Miracle-dz/UniFAR-FTUs huggingface dataset:
MicroRNA-1258 Inhibits the Proliferation and Migration of Human Colorectal Cancer Cells through Suppressing CKS1B Expression

Increasing evidence has demonstrated that increased expression of cyclin-dependent kinase regulatory subunit 1B (CKS1B) is associated with the pathogenesis of many human cancers, including colorectal cancer (CRC). However, the regulatory mechanisms underlying the expression of CKS1B in CRC are not completely understood. Here, we investigate the role played by microRNAs in the expression of CKS1B and carcinogenesis in CRC. Among the six microRNAs predicted to target CKS1B gene expression, only miR-1258 was revealed to downregulate CKS1B expression through binding to its 3’-UTR region, as ectopic miR-1258 expression suppressed CKS1B expression and vice versa. In CRC, miR-1258 expression also decreased cell proliferation and migration in vitro and tumor growth in vivo, similar to cells with silenced CKS1B expression. Considering the highly increased levels of CKS1B and decreased expression of miR-1258 in tumors from CRC patients, these findings suggest that miR-1258 may play tumor-suppressive roles by targeting CKS1B expression in CRC. However, the therapeutic significance of these findings should be evaluated in clinical settings.
Tau PET imaging with 18F-PI-2620 in Patients with Alzheimer Disease and Healthy Controls: A First-in-Humans Study

18F-PI-2620 is a PET tracer with high binding affinity for aggregated tau, a key pathologic feature of Alzheimer disease (AD) and other neurodegenerative disorders. Preclinically, 18F-PI-2620 binds to both 3-repeat and 4-repeat tau isoforms. The purpose of this first-in-humans study was to evaluate the ability of 18F-PI-2620 to detect tau pathology in AD patients using PET imaging, as well as to assess the safety and tolerability of this new tau PET tracer. Methods: Participants with a clinical diagnosis of probable AD and healthy controls (HCs) underwent dynamic 18F-PI-2620 PET imaging for 180 min. 18F-PI-2620 binding was assessed visually and quantitatively using distribution volume ratios (DVR) estimated from noninvasive tracer kinetics and SUV ratio (SUVR) measured at different time points after injection, with the cerebellar cortex as the reference region. Time–activity curves and SUVR were assessed in AD and HC subjects, as well as DVR and SUVR correlations and effect size (Cohen’s d) over time. Results: 18F-PI-2620 showed peak brain uptake around 5 min after injection and fast washout from nontarget regions. In AD subjects, focal asymmetric uptake was evident in temporal and parietal lobes, precuneus, and posterior cingulate cortex. DVR and SUVR in these regions were significantly higher in AD subjects than in HCs. Very low background signal was observed in HCs. 18F-PI-2620 administration was safe and well tolerated. SUVR time–activity curves in most regions and subjects achieved a secular equilibrium after 40 min after injection. A strong correlation (R2 > 0.93) was found between noninvasive DVR and SUVR for all imaging windows starting at more than 30 min after injection. Similar effect sizes between AD and HC groups were obtained across the different imaging windows. 18F-PI-2620 uptake in neocortical regions significantly correlated with the degree of cognitive impairment. Conclusion: Initial clinical data obtained in AD and HC subjects demonstrated a high image quality and excellent signal-to-noise ratio of 18F-PI-2620 PET for imaging tau deposition in AD subjects. Noninvasive quantification using DVR and SUVR for 30-min imaging windows between 30 and 90 min after injection—for example, 45–75 min—provides robust and significant discrimination between AD and HC subjects. 18F-PI-2620 uptake in expected regions correlates strongly with neurocognitive performance.
A Possible Alternative Mechanism for the Oxidation of Formaldehyde to Formate

A survey of the occurrence of a no. of enzymes possibly involved in the C1 dissimilatory pathway in organisms using the serine pathway of C assimilation indicated that neither the methanol dehydrogenase nor the NH4-independent dye-linked formaldehyde dehydrogenase had a specific role in the oxidn. of formaldehyde. Conversely, the activities of enzymes involved in the methenyl-THF pathway were induced during growth on MeOH or MeNH2, suggesting a potential dissimilatory role for this pathway. [on SciFinder (R)]
Biotechnological Potential of Bacteria Isolated from the Sea Cucumber Holothuria leucospilota and Stichopus vastus from Lampung, Indonesia

In order to minimize re-discovery of already known anti-infective compounds, we focused our screening approach on understudied, almost untapped marine environments including marine invertebrates and their associated bacteria. Therefore, two sea cucumber species, Holothuria leucospilota and Stichopus vastus, were collected from Lampung (Indonesia), and 127 bacterial strains were identified by partial 16S rRNA-gene sequencing analysis and compared with the NCBI database. In addition, the overall bacterial diversity from tissue samples of the sea cucumbers H. leucospilota and S. vastus was analyzed using the cultivation-independent Illumina MiSEQ analysis. Selected bacterial isolates were grown to high densities and the extracted biomass was tested against a selection of bacteria and fungi as well as the hepatitis C virus (HCV). Identification of putative bioactive bacterial-derived compounds were performed by analyzing the accurate mass of the precursor/parent ions (MS1) as well as product/daughter ions (MS2) using high resolution mass spectrometry (HRMS) analysis of all active fractions. With this attempt we were able to identify 23 putatively known and two previously unidentified precursor ions. Moreover, through 16S rRNA-gene sequencing we were able to identify putatively novel bacterial species from the phyla Actinobacteria, Proteobacteria and also Firmicutes. Our findings suggest that sea cucumbers like H. leucospilota and S. vastus are promising sources for the isolation of novel bacterial species that produce compounds with potentially high biotechnological potential.
A TLR7 agonist strengthens T and NK cell function during BRAF‐targeted therapy in a preclinical melanoma model

Therapeutic success of targeted therapy with BRAF inhibitors (BRAFi) for melanoma is limited by resistance development. Observations from preclinical mouse models and recent insights into the immunological effects caused by BRAFi give promise for future development of combination therapy for human melanoma. In our study, we used the transplantable D4M melanoma mouse model with the BRAFV600E mutation and concomitant PTEN loss in order to characterize alterations in tumor‐infiltrating effector immune cells when tumors become resistant to BRAFi. We found that BRAFi‐sensitive tumors displayed a pronounced inflammatory milieu characterized by high levels of cytokines and chemokines accompanied by an infiltration of T and NK cells. The tumor‐infiltrating effector cells were activated and produced high levels of IFN‐γ, TNF‐α and granzyme B. When tumors became resistant and progressively grew, they reverted to a low immunogenic state similar to untreated tumors as reflected by low mRNA levels of proinflammatory cytokines and chemokines and fewer tumor‐infiltrating T and NK cells. Moreover, these T and NK cells were functionally impaired in comparison to their counterparts in BRAFi‐sensitive tumors. Their effector cell function could be restored by additional peritumoral treatment with the TLR7 agonist imiquimod, a clinically approved agent for nonmelanoma skin cancer. Indeed, resistance to BRAFi therapy was delayed and accompanied by high numbers of activated T and NK cells in tumors. Thus, combining BRAFi with an immune stimulating agent such as a TLR ligand could be a promising alternative approach for the treatment of melanoma.
THE EFFECTS OF DARK MATTER ANNIHILATION ON COSMIC REIONIZATION

We revisit the possibility of constraining the properties of dark matter (DM) by studying the epoch of cosmic reionization. Previous studies have shown that DM annihilation was unlikely to have provided a large fraction of the photons which ionized the universe, but instead played a subdominant role relative to stars and quasars. The DM might, however, have begun to efficiently annihilate with the formation of primordial microhalos at z ∼ 100–200, much earlier than the formation of the first stars. Therefore, if DM annihilation ionized the universe at even the percent level over the interval z ∼ 20–100, it could leave a significant imprint on the global optical depth, τ. Moreover, we show that cosmic microwave background polarization data and future 21 cm measurements will enable us to more directly probe the DM contribution to the optical depth. In order to compute the annihilation rate throughout the epoch of reionization, we adopt the latest results from structure formation studies and explore the impact of various free parameters on our results. We show that future measurements could make it possible to place constraints on the DM’s annihilation cross-sections, which are at a level comparable to those obtained from the observations of dwarf galaxies, cosmic-ray measurements, and studies of recombination.
Lipid Related Genes Altered in NASH Connect Inflammation in Liver Pathogenesis Progression to HCC: A Canonical Pathway

Nonalcoholic steatohepatitis (NASH) is becoming a public health problem worldwide. While the number of research studies on NASH progression rises every year, sometime their findings are controversial. To identify the most important and commonly described findings related to NASH progression, we used an original bioinformatics, integrative, text-mining approach that combines PubMed database querying and available gene expression omnibus dataset. We have identified a signature of 25 genes that are commonly found to be dysregulated during steatosis progression to NASH and cancer. These genes are implicated in lipid metabolism, insulin resistance, inflammation, and cancer. They are functionally connected, forming the basis necessary for steatosis progression to NASH and further progression to hepatocellular carcinoma (HCC). We also show that five of the identified genes have genome alterations present in HCC patients. The patients with these genes associated to genome alteration are associated with a poor prognosis. In conclusion, using an integrative literature- and data-mining approach, we have identified and described a canonical pathway underlying progression of NASH. Other parameters (e.g., polymorphisms) can be added to this pathway that also contribute to the progression of the disease to cancer. This work improved our understanding of the molecular basis of NASH progression and will help to develop new therapeutic approaches.
Association of EGLN1 gene with high aerobic capacity of Peruvian Quechua at high altitude

Significance Andean highland native populations, such as the Quechua of Peru, have enhanced exercise capacity at altitude and may be genetically adapted to altitude. We identified 5 genetic markers near the Egl-9 homolog 1 gene (EGLN1) gene that were associated with higher aerobic capacity (VO2max) in hypoxia. EGLN1 encodes for a protein that controls the level of the Hypoxia Inducible Factor-α, which in turn regulates the cellular hypoxic response. Advantageous SNP alleles were associated with a significantly higher VO2max and were found at higher frequency in Quechua compared with lowland populations. These results add further context to previous studies that have provided evidence of natural selection at the EGLN1 locus in Andeans. Highland native Andeans have resided at altitude for millennia. They display high aerobic capacity (VO2max) at altitude, which may be a reflection of genetic adaptation to hypoxia. Previous genomewide (GW) scans for natural selection have nominated Egl-9 homolog 1 gene (EGLN1) as a candidate gene. The encoded protein, EGLN1/PHD2, is an O2 sensor that controls levels of the Hypoxia Inducible Factor-α (HIF-α), which regulates the cellular response to hypoxia. From GW association and analysis of covariance performed on a total sample of 429 Peruvian Quechua and 94 US lowland referents, we identified 5 EGLN1 SNPs associated with higher VO2max (L⋅min−1 and mL⋅min−1⋅kg−1) in hypoxia (rs1769793, rs2064766, rs2437150, rs2491403, rs479200). For 4 of these SNPs, Quechua had the highest frequency of the advantageous (high VO2max) allele compared with 25 diverse lowland comparison populations from the 1000 Genomes Project. Genotype effects were substantial, with high versus low VO2max genotype categories differing by ∼11% (e.g., for rs1769793 SNP genotype TT = 34.2 mL⋅min−1⋅kg−1 vs. CC = 30.5 mL⋅min−1⋅kg−1). To guard against spurious association, we controlled for population stratification. Findings were replicated for EGLN1 SNP rs1769793 in an independent Andean sample collected in 2002. These findings contextualize previous reports of natural selection at EGLN1 in Andeans, and support the hypothesis that natural selection has increased the frequency of an EGLN1 causal variant that enhances O2 delivery or use during exercise at altitude in Peruvian Quechua.
Altitudinal bird migration in North America

ABSTRACT Altitudinal bird migration involves annual seasonal movements up and down elevational gradients. Despite the fact that species from montane avifaunas worldwide engage in altitudinal migration, the patterns, causes, and prevalence of these movements are poorly understood. This is particularly true in North America where the overwhelming majority of avian migration research has focused on obligate, long-distance, temperate–tropical movements. Elsewhere in the world, most altitudinal migrants are partial migrants, making downhill movements to nonbreeding areas. However, spatial and temporal patterns, the prevalence and predictability of migration at individual and population levels, and the ultimate ecological factors selecting for movement behavior vary considerably among taxa and regions. I conducted a systematic survey of the evidence for altitudinal migration to fill gaps in our understanding of this behavior among the landbirds of North America and Hawaii. Altitudinal migration was as prevalent as in other avifaunas, occurring in >20% of continental North American and nearly 30% of Hawaiian species. Of the species wintering within the USA and Canada, ∼30% engage in altitudinal migrations. Altitudinal migrants are far more common in the West, are taxonomically and ecologically diverse, and North American species exhibit patterns similar to altitudinal migrants elsewhere in the world. Because altitudinal migration systems are relatively tractable, they present excellent opportunities for testing hypotheses regarding migration generally. Altitudinal migration has likely been overlooked in North America due to contingency in the history of ornithological research. Our need to understand the patterns and causes of altitudinal migrations has never been greater due to emerging environmental threats to montane systems.
Potential Consequences of Climate Change to Persistence of Cutthroat Trout Populations

Abstract Warmer water, changes in stream flow, and the increasing frequency and intensity of other disturbances are among the factors associated with climate change that are likely to impact native trout populations in the western USA. We examined how three of these factors—increased summer temperatures, uncharacteristic winter flooding, and increased wildfires—are likely to affect broad-scale population persistence among three subspecies of cutthroat trout Oncorhynchus clarkii. Our results suggest that as much as 73% of the habitat currently occupied by Bonneville cutthroat trout O. c. utah, 65% of that occupied by westslope cutthroat trout O. c. lewisi, and 29% of that occupied by Colorado River cutthroat trout O. c. pleuriticus will be at high risk from one or more of the these three factors. Within the next 50 years, wildfire, floods, and other disturbances may have a greater impact on population persistence than increasing water temperature alone. Our results also suggest that the risk will vary subs.
Development of a Validated UPLC-MS/MS Method for Analyzing Major Ginseng Saponins from Various Ginseng Species

Ginsenosides, which contain one triterpene and one or more sugar moieties, are the major bioactive compounds of ginseng. The aim of this study was to develop and optimize a specific and reliable ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method for the analysis of twelve different resources of ginseng. The six marker compounds of ginsenoside Rb1, ginsenoside Rb2, ginsenoside Rc, ginsenoside Rd, ginsenoside Re, and ginsenoside Rg1, as well as an internal standard, were separated by a reversed-phase C-18 column with a gradient elution of water and methanol-acetonitrile. The multiple-reaction monitoring (MRM) mode was used to quantify and identify twelve market products. The results demonstrated that not only is the logarithm of its partition coefficient (cLog P; octanol-water partition coefficient) one of the factors, but also the number of sugars, position of sugars, and position of the hydroxyl groups are involved in the complicated separation factors for the analytes in the analytical system. If the amount of ginsenoside Rb1 was higher than 40 mg/g, then the species might be Panax quinquefolius, based on the results of the marker ginsenoside contents of various varieties. In summary, this study provides a rapid and precise analytical method for identifying the various ginsenosides from different species, geographic environments, and cultivation cultures.
Prey and Venom Efficacy of Male and Female Wandering Spider, Phoneutria boliviensis (Araneae: Ctenidae)

Spiders rely on venom to catch prey and few species are even capable of capturing vertebrates. The majority of spiders are generalist predators, possessing complex venom, in which different toxins seem to target different types of prey. In this study, we focused on the trophic ecology and venom toxicity of Phoneutria boliviensis F. O. Pickard-Cambridge, 1897, a Central American spider of medical importance. We tested the hypothesis that its venom is adapted to catch vertebrate prey by studying its trophic ecology and venom toxicity against selected vertebrate and invertebrate prey. We compared both trophic ecology (based on acceptance experiments) and toxicity (based on bioassays) among sexes of this species. We found that P. boliviensis accepted geckos, spiders, and cockroaches as prey, but rejected frogs. There was no difference in acceptance between males and females. The venom of P. boliviensis was far more efficient against vertebrate (geckos) than invertebrate (spiders) prey in both immobilization time and LD50. Surprisingly, venom of males was more efficient than that of females. Our results suggest that P. boliviensis has adapted its venom to catch vertebrates, which may explain its toxicity to humans.
A model‐based motion capture marker location refinement approach using inverse kinematics from dynamic trials

Marker‐based motion capture techniques are commonly used to measure human body kinematics. These techniques require an accurate mapping from physical marker position to model marker position. Traditional methods utilize a manual process to achieve marker positions that result in accurate tracking. In this work, we present an optimization algorithm for model marker placement to minimize marker tracking error during inverse kinematics analysis of dynamic human motion. The algorithm sequentially adjusts model marker locations in 3‐D relative to the underlying rigid segment. Inverse kinematics is performed for a dynamic motion capture trial to calculate the tracking error each time a marker position is changed. The increase or decrease of the tracking error determines the search direction and number of increments for each marker coordinate. A final marker placement for the model is reached when the total search interval size for every coordinate falls below a user‐defined threshold. Individual marker coordinates can be locked in place to prevent the algorithm from overcorrecting for data artifacts such as soft tissue artifact. This approach was used to refine model marker placements for eight able‐bodied subjects performing walking trials at three stride frequencies. Across all subjects and stride frequencies, root mean square (RMS) tracking error decreased by 38.4% and RMS tracking error variance decreased by 53.7% on average. The resulting joint kinematics were in agreement with expected values from the literature. This approach results in realistic kinematics with marker tracking errors well below accepted thresholds while removing variance in the model‐building procedure introduced by individual human tendencies.
Strategic e-business framework: a holistic approach for organisations in the construction industry

Strategic consideration and actions are crucial for organisations in the construction industry to implement e-business successfully and have continuous improvement. However, only focusing on one concept is not sufficient for construction companies to formulate their e-business strategy because of the fragmented needs and requirements within the organisations. To address the industry’s specific needs and requirements, an e- business strategy should include multiple elements rather than one element, and collaboration of partners should lie at the heart of the e-business strategy. Also, the strategic approaches currently available for e- business implementation are mainly ‘reactive’ and lack a long-term consideration or vision. To improve e- business implementation, it is important for organisations in the industry to create a positive organisational culture and consider both the emergent and long-term needs across organisation boundaries. This paper presents a Strategic e-Business Framework for organisations in the construction industry. The Framework provides a holistic approach for e-business strategy formulation and implementation. Organisations in the industry can work out a comprehension business solution for their e-business implementation using the Framework. The recommendations are also presented to illustrate how the Framework can benefit organisations in the construction industry potentially.
Residential satisfaction of military personnel living in privatized and non-privatized housing

AND NON-PRIVATIZED HOUSING by KATIE ROBINSON (Under the Direction of Andrew Carswell) ABSTRACT This research explored the residential satisfaction of military personnel, who live in military housing. Using data obtained from both the military Residential Satisfaction Survey and American Community Survey, ANOVA and ordinary least square regressions were performed to examine the relationship between community type and residential satisfaction. This study also examined the key determinants of military satisfaction compared to key determinants of civilian residential satisfaction. The findings indicate that type of community had no bearing on overall satisfaction, while landscaping, office staff and unit quality were all found to be significantly related.