List Of Candidates Research Articles

An immune signature of postoperative cognitive decline: A prospective cohort study.

Postoperative cognitive decline (POCD) is the predominant complication affecting patients over 60 years old following major surgery, yet its prediction and prevention remain challenging. Understanding the biological processes underlying the pathogenesis of POCD is essential for identifying mechanistic biomarkers to advance diagnostics and therapeutics. This study aimed to provide a comprehensive analysis of immune cell trajectories differentiating patients with and without POCD and to derive a predictive score enabling the identification of high-risk patients during the preoperative period. Twenty-six patients aged 60 years old and older undergoing elective major orthopedic surgery were enrolled in a prospective longitudinal study, and the occurrence of POCD was assessed seven days after surgery. Serial samples collected before surgery, and one, seven, and 90 days after surgery were analyzed using a combined single-cell mass cytometry and plasma proteomic approach. Unsupervised clustering of the high-dimensional mass cytometry data was employed to characterize time-dependent trajectories of all major innate and adaptive immune cell frequencies and signaling responses. Sparse machine learning coupled with data-driven feature selection was applied to the pre-surgery immunological dataset to classify patients at risk for POCD. The analysis identified cell-type and signaling-specific immune trajectories differentiating patients with and without POCD. The most prominent trajectory features revealed early exacerbation of JAK/STAT and dampening of inhibitory κB and nuclear factor-κB immune signaling responses in patients with POCD. Further analyses integrating immunological and clinical data collected before surgery identified a preoperative predictive model comprising one plasma protein and ten immune cell features that classified patients at risk for POCD with excellent accuracy (AUC=0.80, P=2.21e-02 U-test). Immune system-wide monitoring of patients over 60 years old undergoing surgery unveiled a peripheral immune signature of POCD. A predictive model built on immunological data collected before surgery demonstrated greater accuracy in predicting POCD compared to known clinical preoperative risk factors, offering a concise list of biomarker candidates to personalize perioperative management.

Identification of Potential Growth-Related Proteins in Chick Vitreous during Emmetropization Using SWATH-MS and Targeted-Based Proteomics (MRMHR).

The vitreous humor (VH) is a transparent gelatin-like substance that occupies two-thirds of the eyeball and undergoes the most significant changes during eye elongation. Quantitative proteomics on the normal growth period in the VH could provide new insights into understanding its progression mechanism in the early stages of myopia. In this study, a data-independent acquisition (SWATH-MS) was combined with targeted LC-ESI-MS/MS to identify and quantify the relative protein changes in the vitreous during the normal growth period (4, 7, 14, 21 and 28 days old) in the chick model. Chicks were raised under normal growing conditions (12/12 h Dark/light cycle) for 28 days, where ocular measurements, including refractive and biometric measurements, were performed on days 4 (baseline), 7, 14, 21 and 28 (n = 6 chicks at each time point). Extracted vitreous proteins from individual animals were digested and pooled into a left eye pool and a right pool at each time point for protein analysis. The vitreous proteome for chicks was generated using an information-dependent acquisition (IDA) method by combining injections from individual time points. Using individual pool samples, SWATH-MS was employed to quantify proteins between each time point. DEPs were subsequently confirmed in separate batches of animals individually on random eyes (n = 4) using MRMHR between day 7 and day 14. Refraction and vitreous chamber depth (VCD) were found to be significantly changed (p < 0.05, n = 6 at each time point) during the period. A comprehensive vitreous protein ion library was built with 1576 non-redundant proteins (22987 distinct peptides) identified at a 1% false discovery rate (FDR). A total of 12 up-regulated and 26 down-regulated proteins were found across all time points compared to day 7 using SWATH-MS. Several DEPs, such as alpha-fetoprotein, the cadherin family group, neurocan, and reelin, involved in structural and growth-related pathways, were validated for the first time using MRMHR under this experimental condition. This study provided the first comprehensive spectral library of the vitreous for chicks during normal growth as well as a list of potential growth-related protein biomarker candidates using SWATH-MS and MRMHR during the emmetropization period.

Multiwavelength identification of millisecond pulsar candidates in the Galactic bulge

Context. The existence of a population of millisecond pulsars in the Galactic bulge is supported, along with other evidence, by the Fermi GeV excess, an anomalous γ-ray emission detected almost 15 years ago in the direction of the Galactic center. However, radio surveys searching for pulsations have not yet revealed bulge millisecond pulsars. Aims. Identifying promising bulge millisecond pulsar candidates is key to motivating pointed radio pulsation searches. Candidates are often selected among steep-spectrum or polarized radio sources, but multiwavelength information can also be exploited: The aim of this work is to pinpoint strong candidates among the yet unidentified X-ray sources. Methods. We investigated the multiwavelength counterparts of sources detected by the Chandra X-ray observatory that have spectral properties expected for millisecond pulsars in the Galactic bulge. We considered that ultraviolet, optical, and strong infrared counterparts indicate that an X-ray source is not a bulge pulsar, while a radio or a faint infrared counterpart makes it a promising candidate. Results. We identify a large population of more than a thousand X-ray sources without optical, ultraviolet, or strong infrared counterparts. Among them, five are seen for the first time in unpublished radio imaging data from the Very Large Array. We provide the list of promising candidates, for most of which follow-up pulsation searches are ongoing.

Memerna: Sparse RNA folding including coaxial stacking

Determining RNA secondary structure is a core problem in computational biology. Fast algorithms for predicting secondary structure are fundamental to this task. We describe a modified formulation of the Zuker-Stiegler algorithm with coaxial stacking, a stabilising interaction in which the ends of helices in multi-loops are stacked. In particular, optimal coaxial stacking is computed as part of the dynamic programming state, rather than in an inner loop. We introduce a new notion of sparsity, which we call replaceability. Replaceability is a more general condition and applicable in more places than the triangle inequality that is used by previous sparse folding methods. We also introduce non-monotonic candidate lists as an additional sparsification tool. Existing usages of the triangle inequality for sparsification can be thought of as an application of both replaceability and monotonicity together. The modified recurrences along with replaceability allows sparsification to be applied to coaxial stacking as well, which increases the speed of the algorithm. We implemented this algorithm in software we call memerna, which we show to have the fastest exact (non–heuristic) implementation of RNA folding under the complete Turner 2004 model with coaxial stacking, out of several popular RNA folding tools supporting coaxial stacking. We also introduce a new notation for secondary structure which includes coaxial stacking, terminal mismatches, and dangles (CTDs) information. The memerna package 0.1 release is available at https://github.com/Edgeworth/memerna/tree/release/0.1.

EXPLOITATION OF WOMEN IN THE CHANGING POWER DYNAMICS

This research examines the role of women in political oligarchy and their potential to change power dynamics. Political oligarchy concentrates power in the hands of a few, often overlooking women's roles within this structure. Feminist intersectionality reveals that social class significantly influences women's involvement in oligarchy, with greater barriers for women from lower economic classes. Women's participation in politics, both as leaders and members of political parties, is crucial for representing their unique needs in policy-making. However, women in decision-making roles often face cultural and normative dilemmas, needing to overcome negative stereotypes. The feminist movement plays a vital role in addressing gender inequality by changing cultural norms and raising awareness of gender bias. Although the Constitution of Indonesia and international conventions affirm gender equality, implementation requires specific policies. This research employs a qualitative descriptive method, collecting data from literature, official documents, and news sources. Findings indicate that women's roles in political oligarchy are often tied to kinship relations, political clans, and dynasties. Despite affirmative action policies promoting 30% female representation in legislative candidate lists, this representation often serves to validate the interests of certain groups. Nonetheless, women's involvement in politics is a positive step toward gender equality. Addressing gender inequality and increasing women's participation in decision-making requires robust efforts to support women's rights and dismantle social and political barriers. Further policy implementation to support women's political representation is essential for a more inclusive and gender-equal society.

Simulated analogues II: a new methodology for non-parametric matching of models to observations

ABSTRACT Star formation is a multiscale problem, and only global simulations that account for the connection from the molecular cloud-scale gas flow to the accreting protostar can reflect the observed complexity of protostellar systems. Star-forming regions are characterized by supersonic turbulence, and as a result, it is not possible to simultaneously design models that account for the larger environment and in detail reproduce observed stellar systems. Instead, the stellar inventories can be matched statistically, and the best matches found that approximate specific observations. Observationally, a combination of single-dish telescopes and interferometers are now able to resolve the nearest protostellar objects on all scales from the protostellar core to the inner $10\, \mathrm{au}$. We present a new non-parametric methodology which uses high-resolution simulations and post-processing methods to match simulations and observations using deep learning. Our goal is to perform a down-selection from large data sets of synthetic images to a ranked list of best-matching candidates with respect to the observation. This is particularly useful for binary and multiple stellar systems that form in turbulent environments. The objective is to accelerate the rate at which we can do such comparisons, remove biases from hand-picking matches, and contribute to identifying the underlying physical processes that drive the creation and evolution of observed protostellar systems.

“Social science is explanation or it is nothing.” Introduction to a debate

AbstractThis essay introduces contributions to a special section, which documents and extends a debate on the proposition “Social Science is Explanation or it is Nothing” held at the London School of Economics on October 13th, 2022. It discusses the history of the “Group for Theoretical Debates in Anthropology” led by Tim Ingold, Peter Wade and Soumhya Venkatesan, which has handed down a list of credible candidates for issues that had a chance of engaging every anthropologist, including students and those with interdisciplinary interests. It raises questions about the specific affordances of debates as forms of academic engagements. It argues that the chosen proposition concerning explanation invites a discussion about the contributions of the social sciences at a time when impulses from science and technology studies as well as fruitful exchanges across the boundary between “theory” and “method” have helped us moved beyond the older question as to whether or not sociology is “a science”.

Measurement of the 117mSn, 125mTe, 135mBa and 195mPt half-lives for reactor dosimetry application

Nuclear isomers are investigated to perform precise epithermal neutron dosimetry. One key physical property for reactor dosimetry is the precise knowledge of the isomer half-life. In the list of potential candidates, the half-life values available in the literature or in the recommended database for reactor dosimetry for 117mSn, 125mTe, 135mBa and 195mPt show some discrepancy. New half-life measurements are presented in this work. Those isomers were produced by neutron activation at the JSI TRIGA Reactor from tin, tellurium, barium (all three of them enriched in their parent of interest) and natural platinum dosimeters. Precise half-lives measurements were performed at the MADERE platform using gamma and X-ray spectrometry. Special care has been taken on the uncertainty determinations.

Implications for neurosurgery of medical schools leaving the United States News and World Report.

Ranked lists are a highly praised method of assessment in America. Whether it's a list of the top national sports teams, the best restaurants in New York City, or as in this case, the strongest educational institutions, we look to rankings to scrutinize, evaluate, and compare. Unfortunately, not all rankings offer insightful and valuable information. Many use metrics that fall short of an accurate representation of the desired outcome. The U.S. News & World Report (USNWR), one of the most widely regarded rankings of educational institutions, has recently been under the spotlight as several major medical schools have removed themselves from candidate lists. The current USNWR Medical School's rankings are regarded as having a narrow perspective in that the metrics perpetuate a less diverse medical community and fail to recognize worthy institutions that choose to champion a well-rounded student experience. The authors, along with the many others, fear this may deliver a skewed vision of what the USNWR tries to measure: the excellence of a medical education.

The value of simplified models of radionuclide transport for the safety assessment of nuclear waste repositories: A benchmark study

In order to assess sites for a deep geological repository for storing high-level nuclear waste safely in Germany, various numerical models and tools will be in use. For their interaction within one workflow, their reproducibility, and reliability version-controlled open-source solutions and careful documentation of model setups, results and verifications are of special value. However, spatially fully resolved models including all relevant physical and chemical processes are neither computationally feasible for large domains nor is the data typically available to parameterize such models. Thus, simplified models are crucial for the pre-assessment of possible sites to narrow down the list of suitable candidates for which detailed site investigations and fully resolved models will be done at a later stage. Still, the accuracy of these simplified models is of importance as the pre-assessment of suitable sites will be based on them. In this study, we compare the modelling capabilities of TransPyREnd, a one-dimensional transport code based on finite differences, specifically developed for the fast estimation of radionuclide transport by the German federal company for radioactive waste disposal (BGE), with OpenGeoSys, which is a modelling platform based on finite elements in up to three spatial dimensions. Both codes are used in the site selection procedure for the German nuclear waste repository. The comparison of the model results of TransPyREnd and OpenGeoSys is augmented by comparisons with an analytical solution for a homogeneous material. For the purpose of numerical benchmarking, we consider a geological profile located in southern Germany as an example where the hypothetical repository is located in a clay-stone formation. TransPyREnd and OpenGeoSys yield overall similar results. However, both codes use different discretizations which impact is the highest for strongly sorbing compounds, while the difference gets negligible for less sorbing and more diffusive compounds as higher diffusion tends to blur the initial conditions. Overall, the OpenGeoSys model is more exact whereas the TransPyREnd model has considerable faster run times. We found in our example, that significant substance amounts are only leaving the host rock formation, if apparent diffusion is high, for which case both codes give similar results, while relative differences are considerable for strongly sorbing compounds. However, in the latter case no significant substance amount of radionuclides leaves the host-rock formation, thus deeming the differences in the model results minor for the overall safety assessments of sites.

Are contemporary facial recognition algorithms making human facial comparison performance worse?

Facial recognition plays a vital role in several security and law enforcement workflows, such as passport control and criminal investigations. The identification process typically involves a facial recognition system comparing an image against a large database of faces to return a list of probable matches, called a candidate list, for review. A human then looks at the returned images to determine whether there is a match. Most evaluations of these systems tend to examine the performance of the algorithm or human in isolation, not accounting for the interaction that occurs in operational contexts. To ensure optimal whole system performance, it is important to understand how the output produced by an algorithm can impact human performance. Anecdotal claims have been made by users of facial recognition systems that the images being returned by new algorithms in these systems have become more similar in appearance compared to old algorithms, making their job of determining the presence of a match more difficult. This paper explores whether these claims are true and whether the latest facial recognition algorithms decrease human performance compared to an old algorithm from the same company. We examined the performance of 40 novice participants on 120 face matching trials. Each trial required the participant to compare a face image against a candidate list containing eight possible matches returned by either a new or old algorithm (60 trials of each). Overall, participants were more likely to make errors when presented with a candidate list from a new algorithm. Specifically, they were more likely to misidentify an incorrect identity as a match. Participants were more accurate, confident, and faster on candidate lists from the older algorithm. These findings suggest that new algorithms are generating more plausible matches, making the task of determining a match harder for humans. We propose strategies to potentially improve performance and recommendations for future research.

Exportin-5 binding precedes 5′- and 3′-end processing of tRNA precursors in Drosophila

Exportin5 (Exp5) is the major microRNA (miRNA) nuclear export factor and recognizes structural features of pre-miRNA hairpins, while it also exports other minihelix-containing RNAs. In Drosophila, Exp5 is suggested to play a major role in tRNA export because the gene encoding the canonical tRNA export factor Exportin-t is missing in its genome. To understand molecular functions of fly Exp5, we studied the Exp5/RNA interactome in the cell line S2R+ using the CLIP (crosslinking and immunoprecipitation) technology. The CLIP experiment captured known substrates such as tRNAs and miRNAs, and detected candidates of novel Exp5 substrates including various mRNAs and long non-coding RNAs (lncRNAs). Some mRNAs and lncRNAs enriched PAR-CLIP tags compared to their expression levels, suggesting selective binding of Exp5 to them. Intronless mRNAs tended to enrich PAR-CLIP tags, therefore we proposed that Exp5 might play a role in export of specific classes of mRNAs/lncRNAs. This result suggested that Drosophila Exp5 might have a wider variety of substrates than initially thought. Surprisingly, Exp5 CLIP reads often contained sequences corresponding to the flanking 5’-leaders and 3’-trailers of tRNAs, which were thought to be removed prior to nuclear export. In fact, we found pre-tRNAs before end-processing were present in the cytoplasm, supporting the idea that tRNA end-processing is a cytoplasmic event. In summary, our results provide a genome-wide list of Exp5 substrate candidates, and suggest that flies may lack a mechanism to distinguish pre-tRNAs with or without the flanking sequences.

Comparative host transcriptomics as a tool to identify candidate biomarkers for immune reactions in leprosy using meta-analysis.

Background Leprosy is no longer considered an imprecation, as an effective multidrug therapy regimen is available worldwide for its cure. However, its diverse clinical manifestations sometimes involve acute inflammatory reactions. These complications result in irreversible nerve damage, neuritis and anatomical deformities that emerge before, during the treatment or after the completion of treatment. Reversal reaction (Type-I) and erythema nodosum leprosum (Type-II) are the leprosy reactions generally seen in patients with lepromatous and borderline forms of leprosy. At present, there is no accurate diagnostic test available to detect these leprosy reactions. Objectives To identify potential biomarkers indicative of Type-I and Type-II leprosy reactions that could help in their early diagnosis. Methods and Results Host-transcriptomics investigations have been utilised in this study to decipher a correlation between host-gene expression-based biomarkers and exacerbation of leprosy reactions. We present a comparative analysis of publicly available host transcriptomics datasets (from Gene Expression Omnibus) related to leprosy reactions. Individual datasets were analysed and integration of results was carried out using meta-analysis. Common differentially expressed genes (DEGs) were identified using the frequentist and Bayesian ratio association test methods. We have identified several genes - ADAMTS5, ADAMTS9, IFITM2, IFITM3, KIRREL, ANK3, CD1E, CTSF, DOCK9 and KRT73 to name a few - which can serve as potential biomarkers for Type-II reaction. Similarly, ACP5, APOC1, CCL17, S100B, SLC11A1 among others may likely serve as biomarkers for Type-I reaction. Limitations The number of datasets related to leprosy reactions found after the systematic search is less (n = 4) and may limit the accuracy of identified biomarker genes. This could be resolved by including more studies in the data analysis. Conclusion We provide a comprehensive list of gene candidates which could be prioritised further in research focusing on immune reactions in leprosy, as they are likely important in understanding its complexities and could be useful in its early diagnosis.

Catalogue of dual-field interferometric binary calibrators

Context. Dual-field interferometric observations with VLTI/GRAVITY sometimes require the use of a binary calibrator. This is a binary star whose individual components remain unresolved by the interferometer, with a separation between 400 and 2000 mas for observations with the Unit Telescopes (UTs), or 1200–3000 mas for the Auxiliary Telescopes (ATs). The separation vector also needs to be predictable to within 10 mas for a proper pointing of the instrument. Aims. No list of properly vetted calibrators was available so far for dual-field observations with VLTI/GRAVITY on the UTs. Our objective is to compile such a list and make it available to the community. Methods. We identified a list of candidates from the Washington Double Star (WDS) catalogue, all with appropriate separations and brightness, scattered over the southern sky. We observed them as part of a dedicated calibration programme, determined whether these objects were true binaries (excluding higher multiplicities resolved interferometrically, but unseen by imaging), and extracted measurements of the separation vectors. We combined these new measurements with those available in the WDS to determine updated orbital parameters for all our vetted calibrators. Results. We compiled a list of 13 vetted binary calibrators for observations with VLTI/GRAVITY on the UTs, and we provide orbital estimates and astrometric predictions for each of them. We show that our list guarantees that there are always two binary calibrators at least at an airmass &lt; 2 in the sky over the Paranal observatory at any point in time. Conclusions. Any principal investigator wishing to use the dual-field mode of VLTI/GRAVITY with the UTs can now refer to this list to select an appropriate calibrator. We encourage the use of whereistheplanet to predict the astrometry of these calibrators, which seamlessly integrates with p2Gravity for VLTI/GRAVITY dual-field observing material preparation.

Development and usability testing of an online support tool to identify models and frameworks to inform implementation

BackgroundTheories, models and frameworks (TMFs) are useful when implementing, evaluating and sustaining healthcare evidence-based interventions. Yet it can be challenging to identify an appropriate TMF for an implementation project. We developed and tested the usability of an online tool to help individuals who are doing or supporting implementation practice activities to identify appropriate models and/or frameworks to inform their work.MethodsWe used methods guided by models and evidence on implementation science and user-centered design. Phases of tool development included applying findings from a scoping review of TMFs and interviews with 24 researchers/implementers on barriers and facilitators to identifying and selecting TMFs. Based on interview findings, we categorized the TMFs by aim, stage of implementation, and target level of change to inform the tool’s algorithm. We then conducted interviews with 10 end-users to test the usability of the prototype tool and administered the System Usability Scale (SUS). Usability issues were addressed and incorporated into the tool.ResultsWe developed Find TMF, an online tool consisting of 3–4 questions about the user’s implementation project. The tool’s algorithm matches key characteristics of the user’s project (aim, stage, target change level) with characteristics of different TMFs and presents a list of candidate models/frameworks. Ten individuals from Canada or Australia participated in usability testing (mean SUS score 84.5, standard deviation 11.4). Overall, participants found the tool to be simple, easy to use and visually appealing with a useful output of candidate models/frameworks to consider for an implementation project. Users wanted additional instruction and guidance on what to expect from the tool and how to use the information in the output table. Tool improvements included incorporating an overview figure outlining the tool steps and output, displaying the tool questions on a single page, and clarifying the available functions of the results page, including adding direct links to the glossary and to complementary tools.ConclusionsFind TMF is an easy-to-use online tool that may benefit individuals who support implementation practice activities by making the vast number of models and frameworks more accessible, while also supporting a consistent approach to identifying and selecting relevant TMFs.

New quasars behind the Magellanic Clouds

Context. Quasi-stellar objects (QSOs) are a basis for an absolute reference system for astrometric studies. A system like this at the far side of nearby galaxies is required to facilitate measuring of the proper motions of these galaxies. However, the foreground contamination from the galaxies themselves is a problem for the QSO identification. Aims. We search for new QSOs behind the two Magellanic Clouds, the Magellanic Bridge, and the Magellanic Stream. Methods. We identify QSO candidates with a combination of near–infrared colors and variability criteria from the public ESO Visual and Infrared Survey Telescope for Astronomy (VISTA) Magellanic Clouds (VMC) survey. We confirm their nature from broad emission lines with low-resolution optical spectroscopy. Results. We confirmed the QSO nature of 136 objects. They are distributed as follows: 12 behind the Large Magellanic Cloud, 37 behind the Small Magellanic Cloud, 63 behind the Bridge, and 24 behind the Stream. The QSOs span a redshift range from z~0.1 to z~2.9. A comparison of our quasar selection with the Quaia quasar catalog, based on Gaia low-resolution spectra, yields a selection and confirmation success rate of 6–19%, depending on whether the quality of the photometry, the magnitude ranges, and the colors are considered. Our candidate list is rather incomplete, but the objects in it are likely to be confirmed as quasars with a probability of ~90%. Finally, we report a list of 3609 objects in the entire VMC survey that match our color and variability selection criteria; only 1249 of them have Gaia counterparts. Conclusions. Our combined infrared color and variability criteria for the QSO selection prove to be efficient: ~90% of the observed candidates are bona fide QSOs and allow us to generate a list of new high-probability quasar candidates.

Comparative proteomics of sugarcane smut fungus - Sporisorium scitamineum unravels dynamic proteomic alterations during the dimorphic transition

Life cycle of the dimorphic sugarcane smut fungi, Sporisorium scitamineum, involves recognition and mating of compatible saprophytic yeast-like haploid sporidia (MAT-1 and MAT-2) that upon fusion, develop into infective dikaryotic mycelia. Although the dimorphic transition is intrinsically linked with the pathogenicity and virulence of S. scitamineum, it has never been studied using a proteomic approach. In the present study, an iTRAQ-based comparative proteomic analysis of three distinct stages was carried out. The stages were: the dimorphic transition period - haploid sporidial stage (MAT-1 and MAT-2); the transition phase (24 h post co-culturing (hpc)) and the dikaryotic mycelial stage (48 hpc). Functional categorization of differentially abundant proteins showed that the most altered biological processes were energy production, primary metabolism, especially, carbohydrate, amino acid, fatty acid, followed by translation, post-translation and protein turnover. Several differentially abundant proteins (DAPs), especially in the dikaryotic mycelial stage were predicted as effectors. Taken together, key molecular mechanisms underpinning the dimorphic transition in S. scitamineum at the proteome level were highlighted. The catalogue of stage-specific and dimorphic transition-associated-proteins and potential effectors identified herein represents a list of potential candidates for defective mutant screening to elucidate their functional role in the dimorphic transition and pathogenicity in S. scitamineum. Biological significanceBeing the first comparative proteomics analysis of S. scitamineum, this study comprehensively examined three pivotal life cycle stages of the pathogen: the non-pathogenic haploid phase, the transition phase, and the pathogenic dikaryotic mycelial stage. While previous studies have reported the sugarcane and S. scitamineum interactions, this study endeavored to specifically identify the proteins responsible for pathogenicity. By analyzing the proteomic alterations between the haploid and dikaryotic mycelial phases, the study revealed significant changes in metabolic pathway-associated proteins linked to energy production, notably oxidative phosphorylation, and the citrate cycle. Furthermore, this study successfully identified key metabolic pathways that undergo reprogramming during the transition from the non-pathogenic to the pathogenic stage. The study also deciphered the underlying mechanisms driving the morphological and physiological alterations crucial for the S. scitamineum virulence. By studying its life cycle stages, identifying the key metabolic pathways and stage-specific proteins, it provides unprecedented insights into the pathogenicity and potential avenues for intervention. As proteomics continues to advance, such studies pave the way for a deeper understanding of plant-pathogen interactions and the development of innovative strategies to mitigate the impact of devastating pathogens like S. scitamineum.

Identification of brain-enriched proteins in CSF as biomarkers of relapsing remitting multiple sclerosis

BackgroundMultiple sclerosis (MS) is a clinically and biologically heterogenous disease with currently unpredictable progression and relapse. After the development and success of neurofilament as a cerebrospinal fluid (CSF) biomarker, there is reinvigorated interest in identifying other markers of or contributors to disease. The objective of this study is to probe the predictive potential of a panel of brain-enriched proteins on MS disease progression and subtype.MethodsThis study includes 40 individuals with MS and 14 headache controls. The MS cohort consists of 20 relapsing remitting (RR) and 20 primary progressive (PP) patients. The CSF of all individuals was analyzed for 63 brain enriched proteins using a method of liquid-chromatography tandem mass spectrometry. Wilcoxon rank sum test, Kruskal-Wallis one-way ANOVA, logistic regression, and Pearson correlation were used to refine the list of candidates by comparing relative protein concentrations as well as relation to known imaging and molecular biomarkers.ResultsWe report 30 proteins with some relevance to disease, clinical subtype, or severity. Strikingly, we observed widespread protein depletion in the disease CSF as compared to control. We identified numerous markers of relapsing disease, including KLK6 (kallikrein 6, OR = 0.367, p < 0.05), which may be driven by active disease as defined by MRI enhancing lesions. Other oligodendrocyte-enriched proteins also appeared at reduced levels in relapsing disease, namely CNDP1 (carnosine dipeptidase 1), LINGO1 (leucine rich repeat and Immunoglobin-like domain-containing protein 1), MAG (myelin associated glycoprotein), and MOG (myelin oligodendrocyte glycoprotein). Finally, we identified three proteins—CNDP1, APLP1 (amyloid beta precursor like protein 1), and OLFM1 (olfactomedin 1)—that were statistically different in relapsing vs. progressive disease raising the potential for use as an early biomarker to discriminate clinical subtype.ConclusionsWe illustrate the utility of targeted mass spectrometry in generating potential targets for future biomarker studies and highlight reductions in brain-enriched proteins as markers of the relapsing remitting disease stage.

An Integrative Transcriptome Subtraction Strategy to Identify Human lncRNAs That Specifically Play a Role in Activation of Human Hepatic Stellate Cells.

Fibrotic liver features excessive deposition of extracellular matrix (ECM), primarily produced from "activated" hepatic stellate cells (HSCs). While targeting human HSCs (hHSCs) in fibrosis therapeutics shows promise, the overall understanding of hHSC activation remains limited, in part because it is very challenging to define the role of human long non-coding RNAs (lncRNAs) in hHSC activation. To address this challenge, we identified another cell type that acts via a diverse gene network to promote fibrogenesis. Then, we identified the lncRNAs that were differentially regulated in activated hHSCs and the other profibrotic cell. Next, we conducted concurrent analysis to identify those lncRNAs that were specifically involved in fibrogenesis. We tested and confirmed that transdifferentiation of vascular smooth muscle cells (VSMCs) represents such a process. By overlapping TGFβ-regulated lncRNAs in multiple sets of hHSCs and VSMCs, we identified a highly selected list of lncRNA candidates that could specifically play a role in hHSC activation. We experimentally characterized one human lncRNA, named CARMN, which was significantly regulated by TGFβ in all conditions above. CARMN knockdown significantly reduced the expression levels of a panel of marker genes for hHSC activation, as well as the levels of ECM deposition and hHSC migration. Conversely, gain of function of CARMN using CRISPR activation (CRISPR-a) yielded the completely opposite effects. Taken together, our work addresses a bottleneck in identifying human lncRNAs that specifically play a role in hHSC activation and provides a framework to effectively select human lncRNAs with significant pathophysiological role.

Design and Analysis of ONLINE Voting System

A democratic country encourages voting system to decide the future leader. Traditional voting system offers lack of user friendliness in review of votes and voters’ identity security. In this present work, for the first time, a web-based voting architecture is designed and developed. The system has a login page, registration page, and dashboard page for voters to access in a user-friendly manner. The login page is the first page that users see when they access the system through registered mobile number, password, and role. The role is used to distinguish between voters and groups or candidates. The dashboard page is the display unit to exhibit voters’ profile information such as name, image, voting status, and mobile number on the left side of the page. On the right side of the page, there will be a list of groups or candidates whom they can cast their votes. In our proposed system, it is ensured that each voter can only vote once and that duplicate voting is not possible. The system uses password protected voting system and Black Box to administer the security issues for inculcating integrity of the voting process. The system is designed to provide a secure and user-friendly interface for voters to cast their votes online and henceforth the architecture will save the time, energy, and costs. T