•GNSS is used to infer the mean annual water-thickness change of 0.53 m in Taiwan.•Consistent spatio-temporal change of water cycle in geodetic and hydrological data.•Phase shifts among data sets ...reflect the complex nature of transient water storage.•Water storage variation is affected by infiltration rate, capacity, and landscape.
We systematically investigate the spatiotemporal water storage changes in Taiwan using geodetic (GNSS and GRACE) and hydrological (precipitation, GLDAS and LSDM assimilation models, and in-situ groundwater level) datasets. We use GNSS-observed vertical deformation to estimate water storage changes based on elastic loading theory and weighted least-squares inversion, correcting for contributions from global loads using GRACE. The mean annual water-thickness change inferred from GNSS across Taiwan is 0.53 ± 0.17 m and the largest seasonal change of up to 0.91 m is estimated in southwest Taiwan. Comparison of the geodetic and hydrological data shows that the spatial pattern of annual water storage change estimated from GNSS, GLDAS, and precipitation data are generally consistent, indicating significant seasonal water-load fluctuations in Taiwan. However, the GRACE solution significantly underestimates the amplitude of water mass change in Taiwan due to leakage effect, but temporally correlates well with GNSS estimates. Hydrological assimilation model GLDAS, dominated by shallow soil moisture variations, predicts that the average seasonal variation of water thickness is only about 17% of GNSS estimates. This value is about half of the mean annual LSDM water storage change of 0.18 m including an estimate of both soil moisture and surface water. The discrepancy suggests that the contribution of groundwater is substantial and the total water storage change in the hydrological assimilation model is underestimated in Taiwan. The spatiotemporal distributions derived using independent component analysis (ICA) are generally consistent between the geodetic and hydrological data. However, comparisons of seasonal amplitudes and phases between all data pairs reveal different response times to precipitation, reflecting the complex nature of transient water storage due to variable rainfall patterns, infiltration rate, soil saturation, and runoff. The peak rainfall occurs in June-July, which is one-to-two months before the peak GNSS subsidence. Water storage of the GLDAS model also reaches its maximum in August, suggesting the water storage is controlled by the infiltration rate and capacity and the total water recharge from rainfall is generally larger than discharge in the summer. The highest groundwater levels lag one and two months behind the peak GNSS subsidence in western and eastern Taiwan, respectively, indicating a higher infiltration rate in western Taiwan.
•Expository study on adversarial attacks and possible countermeasures for deep speaker recognition systems.•White box attacks: FGSM, PGD, Carlini and Wagner.•Defensive countermeasures: Adversarial ...training, adversarial Lipschitz regularization.•Several ablation studies e.g., varying strength of the attack, measuring signal-to-noise ratio and perceptibility, effect of noise augmentation, transferability analysis.•Strongest attacks: PGD, Carlini & Wagner; most imperceptible adversarial samples: Carlini & Wagner; best defense: PGD-based adversarial training.
Robust speaker recognition, including in the presence of malicious attacks, is becoming increasingly important and essential, especially due to the proliferation of smart speakers and personal agents that interact with an individual’s voice commands to perform diverse and even sensitive tasks. Adversarial attack is a recently revived domain which is shown to be effective in breaking deep neural network-based classifiers, specifically, by forcing them to change their posterior distribution by only perturbing the input samples by a very small amount. Although, significant progress in this realm has been made in the computer vision domain, advances within speaker recognition is still limited. We present an expository paper that considers several adversarial attacks to a deep speaker recognition system, employs strong defense methods as countermeasures, and reports a comprehensive set of ablation studies to better understand the problem. The experiments show that the speaker recognition systems are vulnerable to adversarial attacks, and the strongest attacks can reduce the accuracy of the system from 94% to even 0%. The study also compares the performances of the employed defense methods in detail, and finds adversarial training based on Projected Gradient Descent (PGD) to be the best defense method in our setting. We hope that the experiments presented in this paper provide baselines that can be useful for the research community interested in further studying adversarial robustness of speaker recognition systems.
Temozolomide (TMZ) is a first-line alkylating agent for glioblastoma multiforme (GBM). Clarifying the mechanisms inducing TMZ insensitivity may be helpful in improving its therapeutic effectiveness ...against GBM. Insulin-like growth factor (IGF)-1 signaling and micro (mi)RNAs are relevant in mediating GBM progression. However, their roles in desensitizing GBM cells to TMZ are still unclear. We aimed to identify IGF-1-mediated miRNA regulatory networks that elicit TMZ insensitivity for GBM. IGF-1 treatment attenuated TMZ cytotoxicity via WNT/β-catenin signaling, but did not influence glioma cell growth. By miRNA array analyses, 93 upregulated and 148 downregulated miRNAs were identified in IGF-1-treated glioma cells. miR-513a-5p from the miR-513a-2 gene locus was upregulated by IGF-1-mediated phosphoinositide 3-kinase (PI3K) signaling. Its elevated levels were also observed in gliomas versus normal cells, in array data of The Cancer Genome Atlas (TCGA), and the GSE61710, GSE37366, and GSE41032 datasets. In addition, lower levels of neural precursor cell-expressed developmentally downregulated 4-like (NEDD4L), an E3 ubiquitin protein ligase that inhibits WNT signaling, were found in gliomas by analyzing cells, arrays, and RNA sequencing data of TCGA glioma patients. Furthermore, a negative correlation was identified between miR-513a-5p and NEDD4L in glioma. NEDD4L was also validated as a direct target gene of miR-513a-5p, and it was reduced by IGF-1 treatment. Overexpression of NEDD4L inhibited glioma cell viability and reversed IGF-1-repressed TMZ cytotoxicity. In contrast, miR-513a-5p significantly affected NEDD4L-inhibited WNT signaling and reduced TMZ cytotoxicity. These findings demonstrate a distinct role of IGF-1 signaling through miR-513a-5p-inhibited NEDD4L networks in influencing GBM's drug sensitivity to TMZ.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Temozolomide (TMZ), an alkylating agent of the imidazotetrazine series, is a first-line chemotherapeutic drug used in the clinical therapy of glioblastoma multiforme, the most common and high-grade ...primary glioma in adults. Micro (mi)RNAs, which are small noncoding RNAs, post-transcriptionally regulate gene expressions and are involved in gliomagenesis. However, no studies have reported relationships between TMZ and miRNA gene regulation. We investigated TMZ-mediated miRNA profiles and its molecular mechanisms underlying the induction of glioma cell death. By performing miRNA microarray and bioinformatics analyses, we observed that expression of 248 miRNAs was altered, including five significantly upregulated and 17 significantly downregulated miRNAs, in TMZ-treated U87MG cells. miR-128 expression levels were lower in different glioma cells and strongly associated with poor survival. TMZ treatment significantly upregulated miR-128 expression. TMZ significantly enhanced miR-128-1 promoter activity and transcriptionally regulated miR-128 levels through c-Jun N-terminal kinase 2/c-Jun pathways. The overexpression and knockdown of miR-128 expression significantly affected TMZ-mediated cell viability and apoptosis-related protein expression. Furthermore, the overexpression of miR-128 alone enhanced apoptotic death of glioma cells through caspase-3/9 activation, poly(ADP ribose) polymerase degradation, reactive oxygen species generation, mitochondrial membrane potential loss, and non-protective autophagy formation. Finally, we identified that key members in mammalian target of rapamycin (mTOR) signaling including mTOR, rapamycin-insensitive companion of mTOR, insulin-like growth factor 1, and PIK3R1, but not PDK1, were direct target genes of miR-128. TMZ inhibited mTOR signaling through miR-128 regulation. These results indicate that miR-128-inhibited mTOR signaling is involved in TMZ-mediated cytotoxicity. Our findings may provide a better understanding of cytotoxic mechanisms of TMZ involved in glioblastoma development.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Pathogenic superbugs are the root cause of untreatable complex infections with limited or no treatment options. These infections are becoming more common as clinical antibiotics have lost their ...effectiveness over time. Therefore, the development of novel antibacterial agents is urgently needed to counter these microbes. Antimicrobial peptides (AMPs) are a viable treatment option due to their bactericidal potency against multiple microbial classes. AMPs are naturally selected physiological microbicidal agents that are found in all forms of organisms. In the present study, we developed two tilapia piscidin 2 (TP2)-based AMPs for antimicrobial application. Unlike the parent peptide, the redesigned peptides showed significant antimicrobial activity against multidrug-resistant bacterial species. These peptides also showed minimal cytotoxicity. In addition, they were significantly active in the presence of physiological salts, 50% human serum and elevated temperature. The designed peptides also showed synergistic activity when combined with clinical antibiotics. The current approach demonstrates a fruitful strategy for developing potential AMPs for antimicrobial application. Such AMPs have potential for progression to further trials and drug development investigations.
Auricular therapy includes acupuncture, electroacupuncture, acupressure, lasering, cauterization, moxibustion, and bloodletting in the auricle. For 2500 years, people have employed auricular therapy ...for treating diseases, but the methods have been limited to bloodletting and cauterization. Only after 1957, the international scientific community became aware that the map of the ear resembles an inverted fetus, its introduction has led to auricular acupuncture (AA) becoming a more systemic approach, and, following the identification and standardization of more precise points, AA has been employed in clinical applications. The mechanisms of AA are considered to have a close relationship with the autonomic nervous system, the neuroendocrine system, neuroimmunological factors, neuroinflammation, and neural reflex, as well as antioxidation. Auricular therapy has been applied, for example, for pain relief, for the treatment of epilepsy, anxiety, and obesity, and for improving sleep quality. However, the mechanisms and evidence for auricular therapy warrant further study.
Whereas most economic and ecological impacts of tramp ant species stem in large part from numerical dominance and exacerbated aggressiveness of workers, those imposed by alate (winged) ants have been ...rarely described. In the present study, we report an unprecedented massive alate swarming (i.e., mating flight) event in southern Taiwan by a tramp ant species, Technomyrmex albipes (Smith) (Hymenoptera: Formicidae), that triggers immediate pest management responses, and examine factor(s) that potentially contribute to the remarkably high number of alates. We monitored the seasonal activities of T. albipes workers and phenology of alate swarming, attempting to link the worker foraging dynamics with swarm ontogeny. As it was argued that recent streetlight fixtures converted from high‐pressure sodium to light‐emitting diode (LED) may serve as a major cause of the massive swarming, alates' light color preference was investigated. Sex ratio of trapped alates was also assessed to test whether sex‐specific light preference exists in T. albipes. We showed that foraging intensity of workers increased in the spring, peaked in May, and was followed by the nuptial flight season that began in August and lasted for 4 months. The phenological pattern is consistent with the colony dynamics in many other ant species. Although the two light preference experiments did not yield the same results, T. albipes alates overall preferred lights with shorter wavelengths in the active trapping, partially supporting the argument of white LED streetlights contributing to the massive flight. The sex ratio of trapped alates was overall female‐biased, suggesting female alates are disproportionally produced and/or more sensitive toward lights.
We report an unusual nuisance caused by massive mating flights of a tramp ant, Technomyrmex albipes (Hymenoptera: Formicidae) in southern Taiwan. Two trapping experiments together revealed that winged individuals were attracted more by artificial lights with short wavelengths, supporting the possible connection between the unprecedented swarming and recently installed white LED streetlights. Combined with the seasonal surveillance of workers' and winged individuals' activities, we discuss the potential pest management strategies to this newly emerging ant nuisance.
Clonal reproduction can provide an advantage for invasive species to establish as it can circumvent inbreeding depression which often plagues introduced populations. The world's most widespread ...invasive ant, Paratrechina longicornis, was previously found to display a double‐clonal reproduction system, whereby both males and queens are produced clonally, resulting in separate male and queen lineages, while workers are produced sexually. Under this unusual reproduction mode, inbreeding is avoided in workers as they carry hybrid interlineage genomes. Despite the ubiquitous distribution of P. longicornis, the significance of this reproductive system for the ant's remarkable success remains unclear, as its prevalence is still unknown. Further investigation into the controversial native origin of P. longicornis is also required to reconstruct the evolutionary histories of double‐clonal lineages. Here, we examine genetic variation and characterize the reproduction mode of P. longicornis populations sampled worldwide using microsatellites and mitochondrial DNA sequences to infer the ant's putative native range and the distribution of the double‐clonal reproductive system. Analyses of global genetic variations indicate that the Indian subcontinent is a genetic diversity hotspot of this species, suggesting that P. longicornis probably originates from this geographical area. Our analyses revealed that both the inferred native and introduced populations exhibit double‐clonal reproduction, with queens and males around the globe belonging to two separate, nonrecombining clonal lineages. By contrast, workers are highly heterozygous because they are first‐generation interlineage hybrids. Overall, these data indicate a worldwide prevalence of double clonality in P. longicornis and support the prediction that the unusual genetic system may have pre‐adapted this ant for global colonization by maintaining heterozygosity in the worker force and alleviating genetic bottlenecks.
Abstract
The escape of bladder cancer from immunosurveillance causes monotherapy to exhibit poor efficacy; therefore, designing a multifunctional nanoparticle that boosts programmed cell death and ...immunoactivation has potential as a treatment strategy. Herein, we developed a facile one-pot coprecipitation reaction to fabricate cluster-structured nanoparticles (CNPs) assembled from Fe
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and iron chlorophyll (Chl/Fe) photosensitizers. This nanoassembled CNP, as a multifunctional theranostic agent, could perform red-NIR fluorescence and change the redox balance by the photoinduction of reactive oxygen species (ROS) and attenuate iron-mediated lipid peroxidation by the induction of a Fenton-like reaction. The intravesical instillation of Fe
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@Chl/Fe CNPs modified with 4-carboxyphenylboronic acid (CPBA) may target the BC wall through glycoproteins in the BC cavity, allowing local killing of cancer cells by photodynamic therapy (PDT)-induced singlet oxygen and causing chemodynamic therapy (CDT)-mediated ferroptosis. An interesting possibility is reprogramming of the tumor microenvironment from immunosuppressive to immunostimulatory after PDT-CDT treatment, which was demonstrated by the reduction of PD-L1 (lower “off” signal to the effector immune cells), IDO-1, TGF-β, and M2-like macrophages and the induction of CD8
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T cells on BC sections. Moreover, the intravesical instillation of Fe
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@Chl/Fe CNPs may enhance the large-area distribution on the BC wall, improving antitumor efficacy and increasing survival rates from 0 to 91.7%. Our theranostic CNPs not only demonstrated combined PDT-CDT-induced cytotoxicity, ROS production, and ferroptosis to facilitate treatment efficacy but also opened up new horizons for eliminating the immunosuppressive effect by simultaneous PDT-CDT.
Caffeic acid (CA) and ellagic acid (EA) are phenolic acids naturally occurring in many plant foods. Cardiac protective effects of these compounds against dyslipidemia, hypercoagulability, oxidative ...stress and inflammation in diabetic mice were examined.
Diabetic mice were divided into three groups (15 mice per group): diabetic mice with normal diet, 2% CA treatment, or 2% EA treatment. One group of non-diabetic mice with normal diet was used for comparison. After 12 weeks supplement, mice were sacrificed, and the variation of biomarkers for hypercoagulability, oxidative stress and inflammation in cardiac tissue of diabetic mice were measured.
The intake of CA or EA significantly increased cardiac content of these compounds, alleviated body weight loss, elevated plasma insulin and decreased plasma glucose levels in diabetic mice (p < 0.05). These treatments also significantly enhanced plasma antithrombin-III and protein C activities (p < 0.05); and decreased triglyceride content in cardiac tissue and plasma (p < 0.05), in which the hypolipidemic effects of EA were significantly greater than that of CA (p < 0.05). CA or EA significantly lowered cardiac levels of malondialdehyde, reactive oxygen species, interleukin (IL)-beta, IL-6, tumor necrosis factor (TNF)-alpha and monocyte chemoattractant protein (MCP)-1 (p < 0.05); and retained cardiac activity of glutathione peroxidase (GPX), superoxide dismutase (SOD) and catalase (p < 0.05). These compounds also significantly up-regulated cardiac mRNA expression of GPX1, SOD and catalase; and down-regulated IL-1beta, IL-6, TNF-alpha and MCP-1 mRNA expression in diabetic mice (p < 0.05).
These results support that CA and EA could provide triglyceride-lowering, anti-coagulatory, anti-oxidative, and anti-inflammatory protection in cardiac tissue of diabetic mice. Thus, the supplement of these agents might be helpful for the prevention or attenuation of diabetic cardiomyopathy.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK, VSZLJ
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