Miracle-dz/UniFAR-FTUs huggingface dataset:
P-glycoprotein Modulates Morphine Uptake into the CNS: A Role for the Non-steroidal Anti-inflammatory Drug Diclofenac

Our laboratory has previously demonstrated that peripheral inflammatory pain (PIP), induced by subcutaneous plantar injection of λ-carrageenan, results in increased expression and activity of the ATP-dependent efflux transporter P-glycoprotein (P-gp) that is endogenously expressed at the blood-brain barrier (BBB). The result of increased P-gp functional expression was a significant reduction in CNS uptake of morphine and, subsequently, reduced morphine analgesic efficacy. A major concern in the treatment of acute pain/inflammation is the potential for drug-drug interactions resulting from P-gp induction by therapeutic agents co-administered with opioids. Such effects on P-gp activity can profoundly modulate CNS distribution of opioid analgesics and alter analgesic efficacy. In this study, we examined the ability of diclofenac, a non-steroidal anti-inflammatory drug (NSAID) that is commonly administered in conjunction with the opioids during pain therapy, to alter BBB transport of morphine via P-gp and whether such changes in P-gp morphine transport could alter morphine analgesic efficacy. Administration of diclofenac reduced paw edema and thermal hyperalgesia in rats subjected to PIP, which is consistent with the known mechanism of action of this NSAID. Western blot analysis demonstrated an increase in P-gp expression in rat brain microvessels not only following PIP induction but also after diclofenac treatment alone. Additionally, in situ brain perfusion studies showed that both PIP and diclofenac treatment alone increased P-gp efflux activity resulting in decreased morphine brain uptake. Critically, morphine analgesia was significantly reduced in animals pretreated with diclofenac (3 h), as compared to animals administered diclofenac and morphine concurrently. These novel findings suggest that administration of diclofenac and P-gp substrate opioids during pain pharmacotherapy may result in a clinically significant drug-drug interaction.
Fgf10 maintains notch activation, stimulates proliferation, and blocks differentiation of pancreatic epithelial cells

The pancreas is an endodermally derived organ that initially appears as a dorsal and ventral protrusion of the primitive gut epithelium. The pancreatic progenitor cells present in these early pancreatic anlagen proliferate and eventually give rise to all pancreatic cell types. The fibroblast growth factor receptor (FGFR) 2b high‐affinity ligand FGF10 has been linked to pancreatic epithelial cell proliferation, and we have shown previously that Notch signalling controls pancreatic cell differentiation by means of lateral inhibition. In the developing pancreas, activated intracellular Notch appears to be required for maintaining cells in the progenitor state, in part by blocking the expression of the pro‐endocrine gene neurogenin 3 (ngn3), and hence endocrine cell differentiation. Here, we show that persistent expression of Fgf10 in the embryonic pancreas of transgenic mice also inhibits pancreatic cell differentiation, while stimulating pancreatic epithelial cell proliferation. We provide evidence that one of the effects of the persistent expression of Fgf10 in the developing pancreas is maintained Notch activation, which results in impaired expression of ngn3 within the pancreatic epithelium. Together, our data suggest a role for FGF10/FGFR2b signalling in regulation of pancreatic cell proliferation and differentiation and that FGF10/FGFR2b signalling affects the Notch‐mediated lateral inhibition pathway. Developmental Dynamics 228:185–193, 2003. © 2003 Wiley‐Liss, Inc.
Arabic Syntactic Trees: from Constituency to Dependency

This research note reports on the work in progress which regards automatic transformation of phrase-structure syntactic trees of Arabic into dependency-driven analytical ones. Guidelines for these descriptions have been developed at the Linguistic Data Consortium, University of Pennsylvania, and at the Faculty of Mathematics and Physics and the Faculty of Arts, Charles University in Prague, respectively.The transformation consists of (i) a recursive function translating the topology of a phrase tree into a corresponding dependency tree, and (ii) a procedure assigning analytical functions to the nodes of the dependency tree.Apart from an outline of the annotation schemes and a deeper insight into these procedures, model application of the transformation is given herein.
Antidepressants and risks of suicide and suicide attempts: a 27-year observational study.

OBJECTIVE The 2007 revision of the black box warning for suicidality with antidepressants states that patients of all ages who initiate antidepressants should be monitored for clinical worsening or suicidality. The objective of this study was to examine the association of antidepressants with suicide attempts and with suicide deaths. METHOD A longitudinal, observational study of mood disorders with prospective assessments for up to 27 years was conducted at 5 US academic medical centers. The study sample included 757 participants who enrolled from 1979 to 1981 during an episode of mania, depression, or schizoaffective disorder, each based on Research Diagnostic Criteria. Unlike randomized controlled clinical trials of antidepressants, the analyses included participants with psychiatric and other medical comorbidity and those receiving acute or maintenance therapy, polypharmacy, or no psychopharmacologic treatment at all. Over follow-up, these participants had 6,716 time periods that were classified as either exposed to an antidepressant or not exposed. Propensity score-adjusted mixed-effects survival analyses were used to examine risk of suicide attempt or suicide, the primary outcome. RESULTS The propensity model showed that antidepressant therapy was significantly more likely when participants' symptom severity was greater (odds ratio [OR] = 1.16; 95% CI, 1.12-1.21; z = 8.22; P < .001) or when it was worsening (OR = 1.69; 95% CI, 1.50-1.89; z = 9.02; P < .001). Quintile-stratified, propensity-adjusted safety analyses using mixed-effects grouped-time survival models indicate that the risk of suicide attempts or suicides was reduced by 20% among participants taking antidepressants (hazard ratio, 0.80; 95% CI, 0.68-0.95; z = -2.54; P = .011). CONCLUSIONS This longitudinal study of a broadly generalizable cohort found that, although those with more severe affective syndromes were more likely to initiate treatment, antidepressants were associated with a significant reduction in the risk of suicidal behavior. Nonetheless, we believe that clinicians must closely monitor patients when an antidepressant is initiated.
Mitigating and Resolving Performance Isolation Issues of PCIe Passthrough and SR-IOV in Multi-Core Virtualization

Performance isolation is a key challenge in virtualized multi-core systems. This thesis shows that performance isolation of PCIe passthrough and Single Root I/O Virtualization (SR-IOV), which is the latest generation of I/O virtualization technology, can be broken with Denial-of-Service attacks from malicious or malfunctioning VMs. The resulting performance isolation issues are comprehensively investigated, and two domain specific solutions for cloud and embedded systems are presented, which mitigate and resolve the problem, respectively.
Acoustic Classification of Bird Species from Syllables : an Empirical Study

In order to automatically extract ecologically useful information from audio recordings of birds, we need fast and accurate algorithms to classify bird sounds. We conduct a large-scale empirical study to evaluate algorithms for classifying bird species from audio using combinations of 3 feature sets (Mel-frequency cepstral coefficients, average spectra, and noise-robust measurements), with 10 classifiers including support vector machines and AdaBoost (with J48), on a 2.49 Gb data set consisting of recordings of 20 species of bird from the Cornell Macaulay library. Using implementations from the Weka machine learning system, Random Forest is always close to AdaBoost and usually more accurate than SVM, while being an order of magnitude faster than both.
Comparative evaluation of accuracy of two electronic apex locators in the presence of various irrigants: An in vitro study

Context: The establishment of appropriate working length is one of the most critical steps in endodontic therapy. Electronic apex locators have been introduced to determine the working length. The development of electronic apex locators has helped make the assessment of the working length more accurate and predictable, along with reduction in treatment time and radiation dose. Objectives: The aim of this study was to compare the efficacy of electronic apex locators after cleansing and shaping of the root canals and whether there was any alteration in accuracy when used in the presence of irrigants. Materials and Methods: Seventy extracted human permanent molars with mature apices were selected. Equal number of maxillary and mandibular permanent molars (35 each) were sectioned at the cemento-enamel junction. Access opening was done and only the mesiobuccal root canal was studied for the purpose of standardization. Electronic working length measurements were taken before and after preparation of the mesiobuccal canal with Root ZX and ProPex II using various irrigants. Statistical Analysis Used: The data were statistically analyzed using a paired t-test at 0.05 level of significance. Results: P-values for actual and final canal lengths for Root ZX employing NaoCl(0.001), CHX(0.006), LA(0.020) and for ProPex II was (0.001) respectively. When the data were compared, results were statistically significant (P < 0.05). Conclusion: Within the limitations of this study Root ZX can be considered to be an accurate electronic apex locator and CHX as irrigant matched more precisely with the actual canal length measurements.
A Novel Inhibitor of Signal Transducers And Activators Of Transcription 3 Activation Is Efficacious Against Established Central Nervous System Melanoma and Inhibits Regulatory T Cells

Purpose: Activation of signal transducers and activators of transcription 3 (STAT3) has been identified as a central mediator of melanoma growth and metastasis. We hypothesized that WP1066, a novel STAT3 blockade agent, has marked antitumor activity, even against the melanoma metastasis to brain, a site typically refractory to therapies. Experimental Design: The antitumor activities and related mechanisms of WP1066 were investigated both in vitro on melanoma cell lines and in vivo on mice with subcutaneously syngeneic melanoma or with intracerebral melanoma tumors. Results: WP1066 achieved an IC50 of 1.6, 2.3, and 1.5 μmol/L against melanoma cell line A375, B16, and B16EGFRvIII, respectively. WP1066 suppressed the phosphorylation of Janus-activated kinase 2 and STAT3 (Tyr705) in these cells. Tumor growth in mice with subcutaneously established syngeneic melanoma was markedly inhibited by WP1066 compared with that in controls. Long-term survival (>78 days) was observed in 80% of mice with established intracerebral syngeneic melanoma treated with 40 mg/kg of WP1066 in contrast to control mice who survived for a median of 15 days. Although WP1066 did not induce immunologic memory or enhance humoral responses to EGFRvIII, this compound reduced the production of immunosuppressive cytokines and chemokines (transforming growth factor-β, RANTES, MCP-1, vascular endothelial growth factor), markedly inhibited natural and inducible Treg proliferation, and significantly increased cytotoxic immune responses of T cells. Conclusions: The antitumor cytotoxic effects of WP1066 and its ability to induce antitumor immune responses suggest that this compound has potential for the effective treatment of melanoma metastatic to brain.
Dopamine D3 receptor‐preferring agonists increase dendrite arborization of mesencephalic dopaminergic neurons via extracellular signal‐regulated kinase phosphorylation

Clinical improvements in Parkinson’s disease produced by dopamine D3 receptor‐preferring agonists have been related to their neuroprotective actions and, more recently, to their neuroregenerative properties. However, it is unclear whether dopamine agonists produce their neurotrophic effects by acting directly on receptors expressed by the mesencephalic dopaminergic neurons or indirectly on receptors expressed by astrocytes, via release of neurotrophic factors. In this study, we investigated the effects of the dopamine D3 receptor‐preferring agonists quinpirole and 7‐hydroxy‐N,N‐di‐propyl‐2‐aminotetralin (7‐OH‐DPAT), as well as of the indirect agonist amphetamine, on dopaminergic neurons identified by tyrosine hydroxylase immunoreactivity (TH‐IR). Experiments were performed on neuronal‐enriched primary cultures containing less than 0.5% of astrocytes prepared from the mouse embryo mesencephalon. After 3 days of incubation, both quinpirole (1–10 μm) and 7‐OH‐DPAT (5–500 nm) dose‐dependently increased the maximal dendrite length (P < 0.001), number of primary dendrites (P < 0.01) and [3H]dopamine uptake (P < 0.01) of TH‐IR‐positive mesencephalic neurons. Similar effects were observed with 10 μm amphetamine. All neurotrophic effects were blocked by the unselective D2/D3 receptor antagonist sulpiride (5 μm) and by the selective D3 receptor antagonist SB‐277011‐A at a low dose (50 nm). Quinpirole and 7‐OH‐DPAT also increased the phosphorylation of extracellular signal‐regulated kinase (ERK) within minutes, an effect blocked by pretreatment with SB‐277011‐A. Inhibition of the D2/D3 receptor signalling pathway to ERK was obtained with PD98059, GF109203 or LY294002, resulting in blockade of neurotrophic effects. These data suggest that dopamine agonists increase dendritic arborizations of mesencephalic dopaminergic neurons via a direct effect on D2/D3 receptors, preferentially involving D3 receptor‐dependent neurotransmission.
A Method of Network Topology Visualization Based on SNMP

As the foundation of network management technology, Network topology has been always the research hotspot which reflects the basic characteristic of a network, so from its topology, you can figure out the bottleneck and hidden security problems of a network easily and quickly. The technology of network topology visualization is such a technique that it researches on network topology by discovering, monitoring and displaying it. A network topology visualization system which is based on this technology can help network manager realize and manage the network more convenient. In this paper, we will mainly introduce two popular algorithms--network topology discovery algorithm on the base of SNMP protocol and network topology discovery algorithm on the base of ICMP protocol. Combining with the practical environment of the target network which the system will run on, we design a more suitable program for this network. We firstly research on the structure of network's topology and its model combining with the feature of the target network, and then make use of Flash technology which shows huge advantages on graphic processing and portability, further more its Action Script programming language is very suitable for dynamic graphical development. Thus in this paper, Flash Action Script technology will be used in the development of system's user interface after we solved the difficulties of dynamic interaction between Flash and database, real-time problems.
older exponent spectra for human gait

The stride interval time series in normal human gait is not strictly constant, but 2uctuates from step to step in a complex manner. More precisely, it has been shown that the control process for human gait is a fractal random phenomenon, that is, one with a long-term memory. Herein we study the H older exponent spectra for the slow, normal and fast gaits of 10 young healthy men in both free and metronomically triggered conditions and establish that the stride interval time series is more complex than a monofractal phenomenon. A slightly multifractal and non-stationary time series under the three di5erent gait conditions emerges. c © 2003 Elsevier B.V. All rights reserved. PACS: 87.18. Sn; 05.45. −a; 05.45. Df; 87.17. Nn
The early-adopter graph and its application to web-page recommendation

In this paper we present a novel graph-based data abstraction for modeling the browsing behavior of web users. The objective is to identify users who discover interesting pages before others. We call these users early adopters. By tracking the browsing activity of early adopters we can identify new interesting pages early, and recommend these pages to similar users. We focus on news and blog pages, which are more dynamic in nature and more appropriate for recommendation. Our proposed model is called early-adopter graph. In this graph, nodes represent users and a directed arc between users u and v expresses the fact that u and v visit similar pages and, in particular, that user u tends to visit those pages before user v. The weight of the edge is the degree to which the temporal rule "v visits a page before v" holds. Based on the early-adopter graph, we build a recommendation system for news and blog pages, which outperforms other out-of-the-shelf recommendation systems based on collaborative filtering.
Image Recognition Processor based on Morphological Associative Memories

In this paper, the description of an image recognition processor based on morphological associative memories (MAM) is presented. The combination of the MAM features with its implementation in a programmable logic device grants to the system high speeds of processing, high immunity to the present noise in the images and great capacity of storage; these features make of our proposal a robust system and ideal to work in applications with autonomous real time systems. The described processor, with aid of a binary process of the image, realizing the filter functions, and the use of morphological heteroassociative memories min demonstrated a high performance in the recognition of images corrupted with diverse types of noises.
Finite element analysis on longitudinal and radial functionally graded femoral prosthesis

This study focused on developing a 3D finite element model of functionally graded femoral prostheses to decrease stress shielding and to improve total hip replacement performance. The mechanical properties of the modeled functionally graded femoral prostheses were adjusted in the sagittal and transverse planes by changing the volume fraction gradient exponent. Prostheses with material changes in the sagittal and transverse planes were considered longitudinal and radial prostheses, respectively. The effects of cemented and noncemented implantation methods were also considered in this study. Strain energy and von Mises stresses were determined at the femoral proximal metaphysis and interfaces of the implanted femur components, respectively. Results demonstrated that the strain energy increased proportionally with increasing volume fraction gradient exponent, whereas the interface stresses decreased on the prostheses surfaces. A limited increase was also observed at the surfaces of the bone and cement. The periprosthetic femur with a noncemented prosthesis exhibited higher strain energy than with a cemented prosthesis. Radial prostheses implantation displayed more strain energy than longitudinal prostheses implantation in the femoral proximal part. Functionally graded materials also increased strain energy and exhibited promising potentials as substitutes of conventional materials to decrease stress shielding and to enhance total hip replacement lifespan. Copyright © 2013 John Wiley & Sons, Ltd.
Oral health-related quality of life among HIV-infected and at-risk women.

OBJECTIVES Objective measures of dental diseases reflect only their clinical end-point. There is a need to use multidimensional measures of diseases that consider their psychosocial aspects and functional impact. The aim of this study is to compare the oral health-related quality of life (OHRQOL) between a group of HIV-infected women and a similar group of at-risk HIV-uninfected women, and to investigate the role of potential confounding clinical oral health and behavioral factors. METHODS Our sample included HIV-infected women (87%) and women at risk for HIV infection (13%) followed up for 5.5 years. OHRQOL was measured using the short version of the Oral Health Impact Profile (OHIP-14), which is a validated and reliable instrument. RESULTS HIV-infected women averaged 10% poorer OHRQOL than HIV-uninfected women; this difference was not apparent after adjusting for the number of study visits attended and significant behavioral and clinical oral health factors. The OHRQOL was inversely related to dental and periodontal diseases and to smoking and freebase cocaine use; these relationships were not confounded by HIV status. CONCLUSIONS The study identified specific clinical and behavioral factors where dental professionals can intervene to possibly improve the OHRQOL of HIV-infected or at-risk HIV-uninfected women.
A study of end-to-end web access failures

We present a study of end-to-end web access failures in the Internet. Part of our characterization of failures is based on directly observable end-to-end information. We also present novel analyses that reveal aspects of end-to-end failures that would be hard to discern otherwise. First, we combine end-to-end failure observations across a large number of clients to classify failures as server-related or client-related. Second, we correlate failures attributed to a client or server with BGP churn for the corresponding IP address prefix(es), to shed light on the end-to-end impact of BGP instability. Our study is based on failure observations during a month-long experiment involving 134 client hosts (across Planet-Lab, commercial dialup and broadband ISPs, and a corporate network) repeatedly accessing 80 websites. We find that the median failure rate of web accesses is about 1.5%, which is non-negligible. About 34--42% of the web access failures are due to DNS problems, primarily due to the inability of the client to connect to its local DNS server. The majority of the remaining failures are due to TCP connection establishment failures. Also, by correlating failure observations across clients and servers, we find that server-side problems are the dominant cause of TCP connection failures.
Optimal Transmission Switching

In this paper, we formulate the problem of finding an optimal generation dispatch and transmission topology to meet a specific inflexible load as a mixed integer program. Our model is a mixed-integer linear program because it employs binary variables to represent the state of the equipment and linear relationships to describe the physical system. We find that on the standard 118-bus IEEE test case a savings of 25% in system dispatch cost can be achieved.