Miracle-dz/UniFAR-FTUs huggingface dataset:
Structural and Immunological Effects of Skin Cryoablation in a Mouse Model

Cryoablation is therapeutically applied for various disorders in several organs, and skin diseases are typical targets as this cryotherapy has been widely used for viral warts, benign tumors, and actinic keratosis. The main mechanisms of cryoablation consist of direct freezing effect on skin constituents, thrombosis formation in microcirculation, and subsequent immunological responses. Among them, however, the immunological mechanism remains unelucidated, and it is an issue how the direct freezing injury induces immunological consequences. We established a mouse cryoablation model with liquid nitrogen applied to the shaved back skin, and used this system to study the immunological excitement. After application of liquid nitrogen, the thermal decrease ratio was -25°C/sec or less and the lowest temperature was less than -100°C, which was sufficient to induce ulceration. Destruction of cornified layer and necrosis of epidermal cells were observed in transmission electron microscopy image, and increased transepidermal water loss and skin permeability were detected by the functional measurements. By flow cytometry, antigen-presenting dendritic cells (DCs), including PDCA1+B220+CD19- plasmacytoid DCs (pDCs) and CD11c+ myeloid DCs, as well as neutrophils and macrophages were increased in subcutaneous tissue. In parallel, the mRNA expressions of interferon α1 which are known as pDC-producing cytokines, was elevated. We also found marked degranulation of mast cells, providing a possibility that released histamine attracts pDCs. Finally, FITC migration assay revealed that pDCs and CD11c+ DCs emigrated from the cryoablated skin to the draining lymph nodes. Our study suggests that cryoablation induces destruction of the barrier/epidermis, accumulation of pDCs and CD11c+ DCs to the skin, and migration of DCs to regional lymph nodes. Viral elements or tumor cell lysates released from damaged keratinocytes may stimulate the DCs, thereby leading to antiviral or antitumor effect.
Forestry applications of ground-penetrating radar

Ground-penetrating radar (GPR) is a geophysical and close-range remote sensing technique based on the use of radar pulses to obtain cross-section images of underground features. This method is characterized by the transmission of an electromagnetic short length pulse (1-2 ns), presenting a centre frequency ranging from 10 MHz to 2.5 GHz. The principles of GPR operation are based on the ability of low frequency radar waves to penetrate into a non-conductive medium, usually subsoil, but also walls, concrete or wood. Those waves are detected after suffering a reflection in electromagnetic discontinuities of the propagation medium. Therefore, this is a suitable method to study changes in those physical properties, and also to characterize different mediums and the reflective targets providing information about their physical properties. The aim of this work is to describe and demonstrate different applications of GPR in forestry, showing the obtained results together with their interpretation. Firstly, in this paper, it is illustrated how GPR is able to map shallow bedrock, subsoil stratigraphy and also to estimate shallow watertable depth. Secondly, different tree trunks as well as dry timber are analyzed, evaluating the different radar data obtained in each particular case, and observing differences in their electromagnetic properties related to the GPR response. Finally, several measurements were taken in order to analyze the use of GPR to detect tree root systems using polarimetric techniques, being possible to detect medium and big size roots, together with groups of small roots.
Monitoring Natural Ecosystem and Ecological Gradients: Perspectives with EnMAP

In times of global environmental change, the sustainability of human–environment systems is only possible through a better understanding of ecosystem processes. An assessment of anthropogenic environmental impacts depends upon monitoring natural ecosystems. These systems are intrinsically complex and dynamic, and are characterized by ecological gradients. Remote sensing data repeatedly collected in a systematic manner are suitable for describing such gradual changes over time and landscape gradients, e.g., through information on the vegetation’s phenology. Specifically, imaging spectroscopy is capable of describing ecosystem processes, such as primary productivity or leaf water content of vegetation. Future spaceborne imaging spectroscopy missions like the Environmental Mapping and Analysis Program (EnMAP) will repeatedly acquire high-quality data of the Earth’s surface, and will thus be extremely useful for describing natural ecosystems and the services they provide. In this conceptual paper, we present some of the preparatory research of the EnMAP Scientific Advisory Group (EnSAG) on natural ecosystems and ecosystem transitions. Through two case studies we illustrate the usage of spectral indices derived from multi-date imaging spectroscopy data at EnMAP scale, for mapping vegetation gradients. We thus demonstrate the benefit of future EnMAP data for monitoring ecological gradients and natural ecosystems.
A Mechanism Misregulating p27 in Tumors Discovered in a Functional Genomic Screen

The cyclin-dependent kinase inhibitor p27KIP1 is a tumor suppressor gene in mice, and loss of p27 protein is a negative prognostic indicator in human cancers. Unlike other tumor suppressors, the p27 gene is rarely mutated in tumors. Therefore misregulation of p27, rather than loss of the gene, is responsible for tumor-associated decreases in p27 protein levels. We performed a functional genomic screen in p27+/− mice to identify genes that regulate p27 during lymphomagenesis. This study demonstrated that decreased p27 expression in tumors resulted from altered transcription of the p27 gene, and the retroviral tagging strategy enabled us to pinpoint relevant transcription factors. inhibitor of DNA binding 3 (Id3) was isolated and validated as a transcriptional repressor of p27. We further demonstrated that p27 was a downstream target of Id3 in src-family kinase Lck-driven thymic lymphomagenesis and that p27 was an essential regulator of Lck-dependent thymic maturation during normal T-cell development. Thus, we have identified and characterized transcriptional repression of p27 by Id3 as a new mechanism decreasing p27 protein in tumors.
Novel treatment strategies for unconjugated hyperbilirubinemia

Ongeconjugeerde hyperbilirubinemie (de ophoping van bilirubine in het bloed) komt vooral voor bij mensen met de ziekte van Crigler-Najjar en bij sommige pasgeborenen. De standaardbehandeling voor ongeconjugeerde hyperbilirubinemie bestaat uit fototherapie; de bestraling van de huid met blauw licht. Fototherapie is een relatief veilige en effectieve behandeling, maar heeft toch een aantal nadelen. Patienten met de ziekte van Crigler-Najjar leiden aan een levenslange (erfelijke) vorm van ongeconjugeerde hyperbilirubinemie, en moeten daarom tot 16 uur per dag met fototherapie behandeld worden (e.g. onder een soort zonnebank liggen). Ondanks deze zeer belastende behandeling ontwikkelt tot 25 % van deze patienten alsnog bilirubine- geinduceerde hersenschade. Ook bij hyperbilirubinemische neonaten komt, ondanks fototherapie, ook nog altijd bilirubine-geinduceerde hersenschade voor. Om deze reden ontwikkelden wij, in een diermodel, verschillende nieuwe behandelstrategieen voor ongeconjugeerde hyperbilirubinemie. Deze behandelingen bonden bilirubine in de darm, waardoor de uitscheiding ervan werd bevorderd. Behandeling met het galzout ursodeoxycholaat of met het laxans polyethyleen glycol was net zo effectief als standaard fototherapie. De combinatie van polyethyleen glycol en fototherapie duidelijk effectiever dan alleen fototherapie, en zorgde voor een bilirubinedaling van 70% in het bloed. Ten slotte toonden wij aan, wederom in ons diermodel, dat behandeling met albumine tijdens fototherapie de neerslag van bilirubine in de hersenen kan voorkomen. Dit betekent dat albumine een waardevolle aanvullende therapie kan zijn tijdens ernstige ongeconjugeerde hyperbilirubinemie. De door ons ontwikkelde strategieen kunnen wellicht de belasting van de huidige behandelmethoden (e.g. fototherapie) voor patienten verminderen. Bovendien zouden deze nieuwe behandelingen, alleen of in combinatie met fototherapie, de incidentie van bilirubine-geinduceerde hersenschade verder kunnen terugdringen.
ECNet: Efficient Convolutional Networks for Side Scan Sonar Image Segmentation

This paper presents a novel and practical convolutional neural network architecture to implement semantic segmentation for side scan sonar (SSS) image. As a widely used sensor for marine survey, SSS provides higher-resolution images of the seafloor and underwater target. However, for a large number of background pixels in SSS image, the imbalance classification remains an issue. What is more, the SSS images contain undesirable speckle noise and intensity inhomogeneity. We define and detail a network and training strategy that tackle these three important issues for SSS images segmentation. Our proposed method performs image-to-image prediction by leveraging fully convolutional neural networks and deeply-supervised nets. The architecture consists of an encoder network to capture context, a corresponding decoder network to restore full input-size resolution feature maps from low-resolution ones for pixel-wise classification and a single stream deep neural network with multiple side-outputs to optimize edge segmentation. We performed prediction time of our network on our dataset, implemented on a NVIDIA Jetson AGX Xavier, and compared it to other similar semantic segmentation networks. The experimental results show that the presented method for SSS image segmentation brings obvious advantages, and is applicable for real-time processing tasks.
Phylogenetic analysis of infectious bronchitis coronaviruses newly isolated in China, and pathogenicity and evaluation of protection induced by Massachusetts serotype H120 vaccine against QX-like strains

Seventy-eight isolates of avian infectious bronchitis virus (IBV) were obtained from different field outbreaks in China in 2009 and genotyped with 34 reference strains. Four genotypes of IBV and three new isolates were identified by phylogenetic analysis and BLAST searches of the entire S1 gene. The results showed that most IBV strains that have circulated in China in recent years belong to the genotype of QX-like strains, and that they could be grouped further into two clusters, regardless of the level of genetic variation displayed. A study of pathogenicity that used three QX-like strains—ck/CH/LSD/091003, ck/CH/LDL/091022 and ck/CH/LJL/090330—showed that the isolates caused the most severe lesions in the kidneys and were therefore nephropathogenic strains with various levels of virulence in specific pathogen free chickens. A vaccination–challenge test that was performed using the three QX-like strains showed that the commercially available H120 vaccine did not provide sufficient protection against challenge with the QX-like isolates, as demonstrated by comparison of the clinical signs, pathological lesions and virus recovery from the trachea and kidney of unvaccinated–challenged and vaccinated–challenged birds.
Acute onset of decreased vision and hearing traced to hemodialysis treatment with aged dialyzers.

CONTEXT A recent event in which 7 patients at 1 hospital developed decreased vision and hearing, conjunctivitis, headache, and other severe neurologic symptoms 7 to 24 hours after hemodialysis drew attention to the issue of the long-term integrity of dialysis machines and materials. OBJECTIVE To determine the cause of the adverse reactions that occurred during this event. DESIGN, PATIENTS, AND SETTING Retrospective cohort study of all 9 patients who received hemodialysis at hospital A on September 18, 1996, the day of the outbreak. A case-patient was defined as any hospital A patient with acute onset of decreased vision and hearing and conjunctivitis after dialysis on that day. Non-case-patients were all others who underwent dialysis at hospital A on that day but did not develop adverse reactions. In an attempt to reproduce the conditions of the event, cellulose acetate dialysis membranes of various ages were retrieved from other sources and tested for physical and chemical degradation, and degradation products were identified, characterized, and injected intravenously into rabbits. MAIN OUTCOME MEASURES Clinical signs and symptoms, time to resolution of symptoms, mortality, and dialyzer type and age, for case- vs non-case-patients. RESULTS Seven of the 9 patients met the case definition. In addition to diminished vision and hearing, conjunctivitis, and headache, some case-patients had blood leak alarm activation (n=6), confusion/lethargy (n=5), corneal opacification (n=4), cardiac arrest (n=2), or other neurologic signs and symptoms. One case-patient died during hospitalization after the event; 5 of 7 case-patients died within 13 months. Resolution of signs and symptoms varied but persisted more than 3 years or until death in 3 of the 6 patients who survived hospitalization. All case-patients but no non-case-patients were exposed to 11.5-year-old cellulose acetate dialyzers (all of these dialyzers were discarded by the hospital before our investigation). Laboratory investigation of field-retrieved 0- to 13.6-year-old dialyzers of similar type indicated significant chemical degradation in the older membranes. In vivo injection of extracts of membrane degradation products produced iritis and hemorrhages in rabbits' eyes. CONCLUSIONS Severe patient injury was associated with exposure to aged cellulose acetate membranes of dialyzers, allowing cellulose acetate degradation products to enter the blood. Clinicians should be aware that aged cellulose acetate membranes may cause severe adverse reactions.
In Vitro Model for Hepatotoxicity Studies Based on Primary Human Hepatocyte Cultivation in a Perfused 3D Bioreactor System

Accurate prediction of the potential hepatotoxic nature of new pharmaceuticals remains highly challenging. Therefore, novel in vitro models with improved external validity are needed to investigate hepatic metabolism and timely identify any toxicity of drugs in humans. In this study, we examined the effects of diclofenac, as a model substance with a known risk of hepatotoxicity in vivo, in a dynamic multi-compartment bioreactor using primary human liver cells. Biotransformation pathways of the drug and possible effects on metabolic activities, morphology and cell transcriptome were evaluated. Formation rates of diclofenac metabolites were relatively stable over the application period of seven days in bioreactors exposed to 300 µM diclofenac (300 µM bioreactors (300 µM BR)), while in bioreactors exposed to 1000 µM diclofenac (1000 µM BR) metabolite concentrations declined drastically. The biochemical data showed a significant decrease in lactate production and for the higher dose a significant increase in ammonia secretion, indicating a dose-dependent effect of diclofenac application. The microarray analyses performed revealed a stable hepatic phenotype of the cells over time and the observed transcriptional changes were in line with functional readouts of the system. In conclusion, the data highlight the suitability of the bioreactor technology for studying the hepatotoxicity of drugs in vitro.
Identification of Vibrio hollisae sp. nov. from patients with diarrhea

The name Vibrio hollisae (synonym = Special Bacteriology group EF-13) is proposed for a new group of 16 strains that occurred in stool cultures of patients with diarrhea. V. hollisae is a small gram-negative rod, which is motile with a single polar flagellum. No lateral or peritrichous flagella were observed, even when it was grown on a solid medium. Sodium chloride is required for growth, so V. hollisae is a halophilic vibrio. Strains were positive (36 degrees C, 24 or 48 h) for oxidase (Kovacs), indole production, nitrate reduction to nitrite, and fermentation of D-glucose (acid, no gas), L-arabinose, D-galactose, and D-mannose. Strains were negative for the following tests often used in enteric bacteriology: lipase (corn oil); deoxyribonuclease; gelatinase; methyl red; Voges-Proskauer; utilization of citrate, acetate, and malonate; L-lysine decarboxylase (Møllers); L-ornithine decarboxylase (Møllers); L-arginine dihydrolase (Møllers); growth in KCN medium; and acid production from D-adonitol, D-arabitol, cellobiose, dulcitol, erythritol, glycerol (25% delayed positive at 7 days), i-(myo)-inositol, lactose, maltose, D-mannitol, melibiose, alpha-methyl-D-glucoside, mucate, raffinose, L-rhamnose, salicin, D-sorbitol, sucrose, trehalose, and D-xylose. None of the strains was motile (semisolid medium) at 36 degrees C at 48 h, but by 7 days 88% were motile. The strains did not grow within 2 days when plated on thiosulfate-citrate-bile salts-sucrose (TCBS) agar or MacConkey agar, but they grew on sheep blood agar and marine agar. By DNA-DNA hybridization (75 degrees C, hydroxyapatite with (32)P), V. hollisae was only 0 to 4% related to 21 named species in Vibrio and Photobacterium. The type strain is designated ATCC 33564, which has a mean guanineplus-cytosine content in DNA of 50 mol%. With the disk diffusion method V. hollisae had relatively large zones of inhibition around penicillin, ampicillin, carbenicillin, cephalothin, colistin, polymyxin B, streptomycin, kanamycin, gentamicin, tetracycline, chloramphenicol, and sulfadiazine. Future studies should focus on the isolation of this new vibrio and its ecology and relationship to human diseases.
deltaBLEU: A Discriminative Metric for Generation Tasks with Intrinsically Diverse Targets

We introduce Discriminative BLEU (∆BLEU), a novel metric for intrinsic evaluation of generated text in tasks that admit a diverse range of possible outputs. Reference strings are scored for quality by human raters on a scale of [−1, +1] to weight multi-reference BLEU. In tasks involving generation of conversational responses, ∆BLEU correlates reasonably with human judgments and outperforms sentence-level and IBM BLEU in terms of both Spearman’s ρ and Kendall’s τ .
Targeting the tumor-promoting microenvironment in MET-amplified NSCLC cells with a novel inhibitor of pro-HGF activation

Targeted therapeutic agents, such as inhibitors of epithelial growth factor receptor (EGFR), have transformed the management of non-small cell lung cancer (NSCLC) patients. MET-amplified NSCLC cells display resistance to EGFR-targeting agents, but are addicted to MET signaling for survival and proliferation and are sensitive to MET inhibition. However, responsive cancer cells invariably develop resistance to MET-targeted treatment. The tumor microenvironment plays a major role in resistance to anticancer therapy. We demonstrated that fibroblasts block the response of MET-amplified NSCLC cells to the MET kinase inhibitor, JNJ38877605 in an HGF-dependent manner. Thus, MET-amplified NSCLC cells become addicted to HGF upon pharmacological inhibition of MET. HGF restored phosphorylation of MET, EGFR and RON, and maintained pro-survival AKT and ERK signaling in MET-inhibited cells. We developed a small molecule inhibitor of pro-HGF activation, SRI31215, which acts as a triplex inhibitor of the pro-HGF activating proteases matriptase, hepsin and HGF activator (HGFA). SRI31215 blocked crosstalk between tumor cells and fibroblasts and overcame fibroblast-mediated resistance to MET inhibition by preventing fibroblast-mediated reactivation of AKT and ERK signaling. Structurally unrelated triplex inhibitors of matriptase, hepsin and HGFA that we developed in parallel showed similar biological activity. Our data suggest that simultaneous inhibition of HGF and MET is required to overcome resistance to MET inhibitors in MET-amplified NSCLC cells. This provides a rationale for the development of novel combination therapeutic strategies for the treatment of NSCLC patients with MET amplification.
Cross-entropy vs. squared error training: a theoretical and experimental comparison

In this paper we investigate the error criteria that are optimized during the training of artificial neural networks (ANN). We compare the bounds of the squared error (SE) and the crossentropy (CE) criteria being the most popular choices in stateof-the art implementations. The evaluation is performed on automatic speech recognition (ASR) and handwriting recognition (HWR) tasks using a hybrid HMM-ANN model. We find that with randomly initialized weights, the squared error based ANN does not converge to a good local optimum. However, with a good initialization by pre-training, the word error rate of our best CE trained system could be reduced from 30.9% to 30.5% on the ASR, and from 22.7% to 21.9% on the HWR task by performing a few additional “fine-tuning” iterations with the SE criterion.
Virulence genes in Escherichia coli isolated from feces and urine of cats

Escherichia coli is a normal inhabitant of the intestinal tract of humans and warm blooded animals. Although usually harmless, various E. coli strains have acquired genetic determinants (virulence genes) rendering them pathogenic for both humans and animals. Certain strains of E. coli behave as pathogens in dogs and cats, causing gastrointestinal and extra-intestinal diseases (Beutin, 1999). Shiga toxin-producing E. coli (STEC) are among the most important causes of foodborne diseases. They are responsible for a range of human gastrointestinal diseases, including watery or bloody diarrhea. The common feature and main virulence factor of STEC is the production of Shiga toxin-1 (Stx1) and/or Shiga toxin-2 (Stx-2) or its variants (Kaper et al., 2004; Bentancor et al., 2007). Dogs and cats have also been found to carry STEC strains, but their role as bacterial reservoirs has not been completely elucidated. The prevalence of STEC strains among intestinal bacterial strains in pets has been shown to be of highly variable occurrence (Beutin, 1999; Bentancor et al., 2007).
Consistent Implementation of Decisions in the Brain

Despite the complexity and variability of decision processes, motor responses are generally stereotypical and independent of decision difficulty. How is this consistency achieved? Through an engineering analogy we consider how and why a system should be designed to realise not only flexible decision-making, but also consistent decision implementation. We specifically consider neurobiologically-plausible accumulator models of decision-making, in which decisions are made when a decision threshold is reached. To trade-off between the speed and accuracy of the decision in these models, one can either adjust the thresholds themselves or, equivalently, fix the thresholds and adjust baseline activation. Here we review how this equivalence can be implemented in such models. We then argue that manipulating baseline activation is preferable as it realises consistent decision implementation by ensuring consistency of motor inputs, summarise empirical evidence in support of this hypothesis, and suggest that it could be a general principle of decision making and implementation. Our goal is therefore to review how neurobiologically-plausible models of decision-making can manipulate speed-accuracy trade-offs using different mechanisms, to consider which of these mechanisms has more desirable decision-implementation properties, and then review the relevant neuroscientific data on which mechanism brains actually use.