Rare neglected diseases may be neglected but are hardly rare, affecting hundreds of millions of people around the world. Here, we present a hit identification approach using AtomNet, the world’s ...first deep convolutional neural network for structure-based drug discovery, to identify inhibitors targeting aspartate N-acetyltransferase (ANAT), a promising target for the treatment of patients suffering from Canavan disease. Despite the lack of a protein structure or high sequence identity homologous templates, the approach successfully identified five low-micromolar inhibitors with drug-like properties.
•Potential of acacia sawdust is studied in auger pyrolysis system in range 400 ~ 600 °C.•A detailed characterization of the sawdust prior to pyrolysis investigation is studied.•Bio-oils showed a ...higher conc. of oxygenates with the variance of pyrolysis conditions.•Increase in temperature decreased the % peak areas for organic acids and ketones.•Biochar characterization showed an energy potential comparable to low ranked coals.
This study investigated the potential of sawdust from the processing of Acacia wood for the furniture making industry to produce bio-oil and biochar in an auger pyrolysis reactor system. The necessary characterization to assess the suitability of feedstock and strategies the pyrolysis parameters was also carried out. The volatile matter, ash content, carbon content and the higher heating value of the sawdust feedstock were reported as 68.46 wt%, 1.13 wt%, 47.40 wt% and 19.33 MJ/kg, respectively, with very low nitrogen and sulfur content. The thermogravimetric (TGA and DTG) analysis of sawdust showed that the weight loss from biomass occurred in three main stages as a result of the removal of moisture and extractives, decomposition of hemicellulose, cellulose, and the lignin components. Based on the decomposition temperature window and peak conversion temperature the pyrolysis experiments were carried out in the range of 400–600 ℃ by maintaining the nitrogen flow rate, biomass feeding rate, rotation speed of the conveyer the residence time of materials and biomass particle size as 300 cm3/min, 180 g/h, 4.5 RPM, 5 min, and 0.5–1.0 mm, respectively. The yields of the non-condensable gases, biochar and bio-oil were reported in the ranges 16.70–38.47 wt%, 29.72–51.85 wt% and 29.40–45.10 wt%, respectively. The pyrolysis products were pragmatically analyzed to evaluate the influence on yield and their properties. The higher heating values of bio-oil produced were reported in the range 28.781–29.871 MJ/kg while the pH of bio-oil indicated the strongly acidic nature with values in the range of 2.9–3.4. Chemical compounds in bio-oils were categorized as phenols, nitrogen containing compounds, guaiacols, organic acids, ketones, anhydrous sugars, esters, and aldehydes. Biochar characterization showed an energy potential comparable to those of the low ranked coals with the higher heating values reported in the range of 25.01–25.99 MJ/kg. The surface morphological characteristics and Brunauer–Emmett–Teller (BET) analysis of the biochars indicated potential for other valued applications in the adsorption, environmental, catalyst, and agricultural context.
Primary microcephaly (MCPH) is characterized by reduced brain size and intellectual disability. The exact pathophysiological mechanism underlying MCPH remains to be elucidated, but dysfunction of ...neuronal progenitors in the developing neocortex plays a major role. We identified a homozygous missense mutation (p.W155C) in Ribosomal RNA Processing 7 Homolog A, RRP7A, segregating with MCPH in a consanguineous family with 10 affected individuals. RRP7A is highly expressed in neural stem cells in developing human forebrain, and targeted mutation of Rrp7a leads to defects in neurogenesis and proliferation in a mouse stem cell model. RRP7A localizes to centrosomes, cilia and nucleoli, and patient-derived fibroblasts display defects in ribosomal RNA processing, primary cilia resorption, and cell cycle progression. Analysis of zebrafish embryos supported that the patient mutation in RRP7A causes reduced brain size, impaired neurogenesis and cell proliferation, and defective ribosomal RNA processing. These findings provide novel insight into human brain development and MCPH.
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•Pyrolysis kinetics via iso-conversional and master plot are examined for analysis of kinetic parameters of pseudo components.•A combination of Asym2sig deconvolution and combined ...kinetics is applied.•Activation energy of pseudo cellulose was lower than the hemicellulose and lignin.•The kinetic parameters from combined kinetic agreed well with the experimental data.
This study examined the non-isothermal kinetics of the slow pyrolysis of Imperata Cylindrica (IC). Pyrolysis conditions were developed under the pure N2 flow and non-isothermal conditions at the heating rates of 2.5, 5, 10, and 17.5 K/min and over the temperature range of 303–1173 K. The IC pyrolysis profiles could be identified into three parallel reactions, each of which corresponded to pseudo-hemicelluloses (P-Hem), pseudo-cellulose (P-Cell), and pseudo-lignin (P-Lig) decomposition. A systematic kinetic study of the pyrolysis of IC via thermogravimetric analysis (TGA) deconvolution using Asymmetric Double Sigmoidal (Asym2sig), Friedman differential iso-conversional and combined kinetics of biomass pseudo-components was carried out. The kinetics parameters of pseudo components fitted well with the pyrolysis experimental data for all the heating rates. Differential master-plots showed that the reaction mechanisms for pseudo hemicellulose (P-Hem) and pseudo cellulose (P-Cell) were diffusional and order based, and high order based (3rd order) for the pseudo lignin (P-Lig). Mechanism of P-Hem, P-Cell and P-Lig could be further reconstructed to Sestak and Berggren model of fα=α-0.98751-α1.325-ln(1-α)0.0209,fα=α0.33131-α1.4731-ln(1-α)0.0215 and fα=α-2.95511-α2.7642-ln(1-α)0.0074, respectively. The combined kinetic reported the activation energies of pseudo-components were as 194.709 kJ/mol, 179.968 kJ/mol and 219.226 kJ/mol for P-Hem, P-Cell and P-Lig, respectively.
It has been well recognized that interactions between the gut microbiota and host-metabolism have a proven effect on health. The gut lumen is known for harboring different bacterial communities. ...Microbial by-products and structural components, which are derived through the gut microbiota, generate a signaling response to maintain homeostasis. Gut microbiota is not only involved in metabolic disorders, but also participates in the regulation of reproductive hormonal function. Bacterial phyla, which are localized in the gut, allow for the metabolization of steroid hormones through the stimulation of different enzymes. Reproductive hormones such as progesterone, estrogen and testosterone play a pivotal role in the successful completion of reproductive events. Disruption in this mechanism may lead to reproductive disorders. Environmental bacteria can affect the metabolism, and degrade steroid hormones and their relevant compounds. This behavior of the bacteria can safely be implemented to eliminate steroidal compounds from a polluted environment. In this review, we summarize the metabolism of steroid hormones on the regulation of gut microbiota and vice-versa, and also examined the significant influence this process has on various events of reproductive function. Altogether, the evidence suggests that steroid hormones and gut microbiota exert a central role in the modification of host bacterial action and impact the reproductive efficiency of animals and humans.
Endovascular treatment with mechanical thrombectomy (MT) is beneficial for patients with acute stroke suffering a large-vessel occlusion, although treatment efficacy is highly time-dependent. We ...hypothesized that interhospital transfer to endovascular-capable centers would result in treatment delays and worse clinical outcomes compared with direct presentation.
STRATIS (Systematic Evaluation of Patients Treated With Neurothrombectomy Devices for Acute Ischemic Stroke) was a prospective, multicenter, observational, single-arm study of real-world MT for acute stroke because of anterior-circulation large-vessel occlusion performed at 55 sites over 2 years, including 1000 patients with severe stroke and treated within 8 hours. Patients underwent MT with or without intravenous tissue plasminogen activator and were admitted to endovascular-capable centers via either interhospital transfer or direct presentation. The primary clinical outcome was functional independence (modified Rankin Score 0-2) at 90 days. We assessed (1) real-world time metrics of stroke care delivery, (2) outcome differences between direct and transfer patients undergoing MT, and (3) the potential impact of local hospital bypass.
A total of 984 patients were analyzed. Median onset-to-revascularization time was 202.0 minutes for direct versus 311.5 minutes for transfer patients (
<0.001). Clinical outcomes were better in the direct group, with 60.0% (299/498) achieving functional independence compared with 52.2% (213/408) in the transfer group (odds ratio, 1.38; 95% confidence interval, 1.06-1.79;
=0.02). Likewise, excellent outcome (modified Rankin Score 0-1) was achieved in 47.4% (236/498) of direct patients versus 38.0% (155/408) of transfer patients (odds ratio, 1.47; 95% confidence interval, 1.13-1.92;
=0.005). Mortality did not differ between the 2 groups (15.1% for direct, 13.7% for transfer;
=0.55). Intravenous tissue plasminogen activator did not impact outcomes. Hypothetical bypass modeling for all transferred patients suggested that intravenous tissue plasminogen activator would be delayed by 12 minutes, but MT would be performed 91 minutes sooner if patients were routed directly to endovascular-capable centers. If bypass is limited to a 20-mile radius from onset, then intravenous tissue plasminogen activator would be delayed by 7 minutes and MT performed 94 minutes earlier.
In this large, real-world study, interhospital transfer was associated with significant treatment delays and lower chance of good outcome. Strategies to facilitate more rapid identification of large-vessel occlusion and direct routing to endovascular-capable centers for patients with severe stroke may improve outcomes.
URL: https://www.clinicaltrials.gov. Unique identifier: NCT02239640.
Abstract
Aim
We tested the hypothesis that metformin may regress left ventricular hypertrophy (LVH) in patients who have coronary artery disease (CAD), with insulin resistance (IR) and/or ...pre-diabetes.
Methods and results
We randomly assigned 68 patients (mean age 65 ± 8 years) without diabetes who have CAD with IR and/or pre-diabetes to receive either metformin XL (2000 mg daily dose) or placebo for 12 months. Primary endpoint was change in left ventricular mass indexed to height1.7 (LVMI), assessed by magnetic resonance imaging. In the modified intention-to-treat analysis (n = 63), metformin treatment significantly reduced LVMI compared with placebo group (absolute mean difference −1.37 (95% confidence interval: −2.63 to −0.12, P = 0.033). Metformin also significantly reduced other secondary study endpoints such as: LVM (P = 0.032), body weight (P = 0.001), subcutaneous adipose tissue (P = 0.024), office systolic blood pressure (BP, P = 0.022) and concentration of thiobarbituric acid reactive substances, a biomarker for oxidative stress (P = 0.04). The glycated haemoglobin A1C concentration and fasting IR index did not differ between study groups at the end of the study.
Conclusion
Metformin treatment significantly reduced LVMI, LVM, office systolic BP, body weight, and oxidative stress. Although LVH is a good surrogate marker of cardiovascular (CV) outcome, conclusive evidence for the cardio-protective role of metformin is required from large CV outcomes trials.
Biogas, renewable energy resource for Pakistan Amjid, Syed S.; Bilal, Muhammad Q.; Nazir, Muhammad S. ...
Renewable & sustainable energy reviews,
08/2011, Letnik:
15, Številka:
6
Journal Article
Recenzirano
Developing countries are in critical energy crisis. Pakistan spends almost 7 billion US$ on import of fossil fuels annually to congregate its energy needs. The renewable and sustainable energy ...resources are best substitute to the conventional fuels and energy sources. Pakistan takes the opportunity to have almost 159 million animals producing almost 652
million
kg of manure daily from cattle and buffalo only; that can be used to generate 16.3
million
m
3 biogas per day and 21
million
tons of bio fertilizer per year. That compensate approximately 20% of nitrogen and 66% of phosphorus required in the crop fields. Apart from this sugarcane industry has got the potential to generate 3000
MW energy. Domestic biogas plants were started in Pakistan in 1959 and at present there is significant number of such working units. Biogas Support Program (BSP) was started in 2000 by Pakistani government. So far it has achieved the target of installing 1200 biogas units, whereas another 10,000
units are expected to be set up in coming 05
years that will harvest almost 27% of country's biogas potential. A biogas unit of 10
m
3 size is anticipated to save almost 92,062 PKR per year on account of conventional fuels spent otherwise. Women's opportunity cost, with introduction of biogas units reportedly increased; subsequently impacting positively on household income. Biogas energy generation systems are in demand and their number is increasing steadily. They are low-cost and can be run with very small budget. Biogas energy corridor can work as a good substitute for nearly 70% of country's population residing in rural areas. Installation of plants to bottle the biogas can be additional opportunity. The need of a national policy is imperative to bring this technology at farmer's doorstep.
Mobile stroke treatment units (MSTUs) with on-site treatment teams that include a vascular neurologist can provide thrombolysis in the prehospital setting faster than treatment in the hospital. These ...units can be made more resource efficient if the need for an on-site neurologist can be eliminated by relying solely on telemedicine for physician presence.
To test whether telemedicine is reliable and remote physician presence is adequate for acute stroke treatment using an MSTU.
Prospective observational study conducted between July 18 and November 1, 2014. The dates of the study analysis were November 1, 2014, to March 30, 2015. The setting was a community-based study assessing telemedicine success of the MSTU in Cleveland, Ohio. Participants were the first 100 residents of Cleveland who had an acute onset of stroke-like symptoms between 8 am and 8 pm and were evaluated by the MSTU after the implementation of the MSTU program at the Cleveland Clinic. A vascular neurologist evaluated the first 100 patients via telemedicine, and a neuroradiologist remotely assessed images obtained by mobile computed tomography (CT). Data were entered into the medical record and a prospective registry.
The study compared the evaluation and treatment of patients on the MSTU with a control group of patients brought to the emergency department via ambulance during the same year. Process times were measured from the time the patient entered the door of the MSTU or emergency department, and any problems encountered during his or her evaluation were recorded.
Ninety-nine of 100 patients were evaluated successfully. The median duration of telemedicine evaluation was 20 minutes (interquartile range IQR, 14-27 minutes). One connection failure was due to crew error, and the patient was transported to the nearest emergency department. There were 6 telemedicine disconnections, none of which lasted longer than 60 seconds or affected clinical care. Times from the door to CT completion (13 minutes IQR, 9-21 minutes) and from the door to intravenous thrombolysis (32 minutes IQR, 24-47 minutes) were significantly shorter in the MSTU group compared with the control group (18 minutes IQR, 12-26 minutes and 58 minutes IQR, 53-68 minutes, respectively). Times to CT interpretation did not differ significantly between the groups.
An MSTU using telemedicine is feasible, with a low rate of technical failure, and may provide an avenue for reducing the high cost of such systems.
Biochar production from invasive species biomass discarded as waste was studied in a fixed bed reactor pyrolysis system under different temperature conditions for value-added applications. Prior to ...pyrolysis, the biomass feedstock was characterized by proximate, ultimate, and heating value analyses, while the biomass decomposition behavior was examined by thermogravimetric analysis. The heating values of the feedstock biomass ranged from 18.65 to 20.65 MJ/kg, whereas the volatile matter, fixed carbon, and ash content were 61.54–72.04 wt %, 19.27–26.61 wt % and 1.51–1.86 wt %, respectively. The elemental composition of carbon, hydrogen, and oxygen in the samples was reported to be in the range of 47.41–48.47 wt %, 5.50–5.88 wt % and 46.10–45.18 wt %, respectively, while the nitrogen and sulphur content in the biomass samples were at very low concentrations, making it more useful for valorization from environmental aspects. The biochar yields were reported in the range of 45.36–58.35 wt %, 28.63–44.38 wt % and 22.68–29.42 wt % at a pyrolysis temperature of 400 °C, 500 °C, and 600 °C, respectively. The biochars were characterized from ultimate analysis, heating value, energy densification ratio, energy yield, pH, Fourier transform infrared spectroscopy (FTIR), and scanning electron microscopy and energy dispersive X-ray spectrometry (SEM and EDX), to evaluate their potential for value-added applications. The carbon content, heating value, energy densification ratio, and the porosity of the biochars improved with the increase in pyrolysis temperature, while the energy yield, hydrogen, oxygen, and nitrogen content of the biochars decreased. This study revealed the potential of the valorization of underutilized discarded biomass of invasive species via a pyrolysis process to produce biochar for value-added applications.
•Biochar production from invasive biomass was studied for value-added applications.•The HHV of the feedstock biomass were reported in the range of 18.65–20.65 MJ/kg.•Biochar yield range, 400 (45.36–58.35), 500 (28.63–44.38) and 600 °C (22.68–29.42).•Energy, adsorption, catalyst and agricultural potential of biochars was discussed.•Beneficial and ecofriendly management of underutilized biomass was proposed.
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