Miracle-dz/UniFAR-FTUs huggingface dataset:
Docetaxel prodrug liposomes for tumor therapy: characterization, in vitro and in vivo evaluation

Abstract There is a strong desire to develop docetaxel (DTX) formulation with good therapeutic effectiveness in view of serious adverse reactions of the commercial formulation of DTX (Taxotere®). In this study, a redox-responsive DTX-vitamin E prodrug was successfully formulated into liposomes with the drug loading of 4.14% ± 0.10%. Compared with DTX liposomes, the DTX prodrug liposomes (DPLs) showed good stability for 30-d shelf life and during dilution with different media. In vitro antitumor activity of DPLs on human prostatic carcinoma PC-3 cells and human lung cancer A549 cells was evaluated using cytotoxicity and apoptosis assays. In spite of a decrease in in vitro antitumor activity, the in vivo pharmacokinetic study reveals that DPLs exhibit significantly longer DTX plasma half-life (t1/2, 1.38-fold) and higher bioavailability (AUC0−t, 14.49-fold) compared with DTX liposomes. The antitumor activity of DPLs to the A549 tumor xenograft model showed selective accumulation in tumor tissue, significant inhibition the growth of the tumors and a much lower toxicity as seen in body weight loss, compared with DTX-Solution. Taken together, the results showed that DPLs is a promising strategy for DTX antitumor delivery.
Direct health care costs of Crohn's disease and ulcerative colitis in US children and adults.

BACKGROUND & AIMS Data regarding the health care costs of inflammatory bowel disease (IBD) in the United States are limited. The objectives of this study were to estimate the direct costs of Crohn's disease (CD) and ulcerative colitis (UC) in the United States, describe the distribution of costs among inpatient, outpatient, and pharmaceutical services, and identify sociodemographic factors influencing these costs. METHODS We extracted medical and pharmacy claims from an administrative database containing insurance claims from 87 health plans in 33 states, occurring between 2003 and 2004. We identified cases of CD and UC using an administrative definition. For each case, we selected up to 3 non-IBD controls. Claims were classified as inpatient, outpatient, or pharmaceutical according to Current Procedural Terminology codes or National Drug Codes. Costs were based on the paid amount of each claim. IBD-attributable costs were estimated by subtracting costs for non-IBD patients from those for patients with IBD. Logistic regression was used to identify the sociodemographic factors affecting these costs. RESULTS We identified 9056 patients with CD and 10,364 patients with UC. Mean annual costs for CD and UC were $8265 and $5066, respectively. For CD, 31% of costs were attributable to hospitalization, 33% to outpatient care, and 35% to pharmaceutical claims. The corresponding distribution for UC was 38%, 35%, and 27%, respectively. Costs were significantly higher for children younger than 20 years compared with adults, but this did not vary substantially by sex or region. CONCLUSIONS This study demonstrates a substantial economic burden of IBD and can be used to inform health policy.
Changes are not localized before they are explicitly detected

Change detection is in many ways analogous to visual search. Yet, unlike search, successful detection depends not on the salience of features within a scene, but on the difference between the original and modified scene. If, as in search, pre-attentive mechanisms guide attention to the change location, the change itself must produce a preattentively detectable signal. Despite recent evidence for implicit representation of change in the absence of conscious detection, few studies have yet explored whether attention is guided to a change location prior to explicit detection. In four “change blindness” experiments using several variants of the “flicker” task, we tested the hypothesis that implicit or preattentive mechanisms guide change localization prior to explicit detection. None of the experiments revealed improved localization of changes prior to explicit reports of detection, suggesting that implicit detection of change does not contribute to the eventual explicit localization of a change. Instead, change localization is essentially arbitrary, driven by the salience of features within scenes.
Impact of server dynamic allocation on the response time for energy-efficient virtualized web clusters

Virtualization has been widely adopted in data centers around the world for improving resource usage efficiency; particularly helping to make these computing environments more energy-efficient. Server virtualization allows for on-demand allocation (using either migration or replication) of virtual machines (VMs), which run the web applications and services, to physical servers. In this paper, we measure and analyze the disruptive impact on the QoS (quality-of-service) provided by the applications, in terms of server-side response time and throughput, during dynamic allocation of virtual machines in a server cluster. The response time of the web applications in the cluster is adopted as our main QoS metric since it is crucial for qualifying the end-user experience. In our experiments, we use Xen as the virtual machine manager and Apache servers for running the web applications. Our results show that VM replication with workload balancing may lead to reduced disruption impact on the QoS measures when compared to VM migration.
Possible protection by notoginsenoside R1 against glutamate neurotoxicity mediated by N‐methyl‐D‐aspartate receptors composed of an NR1/NR2B subunit assembly

Notoginsenoside R1 (NTR1) is the main active ingredient in Panax notoginseng, a herbal medicine widely used in Asia for years. The purpose of this study was to investigate pharmacological properties of NTR1 on neurotoxicity of glutamate (Glu) in primary cultured mouse cortical neurons along with its possible mechanism of action. Wefound that NTR1 significantly protected neurons from the loss of cellular viability caused by brief exposure to 10 μM Glu for 1 hr in a dose‐dependent manner at concentrations from 0.1 to 10 μM, without affecting the viability alone. NTR1 significantly inhibited the increased number of cells positive to propidium iodide (PI) staining, increase of intracellular free Ca2+ ions, overproduction of intracellular reactive oxygen species, and depolarization of mitochondrial membrane potential in cultured neurons exposed to Glu, in addition to blocking decreased Bcl‐2 and increased Bax expression levels. We further evaluated the target site at which NTR1 protects neurons from Glu toxicity by using the acquired expression strategy of N‐methyl‐D‐aspartate (NMDA) receptor subunits in human embryonic kidney 293 cells. We found that 10 μM NTR1 protected NR1/NR2B subunit expressing cells from cell death by 100 μM NMDA, but not cells expressing NR1/NR2A subunits, when determined by PI staining. These results suggest that NTR1 may preferentially protect neurons from Glu excitotoxicity mediated by NMDA receptor composed of an NR1/NR2B subunit assembly in the brain. © 2009 Wiley‐Liss, Inc.
Intra-individual variability of CO₂ breath isotope enrichment compared to blood glucose in the oral glucose tolerance test.

BACKGROUND Glucose tolerance can be assessed noninvasively using (13)C-labeled glucose added to a standard oral glucose load, by measuring isotope-enriched CO(2) in exhaled air. In addition to the clear advantage of the noninvasive measurements, this approach may be of value in overcoming the high variability in blood glucose determination. METHODS We compared within-individual variability of breath CO(2) isotope enrichment with that for blood glucose in a 75-g oral glucose tolerance test (OGTT) by adding 150 mg of d-[(13)C]glucose ((13)C 99%) to a standard 75-g glucose load. Measurements of whole blood glucose (by glucose oxidase) and breath isotope enrichment (by isotope ratio mass spectrometry) were made every 30 min for 3 h. Subjects underwent three repeat tests over a 3-week period. Values for variability of breath isotope enrichment at 3 h (∂‰180) and of area under the curve for enrichment to 180 min (AUC180) were compared with variability of the 2-h OGTT blood glucose. RESULTS Breath test-derived measures exhibited lower within-subject variability than the 2-h OGTT glucose. The coefficient of variation for ∂‰180 was 7.4 ± 3.9% (mean ± SD), for AUC180 was 9.4 ± 6.3%, and for 2-h OGTT blood glucose was 13 ± 7.1% (P = 0.005 comparing ∂‰180 versus 2-h blood glucose; P = 0.061 comparing AUC180 versus 2-h blood glucose; P = 0.03 comparing ∂‰180 versus AUC180). CONCLUSIONS Breath test-derived measurements of glucose handling had lower within-subject variability versus the standard 2-h blood glucose reading used in clinical practice. These findings support further development of this noninvasive method for evaluating glucose tolerance.
Grain size effects on NiTi shape memory alloy fatigue crack growth

Fatigue cracking in polycrystalline NiTi was investigated using a multiscale experimental framework for average grain sizes (GS) from 10 to 1500 nm for the first time. Macroscopic fatigue crack growth rates, measured by optical digital image correlation, were connected to microscopic crack opening and closing displacements, measured by scanning electron microscope DIC (SEM-DIC) using a high-precision external SEM scan controller. Among all grain sizes, the 1500 nm GS sample exhibited the slowest crack growth rate at the macroscale, and the largest crack opening level (stress intensity at first crack opening) and minimum crack opening displacements at the microscale. Smaller GS samples (10, 18, 42, and 80 nm) exhibited nonmonotonic trends in their fatigue performance, yet the correlation was strong between macroscale and microscale behaviors for each GS. The samples that exhibited the fastest crack growth rates (42 and 80 nm GS) showed a small crack opening level and the largest crack opening displacements. The irregular trends in fatigue performance across the nanocrystalline GS samples were consistent with nonmonotonic values in the elastic modulus reported previously, both of which may be related to the presence of residual martensite only evident in the small GS samples (10 and 18 nm).
Pharmacologic treatment of schizophrenia

Despite pharmacologic advances, the treatment of schizophrenia remains a challenge, and suboptimal outcomes are still all too frequent. Although treatment goals of response, remission, and recovery have been defined more uniformly, a good “effectiveness” measure mapping onto functional outcomes is still lacking. Moreover, the field has to advance in transferring measurement-based approaches from research to clinical practice. There is an ongoing debate whether, and which, first- or second-generation antipsychotics should be used. However, an individualized treatment approach needs to consider current symptoms, comorbid conditions, past therapeutic response, and adverse effects, as well as patient choice and expectations. Moreover, acute and long-term goals and effects of medication treatment need to be balanced. While the acute response to appropriately dosed first-generation antipsychotics may not differ much from second-generation antipsychotics, advantages of lower rates of extrapyramidal side effects, tardive dyskinesia, and, possibly, relapse may favor second-generation antipsychotics. However, when considering individual adverse effect prof iles, the differentiation into first- and second-generation antipsychotics as unified classes can not be upheld, and a more differentiated view and treatment selection is required. To date, clozapine is the only evidence-based treatment for refractory patients, and the role of antipsychotic polypharmacy and other augmentation strategies remains unclear, at best. To improve the treatment outcomes in schizophrenia, research efforts are needed that elucidate biomarkers of the illness and of treatment response (both therapeutic and adverse effects). Moreover, new treatment options are needed that affect nondopaminergic targets with relevance for symptom reduction, relapse prevention, enhanced efficacy for nonresponders, and reduced key adverse effects.
Spatial variation in abundance, size composition and viable egg production of spawning cod (Gadus morhua L.) in Icelandic waters

Changes in geographical location of spawning and/or in spatial abundance of spawners may influence offspring survival. In Iceland, the spatial dynamics of spawning cod (Gadus morhua L.) are complicated due to unequal distribution of size classes on the main spawning grounds. Information on abundance, age, and size distributions during peak spawning, potential fecundity, egg size, and estimated larval viabilities were used to contrast the reproductive potential of three adjacent spawning areas within the main spawning ground of cod in the Icelandic waters. The three areas differed with respect to age and size distribution, abundance, mean production per female and an index of total egg production. Larger and faster growing cod spawned closer to the coast (area 1). Smaller cod spawned in deeper water out on Selvogsbanki (area 2), and the smallest and youngest cod tended to spawn along the continental edge (area 3). Relative abundance was higher in area 2 than in areas 1 and 3 (640, 153, and 334 kg/net, respectively). Mean production of eggs per female was highest in area 1, while the index of total egg production was highest in area 2. The estimates of viable egg production did not change the general results. Estimates of the proportion of viable eggs produced were slightly higher in area 1 than in areas 2 and 3. However, the influence of the relative abundance of spawners in the different areas overrode any trends due to higher mean production of viable eggs. The results demonstrate that egg production, based on abundance and size and age composition of spawning cod, may vary extensively among different spawning areas. Such information, in conjunction with documentation of spatial and temporal variation in oceanic and environmental conditions, may provide an important contribution towards the understanding of recruitment processes necessary for management of commercially important fish species.
Approximate MVA from Markov model of software client/server systems

Stochastic rendezvous networks (SRVN) are performance models for multitasking parallel software with intertask communication via rendezvous (RV). The paper describes an approximation for the arrival instant probabilities for a class of simple client/server SRVN, based on a rigorous analysis of the Markov chain model describing the interference of different client tasks contending for a single server task with FIFO queueing discipline. The algorithm for a simple client/server SRVN is integrated into an iterative decomposition algorithm for complex SRVN models with any number of servers and multi-layered service. Finally, the SRVN model is used to study an example of software bottleneck. <<ETX>>
The M2 Module of the Cys-His-rich Domain (CHRD) of PCSK9 Protein Is Needed for the Extracellular Low-density Lipoprotein Receptor (LDLR) Degradation Pathway*

Background: PCSK9 regulates low-density lipoprotein receptor levels in the liver. The importance of the M1, M2, and M3 modules within the C terminus of PCSK9 is unknown. Results: The M2 module is needed for the extracellular, but not intracellular, activity of PCSK9. Conclusion: The integrity of the M2 module is essential for the extracellular function of PCSK9. Significance: Targeting the M2 module should neutralize circulating PCSK9 and reduce LDL-cholesterol. PCSK9 enhances the cellular degradation of the LDL receptor (LDLR), leading to increased plasma LDL cholesterol. This multidomain protein contains a prosegment, a catalytic domain, a hinge region, and a cysteine-histidine rich domain (CHRD) composed of three tightly packed modules named M1, M2, and M3. The CHRD is required for the activity of PCSK9, but the mechanism behind this remains obscure. To define the contribution of each module to the function of PCSK9, we dissected the CHRD structure. Six PCSK9 deletants were generated by mutagenesis, corresponding to the deletion of only one (ΔM1, ΔM2, ΔM3) or two (ΔM12, ΔM13, ΔM23) modules. Transfection of HEK293 cells showed that all deletants were well processed and expressed compared with the parent PCSK9 but that only those lacking the M2 module were secreted. HepG2 cells lacking endogenous PCSK9 (HepG2/shPCSK9) were used for the functional analysis of the extracellular or intracellular activity of PCSK9 and its deletants. To analyze the ability of the deletants to enhance the LDLR degradation by the intracellular pathway, cellular expressions revealed that only the ΔM2 deletant retains a comparable total LDLR-degrading activity to full-length PCSK9. To probe the extracellular pathway, HepG2/shPCSK9 cells were incubated with conditioned media from transfected HEK293 or HepG2/shPCSK9 cells, and cell surface LDLR levels were analyzed by FACS. The results showed no activity of any secreted deletant compared with PCSK9. Thus, although M2 is dispensable for secretion, its presence is required for the extracellular activity of PCSK9 on cell surface LDLR.
Adaptive Fractional PID Controller for Robot Manipulator

A Fractional adaptive PID (FPID) controller for a robot manipulator will be proposed. The PID parameters have been optimized by Genetic algorithm. The proposed controller is found robust by means of simulation in a tracking job. The validity of the proposed controller is shown by simulation of two-link robot manipulator. The result then is compared with integer type adaptive PID controller. It is found that when error signals in the learning stage are bounded, the trajectory of the robot converges to the desired one asymptotically.
Participative design of participation structures: a general approach and some risk management case studies

Organising participation of multiple stakeholders is nowadays a widespread request in decision processes, especially for organisations managing environmental risks. Therefore, analysts delivering decision support are expected to provide decision makers with scientifically sound and practically realisable approaches regarding this issue. One of the main challenges in dealing with participation is the definition of the organisation, the so called participative structure, through which stakeholders will contribute and interact during the decision process. Who should participate when and according to which rules are the main questions to be answered. Stakes associated to this challenge are of extreme importance for decision makers since decision legitimacy and acceptance strongly relies on the ability to demonstrate a real transparency and information disclosure during the whole decision process. This paper proposes the iterative comparison approach as a new and original frame to be used by an analyst supporting a client dealing with such questions. Through an unambiguous definition of cognitive artefacts to be constructed when designing participative structures, this paper provides a clear framework that organises an analyst intervention in participative contexts. Furthermore, it offers the opportunity to design tailored participative structures that integrate context specificities in one hand, and satisfies quality criteria being fairness, competence and efficiency on the other hand.
Construction Conceptual Cost Estimates Using Support Vector Machine

Conceptual cost estimate plays an essential role in project feasibility study. In practice, it is performed based on estimator's experience. However, due to the inaccuracy of cost estimate, budgeting and cost control are planned and executed inefficiently. Support Vector Machines (SVMs), an Artificial Intelligent technique, is used to conduct the construction cost estimate. The algorithms of SVMs solve a convex optimization problem in a relative short time with satisfied accurate solution. Applying SVMs, the construction conceptual cost estimate model is developed for owners and planners to predict the construction cost of a project. The impact factors of cost estimate are identified through literature review and interview with experts. The cost data of 29 construction projects are used as training cases. Based on the training results, the average prediction error is less than 10% and the computation time is less than 5 minutes. The error is satisfied for the conceptual cost estimate of a project during the planning and conceptual design phase. Case studies show SVMs can efficiently and accurately assist planners to predict the construction cost. cost based on their experiences. Nevertheless, building cost is effected by numerous factors. Some of these factors are full of uncertainty such as geological property and decorative class. Due to such complex and uncertain evaluation process, estimators evaluate building cost using a simple linear manner cannot accurately evaluate the costs. As a result, present building cost estimates are rough. Hsieh(2002) employs the Evolutionary Fuzzy Neural Inference Model (EFNIM) to develop an evolutionary construction conceptual cost estimate model. In the model, Genetic Algorithms are primarily used for optimization; Fuzzy Logic for representing uncertainty and approximate reasoning; and Neural Networks for fuzzy input-output mapping. However the computation run time to search optimal solution takes very long. In order to reduce run time, this study using Support Vector Machine (SVM) to estimate construction cost. The remainder of the paper is organized as follows: In section 2, we introduce Neural Networks (NNs) and Evolutionary Fuzzy Neural Inference Model (EFNIM). In section 3, We define the regression problem and present our approach using SVMs. In section 4 this study compares prediction accuracy and required effort of the SVMs with EFNIM and NNs. Finally in section 5, we conclude and discuss avenues for future work.