in both 65 nm and 0.18MU m CMOS technologies. The 128-channel ASIC design implemented in a 65 nm CMOS technology occupies 0.096 mm2 silicon area and consumes 4.86MU W from a 1.2 V power supply. The adaptive algorithm achieves a 96% spike detection accuracy on a commonly used synthetic dataset, without the need for any prior training

Interactive Exploration of Chemical Space with Scaffold Hunter

The supporting information is composed of the following files: I. pyruvatekinasedata.zip The pyruvate kinase data set used for the analysis described in the referenced publication is contained in this file. The analysis is based on the Pyruvate Kinase Screen as published in PubChem under the assay ID 361. It contains all compounds checked in this screen together with the scaffold tree generated from it. Scaffold Hunter can be used to query the database and interactively display the scaffold tree. This file is a dump from a MySQL 5.1 database and was generated with MySQL Administrator 1.2.5. It can be restored with the same program. II. scaffoldhunter_profiles.zip Scaffold Hunter saves the user profiles either on the hard disk or in a database. The corresponding database schema is contained in this zip file. This schema must be contained in the MySQL database before Scaffold Hunter can be run. This file is a dump from a MySQL 5.1 database and was generated with MySQL Administrator 1.2.5. It can be restored with the same program. III. InstallationGuide_Databases.pdf This document describes the installation of a local MySQL database server and the graphical user interface MySQL Administrator. Restoration of the profiles and sample databases are also described. IV. run_ScaffoldHunter.bat Windows batch file to run Scaffold Hunter with 1024 MByte of Memory. V. run_ScaffoldTreeGenerator.bat Windows batch file to run ScaffoldTreeGenerator with 1024 MByte of Memory. VI. ScaffoldHunter_readme.txt Textfile with advice for the installation of Scaffold Hunter. VII. ScaffoldTreeGenerator_readme.txt Textfile with advice for the installation of ScaffoldTree Generator

Colon intussusception treated endoscopically (case report)

Secția endoscopie, Institutul Medicinei de Urgență, Chișinău, Republica Moldova, Al XII-lea Congres al Asociației Chirurgilor „Nicolae Anestiadi” din Republica Moldova cu participare internațională 23-25 septembrie 2015Caz clinic: În Clinică la 30 octombrie 2013 s-a adresat pacientul SA de 19 ani, cu acuze la dureri intense în flancul stîng, vomă repetată cu conținut gastric, astenie pronunțată, inapetență, lipsa scaunului (2 zile), lipsa emisiei de gaze (24 ore). Din anamneză, în copilărie – diagnosticat cu megacolon congenital, părinții au refuzat tratamentul chirurgical. La internare: abdomenul moderat balonat, simetric, dolor intens la palpare în flancul stîng și mezogastru, semne peritoneale – absente, per rectum – conținut intestinal, pereții – dilatați. Spitalizat cu diagnosticul de ocluzie intestinală joasă. Ecografia cavității abdominale a evidențiat un minim de lichid liber interileal. Radiografia abdomenului – aerocolie pronunțată. La 31 octombrie 2013 s-a efectuat colonoscopie pînă la flexura lienală, înaintarea fiind neinformativă (în lumen – materii fecale). În sigmoid, la distanța 25 cm de la orificiul anal pînă la 40 cm, peretele intestinului nu se reexpansiona complet, mucoasa – edemațiată, culoare violacee, cu peteșii hemoragice. Lumenul colonului nu se vizualiza. La insuflarea aerului porțiunea proximală de perete intestinal a glisat, eliberînd lumenul sigmoidului. Colonul descendent examenat – mărit în dimensiuni atît longitudinal cît și transversal. Mucoasa examinată subțiată, cu desen vascular pronunțat. Haustrele intestinale – absente. Peristaltismul intestinal – absent. Unghiul lienal – permeabil. Biopsia din mucoasa schimbată macroscopic al sigmoidului nu a fost prelevată din cauza pericolului hemoragiei și a perforației. La pacient s-a constatat o invaginație de colon la nivelul sigmoidului, megadolicocolon. După colonoscopie starea generală a pacientului s-a ameliorat, acesta fiind externat din staționar recomandîndu-se tratamentul chirurgical programat al dolicocolonului.Clinical case: This article reports a clinical case of intestinal obstruction intussusception, which was solved by colonoscopy. A 19-years-old patient was admitted on October 30, 2013 to the Hospital with the following complaints: severe pain in left abdominal flank, repeated vomiting, pronounced asthenia, decreased appetite, constipation and a lack of gas (2 days). In anamnesis, childhood-diagnosed with congenital megadolichocolon, parents refused surgical treatment. Physical exam: the swollen abdomen, abdominal pain on palpation, no peritoneal signs. Hospitalized with intestinal obstruction. Abdomenal cavity ultrasound showed minimal free liquid. X-rays of the abdomen showed a bowel distension. October 31, 2013 was conducted colonoscopy. In the sigmoid, at a distance of 25 cm from the anus, up to 40 cm, the intestinal wall was not deployed fully, the swelling, purple mucous with petechial hemorrhages. The lumen of the colon was not see. Under the inspiration of the air, the proximal portion of the intestinal wall, to drag it, giving the lumen of the sigmoid. Colon descending seen, increased in size, both lengthwise and transversely. Mucous were narrowed, with strikes pronounced. The folds of the intestine absented. Peristalsis was absent. No biopsy was taken of the macroscopic changed mucous of sigmoid, because of the risk of bleeding and perforation. The patient was found to intussusception of the colon sigmoid. After the colonoscopy the general condition of the patient improved, was discharged from the hospital and it was recommended surgical treatment of dolichocolon

Drug Repurposing: Far Beyond New Targets for Old Drugs

Repurposing drugs requires finding novel therapeutic indications compared to the ones for which they were already approved. This is an increasingly utilized strategy for finding novel medicines, one that capitalizes on previous investments while derisking clinical activities. This approach is of interest primarily because we continue to face significant gaps in the drug–target interactions matrix and to accumulate safety and efficacy data during clinical studies. Collecting and making publicly available as much data as possible on the target profile of drugs offer opportunities for drug repurposing, but may limit the commercial applications by patent applications. Certain clinical applications may be more feasible for repurposing than others because of marked differences in side effect tolerance. Other factors that ought to be considered when assessing drug repurposing opportunities include relevance to the disease in question and the intellectual property landscape. These activities go far beyond the identification of new targets for old drugs

Physiochemical property space distribution among human metabolites, drugs and toxins

<p>Abstract</p> <p>Background</p> <p>The current approach to screen for drug-like molecules is to sieve for molecules with biochemical properties suitable for desirable pharmacokinetics and reduced toxicity, using predominantly biophysical properties of chemical compounds, based on empirical rules such as Lipinski's "rule of five" (Ro5). For over a decade, Ro5 has been applied to combinatorial compounds, drugs and ligands, in the search for suitable lead compounds. Unfortunately, till date, a clear distinction between drugs and non-drugs has not been achieved. The current trend is to seek out drugs which show metabolite-likeness. In identifying similar physicochemical characteristics, compounds have usually been clustered based on some characteristic, to reduce the search space presented by large molecular datasets. This paper examines the similarity of current drug molecules with human metabolites and toxins, using a range of computed molecular descriptors as well as the effect of comparison to clustered data compared to searches against complete datasets.</p> <p>Results</p> <p>We have carried out statistical and substructure functional group analyses of three datasets, namely human metabolites, drugs and toxin molecules. The distributions of various molecular descriptors were investigated. Our analyses show that, although the three groups are distinct, present-day drugs are closer to toxin molecules than to metabolites. Furthermore, these distributions are quite similar for both clustered data as well as complete or unclustered datasets.</p> <p>Conclusion</p> <p>The property space occupied by metabolites is dissimilar to that of drugs or toxin molecules, with current drugs showing greater similarity to toxins than to metabolites. Additionally, empirical rules like Ro5 can be refined to identify drugs or drug-like molecules that are clearly distinct from toxic compounds and more metabolite-like. The inclusion of human metabolites in this study provides a deeper insight into metabolite/drug/toxin-like properties and will also prove to be valuable in the prediction or optimization of small molecules as ligands for therapeutic applications.</p

Transition from ballistic to diffusive behavior of graphene ribbons in the presence of warping and charged impurities

We study the effects of the long-range disorder potential and warping on the conductivity and mobility of graphene ribbons using the Landauer formalism and the tight-binding p-orbital Hamiltonian. We demonstrate that as the length of the structure increases the system undergoes a transition from the ballistic to the diffusive regime. This is reflected in the calculated electron density dependencies of the conductivity and the mobility. In particular, we show that the mobility of graphene ribbons varies as mu(n) n^(-lambda), with 0<lambda<0.5. The exponent lambda depends on the length of the system with lambda=0.5 corresponding to short structures in the ballistic regime, whereas the diffusive regime lambda=0 (when the mobility is independent on the electron density) is reached for sufficiently long structures. Our results can be used for the interpretation of experimental data when the value of lambda can be used to distinguish the transport regime of the system (i.e. ballistic, quasi-ballistic or diffusive). Based on our findings we discuss available experimental results

Projects as Knowledge Swirls in the Technological Innovation: Romania's Situation

The present paper uses as research basis a new way of thinking regarding the relation between innovation and knowledge - the Knowledge Flow Percolation Model (KFPM). In this model’s center, human beings are seen as thinking electrons, both consuming and generating knowledge flows. Through the interdependent actions of individuals, knowledge circulates inside organizations, allowing them to innovate in order to obtain competitive advantages. But there is a wide range of barriers which impede the creation and movement of flows in the model grid and consequently, hinder their change into innovation. The solution proposed by this paper as one of the most adequate instruments to make KFPM more spreadable is the project. On this basis, in an empirical study, we try to demonstrate the hypothesis of the positive influence of projects, as knowledge swirls, on the development of innovative skills which will help solving problems in the organization, creating and widening of knowledge and reducing the barriers in knowledge transfer.This work was supported by the project “Post-Doctoral Studies in Economics: training program for elite researchers – SPODE” co-funded from the European Social Fund through the Development of Human Resources Operational Programme 2007-2013, contract no. POSDRU/89/1.5/S/61755

Evaluation of a Bayesian inference network for ligand-based virtual screening

Background Bayesian inference networks enable the computation of the probability that an event will occur. They have been used previously to rank textual documents in order of decreasing relevance to a user-defined query. Here, we modify the approach to enable a Bayesian inference network to be used for chemical similarity searching, where a database is ranked in order of decreasing probability of bioactivity. Results Bayesian inference networks were implemented using two different types of network and four different types of belief function. Experiments with the MDDR and WOMBAT databases show that a Bayesian inference network can be used to provide effective ligand-based screening, especially when the active molecules being sought have a high degree of structural homogeneity; in such cases, the network substantially out-performs a conventional, Tanimoto-based similarity searching system. However, the effectiveness of the network is much less when structurally heterogeneous sets of actives are being sought. Conclusion A Bayesian inference network provides an interesting alternative to existing tools for ligand-based virtual screening

ChemProt: a disease chemical biology database

Systems pharmacology is an emergent area that studies drug action across multiple scales of complexity, from molecular and cellular to tissue and organism levels. There is a critical need to develop network-based approaches to integrate the growing body of chemical biology knowledge with network biology. Here, we report ChemProt, a disease chemical biology database, which is based on a compilation of multiple chemical–protein annotation resources, as well as disease-associated protein–protein interactions (PPIs). We assembled more than 700 000 unique chemicals with biological annotation for 30 578 proteins. We gathered over 2-million chemical–protein interactions, which were integrated in a quality scored human PPI network of 428 429 interactions. The PPI network layer allows for studying disease and tissue specificity through each protein complex. ChemProt can assist in the in silico evaluation of environmental chemicals, natural products and approved drugs, as well as the selection of new compounds based on their activity profile against most known biological targets, including those related to adverse drug events. Results from the disease chemical biology database associate citalopram, an antidepressant, with osteogenesis imperfect and leukemia and bisphenol A, an endocrine disruptor, with certain types of cancer, respectively. The server can be accessed at http://www.cbs.dtu.dk/services/ChemProt/