Concerto of movement: how expertise shapes the synergistic control of upper limb muscles in complex motor tasks with varying tempo and dynamics.

Objective. This research aims to reveal how the synergistic control of upper limb muscles adapts to varying requirements in complex motor tasks and how expertise shapes the motor modules.Approach. We study the muscle synergies of a complex, highly skilled and flexible task-piano playing-and characterize expertise-related muscle-synergy control that permits the experts to effortlessly execute the same task at different tempo and force levels. Surface EMGs (28 muscles) were recorded from adult novice (N= 10) and expert (N= 10) pianists as they played scales and arpeggios at different tempo-force combinations. Muscle synergies were factorized from EMGs.Main results. We found that experts were able to cover both tempo and dynamic ranges using similar synergy selections and achieved better performance, while novices altered synergy selections more to adapt to the changing tempi and keystroke intensities compared with experts. Both groups relied on fine-tuning the muscle weights within specific synergies to accomplish the different task styles, while the experts could tune the muscles in a greater number of synergies, especially when changing the tempo, and switch tempo over a wider range.Significance. Our study sheds light on the control mechanism underpinning expertise-related motor flexibility in highly skilled motor tasks that require decade-long training. Our results have implications on musical and sports training, as well as motor prosthetic design.

Chondroitin sulfate glycan sulfation patterns influence histochemical labeling of perineuronal nets: a comparative study of interregional distribution in human and mouse brain.

Perineuronal nets (PNNs) are a condensed subtype of extracellular matrix that form a net-like coverings around certain neurons in the brain. PNNs are primarily composed of chondroitin sulfate (CS) proteoglycans from the lectican family that consist of CS-glycosaminoglycan (CS-GAG) side chains attached to a core protein. CS disaccharides can exist in various isoforms with different sulfation patterns. Literature suggests that CS disaccharide sulfation patterns can influence the function of PNNs as well as their labeling. This study was conducted to characterize such interregional CS disaccharide sulfation pattern differences in adult human (N = 81) and mouse (N = 19) brains. Liquid chromatography tandem mass spectrometry was used to quantify five different CS disaccharide sulfation patterns, which were then compared to immunolabeling of PNNs using Wisteria Floribunda Lectin (WFL) to identify CS-GAGs and anti-aggrecan to identify CS proteoglycans. In healthy brains, significant regional and species-specific differences in CS disaccharide sulfation and single versus double-labeling pattern were identified. A secondary analysis to investigate how early-life stress (ELS) impacts these PNN features discovered that although ELS increases WFL+ PNN density, the CS-GAG sulfation code and single versus double PNN-labeling distributions remained unaffected in both species. These results underscore PNN complexity in traditional research, emphasizing the need to consider their heterogeneity in future experiments.

Descriptive study of perineuronal net in enteric nervous system of humans and mice.

Perineuronal nets (PNN) are highly specialized structures of the extracellular matrix around specific groups of neurons in the central nervous system (CNS). They play functions related to optimizing physiological processes and protection neurons against harmful stimuli. Traditionally, their existence was only described in the CNS. However, there was no description of the presence and composition of PNN in the enteric nervous system (ENS) until now. Thus, our aim was to demonstrate the presence and characterize the components of the PNN in the enteric nervous system. Samples of intestinal tissue from mice and humans were analyzed by RT-PCR and immunofluorescence assays. We used a marker (Wisteria floribunda agglutinin) considered as standard for detecting the presence of PNN in the CNS and antibodies for labeling members of the four main PNN-related protein families in the CNS. Our results demonstrated the presence of components of PNN in the ENS of both species; however its molecular composition is species-specific.

Evolution of "invasion syndrome" in invasive goldenrod is not constrained by genetic trade-offs.

A suite of plant traits is thought to make weed populations highly invasive, including vigorous growth and reproduction, superior competitive ability, and high dispersal ability. Using a breeding design and a common garden experiment, we tested whether such an "invasion syndrome" has evolved in an invasive range of Solidago altissima, and whether the evolution is likely to be genetically constrained. We found an overall shift in invasive phenotypes between native North American and invasive Japanese populations. The invasive populations were taller and produced more leaves, suggesting a superior ability to exploit limited resources. The populations also produced more allelopathic compounds that can suppress competitor growth. Finally, invasive populations produced more seeds, which are smaller and are released from a greater height, indicating a potential for superior dispersal ability than the native populations. Quantitative genetics analyses found a large amount of additive genetic variation in most focal traits across native and invasive populations, with no systematic differences in its magnitude between the ranges. Genetic covariances among three traits representing invasion strategies (leaf mass, polyacetylene concentration and seed size) were small. The R metric, which measures the effect of genetic covariances on the rate of adaptation, indicated that the covariance neither constrains nor accelerates concerted evolution of these traits. The results suggest that the invasion syndrome in S. altissima has evolved in the novel range due to ample additive genetic variation, and relatively free from genetic trade-offs.

Effect of chloride ions on persulfate/UV-C advanced oxidation of an alcohol ethoxylate (Brij 30).

In the present study, the effect of chloride ions on the oxidative degradation of an alcohol ethoxylate (Brij 30) by persulfate (PS)/UV-C was experimentally explored using Brij 30 aqueous solution (BAS) and a domestic wastewater treatment plant effluent spiked with Brij 30. Brij 30 degradation occurred rapidly during the early stages of oxidation without affecting the water/wastewater matrix. Mineralization of intermediates of Brij 30 degradation markedly influenced by presence of chloride ions. Chloride ions at concentrations up to 50 mg/L accelerated the mineralization through reactions involving reactive chlorine species, which reduced the sink of SO4·- by Cl- scavenging at both initial pH of 6.0 and 3.0 in the case of BAS. The fastest mineralization was achieved under acidic conditions. The WWTP effluent matrix significantly influenced mineralization efficacy of the intermediates. Co-existence of HCO 3 - and Cl- anions accelerated the mineralization of degradation products. Organic matter originating from the WWTP effluent itself had an adverse effect on the mineralization rate. The positive effects of organic and inorganic components present in the WWTP effluent were ranked in the following order of increasing influence: (Organic matter originating from the effluent + Cl- + HCO 3 - ) < (Cl-) < (Cl- + HCO 3 - ).

Cancer treatments as paradoxical catalysts of tumor awakening in the lung.

Much of the fatality of tumors is linked to the growth of metastases, which can emerge months to years after apparently successful treatment of primary tumors. Metastases arise from disseminated tumor cells (DTCs), which disperse through the body in a dormant state to seed distant sites. While some DTCs lodge in pre-metastatic niches (PMNs) and rapidly develop into metastases, other DTCs settle in distinct microenvironments that maintain them in a dormant state. Subsequent awakening, induced by changes in the microenvironment of the DTC, causes outgrowth of metastases. Hence, there has been extensive investigation of the factors causing survival and subsequent awakening of DTCs, with the goal of disrupting these processes to decrease cancer lethality. We here provide a detailed overview of recent developments in understanding of the factors controlling dormancy and awakening in the lung, a common site of metastasis for many solid tumors. These factors include dynamic interactions between DTCs and diverse epithelial, mesenchymal, and immune cell populations resident in the lung. Paradoxically, among key triggers for metastatic outgrowth, lung tissue remodeling arising from damage induced by the treatment of primary tumors play a significant role. In addition, growing evidence emphasizes roles for inflammation and aging in opposing the factors that maintain dormancy. Finally, we discuss strategies being developed or employed to reduce the risk of metastatic recurrence.

Association of germinal matrix hemorrhage volume with neurodevelopment and hydrocephalus.

OBJECTIVE: The objective of this study was to evaluate whether volumetric measurements on early cranial ultrasound (CUS) in high-grade germinal matrix hemorrhage-intraventricular hemorrhage (GMH-IVH) are associated with hydrocephalus and neurodevelopmental metrics. METHODS: A retrospective case series analysis of infants with high-grade GMH-IVH admitted to the St. Louis Children's Hospital neonatal intensive care unit between 2007 and 2015 who underwent neurodevelopmental testing using the Bayley Scales of Infant and Toddler Development, 3rd Edition (Bayley-III) at 2 years of corrected age was performed. GMH volume, periventricular hemorrhagic infarction volume, and frontotemporal horn ratio were obtained from direct review of neonatal CUS studies. Univariate and multivariable regression models were used to evaluate the association between hemorrhage volumes and hydrocephalus requiring permanent CSF diversion with ventricular shunt or endoscopic third ventriculostomy with or without choroid plexus cauterization and composite Bayley-III cognitive, language, and motor scores. RESULTS: Forty-three infants (29 males, mean gestational age 25 weeks) met the inclusion criteria. The mean age at time of the CUS with the largest hemorrhage volume or first diagnosis of highest grade was 6.2 days. Nineteen patients underwent treatment for hydrocephalus with permanent CSF diversion. In multivariable analyses, larger GMH volume was associated with worse estimated Bayley-III cognitive (left-sided GMH volume: p = 0.048, total GMH volume: p = 0.023) and motor (left-sided GMH volume: p = 0.010; total GMH volume: p = 0.014) scores. Larger periventricular hemorrhagic infarction volume was associated with worse estimated Bayley-III motor scores (each side p < 0.04). Larger left-sided (OR 2.55, 95% CI 1.10-5.88; p = 0.028) and total (OR 1.35, 95% CI 1.01-1.79; p = 0.041) GMH volumes correlated with hydrocephalus. There was no relationship between early ventricular volume and hydrocephalus or neurodevelopmental outcomes. CONCLUSIONS: Location-specific hemorrhage volume on early CUS may be prognostic for neurodevelopmental and hydrocephalus outcomes in high-grade GMH-IVH.

Extracellular matrix modulates depot-specific adipogenic capacity in adipose tissue of dairy cattle.

Adipose tissue (AT) expands through both hyperplasia and hypertrophy. During adipogenesis, adipose stromal and progenitor cells (ASPCs) proliferate and then accumulate lipids, influenced by the local AT microenvironment. Increased adipogenic capacity is desirable as it relates to metabolic health, especially in transition dairy cows where excess free fatty acids in circulation can compromise metabolic and immune health. Our aim was to elucidate the depot-specific adipogenic capacity and ECM properties of subcutaneous (SAT) and visceral (VAT) AT of dairy cows and define how the ECM affects adipogenesis. Flank SAT and omental VAT samples were collected from dairy cows in a local abattoir. Tissue samples were utilized for transcriptome analysis, targeted RT-qPCR for adipogenic markers, adipocyte sizing, assessment of viscoelastic properties and collagen accumulation, and then decellularized for native ECM isolation. For in vitro analyses, SAT and VAT samples were digested via collagenase, and ASPCs cultured for metabolic analysis. Adipogenic capacity was assessed by adipocyte size, quantification of ASPCs in stromal vascular fraction (SVF) via flow cytometry, and gene expression of adipogenic markers. In addition, functional assays including lipolysis and glucose uptake were performed to further characterize SAT and VAT adipocyte metabolic function. Data were analyzed using SAS (version 9.4; SAS institute Inc., Cary, NC) and GraphPad Prism 9. Subcutaneous AT adipogenic capacity was greater than VAT's, as indicated by increased ASPCs abundance, increased magnitude of adipocyte ADIPOQ and FASN expression during differentiation, and higher adipocyte lipid accumulation as shown by an increased proportion of larger adipocytes and abundance of lipid droplets. Rheologic analysis revealed that VAT is stiffer than SAT, which led us to hypothesize that differences between SAT and VAT adipogenic capacity were partly mediated by depot-specific ECM microenvironment. Thus, we studied depot-specific ECM-adipocyte crosstalk using a 3D model with native ECM (decellularized AT). Subcutaneous AT and VAT ASPCs were cultured and differentiated into adipocytes within depot-matched and mis-matched ECM for 14d, followed by ADIPOQ expression analysis. Visceral AT ECM impaired ADIPOQ expression in SAT cells. Our results demonstrate that SAT is more adipogenic than VAT and suggest that divergences between SAT and VAT adipogenesis are partially mediated by the depot-specific ECM microenvironment.

Machine learning prediction model for gray-level co-occurrence matrix features of synchronous liver metastasis in colorectal cancer.

BACKGROUND: Synchronous liver metastasis (SLM) is a significant contributor to morbidity in colorectal cancer (CRC). There are no effective predictive device integration algorithms to predict adverse SLM events during the diagnosis of CRC. AIM: To explore the risk factors for SLM in CRC and construct a visual prediction model based on gray-level co-occurrence matrix (GLCM) features collected from magnetic resonance imaging (MRI). METHODS: Our study retrospectively enrolled 392 patients with CRC from Yichang Central People's Hospital from January 2015 to May 2023. Patients were randomly divided into a training and validation group (3:7). The clinical parameters and GLCM features extracted from MRI were included as candidate variables. The prediction model was constructed using a generalized linear regression model, random forest model (RFM), and artificial neural network model. Receiver operating characteristic curves and decision curves were used to evaluate the prediction model. RESULTS: Among the 392 patients, 48 had SLM (12.24%). We obtained fourteen GLCM imaging data for variable screening of SLM prediction models. Inverse difference, mean sum, sum entropy, sum variance, sum of squares, energy, and difference variance were listed as candidate variables, and the prediction efficiency (area under the curve) of the subsequent RFM in the training set and internal validation set was 0.917 [95% confidence interval (95%CI): 0.866-0.968] and 0.09 (95%CI: 0.858-0.960), respectively. CONCLUSION: A predictive model combining GLCM image features with machine learning can predict SLM in CRC. This model can assist clinicians in making timely and personalized clinical decisions.

The journey of decellularized vessel: from laboratory to operating room.

Over the past few decades, there has been a remarkable advancement in the field of transplantation. But the shortage of donors is still an urgent problem that requires immediate attention. As with xenotransplantation, bioengineered organs are promising solutions to the current shortage situation. And decellularization is a unique technology in organ-bioengineering. However, at present, there is no unified decellularization method for different tissues, and there is no gold-standard for evaluating decellularization efficiency. Meanwhile, recellularization, re-endothelialization and modification are needed to form transplantable organs. With this mind, we can start with decellularization and re-endothelialization or modification of small blood vessels, which would serve to address the shortage of small-diameter vessels while simultaneously gathering the requisite data and inspiration for further recellularization of the whole organ-scale vascular network. In this review, we collect the related experiments of decellularization and post-decellularization approaches of small vessels in recent years. Subsequently, we summarize the experience in relation to the decellularization and post-decellularization combinations, and put forward obstacle we face and possible solutions.

Interleukin-1ß activates matrix metalloproteinase-2 to alter lacrimal gland myoepithelial cell structure and function.

The aim of the present study is to investigate the role of c-Jun N-terminal kinase (JNK) and matrix metalloproteinase-2 (MMP-2) in mediating the effects of interleukin-1ß (IL-1ß) on the function of lacrimal gland myoepithelial cells (MECs). MECs isolated from an α-smooth muscle actin-green fluorescent protein (SMA-GFP) transgenic mouse were treated with IL-1ß alone or in the presence of SP600125, a JNK inhibitor, or ARP100, an MMP-2 inhibitor. The GFP intensity and the cell size/area were measured, and on day 7, the SMA, calponin, and pro-MMP-2 protein levels and the MEC contraction were assessed. At baseline, the control and treated cells showed no differences in GFP intensity or cell size. Starting on day 2 and continuing on days 4 and 7, the GFP intensity and cell size were significantly lower in the IL-1ß-treated samples, and these effects were alleviated following inhibition of either JNK or MMP-2. Compared with the control, the levels of SMA and calponin were lower in the IL-1ß-treated samples, and both the JNK and MMP-2 inhibitors reversed this trend. The pro-MMP-2 protein level was elevated in the IL-1ß-treated samples, and this effect was abolished by the JNK inhibitor. Finally, oxytocin-induced MEC contraction was diminished in the IL-1ß-treated samples, and both the JNK and MMP-2 inhibitors reversed this effect. Our data suggest that IL-1ß uses the JNK/MMP-2 pathways to alter MEC functions, which might account for the diminished tears associated with aqueous-deficient dry eye disease.

Excision of a large trichilemmal carcinoma of the back with staged reconstruction using biodegradable temporizing matrix (BTM): A case report.

Trichilemmal carcinomas (TC) are rare skin malignancies that arise from the external root sheet of a hair follicle. Their incidence increases with advanced age and they most commonly occur on sun exposed skin or areas of significant hair growth. They vary significantly in size and appearance. Surgical excision is the most common treatment option. We report the case of a large trichilemmal carcinoma of the back occurring in a woman with poorly controlled diabetes mellitus. The lesion was excised resulting in a very large defect, which was reconstructed in a staged process using biodegradable temporising matrix (BTM) and split-skin grafting. There was 95 % graft take at first graft check and the wound was fully healed at 6 weeks post grafting. BTM, already an established adjunct in the reconstruction of burns, degloving injuries and soft tissue infections, provided an enhanced aesthetic outcome and successful wound healing in this complex skin lesion excision.

Lyssavirus matrix protein inhibits NLRP3 inflammasome assembly by binding to NLRP3.

Lyssavirus is a kind of neurotropic pathogen that needs to evade peripheral host immunity to enter the central nervous system to accomplish infection. NLRP3 inflammasome activation is essential for the host to defend against pathogen invasion. This study demonstrates that the matrix protein (M) of lyssavirus can inhibit both the priming step and the activation step of NLRP3 inflammasome activation. Specifically, M of lyssavirus can compete with NEK7 for binding to NLRP3, which restricts downstream apoptosis-associated speck-like protein containing a CARD (ASC) oligomerization. The serine amino acid at the 158th site of M among lyssavirus is critical for restricting ASC oligomerization. Moreover, recombinant lab-attenuated lyssavirus rabies (rabies lyssavirus [RABV]) with G158S mutation at M decreases interleukin-1ß (IL-1ß) production in bone-marrow-derived dendritic cells (BMDCs) to facilitate lyssavirus invasion into the brain thereby elevating pathogenicity in mice. Taken together, this study reveals a common mechanism by which lyssavirus inhibits NLRP3 inflammasome activation to evade host defenses.

Patch and matrix striatonigral neurons differentially regulate locomotion.

The striatonigral neurons are known to promote locomotion1,2. These neurons reside in both the patch (also known as striosome) and matrix compartments of the dorsal striatum3-5. However, the specific contribution of patch and matrix striatonigral neurons to locomotion remain largely unexplored. Using molecular identifier Kringle-Containing Protein Marking the Eye and the Nose (Kremen1) and Calbidin (Calb1)6, we showed in mouse models that patch and matrix striatonigral neurons exert opposite influence on locomotion. While a reduction in neuronal activity in matrix striatonigral neurons precedes the cessation of locomotion, fiber photometry recording during self-paced movement revealed an unexpected increase of patch striatonigral neuron activity, indicating an inhibitory function. Indeed, optogenetic activation of patch striatonigral neurons suppressed locomotion, contrasting with the locomotion-promoting effect of matrix striatonigral neurons. Consistently, patch striatonigral neuron activation markedly inhibited dopamine release, whereas matrix striatonigral neuron activation initially promoted dopamine release. Moreover, the genetic deletion of inhibitory GABA-B receptor Gabbr1 in Aldehyde dehydrogenase 1A1-positive (ALDH1A1+) nigrostriatal dopaminergic neurons (DANs) completely abolished the locomotion-suppressing effect caused by activating patch striatonigral neurons. Together, our findings unravel a compartment-specific mechanism governing locomotion in the dorsal striatum, where patch striatonigral neurons suppress locomotion by inhibiting the activity of ALDH1A1+ nigrostriatal DANs.

Single-cell RNA sequencing reveals special basal cells and fibroblasts in idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is the most predominant type of idiopathic interstitial pneumonia and has an increasing incidence, poor prognosis, and unclear pathogenesis. In order to investigate the molecular mechanisms underlying IPF further, we performed single-cell RNA sequencing analysis on three healthy controls and five IPF lung tissue samples. The results revealed a significant shift in epithelial cells (ECs) phenotypes in IPF, which may be attributed to the differentiation of alveolar type 2 cells to basal cells. In addition, several previously unrecognized basal cell subtypes were preliminarily identified, including extracellular matrix basal cells, which were increased in the IPF group. We identified a special population of fibroblasts that highly expressed extracellular matrix-related genes, POSTN, CTHRC1, COL3A1, COL5A2, and COL12A1. We propose that the close interaction between ECs and fibroblasts through ligand-receptor pairs may have a critical function in IPF development. Collectively, these outcomes provide innovative perspectives on the complexity and diversity of basal cells and fibroblasts in IPF and contribute to the understanding of possible mechanisms in pathological lung fibrosis.

Recombinant human enamelin produced in Escherichia coli promotes mineralization in vitro.

BACKGROUND: Enamelin is an enamel matrix protein that plays an essential role in the formation of enamel, the most mineralized tissue in the human body. Previous studies using animal models and proteins from natural sources point to a key role of enamelin in promoting mineralization events during enamel formation. However, natural sources of enamelin are scarce and with the current study we therefore aimed to establish a simple microbial production method for recombinant human enamelin to support its use as a mineralization agent. RESULTS: In the study the 32 kDa fragment of human enamelin was successfully expressed in Escherichia coli and could be obtained using immobilized metal ion affinity chromatography purification (IMAC), dialysis, and lyophilization. This workflow resulted in a yield of approximately 10 mg enamelin per liter culture. Optimal conditions for IMAC purification were obtained using Ni2+ as the metal ion, and when including 30 mM imidazole during binding and washing steps. Furthermore, in vitro mineralization assays demonstrated that the recombinant enamelin could promote calcium phosphate mineralization at a concentration of 0.5 mg/ml. CONCLUSIONS: These findings address the scarcity of enamelin by facilitating its accessibility for further investigations into the mechanism of enamel formation and open new avenues for developing enamel-inspired mineralized biomaterials.

Biomarkers of tissue remodelling are elevated in serum of COVID-19 patients who develop interstitial lung disease - an exploratory biomarker study.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is a viral pneumonia that can result in serious respiratory illness. It is associated with extensive systemic inflammation, changes to the lung extracellular matrix, and long-term lung impairment such as interstitial lung disease (ILD). In this study, the aim was to investigate whether tissue remodelling, wound healing, and neutrophil activity is altered in patients with COVID-19 and how these relate to the development of post-COVID ILD. METHOD: Serum samples were collected from 63 patients three months after discharge as part of the Research Evaluation Alongside Clinical Treatment study in COVID-19 (REACT COVID-19), 10 of whom developed ILD, and 16 healthy controls. Samples were quantified using neo-epitope specific biomarkers reflecting tissue stiffness and formation (PC3X, PRO-C3, and PRO-C6), tissue degradation (C1M, C3M, and C6M), wound healing (PRO-FIB and X-FIB), and neutrophil activity (CPa9-HNE and ELP-3). RESULTS: Mean serum levels of PC3X (p < 0.0001), PRO-C3 (p = 0.002), C3M (p = 0.009), PRO-FIB (p < 0.0001), CPa9-HNE (p < 0.0001), and ELP-3 (p < 0.0001) were significantly elevated in patients with COVID-19 compared to healthy controls. Moreover, PC3X (p = 0.023) and PRO-C3 (p = 0.032) were significantly elevated in post-COVID ILD as compared to COVID-19. CONCLUSION: Serological biomarkers reflecting type III collagen remodelling, clot formation, and neutrophil activity were significantly elevated in COVID-19 and type III collagen formation markers were further elevated in post-COVID ILD. The findings suggest an increased type III collagen remodelling in COVID-19 and warrants further investigations to assess the potential of tissue remodelling biomarkers as a tool to identify COVID-19 patients at high risk of developing ILD.

Beyond mutations: Accounting for quantitative changes in the analysis of protein evolution.

Molecular phylogenetic research has relied on the analysis of the coding sequences by genes or of the amino acid sequences by the encoded proteins. Enumerating the numbers of mismatches, being indicators of mutation, has been central to pertinent algorithms. Specific amino acids possess quantifiable characteristics that enable the conversion from "words" (strings of letters denoting amino acids or bases) to "waves" (strings of quantitative values representing the physico-chemical properties) or to matrices (coordinates representing the positions in a comprehensive property space). The application of such numerical representations to evolutionary analysis takes into account not only the occurrence of mutations but also their properties as influences that drive speciation, because selective pressures favor certain mutations over others, and this predilection is represented in the characteristics of the incorporated amino acids (it is not born out solely by the mismatches). Besides being more discriminating sources for tree-generating algorithms than match/mismatch, the number strings can be examined for overall similarity with average mutual information, autocorrelation, and fractal dimension. Bivariate wavelet analysis aids in distinguishing hypermutable versus conserved domains of the protein. The matrix depiction is readily subjected to comparisons of distances, and it allows the generation of heat maps or graphs. This analysis preserves the accepted taxa order where tree construction with standard approaches yields conflicting results (for the protein S100A6). It also aids hypothesis generation about the origin of mitochondrial proteins. These analytical algorithms have been automated in R and are applicable to various processes that are describable in matrix format.

Comprehensive risk assessment of Pakistan railway network: A semi-quantitative risk matrix approach.

Pakistan Railway (PR) is vital to the country's transportation infrastructure, facilitating passenger and freight transportation. However, the growing number of accidents associated with PR has raised concerns about its overall safety. In addition, there have been limited research efforts to investigate PR accidents and their underlying causes The present study conducts a comprehensive risk assessment and safety management of PR using a semi-quantitative risk matrix approach. The study combines historical accident data and expert evaluations to assess the likelihood and consequences of different railway accident types and potential contributing factors. The descriptive statistics analysis has revealed varying degrees of severity for different types of railway accidents in Pakistan. For instance, accidents like passenger and goods train derailments and collisions at unmanned level crossings were identified as extreme and intolerable, whereas train fire accidents were categorized as high and undesirable. Moreover, accidents attributed to human error are classified as extreme and intolerable, while those caused by negligence of road users and track defects are classified as high and undesirable. The study utilized the risk matrix approach and identified critical risk areas that can help the decision-makers prioritize effective risk mitigation strategies. In light of the present study's findings, policy implications, such as investment in infrastructure to mitigate risks associated with aging or deteriorating tracks, bridges, and tunnels, and human resource development for railway personnel to improve their skills, decision-making abilities, and awareness of safety protocols, are recommended.