Research on organizational diversity, heterogeneity, and related concepts has proliferated in the past decade, but few consistent findings have emerged. We argue that the construct of diversity ...requires closer examination. We describe three distinctive types of diversity: separation, variety, and disparity. Failure to recognize the meaning, maximum shape, and assumptions underlying each type has held back theory development and yielded ambiguous research conclusions. We present guidelines for conceptualization, measurement, and theory testing, highlighting the special case of demographic diversity.
In the framework of computer assisted diagnosis of diabetic retinopathy, a new algorithm for detection of exudates is presented and discussed. The presence of exudates within the macular region is a ...main hallmark of diabetic macular edema and allows its detection with a high sensitivity. Hence, detection of exudates is an important diagnostic task, in which computer assistance may play a major role. Exudates are found using their high grey level variation, and their contours are determined by means of morphological reconstruction techniques. The detection of the optic disc is indispensable for this approach. We detect the optic disc by means of morphological filtering techniques and the watershed transformation. The algorithm has been tested on a small image data base and compared with the performance of a human grader. As a result, we obtain a mean sensitivity of 92.8% and a mean predictive value of 92.4%. Robustness with respect to changes of the parameters of the algorithm has been evaluated.
Due to their efficient recognition and lysis of malignant cells, natural killer (NK) cells are considered as specialized immune cells that can be genetically modified to obtain capable effector cells ...for adoptive cellular treatment of cancer patients. However, biological and technical hurdles related to gene delivery into NK cells have dramatically restrained progress. Recent technological advancements, including improved cell expansion techniques, chimeric antigen receptors (CAR), CRISPR/Cas9 gene editing and enhanced viral transduction and electroporation, have endowed comprehensive generation and characterization of genetically modified NK cells. These promising developments assist scientists and physicians to design better applications of NK cells in clinical therapy. Notably, redirecting NK cells using CARs holds important promise for cancer immunotherapy. Various preclinical and a limited number of clinical studies using CAR-NK cells show promising results: efficient elimination of target cells without side effects, such as cytokine release syndrome and neurotoxicity which are seen in CAR-T therapies. In this review, we focus on the details of CAR-NK technology, including the design of efficient and safe CAR constructs and associated NK cell engineering techniques: the vehicles to deliver the CAR-containing transgene, detection methods for CARs, as well as NK cell sources and NK cell expansion. We summarize the current CAR-NK cell literature and include valuable lessons learned from the CAR-T cell field. This review also provides an outlook on how these approaches may transform current clinical products and protocols for cancer treatment.
Neuroimmune Interactions in Peripheral Organs Klein Wolterink, Roel G.J; Wu, Glendon S; Chiu, Isaac M ...
Annual review of neuroscience,
07/2022, Letnik:
45, Številka:
1
Journal Article
Recenzirano
Odprti dostop
Interactions between the nervous and immune systems were recognized long ago, but recent studies show that this crosstalk occurs more frequently than was previously appreciated. Moreover, ...technological advances have enabled the identification of the molecular mediators and receptors that enable the interaction between these two complex systems and provide new insights on the role of neuroimmune crosstalk in organismal physiology. Most neuroimmune interactions occur at discrete anatomical locations in which neurons and immune cells colocalize. Here, we describe the interactions of the different branches of the peripheral nervous system with immune cells in various organs, including the skin, intestine, lung, and adipose tissue. We highlight how neuroimmune crosstalk orchestrates physiological processes such as host defense, tissue repair, metabolism, and thermogenesis. Unraveling these intricate relationships is invaluable to explore the therapeutic potential of neuroimmune interactions.
The private sector’s role in climate finance is increasingly subject to political and scientific debate. Yet there is poor empirical evidence of private engagement in adaptation and its potential ...contribution to the industrialised countries’ mobilisation of USD 100 billion of annual climate finance from 2020 onwards to support developing countries to address climate change. This paper analysed 101 case studies of private sector adaptation under the Private Sector Initiative (PSI) of the UNFCCC Nairobi work programme, and examined these against ten ‘adaptation finance criteria’ that were distilled from UN climate negotiation outcomes. Results show that private adaptation interventions complement public adaptation activities. Yet the ten adaptation finance criteria are not met, which demonstrates that the diplomatic UNFCCC conceptualisation of financing adaptation is dissonant from the private sector reality. For example, while the case studies’ investments are ‘new and additional’ to Official Development Assistance (ODA), their ‘predictability’ remains unclear. And despite some commitment for ‘up-scaling’, plans and associated costs for doing so remain undisclosed. Developed countries’ role in ‘mobilising’ private financial resources under the PSI seems limited. It is unrealistic to expect that the UNFCCC alters existing criteria to suit private initiatives, or that the private sector aligns its initiatives to meet existing criteria. This paper advocates monitoring and reporting only of those private investments that principally finance adaptation. This practical way forward would allow private finance to meet criteria such as predictability, transparency, and mobilisation, but would drastically reduce the amount of private investment that could contribute to reaching the USD 100 billion climate finance target.
There is a need for materials that are well suited for cartilage tissue engineering. Hydrogels have emerged as promising biomaterials for cartilage repair, since, like cartilage, they have high water ...content, and they allow cells to be encapsulated within the material in a genuinely three-dimensional microenvironment. In this study, we investigated the mechanical properties of tissue-engineered cartilage constructs using in vitro culture models incorporating human chondrocytes from osteoarthritis patients. We evaluated hydrogels formed from mixtures of photocrosslinkable gelatin-methacrylamide (Gel-MA) and varying concentrations (0-2%) of hyaluronic acid methacrylate (HA-MA). Initially, only small differences in the stiffness of each hydrogel existed. After 4 weeks of culture, and to a greater extent 8 weeks of culture, HA-MA had striking and concentration dependent impact on the changes in mechanical properties. For example, the initial compressive moduli of cell-laden constructs with 0 and 1% HA-MA were 29 and 41 kPa, respectively. After 8 weeks of culture, the moduli of these constructs had increased to 66 and 147 kPa respectively, representing a net improvement of 69 kPa for gels with 1% HA-MA. Similarly the equilibrium modulus, dynamic modulus, failure strength and failure strain were all improved in constructs containing HA-MA. Differences in mechanical properties did not correlate with glycosaminoglycan content, which did not vary greatly between groups, yet there were clear differences in aggrecan intensity and distribution as assessed using immunostaining. Based on the functional development with time in culture using human chondrocytes, mixtures of Gel-MA and HA-MA are promising candidates for cartilage tissue-engineering applications.
Genetically encoded voltage indicators (GEVIs) can report cellular electrophysiology with high resolution in space and time. Two-photon (2P) fluorescence has been explored as a means to image voltage ...in tissue. Here, we used the 2P electronic excited-state lifetime to probe absolute membrane voltage in a manner that is insensitive to the protein expression level, illumination intensity, or photon detection efficiency. First, we tested several GEVIs for 2P brightness, response speed, and voltage sensitivity. ASAP1 and a previously described citrine-Arch electrochromic Förster resonance energy transfer sensor (dubbed CAESR) showed the best characteristics. We then characterized the voltage-dependent lifetime of ASAP1, CAESR, and ArcLight under voltage-clamp conditions. ASAP1 and CAESR showed voltage-dependent lifetimes, whereas ArcLight did not. These results establish 2P fluorescence lifetime imaging as a viable means of measuring absolute membrane voltage. We discuss the prospects and improvements necessary for applications in tissue.
Objective
To evaluate the incidence and prevalence of autoimmune encephalitis and compare it to that of infectious encephalitis.
Methods
We performed a population‐based comparative study of the ...incidence and prevalence of autoimmune and infectious encephalitis in Olmsted County, Minnesota. Autoimmune encephalitis diagnosis and subgroups were defined by 2016 diagnostic criteria, and infectious encephalitis diagnosis required a confirmed infectious pathogen. Age‐ and sex‐adjusted prevalence and incidence rates were calculated. Patients with encephalitis of uncertain etiology were excluded.
Results
The prevalence of autoimmune encephalitis on January 1, 2014 of 13.7/100,000 was not significantly different from that of all infectious encephalitides (11.6/100,000; p = 0.63) or the viral subcategory (8.3/100,000; p = 0.17). The incidence rates (1995–2015) of autoimmune and infectious encephalitis were 0.8/100,000 and 1.0/100,000 person‐years, respectively (p = 0.58). The number of relapses or recurrent hospitalizations was higher for autoimmune than infectious encephalitis (p = 0.03). The incidence of autoimmune encephalitis increased over time from 0.4/100,000 person‐years (1995–2005) to 1.2/100,000 person‐years (2006–2015; p = 0.02), attributable to increased detection of autoantibody‐positive cases. The incidence (2.8 vs 0.7/100,000 person‐years, p = 0.01) and prevalence (38.3 vs 13.7/100,000, p = 0.04) of autoimmune encephalitis was higher among African Americans than Caucasians. The prevalence of specific neural autoantibodies was as follows: myelin oligodendrocyte glycoprotein, 1.9/100,000; glutamic acid decarboxylase 65, 1.9/100,000; unclassified neural autoantibody, 1.4/100,000; leucine‐rich glioma‐inactivated protein 1, 0.7/100,000; collapsin response‐mediator protein 5, 0.7/100,000; N‐methyl‐D‐aspartate receptor, 0.6/100,000; antineuronal nuclear antibody type 2, 0.6/100,000; and glial fibrillary acidic protein α, 0.6/100,000.
Interpretation
This study shows that the prevalence and incidence of autoimmune encephalitis are comparable to infectious encephalitis, and its detection is increasing over time. Ann Neurol 2018;83:166–177
Abstract A complete prototype for the automatic detection of normal examinations on a teleophthalmology network for diabetic retinopathy screening is presented. The system combines pathological ...pattern mining methods, with specific lesion detection methods, to extract information from the images. This information, plus patient and other contextual data, is used by a classifier to compute an abnormality risk. Such a system should reduce the burden on readers on teleophthalmology networks.
Global warming and the alteration of the global nitrogen cycle are major anthropogenic threats to the environment. Denitrification, the biological conversion of nitrate to gaseous nitrogen, removes a ...substantial fraction of the nitrogen from aquatic ecosystems, and can therefore help to reduce eutrophication effects. However, potential responses of denitrification to warming are poorly understood. Although several studies have reported increased denitrification rates with rising temperature, the impact of temperature on denitrification seems to vary widely between systems.
We explored the effects of warming on denitrification rates using microcosm experiments, field measurements and a simple model approach. Our results suggest that a three degree temperature rise will double denitrification rates. By performing experiments at fixed oxygen concentrations as well as with oxygen concentrations varying freely with temperature, we demonstrate that this strong temperature dependence of denitrification can be explained by a systematic decrease of oxygen concentrations with rising temperature. Warming decreases oxygen concentrations due to reduced solubility, and more importantly, because respiration rates rise more steeply with temperature than photosynthesis.
Our results show that denitrification rates in aquatic ecosystems are strongly temperature dependent, and that this is amplified by the temperature dependencies of photosynthesis and respiration. Our results illustrate the broader phenomenon that coupling of temperature dependent reactions may in some situations strongly alter overall effects of temperature on ecological processes.
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