Miracle-dz/UniFAR-FTUs huggingface dataset:
COOH-terminal Disruption of Lipoprotein Lipase in Mice Is Lethal in Homozygotes, but Heterozygotes Have Elevated Triglycerides and Impaired Enzyme Activity (*)

The role of the enzyme lipoprotein lipase (LPL) in atherosclerosis is uncertain. To generate an animal model of LPL deficiency, we targeted the LPL gene in embryonic stem cells with a vector designed to disrupt the COOH terminus of the protein and used these cells to generate LPL-deficient mice. Germ line transmission of the disrupted LPL allele was achieved with two chimeric males, and offspring from each of these animals were phenotypically identical. Pups homozygous (-/-) for LPL deficiency died within 48 h of birth with extreme elevations of serum triglycerides (13,327 mg/dl) associated with essentially absent LPL enzyme activity in heart and carcass. Newborn heterozygous (+/-) LPL-deficient pups had lower LPL enzyme activity and higher triglycerides (370 versus 121 mg/dl) than wild type (+/+) littermates. Adult heterozygotes had higher triglycerides than wild type mice with ad libitum feeding (236 mg/dl for +/- versus 88 mg/dl for +/+) and after fasting for 4 h (98 mg/dl for +/- versus 51 for +/+) or 12 h (109 mg/dl for +/- versus 56 mg/dl for +/+). Triglycerides were present as very low density lipoprotein particles and chylomicrons, but high density lipoprotein cholesterol levels were not decreased in +/- animals. Plasma heparin-releasable LPL activity was 43% lower in +/- versus +/+ adult animals. LPL activity, mRNA, and protein were lower in the tissues of +/- versus +/+ mice. Homozygous LPL deficiency caused by disruption of the COOH terminus of the enzyme is lethal in mice. Heterozygous LPL deficiency caused by this mutation is associated with mild to moderate hypertriglyceridemia without affecting static HDL cholesterol levels. Heterozygous LPL-deficient mice could be useful for determining if hypertriglyceridemia, independently or in combination with other discrete defects, influences atherosclerosis.
Interaction of small dermatan sulfate proteoglycan from fibroblasts with fibronectin

Immunogold labeling was used to localize the core protein of small dermatan sulfate proteoglycan (DS-PG) on the surface of cultured human fibroblasts. At 4 degrees C, DS-PG core protein was uniformly distributed over the cell surface. At 37 degrees C, gold particles either became rearranged in form of clusters or remained associated with fibrils. Double-label immunocytochemistry indicated the co- distribution of DS-PG core protein and fibronectin in the fibrils. In an enzyme-linked immunosorbent assay, binding of DS-PG from fibroblast secretions and of its core protein to fibronectin occurred at pH 7.4 and at physiological ionic strength. Larger amounts of core protein than of intact proteoglycan could be bound. Fibronectin peptides containing either the heparin-binding domain near the COOH-terminal end or the heparin-binding NH2 terminus were the only fragments interacting with DS-PG and core protein. Competition and replacement experiments with heparin and dermatan sulfate suggested the existence of adjacent binding sites for heparin and DS-PG core protein. It is hypothesized that heparan sulfate proteoglycans and DS-PG may competitively interact with fibronectin.
Protection against Enterovirus 71 with Neutralizing Epitope Incorporation within Adenovirus Type 3 Hexon

Enterovirus 71 (EV71) is responsible for hand, foot and mouth disease with high mortality among children. Various neutralizing B cell epitopes of EV71 have been identified as potential vaccine candidates. Capsid-incorporation of antigens into adenovirus (Ad) has been developed for a novel vaccine approach. We constructed Ad3-based EV71 vaccine vectors by incorporating a neutralizing epitope SP70 containing 15 amino acids derived from capsid protein VP1 of EV71 within the different surface-exposed domains of the capsid protein hexon of Ad3EGFP, a recombinant adenovirus type 3 (Ad3) expressing enhanced green fluorescence protein. Thermostability and growth kinetic assays suggested that the SP70 epitope incorporation into hypervariable region (HVR1, HVR2, or HVR7) of the hexon did not affect Ad fitness. The SP70 epitopes were thought to be exposed on all hexon-modified intact virion surfaces. Repeated administration of BALB/c mice with the modified Ads resulted in boosting of the anti-SP70 humoral immune response. Importantly, the modified Ads immunization of mother mice conferred protection in vivo to neonatal mice against the lethal EV71 challenge, and the modified Ads-immunized mice serum also conferred passive protection against the lethal challenge in newborn mice. Compared with the recombinant GST-fused SP70 protein immunization, immunization with the Ads containing SP70 in HVR1 or HVR2 elicited higher SP70-specific IgG titers, higher neutralization titers, and conferred more effective protection to neonatal mice. Thus, this study provides valuable information for hexon-modified Ad3 vector development as a promising EV71 vaccine candidate and as an epitope-delivering vehicle for other pathogens.
CFP: Cooperative Fast Protection

We introduce a novel protection scheme, called cooperative fast protection (CFP), to fight against a single link failure in survivable(wavelength division multiplexing (WDM) mesh networks. CFP achieves capacity-efficient fast protection with features of node-autonomy and failure-independency. Though CFP organizes spare capacity into pre-cross-connected cycles, it differs from p-cycle by reusing the released working capacity of the disrupted lightpaths (i.e., stubs) in a cooperative manner, and utilizing both the released stubs and the spare capacity on the cycles to set up backup paths. This is achieved by allowing all failure-aware nodes to switch traffic upon a link failure, such that the disrupted lightpaths can be restored even if the end nodes of the failed link are not on the cycles. CFP also differs from FIPP (Failure Independent Path Protecting) p-cycle by reducing optical recovery time, and not requiring the cycles to pass through the source nodes of the protected lightpaths. By jointly optimizing both working and spare capacity placement, we formulate an ILP (Integer Linear Program) for CFP design without candidate cycle enumeration. Theoretical analysis and numerical results show that CFP significantly outperforms p-cycle based schemes by achieving faster optical recovery speed with much higher capacity efficiency. The performance gain is achieved at the expense of higher computation complexity, but without involving any additional signaling mechanism in the optical domain.
Prospects and Limitations of Power Balance Approach for Studying Forces and Electromagnetic Damping in Electrical Machines

A cage induction machine with dynamic rotor eccentricity is considered. In general, force and torque computations in the finite-element analysis of electrical machines are done using conventional direct methods. Many methods have been put forward with a claim to be more accurate than one another. In this paper, we assess the accuracy of the typical force computation method used in the finite-element analysis of electrical machines, for various types of mesh used in the machine’s air gap during simulations. The possibility of using the power balance of the machine to validate the force calculation and alternatively calculate the force is discussed. Besides, its applicability to study the electromagnetic damping of mechanical vibrations due to unbalanced magnetic pull is presented.
Microenvironmental influences on human B‐cell development

Summary: Mammalian B‐cell development can be viewed as a developmental performance with several acts. The acts are represented by checkpoints centered around commitment to the B‐lineage and functional Ig gene rearrangement – culminating in expression of the pre‐B‐cell receptor (pre‐BCR) and the BCR. Progression of cells through these checkpoints is profoundly influenced by the fetal liver and adult bone marrow (BM) stromal cell microenvironments. Our laboratory has developed a model of human B‐cell development that utilizes freshly isolated/non‐transformed human BM stromal cells as an in vitro microenvironment. Human CD34+ hematopoietic stem cells plated in this human BM stromal cell microenvironment commit to the B lineage and progress through the pre‐BCR and BCR checkpoints. This human BM stromal cell microenvironment also provides survival signals that prevent apoptosis in human B‐lineage cells. Human B‐lineage cells exhibit differential expression of Notch receptors and human BM stromal cells express the Notch ligand Jagged‐1. These results suggest a potential role for Notch in regulating B‐lineage commitment and/or progression through the pre‐BCR and BCR checkpoints.
The Experimental Study of Hemodynamic Changes and Pathological Morphology After Artery Anastomosis

The purpose of this article is to dynamically observe hemodynamic and medium-term pathomorphological changes and to investigate the pathophysiological variation at the vascular anastomotic stoma. Eighteen New Zealand white rabbits underwent right common carotid artery in situ anastomosis, and the hemodynamic changes of anastomotic stoma were recorded by color Doppler ultrasonography before surgery and 5 minutes, 1 week, 2 weeks, 3 weeks, 4 weeks, 8 weeks, 12 weeks, and 16 weeks after surgery. Pathological sections of stoma were made and the pathomorphological changes viewed. Artery anastomoses were preformed successfully in 15 rabbits; 4 rabbits suffered postoperative death. It took 1.22 ± 0.77 hours to complete every operation. All the data involved, mean velocity, peak systolic velocity, and resistant index, had no significant differences between preoperative and postoperative follow-up. The obvious differences were found in the diameters of stoma 5 minutes, 1 week, 2 weeks, and 3 weeks after operation (P values were .002, .001, .003, and .008, respectively). The variance of stoma diameters 2 weeks later was also different from those after 1 week, but no other differences were observed during other weeks. The decrease in stoma diameters after anastomosis was clear, with the maximum decrease occurring 2 weeks after the operation, after which the diameters of stoma became stable 16 weeks after the operation. Some collagens around anastomoses could be found by the pathological sections of stoma, which indicated that the deposition of collagen might be related to the decrease in stoma diameter.
Graph Algorithms with Small Communication Costs

We study minimizing communication cost in parallel algorithm design, by minimizing the number of communication phases in coarse-grained parallel computers. There have been several recent papers dealing with parallel algorithms of small communication cost under different models. Most of these results are for computational geometry problems. For these problems it has been possible to decompose tasks into appropriate subproblems in a communication-efficient way. It appears to be somewhat more difficult to design parallel algorithms with small communication phases for graph theory problems. In this paper we focus on the design of deterministic algorithms with a small number of communication phases for the list ranking problem and the shortest path problem.
Nucleotide synthesis is regulated by cytoophidium formation during neurodevelopment and adaptive metabolism

ABSTRACT The essential metabolic enzyme CTP synthase (CTPsyn) can be compartmentalised to form an evolutionarily-conserved intracellular structure termed the cytoophidium. Recently, it has been demonstrated that the enzymatic activity of CTPsyn is attenuated by incorporation into cytoophidia in bacteria and yeast cells. Here we demonstrate that CTPsyn is regulated in a similar manner in Drosophila tissues in vivo. We show that cytoophidium formation occurs during nutrient deprivation in cultured cells, as well as in quiescent and starved neuroblasts of the Drosophila larval central nervous system. We also show that cytoophidia formation is reversible during neurogenesis, indicating that filament formation regulates pyrimidine synthesis in a normal developmental context. Furthermore, our global metabolic profiling demonstrates that CTPsyn overexpression does not significantly alter CTPsyn-related enzymatic activity, suggesting that cytoophidium formation facilitates metabolic stabilisation. In addition, we show that overexpression of CTPsyn only results in moderate increase of CTP pool in human stable cell lines. Together, our study provides experimental evidence, and a mathematical model, for the hypothesis that inactive CTPsyn is incorporated into cytoophidia.
Physiological and Psychological Effects of Viewing a Kiwifruit (Actinidia deliciosa ‘Hayward’) Orchard Landscape in Summer in Japan

The physiological and psychological relaxation effects of viewing a kiwifruit (Actinidia deliciosa ‘Hayward’) orchard landscape were investigated. Seventeen Japanese adult females (46.1 ± 8.2 years) viewed a kiwifruit orchard landscape or a building site (control) for 10 min. The heart rate variability and heart rate were determined. The modified semantic differential method and the short-form Profile of Mood States were used to assess the psychological effects. Compared with viewing the building site, viewing the kiwifruit orchard landscape resulted in a significant increase in the parasympathetic activity, a marginally significant decrease in the heart rate, a significant increase in “comfortable”, “relaxed” and “natural” feelings and a significant improvement in mood states.
Percutaneous Biliary Drainage Using Open Cell Stents for Malignant Biliary Hilar Obstruction

Objective To evaluate the feasibility, safety and the effectiveness of the complex assembly of open cell nitinol stents for biliary hilar malignancy. Materials and Methods During the 10 month period between January and October 2007, 26 consecutive patients with malignant biliary hilar obstruction underwent percutaneous insertion of open cell design nitinol stents. Four types of stent placement methods were used according to the patients' ductal anatomy of the hilum. We evaluated the technical feasibility of stent placement, complications, patient survival, and the duration of stent patency. Results Bilobar biliary stent placement was conducted in 26 patients with malignant biliary obstruction-T (n = 9), Y (n = 7), crisscross (n = 6) and multiple intersecting types (n = 4). Primary technical success was obtained in 24 of 26 (93%) patients. The crushing of the 1st stent during insertion of the 2nd stent occurred in two cases. Major complications occurred in 2 of 26 patients (7.7%). One case of active bleeding from hepatic segmental artery and one case of sepsis after procedure occurred. Clinical success was achieved in 21 of 24 (87.5%) patients, who were followed for a mean of 141.5 days (range 25-354 days). The mean primary stent patency period was 191.8 days and the mean patient survival period was 299 days. Conclusion Applying an open cell stent in the biliary system is feasible, and can be effective, especially in multiple intersecting stent insertions in the hepatic hilum.
Transcriptional Organization of the Pseudomonas putida tol-oprL Genes

ABSTRACT Proteins of the Tol system play a key role in the maintenance of outer membrane integrity and cell morphology in gram-negative bacteria. In Pseudomonas putida, the seven genes, orf1, tolQ, tolR, tolA, tolB, oprL, and orf2, which encode the proteins of this complex, are clustered in a 5.8-kb region of chromosomal DNA. Analysis of polar mutations, reverse transcriptase PCR assays, and transcriptional fusion constructs with a promoterless lacZ gene revealed that the genes are arranged in two operons: orf1 tolQ tolR tolA tolB and oprL orf2. We were also able to find a transcript that was initiated at the orf1 promoter and covered the two operons in a single mRNA. On the basis of the OprL protein level, we surmised that this transcript contributed only about 10 to 15% of the total OprL protein. Primer extension analysis identified the oprL orf2 operon promoter within the tolB gene, and the −10 and −35 regions exhibited some similarity to those of σ70-recognized promoters. The transcription start point of orf1 was located 91 bp upstream of the orf1 start codon, and the −10/−35 region also exhibited σ70 −10/−35 recognition sequences. The expression from both promoters in rich and minimal media was constitutive and was very little influenced by the growth phase or iron-deficient conditions. In addition, analyses of the β-galactosidase activities of different translational fusion constructs revealed that translation of tolA and orf2 genes was dependent on the translation of their corresponding upstream genes (tolR and oprL, respectively).
Failure Prediction of Aluminum Laser-Welded Blanks

The formability of aluminum-3% magnesium laser-welded blanks manufactured by 3kW YAG laser welding process is investigated in this paper. Previous experimental results showed that shear failure occurs in the welds of these blanks during tensile testing with the weld line perpendicular to the tensile axis. In order to further understand the failure in these blanks under uniaxial and biaxial straining conditions, finite element computations under generalized plane strain conditions are conducted to understand the effects of weld geometry and strength on the shear failure. The results indicate that the average plastic stress-strain behavior of the weld should be softer than that in the base metal in the direction perpendicular to the weld line. The results also show that the weld geometry has significant effects on strain localization in the weld under the tensile loading perpendicular to the weld line. The stress-strain histories of the material elements of the weld metal in tensile specimens obtained from the finite element computation are used for a failure/localization analysis. The imperfection approach of Marciniak and Kuczynski is employed to examine the failure/localization in the weld of the tensile specimens. The failure/localization analysis is based on an elastic-viscoplastic constitutive law that accounts for the potential surface curvature, material plastic anisotropy, material rate sensitivity and softening due to nucleation, growth and coalescence of microvoids. The material imperfection parameters for void nucleation and growth are obtained by fitting the results of the failure/localization analysis to those of the uniaxial tensile tests. The material imperfection parameters are then used to predict the failure strains of the blanks under biaxial straining conditions based on the stress-strain histories of the material elements obtained from finite element computations under generalized plane strain conditions. The results indicate that the forming limits of the blanks under plane strain tension and equal biaxial tension are reduced significantly when compared with that under uniaxial tension. Finally, a finite element simulation of the welded sheet under uniaxial tension is carried out with consideration of void nucleation and growth for all the material elements in the weld. Our computational results indicate that without consideration of the failure/localization analysis presented in this paper, an unrealistically high volume fraction for void nucleation must be assumed in our finite element simulation of the tensile tests in order to match the failure strains observed in the uniaxial tensile tests.
Forecasting time series with complex seasonal patterns using exponential smoothing

A new innovations state space modeling framework, incorporating Box-Cox transformations, Fourier series with time varying coefﬁcients and ARMA error correction, is introduced for forecasting complex seasonal time series that cannot be handled using existing forecasting models. Such complex time series include time series with multiple seasonal periods, high frequency seasonality, non-integer seasonality and dual-calendar effects. Our new modelling framework provides an alternative to existing exponential smoothing models, and is shown to have many advantages. The methods for initialization and estimation, including likelihood evaluation, are presented, and analytical expressions for point forecasts and interval predictions under the assumption of Gaussian errors are derived, leading to a simple, comprehensible approach to forecasting complex seasonal time series. Our trigonometric formulation is also presented as a means of decomposing complex seasonal time series, which cannot be decomposed using any of the existing decomposition methods. The approach is useful in a broad range of applications, and we illustrate its versatility in three empirical studies where it demonstrates excellent forecasting performance over a range of prediction horizons. In addition, we show that our trigonometric decomposition leads to the identiﬁcation and extraction of seasonal components, which are otherwise not apparent in the time series plot itself.
Impact of Basal-Like Breast Carcinoma Determination for a More Specific Therapy

Recent advances in high-throughput molecular technologies have made it possible to begin to tackle the molecular complexity of breast cancer and have contributed to the realisation that this biologic heterogeneity has implications for treatment. One of the major achievements of class discovery studies in breast cancer is the identification of a basal-like subtype that is characterised by absence of expression of hormone receptors and HER2 and has molecular features in common with basal/myoepithelial cells of the breast. Basal-like cancers have attracted attention as a poor prognostic class of tumours that lack the benefit of currently available targeted therapy. However, basal-like cancer as a distinct class of tumours, which share a specific molecular profile, are characterised by high proliferative activity and express specific markers, is a good candidate for development of specific targeted therapy. It is likely that in the near future, the ongoing research studies and clinical trials will provide an evidence-based approach to the best treatment strategy that can be applied to these tumours. In this review, we discuss the main features of basal-like tumours and recent evidence on the different available therapeutic approaches.