Conservation Value Of A Living Heritage Site On Penang Island, Malaysia

George Town is the capital of Penang Island, a town of rich and diverse history which reflect the cultures brought by the trade-winds since the 18th century. Many of the heritage buildings and the businesses or activities, that took place within them still survive until today, many of which involve skills passed down through the generations, making George Town a town with a ‘living’ heritage. The objectives of this study were to estimate the value of Penang Island households’ willingness to pay for the conservation of a living heritage in George Town, and to identify the determinants of the willingness-to-pay. This study aimed to add to the scarce literature of this type of research, and reduce the dependence on benefit transfers for cultural heritage goods, which are often sitespecific, and therefore unsuitable.The Stated Preference (SP) method of Contingent Valuation (CV) was applied in this study, concentrating on the living heritage existing within inner George Town, covering about 3,700 pre-colonial shophouses. A total of 320 in-person interviews of citizens of Penang Island were conducted in the first-quarter of 2006, out of which 283 questionnaire responses were usable. The results showed that the Contingent Valuation Method (CVM) can be successfully applied to value a living cultural heritage in Penang Island, where the mean willingness-to-pay for the conservation of inner George Town’s living heritage is about RM94.50 as a once-off contribution amount. The results showed that attitudinal aspects like interest and concern for the condition of the ‘living’ heritage play an important factor in the probability that respondents would be willing-to-pay for its conservation, together with the respondents’ level of income. Behavioural aspects like knowledge regarding the heritage, frequency of visits, and emotional regard for the heritage are not significant to the probability that the respondents would be willing to contribute towards the heritage conservation. The results of this research can be used by policy-makers and NGOs to rank the importance of conserving the ‘living’ heritage relative to competing projects, and help improve the management of heritage conservation and resource allocation

Intraspecific variation in sensitivity to ultraviolet-B radiation in endogenous hormones and photosynthetic characteristics of 10 wheat cultivars grown under field conditions

AbstractField studies were conducted to determine the potential of altering endogenous hormones and photosynthetic characteristics and intraspecific variation in sensitivity of 10 wheat (Triticum aestivum) cultivars (four tolerant, two middle sensitive and four sensitive) to enhanced ultraviolet-B (UV-B, 280–315nm) radiation under field conditions. The supplemental UV-B radiation was 5.00kJm−2, simulating a depletion of 20% stratospheric ozone. Responses were cultivar-specific. Out of the 10 tested wheat cultivars, six showed significant decrease in IAA content. UV-B radiation significantly increased ZR content in two wheat cultivars and significantly decreased in five cultivars. ABA content of three wheat cultivars was increased significantly, while that of five cultivars was decreased significantly. UV-B radiation significantly increased the stomatal conductance of three cultivars, and significantly decreased that of four cultivars. Intercellular CO2 concentrations were significantly increased in five cultivars and significantly decreased in one cultivar (Mianyang 20). Transpiration rate of three cultivars significantly increased, while that of three cultivars significantly decreased. UV-B radiation significantly decreased the net photosynthetic rate of six cultivars. Intraspecific differences were found for the different measured parameters. For seven measured parameters, UV-B radiation had significant effects on five wheat cultivars, while no effect on the others. Significant correlations were observed between net photosynthetic rate and stomatal conductance, intercellular CO2 concentrations and transpiration rate in eight cultivars. UV-B radiation might change stomatal conductance, intercellular CO2 concentrations and transpiration rate, thus resulting in changes in net photosynthetic rate

Glucocorticoid-Induced Bone Fragility Is Prevented in Female Mice by Blocking Pyk2/Anoikis Signaling

Excess of glucocorticoids (GCs) is a leading cause of bone fragility, and therapeutic targets are sorely needed. We report that genetic deletion or pharmacological inhibition of proline-rich tyrosine kinase 2 (Pyk2) prevents GC-induced bone loss by overriding GC effects of detachment-induced bone cell apoptosis (anoikis). In wild-type or vehicle-treated mice, GCs either prevented osteoclast apoptosis or promoted osteoblast/osteocyte apoptosis. In contrast, mice lacking Pyk2 [knockout (KO)] or treated with Pyk2 kinase inhibitor PF-431396 (PF) were protected. KO or PF-treated mice were also protected from GC-induced bone resorption, microarchitecture deterioration, and weakening of biomechanical properties. In KO and PF-treated mice, GC increased osteoclasts in bone and circulating tartrate-resistant acid phosphatase form 5b, an index of osteoclast number. However, bone surfaces covered by osteoclasts and circulating C-terminal telopeptides of type I collagen, an index of osteoclast function, were not increased. The mismatch between osteoclast number vs function induced by Pyk2 deficiency/inhibition was due to osteoclast detachment and anoikis. Further, GC prolongation of osteoclast lifespan was absent in KO and PF-treated osteoclasts, demonstrating Pyk2 as an intrinsic osteoclast-survival regulator. Circumventing Pyk2 activation preserves skeletal integrity by preventing GC effects on bone cell survival (proapoptotic for osteoblasts/osteocytes, antiapoptotic for osteoclasts) and GC-induced bone resorption. Thus, Pyk2/anoikis signaling as a therapeutic target for GC-induced osteoporosis

Patient Priorities-Aligned Care For Older adults With Multiple Conditions: a Nonrandomized Controlled Trial

IMPORTANCE: Older adults with multiple conditions receive health care that may be burdensome, of uncertain benefit, and not focused on what matters to them. Identifying and aligning care with patients\u27 health priorities may improve outcomes. OBJECTIVE: to assess the association of receiving patient priorities care (PPC) vs usual care (UC) with relevant clinical outcomes. DESIGN, SETTING, AND PARTICIPANTS: In this nonrandomized controlled trial with propensity adjustment, enrollment occurred between August 21, 2020, and May 14, 2021, with follow-up continuing through February 26, 2022. Patients who were aged 65 years or older and with 3 or more chronic conditions were enrolled at 1 PPC and 1 UC site within the Cleveland Clinic primary care multisite practice. Data analysis was performed from March 2022 to August 2023. INTERVENTION: Health professionals at the PPC site guided patients through identification of values, health outcome goals, health care preferences, and top priority (ie, health problem they most wanted to focus on because it impeded their health outcome goal). Primary clinicians followed PPC decisional strategies (eg, use patients\u27 health priorities as focus of communication and decision-making) to decide with patients what care to stop, start, or continue. MAIN OUTCOMES AND MEASURES: Main outcomes included perceived treatment burden, Patient-Reported Outcomes Measurement Information System (PROMIS) social roles and activities, CollaboRATE survey scores, the number of nonhealthy days (based on healthy days at home), and shared prescribing decision quality measures. Follow-up was at 9 months for patient-reported outcomes and 365 days for nonhealthy days. RESULTS: A total of 264 individuals participated, 129 in the PPC group (mean [SD] age, 75.3 [6.1] years; 66 women [48.9%]) and 135 in the UC group (mean [SD] age, 75.6 [6.5] years; 55 women [42.6%]). Characteristics between sites were balanced after propensity score weighting. At follow-up, there was no statistically significant difference in perceived treatment burden score between groups in multivariate models (difference, -5.2 points; 95% CI, -10.9 to -0.50 points; P = .07). PPC participants were almost 2.5 times more likely than UC participants to endorse shared prescribing decision-making (adjusted odds ratio, 2.40; 95% CI, 0.90 to 6.40; P = .07), and participants in the PPC group experienced 4.6 fewer nonhealthy days (95% CI, -12.9 to -3.6 days; P = .27) compared with the UC participants. These differences were not statistically significant. CollaboRATE and PROMIS Social Roles and Activities scores were similar in the 2 groups at follow-up. CONCLUSIONS AND RELEVANCE: This nonrandomized trial of priorities-aligned care showed no benefit for social roles or CollaboRATE. While the findings for perceived treatment burden and shared prescribing decision-making were not statistically significant, point estimates for the findings suggested that PPC may hold promise for improving these outcomes. Randomized trials with larger samples are needed to determine the effectiveness of priorities-aligned care. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04510948

Deletion of tumor necrosis factor death receptor inhibits amyloid β generation and prevents learning and memory deficits in Alzheimer's mice

The tumor necrosis factor type 1 death receptor (TNFR1) contributes to apoptosis. TNFR1, a subgroup of the TNFR superfamily, contains a cytoplasmic death domain. We recently demonstrated that the TNFR1 cascade is required for amyloid β protein (Aβ)–induced neuronal death. However, the function of TNFR1 in Aβ plaque pathology and amyloid precursor protein (APP) processing in Alzheimer's disease (AD) remains unclear. We report that the deletion of the TNFR1 gene in APP23 transgenic mice (APP23/TNFR1−/−) inhibits Aβ generation and diminishes Aβ plaque formation in the brain. Genetic deletion of TNFR1 leads to reduced β-secretase 1 (BACE1) levels and activity. TNFR1 regulates BACE1 promoter activity via the nuclear factor-κB pathway, and the deletion of TNFR1 in APP23 transgenic mice prevents learning and memory deficits. These findings suggest that TNFR1 not only contributes to neurodegeneration but also that it is involved in APP processing and Aβ plaque formation. Thus, TNFR1 is a novel therapeutic target for AD

Complete genome sequence of biocontrol strain Bacillus velezensis YC89 and its biocontrol potential against sugarcane red rot

IntroductionSugarcane is one of the most important sugar crops worldwide, however, sugarcane production is seriously limited by sugarcane red rot, a soil-borne disease caused by Colletotrichum falcatum. Bacillus velezensis YC89 was isolated from sugarcane leaves and can significantly inhibited red rot disease caused by C. falcatum.MethodsIn this study, the genome of YC89 strain was sequenced, its genome structure and function were analyzed using various bioinformatics software, and its genome was compared with those of other homologous strains. In addition, the effectiveness of YC89 against sugarcane red rot and the evaluation of sugarcane plant growth promotion were also investigated by pot experiments.ResultsHere, we present the complete genome sequence of YC89, which consists of a 3.95 Mb circular chromosome with an average GC content of 46.62%. The phylogenetic tree indicated that YC89 is closely related to B. velezensis GS-1. Comparative genome analysis of YC89 with other published strains (B. velezensis FZB42, B. velezensis CC09, B. velezensis SQR9, B. velezensis GS-1, and B. amyloliquefaciens DSM7) revealed that the strains had a part common coding sequences (CDS) in whereas 42 coding were unique of strain YC89. Whole-genome sequencing revealed 547 carbohydrate-active enzymes and identified 12 gene clusters encoding secondary metabolites. Additionally, functional analysis of the genome revealed numerous gene/gene clusters involved in plant growth promotion, antibiotic resistance, and resistance inducer synthesis. In vitro pot tests indicated that YC89 strain controlled sugarcane red rot and promoted the growth of sugarcane plants. Additionally, it increased the activity of enzymes involved in plant defense, such as superoxide dismutase, peroxidase, polyphenol oxidase, chitinase, and β-1,3-glucanase.DiscussionThese findings will be helpful for further studies on the mechanisms of plant growth promotion and biocontrol by B. velezensis and provide an effective strategy for controlling red rot in sugarcane plants

Copper-containing mesoporous bioactive glass promotes angiogenesis in an in vivo zebrafish model

The osteogenic and angiogenic responses of organisms to the ionic products of degradation of bioactive glasses (BGs) are being intensively investigated. The promotion of angiogenesis by copper (Cu) has been known for more than three decades. This element can be incorporated to delivery carriers, such as BGs, and the materials used in biological assays. In this work, Cu-containing mesoporous bioactive glass (MBG) in the SiO2-CaO-P2O5 compositional system was prepared incorporating 5% mol Cu (MBG-5Cu) by replacement of the corresponding amount of Ca. The biological effects of the ionic products of MBG biodegradation were evaluated on a well-known endothelial cell line, the bovine aorta endothelial cells (BAEC), as well as in an in vivo zebrafish (Danio rerio) embryo assay. The results suggest that ionic products of both MBG (Cu free) and MBG-5Cu materials promote angiogenesis. In vitro cell cultures show that the ionic dissolution products of these materials are not toxic and promote BAEC viability and migration. In addition, the in vivo assay indicates that both exposition and microinjection of zebrafish embryos with Cu free MBG material increase vessel number and thickness of the subintestinal venous plexus (SIVP), whereas assays using MBG-5Cu enhance this effect.The authors gratefully acknowledge the financial support provided by the Andalusian Ministry of Economy, Science and Innovation (Proyectos Excelencia Grants no. P10-CTS-6681 and no. P12-CTS-1507) and Spanish Ministry of Economy and Competitivity (BIO2014-56092-R). LBRS acknowledges the CONACYT-Mexico Fellowship PhD Program

Optimization of Transcutaneous Oxygenation Wearable Sensors for Clinical Applications

In this manuscript, the development of an experimental and mathematical toolset is reported that allows for improved in vivo measurements of optical transcutaneous oxygen tension measurements (TCOM) wearable technology in humans. In addition to optimizing O2-sensing films for higher sensitivity oxygen detection, calibration algorithms are additionally developed to account for excitation source leakage, as well as algorithms to combine readings of partial pressure of oxygen (pO2), derived from phosphorescence intensity and lifetime, into a single metric. This new iteration of the TCOM wearable device is then tested in a pilot human study. By implementing characterization and calibration algorithms, the data from the pilot study demonstrates the ability to obtain reliable transcutaneous pO2 readings with a TCOM sensor regardless of size and without the need for strict conditions of constant temperature, humidity, or motion that have limited the range of applications of this technology in the past

The use of global transcriptional analysis to reveal the biological and cellular events involved in distinct development phases of Trichophyton rubrum conidial germination

<p>Abstract</p> <p>Background</p> <p>Conidia are considered to be the primary cause of infections by <it>Trichophyton rubrum</it>.</p> <p>Results</p> <p>We have developed a cDNA microarray containing 10250 ESTs to monitor the transcriptional strategy of conidial germination. A total of 1561 genes that had their expression levels specially altered in the process were obtained and hierarchically clustered with respect to their expression profiles. By functional analysis, we provided a global view of an important biological system related to conidial germination, including characterization of the pattern of gene expression at sequential developmental phases, and changes of gene expression profiles corresponding to morphological transitions. We matched the EST sequences to GO terms in the <it>Saccharomyces </it>Genome Database (SGD). A number of homologues of <it>Saccharomyces cerevisiae </it>genes related to signalling pathways and some important cellular processes were found to be involved in <it>T. rubrum </it>germination. These genes and signalling pathways may play roles in distinct steps, such as activating conidial germination, maintenance of isotropic growth, establishment of cell polarity and morphological transitions.</p> <p>Conclusion</p> <p>Our results may provide insights into molecular mechanisms of conidial germination at the cell level, and may enhance our understanding of regulation of gene expression related to the morphological construction of <it>T. rubrum</it>.</p

Visually-Aware Audio Captioning With Adaptive Audio-Visual Attention

Audio captioning aims to generate text descriptions of audio clips. In the real world, many objects produce similar sounds. How to accurately recognize ambiguous sounds is a major challenge for audio captioning. In this work, inspired by inherent human multimodal perception, we propose visually-aware audio captioning, which makes use of visual information to help the description of ambiguous sounding objects. Specifically, we introduce an off-the-shelf visual encoder to extract video features and incorporate the visual features into an audio captioning system. Furthermore, to better exploit complementary audio-visual contexts, we propose an audio-visual attention mechanism that adaptively integrates audio and visual context and removes the redundant information in the latent space. Experimental results on AudioCaps, the largest audio captioning dataset, show that our proposed method achieves state-of-the-art results on machine translation metrics.Comment: INTERSPEECH 202