Surface-Area-to-Volume Ratio Determines Surface Tensions in Microscopic, Surfactant-Containing Droplets.

The surface composition of aerosol droplets is central to predicting cloud droplet number concentrations, understanding atmospheric pollutant transformation, and interpreting observations of accelerated droplet chemistry. Due to the large surface-area-to-volume ratios of aerosol droplets, adsorption of surfactant at the air-liquid interface can deplete the droplet's bulk concentration, leading to droplet surface compositions that do not match those of the solutions that produced them. Through direct measurements of individual surfactant-containing, micrometer-sized droplet surface tensions, and fully independent predictive thermodynamic modeling of droplet surface tension, we demonstrate that, for strong surfactants, the droplet's surface-area-to-volume ratio becomes the key factor in determining droplet surface tension rather than differences in surfactant properties. For the same total surfactant concentration, the surface tension of a droplet can be >40 mN/m higher than that of the macroscopic solution that produced it. These observations indicate that an explicit consideration of surface-area-to-volume ratios is required when investigating heterogeneous chemical reactivity at the surface of aerosol droplets or estimating aerosol activation to cloud droplets.

Miniature microscopes for manipulating and recording in vivo brain activity.

Here we describe the development and application of miniature integrated microscopes (miniscopes) paired with microendoscopes that allow for the visualization and manipulation of neural circuits in superficial and subcortical brain regions in freely behaving animals. Over the past decade the miniscope platform has expanded to include simultaneous optogenetic capabilities, electrically-tunable lenses that enable multi-plane imaging, color-corrected optics, and an integrated data acquisition platform that streamlines multimodal experiments. Miniscopes have given researchers an unprecedented ability to monitor hundreds to thousands of genetically-defined neurons from weeks to months in both healthy and diseased animal brains. Sophisticated algorithms that take advantage of constrained matrix factorization allow for background estimation and reliable cell identification, greatly improving the reliability and scalability of source extraction for large imaging datasets. Data generated from miniscopes have empowered researchers to investigate the neural circuit underpinnings of a wide array of behaviors that cannot be studied under head-fixed conditions, such as sleep, reward seeking, learning and memory, social behaviors, and feeding. Importantly, the miniscope has broadened our understanding of how neural circuits can go awry in animal models of progressive neurological disorders, such as Parkinson's disease. Continued miniscope development, including the ability to record from multiple populations of cells simultaneously, along with continued multimodal integration of techniques such as electrophysiology, will allow for deeper understanding into the neural circuits that underlie complex and naturalistic behavior.

An application of probability density function for the analysis of PM2.5 concentration during the COVID-19 lockdown period.

The first Covid-19 patient in India was reported on January 30, 2020 at the state of Kerala. The patient number rose to three by February 3, 2020. In the month of March 2020, the transmissions started to increase when the people started to return back to India from the Covid-19 affected countries. On March 12, a 76-year-old man having a travel history to Saudi Arabia was the first reported fatality in India due to Covid 19. Then for the prevention of the propagation of Covid, the Indian government declared a state of health emergency and strict counter measures were taken, including locking down of cities, prohibiting almost all avoidable activities and restricting population's mobility. From March 24, 2020 due to the complete lockdown in the country, human activities were heavily restricted in the whole geographical regions of India. This pandemic lockdown eventually serves as an opportunity to observe the background concentrations of pollutants in the atmosphere. The PM 2.5 distribution can affect human health and to overcome this problem, setting up of regulation for PM is necessary. In the present study Probability density functions (PDF) method have been utilised for the investigation of PM 2.5 pollutant data distribution of five countries namely, India, China, France, Brazil and United States of America (USA) for their respective lockdown period of 2020 and corresponding same period of 2019. A detailed study has been done for India, and for that purpose India has been divided into three regions (Central India, Coastal India and Indo-Gangetic Plain (IGP)) on the basis of different meteorological conditions. PM 2.5 concentration for hourly basis has been analysed for the lockdown period 24th March to 15th June 2020 and compared with the PM 2.5 concentration of previous year 2019 for the same time period. To understand the effect of lockdown in PM 2.5 emission in India, which will give us an idea about the background concentration, PDFs (probability density functions) have also been generated for the whole year from 2015 to 2019. The "goodness-of-fit" of the probability density functions, to the data, was assessed, using various statistical indices (Chi-square test). Results show that the PM 2.5 reduction during the lockdown period of 2020 as compared to the same period of 2019 is sufficiently large. This study will give a certain degree of idea to the regulatory bodies on planning and implementation of strict air quality control plans.

Hair transplantation by follicular unit extraction for male androgenetic alopecia: A retrospective observational study from two centers.

BACKGROUND: Follicular unit extraction (FUE) is the most popular method of hair transplantation in today's world. Hair transplantation in androgenetic alopecia (AGA) in males can restore the frontal hairline and provide hair density in alopecic areas to the satisfaction of most patients. METHODS: Consecutive male patients of AGA who underwent hair transplantation by FUE method in two centers between the period of January 2016 and June 2017 have been included in this study based on inclusion and exclusion criteria. Photographic images, trichoscopy and Likert's scale were used to assess patient's improvement in hair density after the transplantation procedure. Statistical methods using SPSS software was used to analyze the results. Institutional ethical clearance and patients' written consent for procedure and images was obtained. The study was an observational retrospective study using data and images from records for which consent and ethical clearance was obtained from patients and the institution. RESULTS: Average number of follicular units transplanted in patients was 1290 (improvement in hair density: of 30.61 follicular units/sq cm). There was a statistically significant difference in improvement in hair density in patients younger than 33 years and in patients with Norwood classification below stage 4a. Forty-nine patients were satisfied with the results after assessment by the Likert scale. CONCLUSION: Hair transplantation by follicular extraction method provides good hair cover in AGA in males. This modern dermatosurgical technique with its many innovations is a very helpful technique to improve quality of life in male pattern baldness.

Chemical diversity in molecular orbital energy predictions with kernel ridge regression.

Instant machine learning predictions of molecular properties are desirable for materials design, but the predictive power of the methodology is mainly tested on well-known benchmark datasets. Here, we investigate the performance of machine learning with kernel ridge regression (KRR) for the prediction of molecular orbital energies on three large datasets: the standard QM9 small organic molecules set, amino acid and dipeptide conformers, and organic crystal-forming molecules extracted from the Cambridge Structural Database. We focus on the prediction of highest occupied molecular orbital (HOMO) energies, computed at the density-functional level of theory. Two different representations that encode the molecular structure are compared: the Coulomb matrix (CM) and the many-body tensor representation (MBTR). We find that KRR performance depends significantly on the chemistry of the underlying dataset and that the MBTR is superior to the CM, predicting HOMO energies with a mean absolute error as low as 0.09 eV. To demonstrate the power of our machine learning method, we apply our model to structures of 10k previously unseen molecules. We gain instant energy predictions that allow us to identify interesting molecules for future applications.

Deep Learning Spectroscopy: Neural Networks for Molecular Excitation Spectra.

Deep learning methods for the prediction of molecular excitation spectra are presented. For the example of the electronic density of states of 132k organic molecules, three different neural network architectures: multilayer perceptron (MLP), convolutional neural network (CNN), and deep tensor neural network (DTNN) are trained and assessed. The inputs for the neural networks are the coordinates and charges of the constituent atoms of each molecule. Already, the MLP is able to learn spectra, but the root mean square error (RMSE) is still as high as 0.3 eV. The learning quality improves significantly for the CNN (RMSE = 0.23 eV) and reaches its best performance for the DTNN (RMSE = 0.19 eV). Both CNN and DTNN capture even small nuances in the spectral shape. In a showcase application of this method, the structures of 10k previously unseen organic molecules are scanned and instant spectra predictions are obtained to identify molecules for potential applications.

View from Silicon Valley: Maximizing the Scientific Impact of Global Brain Initiatives through Entrepreneurship.

In this era of technology-driven global neuroscience initiatives, the role of the neurotechnology industry remains woefully ambiguous. Here, we explain why industry is essential to the success of these global initiatives, and how it can maximize the scientific impact of these efforts by (1) scaling and ultimately democratizing access to breakthrough neurotechnologies, and (2) commercializing technologies as part of integrated, end-to-end solutions that accelerate neuroscientific discovery.

Direct Imaging of Hippocampal Epileptiform Calcium Motifs Following Kainic Acid Administration in Freely Behaving Mice.

Prolonged exposure to abnormally high calcium concentrations is thought to be a core mechanism underlying hippocampal damage in epileptic patients; however, no prior study has characterized calcium activity during seizures in the live, intact hippocampus. We have directly investigated this possibility by combining whole-brain electroencephalographic (EEG) measurements with microendoscopic calcium imaging of pyramidal cells in the CA1 hippocampal region of freely behaving mice treated with the pro-convulsant kainic acid (KA). We observed that KA administration led to systematic patterns of epileptiform calcium activity: a series of large-scale, intensifying flashes of increased calcium fluorescence concurrent with a cluster of low-amplitude EEG waveforms. This was accompanied by a steady increase in cellular calcium levels (>5 fold increase relative to the baseline), followed by an intense spreading calcium wave characterized by a 218% increase in global mean intensity of calcium fluorescence (n = 8, range [114-349%], p < 10(-4); t-test). The wave had no consistent EEG phenotype and occurred before the onset of motor convulsions. Similar changes in calcium activity were also observed in animals treated with 2 different proconvulsant agents, N-methyl-D-aspartate (NMDA) and pentylenetetrazol (PTZ), suggesting the measured changes in calcium dynamics are a signature of seizure activity rather than a KA-specific pathology. Additionally, despite reducing the behavioral severity of KA-induced seizures, the anticonvulsant drug valproate (VA, 300 mg/kg) did not modify the observed abnormalities in calcium dynamics. These results confirm the presence of pathological calcium activity preceding convulsive motor seizures and support calcium as a candidate signaling molecule in a pathway connecting seizures to subsequent cellular damage. Integrating in vivo calcium imaging with traditional assessment of seizures could potentially increase translatability of pharmacological intervention, leading to novel drug screening paradigms and therapeutics designed to target and abolish abnormal patterns of both electrical and calcium excitation.

Miniature microscopes for large-scale imaging of neuronal activity in freely behaving rodents.

Recording neuronal activity in behaving subjects has been instrumental in studying how information is represented and processed by the brain. Recent advances in optical imaging and bioengineering have converged to enable time-lapse, cell-type specific recordings of neuronal activities from large neuronal populations in deep-brain structures of freely behaving rodents. We will highlight these advancements, with an emphasis on miniaturized integrated microscopy for large-scale imaging in freely behaving mice. This technology potentially enables studies that were difficult to perform using previous generation imaging and current electrophysiological techniques. These studies include longitudinal and population-level analyses of neuronal representations associated with different types of naturalistic behaviors and cognitive or emotional processes.

Zolpidem reduces hippocampal neuronal activity in freely behaving mice: a large scale calcium imaging study with miniaturized fluorescence microscope.

Therapeutic drugs for cognitive and psychiatric disorders are often characterized by their molecular mechanism of action. Here we demonstrate a new approach to elucidate drug action on large-scale neuronal activity by tracking somatic calcium dynamics in hundreds of CA1 hippocampal neurons of pharmacologically manipulated behaving mice. We used an adeno-associated viral vector to express the calcium sensor GCaMP3 in CA1 pyramidal cells under control of the CaMKII promoter and a miniaturized microscope to observe cellular dynamics. We visualized these dynamics with and without a systemic administration of Zolpidem, a GABAA agonist that is the most commonly prescribed drug for the treatment of insomnia in the United States. Despite growing concerns about the potential adverse effects of Zolpidem on memory and cognition, it remained unclear whether Zolpidem alters neuronal activity in the hippocampus, a brain area critical for cognition and memory. Zolpidem, when delivered at a dose known to induce and prolong sleep, strongly suppressed CA1 calcium signaling. The rate of calcium transients after Zolpidem administration was significantly lower compared to vehicle treatment. To factor out the contribution of changes in locomotor or physiological conditions following Zolpidem treatment, we compared the cellular activity across comparable epochs matched by locomotor and physiological assessments. This analysis revealed significantly depressive effects of Zolpidem regardless of the animal's state. Individual hippocampal CA1 pyramidal cells differed in their responses to Zolpidem with the majority (∼ 65%) significantly decreasing the rate of calcium transients, and a small subset (3%) showing an unexpected and significant increase. By linking molecular mechanisms with the dynamics of neural circuitry and behavioral states, this approach has the potential to contribute substantially to the development of new therapeutics for the treatment of CNS disorders.

Long-term dynamics of CA1 hippocampal place codes.

Using Ca(2+) imaging in freely behaving mice that repeatedly explored a familiar environment, we tracked thousands of CA1 pyramidal cells' place fields over weeks. Place coding was dynamic, as each day the ensemble representation of this environment involved a unique subset of cells. However, cells in the ∼15-25% overlap between any two of these subsets retained the same place fields, which sufficed to preserve an accurate spatial representation across weeks.

Miniaturized integration of a fluorescence microscope.

The light microscope is traditionally an instrument of substantial size and expense. Its miniaturized integration would enable many new applications based on mass-producible, tiny microscopes. Key prospective usages include brain imaging in behaving animals for relating cellular dynamics to animal behavior. Here we introduce a miniature (1.9 g) integrated fluorescence microscope made from mass-producible parts, including a semiconductor light source and sensor. This device enables high-speed cellular imaging across ∼0.5 mm2 areas in active mice. This capability allowed concurrent tracking of Ca2+ spiking in >200 Purkinje neurons across nine cerebellar microzones. During mouse locomotion, individual microzones exhibited large-scale, synchronized Ca2+ spiking. This is a mesoscopic neural dynamic missed by prior techniques for studying the brain at other length scales. Overall, the integrated microscope is a potentially transformative technology that permits distribution to many animals and enables diverse usages, such as portable diagnostics or microscope arrays for large-scale screens.

Advances in light microscopy for neuroscience.

Since the work of Golgi and Cajal, light microscopy has remained a key tool for neuroscientists to observe cellular properties. Ongoing advances have enabled new experimental capabilities using light to inspect the nervous system across multiple spatial scales, including ultrastructural scales finer than the optical diffraction limit. Other progress permits functional imaging at faster speeds, at greater depths in brain tissue, and over larger tissue volumes than previously possible. Portable, miniaturized fluorescence microscopes now allow brain imaging in freely behaving mice. Complementary progress on animal preparations has enabled imaging in head-restrained behaving animals, as well as time-lapse microscopy studies in the brains of live subjects. Mouse genetic approaches permit mosaic and inducible fluorescence-labeling strategies, whereas intrinsic contrast mechanisms allow in vivo imaging of animals and humans without use of exogenous markers. This review surveys such advances and highlights emerging capabilities of particular interest to neuroscientists.

Intra-peritoneal duodenal perforation caused by delayed migration of endobiliary stent: a case report.

Endoscopic biliary stenting is an accepted modality of palliation of malignant biliary obstructions. Delayed stent migration causing intra-peritoneal perforation of duodenum, is a rare life threatening complication. Proximal adhesion of stent to the tumor is believed to increase the intensity of distal trauma produced by the intra-duodenal segment, preventing its adaptation to intestinal peristalsis and causing perforation. Low bacterial load and containment of leak by gut and omentum blunts the clinical features. Unexplained abdominal discomfort in stented patients should alert the clinician to its possibility, irrespective of the delay between stent placement and onset of symptoms. Early diagnosis and treatment is desirable but aggressive surgical management with gastro-biliary diversion, tube duodenostomy, antibiotics, bowel rest and parenteral alimentation followed by distal alimentation, may make up for the delay in those presenting late. A case of 7 days old intra-peritoneal duodenal perforation following delayed migration (3 months) of endobiliary stent presenting with atypical features is reported. Stent's distal end was protruding through the duodenum with its proximal end in CBD. Mortality, fistulization, abscesses and sepsis are known complications but were not observed in our case. Much of the management can be done minimally invasively, if recognized early.

New slow-releasing molybdenum fertilizer.

This paper describes a new water-insoluble molybdenum compound that has been developed as a slow-release fertilizer. The compound is an inorganic polymer formed by inclusion of molybdenum within a long-chain polyphosphate structure. It was designed by a process of "reverse engineering" of the molecule. Synthesis involved reaction of phosphoric acid with magnesium oxide, molybdenum trioxide, and sodium carbonate at 275 degrees C. Kinetics of reaction revealed complex multistage processes. X-ray diffraction patterns showed a crystalline nature with short-range as well as long-range ordering. The magnesium sodium polymolybdophosphate had ideal slow-release characteristics; it had low water solubility and high citrate solubility and was powdery, free flowing, and nonhygroscopic. Field testing showed an 80% increase in yield of green gram at a low dose of 0.04 kg/ha Mo. Nodulation increased by over 161%, and N content of gram increased by 20%. The slow-release fertilizer would provide an effective, low-cost, and environmentaly friendly alternative to Mo fertilization.

Splenic artery aneurysm--a rare cause for extrahepatic portal venous obstruction: a case report.

Splenic artery aneurysm is a rare yet very important clinical entity because of its potential for rupture with fatal consequences. Most of the splenic artery aneurysms are found in the middle and distal third of the splenic artery and are usually small (< or = 2 cm) at the time of diagnosis. We describe a rare case of large (5x4 cm) juxta-ostial splenic artery aneurysm causing compression of the splenoportal confluence and adjoining proximal portal vein in a 40-year-old woman.