Miracle-dz/UniFAR-FTUs huggingface dataset:
L-DOS47 enhances response to immunotherapy in pancreatic cancer tumor

Acidosis is an important immunosuppressive mechanism that leads to tumor growth. Therefore, we investigated the neutralization of tumor acidity to improve immunotherapy response. L-DOS47, a new targeted urease immunoconjugate designed to neutralize tumor acidity, has been well tolerated in phase I/IIa trials. L-DOS47 binds CEACAM6, a cell surface protein highly expressed in gastrointestinal cancers, allowing urease to cleave endogenous urea into two NH4+ and one CO2, thereby raising local pH. To test the synergetic effect of neutralizing tumor acidity with immunotherapy, we developed a pancreatic orthotopic murine tumor model (KPC961) expressing human CEACAM6. Our results demonstrate that combining L DOS47 with anti-PD1 significantly increases the efficacy of anti-PD1 monotherapy, reducing tumor growth for up to 4 weeks.
Inhibiting sorting nexin 10 promotes mucosal healing through SREBP2-mediated stemness restoration of intestinal stem cells

Intestinal stem cell (ISC) is a promising therapeutic target for inflammatory bowel disease. Cholesterol availability is critical for ISC stemness. Low plasma cholesterol is a typical feature of Crohn’s disease (CD); however, its impact on mucosal healing remains unclear. Here, we identified an essential role of sorting nexin 10 (SNX10) in maintaining the stemness of ISCs. SNX10 expression in intestinal tissues positively correlates with the severity of human CD and mouse colitis. Conditional SNX10 knockout in intestinal epithelial cells or ISCs promotes intestinal mucosal repair by maintaining the ISC population associated with increased intracellular cholesterol synthesis. Disassociation of ERLIN2 with SCAP by SNX10 deletion enhances the activation of SREBP2, resulting in increased cholesterol biosynthesis. DC-SX029, a small-molecule inhibitor of SNX10, was used to verify the druggable potential of SNX10 for the treatment of patients with CD. Our study provides a strategy for mucosal healing through SREBP2-mediated stemness restoration of ISCs.
The link between the popularity of cremation in the Czech Republic and religious faith

In the last one hundred years, Czech lands and Europe in general have witnessed a significant change in burial culture. In some countries, cremation has evolved into a dominant method of human burial, but Europe is highly differentiated in this respect despite its common Christian tradition. Does this change in burial culture reflect changes in religiosity? The largely secular Czechia ranks first in the practice of cremation not only in Europe but also worldwide. This paper discusses changes in burial methods in Europe, which are a reflection of socio-political processes that ultimately lead to more frequent cremation, and the role of cremation in religion is also discussed. One of the aims of the paper is to stimulate the geographer’s/reader’s interest in the subject of death and burial, which are issues that remain on the margins of world geography, and yet say so much about the cultural development of our society.
Diabetic retinopathy in African Americans with type 1 diabetes: The New Jersey 725: I. Methodology, population, frequency of retinopathy, and visual impairment.

OBJECTIVE To determine the frequency and severity of diabetic retinopathy, as well as associated visual impairment, among African Americans with type 1 diabetes. METHODS A total of 725 African Americans with type 1 diabetes were enrolled in the study (The New Jersey 725). Clinical evaluations included structured clinical interview, ocular examination, stereoscopic fundus photography, and blood pressure measurements. Severity of retinopathy was determined via masked grading of fundus photographs. Biological evaluations included blood and urine assays. RESULTS Of the 725 patients, 463 (63.9%) presented with any diabetic retinopathy and 137 (18.9%) with proliferative diabetic retinopathy. The frequency and severity of retinopathy were both significantly associated with older age at examination. Visual impairment (visual acuity in the better eye < or =20/40) was present in 79 (11.0%) and legal blindness in 22 (3.1%) of the patients. Diabetic retinopathy was responsible for 90.9% of the blindness. Frequency of visual impairment was significantly associated with older age and female sex, and only weakly with lower education. CONCLUSIONS Diabetic retinopathy in African Americans with type 1 diabetes is common, being found in almost two thirds of the patients studied. Its frequency and severity increase with age. Visual impairment is common, increasing with age and duration of diabetes and is more frequent in women than in men.
A H\"older-type inequality for the Hausdorff distance between Lagrangians

We prove a H\"older-type inequality for the Hausdorff distance between Lagrangians with respect to the Lagrangian spectral distance or the Hofer-Chekanov distance in the spirit of Joksimovi\'c-Seyfaddini [arXiv:2207.11813]. This inequality is established via methods developped by the first author [arXiv:2204.02468, arXiv:2108.00555] in order to understand the symplectic geometry of certain collections of Lagrangians under metric constraints.
The utility of CRISPR activation as a platform to identify interferon stimulated genes with anti-viral function

Interferon Stimulated Genes (ISGs) play key roles in the control of viral replication and dissemination. Understanding this dynamic relationship between the pathogen and host is critical to our understanding of viral life-cycles and development of potential novel anti-viral strategies. Traditionally, plasmid based exogenous prompter driven expression of ISGs has been used to investigate anti-viral ISG function, however there are deficiencies in this approach. To overcome this, we investigated the utility of CRISPR activation (CRISPRa), which allows for targeted transcriptional activation of a gene from its endogenous promoter. Using the CRISPRa-SAM system to induce targeted expression of a panel of anti-viral ISGs we showed robust induction of mRNA and protein expression. We then employed our CRISPRa-SAM ISG panel in several antiviral screen formats to test for the ability of ISGs to prevent viral induced cytopathic cell death (CPE) and replication of Dengue Virus (DENV), Zika Virus (ZIKV), West Nile Virus Kunjin (WNVKUNV), Hepatitis A Virus (HAV) and Human Coronavirus 229E (HCoV-229E). Our CRISPRa approach confirmed the anti-viral activity of ISGs like IFI6, IFNβ and IFNλ2 that prevented viral induced CPE, which was supported by high-content immunofluorescence imaging analysis. This work highlights CRISPRa as a rapid, agile, and powerful methodology to identify and characterise ISGs and viral restriction factors.
Impacts of environmental decontamination on the rebuilding of returnees’ lives after the Fukushima accident

Environmental decontamination after a nuclear disaster not only contributes to reducing the public’s exposure to radiation, it also introduces waste disposal issues arising from the decontamination process. In addition to that issue, the optimisation of decontamination efforts necessitates the consideration of various environmental, economic, and societal factors. Stakeholders’ perspectives are important for identifying the multifaceted aspects to be considered. We conducted a semi-structured interview survey in 2019 with ten residents in a rural community in Fukushima, Japan, which experienced a six-year-long evacuation due to the 2011 Fukushima Daiichi Nuclear Power Plant accident. The main survey questions addressed returnees’ perceptions of the decontamination of farmlands and forests. The ‘Steps for Coding and Theorization’ procedure was used for qualitative analysis. The analysis illuminated the positive and negative impacts of the decontamination process on the rebuilding of the returnees’ rural lives from various perspectives and identified elements to be considered for the optimisation of future remediation efforts. The removal of radioactive materials had a positive psychological impact on the returnees, fostering a sense of security that their crops were safe and instilling confidence that the high-quality environment of the region had been restored. These aspects were not included among the initial governmental objectives for decontamination, which were aimed solely at reducing radiation exposure. By contrast, the removal of fertile topsoil from farmland had a negative impact on the residents, making them hesitant to resume farming. Our findings suggest that emphasising procedural fairness in decision-making of decontamination options such as reflection of stakeholders’ opinions led to residents perceiving their post-decontamination situation more positively. Our results provide valuable insights for optimising remediation strategies for the recovery process following a significant nuclear accident.
A Technique for Removing Large-scale Variations in Regularly and Irregularly Spaced Data

In many astrophysical systems, smooth large-scale variations coexist with small-scale fluctuations. For example, a large-scale velocity or density gradient can exist in molecular clouds that have small-scale fluctuations by turbulence. In redshifted 21 cm observations, we also have two types of signals—the Galactic foreground emissions that change smoothly and the redshifted 21 cm signals that fluctuate fast in frequency space. In many cases, the large-scale variations make it difficult to extract information on small-scale fluctuations. We propose a simple technique to remove smooth large-scale variations. Our technique relies on multi-point structure functions and can obtain the magnitudes of small-scale fluctuations. It can also be used to design filters that can remove large-scale variations and retrieve small-scale data. We discuss how to apply our technique to irregularly spaced data, such as rotation measure observations toward extragalactic radio point sources.
Health action process approach: promoting physical activity, and fruit and vegetable intake among Australian adults

Abstract Based on the health action process approach (HAPA) this study examined whether changes in social cognition constructs could predict change in physical activity and fruit and vegetable intake for adult participants in My health for life, an Australian health promotion behaviour change program. Variance-based structural equation modelling was used to analyse data obtained from Australian adult program participants (n = 167) at baseline (T1), week 14 (T2), week 26 (T2), and 6-month post-program (T4). Change scores were calculated for the social cognition constructs and behaviour. Changes in action self-efficacy and outcome expectancies positively predicted changes in intentions. Action self-efficacy changes also predicted changes in maintenance self-efficacy which, in turn, mediated the effect of action self-efficacy on recovery self-efficacy and planning. Planning was predicted by changes in intentions and maintenance self-efficacy. Findings support the use of the HAPA model in designing complex health behaviour change interventions to achieve sustained behaviour change.
Observations and modelling of the variability of the Solent-Southampton Water estuarine system

Understanding the effect of physical forcing on estuarine functioning is of major importance to determine the rate of exchange of water, sediments, pollutants and nutrients between the continent and the ocean. The combination of numerical models and discrete datasets is used to describe and investigate processes of natural variability in the partially-mixed, non-turbid, macrotidal Solent-Southampton Water estuarine system (UK). The estuarine circulation and the response of wind forcing is examined using a three dimensional, free surface, finite volume and finite element grid model. Results from short-term (three months) simulations have been compared against data (ADCP measurements, tidal elevations and salinity distributions) collected in spring 2001 in Southampton Water and the Solent. The model reproduces the unique tidal curve of Southampton Water and the partially-mixed conditions prevailing in the upper estuary. The contribution of the local wind forcing (wind intensity · 12 m s? 1) to changes in water level is estimated to be up to 6 cm in Southampton Water in the model. The modelled salinity stratification varies over a semi-diurnal cycle with the highest stratification occuring at mid-ebb. Wind forcing is more efficient in altering stratification at ebb than flood. The temporal and spatial variability of light attenuation is also investigated. Turbidity is demonstrated to be the major contribution to light attenuation using a time-series of discrete data collected in 2001, 2002 and 2003. A typical seasonal cycle of the coefficient of light attenuation is revealed, with a minimum in May-June and a maximum occuring in September-October. A second dataset of continuous measurements (10-minute interval) demonstrates the spring-neap modulation of the turbidity. The mouth of Southampton Water is more exposed to tidal mixing and therefore more turbid than the mid-estuary. A five-compartment zero-dimensional pelagic ecosystem model including a sediment compartment has been developed to assess the impact of the variability of the light attenuation on the timing and the magnitude of the spring phytoplankton bloom. Using high resolution irradiance forcing and a constant coefficient of attenuation k set to the minimum May-June value, simulations compare well with discrete data of chlorophyll a, and less successfully with zooplankton and Dissolved Inorganic Nitrogen. A sensitivity analysis indicates that interranual variability in the phytoplankton spring bloom originates in order of importance from 1) parameterization of k 2) the variation of the seasonal cycle of surface irradiance 3) the intrinsic dynamics determined by the combination of fixed parameters of the ecosystem model.
A Survey on Deep Learning Based Forest Environment Sound Classification at the Edge

Forest ecosystems are of paramount importance to the sustainable existence of life on earth. Unique natural and artificial phenomena pose severe threats to the perseverance of such ecosystems. With the advancement of artificial intelligence technologies, the effectiveness of implementing forest monitoring systems based on acoustic surveillance has been established due to the practicality of the approach. It can be identified that with the support of transfer learning, deep learning algorithms outperform conventional machine learning algorithms for forest acoustic classification. Further, a clear requirement to move the conventional cloud-based sound classification to the edge is raised among the research community to ensure real-time identification of acoustic incidents. This article presents a comprehensive survey on the state-of-the-art forest sound classification approaches, publicly available datasets for forest acoustics, and the associated infrastructure. Further, we discuss the open challenges and future research aspects that govern forest acoustic classification.
Statistical properties of the deviations of f 0 F 2 from monthly medians

The deviations of hourly f 0 F 2 from monthly medians for 20 stations in Europe during the period 1958-1998 are studied. Spectral analysis is used to show that, both for original data (for each hour) and for the deviations from monthly medians, the deterministic components are the harmonics of 11 years (solar cycle), 1 year and its harmonics, 27 days and 12 h 50.49 m (2nd harmonic of lunar rotation period L 2 ) periodicities. Using histograms for one year samples, it is shown that the deviations from monthly medians are nearly zero mean (mean < 0.5) and approximately Gaussian (relative difference range between %10 to %20) and their standard deviations are larger for daylight hours (in the range 5-7). It is shown that the amplitude distribution of the positive and negative deviations is nearly symmetrical at night hours, but asymmetrical for day hours. The positive and negative deviations are then studied separately and it is observed that the positive deviations are nearly independent of R12 except for high latitudes, but negative deviations are modulated by R12 . The 90% confidence interval for negative deviations for each station and each hour is computed as a linear model in terms of R12. After correction for local time, it is shown that for all hours the confidence intervals increase with latitude but decrease above 60N. Long-term trend analysis showed that there is an increase in the amplitude of positive deviations from monthly means irrespective of the solar conditions. Using spectral analysis it is also shown that the seasonal dependency of negative deviations is more accentuated than the seasonal dependency of positive deviations especially at low latitudes. In certain stations, it is also observed that the 4th harmonic of 1 year corresponding to a periodicity of 3 months, which is missing in f 0 F 2 data, appears in the spectra of negative variations.
falsify: Internal Shrinking Reimagined for Haskell

In unit testing we apply the function under test to known inputs and check for known outputs. By contrast, in property based testing we state properties relating inputs and outputs, apply the function to random inputs, and verify that the property holds; if not, we found a bug. Randomly generated inputs tend to be large and should therefore be minimised. Traditionally this is done with an explicitly provided shrinker, but in this paper we propose a way to write generators that obsoletes the need to write a separate shrinker. Inspired by the Python library Hypothesis, the approach can work even across monadic bind. Compared to Hypothesis, our approach is more suitable to the Haskell setting: it depends on a minimal set of core principles, and handles generation and shrinking of infinite data structures, including functions.
El Niño oscillations impact anti-predator defences to alter survival of an herbivorous beetle in a neotropical wet forest

Abstract Little is known about the effects of El Niño-Southern Oscillation (ENSO) on tropical insect communities, even though they are suffering rapid declines in complexity and stability due to climate change. We explore the impact of fluctuations in local climate imposed by ENSO on the performance of herbivore defences mediating enemy interactions. In a widespread rainforest edge community, we quantified the mortality caused by five enemy guilds on the immature stages of the herbivorous beetle, Acromis sparsa. ENSO was a significant determinant of beetle mortality. During warmer, drier El Niño years, the survival of beetles decreased. This was due to increased egg parasitism by wasps, which reduced hatching. Additionally, ant predation on beetle larvae increased. Flies and wasps were in competition for larval prey in wetter, cooler La Niña years. Experimental removal of maternal guards or chemical shields revealed which ENSO-related parameters predicted larval mortality. Guarding was most effective against social wasps in La Niña, whereas shields proved most effective in El Niño. Two ENSO-related defence–enemy breakdowns occurred: (1) decoupling whereby the efficacy of a narrow defensive adaptation was reduced to increase mortality, and (2) mismatching whereby the resistance of a narrow defensive adaptation against non-targeted enemies was further reduced to increase mortality. These results highlight that defence efficacy against natural enemies can vary predictably with biotic and abiotic environmental conditions. ENSO events will increase breakdowns in defence-mediated interactions, shifts in competition among enemies, and species loss.
Brain mechanisms underlying the emotion processing bias in treatment-resistant depression

Depression is associated with a cognitive bias towards negative information and away from positive information. This biased emotion processing may underlie core depression symptoms, including persistent feelings of sadness or low mood and a reduced capacity to experience pleasure. The neural mechanisms responsible for this biased emotion processing remain unknown. Here, we had a unique opportunity to record stereotactic electroencephalography (sEEG) signals in the amygdala and prefrontal cortex (PFC) from 5 treatment-resistant depression (TRD) patients and 12 epilepsy patients (as control) while they participated in an affective bias task in which happy and sad faces were rated. First, compared with the control group, patients with TRD showed increased amygdala responses to sad faces in the early stage (around 300 ms) and decreased amygdala responses to happy faces in the late stage (around 600 ms) following the onset of faces. Further, during the late stage of happy face processing, alpha-band activity in PFC as well as alpha-phase locking between the amygdala and PFC were significantly greater in TRD patients compared to the controls. Second, after deep brain stimulation (DBS) delivered to bilateral subcallosal cingulate (SCC) and ventral capsule/ventral striatum (VC/VS), atypical amygdala and PFC processing of happy faces in TRD patients remitted toward the normative pattern. The increased amygdala activation during the early stage of sad face processing suggests an overactive bottom-up processing system in TRD. Meanwhile, the reduced amygdala response during the late stage of happy face processing could be attributed to inhibition by PFC through alpha-band oscillation, which can be released by DBS in SCC and VC/VS.
Detecting entrainment in Fermi-Bose mixtures

We propose an experimental protocol to directly detect the Andreev-Bashkin effect (entrainment) in the bulk mixture of a bosonic and fermionic superfluid using a ring geometry. Our protocol involves the interferometric detection of the entrainment-induced phase gradient across a superfluid due to the flow of another in which it is immersed. The choice of ring geometry eliminates variations in the stronger mean-field interaction which can thwart the detection of entrainment in other geometries. A significant enhancement of the entrainment phase shift signal is possible, if the dimer-boson scattering length turns out to be large, which can be measured by tuning the interaction to the limit of miscibility of the two superfluids. With suggested improvements and careful design implementation, one may achieve $\approx 67$% shift in the interferometer fringes.
Qualitative Corporate Disclosure and Credit Analysts' Soft Rating Adjustments

Several factors comprise the credit ratings analysts publicly report. While academics have extensively studied the quantitative models credit analysts employ, far less is known about the qualitative adjustments analysts make to their models’ outputs (\soft adjustments"). We examine whether and how credit analysts employ credit-relevant qualitative disclosure in making their credit risk assessments. Our results indicate that credit analysts impound the information conveyed by rms’ qualitative disclosure in their publicly-reported ratings. Our results further suggest that the \soft", but not \hard", adjustments are the mechanism by which the information in qualitative disclosure is impounded into the rating. While disclosure opacity plays a relatively minor role in analysts’ use of soft information, the extent of numerical disclosure that accompanies qualitative disclosure appears to convey precision and credibility. We then analyze the informativeness of credit rating changes that involve soft adjustments following Jorion et al. (2005). We nd that credit rating changes that involve soft adjustments are more informative than those that do not; however, the increase in informativeness diminishes after the repeal of the Regulation Fair Disclosure exemption for credit rating agencies.