Miracle-dz/UniFAR-FTUs huggingface dataset:
Survival Improvement in Korean Breast Cancer Patients Due to Increases in Early-Stage Cancers and Hormone Receptor Positive/HER2 Negative Subtypes: A Nationwide Registry-Based Study

Purpose The aim of this study was to investigate whether the observed changes over time in the survival rates vary according to the intrinsic subtypes of breast cancer diagnosed. Methods Data from 46,320 breast cancer patients in the Korean Breast Cancer Registry who underwent surgery between 1999 and 2006 were reviewed. Among them, results from 25,887 patients with available data about the status of estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 (HER2) were analyzed. Patients were classified into two cohorts according to the year in which they underwent surgery: 1999-2002 and 2003-2006. Results The patients treated in the latter time period showed significantly better overall survival (OS) compared with those in the former period when adjusted for follow-up duration. The proportion of hormone receptor+/HER2-subtype and stage I breast cancer were significantly higher in the latter period (47.4% vs. 54.6%, p<0.001; 31.0% vs. 39.6%, p<0.001, respectively). Improvement in OS between the former and latter periods was seen in all subtypes of breast cancer, including triple-negative cancers (all p-values <0.001 in univariate and multivariate analyses). Conclusion Improvement in survival in Korean breast cancer patients over the study years is being observed in all subtypes of breast cancer, implying that increases in both early-stage detection and the proportion of less aggressive cancers contribute to this improvement.
The point prevalence of an abnormal ankle-brachial index in antiphospholipid antibody negative patients with livedo reticularis: a controlled study

Livedo reticularis (livedo) is characterised by reticular cyanotic cutaneous discolouration surrounding a pale central area. Physiological livedo, also known as cutis marmorata, is common in young women on exposure to cold. Pathological livedo is characterised by a fixed broken pattern, which is occasionally associated with ulceration. Livedo is frequently seen in antiphospholipid (Hughes) syndrome (APS), and appears to be associated with a worse prognosis.1 A number of patients have recently been described who have many features of APS including thrombosis, livedo and pregnancy morbidity in the absence of antiphospholipid antibodies (aPL). 2 Our aim was to assess the prevalence and …
The Noc-Domain Containing C-Terminus of Noc4p Mediates Both Formation of the Noc4p-Nop14p Submodule and Its Incorporation into the SSU Processome

Noc1p, Noc3p and Noc4p are eukaryotic proteins which play essential roles in yeast ribosome biogenesis and contain a homologous stretch of about 45 aminoacids (Noc-domain) of unknown function. Yeast Noc4p is a component of the small ribosomal subunit (SSU) processome, can be isolated as a stable Noc4p-Nop14p SSU-processome submodule from yeast cells, and is required for nuclear steps of small ribosomal subunit rRNA maturation. We expressed a series of mutated alleles of NOC4 in yeast cells and analysed whether the corresponding protein variants support vegetative growth, interact with Nop14p, and are incorporated into the SSU-processome. The data reveal that the essential C-terminus of Noc4p which contains 237 aminoacids including the Noc-domain represents a protein-protein interaction module. It is required and sufficient for its association with Nop14p and several nuclear precursors of the small ribosomal subunit. The N-terminal Noc4-part seems to be targeted to pre-ribosomes via the C-terminus of Noc4p and plays there an essential role in SSU-processome function. Replacement of the Noc4p-Noc-domain by its homologues Noc1p-counterpart results in a hybrid Noc4p variant which fails to associate with Nop14p and pre-ribosomes. On the other hand, exchange of 6 amino acids in the Noc1-Noc-domain of this hybrid Noc4p protein is sufficient to restore its essential in vivo functions. These data suggest that Noc-domains of Noc1p and Noc4p share a common structural backbone in which diverging amino acids play crucial roles in mediating specific regulated interactions. Our analysis allows us to distinguish between different functions of certain domains within Noc4p and contribute to the understanding of how incorporation of Noc4p into ribosomal precursors is coupled to rRNA processing and maturation of the small ribosomal subunit.
Base Excision Repair in Physiology and Pathology of the Central Nervous System

Relatively low levels of antioxidant enzymes and high oxygen metabolism result in formation of numerous oxidized DNA lesions in the tissues of the central nervous system. Accumulation of damage in the DNA, due to continuous genotoxic stress, has been linked to both aging and the development of various neurodegenerative disorders. Different DNA repair pathways have evolved to successfully act on damaged DNA and prevent genomic instability. The predominant and essential DNA repair pathway for the removal of small DNA base lesions is base excision repair (BER). In this review we will discuss the current knowledge on the involvement of BER proteins in the maintenance of genetic stability in different brain regions and how changes in the levels of these proteins contribute to aging and the onset of neurodegenerative disorders.
Computer assisted cervical cytological nucleus localization

Cervical cancer is the second most common form of malignancy among women in India. Regular screening of cervix can mollify its incidence thus enabling adoption of better prevention strategies. Proper localization and delineation of nuclear attributes for identification of crucial cellular features in Papanicolau stained cervical liquid based cytological images are tricky. Reduction of false negativity in the screening technique is the need of the hour. These ambiguities in the detection of nuclei are due to relative differences in staining intensity, presence of inflammatory cells, necrotic background, presence of bacteria, cellular overlapping causing super-imposition of nuclei, and clustering/clumping of cells etc. In this paper we present here a computationally lightweight yet elegant computer assisted automated technique for localization of epithelial cell nuclei in optical microscopic images of Pap stained monolayer cervical smears. The set of developed algorithms efficiently handle background separation and identification of nuclei in overlapping cells occurring as clusters. It uses morphological selection of region of interest preceded by intensity based object separation. The region of interest is iteratively bound using minimum bounding rectangles, to locate nuclei in the cell clusters. This method accurately inserts seed points, eliminates false seeds and detects nucleus. Thereafter region growing technique is applied considering obtained seed points to segment the nucleus from cells. It is inferred that most of the problems faced while locating nuclei are overcome with the above algorithm; the only cases when it fails is in presence of overlapping nuclei and in presence of overlapping neutrophils.
Afferent pathway(s) for pharyngeal dilator reflex to negative pressure in man: a study using upper airway anaesthesia.

1. To determine the afferent pathways mediating pharyngeal dilator muscle activation in response to negative airway pressure in man, we recorded genioglossus electromyogram (EMG) activity (via intra‐oral bipolar surface electrodes) in response to 500 ms duration pressure stimuli of ‐15 and ‐25 cm H2O in normal, conscious, supine subjects relaxed at end‐expiration; responses were compared before and after upper airway anaesthesia. 2. Six rectified and integrated EMG responses were bin averaged for pressure stimuli applied with the glottis open (GO) and closed (GC) and to the outside of the face only (controls). Response magnitude was quantified as the ratio of the EMG activity for an 80 ms post‐stimulus period (before the subject's reaction time for tongue protrusion) to an 80 ms pre‐stimulus period. 3. In eight subjects, upper airway anaesthesia reduced the EMG responses with GC to a level indistinguishable from controls. After anaesthesia, responses with GO remained higher than those with GC. 4. With GC, the mean EMG responses decreased by 43% after selective anaesthesia of the nasal mucosa (trigeminal nerves) in two subjects, 32% after selective anaesthesia of the laryngeal mucosa (superior laryngeal nerves) in six subjects and by 21% after selective anaesthesia of the oropharyngeal mucosa (glossopharyngeal and lingual nerves) in four subjects. 5. We conclude that upper airway afferents mediate pharyngeal dilator muscle activation in response to negative pressure with GC and that subglottal receptors caused the increased activation with GO. With GC, the trigeminal and superior laryngeal nerves mediate an important component of the responses with the glossopharyngeal nerves playing a less important role.
Hierarchical Solution of Large Markov Decision Processes

This paper presents an algorithm for finding approximately optimal policies in very large Markov decision processes by constructing a hierarchical model and then solving it. This strategy sacrifices optimality for the ability to address a large class of very large problems. Our algorithm works efficiently on enumerated-states and factored MDPs by constructing a hierarchical structure that is no larger than both the reduced model of the MDP and the regression tree for the goal in that MDP, and then using that structure to solve for a policy.
Enhanced oral bioavailability of silymarin using liposomes containing a bile salt: preparation by supercritical fluid technology and evaluation in vitro and in vivo

The aim of this investigation was to develop a procedure to improve the dissolution and bioavailability of silymarin (SM) by using bile salt-containing liposomes that were prepared by supercritical fluid technology (ie, solution-enhanced dispersion by supercritical fluids [SEDS]). The process for the preparation of SM-loaded liposomes containing a bile salt (SM-Lip-SEDS) was optimized using a central composite design of response surface methodology with the ratio of SM to phospholipids (w/w), flow rate of solution (mL/min), and pressure (MPa) as independent variables. Particle size, entrapment efficiency (EE), and drug loading (DL) were dependent variables for optimization of the process and formulation variables. The particle size, zeta potential, EE, and DL of the optimized SM-Lip-SEDS were 160.5 nm, −62.3 mV, 91.4%, and 4.73%, respectively. Two other methods to produce SM liposomes were compared to the SEDS method. The liposomes obtained by the SEDS method exhibited the highest EE and DL, smallest particle size, and best stability compared to liposomes produced by the thin-film dispersion and reversed-phase evaporation methods. Compared to the SM powder, SM-Lip-SEDS showed increased in vitro drug release. The in vivo AUC0−t of SM-Lip-SEDS was 4.8-fold higher than that of the SM powder. These results illustrate that liposomes containing a bile salt can be used to enhance the oral bioavailability of SM and that supercritical fluid technology is suitable for the preparation of liposomes.
The Limits of Linked Suppression for Regulatory T Cells

Background We have previously found that CD4+CD25+ regulatory T cells (Tregs) can adoptively transfer tolerance after its induction with costimulatory blockade in a mouse model of murine cardiac allograft transplantation. In these experiments, we tested an hypothesis with three components: (1) the Tregs that transfer tolerance have the capacity for linked suppression, (2) the determinants that stimulate the Tregs are expressed by the indirect pathway, and (3) the donor peptides contributing to these indirect determinants are derived from donor major histocompatibility complex (MHC) antigens (Ags). Methods First heart transplants were performed from the indicated donor strain to B10.D2 recipients along with costimulatory blockade treatment (250 μg i.p. injection of MR1 on day 0 and 250 μg i.p. injection of CTLA-4 Ig on day 2). At least 8 weeks later, a second heart transplant was performed to a new B10.D2 recipient who had been irradiated with 450 cGy. This recipient was given 40 × 106 naive B10.D2 spleen cells + 40 × 106 B10.D2 spleen cells from the first (tolerant) recipient. We performed three different types of heart transplants using various donors. Results (1) Tregs suppress the graft rejection in an Ag-specific manner. (2) Tregs generated in the face of MHC disparities suppress the rejection of grafts expressing third party MHC along with tolerant MHC. Conclusion The limits of linkage appear to be quantitative and not universally determined by either the indirect pathway or by peptides of donor MHC Ags.
Microbial Symphony: Navigating the Intricacies of the Human Oral Microbiome and Its Impact on Health

This comprehensive review delves into the forefront of research on the human oral microbiome, exploring recent advancements that span microbial colonization, state-of-the-art detection methodologies, and the complex interplay involved in disease progression. Through an exhaustive analysis of the contemporary literature, we illuminate the dynamic orchestration of microbial communities within the oral cavity, underscoring their pivotal role in health and disease. Cutting-edge detection techniques, including metagenomics and high-throughput sequencing, are discussed regarding their transformative impact on understanding the intricacies of oral microbial ecosystems. As we stand on the cusp of a new decade, this review anticipates a paradigm shift in the field, emphasizing the potential for rapid identification and targeted management of detrimental oral microorganisms. Insights gained from this exploration not only contribute to our fundamental understanding of the oral microbiome but also hold promise for the development of innovative therapeutic strategies to maintain oral health. This article aims to serve as a valuable resource for researchers, clinicians, and public health professionals engaged in unraveling the mysteries of the microbial symphony within the human oral cavity.
Modulation of the glycogen synthase kinase‐3 family by tyrosine phosphorylation.

Glycogen synthase kinase‐3 (GSK‐3) is a protein serine kinase implicated in the cellular response to insulin. The enzyme is the mammalian homologue of the zeste‐white3 (shaggy) homeotic gene of Drosophila melanogaster and has been implicated in the regulation of the c‐Jun/AP‐1 transcription factor. In mammals this protein serine kinase is encoded by two related genes termed GSK‐3 alpha and beta. Here, we demonstrate that these two proteins and the fruit fly protein are phosphorylated on tyrosine in vivo. Moreover, GSK‐3 beta activity and function are shown to be dependent on tyrosine phosphorylation. The modified tyrosine residue is conserved in all members of the GSK‐3 family and is equivalent to that required for activity by mitogen‐activated protein (MAP) kinases. However, unlike MAP kinases, GSK‐3 is highly phosphorylated on tyrosine and thus active in resting cells.
Including workers with disabilities in flow shop scheduling

Persons with disabilities have severe problems participating in the job market and their unemployment rate is usually much higher than the average of the population. This motivates the research of new modes of production which allow to include these persons at a low overhead. In this paper we study the inclusion of persons with disabilities into flow shops with the objective of minimizing the makespan. Since flow shops usually have only a few machines, we focus on the inclusion of one and two workers. We define the problem, propose mathematical models and a heuristic solution, as well as realistic test instances. In computational tests we evaluate the performance of the models and the heuristic, and assess the utility of such a model of inclusion. We conclude that the problem can be solved satisfactorily, and that including workers with disabilities into flow shops is economically feasible.
An Improved Information Value Model Based on Gray Clustering for Landslide Susceptibility Mapping

Landslides, as geological hazards, cause significant casualties and economic losses. Therefore, it is necessary to identify areas prone to landslides for prevention work. This paper proposes an improved information value model based on gray clustering (IVM-GC) for landslide susceptibility mapping. This method uses the information value derived from an information value model to achieve susceptibility classification and weight determination of landslide predisposing factors and, hence, obtain the landslide susceptibility of each study unit based on the clustering analysis. Using a landslide inventory of Chongqing, China, which contains 8435 landslides, three landslide susceptibility maps were generated based on the common information value model (IVM), an information value model improved by an analytic hierarchy process (IVM-AHP) and our new improved model. Approximately 70% (5905) of the inventory landslides were used to generate the susceptibility maps, while the remaining 30% (2530) were used to validate the results. The training accuracies of the IVM, IVM-AHP and IVM-GC were 81.8%, 78.7% and 85.2%, respectively, and the prediction accuracies were 82.0%, 78.7% and 85.4%, respectively. The results demonstrate that all three methods perform well in evaluating landslide susceptibility. Among them, IVM-GC has the best performance.
Characterization of Novel OmpA-Like Protein of Leptospira interrogans That Binds Extracellular Matrix Molecules and Plasminogen

Leptospira interrogans is the etiological agent of leptospirosis, a zoonotic disease of human and veterinary concern. The identification of novel proteins that mediate host-pathogen interactions is important for understanding the bacterial pathogenesis as well as to identify protective antigens that would help fight the disease. We describe in this work the cloning, expression, purification and characterization of three predicted leptospiral membrane proteins, LIC10258, LIC12880 (Lp30) and LIC12238. We have employed Escherichia coli BL21 (SI) strain as a host expression system. Recently, we have identified LIC12238 as a plasminogen (PLG)-binding receptor. We show now that Lp30 and rLIC10258 are also PLG-receptors of Leptospira, both exhibiting dose-dependent and saturating binding (K D, 68.8±25.2 nM and 167.39±60.1 nM, for rLIC10258 and rLIC12880, respectively). In addition, LIC10258, which is a novel OmpA-like protein, binds laminin and plasma fibronectin ECM molecules and hence, it was named Lsa66 (Leptospiral surface adhesin of 66 kDa). Binding of Lsa66 to ECM components was determined to be specific, dose-dependent and saturable, with a K D of 55.4±15.9 nM to laminin and of 290.8±11.8 nM to plasma fibronectin. Binding of the recombinant proteins to PLG or ECM components was assessed by using antibodies against each of the recombinant proteins obtained in mice and confirmed by monoclonal anti-polyhistidine antibodies. Lsa66 caused partial inhibition on leptospiral adherence to immobilized ECM and PLG. Moreover, this adhesin and rLIC12238 are recognized by antibodies in serum samples of confirmed leptospirosis cases. Thus, Lsa66 is a novel OmpA-like protein with dual activity that may promote the attachment of Leptospira to host tissues and may contribute to the leptospiral invasion. To our knowledge, this is the first leptospiral protein with ECM and PLG binding properties reported to date.
An Adaptive Resource Monitoring Method for Distributed Heterogeneous Computing Environment

Resource performance monitoring is among the most active research topics in distributed computing. In this paper, we propose an adaptive resource monitoring method for applications in heterogeneous computing environment. According to the operating environment of distributed heterogeneous system and the changes of system resource workload, the method combines periodic pull mode with event-driven push mode to adaptively publish and retrieve system resource information. Preliminary experiments reveal that, by using our adaptive monitoring method, the efficiency of system monitoring is improved over that accrued by using regular monitoring approaches.
Architecture-level performance evaluation of component-based embedded systems

A static performance evaluation technique is proposed to support early, architecture-level design space exploration for component-based embedded systems. The novel contribution is the use of a designer-specified evaluation scenario to identify a characteristic subset of system functionality that serves as a context for a rapid performance evaluation between candidate architectures. Fidelity is demonstrated with a case study that compares performance estimates of several candidate architectures to measurements from respective implementations.
Detailed Analysis of Uphill Moves in Temperature Parallel Simulated Annealing and Enhancement of Exchange Probabilities

This paper demonstrates that the probability of the occurrence of uphill moves in temperature parallel simulated annealing is so small that the effects of parallelization might be lost when the number of processing nodes is small. A modification in the probability of solution exchange between the processes is one tactic to recover the parallelization effects. This method is evaluated by a traveling salesman problem with 33 cities in China. The results of the experiments show that, although it violates the detailed balance condition, the modification can improve the quality of the solutions.
Hanging-wall colluvial cementation along active normal faults

Abstract Many active normal faults throughout the Aegean juxtapose footwall limestone against hanging-wall colluvium. In places, this colluvium becomes cemented and forms large hanging-wall lobes or sheets of varying thickness attached to the bedrock fault. Investigations at the Lastros Fault in eastern Crete allow us to define criteria to distinguish between cemented colluvium and fault cataclasite (tectonic breccia), which is often present at bedrock faults. Macro- and microscopic descriptions of the cemented colluvium show that the colluvium was originally deposited through both rockfalls and debris flows. Stable isotope analyses of oxygen and carbon from 83 samples indicate that cementation then occurred through meteoric fluid flow in the fault zone from springs at localised positions along strike. Palaeotemperature calculations of the parent water from which the calcite cement precipitated are indicative of a climate between 7°C and 10°C colder than Crete’s present average annual temperature. This most likely represents the transition between a glacial and interglacial period in the late Pleistocene. Ground-penetrating radar also indicates that cemented colluvium is present in the hanging-wall subsurface below uncemented colluvium. Using these results, a model for the temporal development of the fault and formation of the cemented colluvium is proposed.