Transport of organelles by elastically coupled motor proteins

Motor-driven cargo transport is a complex phenomenon where multiple motor proteins attached on to a cargo engage in pulling activity, often leading to tug-of-war, displaying bidirectional motion. However, most mathematical and computational models ignore the details of the motor-cargo interaction. Here, we study a generic model in which N motors are elastically coupled to a cargo, which itself is subjected to thermal noise in the cytoplasm and to an additional external applied force. The motor-hopping rates are chosen to satisfy detailed balance with respect to the energy of elastic stretching. With these assumptions, an (N+1)-variable master equation is constructed for dynamics of the motor-cargo complex. By expanding the hopping rates to linear order in fluctuations in motor positions, we obtain a linear Fokker-Planck equation. The deterministic equations governing the average quantities are separated out and explicit analytical expressions are obtained for the mean velocity and diffusion coefficient of the cargo. We also study the statistical features of the force experienced by an individual motor and quantitatively characterize the load-sharing among the cargo-bound motors. The mean cargo velocity and the effective diffusion coefficient are found to be decreasing functions of the stiffness. While increase in the number of motors N does not increase the velocity substantially, it decreases the effective diffusion coefficient which falls as 1/N asymptotically. We further show that the cargo-bound motors share the force exerted on the cargo equally only in the limit of vanishing elastic stiffness; as stiffness is increased, deviations from equal load sharing are observed. Numerical simulations agree with our analytical results where expected. Interestingly, we find in simulations that the stall force of a cargo elastically coupled to motors is independent of the stiffness

Stall force of a cargo driven by N interacting motor proteins

We study a generic one-dimensional model for an intracellular cargo driven by N motor proteins against an external applied force. The model includes motor-cargo and motor-motor interactions. The cargo motion is described by an over-damped Langevin equation, while motor dynamics is specified by hopping rates which follow a local detailed balance condition with respect to change in energy per hopping event. Based on this model, we show that the stall force, the mean external force corresponding to zero mean cargo velocity, is completely independent of the details of the interactions and is, therefore, always equal to the sum of the stall forces of the individual motors. This exact result is arrived on the basis of a simple assumption: the (macroscopic) state of stall of the cargo is analogous to a state of thermodynamic equilibrium, and is characterized by vanishing net probability current between any two microstates, with the latter specified by motor positions relative to the cargo. The corresponding probability distribution of the microstates under stall is also determined. These predictions are in complete agreement with numerical simulations, carried out using specific forms of interaction potentials.Comment: Accepted in Europhysics Letter

Invasive plant species as potential bioenergy producers and carbon contributors

Among recent advances in developing cellulosic and noncellulosic biofuel sources, corn, switchgrass, and others (e.g., camelina, canola) have risen to the top. In surveying the landscape, a potentially promising new area of bioenergy production exists—invasive plant species. The addition of invasive plant species as a bioenergy source will help to diversify the nation’s energy dependence and help in the reduction of the negative environmental and social impacts from energy crop production. In addition, belowground carbon stores may provide an opportunity to reduce the impacts associated with global climate change. In the agriculture sector, harvesting equipment is well advanced for facilitating efficient crop production on both small and large scales. In noncrop systems, the number of limitations and lack of need have slowed the progress of equipment development for biomass harvesting (Graneli 1984). The lack of economic return is an important reason for less intensive management in noncrop areas. With new markets emerging for cellulosic energy sources and advances in equipment technology, this increased incentive could help improve the level of management of invasive plant species in noncrop areas and subsequent harvest or removal of excess biomass. Using invasive plant species in bioenergy facilities would provide enticing opportunities for land managers and business developers. Since the primary focus of most invasive plant species management is on control of unwanted vegetation, the massive amounts of biomass from high cellulosic plants creates a challenge for disposal. Research has shown that piling or dispersing cut portions of many woody and herbaceous invasive plant species can result in the reestablishment by new plants from propagule segments (Boose and Holt 1999; Decruyenaere and Holt 2001). With advances in processing equipment, invasive plant species biomass could be processed into pellets for transporting to facilities that burn biomass or convert biomass to liquid biofuels. The processing of invasive plant species into a useable form (i.e., pellets) that does not promote the spread or introduction of unwanted vegetation minimizes the risks of environmental contamination and provides an economic opportunity for business development in rural communities. While corn and switchgrass are the leading plant candidates for biofuel production, they may not be the most sustainable. Alternatively, the removal of existing invasive plant species biomass and processing into pellets for combustion or liquid fuel conversion maybe more sustainable as it would comply with the US Executive Order 13112 on invasive species (Clinton 1999), support climate change initiatives (Crowl et al. 2008), and expand economic opportunities in rural areas by helping fulfill the mandate by the US Renewable Fuels Standards (USDA 2010)

Critical Aspects of Electric Motor Drive Controllers and Mitigation of Torque Ripple - Review

Electric vehicles (EVs) are playing a vital role in sustainable transportation. It is estimated that by 2030, Battery EVs will become mainstream for passenger car transportation. Even though EVs are gaining interest in sustainable transportation, the future of EV power transmission is facing vital concerns and open research challenges. Considering the case of torque ripple mitigation and improved reliability control techniques in motors, many motor drive control algorithms fail to provide efficient control. To efficiently address this issue, control techniques such as Field Orientation Control (FOC), Direct Torque Control (DTC), Model Predictive Control (MPC), Sliding Mode Control (SMC), and Intelligent Control (IC) techniques are used in the motor drive control algorithms. This literature survey exclusively compares the various advanced control techniques for conventionally used EV motors such as Permanent Magnet Synchronous Motor (PMSM), Brushless Direct Current Motor (BLDC), Switched Reluctance Motor (SRM), and Induction Motors (IM). Furthermore, this paper discusses the EV-motors history, types of EVmotors, EV-motor drives powertrain mathematical modelling, and design procedure of EV-motors. The hardware results have also been compared with different control techniques for BLDC and SRM hub motors. Future direction towards the design of EV by critical selection of motors and their control techniques to minimize the torque ripple and other research opportunities to enhance the performance of EVs are also presented.publishedVersio

EBBINNOT: A Hardware Efficient Hybrid Event-Frame Tracker for Stationary Dynamic Vision Sensors

As an alternative sensing paradigm, dynamic vision sensors (DVS) have been recently explored to tackle scenarios where conventional sensors result in high data rate and processing time. This paper presents a hybrid event-frame approach for detecting and tracking objects recorded by a stationary neuromorphic sensor, thereby exploiting the sparse DVS output in a low-power setting for traffic monitoring. Specifically, we propose a hardware efficient processing pipeline that optimizes memory and computational needs that enable long-term battery powered usage for IoT applications. To exploit the background removal property of a static DVS, we propose an event-based binary image creation that signals presence or absence of events in a frame duration. This reduces memory requirement and enables usage of simple algorithms like median filtering and connected component labeling for denoise and region proposal respectively. To overcome the fragmentation issue, a YOLO inspired neural network based detector and classifier to merge fragmented region proposals has been proposed. Finally, a new overlap based tracker was implemented, exploiting overlap between detections and tracks is proposed with heuristics to overcome occlusion. The proposed pipeline is evaluated with more than 5 hours of traffic recording spanning three different locations on two different neuromorphic sensors (DVS and CeleX) and demonstrate similar performance. Compared to existing event-based feature trackers, our method provides similar accuracy while needing approx 6 times less computes. To the best of our knowledge, this is the first time a stationary DVS based traffic monitoring solution is extensively compared to simultaneously recorded RGB frame-based methods while showing tremendous promise by outperforming state-of-the-art deep learning solutions.Comment: 16 pages, 13 figure

Fermentative valorisation of xylose-rich hemicellulosic hydrolysates from agricultural waste residues for lactic acid production under non-sterile conditions

Lactic acid (LA) is a platform chemical with diverse industrial applications. Presently, commercial production of LA is dominated by microbial fermentation using sugary or starch-based feedstocks. Research pursuits emphasizing towards sustainable production of LA using non-edible and renewable feedstocks have accelerated the use of lignocellulosic biomass (LCB). The present study focuses on the valorisation of xylose derived from sugarcane bagasse (SCB) and olive pits (OP) through hydrothermal and dilute acid pretreatment, respectively. The xylose-rich hydrolysate obtained was used for LA production by homo-fermentative and thermophilic Bacillus coagulans DSM2314 strain under non-sterile conditions. The fed-batch mode of fermentation resulted in maximum LA titers of 97.8, 52.4 and 61.3 g/L with a yield of 0.77, 0.66 and 0.71 g/g using pure xylose, xylose-rich SCB and OP hydrolysates, respectively. Further, a two-step aqueous two-phase system (ATPS) extraction technique was employed for the separation and recovery of LA accumulated on pure and crude xylose. The LA recovery was 45 – 65% in the first step and enhanced to 80–90% in the second step.The study demonstrated an efficient integrated biorefinery approach to valorising the xylose-rich stream for cost-effective LA production and recovery.Biotechnology and Biological Sciences Research Council (BBSRC): BB/S011951/1. Engineering and Physical Sciences Research Council (EPSRC): EP/L016389/1. Innovate UK. Department of Biotechnology, Indi

Canagliflozin and Cardiovascular and Renal Outcomes in Type 2 Diabetes Mellitus and Chronic Kidney Disease in Primary and Secondary Cardiovascular Prevention Groups

Background: Canagliflozin reduces the risk of kidney failure in patients with type 2 diabetes mellitus and chronic kidney disease, but effects on specific cardiovascular outcomes are uncertain, as are effects in people without previous cardiovascular disease (primary prevention). Methods: In CREDENCE (Canagliflozin and Renal Events in Diabetes With Established Nephropathy Clinical Evaluation), 4401 participants with type 2 diabetes mellitus and chronic kidney disease were randomly assigned to canagliflozin or placebo on a background of optimized standard of care. Results: Primary prevention participants (n=2181, 49.6%) were younger (61 versus 65 years), were more often female (37% versus 31%), and had shorter duration of diabetes mellitus (15 years versus 16 years) compared with secondary prevention participants (n=2220, 50.4%). Canagliflozin reduced the risk of major cardiovascular events overall (hazard ratio [HR], 0.80 [95% CI, 0.67-0.95]; P=0.01), with consistent reductions in both the primary (HR, 0.68 [95% CI, 0.49-0.94]) and secondary (HR, 0.85 [95% CI, 0.69-1.06]) prevention groups (P for interaction=0.25). Effects were also similar for the components of the composite including cardiovascular death (HR, 0.78 [95% CI, 0.61-1.00]), nonfatal myocardial infarction (HR, 0.81 [95% CI, 0.59-1.10]), and nonfatal stroke (HR, 0.80 [95% CI, 0.56-1.15]). The risk of the primary composite renal outcome and the composite of cardiovascular death or hospitalization for heart failure were also consistently reduced in both the primary and secondary prevention groups (P for interaction >0.5 for each outcome). Conclusions: Canagliflozin significantly reduced major cardiovascular events and kidney failure in patients with type 2 diabetes mellitus and chronic kidney disease, including in participants who did not have previous cardiovascular disease

Canagliflozin and renal outcomes in type 2 diabetes and nephropathy

BACKGROUND Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium–glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. METHODS In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to <90 ml per minute per 1.73 m2 of body-surface area and albuminuria (ratio of albumin [mg] to creatinine [g], >300 to 5000) and were treated with renin–angiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of <15 ml per minute per 1.73 m2), a doubling of the serum creatinine level, or death from renal or cardiovascular causes. Prespecified secondary outcomes were tested hierarchically. RESULTS The trial was stopped early after a planned interim analysis on the recommendation of the data and safety monitoring committee. At that time, 4401 patients had undergone randomization, with a median follow-up of 2.62 years. The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P=0.00001). The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P<0.001), and the relative risk of end-stage kidney disease was lower by 32% (hazard ratio, 0.68; 95% CI, 0.54 to 0.86; P=0.002). The canagliflozin group also had a lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01) and hospitalization for heart failure (hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P<0.001). There were no significant differences in rates of amputation or fracture. CONCLUSIONS In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years

Global, regional, and national under-5 mortality, adult mortality, age-specific mortality, and life expectancy, 1970–2016: a systematic analysis for the Global Burden of Disease Study 2016

BACKGROUND: Detailed assessments of mortality patterns, particularly age-specific mortality, represent a crucial input that enables health systems to target interventions to specific populations. Understanding how all-cause mortality has changed with respect to development status can identify exemplars for best practice. To accomplish this, the Global Burden of Diseases, Injuries, and Risk Factors Study 2016 (GBD 2016) estimated age-specific and sex-specific all-cause mortality between 1970 and 2016 for 195 countries and territories and at the subnational level for the five countries with a population greater than 200 million in 2016. METHODS: We have evaluated how well civil registration systems captured deaths using a set of demographic methods called death distribution methods for adults and from consideration of survey and census data for children younger than 5 years. We generated an overall assessment of completeness of registration of deaths by dividing registered deaths in each location-year by our estimate of all-age deaths generated from our overall estimation process. For 163 locations, including subnational units in countries with a population greater than 200 million with complete vital registration (VR) systems, our estimates were largely driven by the observed data, with corrections for small fluctuations in numbers and estimation for recent years where there were lags in data reporting (lags were variable by location, generally between 1 year and 6 years). For other locations, we took advantage of different data sources available to measure under-5 mortality rates (U5MR) using complete birth histories, summary birth histories, and incomplete VR with adjustments; we measured adult mortality rate (the probability of death in individuals aged 15-60 years) using adjusted incomplete VR, sibling histories, and household death recall. We used the U5MR and adult mortality rate, together with crude death rate due to HIV in the GBD model life table system, to estimate age-specific and sex-specific death rates for each location-year. Using various international databases, we identified fatal discontinuities, which we defined as increases in the death rate of more than one death per million, resulting from conflict and terrorism, natural disasters, major transport or technological accidents, and a subset of epidemic infectious diseases; these were added to estimates in the relevant years. In 47 countries with an identified peak adult prevalence for HIV/AIDS of more than 0·5% and where VR systems were less than 65% complete, we informed our estimates of age-sex-specific mortality using the Estimation and Projection Package (EPP)-Spectrum model fitted to national HIV/AIDS prevalence surveys and antenatal clinic serosurveillance systems. We estimated stillbirths, early neonatal, late neonatal, and childhood mortality using both survey and VR data in spatiotemporal Gaussian process regression models. We estimated abridged life tables for all location-years using age-specific death rates. We grouped locations into development quintiles based on the Socio-demographic Index (SDI) and analysed mortality trends by quintile. Using spline regression, we estimated the expected mortality rate for each age-sex group as a function of SDI. We identified countries with higher life expectancy than expected by comparing observed life expectancy to anticipated life expectancy on the basis of development status alone. FINDINGS: Completeness in the registration of deaths increased from 28% in 1970 to a peak of 45% in 2013; completeness was lower after 2013 because of lags in reporting. Total deaths in children younger than 5 years decreased from 1970 to 2016, and slower decreases occurred at ages 5-24 years. By contrast, numbers of adult deaths increased in each 5-year age bracket above the age of 25 years. The distribution of annualised rates of change in age-specific mortality rate differed over the period 2000 to 2016 compared with earlier decades: increasing annualised rates of change were less frequent, although rising annualised rates of change still occurred in some locations, particularly for adolescent and younger adult age groups. Rates of stillbirths and under-5 mortality both decreased globally from 1970. Evidence for global convergence of death rates was mixed; although the absolute difference between age-standardised death rates narrowed between countries at the lowest and highest levels of SDI, the ratio of these death rates-a measure of relative inequality-increased slightly. There was a strong shift between 1970 and 2016 toward higher life expectancy, most noticeably at higher levels of SDI. Among countries with populations greater than 1 million in 2016, life expectancy at birth was highest for women in Japan, at 86·9 years (95% UI 86·7-87·2), and for men in Singapore, at 81·3 years (78·8-83·7) in 2016. Male life expectancy was generally lower than female life expectancy between 1970 and 2016, an

Global, regional, and national disability-adjusted life-years (DALYs) for 333 diseases and injuries and healthy life expectancy (HALE) for 195 countries and territories, 1990–2016: a systematic analysis for the Global Burden of Disease Study 2016

BACKGROUND: Measurement of changes in health across locations is useful to compare and contrast changing epidemiological patterns against health system performance and identify specific needs for resource allocation in research, policy development, and programme decision making. Using the Global Burden of Diseases, Injuries, and Risk Factors Study 2016, we drew from two widely used summary measures to monitor such changes in population health: disability-adjusted life-years (DALYs) and healthy life expectancy (HALE). We used these measures to track trends and benchmark progress compared with expected trends on the basis of the Socio-demographic Index (SDI). METHODS: We used results from the Global Burden of Diseases, Injuries, and Risk Factors Study 2016 for all-cause mortality, cause-specific mortality, and non-fatal disease burden to derive HALE and DALYs by sex for 195 countries and territories from 1990 to 2016. We calculated DALYs by summing years of life lost and years of life lived with disability for each location, age group, sex, and year. We estimated HALE using age-specific death rates and years of life lived with disability per capita. We explored how DALYs and HALE differed from expected trends when compared with the SDI: the geometric mean of income per person, educational attainment in the population older than age 15 years, and total fertility rate. FINDINGS: The highest globally observed HALE at birth for both women and men was in Singapore, at 75·2 years (95% uncertainty interval 71·9-78·6) for females and 72·0 years (68·8-75·1) for males. The lowest for females was in the Central African Republic (45·6 years [42·0-49·5]) and for males was in Lesotho (41·5 years [39·0-44·0]). From 1990 to 2016, global HALE increased by an average of 6·24 years (5·97-6·48) for both sexes combined. Global HALE increased by 6·04 years (5·74-6·27) for males and 6·49 years (6·08-6·77) for females, whereas HALE at age 65 years increased by 1·78 years (1·61-1·93) for males and 1·96 years (1·69-2·13) for females. Total global DALYs remained largely unchanged from 1990 to 2016 (-2·3% [-5·9 to 0·9]), with decreases in communicable, maternal, neonatal, and nutritional (CMNN) disease DALYs offset by increased DALYs due to non-communicable diseases (NCDs). The exemplars, calculated as the five lowest ratios of observed to expected age-standardised DALY rates in 2016, were Nicaragua, Costa Rica, the Maldives, Peru, and Israel. The leading three causes of DALYs globally were ischaemic heart disease, cerebrovascular disease, and lower respiratory infections, comprising 16·1% of all DALYs. Total DALYs and age-standardised DALY rates due to most CMNN causes decreased from 1990 to 2016. Conversely, the total DALY burden rose for most NCDs; however, age-standardised DALY rates due to NCDs declined globally. INTERPRETATION: At a global level, DALYs and HALE continue to show improvements. At the same time, we observe that many populations are facing growing functional health loss. Rising SDI was associated with increases in cumulative years of life lived with disability and decreases in CMNN DALYs offset by increased NCD DALYs. Relative compression of morbidity highlights the importance of continued health interventions, which has changed in most locations in pace with the gross domestic product per person, education, and family planning. The analysis of DALYs and HALE and their relationship to SDI represents a robust framework with which to benchmark location-specific health performance. Country-specific drivers of disease burden, particularly for causes with higher-than-expected DALYs, should inform health policies, health system improvement initiatives, targeted prevention efforts, and development assistance for health, including financial and research investments for all countries, regardless of their level of sociodemographic development. The presence of countries that substantially outperform others suggests the need for increased scrutiny for proven examples of best practices, which can help to extend gains, whereas the presence of underperforming countries suggests the need for devotion of extra attention to health systems that need more robust support. FUNDING: Bill & Melinda Gates Foundation