Surface-functionalized chemiresistive films that exploit h-bonding, cation-pi, and metal-halide interactions.

The development of gas sensors for detection of volatile organic compounds (VOCs) has been of interest in the sensing field for decades. To date, the use of metal nanoparticle-based chemiresistors for trace VOC detection, particularly gold nanoparticle-based sensors, is of great interest due to their high chemical stability, ease of synthesis, unique optical properties, large surface to volume ratio, and high level of conductivity. Much effort has been devoted towards gold monolayer protected clusters (Au MPCs) as chemiresistors to detect harmful VOCs. The present thesis documents the results of our efforts to exploit the advantages of functionalized Au MPCs chemiresistors for selective VOCs sensing by changing Au MPCs surface functionality. Our concept is to incorporate binding motifs onto Au MPCs to selectively bind target VOCs and thereby improve the sensing capabilities of chemiresistors derived from casting the functionalized Au MPCs on interdigitated electrodes (IDEs). Chapter 1 in this thesis provides a review of nanoparticle-based chemiresistors for VOCs detection, the use of MEMS technology to prepare Au MPCs-based chemiresistors, and surface functionalized Au MPCs for VOCs detection. As inceptive studies, we were able to prepare urea-functionalized Au MPCs that demonstrated remarkable sensitivity and selectivity toward acetone serving as a representative carbonyl VOC. Chapter 2 describes the urea-functionalized Au MPCs approach for acetone sensing. We examined several structural elements of thiol urea ligands to change the degree of H-bonding between adjacent urea motifs on the Au MPCs surface as well as varied the steric properties of terminal groups on the urea-functionalized chains. The responses of the developed sensors were notably affected by the urea functional motifs. A tert-butyl end group on the thiol urea sensors resulted in high sensitivity and selectivity toward acetone and delivered a sensor capable of detecting acetone in air at concentrations from 10 ppb to 10 ppm. Next, we expanded our functionalized Au MPCs-based chemiresistive studies toward detection of aromatic VOCs. We explored metal carboxylate-functionalized Au MPCs chemiresistors as a means to selectively detect aromatic hydrocarbons, such as benzene, toluene, ethylbenzene, and xylene (BTEX), at trace levels in outdoor and indoor air. Here, we exploited the strong cation-π noncovalent interactions between metal cations bound to the Au MPCs-based chemiresistor surface and the π-systems of BTEX as a principal sensing mechanism. In this study, we synthesized alkali-metal carboxylate-functionalized Au MPCs by modifying the surface chemistry of Au MPCs via an oxime ether approach. Chapter 3 includes our alkali-metal carboxylate-functionalized Au MPCs chemiresistor synthesis and their selective binding strategy for aromatic VOCs capturing over non-aromatic VOCs. For our study, Li+, Na+, and K+ ion functionalized Au MPC sensors were developed. The K+- and Na+- functionalized Au MPCs sensors show a higher response to electron rich BTEX VOCs over electron deficient nitrobenzene, cyclohexene, acetone, and methanol vapors. Response of Li+ sensor for all the analytes were very low than the Na+ and K+ ion sensors. The developed sensors response to selected aromatic and non-aromatic VOCs suggests cation-π interactions arising between the positively charged cations and the electron-rich aromatic π-systems. The results open a promising research direction for harnessing cation-π interaction to create aromatic VOC-selective sensors. Chapter 4 details our primary investigation into the use of the unusual binding ability of a cesium cation to vicinal alkyl and vinyl chlorides to detect trichloroethylene (TCE). This chapter describes the sensor response patterns of cesium carboxylate-functionalized Au MPCs chemiresistors on exposure to different alkyl and vinyl chlorides to explore the influence of structural features on TCE detection. The developed Cs+-Au MPCs sensor exhibits a higher response to analytes with vinyl 1,2-dichlorounit than the other chloro analytes. Moreover, TCE exhibits a high sensor response at 1 ppm – 5 ppm vapor concentration than the other declared harmaful chloro analytes. Hence, this study revealed the different binding affinities of cesium cation toward the geminal, vicinal and vinyl halides and how it affects for sensor response. In summary, these results show that the outer ligand structure of thiolate-protected Au MPCs plays a major role in enhancing selectivity and sensitivity toward VOCs and suggests this approach as an effective means for targeting analytes

Time-Course of Changes in the Myonuclear Domain During Denervation in Young-Adult and Old Rat Gastrocnemius Muscle

If myonuclear loss initiates muscle wasting, it should precede the loss of muscle mass. As aging affects muscle plasticity, the time-course of muscle atrophy during disuse may differ between young and old animals. To investigate this, gastrocnemius muscles of 5- and 25-month-old rats were exposed to 1, 2, or 4 weeks of denervation, whereas the contralateral gastrocnemius muscles served as controls. Muscle fibers of each type responded similarly to 4 weeks of denervation. For both ages most of the atrophy (36%; P < 0.001) occurred in the first 2 weeks. In young-adult muscles, the myonuclear number remained constant, but in old muscles it decreased to below control level after 4 weeks of denervation (P < 0.05). Despite this differential response, myonuclear domain size decreased similarly at both ages (P < 0.001). In both young-adult and old rats, denervation-induced atrophy was not preceded by a loss of myonuclei. © 2011 Wiley Periodicals, Inc

Generate Comic Strips Using AI

The art of storytelling through comic strips has long been a favorite, grabbing the interest of readers of all ages and developing into a variety of genres today, from superhero comics to political comics. Comic strip readers are more literate, empathic, and open to social issues, according to studies. Comics have the power to change the way we see the world. This research paper presents a system (ComicGenie) for automatically creating comic strips for Batman based on user-entered text descriptions. The proposed system consists of distinct components such as character detection, environment detection, text bubble generation, and voiceover over the scenario, each specializing in different aspects of comic strip creation. SVM and fastText technologies in NLP were utilized for text classification when developing models. Overall, this research contributes to the field of comic strip creation, offering a comprehensive web application. The ComicGenie holds significant potential to revolutionize the comic industry and inspire new avenues for computer-generated storytelling

Global proteome changes in the rat diaphragm induced by endurance exercise training

Mechanical ventilation (MV) is a life-saving intervention for many critically ill patients. Unfor- tunately, prolonged MV results in the rapid development of diaphragmatic atrophy and weakness. Importantly, endurance exercise training results in a diaphragmatic phenotype that is protected against ventilator-induced diaphragmatic atrophy and weakness. The mechanisms responsible for this exercise-induced protection against ventilator-induced dia- phragmatic atrophy remain unknown. Therefore, to investigate exercise-induced changes in diaphragm muscle proteins, we compared the diaphragmatic proteome from sedentary and exercise-trained rats. Specifically, using label-free liquid chromatography-mass spectrome- try, we performed a proteomics analysis of both soluble proteins and mitochondrial proteins isolated from diaphragm muscle. The total number of diaphragm proteins profiled in the sol- uble protein fraction and mitochondrial protein fraction were 813 and 732, respectively. Endurance exercise training significantly (P<0.05, FDR <10%) altered the abundance of 70 proteins in the soluble diaphragm proteome and 25 proteins of the mitochondrial proteome. In particular, key cytoprotective proteins that increased in relative abundance following exer- cise training included mitochondrial fission process 1 (Mtfp1; MTP18), 3-mercaptopyruvate sulfurtransferase (3MPST), microsomal glutathione S-transferase 3 (Mgst3; GST-III), and heat shock protein 70 kDa protein 1A/1B (HSP70). While these proteins are known to be cytoprotective in several cell types, the cyto-protective roles of these proteins have yet to be fully elucidated in diaphragm muscle fibers. Based upon these important findings, future experiments can now determine which of these diaphragmatic proteins are sufficient and/or required to promote exercise-induced protection against inactivity-induced muscle atrophy

The impact of aging on mitochondrial function and biogenesis pathways in skeletal muscle of sedentary high- and low-functioning elderly individuals

Age-related loss of muscle mass and strength (sarcopenia) leads to a decline in physical function and frailty in the elderly. Among the many proposed underlying causes of sarcopenia, mitochondrial dysfunction is inherent in a variety of aged tissues. The intent of this study was to examine the effect of aging on key groups of regulatory proteins involved in mitochondrial biogenesis and how this relates to physical performance in two groups of sedentary elderly participants, classified as high- and low-functioning based on the Short Physical Performance Battery test. Muscle mass was decreased by 38% and 30% in low-functioning elderly (LFE) participants when compared to young and high-functioning elderly participants, respectively, and positively correlated to physical performance. Mitochondrial respiration in permeabilized muscle fibers was reduced (41%) in the LFE group when compared to the young, and this was associated with a 30% decline in cytochrome c oxidase activity. Levels of key metabolic regulators, SIRT3 and PGC-1\u3b1, were significantly reduced (50%) in both groups of elderly participants when compared to young. Similarly, the fusion protein OPA1 was lower in muscle from elderly subjects; however, no changes were detected in Mfn2, Drp1 or Fis1 among the groups. In contrast, protein import machinery components Tom22 and cHsp70 were increased in the LFE group when compared to the young. This study suggests that aging in skeletal muscle is associated with impaired mitochondrial function and altered biogenesis pathways and that this may contribute to muscle atrophy and the decline in muscle performance observed in the elderly population. \ua9 2012 The Authors. Aging Cell \ua9 2012 Blackwell Publishing Ltd/Anatomical Society of Great Britain and Ireland

Guidelines for the use and interpretation of assays for monitoring autophagy (2nd edition)

In 2008 we published the first set of guidelines for standardiz- ing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new tech- nologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in differ- ent organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes..

Metabolic myopathy presenting with polyarteritis nodosa: a case report

<p>Abstract</p> <p>Introduction</p> <p>To the best of our knowledge, we describe for the first time a patient in whom an unusual metabolic myopathy was identified after failure to respond to curative therapy for a systemic vasculitis, polyarteritis nodosa. We hope this report will heighten awareness of common metabolic myopathies that may present later in life. It also speculates on the potential relationship between metabolic myopathy and systemic vasculitis.</p> <p>Case presentation</p> <p>A 78-year-old African-American woman with a two-year history of progressive fatigue and exercise intolerance presented to our facility with new skin lesions and profound muscle weakness. Skin and muscle biopsies demonstrated a medium-sized artery vasculitis consistent with polyarteritis nodosa. Biochemical studies of the muscle revealed diminished cytochrome C oxidase activity (0.78 μmol/minute/g tissue; normal range 1.03 to 3.83 μmol/minute/g tissue), elevated acid maltase activity (23.39 μmol/minute/g tissue; normal range 1.74 to 9.98 μmol/minute/g tissue) and elevated neutral maltase activity (35.89 μmol/minute/g tissue; normal range 4.35 to 16.03 μmol/minute/g tissue). Treatment for polyarteritis nodosa with prednisone and cyclophosphamide resulted in minimal symptomatic improvement. Additional management with a diet low in complex carbohydrates and ubiquinone, creatine, carnitine, folic acid, α-lipoic acid and ribose resulted in dramatic clinical improvement.</p> <p>Conclusions</p> <p>Our patient's initial symptoms of fatigue, exercise intolerance and progressive weakness were likely related to her complex metabolic myopathy involving both the mitochondrial respiratory chain and glycogen storage pathways. Management of our patient required treatment of both the polyarteritis nodosa as well as metabolic myopathy. Metabolic myopathies are common and should be considered in any patient with exercise intolerance. Metabolic myopathies may complicate the management of various disease states.</p

PGC-1alpha Down-Regulation Affects the Antioxidant Response in Friedreich's Ataxia

BACKGROUND: Cells from individuals with Friedreich's ataxia (FRDA) show reduced activities of antioxidant enzymes and cannot up-regulate their expression when exposed to oxidative stress. This blunted antioxidant response may play a central role in the pathogenesis. We previously reported that Peroxisome Proliferator Activated Receptor Gamma (PPARgamma) Coactivator 1-alpha (PGC-1alpha), a transcriptional master regulator of mitochondrial biogenesis and antioxidant responses, is down-regulated in most cell types from FRDA patients and animal models. METHODOLOGY/PRINCIPAL FINDINGS: We used primary fibroblasts from FRDA patients and the knock in-knock out animal model for the disease (KIKO mouse) to determine basal superoxide dismutase 2 (SOD2) levels and the response to oxidative stress induced by the addition of hydrogen peroxide. We measured the same parameters after pharmacological stimulation of PGC-1alpha. Compared to control cells, PGC-1alpha and SOD2 levels were decreased in FRDA cells and did not change after addition of hydrogen peroxide. PGC-1alpha direct silencing with siRNA in control fibroblasts led to a similar loss of SOD2 response to oxidative stress as observed in FRDA fibroblasts. PGC-1alpha activation with the PPARgamma agonist (Pioglitazone) or with a cAMP-dependent protein kinase (AMPK) agonist (AICAR) restored normal SOD2 induction. Treatment of the KIKO mice with Pioglitazone significantly up-regulates SOD2 in cerebellum and spinal cord. CONCLUSIONS/SIGNIFICANCE: PGC-1alpha down-regulation is likely to contribute to the blunted antioxidant response observed in cells from FRDA patients. This response can be restored by AMPK and PPARgamma agonists, suggesting a potential therapeutic approach for FRDA.Journal ArticleResearch Support, Non-U.S. Gov'tSCOPUS: ar.jinfo:eu-repo/semantics/publishe

Modeling mitochondrial dysfunctions in the brain: from mice to men

The biologist Lewis Thomas once wrote: “my mitochondria comprise a very large proportion of me. I cannot do the calculation, but I suppose there is almost as much of them in sheer dry bulk as there is the rest of me”. As humans, or indeed as any mammal, bird, or insect, we contain a specific molecular makeup that is driven by vast numbers of these miniscule powerhouses residing in most of our cells (mature red blood cells notwithstanding), quietly replicating, living independent lives and containing their own DNA. Everything we do, from running a marathon to breathing, is driven by these small batteries, and yet there is evidence that these molecular energy sources were originally bacteria, possibly parasitic, incorporated into our cells through symbiosis. Dysfunctions in these organelles can lead to debilitating, and sometimes fatal, diseases of almost all the bodies’ major organs. Mitochondrial dysfunction has been implicated in a wide variety of human disorders either as a primary cause or as a secondary consequence. To better understand the role of mitochondrial dysfunction in human disease, a multitude of pharmacologically induced and genetically manipulated animal models have been developed showing to a greater or lesser extent the clinical symptoms observed in patients with known and unknown causes of the disease. This review will focus on diseases of the brain and spinal cord in which mitochondrial dysfunction has been proven or is suspected and on animal models that are currently used to study the etiology, pathogenesis and treatment of these diseases