Miracle-dz/UniFAR-FTUs huggingface dataset:
Compound Heterozygosity in Cerebellar Ataxia, Mental Retardation, and Disequilibrium Syndrome Type 4

Abstract Cerebellar ataxia, mental retardation, and disequilibrium syndrome (CAMRQ) is a genetically and clinically heterogeneous disorder with four described subtypes. Autosomal recessive syndrome of cerebellar ataxia, mental retardation, and disequilibrium type 4 (CAMRQ4) is caused by mutations in the ATP8A2 gene. We report an 8-year-old boy with choreoathetosis, hypotonia, without the ability to keep his head up and profound mental retardation. There was quadrupedal locomotion, as well. MRI of the brain revealed a hypotrophy of the corpus callosum, diffuse white matter reduction, widespread delayed myelination and ventriculomegaly. Trio whole-exome sequencing revealed compound heterozygosity in the ATP8A2 gene consisting of a known variant c.1756C>T (p.Arg586*) inherited from the mother and a novel variant c. 691_701delCTGATGAAGTT (p.Leu231fs) inherited from the father. CAMRQ type 4 has been found in about 50 patients. To the best of our knowledge, this is the first reported patient with CAMRQ4 with these gene variants. The clinical presentation is severe.
Commodity Treatment and Quarantine Entomology Loop-mediated isothermal amplification of economically important Ceratitis species (Diptera: Tephritidae)

Ceratitis is an economically important genus of fruit flies that originated in Africa, has a wide host range, and causes serious economic losses due to its invasive damage. As a result, it is critical to identify them accurately and quickly in the world. Loop-mediated isothermal amplification (LAMP), as one of the representatives of isothermal amplification technology, has been widely used in the rapid nucleic acid detection of human pathogens and has shown its advantages in the identification of insect agricultural pests. In this study, using the mitochondrial cox1 and cob genes as target genes, the rapid molecular identification of the Ceratitis FARQ complex, C. cosyra, and C. capitata was realized based on LAMP. The experimental conditions optimization results showed that F3/B3:FIP/BIP = 1:8 was the optimal primer concentration ratio and 63 °C was the optimal reaction temperature. The sensitivity of the primers obtained in this study can reach up to 0.01 ng/ μ l DNA. A loop-mediated isothermal amplification identification technology system was established based on rapid, rough DNA extraction and visual detection of Ceratitis economically important fruit flies. The positive reaction system changed from pink to khaki by visual detection. The identification flow can be completed within 1 hour, including sample processing, DNA extraction, and LAMP visual detection.
Predicting neutralization susceptibility to combination HIV-1 monoclonal broadly neutralizing antibody regimens

Combination monoclonal broadly neutralizing antibodies (bnAbs) are currently being developed for preventing HIV-1 infection. Recent work has focused on predicting in vitro neutralization potency of both individual bnAbs and combination regimens against HIV-1 pseudoviruses using Env sequence features. To predict in vitro combination regimen neutralization potency against a given HIV-1 pseudovirus, previous approaches have applied mathematical models to combine individual-bnAb neutralization and have predicted this combined neutralization value; we call this the combine-then-predict (CP) approach. However, prediction performance for some individual bnAbs has exceeded that for the combination, leading to another possibility: combining the individual-bnAb predicted values and using these to predict combination regimen neutralization; we call this the predict-then-combine (PC) approach. We explore both approaches in both simulated data and data from the Los Alamos National Laboratory’s Compile, Neutralize, and Tally NAb Panels repository. The CP approach is superior to the PC approach when the neutralization outcome of interest is binary (e.g., neutralization susceptibility, defined as inhibitory concentration < 1 µg/mL. For continuous outcomes, the CP approach performs at least as well as the PC approach, and is superior to the PC approach when the individual-bnAb prediction algorithms have poor performance. This knowledge may be used when building prediction models for novel antibody combinations in the absence of in vitro neutralization data for the antibody combination; this, in turn, will aid in the evaluation and down-selection of these antibody combinations into prevention efficacy trials.
Music Source Separation With MLP Mixing of Time, Frequency, and Channel

This paper proposes a new music source separation (MSS) model based on an architecture with MLP-Mixer that leverages multilayer perceptrons (MLPs). Most of the recent MSS techniques are based on architectures with CNNs, RNNs, and attention-based transformers that take wave-forms or complex spectrograms or both as inputs. For the growth of the research ﬁeld, we believe it is important to study not only the current established methodologies but also diverse perspectives. Therefore, since the MLP-Mixer-based architecture has been reported to perform as well as or better than architectures with CNNs and transformers in the computer vision ﬁeld despite the MLP’s simple computation, we report a way to effectively apply such an architecture to MSS as a reusable insight. In this paper we propose a model called TFC-MLP, which is a variant of the MLP-Mixer architecture that preserves time-frequency positional relationships and mixes time, frequency, and channel dimensions separately, us-ing complex spectrograms as input. The TFC-MLP was evaluated with source-to-distortion ratio (SDR) using the MUSDB18-HQ dataset. Experimental results showed that the proposed model can achieve competitive SDRs when compared with state-of-the-art MSS models.
ATOM-1: A Foundation Model for RNA Structure and Function Built on Chemical Mapping Data

RNA-based medicines and RNA-targeting drugs are emerging as promising new approaches for treating disease. Optimizing these therapeutics by naive experimental screening is a time-consuming and expensive process, while rational design requires an accurate understanding of the structure and function of RNA. To address this design challenge, we present ATOM-1, the first RNA foundation model trained on chemical mapping data, enabled by data collection strategies purposely developed for machine learning training. Using small probe neural networks on top of ATOM-1 embeddings, we demonstrate that this model has developed rich internal representations of RNA. Trained on limited amounts of additional data, these small networks achieve state-of-the-art accuracy on key RNA prediction tasks, suggesting that this approach can enable the design of therapies across the RNA landscape.
The Impact of the COVID-19 Pandemic on Christian Higher Education in Indonesia: Natural and Moral Evil

Abstract The study aimed to (1) assess the empirical views of the Christian community in Christian higher education on the causes and impacts of the COVID-19 pandemic; (2) investigate the relationship between the causes and effects of the COVID-19 pandemic; and (3) determine differences in cause and effect between gender groups, academic status, and education levels. The method used was quantitative. The results show that (1) the Christian higher education community in Indonesia’s understanding of evil as the cause of COVID-19 is dominated by natural evil; (2) such perception has a positive and significant correlation with spiritual impact; and (3) males, females, lecturers, and students respond differently to the causes of the pandemic.
Network Traffic Anomaly Detection and Analysis - from Research to the Implementation

Withaconstantlyincreasingamountofencryptednetworktrafficandanewtypeofattack(“zero-day”),networktrafficanomalydetectionshowssignificantbenefitsovertraditionallyusedsignature-basedpacketinspectionmethodsforcybersecurity attackdetection.UsingNetFloworsimilarprotocolsisanattractiveapproachtoprovidingaccountinginformationaboutnetworkcommunicationsduetoitssimplicityandapplicabilityinareal-lifenetworkenvironment.Eventhoughthebasicset ofinformationinflowdataisnotsufficientforefficientmachinelearningtechniques,theyarequitesuitablefortheapplicationofentropy-basedanomalydetectiontechniques.Inthispaper,wepresentcomprehensiveworkinresearch,development andimplementationofnetworktrafficanomalydetectionsolutionsbasedontheentropyofflowdata.Startingfromthewell-knownentropy-basedapproach,werevealtheresultsofourmethodicworkinsolvingthemainchallengesindesigning anefficientanomalydetectionsolutionempoweredwiththeoriginalclassificationmethod.Sincetheproofofconceptwasachievedinthelaboratoryenvironmentusingofflinedatasets,thesolutionhasbeenimplementedrelyingontheexisting NetFlowAnalyzersoftwareproductNetVizura.Evenattheminimumviableproductstage,theapplicationconfirmshighperformancesandgreatapplicabilityoftheanomalydetectionandclassificationmethodinreal-lifenetworkenvironments.
A site-specific analysis of the ADP-Ribosylome unveils Homogeneous DNA Damage-Induced Serine ADP-Ribosylation across wild-type and BRCA-mutant Breast Cancer cell lines

ADP-ribosylation (ADPr) signaling plays a crucial role in the DNA damage response. Inhibitors against the main enzyme catalyzing ADPr after DNA damage – PARP1 – are used as targeted therapies against breast cancers with BRCA1/2 mutations. However, development of resistance to PARP inhibitors (PARPi) is a major obstacle in treating patients. To better understand the role of ADPr in PARPi sensitivity, we used Liquid Chromatography-Mass Spectrometry (LC-MS) for systems level analysis of the ADP-ribosylome in six breast cancer cell lines exhibiting different PARPi sensitivities. We identified 1,632 sites on 777 proteins across all cell lines, primarily on serine residues, with site-specific overlap of targeted residues across DNA damage-related proteins across all cell lines, demonstrating high conservation of serine ADPr signaling networks upon DNA damage. We furthermore observed site-specific differences in ADPr intensities in PARPi-sensitive BRCA mutants, and unique ADPr sites in PARPi-resistant BRCA mutant cells, which we notably show to have low PARG levels and longer ADPr chains on PARP1.
Inoculation dose, formulation and air temperature shape Metarhizium anisopliae virulence against the oriental fruit fly: lessons for improving on-target control strategies

Entomopathogenic fungi are a promising tool for the biological control of crop pests provided low or no impact on non-target organisms. Selection for host specificity as well as on-target applications open new avenues for more sustainable strategies for pest management. Isolates of Metarhizium anisopliae (Metschn.) Sorokin have been identified as promising for developing innovative entomovection-based strategies for the control of the oriental fruit fly, Bactrocera dorsalis (Hendel) (Diptera: Tephritidae), in Africa. To be effective, this technology requires high strain virulence at a low number of spores, in field conditions, but sufficient incubation time to allow transmission to wild conspecifics. In the present study, we investigated the virulence of the Met69 OD strain against adult flies, depending on the inoculation dose, formulation and air temperature. High pathogenicity was observed at very low inoculation doses (LT50 of 4.85 days with 6100 spores per fly) independently of fly sex. Virulence increased with spore load in a tight range (5600 and 6100 spores per fly) and with air temperature observed in the field (20-28°C). Unexpectedly, corn starch used as an adjuvant to increase the carrying capacity of insects decreased the virulence of the pathogen. Results are of utmost importance to improve area-wide control strategies based on contamination of wild flies in mango orchards through auto-inoculation devices or interactions with released mass-reared sterile males coated with fungal spores.
Hidden hearing loss in hereditary demyelinating neuropathies: insights from Charcot-Marie-Tooth mouse models

Hidden hearing loss (HHL) is a recently described auditory neuropathy characterized by normal audiometric thresholds but reduced sound-evoked potentials. It has been proposed that HHL contributes to hearing difficulty in noisy environments in people with normal audiometric thresholds, a widespread complaint. While most studies on HHL pathogenesis have focused on inner hair cell (IHC) synaptopathy, recent research suggests that transient auditory nerve (AN) demyelination may also cause HHL. To test the impact of myelinopathy in a clinically relevant model, we studied a mouse model of Charcot-Marie-Tooth type 1A (CMT1A), the most prevalent hereditary peripheral neuropathy in humans. CMT1A mice exhibit the functional hallmarks of HHL, together with disorganization of AN heminodes near the IHCs with minor loss of AN fibers. Our results support the hypothesis that mild disruptions of AN myelination can cause HHL, and that heminodal defects contribute to the alterations in action potential amplitudes and latencies seen in these models. Also, these findings suggest that patients with CMT1A or other mild peripheral neuropathies are likely to suffer from HHL. Furthermore, these results suggest that studies of hearing in CMT1A patients might help develop robust clinical tests for HHL, which are currently lacking.
Development of an automated high-content immuno-fluorescence assay of pSmads quantification: proof-of-concept with drugs inhibiting the BMP/TGFβ pathways

Bone morphogenetic proteins (BMPs) and transforming growth factors (TGF-β) are members of the transforming growth factors superfamily, known for their role in several physiological and pathological processes. These factors are known to bind in vivo to BMP and TGF-β receptors respectively, which induces the phosphorylation of the Smad (pSmad) transcription factors. This pathway is generally studied with western blot and luciferase bioluminescence assay, which present some limitations. In our work, we developed and optimized a high-content immunofluorescence assay to study the pSmad pathway on glass as well as on biomaterials by overcoming the technical challenges raised by image acquisition and analysis. Furthermore, with this assay, we present here a proof-of concept for drug testing on glass and on biomimetic films using drug inhibitors of the BMP receptor and of the TGF-β receptors. Altogether, our results open perspectives for future drug testing on biomimetic films that present various growth factors and extracellular matrix proteins or peptides.
Cyanobacterial sigma factor controls biofilm-promoting genes through intra- and intercellular pathways

Cyanobacteria frequently constitute integral components of microbial communities known as phototrophic biofilms. These assemblages are not only widespread in various environmental contexts but also hold significant industrial relevance. Nevertheless, the governing elements responsible for cyanobacterial biofilm development have remained elusive. This study, which employs the model cyanobacterium Synechococcus elongatus PCC 7942, demonstrates that the RNA polymerase sigma factor SigF1, but not its paralog SigF2, is required for a biofilm-suppression mechanism that operates in this organism. Comprehensive transcriptome analyses identified distinct regulons under the control of each of these sigma factors. Additional data indicate that SigF1 regulates biofilm through its involvement in transcriptional induction of genes that include those for the primary pilus subunit: sigF1 inactivation both prevents pilus assembly and abrogates secretion of a biofilm inhibitor. Consequently, expression is significantly upregulated for the ebfG-operon that encodes matrix components and the genes that encode their corresponding secretion system. Thus, this study uncovers a basic regulatory component of cyanobacterial communal behavior. Elevated expression of biofilm-promoting genes in a sigF1 mutant supports an additional layer of regulation by SigF1 that operates via an intracellular mechanism.
Scalable, Robust, High-throughput Expression, Purification & Characterization of Nanobodies Enabled by 2-Stage Dynamic Control

Nanobodies are single-domain antibody fragments that have garnered considerable use as diagnostic and therapeutic agents as well as research tools. However, obtaining pure VHHs, like many proteins, can be laborious and inconsistent. High level cytoplasmic expression in E. coli can be challenging due to improper folding and insoluble aggregation caused by reduction of the conserved disulfide bond. We report a systems engineering approach leveraging engineered strains of E. coli, in combination with a two-stage process and simplified downstream purification, enabling improved, robust soluble cytoplasmic nanobody expression, as well as rapid cell autolysis and purification. This approach relies on the dynamic control over the reduction potential of the cytoplasm, in combination with dynamic expression of chaperones and lysis enzymes needed for purification. Collectively, the engineered system results in more robust growth and protein expression, enabling efficient scalable nanobody production, and purification from high throughput microtiter plates, to routine shake flask cultures and larger instrumented bioreactors. We expect this system will expedite VHH development.
Accounting for the gender gap in adolescents’ life satisfaction: evidence from nationally representative samples of school attendees in Luxembourg

ABSTRACT Research on gender differences in adolescents’ life satisfaction has reported inconsistent findings to date. The present study aimed to (a) ascertain whether a gender gap in life satisfaction exists in Luxembourg, (b) estimate the predictive power of gender when controlling for well-identified predictors of life satisfaction, and (c) assess potential gender differences in our predictors’ influence on life satisfaction. We used data from 2006 to 2022 pertaining to nationally representative samples of school attendees in Luxembourg (n = 46,937) to achieve our first research goal. We relied on data collected in 2022 (n = 9,432) to achieve our two other research goals. We found boys to consistently report higher life satisfaction than girls over time. However, gender did not predict life satisfaction when controlling for our other predictors. Moreover, the influence of most of the examined factors on life satisfaction did not vary with gender.
Key Distribution and Authentication Protocols in Wireless Sensor Networks: A Survey

We use sensor technologies in many areas of everyday life. We use sensors to check and study various phenomena and to improve our lives. Hence, the sensors are used in medicine, industry, sports and many other aspects of everyday life. Interconnected sensors and other wireless devices and servers form Wireless Sensor Networks. During communication between the nodes of such networks, we often send private and sensitive. These data should be properly secured. Securing communication in a Wireless Sensor Network mainly affects the reconciliation and distribution of session keys and authentication. Specially designed protocols must protect both methods. In turn, the protocols may be exposed to dishonest users of such networks and thus exposed to various attacks (for example, replay attacks and smart card stolen attacks). This article surveys the existing session key negotiation, distribution and authentication protocols. We will explain the security problems and threats to which the sensor networks are exposed. We will discuss the security levels implemented by the protocols currently used in sensor networks. We will analyze the challenges and requirements faced by the newly designed protocols.
Appraisal of dispersion damping functions for the effective fragment potential method

The effective fragment potential (EFP) is a polarizable force field whose physically-motivated functional form is parameterized in an automated way from ab initio calculations, and whose dispersion potential has been suggested as a correction for Hartree-Fock or density functional theory calculations. However, the parameter-free dispersion damping potentials that are currently used in EFP do not follow from a rigorous derivation and do not satisfy simple limits for the dispersion energy. We introduce several new damping expressions that correct these deficiencies, then evaluate their performance alongside existing damping functions using a new database of ionic liquid constituents. This data set, which we call IL195×8, consists of complete-basis coupled-cluster interaction energies for 195 ion pairs at each of 8 different intermolecular separations. Ultimately, we recommend a new parameter-free dispersion damping function as a replacement for the one that is currently used in EFP. GRAPHICAL ABSTRACT
Cities as parasitic amplifiers? Malaria prevalence and diversity in great tits along an urbanization gradient

Urbanization is a worldwide phenomenon that modifies the environment. By affecting the reservoirs of pathogens and the body and immune conditions of hosts, urbanization alters the epidemiological dynamics and diversity of diseases. Cities could act as areas of pathogen dilution or amplification, depending on whether urban features have positive or negative effects on vectors and hosts. In this study, we focused on a host species and investigated the prevalence and diversity of avian malaria parasites (Plasmodium/Haemoproteus sp. and Leucocytozoon sp.) in great tits (Parus major) living across an urbanization gradient. In general, we observed high prevalence in adult birds (from 95% to 100%), yet lower prevalence in fledglings (from 0% to 38%). We found a slight tendency for increased Plasmodium sp. prevalence with increasing urbanization in adults. Urban nestlings had higher Plasmodium sp. infection rates than non-urban nestlings. We found evidence of higher diversity of parasites in the most natural urban park; however, parasite diversity was similar across other urbanization levels (e.g. from a little artificialized park to a highly anthropized industrial area). Parasite lineages were not habitat specific. Only one Plasmodium sp. lineage (YWT4) was associated with urban areas and some rare lineages (e.g., AFR065) were present only in a zoo area, perhaps because of the presence of African birds. This study suggests that urbanization can lead to a parasite amplification effect and can favor different avian malaria lineages.
Airway epithelial cells as a novel intracellular host reservoir for Cryptococcus spores

Human fungal pathogens cause an estimated 1.5 million annual deaths and Cryptococcus neoformans, an inhaled facultative intracellular pathogen, is at the top of the WHO’s priority list of fungal pathogens. Cryptococcus causes disease when it disseminates out of the lung and into the brain which can occur years after initial exposure. However, the mechanisms of both Cryptococcus dissemination and latency are still unclear. One potential reason that these mechanisms remain unknown is that the morphotype used for the vast majority of studies is the yeast form and not the dormant and stress resistant spore morphotype. The inhalation of Cryptococcus spores initiates infections and recent evidence in vivo has shown that spores display unique host-pathogen interactions and are able to escape the lung and disseminate to the brain more readily than yeast. Due to the difficulties associated working with these spores, little is known about how they interact with host cells. Airway Epithelial Cells (AECs), which cover the entire alveolar surface and comprise 24% of all cells in the human lung parenchyma, likely have instant and extensive contact with inhaled spores. In this study, we demonstrated that Cryptococcus spores can invade AECs both in vitro and in vivo. Once inside spores can germinate and subsequently replicate, persist and/or escape. This ability to enter AECs correlates with a preferential ability of spore to cross AEC barriers. Together our work indicates AECs may serve as a previously ignored intracellular host reservoir and challenges the current paradigms of both Cryptococcus dissemination and latency.