Vaporized cannabis is believed to be safer than smoking, but when heated to excessive temperatures nearing combustion (>900 °C) harmful byproducts may form. While some cannabis extract vaporizers ...operate well below these high temperatures, heating coil temperatures obtained during actual use are frequently not reported and many operate at high temperatures. We report on two major objectives: 1) development of an infrared thermography method to measure heating coil temperatures in cannabis extract vaporizers during a simulated puff and 2) a comparison of temperature- to voltage- controlled cannabis extract vaporization systems during a puff. Infrared thermography was used to measure heating coil temperatures in one temperature-controlled and two voltage-controlled systems. The cartridges were modified for direct line-of-sight on the heating coils, the wick and coils were saturated with cannabis extract, and fixtures were developed to force two liters per minute air flow past the coils for the full duration of the puff allowed by the device. The voltage-controlled systems produced higher temperatures with greater variability than the temperature-controlled system. At the highest temperature setting (420 °C) the temperature-controlled system reached an average heating coil temperature of 420 ± 9.5 °C whereas the 4.0V setting on the variable voltage system reached an average temperature of 543 ± 95.9 °C and the single voltage (3.2V) system an average of 450 ± 60.8 °C. The average temperature at the lowest setting (270 °C) on the temperature-controlled system was 246 ± 5.1 °C and the variable voltage system (2.4V) was 443 ± 56.1 °C. Voltage alone was a poor indicator of coil temperature and only the temperature-controlled system consistently maintained temperatures less than 400 °C for the full puff duration. These lower temperatures could reduce the likelihood of harmful thermal degradation products and thus may reduce potential health risk to consumers when vaporizing cannabis extracts.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Aedes (Stegomyia) aegypti (L.) and Ae. (Stegomyia) albopictus (Skuse) mosquitoes can transmit dengue, chikungunya, yellow fever, and Zika viruses. Limited surveillance has led to uncertainty ...regarding the geographic ranges of these vectors globally, and particularly in regions at the present-day margins of habitat suitability such as the contiguous United States. Empirical habitat suitability models based on environmental conditions can augment surveillance gaps to describe the estimated potential species ranges, but model accuracy is unclear. We identified previously published regional and global habitat suitability models for Ae. aegypti (n = 6) and Ae. albopictus (n = 8) for which adequate information was available to reproduce the models for the contiguous U.S. Using a training subset of recently updated county-level surveillance records of Ae. aegypti and Ae. albopictus and records of counties conducting surveillance, we constructed accuracy-weighted, probabilistic ensemble models from these base models. To assess accuracy and uncertainty we compared individual and ensemble model predictions of species presence or absence to both training and testing data. The ensemble models were among the most accurate and also provided calibrated probabilities of presence for each species. The quantitative probabilistic framework enabled identification of areas with high uncertainty and model bias across the U.S. where improved models or additional data could be most beneficial. The results may be of immediate utility for counties considering surveillance and control programs for Ae. aegypti and Ae. albopictus. Moreover, the assessment framework can drive future efforts to provide validated quantitative estimates to support these programs at local, national, and international scales.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Objectives
To investigate the image quality and perception of a sinogram-based deep learning image reconstruction (DLIR) algorithm for single-energy abdominal CT compared to standard-of-care strength ...of ASIR-V.
Methods
In this retrospective study, 50 patients (62% F; 56.74 ± 17.05 years) underwent portal venous phase. Four reconstructions (ASIR-V at 40%, and DLIR at three strengths: low (DLIR-L), medium (DLIR-M), and high (DLIR-H)) were generated. Qualitative and quantitative image quality analysis was performed on the 200 image datasets. Qualitative scores were obtained for image noise, contrast, small structure visibility, sharpness, and artifact by three blinded radiologists on a 5-point scale (1, excellent; 5, very poor). Radiologists also indicated image preference on a 3-point scale (1, most preferred; 3, least preferred). Quantitative assessment was performed by measuring image noise and contrast-to-noise ratio (CNR).
Results
DLIR had better image quality scores compared to ASIR-V. Scores on DLIR-H for noise (1.40 ± 0.53), contrast (1.41 ± 0.55), small structure visibility (1.51 ± 0.61), and sharpness (1.60 ± 0.54) were the best (
p
< 0.05) followed by DLIR-M (1.85 ± 0.52, 1.66 ± 0.57, 1.69 ± 0.59, 1.68 ± 0.46), DLIR-L (2.29 ± 0.58, 1.96 ± 0.61, 1.90 ± 0.65, 1.86 ± 0.46), and ASIR-V (2.86 ± 0.67, 2.55 ± 0.58, 2.34 ± 0.66, 2.01 ± 0.36). Ratings for artifacts were similar for all reconstructions (
p
> 0.05). DLIRs did not influence subjective textural perceptions and were preferred over ASIR-V from the beginning. All DLIRs had a higher CNR (26.38–102.30%) and lower noise (20.64–48.77%) than ASIR-V. DLIR-H had the best objective scores.
Conclusion
Sinogram-based deep learning image reconstructions were preferred over iterative reconstruction subjectively and objectively due to improved image quality and lower noise, even in large patients. Use in clinical routine may allow for radiation dose reduction.
Key Points
•
Deep learning image reconstructions (DLIRs) have a higher contrast-to-noise ratio compared to medium-strength hybrid iterative reconstruction techniques
.
•
DLIR may be advantageous in patients with large body habitus due to a lower image noise
.
•
DLIR can enable further optimization of radiation doses used in abdominal CT
.
Non-human primates (NHPs) are a preferred animal model for optimizing adeno-associated virus (AAV)-mediated CNS gene delivery protocols before clinical trials. In spite of its inherent appeal, it is ...challenging to compare different serotypes, delivery routes, and disease indications in a well-powered, comprehensive, multigroup NHP experiment. Here, a multiplex barcode recombinant AAV (rAAV) vector-tracing strategy has been applied to a systemic analysis of 29 distinct, wild-type (WT), AAV natural isolates and engineered capsids in the CNS of eight macaques. The report describes distribution of each capsid in 15 areas of the macaques’ CNS after intraparenchymal (putamen) injection, or cerebrospinal fluid (CSF)-mediated administration routes (intracisternal, intrathecal, or intracerebroventricular). To trace the vector biodistribution (viral DNA) and targeted tissues transduction (viral mRNA) of each capsid in each of the analyzed CNS areas, quantitative next-generation sequencing analysis, assisted by the digital-droplet PCR technology, was used. The report describes the most efficient AAV capsid variants targeting specific CNS areas after each route of administration using the direct side-by-side comparison of WT AAV isolates and a new generation of rationally designed capsids. The newly developed bioinformatics and visualization algorithms, applicable to the comparative analysis of several mammalian brain models, have been developed and made available in the public domain.
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Kondratov and colleagues performed a systemic analysis of 29 distinct rAAV capsids after intraparenchymal, intracisternal, intrathecal, or intracerebroventricular injections in the CNS of macaques using qNGS coupled with ddPCR and bioinformatics pipelines. Specific CSF-mediated and parenchymal-distribution profiles of AAV libraries were identified.
Ceragenins are a family of synthetic amphipathic molecules designed to mimic the properties of naturally occurring cationic antimicrobial peptides (CAMPs). Although ceragenins have potent ...antimicrobial activity, whether their mode of action is similar to that of CAMPs has remained elusive. Here, we reported the results of a comparative study of the bacterial responses to two well-studied CAMPs, LL37 and colistin, and two ceragenins with related structures, CSA13 and CSA131. Using transcriptomic and proteomic analyses, we found that Escherichia coli responded similarly to both CAMPs and ceragenins by inducing a Cpx envelope stress response. However, whereas E. coli exposed to CAMPs increased expression of genes involved in colanic acid biosynthesis, bacteria exposed to ceragenins specifically modulated functions related to phosphate transport, indicating distinct mechanisms of action between these two classes of molecules. Although traditional genetic approaches failed to identify genes that confer high-level resistance to ceragenins, using a Clustered Regularly Interspaced Short Palindromic Repeats interference (CRISPRi) approach we identified E. coli essential genes that when knocked down modify sensitivity to these molecules. Comparison of the essential gene-antibiotic interactions for each of the CAMPs and ceragenins identified both overlapping and distinct dependencies for their antimicrobial activities. Overall, this study indicated that, while some bacterial responses to ceragenins overlap those induced by naturally occurring CAMPs, these synthetic molecules target the bacterial envelope using a distinctive mode of action.
The development of novel antibiotics is essential because the current arsenal of antimicrobials will soon be ineffective due to the widespread occurrence of antibiotic resistance. The development of naturally occurring cationic antimicrobial peptides (CAMPs) for therapeutics to combat antibiotic resistance has been hampered by high production costs and protease sensitivity, among other factors. The ceragenins are a family of synthetic CAMP mimics that kill a broad spectrum of bacterial species but are less expensive to produce, resistant to proteolytic degradation, and seemingly resistant to the development of high-level resistance. Determining how ceragenins function may identify new essential biological pathways of bacteria that are less prone to the development of resistance and will further our understanding of the design principles for maximizing the effects of synthetic CAMPs.
Patients with dementia with Lewy bodies (DLB) often experience visual hallucinations, which are related to decreased quality of life for patients and increased caregiver distress. The pathologic ...changes that contribute to visual hallucinations are not known, but several hypotheses implicate deficient attentional processing. The superior colliculus has a role in visual attention and planning eye movements and has been directly implicated in several models of visual hallucinations. Therefore, the present study sought to identify neurodegenerative changes that may contribute to hallucinations in DLB.
Postmortem superior colliculus tissue from 13 comparison, 10 DLB, and 10 Alzheimer disease (AD) cases was evaluated using quantitative neuropathologic methods.
α-Synuclein and tau deposition were more severe in deeper layers of the superior colliculus. DLB cases had neuronal density reductions in the stratum griseum intermedium, an important structure in directing attention toward visual targets. In contrast, neuronal density was reduced in all laminae of the superior colliculus in AD.
These findings suggest that regions involved in directing attention toward visual targets are subject to neurodegenerative changes in DLB. Considering several hypotheses of visual hallucinations implicating dysfunctional attention toward external stimuli, these findings may provide evidence of pathologic changes that contribute to the manifestation of visual hallucinations in DLB.
Abstract Background Neuroblastoma is a common pediatric cancer, where preclinical studies suggest that a mesenchymal-like gene expression program contributes to chemotherapy resistance. However, ...clinical outcomes remain poor, implying we need a better understanding of the relationship between patient tumor heterogeneity and preclinical models. Results Here, we generate single-cell RNA-seq maps of neuroblastoma cell lines, patient-derived xenograft models (PDX), and a genetically engineered mouse model (GEMM). We develop an unsupervised machine learning approach (“automatic consensus nonnegative matrix factorization” (acNMF)) to compare the gene expression programs found in preclinical models to a large cohort of patient tumors. We confirm a weakly expressed, mesenchymal-like program in otherwise adrenergic cancer cells in some pre-treated high-risk patient tumors, but this appears distinct from the presumptive drug-resistance mesenchymal programs evident in cell lines. Surprisingly, however, this weak-mesenchymal-like program is maintained in PDX and could be chemotherapy-induced in our GEMM after only 24 h, suggesting an uncharacterized therapy-escape mechanism. Conclusions Collectively, our findings improve the understanding of how neuroblastoma patient tumor heterogeneity is reflected in preclinical models, provides a comprehensive integrated resource, and a generalizable set of computational methodologies for the joint analysis of clinical and pre-clinical single-cell RNA-seq datasets.
Measurements of landslide movement made by global positioning system surveys and extensometers over a 3.5-year period show that the Slumgullion landslide in the San Juan Mountains of southwest ...Colorado moved throughout the monitoring period, but that daily velocities varied on a seasonal basis. Landslide velocities peaked in the early spring and summer in response to snowmelt and summer thunderstorms, respectively. Velocities were slowest in mid-winter when air and soil temperatures were coldest and precipitation was generally low and/or in the form of snow with a low water content. We hypothesize that the seasonal variability in velocities is due to ground-water levels and corresponding pore pressures that decrease when surface water is unavailable or cannot infiltrate frozen landslide material, and increase when surface water from melting snow or rainfall infiltrates unfrozen landslide material. We also suggest that patches of bouldery debris and fractures (created by continuous movement of the landslide) are conduits through which surface water can infiltrate, regardless of the frozen or unfrozen state of the landslide matrix material. Therefore, the availability of surface water is more important than landslide temperature in controlling the rate of landslide movement. This hypothesis is supported by field instrumentation data that show (1) landslide velocities coinciding with precipitation amounts regardless of the depth of freezing of landslide material, (2) spring and annual landslide velocities that were greatest when the depth of freezing was also the greatest, and (3) a rapid (several weeks or less) velocity and pore pressure response to rainfall.
The persistent, but seasonally variable movement of the landslide, fits the bathtub model for landslide movement described by Baum and Reid Baum, R.L., Reid, M.E., 2000. Ground water isolation by low-permeability clays in landslide shear zones. In: Bromhead, E.N., Dixon, N., Ibsen, M.-L. (Eds.), Landslides in Research, Theory and Practice. Proc. 8th Int. Symp. on Landslides, Cardiff, Wales, vol. 1, 139–144. In their model, the landslide is isolated both mechanically and hydrologically from adjacent materials by low permeability clays. These clays cause the landslide to retain water. Our data support this model by suggesting that pore pressures at the basal landslide surface are always adequate to maintain landslide movement and that any infiltration of water at the surface of the landslide is adequate to rapidly increase landslide velocity.
Exhausted CD8 T cells (T
) are associated with worse outcome in cancer yet better outcome in autoimmunity. Building on our past findings of increased TIGIT
KLRG1
T
with teplizumab therapy in type 1 ...diabetes (T1D), in the absence of treatment we found that the frequency of TIGIT
KLRG1
T
is stable within an individual but differs across individuals in both T1D and healthy control (HC) cohorts. This TIGIT
KLRG1
CD8 T
population shares an exhaustion-associated EOMES gene signature in HC, T1D, rheumatoid arthritis (RA), and cancer subjects, expresses multiple inhibitory receptors, and is hyporesponsive
, together suggesting co-expression of TIGIT and KLRG1 may broadly define human peripheral exhausted cells. In HC and RA subjects, lower levels of EOMES transcriptional modules and frequency of TIGIT
KLRG1
T
were associated with RA HLA risk alleles (DR0401, 0404, 0405, 0408, 1001) even when considering disease status and cytomegalovirus (CMV) seropositivity. Moreover, the frequency of TIGIT
KLRG1
T
was significantly increased in RA HLA risk but not non-risk subjects treated with abatacept (CTLA4Ig). The DR4 association and selective modulation with abatacept suggests that therapeutic modulation of T
may be more effective in DR4 subjects and T
may be indirectly influenced by cellular interactions that are blocked by abatacept.
Bexarotene is an FDA-approved drug for the treatment of cutaneous T-cell lymphoma (CTCL); however, its use provokes or disrupts other retinoid-X-receptor (RXR)-dependent nuclear receptor pathways and ...thereby incites side effects including hypothyroidism and raised triglycerides. Two novel bexarotene analogs, as well as three unique CD3254 analogs and thirteen novel NEt-TMN analogs, were synthesized and characterized for their ability to induce RXR agonism in comparison to bexarotene (
). Several analogs in all three groups possessed an isochroman ring substitution for the bexarotene aliphatic group. Analogs were modeled for RXR binding affinity, and EC
as well as IC
values were established for all analogs in a KMT2A-MLLT3 leukemia cell line. All analogs were assessed for liver-X-receptor (LXR) activity in an LXRE system to gauge the potential for the compounds to provoke raised triglycerides by increasing LXR activity, as well as to drive LXRE-mediated transcription of brain ApoE expression as a marker for potential therapeutic use in neurodegenerative disorders. Preliminary results suggest these compounds display a broad spectrum of off-target activities. However, many of the novel compounds were observed to be more potent than
. While some RXR agonists cross-signal the retinoic acid receptor (RAR), many of the rexinoids in this work displayed reduced RAR activity. The isochroman group did not appear to substantially reduce RXR activity on its own. The results of this study reveal that modifying potent, selective rexinoids like bexarotene, CD3254, and NEt-TMN can provide rexinoids with increased RXR selectivity, decreased potential for cross-signaling, and improved anti-proliferative characteristics in leukemia models compared to
.
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