Miracle-dz/UniFAR-FTUs huggingface dataset:
Modeling the Response of the Langtang Glacier and the Hintereisferner to a Changing Climate Since the Little Ice Age

This study aims at developing and applying a spatially-distributed coupled glacier mass balance and ice-flow model to attribute the response of glaciers to natural and anthropogenic climate change. We focus on two glaciers with contrasting surface characteristics: a debris-covered glacier (Langtang Glacier in Nepal) and a clean-ice glacier (Hintereisferner in Austria). The model is applied from the end of the Little Ice Age (1850) to the present-day (2016) and is forced with four bias-corrected General Circulation Models (GCMs) from the historical experiment of the CMIP5 archive. The selected GCMs represent region-specific warm-dry, warm-wet, cold-dry, and cold-wet climate conditions. To isolate the effects of anthropogenic climate change on glacier mass balance and flow runs from these GCMs with and without further anthropogenic forcing after 1970 until 2016 are selected. The outcomes indicate that both glaciers experience the largest reduction in area and volume under warm climate conditions, whereas area and volume reductions are smaller under cold climate conditions. Simultaneously with changes in glacier area and volume, surface velocities generally decrease over time. Without further anthropogenic forcing the results reveal a 3% (9%) smaller decline in glacier area (volume) for the debris-covered glacier and a 18% (39%) smaller decline in glacier area (volume) for the clean-ice glacier. The difference in the magnitude between the two glaciers can mainly be attributed to differences in the response time of the glaciers, where the clean-ice glacier shows a much faster response to climate change. We conclude that the response of the two glaciers can mainly be attributed to anthropogenic climate change and that the impact is larger on the clean-ice glacier. The outcomes show that the model performs well under different climate conditions and that the developed approach can be used for regional-scale glacio-hydrological modeling.
Influence of Transient Hypoxia and Reoxygenation on the Pre‐Ejection Period of the Heart

Using 1/PEP2 (PEP = pre‐ejection period of the heart) and PEP/LVET‐ratio (LVET = left ventricular ejection time) as parameters it was shown that 1/PEP2 increased and PEP/LVET decreased during hypoxia, and when pure oxygen breathing was started, the hypoxic changes were reversed.
A next-generation-sequencing panel for mutational analysis of dominant acute hepatic porphyrias

Abstract Molecular diagnosis of autosomal dominant acute hepatic porphyrias (AHPs) plays an important role in the management of these disorders. To introduce next generation sequencing (NGS) to the porphyria diagnosis, we designed a panel that contained four genes, ALAS1, HMBS, CPOX and PPOX for mutational analysis of acute intermittent porphyria (AIP), hereditary coproporphyria (HCP) and variegate porphyria (VP). To validate the AHP panel, 30 samples with known pathogenic variants as determined by Sanger sequencing, were analyzed using the Ion PGM™. Among them, nine have so far not been reported. The pathogenic variants were identified and annotated manually in IGV by three individuals who were blinded to the Sanger results. The AHP panel consists of 95 amplicons that covers 92% of the coding region of the four genes. Of the 95 amplicons, 93 had an average read-depth of >500 reads. In 29 of the 30 tested samples, pathogenic variants were correctly identified and annotated. The number of reads from the mutated alleles were approximately 50% of the total. The annotation of a 22-bp duplication with NGS differed from that of Sanger by one nucleotide. NGS showed an advantage in allelic discrimination over Sanger sequencing and was also able to detect a known somatic variant in the HMBS gene. The AHP panel will be applied in the initial diagnosis of new patients. Any sequence variations with a frequency of ≥10% will be confirmed by Sanger sequencing. The cost-effectiveness of a NGS approach for AHP in a diagnostic laboratory needs to be further assessed.
Aversive Training of Honey Bees in an Automated Y-Maze

Honeybees have remarkable learning abilities given their small brains, and have thus been established as a powerful model organism for the study of learning and memory. Most of our current knowledge is based on appetitive paradigms, in which a previously neutral stimulus (e.g., a visual, olfactory, or tactile stimulus) is paired with a reward. Here, we present a novel apparatus, the yAPIS, for aversive training of walking honey bees. This system consists in three arms of equal length and at 120° from each other. Within each arm, colored lights (λ = 375, 465 or 520 nm) or odors (here limonene or linalool) can be delivered to provide conditioned stimuli (CS). A metal grid placed on the floor and roof delivers the punishment in the form of mild electric shocks (unconditioned stimulus, US). Our training protocol followed a fully classical procedure, in which the bee was exposed sequentially to a CS paired with shocks (CS+) and to another CS not punished (CS-). Learning performance was measured during a second phase, which took advantage of the Y-shape of the apparatus and of real-time tracking to present the bee with a choice situation, e.g., between the CS+ and the CS-. Bees reliably chose the CS- over the CS+ after only a few training trials with either colors or odors, and retained this memory for at least a day, except for the shorter wavelength (λ = 375 nm) that produced mixed results. This behavior was largely the result of the bees avoiding the CS+, as no evidence was found for attraction to the CS-. Interestingly, trained bees initially placed in the CS+ spontaneously escaped to a CS- arm if given the opportunity, even though they could never do so during the training. Finally, honey bees trained with compound stimuli (color + odor) later avoided either components of the CS+. Thus, the yAPIS is a fast, versatile and high-throughput way to train honey bees in aversive paradigms. It also opens the door for controlled laboratory experiments investigating bimodal integration and learning, a field that remains in its infancy.
Hypofractionated Image-Guided Radiation Therapy With Simultaneous-Integrated Boost Technique for Limited Metastases: A Multi-Institutional Analysis

Purpose: To perform a multi-institutional analysis following treatment of limited osseous and/or nodal metastases in patients using a novel hypofractionated image-guided radiotherapy with simultaneous-integrated boost (HIGRT-SIB) technique. Methods: Consecutive patients treated with HIGRT-SIB for ≤5 active metastases at Duke University Medical Center or Durham Veterans' Affairs Medical Center between 2013 and 2018 were analyzed to determine toxicities and recurrence patterns following treatment. Most patients received 50 Gy to the PTVboost and 30 Gy to the PTVelect simultaneously in 10 fractions. High-dose treatment volume recurrence (HDTVR) and low-dose treatment volume recurrence (LDTVR) were defined as recurrences within PTVboost and PTVelect, respectively. Marginal recurrence (MR) was defined as recurrence outside PTVelect, but within the adjacent bone or nodal chain. Distant recurrence (DR) was defined as recurrences not meeting HDTVR, LDTVR, or MR criteria. Freedom from pain recurrence (FFPR) was calculated in patients with painful osseous metastases prior to HIGRT-SIB. Outcome rates were estimated at 12 months using the Kaplan-Meier method. Results: Forty-two patients met inclusion criteria with 59 sites treated with HIGRT-SIB (53% nodal and 47% osseous). Median time from diagnosis to first metastasis was 31 months and the median age at HIGRT-SIB was 69 years. The most common primary tumors were prostate (36%), gastrointestinal (24%), and lung (24%). Median follow-up was 11 months. One acute grade ≥3 toxicity (febrile neutropenia) occurred after docetaxel administration immediately following HIGRT-SIB. Four patients developed late grade ≥3 toxicities: two ipsilateral vocal cord paralyzes and two vertebral compression fractures. The overall pain response rate was 94% and the estimated FFPR at 12 months was 72%. The estimated 12 month rate of HDTVR, LDTVR, MR, and DR was 3.6, 6.2, 7.6, and 55.8%, respectively. DR preceded MR, HDTVR, or LDTVR in each instance. The estimated 12 month probability of in-field and marginal control was 90.0%. Conclusion: Targeting areas at high-risk for occult disease with a lower radiation dose, while simultaneously boosting gross disease with HIGRT in patients with limited osseous and/or nodal metastases, has a high rate of treated metastasis control, a low rate of MR, acceptable toxicity, and high rate of pain palliation. Further investigation with prospective trials is warranted.
Characterization and identification of antimicrobial peptides with different functional activities

In recent years, antimicrobial peptides (AMPs) have become an emerging area of focus when developing therapeutics hot spot residues of proteins are dominant against infections. Importantly, AMPs are produced by virtually all known living organisms and are able to target a wide range of pathogenic microorganisms, including viruses, parasites, bacteria and fungi. Although several studies have proposed different machine learning methods to predict peptides as being AMPs, most do not consider the diversity of AMP activities. On this basis, we specifically investigated the sequence features of AMPs with a range of functional activities, including anti-parasitic, anti-viral, anti-cancer and anti-fungal activities and those that target mammals, Gram-positive and Gram-negative bacteria. A new scheme is proposed to systematically characterize and identify AMPs and their functional activities. The 1st stage of the proposed approach is to identify the AMPs, while the 2nd involves further characterization of their functional activities. Sequential forward selection was employed to extract potentially informative features that are possibly associated with the functional activities of the AMPs. These features include hydrophobicity, the normalized van der Waals volume, polarity, charge and solvent accessibility-all of which are essential attributes in classifying between AMPs and non-AMPs. The results revealed the 1st stage AMP classifier was able to achieve an area under the receiver operating characteristic curve (AUC) value of 0.9894. During the 2nd stage, we found pseudo amino acid composition to be an informative attribute when differentiating between AMPs in terms of their functional activities. The independent testing results demonstrated that the AUCs of the multi-class models were 0.7773, 0.9404, 0.8231, 0.8578, 0.8648, 0.8745 and 0.8672 for anti-parasitic, anti-viral, anti-cancer, anti-fungal AMPs and those that target mammals, Gram-positive and Gram-negative bacteria, respectively. The proposed scheme helps facilitate biological experiments related to the functional analysis of AMPs. Additionally, it was implemented as a user-friendly web server (AMPfun, http://fdblab.csie.ncu.edu.tw/AMPfun/index.html) that allows individuals to explore the antimicrobial functions of peptides of interest.
Cassava brown streak virus Ham1 protein hydrolyses mutagenic nucleotides and is a necrosis determinant

Summary Cassava brown streak disease (CBSD) is a leading cause of cassava losses in East and Central Africa, and is currently having a severe impact on food security. The disease is caused by two viruses within the Potyviridae family: Cassava brown streak virus (CBSV) and Ugandan cassava brown streak virus (UCBSV), which both encode atypical Ham1 proteins with highly conserved inosine triphosphate (ITP) pyrophosphohydrolase (ITPase) domains. ITPase proteins are widely encoded by plant, animal, and archaea. They selectively hydrolyse mutagenic nucleotide triphosphates to prevent their incorporation into nucleic acid and thereby function to reduce mutation rates. It has previously been hypothesized that U/CBSVs encode Ham1 proteins with ITPase activity to reduce viral mutation rates during infection. In this study, we investigate the potential roles of U/CBSV Ham1 proteins. We show that both CBSV and UCBSV Ham1 proteins have ITPase activities through in vitro enzyme assays. Deep‐sequencing experiments found no evidence of the U/CBSV Ham1 proteins providing mutagenic protection during infections of Nicotiana hosts. Manipulations of the CBSV_Tanza infectious clone were performed, including a Ham1 deletion, ITPase point mutations, and UCBSV Ham1 chimera. Unlike severely necrotic wild‐type CBSV_Tanza infections, infections of Nicotiana benthamiana with the manipulated CBSV infectious clones do not develop necrosis, indicating that that the CBSV Ham1 is a necrosis determinant. We propose that the presence of U/CBSV Ham1 proteins with highly conserved ITPase motifs indicates that they serve highly selectable functions during infections of cassava and may represent a euphorbia host adaptation that could be targeted in antiviral strategies.
Colorectal Poorly Differentiated Neuroendocrine Carcinomas and Mixed Adenoneuroendocrine Carcinomas: Insights Into the Diagnostic Immunophenotype, Assessment of Methylation Profile, and Search for Prognostic Markers

Colorectal poorly differentiated neuroendocrine carcinomas (NECs) and mixed adenoneuroendocrine carcinomas (MANECs) are well-recognized entities generally known to be associated with biological aggressiveness and poor patient survival. However, a few published papers have highlighted the existence of a subgroup of tumors with a better survival than expected; however, to date, there are no established parameters that usefully identify this category. In the present study we have investigated the morphologic features, the CpG methylator phenotype (CIMP), microsatellite instability (MSI), and the immunohistochemical profile, including the expression of transcription factors (TTF1, ASH1, CDX2, and PAX5), stem cell markers (CD117 and CD34), and cytokeratins 7 and 20, in a series of 39 carcinomas (27 NECs and 12 MANECs) to better characterize such neoplasms and to search for prognostic indicators. No different patient survival was observed between NECs and MANECs. Neoplasms showed a heterogenous spectrum of morphologic and immunohistochemical features; however, only large-cell subtype, significant peritumoral lymphoid reaction, CD117 immunoreactivity, vascular invasion, and MSI/CIMP+ status were significantly correlated with prognosis on univariable analysis. Furthermore, vascular invasion and CD117 immunoreactivity were independent prognostic markers on multivariable analysis. In addition to these prognostic features, neoplasms showed different expression of transcription factors, stem cell markers, and cytokeratins that should be considered for diagnostic purposes and, especially, for discriminating among possible differential diagnoses.
Single-Step PCR Using (GACA)4 Primer: Utility for Rapid Identification of Dermatophyte Species and Strains

ABSTRACT Dermatophytes are fungi that belong to three genera: Epidermophyton, Microsporum, and Trichophyton. Identification of dermatophyte species is essential for appropriate diagnosis and treatment of dermatophytosis. Routine identification depends on macroscopic and microscopic morphology, which is time-consuming and does not identify dermatophyte strains. In this study, two PCR-based methods were compared for their abilities to identify 21 dermatophyte isolates obtained from Egyptian patients to the species and strain levels. The first method employed a two-step method: PCR amplification, using ITS1 and ITS4 as primers, followed by restriction enzyme digestion using the endonuclease MvaI. The second method employed a one-step approach employing the repetitive oligonucleotide (GACA)4 as a primer. Dermatophyte strains were also identified using a conventional culture method. Our results showed that the conventional culture method identified four species: Microsporum canis, Trichophyton mentagrophytes, Trichophyton rubrum, and Trichophyton violaceum. Moreover, both PCR methods agreed with the diagnosis made using the conventional approach. Furthermore, ITS1/ITS4-based PCR provided no strain differentiation, while (GACA)4-based PCR identified different varieties among the T. mentagrophytes isolates. Taken together, our results suggest that (GACA)4-based PCR has utility as a simple and rapid method for identification of dermatophyte species as well as utility for differentiation of T. mentagrophytes variants.
Probing the folding mechanism of a leucine zipper peptide by stopped-flow circular dichroism spectroscopy.

Leucine zipper peptides provide simple model systems for studying both the intramolecular and intermolecular interactions that govern protein folding. The synthetic 33-residue peptide GCN4-p1, derived from the yeast transcriptional activator GCN4, forms a stable biomolecular coiled-coil structure [O'Shea, E. K. , Klemm, J. D. , Kim, P. S. , & Alber, T. (1991) Science 254, 539-544]. The guanidine-HCl induced equilibrium unfolding of this peptide at 5 degrees C and pH 7.0 yields a standard state free energy of 10.49 +/- 0.23 kcal (mol dimer)-1 when fit to a two-state model involving the native dimer and the unfolded monomer. The unfolding and refolding kinetics of GCN4-p1 were monitored by stopped-flow circular dichroism spectroscopy as a function of both peptide concentration and final denaturant concentration. The unfolding kinetics displayed single-exponential behavior, consistent with a unimolecular reaction. The refolding kinetics, which are dependent on both peptide and guanidine concentration, are well described by a simple bimolecular association reaction. A simultaneous fit of all of the unfolding and refolding kinetic data to the model, N2[symbol: see text]2U, yields refolding and unfolding rate constants in the absence of denaturant of 4.2 x 10(5) M-1 S-1 and 3.3 x 10(-3) S-1, respectively. The equilibrium unfolding curve is accurately predicted from these rate constants, providing further support for the validity of the two-state kinetic model.
Functional Outcome after Endoscopic Lumbar Discectomy by Destandau’s Technique: A Prospective Study of 614 Patients

Study Design Prospective study. Purpose To investigate the efficacy of the lumbar discectomy procedure using the Destandau Endospine System by assessing the functional outcome and complication rate in 614 patients. Overview of Literature Endoscopic Spine Surgery (Endospine) using Destandau’s technique is an established treatment method of lumbar disk herniation; it was introduced in 1993 and is gaining prominence for its small skin incision and minimal tissue dissection with excellent visualization. Methods Of 840 patients, we selected 614 patients, based on the strict inclusion criteria, who underwent endoscopic lumbar discectomy (ELD) between August 2008 and November 2015. The technique comprised localization of the symptomatic level followed by insertion of an endospine system device through a 15–20-mm skin and fascial incision to perform a discectomy. We evaluated results by Macnab’s criteria, Oswestry Disability Index (ODI) and Visual Analog Scale (VAS) score after a minimum follow-up of 12 months and maximum up to 54 months. Results Based on the modified Macnab’s criteria, 479 patients (78.01%) exhibited excellent, 110 (17.9%) good, 19 (3.09%) fair, and 6 (0.97%) poor results. The average ODI score was improved from 64 (range, 44–86; standard deviation [SD]=9.2) to 14 (range, 2–31; SD=4.4), and the average VAS score from 7.8 (range, 6–10; SD=0.9) to 2 (range, 0–7; SD=1.2) in a year. On 1-year follow-up, 589 patients (95.9%) were completely pain-free and satisfied with the procedure. Conclusions ELD provides a safe, effective, and minimal access corridor for lumbar discectomy. The technique also allows early postoperative mobilization and faster return-to-work.
Ecological factors and morphological traits are associated with repeated genomic differentiation between lake and stream stickleback

The repeated evolution of similar phenotypes in independent populations (i.e. parallel or convergent evolution) provides an opportunity to identify genetic and ecological factors that influence the process of adaptation. Threespine stickleback fish (Gasterosteus aculeatus) are an excellent model for such studies, as they have repeatedly adapted to divergent habitats across the Northern hemisphere. Here, we use genomic, ecological and morphological data from 16 independent pairs of stickleback populations adapted to divergent lake and stream habitats. We combine a population genomic approach to identify regions of the genome that are likely under selection in these divergent habitats with an association mapping approach to identify regions of the genome that underlie variation in ecological factors and morphological traits. Over 37% of genomic windows are repeatedly differentiated across lake–stream pairs. Similarly, many genomic windows are associated with variation in abiotic factors, diet items and morphological phenotypes. Both the highly differentiated windows and candidate trait windows are non-randomly distributed across the genome and show some overlap. However, the overlap is not significant on a genome-wide scale. Together, our data suggest that adaptation to divergent food resources and predation regimes are drivers of differentiation in lake–stream stickleback, but that additional ecological factors are also important. This article is part of the theme issue ‘Convergent evolution in the genomics era: new insights and directions’.
The implementation of high-speed FFT processor based on FPGA

A method of implementing 256-point, high-speed and 16-bit complex FFT is presented on the radix-4 FFT algorithm. By using a fixed geometry addressing, pipeline designing and block floating point structure, the data has the greater precision and dynamic range. The results show that the design is efficient, strongly extensive and occupies less resource. It is a good method to meet the high-speed digital signal processing requirements.