Miracle-dz/UniFAR-FTUs huggingface dataset:
Targeting of Splice Variants of Human Cytochrome P450 2C8 (CYP2C8) to Mitochondria and Their Role in Arachidonic Acid Metabolism and Respiratory Dysfunction*

Background: Human CYP2C8 is involved in the metabolism of >20% of drugs on the market. Results: Both full-length (WT) CYP2C8 and splice variant 3 are bimodally targeted to mitochondria. Conclusion: Mitochondrial CYP2C8 metabolizes paclitaxel and arachidonic acid (ω-hydroxylation). Significance: Mitochondrial CYP2C8 is likely to play role in ischemic injury and oxidative stress. In this study, we found that the full-length CYP2C8 (WT CYP2C8) and N-terminal truncated splice variant 3 (∼44-kDa mass) are localized in mitochondria in addition to the endoplasmic reticulum. Analysis of human livers showed that the mitochondrial levels of these two forms varied markedly. Molecular modeling based on the x-ray crystal structure coordinates of CYP2D6 and CYP2C8 showed that despite lacking the N-terminal 102 residues variant 3 possessed nearly complete substrate binding and heme binding pockets. Stable expression of cDNAs in HepG2 cells showed that the WT protein is mostly targeted to the endoplasmic reticulum and at low levels to mitochondria, whereas variant 3 is primarily targeted to mitochondria and at low levels to the endoplasmic reticulum. Enzyme reconstitution experiments showed that both microsomal and mitochondrial WT CYP2C8 efficiently catalyzed paclitaxel 6-hydroxylation. However, mitochondrial variant 3 was unable to catalyze this reaction possibly because of its inability to stabilize the large 854-Da substrate. Conversely, mitochondrial variant 3 catalyzed the metabolism of arachidonic acid into 8,9-, 11,12-, and 14,15-epoxyeicosatrienoic acids and 20-hydroxyeicosatetraenoic acid when reconstituted with adrenodoxin and adrenodoxin reductase. HepG2 cells stably expressing variant 3 generated higher levels of reactive oxygen species and showed a higher level of mitochondrial respiratory dysfunction. This study suggests that mitochondrially targeted variant 3 CYP2C8 may contribute to oxidative stress in various tissues.
Collaborative optimization design of reinforcement concrete bridge considering aseismic requirements

Collaborative Optimization (CO) strategy is applied to aseismatic design of reinforcement concrete bridge. The design procedure is regarded as a whole system. The procedure is decomposed into a double-level nonlinear optimization problem. Besides system level, disciplines level is subdivided into three disciplines in term of stress states of the bridge: statics discipline, linear dynamics discipline, and nonlinear dynamics discipline. Corresponding finite element model is builded as discipline analysis model respectively. Gradient-based strategy is adopted as the optimizer of system level, statics discipline and linear dynamics discipline. Genetic algorithm is adopted as the optimizer of nonlinear dynamics discipline. The validity of Collaborative Optimization strategy is examined by comparing optimum results from Collaborative Optimization to optimum results from traditional optimization method. By comparison, Collaborative Optimization strategy is time saving and more efficient than traditional optimization method with the same optimization results.
A new topology for multilevel current source inverter with reduced number of switches

In this paper, a new topology for multilevel current source inverter (CSI) is presented. The proposed topology employs reduced switches number to generate desired multilevel output current. The proposed topology uses (n + 7) / 2 switches and (n -1) / 2 current-sharing inductors for an n-level CSI. Two modulation methods are applied for the proposed topology. One method is fundamental frequency modulation method and the other is carrier phase-shifted sinusoidal pulse width modulation (SPWM) method. As simulation results using PSCAD/EMTDC will show, the proposed topology can generate the desired output current levels and current balance of the current-sharing inductors is completely provided in each control method.
Never Say No to a Damaged Muscle: The Applications of Previously Damaged Pectoralis Major and Latissimus Dorsi Muscles for Chest Wall Reconstruction

The nondamaged latissimus dorsi and pectoralis major muscles are widely reported in the literature as being the most frequently used for chest wall reconstruction. In this study, we report a series of 9 patients with full-thickness chest wall defects who underwent reconstruction with previously damaged latissimus dorsi or pectoralis major muscles. Nine patients underwent chest wall reconstruction over a period of 3 years using previously damaged latissimus dorsi or pectoralis major muscles. The thoracic defect was posttraumatic in 3 patients and post-tumor resection in 6 patients. Three patients had previous radiation therapy. In 8 cases, the full-thickness chest wall defects were completely closed. The only failure encountered was in one patient who had a long lasting fistula. The proximal based island flap that was inserted into the tract showed good vascular supply and viability; however, it did not solve the clinical problem. Keeping in mind the basic rule of medicine (“Primum Non Nocere”) and a thorough knowledge of the surgical anatomy of these muscles are essential for the successful application of these previously damaged muscles for chest wall reconstruction.
Associations between single nucleotide polymorphisms of COX-2 and MMP-2 genes and colorectal cancer susceptibility in the Saudi population.

BACKGROUND It has been reported that COX-2 expression is associated with MMP-2 expression in thyroid and breast cancers, suggesting that MMPs are linked to COX-2-mediated carcinogenesis. Several polymorphisms within the MMP2 promoter region have been reported in cases with oncogenesis and tumor progression, especially in colorectal carcinogenesis. MATERIALS AND METHODS This research evaluated risk of association of the SNPs, including genes for COX-2 (A/G transition at +202) and MMP-2 (C/T transition at-1306), with colorectal cancer in 125 patients and 125 healthy controls. RESULTS AND CONCLUSIONS Our data confirmed that MMP2 C-1306 T mutations were significantly more common in colon cancer patients than in our control Saudi population; p=0.0121. On the other hand in our study, there was no significant association between genotype distribution of the COX2 polymorphism and colorectal cancer; p=0.847. An elevated frequency of the mutated genotype in the control group as compared to the patients subjects indeed suggested that this polymorphism could decrease risk in the Saudi population. Our study confirmed that the polymorphisms that could affect the expressions of MMP-2 and COX-2 the colon cancer patients were significantly higher than that in the COX-2 negative group. The frequency of individuals with MMP2 polymorphisms in colon cancer patients was higher than individuals with combination of COX2 and MMP2 polymorphisms. Our study confirmed that individuals who carried the polymorphisms that could affect the expressions of COX2 are more susceptible to colon cancer. MMP2 regulatory polymorphisms could be considered as protective; further studies need to confirm the results with more samples and healthy subjects.
Clinicopathological correlations and prognostic factors in lupus nephritis.

OBJECTIVE To define prognostic factors at the moment of the diagnosis in lupus nephritis, and to assess the contribution of renal histologic data. PATIENTS AND METHODS Sixty-two patients with systemic lupus erythematosus (SLE) and histologic evidence of nephritis were studied for renal outcome. Correlations between clinical or biological and histological data were carried out as an indicator of the utility of the renal biopsy. RESULTS There were no significant differences in creatinine between the different histologic classes at the moment of the diagnosis, although the WHO classification correlated well with proteinuria and immunologic activity. There was a strong correlation between clinical and histological activity as measured by the activity index in proliferative glomerulonephritis, mainly with creatinine and proteinuria, but not with haematuria or immunological activity. Young age at the time of renal biopsy, proliferative classes III and IV, and the chronicity index were associated with a poorer renal prognosis. CONCLUSIONS High immunologic activity, mainly elevated anti-DNA titers and decreased levels of CH100, is highly suggestive of proliferative glomerulonephritis. Proliferative classes III and IV and high chronicity indexes are associated with a worse prognosis in lupus nephritis.
Deep Proteome Mapping of Mouse Kidney Based on OFFGel Prefractionation Reveals Remarkable Protein Post- Translational Modifications

Performing a comprehensive nonbiased proteome analysis is an extraordinary challenge due to sample complexity and wide dynamic range, especially in eukaryotic tissues. Thus, prefractionation steps conducted prior to mass spectrometric analysis are critically important to reduce complex biological matrices and allow in-depth analysis. Here we demonstrated the use of OFFGel prefractionation to identify more low abundant and hydrophobic proteins than in a nonfractionated sample. Moreover, OFFGel prefractionation of a kidney protein sample was able to unveil protein functional relevance by detecting PTMs, especially when prefractionation was augmented with a targeted enrichment strategy such as TiO2 phospho-enrichment. The OFFGel-TiO2 combination used in this study was comparable to other global phosphoproteomics approaches (SCX-TiO2, ERLIC-TiO2, or HILIC-TiO2). The detailed mouse kidney proteome with the phosphopeptide enrichment presented here serves as a useful platform for a better understanding of how the renal protein modification machinery works and, ultimately, will contribute to our understanding of pathological processes as well as normal physiological renal functions.
Temperature Sensitivity Caused by Mutant Release Factor 1 Is Suppressed by Mutations That Affect 16S rRNA Maturation

ABSTRACT To study the effect of slow termination on the protein synthesizing machinery, we isolated suppressors to a temperature-sensitive release factor 1 (RF1). Of 26 independent clones, five complementation groups have been identified, two of which are presented here. The first mutation disrupts a base pair in the transcription terminator stem for the rplM-rpsI operon, which encodes ribosomal proteins L13 and S9. We have found that this leads to readthrough of the terminator and that lower levels of transcript (compared to the results seen with the wild type) are found in the cell. This probably leads to decreased expression of the two proteins. The second mutation is a small deletion of the yrdC open reading frame start site, and it is not likely that the protein is expressed. Both mutant strains show an increased accumulation of 17S rRNA (immature 16S rRNA). Maturation of 16S rRNA is dependent on proper assembly of the ribosomal proteins, a process that is disturbed when proteins are missing. The function of the YrdC protein is not known, but it is able to bind to double-stranded RNA; therefore, we suggest that it is an assembly factor important for 30S subunit biogenesis. On the basis of our findings, we propose that lesser amounts of S9 or a lack of YrdC causes the maturation defect. We have shown that as a consequence of the maturation defect, fewer 70S ribosomes and polysomes are formed. This and other results suggest that it is the lowered concentration of functional ribosomes that suppresses the temperature sensitivity caused by the mutant RF1.
Preclinical validation of automated dual-energy X-ray absorptiometry and computed tomography-based body composition measurements.

BACKGROUND The aim of this study was to determine and validate a set of Hounsfield unit (HU) ranges to segment computed tomography (CT) images into tissue types and to test the validity of dual-energy X-ray absorptiometry (DXA) tissue segmentation on pure, unmixed porcine tissues. METHODS This preclinical prospective study was approved by the local ethical committee. Different quantities of porcine bone tissue (BT), lean tissue (LT) and adipose tissue (AT) were scanned using DXA and CT. Tissue type segmentation in DXA was performed via the standard clinical protocol and in CT through different sets of HU ranges. Percent coefficients of variation (%CV) were used to assess precision while % differences of observed masses were tested against zero using the Wilcoxon signed-rank Test. RESULTS Total mass DXA measurements differ little but significantly (P=0.016) from true mass, while total mass CT measurements based on literature values show non-significant (P=0.69) differences of 1.7% and 2.0%. BT mass estimates with DXA differed more from true mass (median -78.2 to -75.8%) than other tissue types (median -11.3 to -8.1%). Tissue mass estimates with CT and literature HU ranges showed small differences from true mass for every tissue type (median -10.4 to 8.8%). CONCLUSION The most suited method for automated tissue segmentation is CT and can become a valuable tool in quantitative nuclear medicine.
Flexible Grid Connection and Islanding of SPC-Based PV Power Converters

At the present time, distributed generation systems are required to disconnect from the main grid when there is an outage. In order to fulfill this requirement, photovoltaic (PV) power plants are equipped with anti-islanding algorithms, embedded in the converters controller, to avoid the island operation. However, the current trends in the development of the future electrical networks evidence that it is technically feasible and economically advantageous to keep feeding islanded systems under these situations, without cutting the power supply to the loads connected to the network. Nevertheless, commercial PV power converters are programmed as grid-feeding converters and they are unable to work in island mode if there is not an agent forming the grid. In order to overcome this problem, the synchronous power controller (SPC) is presented in this paper as a suitable alternative for controlling PV inverters. As will be further discussed, this controller permits PV plants to operate seamlessly in grid-connected and island mode, with no need of changing the control structure in either case. Moreover, the participation of SPC-based power converters integrating energy storage enables other grid-feeding systems to contribute to the grid operation in island conditions. The good results achieved with the SPC in different conditions will be shown in simulations, and also with experiments considering a real PV power plant combining SPC and commercial PV inverters.
Skeletal Metastasis of Canine Urothelial Carcinoma: Pathologic and Computed Tomographic Features

Invasive urothelial (transitional cell) carcinoma (UC) is the most common cancer in the canine urinary tract. Prolonged survival of dogs with UC due to better management of the primary tumor and prevention of urethral obstruction might have contributed to an apparent increase in distant metastasis. Metastasis to bone is particularly concerning because the ensuing pain often leads to euthanasia; however, little is known of the frequency, site, or nature of UC skeletal metastasis. In a retrospective analysis, 17 (9%) of 188 canine UC cases had histologically confirmed skeletal metastasis, mainly to the vertebrae. In a prospective analysis of 21 dogs with UC that underwent total body computed tomography (CT) at euthanasia followed by a standardized pathologic examination, skeletal lesions detected on CT were suspected to be metastatic in 4 dogs and were confirmed as metastatic UC histologically in 3 (14%) dogs. In all 3 cases, skeletal metastasis had been suspected based on history and physical examination; however, 1 dog had additional CT-detected skeletal metastases in a clinically unsuspected location, and 2 dogs had histologically confirmed skeletal metastases that corresponded to nonspecific osseous lesions on CT. These findings suggest that total body CT could be helpful in detecting skeletal metastasis as a cause of bone pain in dogs with UC as well as in identifying clinically “silent” sites of skeletal metastasis.
Damp housing conditions and respiratory symptoms in primary school children

There is evidence that indoor air pollution contributes to the development of respiratory symptoms. This study examined the relationships between dampness in houses and respiratory symptoms in 4,164 primary school children in the subtropical rural areas of the Kaohsiung region, Taiwan. Dampness in homes was assessed by questionnaires that reported (1) general dampness, (2) mold or mildew inside the home, or (3) flooding (appearance of standing water within the home, water damage, or leaks of water into the building). Evidence for upper and lower respiratory symptoms were also collected by questionnaires. Recorded symptoms included cough, wheezing, pneumonia, bronchitis, and asthma.
Desorption kinetics of hydrophobic organic chemicals from sediment to water: A review of data and models

Resuspension of contaminated sediment can lead to the release of toxic compounds to surface waters where they are more bioavailable and mobile. Because the timeframe of particle resettling during such events is shorter than that needed to reach equilibrium, a kinetic approach is required for modeling the release process. Due to the current inability of common theoretical approaches to predict site‐specific release rates, empirical algorithms incorporating the phenomenological assumption of biphasic, or fast and slow, release dominate the descriptions of nonpolar organic chemical release in the literature. Two first‐order rate constants and one fraction are sufficient to characterize practically all of the data sets studied. These rate constants were compared to theoretical model parameters and functionalities, including chemical properties of the contaminants and physical properties of the sorbents, to determine if the trends incorporated into the hindered diffusion model are consistent with the parameters used in curve fitting. The results did not correspond to the parameter dependence of the hindered diffusion model. No trend in desorption rate constants, for either fast or slow release, was observed to be dependent on KOC or aqueous solubility for six and seven orders of magnitude, respectively. The same was observed for aqueous diffusivity and sediment fraction organic carbon. The distribution of kinetic rate constant values was approximately log‐normal, ranging from 0.1 to 50 d−1 for the fast release (average ∼5 d−1) and 0.0001 to 0.1 d−1 for the slow release (average ∼0.03 d−1). The implications of these findings with regard to laboratory studies, theoretical desorption process mechanisms, and water quality modeling needs are presented and discussed.
Axonal Transport in the Rat Optic Nerve Following Short-Term Reduction in Cerebrospinal Fluid Pressure or Elevation in Intraocular Pressure.

PURPOSE To examine the influence of short-term reduction in cerebrospinal fluid pressure (CSFP) as compared with short-term elevation in IOP on axonal transport. METHODS The study included 111 adult Sprague-Dawley rats. For 6 hours, IOP was unilaterally elevated to 40 mm Hg (IOP40-group; n = 27), IOP was unilaterally increased to a value of 25 mm Hg below the mean blood pressure (PP25-group; n = 27), or CSFP was reduced by continuous aspiration of cerebrospinal fluid (Low-CSFP-group; n = 27). A sham control group (with a trocar in cisterna magna without cerebrospinal fluid release) included 24 rats. The left eyes of the IOP40 study group and PP25 study group served as additional contralateral control group. Orthograde axonal transport was examined by intravitreally injected rhodamine-β-isothiocyanate; retrograde axoplasmic flow was assessed by fluorogold injected into the superior colliculi. RESULTS At 24 hours after baseline, rhodamine-β-isothiocyanate (RITC) staining intensity of the optic nerve was lower (P < 0.05) in the IOP40-group, PP25-group, and Low-CSFP-group than in the control groups. At 6 hours after the fluorogold injection, fluorogold fluorescence was significantly lower in the IOP40-group, the PP25-group, and the Low-CSFP-group than in the control groups. At 5 days after baseline, the fluorogold fluorescence no longer differed significantly between the IOP40-group or the Low-CSFP-group and the control groups. At 1 week after baseline, retinal ganglion cell density was markedly reduced only in the PP25-group. CONCLUSIONS Both short-term lowering of CSFP and short-term rise in IOP were associated with a disturbance of both the orthograde and retrograde axonal transport. The findings support the notion of an association between abnormally low CSFP and optic nerve damage.
A Miniaturized Force Sensor Based on Hair-Like Flexible Magnetized Cylinders Deposited Over a Giant Magnetoresistive Sensor

The detection of force with higher resolution than observed in humans (~1 mN) is of great interest for emerging technologies, especially surgical robots, since this level of resolution could allow these devices to operate in extremely sensitive environments without harming these. In this paper, we present a force sensor fabricated with a miniaturized footprint (9 mm<sup>2</sup>), based on the detection of the magnetic field generated by magnetized flexible pillars over a giant magnetoresistive sensor. When these flexible pillars deflect due to external loads, the stray field emitted by these will change, thus varying the GMR sensor resistance. A sensor with an array of five pillars with <inline-formula> <tex-math notation="LaTeX">$200~\mu \text{m}$ </tex-math></inline-formula> diameter and 1 mm height was fabricated, achieving a 0 to 26 mN measurement range and capable of detecting a minimum force feature of <inline-formula> <tex-math notation="LaTeX">$630~\mu \text{N}$ </tex-math></inline-formula>. A simulation model to predict the distribution of magnetic field generated by the flexible pillars on the sensitive area of the GMR sensor in function of the applied force was developed and validated against the experimental results reported in this paper. The sensor was finally tested as a texture classification system, with the ability of differentiating between four distinct surfaces varying between 0 and <inline-formula> <tex-math notation="LaTeX">$162~\mu \text{m}$ </tex-math></inline-formula> root mean square surface roughness.
Theileria annulata in CD5+Macrophages and B1 B Cells

ABSTRACT Theileria parasites infect and transform bovine leukocytes. We have analyzed laboratory-establishedTheileria sp. -infected leukocyte lines and observed that transformed macrophages express CD5. Low-level expression of CD5 by macrophages was further confirmed on three independent Theileria annulata clinical isolates from Tunisia. Interestingly, the fourth CD5+ clinical isolate (MB2) was morphologically different, expressed surface immunoglobulin M (IgM) and BoLA class II, and had rearranged Ig light-chain genes. To demonstrate that MB2 did indeed contain CD5+ B cells, individual clonal lines were obtained by limiting dilution, and CD5 expression and Ig gene rearrangement were confirmed. This suggests that in natural infectionsT. annulata can invade and transform CD5+ B cells.