Development and proof-testing of advanced absorption refrigeration cycle concepts. Report on Phases 1 and 1A

The overall objectives of this project are to evaluate, develop, and proof-test advanced absorption refrigeration cycles that are applicable to residential and commercial heat pumps for space conditioning. The heat pump system is to be direct-fired with natural gas and is to use absorption working fluids whose properties are known. Target coefficients of performance (COPs) are 1.6 at 47{degrees}F and 1.2 at 17{degrees} in the heating mode, and 0.7 at 95{degree}F in the cooling mode, including the effect of flue losses. The project is divided into three phases. Phase I entailed the analytical evaluation of advanced cycles and included the selection of preferred concepts for further development. Phase II involves the development and testing of critical components and of a complete laboratory breadboard version of the selected system. Phase III calls for the development of a prototype unit and is contingent on the successful completion of Phase II. This report covers Phase I work on the project. In Phase 1, 24 advanced absorption cycle/fluid combinations were evaluated, and computer models were developed to predict system performance. COP, theoretical pump power, and internal heat exchange were calculated for each system, and these calculations were used as indicators of operating and installed costs in order to rank the relative promise of each system. The highest ranking systems involve the cycle concept of absorber/generator heat exchange, generator heat exchanger/absorber heat exchange, regeneration, and resorption/desorption, in combination with the NH{sub 3}/H{sub 2}O/LiBr ternary absorption fluid mixture or with the NH{sub 3}/H{sub 2}O binary solution. Based upon these conclusions, the recommendation was made to proceed to Phase II, the laboratory breadboard proof-of- concept

Development and proof-testing of advanced absorption refrigeration cycle concepts

The overall objectives of this project are to evaluate, develop, and proof-test advanced absorption refrigeration cycles that are applicable to residential and commercial heat pumps for space conditioning. The heat pump system is to be direct-fired with natural gas and is to use absorption working fluids whose properties are known. Target coefficients of performance (COPs) are 1.6 at 47{degrees}F and 1.2 at 17{degrees} in the heating mode, and 0.7 at 95{degree}F in the cooling mode, including the effect of flue losses. The project is divided into three phases. Phase I entailed the analytical evaluation of advanced cycles and included the selection of preferred concepts for further development. Phase II involves the development and testing of critical components and of a complete laboratory breadboard version of the selected system. Phase III calls for the development of a prototype unit and is contingent on the successful completion of Phase II. This report covers Phase I work on the project. In Phase 1, 24 advanced absorption cycle/fluid combinations were evaluated, and computer models were developed to predict system performance. COP, theoretical pump power, and internal heat exchange were calculated for each system, and these calculations were used as indicators of operating and installed costs in order to rank the relative promise of each system. The highest ranking systems involve the cycle concept of absorber/generator heat exchange, generator heat exchanger/absorber heat exchange, regeneration, and resorption/desorption, in combination with the NH{sub 3}/H{sub 2}O/LiBr ternary absorption fluid mixture or with the NH{sub 3}/H{sub 2}O binary solution. Based upon these conclusions, the recommendation was made to proceed to Phase II, the laboratory breadboard proof-of- concept

Alterations of prolyl endopeptidase activity in the plasma of children with autistic spectrum disorders

BACKGROUND: Prolyl Endopeptidase (PEP, EC 3.4.21.26), a cytosolic endopeptidase, hydrolyses peptide bonds on the carboxyl side of proline residue in proteins with a relatively small molecular weight. It has been shown that altered PEP activity is associated with various psychological diseases such as schizophrenia, mania and depression. Autistic Spectrum Disorders (ASD) are neuropsychiatric and behavioural syndromes affecting social behaviours and communication development. They are classified as developmental disorders. The aim of this study was to examine the hypothesis that PEP activity is also associated with ASDs. METHODS: Fluorometric assay was used to measure PEP activity in EDTA plasma in children with ASD (n = 18) aged 4–12 years (mean ± SD: 7.9 ± 2.5). These results were then compared to PEP activity in a control group of non-ASD children (n = 15) aged 2–10 years (mean ± SD: 6.4 ± 2.2). RESULTS: An alteration in PEP activity was found in the children with ASD compared to the control group. There was much greater variation of PEP activity in the group of ASD children when compared to the controls (SD= 39.9 and SD 9.6, respectively). This variation was significant (p < 0.0005), although the mean level of PEP activity in the group of ASD children was slightly higher than in the control group (124.4 and 134.1, respectively). CONCLUSION: Our preliminary finding suggests a role for PEP enzyme in the pathophysiology of autism but further research should be conducted to establish its role in the aetiology of psychiatric and neurological disorders, including autism and related spectrum disorders

Midgut transcriptomic responses to dengue and chikungunya viruses in the vectors Aedes albopictus and Aedes malayensis

Dengue (DENV) and chikungunya (CHIKV) viruses are among the most preponderant arboviruses. Although primarily transmitted through the bite of Aedes aegypti mosquitoes, Aedes albopictus and Aedes malayensis are competent vectors and have an impact on arbovirus epidemiology. Here, to fill the gap in our understanding of the molecular interactions between secondary vectors and arboviruses, we used transcriptomics to profile the whole-genome responses of A. albopictus to CHIKV and of A. malayensis to CHIKV and DENV at 1 and 4 days post-infection (dpi) in midguts. In A. albopictus, 1793 and 339 genes were significantly regulated by CHIKV at 1 and 4 dpi, respectively. In A. malayensis, 943 and 222 genes upon CHIKV infection, and 74 and 69 genes upon DENV infection were significantly regulated at 1 and 4 dpi, respectively. We reported 81 genes that were consistently differentially regulated in all the CHIKV-infected conditions, identifying a CHIKV-induced signature. We identified expressed immune genes in both mosquito species, using a de novo assembled midgut transcriptome for A. malayensis, and described the immune architectures. We found the JNK pathway activated in all conditions, generalizing its antiviral function to Aedines. Our comprehensive study provides insight into arbovirus transmission by multiple Aedes vectors

A case of autism with an interstitial deletion on 4q leading to hemizygosity for genes encoding for glutamine and glycine neurotransmitter receptor sub-units (AMPA 2, GLRA3, GLRB) and neuropeptide receptors NPY1R, NPY5R

BACKGROUND: Autism is a pervasive developmental disorder characterized by a triad of deficits: qualitative impairments in social interactions, communication deficits, and repetitive and stereotyped patterns of behavior. Although autism is etiologically heterogeneous, family and twin studies have established a definite genetic basis. The inheritance of idiopathic autism is presumed to be complex, with many genes involved; environmental factors are also possibly contributory. The analysis of chromosome abnormalities associated with autism contributes greatly to the identification of autism candidate genes. CASE PRESENTATION: We describe a child with autistic disorder and an interstitial deletion on chromosome 4q. This child first presented at 12 months of age with developmental delay and minor dysmorphic features. At 4 years of age a diagnosis of Pervasive Developmental Disorder was made. At 11 years of age he met diagnostic criteria for autism. Cytogenetic studies revealed a chromosome 4q deletion. The karyotype was 46, XY del 4 (q31.3-q33). Here we report the clinical phenotype of the child and the molecular characterization of the deletion using molecular cytogenetic techniques and analysis of polymorphic markers. These studies revealed a 19 megabase deletion spanning 4q32 to 4q34. Analysis of existing polymorphic markers and new markers developed in this study revealed that the deletion arose on a paternally derived chromosome. To date 33 genes of known or inferred function are deleted as a consequence of the deletion. Among these are the AMPA 2 gene that encodes the glutamate receptor GluR2 sub-unit, GLRA3 and GLRB genes that encode glycine receptor subunits and neuropeptide Y receptor genes NPY1R and NPY5R. CONCLUSIONS: The deletion in this autistic subject serves to highlight specific autism candidate genes. He is hemizygous for AMPA 2, GLRA3, GLRB, NPY1R and NPY5R. GluR2 is the major determinant of AMPA receptor structure. Glutamate receptors maintain structural and functional plasticity of synapses. Neuropeptide Y and its receptors NPY1R and NPY5R play a role in hippocampal learning and memory. Glycine receptors are expressed in very early cortical development. Molecular cytogenetic studies and DNA sequence analysis in other patients with autism will be necessary to confirm that these genes are involved in autism

Brief Report: Theatre as Therapy for Children with Autism Spectrum Disorder

The pilot investigation evaluated a theatrical intervention program, Social Emotional NeuroScience Endocrinology (SENSE) Theatre, designed to improve socioemotional functioning and reduce stress in children with autism spectrum disorder (ASD). Eight children with ASD were paired with typically developing peers that served as expert models. Neuropsychological, biological (cortisol and oxytocin), and behavioral measures were assessed in a pretest–posttest design. The intervention was embedded in a full musical theatrical production. Participants showed some improvement in face identification and theory of mind skills. The intervention shows potential promise in improving the socioemotional functioning in children with ASD through the utilization of peers, video and behavioral modeling, and a community-based theatrical setting

ASSESSING TARGET SPECIFICITY OF THE SMALL MOLECULE INHIBITOR MARIMASTAT TO SNAKE VENOM TOXINS: A NOVEL APPLICATION OF THERMAL PROTEOME PROFILING

New treatments that circumvent the pitfalls of traditional antivenom therapies are critical to address the problem of snakebite globally. Numerous snake venom toxin inhibitors have shown promising cross-species neutralization of medically significant venom toxins in vivo and in vitro. The development of high-throughput approaches for the screening of such inhibitors could accelerate their identification, testing, and implementation, and thus holds exciting potential for improving the treatments and outcomes of snakebite envenomation worldwide. Energetics-based proteomic approaches, including Thermal Proteome Profiling (TPP) and Proteome Integral Solubility Alteration (PISA) assays, represent “deep proteomics” methods for high throughput, proteome-wide identification of drug targets and ligands. In the following study, we apply TPP and PISA methods to characterize the interactions between venom toxin proteoforms in Crotalus atrox (Western Diamondback Rattlesnake) and the snake venom metalloprotease (SVMP) inhibitor marimastat. We investigate its venom proteome-wide effects and characterize its interactions with specific SVMP proteoforms, as well as its potential targeting of non-SVMP venom toxin families. We also compare the performance of PISA thermal window and soluble supernatant with insoluble precipitate using two inhibitor concentrations, providing the first demonstration of the utility of a sensitive high-throughput PISA-based approach to assess the direct targets of small molecule inhibitors for snake venom

Dermonecrosis caused by a spitting cobra snakebite results from toxin potentiation and is prevented by the repurposed drug varespladib

Snakebite envenoming is a neglected tropical disease that causes substantial mortality and morbidity globally. The venom of African spitting cobras often causes permanent injury via tissue-destructive dermonecrosis at the bite site, which is ineffectively treated by current antivenoms. To address this therapeutic gap, we identified the aetiological venom toxins in Naja nigricollis venom responsible for causing local dermonecrosis. While cytotoxic three-finger toxins were primarily responsible for causing spitting cobra cytotoxicity in cultured keratinocytes, their potentiation by phospholipases A2 toxins was essential to cause dermonecrosis in vivo. This evidence of probable toxin synergism suggests that a single toxin-family inhibiting drug could prevent local envenoming. We show that local injection with the repurposed phospholipase A2-inhibiting drug varespladib significantly prevents local tissue damage caused by several spitting cobra venoms in murine models of envenoming. Our findings therefore provide a new therapeutic strategy to more effectively prevent life-changing morbidity caused by snakebite in rural Africa

A novel blood-based biomarker for detection of autism spectrum disorders

Autism spectrum disorders (ASD) are classified as neurological developmental disorders. Several studies have been carried out to find a candidate biomarker linked to the development of these disorders, but up to date no reliable biomarker is available. Mass spectrometry techniques have been used for protein profiling of blood plasma of children with such disorders in order to identify proteins/peptides that may be used as biomarkers for detection of the disorders. Three differentially expressed peptides with mass–charge (m/z) values of 2020±1, 1864±1 and 1978±1 Da in the heparin plasma of children with ASD that were significantly changed as compared with the peptide pattern of the non-ASD control group are reported here. This novel set of biomarkers allows for a reliable blood-based diagnostic tool that may be used in diagnosis and potentially, in prognosis of ASD

Oxytocin attenuates feelings of hostility depending on emotional context and individuals' characteristics

In humans, oxytocin (OT) enhances prosocial behaviour. However, it is still unclear how the prosocial effects of OT are modulated by emotional features and/or individuals' characteristics. In a placebo-controlled design, we tested 20 healthy male volunteers to investigate these behavioural and neurophysiological modulations using magnetoencephalography. As an index of the individuals' characteristics, we used the empathy quotient (EQ), the autism spectrum quotient (AQ), and the systemising quotient (SQ). Only during the perception of another person's angry face was a higher SQ a significant predictor of OT-induced prosocial change, both in the behavioural and neurophysiological indicators. In addition, a lower EQ was only a significant predictor of OT-induced prosocial changes in the neurophysiological indicators during the perception of angry faces. Both on the behavioural and the neurophysiological level, the effects of OT were specific for anger and correlated with a higher SQ