Contribution of microreactor technology and flow chemistry to the development of green and sustainable synthesis

Microreactor technology and flow chemistry could play an important role in the development of green and sustainable synthetic processes. In this review, some recent relevant examples in the field of flash chemistry, catalysis, hazardous chemistry and continuous flow processing are described. Selected examples highlight the role that flow chemistry could play in the near future for a sustainable development

Shape annotation for intelligent image retrieval

Annotation of shapes is an important process for semantic image retrieval. In this paper, we present a shape annotation framework that enables intelligent image retrieval by exploiting in a unified manner domain knowledge and perceptual description of shapes. A semi-supervised fuzzy clustering process is used to derive domain knowledge in terms of linguistic concepts referring to the semantic categories of shapes. For each category we derive a prototype that is a visual template for the category. A novel visual ontology is proposed to provide a description of prototypes and their salient parts. To describe parts of prototypes the visual ontology includes perceptual attributes that are defined by mimicking the analogy mechanism adopted by humans to describe the appearance of objects. The effectiveness of the developed framework as a facility for intelligent image retrieval is shown through results on a case study in the domain of fish shapes

KERNEL: A Matlab Toolbox for Knowledge Extraction and Refinement by NEural Learning

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Evaluation of the Acceleration and Deceleration Phase-Rectified Slope to Detect and Improve IUGR Clinical Management

Objective. This study used a new method called Acceleration (or Deceleration) Phase-Rectified Slope, APRS (or DPRS) to analyze computerized Cardiotocographic (cCTG) traces in intrauterine growth restriction (IUGR), in order to calculate acceleration- and deceleration-related fluctuations of the fetal heart rate, and to enhance the prediction of neonatal outcome. Method. Cardiotocograms from a population of 59 healthy and 61 IUGR fetuses from the 30th gestation week matched for gestational age were included. APRS and DPRS analysis was compared to the standard linear and nonlinear cCTG parameters. Statistical analysis was performed through the -test, ANOVA test, Pearson correlation test and receiver operator characteristic (ROC) curves (). Results. APRS and DPRS showed high performance to discriminate between Healthy and IUGR fetuses, according to gestational week. A linear correlation with the fetal pH at birth was found in IUGR. The area under the ROC curve was 0.865 for APRS and 0.900 for DPRS before the 34th gestation week. Conclusions. APRS and DPRS could be useful in the identification and management of IUGR fetuses and in the prediction of the neonatal outcome, especially before the 34th week of gestation

Regulatory T Cell-Derived Exosomes: Possible Therapeutic and Diagnostic Tools in Transplantation

Exosomes are extracellular vesicles released by many cells of the body. These small vesicles play an important part in intercellular communication both in the local environment and systemically, facilitating in the transfer of proteins, cytokines as well as miRNA between cells. The observation that exosomes isolated from immune cells such as dendritic cells (DCs) modulate the immune response has paved the way for these structures to be considered as potential immunotherapeutic reagents. Indeed, clinical trials using DC derived exosomes to facilitate immune responses to specific cancer antigens are now underway. Exosomes can also have a negative effect on the immune response and exosomes isolated from regulatory T cells (Tregs) and other subsets of T cells have been shown to have immune suppressive capacities. Here, we review what is currently known about Treg derived exosomes and their contribution to immune regulation, as well as highlighting their possible therapeutic potential for preventing graft rejection, and use as diagnostic tools to assess transplant outcome

Mesenchymal stem cells inhibit T-cell function through conserved induction of cellular stress

The physiological role of mesenchymal stem cells (MSCs) is to provide a source of cells to replace mesenchymal-derivatives in stromal tissues with high cell turnover or following stromal tissue damage to elicit repair. Human MSCs have been shown to suppress in vitro T-cell responses via a number of mechanisms including indoleamine 2,3-dioxygenase (IDO). This immunomodulatory capacity is likely to be related to their in vivo function in tissue repair where local, transient suppression of immune responses would benefit differentiation. Further understanding of the impact of locally modulated immune responses by MSCs is hampered by evidence that IDO is not produced or utilized by mouse MSCs. In this study, we demonstrate that IDO-mediated tryptophan starvation triggered by human MSCs inhibits T-cell activation and proliferation through induction of cellular stress. Significantly, we show that despite utilizing different means, immunomodulation of murine T-cells also involves cellular stress and thus is a common strategy of immunoregulation conserved between mouse and humans.</div

High incidence of severe cyclosporine neurotoxicity in children affected by haemoglobinopaties undergoing myeloablative haematopoietic stem cell transplantation: early diagnosis and prompt intervention ameliorates neurological outcome

<p>Abstract</p> <p>Background</p> <p>Neurotoxicity is a recognized complication of cyclosporine A (CSA) treatment. The incidence of severe CSA-related neurological complications following hematopoietic stem cell transplantation (HSCT) is 4-11%.</p> <p>Methods</p> <p>We describe 6 cases of CSA related neurotoxicity out of 67 matched related HSCT performed in paediatric Middle East patients affected by haemoglobinopaties (5 beta thalassemia major, 1 sickle cell disease-SCD). Conditioning regimen consisted of iv busulphan, cyclophosphamide and graft-versus-host-disease (GvHD) prophylaxis with CSA, methylprednisolone, methotrexate and ATG.</p> <p>Results</p> <p>All 6 patients presented prodromes such as arterial hypertension, headache, visual disturbances and vomiting, one to two days before overt CSA neurotoxicity. CSA neurotoxicity consisted of generalized seizures, signs of endocranial hypertension and visual disturbances at a median day of onset of 11 days after HSCT (range +1 to +40). Brain magnetic resonance imaging (MRI) performed in all subjects showed reversible leukoencephalopathy predominantly in the posterior regions of the brain (PRES) in 5/6 patients. EEG performed in 5/6 patients was always abnormal. Neurotoxicity was not explainable by high CSA blood levels, as all patients had CSA in the therapeutic range with a median of 178 ng/ml (range 69-250). CSA was promptly stopped and switched to tacrolimus with disappearance of clinical and radiological findings. All patients are symptoms-free at a median follow up of 882 days (range 60-1065).</p> <p>Conclusions</p> <p>Our experience suggests that paediatric patients with haemoglobinopaties have a high incidence of CSA related neurological events with no correlation between serum CSA levels and neurotoxicity. Prognosis is good following CSA removal. Specific prodromes such as arterial hypertension, headache or visual disturbances occurring in the early post-transplant period should be carefully evaluated with electrophysiological and MRI-based imaging in order to intervene promptly and avoid irreversible sequels.</p

Pluripotent Stem Cell-Derived Hepatocytes Inhibit T Cell Proliferation In Vitro through Tryptophan Starvation.

Regenerative medicine aims to replace damaged tissues by stimulating endogenous tissue repair or by transplanting autologous or allogeneic cells. Due to their capacity to produce unlimited numbers of cells of a given cell type, pluripotent stem cells, whether of embryonic origin or induced via the reprogramming of somatic cells, are of considerable therapeutic interest in the regenerative medicine field. However, regardless of the cell type, host immune responses present a barrier to success. The aim of this study was to investigate in vitro the immunological properties of human pluripotent stem cell (PSC)-derived hepatocyte-like cells (HLCs). These cells expressed MHC class I molecules while they lacked MHC class II and co-stimulatory molecules, such as CD80 and CD86. Following stimulation with IFN-γ, HLCs upregulated CD40, PD-L1 and MHC class I molecules. When co-cultured with allogeneic T cells, HLCs did not induce T cell proliferation; furthermore, when T cells were stimulated via αCD3/CD28 beads, HLCs inhibited their proliferation via IDO1 and tryptophan deprivation. These results demonstrate that PSC-derived HLCs possess immunoregulatory functions, at least in vitro

A new method for measuring and calibrating cinema audio systems for optimal sound quality

The aim of this research is to utilize new methodologies and technology in order to gain insight into how the modern cinema audio system could be calibrated to provide improved audio performance. To this end, both objective and subjective measurements were developed to better understand the audio preferences of listeners, the requirements of the audio systems inclusive of the acoustic environment, and how the two are related. Part of the data for this research was derived from a survey of re-recording mixers regarding their use and opinion of the current SMPTE standard. The survey confirmed anecdotal information suggesting that re-recording mixers use high-end pre-emphasis to compensate for the severe roll-off induced by the SMPTE X-curve. It is also noted that the re-recording mixers' opinions of how well their mix translates from dub-stage to cinema is correlated to how many years they have spent in the industry. The aim of this research is to utilize new methodologies and technology in order to gain insight into how the modern cinema audio system could be calibrated to provide improved audio performance. To this end, both objective and subjective measurements were developed to better understand the audio preferences of listeners, the requirements of the audio systems inclusive of the acoustic environment, and how the two are related. Part of the data for this research was derived from a survey of re-recording mixers regarding their use and opinion of the current SMPTE standard. The survey confirmed anecdotal information suggesting that re-recording mixers use high-end pre-emphasis to compensate for the severe roll-off induced by the SMPTE X-curve. It is also noted that the re-recording mixers' opinions of how well their mix translates from dub-stage to cinema is correlated to how many years they have spent in the industry. To further understand listener preference to in-room responses curves, a series of listening tests utilizing the BRS system were conducted using various sized cinemas, seating positions within the cinemas, audio tracks (including those mixed on a SMPTE calibrated dub-stage) and target curves. The overwhelming outcome was that regardless of cinema size, seating position or audio track utilized; the "curve" that listeners preferred is a relatively flat 0.9dB/octave slope with a 6.5dB bass boost below 105Hz and a -2.5dB roll off above 2.5kHz. Of the 5 target curves presented, the SMPTE X-curve place fourth with scores very near the low-rated perceptual anchor. This calls into question the notion of the X-curve providing "ideal" translation between dub-stage and cinema and in fact, challenges the concept of translation all together. Research was completed in an effort to identifying the number of microphone positions required, along with their placement, in order to accurately capture a cinema's response for calibration purposes. A novel experiment utilizing anechoic loudspeaker data as a guideline for xxi analysis demonstrated that, with proper data, the number of microphones and their positions plays a less critical factor in determining the room response. The collected data shows that even with as few as 4 microphones at varied positions, the resultant room response will trend towards the anechoic data above 1kHz. From around 300Hz to 1kHz, there is evidence of seat effects that may be resolved through randomizing the microphone heights. Below 300Hz, the room becomes the dominating factor and more than 5 microphone positions will be required to properly identify any problems

The U-shaped relationship between parental age and the risk of bipolar disorder in the offspring: A systematic review and meta-analysis

Parenthood age may affect the risk for the development of different psychiatric disorders in the offspring, including bipolar disorder (BD). The present systematic review and meta-analysis aimed to appraise the relationship between paternal age and risk for BD and to explore the eventual relationship between paternal age and age at onset of BD. We searched the MEDLINE, Scopus, Embase, PsycINFO online databases for original studies from inception, up to December 2021. Random-effects meta-analyses were conducted. Sixteen studies participated in the qualitative synthesis, of which k = 14 fetched quantitative data encompassing a total of 13,424,760 participants and 217,089 individuals with BD. Both fathers [adjusted for the age of other parent and socioeconomic status odd ratio - OR = 1.29(95%C.I. = 1.13-1.48)] and mothers aged ≤ 20 years [(OR = 1.23(95%C.I. = 1.14-1.33)] had consistently increased odds of BD diagnosis in their offspring compared to parents aged 25-29 years. Fathers aged ≥ 45 years [adjusted OR = 1.29 (95%C.I. = 1.15-1.46)] and mothers aged 35-39 years [OR = 1.10(95%C.I. = 1.01-1.19)] and 40 years or older [OR = 1.2(95% C.I. = 1.02-1.40)] likewise had inflated odds of BD diagnosis in their offspring compared to parents aged 25-29 years. Early and delayed parenthood are associated with an increased risk of BD in the offspring. Mechanisms underlying this association are largely unknown and may involve a complex interplay between psychosocial, genetic and biological factors, and with different impacts according to sex and age range. Evidence on the association between parental age and illness onset is still tentative but it points towards a possible specific effect of advanced paternal age on early BD-onset