The notion of transformation is gaining traction in contemporary sustainability debates. New ways of theorising and supporting transformations are emerging and, so the argument goes, opening exciting ...spaces to (re)imagine and (re)structure radically different futures. Yet, questions remain about how the term is being translated from an academic concept into an assemblage of normative policies and practices, and how this process might shape social, political, and environmental change. Motivated by these questions, we identify five latent risks associated with discourse that frames transformation as apolitical and/or inevitable. We refer to these risks as the dark side of transformation. While we cannot predict the future of radical transformations towards sustainability, we suggest that scientists, policymakers, and practitioners need to consider such change in more inherently plural and political ways.
STUDY DESIGN.Retrospective study of prospectively collected data.
OBJECTIVE.To determine if the modified Frailty Index (mFI) could be used to predict postoperative complications in patients ...undergoing surgery for adult spinal deformity (ASD).
SUMMARY OF BACKGROUND DATA.Surgery for patients with ASD is associated with high complication rates and significant concerns present during risk stratification with older patients. The mFI is an evaluation tool to describe the frailness of an individual and how their preoperative status may impact postoperative survival and outcomes. Using a large nationwide database, we assessed the utility of this instrument in patients undergoing surgery for ASD.
METHODS.The American College of Surgeons National Surgical Quality Improvement Program is a large multicenter clinical registry that prospectively collects preoperative variables, patient demographics, operative factors, and 30-day postoperative morbidity and mortality outcomes from about 400 hospitals nationwide. Current Procedural Terminology codes were used to query the database for adults who underwent fusion for spinal deformity. The previously described mFI was calculated based on the number of positive factors and univariate and multivariate logistic regression analysis were used to analyze the risk factors associated with mortality.
RESULTS.Overall, 1001 patients were identified and the mean mFI score was 0.09 (range0–0.545). Increasing mFI score was associated with higher complication, reoperation, and mortality rates (P < 0.05). mFI of 0.09 and 0.18 was an independent predictor of any complication, mortality, requiring a blood transfusion, pulmonary embolism/deep vein thrombosis, and reoperation (all P < 0.05). In comparison with age >60 years obesity class III, mFI was a superior predictor of several postoperative complications and reoperation.
CONCLUSION.Frailty was an independent predictor of postoperative complications, mortality, and reoperation in patients undergoing surgery for ASD. Preoperative assessment of the mFI in this patient population can be utilized to improve current risk models.Level of Evidence3
Targeted proteomics is a convenient method determining enzyme expression levels, but a quantitative analysis of these proteomic data has not been fully explored yet. Here, we present and demonstrate ...a computational tool (principal component analysis of proteomics, PCAP) that uses quantitative targeted proteomics data to guide metabolic engineering and achieve higher production of target molecules from heterologous pathways. The method is based on the application of principal component analysis to a collection of proteomics and target molecule production data to pinpoint specific enzymes that need to have their expression level adjusted to maximize production. We illustrated the method on the heterologous mevalonate pathway in Escherichia coli that produces a wide range of isoprenoids and requires balanced pathway gene expression for high yields and titers. PCAP-guided engineering resulted in over a 40% improvement in the production of two valuable terpenes. PCAP could potentially be productively applied to other heterologous pathways as well.
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•We report quantitative analysis method for proteomics data using PCA.•Principal component analysis of proteomics (PCAP) can direct metabolic engineering.•PCAP provides information not apparent by the simple observation of proteomics data.•PCAP was successfully applied to improve the mevalonate pathway (MEV) in E. coli.•Limonene and bisabolene production increased about 40% using PCAP-based strategy.
We demonstrated the in vivo feasibility of using focused ultrasound (FUS) to transiently modulate (through either stimulation or suppression) the function of regional brain tissue in rabbits. FUS was ...delivered in a train of pulses at low acoustic energy, far below the cavitation threshold, to the animal's somatomotor and visual areas, as guided by anatomical and functional information from magnetic resonance imaging (MRI). The temporary alterations in the brain function affected by the sonication were characterized by both electrophysiological recordings and functional brain mapping achieved through the use of functional MRI (fMRI). The modulatory effects were bimodal, whereby the brain activity could either be stimulated or selectively suppressed. Histological analysis of the excised brain tissue after the sonication demonstrated that the FUS did not elicit any tissue damages. Unlike transcranial magnetic stimulation, FUS can be applied to deep structures in the brain with greater spatial precision. Transient modulation of brain function using image-guided and anatomically-targeted FUS would enable the investigation of functional connectivity between brain regions and will eventually lead to a better understanding of localized brain functions. It is anticipated that the use of this technology will have an impact on brain research and may offer novel therapeutic interventions in various neurological conditions and psychiatric disorders.
► Focused ultrasound (FUS) was applied for the modulation of regional brain activity. ► Pulsed FUS was delivered to the rabbit somatomotor and visual areas. ► The brain function was characterized by electroencephalogram and functional MRI. ► The effects were bimodal—neural excitability can be either increased or suppressed. ► FUS provides non-invasive regional modulation of neural tissue excitability.
Given the widespread adoption of social media for sharing and accessing news, as well as the possibility of news consumers' direct interactions with journalists through social media, this study ...analyzed the relationships among news access via social media (NASM), perceived news information overload (NIO), news consumption, and perceptions of journalistic norms and practices. The results indicated that NIO moderated the relationships between NASM and selective exposure and between NASM and willingness to pay for quality news. Regarding journalistic norms and practices, participants valued the speed of journalism when they frequently accessed news on social media more so than traditional journalistic norms. Finally, there were statistically significant interactions between NIO and two types of news consumption behaviors (i.e., selective exposure and news avoidance) concerning participants' perceptions of news quality.
•The impact of social media news use on selective exposure is conditioned by news information overload.•The impact of social media news use on willingness to pay is conditioned by news information overload.•Frequent social media news use is associated with speed of journalism.•Frequent social media news use is related to disagreement with traditional journalistic norms.•News consumptions interact with news information overload and influence perceived news quality.
Nano-based drug delivery devices allowing for effective and sustained targeted delivery of therapeutic agents to solid tumors have revolutionized cancer treatment. As an emerging biomedical ...technique, cold atmospheric plasma (CAP), an ionized non-thermal gas mixture composed of various reactive oxygen species, reactive nitrogen species, and UV photons, shows great potential for cancer treatment. Here we seek to develop a new dual cancer therapeutic method by integrating promising CAP and novel drug loaded core-shell nanoparticles and evaluate its underlying mechanism for targeted breast cancer treatment. For this purpose, core-shell nanoparticles were synthesized via co-axial electrospraying. Biocompatible poly (lactic-co-glycolic acid) was selected as the polymer shell to encapsulate anti-cancer therapeutics. Results demonstrated uniform size distribution and high drug encapsulation efficacy of the electrosprayed nanoparticles. Cell studies demonstrated the effectiveness of drug loaded nanoparticles and CAP for synergistic inhibition of breast cancer cell growth when compared to each treatment separately. Importantly, we found CAP induced down-regulation of metastasis related gene expression (VEGF, MTDH, MMP9, and MMP2) as well as facilitated drug loaded nanoparticle uptake which may aid in minimizing drug resistance-a major problem in chemotherapy. Thus, the integration of CAP and drug encapsulated nanoparticles provides a promising tool for the development of a new cancer treatment strategy.
This perspective gives an overview of recent developments in surface-enhanced Raman scattering (SERS) for biosensing. We focus this review on SERS papers published in the last 10 years and to ...specific applications of detecting biological analytes. Both intrinsic and extrinsic SERS biosensing schemes have been employed to detect and identify small molecules, nucleic acids, lipids, peptides, and proteins, as well as for in vivo and cellular sensing. Current SERS substrate technologies along with a series of advancements in surface chemistry, sample preparation, intrinsic/extrinsic signal transduction schemes, and tip-enhanced Raman spectroscopy are discussed. The progress covered herein shows great promise for widespread adoption of SERS biosensing.
Coastal Ecosystem Values, Threats, and Decline Coastal wetlands, such as seagrass beds, mangrove wetlands, salt marshes, macroalgal, and seaweed beds, shellfish reefs, tidal freshwater wetlands, and ...coral reefs, are remarkable features of tropical and temperate coastlines. ...these systems are subject to what may be called “a triple whammy” of increasing industrialization and urbanization, an increased loss of biological and physical resources (fish, water, energy, space), and a decreased resilience to the consequences of a warming climate and sea level rise (Elliott et al., 2016). Trans-Disciplinary Teams Looking forward into the next decade, coastal habitat restoration will truly require a trans-disciplinary approach with skills drawn from engineering, modeling, ecology, chemistry, hydrology, social sciences including economics, financial, and project planning, governance, and integrated land, and sea spatial planning and management. Coastal ecosystems are at least as complex as terrestrial ecosystems, although arguably more dynamic, with the added gravity of the “triple whammy”—future development expansion that further alters shoreline ecosystems, loss of biodiversity and environmental conditions (e.g., water quality), and changing climate which alters sea level in many complex ways.
A common key regulator of oncogenic signaling pathways in multiple tumor types is the unique isomerase Pin1. However, available Pin1 inhibitors lack the required specificity and potency for ...inhibiting Pin1 function in vivo. By using mechanism-based screening, here we find that all-trans retinoic acid (ATRA)--a therapy for acute promyelocytic leukemia (APL) that is considered the first example of targeted therapy in cancer, but whose drug target remains elusive--inhibits and degrades active Pin1 selectively in cancer cells by directly binding to the substrate phosphate- and proline-binding pockets in the Pin1 active site. ATRA-induced Pin1 ablation degrades the protein encoded by the fusion oncogene PML-RARA and treats APL in APL cell and animal models as well as in human patients. ATRA-induced Pin1 ablation also potently inhibits triple-negative breast cancer cell growth in human cells and in animal models by acting on many Pin1 substrate oncogenes and tumor suppressors. Thus, ATRA simultaneously blocks multiple Pin1-regulated cancer-driving pathways, an attractive property for treating aggressive and drug-resistant tumors.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SBMB, UILJ, UKNU, UL, UM, UPUK
This study reports a systematic techno-economic assessment of the cost-optimal transmission for air as the heat transfer fluid at temperatures of up to 1200 °C, at scales of 1 to 1000 MW and at ...distances of up to 10 km. It employs a steady state heat transfer analysis, with energy balances, to assess the effect of scale, temperature and insulation on the heat losses and efficiency of the thermal transmission system, following by a techno-economic assessment. The sensitivity of the Levelised Cost of Heat, LCOHtr, to variations in thermal scale, operating temperature, distance, refractory and insulation thickness, ratio of the thickness of refractory and insulation, cost of any supplementary heat and lifetime is reported. The results show that LCOHtr decreases with an increase in thermal scale, as expected. The role of insulation is much more complex, since increasing the thickness of thermal barrier increases both cost and efficiency of the transmission, requiring an economic optimum to be determined for each of the various conditions assessed. Parameters are also coupled because a higher cost of supplied energy/ heat justifies the use of more insulation material. For a large GW scale thermal system, we estimate that it is possible to achieve a minimum overall LCOHtr,min of 0.16–0.36 USD/GJ/km of the length of the thermal transmission system, excluding additional location-specific costs such as land-access and local construction costs. These estimated costs are sufficiently attractive to justify ongoing development of systems to transport renewable heat to industry from sources such as concentrated solar thermal energy.
•A thermal transmission for air up to 1200 °C, 1GW and 10 km.•Efficiency and LCOH of the transmission were reported for cost-optimal situations.•The cost-optimised efficiency is strongly dependent on the cost of energy.•Cost-optimised efficiency can be above 98% for thermal transmission system >100 MW.•The cost of GW scale thermal transmission <1% of the cost of energy being transmitted.
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