Miracle-dz/UniFAR-FTUs huggingface dataset:
Design and characterization of a novel tumor‐homing cell‐penetrating peptide for drug delivery in TGFBR3 high‐expressing tumors

Targeted therapy has attracted more and more attention in cancer treatment in recent years. However, due to the diversity of tumor types and the mutation of target sites on the tumor surface, some existing targets are no longer suitable for tumor therapy. In addition, the long‐term administration of a single targeted drug can also lead to drug resistance and attenuate drug potency, so it is important to develop new targets for tumor therapy. The expression of Type III transforming growth factor β receptor (TGFBR3) is upregulated in colon, breast, and prostate cancer cells, and plays an important role in the occurrence and development of these cancers, so TGFBR3 may be developed as a novel target for tumor therapy, but so far there is no report on this research. In this study, the structure of bone morphogenetic protein 4 (BMP4), one of the ligands of TGFBR3 was analyzed through the docking analysis with TGFBR3 and sequence charge characteristic analysis, and a functional tumor‐targeting penetrating peptide T3BP was identified. The results of fluorescent labeling experiments showed that T3BP could target and efficiently enter tumor cells with high expression of TGFBR3, especially A549 cells. When the expression of TGFBR3 on the surface of tumor cells (HeLa) was knocked down by RNA interference, the high delivery efficiency of T3BP was correspondingly reduced by 40%, indicating that the delivery was TGFBR3‐dependent. Trichosanthin (TCS, a plant‐derived ribosome inactivating protein) fused with T3BP can enhance the inhibitory activity of the fusion protein on A549 cells by more than 200 times that of TCS alone. These results indicated that T3BP, as a novel targeting peptide that can efficiently bind TGFBR3 and be used for targeted therapy of tumors with high expression of TGFBR3. This study enriches the supply of tumor‐targeting peptides and provides a new potential application option for the treatment of tumors with high expression of TGFBR3.
Determination of internal reflectance for photonic glasses

We experimentally show that the angular distribution of diﬀusely transmitted light from highly scattering dense media, such as photonic glasses, deviates signiﬁcantly from Fresnel’s law. We model a system of a photonic glass on a substrate by introducing an optical boundary layer that is sandwiched between the bulk eﬀective medium and the substrate. Based on the model, we calculate the extrapolation length ratio, the photon transport/scattering mean free paths, and the angular distribution of transmitted light intensity. The internal reﬂectance of the photonic glass is accurately determined by considering the diﬀuse scattering in the boundary layer. The modeling results agree well with the experimentally measured angular distribution and transport mean free path. Our modeling also reaﬃrms that the real physical process of light scattering near the interface between photonic glass and the substrate cannot be simply described as internal reﬂection from a ﬂat surface. The extrapolation length ratio of a photonic glass calculated from our boundary layer model is considerably larger than that from Fresnel’s law. This indicates that the transport mean free paths determined in other reported experiments for highly scattering dense media may have included signiﬁcant errors and that the boundary layer analysis could be a good replacement to accurately describe the internal reﬂectance for photonic glasses.
Effects of Maternal Cigarette Smoking on Trace Element Levels and Steroidogenesis in the Maternal–Placental–Fetal Unit

This study evaluates the interaction of toxic elements cadmium (Cd) and lead (Pb) due to exposure from cigarette smoking, essential elements, and steroidogenesis in the maternal–placental–fetal unit. In a cohort of 155 healthy, postpartum women with vaginal term deliveries in clinical hospitals in Zagreb, Croatia, samples of maternal blood/serum and urine, placental tissue, and umbilical cord blood/serum were collected at childbirth. The biomarkers determined were concentrations of Cd, Pb, iron (Fe), zinc (Zn), copper (Cu), and selenium (Se), and steroid hormones progesterone and estradiol in maternal and umbilical cord blood and the placenta. Three study groups were designated based on self-reported data on cigarette smoking habits and confirmed by urine cotinine levels: never smokers (n = 71), former smokers (n = 48), and active smokers (n = 36). Metal(loid)s, steroid hormones, urine cotinine, and creatinine levels were analyzed by ICP–MS, ELISA, GC–MS, and spectrophotometry. Cigarette smoking during pregnancy was associated with increased Cd levels in maternal, placental, and fetal compartments, Pb in the placenta, and with decreased Fe in the placenta. In active smokers, decreased progesterone and estradiol concentrations in cord blood serum were found, while sex steroid hormones did not change in either maternal serum or placenta. This study provides further evidence regarding toxic and essential metal(loid) interactions during prenatal life, and new data on sex steroid disruption in cord serum related to cigarette smoking. The results indicate that umbilical cord sex steroid levels may be a putative early marker of developmental origins of the future burden of disease related to harmful prenatal exposure to cigarette smoke.
Patient satisfaction following resin‐bonded fixed dental prostheses cemented by using the Dahl concept

Resin‐bonded fixed dental prostheses (RBFDPs) cemented at an increased occlusal vertical dimension (OVD) (the Dahl concept) to create space for a metal retainer remains controversial because of the lack of reported clinical studies. This study analyzed the demographic (age and sex) and clinical factors (location and arch of prosthesis) affecting the patients' perception of RBFDPs cemented at an increased OVD.
Real-World Treatment Patterns among Patients with Alopecia Areata in the USA: A Retrospective Claims Analysis

Alopecia areata is an autoimmune disorder characterized by hair loss, for which there are few treatment options. This claims-based study characterized recent real-world treatment patterns among patients in the USA with alopecia areata, including the subtypes alopecia totalis and alopecia universalis, in the first year after diagnosis of an episode of alopecia areata. Approximately 5% of all patients (adults (age ≥ 18 years), n = 7,703; adolescents (age 12–17 years), n = 595) had alopecia totalis or alopecia universalis. Corticosteroids were the most common first-line (1L) and second-line (2L) treatments. The mean time from diagnosis of alopecia areata to initiation of 1L treatment was 2.2 days for adults and 2.6 days for adolescents; mean 1L duration was 76.9 and 64.3 days, respectively. For adults (57.5%) and adolescents (59.7%) with 2L therapy, the mean time from 1L discontinuation to 2L initiation was 57.2 and 53.6 days, respectively; the mean duration of 2L treatment was 55.5 and 50.1 days, respectively. More patients with vs without alopecia totalis or alopecia universalis initiated 2L therapy (adults: 71.9% vs 56.8%; adolescents: 71.4% vs 58.9%). The proportion of days covered during the first year post-diagnosis was 36.7% (adults) and 34.1% (adolescents). These results highlight the substantial disease burden of alopecia areata and a need for more effective treatments. SIGNIFICANCE This study examined treatments received by patients in the USA with the hair loss disorder alopecia areata in the first year after diagnosis. The most common treatment was corticosteroids. On average, adult (adolescent) patients started their first treatment 2.2 (2.6) days after diagnosis and remained on this treatment for 76.9 (64.3) days. Nearly 60% of patients received a second treatment, which was continued for 55.5 (50.1) days. Only a minority of patients (37% of adults and 34% of adolescents) stayed on their medication. These results highlight a need for more effective treatments for alopecia areata.
Correcting for forecast bias in soil moisture assimilation with the ensemble Kalman filter

Land surface models are usually biased in at least a subset of the simulated variables even after calibration. Bias estimation may therefore be needed for data assimilation. Here, in situ soil moisture profile observations in a small agricultural field were merged with Community Land Model (CLM2.0) simulations using different algorithms for state and forecast bias estimation with and without bias correction feedback. Simple state updating with the conventional ensemble Kalman filter (EnKF) allows for some implicit forecast bias correction. It is possible to estimate the soil moisture bias explicitly and derive superior soil moisture estimates with a generalized EnKF that uses a simple persistence model for the bias and assumes that the a priori bias error covariance is proportional to the a priori state error covariance. For the case of bi‐weekly assimilation of the entire profile of soil moisture observations, bias estimation and correction typically reduces the RMSE in soil moisture (over the standard EnKF without bias correction) by around 60 percent. However, under the above assumptions, significant improvements are limited to state variables for which observations are available. Therefore, it is crucial to measure the state variables of interest. The best variant for state and bias estimation depends on the nature of the model bias and the output of interest to the user. In a model that is only biased for soil moisture, large and frequent increments for soil moisture updating may be required, which in turn may negatively impact the water balance and output fluxes. It is then better to post‐process the soil moisture with the bias analysis without updating the model state.
Relationship between Thyroid Hormones and Plasma D-dimer Levels

Summary High serum levels of cholesterol and triglycerides are risk factors for coronary heart disease and are strongly related to several haemostatic parameters. Thyroid disorders are a frequent feature in hyperlipidemic patients and are also associated with a variety of haemostatic abnormalities. Therefore, we analysed the relationships between free T4 (fT4) levels and Factor VII and VIII activities (FVIIc and FVIIIc), D-Dimers (DDI) and Plasminogen Activator Inhibitor type 1 (PAI-1), in a group of 472 healthy patients referred for hyperlipidemia. Fourty patients were found to have primary hypothyroidism. A negative correlation was found in the whole study population between fT4 and DDI (p = 0.0001, r = –0.21) and the same results were found after exclusion of the patients with fT4 below the normal range (p = 0.0007, r = –0.17). In a multivariate regression analysis, the relationship between DDI and fT4 was independent of age, Body Mass Index (BMI), gender and total cholesterol. Less impressive correlation coefficients were found with FVIIc (r = –0.10), FVIIIc (r = –0.09) and PAI-1 (r = –0.09). These results suggest that fT4 may play a physiological role in the regulation of the haemostatic equilibrium in hyperlipidemic patients and that low levels of fT4 are associated with a hypercoagulable state.
Influence of Femoral Position and Pelvic Projection on Norberg Angle Measurements

Abstract Objective Canine hip dysplasia is a common orthopaedic disease in dogs. The Norberg angle value is a measure of hip joint laxity. The aim of this study was to quantify the degree of rotation necessary to consider the radiograph as inadequately positioned and to determine the influence of rotation on the Norberg angle. Study Design Three sets of radiographs with different positioning and projections were acquired using 10 canine cadavers. Rotation of the pelvis was simulated by rotating the X-ray tube without changing the position of the patient. Results In dorsoventral projections, the Norberg angle value is increased by 3.2 to 5.8%. Due to rotation along the long axis, the Norberg angle increases on one side and decreases on the contralateral side by approximately the same value. Rotation of greater than 2 degrees in a lateral direction is visually perceived by the observer as tilted. Rotation of the projection in the caudoventral to craniodorsal direction causes mild increase of the Norberg angle (≤1%), while rotation of the projection in a cranioventral to caudodorsal direction causes moderate (≤2%) decrease of the Norberg angle. Rotation of less than –10 degrees (caudoventral to craniodorsal) or greater than 10 degrees (cranioventral to caudodorsal) is visually perceived as tilted. Conclusion Tilted images that are subjectively perceived evaluable have only little effect on the Norberg angle and are therefore probably acceptable. Dorsoventral projections can be recognized based on the proximal position of the patella and should be excluded from evaluation, as the Norberg angle value can be falsely increased.
Dual-Timescale Spectrum Management in Small-Cell Wireless Networks

To attain the targeted data rates of next generation cellular networks requires dense deployment of small cells in addition to macro cells which provide wide coverage. Dynamic radio resource management is crucial to the success of such heterogeneous networks due to much more pronounced traffic and interference variations in small cells. This work proposes a framework for spectrum management organized according to two timescales, which include 1) centralized optimization on a moderate timescale corresponding to typical duration of user sessions (several seconds to minutes in today's networks), and 2) distributed spectrum allocation on a fast timescale corresponding to typical latency requirements (a few milliseconds). An optimization problem is formulated to allocate resources on the slower timescale with consideration of (distributed) opportunistic scheduling on the faster timescale. Both fixed and fully flexible user association schemes are considered. Iterative algorithms are developed to solve these optimization problems efficiently for a cluster of cells with guaranteed convergence. Simulation results demonstrate advantages of the proposed framework and algorithms.
The pathogenic roles of the p.R130S prestin variant in DFNB61 hearing loss

DFNB61 is a recessively inherited nonsyndromic hearing loss caused by mutations in SLC26A5, the gene that encodes the voltage-driven motor protein, prestin. Prestin is abundantly expressed in the auditory outer hair cells that mediate cochlear amplification. Two DFNB61-associated SLC26A5 variants, p.W70X and p.R130S, were identified in patients who are compound heterozygous for these nonsense and missense changes (SLC26A5W70X/R130S). Our recent study showed that mice homozygous for p.R130S (Slc26a5R130S/R130S) suffer from hearing loss that is ascribed to significantly reduced motor kinetics of prestin. Given that W70X-prestin is nonfunctional, compound heterozygous Slc26a5R130S/- mice were used as a model for human SLC26A5W70X/R130S. By examining the pathophysiological consequences of p.R130S prestin when it is the sole allele for prestin protein production, we determined that this missense change results in progressive outer hair cell loss in addition to its effects on prestin’s motor action. Thus, this study fully defines the pathogenic roles for the p.R130S prestin, which points to the presence of a limited time window for potential clinical intervention.
Cognitive limits of larval Drosophila: Testing for conditioned inhibition, sensory preconditioning and second-order conditioning

Drosophila larvae are an established model system for studying the mechanisms of innate and simple forms of learned behaviour. They have about 10 times fewer neurons than adult flies, and it was the low total number of their neurons that allowed for an electron microscopic reconstruction of their brain at synaptic resolution. Regarding the mushroom body, a central brain structure for associative learning in insects, it turned out that more than half of the classes of synaptic connection had previously escaped attention. Understanding the function of these circuit motifs, subsequently confirmed in adult flies, is an important current research topic. In this context, we test larval Drosophila for their cognitive abilities in three tasks that are characteristically more complex than those previously studied. Our data provide evidence for (i) conditioned inhibition, as has previously been reported for adult flies and honeybees. Unlike what is described for adult flies and honeybees, however, our data do not provide evidence for (ii) sensory preconditioning or (iii) second-order conditioning in Drosophila larvae. We discuss methodological features of our experiments as well as four specific aspects of the organisation of the larval brain that may explain why these two forms of learning are observed in honeybees and adult flies, but not in larval Drosophila.
Digital Peter: Dataset, Competition and Handwriting Recognition Methods

This paper presents a new dataset of Peter the Great’s manuscripts and describes a segmentation procedure that converts initial images of documents into the lines. The new dataset may be useful for researchers to train handwriting text recognition models as a benchmark for comparing diﬀerent models. It consists of 9 694 images and text ﬁles corresponding to lines in historical documents. The open machine learning competition Digital Peter was held based on the considered dataset. The baseline solution for this competition as well as more advanced methods on handwritten text recognition are described in the article. Full dataset and all code are publicly available.
Structure and Properties of Polyamide 11 Nanocomposites Filled with Fibrous Palygorskite Clay

Various amounts (up to 10 wt%) of palygorskite nanofibers functionalized by 3-aminopropyltriethoxysilane (APTES) coupling agent were used to reinforce polyamide 11 nanocomposites prepared by melt compounding. The covalent bonding of the silane on the palygorskite surface was confirmed by infrared spectroscopy and thermogravimetric analysis. X-ray diffraction revealed the retention of the α-form of polyamide crystals upon the addition of both natural and silane treated palygorskite nanorods. All the investigated nanocomposites showed an improvement of the thermal stability, especially when surface treated palygorskite nanofibers were considered. Tensile tests and dynamic mechanical thermal analyses on the prepared materials evidenced how the incorporation of palygorskite nanofibers significantly increased the elastic and the storage moduli of polyamide, and this enhancement was more evident when natural palygorskite nanorods were used.
Active learning of enhancer and silencer regulatory grammar in photoreceptors

Cis-regulatory DNA elements (CRE) are composed of transcription factor (TF) binding sites that direct cell type-specific gene expression. Deep learning is an emerging strategy to model CREs, but the genome offers too few training examples to learn the complex interactions between TF binding sites that govern CRE activities. We address this limitation using active learning to iteratively train models that predict enhancer and silencer activities in the developing mouse retina. Active learning doubled the performance of models trained on genomic data, resulting in models that accurately distinguish between enhancers and silencers composed of the same TF binding sites. The ability of these models to discriminate between functionally non-equivalent binding sites establishes active learning as an effective strategy for modeling regulatory DNA. One sentence summary Models of regulatory DNA learn critical interactions between transcription factor binding sites with active machine learning.
Snakes of the lower/middle Miocene transition at Vieux Collonges (Rhône, France), with comments on the colonisation of western Europe by colubroids

The snake assemblage of the Lower / Middle Miocene (MN 4/5) site Vieux Collonges (France) includes Boidae (Python sp., Eryx sp., Boidae B & C), Colubridae (Texasophis sp., Neonatrix cf. europaea, Natrix aff. sansaniensis, Natricinae A, B, C, & D), Elapidae (Micrurus aff. gallicus, Naja cf. romani, Naja sp. 1, Elapidae A & B), and Viperidae [Viperinae A, Vipera (Oriental vipers) or Daboia]. The Boidae represent an ancient component of the snake fauna. Although the representatives of the family Boidae were still common in West Europe at the Lower / Middle Miocene transition (Vieux Collonges), the representatives of the Colubridae were predominant in Central Europe already during the Lower Miocene. It may be possible that the first Colubridae have immigrated into the Central European areas across the Mazury-Mazowsze continental bridge (Poland) in the Lower Oligocene and then penetrated into West Europe across the Rhine Graben in several waves of dispersal. The small representatives of family Elapidae appeared in Europe most probably slightly earlier (MN 3a) than the large representatives of the genus Naja. The oldest European viperids are typical small vipers, the large Oriental vipers appeared later (MN 3) in Europe.
Volumetric trans-scale imaging of massive quantity of heterogeneous cell populations in centimeter-wide tissue and embryo

We established a volumetric trans-scale imaging system with an ultra-large field-of-view (FOV) that enables simultaneous observation of millions of cellular dynamics in centimeter-wide three-dimensional (3D) tissues and embryos. Using a custom-made giant lens system with a magnification of 2× and a numerical aperture (NA) of 0.25, and a CMOS camera with more than 100 megapixels, we built a trans-scale scope AMATERAS-2, and realized fluorescence imaging with a lateral spatial resolution of approximately 1.2 µm across an FOV of approximately 1.5 × 1.0 cm2. The 3D resolving capability was realized through a combination of optical and computational sectioning techniques tailored for our low-power imaging system. We applied the imaging technique to 1.2 cm-wide section of mouse brain, and successfully observed various regions of the brain with sub-cellular resolution in a single FOV. We also performed time-lapse imaging of a 1-cm-wide vascular network during quail embryo development for over 24 hours, visualizing the movement of over 4.0 × 105 vascular endothelial cells and quantitatively analyzing their dynamics. Our results demonstrate the potential of this technique in accelerating production of comprehensive reference maps of all cells in organisms and tissues, which contributes to understanding developmental processes, brain functions, and pathogenesis of disease, as well as high-throughput quality check of tissues used for transplantation medicine.