Miracle-dz/UniFAR-FTUs huggingface dataset:
Bayesian Hierarchical Varying-Sparsity Regression Models with Application to Cancer Proteogenomics

ABSTRACT Identifying patient-specific prognostic biomarkers is of critical importance in developing personalized treatment for clinically and molecularly heterogeneous diseases such as cancer. In this article, we propose a novel regression framework, Bayesian hierarchical varying-sparsity regression (BEHAVIOR) models to select clinically relevant disease markers by integrating proteogenomic (proteomic+genomic) and clinical data. Our methods allow flexible modeling of protein–gene relationships as well as induces sparsity in both protein–gene and protein–survival relationships, to select genomically driven prognostic protein markers at the patient-level. Simulation studies demonstrate the superior performance of BEHAVIOR against competing method in terms of both protein marker selection and survival prediction. We apply BEHAVIOR to The Cancer Genome Atlas (TCGA) proteogenomic pan-cancer data and find several interesting prognostic proteins and pathways that are shared across multiple cancers and some that exclusively pertain to specific cancers. Supplementary materials for this article, including a standardized description of the materials available for reproducing the work, are available online.
Real‐time influence of intracellular acidification and Na+/H+ exchanger inhibition on in‐cell pyruvate metabolism in the perfused mouse heart: A 31P‐NMR and hyperpolarized 13C‐NMR study

Disruption of acid–base balance is linked to various diseases and conditions. In the heart, intracellular acidification is associated with heart failure, maladaptive cardiac hypertrophy, and myocardial ischemia. Previously, we have reported that the ratio of the in‐cell lactate dehydrogenase (LDH) to pyruvate dehydrogenase (PDH) activities is correlated with cardiac pH. To further characterize the basis for this correlation, these in‐cell activities were investigated under induced intracellular acidification without and with Na+/H+ exchanger (NHE1) inhibition by zoniporide. Male mouse hearts (n = 30) were isolated and perfused retrogradely. Intracellular acidification was performed in two ways: (1) with the NH4Cl prepulse methodology; and (2) by combining the NH4Cl prepulse with zoniporide. 31P NMR spectroscopy was used to determine the intracellular cardiac pH and to quantify the adenosine triphosphate and phosphocreatine content. Hyperpolarized [1‐13C]pyruvate was obtained using dissolution dynamic nuclear polarization. 13C NMR spectroscopy was used to monitor hyperpolarized [1‐13C]pyruvate metabolism and determine enzyme activities in real time at a temporal resolution of a few seconds using the product‐selective saturating excitation approach. The intracellular acidification induced by the NH4Cl prepulse led to reduced LDH and PDH activities (−16% and −39%, respectively). This finding is in line with previous evidence of reduced myocardial contraction and therefore reduced metabolic activity upon intracellular acidification. Concomitantly, the LDH/PDH activity ratio increased with the reduction in pH, as previously reported. Combining the NH4Cl prepulse with zoniporide led to a greater reduction in LDH activity (−29%) and to increased PDH activity (+40%). These changes resulted in a surprising decrease in the LDH/PDH ratio, as opposed to previous predictions. Zoniporide alone (without intracellular acidification) did not change these enzyme activities. A possible explanation for the enzymatic changes observed during the combination of the NH4Cl prepulse and NHE1 inhibition may be related to mitochondrial NHE1 inhibition, which likely negates the mitochondrial matrix acidification. This effect, combined with the increased acidity in the cytosol, would result in an enhanced H+ gradient across the mitochondrial membrane and a temporarily higher pyruvate transport into the mitochondria, thereby increasing the PDH activity at the expense of the cytosolic LDH activity. These findings demonstrate the complexity of in‐cell cardiac metabolism and its dependence on intracellular acidification. This study demonstrates the capabilities and limitations of hyperpolarized [1‐13C]pyruvate in the characterization of intracellular acidification as regards cardiac pathologies.
Exercise therapy including the cervical extensor muscles in individuals with neck pain: A systematic review

Objective To review the use (dosage parameters and combination with other therapeutic interventions) of cervical extensor muscle exercises and their effect on pain, disability (primary outcomes), range of motion, endurance and strength (secondary outcomes) in people with neck pain. Data sources An extensive literature search was conducted through MEDLINE (Ovid), Scopus (Elsevier) and Physiotherapy Evidence Database (PEDro) up to May 2023. The reference lists of all included studies and relevant reviews were screened for additional studies. Review methods Randomised controlled trials reporting the use of cervical extensor muscle exercises (alone or combined) applied to adults with idiopathic or traumatic neck pain were included. Study selection, data extraction and critical appraisal (PEDro assessment scale) were performed by two blinded reviewers. Data extraction included dosage parameters, other modalities combined with these exercises and outcomes. Results Thirty-five randomised controlled trails (eight of which were complementary analyses) with 2409 participants fulfilled the inclusion criteria. Twenty-six were of moderate to high quality. In most studies, cervical extensor muscle exercises were combined with various other therapeutic modalities and applied at different dosages. Only two studies (one high and one low quality) specifically assessed their effectiveness. The high-quality study showed significant improvements in neck pain and disability, pressure point threshold and neck mobility after both low load and high load training for 6 weeks. Conclusion The results suggest cervical extensor muscle exercises may reduce neck pain and disability; however firm conclusions cannot be drawn because of the few studies that addressed this question and the heterogeneity of the dosage parameters.
Effects of exogenous indole‐3‐acetic acid on the density of trichomes, expression of artemisinin biosynthetic genes, and artemisinin biosynthesis in Artemisia annua

Artemisinin is the most practical medication for the treatment of malaria, but is only very minimally synthesized in Artemisia annua, significantly less than the market needs. In this study, indole‐3‐acetic acid (IAA) was used to investigate its effects on trichomes, artemisinin accumulation, and biosynthetic gene expression in A. anuua. The results showed that exogenous IAA could contribute to the growth and development of A. annua and increase the density of trichomes. Analysis using liquid chromatography‐tandem mass spectrometry (LC‒MS/MS) indicated that artemisinin and dihydroartemisinic acid (DHAA) contents were increased by 1.9‐fold (1.1 mg/g) and 2.1‐fold (0.51 mg/g) after IAA treatment in comparison with control lines (CK), respectively. Furthermore, quantitative real‐time PCR results showed that AaADS, AaCYP71AV1, AaALDH1, and AaDBR2, four critical enzyme genes for the biosynthesis of artemisinin, had relatively high transcription levels in leaves of A. annua treated with IAA. In summary, this study indicated that exogenous IAA treatment was a feasible strategy to enhance artemisinin production, which paves the way for further metabolic engineering of artemisinin biosynthesis.
Simulated and measured neutron/gamma light output distribution for poly-energetic neutron/gamma sources

In the present paper, the light output distribution due to poly-energetic neutron/gamma (neutron or gamma) source was calculated using the developed MCNPX-ESUT-PE (MCNPX-Energy engineering of Sharif University of Technology-Poly Energetic version) computational code. The simulation of light output distribution includes the modeling of the particle transport, the calculation of scintillation photons induced by charged particles, simulation of the scintillation photon transport and considering the light resolution obtained from the experiment. The developed computational code is able to simulate the light output distribution due to any neutron/gamma source. In the experimental step of the present study, the neutron-gamma discrimination based on the light output distribution was performed using the zero crossing method. As a case study, 241Am–9Be source was considered and the simulated and measured neutron/gamma light output distributions were compared. There is an acceptable agreement between the discriminated neutron/gamma light output distributions obtained from the simulation and experiment.
Overlap extension cloning of PCR products into a Gateway-compatible plasmid vector

A PCR cloning method that combines a dual selection pGATE-1 plasmid vector and an improved overlap extension cloning was developed. This efficient and cost-effective method allows for the introduction of DNA fragments into the Gateway cloning pipeline. The cloning efficiency is facilitated by a dual selection that includes the ccdB gene and gentamicin resistance. For users of the Gateway cloning system, substantial cost saving comes from eliminating BP recombination and ligation reactions to introduce DNA fragments into pDONR or pENTR vectors. Beyond the Gateway technology, this recombination-based cloning system can be used to efficiently clone PCR amplicons by adding 24-base pair adaptor sequences that are utilized by bacterial homologous recombination mechanism.
Comparative evaluation of glomerular morphometric techniques reveals differential technical artifacts between focal segmental glomerulosclerosis and normal glomeruli

Morphometric estimates of mean or individual glomerular volume (MGV, IGV) have biological implications, over and above qualitative histologic data. However, morphometry is time‐consuming and requires expertise limiting its utility in clinical cases. We evaluated MGV and IGV using plastic‐ and paraffin‐embedded tissue from 10 control and 10 focal segmental glomerulosclerosis (FSGS) mice (aging and 5/6th nephrectomy models) using the gold standard Cavalieri (Cav) method versus the 2‐profile and Weibel–Gomez (WG) methods and a novel 3‐profile method. We compared accuracy, bias and precision, and quantified results obtained when sampling differing numbers of glomeruli. In both FSGS and controls, we identified an acceptable precision for MGV of 10‐glomerular sampling versus 20‐glomerular sampling using the Cav method, while 5‐glomerular sampling was less precise. In plastic tissue, 2‐ or 3‐profile MGVs showed greater concordance with MGV when using Cav, versus MGV with WG. IGV comparisons using the same glomeruli reported a consistent underestimation bias with both 2‐ or 3‐profile methods versus the Cav method. FSGS glomeruli showed wider variations in bias estimation than controls. Our 3‐profile method offered incremental benefit to the 2‐profile method in both IGV and MGV estimation (improved correlation coefficient, Lin's concordance and reduced bias). In our control animals, we quantified a shrinkage artifact of 52% from tissue processed for paraffin‐embedded versus plastic‐embedded tissue. FSGS glomeruli showed overall reduced shrinkage albeit with variable artifact signifying periglomerular/glomerular fibrosis. A novel 3‐profile method offers slightly improved concordance with reduced bias versus 2‐profile. Our findings have implications for future studies using glomerular morphometry.
TBK1 variants in Chinese patients with amyotrophic lateral sclerosis: Genetic analysis and clinical features

Haploinsufficiency of TANK‐binding kinase 1 (TBK1) loss‐of‐function (LoF) variants has been shown to be pathogenic in amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). However, the genetic spectrum of TBK1 and clinical features of ALS patients with TBK1 variants remain largely unknown in Asians.
Fast in vivo assay of creatine kinase activity in the human brain by 31P magnetic resonance fingerprinting

A new and efficient magnetisation transfer 31P magnetic resonance fingerprinting (MT‐31P‐MRF) approach is introduced to measure the creatine kinase metabolic rate kCK between phosphocreatine (PCr) and adenosine triphosphate (ATP) in human brain. The MRF framework is extended to overcome challenges in conventional 31P measurement methods in the human brain, enabling reduced acquisition time and specific absorption rate (SAR). To address the challenge of creating and matching large multiparametric dictionaries in an MRF scheme, a nested iteration interpolation method (NIIM) is introduced. As the number of parameters to estimate increases, the size of the dictionary grows exponentially. NIIM can reduce the computational load by breaking dictionary matching into subsolutions of linear computational order. MT‐31P‐MRF combined with NIIM provides T1PCr , T1ATP and kCK estimates in good agreement with those obtained by the exchange kinetics by band inversion transfer (EBIT) method and literature values. Furthermore, the test–retest reproducibility results showed that MT‐31P‐MRF achieves a similar or better coefficient of variation (<12%) for T1ATP and kCK measurements in 4 min 15 s, than EBIT with 17 min 4 s scan time, enabling a fourfold reduction in scan time. We conclude that MT‐31P‐MRF in combination with NIIM is a fast, accurate, and reproducible approach for in vivo kCK assays in the human brain, which enables the potential to investigate energy metabolism in a clinical setting.
Picturing local adaptation: Spectral and structural traits from drone remote sensing reveal clinal responses to climate transfer in common‐garden trials of interior spruce (Picea engelmannii × glauca)

Common‐garden trials of forest trees provide phenotype data used to assess growth and local adaptation; this information is foundational to tree breeding programs, genecology, and gene conservation. As jurisdictions consider assisted migration strategies to match populations to suitable climates, in situ progeny and provenance trials provide experimental evidence of adaptive responses to climate change. We used drone technology, multispectral imaging, and digital aerial photogrammetry to quantify spectral traits related to stress, photosynthesis, and carotenoids, and structural traits describing crown height, size, and complexity at six climatically disparate common‐garden trials of interior spruce (Picea engelmannii × glauca) in western Canada. Through principal component analysis, we identified key components of climate related to temperature, moisture, and elevational gradients. Phenotypic clines in remotely sensed traits were analyzed as trait correlations with provenance climate transfer distances along principal components (PCs). We used traits showing clinal variation to model best linear unbiased predictions for tree height (R2 = .98–.99, root mean square error [RMSE] = 0.06–0.10 m) and diameter at breast height (DBH, R2 = .71–.97, RMSE = 2.57–3.80 mm) and generated multivariate climate transfer functions with the model predictions. Significant (p < .05) clines were present for spectral traits at all sites along all PCs. Spectral traits showed stronger clinal variation than structural traits along temperature and elevational gradients and along moisture gradients at wet, coastal sites, but not at dry, interior sites. Spectral traits may capture patterns of local adaptation to temperature and montane growing seasons which are distinct from moisture‐limited patterns in stem growth. This work demonstrates that multispectral indices improve the assessment of local adaptation and that spectral and structural traits from drone remote sensing produce reliable proxies for ground‐measured height and DBH. This phenotyping framework contributes to the analysis of common‐garden trials towards a mechanistic understanding of local adaptation to climate.
A new two-parameter distribution: properties and applications

In this paper, a new two-parameter lifetime distribution called ``the exponentiated Shanker distribution" is suggested. The new distribution has an increasing, decreasing and bathtub-shaped hazard rate function (hrf) for modeling lifetime data. Various mathematical and statistical properties of the proposed distribution including its hrf, complete and incomplete moments, skewness and kurtosis, mean deviations, Bonferroni and Lorenz curves are discussed. Estimation of its parameters is also discussed using the method of maximum likelihood estimation and a simulation study is given. Finally, two applications of the new distribution are presented using two real data sets. The results also confirmed the suitability of the proposed model for the real data sets.
The thermogravitational effect in thermal field-flow fractionation

Les temps de retention observes pour des polymeres dissous dans le liquide vecteur dans un canal vertical ou incline de fractionnement par couplage flux-force avec gradient thermique (FFF thermique) different de ceux observes en configuration horizontale, pour des conditions identiques de temperature et de debit. On interprete ce phenomene comme provenant de l'effet thermogravitationnel. Un modele de retention est developpe pour decrire ces variations. L 'accord avec les donnees experimentales est relativement satisfaisant. L'observation de la variation du temps de retention avec le debit dans un canal vertical et/ou avec l'angle d'inclinaison dans un canal incline offre un moyen d'acces au signe du coefficient Soret par FFF thermique.
WIDEBAND RADAR CROSS SECTION REDUCTION USING ARTIFICIAL MAGNETIC CONDUCTOR CHECKERBOARD SURFACE

This paper presents a combinatorial triangle type artificial magnetic conductor checkerboard surface for wideband radar cross section reduction. The structure consists of a combination of a single band and dual band AMC unit cells with 180±37◦ phase difference from 4.06 GHz to 11.2 GHz. 10 dB RCS reduction compared to PEC surface is realized from 4.4 GHz to 11.68 GHz (91%) for the proposed structure. The performance of the structure is compared with the conventional checkerboard surface. The distribution of scattered fields from both the structures are analyzed using array theory. The angular stability of the structures are also studied for TE and TM polarized wave incidences. A prototype of the proposed structure is fabricated, and the measured data are in good agreement with simulated results.
In Silico Evaluation of Variant Calling Methods for Bacterial Whole-Genome Sequencing Assays

Identification and analysis of clinically relevant strains of bacteria increasingly relies on whole-genome sequencing. The downstream bioinformatics steps necessary for calling variants from short-read sequences are well-established but seldom validated against haploid genomes. ABSTRACT Identification and analysis of clinically relevant strains of bacteria increasingly relies on whole-genome sequencing. The downstream bioinformatics steps necessary for calling variants from short-read sequences are well-established but seldom validated against haploid genomes. We devised an in silico workflow to introduce single nucleotide polymorphisms (SNP) and indels into bacterial reference genomes, and computationally generate sequencing reads based on the mutated genomes. We then applied the method to Mycobacterium tuberculosis H37Rv, Staphylococcus aureus NCTC 8325, and Klebsiella pneumoniae HS11286, and used the synthetic reads as truth sets for evaluating several popular variant callers. Insertions proved especially challenging for most variant callers to correctly identify, relative to deletions and single nucleotide polymorphisms. With adequate read depth, however, variant callers that use high quality soft-clipped reads and base mismatches to perform local realignment consistently had the highest precision and recall in identifying insertions and deletions ranging from1 to 50 bp. The remaining variant callers had lower recall values associated with identification of insertions greater than 20 bp.
Maturation of the gut metabolome during the first year of life in humans

ABSTRACT The gut microbiota is involved in the production of numerous metabolites that maintain host wellbeing. The assembly of the gut microbiome is highly dynamic, and influenced by many postnatal factors, moreover, little is known about the development of the gut metabolome. We showed that geography has an important influence on the microbiome dynamics in the first year of life based on two independent cohorts from China and Sweden. Major compositional differences since birth were the high relative abundance of Bacteroides in the Swedish cohort and Streptococcus in the Chinese cohort. We analyzed the development of the fecal metabolome in the first year of life in the Chinese cohort. Lipid metabolism, especially acylcarnitines and bile acids, was the most abundant metabolic pathway in the newborn gut. Delivery mode and feeding induced particular differences in the gut metabolome since birth. In contrast to C-section newborns, medium- and long-chain acylcarnitines were abundant at newborn age only in vaginally delivered infants, associated by the presence of bacteria such as Bacteroides vulgatus and Parabacteroides merdae. Our data provide a basis for understanding the maturation of the fecal metabolome and the metabolic role of gut microbiota in infancy.
Calculating Originality of LLM Assisted Source Code

The ease of using a Large Language Model (LLM) to answer a wide variety of queries and their high availability has resulted in LLMs getting integrated into various applications. LLM-based recommenders are now routinely used by students as well as professional software programmers for code generation and testing. Though LLM-based technology has proven useful, its unethical and unattributed use by students and professionals is a growing cause of concern. As such, there is a need for tools and technologies which may assist teachers and other evaluators in identifying whether any portion of a source code is LLM generated. In this paper, we propose a neural network-based tool that instructors can use to determine the original effort (and LLM's contribution) put by students in writing source codes. Our tool is motivated by minimum description length measures like Kolmogorov complexity. Our initial experiments with moderate sized (up to 500 lines of code) have shown promising results that we report in this paper.
A Survey of Spiking Neural Network Accelerator on FPGA

Due to the ability to implement customized topology, FPGA is increasingly used to deploy SNNs in both embedded and high-performance applications. In this paper, we survey state-of-the-art SNN implementations and their applications on FPGA. We collect the recent widely-used spiking neuron models, network structures, and signal encoding formats, followed by the enumeration of related hardware design schemes for FPGA-based SNN implementations. Compared with the previous surveys, this manuscript enumerates the application instances that applied the above-mentioned technical schemes in recent research. Based on that, we discuss the actual acceleration potential of implementing SNN on FPGA. According to our above discussion, the upcoming trends are discussed in this paper and give a guideline for further advancement in related subjects.