Miracle-dz/UniFAR-FTUs huggingface dataset:
Key Anti-Fibrosis Associated Long Noncoding RNAs Identified in Human Hepatic Stellate Cell via Transcriptome Sequencing Analysis

Hepatic fibrosis is the main pathological basis for chronic cirrhosis, and activated hepatic stellate cells (HSCs) are the primary cells involved in liver fibrosis. Our study analyzed anti-fibrosis long noncoding RNAs (lncRNAs) in activated human HSCs (hHSCs). We performed RNA sequencing (RNA-seq) and bioinformatics analysis to determine whether lncRNA expression profile changes between hHSCs activation and quiescence. Eight differentially expressed (DE) lncRNAs and three pairs of co-expression lncRNAs-mRNAs were verified by quantitative Real-Time Polymerase Chain Reaction (qRT-PCR). A total of 34146 DE lncRNAs were identified in this study. Via gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses, we found several DE lncRNAs regulated hHSC activation by participating in DNA bending/packaging complex, growth factor binding and the Hippo signaling pathway (p < 0.05). With lncRNA–mRNA co-expression analysis, three lncRNAs were identified to be associated with connective tissue growth factor (CTGF), fibroblast growth factor 2 (FGF2) and netrin-4 (NTN4). The quantitative Real-Time Polymerase Chain Reaction (qRT-PCR) results of the eight DE lncRNAs and three pairs of co-expression lncRNAs–mRNAs were consistent with the RNA-seq data and previous reports. Several lncRNAs may serve as potential targets to reverse the progression of liver fibrosis. This study provides a first insight into lncRNA expression profile changes associated with activated human HSCs.
Session 4: Dietary strategies to prevent and mitigate inflammatory diseases Anti-inflammatory effects of the Mediterranean diet: the experience of the PREDIMED study

Several epidemiological and clinical studies have evaluated the effects of a Mediterranean diet (Med-Diet) on total cardiovascular mortality, and all concluded that adherence to the traditional Med-Diet is associated with reduced cardiovascular risk. However, the molecular mechanisms involved are not fully understood. Since atherosclerosis is nowadays considered a low-grade inflammatory disease, recent studies have explored the anti-inflammatory effects of a Med-Diet intervention on serum and cellular biomarkers related to atherosclerosis. In a pilot study of the PREvencion con DIeta MEDiterranea (PREDIMED) trial, we analysed the short-term effects of two Med-Diet interventions, one supplemented with virgin olive oil and another with nuts, on vascular risk factors in 772 subjects at high risk for CVD, and in a second study we evaluated the effects of these interventions on cellular and serum inflammatory biomarkers in 106 highrisk subjects. Compared to a low-fat diet, the Med-Diet produced favourable changes in all risk factors. Thus, participants in both Med-Diet groups reduced blood pressure, improved lipid profile and diminished insulin resistance compared to those allocated a low-fat diet. In addition, the Med-Diet supplemented with virgin olive oil or nuts showed an anti-inflammatory effect reducing serum C-reactive protein, IL-6 and endothelial and monocytary adhesion molecules and chemokines, whereas these parameters increased after the low-fat diet intervention. In conclusion, Med-Diets down-regulate cellular and circulating inflammatory biomarkers related to atherogenesis in subjects at high cardiovascular risk. These results support the recommendation of the Med-Diet as a useful tool against CVD. Inflammation: Mediterranean diet: Atherosclerosis
Evaluating preferences for profiles of GLP-1 receptor agonists among injection-naïve type 2 diabetes patients in the UK

Objective To use a discrete choice experiment (DCE) to evaluate preferences for the actual treatment features and overall profiles of two injectable glucagon-like peptide-1 receptor agonists (dulaglutide and liraglutide) among patients with type 2 diabetes mellitus (T2DM) in the UK. Methods In-person interviews were conducted in the UK to administer a DCE to patients with self-reported T2DM, naïve to treatment with injectable medications. The DCE examined six attributes of T2DM treatment each described by two levels: “dosing frequency,” “hemoglobin A1c change,” “weight change,” “type of delivery system,” “frequency of nausea,” and “frequency of hypoglycemia. ” Part-worth utilities were estimated using random effects logit models and were used to calculate relative importance (RI) values for each attribute. A chi-square test was used to determine differences in preferences for dulaglutide versus liraglutide profiles. Results A total of 243 participants [mean age: 60.5 (standard deviation 10.9) years; 76.1% male; mean body mass index: 29.8 (standard deviation 5.4) kg/m2] completed the study. RI values for the attributes in rank order were: “dosing frequency” (41.6%), “type of delivery system” (35.5%), “frequency of nausea” (10.4%), “weight change” (5.9%), “hemoglobin A1c change” (3.6%), and “frequency of hypoglycemia” (3.0%). Significantly more participants preferred the dulaglutide profile (83.1%) compared with the liraglutide profile (16.9%; P<0.0001). Conclusion This study elicited patients’ preferences for attributes and levels representing the actual characteristics of two specific glucagon-like peptide-1 medications. In this context, dosing frequency and type of delivery system were most important, accounting for over 75% of the RI. While previous studies have identified efficacy as highly important in T2DM medication decisions, this study suggests that when differences in efficacy between medications are small, other treatment features (eg, dosing frequency and delivery system) are of much greater importance to patients.
Evaluation of a Stream-Aquifer Analysis Test for Deriving Reach-Scale Streambed Conductance

Extracting groundwater from pumping wells located adjacent to streams can reduce streamflow, a result that is known as alluvial well depletion. Numerous analytical solutions have been developed for alluvial well depletion that vary in their mathematical complexity. Predicted drawdown by the analytical solutions can be matched to observed drawdown from a stream-aquifer analysis (SAA) test (i.e., a pumping test adjacent to a stream) to simultaneously estimate aquifer and streambed hydrologic parameters. However, only a few SAA tests have been documented in the literature and compared to field-measured streambed parameters. Therefore, the objective of this research was to perform an SAA test for the purpose of evaluating the ability of analytical solutions, when applied to the SAA test data, to estimate reach-scale streambed conductance. The SAA test was performed at a well site located adjacent to the North Canadian River in central Oklahoma. Observation wells were installed between the stream and the pumping well and were instrumented with automated water level loggers. The pumping well, located approximately 85 m from the North Canadian River, discharged at a constant rate (2180 m3 d-1) for 90 h. Predicted drawdown by an analytical solution was fit to the observed drawdown to inversely estimate the transmissivity (790 to 950 m2 d-1), specific yield (0.19 to 0.28), and streambed conductance (600 to 1500 m d-1), which was compared to values derived from in-stream measurements (i.e., grain-size analyses on streambed sediment samples and in-stream falling-head permeameter tests). Estimated streambed conductance from the in-stream measurements and the SAA test were both on the order of 1000 m d-1. The similarity in estimates supported the use of SAA tests to derive reach-scale streambed conductance. Both the SAA test and in-stream conductivity measurements suggested minimal streambed hydraulic resistance. Therefore, for this and other streams, simpler analytical solutions may be adequate to inversely estimate the aquifer and streambed hydrologic parameters.
Curing and Mechanical Properties of Nitrile and Natural Rubber Blends

The curing and mechanical properties of nitrile (NBR) and natural rubber (NR) blends were carried out. Two series of blends were prepared, i.e., NBR/SMR L and NBR/ENR 50 blends. Blends were prepared using a Brabender at a temperature of 60°C. Results indicate that the scorch time, t 2 and cure time, t 90 increase with increasing NBR content in both blends. In NBR/ENR 50 blends the increasing content of NBR increases the maximum elastic torque, torque difference, tan δ @ MH and viscous torque. However, in NBR/SMR L blends the opposite trend is observed for maximum elastic torque and torque difference. In both blends modulus at 100% elongation (M100) and at 300% elongation (M300) increases with increasing NBR content, whereas tensile strength and elongation at break show a decreasing trend.
Selection of Nontarget Arthropod Taxa for Field Research on Transgenic Insecticidal Crops: Using Empirical Data and Statistical Power

Abstract One of the possible adverse effects of transgenic insecticidal crops is the unintended decline in the abundance of nontarget arthropods. Field trials designed to evaluate potential nontarget effects can be more complex than expected because decisions to conduct field trials and the selection of taxa to include are not always guided by the results of laboratory tests. Also, recent studies emphasize the potential for indirect effects (adverse impacts to nontarget arthropods without feeding directly on plant tissues), which are difficult to predict because of interactions among nontarget arthropods, target pests, and transgenic crops. As a consequence, field studies may attempt to monitor expansive lists of arthropod taxa, making the design of such broad studies more difficult and reducing the likelihood of detecting any negative effects that might be present. To improve the taxonomic focus and statistical rigor of future studies, existing field data and corresponding power analysis may provide useful guidance. Analysis of control data from several nontarget field trials using repeated-measures designs suggests that while detection of small effects may require considerable increases in replication, there are taxa from different ecological roles that are sampled effectively using standard methods. The use of statistical power to guide selection of taxa for nontarget trials reflects scientists’ inability to predict the complex interactions among arthropod taxa, particularly when laboratory trials fail to provide guidance on which groups are more likely to be affected. However, scientists still may exercise judgment, including taxa that are not included in or supported by power analyses.
Secondary malignancies in patients with multiple myeloma, Waldenström macroglobulinemia and monoclonal gammopathy of undetermined significance

Abstract In recent years, the survival of patients with plasma cell dyscrasias has improved due to improvements in anticancer and supportive therapy. However, the risk of secondary malignancies has increased, thought to be due to a combination of environmental and disease-related factors, as well as treatment. In the present review, we evaluate the risk of secondary malignancies in patients with monoclonal gammopathy of undetermined significance (MGUS), multiple myeloma (MM) and Waldenström macroglobulinemia (WM). Patients with MGUS appear to have a higher risk of developing myeloid malignancies such as myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML). In patients with MM, the risk of AML, acute lymphoblastic leukemia and some solid tumors appears increased. Finally, in WM patients, there seems to be increased risk of AML, diffuse large B-cell lymphoma, thyroid cancer and melanoma.
An unfolded protein-induced conformational switch activates mammalian IRE1

The unfolded protein response (UPR) adjusts the cell’s protein folding capacity in the endoplasmic reticulum (ER) according to need. IRE1 is the most conserved UPR sensor in eukaryotic cells. It has remained controversial, however, whether mammalian and yeast IRE1 use a common mechanism for ER stress sensing. Here, we show that similar to yeast, human IRE1α’s ER-lumenal domain (hIRE1α LD) binds peptides with a characteristic amino acid bias. Peptides and unfolded proteins bind to hIRE1α LD’s MHC-like groove and induce allosteric changes that lead to its oligomerization. Mutation of a hydrophobic patch at the oligomerization interface decoupled peptide binding to hIRE1α LD from its oligomerization, yet retained peptide-induced allosteric coupling within the domain. Importantly, impairing oligomerization of hIRE1α LD abolished IRE1’s activity in living cells. Our results provide evidence for a unifying mechanism of IRE1 activation that relies on unfolded protein binding-induced oligomerization.
Accounting for Apparent Deviations between Calorimetric and van’t Hoff Enthalpies

Background In theory, binding enthalpies directly obtained from calorimetry (such as ITC) and the temperature dependence of the binding free energy (van’t Hoff method) should agree. However, previous studies have often found them to be discrepant. Methods Experimental binding enthalpies (both calorimetric and van’t Hoff) are obtained for two host-guest pairs using ITC, and the discrepancy between the two enthalpies is examined. Modeling of artificial ITC data is also used to examine how different sources of error propagate to both types of binding enthalpies. Results For the host-guest pairs examined here, good agreement, to within about 0.4 kcal/mol, is obtained between the two enthalpies. Additionally, using artificial data, we find that different sources of error propagate to either enthalpy uniquely, with concentration error and heat error propagating primarily to calorimetric and van’t Hoff enthalpies, respectively. Conclusions With modern calorimeters, good agreement between van’t Hoff and calorimetric enthalpies should be achievable, barring issues due to non-ideality or unanticipated measurement pathologies. Indeed, disagreement between the two can serve as a flag for error-prone datasets. A review of the underlying theory supports the expectation that these two quantities should be in agreement. General Significance We address and arguably resolve long-standing questions regarding the relationship between calorimetric and van’t Hoff enthalpies. In addition, we show that comparison of these two quantities can be used as an internal consistency check of a calorimetry study. Highlights Agreement within ~0.4 kcal/mol between calorimetric and van’t Hoff enthalpies can be achieved for systems with typical heat and concentration errors, if solution non-ideality is not an issue. Concentration error chiefly affects calorimetric enthalpies, while error in measured heat chiefly affects van’t Hoff enthalpies. Large discrepancies between calorimetric and van’t Hoff enthalpies can be used to flag experimental error. There is no theoretical basis to expect discrepancies between these two methods of determining the binding enthalpy.
Nicotine Induces Podocyte Apoptosis through Increasing Oxidative Stress

Background Cigarette smoking plays an important role in the progression of chronic kidney disease (CKD). Nicotine, one of the major components of cigarette smoking, has been demonstrated to increase proliferation of renal mesangial cells. In this study, we examined the effect of nicotine on podocyte injury. Methods To determine the expression of nicotinic acetylcholine receptors (nAChR subunits) in podocytes, cDNAs and cell lysate of cultured human podocytes were used for the expression of nAChR mRNAs and proteins, respectively; and mouse renal cortical sections were subjected to immunofluorescant staining. We also studied the effect of nicotine on podocyte nephrin expression, reactive oxygen species (ROS) generation (via DCFDA loading followed by fluorometric analysis), proliferation, and apoptosis (morphologic assays). We evaluated the effect of nicotine on podocyte downstream signaling including phosphorylation of ERK1/2, JNK, and p38 and established causal relationships by using respective inhibitors. We used nAChR antagonists to confirm the role of nicotine on podocyte injury. Results Human podocytes displayed robust mRNA and protein expression of nAChR in vitro studies. In vivo studies, mice renal cortical sections revealed co-localization of nAChRs along with synaptopodin. In vitro studies, nephrin expression in podocyte was decreased by nicotine. Nicotine stimulated podocyte ROS generation; nonetheless, antioxidants such as N-acetyl cysteine (NAC) and TEMPOL (superoxide dismutase mimetic agent) inhibited this effect of nicotine. Nicotine did not modulate proliferation but promoted apoptosis in podocytes. Nicotine enhanced podocyte phosphorylation of ERK1/2, JNK, and p38, and their specific inhibitors attenuated nicotine-induced apoptosis. nAChR antagonists significantly suppressed the effects of nicotine on podocyte. Conclusions Nicotine induces podocyte apoptosis through ROS generation and associated downstream MAPKs signaling. The present study provides insight into molecular mechanisms involved in smoking associated progression of chronic kidney disease.
The power of block-encoded matrix powers: improved regression techniques via faster Hamiltonian simulation

We apply the framework of block-encodings, introduced by Low and Chuang (under the name standard-form), to the study of quantum machine learning algorithms and derive general results that are applicable to a variety of input models, including sparse matrix oracles and matrices stored in a data structure. We develop several tools within the block-encoding framework, such as singular value estimation of a block-encoded matrix, and quantum linear system solvers using block-encodings. The presented results give new techniques for Hamiltonian simulation of non-sparse matrices, which could be relevant for certain quantum chemistry applications, and which in turn imply an exponential improvement in the dependence on precision in quantum linear systems solvers for non-sparse matrices. In addition, we develop a technique of variable-time amplitude estimation, based on Ambainis' variable-time amplitude amplification technique, which we are also able to apply within the framework. As applications, we design the following algorithms: (1) a quantum algorithm for the quantum weighted least squares problem, exhibiting a 6-th power improvement in the dependence on the condition number and an exponential improvement in the dependence on the precision over the previous best algorithm of Kerenidis and Prakash; (2) the first quantum algorithm for the quantum generalized least squares problem; and (3) quantum algorithms for estimating electrical-network quantities, including effective resistance and dissipated power, improving upon previous work.
A cucurbit androecy gene reveals how unisexual flowers develop and dioecy emerges

How flowers separate males and females Most flowering plant families have bisexual flowers with both male and female function. However, most members of the Cucurbiticeae family, which includes melons, cucumbers, and gourds, have unisexual flowers. To understand this difference in sex expression, Boualem et al. identified a cucumber gene expressed in the female flowers. Mutations in this gene were associated with solely male flowers. By integrating this finding into a sex determination model, the authors explain how unisexual flowers can coexist in the same plant. Science, this issue p. 688 A gene in melon and cucumber explains how separate-sex flowers can develop and coexist on the same plant. Understanding the evolution of sex determination in plants requires identifying the mechanisms underlying the transition from monoecious plants, where male and female flowers coexist, to unisexual individuals found in dioecious species. We show that in melon and cucumber, the androecy gene controls female flower development and encodes a limiting enzyme of ethylene biosynthesis, ACS11. ACS11 is expressed in phloem cells connected to flowers programmed to become female, and ACS11 loss-of-function mutants lead to male plants (androecy). CmACS11 represses the expression of the male promoting gene CmWIP1 to control the development and the coexistence of male and female flowers in monoecious species. Because monoecy can lead to dioecy, we show how a combination of alleles of CmACS11 and CmWIP1 can create artificial dioecy.
Energy Optimization and Fuel Economy Investigation of a Series Hybrid Electric Vehicle Integrated with Diesel/RCCI Engines

Among different types of low temperature combustion (LTC) regimes, eactively controlled compression ignition (RCCI) has received a lot of attention as a promising advanced combustion engine technology with high indicated thermal efficiency and low nitrogen oxides ( NO x ) and particulate matter (PM) emissions. In this study, an RCCI engine for the purpose of fuel economy investigation is incorporated in series hybrid electric vehicle (SHEV) architecture, which allows the engine to run completely in the narrow RCCI mode for common driving cycles. Three different types of energy management control (EMC) strategies are designed and implemented to achieve the best fuel economy. The EMC strategies encompass rule-based control (RBC), offline, and online optimal controllers, including dynamic programing (DP) and model predictive control (MPC), respectively. The simulation results show a 13.1% to 14.2% fuel economy saving by using an RCCI engine over a modern spark ignition (SI) engine in SHEV for different driving cycles. This fuel economy saving is reduced to 3% in comparison with a modern compression ignition (CI) engine, while NO x emissions are significantly lower. Simulation results show that the RCCI engine offers more fuel economy improvement in more aggressive driving cycles (e.g., US06), compared to less aggressive driving cycles (e.g., UDDS). In addition, the MPC results show that sub-optimal fuel economy is achieved by predicting the vehicle speed profile for a time horizon of 70 s.
Mice harbouring an oculodentodigital dysplasia-linked Cx43 G60S mutation have severe hearing loss

ABSTRACT Given the importance of connexin43 (Cx43, encoded by GJA1) function in the central nervous system and sensory organ processing, we proposed that it would also be crucial in auditory function. To that end, hearing was examined in two mouse models of oculodentodigital dysplasia that globally express GJA1 mutations resulting in mild or severe loss of Cx43 function. Although Cx43I130T/+ mutant mice, with ∼50% Cx43 channel function, did not have any hearing loss, Cx43G60S/+ mutant mice, with ∼20% Cx43 channel function, had severe hearing loss. There was no evidence of inner ear sensory hair cell loss, suggesting that the mechanism for Cx43-linked hearing loss lies downstream in the auditory pathway. Since evidence suggests that Cx26 function is essential for hearing and may be protective against noise-induced hearing loss, we challenged Cx43I130T/+ mice with a loud noise and found that they had a similar susceptibility to noise-induced hearing loss to that found in controls, suggesting that decreased Cx43 function does not sensitize the mice for environmentally induced hearing loss. Taken together, this study suggests that Cx43 plays an important role in baseline hearing and is essential for auditory processing. This article has an associated First Person interview with the first author of the paper. Summary: Mutant mice harbouring a severe loss-of-function mutation in Gja1, encoding Cx43, that is associated with the human-linked disease oculodentodigital dysplasia, leads to severe hearing loss and central auditory defects.