Miracle-dz/UniFAR-FTUs huggingface dataset:
Estimation of Multiple Response Rates in Phase II Clinical Trials with Missing Observations

Responses are often correlated in clinical trials. A patient who is not evaluable for a response may still provide some information to the response through his or her status on other responses. Under the assumption of missing at random, we propose the utilization of a self-consistent estimator. We show that the proposed estimators are more efficient than the conventional estimators by asymptotic relative efficiency and simulation study. An example from a Phase II clinical trial on children with chronic myelogenous leukemia is provided.
Rho kinase as potential therapeutic target for cardiovascular diseases: opportunities and challenges

Rho kinase (ROCK) belongs to a family of Ser/Thr protein kinases that are activated via interaction with the small GTP-binding protein RhoA. Growing evidence suggests that RhoA and ROCK participate in a variety of important physiological functions in vasculature including smooth muscle contraction, cell proliferation, cell adhesion and migration, and many aspects of inflammatory responses. As these processes mediate the onset and progression of cardiovascular disease, modulation of the Rho/ROCK signalling pathway is a potential strategy for targeting an array of cardiovascular indications. Two widely employed ROCK inhibitors, fasudil and Y-27632, have provided preliminary but compelling evidence supporting the potential cardiovascular benefits of ROCK inhibition in preclinical animal disease models and in the clinic. This review summarises the molecular biology of ROCK and its biological functions in smooth muscle, endothelium and other vascular tissues. In addition, there will be a focus on recent progress demonstrating the benefits of ROCK inhibition in several animal models of cardiovascular diseases. Finally, recent progress in the identification of novel ROCK inhibitors and challenges associated with their development for clinical use will be discussed.
Open loop resonator bandpass filter with wide stopband using spurlines and microstrip stubs

This paper presents a new microstrip open loop resonator bandpass filter (BPF) for wireless local area networks (WLAN) with wide stopband response. The proposed BPF is composed of a pair of half-wavelength open loop resonators and two additional resonators operating at the center frequency of 2.44 GHz. Two novel resonators consisted of asymmetrical spurlines and quarter-wavelength open-circuited stubs are adopted at the input/output (I/O) feed lines to improve its stopband performance. For the outband spurious respond suppression, its upper stopband attenuation loss is lower than −20 dB from 2.6 GHz to 10 GHz, without affecting the center frequency and insertion loss. Good agreement between simulated and measured results.
Rectifier of aberrant mRNA splicing recovers tRNA modification in familial dysautonomia

Significance Familial dysautonomia (FD) is caused by missplicing of the IκB kinase complex-associated protein (IKAP) gene, which results in the skipping of exon 20, especially in neurons. FD would be treatable if exon 20 inclusion were increased correctly to reestablish correct splicing. Here, we have established a dual-color splicing reporter that recapitulates FD-type splicing. By using this reporter, we have identified a small chemical compound, named rectifier of aberrant splicing (RECTAS), that rectifies the aberrant splicing of FD. RECTAS promotes both exon 20 inclusion and the product IKAP expression in cells of patients with FD. Furthermore, we have demonstrated that modification levels of wobble uridine residues of several tRNAs are reduced in FD cells and that RECTAS can recover not only tRNA modifications but also cell viability of FD cells. Familial dysautonomia (FD), a hereditary sensory and autonomic neuropathy, is caused by missplicing of exon 20, resulting from an intronic mutation in the inhibitor of kappa light polypeptide gene enhancer in B cells, kinase complex-associated protein (IKBKAP) gene encoding IKK complex-associated protein (IKAP)/elongator protein 1 (ELP1). A newly established splicing reporter assay allowed us to visualize pathogenic splicing in cells and to screen small chemicals for the ability to correct the aberrant splicing of IKBKAP. Using this splicing reporter, we screened our chemical libraries and identified a compound, rectifier of aberrant splicing (RECTAS), that rectifies the aberrant IKBKAP splicing in cells from patients with FD. Here, we found that the levels of modified uridine at the wobble position in cytoplasmic tRNAs are reduced in cells from patients with FD and that treatment with RECTAS increases the expression of IKAP and recovers the tRNA modifications. These findings suggest that the missplicing of IKBKAP results in reduced tRNA modifications in patients with FD and that RECTAS is a promising therapeutic drug candidate for FD.
Multivariate Statistical Analysis on Anomaly P 2 P Botnets Detection

Botnets population is rapidly growing and they become a huge threat on the Internet. Botnets has been declared as Advanced Malware (AM) and Advanced Persistent Threat (APT) listed attacks which is able to manipulate advanced technology where the intricacy of threats need for continuous detection and protection. These attacks will be almost exclusive for financial gain. P2P botnets act as bots that use P2P technology to accomplish certain tasks. The evolution of P2P technology had generated P2P botnets to become more resilient and robust than centralized botnets. This poses a big challenge on detection and defences. In order to detect these botnets, a complete flow analysis is necessary. In this paper, we proposed anomaly detection through chi-square multivariate statistical analysis which currently focuses on time duration and time slot. This particular time is considered to identify the existence of botserver. We foiled both of host level and network level to make coordination within a P2P botnets and the malicious behaviour each bot exhibits for making detection decisions. The statistical approach result show a high detection accuracy and low false positive that make it as one of the promising approach to reveal botserver. Keywords—P2P botnets; anomaly-based; chi-square; multivariate; statistical-based
DSM-PM2 : une plate-forme portable pour l'implémentation de protocoles de cohérence multithreads pour systèmes à mémoire virtuellement partagée. (DSM-PM2: a portable platform for implementing multithreaded consistency protocols pour distributed shared memory systems)

Dans leur presentation traditionnelle, les systemes a memoire distribuee virtuellement partagee (MVP, en anglais DSM) permettent a des processus de partager un espace d'adressage commun selon un modele de coherence fixe : coherence sequentielle, a la liberation, etc. Les pro- cessus peuvent habituellement etre distribues sur des noeuds physiquement distincts et leurs in- teractions par la memoire commune sont implementees (de maniere transparente) par la MVP, en utilisant une bibliotheque de communication. Dans la plupart de travaux dans ce domaine, il est sous-entendu que la MVP et l'architecture sous-jacente sont donnees. Le programmeur doit alors adapter son application a ce cadre fixe, afin d'obtenir une execution efficace. Cette approche impose des limitations statiques et ne permet pas de comparer des approches alternatives. La contribution de cette these consiste a proposer une plate-forme generique d'implementation et d'experimentation appelee DSM-PM2, qui permet de developper et d'optimiser conjointement les applications distribuees et le(s) protocole(s) de coherence de la MVP sous-jacente. Cette plate-forme, implementee entierement au niveau logiciel, est portable sur plusieurs architectures de grappes hautes performances. Elle fournit les briques de bases necessaires pour implementer et evaluer une large classe de protocoles de coherence multithreads dans un cadre unifie. Trois mo- deles de coherence sont actuellement supportes : la coherence sequentielle, la coherence a la libera- tion et la coherence Java. Plusieurs etudes de performance ont ete effectuees a l'aide d'applications multithreads pour l'ensemble des protocoles proposes, sur differentes plates-formes. DSM-PM a ete valide par son utilisation en tant que cible d'un systeme de compilation Java pour des grappes appele Hyperion.
Design Guidelines for Wearable Pointing Devices

This paper presents design guidelines and recommendations for developing cursor manipulation interaction devices to be employed in a wearable context. The work presented in this paper is the culmination three usability studies designed to understand commercially available pointing (cursor manipulation) devices suitable for use in a wearable context. The set of guidelines and recommendations presented are grounded on experimental and qualitative evidence derived from three usability studies and are intended to be used in order to inform the design of future wearable input devices. In addition to guiding the design process, the guidelines and recommendations may also be used to inform users of wearable computing devices by guiding towards the selection of a suitable wearable input device. The synthesis of results derived from a series of usability studies provide insights pertaining to the choice and usability of the devices in a wearable context. That is, the guidelines form a checklist that may be utilized as a point of comparison when choosing between the different input devices available for wearable interaction.
Coverage opportunities for global ocean color in a multimission era

The international community, recognizing the importance of global ocean color observations in the global carbon cycle, has proposed or flown six global ocean color missions over the next decade: the Ocean Color and Temperature Sensor (OCTS), Sea-viewing Wide Field-of-view Sensor (SeaWiFs), Moderate Resolution Imaging Spectrometer-AM (MODIS-AM), Medium Resolution Imaging Spectrometer (MERIS), Global Imager (GLI), and MODIS-PM. Each of these missions contains the spectral band complement considered necessary to derive oceanic pigment concentrations (i.e., phytoplankton abundance). This paper assesses whether assembling and merging data from these missions can improve ocean coverage, since clouds and Sun glint prevent any single satellite from observing more than about 15% of the ocean surface in a single day, and whether new information about diel cycles of phytoplankton abundance is possible. Extensive numerical analysis, given the orbit and sensor characteristics of each mission, showed that merging data form three satellites can produce better ocean coverage in less time. Data from three satellites can improve coverage by 58% for a single day, including the obscuring effects of clouds and sun glint. Thus, observation of approximately 25% of the ocean can be provided, instead of only about 15-16% from a single satellite. After four days, approximately 62% of the ocean surface was observed, an increase from 43% observed by a single satellite. The addition of more satellites produced diminishing returns. Since the proposed missions have different orbits, the view the same location of the ocean at different times of day. This leads to the possibility of using data from the set of six missions to help understand diel phytoplankton dynamics.
Consciousness in the Universe: Neuroscience, Quantum Space-Time Geometry and Orch OR Theory

The nature of consciousness, its occurrence in the brain, and its ultimate place in the universe are unknown. We proposed in the mid 1990's that consciousness depends on biologically 'orchestrated' quantum computations in collections of microtubules within brain neurons, that these quantum computations correlate with and regulate neuronal activity, and that the continuous Schrodinger evolution of each quantum computation terminates in accordance with the specific Diosi‐Penrose (DP) scheme of 'objective reduction' of the quantum state (OR). This orchestrated OR activity (Orch OR) is taken to result in a moment of conscious awareness and/or choice. This particular (DP) form of OR is taken to be a quantum-gravity process related to the fundamentals of spacetime geometry, so Orch OR suggests a connection between brain biomolecular processes and fine-scale structure of the universe. Here we review and update Orch OR in light of criticisms and developments in quantum biology, neuroscience, physics and cosmology. We conclude that consciousness plays an intrinsic role in the universe.
Transforming growth factor‐β1 causes transcriptional activation of CD34 and preserves haematopoietic stem/progenitor cell activity

Summary. Stem/progenitor cells endowed with in vitro and in vivo haematopoietic activity express the surface protein CD34. Transforming growth factor β1 (TGF‐β1) is one of the soluble molecules that regulate cell cycle and differentiation of haematopoietic cells, but has pleiotropic activities depending on the state of responsiveness of the target cells. It has previously been shown that TGF‐β1 maintains human CD34+ haematopoietic progenitors in an undifferentiated state, independently of any cell cycle effect. Here, we have shown that TGF‐β1 upregulates the human CD34, an effect that was evident in primary stem/progenitor cells (CD34+lin–) both at the transcriptional and protein levels, and was not associated with any relevant effect on cell growth. The presence of TGF‐β1 influenced differentiation, maintaining primary CD34+/Lin– in an undifferentiated state. This effect was associated with Smad activation and with a dramatic decrease in p38 phosphorylation. Moreover, blocking p38 phosphorylation by the SB202190 inhibitor increased CD34 RNA levels but did not enhance CD34 protein expression in CD34+/Lin– cells, suggesting that modulation of multiple signalling pathways is necessary to reproduce TGF‐β1 effects. These data establish the role that TGF‐β1 has in the modulation of the CD34 stem/progenitor protein and stem/progenitor functions, providing important clues for understanding haematopoietic development and a potential tool for the modulation of human haematopoiesis.
Serum Leptin Levels Increase following Acute Myocardial Infarction

Leptin is secreted into the circulation and communicates the peripheral nutritional status to specific hypothalamic centers. Recent studies suggest that leptin may be involved in the acute response to stress, and that its interaction with the hypothalamo-pituitary-adrenal axis and the inflammatory cytokine system may be of clinical importance. Since these systems are activated during acute myocardial infarction (AMI), we studied leptin and cortisol levels during hospitalization in 30 consecutive patients admitted for AMI. The results show that leptin reached its peak on the second day of hospitalization, with a 2-fold increase from its baseline level on admission (p < 0.02). On day 3, leptin levels declined, and were 46%, 9%, and 6% above baseline on days 3, 4 and 5, respectively. The mean cortisol level was elevated on day 1 and decreased toward normal levels thereafter (p < 0.001). The cortisol level did not correlate with leptin concentration throughout the study. These findings suggest that leptin may have a role in the metabolic changes taking place during the first days after an AMI.
Adaptive Regularized Level Set Method for Weak Boundary Object Segmentation

An adaptive regularized level set method for image segmentation is proposed. A weighted -Dirichlet integral is presented as a geometric regularization on zero level curve, which is used to diminish the influence of image noise on level set evolution while ensuring the active contours not to pass through weak object boundaries. The idea behind the new energy integral is that the amount of regularization on the zero level curve can be adjusted automatically by the variable exponent to fit the image data. This energy is then incorporated into a level set formulation with an external energy term that drives the motion of the zero level set toward the desired objects boundaries, and a level set function regularization term that is necessary for maintaining stable level set evolution. The proposed model has been applied to a wide range of both real and synthetic images with promising results.
Peroxisome proliferation, adipocyte determination and differentiation of C3H10T1/2 fibroblast cells induced by humic acid: Induction of PPAR in diverse cells

Humic acid, a high‐molecular‐weight polyphenolic compound, exists abundantly in soil, natural water, and various terrestrial and aquatic environments. Humic acid causes peroxisome proliferation in mouse liver and induces the expression of peroxisome proliferator activated receptor (PPAR) in BNL CL.2 cells. Both cytotoxicity and flow cytometry show that humic acid inhibits the growth of C3H10T1/2 cells at G1 phase. C3H10T1/2 fibroblast cells express PPARγ and the adipocyte P2 (aP2) genes which convert into adipocytes after being treated with humic acid. Our findings may provide a unique model for studying the molecular control of determination and differentiation of mesodermal cell lineages. J. Cell. Physiol. 179:218–225, 1999. © 1999 Wiley‐Liss, Inc.
The Relationship between Customer Satisfaction and Relationship Marketing Benefits

Today, service companies and institutions worldwide, compete in space that due to the demands and expectations of the customers introduce a factor for the survival of their professional and only those groups of the institutions will be more successful that correctly recognize, customer is valuable investment. Banks and financial institutions are not exempt from this issue. Banks must attempt by new marketing strategies for attract more customers satisfaction. One of the new strategies is relationship marketing strategy. Todays, relationship marketing is business art. The importance of this research toward marketing, service quality and consumer satisfaction as key to success elements of financial businesses faced with escalating competition and market changes recently. Society statistical present study is all customers having accounts at Saderat bank branches in Iran (Anzali) city. Sampling method is available non-probability. Data collection methods were field and Collection tool was questionnaire. Data analytical method was the correlation coefficient that finally, the hypothesis was confirmed.
Extracting Components from Object-Oriented System: A Transformational Approach

The increasing complexity and shorter life cycle of software have made it necessary to reuse software. Object-oriented development has not facilitated extensive reuse of software and it has become difficult to manage and understand modern object-oriented systems which have become very extensive and complex. However, components, compared with objects, provide more advanced means of structuring, describing and developing systems, because they are more coarse grained and have more domain-specific aspects than objects. In addition, they are also suited to a current distributed environment due to their reusability, maintainability and granularity. In this paper, we present a process of extracting components from object-oriented systems. We define some static metrics and guidelines that can be applied to transform object-oriented systems into component-based systems. Our process consists of two parts. First, basic components are created based on composition and inheritance relationships between classes. Second, the intermediate system is refined into a component-based system with our proposed static metrics and guidelines.
Stroke and atrial fibrillation: is stroke prevention treatment appropriate beforehand?

OBJECTIVE To undertake a pilot study before conducting a large European multicentre prospective study, to determine the proportion of patients with atrial fibrillation who were not receiving antithrombotic treatment before stroke onset, and their characteristics. DESIGN AND PATIENTS The stroke in atrial fibrillation ensemble (SAFE) I study was an observational study conducted in 213 patients with atrial fibrillation consecutively admitted in 1997 to three European centres for an acute stroke or transient ischaemic attack (TIA). It was determined whether they were receiving prior antithrombotic treatment. RESULTS Atrial fibrillation was known before stroke in 148 patients (69.5%). Of 213 patients, 34 (16.0%) were receiving anticoagulation treatment before stroke, but only six had an international normalised ratio between 2.0 and 3.5; 65 (30.5%) were receiving antiplatelet treatment; and three (1.4%) were receiving both anticoagulation and antiplatelet treatment. Of 137 patients eligible for oral anticoagulation, 108 (78.8%) did not receive treatment. Of 142 patients eligible for any antithrombotic treatment, 62 (43.7%) were not treated. The logistic regression analysis, assuming anticoagulation treatment as a dependent variable, found digoxin treatment, absence of arterial hypertension, mitral stenosis, and cardioversion as independent factors. Assuming any antithrombotic treatment as a dependent variable, previously known atrial fibrillation, lower age, being a non-smoker, and absence of arterial hypertension were found to be independent factors. CONCLUSION More than half of the patients with atrial fibrillation admitted for acute stroke or TIA were not receiving any antithrombotic treatment beforehand. New onset atrial fibrillation and contraindications account for a minority of non-prescriptions; thus, other reasons should be identified to improve stroke prevention in the community.
Pueraria mirifica, phytoestrogen-induced change in synaptophysin expression via estrogen receptor in rat hippocampal neuron.

OBJECTIVE To examine Pueraria mirifica (Leguminosae) containing-phytoestrogen effect on synaptic density and involvement of estrogen receptor. MATERIAL AND METHOD The level of synaptophysin, a presynaptic vesicle protein, was measured using Western blot analysis and immunocytochemistry in hippocampal primary cell cultures at 6 days in vitro. RESULTS P. mirifica and 17beta-estradiol (0.1 microM) treatment for 4 days, but not for 2 days, significantly increased synaptophysin immunoreactivity and level of synaptophysin. P. mirifica up to 60 microg/ml resulted in a dose related increase in the level of synaptophysin immunoreactivity. The classical estrogen receptor antagonist, ICI 182 780, significantly blocked P. mirifica-induced increase in synaptophysin. CONCLUSION P. mirifica-containing phytoestrogen affects synaptic density by inducing synaptophysin expression via estrogen receptor.