Miracle-dz/UniFAR-FTUs huggingface dataset:
Most Monogenic Disorders Are Caused by Mutations Altering Protein Folding Free Energy

Revealing the molecular effect that pathogenic missense mutations have on the corresponding protein is crucial for developing therapeutic solutions. This is especially important for monogenic diseases since, for most of them, there is no treatment available, while typically, the treatment should be provided in the early development stages. This requires fast targeted drug development at a low cost. Here, we report an updated database of monogenic disorders (MOGEDO), which includes 768 proteins and the corresponding 2559 pathogenic and 1763 benign mutations, along with the functional classification of the corresponding proteins. Using the database and various computational tools that predict folding free energy change (ΔΔG), we demonstrate that, on average, 70% of pathogenic cases result in decreased protein stability. Such a large fraction indicates that one should aim at in silico screening for small molecules stabilizing the structure of the mutant protein. We emphasize that knowledge of ΔΔG is essential because one wants to develop stabilizers that compensate for ΔΔG, but do not make protein over-stable, since over-stable protein may be dysfunctional. We demonstrate that, by using ΔΔG and predicted solvent exposure of the mutation site, one can develop a predictive method that distinguishes pathogenic from benign mutations with a success rate even better than some of the leading pathogenicity predictors. Furthermore, hydrophobic–hydrophobic mutations have stronger correlations between folding free energy change and pathogenicity compared with others. Also, mutations involving Cys, Gly, Arg, Trp, and Tyr amino acids being replaced by any other amino acid are more likely to be pathogenic. To facilitate further detection of pathogenic mutations, the wild type of amino acids in the 768 proteins mentioned above was mutated to other 19 residues (14,847,817 mutations), the ΔΔG was calculated with SAAFEC-SEQ, and 5,506,051 mutations were predicted to be pathogenic.
Treated and Untreated Primary Progressive Multiple Sclerosis: Walkthrough Immunological Changes of Monocytes and T Regulatory Cells

The objective of this study was to investigate regulatory T cells (Tregs) and monocytes; specifically, the expression of CTLA-4 (CD152) and FOXP3+ in CD4+CD25+ Tregs and the expression of CD40+ and CD192+ monocyte subpopulations in subjects with primary progressive multiple sclerosis (PPMS). Immunological analysis was conducted on peripheral blood samples collected from the 28 PPMS subjects (15 treated with ocrelizumab and 13 untreated PPMS subjects) and 10 healthy control subjects (HCs). The blood samples were incubated with antihuman CD14, CD16, CD40, and CD192 antibodies for monocytes and antihuman CD4, CD25, FOXP3, and CTLA-4 antibodies for lymphocytes. The study results showed that in comparison to HCs both ocrelizumab treated (N = 15) and untreated (N = 13) PPMS subjects had significantly increased percentages of CTLA-4+ and FOXP3+ in CD4+CD25+ Tregs. Further, ocrelizumab treated PPMS subjects, compared to the untreated ones, had significantly decreased percentages of CD192+ and CD40+ nonclassical monocytes. Increased percentages of CTLA-4+ and FOXP3+ in CD4+CD25+ Tregs in both ocrelizumab treated and untreated PPMS subjects indicates the suppressive (inhibitory) role of Tregs in abnormal immune responses in PPMS subjects. Decreased percentages of CD40+, CD192+, and CD14+CD16++ monocytes for treated compared to untreated PPMS subjects suggests a possible role for ocrelizumab in dampening CNS inflammation.
Indicators of Disaster Risk and Risk Management: Program for Latin America and the Caribbean: Summary Report

This technical notes summarizes the results of the application and update of the IDB's Indicators of Disaster Risk and Risk Management for borrowing member countries. The four indicators -Disaster Deficit Index (DDI), the Local Disaster Index (LDI), the Prevalent Vulnerability Index (PVI), and the Risk Management Index (RMI)- measure a country's economic capacity to recover from a catastrophic event; susceptibility due to exposed infrastructure and people; social and environmental risk associated with small-scale disasters; and past risk management performance.
Multi-Physics Modeling of Melting-Solidification Characteristics in Laser Powder Bed Fusion Process of 316L Stainless Steel

In the laser powder bed fusion process, the melting-solidification characteristics of 316L stainless steel have a great effect on the workpiece quality. In this paper, a multi-physics model was constructed using the finite volume method (FVM) to simulate the melting-solidification process of a 316L powder bed via laser powder bed fusion. In this physical model, the phase change process, the influence of temperature gradient on surface tension of molten pool, and the influence of recoil pressure caused by the metal vapor on molten pool surface were considered. Using this model, the effects of laser scanning speed, hatch space, and laser power on temperature distribution, keyhole depth, and workpiece quality were studied. This study can be used to guide the optimization of process parameters, which is beneficial to the improvement of workpiece quality.
Recognition for acyclic context-sensitive grammars is NP-complete

Context-sensitive grammars in which each rule is of the form ~ZA -~ ary~3 are acyclic iï the associated context-free grammar with the rules Z~ ry is acyclic. The problem whether an input atring is in the language generated by an acyclic context-sensitive grammar is NP-complete. Introduction One of the most well-known classifications of rewrite grammars is the Chomsky hierarchy. Grammars and languages are of type 0(unrestricted), type 1(context-sensitive), type 2(context-free) or of type 3(regular). Much reseazch has been done involving regulaz and context-free grammazs. Contextfree languages can be recognized in a time that is polynomial in the length of the input and the length of the grammar [Eazley, 1970]. Recognition of type 0 languages is undecidable. We see two majors tracks for the reseazch on grammazs which lie between these two grammaz classes. First, people have tried to put restrictions on context-sensitive grammazs in order to generate context-free languages. Among them are Book [1972], Hibbard [1974] and Ginsburg and Greibach [1966]. Baker [1974] has shown that these attacks come down to the same more or less. They all block the use of context to pass information through the string. Book [1973] gives an overview of attempts to generate context-free languages with non-contextfree grammazs. How to restrict permutative grammars in order to generate context-free languages is described in Malckinen [1985]. The other track is the track of complexity of recognition. One of the best introductions to complexity theory is Gazey and Johnson [1979]. They state that recognition for context-sensitive grammazs is PSPACE-complete (referring to [Kuroda, 1964] and [Karp, 1972]). Some people have tried to put restrictions on CSG's so that recognition lies somewhere between PSPACE and P. Book [1978] has shown that for linear time CSG's recognition is NPcomplete even for (some) fixed grammars. Furthermore there is a result that recognition for gmwing CSG's is polynomial for fixed grammazs [Dahlhaus and Wazmuth, 1986]. This is the line I am following. In this azticle I will consider one type of restricted context-sensitive grammars, the acyclic context sensitive grammars. The complexity of recognition is lower than in the unrestricted case because we restrict the amount of information that can be sent (and we do not block it by bazriers! ). In the unrestricted case we can send messages that leave no trace. After a message
Expansion of Mental Health Care in Japanese Obstetric Institutes

Background: The Japan Association of Obstetricians and Gynecologists (JAOG) has raised awareness of the usefulness of identifying pregnant women with mental health problems and supporting them through multi-professional collaboration. We evaluated the results of questionnaire surveys on mental health care conducted in all obstetric institutes that are members of the JAOG annually. Methods: Between 2017 and 2023, we requested all obstetric institutes (n = 2,073-2,427) that are members of the JAOG to provide information concerning mental health care for pregnant and postpartum women about the situation in December every year from 2017. Here, we evaluated the results of the questionnaire surveys. Results: During the study periods, 56.9-74.8% of the 2,073-2,427 institutes responded with valid information. The percentage of obstetric institutes screening for mental health problems during pregnancy and the postpartum period increased from 54.3% and 53.7% to 87.1% and 83.8%, respectively (p < 0.01). However, the proportion of obstetric institutes able to manage pregnant women with mental disorders did not change significantly during the study period. Conclusion: There has been progress in the active identification of women with mental health problems during pregnancy and the postpartum period. However, the proportion of institutes managing mental disorders has not changed.
Skeletal abnormalities caused by a Connexin43R239Q mutation in a mouse model for autosomal recessive craniometaphyseal dysplasia

Craniometaphyseal dysplasia (CMD), a rare craniotubular disorder, occurs in an autosomal dominant (AD) or autosomal recessive (AR) form. CMD is characterized by hyperostosis of craniofacial bones and flaring metaphyses of long bones. Many patients with CMD suffer from neurological symptoms. To date, the pathogenesis of CMD is not fully understood. Treatment is limited to decompression surgery. Here, we report a knock in (KI) mouse model for AR CMD carrying a R239Q mutation in CX43. Cx43KI/KI mice replicate many features of AR CMD in craniofacial and long bones. In contrast to Cx43+/+ littermates, Cx43KI/KI mice exhibit periosteal bone deposition and increased osteoclast (OC) numbers in the endosteum of long bones, leading to an expanded bone marrow cavity and increased cortical bone thickness. Although formation of Cx43+/+ and Cx43KI/KI resting OCs are comparable, on bone chips the actively resorbing Cx43KI/KI OCs resorb less bone. Cortical bones of Cx43KI/KI mice have an increase in degenerating osteocytes and empty lacunae. Osteocyte dendrite formation is decreased with reduced expression levels of Fgf23, Sost, Tnf-α, IL-1β, Esr1, Esr2, and a lower Rankl/Opg ratio. Female Cx43KI/KI mice display a more severe phenotype. Sexual dimorphism in bone becomes more evident as mice age. Our data show that the CX43R239Q mutation results in mislocalization of CX43 protein and impairment of gap junction and hemichannel activity. Different from CX43 ablation mouse models, the CX43R239Q mutation leads to the AR CMD-like phenotype in Cx43KI/KI mice not only by loss-of-function but also via a not yet revealed dominant function.
Evaluation of Strawberry Germplasm at Sher-E-Bangla Agricultural University, Bangladesh

An experiment was accomplished at Sher-e-Bangla Agricultural University (SAU), Bangladesh during June 2011 to March 2012 to evaluate the performance of strawberry germplasm. Three Strawberry germplasm viz. V 1 (Germplasm-01), V 2 (Germplasm-02), V 3 (Germplasm-03) were exploited on the experiment; which was outlined in Complete Randomized Design (CRD) with five replication each. Among germplasm, utmost fruits number (16.5 plant 1), single fruit weight (14.1 g), total fruit weight (244.9 g plant -1 ), brix percentage (8.3%) were found from V 1 whereas least for the same were recorded in V 2 . In view of overall performances, this study suggests that V 1 can be used as a potential germplasm for sustainable yield production.
CENTERIS 2014-Conference on ENTERprise Information Systems / ProjMAN 2014-International Conference on Project MANagement / HCIST 2014-International Conference on Health and Social Care Information Systems and Technologies Software as a Service Value and Firm Performance-a literature review synthesis

It is consensual that Software as a Service (SaaS) has significant effects on enterprise costs and return on investment (ROI) in information technologies (IT) and information systems (IS). However, as a distribution model which is still relatively recent and a fraction of all IT invested, even if growing at a faster pace than traditional distribution models, the impact in Firm Performance is still an area of research which is very much under covered especially in the small and medium enterprises (SMEs) segment. Literature reviews to support research of SaaS applications impact in SMEs Firm Performance are unknown to the best of our knowledge and this review in selected publications is a starting point to fill this gap and looks at some of the cross-road subjects that might be combined to build on greater knowledge and research work on the subject, such as Firm Performance influenced by (not specified genre of) IT/IS adoption; Cloud Computing and Performance, and, Enterprise Systems Software and Firm Performance. It provides an updated bibliography of the most relevant publications about these subjects, published mainly during the period of 2001 to 2014, for the exception of a seminal article published in 1995. A total of 32 articles from 30 journals and 2 conferences are reviewed. The main focus of this paper is to shed the light on the areas that researchers should consider in the research of the impact of SaaS business applications adoption in SMEs Firm Performance, and which are the major variables that explain SaaS Value influence to these organizations. © 2014 The Authors. Published by Elsevier Ltd. Peer-review under responsibility of the Organizing Committees of CENTERIS 2014
The Building Blocks of a Cloud Strategy : Evidence from Three SaaS Providers

With all the hype about how easy it is to jump to the cloud, and master the art of offering application software via the cloud, it is hardly surprising that many firms have approached the cloud without a clear strategy in mind, which has resulted in numerous downfalls. Analyzing three firms on the point of deciding to offer cloud-based application software, we show how the decision to utilize the cloud is informed by the characteristics of the firm’s respective industry, as well as by the existing stock of their internal systems and processes (also known as its design capital). These two dimensions comprise five building blocks that largely determine the unfolding of a cloud strategy. The five blocks include the turbulence, concentration and growth that characterize a firm’s industry, a firm’s option value (i.e. the breadth of a firm’s opportunities afforded by its design capital), and the expected cost or effort entailed in exercising the opportunities embedded in that design capital (also known as its technical debt). Most importantly, our case analysis reveals two additional blocks related to customers’ perceptions and concerns with the cloud-based SaaS offering. These include the criticality of security optimization and the demand for software customization in the firm’s offering. We argue that firms wishing to offer cloud-based application software need to consider these seven blocks in order to develop a successful cloud-based SaaS strategy.
Using Liver Organoids as Models to Study the Pathobiology of Rare Liver Diseases

Liver organoids take advantage of several important features of pluripotent stem cells that self-assemble in a three-dimensional culture matrix and reproduce many aspects of the complex organization found within their native tissue or organ counterparts. Compared to other 2D or 3D in vitro models, organoids are widely believed to be genetically stable or docile structures that can be programmed to virtually recapitulate certain biological, physiological, or pathophysiological features of original tissues or organs in vitro. Therefore, organoids can be exploited as effective substitutes or miniaturized models for the study of the developmental mechanisms of rare liver diseases, drug discovery, the accurate evaluation of personalized drug responses, and regenerative medicine applications. However, the bioengineering of organoids currently faces many groundbreaking challenges, including a need for a reasonable tissue size, structured organization, vascularization, functional maturity, and reproducibility. In this review, we outlined basic methodologies and supplements to establish organoids and summarized recent technological advances for experimental liver biology. Finally, we discussed the therapeutic applications and current limitations.
Gas concentration mapping and source localization for environmental monitoring through unmanned aerial systems using model-free reinforcement learning agents

There are three primary objectives of this work; first: to establish a gas concentration map; second: to estimate the point of emission of the gas; and third: to generate a path from any location to the point of emission for UAVs or UGVs. A mountable array of MOX sensors was developed so that the angles and distances among the sensors, alongside sensors data, were utilized to identify the influx of gas plumes. Gas dispersion experiments under indoor conditions were conducted to train machine learning algorithms to collect data at numerous locations and angles. Taguchi’s orthogonal arrays for experiment design were used to identify the gas dispersion locations. For the second objective, the data collected after pre-processing was used to train an off-policy, model-free reinforcement learning agent with a Q-learning policy. After finishing the training from the training data set, Q-learning produces a table called the Q-table. The Q-table contains state-action pairs that generate an autonomous path from any point to the source from the testing dataset. The entire process is carried out in an obstacle-free environment, and the whole scheme is designed to be conducted in three modes: search, track, and localize. The hyperparameter combinations of the RL agent were evaluated through trial-and-error technique and it was found that ε = 0.9, γ = 0.9 and α = 0.9 was the fastest path generating combination that took 1258.88 seconds for training and 6.2 milliseconds for path generation. Out of 31 unseen scenarios, the trained RL agent generated successful paths for all the 31 scenarios, however, the UAV was able to reach successfully on the gas source in 23 scenarios, producing a success rate of 74.19%. The results paved the way for using reinforcement learning techniques to be used as autonomous path generation of unmanned systems alongside the need to explore and improve the accuracy of the reported results as future works.
Peak-to-mean Power Control in Ofdm, Golay Complementary Sequences and Reed-muller Codes

We present a range of coding schemes for OFDM transmission using binary, quaternary, octary and higher-order modulation that give high code rates for moderate numbers of carriers. These schemes have tightly bounded peak-to-mean envelope power ratio (PMEPR) and simultaneously have good error correction capability. The key theoretical result is a previously unrecognised connection between Golay complementary sequences and second-order Reed-Muller codes over alphabets Z 2 h. We obtain additional exibility in trading oo code rate, PMEPR and error correction capability by partitioning the second-order Reed-Muller code into cosets such that codewords with large values of PMEPR are isolated. For all the proposed schemes we show that encoding is straightforward and give an eecient decoding algorithm involving multiple fast Hadamard transforms. Since the coding schemes are all based on the same formal generator matrix we can deal adaptively with varying channel constraints and evolving system requirements. I. The envelope power problem in OFDM transmission Orthogonal frequency division multiplexing (OFDM) is a method of transmitting data simultaneously over multiple equally-spaced carrier frequencies, using Fourier transform processing for modulation and demod-ulation 10]. The method has been proposed or adopted for many types of radio systems such as wireless Local Area Networks 2] and digital audio and digital video broadcasting 1], 44]. OFDM ooers many well-documented advantages for multicarrier transmission at high data rates, particularly in mobile applications. Speciically, it has inherent resistance to dispersion in the propagation channel 5]. Furthermore when coding is added it is possible to exploit frequency diversity in frequency selective fading channels to obtain excellent performance under low signal-to-noise conditions 43]. For these reasons OFDM is often preferable to constant envelope modulation with adaptive equalisation (and indeed is arguably less complex to implement 32]). The principal diiculty with OFDM is that when the sinusoidal signals of the n carriers add mostly constructively the peak envelope power is as much as n times the mean envelope power. If the peak envelope power is subject to a design or regulatory limit then this has the eeect of reducing the mean envelope power allowed under OFDM relative to that allowed under constant envelope modulation. If battery power is a constraint , as is typically the case with portable equipment, then the power ampliiers required to behave linearly up to the peak envelope power must be operated ineeciently (with considerable backoo from compression). Digital hard limiting of the transmitted signal has been shown …
Stability, survival, patient satisfaction, and cost-minimization of CAD/CAM versus conventional multistranded fixed retainers in orthodontic patients: a 2-year follow-up of a two-centre randomized controlled trial

Summary Background CAD/CAM (computer-aided design/computer-aided manufacturing) fixed retainers (FRs) as an alternative to multistranded FRs to maintain orthodontic treatment outcome. Objectives The primary aim was to compare CAD/CAM versus conventional multistranded FRs in terms of stability until 2 years. Secondary outcomes were failure rates, patient satisfaction, and cost-minimization. Trial design 2-arm parallel, two-centre randomized controlled trial. Methods Patients were randomized to CAD/CAM or conventional FRs in both arches, in a 1:1 ratio and blocks of four. Allocation concealment was secured by using sequentially numbered envelopes. Patients were blinded. FRs were bonded at the end of treatment, and patients were recalled after 12 and 24 months. First-time retainer failures were recorded and digital impressions were taken. Arch widths and lengths, as well as Little’s Irregularity Index (LII), were measured. Additionally, patients answered satisfaction questionnaires. Linear mixed models were applied for measurements and patient satisfaction. Survival analyses were estimated with Kaplan–Meier curves, along with Cox-regression modelling. Cost-minimization analysis was undertaken. Results One hundred and eighty-one patients were randomized (98 in Centre 1, and 83 in Centre 2): 90 in CAD/CAM and 91 in conventional group. One hundred and fifty three patients attended T24 follow-up. There were no significant differences in LII and arch dimensions between groups for failure-free patients. Within 24 months, 34% maxillary CAD/CAM FRs and 38% maxillary conventional FRs failed, along with 42% mandibular CAD/CAM FRs and 40% mandibular conventional FRs, with no significant difference in survival between groups (hazard ratios conventional to CAD/CAM: maxillary arch: 1.20 [P = 0.46], mandibular arch: 0.98 [P = 0.94]). There were no significant differences in patient satisfaction between groups. No harms were observed. Cost-minimization analysis showed that CAD/CAM FRs were slightly cheaper than conventional FRs. Conclusions There were no clinically significant differences in LII, arch widths, and lengths between CAD/CAM and conventional FRs after 24 months. There were no differences in failures and patient satisfaction between groups. CAD/CAM FRs were slightly cheaper than conventional FRs. Trial registration ClinicalTrials.gov NCT04389879.