Miracle-dz/UniFAR-FTUs huggingface dataset:
Wnt signalling is a bi-directional vulnerability of cancer cells

Wnt signalling is involved in the formation, metastasis and relapse of a wide array of cancers. However, there is ongoing debate as to whether activation or inhibition of the pathway holds the most promise as a therapeutic treatment for cancer, with conflicting evidence from a variety of tumour types. We show that Wnt/β-catenin signalling is a bi-directional vulnerability of neuroblastoma, malignant melanoma and colorectal cancer, with hyper-activation or repression of the pathway both representing a promising therapeutic strategy, even within the same cancer type. Hyper-activation directs cancer cells to undergo apoptosis, even in cells oncogenically driven by β-catenin. Wnt inhibition blocks proliferation of cancer cells and promotes neuroblastoma differentiation. Wnt and retinoic acid co-treatments synergise, representing a promising combination treatment for MYCN-amplified neuroblastoma. Additionally, we report novel cross-talks between MYCN and β-catenin signalling, which repress normal β-catenin mediated transcriptional regulation. A β-catenin target gene signature could predict patient outcome, as could the expression level of its DNA binding partners, the TCF/LEFs. This β-catenin signature provides a tool to identify neuroblastoma patients likely to benefit from Wnt-directed therapy. Taken together, we show that Wnt/β-catenin signalling is a bi-directional vulnerability of a number of cancer entities, and potentially a more broadly conserved feature of malignant cells.
Bandwidth improvement of a limit-cycle amplifier using a novel hysteretic relay

Limit-cycle or self-oscillating power amplifiers (SOPAs) are seen as a compact option to achieve efficient yet linear amplification of either complete RF signals or only their base-band envelopes. Unfortunately, one of their undesired drawbacks is that their self-oscillating frequency, and thus available bandwidth, is reduced when a significant propagation delay exists in the feedback loop, typically from the power stage. To remedy this SOPAs' pitfall, this paper presents a method to increase the self-oscillation frequency for a fixed propagation delay and loop filter. This is achieved using a relay that exhibits a novel kind of hysteresis. For that, the theory of its working principle is discussed, and a suitable implementation is proposed. To validate the concept, simulations are carried out to compare the behavior of existing types of SOPA with the proposed one.
Infection and Drug Resistance Dovepress Resistance to Antimicrobial Drugs in Ghana

Background: Antimicrobial drug resistance is a global issue that affects health, economic, and social development. The problem has been attributed to misuse of antimicrobial agents. Purpose: To identify the agents of bacterial infection in Ghana, determine their antibiogram, and the possibility of setting up a surveillance program. Patients and methods: A prospective quantitative study set in various hospitals including two teaching hospitals, seven regional hospitals, and two district hospitals in Ghana. A total of 5099 bacterial isolates from various clinical specimens were collected over a period of 1 year, including data related to the patients. Susceptibility of the isolates was determined by the Kirby– Bauer method. In addition, the minimum inhibitory concentration (MIC) of multidrug-resistant isolates of epidemiological significance was also determined using the E-test. Results: A wide range of bacterial isolates were identified in both teaching and regional hospitals. High percentage of resistance was observed for tetracycline (82%), cotrimoxazole (73%), ampicillin (76%), and chloramphenicol (75%). Multidrug resistance was observed to a combination of ampicillin, tetracycline, chloramphenicol, and cotrimoxazole. On the other hand, a lower percentage of resistance was observed for ceftriaxone (6.3%), ciprofloxacin (11%), and amikacin (9.9%). Conclusion: Generally, the prevalence of multidrug resistance was widespread among the various isolates. Some multidrug-resistant strains of Staphylococcus aureus, Salmonella typhi, and non-typhoidal Salmonella (NTS) had high MIC to cefuroxime (.256), gentamicin (.256), and ciprofloxacin (.32).
Physical Warmth and Perceptual Focus: A Replication of IJzerman and Semin (2009)

With the changing of modal research practices in psychology, the grounded cognition perspective (sometimes categorized under the more popular term of “social priming”) has become heavily criticized. Specifically, LeBel and Campbell (2013) reported a failed replication of a study involving what some would call “social priming. ” We sought to replicate a study from our own lab (IJzerman & Semin, 2009), to investigate the reproducibility of the reported effect that physical warmth leads to a greater focus on perceptual relations. We also improved our methods to reduce potential experimenter's bias (cf. Doyen, Klein, Pichon, & Cleeremans, 2012). We successfully replicated the finding that a simple cue of physical warmth makes people more likely to adopt a relational focus.
ShieldFS: a self-healing, ransomware-aware filesystem

Preventive and reactive security measures can only partially mitigate the damage caused by modern ransomware attacks. Indeed, the remarkable amount of illicit profit and the cyber-criminals' increasing interest in ransomware schemes suggest that a fair number of users are actually paying the ransoms. Unfortunately, pure-detection approaches (e.g., based on analysis sandboxes or pipelines) are not sufficient nowadays, because often we do not have the luxury of being able to isolate a sample to analyze, and when this happens it is already too late for several users! We believe that a forward-looking solution is to equip modern operating systems with practical self-healing capabilities against this serious threat. Towards such a vision, we propose ShieldFS, an add-on driver that makes the Windows native filesystem immune to ransomware attacks. For each running process, ShieldFS dynamically toggles a protection layer that acts as a copy-on-write mechanism, according to the outcome of its detection component. Internally, ShieldFS monitors the low-level filesystem activity to update a set of adaptive models that profile the system activity over time. Whenever one or more processes violate these models, their operations are deemed malicious and the side effects on the filesystem are transparently rolled back. We designed ShieldFS after an analysis of billions of low-level, I/O filesystem requests generated by thousands of benign applications, which we collected from clean machines in use by real users for about one month. This is the first measurement on the filesystem activity of a large set of benign applications in real working conditions. We evaluated ShieldFS in real-world working conditions on real, personal machines, against samples from state of the art ransomware families. ShieldFS was able to detect the malicious activity at runtime and transparently recover all the original files. Although the models can be tuned to fit various filesystem usage profiles, our results show that our initial tuning yields high accuracy even on unseen samples and variants.
Analysis of Geometric Primitives in Quantitative Structure Models of Tree Stems

One way to model a tree is to use a collection of geometric primitives to represent the surface and topology of the stem and branches of a tree. The circular cylinder is often used as the geometric primitive, but it is not the only possible choice. We investigate various geometric primitives and modelling schemes, discuss their properties and give practical estimates for expected modelling errors associated with the primitives. We find that the circular cylinder is the most robust primitive in the sense of a well-bounded volumetric modelling error, even with noise and gaps in the data. Its use does not cause errors significantly larger than those with more complex primitives, while the latter are much more sensitive to data quality. However, in some cases, a hybrid approach with more complex primitives for the stem is useful.
Treatment of db/db diabetic mice with triptolide: a novel therapy for diabetic nephropathy.

BACKGROUND Current research on the progression of diabetic nephropathy (DN) suggests many important factors; metabolic disturbance, haemodynamic abnormity, chronic inflammation, oxidative stress, innate immune system activation and podocyte lesion. Triptolide, which is active diterpene purified from the traditional Chinese medicine Tripterygium wilfordii Hook F (TwHF), has anti-inflammatory, anti-oxidative, immunosuppressive and podocyte-protective effects. Herein, we investigated the therapeutic effects of triptolide on DN in db/db diabetic mice and studied the potential mechanisms. METHODS db/db mice with DN were administrated with triptolide or valsartan. After 4, 8 and 12 weeks of treatment, 24-h urine albumin level, blood biochemical parameters and body weight were measured. Glomerulus area, glomerulus volume to Bowman's capsule volume ratio, podocyte changes and inflammatory and oxidative stress markers were quantitatively determined to evaluate renal lesions. RESULTS The albuminuria in db/db diabetic mice was markedly attenuated after triptolide treatment, accompanied with alleviated glomerular hypertrophy and podocyte injury. In addition, the inflammation and oxidative stress in the kidneys were also attenuated, accompanied with improved hyperlipidaemia and obesity. The efficacy increased with the prolonging of triptolide treatment, and the efficacy in high-dose triptolide group was superior to that in the low-dose group. The effect of triptolide on glomerular hypertrophy was similar to valsartan, but the effects of triptolide on renal inflammation and oxidative stress were more profound than those of valsartan. CONCLUSIONS Triptolide can dramatically attenuate albuminuria and renal lesion accompanied with dyslipidaemia and obesity in db/db diabetic mice. It is a new drug that exerts comprehensive protective effects on preventing DN progression.
Tradition and Change in Legal English

In this volume the author examines verbal constructions in prescriptive legal texts written in English. Modal auxiliaries such as shall, may and must are analysed, as well as indicative tenses such as the present simple, and also nonfinite constructions such as the -ing form and -ed participles. Results are based on specially compiled corpora of prescriptive texts coming from a wide range of English-speaking countries and also international organizations such as the European Union and the UN. The author also analyses the nature, extent and impact of the calls for change in legal language coming from the Plain Language Movement. Although legal language tends to be depicted as being highly conservative and unchanging, the author shows that in certain parts of the English-speaking world a minor revolution would appear to be taking place, while in other parts there is greater resistance to change.
Acoustic emissions document stress changes over many seismic cycles in stick‐slip experiments

The statistics of large earthquakes commonly involve large uncertainties due to the lack of long‐term, robust earthquake recordings. Small‐scale seismic events are abundant and can be used to examine variations in fault structure and stress. We report on the connection between stress and microseismic event statistics prior to the possibly smallest earthquakes: those generated in the laboratory. We investigate variations in seismic b value of acoustic emission events during the stress buildup and release on laboratory‐created fault zones. We show that b values mirror periodic stress changes that occur during series of stick‐slip events, and are correlated with stress over many seismic cycles. Moreover, the amount of b value increase associated with slip events indicates the extent of the corresponding stress drop. Consequently, b value variations can be used to approximate the stress state on a fault: a possible tool for the advancement of time‐dependent seismic hazard assessment.
Flutamide induces relaxation in large and small blood vessels.

HYPOTHESIS Flutamide, a testosterone receptor antagonist, produces various beneficial effects in male rats following hemorrhagic shock, possibly as a result of a direct vasodilating effect on large and small vessels in the rat. DESIGN, INTERVENTIONS, AND MAIN OUTCOME MEASURES The aorta and the small intestine were isolated from normal male and female Sprague-Dawley rats. Isolated aortic rings were placed in the organ bath and constricted by 2 x 10(-7)M norepinephrine bitartrate (Sigma, St Louis, Mo). Flutamide-induced and testosterone-induced vascular relaxation dose-response curves were then determined. The dose-response curves of flutamide were also determined in the small blood vessels of the isolated small intestine under conditions of constant flow following preconstriction induced by 5 x 10(-6 )M norepinephrine bitartrate. The effects of prior incubation with testosterone (8 x 10(-5)M) and sex differences on flutamide-induced vascular relaxation were also examined in aortic rings and in the small intestine. Moreover, flutamide-induced relaxation in endothelium-denuded aortic rings and in aortic rings from animals subjected to trauma and hemorrhagic shock was examined. RESULTS Flutamide induced significant relaxation in aortic rings and small intestinal blood vessels in healthy males. The flutamide-induced relaxation in vessels from normal males was partially attenuated by prior incubation with the male sex steroid testosterone, and was significantly lower in females. Flutamide-induced vascular relaxation in the aorta was partially attenuated by endothelium removal, but it was not significantly affected by trauma and hemorrhagic shock in male rats. CONCLUSIONS Flutamide has a direct vasodilating effect on large and small vessels in rats, which involves sex-dependent mechanisms. Thus, the beneficial effects of flutamide on cardiovascular responses in males following trauma and hemorrhagic shock may be due to the direct vascular relaxation induced by this agent.
Posterior Sampling for Reinforcement Learning Without Episodes

This is a brief technical note to clarify some of the issues with applying the application of the algorithm posterior sampling for reinforcement learning (PSRL) in environments without fixed episodes. In particular, this paper aims to: - Review some of results which have been proven for finite horizon MDPs (Osband et al 2013, 2014a, 2014b, 2016) and also for MDPs with finite ergodic structure (Gopalan et al 2014). - Review similar results for optimistic algorithms in infinite horizon problems (Jaksch et al 2010, Bartlett and Tewari 2009, Abbasi-Yadkori and Szepesvari 2011), with particular attention to the dynamic episode growth. - Highlight the delicate technical issue which has led to a fault in the proof of the lazy-PSRL algorithm (Abbasi-Yadkori and Szepesvari 2015). We present an explicit counterexample to this style of argument. Therefore, we suggest that the Theorem 2 in (Abbasi-Yadkori and Szepesvari 2015) be instead considered a conjecture, as it has no rigorous proof. - Present pragmatic approaches to apply PSRL in infinite horizon problems. We conjecture that, under some additional assumptions, it will be possible to obtain bounds $O( \sqrt{T} )$ even without episodic reset. We hope that this note serves to clarify existing results in the field of reinforcement learning and provides interesting motivation for future work.
A Cross-language Corpus for Studying the Phonetics and Phonology of Prominence

The present article describes a corpus which was collected for the cross-language comparison of prominence. In the data analysis, the acoustic-phonetic properties of words spoken with two different levels of accentuation (de-accented and nuclear accented in non-contrastive narrow-focus) are examined in question-answer elicited sentences and iterative imitations (on the syllable da) produced by Bulgarian, Russian, French, German and Norwegian speakers (3 male and 3 female per language). Normalized parameter values allow a comparison of the properties employed in differentiating the two levels of accentuation. Across the five languages there are systematic differences in the degree to which duration, f0, intensity and spectral vowel definition change with changing prominence under different focus conditions. The link with phonological differences between the languages is discussed.
Punica Granatum Juice Effects on Oxidative Stress in Severe Physical Activity

Aim: The aim of this study was to investigate Punica granatum juice effects on oxidative stress in young healthy males during severe physical activity. Methods: Our subjects were selected from healthy males at 18 - 24 years. They were enrolled and randomly distributed into control and supplemented groups. 240 ml of Punica granatum juice and tap water were given to supplement and control groups daily for two weeks, respectively. Fasting blood samples were taken at the starting and the end of two weeks of intervention. Subjects were given once severe physical activity and then fasting blood samples were taken. Fasting blood samples were used for testing of oxidative and antioxidative factors. Data were analyzed using descriptive statistical tests, paired samples t-test, and independent samples t-test. Results: The levels of arylesterase, superoxide dismutase, glutathione peroxidase and total antioxidant capacity after severe physical activity in supplement group were significantly increased (p<0.05), while the content of malondialdehyde showed a significantly decrease in comparison to control group (p<0.05). Conclusion: Our findings indicate that regular intake of Punica granatum juice significantly modulates oxidative stress and thus protects against severe physical activity oxidative injury in young healthy males.
The BeppoSAX View of the X-Ray Active Nucleus of NGC 4258

BeppoSAX observed the Seyfert 1.9 galaxy NGC 4258 in 1998 December, when its 2-10 keV luminosity was about 1041 ergs s-1. Large amplitude (100%) variability is observed in the 3-10 keV band on timescales of a few tens of thousands of seconds, while variability of ~20% is observed on timescales as short as 1 hr. The nuclear component is visible above 2 keV only, being obscured by a column density of (9.5 ± 1.2) × 1022 cm-2; this component is detected at up to 70 keV with a signal-to-noise ratio of ≳3 and with a steep power-law energy spectral index of αE = 1.11 ± 0.14. Bremsstrahlung emission for the 2-70 keV X-ray luminosity, as expected in advection-dominated accretion flow models with strong winds, is ruled out by the data. The ratio between the nuclear radio (22 GHz) luminosity and the X-ray (5 keV) luminosity is consistent with that of radio-quiet quasars and Seyfert galaxies. X-ray variability, spectral shape, and radio/X-ray and near-IR/X-ray luminosity ratios suggest that the nucleus of NGC 4258 could be a scaled down version of a Seyfert nucleus and that the X-ray nuclear luminosity can be explained in terms of Comptonization in a hot corona. The soft (E ≲ 2 keV) X-ray emission is complex. There are at least two thermal-like components with temperatures of 0.6 ± 0.1 keV and ≳1.3 keV. The cooler (L0.1-2.4 keV~ 1040 ergs s-1) component is probably associated with the jet, resolved in X-rays by the ROSAT HRI (Cecil et al. 1994). The luminosity of the second component, which can be modeled equally well by an unobscured power-law model with αE = 0.2, is L0.1-2.4 keV~ 7 × 1039 ergs s-1, consistent with that expected from discrete X-ray sources (binaries and supernova remnants) in the host galaxy. Observations of NGC 4258 and other maser active galactic nuclei (AGNs) show strong nuclear X-ray absorption. We propose that this large column of gas might be responsible for shielding the regions of water maser emission from X-ray illumination. So a large column density absorbing gas may be a necessary property of masing AGNs.
Effects of PKA-Mediated Phosphorylation of Snapin on Synaptic Transmission in Cultured Hippocampal Neurons

Use-dependent activation of protein kinase A (PKA) modulates transmitter release, contributing to synaptic plasticity. Snapin, a PKA substrate in neurons, associates with the soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complex, and its phosphorylation leads to increased binding of synaptotagmin to the SNARE complex. We investigated the role of PKA-dependent phosphorylation of Snapin in hippocampal neurons. Overexpression of Snapin S50D, a mutant mimicking the phosphorylated state, resulted in a decreased number of readily releasable vesicles. In addition, both the release probability of individual vesicles and the depression rate during high-frequency stimulation were increased. Overexpression of Snapin S50A, a mutant that cannot be phosphorylated, did not alter the size of the pool or the probability of release. Furthermore, dialysis of Sp-cAMPS, a nonhydrolyzable analog of cAMP that will promote phosphorylation by PKA, also led to increased synaptic depression in cells overexpressing wild-type Snapin. These results establish Snapin as an important target of PKA in CNS synapses and indicate a role for Snapin in the plasticity of transmitter release.
IPACT: A dynamic protocol for an Ethernet PON (EPON)

We investigate design issues for access networks based on passive optical network technology. A PON based on polling, with data encapsulated in Ethernet frames, possesses many desirable qualities, such as dynamic bandwidth distribution, use of a single downstream and a single upstream wavelength, ability to provision a fractional wavelength capacity to each user, and ease of adding a new user. To support dynamic bandwidth distribution, we propose an interleaved polling algorithm called IPACT. We also suggest a scheme for in-band signaling that allows using a single wavelength for both downstream data and control message transmission. To obtain realistic simulation results, we generated synthetic traffic that exhibits the properties of self-similarity and long-range dependence. We then analyzed the network performance under varying offered loads.
Quantile Regression for Dynamic Panel Data

This paper studies estimation and inference in a quantile regression dynamic panel model with fixed effects. To reduce the dynamic bias we develop an instrumental variables approach that employs lagged regressors as instruments. We show that the proposed estimators are consistent and asymptotically normal. We suggest Wald and Kolmogorov-Smirnov type tests for general linear restrictions. Monte Carlo studies are conducted to evaluate the finite sample properties of the estimators and tests. The instrumental variables approach turns out to be especially advantageous in terms of the bias, root mean square error, and power of the test statistics when innovations are non-Gaussian and heavy-tailed. We illustrate the new approach by testing for the presence of time non-separability in utility using household consumption panel data. The results show evidence of asymmetric persistence in consumption dynamics.