Faster Rate Research Articles

Behavior of leadless atrioventricular synchronous pacing during exercise

BackgroundThe leadless Micra AV pacemaker is designed to provide atrioventricular (AV) synchronous tracking by detecting atrial contraction. Detection of the mechanical atrial signals can become challenging at a fast sinus rate. ObjectiveThe purpose of the study was to evaluate the AV synchronous performance at exercise in outpatients implanted with a Micra AV pacemaker. MethodsPatients were enrolled at least 1 month after Micra AV implantation and underwent a cycle test protocol. Serial device interrogations (each minute) and continuous electrocardiograms were collected to measure AV synchrony and determine maximum achieved sinus and ventricular rates for each patient. In addition, the A1, A2, A3, and A4 accelerometer signal amplitudes were measured at the start and peak of exercise. ResultsThirty-five patients (mean age 75.6 ± 13.4 years; 80% male) were enrolled in the study; 22 (64%) were predominantly ventricular paced (>90%) during exercise. Average AV synchrony was 90.4% in the entire cohort and 84.7% in patients with high-degree AV block. The mean amplitude of the accelerometer signals increased significantly from the start to the peak of exercise: A1, 4.1–6.3 m/s2; A2, 2.4–3.8 m/s2; and A4, 4.5–7.6 m/s2 (P < .01 for all). The time from the VP-A2 decreased 25 ms for each 100 ms of the R-R interval decrease. ConclusionMaintaining AV synchrony during maximal exercise in elderly patients is achievable by adequate detection of atrial contraction at high sinus rates by the leadless Micra AV pacemaker. All components of the accelerometer signal increased, likely because of increased contractility related to exercise.

Biophysical factors affecting transpiration of typical afforestation species under environmental change in the Loess Plateau, China

Transpiration in artificial forests has a vital role in the ecohydrological cycle and evolution of afforestation in semi-arid regions. However, further research is required to understand the impacts of biotic and abiotic factors on transpiration and water regulation strategies in tree species under climate change. We used the sap flow method to quantify transpiration in three adjacent plantations (Pinus tabuliformis, Populus simonii, and Ulmus pumila) spaced 40 m apart, and concurrently monitored soil moisture and meteorological variables. Significant differences in average transpiration were observed in the following order: P. simonii (1.31 ± 0.49 mm d–1) > U. pumila (1.04 ± 0.45 mm d–1) > P. tabuliformis (0.75 ± 0.31 mm d–1), due to differences in the canopy conductance, which followed the order of P. simonii (2.02 ± 0.18 mm/s) > U. pumila (1.70 ± 0.15 mm/s) > P. tabuliformis (1.26 ± 0.11 mm/s) (P < 0.05). Under severe soil water stress, high vapor pressure deficit, and high solar radiation, transpiration was reduced in all species during the drought period in 2022 because of reduced canopy conductance (P < 0.05). Our findings demonstrate that a fast growth rate, deep root systems, and close relationships between the leaf water potential and stomatal regulation are vital strategies for trees responding to drought. Consequently, we recommend P. simonii for shelter forests and P. tabuliformis for ecological landscape forests to improve the stability of afforestation in semi-arid regions.

Acid Fast Positivity Rate and Associated Factors of Leprosy in a Tertiary Care Hospital of Northeastern Ethiopia: Its Implication for Evidence-Based Leprosy Prevention and Control.

Leprosy is one of the most common skin neglected tropical diseases in Ethiopia posing social stigma, physical disability, deformity, discrimination, loss of social status, and poor quality of life in families. Hence, evidence-based collaborative inter-sectoral actions should be performed to reduce and eliminate its burden in endemic areas. Thus, the aim of this study was to assess the acid-fast positivity rate and associated factors of leprosy among suspected cases in Northeastern Ethiopia: a cross-sectional study. A cross-sectional study was conducted from September 2022 to March 2023 among 256 leprosy-suspected cases selected using a simple random sampling technique. A semi-structured questionnaire was used to collect socio-demographic, clinical, and predictor variables of leprosy through face-to-face interviews. Skin slit specimens were collected and stained using Ziehl-Neelsen staining technique. STATA 17 was used for analysis. The scale reliability coefficient was checked using Cronbach's α and the goodness-of-fit test of the model was assessed by the Hosmer-Lemshow test. Moreover, bivariable and multivariable logistic regression were computed. Finally, variables with an adjusted odds ratio and their p < 0.05 were taken as statistically significant. The mean ± standard deviation of the age of participants was 43.25 ± 16.35. The overall, prevalence of acid-fast positivity among suspected cases was 19.6% (95% CI: 15.8%, 23.4%). Multivariable logistic regression analysis showed that sex being male (p = 0.045), rural residence (p = 0.047), not eating three times meals frequency (p = 0.014), not eating a balanced diet (p = 0.036), poor personal hygiene (p = 0.028), distant from health facility (p = 0.039), not washing hands usually (p = 0.013), presence of current co-infection (p = 0.002), type of leprosy (p = 0.004), and close contact with leprosy cases (p = 0.003) were more likely to be positive for leprosy. The prevalence of leprosy was remained high. Thus, early detection and treatment are necessary to reduce delayed diagnosis and hidden transmission of leprosy in the community. By addressing the driving factors through evidence-based intervention, we can significantly control the burden of leprosy in the affected communities, and improve their health outcomes and quality of life.

Mitigation of phosphorus contamination from livestock farms with La-containing hydrochar adsorbent

Phosphorus releases from livestock and poultry farms cause environmental contamination that must be mitigated through robust and effective recycle technologies. Lanthanum-modified hydrochars (La-HCN) prepared via mechanochemical modification had 96.8 mg g−1 phosphorus adsorption capacities and unprecedented fast uptake rates (half-maximum absorption capacity in 1.5 min). Presence of nitrogen in the hydrochars enhanced ion electrostatic interactions between lanthanum and carbon and accelerated phosphorus adsorption, which was confirmed theoretically with density functional theory calculations. Life cycle assessment (LCA) on a one-animal one-year basis revealed that production of La-containing hydrochar required fewer resources, had lower greenhouse gas emissions (171 kg CO2) and lower environmental impact than comparable adsorbent materials. Phosphorus removal levels achieved using the La-HCN adsorbent on actual wastewater from livestock and poultry breeding farms reached an adsorption rate of 93.6 %, exceeded sewage effluent standards of China, US EPA and EU, thus, demonstrate the practicality and scope of the developed technology.

A minute-resolution downscaling algorithm for high-resolution global irradiance time series

Numerous studies have demonstrated the significant impact of the resolution of solar irradiation data on the outcomes of hourly production models. Accurate integration of photovoltaic (PV) systems sometimes demands a high-resolution global horizontal irradiance (GHI) time series to capture the rapid fluctuations in PV power output induced by swift irradiance changes. Most of the available databases provide data at hourly resolution, leading to a lack of accuracy in PV simulations. Those existing hourly averages of global horizontal irradiance in open sources fail to represent this volatility adequately, especially when PV systems are coupled with fast ramp rate technologies. In the present work, an easy-to-use algorithm is implemented to synthesize high-resolution GHI time series from hourly averaged and clear sky irradiance datasets. By employing Linear interpolation, a technique that helps to achieve the desired time resolution and afterward computing critical factors, the algorithm identifies periods characterized by short-term weather phenomena, thus creating a high-resolution time series that accurately represents these dynamics. Avoiding the probabilistic components and machine learning techniques conserves computational power and reduces calculation time, but this comes at the cost of reduced fidelity in reproducing the results. Improving accuracy in PV simulations is not always directly related to reproducing real phenomena, but enhancing the amount of information contained in the data is sufficient. This study’s approach enhances user-friendliness and facilitates seamless integration into existing energy modeling frameworks, aiming for representation with sub-hourly time steps. The algorithm’s effectiveness is demonstrated by applying the model to hourly averaged data to revert them to a one-minute time step, and finally comparing the synthetically produced one-minute GHI data to the original measured data. The comparative analysis between synthesized and measured data demonstrated a strong agreement, with normalized mean bias error (MBE) values ranging between 1.8% and 9.6% and normalized root mean square error (NRMSE) values between 2.7% and 16.1%, depending on weather conditions. Additionally, the coefficient of determination (R2) consistently remained above 0.64. Successful algorithm validation makes our algorithm suitable for use in meteorological datasets and locations, with similar climatic characteristics.

Custom-shaped malleable, recyclable and reversible structural adhesives based on vanillin polyimine vitrimers

A series of polyimine vitrimers were prepared from a synthesized dialdehyde derivative of vanillin. This derivative was then crosslinked with two different ratios of amines (Jeffamine T403 and m-xylylenediamine), forming imine bonds responsible for the exchange reactions. This process resulted in three distinct materials which exhibited glass transition temperatures (Tgs) ranging from 20 to 60 °C, along with good thermal stability, and strong mechanical and thermomechanical properties.Their dynamicity resulted in a fast relaxation rate achieving a complete relaxation in less than 15 min at 140 °C. Additionally, the polyimines could be mechanically recycled up to three times without significant loss in their final properties, demonstrating the possible enhancement of their lifespan. Moreover, they could be chemically recycled under mild conditions through acid hydrolysis or transamination, which significantly contributes towards a better circular economy. Furthermore, these vitrimers were tested as reversible structural adhesives, achieving initial lap-shear strength values of 12.4 MPa and up to 97 % of efficiency after re-bonding, highlighting their huge potential for industrial applications. Due to their pre-cured state, these adhesives were malleable, which allow them to be custom-shaped into different complex shapes. Finally, these imine materials showed outstanding self-welding capabilities with the repaired versions showing comparable performance to the original.

Dielectric and magnetic properties of microwave-absorbing FeAlxOy catalysts fabricated via solution combustion synthesis

Iron-based alumina (FeAlxOy) nanocomposites are microwave-absorbers and catalysts, which makes them promising for emerging microwave-assisted thermocatalytic technologies. Solution combustion synthesis (SCS) has been used to synthesize FeAlxOy powders, and prior work has demonstrated that adjusting SCS parameters significantly changes phase composition and specific surface area of the products. However, it is unclear how synthesis parameters affect their microwave-absorbing properties, which are essential for optimizing microwave-assisted technologies. To address this challenge, in the present work, twelve different FeAlxOy products were synthesized at different combinations of the SCS parameters such as two fuels (citric acid and glycine), two heating modes (hotplate and muffle furnace), and three Fe:Al molar ratios (2:1, 1:1, 1:2). Dielectric and magnetic properties of the products were characterized using a network analyzer and a vibrating sample magnetometer. Based on the measured permittivity and permeability, penetration depth and reflection loss were calculated as a function of frequency and bed thickness. The products were heated by microwaves at 2.45 GHz and then examined with X-ray diffraction (XRD) analysis. For all products, the magnetic saturation was lower than for bulk iron oxides because of the small crystallite size and aluminum substitution. The use of glycine induced high dielectric losses and enabled fast microwave-heating rates compared to citric acid. Higher Fe:Al ratio also led to higher dielectric and magnetic losses. With glycine fuel, SCS in a furnace induced larger penetration depth and lower microwave absorption than SCS on a hotplate. The minimization of reflected power was more sensitive to the thickness of the product bed than to the frequency of the electromagnetic field. Post-heating XRD analysis revealed different phase transformations in the FeAlxOy powders depending on the SCS parameters. An FeAlxOy material, synthesized via incipient wetness impregnation, lacked magnetic losses and did not heat well as compared to the SCS products.

Thermal performance analysis of new bionic “fishbone” fins in a triplex-tube latent heat storage system with single cycle process

Targeting the low thermal conductivity characteristics of energy storage materials in latent heat thermal energy storage (LHTES) systems, a novel bionic fish bone fin design is proposed in this paper, and the numerical simulation is employed to analyze the thermal performance of a system during single charging and discharging cycle. In assessing the system, consideration is given to the time required to complete a cycle, mean temperature change rate, and charging and discharging efficiency over the course of a cycle. The temperature response of each monitoring point within the system was first analyzed for fishbone fins of different curvatures and found that the 30° and 60° fishbone fins have the fastest heat transfer rates and shortest cycle times, respectively. Subsequently, the effect of fishbone fractal position on the thermal performance of the system was investigated. The results showed that the system achieves the best circulating thermal performance when the fishbone fins are positioned in the middle of the straight fins. An increase in the dimensionless position of the fins from 0.2 to 0.5 produced a reduction in the cycle time of 28.03 % and an increase in the energy transfer efficiency of 38.15 %. Finally, the shortest cyclic cycle and the fastest heat transfer rate were taken as the optimization objectives to optimize and predict the thermal performance of the system through the response surface method. The findings demonstrated that the system exhibited optimal thermal performance when the radian angle of the fishbone fin is 44.43° and the dimensionless position is 0.45. Compared to traditional rectangular straight fins, the optimized structure reduces the cycle time by 52.64 % and increases the average heat transfer rate by 101.58 %.

Mechanistic insights into the roles of copper in enhanced peroxymonosulfate activation for tetracycline degradation by copper ferrite composite catalyst

Tetracycline (TC) pollution has attracted great attention due to its wide use, non-biodegradability and potential carcinogenicity. Bimetallic catalysts/peroxymonosulfate (PMS) systems have been considered as powerful technologies for TC degradation. Although the excellent catalytic activity of copper ferrite (CuFe2O4) composite oxides for PMS has been already elucidated, the roles of increased Cu in the degradation especially from non-radical pathways are not clarified clearly. In this study, we prepared a series of CuO/CuFe2O4/Fe2O3 (CCF) catalysts to confirm the key role of molar ratios of Cu: Fe (ranging from 1:2 to 2:1) in the enhanced degradation. The optimized CCF-3 catalyst with the Cu: Fe molar ratio of 2:1 showed the best degradation efficiency up to 95.6 % and the fastest apparent degradation rate of 0.135 min−1 towards TC. In addition, the CCF-3/PMS system showed excellent adaptability and good stability in TC degradation. Importantly, a novel molecular-scale mechanism was proposed. Both radical (SO4∙-, ∙OH, O2∙ –) and non-radical (1O2, direct electron transfer) pathways were associated with the CCF-3/PMS catalytic system, where 1O2 played the dominant roles. The increased Cu significantly boosted the non-radical pathways via promoting the formation of oxygen vacancies (Ov) and its further conversion to 1O2, and facilitating electron transfer between bimetallic Cu/Fe interface. This work provides a deep insight into the formation and reaction mechanisms of non-radical species for CCF/PMS systems, and a novel foundation for the design of CuFe2O4 composite catalysts

Synthesis, characterization and anticancer activity of zinc sulfide nanoparticle using heterocyclic Zn (II) thiosemicarbazone complex as a single source

The green synthesis of zinc sulphide nanoparticles (Zn S NPs) using Zn(II) complex as a single molecular precursor is gaining importance due to its simplicity, cost – effectiveness and pharmacologically active nature. Now – a- day’s nanobiotechnolgy is increasing at a fast rate due to its many possible applications in the biomedical and, pharmaceuticals fields. In this paper, we have reported the synthesis of Chalcogenide nanostructured pharmacologically active Zn S nanoparticles using Zn (II) Heterocyclic thiosemicarbazone Complex as a Single Source. Zn (II) complex was synthesized by the reaction between Schiff base ligand and Zinc acetate salt in 2:1 molar ratio. Thiosemicarbazone have a wide clinical antitumor spectrum with efficacy in various tumor types such as leukemia, pancreatic cancer, breast cancer, non- small cell lung cancer, cervical cancer, prostate cancer and bladder cancer. These compounds possessed significant antineoplastic activity when the carbonyl group attachment of the side chain was located at a position alpha to the heterocyclic nitrogen atom, whereas attachment of the side chain ꞵ or gamma to the heterocyclic nitrogen atom, resulted in inactive antitumor agents. In addition, replacement of the heterocyclic ring N with carbon also resulted in a biologically inactive compound suggesting that a conjugated N, N, S -tridentate donor set is essential for the biological activities of thiosemicarbazone ligands. In our study, for synthesis of Zn S nanoparticles, the synthesized Zn(II) complex of thiosemicarbazone ligand was treated with aqueous extract of Parmotrema perlatum flowers. The use of aqueous extract of Parmotrema perlatum flowers in the synthesis of ZnS particles plays a very important role in reducing reaction time, reducing minimum possibility of side reactions and conversion of metal complexes into its nanoparticles in a very less time. All synthesized compounds were characterized by various structural, morphological, electronic and vibrational spectroscopic techniques and also evaluate the pharmacological activities of compounds like antioxidant, anti-inflammatory and anticancer activities. The peaks at 3414.82 cm-1 in FT-IR spectra confirms the presence of –OH groups and other bioactive agents in the aqueous extract of Parmotrema perlatum flowers, which acts as a capping and stabilizing agents in the synthesis of Zn S nano particles. The effective results of anti-cancer activity of compounds showed that the ZnS nanoparticles shows good cytotoxic activity against human breast cancer cell lines (MCF-7) using MTT assay. In this study, normal human cell lines used as standard for comparison purpose. The CTC50 values of ZnS nanoparticles was found to be 49.375µg/ml respectively. Therefore, it could be concluded that this biogenic method is effective for synthesis of Zn S nanoparticles from Zn(II) complex with desirable properties for potential biomedical applications which can be consider as a good drug candidate for anti-cancer therapy

Fluorescence Modulation through the Inverted Energy Gap Law in Triply N─B←N‐Containing Windmill‐Shaped Triazines

A series of windmill‐shape heterocyclic molecules containing three N─B←N units, TBN and its derivatives, with quasi‐planar C3 symmetric backbone, are synthesized. The parent TBN exhibits a strongly allowed, doubly degenerate lowest excited state but suffers from very low fluorescence, due to very fast nonradiative decay rate through a conical intersection (CI) as revealed by femtosecond transient absorption spectroscopy and quantum‐chemical calculations. Introducing peripheral phenyl‐ or thienyl‐groups (Ph‐TBN or Th‐TBN) induces pronounced bathochromic shifts and enhances fluorescence, which is beneficial from inhibited nonradiative pathway by the increased energy barriers to access the CI at excited state. The understanding of this rather uncommon behaviour may open routes for the design of novel fluorescence materials.

Sulfonated Hydroxyaryl-Tetrazines with Increased pKa for Accelerated Bioorthogonal Click-to-Release Reactions in Cells.

Bioorthogonal reactions that enable switching molecular functions by breaking chemical bonds have gained prominence, with the tetrazine-mediated cleavage of trans-cyclooctene caged compounds (click-to-release) being particularly noteworthy for its high versatility, biocompatibility, and fast reaction rates. Despite several recent advances, the development of highly reactive tetrazines enabling quantitative elimination from trans-cyclooctene linkers remains challenging. In this study, we present the synthesis and application of sulfo-tetrazines, a class of derivatives featuring phenolic hydroxyl groups with increased acidity constants (pKa). This unique property leads to accelerated elimination and complete release of the caged molecules within minutes. Moreover, the inclusion of sulfonate groups provides a valuable synthetic handle, enabling further derivatization into sulfonamides, modified with diverse substituents. Significantly, we demonstrate the utility of sulfo-tetrazines in efficiently activating fluorogenic compounds and prodrugs in living cells, offering exciting prospects for their application in bioorthogonal chemistry.

Sulfonated Hydroxyaryl‐Tetrazines with Increased pKa for Accelerated Bioorthogonal Click‐to‐Release Reactions in Cells

AbstractBioorthogonal reactions that enable switching molecular functions by breaking chemical bonds have gained prominence, with the tetrazine‐mediated cleavage of trans‐cyclooctene caged compounds (click‐to‐release) being particularly noteworthy for its high versatility, biocompatibility, and fast reaction rates. Despite several recent advances, the development of highly reactive tetrazines enabling quantitative elimination from trans‐cyclooctene linkers remains challenging. In this study, we present the synthesis and application of sulfo‐tetrazines, a class of derivatives featuring phenolic hydroxyl groups with increased acidity constants (pKa). This unique property leads to accelerated elimination and complete release of the caged molecules within minutes. Moreover, the inclusion of sulfonate groups provides a valuable synthetic handle, enabling further derivatization into sulfonamides, modified with diverse substituents. Significantly, we demonstrate the utility of sulfo‐tetrazines in efficiently activating fluorogenic compounds and prodrugs in living cells, offering exciting prospects for their application in bioorthogonal chemistry.

Fluorescence Modulation through the Inverted Energy Gap Law in Triply N─B←N-Containing Windmill-Shaped Triazines.

A series of windmill-shape heterocyclic molecules containing three N─B←N units, TBN and its derivatives, with quasi-planar C3 symmetric backbone, are synthesized. The parent TBN exhibits a strongly allowed, doubly degenerate lowest excited state but suffers from very low fluorescence, due to very fast nonradiative decay rate through a conical intersection (CI) as revealed by femtosecond transient absorption spectroscopy and quantum-chemical calculations. Introducing peripheral phenyl- or thienyl-groups (Ph-TBN or Th-TBN) induces pronounced bathochromic shifts and enhances fluorescence, which is beneficial from inhibited nonradiative pathway by the increased energy barriers to access the CI at excited state. The understanding of this rather uncommon behaviour may open routes for the design of novel fluorescence materials.

Chromosome level genome assembly of giant freshwater prawn (Macrobrachium rosenbergii)

The giant freshwater prawn (Macrobrachium rosenbergii) has many advantages in aquaculture, such as fast growth rate, short breeding cycle and good nutrition, which makes it a freshwater shrimp with high economic value. Herein, high-quality chromosome-level genome of both female and male prawns were obtained by combining Illumina paired-end sequencing, PacBio single molecule sequencing technique and High-through chromosome conformation capture (Hi-C) technologies. In ZZ male prawn, a final contig assembly of 3118.58 Mb with a N50 length of 956,237 bp was obtained. In WW female prawn, a final contig assembly of 3333.31 Mb with a N50 length of 1,143,555 bp was obtained. The assembled genome sequences from prawns were anchored to 59 chromosomes. Moreover, the sex chromosomes including W chromosome and Z chromosome were generated in prawn with the length of 36.23 Mb and 27.33 Mb, respectively. The sequence similarity of Z chromosome and W chromosome reached to 74.90%. The high-quality genome resource will be useful for further molecular breeding and functional genomic research of giant freshwater prawns.

Phase change material performance in chamfered dual enclosures: Exploring the roles of geometry, inclination angles and heat flux

This study presents a comprehensive thermal performance analysis of phase change materials (PCMs) within a chamfered dual enclosures subjected to constant heat flux. Utilizing numerical simulations, we investigate the impact of various PCM types, inclination angles (α = 0°, 15°, 30°, 45°, 60°, 75°, 90°), and heat flux levels (Q = 500, 1000, 1500, 2000 W/m²) on melting rates, temperature distribution, and energy storage efficiency. The study examines commercially available PCMs, including RT-25, RT-27, RT-31, RT-35, RT-38, RT-42, RT-47, and RT-50. Our findings reveal that the inclination angle significantly influences thermal performance, with optimal performance observed at angles between 45° and 90° The PCM at 45° exhibited the fastest melting rate and demonstrating the highest energy storage efficiency. Among the PCMs, RT-27 showed the slowest temperature increase, while RT-50 exhibited the highest heat absorption efficiency and rapid temperature rise, making it suitable for applications requiring quick thermal management. Additionally, higher heat flux levels accelerated the phase transition process, with melting rates increases higher at 2000 W/m² compared to 500 W/m². The energy storage capacity varied, with RT-47 and RT-50 demonstrating the highest storage rates, while RT-27 was effective for sustained thermal energy release despite its slower phase change rate. This research bridges gaps in the existing literature by integrating various parameters and providing a holistic understanding of PCM behaviour in thermal energy storage systems. The insights gained from this study can inform the design and optimization of PCM-based thermal management solutions across various applications, including solar heating systems, electronic device cooling, and industrial waste heat recovery.

Review on Ensemble Based Learning for Malware Detection: A Review

Malware analysis becomes one of the main issues in today's world since attackers are producing a variety of malwares, and even their characteristics are updating at an incredibly fast rate. Malware has to be discovered before it impacts a lot of systems to safeguard computer systems and the internet from them. Several types of research on malware detection techniques have recently been conducted. But it is still difficult to identify malware. For identifying malware, there are essentially two methods: One is an identification method that is based on signatures, and the other is dependent on behaviour. The behaviour-based strategy may detect new and complicated malware to some degree utilizing machine learning and other techniques, but it is a difficult one. Signature-based is rapid and effective just for detecting known malware. In this paper, various techniques of malware detection are reviewed and analysed in terms of certain parameters.

Daily Subcutaneous injections of Relaxin is a therapy for heart failure with preserved ejection fraction

Abstract Background and Significance: Relaxin (RLX), a hormone of pregnancy has engendered a great deal of excitement as a therapy for cardiovascular diseases. Clinical trials treated patients with acute decompensated Heart Failure (HF) with RLX (i.v. 30µg/kg/day-2 days) and reported a 37% decrease in mortality during a 6-months follow up. This led the FDA to declare RLX a ‘break-through’ therapy. However, a larger trial failed to meet the sought-after end points. Here, we propose that periodic subQ RLX pulses are more effective. We measured the pharmacokinetics of serum RLX following subQ injections of RLX in Sprague Dawley rats. Further, we treated rats with confirmed HFpEF with daily subQ RLX (2-weeks) to reverse the diastolic dysfunction (DD), arrhythmia and fibrotic profile. Methods Sprague-Dawley (250 g, n=20, either sex) received 2-subQ injections 12 hrs apart of RLX (from Relaxera) or the vehicle. Serial blood samples were drawn following each injection to measure [RLX]. ZSF1 rats (9-weeks old, either sex) were placed on a high fat diet (HFD) and serial echos tracked the DD. Once severe DD was established (25-35 weeks of HFD), rats received daily subQ injections of RLX (100µg/kg) or vehicle. After 2-weeks, hearts were perfused to optically map action potentials and Ca2+ transients, and analyze the arrhythmia profile. IF and Westerns were used to measure changes in fibrosis (collagen 1), Nav1.5, connexin 43, Wnt1 and β-catenin. Results After an injection, RLX reached a peak in ~60 min, fell to 50% in 5-6 hours. Injections of 0, 30, 100 or 500 µg/kg yielded peak levels of 0, 11.26±3.52, 58.33±16.10, and 209.42±29.04 ng/ml and residual levels after 24-hrs of 0, 4.9, 45.1 and 156 pg/ml, respectively. The 30µg/kg injections had no effect and 100 µg/kg increased Nav1.5 (25%), Cx43 (30%) and β-catenin (90%). The 500 µg/kg injections increased Nav1.5 and Cx43 but upregulated β-catenin, only slightly. In ZSF1 HFpEF rats that received the vehicle (n=12), a premature stimulus (at 30 ms) elicited arrhythmia in 67% of the hearts. RLX injections reversed DD, suppressed sustained atrial and ventricular arrhythmias (n=0/12) but not self-terminating arrhythmias, lasting &amp;lt; 10sec. RLX improved the conduction velocity (CV), particularly at fast rates (100ms) from 0.74 to 0.9 m/s (p&amp;lt;0.001, n=12). RLX significantly increased Cx43 expression, Nav1.5 and β-catenin at intercalated disks. RLX reduced collagen deposition in HFpEF rats, to normal levels and increased Wnt1 compared to control HFpEF rats. Conclusions The ZSF1 diabetic rat on a HFD recapitulates human HFpEF, high blood pressure, fibrosis, DD, AF and VF. SubQ RLX injections reversed DD i.e. enlarged Left Atrium, E/e’ ratio, fibrosis, and the arrhythmia vulnerability by increasing CV, Cx43, and Nav1.5. Daily subQ RLX injections were highly effective as a therapy for HFpEF.Echo parameterHFpEF + RLX

Least squares regression under weak moment conditions

In this paper we consider the robust regression problem when the output variable may be heavy-tailed. In such scenarios, the traditional least squares regression paradigm is usually thought to be not a good choice as it lacks robustness to outliers. By projecting the outputs onto an adaptive interval, we show the regularized least squares regression can still work well when the conditional distribution satisfies a weak moment condition. Fast convergence rates in various norm are derived by tuning the projection scale parameter and regularization parameter in according with the sample size and the moment condition.

E-Waste and Hazardous Elements: A Comprehensive Study of Chemical Components and Environmental Threats

Electronic waste, or "e-waste," has grown significantly as a result of the exponential rise of electronic gadgets and is currently one of the waste streams with the fastest rate of growth in the world. Many dangerous substances, such as organic pollutants like brominated flame retardants and heavy metals like lead, mercury, and cadmium, can be found in e-waste. The chemical components of e-waste are thoroughly analyzed in this work, with an emphasis on the identification, measurement, and health and environmental effects of these hazardous materials. According to study, e-waste improper disposal and unofficial recycling can release dangerous substances into the environment, posing a major risk to human health including endocrine disruption and neurological damage. This can result in soil, water, and air contamination. The results highlight the necessity of more advanced recycling technology, stringent laws, and environmentally friendly design principles in order to reduce these hazards. This study adds to the expanding body of information on e-waste and urges immediate action to mitigate the risks that electronic trash poses to the environment and public health.