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Tomatoes (Solanum lycopersicum L.) are some of the most important vegetable foods worldwide. They are the second largest grown vegetable in both terms of production and consumption. Demand for tomatoes has been increasing recently due to their high content of nutritionally- acclaimed carotenoids, fibers, vitamins, and minerals, hence it has been the subject of numerous studies both in the laboratory and under field conditions. The quality of a tomato is determined by internal and external attributes, internal such as texture, sweetness, acidity, aroma, flavor, and nutritional value, and external which are appearance factors such as color, shape, size, and firmness. This review aims to investigate the chemical composition of tomato fruits and how they influence their quality. The findings of chemical composition (minor and major) components that were reported by many researchers are reviewed in this article. Also, this review focuses on the effect of tomato variety on the chemical composition of this fruit, and how these components are varied during the ripening process. In addition, chemical, physical and sensory quality factors were discussed in this review.

Purpose:Cisplatin-based chemotherapy is a first-line treatment for muscle-invasive and metastatic urothelial cancer. Approximately 10% of bladder urothelial tumors have a somatic missense mutation in the nucleotide excision repair (NER) gene, ERCC2, which confers increased sensitivity to cisplatin-based chemotherapy. However, a significant subset of patients is ineligible to receive cisplatin-based therapy due to medical contraindications, and no NER-targeted approaches are available for platinum-ineligible or platinum-refractory ERCC2-mutant cases.Experimental Design:We used a series of NER-proficient and NER-deficient preclinical tumor models to test sensitivity to irofulven, an abandoned anticancer agent. In addition, we used available clinical and sequencing data from multiple urothelial tumor cohorts to develop and validate a composite mutational signature of ERCC2 deficiency and cisplatin sensitivity.Results:We identified a novel synthetic lethal relationship between tumor NER deficiency and sensitivity to irofulven. Irofulven specifically targets cells with inactivation of the transcription-coupled NER (TC-NER) pathway and leads to robust responses in vitro and in vivo, including in models with acquired cisplatin resistance, while having minimal effect on cells with intact NER. We also found that a composite mutational signature of ERCC2 deficiency was strongly associated with cisplatin response in patients and was also associated with cisplatin and irofulven sensitivity in preclinical models.Conclusions:Tumor NER deficiency confers sensitivity to irofulven, a previously abandoned anticancer agent, with minimal activity in NER-proficient cells. A composite mutational signature of NER deficiency may be useful in identifying patients likely to respond to NER-targeting agents, including cisplatin and irofulven.See related commentary by Jiang and Greenberg, p. 1833

Supplementary Methods

Background: Although combination immunotherapies incorporating local and systemic components have shown promising results in treating solid tumors, varied tumor microenvironments (TMEs) can impact immunotherapeutic efficacy. Method: We designed and evaluated treatment strategies for breast and pancreatic cancer combining magnetic resonance-guided focused ultrasound (MRgFUS) ablation and antibody therapies. With a combination of single-cell sequencing, spectral flow cytometry, and histological analyses, we profiled an immune-suppressed KPC (Kras+/LSL-G12D; Trp53+/LSL-R172H; Pdx1-Cre) pancreatic adenocarcinoma (MT4) model and a dense epithelial neu deletion (NDL) HER2+ mammary adenocarcinoma model with a greater fraction of lymphocytes, natural killer cells and activated dendritic cells. We then performed gene ontology analysis, spectral and digital cytometry to assess the immune response to combination immunotherapies and correlation with survival studies. Result: Based on gene ontology analysis, adding ablation to immunotherapy enriched immune cell migration pathways in the pancreatic cancer model and extensively enriched wound healing pathways in the breast cancer model. With CIBERSORTx digital cytometry, aCD40 + aPD-1 immunotherapy combinations enhanced dendritic cell activation in both models. In the MT4 TME, adding the combination of aCD40 antibody and checkpoint inhibitors (aPD-1 and aCTLA-4) with ablation was synergistic, increasing activated natural killer cells and T cells in distant tumors. Furthermore, ablation with immunotherapy upregulated critical Ly6c myeloid remodeling phenotypes that enhance T-cell effector function and increased granzyme and protease encoding genes by as much as 100-fold. Ablation combined with immunotherapy then extended survival in the MT4 model to a greater extent than immunotherapy alone. Conclusion: In summary, TME profiling informed a successful multicomponent treatment protocol incorporating ablation and facilitated differentiation of TMEs in which ablation is most effective.

This study aims to study the effect of different combinations of Laser or/and Rhizobium on the growth parameters of clover plants. To carry out this study, irradiation of seeds by laser radiation and seeds incubation by Rhizobium combination with laser exposure times 5, 10, and 15 minutes compared to untreated seeds were used. Growth plants were cut four times during the growing season every 40–45 days, then growth parameters were measured. Obtained results showed that using treated seeds by combination laser exposed for 5 minutes and Rhizobium gave higher growth parameters followed by 10 minutes and control. While the exposure time of 15 minutes was less value. By using Laser excised times or/and Rhizobium, the results indicated that the growth parameters values of cover plants at irrigated with fresh water were higher than clover plants irrigated with groundwater. So, the authors recommended to use of irridiation by Laser beam and/or incubation by Rhizobium of clover seeds or any different seeds crops in order to improve vegetation and productivity of crops.

Käesolevas töös uuriti Eesti graptoliitargilliiti eesmärgiga välja selgitada Zn esinemisvorm, selle petrograafilised omadused ning analüüsida jälgelemendilist koostist. Eelnimetatule toetudes, kirjeldati sfaleriidi võimalikku geneesi. Mineralisatsiooni petrograafilised suhted näitavad, et sfaleriit on tekkinud graptoliitargilliiti viimase faasina läbi diageneetilise settimise, levides tühimikes ning poorsetes liivakates vahekihtides. Sfaleriidi jälgelemendid omavad erinevaid signatuure lääne ja idatsoonis, kuid kaasneva markasiidi kristallivormide ja korrodeerunud servadega kvartsi põhjal võib öelda, et sfaleriidi esinemine graptoliit-argilliidi kihtides on tingitud kõrgtemperatuurilistest, madala pH-ga hüdrotermaalsetest fluididest., https://www.ester.ee/record=b5563311

An enhancement strategy for the bio-reduction of Cr6+ in the presence of manganese ferrite nanostructures using Shewanella oneidensis.

User involvement is becoming more prevalent in system development as it has been shown to improve user satisfaction, usability, and the overall quality of the finished system. However, users have often been only minimally involved in traditional development methods. This study examines the impact of user involvement on work processes within companies that adopt this approach. Data was collected through semi-structured interviews in a N-study of several companies. The results provide a deeper understanding of how companies can involve users in their projects, and how this affects their work processes, as well as the study shows which methods are currently used for user participation. Additionally, the study discusses both the positive and negative aspects of user involvement. An interesting aspect that emerges in the study is that many companies do not use formal methods or guidelines when involving users in system development. Användarmedverkan blir allt vanligare inom systemutveckling då det kan förbättra användarnöjdhet, användbarhet och kvaliteten på det färdiga systemet. Trots detta involveras användare ofta endast i begränsad omfattning i traditionella utvecklingsmetoder. Denna studie undersöker vilken påverkan användarmedverkan har på arbetsprocessen inom företag som tillämpar detta tillvägagångssätt. Flera företag har jämförts i en N-studie, där data samlats in genom semi-strukturerade intervjuer. Resultatet ger en djupare förståelse av hur företag kan involvera användare i sina projekt, och hur detta påverkar deras arbetsprocess, samt visar vilka metoder som används vid användarmedverkan idag. I studien diskuteras också de positiva och negativa aspekterna av användarmedverkan. En intressant aspekt som framkommer i studien är att många företag inte använder formella metoder eller riktlinjer när de involverar användare i systemutvecklingen.

Correction for ‘Enhanced detoxification of Cr6+ by Shewanella oneidensis via adsorption on spherical and flower-like manganese ferrite nanostructures’ by Diana S. Raie et al., Nanoscale Adv., 2023, https://doi.org/10.1039/d2na00691j.

In microwave negative resistance oscillators, the RF transistor presents impedance with a negative real part at either of its input or output ports. According to the conventional theory of microwave negative resistance oscillators, in order to sustain oscillation and optimize the output power of the circuit, the magnitude of the negative real part of the input/output impedance should be maximized. This paper discusses the effect of the circuit’s load impedance on the input negative resistance and other oscillator performance characteristics in common base microwave oscillators. New closed-form relations for the optimum load impedance that maximizes the magnitude of the input negative resistance have been derived analytically in terms of the Z-parameters of the RF transistor. Furthermore, nonlinear CAD simulation is carried out to show the deviation of the large-signal optimum load impedance from its small-signal value. It has been shown also that the optimum load impedance for maximum negative input resistance differs considerably from its value required for maximum output power under large-signal conditions. A 1.8 GHz oscillator circuit has been designed and simulated using a typical SiGe hetero-junction bipolar transistor (HBT) to verify the proposed approach of analysis.

Background Strawberry fruit is a rich source of antioxidants that are beneficial for human health. However, the rapid decline of strawberries dramatically reduces the shelf life and raises postharvest losses. To develop an efficient and ecological approach for maintaining the quality, strawberries (Fragaria x ananassa, cv. Festival) were treated with 0.5% chitosan coating (0.5% Ch), guava leaf-based chitosan nanoparticles coating (Gl-ChNps), and a combination treatment of 1.3 mW/cm2 laser light followed by Gl-ChNps coating (combined treatment), then stored for 12 days at 10 °C and 85–90% RH. The untreated fruit served as a control. Results Semi-spherical particles with an average size of 21.92 nm, a monodisperse nature, and high solution stability were formed. The findings revealed that the combined treatment completely suppressed fungal decay compared to 50% decay in control, and significantly reduced weight loss percentage to 4.68% compared to 27.35% in control. In accordance, the combined treatment had the maximum anthocyanin content and vitamin C, at 42 and 81.1 mg/100 g, respectively. The results showed that treated strawberries had less change in color, total soluble solids, titratable acidity, and pH during storage than untreated strawberries, which exhibited higher chemical changes. Conclusions The edible film of chitosan nanoparticles acted as a semi-permeable barrier that modified and restricted gas exchange, reduced water loss, and delayed fruit senescence. In addition, the combination of laser light with chitosan nanoparticles has been shown to control the pathogens and retain the freshness of strawberries. Graphical Abstract

The development of gene delivery vehicles with high organ specificity when administered systemically is a critical goal for gene therapy. We combine optical and positron emission tomography (PET) imaging of 1) reporter genes and 2) capsid tags to assess the temporal and spatial distribution and transduction of adeno-associated viruses (AAVs). AAV9 and two engineered AAV vectors (PHP.eB and CAP-B10) that are noteworthy for maximizing blood-brain barrier transport were compared. CAP-B10 shares a modification in the 588 loop with PHP.eB, but also has a modification in the 455 loop, added with the goal of reducing off-target transduction. PET and optical imaging revealed that the additional modifications retained brain receptor affinity. In the liver, the accumulation of AAV9 and the engineered AAV capsids was similar (∼15% of the injected dose per cc and not significantly different between capsids at 21 h). However, the engineered capsids were primarily internalized by Kupffer cells rather than hepatocytes, and liver transduction was greatly reduced. PET reporter gene imaging after engineered AAV systemic injection provided a non-invasive method to monitor AAV-mediated protein expression over time. Through comparison with capsid tagging, differences between brain localization and transduction were revealed. In summary, AAV capsids bearing imaging tags and reporter gene payloads create a unique and powerful platform to assay the pharmacokinetics, cellular specificity and protein expression kinetics of AAV vectors in vivo, a key enabler for the field of gene therapy.

Resiquimod (R848) is a toll-like receptor 7 and 8 (TLR7/8) agonist with potent antitumor and immunostimulatory activity. However, systemic delivery of R848 is poorly tolerated because of its poor solubility in water and systemic immune activation. In order to address these limitations, we developed an intravenously-injectable formulation with R848 using thermosensitive liposomes (TSLs) as a delivery vehicle. R848 was remotely loaded into TSLs composed of DPPC: DSPC: DSPE-PEG2K (85:10:5, mol%) with 100mM FeSO4 as the trapping agent inside. The final R848 to lipid ratio of the optimized R848-loaded TSLs (R848-TSLs) was 0.09 (w/w), 10-fold higher than the previously-reported values. R848-TSLs released 80% of R848 within 5min at 42°C. These TSLs were then combined with αPD-1, an immune checkpoint inhibitor, and ultrasound-mediated hyperthermia in a neu deletion (NDL) mouse mammary carcinoma model (Her2+, ER/PR negative). Combined with αPD-1, local injection of R848-TSLs showed superior efficacy with complete NDL tumor regression in both treated and abscopal sites achieved in 8 of 11 tumor bearing mice over 100days. Immunohistochemistry confirmed enhanced CD8+ T cell infiltration and accumulation by R848-TSLs. Systemic delivery of R848-TSLs, combined with local hyperthermia and αPD-1, inhibited tumor growth and extended median survival from 28days (non-treatment control) to 94days. Upon re-challenge with reinjection of tumor cells, none of the previously cured mice developed tumors, as compared with 100% of age-matched control mice. The dose of R848 (10μg for intra-tumoral injection or 6mg/kg for intravenous injection delivered up to 4 times) was well-tolerated without weight loss or organ hypertrophy. In summary, we developed R848-TSLs that can be administered locally or systematically, resulting in tumor regression and enhanced survival when combined with αPD-1 in mouse models of breast cancer.

Strawberry fruits are perishable fruits and deteriorate vastly after harvest. This study aimed to maintain the quality attributes of strawberry fruit during seven days of cold storage using diode laser irradiation. Strawberries (Fragaria × ananassa, cv. Festival) were irradiated with diode laser at wavelength of 450 nm and light intensity of 1.3 mWcm−2 for 3, 6, and 12 min, while the non-irradiated fruits served as the control sample, then the fruit was packed and stored for 7 days at 10 °C and 85–90% relative humidity. The findings showed a significant reduction in weight loss and decay percentages of treated strawberries with 3 and 6 min of laser light, while control and 12 min laser irradiated samples exhibited the highest significant increase in weight loss and fungal decay. All laser treatments retained firmness of the flesh until the fifth day of storage, meanwhile the control sample became softer and fully mature, and at the end of the storage period, the control sample lost 77.9% of the firmness compared to 9.94% of 3 min treated fruit. Laser light had a marginal effect on pH, titratable acidity, and the content of anthocyanin. The results revealed that low exposure duration of laser treatment decreased darkness, and Chroma and total soluble solids (TSS) were maintained. Vitamin C showed a slight increase for all treatments and by the end of the storage period, the 3 min treated sample had the highest significant value of 73.04 mg/100 g compared to the lowest significant value of 65.86 mg/100 g of control. It was noticed that laser irradiation significantly reduced the reduction percentage of antioxidant activity compared to the control sample even with the highest exposure time of laser irradiation.

Using multiple feature descriptors simultaneously increases the accuracy of object recognition. Usage of dynamic coefficients, in other words, non-identical and proportional to the importance of each descriptor for each class, is an appropriate and efficient way to combine different feature descriptors. In this paper, a new and efficient structure is proposed that calculates these coefficients using the sparse representation classifier. For each feature descriptor, we propose an important criterion based on the reconstruction error of the images via the sparse representation. The assigned importance of each descriptor for each class is different and calculated based on the reconstruction errors of the images when only their classmate images contribute in the reconstruction process. In addition, an innovative method is proposed which can be used to help classes that are not well described by any descriptor as well. In this method, using the residual criteria, these classes are identified and using a defined notion of similarity among classes, the accuracy of these classes with the support of the similar ones is enhanced. The experimental results of the proposed work on Caltech-101 and Caltech-256 databases show the success of approaches compared with state-of-the-art ones on the same databases.

Background: Preterm birth and admission to neonatal intensive care unit as stressors can cause physiologicalinstability that may lead to prolong hospitalization and mortality. This study aimed to determine the effect of artificialnights and facilitated tucking on the physiological indices of premature infants.Methods: This randomized clinical trial was conducted on 60 preterm infants admitted to the neonatal intensive careunit at Shohadaye Kargar Hospital in Yazd, Iran, during 2017-18. The infants were selected through a convenientsampling method, and were randomly assigned into three groups of arti icial nights with facilitated tucking (group 1)(n=20), arti icial nights (group 2) (n=20) and control group (group 3) (n=20). Subsequently, the physiological indices(i.e., heart rate, respiration rate, arterial oxygen saturation) were measured twice a day at 7:00 a.m. and 19:00 p.m. for3 days. The data were analyzed in SPSS software (version 20). A p-value less than 0.05 was considered statisticallysignificant.Results: There was a significant difference among the three groups in terms of mean values of heart, respiratory, andarterial oxygen saturation rates (Prespiratory rate on the third day (at 19:00 p.m.), as well as a greater increase in arterial oxygen saturation rate on thesecond (at 19:00 p.m.) and third days (at 7:00 a.m. and 19:00 p.m.), compared to the other two groups (PAdditionally, , the mean value of heart and respiratory rates were lower and arterial oxygen saturation rates werehigher in the intervention group 1, compared to the other groups.Conclusion: According to the results of the study, the simulation of the mother’s womb environment through creatingartificial night and maintaining facilitated tucking resulted in the improvement of physiological indices of thepremature infants. Furthermore, artificial night together with facilitated tucking leads to better results, compared toartificial night alone.

The aim of this paper is to propose a novel switching control method to improve the efficiency of the basic half-bridge converter for the whole range of the load current. Using multimode control for this purpose, instead of modifying the structure of the converter, is proposed for the first time. Efficiency improvement is achieved by using a digital controller to select and change the control mode to the most efficient one, for each of the load sub-ranges. Control modes are prominent ones, including asymmetric, duty phase shift, pulsewidth modulation, and burst control, and are selected in turn, while the load current varies in its entire range from the full down to the no-load. The three transition points between control modes, being specific values of the load current, are analytically determined based on comparing the half-bridge converter power losses for different control modes. The digital controller compares the load current with the transition points and puts the converter in the control mode with the highest efficiency. The accuracy of the analytically determined transition points and the efficiency improvement of the proposed control method over the previous ones are investigated and approved by the experimental results.

Background: Little evidence has noted that psychological factors are risk factors of post-operative pain intensity in women undergoing cesarean section. Objectives: The aim of study was to determine predictive psychosocial factors for post-cesarean pain intensity using assessment of depression, anxiety, self-efficacy, and quality of relationship. Methods: This prospective descriptive-analytic study was carried out on 150 healthy women scheduled for cesarean section under spinal anesthesia. The day before the surgery, the patients completed three questionnaires including Hospital Anxiety and Depression Scale (HADS), and General Self-efficacy. Also, 24 hours after the surgery, the intensity of pain in the patients was assessed with filling McGill Pain Questionnaire (MPQ). Linear regression was used to predict the factors of pain intensity. Results: The anxiety was a positive predictor of pain intensity of women after C-section (β = 0. 0.22, P = 0.014). However, depression score, and self-efficacy were not predicting factors of pain intensity of women after C-section. Conclusions: Preoperative anxiety increases post-operative pain intensity in women undergoing cesarean section.

This thesis was scanned from the print manuscript for digital preservation and is copyright the author. Researchers can access this thesis by asking their local university, institution or public library to make a request on their behalf. Monash staff and postgraduate students can use the link in the References field.

Bladder cancer is a genetically heterogeneous disease and novel therapeutic strategies are needed to expand treatment options and improve clinical outcomes. Here we identified a unique subset of urothelial tumors with focal amplification of the RAF1 (CRAF) kinase gene. RAF1-amplified tumors had activation of the RAF/MEK/ERK signaling pathway and exhibited a luminal gene expression pattern. Genetic studies demonstrated that RAF1-amplified tumors were dependent upon RAF1 activity for survival, and RAF1-activated cell lines and patient-derived models were sensitive to available and emerging RAF inhibitors as well as combined RAF plus MEK inhibition. Furthermore, we found that bladder tumors with HRAS or NRAS activating mutations were dependent on RAF1-mediated signaling and were sensitive to RAF1-targeted therapy. Together, these data identified RAF1 activation as a novel dependency in a subset comprising nearly 20% of urothelial tumors and suggested that targeting RAF1-mediated signaling represents a rationale therapeutic strategy.

PARP inhibitors were recently approved for treatment of molecularly-defined subsets of metastatic castrate-resistant prostate cancer (mCRPC) patients. Although the PARP inhibitor olaparib was approved for use in patients with a mutation in one of fourteen genes, the mutation frequency of the genes varies widely in mCRPC and the impact of the less commonly altered genes on PARP inhibitor sensitivity is uncertain. We used functional approaches to directly test the impact of PALB2 and BARD1 loss on homologous recombination (HR) function and PARP inhibitor sensitivity in prostate cancer cell lines. PALB2 or BARD1 loss led to decreased HR function as measured by loss of radiation-induced Rad51 foci formation as well as decreased HR capacity in a cell-based reporter assay. PALB2 or BARD1 loss also significantly increased sensitivity to the PARP inhibitors olaparib and rucaparib across a panel of prostate cancer cell lines. These data support PALB2 and BARD1 loss as markers of clinically relevant PARP inhibitor sensitivity and highlight the potential to use functional approaches to complement and extend findings from clinical trials of targeted agents.

Facial expression recognition is an interesting and challenging problem in computer vision. So far, much research has been performed in this area; however, facial expression recognition in uncontrolled conditions has remained an unresolved problem. The widely-used feature descriptors in computer vision are often histogram data. In this paper, a new metric learning method is presented for histogram data classification. In this method, chi-squared distance is appropriately modified for metric learning. Then, a convex cost function is proposed to use in metric learning optimization. Moreover, the proposed algorithm is redefined as Local Metric Learning for facial expression recognition problem. In this definition, the proposed metric learning method is applied locally on facial sub-regions. Experimental results on four histogram datasets (dslr, webcam, amazon, and caltech) as well as controlled and uncontrolled facial expression recognition datasets (CK+, SFEW, and RAF-DB) show that the proposed method has superior performance compared to the state-of-art methods.

Facial expression is a powerful way for human emotional communications. According to various applications, automatic facial expression recognition becomes an interesting problem for researchers in different areas. An automatic facial expression recognition system recognizes the expressed emotion in input facial image using several processing stages. Feature extraction is a vital step in facial expression recognition. One of the most widely used techniques for feature extraction in machine vision is utilizing Gabor filter which is sensitive to lines at various orientations. The disadvantage of Gabor filters is their computational cost and large feature vector length. Inspiring the human vision system and stimulations of complex cells, in this paper, firstly, facial image is convolved with Gabor filters. Then, the achieved convolution matrices are properly coded based on the maximum and minimum responses. Finally, the feature vector is obtained by calculating the histogram of these codes. The length of achieved histogram for 16 and 8 Gabor filters are 240 and 56, respectively, which is considerably less than keeping all Gabor responses. The proposed method is (person-independently) evaluated on four facial expression recognition datasets including CK+, SFEW, MMI, and RAF-DB. The experimental results show that the proposed method outperforms existing image texture descriptors in facial expression recognition in both controlled and uncontrolled images.

The theme of this article is to propose a general multi-mode control method to optimise the efficiency of the full-bridge converter based on prominent control modes for the whole range of load variations. This method selects the most efficient prominent control mode in each load sub-range, including variable delay phase shift, fixed delay phase shift, pulse width modulation (PWM) and burst control while the load current varies in its entire range from full down to no load. In this regard, for the first time, three transition points between control modes are analytically determined based on full-bridge converter power losses analysis. Determining transition points and load current sub-ranges, being functions of converter parameters, is in fact the process of optimising the proposed method for the entire range of the load current in terms of four control modes. The accuracy of the analytically determined transition points and the optimal control mode selection over the load variations are justified by experimental results on digitally implemented proposed control method and full-bridge converter.

Different causes lead to accidental oil spills from fixed and mobile sources in the marine environment. Therefore, it is essential to have a systematic plan for mitigating oil spill consequences. In this research, a general DSS is proposed for passive and active response planning in Persian Gulf, before and after a spill. The DSS is based on NOAA's advanced oil spill model (GNOME), which is now linked with credible met-ocean datasets of CMEMS and ECMWF. The developed open-source tool converts the results of the Lagrangian oil spill model to quantitative parameters such as mean concentration and time of impact of oil. Using them, two new parameters, emergency response priority number (ERPN) and risk index (RI), are defined and used for response planning. The tool was tested in both deterministic and probabilistic modes, and found to be useful for evaluation of emergency response drills and risk-based prioritization of coastal areas.

Sleep-related breathing disorders (SBDs) are characterized by abnormal respiration during sleep. Obstructive sleep apnea (OSA), a common SBD increasingly recognized by physicians, is characterized by recurrent episodes of partial or complete closure of the upper airway resulting in disturbed breathing during sleep. OSA syndrome (OSAS) is associated with decreased patients' quality of life (QoL) and the presence of significant comorbidities, such as daytime sleepiness. Similarly to what seen for OSAS, the prevalence of asthma has been steadily rising in recent years. Interestingly, severe asthma (SA) patients are also affected by poor sleep quality—often attributed to nocturnal worsening of their asthma—and increased daytime sleepiness and snoring compared to the general population. The fact that such symptoms are also found in OSAS, and that these two conditions share common risk factors, such as obesity, rhinitis, and gastroesophageal reflux, has led many to postulate an association between these two conditions. Specifically, it has been proposed a bidirectional correlation between SA and OSAS, with a mutual negative effect in term of disease severity. According to this model, OSAS not only acts as an independent risk factor of asthma exacerbations, but its co-existence can also worsen asthma symptoms, and the same is true for asthma with respect to OSAS. In this comprehensive review, we summarize past and present studies on the interrelationship between OSAS and SA, from endo-phenotype to clinical aspects, highlighting possible implications for clinical practice and future research directions.

Immunotherapy is an important cancer treatment strategy; nevertheless, the lack of robust immune cell infiltration in the tumor microenvironment remains a factor in limiting patient response rates. In vivo gene delivery protocols can amplify immune responses and sensitize tumors to immunotherapies, yet non-viral transfection methods often sacrifice transduction efficiency for improved safety tolerance. To improve transduction efficiency, we optimized a strategy employing low ultrasound transmission frequency-induced bubble oscillation to introduce plasmids into tumor cells. Differential centrifugation isolated size-specific microbubbles. The diameter of the small microbubble population was 1.27 ± 0.89 μm and that of larger population was 4.23 ± 2.27 μm. Upon in vitro insonation with the larger microbubble population, 29.7% of cancer cells were transfected with DNA plasmids, higher than that with smaller microbubbles (18.9%, P

Event Recognition aims to classify activities done by a group of people and/or objects in a video into different classes. Convolutional Neural Networks (CNNs) have shown promising results in computer vision tasks, specifically human activity recognition. This paper presents a Two-Stream Convolutional Neural Network for video Event Recognition which uses Xception architecture as its backbone. The dual streams of this method are responsible for extracting spatial and temporal features. The first stream extracts spatial features from RGB frames and the second stream extracts motion features from optical flow images. Due to optical flow estimation complexity, another method for motion estimation between two frames called Thresholding Frame Subtraction (TFS) is used which can speed up the preprocessing phase. The method showed recognition accuracies of 85.6% and 73.2% on VIRAT ground dataset in the best case using optical flow and TFS images respectively which outperform other works on this dataset.

This research aims to improve simultaneous nitrification-denitrification and phosphorus removal (SNDPR) using novel carriers and to demonstrate the effect of carrier characteristics on nutrient removal in a biofilm reactor. For this purpose, biofilms enriched with both polyphosphate-accumulating organisms (PAOs) and nitrifiers were cultivated in two parallel sequencing batch reactors containing conventional moving bed bioreactor carriers (MBBR) and a novel type of carriers (carbon-based moving carriers (CBMC)). The new carriers were produced based on recycled waste materials via a chemical-thermal process and their specific surface area were 10.4 times higher than typical MBBR carriers of similar dimensions. The results showed that the use of CBMC carriers increased bacterial adhesion by about 18.5% and also affected the microbial population inside the biofilms, leading to an increase in PAOs abundancy and thus an increase in biological phosphorus removal up to 12.5%. Additionally, it was corroborated that the volume of the anoxic zones with dynamic behavior is strictly influenced by the carrier structure and biofilm thickness due to a limitation in oxygen penetration. Accordingly, the formation of broader anoxic zones and shrinkage of these zones to a lesser extent resulted in the continuation of anoxic reactions for longer periods using the novel carriers. Thereby, an increase in nitrogen removal by about 15% was obtained mainly by denitrifying PAOs. The results also exhibited that a higher simultaneous nitrification-denitrification (SND) efficiency can be achieved by selecting an appropriate aeration program influencing the dynamic changes of anoxic zones. Overall, a biofilm system using the new carriers, with phosphorus and nitrogen removal efficiencies of 97.5% and 92.3%, was presented as an efficient, compact, and simple operation SNDPR process. ispartof: JOURNAL OF ENVIRONMENTAL MANAGEMENT vol:302 issue:Pt A ispartof: location:England status: published

The tumor microenvironment (TME) subtype is a critical factor when combining immunotherapy with tumor debulking strategies such as ultrasound ablation. To understand the effects of the TME subtype, we studied two multi-site murine cancer models, an immune-suppressed KPC (Kras+/LSL-G12D; Trp53+/LSL-R172H; Pdx1-Cre) pancreatic adenocarcinoma (MT4) model and a neu deletion HER2+ (NDL) mammary adenocarcinoma model with a larger naïve lymphocyte population. After profiling the two models with histology and single-cell sequencing, we designed immunotherapy combinations with Magnetic Resonance-guided Focused Ultrasound (MRgFUS) thermal ablation that were specific to each TME subtype. To understand the impact of the molecular and cellular differences upon each model, we characterized the treatment effect with transcriptomic analysis and digital cytometry. We found that combining MRgFUS ablation with immunotherapy reduced tumor growth and extended survival by at least 2-fold in the MT4 pancreatic cancer model. Gene set enrichment analysis (GSEA) of bulk RNA sequencing data indicated that the combination of ablation with immunotherapy preferentially enriched functional annotations for leukocyte migration in the MT4 model and wound healing and inflammatory cytokines in the NDL model (e.g. for IL6: 1.6 fold increase in MT4 vs 10.3 fold in NDL tumors). We then particularly focused on whether dendritic cell (DC) activation and CD4 T cell populations could be enhanced when ablating pancreatic tumors. By CIBERSORTx digital cytometry, aCD40 + aPD-1 combinations increased the presence of activated DCs in MT4 tumors by 2.4-fold. Activated DCs were also increased by CP4 (aCD40 + aPD-1 + CTLA-4) alone 1.7 fold or in combination with ablation in both treated (2.4 fold) and distant (2.2 fold) lesions. Ablation combined with aPD-1 alone did not significantly impact DCs in the MT4 model. In addition, CD4 lymphocytes increased 5 and 8 fold in treated and distant tumors by ablation combined with CP4 in the MT4 model. Taken together, inflammatory cytokines were preferentially elevated by ablation in a dense epithelial breast cancer as compared with a pancreatic tumor model. Further, the results suggest that aCD40 immunotherapy retains efficacy when combined with thermal ablation in pancreatic tumors. This work can inform clinical translation of ablative and immunotherapy combination protocols. Citation Format: James Wang, Brett Z. Fite, Aris Kare, Bo Wu, Marina N. Raie, Spencer Tumbale, Ryan R. Davis, Clifford G. Tepper, Katherine Ferrara. TME subtype impacts response to combined thermal ablation and immunotherapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 6314.

Introduction: Adoptive cell transfer (ACT) of T cells has emerged in recent years as a powerful immunotherapy against cancer. Currently, T cells are harvested from the patient or donor and are genetically modified ex vivo to enhance their cancer-fighting capabilities. However, this process is costly and more complex than administering off-the-shelf therapies such as small molecule drugs or monoclonal antibodies. The development of methods to transfect T cells in vivo remains an important endeavor for immunotherapies. Ionizable lipid nanoparticles (LNPs) have recently played a key role as carrier vehicles for mRNA in the Pfizer-BioNTech and Moderna mRNA vaccines. While ionizable LNPs delivering mRNA have now been FDA-approved for non-targeted immune cell delivery, their potential for targeting specific immune cell subtypes has yet to be fully realized. Delivering therapeutic genes that could reprogram T cells in vivo to recognize disease-relevant antigens would be of great clinical significance in reducing the lead time and cost of current ACT therapies. Methods: Ionizable LNPs were synthesized to encapsulate mCherry or Firefly Luciferase (FLuc) reporter gene mRNA with a fluorescent Cy7-labeled lipid on the LNP surface. CD3 monoclonal antibody, F(ab’)2 CD3e fragment, or CD8 diabody was conjugated to the LNP surface. In vitro, the aCD3- or aCD8-LNPs were incubated with Jurkat or TK-1 cell lines, respectively. LNP uptake was imaged using fluorescent confocal microscopy, and mCherry expression was quantified via flow cytometry. For in vivo delivery, the ionizable LNPs were injected i.v., and reporter gene expression and cell activation were analyzed via flow cytometry and bioluminescence imaging. Results: Confocal microscopy of ionizable LNP uptake in vitro highlighted differences in the internalization of the aCD3- and aCD8-LNPs in their respective cell lines, and transfection was observed with each targeting ligand. In murine models, aCD3-LNPs led to FLuc expression in the spleen and liver with increased accumulation in lymph nodes. aCD3-LNPs also transfected mCherry mRNA and activated splenic and circulating T cells. Cytokine concentrations were elevated in blood 5 and 24 h after aCD3-LNP injection. The impact of LNP lipid composition on transfection will be detailed in the presentation. Conclusions: We successfully packaged mRNAs of mCherry and FLuc reporter genes within ionizable LNPs and targeted them to T cells via the CD3 or CD8 receptor. The ionizable LNPs were capable of transfecting T cells in vitro and in vivo while causing transient activation, depletion, migration, cytokine release, and phenotypic shifts. Working towards the goal of receptor-mediated T cell targeting in vivo, we elucidate the circulation time, transfection efficiency, and activating potential of ionizable LNPs targeted to T cells in the spleen and blood via two potential targets, the CD3 and CD8 receptors. Citation Format: Elise R. Robinson, Aris J. Kare, Azadeh Kheirolomoom, Mohammed Inayathullah, Spencer K. Tumbale, Bo Wu, Marina N. Raie, Jai W. Seo, Felix B. Salazar, Ramasamy Paulmurugan, Anna M. Wu, Katherine W. Ferrara. CD3 and CD8 targeting of ionizable lipid nanoparticles for in vivo mRNA delivery to T cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5372.

Resiquimod is an immunopotent toll-like receptor 7/8 agonist with antitumor activity. Despite being potent against skin cancers, it is poorly tolerated systemically due to toxicity. Integrating resiquimod into nanoparticles presents an avenue to circumvent the toxicity problem. Herein, the preparation of degradable nanoparticles with covalently bound resiquimod and their systemic application in cancer immunotherapy is reported. Dispersion in water of amphiphilic constructs integrating resiquimod covalently bound via degradable amide or ester linkages yields immune-activating nanoparticles. The degradable agonist-nanoparticle bonds allow the release of resiquimod from the carrier nanoparticles. In vitro assays with antigen presenting cells demonstrate that the nanoparticles retain the immunostimulatory activity of resiquimod. Systemic administration of the nanoparticles and checkpoint blockade (aPD-1) to a breast cancer mouse model with multiple established tumors triggers antitumor activity evidenced by suppressed tumor growth and enhanced CD8+ T-cell infiltration. Nanoparticles with ester links, which hydrolyze more readily, yield a stronger immune response with 75% of tumors eliminated when combined with aPD-1. The reduced tumor growth and the presence of activated CD8+ T-cells across multiple tumors suggest the potential for treating metastatic cancer.

The unicellular spore-forming parasites Nosema apis and Nosema ceranae are considered to be one of the causes of increased honey bee mortality in recent years. These pathogens attack their honey bee hosts through their gut, causing changes in behavioral stress responses and possibly resulting in decreased honey yield and increased honey bee mortality. The present study aimed to determine the prevalence of Nosema spp. (nosemosis) in Estonia and Latvia, as well as the persistence of the disease in previously infected hives. Currently, N. ceranae is considered the most virulent species and is predominant worldwide. However, in some regions, usually with colder climates, N. apis is still prevalent. To achieve better disease control, it is important to determine the species distribution. For this purpose, we selected 30 apiaries in Estonia and 60 in Latvia that were positive for Nosema spp. in the EPILOBEE (2012–2014) study, which was 5 years prior to the present study. The results show that, while both species are present in Estonia and Latvia, N. apis is dominant in Estonia (43%), and N. ceranae is dominant in Latvia (47%). We also found that the pathogens are very persistent, since 5 years later, only 33% of infected apiaries in Estonia and 20% of infected apiaries in Latvia, we could not detect any pathogens at the time of sampling.

Introduction. The clinical course of Coronavirus Disease 2019 (COVID-19) is highly heterogenous, ranging from asymptomatic to fatal forms. The identification of clinical and laboratory predictors of poor prognosis may assist clinicians in monitoring strategies and therapeutic decisions. Materials and Methods. In this study, we retrospectively assessed the prognostic value of a simple tool, the complete blood count, on a cohort of 664 patients ( F 260; 39%, median age 70 (56-81) years) hospitalized for COVID-19 in Northern Italy. We collected demographic data along with complete blood cell count; moreover, the outcome of the hospital in-stay was recorded. Results. At data cut-off, 221/664 patients (33.3%) had died and 453/664 (66.7%) had been discharged. Red cell distribution width (RDW) ( χ 2 10.4; p < 0.001 ), neutrophil-to-lymphocyte (NL) ratio ( χ 2 7.6; p = 0.006 ), and platelet count ( χ 2 5.39; p = 0.02 ), along with age ( χ 2 87.6; p < 0.001 ) and gender ( χ 2 17.3; p < 0.001 ), accurately predicted in-hospital mortality. Hemoglobin levels were not associated with mortality. We also identified the best cut-off for mortality prediction: a NL ratio > 4.68 was characterized by an odds ratio for in-hospital mortality OR = 3.40 (2.40-4.82), while the OR for a RDW > 13.7 % was 4.09 (2.87-5.83); a platelet count > 166,000 /μL was, conversely, protective (OR: 0.45 (0.32-0.63)). Conclusion. Our findings arise the opportunity of stratifying COVID-19 severity according to simple lab parameters, which may drive clinical decisions about monitoring and treatment.

Starting from a context in which sustainable construction and the efficient use of natural resources are being promoted more every day, the COMPOP project appears where it is intended to develop new composite materials for construction combining laminated poplar wood (Glulam) and reinforcing it with carbon fiber. The COMPOP project has been active for a few years and has reached a stage in which they want to demonstrate the effectiveness of these new materials in real constructions. With this, the need arises to monitor the stresses supported by these structures that are still in the prototype phase. This Final Degree Project aims to develop a device that meets this need, that is, it measures the stresses that each beam of a structure supports and analyzes these data, checking that the deformations suffered are within the operating margin at all times. The development and implementation of this project is performed following methodologies of Systems Engineering, giving realism and getting the student closer to professional techniques, widely recognized in the job market. Furthermore, the complexity and multidisciplinary scope of this Bachelor’s Thesis allows covering not only the different specialties of the Bachelor in Telecommunication Engineering but also acquiring knowledge and transversal abilities from other fields of the Engineering, such as Mechanical or Building Engineering. Besides specific software of each of the mentioned areas, advanced techniques of machining, manufacturing or characterization of different devices, among others, have been analyzed and applied., Partiendo de un contexto en el que cada día se fomenta más la construcción sostenible y el uso eficiente de los recursos naturales, aparece el proyecto COMPOP donde se pretende desarrollar nuevos materiales compuestos para construcción combinando madera laminada de chopo (Glulam) y reforzándolo con fibra de carbono. El proyecto COMPOP lleva activo unos cuantos años y ha llegado a una fase en la que se quiere demostrar la eficacia de estos nuevos materiales en construcciones reales. Con ello surge la necesidad de monitorizar los esfuerzos que soportan estas estructuras que están aún en fase de prototipo. Este Trabajo Final de Grado pretende desarrollar un dispositivo que cubra esta necesidad, es decir que mida los esfuerzos que soportan cada viga de una estructura y analice esos datos comprobando que en todo momento las deformaciones sufridas están dentro del margen de operación. El desarrollo e implementación de este proyecto se lleva a cabo siguiendo metodologías de Ingeniería de Sistemas, dotándolo de realismo y acercando al alumno a técnicas profesionales de amplio reconocimiento en el mercado de trabajo. Asimismo, la complejidad y ámbito multidisciplinar de este Trabajo Fin de Grado le permite cubrir, no sólo las diferentes especialidades del Grado de Ingeniería de Telecomunicación, sino también adquirir conocimientos y habilidades transversales o específicos de otros campos de la Ingeniería, como la Mecánica o la Edificación. Así, además de software especialista de cada uno de los campos mencionados, se han analizado y aplicado técnicas avanzadas de mecanizado, fabricación (soldadura utilizando técnicas de reflow) o caracterización de diferentes dispositivos, entre otros.

BACKGROUND: A novel [(64)Cu]Cu-NOTA-aCD40 immunoPET tracer was developed to image a CD40(+) pancreatic tumor model in C57BL/6 mice and to study the biodistribution profile of the agonist CD40 (aCD40) monoclonal antibody (mAb) alone or combined with other mAbs. PROCEDURES: Copper-64 ([(64)Cu]Cu) labeled NOTA-aCD40 and NOTA-IgG (10 μg; 7 MBq) were injected intravenously into C57BL/6 mice with subcutaneous mT4 tumors to assess specificity 48 h post injection (p.i.) through positron emission tomography/computed tomography (PET/CT) imaging and biodistribution studies (n = 5). [(64)Cu]Cu-NOTA-aCD40 was injected alone or simultaneously in combination with a therapeutic mass of cold aCD40 (100 μg), aPD-1 (200 μg) and aCTLA-4 (200 μg) mAbs. A group of mice with or without tumor received the second round of injections 1 or 3 weeks apart, respectively. PET/CT imaging and biodistribution studies were performed at 48 h p.i. The organ dose for [(64)Cu]Cu was estimated based on biodistribution studies with 2 μg [(64)Cu]Cu-NOTA-aCD40 (corresponds to 5 mg patient dose) in non-tumor bearing mice. RESULTS: [(64)Cu]Cu-NOTA-aCD40 accumulation was 2.3- and 7.8-fold higher than [(64)Cu]Cu-NOTA-IgG in tumors and spleen, respectively, indicating the specificity of aCD40 mAb in a mouse pancreatic tumor model. Tumor accumulation of [(64)Cu]Cu-NOTA-aCD40 was 21.2 ± 7.3 %ID/g at 48 h after injection. Co-injection of [(64)Cu]Cu-NOTA-aCD40 with cold aCD40 mAb alone or with PD-1 and CTLA-4 mAbs reduced both spleen and tumor uptake, whereas liver uptake was increased. With the second round of injections, the liver was the only organ with substantial uptake. With a 2 μg administered dose of [(64)Cu]Cu-NOTA-aCD40 in a dosimetry study, the liver to spleen ratio was greater compared to the 10 μg dose (2.8 vs 0.37; respectively). The human equivalent for the highest dose organ (liver) was 198 ± 28.7 μSv/MBq. CONCLUSIONS: A CD40-immunoreactive [(64)Cu]Cu-NOTA-aCD40 probe was developed. The ratio of spleen to liver accumulation exceeded that of the IgG isotype and was greatest with a single small, injected mass. The safety of human patient imaging with [(64)Cu]Cu was established based on extrapolation of the organ specificity to human imaging.

Purpose: Cisplatin-based chemotherapy is a first-line treatment for muscle-invasive and metastatic urothelial cancer. Approximately 10% of bladder urothelial tumors have a somatic missense mutation in the nucleotide excision repair (NER) gene, ERCC2, which confers increased sensitivity to cisplatin-based chemotherapy. However, a significant subset of patients is ineligible to receive cisplatin-based therapy due to medical contraindications, and no NER-targeted approaches are available for platinum-ineligible or platinum-refractory ERCC2-mutant cases. Experimental Design: We used a series of NER-proficient and NER-deficient preclinical tumor models to test sensitivity to irofulven, an abandoned anticancer agent. In addition, we used available clinical and sequencing data from multiple urothelial tumor cohorts to develop and validate a composite mutational signature of ERCC2 deficiency and cisplatin sensitivity. Results: We identified a novel synthetic lethal relationship between tumor NER deficiency and sensitivity to irofulven. Irofulven specifically targets cells with inactivation of the transcription-coupled NER (TC-NER) pathway and leads to robust responses in vitro and in vivo, including in models with acquired cisplatin resistance, while having minimal effect on cells with intact NER. We also found that a composite mutational signature of ERCC2 deficiency was strongly associated with cisplatin response in patients and was also associated with cisplatin and irofulven sensitivity in preclinical models. Conclusions: Tumor NER deficiency confers sensitivity to irofulven, a previously abandoned anticancer agent, with minimal activity in NER-proficient cells. A composite mutational signature of NER deficiency may be useful in identifying patients likely to respond to NER-targeting agents, including cisplatin and irofulven. See related commentary by Jiang and Greenberg, p. 1833

Artificial neural networks (ANNs), implied models of the biological human brain's neuron, have now a long history as prime techniques in machine learning and computational intelligence with a wide range of applications, and are of great interest thanks to their great success. Classification is one of the most populous realms of research in ANNs with a vast and growing literature. Our innovation is to revolutionize loss function for ANNs, in accordance with a novel architecture for the last layer of the neural net (NN), that empowers them to apply dynamic thresholding while deciding the label of a sample based on its probability-of-belonging values; hence, to model complexities of the data more discriminatingly and attain better quantitative results. Although we established our approach through mathematical argument particularly for binary classification, the concept and formulation are entirely and purposefully generalizable to multiclass classification problems.

Robust cytotoxic T cell infiltration has proven to be difficult to achieve in solid tumors. We set out to develop a flexible protocol to efficiently transfect tumor and stromal cells to produce immune-activating cytokines, and thus enhance T cell infiltration while debulking tumor mass. By combining ultrasound with tumor-targeted microbubbles, membrane pores are created and facilitate a controllable and local transfection. Here, we applied a substantially lower transmission frequency (250 kHz) than applied previously. The resulting microbubble oscillation was significantly enhanced, reaching an effective expansion ratio of 35 for a peak negative pressure of 500 kPa in vitro. Combining low-frequency ultrasound with tumor-targeted microbubbles and a DNA plasmid construct, 20% of tumor cells remained viable, and ∼20% of these remaining cells were transfected with a reporter gene both in vitro and in vivo. The majority of cells transfected in vivo were mucin 1 + /CD45 − tumor cells. Tumor and stromal cells were then transfected with plasmid DNA encoding IFN-β, producing 150 pg/10 6 cells in vitro, a 150-fold increase compared to no-ultrasound or no-plasmid controls and a 50-fold increase compared to treatment with targeted microbubbles and ultrasound (without IFN-β). This enhancement in secretion exceeds previously reported fourfold to fivefold increases with other in vitro treatments. Combined with intraperitoneal administration of checkpoint inhibition, a single application of IFN-β plasmid transfection reduced tumor growth in vivo and recruited efficacious immune cells at both the local and distant tumor sites.

Plants have numerous biological, clinical, pharmaceutical and medicinal purposes for many years; however, their use as a general platform for preparation of desired pharmaceutical and biomedical is relatively current. Secondary metabolites with remarkable and diverse biological functions are produced by medicinal plants. Significant advancements in nanosciences have enabled various applications in the development of new generation of drug molecules. Due to the application of toxic solvents and high energy consumption of conventional physical and chemical approaches, greener and eco-friendly methods are essential and vital. Plants can provide an outstanding alternative for the production of phytomaterials and biomaterials, and this review highlights the exogenous and endogenous syntheses of nanoparticles using living plants. Additionally, the plant nano-molecular farming of proteins including collagen, gelatin, elastin, recombinant anti-cancer monoclonal antibodies and recombinant anti-cancer vaccines, are discussed., 0, SCOPUS: re.j, info:eu-repo/semantics/published

Two most important evaluation parameters of any stereo matching algorithm are the execution speed and the accuracy of generated results. Commonly, reported real-time works provide fast depth calculation based on highly specialized hardware. Thus, algorithmic techniques for increasing the speed which can be employed on every general hardware, are more valuable. In this paper an efficient technique has been proposed in order to improve dynamic programming (dp) based dense stereo matching. The main idea is using a fast and efficient search space reduction algorithm and successively forcing dp based matching process to operate on this reduced search space (RSS). Effective ideas have been proposed to correct RSS and emphasize on more qualified candidates in RSS to facilitate and improve matching process in this space. Experimental results on standard stereo images show significant increasing of execution speed as well as error reduction for two traditional and basic versions of dp based matching algorithms. These simultaneous improvements in both speed and accuracy, considering their usual inverse relationship in other algorithms, seems to be very valuable.

The authenticity of honey is of great importance for commercial and health reasons, because adulteration of bee honey with cheaper sweetening materials is sometimes carried out for financial gain. The objectives of this study were to evaluate clover honey quality according to physicochemical characteristics, to measure light transmission through honey samples using a visible laser technique (He-Ne laser at 632.8 nm) and to predict types of adulterants of clover honey according to the transmission intensity of the laser beam through the sample.; Results: The transmission intensity of pure clover honey was 3520 lx. Addition of water or sugar solution at various concentrations led to increased transmission intensities in the range 4720-6980 lx, while addition of glucose honey led to increased transmission intensities in the range 3570-4120 lx. However, addition of starch suspension or black honey led to decreased transmission intensities in the ranges 3440-120 and 2770-85 lx respectively. The physicochemical properties of pure clover honey were within the standard limits. The light microscope image of pollen in the honey indicated that the pollen came from the clover plant.; Conclusion: The transmission intensity method using visible laser light to predict the type of adulteration of clover honey can be considered a fast and accurate method. © 2018 Society of Chemical Industry.; © 2018 Society of Chemical Industry.

Ex vivo programming of T cells can be efficacious but is complex and expensive; therefore, the development of methods to transfect T cells in situ is important. We developed and optimized anti-CD3-targeted lipid nanoparticles (aCD3-LNPs) to deliver tightly packed, reporter gene mRNA specifically to T cells. In vitro, targeted LNPs efficiently delivered mCherry mRNA to Jurkat T cells, and T-cell activation and depletion were associated with aCD3 antibody coating on the surface of LNPs. aCD3-LNPs, but not non-targeted LNPs, accumulated within the spleen following systemic injection, with mCherry and Fluc signals visible within 30 minutes after injection. At 24 h after aCD3-LNP injection, 2-4% of all splenic T cells and 2-7% of all circulating T cells expressed mCherry, and this was dependent on aCD3 coating density. Targeting and transfection were accompanied by systemic CD25(+), OX40(+), and CD69(+) T-cell activation with temporary CD3e ligand loss and depletion of splenic and circulating subsets. Migration of splenic CD8a(+) T cells from the white-pulp to red-pulp, and differentiation from naïve to memory and effector phenotypes, followed upon aCD3-LNP delivery. Additionally, aCD3-LNP injection stimulated the secretion of myeloid-derived chemokines and T-helper cytokines into plasma. Lastly, we administered aCD3-LNPs to tumor bearing mice and found that transfected T cells localized within tumors and tumor-draining lymph nodes following immunotherapy treatment. In summary, we show that CD3-targeted transfection is feasible, yet associated with complex immunological consequences that must be further studied for potential therapeutic applications.