Miracle-dz/UniFAR-FTUs huggingface dataset:
The Multi-kinase Inhibitor Debio 0617B Reduces Maintenance and Self-renewal of Primary Human AML CD34+ Stem/Progenitor Cells

Acute myelogenous leukemia (AML) is initiated and maintained by leukemia stem cells (LSC). LSCs are therapy-resistant, cause relapse, and represent a major obstacle for the cure of AML. Resistance to therapy is often mediated by aberrant tyrosine kinase (TK) activation. These TKs primarily activate downstream signaling via STAT3/STAT5. In this study, we analyzed the potential to therapeutically target aberrant TK signaling and to eliminate LSCs via the multi-TK inhibitor Debio 0617B. Debio 0617B has a unique profile targeting key kinases upstream of STAT3/STAT5 signaling such as JAK, SRC, ABL, and class III/V receptor TKs. We demonstrate that expression of phospho-STAT3 (pSTAT3) in AML blasts is an independent prognostic factor for overall survival. Furthermore, phospho-STAT5 (pSTAT5) signaling is increased in primary CD34+ AML stem/progenitors. STAT3/STAT5 activation depends on tyrosine phosphorylation, mediated by several upstream TKs. Inhibition of single upstream TKs did not eliminate LSCs. In contrast, the multi-TK inhibitor Debio 0617B reduced maintenance and self-renewal of primary human AML CD34+ stem/progenitor cells in vitro and in xenotransplantation experiments resulting in long-term elimination of human LSCs and leukemia. Therefore, inhibition of multiple TKs upstream of STAT3/5 may result in sustained therapeutic efficacy of targeted therapy in AML and prevent relapses. Mol Cancer Ther; 16(8); 1497–510. ©2017 AACR.
Anatomy, Biochemistry, and Physiology of Articular Cartilage

Huber M, Trattnig S, Lintner F. Anatomy, biochemistry, and physiology of articular cartilage. Invest Radiol 2000;35:573–580. ABSTRACT.Articular cartilage serves as a load-bearing elastic material that is responsible for the frictionless movement of the surfaces of articulating joints. Its ability to undergo reversible deformation depends on its structural organization, including the specific arrangement of the matrix macromolecules and the chondrocytes. Interactions between the matrix and chondrocytes are responsible for the biological and mechanical properties of articular cartilage and enable it to respond by effecting a balance between anabolism and catabolism as well as continual internal remodeling. Age-related changes in the function of chondrocytes may contribute to the initiation and progression of osteoarthritis.
Mitochondrial Phylogeography of the Vegetable Pest Liriomyza trifolii (Diptera: Agromyzidae): Diverged Clades and Invasive Populations

Abstract The leafmining fly Liriomyza trifolii (Burgess) (Diptera: Agromyzidae) is an important pest of vegetable and cut-flower crops. In recent decades, this species has become invasive, spreading from the Americas to the rest of the world. Despite substantial losses caused by Liriomyza leafminers, the systematics of these flies has remained poorly understood because of their small size and morphological homogeneity. Previous molecular research on other polyphagous Liriomyza pests has suggested that cryptic species may be present. Here, we use mitochondrial cytochrome oxidase I sequence variation to investigate phylogeographic structure within L. trifolii. Our results indicate that L. trifolii harbors distinct phylogenetic clades, suggesting the presence of cryptic species. There is also evidence of a recently derived, highly specialized pepper (Capsicum spp., Solanaceae)-feeding population within L. trifolii that may represent a host race or even a distinct species. Introduced populations from various locations contained a highly restricted subset of the mitochondrial variation present within L. trifolii, suggesting one or more bottlenecks during colonization.
Warming, photoperiods, and tree phenology.

C. Korner and D. Basler (“Phenology under global warming,” Perspectives, 19 March, p. [1461][1]) suggest that because of photoperiodic constraints, observed effects of temperature on spring life-cycle events cannot be extrapolated to future temperature conditions. However, no study has
Oscillatory motion application of tubular linear permanent magnet machine

Tubular linear permanent magnet machine with gas springs using for drilling applications is presented. This machine has the advantage of directly transmitting electric power to rock without gears. In this paper, mathematical model with hammering effect is established and dynamic process of oscillatory motion is analyzed. Simulation results show that this machine is suitable for drilling application.
Silicone rubber as aortic grafting material.

The introduction of Vinyon-N cloth by Voorhees, Jaretzki, and Blakemore in 1952 opened a new era in vascular grafting. 1 A follow-up study by the same group 2 reported 18 clinical cases of arteriosclerotic aneurysm resection, with replacement by Vinyon-N cloth. The material is easy to suture, strong, readily obtainable, and relatively inexpensive. Grafts fashioned from Vinyon-N cloth maintain a patency comparable with that of aortic homografts. Other plastic cloths, such as Dacron, nylon, and Orlon, 3 have been used recently, with considerable success. Much research is being done at many centers in an effort to determine the best plastic cloth and the most favorable method of application. Despite these enthusiastic reports, there are certain inherent disadvantages of all such plastic cloths being used for vascular grafts at present. None is truly elastic, and the ultimate fate of all is to become incased in a fibrous restraining capsule. Although even
Coincidence Detection of Double-Layered Current-Biased Kinetic Inductance Detectors Using a 20 ps Pulsed Laser

We demonstrated the operation of double-layered current-biased kinetic inductance detectors (CB-KIDs) made of Nb by irradiating pulsed laser. A Nb-based CB-KID operates at temperatures appreciably lower than a superconducting transition temperature Tc because it senses a time derivative of kinetic inductance dLk/dt in a Nb meanderline. We fabricated double-layered meanderlines to detect a coordinate. Two meanderlines of 40 nm thickness and 1 μm line width have an orthogonal configuration with each other. We deposited a 10B layer of thickness 300 nm to insulate between two Nb meanderlines. The total area of the meanderlines is 10.4 mm × 10.4 mm at the center of chip with the size of 22 mm × 22 mm. The pulse width and wavelength of pulsed laser is 20 ps and 1547 nm, respectively. We obtained the output signals from two CB-KIDs simultaneously by irradiating a focused pulsed laser. The response time is a few tens ns, and operating margin is 300-350 μA.
Signal Thresholds and Modular Synergy During Expression of Costimulatory Molecules in B Lymphocytes

We analyzed intracellular pathways modulating surface densities of CD80 and CD86 in B cells activated through ligation of the Ag receptor, and the adhesion molecule CD54. Whereas B cell Ag receptor (BCR) cross-linking alone stimulated increased expression of CD86, up-regulation of CD80 required dual stimulation with anti-IgM and anti-CD54. The principal downstream component contributed by BCR signaling, toward both CD80 and CD86 induction, was the elevated concentration of free cytoplasmic Ca2+, recruited by way of capacitative influx. This alone was sufficient to generate an increase in CD86 levels. However, CD80 enhancement required the concerted action of both intracellular Ca2+ concentration and CD54-initiated pathways. The nexus between anti-IgM and anti-CD54 stimulation, in the context of CD80 regulation, was identified to involve a self-propagating process of sequential synergy. The first step involved amplified accumulation of intracellular cAMP, as a result of cross-talk between BCR-mobilized Ca2+ and CD54-derived signals. This then facilitated a second synergistic interaction between Ca2+ and cAMP, culminating in CD80 expression. Our findings of distinct signal transducer requirements, with the added consequences of cross-talk, offers an explanation for variable modulation of costimulatory molecule expression in response to diverse physiological stimuli. Importantly, these results also reveal how concentration threshold barriers for recruitment of individual second messengers can be overcome by constructive convergence of signaling modules.
Activation of the Abl Tyrosine Kinase in Vivo by Src Homology 3 Domains from the Src Homology 2/Src Homology 3 Adaptor Nck*

The nonreceptor tyrosine kinase c-Abl is tightly regulated in vivo, but the mechanisms that normally repress its activity are not well understood. We find that a construct encoding the first two Src homology 3 (SH3) domains of the Src homology 2/SH3 adaptor protein Nck can activate c-Abl in human 293T cells. A myristoylated Nck SH3 domain construct, which is expected to localize to membranes, potently activated Abl when expressed at low levels. An unmyristoylated Nck SH3 domain construct, which localizes to the cytosol and nucleus, also activated Abl but only at high levels of expression. Activation by both myristoylated and unmyristoylated Nck constructs required the C terminus of Abl; a C-terminally truncated form of Abl was not activated, although this construct could still be activated by deletion of its SH3 domain. Activation did not require the major binding sites in the Abl C terminus for Nck SH3 domains, however, suggesting that the mechanism of activation does not require direct binding to the C terminus. Activation of c-Abl by Nck SH3 domains provides a robust experimental system for analyzing the mechanisms that normally repress Abl activity and how that normal regulation can be perturbed.
An Intelligent Building Occupancy Detection System Based on Sparse Auto-Encoder

Energy saving in buildings has attracted many researchers attention. One of the research topics is occupancy detection for each room to automatically control airconditioner, light, heating, etc. by monitoring the temperature, humidity, light, and co2 using the corresponding sensors. For existing data analysis, traditional regression methods such as CART, RF, LDA are often used to predict the occupancy status after the data are collected. However, traditional methods have disadvantages of difficult adaptation to large data sets and bad generalization. In this paper, deep learning technology is used to perform occupancy detection. We construct sparse auto-encoder to learn features from data, then the learned features are input to Softmax, SVM and Liblinear classifiers to detect the room occupancy status. Experiments and results show the efficiency of the proposed algorithm whose detection accuracy outperforms that of benchmark project. Moreover, proposed algorithm has very low computation overhead which facilitates the real-time detection.
Current status of preemptive analgesia.

PURPOSE OF REVIEW The controversy over preemptive analgesia continues unabated, with studies both supporting and refuting its efficacy. The timing of an analgesic intervention and presence of a placebo control may have significant impact on the interpretation of results and may have led to the premature conclusion that preemptive analgesia is of limited clinical utility. A review of the recent literature using strict definitions of preemptive and preventive analgesia is required in order to clarify the broader issue of the benefits of perioperative analgesia. RECENT FINDINGS A total of 27 studies, published from April 2001 to April 2002, were found to evaluate preemptive (n = 12) or preventive analgesia (n = 15). Evidence for a benefit of preventive analgesia was strong, with 60% of studies finding reduced pain or analgesic consumption beyond the clinical duration of action of the analgesic intervention. Evidence for a benefit of preemptive analgesia was equivocal, with 41.7% of studies demonstrating that preincisional treatment reduces pain or analgesic consumption to a greater extent than does postincisional treatment. SUMMARY Studies that used a preventive design had a greater likelihood of finding a beneficial effect. The application of preventive perioperative analgesia (not necessarily preincisional) is associated with a significant reduction in pain beyond the clinical duration of action of the analgesic agent, in particular for the N-methyl-D-aspartate antagonists. The classical definition of preemptive analgesia should be abandoned in favor of preventive analgesia. This will broaden the scope of inquiry from a narrow focus on preincisional versus postincisional interventions to one that aims to minimize postoperative pain and analgesic requirements by reducing peripheral and central sensitization arising from noxious preoperative, intraoperative and postoperative inputs.
Analytical Modeling of the Effect of Nonlinear Switching Transition Curves on Harmonic Distortion in Class D Audio Amplifiers

Practical switching transition times typically occupy less than one percent of the switching period in class D audio amplifiers. These transitions, however, are a very nonlinear function of current, which give rise to significant levels of distortion. This paper presents a method for determining the effect of nonlinear switching transition curves on harmonic distortion within half-bridge and full-bridge topologies, taking into account the interaction between the various dominant pulse-timing errors. An accurate analytical model, based on the well-established double Fourier series method of analysis, for determining the effect on harmonic distortion is introduced. The analytical model is accompanied by an equivalent simulation model using an existing strategy, and the results are verified experimentally.
Associations of medical comorbidity, psychosis, pain, and capacity with psychiatric hospital length of stay in geriatric inpatients with and without dementia

ABSTRACT Background: Geriatric psychiatry hospital beds are a limited resource. Our aim was to determine predictors of hospital length of stay (LOS) for geriatric patients with dementia admitted to inpatient psychiatric beds. Methods: Admission and discharge data from a large urban mental health center, from 2005 to 2010 inclusive, were retrospectively analyzed. Using the resident assessment instrument - mental health (RAI-MH), an assessment that is used to collect demographic and clinical information within 72 hours of hospital admission, 169 geriatric patients with dementia were compared with 308 geriatric patients without dementia. Predictors of hospital LOS were determined using a series of general linear models. Results: A diagnosis of dementia did not predict a longer LOS in this geriatric psychiatry inpatient population. The presence of multiple medical co-morbidities had an inverse relationship to length of hospital LOS – a greater number of co-morbidities predicted a shorter hospital LOS in the group of geriatric patients who had dementia compared to the without dementia study group. The presence of incapacity and positive psychotic symptoms predicted longer hospital LOS, irrespective of admission group (patients with dementia compared with those without). Conversely, pain on admission predicted shorter hospital LOS. Conclusions: Specific clinical characteristics generally determined at the time of admission are predictive of hospital LOS in geriatric psychiatry inpatients. Addressing these factors early on during admission and in the community may result in shorter hospital LOS and more optimal use of resources.
Non-Destructive Examination of Interfacial Debonding in Dental Composite Restorations Using Acoustic Emission

© 2012 Li et al., licensee InTech. This is an open access chapter distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Non-Destructive Examination of Interfacial Debonding in Dental Composite Restorations Using Acoustic Emission
Pharmacokinetics and Tolerability of a New Manidipine and Delapril Fixed Oral Combination in Young and Elderly Subjects

Summary Objectives: The aim of the present study was to compare the pharmacokinetic and pharmacodynamic properties of a fixed combination tablet containing 10 mg of manidipine dihydrochloride (CAS 89226-75-5), a calcium channel antagonist, and 30 mg of delapril hydrochloride (CAS 83435-67-0), an angiotensin converting enzyme (ACE) inhibitor, during once daily repeated dosing in young and elderly subjects and to assess the bioequivalence of the fixed combination tablet and the single ingredient tablets taken simultaneously in young healthy subjects after a single dose administration. Methods: Eighteen young healthy male volunteers received a single oral dose of 10 mg manidipine and 30 mg delapril as two separate tablets or a fixed combination tablet, followed by a week of once daily dosing with the fixed combination. Eight male and eight female elderly volunteers also received a week of once daily dosing with the fixed combination. Blood samples were collected during 24 h on the first and last treatment day for plasma determination of manidipine, delapril and their main metabolites, using specific LC-MS/MS methods. Blood pressure and heart rate were also recorded during 24 h. Results: Bioequivalence was strictly demonstrated between the extemporaneous and the fixed combination tablet after single dose administration. At steady-state in young subjects, manidipine AUC and Cmax were lower (-8 and −12 %) and t1⁄2 was longer (+ 45 %), while delapril and metabolites were little affected as compared to single dose. In elderly subjects, manidipine Cmax was 4 % lower than after single dose, AUC was 13 % higher, and t1⁄2 was increased 2.4-fold. For delapril and active metabolites, Cmax and AUC increased modestly. Blood pressure and heart rate versus time profiles after single dose and at steady-state were almost superimposable. In elderly compared to young subjects at steady-state, peak concentrations of manidipine and delapril changed by + 35 % and −15 % while AUCs increased by + 70 % and + 9.7 %. Conclusion: The fixed combination tablet of 10 mg manidipine and 30 mg delapril is bioequivalent to mono-ingredient tablets. At steady-state, the pharmacokinetic and pharmacodynamic profiles in young and elderly subjects undergo minor changes and indicate negligible accumulation. Drug exposure is higher in elderly subjects.
An efficient route generation algorithm for distributed multi-layered network

Minimizing the cost of routing calculations is crucial for scaling up networks. This paper outlines a method for computing the shortest path in a hierarchical network by applying Dijkstra's (1959) algorithm to various subsets in an entire graph. In the proposed method, the routing calculations increase linearly with the number of layers, while they increase as a square of the number of layers in the existing method.
Conflict-handling mode scores of three crews before and after a 264-day spaceflight simulation.

INTRODUCTION In both the Russian and U.S. space programs, crew safety and mission success have at times been jeopardized by critical incidents related to psychological, behavioral, and interpersonal aspects of crew performance. The modes used for handling interpersonal conflict may play a key role in such situations. METHODS This study analyzed conflict-handling modes of three crews of four people each before and after a 264-d spaceflight simulation that was conducted in Russia in 1999-2000. Conflict was defined as a situation in which the concerns of two or more individuals appeared to be incompatible. Participants were assessed using the Thomas-Kilmann Conflict Mode Instrument, which uses 30 forced-choice items to produce scores for five modes of conflict handling. Results were compared to norms developed using managers at middle and upper levels of business and government. RESULTS Both before and after isolation, average scores for all crews were above 75% for Accommodating, below 25% for Collaborating, and within the middle 50% for Competing, Avoiding, and Compromising. Statistical analyses showed no significant difference between the crews and no statistically significant shift from pre- to post-isolation. DISCUSSION A crew predisposition to use Accommodating most and Collaborating least may be practical in experimental settings, but is less likely to be useful in resolving conflicts within or between crews on actual flights. Given that interpersonal conflicts exist in any environment, crews in future space missions might benefit from training in conflict management skills.
Does Antitrust Have a Role to Play in Regulating Big Data?

The collection of user data online has seen enormous growth in recent years. Consumers have benefitted from the growth through an increase in free or heavily subsidized services, better quality offerings, and rapid innovation. At the same time, the debate about Big Data, and what it really means for consumers and competition, has grown louder. Many have focused on whether Big Data even presents an antitrust issue, and whether and how harms resulting from Big Data should be analyzed and remedied under the antitrust laws. The academic literature, however, has somewhat lagged behind the debate, and a closer inspection of existing scholarly works reveals a dearth of thorough study of the issue. Commentators generally split into two camps: one in favor of more proactive antitrust enforcement in the Big Data realm, and one opposing such intervention, considering antitrust inappropriate for regulation of Big Data. The academic case for the former has not, as yet, been fully developed, and is relatively light at present. Meanwhile, policy-focused work by academics practitioners in this arena suggests that antitrust intervention in Big Data would be premature and misguided, especially considering the myriad pro-competitive benefits offered by Big Data.In this handbook chapter, we review the scholarly work on the implications of Big Data on competition, and consider the potential role of antitrust in the regulation of Big Data. Part I provides an overview of current, scarce, academic literature specifically addressing the role of antitrust in Big Data issues. Parts II and III delve into the policy issues surrounding Big Data and whether it poses a risk to competition that warrants antitrust intervention. Part II details the ways in which Big Data may prove pro-competitive while Part III reviews and critiques the suggested potential harms to competition from Big Data. Part IV discusses the suitability of antitrust as the institutional choice for Big Data issues, and Part V concludes that, at present, antitrust is ill suited as the institutional choice. This conclusion is further born by the fact that thus far there have been no cases in the United States or Europe that have found Big Data itself to be a basis for a theory of harm on antitrust grounds for mergers or conduct cases. Further, the scholarly case for such harm has not yet been adequately established.
A New Method of Dimensional Analysis ( Fluid Mechanics Applications )

A new simple method of dimensional analysis is developed. The new method can handle any number of variables. This method needs only finding the inverse of the repeated variables’ matrix. Since A-1 can be obtained numerically, this method can be easily programmed, and thus time is saved and the error that may occur at any step of hand calculations is avoided. Additionally, the combinations are used for the first time in the dimensional analysis subject. The procedure of the new method and the use of combinations in the dimensional analysis are illustrated through four different examples, which represent all the possible problems in the dimensional analysis