Miracle-dz/UniFAR-FTUs huggingface dataset:
Small Maf proteins heterodimerize with Fos and may act as competitive repressors of the NF-E2 transcription factor

The maf oncogene encodes a bZip nuclear protein which recognizes sequences related to an AP-1 site either as a homodimer or as heterodimers with Fos and Jun. We describe here a novel maf-related gene, mafG, which shows extensive homology with two other maf-related genes, mafK and mafF. These three maf-related genes encode small basic-leucine zipper proteins lacking the trans-activator domain of v-Maf. Bacterially expressed small Maf proteins bind to DNA as homodimers with a sequence recognition profile that is virtually identical to that of v-Maf. As we have previously described, the three small Maf proteins also dimerize with the large subunit of NF-E2 (p45) to form an erythroid cell-specific transcription factor, NF-E2, which has distinct DNA-binding specificity. This study shows that the small Maf proteins can also dimerize among themselves and with Fos and a newly identified p45-related molecule (Ech) but not with v-Maf or Jun. Although the small Maf proteins preferentially recognize the consensus NF-E2 sequence as heterodimers with either NF-E2 p45, Ech, or Fos, these heterodimers seemed to be different in their transactivation potentials. Coexpression of Fos and small Mafs could not activate a promoter with tandem repeats of the NF-E2 site. These results raise the possibility that tissue-specific gene expression and differentiation of erythroid cells are regulated by competition among Fos, NF-E2 p45, and Ech for small Maf proteins and for binding sites.
TEMPORAL CAUSALITY BETWEEN POPULATION AND INCOME IN TURKEY: AN ARDL BOUNDS TESTING APPROACH

Bu calisma Turkiye'de, nufus ve kisi basina ekonomik buyume arasindaki nedensellik iliskisini arastirmayi amaclamaktadir. ARDL esbutunlesme yaklasimi kullanilarak, uzun donemde kisi basina ekonomik buyume ve nufus arasinda cift yonlu nedensellik iliskisi kanitlanmistir.
Controller design and experimental approach on the dynamic walking on the spot in planar biped robot

This paper addresses the controller design of dynamic walking on the spot and describes the experimental approach in a 5-DOF under-actuated planar biped robot. The angle and the angular velocity of the robot with respect to the ground were measured at a specific time, and the next landing position of a swing leg was controlled for the dynamically stable walking on the spot. The next landing position was determined by a numerical procedure, as walking is composed of a single support phase and an impact phase. The validity of the control method was shown by a simulation using a mathematical model regarding various initial conditions and via as experimental approach using an actual robot. In the experiment, the planar biped robot successfully walked dynamically on the spot for long time. Given that a real experimental system is different from a mathematical model, the controller is tuned using experimental try and error. In a later project, this control method will be extended for dynamic forward and backward walking.
A comprehensive study on object proposals methods for vehicle detection in aerial images

Detecting vehicles in aerial images is an important task in many applications such as traffic monitoring or screening of large areas. In general, vehicle detection in aerial images is performed by applying classifiers or a cascade of classifiers within a sliding window algorithm. However, detecting vehicles in a real-time system is limited by the huge number of windows to classify, especially in case of varying object scales, aspect ratios or object orientations. To reduce the high number of windows, we propose to apply so called object proposals methods. In recent years, several object proposals methods have been proposed for generating candidate windows in detection frameworks. However, aerial images differ considerably from datasets that are typically used for exploring such methods. To examine the applicability of such methods for aerial images, we evaluate 11 state-of-the-art object proposals methods on the publicly available DLR 3K Munich Vehicle Aerial Image Dataset. First, we manually modified the provided ground truth data to enable comparison to the generated object proposals. To compensate for the differing characteristics of the aerial images, we adapted seven methods by examining different parameter settings and extensions for each method separately. Finally, we demonstrate the potential of such methods for a detection framework for aerial images as significantly fewer candidate windows are generated in comparison to sliding window.
Effects of ovariohysterectomy on canine blood neutrophil respiratory burst: a chemiluminescence study.

OBJECTIVE To examine blood neutrophil counts and luminol-enhanced chemiluminescence (CL) responses in dogs undergoing ovariohysterectomy (OH), premedicated with 2 different drugs. STUDY DESIGN Randomized clinical study. ANIMALS Forty-two healthy client-owned bitches. METHODS Dogs had OH under isoflurane anesthesia with either acepromazine or medetomidine, both in combination with butorphanol, administered as preanesthetic medication. Blood samples were collected when the dog was admitted, at the end of surgery, and the next day (approximately 20 hours after surgery). Blood neutrophils were counted automatically, and neutrophil oxidative activity was assessed by measuring blood CL responses (induced by opsonized zymosan and enhanced by luminol) at 37 degrees C for 40 minutes. RESULTS Number of circulating neutrophils was significantly increased the day after surgery reflected by enhanced blood CL responses. Neutrophil CL, however, was not significantly altered. No significant differences were detected for perioperative Polymorphonuclear neutrophil (PMN) characteristics between the 2 preanesthetic regimens. CONCLUSIONS In conclusion, despite clearly increasing the number of circulating neutrophils, OH did not significantly affect neutrophil respiratory burst, as measured by whole-blood CL responses. CLINICAL RELEVANCE Surgical operation of moderate intensity (e.g., OH) did not significantly alter one of the important immune functions, neutrophil oxidative activity. Further studies are warranted to confirm the significance of this finding, and to assess the value of following this variable in different animal patient populations.
5-hydroxytryptamine (HT)1A receptors and the tail-flick response. II. High efficacy 5-HT1A agonists attenuate morphine-induced antinociception in mice in a competitive-like manner.

This study examined the influence of s.c. administration of 5-hydroxytryptamine (HT)1A agonists upon the antinociceptive action of s.c. injected morphine in tail-flick tests to noxious heat and pressure. The selective 5-HT1A agonist, (+-)-8-hydroxy-diprolaminotetralin HBr (8-OH-DPAT), dose-dependently antagonized morphine-induced antinociception (MIA) without affecting the latency to respond when applied alone. In the presence of increasing doses of 8-OH-DPAT (0.16-0.63 mg/kg), the morphine dose-response curve was shifted progressively in parallel to the right and the maximal effect of morphine was not altered; Schild analysis yielded a slope of close to -1.0. 8-OH-DPAT both prevented and reversed the action of morphine. The action of 8-OH-DPAT was reversible (at 24 hr). In distinction, 8-OH-DPAT neither blocked morphine-induced Straub tail nor precipitated withdrawal in morphine-dependent animals; thus, it lacked opioid-antagonist properties. The antagonism of MIA by 8-OH-DPAT was mimicked by additional drugs acting as high efficacy 5-HT1A agonists: lisuride, 5-methoxy-N,N-dimethyltryptamine hydrogen oxalate, RU 24969 [methoxy-3-(1,2,3.6-tetrahydropyridin-4-yl)-1H-indole] and d-lysergic acid diethylamide. In contrast, the 5-HT1B/1C agonist, TFMPP m-trifluromethylphenylpiperazine HCl, and the 5-HT1C/2 agonist, DOI (+-)-2,5-dimethoxy-4-iodophenyl-2-aminopropane HCI, were ineffective. The putative selective 5-HT1A antagonists, BMY 7378 [(8-[-[4-(2-,ethoxyphenyl)-1-piperazinyl]ethyl]-8-azaspirol[4]- decane-7,9-dione-2-HCL] and spiperone, did not reduce MIA. Indeed, BMY 7378 blocked the ability of 8-OH-DPAT to antagonize MIA. Under the present conditions, agonists and antagonists at adrenergic and dopaminergic receptors did not attenuate MIA. These data show that, over a certain range of doses, the systemic administration of 8-OH-DPAT and other high efficacy 5-HT1A agonists functionally antagonizes the antinociceptive action of systemically applied morphine in a competitive-like manner. It is suggested that 5-HT1A receptors play an important role in the modulation of opioidergic antinociceptive mechanisms.
Age‐dependent reduction of cortical contusion volume by ketones after traumatic brain injury

Although the adult brain primarily metabolizes glucose, the evidence from the starvation literature has demonstrated that the adult brain retains some potential to revert to ketone metabolism. This attribute has been exploited recently to shift the adult brain toward ketone metabolism after traumatic brain injury (TBI), resulting in increased cerebral uptake and oxidation of exogenously administered ketones and improved cerebral energy. The ability to utilize ketones as an alternative substrate decreases with cerebral maturation, suggesting that the younger brain has a greater ability to metabolize this substrate and may be more receptive to this therapy. It was hypothesized that the administration of ketones after TBI in the developing brain will decrease lesion size in an age‐dependent manner. Postnatal day (PND) 17, 35, 45, and 65 rats were placed on either a standard or ketogenic (KG) diet after controlled cortical impact (CCI) injury. PND35 and PND45 KG‐fed animals showed a 58% and 39% reduction in cortical contusion volume, respectively, at 7 days post‐injury. The KG diet had no effect on contusion volume in PND17 and PND65 injured rats. Both PND35 and PND45 KG‐fed groups revealed fewer Fluoro‐Jade–positive cells in the cortex and hippocampus at 6 hr and showed earlier decreases in plasma lactate compared to standard‐fed animals. The age‐dependent ketogenic neuroprotection is likely related to age‐related differences in cerebral metabolism of ketones and suggests that alternative substrate therapy has potential applications for younger head‐injured patients. © 2005 Wiley‐Liss, Inc.
Development and optimization of sulforaphane-loaded nanostructured lipid carriers by the Box-Behnken design for improved oral efficacy against cancer: in vitro, ex vivo and in vivo assessments

Abstract In the present study, sulforaphane (SFN)-loaded nanostructured lipid carriers (NLC) were developed and optimized for improved oral efficacy against cancer. The SFN-loaded NLC formulation was developed by melt emulsification ultrasonication technique and optimized by Box–Behnken statistical design. The optimized SFN-loaded NLC formulation composed of precirol® ATO 5 (solid lipid) and vitamin E (liquid lipid) as lipid phase (3% w/v), poloxamer 188 (1%) and Tween 80 (1%) as surfactant. The mean particle size, polydispersity index, zeta potential, entrapment efficiency (%) and drug loading (%) of optimized SFN-loaded NLC formulation was observed to be 145.38 ± 4.46 nm, 0.181 ± 0.023, −25.12 ± 2.36 mV, 84.94 ± 3.82% and 14.82 ± 3.46%, respectively. In vitro drug release studies showed that the release of SFN from optimized NLC formulation was significantly higher (86.52 ± 5.48%) compared to SFN suspension (38.47 ± 5.52%) up to 24 h. Ex vivo gut permeation studies revealed a very good enhancement in permeation of drug present in the NLC compared to plain SFN solution and were further confirmed by CLSM. MTT assay in different cancer cell lines showed that the optimized SFN-loaded NLC formulation exhibited significantly improved (p < .05) cytotoxicity compared to free SFN solution. SFN-loaded NLC formulation showed significantly improved antioxidant activity compared to free SFN solution. Furthermore, pharmacokinetic study on albino Wistar rats showed 5.04-fold increase in relative oral bioavailability with NLC (p < .05) compared to SFN suspension. Therefore, NLC represents a great potential for improved efficacy of SFN after oral administration.
Benefits and Challenges of Cloud Technologies for 5G Architecture

This paper focuses on the practical implementation of a Cloud-RAN architecture in the context of future 5G systems, with particular emphasis on different aspects of the functional split between the cloud platform and the radio access points. First, we provide a comprehensive overview of implementation aspects and how different hardware options impact the implementation of RAN functionality. We further discuss a virtualized infrastructure which may have a significant impact on how algorithms are implemented, how they interact with each other, and how they can be scaled within the RAN. We also analyze implementation constraints to be considered to provide backwards compatibility with 3GPP LTE; such constraints on the computing platforms result from the RAN requirements in terms of latency and throughput. Finally, the level of flexibility achievable by the proposed architecture is described from a practical point of view.
Global Analysis of Cdk1 Substrate Phosphorylation Sites Provides Insights into Evolution

Cataloging Kinase Targets Protein phosphorylation is a central mechanism in the control of many biological processes (see the Perspective by Collins). It remains a challenge to determine the complete range of substrates and phosphorylation sites altered by a kinase like cyclin-dependent kinase 1 (Cdk1), which controls cell division in yeast. Holt et al. (p. 1682) engineered a strain of yeast to express a modified Cdk1 molecule that could be inhibited by a specific small-molecule inhibitor. The range of Cdk1-dependent phosphorylation was assessed by quantitative mass spectrometry, which revealed many previously uncharacterized substrates for Cdk1. In addition to phosphorylation on serine and threonine residues, which appears to be evolutionarily ancient, tyrosine phosphorylation occurs primarily in multicellular organisms. Tan et al. (p. 1686, published online 9 July) compared the overall presence of tyrosine residues in human proteins (which are frequently phosphorylated) and in yeast proteins (which are not). Loss of tyrosine residues has occurred during evolution, presumably to reduce adventitious tyrosine phosphorylation. The range of sites phosphorylated by a protein kinase in yeast provides clues to the evolution of such regulatory mechanisms. To explore the mechanisms and evolution of cell-cycle control, we analyzed the position and conservation of large numbers of phosphorylation sites for the cyclin-dependent kinase Cdk1 in the budding yeast Saccharomyces cerevisiae. We combined specific chemical inhibition of Cdk1 with quantitative mass spectrometry to identify the positions of 547 phosphorylation sites on 308 Cdk1 substrates in vivo. Comparisons of these substrates with orthologs throughout the ascomycete lineage revealed that the position of most phosphorylation sites is not conserved in evolution; instead, clusters of sites shift position in rapidly evolving disordered regions. We propose that the regulation of protein function by phosphorylation often depends on simple nonspecific mechanisms that disrupt or enhance protein-protein interactions. The gain or loss of phosphorylation sites in rapidly evolving regions could facilitate the evolution of kinase-signaling circuits.
The beneficial effect of L-thyroxine on cardiovascular risk factors, endothelial function, and quality of life in subclinical hypothyroidism: randomized, crossover trial.

CONTEXT Subclinical hypothyroidism (SCH) is defined as raised serum TSH levels with circulating thyroid hormones within the reference range. It is uncertain whether treatment of SCH with L-thyroxine improves cardiovascular (CV) risk factors and quality of life. OBJECTIVE The objective of the study was to assess CV risk factors and patient-reported outcomes after treatment. DESIGN This was a randomized, double-blind, crossover study of L-thyroxine and placebo. SETTING The study was conducted with community-dwelling patients. PATIENTS One hundred patients [mean age (sd) 53.8 (12) yr, 81 females] with SCH [mean TSH 6.6 (1.3) mIU/liter] without previously treated thyroid or vascular disease. INTERVENTION Intervention consisted of 100 microg L-thyroxine or placebo daily for 12 wk each. MEASUREMENTS Primary parameters were total cholesterol (TC) and endothelial function [brachial artery flow-mediated dilatation (FMD)], an early marker of atherosclerosis. Patient-reported outcomes were also assessed. RESULTS L-thyroxine treatment reduced TC (vs. placebo) from 231.6 to 220 mg/dl, P < 0.001; low-density lipoprotein cholesterol from 142.9 to 131.3 mg/dl, P < 0.05; waist to hip ratio from 0.83 to 0.81, P < 0.006; and improved FMD from 4.2 to 5.9%, P < 0.001. Multivariate analysis showed that increased serum free T(4) level was the most significant variable predicting reduction in TC or improvement in FMD. Furthermore, the symptom of tiredness improved on L-thyroxine therapy, but other patient-reported outcomes were not significantly different after correction for multiple comparisons. CONCLUSION SCH treated by L-thyroxine leads to a significant improvement in CV risk factors and symptoms of tiredness. The CV risk factor reduction is related to the increased level of achieved free T(4) concentration.
The Effect of US Troop Deployments on Human Rights

US noninvasion troops deployed abroad often try to promote greater respect for human rights in the host country. The host country, having an incentive to retain the troop presence, may choose to comply with these requests. We argue that this effect will not be at play in states with high security salience for the United States (US) (for which the US may not be able to credibly threaten to remove the troops). In these cases, US deployments will provide the leader with security from both internal and external threats that is independent of the local population’s support for the leader. Host state leaders thus become less reliant on (and potentially less responsive to) their local populations, which in turn may lead to increased human rights violations. In this article, we use data on both US troop deployments abroad and on human rights violations to test these arguments from 1982 to 2005.
Bladder cancer following upper tract urothelial carcinoma

Upper tract urothelial carcinoma (UTUC) is uncommon relative to primary bladder transitional cell carcinoma, with notable differences at the genetic, molecular and clinical levels. A variety of management options with similar oncologic outcomes are available for UTUC. Regardless of upper tract treatment modality, recurrence in the bladder consistently occurs in 20–50% of patients, thus presenting a significant clinical challenge. The initial intravesical relapse typically occurs within the first 2 years following upper tract therapy, but the risk is lifelong and repeat episodes are common. The identification of variables that allow accurate risk stratification of UTUC patients with regards to future bladder relapse is crucial. Unfortunately, to date, no variables have been identified that can reliably predict such bladder recurrences. A history of bladder cancer prior to UTUC resection and upper tract tumor multifocality are frequently reported clinical risk factors. Candidate molecular markers, such as E-cadherin, also hold promise for improving patient risk stratification. The impact of bladder recurrences on patient survival is still poorly defined. The risk of progression to invasive bladder disease is not well documented but appears to be an infrequent event. This article highlights important recent observations and key current issues regarding UTUC and subsequent bladder cancer. In addition, we suggest a bladder surveillance regimen following UTUC and provide recommendations for managing patients with intravesical recurrences.
Deleterious Impact of Donor-Specific Anti-HLA Antibodies Toward HLA-Cw and HLA-DP in Kidney Transplantation

Background It is widely accepted that HLA donor-specific antibodies (DSA) are associated with antibody-mediated rejection and graft loss. However, in many transplant programs, preformed anti–HLA-Cw and anti–HLA-DP DSA are not considered in organ allocation policies because their clinical relevance is still uncertain. Methods We analyzed the clinical impact of Cw/DP DSA through a retrospective study, comparing 48 patients transplanted with isolated preformed Cw/DP DSA (Cw/DP DSA group) with (i) 104 matched HLA-sensitized kidney transplant recipients with No DSA at D0 (No DSA group) and (ii) 47 kidney transplant recipients with preformed A, −B, −DR, −DQ DSA (A/B/DR/DQ DSA group). Results A positive flow cytometry crossmatch in the Cw/DP DSA group was more frequent than in the No DSA group and as frequent as in the A/B/DR/DQDSA group. Two years after transplantation, the biopsy-proven acute rejection-free survival was worse in the Cw/DP and A/B/DR/DQ DSA groups than in the No DSA group (65%, 84%, 93%, P = 0.001 and P = 0.05, respectively). Accordingly, graft survival was lower in the Cw/DP and the A/B/DR/DQ DSA groups than in the No DSA group (87%, 89%, 95%, P = 0.02 and P = 0.1, respectively). Conclusions These results suggest that preformed anti–HLA-Cw and anti–HLA-DP DSA are as deleterious as anti–HLA A/B/DR/DQ DSA. It justifies their inclusion in kidney allocation programs and in immunological risk stratification algorithms.
Virtual machine support for aspect-oriented programming languages

Among implementations of the aspect-oriented programming paradigm, some approaches have been developed in which aspect weaving does not necessarily occur at compile-time, but at run-time of an application. Weaving at run-time has the advantage that, e.g., in the context of J2EE applications, objects can be dynamically and transparently decorated with certain services that are important in J2EE applications. Moreover, dynamic weaving makes more allowance for the inherently dynamic nature of pointcuts than static weaving - pointcuts quantify over the execution of an application. The different approaches to dynamic weaving however lack the kind of support for AOP language mechanisms that is common for mechanisms of other paradigms: direct support from the run-time environment. For example, virtual machines for object-oriented programming languages offer direct support for resolving virtual methods via method tables. Such support is at present not available for aspect-oriented mechanisms. Instead, the implementation of a run-time environment for AOP languages is simulated at application level. This is where this work applies. In the course of this work, Steamloom was implemented, a virtual machine with explicit support for AOP mechanisms. Steamloom is an extension of an existing virtual machine for the Java programming language. Steamloom provides a unified representation of Java bytecodes that is accessed by both the virtual machine and the AOP functionality. The latter utilises the bytecode representation's capabilities to evaluate pointcuts and for weaving. Moreover, Steamloom supports dynamic weaving by utilising the just-in-time compilers of the virtual machine for dynamically recompiling methods affected by weaving. Apart from that, Steamloom has integrated support for some other AOP mechanisms, of which an efficient evaluation of control flow-dependent residues is especially important. Steamloom is conceived as a platform on whose basis AOP languages can be implemented experimentally. The pointcut model and weaver are extensible, which allows for the implementation of new elements. This extensibility was used in this work to implement and evaluate three different strategies for control flow-dependent pointcuts. To measure the value of Steamloom, a comprehensive analysis of different aspects of performance and efficiency of a representative collection of AOP implementations was conducted. It is based on a presentation of implementation details of these AOP implementations that has been achieved on the basis of a unified presentation framework.