Plants and Small Molecules: An Up-and-Coming Synergy

The emergence of Arabidopsis thaliana as a model system has led to a rapid and wide improvement in molecular genetics techniques for studying gene function and regulation. However, there are still several drawbacks that cannot be easily solved with molecular genetic approaches, such as the study of unfriendly species, which are of increasing agronomic interest but are not easily transformed, thus are not prone to many molecular techniques. Chemical genetics represents a methodology able to fill this gap. Chemical genetics lies between chemistry and biology and relies on small molecules to phenocopy genetic mutations addressing specific targets. Advances in recent decades have greatly improved both target specificity and activity, expanding the application of this approach to any biological process. As for classical genetics, chemical genetics also proceeds with a forward or reverse approach depending on the nature of the study. In this review, we addressed this topic in the study of plant photomorphogenesis, stress responses and epigenetic processes. We have dealt with some cases of repurposing compounds whose activity has been previously proven in human cells and, conversely, studies where plants have been a tool for the characterization of small molecules. In addition, we delved into the chemical synthesis and improvement of some of the compounds described

Efficient Excitation of Micro/Nano Resonators and Their Higher Order Modes

We demonstrate a simple and flexible technique to efficiently activate micro/nano-electromechanical systems (MEMS/NEMS) resonators at their fundamental and higher order vibration modes. The method is based on the utilization of the amplified voltage across an inductor, L, of an LC tank resonant circuit to actuate the MEMS/NEMS resonator. By matching the electrical and mechanical resonances, significant amplitude amplification is reported across the resonators terminals. We show experimentally amplitude amplification up to twelve times, which is demonstrated to efficiently excite several vibration modes of a microplate MEMS resonator and the fundamental mode of a NEMS resonator

Estimativa da irradiação solar difusa no plano inclinado de painéis solares fotovoltaicos

Solar energy, in the recent decades has gained a great attention due to its clean, simple and easy adaptable process. The effective utilization of solar energy is possible only if proper data of incident solar radiation is available. There are number of solar models based on different climatical factors, for the assessment of radiation on plane and sloped surfaces are available in the literature but the selection of best possible model is a challenging task. Here, different isotropic and anisotropic solar models have been utilized for the estimation of overall radiation incident on the sloped surface in Karachi then estimation was compared with the experimental values. The models selected for this study includes Liu and Jordan, Koronakis, Badescue, Hay and Davies, Temps and Coulson and HDKR. The predicted values and measured values are compared by using different statistical techniques like Mean Absolute Percentage Error (MAPE), Mean Biased Error (MBE), Root Mean Square Error (RMSE) and t-stats. The outcomes revealed that isotropic models are more suitable model than the anisotropic models. Among all models, Badescue is the best suitable model for the estimation of radiations on sloped surfaces with lowest value of MBE, RMSE and t-stats while Temps and Coulson model, on the basis of MAPE, MBE, RMSE and t-stats is the most inappropriate correlation for the assessment of solar radiations on sloped surface. Overall, for the solar radiation estimation on any sloped plane in Karachi isotropic models have shown a good agreement.La energía solar, en las últimas décadas ha ganado una gran atención debido a su proceso limpio, simple y fácilmente adaptable. La utilización eficaz de la energía solar solo es posible si se dispone de datos adecuados de la radiación solar incidente. Hay varios modelos solares basados en diferentes factores climáticos, para la evaluación de la radiación en superficies planas e inclinadas están disponibles en la literatura, pero la selección del mejor modelo posible es una tarea desafiante. Aquí, se han utilizado diferentes modelos solares isotrópicos y anisotrópicos para la estimación de la radiación total incidente en la superficie inclinada de Karachi y luego se comparó la estimación con los valores experimentales. Los modelos seleccionados para este estudio incluyen a Liu y Jordan, Koronakis, Badescue, Hay y Davies, Temps y Coulson y HDKR. Los valores pronosticados y los valores medidos se comparan utilizando diferentes técnicas estadísticas como el error porcentual absoluto medio (MAPE), el error sesgado medio (MBE), el error cuadrático medio (RMSE) y t-stats. Los resultados revelaron que los modelos isotrópicos son un modelo más adecuado que los modelos anisotrópicos. Entre todos los modelos, Badescue es el modelo más adecuado para la estimación de radiaciones en superficies inclinadas con el valor más bajo de MBE, RMSE y t-stats mientras que el modelo de Temps y Coulson, basado en MAPE, MBE, RMSE y t-stats es la correlación más inapropiada para la evaluación de las radiaciones solares en superficies inclinadas. En general, para la estimación de la radiación solar en cualquier plano inclinado en Karachi, los modelos isotrópicos han mostrado una buena concordancia.A energia solar, nas últimas décadas, ganhou grande atenção devido ao seu processo limpo, simples e de fácil adaptação. A utilização efetiva da energia solar só é possível se dados adequados da radiação solar incidente estiverem disponíveis. Existem vários modelos solares baseados em diferentes fatores climáticos, para a avaliação da radiação em superfícies planas e inclinadas estão disponíveis na literatura, mas a seleção do melhor modelo possível é uma tarefa desafiadora. Aqui, diferentes modelos solares isotrópicos e anisotrópicos foram utilizados para a estimativa da radiação total incidente na superfície inclinada em Karachi, então a estimativa foi comparada com os valores experimentais. Os modelos selecionados para este estudo incluem Liu e Jordan, Koronakis, Badescue, Hay e Davies, Temps e Coulson e HDKR. Os valores previstos e os valores medidos são comparados usando diferentes técnicas estatísticas como Erro Percentual Médio Absoluto (MAPE), Erro Viés Médio (MBE), Erro Quadrático Médio Raiz (RMSE) e t-stats. Os resultados revelaram que os modelos isotrópicos são modelos mais adequados do que os modelos anisotrópicos. Entre todos os modelos, Badescue é o modelo mais adequado para a estimativa de radiações em superfícies inclinadas com o menor valor de MBE, RMSE e t-stats, enquanto o modelo Temps e Coulson, com base em MAPE, MBE, RMSE e t-stats é o correlação mais inadequada para a avaliação de radiações solares em superfície inclinada. No geral, para a estimativa da radiação solar em qualquer plano inclinado em Karachi, os modelos isotrópicos mostraram uma boa concordância

Evidence for a Founder Effect among HIV-infected injection drug users (IDUs) in Pakistan.

Background: We have previously reported a HIV-1 subtype A infection in a community of injection drug users (IDUs) in Karachi, Pakistan. We now show that this infection among the IDUs may have originated from a single source. Methods: Phylogenetic analysis was performed of partial gag sequences, generated using PCR, from 26 HIV-positive IDU samples. Results: Our results showed formation of a tight monophyletic group with an intra-sequence identity of \u3c 98% indicating a founder effect . Our data indicate that the HIV-1 epidemic in this community of IDUs may have been transmitted by an HIV positive overseas contract worker who admitted to having contact with commercial sex workers during stay abroad. Conclusion: Specific measures need to implemented to control transmission of HIV infection in Pakistan through infected migrant workers

A 10-year experience of infection following carotid endarterectomy with patch angioplasty

ObjectiveAlthough infection following carotid endarterectomy is rare, consequences of this seldom seen complication can be devastating. Polyester, polytetrafluoroethylene (PTFE), and vein patches have all been used by many institutions for patch angioplasty, each with reported cases of infection following surgery. Our institution has preferentially used PTFE for the majority of cases, and here, we report our experience with postoperative infection following endarterectomy over the last decade.MethodsFrom January 2000 through July 2009, we treated infections following carotid endarterectomy in 25 patients.ResultsOf the 25 patients undergoing treatment for postoperative infection, 21 had PTFE patches placed during the initial surgery. The remaining four consisted of two polyester patches and two bovine pericardial patches. Twenty-three of the 25 initial endarterectomies were performed at our institution, and the other two were referrals. The majority of cases (56%) were due to gram-positive organisms, with only two cases being polymicrobial. The interval from the original surgery to clinical presentation ranged from 7 days to 85 months, with 20 patients (80%) presenting within 60 days of the first operation. Thirteen patients underwent incision and drainage with antibiotics, and 12 patients underwent definitive surgical treatment. Four received patch excision with vein patch angioplasty, four received patch excision with vein interposition, and four received sternocleidomastoid flaps. The 30-day stroke rate was 8%, and the freedom from recurrent infection was 100% at a mean follow-up of 32 months.ConclusionInfection following carotid endarterectomy occurs <1% of the time; however, the potential for morbidity is significant. Our results show that most infections following PTFE patch angioplasty occur in the early postoperative period (<60 days) and that simple drainage with antibiotics may be an adequate form of treatment in select cases

A Phase IB open-label, dose-escalation study of NUC 1031 in combination with carboplatin for recurrent ovarian cancer

Funding: The study was funded and the investigational drug NUC-1031 was supplied by NuCana plc.Purpose: NUC-1031 is a first-in-class ProTide modification of gemcitabine. In PRO-002, NUC‑1031 was combined with carboplatin in recurrent ovarian cancer (OC). Experimental Design: NUC-1031 was administered on days 1 & 8 with carboplatin on day 1 every 3 weeks for up to 6 cycles. Four dose cohorts of NUC-1031 (500, 625 and 750 mg/m2) with carboplatin (AUC4 or 5) were investigated. Primary endpoint was RP2CD. Secondary endpoints included safety, investigator-assessed objective response rate (ORR), clinical benefit rate (CBR), progression-free survival (PFS) and pharmacokinetics (PK). Results: 25 women with recurrent OC, a mean of 3.8 prior lines of chemotherapy and a median platinum-free interval (PFI) of 5 months (range: 7 - 451 days) were enrolled, 15/25 (60%) platinum-resistant; 9 (36%) partially platinum-sensitive and 1 (4%) platinum-sensitive. Of the 23 response-evaluable: there was 1 confirmed complete response (CR, 4%), 5 partial responses (PR, 17%) and 8 (35%) stable disease (SD). The ORR was 26% and CBR was 74% across all doses and 100% in the RP2CD cohort. Median PFS was 27.1 weeks. NUC-1031 was stable in the plasma and rapidly generated high intracellular dFdCTP levels that were unaffected by carboplatin. Conclusions: NUC-1031 combined with carboplatin is well tolerated in recurrent OC. Highest efficacy was observed at the RP2CD of 500 mg/m2 NUC-1031 on days 1 & 8 with AUC5 carboplatin day 1, every 3 weeks for 6 cycles. The ability to deliver carboplatin at AUC5 and the efficacy of this schedule even in patients with platinum-resistant disease makes this an attractive therapeutic combination.PostprintPeer reviewe

Decentralized smart energy management in hybrid microgrids: Evaluating operational modes, resources optimization, and environmental impacts

Escalating energy demands and climate change challenges necessitate the adaptation of renewable-based microgrid systems in the energy sector. The proposed work employs a robust Multi Agent System (MAS) technique to achieve efficient and automated control of the hybrid microgrid operation. The hybrid microgrid system incorporates Renewable Energy Sources (RES), a diesel generator, and a battery storage system. The operation of the hybrid microgrid consists of three distinct modes: islanded, transition to grid, and grid-oriented mode. The system’s performance is optimized by considering factors like climatic patterns, energy costs, connected source characteristics, and load demand. Different climatic scenarios are assessed for each mode of operation, where the best, extreme sunny, extreme cloudy, and worst climate conditions are considered for islanded mode; sunny and cloudy scenarios are considered for transition to grid mode as well as grid-feed and grid-tied modes are considered for grid-oriented operation of the microgrid. The simulation studies are performed using the MATLAB/Simulink R2021a environment. Furthermore, Particle Swarm Optimization (PSO) is implemented to optimize power allocation within the microgrid and enhance its cost-effectiveness. The optimization results demonstrate efficient utilization of available energy sources along with effective energy management facilitated by the MAS control system. The results emphasize the importance of adopting a MAS approach for achieving smart energy management through comprehensive analysis and integrating decentralized energy management techniques for optimal accommodation of distributed energy resources in hybrid microgrids

Recombinant ADAMTS13 reduces abnormally up-regulated von Willebrand factor in plasma from patients with severe COVID-19

Thrombosis affecting the pulmonary and systemic vasculature is common during severe COVID-19 and causes adverse outcomes. Although thrombosis likely results from inflammatory activation of vascular cells, the mediators of thrombosis remain unconfirmed. In a cross-sectional cohort of 36 severe COVID-19 patients, we show that markedly increased plasma von Willebrand factor (VWF) levels were accompanied by a partial reduction in the VWF regulatory protease ADAMTS13. In all patients we find this VWF/ADAMTS13 imbalance to be associated with persistence of ultra-high-molecular-weight (UHMW) VWF multimers that are highly thrombogenic in some disease settings. Incubation of plasma samples from patients with severe COVID-19 with recombinant ADAMTS13 (rADAMTS13) substantially reduced the abnormally high VWF activity, reduced overall multimer size and depleted UHMW VWF multimers in a time and concentration dependent manner. Our data implicate disruption of normal VWF/ADAMTS13 homeostasis in the pathogenesis of severe COVID-19 and indicate that this can be reversed ex vivo by correction of low plasma ADAMTS13 levels. These findings suggest a potential therapeutic role for rADAMTS13 in helping restore haemostatic balance in COVID-19 patients

Recommendations for the management of secondary hypogammaglobulinaemia due to B cell targeted therapies in autoimmune rheumatic diseases

OBJECTIVES: The association of B cell targeted therapies with development of hypogammaglobulinaemia and infection is increasingly recognized. Our aim was to develop consensus recommendations for immunoglobulin replacement therapy for management of hypogammaglobulinaemia following B cell targeted therapies in autoimmune rheumatic diseases. // METHODS: A modified Delphi exercise involved a 17-member Taskforce committee, consisting of immunologists, rheumatologists, nephrologists, haematologists, a gastroenterologist, an immunology specialist nurse and a patient representative. The first round identified the most pertinent topics to address in the recommendations. A search string was agreed upon for the identification of publications in PubMed focusing on these areas, for a systematic literature review. Original data was presented from this review to the Taskforce committee. Recommendations from the British Society for Rheumatology, the UK Department of Health, EULAR, the ACR, and the American Academy of Allergy, Asthma, and Immunology were also reviewed. The evidence was discussed in a face-to-face meeting to formulate recommendation statements. The levels of evidence and statements were graded according to Scottish Intercollegiate Guidelines Network methodology. // RESULTS: Three overarching principles, eight recommendation statements and a research agenda were formulated. The Taskforce committee voted on these statements, achieving 82–100% agreement for each recommendation. The strength of the recommendations was restricted by the low quality of the available evidence, with no randomized controlled trial data. The recommendations cover risk factors, monitoring, referral for hypogammaglobulinaemia; indications, dosage and discontinuation of immunoglobulin replacement therapy. // CONCLUSION: These are the first recommendations specifically formulated for B cell targeted therapies related to hypogammaglobulinaemia in autoimmune rheumatic diseases. The recommendations are to aid health-care professionals with clinical decision making for patients with hypogammaglobulinaemia