LARGE-SCALE HIGH-THROUGHPUT APPROACHES FOR OPTICAL IMAGING AND STIMULATION OF THE BRAIN

2016 ◽  
Author(s):  
Peter Saggau
Keyword(s):  
Optical Imaging ◽  
High Throughput ◽  
Large Scale ◽  
The Brain ◽  
Stimulation Of

scholarly journals A Scalable and Modular Automated Pipeline for Stitching of Large Electron Microscopy Datasets

2021 ◽  
Author(s):  
Gayathri Mahalingam ◽  
Russel Torres ◽  
Daniel Kapner ◽  
Eric T Trautman ◽  
Tim Fliss ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Visual Cortex ◽  
High Throughput ◽  
Serial Section ◽  
Large Scale ◽  
Software Pipeline ◽  
Array Tomography ◽  
Automated Quality Control ◽  
Mouse Visual Cortex ◽  
The Brain

Serial section Electron Microscopy can produce high throughput imaging of large biological specimen volumes. The high-resolution images are necessary to reconstruct dense neural wiring diagrams in the brain, so called connectomes. A high fidelity volume assembly is required to correctly reconstruct neural anatomy and synaptic connections. It involves seamless 2D stitching of the images within a serial section followed by 3D alignment of the stitched sections. The high throughput of ssEM necessitates 2D stitching to be done at the pace of imaging, which currently produces tens of terabytes per day. To achieve this, we present a modular volume assembly software pipeline ASAP(Assembly Stitching and Alignment Pipeline) that is scalable and parallelized to work with distributed systems. The pipeline is built on top of the Render [18] services used in the volume assembly of the brain of adult Drosophila melanogaster [2]. It achieves high throughput by operating on the meta-data and transformations of each image stored in a database, thus eliminating the need to render intermediate output. The modularity of ASAP allows for easy adaptation to new algorithms without significant changes to the workflow. The software pipeline includes a complete set of tools to do stitching, automated quality control, 3D section alignment, and rendering of the assembled volume to disk. We also implemented a workflow engine that executes the volume assembly workflow in an automated fashion triggered following the transfer of raw data. ASAP has been successfully utilized for continuous processing of several large-scale datasets of the mouse visual cortex and human brain samples including one cubic millimeter of mouse visual cortex [1, 25]. The pipeline also has multi-channel processing capabilities and can be applied to fluorescence and multi-modal datasets like array tomography.

scholarly journals Large-scale all-optical dissection of motor cortex connectivity reveals a segregated functional organization of mouse forelimb representations

2021 ◽  
Author(s):  
Francesco Resta ◽  
Elena Montagni ◽  
Giuseppe de Vito ◽  
Alessandro Scaglione ◽  
Anna Letizia Allegra Mascaro ◽  
...  
Keyword(s):  
Motor Cortex ◽  
Large Scale ◽  
Functional Organization ◽  
Voluntary Movements ◽  
Motor Representation ◽  
Activation Patterns ◽  
Optogenetic Stimulation ◽  
All Optical ◽  
The Brain ◽  
Stimulation Of

In rodent motor cortex, the rostral forelimb area (RFA) and the caudal forelimb area (CFA) are major actors in orchestrating the control of forelimb complex movements. However, their intrinsic connections and reciprocal functional organization are still unclear, limiting our understanding of how the brain coordinates and executes voluntary movements. Here we causally probed cortical connectivity and activation patterns triggered by transcranial optogenetic stimulation of ethologically relevant complex movements exploiting a novel large-scale all-optical method in awake mice. Results show specific activation features for each movement class, providing evidence for a segregated functional organization of CFA and RFA. Importantly, we identified a second discrete lateral grasping representation area, namely lateral forelimb area (LFA), with unique connectivity and activation patterns. Therefore, we propose the LFA as a distinct motor representation in the forelimb somatotopic motor map.

scholarly journals Coordination of brain wide activity dynamics by dopaminergic neurons

2016 ◽  
Author(s):  
Garret Stuber ◽  
Heather Decot ◽  
Vijay Namboodiri ◽  
Wei Gao ◽  
Jenna McHenry ◽  
...  
Keyword(s):  
Dopaminergic Neurons ◽  
Large Scale ◽  
Cerebral Blood Volume ◽  
Brain Activity ◽  
Functional Magnetic Resonance ◽  
Transgenic Rats ◽  
Optogenetic Stimulation ◽  
The Brain ◽  
Neuropsychiatric Conditions ◽  
Stimulation Of

Several neuropsychiatric conditions, such as addiction, schizophrenia, and depression may arise in part from dysregulated activity of ventral tegmental area dopaminergic (THVTA) neurons, as well as from more global maladaptation in neurocircuit function. However, whether THVTA activity affects large-scale brain-wide function remains unknown. Here, we selectively activated THVTA neurons in transgenic rats and measured resulting changes in whole-brain activity using stimulus-evoked functional magnetic resonance imaging (fMRI). Selective optogenetic stimulation of THVTA neurons not only enhanced cerebral blood volume (CBV) signals in striatal target regions in a dopamine receptor dependent fashion, but also engaged many additional anatomically defined regions throughout the brain. In addition, repeated pairing of THVTA neuronal activity with forepaw stimulation, produced an expanded brain-wide sensory representation. These data suggest that modulation of THVTA neurons can impact brain dynamics across many distributed anatomically distinct regions, even those that receive little to no direct THVTA input.

Chemical Stimulation of the Brain Makes Stimulating Reading

1975 ◽  
Vol 20 (12) ◽  
pp. 923-924
Author(s):  
MADGE E. SCHEIBEL ◽  
ARNOLD B. SCHEIBEL
Keyword(s):  
Chemical Stimulation ◽  
The Brain ◽  
Stimulation Of

Accelerated Discovery of High-Refractive-Index Polyimides via First-Principles Molecular Modeling, Virtual High-Throughput Screening, and Data Mining

2019 ◽  
Author(s):  
Mohammad Atif Faiz Afzal ◽  
Mojtaba Haghighatlari ◽  
Sai Prasad Ganesh ◽  
Chong Cheng ◽  
Johannes Hachmann
Keyword(s):  
Data Mining ◽  
Refractive Index ◽  
High Throughput ◽  
First Principles ◽  
High Throughput Screening ◽  
Large Scale ◽  
Computational Study ◽  
High Refractive Index ◽  
Structural Features ◽  
Learning Program

<div>We present a high-throughput computational study to identify novel polyimides (PIs) with exceptional refractive index (RI) values for use as optic or optoelectronic materials. Our study utilizes an RI prediction protocol based on a combination of first-principles and data modeling developed in previous work, which we employ on a large-scale PI candidate library generated with the ChemLG code. We deploy the virtual screening software ChemHTPS to automate the assessment of this extensive pool of PI structures in order to determine the performance potential of each candidate. This rapid and efficient approach yields a number of highly promising leads compounds. Using the data mining and machine learning program package ChemML, we analyze the top candidates with respect to prevalent structural features and feature combinations that distinguish them from less promising ones. In particular, we explore the utility of various strategies that introduce highly polarizable moieties into the PI backbone to increase its RI yield. The derived insights provide a foundation for rational and targeted design that goes beyond traditional trial-and-error searches.</div>

High Frequency Vibration of Worst Ear Lobule induced short period of Rapid Inhibition of any Cancer Activity including Advanced Terminal Cancers, Most Malignant Brain Tumor "Glioblastoma" as well as Cancer of Lung, Breast & Gastrointestinal Cancers particularly Pancreatic Cancer.

2020 ◽  
Vol 44 (3) ◽  
pp. 241-249
Author(s):  
Yoshiaki Omura
Keyword(s):  
Pancreatic Cancer ◽  
Vitamin D3 ◽  
High Frequency ◽  
Optimal Dose ◽  
High Frequency Stimulation ◽  
Frequency Stimulation ◽  
Short Time ◽  
The Brain ◽  
Cancer Activity ◽  
Stimulation Of

While a visiting Professor at the University of Paris, VI (formerly Sorvonne) more than 40 years ago, the Author became very good friends with Dr. Paul Nogier who periodically gave seminars and workshops in Paris. After the author diagnosed his cervical problem & offered him simple help, Dr. Nogier asked the Author to present lectures and demonstrations on the effects of ear stimulation, namely the effects of acupuncture & electrical stimulation of the ear lobules. It is only now, in 2019 that we have discovered 2–5 minute high frequency stimulation of the ear lobule inhibits cancer activity for 1– 4 hours post stimulation. Although the procedure is extremely simple. First take optimal dose of Vitamin D3, which has the most essential 10 unique beneficial factors required for every human cell activity. Next, apply high frequency stimulation to ear lobule while the worst ear lobule is held by all fingers with vibrator directly touching the surface of the worst ear lobule, preferably after patient repeatedly takes optimal dose of Vitamin D3. When the worst ear lobule is held between thumb & index fingers and applying mechanical stimulation of 250 ~ 500 mechanical vibration/second for 2 ~ 5 minutes using an electrical vibrator, there is rapid disappearance of cancer activity in both the brain and rest of the body for short time duration 1 ~ 4 hours. The effect often increases by additional pressure by holding fingers. As of May 2019, the Author found that many people from various regions of the world developed early stages of multiple cancers. For evaluation of this study, U. S. patented Bi-Digital O-Ring Test (BDORT) was used which was developed by the Author while doing his Graduate experimental physics research at Colombia University. BDORT was found to be most essential for determining the beneficial effects as well as harmful effects of any substance or treatment. Using BDORT, Author was the first to recognize severe increasing mid-backache was an early sign of pancreatic cancer of President of New York State Board of Medicine after top pain specialists failed to detect the cause after 3 years of effort, while the BDORT showed early stages of cancer whereas conventional X-Ray of the pancreas did not show any cancer image until 2 months after Author detected with BDORT. For example, the optimal dose of the banana is usually about 2.0 - 2.5 millimeters cross section of the banana. A whole banana is more than 50 ~ 100 times the optimal dose. Any substance eaten in more than 25 times of its optimal dose becomes highly toxic and creates DNA mutations which can cause multiple malignancies in the presence of strong electro-magnetic field. With standard medication given by doctor, patients often become sick and they are unable to reduce body weight, unless medication is reduced or completely stopped. When the amount of zinc is very high, DNA often becomes unstable and multiple cancers can grow rapidly in the presence of strong electromagnetic field. Large amount of Vitamin C from regular orange or orange juice inhibit the most important Vitamin D3 effects. At least 3 kinds of low Vitamin C oranges will not inhibit Vitamin D3. Since B12 particularly methyl cobalamin which is a red small tablet is known to improve brain circulation very significantly we examined its effect within 20 seconds of oral intake we found the following very significant changes. Acetylcholine in both sides of the brain often increases over 4,500 ng. Longevity gene Sirtuin 1 level increases significantly for short time of few hours. Thymosin α1 and Thymosinβ4 both increase to over 1500 ng from 20 ng or less.

Next-Generation Sequencing: An Emerging Tool for Drug Designing

2019 ◽  
Vol 25 (31) ◽  
pp. 3350-3357 ◽  
Author(s):  
Pooja Tripathi ◽  
Jyotsna Singh ◽  
Jonathan A. Lal ◽  
Vijay Tripathi
Keyword(s):  
Next Generation Sequencing ◽  
High Throughput ◽  
Large Scale ◽  
Massively Parallel Sequencing ◽  
Genomic Research ◽  
Biological Research ◽  
Next Generation ◽  
Human Welfare ◽  
Drug Designing ◽  
Generation Sequencing

Background: With the outbreak of high throughput next-generation sequencing (NGS), the biological research of drug discovery has been directed towards the oncology and infectious disease therapeutic areas, with extensive use in biopharmaceutical development and vaccine production. Method: In this review, an effort was made to address the basic background of NGS technologies, potential applications of NGS in drug designing. Our purpose is also to provide a brief introduction of various Nextgeneration sequencing techniques. Discussions: The high-throughput methods execute Large-scale Unbiased Sequencing (LUS) which comprises of Massively Parallel Sequencing (MPS) or NGS technologies. The Next geneinvolved necessarily executes Largescale Unbiased Sequencing (LUS) which comprises of MPS or NGS technologies. These are related terms that describe a DNA sequencing technology which has revolutionized genomic research. Using NGS, an entire human genome can be sequenced within a single day. Conclusion: Analysis of NGS data unravels important clues in the quest for the treatment of various lifethreatening diseases and other related scientific problems related to human welfare.

Large-scale High-throughput Screening Revealed 5'-(carbonylamino)-2,3'- bithiophene-4'-carboxylate as Novel Template for Antibacterial Agents

2020 ◽  
Vol 17 (5) ◽  
pp. 716-724
Author(s):  
Yan A. Ivanenkov ◽  
Renat S. Yamidanov ◽  
Ilya A. Osterman ◽  
Petr V. Sergiev ◽  
Vladimir A. Aladinskiy ◽  
...  
Keyword(s):  
Antibacterial Activity ◽  
High Throughput ◽  
High Throughput Screening ◽  
Large Scale ◽  
Antibacterial Agents ◽  
Sos Response ◽  
Luciferase Assay ◽  
Translational Machinery ◽  
E Coli ◽  
New Class

Background: The key issue in the development of novel antimicrobials is a rapid expansion of new bacterial strains resistant to current antibiotics. Indeed, World Health Organization has reported that bacteria commonly causing infections in hospitals and in the community, e.g. E. Coli, K. pneumoniae and S. aureus, have high resistance vs the last generations of cephalosporins, carbapenems and fluoroquinolones. During the past decades, only few successful efforts to develop and launch new antibacterial medications have been performed. This study aims to identify new class of antibacterial agents using novel high-throughput screening technique. Methods: We have designed library containing 125K compounds not similar in structure (Tanimoto coeff.< 0.7) to that published previously as antibiotics. The HTS platform based on double reporter system pDualrep2 was used to distinguish between molecules able to block translational machinery or induce SOS-response in a model E. coli system. MICs for most active chemicals in LB and M9 medium were determined using broth microdilution assay. Results: In an attempt to discover novel classes of antibacterials, we performed HTS of a large-scale small molecule library using our unique screening platform. This approach permitted us to quickly and robustly evaluate a lot of compounds as well as to determine the mechanism of action in the case of compounds being either translational machinery inhibitors or DNA-damaging agents/replication blockers. HTS has resulted in several new structural classes of molecules exhibiting an attractive antibacterial activity. Herein, we report as promising antibacterials. Two most active compounds from this series showed MIC value of 1.2 (5) and 1.8 μg/mL (6) and good selectivity index. Compound 6 caused RFP induction and low SOS response. In vitro luciferase assay has revealed that it is able to slightly inhibit protein biosynthesis. Compound 5 was tested on several archival strains and exhibited slight activity against gram-negative bacteria and outstanding activity against S. aureus. The key structural requirements for antibacterial potency were also explored. We found, that the unsubstituted carboxylic group is crucial for antibacterial activity as well as the presence of bulky hydrophobic substituents at phenyl fragment. Conclusion: The obtained results provide a solid background for further characterization of the 5'- (carbonylamino)-2,3'-bithiophene-4'-carboxylate derivatives discussed herein as new class of antibacterials and their optimization campaign.

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