Miracle-dz/UniFAR-FTUs huggingface dataset:
Loss of the Inducible Hsp70 Delays the Inflammatory Response to Skeletal Muscle Injury and Severely Impairs Muscle Regeneration

Skeletal muscle regeneration following injury is a highly coordinated process that involves transient muscle inflammation, removal of necrotic cellular debris and subsequent replacement of damaged myofibers through secondary myogenesis. However, the molecular mechanisms which coordinate these events are only beginning to be defined. In the current study we demonstrate that Heat shock protein 70 (Hsp70) is increased following muscle injury, and is necessary for the normal sequence of events following severe injury induced by cardiotoxin, and physiological injury induced by modified muscle use. Indeed, Hsp70 ablated mice showed a significantly delayed inflammatory response to muscle injury induced by cardiotoxin, with nearly undetected levels of both neutrophil and macrophage markers 24 hours post-injury. At later time points, Hsp70 ablated mice showed sustained muscle inflammation and necrosis, calcium deposition and impaired fiber regeneration that persisted several weeks post-injury. Through rescue experiments reintroducing Hsp70 intracellular expression plasmids into muscles of Hsp70 ablated mice either prior to injury or post-injury, we confirm that Hsp70 optimally promotes muscle regeneration when expressed during both the inflammatory phase that predominates in the first four days following severe injury and the regenerative phase that predominates thereafter. Additional rescue experiments reintroducing Hsp70 protein into the extracellular microenvironment of injured muscles at the onset of injury provides further evidence that Hsp70 released from damaged muscle may drive the early inflammatory response to injury. Importantly, following induction of physiological injury through muscle reloading following a period of muscle disuse, reduced inflammation in 3-day reloaded muscles of Hsp70 ablated mice was associated with preservation of myofibers, and increased muscle force production at later time points compared to WT. Collectively our findings indicate that depending on the nature and severity of muscle injury, therapeutics which differentially target both intracellular and extracellular localized Hsp70 may optimally preserve muscle tissue and promote muscle functional recovery.
Detecting Adversarial Examples - A Lesson from Multimedia Forensics

Adversarial classification is the task of performing robust classification in the presence of a strategic attacker. Originating from information hiding and multimedia forensics, adversarial classification recently received a lot of attention in a broader security context. In the domain of machine learning-based image classification, adversarial classification can be interpreted as detecting so-called adversarial examples, which are slightly altered versions of benign images. They are specifically crafted to be misclassified with a very high probability by the classifier under attack. Neural networks, which dominate among modern image classifiers, have been shown to be especially vulnerable to these adversarial examples. However, detecting subtle changes in digital images has always been the goal of multimedia forensics and steganalysis. In this paper, we highlight the parallels between these two fields and secure machine learning. Furthermore, we adapt a linear filter, similar to early steganalysis methods, to detect adversarial examples that are generated with the projected gradient descent (PGD) method, the state-of-the-art algorithm for this task. We test our method on the MNIST database and show for several parameter combinations of PGD that our method can reliably detect adversarial examples. Additionally, the combination of adversarial re-training and our detection method effectively reduces the attack surface of attacks against neural networks. Thus, we conclude that adversarial examples for image classification possibly do not withstand detection methods from steganalysis, and future work should explore the effectiveness of known techniques from multimedia forensics in other adversarial settings.
Basinwide Integrated Volume Transports in an Eddy-Filled Ocean

The temporal evolution of the strength of the Atlantic Meridional Overturning Circulation (AMOC) in the subtropical North Atlantic is affected by both remotely forced, basin-scale meridionally coherent, climate-relevant transport anomalies, such as changes in high-latitude deep water formation rates, and locally forced transport anomalies, such as eddies or Rossby waves, possibly associated with small meridional coherence scales, which can be considered as noise. The focus of this paper is on the extent to which local eddies and Rossby waves when impinging on the western boundary of the Atlantic affect the temporal variability of the AMOC at 26.5 degrees N. Continuous estimates of the AMOC at this latitude have been made since April 2004 by combining the Florida Current, Ekman, and midocean transports with the latter obtained from continuous density measurements between the coasts of the Bahamas and Morocco, representing, respectively, the western and eastern boundaries of the Atlantic at this latitude.Within 100 km of the western boundary there is a threefold decrease in sea surface height variability toward the boundary, observed in both dynamic heights from in situ density measurements and altimetric heights. As a consequence, the basinwide zonally integrated upper midocean transport shallower than 1000 m-as observed continuously between April 2004 and October 2006-varies by only 3.0 Sv (1 Sv = 10(6) m(3) s(-1)) RMS. Instead, upper midocean transports integrated from western boundary stations 16, 40, and 500 km offshore to the eastern boundary vary by 3.6, 6.0, and 10.7 Sv RMS, respectively. The reduction in eddy energy toward the western boundary is reproduced in a nonlinear reduced-gravity model suggesting that boundary-trapped waves may account for the observed decline in variability in the coastal zone because they provide a mechanism for the fast equatorward export of transport anomalies associated with eddies impinging on the western boundary. An analytical model of linear Rossby waves suggests a simple scaling for the reduction in thermocline thickness variability toward the boundary. Physically, the reduction in amplitude is understood as along-boundary pressure gradients accelerating the fluid and rapidly propagating pressure anomalies along the boundary. The results suggest that the local eddy field does not dominate upper midocean transport or AMOC variability at 26.5 degrees N on interannual to decadal time scales.
Human L- and M-opsins restore M-cone function in a mouse model for human blue cone monochromacy

Purpose Blue cone monochromacy (BCM) is an X-linked congenital vision disorder characterized by complete loss or severely reduced L- and M-cone function. Patients with BCM display poor visual acuity, severely impaired color discrimination, myopia, nystagmus, and minimally detectable cone-mediated electroretinogram. Recent studies of patients with BCM with adaptive optics scanning laser ophthalmoscopy (AOSLO) showed that they have a disrupted cone mosaic with reduced numbers of cones in the fovea that is normally dominated by L- and M-cones. The remaining cones in the fovea have significantly shortened outer segments but retain sufficient structural integrity to serve as potential gene therapy targets. In this study, we tested whether exogenously expressed human L- and M-opsins can rescue M-cone function in an M-opsin knockout (Opn1mw−/−) mouse model for BCM. Methods Adeno-associated virus type 5 (AAV5) vectors expressing OPN1LW, OPN1MW, or C-terminal tagged OPN1LW-Myc, or OPN1MW-HA driven by a cone-specific promoter were injected subretinally into one eye of Opn1mw−/− mice, while the contralateral eye served as the uninjected control. Expression of cone pigments was determined with western blotting and their cellular localization identified with immunohistochemistry. M-cone function was analyzed with electroretinogram (ERG). Antibodies against cone phototransduction proteins were used to study cone outer segment (OS) morphology in untreated and treated Opn1mw−/− eyes. Results We showed that cones in the dorsal retina of the Opn1mw−/− mouse do not form outer segments, resembling cones that lack outer segments in the human BCM fovea. We further showed that AAV5-mediated expression of either human M- or L-opsin individually or combined promotes regrowth of cone outer segments and rescues M-cone function in the treated Opn1mw−/− dorsal retina. Conclusions Exogenously expressed human opsins can regenerate cone outer segments and rescue M-cone function in Opn1mw−/− mice, thus providing a proof-of-concept gene therapy in an animal model of BCM.
Worldwide Distribution of the MYH9 Kidney Disease Susceptibility Alleles and Haplotypes: Evidence of Historical Selection in Africa

MYH9 was recently identified as renal susceptibility gene (OR 3–8, p<10−8) for major forms of kidney disease disproportionately affecting individuals of African descent. The risk haplotype (E-1) occurs at much higher frequencies in African Americans (≥60%) than in European Americans (<4%), revealing a genetic basis for a major health disparity. The population distributions of MYH9 risk alleles and the E-1 risk haplotype and the demographic and selective forces acting on the MYH9 region are not well explored. We reconstructed MYH9 haplotypes from 4 tagging single nucleotide polymorphisms (SNPs) spanning introns 12–23 using available data from HapMap Phase II, and by genotyping 938 DNAs from the Human Genome Diversity Panel (HGDP). The E-1 risk haplotype followed a cline, being most frequent within sub-Saharan African populations (range 50–80%), less frequent in populations from the Middle East (9–27%) and Europe (0–9%), and rare or absent in Asia, the Americas, and Oceania. The fixation indexes (FST) for pairwise comparisons between the risk haplotypes for continental populations were calculated for MYH9 haplotypes; FST ranged from 0.27–0.40 for Africa compared to other continental populations, possibly due to selection. Uniquely in Africa, the Yoruba population showed high frequency extended haplotype length around the core risk allele (C) compared to the alternative allele (T) at the same locus (rs4821481, iHs = 2.67), as well as high population differentiation (FST(CEU vs. YRI) = 0.51) in HapMap Phase II data, also observable only in the Yoruba population from HGDP (FST = 0.49), pointing to an instance of recent selection in the genomic region. The population-specific divergence in MYH9 risk allele frequencies among the world's populations may prove important in risk assessment and public health policies to mitigate the burden of kidney disease in vulnerable populations.
Effect of pre-ozonation-enhanced coagulation on dissolved organic nitrogen in municipal wastewater treatment plant effluent

ABSTRACT Municipal wastewater treatment plant (WWTP) effluent is increasingly used as reclaimed water and as water sources for downstream areas. Effluent dissolved organic nitrogen (DON) is considered to be the precursor to nitrogen disinfection by-products (N-DBPs). Here, we investigated DON removal by pre-ozonation-enhanced coagulation and found that (1) pre-ozonation significantly enhanced the removal of DON, dissolved organic carbon (DOC), and UV254 by coagulation. (2) pH had an important impact on the pre-ozonation-enhanced coagulation. At lower pH, the removal of DON, DOC, and UV254 is higher. (3) As ozone dosage increased, zeta potential gradually increased, while dissolved calcium concentrations declined and there was a strong correlation between zeta potential and dissolved calcium concentrations. (4) Small (<6 kDa) molecular weight DON was dominant in the effluent. Hydrophilic and hydrophobic DON accounted for 58.5% and 30.8% of the total, respectively. (5) Coagulation reduced overall DBP formation potentials to less than 20%. In contrast, overall DBP formation potentials increased after ozonation. However, pre-ozonation-enhanced coagulation not only removed 71% DON, but also reduced overall DBP formation potentials by more than 40%. (6) 3-DEEM spectra indicated that DBP formation potentials and DON concentrations were related to three main peaks, which corresponded to tryptophan-based proteins, aromatic proteins, and fulvic acids.
HDAC1 knockdown inhibits invasion and induces apoptosis in non-small cell lung cancer cells

Abstract Non-small cell lung cancer (NSCLC) is a common malignant tumor. Although the abnormal expression and potential clinical prognostic value of histone deacetylase 1 (HDAC1) were recently discovered in many kinds of cancer, the roles and molecular mechanisms of HDAC1 in NSCLC is still limited. The CCK-8 assay is used to evaluate the viability of NSCLC cells. Downregulation of HDAC1 by shRNA. The TUNEL assay was used to evaluate the role of HDAC1 in NSCLC apoptosis. To evaluate the role of HDAC1 in NSCLC cells migration, the Boyden chamber transwell assay and wound healing assay were used. To evaluate the cells invasion, the matrigel precoated Transwell assay was used. Enzyme-linked immunosorbent assays (ELISAs) were used to detect the level of vascular endothelial growth factor (VEGF) and IL-8 in NSCLC. To investigate the role of HDAC1 in angiogenesis, the tube formation assay was investigated. In this study, we showed that HDAC1 expression was elevated in NSCLC lines compared to that in normal liver cells LO2. Furthermore, downregulation of HDAC1 inhibited cell proliferation, prevented cell migration, decreased cell invasion, reduced tumor angiogenesis and induced cell apoptosis. In summary, HDAC1 may be regarded as a potential indicator for NSCLC patient treatment.
Dobrava hantavirus variants found in Apodemus flavicollis mice in Kırklareli Province, Turkey

Hantaviruses infect humans via inhalation of viral particles within secretions of infected rodents or rarely through direct contact with infected rodents. Determining the prevalence of hantavirus infections among rodent populations is of vital importance to obtain information on hantavirus‐related cases and to predict possible outbreaks. We hypothesized that DOBV strains circulating in the Thrace Region in Turkey would be related to other Balkan DOBV strains. In this study, hantavirus infections in the rodent population of the Kırklareli‐İğneada Region (north‐western Turkey, near the Bulgarian border) were investigated. This region is of particular importance, as it is located in the south‐eastern margin of the European continent and was used as an entrance point of Asian faunal elements into Europe. DOBV infection was detected in eight of 73 rodents; all were of the Apodemus flavicollis species. Partial sequences of the viral S‐, M‐, and L‐genome segments were recovered and compared with previously reported DOBV sequences. The newly characterized Turkish strains were similar to other DOBV variants. Silent nucleotide mutations were dominant. The hantavirus prevalence in the İğneada region was similar to what has been reported in Greece and Bulgaria. For the first time, the M‐segment sequences of DOBV from Turkey were recovered and genetic data of hantaviruses from Thrace region of Turkey were obtained.
Offspring in Response to Parental Female Densities in the Fruit Fly Parasitoid DIACHASMIMORPHA LONGICAUDATA (Hymenoptera: Braconidae: Opiinae)

Abstract As part of an evaluation of the braconid parasitoid Diachasmimorpha longicaudata (Ashmead) as a biocontrol agent of Ceratitis capitata (Wiedemann) in Brazil, the aims in the current study were to find the best parental ratio of females to males in the rearing cages in order to get the highest female biased offspring in the parasitoid rearing process, and to verify the parasitism efficiency on C. capitata according to parental female densities. Three treatments were assessed: T1 (20 females: 20 males), T2 (60 females: 20 males) and T3 (100 females: 20 males). Ten late-third instars of C. capitata were offered daily to each female parasitoid from the 1st to the 12th d of age. The parental female productivity, fecundity, offspring sex ratio, percentage of parasitoid emergence, and daily mortality of parental females and males at different female/male densities were evaluated. The results indicated that numbers higher than 20 parental females did not affect offspring sex ratio, overall offspring production, nor the percent parasitism. Female biased offspring occurred in all three parental female/male ratios analyzed in this study, except that predominately males developed from parasitoid eggs laid in the age interval 1-2 d post emergence. Higher parasitoid female productivity and fecundity were found at the 1:1 female/male per cage density whereas lower productivity and fecundity were recorded at the 5:1 female/male ratio. Higher female/male ratio in the parental cages increased the mortality rate of females but did not influence the number of parental male deaths. The results may facilitate advancement of an optimum mass-rearing system to aid in control of C. capitata in Brazil.
TC-Release++: An Efficient Timestamp-Based Coherence Protocol for Many-Core Architectures

As we enter the era of many-core, providing the shared memory abstraction through cache coherence has become progressively difficult. The standard directory-based coherence does not scale well with increasing core count. Timestamp-based hardware coherence protocols introduced recently offer an attractive alternative solution. This paper proposes a timestamp-based coherence protocol, called TC-Release++ , that efficiently supports cache coherence in large-scale systems. Our approach is inspired by TC-Weak, a recently proposed timestamp-based coherence protocol targeting GPU architectures. We first design TC-Release in an attempt to straightforwardly port TC-Weak to general-purpose many-cores. But re-purposing TC-Weak for general-purpose many-core architectures is challenging due to significant differences both in architecture and the programming model. Indeed the performance of TC-Release turns out to be worse than conventional directory protocols. We overcome the limitations and overheads of TC-Release by exploiting simple hardware support to eliminate frequent memory stalls, and an optimized lifetime prediction mechanism to improve cache performance. The resulting optimized coherence protocol TC-Release++ is highly scalable (storage scales logarithmically with core count) and shows better performance (3.0 percent) and comparable network traffic (within 1.3 percent) relative to the baseline MESI directory protocol. We use Murphi to formally verify that TC-Release ++ is error-free and imposes small verification cost.
Protective effects of agomelatine on testicular damage caused by bortezomib

Abstract Bortezomib is a chemotherapeutic agent used to treat several cancers; however, it exhibits severe side effects in testicular tissue. We investigated the use of agomelatine to prevent testicular tissue damage caused by bortezomib. We used 36 male Sprague-Dawley rats divided randomly into six equal groups: group 1, no treatment control; group 2, agomelatine treatment only; group 3, bortezomib treatment only for 48 h; group 4, bortezomib + agomelatine treatment for 48 h; group 5, bortezomib treatment only for 72 h; and group 6, bortezomib + agomelatine treatment for 72 h. After treatments, the rats were sacrificed and testicular tissue was harvested. Lipid oxidation (LPO) and superoxide dismutase (SOD) levels in the tissues were determined using biochemical methods. Tissue samples also were examined using histopathological and immunohistochemical techniques. The LPO level was increased, while the SOD level was decreased in the bortezomib treated groups. We found that agomelatine treatment normalized LPO and SOD activities in the bortezomib treated groups. In the spermatogonia and Sertoli cells, the staining density of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) and caspase 3 were decreased in the bortezomib + agomelatine groups at both 48 and 72 h compared to bortezomib only treated groups. We observed maturation arrest, basal membrane thickening, increase in inflammatory cells and connective tissue, and edema between germ cells in the bortezomib only treated groups. By contrast, normal basal membrane, less edema and more normal maturation were observed in the bortezomib + agomelatine groups at 48 and 72 h. We found that agomelatine reduced the damaging effects of bortezomib. The use of agomelatine to prevent bortezomib induced testicular tissue damage in human patients should be investigated further.
Cognitive behavioural interventions in addictive disorders

Cognitive behaviour therapy is a structured, time limited, psychological intervention that has is empirically supported across a wide variety of psychological disorders. CBT for addictive behaviours can be traced back to the application of learning theories in understanding addiction and subsequently to social cognitive theories. The focus of CBT is manifold and the focus is on targeting maintaining factors of addictive behaviours and preventing relapse. Relapse prevention programmes are based on social cognitive and cognitive behavioural principles. Interventions for preventing relapse include, behavioural strategies to decrease the valence of addictive behaviours, coping skills to deal with craving, arousal, negative mood states, assertiveness skills to manage social pressures, family psychoeducation and environmental manipulation and cognitive strategies to enhance self-efficacy beliefs and modification of outcome expectancies related to addictive behaviours. More recent developments in the area of managing addictions include third wave behaviour therapies. Third wave behaviour therapies are focused on improving building awareness, and distress tolerance skills using mindfulness practices. These approaches have shown promise, and more recently the neurobiological underpinnings of mindfulness strategies have been studied. The article provides an overview of cognitive behavioural approaches to managing addictions.
The cystine‐glutamate exchanger (xCT, Slc7a11) is expressed in significant concentrations in a subpopulation of astrocytes in the mouse brain

The cystine‐glutamate exchanger (xCT) promotes glutathione synthesis by catalyzing cystine uptake and glutamate release. The released glutamate may modulate normal neural signaling and contribute to excitotoxicity in pathological situations. Uncertainty, however, remains as neither the expression levels nor the distribution of xCT have been unambiguously determined. In fact, xCT has been reported in astrocytes, neurons, oligodendrocytes and microglia, but most of the information derives from cell cultures. Here, we show by immunohistochemistry and by Western blotting that xCT is widely expressed in the central nervous system of both sexes. The labeling specificity was validated using tissue from xCT knockout mice as controls. Astrocytes were selectively labeled, but showed greatly varying labeling intensities. This astroglial heterogeneity resulted in an astrocyte domain‐like labeling pattern. Strong xCT labeling was also found in the leptomeninges, along some blood vessels, in selected circumventricular organs and in a subpopulation of tanycytes residing the lateral walls of the ventral third ventricle. Neurons, oligodendrocytes and resting microglia, as well as reactive microglia induced by glutamine synthetase deficiency, were unlabeled. The concentration of xCT protein in hippocampus was compared with that of the EAAT3 glutamate transporter by immunoblotting using a chimeric xCT‐EAAT3 protein to normalize xCT and EAAT3 labeling intensities. The immunoblots suggested an xCT/EAAT3 ratio close to one (0.75 ± 0.07; average ± SEM; n = 4) in adult C57BL6 mice. Conclusions: xCT is present in select blood/brain/CSF interface areas and in an astrocyte subpopulation, in sufficient quantities to support the notion that system xc− provides physiologically relevant transport activity.