Miracle-dz/UniFAR-FTUs huggingface dataset:
Tumor Agnostic Drug Delivery with Self-Agglomerating Nanohydrogels (SANGs)

RNA interference (RNAi) holds unique potential as a clinically viable modality to pharmacologically regulate oncogenes in sequence-specific manner. Despite its potential, systemic delivery of RNAi to tumors encounters myriad obstructions and strategies to overcome barriers have largely consisted of academic demonstrations, with few approaches reaching patients. Here, we report the development of a self-agglomerating nanohydrogel (SANGs) platform that is efficiently internalized by cancer cells, is agnostic to RNAi payload, and achieves functional suppression of multiple oncogene targets. After intravenous injection, SANGs preferentially accumulated and were retained ubiquitously in primary and metastatic loci in three aggressive cancer models in a species-agnostic manner. SANGs efficiently delivered multiple RNAi payloads that significantly suppressed oncogene expression and sensitized previously resistance tumors in vivo. SANGs were found to be safe and well tolerated in simulated clinical applications across three species. We then propose and verify a novel emergent mechanism by which SANGs achieve durable solid-tumor delivery without direct functionalization. Overall, our SANGs platform is an enabling technology for RNAi-based cancer therapeutics and is poised for advanced pharmaceutical development with multiple solid-tumor indications. One-Sentence Summary Our nanostructure achieves safe and durable tumor-agnostic delivery through a newly described environmentally-responsive mechanism.
Characteristics of the Low-Level Temperature Inversion at the North Slope of Alaska on the Base of Microwave Remote Sensing Data

In Barrow, Alaska, during the winter period from January to April, 85% of radiosonde soundings detected the first type, and only about 10% elevated inversion (Busch et al. 1982) (not more than 25% according to Kahl [1990]). Usually radiation inversions are connected with a downward turbulent flux of sensible heat at the surface and thus have negative net radiation. All those inversions are the surface inversion. The analysis of radiation climate at Barrow (Maykut et al. 1973) shows that, between October and April, the radiation balance is dominated by the net longwave radiation resulting in its negative values during these months. Melting is the other surface type inversion typical for summer (20% to 30%). Lifted inversions are controlled by thermodynamic budgets of the layers of concern and by the surface energy fluxes.
Information Dynamics of the Heart and Respiration Rates: a Novel Venue for Digital Phenotyping in Humans

In recent decade, wearable digital devices have shown potentials for the discovery of novel biomarkers of humans’ physiology and behavior. Heart rate (HR) and respiration rate (RR) are most crucial bio-signals in humans’ digital phenotyping research. HR is a continuous and non-invasive proxy to autonomic nervous system and ample evidence pinpoints the critical role of respiratory modulation of cardiac function. In the present study, we recorded longitudinal (up to 6 days, 4.63 ± 1.52) HR and RR of 89 freely-behaving human subjects (Female: 39, age 57.28 ± 5.67, Male: 50, age 58.48 ± 6.32) and analyzed their HR and RR dynamics using linear models and information theoretic measures. While the predictability by linear autoregressive (AR) showed correlation with subjects’ age, an information theoretic measure of predictability, active information storage (AIS), captured these correlations more clearly. Furthermore, analysis of the information flow between HR and RR by transfer entropy (i.e., HR → RR and RR → HR) revealed that RR → HR is correlated with alcohol consumption and exercise habits. Thus we propose the AIS of HR and the transfer entropy RR → HR as two-dimensional biomarkers of cardiorespiratory physiology for digital phenotyping. The present findings provided evidence for the critical role of the respiratory modulation of HR, which was previously only studied in non-human animals.
Mechanosensitivity of an ABC Membrane Transporter Revealed by Single Molecule FRET and Activity Measurement

While mechanosensitive ion channels’ gating has been well documented, the effect of membrane mechanics, in particular membrane curvature, on the function of transporters remains elusive. Since conical shape transmembrane proteins locally deform membranes, conversely membrane bending could impact their conformations and their function. We tested this hypothesis using BmrA, a bacterial ABC exporter that exhibits large conformational changes upon ATP hydrolysis, switching between open and closed states with opposite V-shapes. After reconstitution in liposomes of controlled curvature, we showed that BmrA ATPase activity decreases by 2.9-fold when their diameter decreases from 125 to 29 nm. Moreover, using single-molecule FRET, we observed that the fraction of closed conformations is significantly reduced in highly curved vesicles when adding ATP or non-hydrolysable AMP-PNP. Our results are well explained by a theoretical 2-states model including the effect of membrane mechanics on protein shape transition. Our work reveals that the functional cycle of conical transporters is curvature sensitive, to an extent depending on protein geometry. Teaser High membrane curvature strongly impacts the functional cycle of transporters
Treatment of a genetic liver disease in mice through transient prime editor expression

Prime editing is a versatile genome editing technology that does not rely on DNA double-strand break formation and homology-directed repair (HDR). This makes it a promising tool for correcting pathogenic mutations in tissues consisting predominantly of postmitotic cells, such as the liver. While recent studies have already demonstrated proof-of-concept for in vivo prime editing, the use of viral delivery vectors resulted in prolonged prime editor (PE) expression, posing challenges for clinical application. Here, we developed an in vivo prime editing approach where we delivered the pegRNA using self-complementary adeno-associated viral (scAAV) vectors and the prime editor using nucleoside-modified mRNA encapsulated in lipid nanoparticles (LNPs). This methodology led to transient expression of the PE for 48h and 26% editing at the Dnmt1 locus using AAV doses of 2.5×1013 vector genomes (vg)/kg and a single dose of 3mg/kg mRNA-LNP. When targeting the pathogenic mutation in the Pahenu2 mouse model of phenylketonuria (PKU), we achieved 4.3% gene correction using an AAV dose of 2.5×1013 vg/kg and three doses of 2 mg/kg mRNA-LNP. Editing was specific to the liver and the intended locus, and was sufficient to reduce blood L-phenylalanine (Phe) levels from over 1500 µmol/l to below the therapeutic threshold of 600 µmol/l. Our study demonstrates the feasibility of in vivo gene correction in the liver with transient PE expression, bringing prime editing closer to clinical application.
Bridging DNA contacts allow Dps from E. coli to condense DNA

The DNA-binding protein from starved cells (Dps) plays a crucial role in maintaining bacterial cell viability during periods of stress. Dps is a nucleoid-associated protein that interacts with DNA to create biomolecular condensates in live bacteria. Purified Dps protein can also rapidly form large complexes when combined with DNA in vitro. However, the mechanism that allows these complexes to nucleate on DNA remains unclear. Here, we examine how DNA topology influences the formation of Dps-DNA complexes. We find that DNA supercoils offer the most preferred template for the nucleation of condensed Dps structures. More generally, bridging contacts between different regions of DNA can facilitate the nucleation of condensed Dps structures. In contrast, Dps shows little affinity for stretched linear DNA before it is relaxed. Once DNA is condensed, Dps forms a stable complex that can form inter-strand contacts with nearby DNA, even without free Dps present in solution. Taken together, our results establish the important role played by bridging contacts between DNA strands in nucleating and stabilizing Dps complexes. Graphical Abstract Graphical Abstract. Working model of nucleation and formation of Dps-DNA complex. Regions of supercoiled or stochastically bent DNA act as nucleation points for the formation of Dps-DNA complexes by allowing Dps to form bridging contacts. Dps does not readily bind to straight stretches of DNA in isolation. Once Dps-DNA complexes are formed they can form bridging contacts to bind additional DNA.
The changed pattern of malaria endemicity and transmission at Amani in the eastern Usambara mountains, north-eastern Tanzania.

: Parasitological and entomological studies on malaria were conducted between 1980 and 1982 on the Amani hills in the eastern Usambara mountains of north-eastern Tanzania. Malaria vectors were scarce on the Amani hills until the late 1960s and it was generally presumed that any cases of malaria transmission must have been contracted by people while visiting lower altitudes where malaria is holoendemic. However, the malaria vectors Anopheles funestus and An. gambiae have both become more abundant during the 1970s and 1980s and sporozoite-positive specimens of both have been found. Malaria asexual parasite rates have been shown to have increased, for instance from 52.7% in 1980 to 53.8% and 63.7% in 1981 and 1982, respectively. The percentage of parasitized children aged below 1 year whose parents report that they have not visited lowland localities away from the Amani hills has increased, from 71.4% in 1980 to 80.0% and 91.0% in 1981 and 1982, respectively, suggesting possible local malaria acquisition. These parameters have been confirmed by increasing sporozoite rates from 0.0% in 1967-1971 to 0.09% in May-June 1973 and 11.1% in August and December 1980. Various factors including climatological changes and increased agricultural activities are attributable to this changed malaria endemicity and transmission.
Understanding the spatio‐temporal influence of climate variability on Australian heatwaves

Some of the major drivers of extreme temperatures in Australia are related to large‐scale variations in the climate. While many of the relationships between climate variability and heatwaves have been described, the preceding climate conditions and the circulation patterns responsible for interannual heatwave variations are still poorly understood. We have used rotated principal component analysis (PCA) to describe the variance of frequency, duration, magnitude and timing of Australian summer heatwaves. This provides a simple means of investigating both the spatial patterns of circulation and the preceding climate mode conditions of summer heatwaves. We find that spatial patterns of heatwave variability associated with El Niño‐Southern Oscillation (ENSO) were focused in the north and northeast of Australia for heatwave occurrence. Patterns of heatwave amplitude in southeastern Australia were also weakly related to ENSO. The PCA did not find any direct, concurrent Indian Ocean Dipole (IOD) or Southern Annular Mode (SAM) signal. However, lead correlations indicate that winter IOD conditions can have a weak indirect effect on heatwave occurrence in northeast Australia and similarly, winter SAM conditions can affect heatwave timing in central eastern Australia. Regressions reveal that ENSO related heatwave duration and frequency in the northeast are related to the movement of the Walker circulation, while southeastern heatwave amplitude is associated with a north–south movement of the Tasman high pressure system. These results may lead to improvements in understanding the predictability and general preparedness for heatwaves in the summer season.
CDK5RAP3 Participates in Autophagy Regulation and Is Downregulated in Renal Cancer

Renal cancer is one of the most common malignant urological tumors; however, its diagnosis and treatment are not well established. In the present study, we identified that CDK5 regulatory subunit-associated protein 3 (CDK5RAP3), a putative tumor suppressor in many cancers, was downregulated in renal cancer tissues. Through loss- and gain-of-function experiments, we observed that the action of CDK5RAP3 in renal cancer cells was different in Caki-1 and 769-P cell lines. Knockdown of endogenous CDK5RAP3 in Caki-1 slightly increased cell viability, whereas overexpression of CDK5RAP3 in 769-P cells inhibited cell viability. In addition, we observed that CDK5RAP3 participated in the regulation of autophagy in renal cancer. Knockdown of CDK5RAP3 induced significant inhibition of autophagy in Caki-1 cells but not in 769-P cells. In contrast, overexpression of CDK5RAP3 significantly activated autophagy in 769-P cells, as evidenced by increased LC3-II levels. However, the LC3-II could not be altered by CDK5RAP3 overexpression in Caki-1 cells. These findings demonstrated that CDK5RAP3 is downregulated in renal cancer and may be associated with autophagy.
Markups, Profit Shares, and Cost-Push-Profit-Led Inflation by

The post-pandemic surge in inﬂation was accompanied by a surge in the corporate share of proﬁts. As a result, several economists and policy makers have given to it names such as “proﬁt-led inﬂation” or “sellers’ inﬂation. ” The present paper discusses the extent to which proﬁt-led inﬂation, as an explanation for the recent surge in inﬂation, is compatible with what we know about the price-setting behavior of ﬁrms, income distribution, and inﬂation. We do that in juxtaposition to two recent critiques: that the increase in the proﬁt share is the result of cyclical factors, and that the increase in import prices leads to higher proﬁt shares even under constant markups. We show that there is little evidence that the recent surge in proﬁtability is cyclical in nature. Moreover, after outlining the Structuralist/Kaleckian theories of prices and inﬂation we argue that proﬁt-led inﬂation does not require an increase in the markup of the ﬁrms and is consistent with these theories. In the face of large import and other price shocks even under constant markups, ﬁrms are able to pass the burden of adjustment to real wages. Thus, the term proﬁt-led emphasizes the distributional source and consequences of inﬂation. We also provide an empirical examination of the markups in the post-pandemic period using data from the Compustat database. We show that, on average, ﬁrms were able to increase or maintain their markups, although there is signiﬁcant heterogeneity across sectors or the position of the ﬁrms in the distribution of markups.
Feeding management practices followed by farmers rearing Hariana cattle in its breeding tract

The study was conducted in Hisar, Biwani, Rohtak and Jhajjar districts of Haryana state in India to assess the socioeconomic profile, technology adoption and constraints of the farmers rearing Hariana cattle in its breeding tract. A total of 240 respondents (60 respondents from each district) were purposively selected and interviewed individually using structured questionnaire prepared for the purpose. Different feeding management practices were recorded and it was found that 41.7% of the respondents preferred grazing and stall feeding system and 58.3 % of them practiced only stall feeding. In the case of types of fodder fed to cattle, mostly dry fodders like wheat straw and paddy straw were fed due to its availability round the year and easy to preserve for its less moisture content which reduce the chances of mould growth and spoilage. Green fodder availability was more during winter and rainy seasons than summer. The respondents provided concentrate feed only to milch cattle and the average quantity of concentrate feed given was 2 to 4 kg/day/animal supplemented with 0-40 kg green fodder and 2-8 kg straw depending upon the seasons. Majority (90.0%) of the respondents were not using mineral mixture in animal‘s diet. None of farmer were aware about preservation of fodder crop methods like hay and silage as farmers are having poor economic status, non-availability of skilled workers and poor knowledge about preservation methods. In respect to calf feeding practices, 63.8 per cent of the respondents are feeding colostrum to calf after the placenta was shed and others are feeding colostrum immediately. The results helps in educating the farmers regarding the advanced feeding methods and feeding interventions during different physiological status of the animal depending on their feeding strategies.
Effects of Epistemological and Pedagogical Beliefs on the Effects of Epistemological and Pedagogical Beliefs on the Instructional Practices of Teachers: A Chinese Perspective Instructional Practices of Teachers: A Chinese Perspective

: This study examines how the beliefs of Chinese in-service teachers regarding knowledge and knowledge acquisition influence their instructional classroom practices in junior secondary schools directly or indirectly through their conceptions of teaching and learning. The results indicate that the factor of learning effort/process is highly valued by Chinese in-service teachers in their epistemological beliefs, and that the constructivist approach is the dominant conception on teaching and learning for junior secondary school teachers. In addition, the constructivist conception of teaching and learning is found to be positively related to three types of classroom instructional practices, whereas the traditional conception about teaching and learning is found to be only significantly and negatively linked to standard contemporary practices.
Cenozoic pelagic accumulation rates and biased sampling of the deep sea record

Global weathering is a primary control of the earth’s climate over geologic time scales: converting atmospheric p CO 2 into dissolved bicarbonate; with carbon sequestration by marine plankton as carbonate and organic carbon on the ocean ﬂoor. The accumulation rate of pelagic marine biogenic sediments are thus a measure of weathering history. Previous studies of Cenozoic pelagic sedimentation have yielded contrasting results, though most show a dramatic rise (up to 6 times) in rates over the Cenozoic. This contrasts with model expectations for approximate steady state in weathering, p CO 2 , and sequestration 5 over time. Here we show that the Cenozoic record of sedimentation recovered by deep sea drilling has a strong, systematic bias towards lower rates of sedimentation with increasing age. When this bias is removed accumulation rates are shown to actually decline by ca 2 times over the Cenozoic. When accumulation area however is adjusted for changes in available deposition area, global weathering is shown to have nearly doubled at the Eocene-Oligocene boundary, but was otherwise essentially constant. Compilations of other metrics correlated to sedimentation rate (e.g. productivity, biotic composition) also must have a strong 10 age bias, which will need to be considered in future paleoceanographic studies.
Food waste in the context of Poland’s food security: identifying research path dependency through bibliometric research

Laba, S. & Olech, I. (2023). Food waste in the context of Poland’s food security: identifying research path dependency through bibliometric research. Bulg. J. Agric. Sci. , 29 (Supplement 1), 140–146 Food waste is often mentioned in the context of food security. Meanwhile, the research on the subject of food waste mainly focuses on the ex-post management of the food waste (i.e. the waste that is , mainly through channelling food waste as a bioenergy source), rather than on the ex-ante management (i.e. limiting the amount of food waste to-be ). Thus, food waste research trends towards energy security, rather than food security. The goal of our research was to identify whether it is a similar case for the Polish research on the topic. We have applied the method of bibliometric analysis using the software RStudio and VOSviewer to identify potential keyword overlap and to identify the common points between food waste and food security in Polish publications.
Correct-By-Construction Microservices with Model-Driven Engineering The Case for Architectural Pattern Conformance Checking and Pattern-Conform Code Generation

Patterns are a common metaphor in software engineering that denotes reusable solutions for recurring software engineering problems. Architectural patterns focus on the interplay or organization of two or more components of a software system, and are particularly helpful in the design of complex software architectures such as those produced by Microservice Architecture (MSA). This paper presents an approach for the language-based reification of architectural MSA patterns. To this end, we introduce a method to flexibly retrofit LEMMA (Language Ecosystem for Modeling Microservices) with support for modeling and implementing architectural MSA patterns. The method relies on the (i) specification of aspects to reify pattern applications in MSA models; (ii) validation of pattern applications; and (iii) code generation from correct pattern applications. Consequently, it contributes to correct-by-construction microservices by abstracting from the complexity of pattern implementations, yet still enabling their automated production with Model-Driven Engineering. We validate our method with the popular Domain Event and Command Query Responsibility Segregation patterns, and assess its applicability for 28 additional patterns. Our results show that LEMMA’s expressivity covers the model-based expression of complex architectural MSA patterns and that its model processing facilities support pattern-specific extensions such that conformance checking and pattern-conform code generation can be modularized into reusable model processors.
Polymers & biopolymers The effect of high‑intensity gamma radiation on PETG and ASA polymer‑based fused deposition modelled 3D printed parts

There is growing interest in the application of 3D printing for demanding environments subject to gamma radiation in areas such as the nuclear industry and space exploration. In this work, the effect of gamma radiation on fused deposition modelled 3D printed parts composed of polyethylene terephthalate glycol (PETG) and acrylic styrene acrylonitrile (ASA) polymers was studied. Dose levels of up to 2.25 MGy were applied to the printed components, doses equivalent to over 1 year operating near spent nuclear fuel cells. Infrared spectroscopy showed the evidence of cross-linking by the formation of peaks corresponding to –OH and C–H bonds. Tensile and hardness testing was used to assess changes in mechanical properties and showed a reduction in ultimate tensile stress and maximum strain in parts made from both polymers, but with PETG retaining greater strength and ductility than ASA, especially at intermediate gamma exposure. Young’s modulus and hardness showed either modest increases or a fairly flat response with exposure. Mechanical properties were heavily dependent on the build structure, with horizontal build samples pulled parallel to the filament direction being several times stronger than vertical build samples pulled normal to the layers. Non-irradiated samples pulled parallel to the filament direction were indicative of ductile failure, with rough surfaces, distinct infill and wall regions and evidence of thinning occurring after fracture, but irradiated fracture surfaces were flat-ter, smoother and without local thinning, suggesting gamma radiation-induced embrittlement