Miracle-dz/UniFAR-FTUs huggingface dataset:
Hybrid sequence-structure based HMM models leverage the identification of homologous proteins: the example of class II fusion proteins

We present a sequence-structure based method characterizing a set of functionally related proteins exhibiting low sequence identity and loose structural conservation. Given a (small) set of structures, our method consists of three main steps. First, pairwise structural alignments are combined with multi-scale geometric analysis to produce structural motifs i.e. regions structurally more conserved than the whole structures. Second, the sub-sequences of the motifs are used to build profile hidden Markov models (HMM) biased towards the structurally conserved regions. Third, these HMM are used to retrieve from UniProtKB proteins harboring signatures compatible with the function studied, in a bootstrap fashion. We apply these hybrid HMM to investigate two questions related to class II fusion proteins, an especially challenging class since known structures exhibit low sequence identity (less than 15%) and loose structural similarity (of the order of 15Å in lRMSD). In a first step, we compare the performances of our hybrid HMM against those of sequence based HMM. Using various learning sets, we show that both classes of HMM retrieve unique species. The number of unique species reported by both classes of methods are comparable, stressing the novelty brought by our hybrid models. In a second step, we use our models to identify 17 plausible HAP2-GSC1 candidate sequences in 10 different drosophila melanogaster species. These models are not identified by the PFÅM family HAP2-GCS1 (PF10699), stressing the ability of our structural motifs to capture signals more subtle than whole Pfam domains. In a more general setting, our method should be of interest for all cases functional families with low sequence identity and loose structural conservation. Our software tools are available from the FunChaT package of the Structural Bioinformatics Library (http://sbl.inria.fr).
Sample Complexity of Linear Quadratic Gaussian (LQG) Control for Output Feedback Systems

This paper studies a class of partially observed Linear Quadratic Gaussian (LQG) problems with unknown dynamics. We establish an end-to-end sample complexity bound on learning a robust LQG controller for open-loop stable plants. This is achieved using a robust synthesis procedure, where we first estimate a model from a single input-output trajectory of finite length, identify an H-infinity bound on the estimation error, and then design a robust controller using the estimated model and its quantified uncertainty. Our synthesis procedure leverages a recent control tool called Input-Output Parameterization (IOP) that enables robust controller design using convex optimization. For open-loop stable systems, we prove that the LQG performance degrades linearly with respect to the model estimation error using the proposed synthesis procedure. Despite the hidden states in the LQG problem, the achieved scaling matches previous results on learning Linear Quadratic Regulator (LQR) controllers with full state observations.
Safety and survival outcomes of transanal natural orifice specimen extraction using prolapsing technique for patients with middle- to low-rectal cancer

Objective The transanal approach to specimen collection, combined with the prolapsing technique, is a well-established and minimally invasive surgery for treating rectal cancer. However, reports on outcomes for this approach are sparse. We compared short- and long-term outcomes of conventional laparoscopic surgery (CLS) vs. transanal natural orifice specimen extraction (NOSE) using the prolapsing technique for patients with middle- to low-rectal cancer. Methods From January 2013 to December 2017, we enrolled consecutive patients with middle- to low-rectal cancer undergoing laparoscopic anterior resection. Totally, 50 patients who underwent transanal NOSE using the prolapsing technique were matched with 50 patients who received CLS. Clinical parameters and survival outcomes between the two groups were compared. Results Estimated blood loss (29.70±29.28 vs. 52.80±45.09 mL, P=0.003), time to first flatus (2.50±0.79 vs. 2.86±0.76, P=0.022), time to liquid diet (3.62±0.64 vs. 4.20±0.76 d, P<0.001), and the need for analgesics (22%vs. 48%, P=0.006) were significantly lower for the NOSE group compared to the CLS group. The incidences of overall complications and fecal incontinence were comparable in both groups. After a median follow-up of 44.52 months, the overall local recurrence rate (6% vs. 5%, P=0.670), 3-year disease-free survival (86.7% vs. 88.0%, P=0.945) and 3-year overall survival (95.6% vs. 96.0%, P=0.708), were not significantly different. Conclusions For total laparoscopic rectal resection, transanal NOSE using the prolapsing technique is effective and safe, and associated with less trauma and pain, a faster recovery, and similar survival outcomes compared to CLS.
A new species of diminutive salamander (Amphibia: Caudata: Plethodontidae: Nototriton) from the Montanas del Mico of Guatemala

-Nototriton stuarti, a new species of salamander belonging to the tribe Bolitoglossini, family Plethodontidae, is described from the Montaiias del Mico, north of the Motagua Valley, in eastern Guatemala. The species is geographically isolated from congeneric species, and represents the northwesternmost record for the genus, which ranges from eastern Guatemala to central Costa Rica. This poorly known species is morphologically most similar to Nototriton barbouri, which occurs in northwestern Honduras. Homoplastic evolution has produced diminutive, attenuate salamanders in many different clades of plethodontid salamanders in Middle America. These tiny species are difficult taxonomically and it has taken much effort to recognize that there are many more species than have been named throughout this region. New discoveries and new data have led to taxonomic revisions that are gradually identifying monophyletic groups, and as this process goes forward the generic level taxonomy has changed repeatedly. This is especially true of the genus Chiropterotriton Taylor, 1944, which as formerly recognized ranged from northeastern Mexico to Costa Rica, but which was not monophyletic and now has been fragmented into four genera (Chiropterotriton, Cryptotriton Garcia-Paris & Wake, 2000, Dendrotriton Wake & Elias, 1983, and Nototriton Wake & Elias, 1983). At present diminutive plethodontids found to the north and west of the Isthmus of Tehuantepec are assigned to Chiropterotriton (Darda, 1994), but, in addition, all members of the genera Pawimolge Taylor, 1944, Lineatriton Tanner, 1950, and especially Thorius Cope, 1869, none closely related to Chiropterotriton and all endemic to this area, are also diminutive. To the south and east of the Isthmus of Tehuantepec, extending as far as central Costa Rica, diminutive species are found in one well-supported clade (Garcia-Paris & Wake 2000). This clade includes the genera Cryptotriton, Dendrotriton, Nototriton and Oedipina, and possibly the poorly known Bradytriton Wake & Elias 1983 (G. Parra-Olea, pers. comm.). Oedipina Keferstein 1868 includes some diminutive species, but also some large and relatively robust, although elongated, species. The phylogenetic diversity of this clade is now understood, at least in broad outlines. Oedipina and Nototriton appear to be the most deeply nested groups (Garcia-Pm’s & Wake 2000), and they are also the most southerly in distribution, extending to Ecuador (moderately large species of Oedipina occur in South America, Brame & Wake 1963) and central Costa Rica, respectively. Both occur as far north as Guatemala, and Oedipina ranges into Chiapas, Mexico. Cryptotriton and Dendrotriton range from Honduras into Mexico, the former possibly even north and west of the Isthmus of Tehuantepec [the species 816 PROCEEDINGS OF THE BIOLOGICAL SOCIETY OF WASHINGTON
sEMG-Based Neural Network Prediction Model Selection of Gesture Fatigue and Dataset Optimization

The fatigue energy consumption of independent gestures can be obtained by calculating the power spectrum of surface electromyography (sEMG) signals. The existing research studies focus on the fatigue of independent gestures, while the research studies on integrated gestures are few. However, the actual gesture operation mode is usually integrated by multiple independent gestures, so the fatigue degree of integrated gestures can be predicted by training neural network of independent gestures. Three natural gestures including browsing information, playing games, and typing are divided into nine independent gestures in this paper, and the predicted model is established and trained by calculating the energy consumption of independent gestures. The artificial neural networks (ANNs) including backpropagation (BP) neural network, recurrent neural network (RNN), and long short-term memory (LSTM) are used to predict the fatigue of gesture. The support vector machine (SVM) is used to assist verification. Mean square error (MSE), root mean square error (RMSE), and mean absolute error (MAE) are utilized to evaluate the optimal prediction model. Furthermore, the different datasets of the processed sEMG signal and its decomposed wavelet coefficients are trained, respectively, and the changes of error functions of them are compared. The experimental results show that LSTM model is more suitable for gesture fatigue prediction. The processed sEMG signals are appropriate for using as the training set the fatigue degree of one-handed gesture. It is better to use wavelet decomposition coefficients as datasets to predict the high-dimensional sEMG signals of two-handed gestures. The experimental results can be applied to predict the fatigue degree of complex human-machine interactive gestures, help to avoid unreasonable gestures, and improve the user's interactive experience.
Stable and efficient immobilization of bi-enzymatic NADPH cofactor recycling system under consecutive microwave irradiation

One of the challenges in biocatalysis is the development of stable and efficient bi-enzymatic cascades for bio-redox reactions coupled to the recycling of soluble cofactors. Aldo-keto reductase (LEK) and glucose dehydrogenase (GDH) can be utilized as the NADPH recycling system for economic and efficient biocatalysis of (R)-4-chloro-3-hydroxybutanoate ((R)-CHBE), an important chiral pharmaceutical intermediate. The LEK and GDH was efficiently co-immobilized in mesocellular siliceous foams (MCFs) under microwave irradiation (CoLG-MIA). while they were also co-immobilized by entrapment in calcium alginate without MIA as control (CoLG-CA). The relative activity of CoLG-MIA was increased to 140% compared with that of free LEK. The CoLG-MIA exhibited a wider range of pH and temperature stabilities compared with other preparations. The thermal, storage and batch operational stabilities of microwave-assisted immobilized LEK-GDH were also improved. The NADPH recycling system exhibited the potential as the stable and efficient catalyst for the industrial preparation of (R)-CHBE.
STAT3 decoy oligonucleotide-carrying microbubbles with pulsed ultrasound for enhanced therapeutic effect in head and neck tumors

Signal transducer and activator of transcription-3 (STAT3) is an oncogenic transcription factor implicated in carcinogenesis, tumor progression, and drug resistance in head and neck squamous cell carcinoma (HNSCC). A decoy oligonucleotide targeting STAT3 offers a promising anti-tumor strategy, but achieving targeted tumor delivery of the decoy with systemic administration poses a significant challenge. We previously showed the potential for STAT3 decoy-loaded microbubbles, in conjunction with ultrasound targeted microbubble cavitation (UTMC), to decrease tumor growth in murine squamous cell carcinoma. As a next step towards clinical translation, we sought to determine the anti-tumor efficacy of our STAT3 decoy delivery platform against human HNSCC and the effect of higher STAT3 decoy microbubble loading on tumor cell inhibition. STAT3 decoy was loaded on cationic lipid microbubbles (STAT3-MB) or loaded on liposome-conjugated lipid microbubbles to form STAT3-loaded liposome-microbubble complexes (STAT3-LPX). UTMC treatment efficacy with these two formulations was evaluated in vitro using viability and apoptosis assays in CAL33 (human HNSCC) cells. Anti-cancer efficacy in vivo was performed in a CAL33 tumor murine xenograft model. UTMC with STAT3-MB caused significantly lower CAL33 cell viability compared to UTMC with STAT3-LPX (56.8±8.4% vs 84.5±8.8%, respectively, p<0.05). In vivo, UTMC with STAT3-MB had strong anti-tumor effects, with significantly less tumor burden and greater survival compared to that of UTMC with microbubbles loaded with a mutant control decoy and untreated control groups (p<0.05). UTMC with STAT3 decoy-loaded microbubbles significantly decreases human HNSSC tumor progression. These data set the stage for clinical translation of our microbubble platform as an imaged-guided, targeted delivery strategy for STAT3 decoy, or other nucleotide-based therapeutics, in human cancer treatment.
Dentogingival Smile Analysis of Young Adults of Al Qassim Province, Saudi Arabia: A Cross-Sectional Study

Objectives The present study aims to analyse the smiling components among young adults within Al Qassim region by evaluating typical smile parameters. Methodology. A cross-sectional study was conducted among 324 female and male participants between 18 and 35 years, within Al Qassim Province of Saudi Arabia. The dentogingival macro-aesthetic elements of the smile, the parallelism between the incisal curve and lower lip line, midline, and buccal corridors were determined by using Canon Rebel t7i (Canon, Melville, NY, USA) and evaluated by photo editing software Adobe Photoshop CC2019. The data were analysed using a chi-square test and Spearman's correlation test for nonparametric data. Results 62.5% of young adults had no buccal corridors. The nonparallel smile was found in 53.2% of young adults. A high smile line was observed in 33% of participants. 59.3% of young adults lacked a coinciding dental and facial midline. There was a statistically significant difference in the parallelism of the incisal curve and lower lip line as well as in the position of the upper lip line across genders (P < 0.05). Conclusion Understanding macro-aesthetic elements of teeth and their interrelation with the surrounding oral structures can be a guide in creating natural and aesthetically pleasing restorative treatment.
High-Frequency Synchronization Improves Firing Rate Contrast and Information Transmission Efficiency in E/I Neuronal Networks

High-frequency synchronization has been found in many real neural systems and is confirmed by excitatory/inhibitory (E/I) network models. However, the functional role played by it remains elusive. In this paper, it is found that high-frequency synchronization in E/I neuronal networks could improve the firing rate contrast of the whole network, no matter if the network is fully connected or randomly connected, with noise or without noise. It is also found that the global firing rate contrast enhancement can prevent the number of spikes of the neurons measured within the limited time window from being confused by noise, thereby enhancing the information encoding efficiency (quantified by entropy theory here) of the neuronal system. The mechanism of firing rate contrast enhancement is also investigated. Our work implies a possible functional role in information transmission of high-frequency synchronization in neuronal systems.
Production, Analysis and in Vivo Antihypertensive Evaluation of Novel Angiotensin-I-converting Enzyme Inhibitory Peptides from Porcine Brain

National Chung Hsing University, 145 Xingda Rd., South Dist. , Taichung City 402, Taiwan Toko University, No.51, Sec. 2, Xuefu Rd., Puzi City, Chiayi County 61363, Taiwan Department of Animal Science and Biotechnology, School of Veterinary Medicine, Azabu University, 1-17-71 Fuchinobe, Sagamihara, Kanagawa 252-0206, Japan Department of Biosciences, Faculty of Science and Engineering, Teikyo Unibersity, 1-1 Toyosatodai Utsunomiya Tochigi, 320-8551 Japan
The Short QTc Is a Marker for the Development of Atrial Flutter and Atrial Fibrillation

A short QT interval has been difficult to define, and there is debate whether it exists outside of an extremely small group of individuals with inherited channelopathies and whether it predicts cardiac arrhythmias. The objective was to identify cases with short QT and their consequences. Our hospital ECG database was screened for cases with a QTc based on the Bazett formula (QTcBZT) of less than 340 ms. The QTc was recalculated using the spline (QTcRBK) formula, which more accurately adjusts for the heart rate and identifies cases based on percentile distribution of the QT interval. The exclusion criteria were presence of bundle branch block, arrhythmias, or electronic pacemakers. An age- and sex-matched cohort was obtained from individuals with normal QT intervals with the same exclusion criteria. There were 28 cases with a short QTc (QTcRBK < 380 ms). The age was 69.6 ± 14.6 years (mean ± SD) (50% males). The QT interval was 305.7 ± 61.1 ms with QTcRBK 308.4 ± 31.4 ms. Subsequent ECGs showed atrial flutter in 21%, atrial fibrillation in 18%, and atrial tachycardia in 4% of cases. Thus, atrial arrhythmias occurred in 43% of cases. This incidence was significantly (p < 0.0001) greater than the incidence of atrial arrhythmias in age- and sex-matched controls. In conclusion, a short QT interval can be readily identified based on the first percentile of the new QTc formula. A short QTc is an important marker for the development of atrial arrhythmias, including atrial flutter and atrial fibrillation, with the former predominating. It should be part of patient assessment and warrants consideration to develop strategies for detection and prevention of atrial arrhythmias.
Short Messaging Services and Educational Information sharing by Students in Selected Public Universities in Nigeria

Questionnaire was used to collect data from 1676 undergraduate and postgraduate students randomly selected from three large public universities in Nigeria to determine how the students use text messaging or short messaging services (SMS) to exchange educational information. Uses and gratification theory, which emphasises that individuals are usually goal-directed in information search and use, and would often prefer media that would give them control of content choices, guided the study. Sixty-five percent and 63% of the respondents reported using the technology for contacting peers and lecturers respectively for educational matters, while less than 40% used the technology to contact others. Generally, closeness to mothers and education of parents influence use of the technology for educational contact. The instrumental gratifications of SMS capability to enable students escape face to face communication as well as its convenience explain use of SMS to make educational contacts. However, SMS use is mainly constrained by the difficulty to decipher the intention of the messages and by the confusion that often arises due to unclear acronyms often used by texters.
Onecut Factors and Pou2f2 Regulate the Distribution of V2 Interneurons in the Mouse Developing Spinal Cord

Acquisition of proper neuronal identity and position is critical for the formation of neural circuits. In the embryonic spinal cord, cardinal populations of interneurons diversify into specialized subsets and migrate to defined locations within the spinal parenchyma. However, the factors that control interneuron diversification and migration remain poorly characterized. Here, we show that the Onecut transcription factors are necessary for proper diversification and distribution of the V2 interneurons in the developing spinal cord. Furthermore, we uncover that these proteins restrict and moderate the expression of spinal isoforms of Pou2f2, a transcription factor known to regulate B-cell differentiation. By gain- or loss-of-function experiments, we show that Pou2f2 contribute to regulate the position of V2 populations in the developing spinal cord. Thus, we uncovered a genetic pathway that regulates the diversification and the distribution of V2 interneurons during embryonic development. Significance statement In this study, we identify the Onecut and Pou2f2 transcription factors as regulators of spinal interneuron diversification and migration, two events that are critical for proper CNS development.
The road to cloning of factor VIII and the recombinant era

Abstract Use of recombinant clotting factor now represents the standard of care in haemophilia across the developed world. But the recombinant era would not have occurred without the isolation from plasma of factor VIII in sufficient quantities to allow characterisation and cloning. Much of this development work occurred at the Royal Free Hospital.
Some Common SNPs of the T-Cell Homeostasis-Related Genes Are Associated with Multiple Sclerosis, but Not with the Clinical Manifestations of the Disease, in the Polish Population

Purpose Multiple sclerosis (MS) is an autoimmune disease, and genetic factors play an important role in its pathogenesis and progression. The aim of our study was to evaluate the frequencies of alleles and genetic variants of the T-cell homeostasis-related genes, in subjects with MS, as well as to investigate the association with MS clinical manifestations and disability. Methods 94 subjects with MS and 160 healthy individuals have been genotyped for seven common single-nucleotide variants in IL-2RA, CTLA4, CD40, and PADI4 genes. The ages of onset, duration of the disease, and clinical condition of the MS subjects were analysed. We used the Chi2 test confirmed with Fisher's exact test for statistical analysis. Results The frequency of allele T and CT/TT genotypes (rs7093069) in the IL2RA gene, as well as the T allele and CT/TT genotypes in rs12722598, were significantly higher in the control group. The significant differences between studied groups we also found for the G allele and GG/GA genotypes of rs3087243 in CTLA4 gene, which were more common among the control group. The heterozygous genotype TC (rs1883832) of CD40 gene was more common in the control subjects, and the frequency of the alleles and genotypes in the rs1748033 of the PADI4 gene did not differ between the studied groups. Between the studied genotypes, we did not observe any significant differences in the age of onset and duration of disease, including sex stratification. Conclusion Our results highlight the protective role of some of the T-cell homeostasis-related genetic variants in MS development, but not in its clinical manifestation.
Developments in mycotoxin analysis: an update for 2017-2018

This review summarises developments that have been published in the period from mid-2017 to mid-2018 on the analysis of various matrices for mycotoxins. Analytical methods to determine aflatoxins, Alternaria toxins, ergot alkaloids, fumonisins, ochratoxins, patulin, trichothecenes, and zearalenone are covered in individual sections. Advances in sampling strategies are discussed in a dedicated section, as are methods used to analyse botanicals and spices, and newly developed comprehensive liquid chromatographic-mass spectrometric based multi-mycotoxin methods. This critical review aims to briefly discuss the most important recent developments and trends in mycotoxin determination as well as to address limitations of the presented methodologies.