This tutorial review will introduce and explore the fundamental aspects of nanopore (bio)sensing, fabrication, modification, and the emerging technologies and applications that both intrigue and inspire those working in and around the field. Although nanopores can be classified into two categories, solid-state and biological, they are essentially two sides of the same coin. For instance, both garner popularity due to their ability to confine analytes of interest to a nanoscale volume. Due to the vast diversity of nanopore platforms and applications, no single review can cover the entire landscape of published work in the field. Therefore, in this article focus will be placed on recent advancements and developments taking place in the field of solid-state nanopores. It should be stated that the intention of this tutorial review is not to cite all articles relating to solid-state nanopores, but rather to highlight recent, select developments that will hopefully benefit the new and seasoned scientist alike. Initially we begin with the fundamentals of solid-state nanopore sensing. Then the spotlight is shone on the sophisticated fabrication methods that have their origins in the semiconductor industry. One inherent advantage of solid-state nanopores is in the ease of functionalizing the surface with a range of molecules carrying functional groups. Therefore, an entire section is devoted to highlighting various chemical and bio-molecular modifications and explores how these permit the development of novel sensors with specific targets and functions. The review is completed with a discussion on novel detection strategies using nanopores. Although the most popular mode of nanopore sensing is based upon what has come to be known as ionic-current blockade sensing, there is a vast, growing literature based around exploring alternative detection techniques to further expand on the versatility of the sensors. Such techniques include optical, electronic, and force based methods. It is perhaps fair to say that these new frontiers have caused further excitement within the sensing community.
The aim of this study is to investigate the morphological and chemical changes of demineralized dentin collagen-matrix and resin/dentin interface associated with chitosan/riboflavin modification. Dentin disc specimens were prepared from sound molars, acid-etched with 35% phosphoric acid and modified with either 0.1% riboflavin or chitosan/riboflavin (Ch/RF ratios 1:4 or 1:1) and photo-activated by UVA. Morphological and chemical changes associated with surface modification were characterized by SEM and micro-Raman spectroscopy. Dentin surfaces of sound molars were exposed, acid-etched, and modified as described before. Etch-and-rinse dentin adhesive was applied, light-cured, and layered with resin-restorative composite. The resin infiltration and resin/dentin interface were characterized by micro-Raman spectroscopy and SEM. An open-intact collagen network-structure, formation of uniform hybrid-layer and higher resin infiltration were found with 0.1%RF and Ch/RF 1:4 modifications. Raman analysis revealed chemical changes and shifts in Amide bands with the modification of dentin collagen-matrix. The use of riboflavin and chitosan/riboflavin formulations to modify dentin-collagen matrix, with the defined ratios, stabilizes the collagen fibrillar network and enhances resin infiltration and hybrid layer formation. These preliminary results are encouraging for subsequent consideration of chitosan/riboflavin modification in adhesive dentistry. © 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2012.
Humans easily and flexibly complete a wide variety of tasks. To accomplish this feat, the brain appears to subtly adjust stable brain networks. Here, we investigate what regional factors underlie these modifications, asking whether networks are either altered at (1) regions activated by a given task or (2) hubs that interconnect different networks. We used fMRI “functional connectivity” (FC) to compare networks during rest and three distinct tasks requiring semantic judgments, mental rotation, and visual coherence. We found that network modifications during these tasks were independently associated with both regional activation and network hubs. Furthermore, active and hub regions were associated with distinct patterns of network modification (differing in their localization, topography of FC changes, and variability across tasks), with activated hubs exhibiting patterns consistent with task control. These findings indicate that task goals modify brain networks through two separate processes linked to local brain function and network hubs.
Healthcare consumers, researchers, patients and policy makers increasingly use systematic reviews (SRs) to aid their decision-making process. However, the conduct of SRs can be a time-consuming and resource-intensive task. Often, clinical practice guideline developers or other decision-makers need to make informed decisions in a timely fashion (e.g. outbreaks of infection, hospital-based health technology assessments). Possible approaches to address the issue of timeliness in the production of SRs are to (a) implement process parallelisation, (b) adapt and apply innovative technologies, and/or © modify SR processes (e.g. study eligibility criteria, search sources, data extraction or quality assessment). Highly parallelised systematic reviewing requires substantial resources to support a team of experienced information specialists, reviewers and methodologists working alongside with clinical content experts to minimise the time for completing individual review steps while maximising the parallel progression of multiple steps. Effective coordination and management within the team and across external stakeholders are essential elements of this process. Emerging innovative technologies have a great potential for reducing workload and improving efficiency of SR production. The most promising areas of application would be to allow automation of specific SR tasks, in particular if these tasks are time consuming and resource intensive (e.g. language translation, study selection, data extraction). Modification of SR processes involves restricting, truncating and/or bypassing one or more SR steps, which may risk introducing bias to the review findings. Although the growing experiences in producing various types of rapid reviews (RR) and the accumulation of empirical studies exploring potential bias associated with specific SR tasks have contributed to the methodological development for expediting SR production, there is still a dearth of research examining the actual impact of methodological modifications and comparing the findings between RRs and SRs. This evidence would help to inform as to which SR tasks can be accelerated or truncated and to what degree, while maintaining the validity of review findings. Timely delivered SRs can be of value in informing healthcare decisions and recommendations, especially when there is practical urgency and there is no other relevant synthesised evidence.
- Proceedings of the National Academy of Sciences of the United States of America
- Published about 4 years ago
The covalent modification of therapeutic biomolecules has been broadly explored, leading to a number of clinically approved modified protein drugs. These modifications are typically intended to address challenges arising in biopharmaceutical practice by promoting improved stability and shelf life of therapeutic proteins in formulation, or modifying pharmacokinetics in the body. Toward these objectives, covalent modification with poly(ethylene glycol) (PEG) has been a common direction. Here, a platform approach to biopharmaceutical modification is described that relies on noncovalent, supramolecular host-guest interactions to endow proteins with prosthetic functionality. Specifically, a series of cucurbituril (CB)-PEG conjugates are shown to substantially increase the stability of three distinct protein drugs in formulation. Leveraging the known and high-affinity interaction between CB and an N-terminal aromatic residue on one specific protein drug, insulin, further results in altering of its pharmacological properties in vivo by extending activity in a manner dependent on molecular weight of the attached PEG chain. Supramolecular modification of therapeutic proteins affords a noncovalent route to modify its properties, improving protein stability and activity as a formulation excipient. Furthermore, this offers a modular approach to append functionality to biopharmaceuticals by noncovalent modification with other molecules or polymers, for applications in formulation or therapy.
A Geographical Analysis of Emergency Medical Service Calls and Extreme Heat in King County, WA, USA (2007-2012)
- International journal of environmental research and public health
- Published over 3 years ago
This research analyzed the relationship between extreme heat and Emergency Medical Service (EMS) calls in King County, WA, USA between 2007 and 2012, including the effect of community-level characteristics. Extreme heat thresholds for the Basic Life Support (BLS) data and the Advanced Life Support (ALS) data were found using a piecewise generalized linear model with Akaike Information Criterion (AIC). The association between heat exposure and EMS call rates was investigated using a generalized estimating equations with Poisson mean model, while adjusting for community-level indicators of poverty, impervious surface, and elderly population (65+). In addition, we examined the effect modifications of these community-level factors. Extreme-heat thresholds of 31.1 °C and 33.5 °C humidex were determined for the BLS and ALS data, respectively. After adjusting for other variables in the model, increased BLS call volume was significantly associated with occurring on a heat day (relative rate (RR) = 1.080, p < 0.001), as well as in locations with higher percent poverty (RR = 1.066, p < 0.001). No significant effect modification was identified for the BLS data on a heat day. Controlling for other variables, higher ALS call volume was found to be significantly associated with a heat day (RR = 1.067, p < 0.001), as well as in locations with higher percent impervious surface (RR = 1.015, p = 0.039), higher percent of the population 65 years or older (RR = 1.057, p = 0.005), and higher percent poverty (RR = 1.041, p = 0.016). Furthermore, percent poverty and impervious surface were found to significantly modify the relative rate of ALS call volumes between a heat day and non-heat day. We conclude that EMS call volume increases significantly on a heat day compared to non-heat day for both call types. While this study shows that there is some effect modification between the community-level variables and call volume on a heat day, further research is necessary. Our findings also suggest that with adequate power, spatially refined analyses may not be necessary to accurately estimate the extreme-heat effect on health.
Psychedelics induce intense modifications in the sensorium, the sense of “self,” and the experience of reality. Despite advances in our understanding of the molecular and cellular level mechanisms of these drugs, knowledge of their actions on global brain dynamics is still incomplete. Recent imaging studies have found changes in functional coupling between frontal and parietal brain structures, suggesting a modification in information flow between brain regions during acute effects.
The McGill Quality of Life Questionnaire has been widely used with people with life-threatening illnesses without modification since its publication in 1996. With use, areas for improvement have emerged; therefore, various minor modifications were tested over time.
Surface modification of a Cu(In,Ga)(S,Se)2(CIGSSe) absorber layer is commonly required to obtain high performance CIGSSe photocathodes. However, surface modifications can cause disadvantages such as optical loss, low stability, the use of toxic substances and an increase in complexity. In this work, we demonstrate that a double-graded bandgap structure (top-high, middle-low and bottom-high bandgaps) can achieve high performance in bare CIGSSe photocathodes without any surface modifications via a hetero-materials overlayer that have been fabricated in a cost-effective solution process. We used two kinds of CIGSSe film produced by different precursor solutions consisting of different solvents and binder materials, and both revealed a double-graded bandgap structure composed of an S-rich top layer, Ga- and S-poor middle layer and S- and Ga-rich bottom layer. The bare CIGSSe photocathode without surface modification exhibited a high photoelectrochemical activity of ~6 mA·cm-2at 0 V vs. RHE and ~22 mA·cm-2at -0.27 V vs. RHE, depending on the solution properties used in the CIGSSe film preparation. The incorporation of a Pt catalyst was found to further increase their PEC activity to ~26 mA·cm-2at -0.16 V vs. RHE.
Ferroptosis is a regulated form of necrotic cell death implicated in carcinogenesis and neurodegeneration that is driven by phospholipid peroxidation. Lipid-derived electrophiles (LDEs) generated during this process can covalently modify proteins (“carbonylation”) and affect their functions. Here we report the development of a quantitative chemoproteomic method to profile carbonylations in ferroptosis by an aniline-derived probe. Using the method, we established a global portrait of protein carbonylations in ferroptosis with >400 endogenously modified proteins and for the first time, identified >20 residue sites with endogenous LDE modifications in ferroptotic cells. Specifically, we discovered and validated a novel cysteine site of modification on voltage-dependent anion-selective channel protein 2 (VDAC2) that might play an important role in sensitizing LDE signals and mediating ferroptosis. Our results will contribute to the understanding of ferroptotic signaling and pathogenesis and provide potential biomarkers for ferroptosis detection.