Miracle-dz/UniFAR-FTUs huggingface dataset:
Boron–oxygen complex yields n-type surface layer in semiconducting diamond

Significance Diamond is a uniquely attractive wide-bandgap semiconductor for future electronic devices where its remarkable physical properties may enable switches, transistors, and diodes for extreme applications. Whereas p-type semiconducting diamond is well developed with boron doping, the synthesis of n-type diamond, required to complete purely diamond-based electronics, has been a great challenge in materials science. We report the creation of n-type diamond via a new type of defect complexes of boron and oxygen that can be tuned by controlling the experimental parameters for diamond crystallization, leading to a shallow donor state with high carrier concentration that is several orders of magnitude higher than achieved by sulfur or phosphorus doping. The results provide a new strategy for producing n-type diamond-based devices. Diamond is a wide-bandgap semiconductor possessing exceptional physical and chemical properties with the potential to miniaturize high-power electronics. Whereas boron-doped diamond (BDD) is a well-known p-type semiconductor, fabrication of practical diamond-based electronic devices awaits development of an effective n-type dopant with satisfactory electrical properties. Here we report the synthesis of n-type diamond, containing boron (B) and oxygen (O) complex defects. We obtain high carrier concentration (∼0.778 × 1021 cm−3) several orders of magnitude greater than previously obtained with sulfur or phosphorous, accompanied by high electrical conductivity. In high-pressure high-temperature (HPHT) boron-doped diamond single crystal we formed a boron-rich layer ∼1–1.5 μm thick in the {111} surface containing up to 1.4 atomic % B. We show that under certain HPHT conditions the boron dopants combine with oxygen defects to form B–O complexes that can be tuned by controlling the experimental parameters for diamond crystallization, thus giving rise to n-type conduction. First-principles calculations indicate that B3O and B4O complexes with low formation energies exhibit shallow donor levels, elucidating the mechanism of the n-type semiconducting behavior.
Follow-Up Liver Stiffness Measurements after Liver Resection Influence Oncologic Outcomes of Hepatitis-B-Associated Hepatocellular Carcinoma with Liver Cirrhosis

The severity of liver fibrosis can be noninvasively evaluated by measuring liver stiffness (LS) using transient elastography. This study aimed to evaluate the prognostic value of achieving low liver stiffness measurement (LSM) in patients with cirrhosis confirmed from the resected liver due to hepatocellular carcinoma (HCC). A total of 184 patients that received curative surgery for HCC related to the hepatitis B virus at Barcelona Clinic Liver Cancer stage 0–A, and had a METAVIR fibrosis score of 4 were investigated. LSM significantly decreased after antiviral therapy during follow-up (p = 0.001), and achieving LSM ≤8 kilopascal (kPa) suggested a reduced risk of late recurrence (>12 months) (hazard ratio (HR), 0.519; 95% confidence interval (CI), 0.307–0.877; p = 0.014). Older age at surgery (≥45 years) and multiple HCC nodules predicted an increased risk of late recurrence (HR, 3.270; 95% CI, 1.296–8.251; p = 0.012; and HR, 3.146; 95% CI, 1.396–7.089; p = 0.006). Decreased LSM also suggested decreased mortality (HR, 0.251; 95% CI, 0.086–0.756; p = 0.045) along with baseline low aspartate aminotransferase-to-platelet ratio index (APRI) score (<1.5) (HR, 0.251; 95% CI, 0.086–0.759; p = 0.041). Having early HCC recurrence (HR, 9.416; 95% CI, 3.566–24.861; p < 0.001) and microvascular tumor invasion (HR, 3.191; 95% CI, 1.188–8.568; p = 0.021) predicted increased mortality. Among HCC patients with liver cirrhosis under antiviral therapy, achieving low LSM (≤8 kPa) predicted reduced late HCC recurrence.
A Structural Analysis for the Categorization of the Negative Externalities of Transport and the Hierarchical Organization of Sustainable Mobility’s Strategies

Transport systems are capable of contributing to the economic robustness of a geographic area and the well-being of its inhabitants via the supply of the necessary assets for the mobility of people and goods. However, transport projects have the capacity to produce several negative externalities such as water pollution, air pollution, barrier effects, noise, and ecological impact, which affect the quality of people’s life. Considering these facts, the main purpose of this study is to indicate methodologically how the negative externalities of transport are interlinked, so that to promote sustainable mobility development. This paper reveals via the method of structural analysis, the interrelations between the negative externalities of transport, firstly to organize them hierarchically and secondly to evaluate the potential of sustainable mobility strategies concerning the co-benefits generated by their implementation for society. The results show that the negative externalities of transport are not isolated phenomena; on the contrary, they are interlinked and can be organised hierarchically according to the relationships between them so that certain public policies can be prioritized and the negative impacts of transport can be tackled more effectively. The most critical negative externalities are the invasion of public space for the construction of more roads, along with road accidents, congestion, and local air pollution. On the other hand, the most important group of strategies for sustainable mobility are the ones oriented to urban design, and more specifically to transit-oriented development.
Intrinsic lipid binding activity of ATG16L1 supports efficient membrane anchoring and autophagy

Membrane targeting of autophagy‐related complexes is an important step that regulates their activities and prevents their aberrant engagement on non‐autophagic membranes. ATG16L1 is a core autophagy protein implicated at distinct phases of autophagosome biogenesis. In this study, we dissected the recruitment of ATG16L1 to the pre‐autophagosomal structure (PAS) and showed that it requires sequences within its coiled‐coil domain (CCD) dispensable for homodimerisation. Structural and mutational analyses identified conserved residues within the CCD of ATG16L1 that mediate direct binding to phosphoinositides, including phosphatidylinositol 3‐phosphate (PI3P). Mutating putative lipid binding residues abrogated the localisation of ATG16L1 to the PAS and inhibited LC3 lipidation. On the other hand, enhancing lipid binding of ATG16L1 by mutating negatively charged residues adjacent to the lipid binding motif also resulted in autophagy inhibition, suggesting that regulated recruitment of ATG16L1 to the PAS is required for its autophagic activity. Overall, our findings indicate that ATG16L1 harbours an intrinsic ability to bind lipids that plays an essential role during LC3 lipidation and autophagosome maturation.
Hydroxychloroquine — How Much Is Too Much?

Although initially approved for medical use in the United States by the Food and Drug Administration in the 1950s, antimalarial treatment of clinical disease actually dates back to the 1630s in Peru, stemming from the “fever tree,” later identified as Cinchona officialis in 1742 by Carl Linnaeus in Europe1. Later, quinine was isolated from Cinchona bark2, yielding the subsequent boom in the development of these agents for the antimalarial market. When the Dutch Cinchona plantations were overrun and captured during World War II, a synthetic version of quinine was created — quinacrine — and was used for malaria prevention, an activity funded and supported by the war effort in the United States3,4. The quinacrine story bears an uncanny similarity to the development of synthetic corticosteroids, which was also supported by the needs of the US government for the war effort during the exact same time period. It was in 1951, after the war was over, that Allied soldiers taking longterm quinacrine demonstrated improved signs and symptoms of systemic lupus erythematosus (SLE)5. Just a few years later (1955), hydroxychloroquine (HCQ) was synthesized, and a successful scale-up created this cornerstone drug for treating SLE. It is now on the World Health Organization list of essential medications needed in a basic health system6. In this issue of The Journal , Tselios, et al … Address correspondence to Dr. V.K. Sandhu, Loma Linda University Medical Center, Rheumatology, 11375 Campus St., Loma Linda, California 92354, USA. E-mail: vksandhu{at}llu.edu
The Activation State of CD4 T Cells Alters Cellular Peptidase Activities, HIV Antigen Processing, and MHC Class I Presentation in a Sequence-Dependent Manner

CD4 T cell activation is critical to the initiation of adaptive immunity. CD4 T cells are also the main targets of HIV infection, and their activation status contributes to the maintenance and outcome of infection. Although the role of activation in the differentiation and proliferation of CD4 T cells is well studied, its impact on the processing and MHC class I (MHC-I) presentation of epitopes and immune recognition by CD8 T cells are not investigated. In this study, we show that the expression and hydrolytic activities of cellular peptidases are increased upon TCR-dependent and MHC–peptide activation of primary CD4 T cells from healthy or HIV-infected persons. Changes in peptidase activities altered the degradation patterns of HIV Ags analyzed by mass spectrometry, modifying the amount of MHC-I epitopes produced, the antigenicity of the degradation products, and the coverage of Ags by degradation peptides presentable by MHC-I. The computational analysis of 2237 degradation peptides generated during the degradation of various HIV-antigenic fragments in CD4 T cells identified cleavage sites that were predictably enhanced, reduced, or unchanged upon cellular activation. Epitope processing and presentation by CD4 T cells may be modulated by the activation state of cells in a sequence-dependent manner. Accordingly, cellular activation modified endogenous Ag processing and presentation and killing of HIV-infected CD4 T cells by CD8 T cells in a way that mirrored differences in in vitro epitope processing. The clearance of HIV-infected cells may rely on different immune responses according to activation state during HIV infection.
Dynamic Coastal-Shelf Seascapes to Support Marine Policies Using Operational Coastal Oceanography: The French Example

In the context of maritime spatial planning and the implementation of spatialized Good Environmental Status indicators in the Marine Strategy Framework Directive (MSFD), the definition of a mosaic composed of coherent and standardised spatial units is necessary. We propose here a characterization of seascapes in time and space within the specific framework of the MSFD in the English Channel and the Bay of Biscay areas. A spatio-temporal classification of coastal-shelf water masses is carried out using twelve essential oceanographic and derived variables from operational coastal oceanography using the HYCOM model. Partitioning is computed using a multivariate hybrid two-step clustering process defining a time series of categorical maps representing hydrographical patch classes. Main patch occurrence is analyzed to understand their spatio-temporal dynamics and their oceanographic characteristics. Finally, patch classes are combined with MSFD marine sub-region delimitations to build seascapes, including ecosystem approach management and marine policy considerations.
Lateral size reduction of graphene oxide preserving its electronic properties and chemical functionality

Graphene oxide (GO) is widely considered as a graphene precursor when chemically reduced. Nevertheless, through the precise control of two parameters: lateral size and oxidation degree, GO can be useful in many applications as modified graphene oxide or functional reduced graphene oxide. Commonly, the decrease in GO lateral size, involves a change in the C/O ratio and therefore a modification in a large number of characteristics. Here, a simple but effective approach to synthesize GO with lateral dimensions below 100 nm and without modification of its chemical, optical and electronic features is presented. The use of a sonifier at low temperature allows to rapidly reduce the lateral size in ∼82% while preserving the C/O ratio and consequently the chemical stability, the band gap, the electronic energy levels and the functionality. This method will allow several applications from biomedicine to energy, where reliable reduced size of GO is required.
Dual control of Kinesin-1 recruitment to microtubules by Ensconsin in Drosophila neuroblasts and oocytes

ABSTRACT Drosophila Ensconsin (also known as MAP7) controls spindle length, centrosome separation in brain neuroblasts (NBs) and asymmetric transport in oocytes. The control of spindle length by Ensconsin is Kinesin-1 independent but centrosome separation and oocyte transport require targeting of Kinesin-1 to microtubules by Ensconsin. However, the molecular mechanism used for this targeting remains unclear. Ensconsin contains a microtubule (MT)-binding domain (MBD) and a Kinesin-binding domain (KBD). Rescue experiments show that only full-length Ensconsin restores the spindle length phenotype. KBD expression rescues ensc centrosome separation defects in NBs, but not the fast oocyte streaming and the localization of Staufen and Gurken. Interestingly, the KBD can stimulate Kinesin-1 targeting to MTs in vivo and in vitro. We propose that a KBD and Kinesin-1 complex is a minimal activation module that increases Kinesin-1 affinity for MTs. Addition of the MBD present in full-length Ensconsin allows this process to occur directly on the MT and triggers higher Kinesin-1 targeting. This dual regulation by Ensconsin is essential for optimal Kinesin-1 targeting to MTs in oocytes, but not in NBs, illustrating the importance of adapting Kinesin-1 recruitment to different biological contexts. Summary: A combination of genetic studies with rescue constructs and in vitro experiments reveal that Drosophila Ensconsin recruits but also stimulates Kinesin-1 affinity for microtubules.
Discovery of tandem and interspersed segmental duplications using high throughput sequencing

Motivation Several algorithms have been developed that use high throughput sequencing technology to characterize structural variations. Most of the existing approaches focus on detecting relatively simple types of SVs such as insertions, deletions, and short inversions. In fact, complex SVs are of crucial importance and several have been associated with genomic disorders. To better understand the contribution of complex SVs to human disease, we need new algorithms to accurately discover and genotype such variants. Additionally, due to similar sequencing signatures, inverted duplications or gene conversion events that include inverted segmental duplications are often characterized as simple inversions; and duplications and gene conversions in direct orientation may be called as simple deletions. Therefore, there is still a need for accurate algorithms to fully characterize complex SVs and thus improve calling accuracy of more simple variants. Results We developed novel algorithms to accurately characterize tandem, direct and inverted interspersed segmental duplications using short read whole genome sequencing data sets. We integrated these methods to our TARDIS tool, which is now capable of detecting various types of SVs using multiple sequence signatures such as read pair, read depth and split read. We evaluated the prediction performance of our algorithms through several experiments using both simulated and real data sets. In the simulation experiments, TARDIS achieved 97.67% sensitivity with only 1.12% false discovery rate. For experiments that involve real data, we used two haploid genomes (CHM1 and CHM13) and one human genome (NA12878) from the Illumina Platinum Genomes set. Comparison of our results with orthogonal PacBio call sets from the same genomes revealed higher accuracy for TARDIS than state of the art methods. Furthermore, we showed a surprisingly low false discovery rate of our approach for discovery of tandem, direct and inverted interspersed segmental duplications prediction on CHM1 (less than 5% for the top 50 predictions). The algorithms we describe here are the first to predict insertion location and the various types of new segmental duplications using HTS data. Availability TARDIS software is available al https://gilhub.com/BilkenICompGen/lardis Contact fhormozd@ucdavis.edu and calkan@cs.bilkent. edu.tr.
The Impact of Cisplatin- or Non-Cisplatin-Containing Chemotherapy on Long-Term and Conditional Survival of Patients with Advanced Urinary Tract Cancer.

BACKGROUND The impact of cisplatin use on long-term survival of unselected patients with advanced urinary tract cancer (aUTC) has not been adequately investigated. We used a multinational database to study long-term survival and the impact of treatment type in unselected patients with aUTC. MATERIALS AND METHODS A total of 1,333 patients with aUTC (cT4bN0M0, cTanyN+M0, cTanyNanyM+), transitional-cell, squamous, or adenocarcinoma histology who received systemic chemotherapy and had available survival data were selected. Long-term survival was defined as alive at 3 years following initiation of first-line chemotherapy. Conditional overall survival (COS) analysis was employed to study change in prognosis given time survived from initiation of first-line chemotherapy. RESULTS Median follow-up was 31.7 months. The combination of cisplatin use and cisplatin eligibility accurately predicted long-term survival. Eligible patients treated with cisplatin conferred a 31.6% probability of 3-year survival (95% confidence interval [CI]: 25.1-38.3), and 2-year COS for patients surviving 3 years after initiation of cisplatin-based chemotherapy was 83% (95% CI: 59.7-93.5). The respective probabilities for patients who were ineligible for cisplatin or not treated with cisplatin despite eligibility were 14% (95% CI: 10.8-17.6) and 49.3% (95% CI: 28.2-67.4). Two-year COS remained significantly different between these two groups up to 3 years after chemotherapy initiation. CONCLUSION Cisplatin-based therapy was associated with the highest likelihood of long-term survival in patients with aUTC and should be used in patients who fulfill the established eligibility criteria. Novel therapies are necessary to increase long-term survival in cisplatin-ineligible patients. IMPLICATIONS FOR PRACTICE Long-term, disease-free survival is possible in one in four eligible-for-cisplatin patients with advanced urinary tract cancer (aUTC) treated with cisplatin-based combination chemotherapy. Therefore, deviations from eligibility criteria should be avoided. Consolidation surgery should be considered in responders. These data provide benchmarks for the study of novel therapies in aUTC.
Simulation of the 2018 Tsunami Due to the Flank Failure of Anak Krakatau Volcano and Implication for Future Observing Systems

Motivated by the unwarned tsunami disaster caused by the flank collapse of the Anak Krakatau volcano on 22 December 2018, we used a landslide tsunami model to explore potential tsunami observing and warning systems for the region. With the estimated volume of 0.24 km3 and the relatively short duration (~3 to 5 min), the landslide of the volcanic edifice in the southwest sector triggered a tsunami of higher than 40 m in the vicinity. The tsunami, however, attenuated rapidly as it propagated away from the generation area, resulting in lower than 2 m wave heights at tide gauges around the Sunda Strait. Using the tsunami model, we demonstrated the capability of a ship height positioning method to detect the tsunami of amplitude ~20 cm associated with the event. Furthermore, assimilating the tsunami current velocity observed by high‐frequency oceanographic radars can produce accurate forecasts of coastal tsunami heights.
Therapeutic Effects of Resveratrol Liposome on Muscle Injury in Rats

Background In this study we prepared liposome microbubbles loading resveratrol (LMLR) and evaluated its therapeutic effect on injury of gastrocnemius muscle in rats. Material/Methods LMLR was prepared and characterized by particle size, potential, and microscopy, and a rat model of acute blunt injury of gastrocnemius muscle was established. After treatments with resveratrol or LMLR, the therapeutic effects were evaluated by hematoxylin-eosin (HE) staining. The expression of MHCIIB and vimentin in mRNA level was measured by real-time PCR. The expression of desmin and collagen I protein was assessed by immunohistochemistry. Results LMLR showed regular cycle shape in a size of ~1000 nm. LMLR was negatively charged (−30 mV). The in vitro release of LMLR was close to 80% at 10 h and 90% at 48 h. Acute gastrocnemius muscle injury was established in rats and tissue recovery was observed after LMLR treatment as evidenced by HE staining, decreased expression of MHCIIB, and increased expression of vimentin. Moreover, LMLR treatment obviously facilitated desmin expression and reduced collagen I expression. Conclusions LMLR is effective in treating acute blunt injury of gastrocnemius muscle in rats.
The evolving landscape of human papillomavirus-related oropharyngeal squamous cell carcinoma at a single institution in Northern Italy

SUMMARY The increasing incidence of HPV-related oropharyngeal squamous cell carcinoma (OPSCC) observed in several developed countries has not yet been documented in Italy. To investigate changes in the epidemiology of HPV-related OPSCC we reviewed the HPV status of cases evaluated at our centre in northern Italy before and after 2010. The results were correlated with patient age, sex, oropharyngeal subsite (classified as palatine tonsil, tongue base, palatine arch/palate/uvula, posterior oropharyngeal wall, and oropharynx not otherwise specified), AJCC tumour stage, risk factor exposure (smoke, alcohol), disease history (recurrence, metastasis, second tumours), outcome and survival. Positivity for p16 and HR HPV DNA was required to classify HPV-related OPSCC. HPV-related tonsillar OPSCC increased significantly after 2010, while a non-significant reduction of HPV-related extra-tonsillar OPSCC was observed. Non-keratinising morphology was strongly associated with HPV positivity. HPV16 was the most common genotype; the frequency of other high-risk genotype infections decreased after 2010. At multivariate analysis, HPV status showed a significant association with better outcome. We documented an increase of HPV-related OPSCC in our Italian population, synchronous with the increase observed in several Western countries, which in recent years reached a prevalence similar to that reported in central European countries. Our results indicate that HPV infection in head and neck oncology is relevant in Italy and needs to be considered for accurate patient stratification.