Miracle-dz/UniFAR-FTUs huggingface dataset:
Checkpoint Kinase 1 Down-Regulation by an Inducible Small Interfering RNA Expression System Sensitized In vivo Tumors to Treatment with 5-Fluorouracil

Purpose: After DNA damage, checkpoints pathways are activated in the cells to halt the cell cycle, thus ensuring repair or inducing cell death. To better investigate the role of checkpoint kinase 1 (Chk1) in cellular response to different anticancer agents, Chk1 was knocked down in HCT-116 cell line and in its p53-deficient subline by using small interfering RNAs (siRNA). Experimental Design: Chk1 was abrogated by transient transfection of specific siRNA against it, and stable tetracycline-inducible Chk1 siRNA clones were obtained transfecting cells with a plasmid expressing two siRNA against Chk1. The validated inducible system was then translated in an in vivo setting by transplanting the inducible clones in nude mice. Results: Transient Chk1 down-regulation sensitized HCT-116 cells, p53−/− more than the p53 wild-type counterpart, to DNA-damaging agents 5-fluorouracil (5-FU), doxorubicin, and etoposide treatments, with no modification of Taxol and PS341 cytotoxic activities. Inhibition of Chk1 protein levels in inducible clones on induction with doxycycline correlated with an increased cisplatin and 5-FU activity. Such effect was more evident in a p53-deficient background. These clones were transplanted in nude mice and a clear Chk1 down-regulation was shown in tumor samples of mice given tetracycline in the drinking water by immunohistochemical detection of Chk1 protein. More importantly, an increased 5-FU antitumor activity was found in tumors with the double Chk1 and p53 silencing. Conclusions: These findings corroborate the fact that Chk1 protein is a molecular target to be inhibited in tumors with a defective G1 checkpoint to increase the selectivity of anticancer treatments.
Authentication protocols based on low-bandwidth unspoofable channels: A comparative survey

One of the main challenges in pervasive computing is how we can establish secure communication over an untrusted high-bandwidth network without any initial knowledge or a Public Key Infrastructure. An approach studied by a number of researchers is building security though human work creating a low-bandwidth empirical (or authentication) channel where the transmitted information is authentic and cannot be faked or modified. In this paper, we give an analytical survey of authentication protocols of this type. We start with non-interactive authentication schemes, and then move on to analyse a number of strategies used to build interactive pair-wise and group protocols that minimise the human work relative to the amount of security obtained as well as optimising the computation processing. In studying these protocols, we will discover that their security is underlined by the idea of commitment before knowledge, which is refined by two protocol design principles introduced in this survey.
Elimination of Iron Deficiency Anemia and Soil Transmitted Helminth Infection: Evidence from a Fifty-four Month Iron-Folic Acid and De-worming Program

Background Intermittent iron-folic acid supplementation and regular de-worming are effective initiatives to reduce anemia, iron deficiency, iron deficiency anemia, and soil transmitted helminth infections in women of reproductive age. However, few studies have assessed the long-term effectiveness of population-based interventions delivered in resource-constrained settings. Methodology/Principal Findings The objectives were to evaluate the impact of weekly iron-folic acid supplementation and de-worming on mean hemoglobin and the prevalence of anaemia, iron deficiency, and soil transmitted helminth infection in a rural population of women in northern Vietnam and to identify predictive factors for hematological outcomes. A prospective cohort design was used to evaluate a population-based supplementation and deworming program over 54 months. The 389 participants were enrolled just prior to commencement of the intervention. After 54 months 76% (95% CI [68%, 84%]) were taking the iron-folic acid supplement and 95% (95% CI [93%, 98%]) had taken the most recently distributed deworming treatment. Mean hemoglobin rose from 122 g/L (95% CI [120, 124]) to 131 g/L (95% CI [128, 134]) and anemia prevalence fell from 38% (95% CI [31%, 45%]) to 18% (95% CI [12%, 23%]); however, results differed significantly between ethnic groups. Iron deficiency fell from 23% (95% CI [17%, 29%]) to 8% (95% CI [4%, 12%]), while the prevalence of iron deficiency anemia was reduced to 4% (95% CI [1%, 7%]). The prevalence of hookworm infection was reduced from 76% (95% CI [68%, 83%]) to 11% (95% CI [5%, 18%]). The level of moderate or heavy infestation of any soil-transmitted helminth was reduced to less than 1%. Conclusions/Significance Population-based interventions can efficiently and effectively reduce anemia and practically eliminate iron deficiency anemia and moderate to heavy soil transmitted helminth infections, maintaining them below the level of public health concern.
Spatio-semantic coherence in the integration of 3D city models

An increasing number of applications rely on 3D geoinformation. In addition to 3D geometry, these applications particularly require complex semantic information. In the context of spatial data infrastructures the needed data are drawn from distributed sources and often are thematically and spatially fragmented. Straight forward joining of 3D objects would inevitably lead to geometrical inconsistencies such as cracks, permeations, or other inconsistencies. Semantic information can help to reduce the ambiguities for geometric integration, if it is coherently structured with respect to geometry. The paper discusses these problems with special focus on virtual 3D city models and the semantic data model CityGML, an emerging standard for the representation and the exchange of 3D city models based on ISO 191xx standards and GML3. Different data qualities are analyzed with respect to their semantic and spatial structure leading to the distinction of six categories regarding the spatio-semantic coherence of 3D city models. Furthermore, it is shown how spatial data with complex object descriptions support the integration process. The derived categories will help in the future development of automatic integration methods for complex 3D geodata.
Expression Cloning of a Novel Suppressor of the Lec15 and Lec35 Glycosylation Mutations of Chinese Hamster Ovary Cells*

Lec15 and Lec35 are recessive Chinese hamster ovary (CHO) cell glycosylation mutations characterized by inefficient synthesis and utilization, respectively, of mannose-P-dolichol (MPD). Consequently, Lec15 and Lec35 cells accumulate Man5GlcNAc2-P-P-dolichol and glucosaminyl-acylphosphatidylinositol. This report describes the cloning of a suppressor (termed SL15) of the Lec15 and Lec35 mutations from a CHO cDNA library by functional expression in Lec15 cells, employing phytohemagglutinin/swainsonine selection. The SL15 protein has a predicted molecular weight of 26,693 with two potential membrane spanning regions and a likely C-terminal endoplasmic reticulum retention signal (Lys-Lys-Glu-Gln). Lec15 cells transfected with SL15 have normal levels of MPD synthase activity in vitro and convert Man5GlcNAc2-P-P-dolichol to Glc0-3Man9GlcNAc2-P-P-dolichol in vivo. Surprisingly, SL15 also corrects the defective mannosylation in Lec35 cells. The SL15 protein bears no apparent similarity to Saccharomyces cerevisiae MPD synthase (the DPM1 protein), but is highly similar to the hypothetical F38E1.9 protein encoded on Caenorhabditis elegans chromosome 5. These results indicate a novel function for the SL15 protein and suggest that MPD synthesis is more complex than previously suspected.
[Effect of whisker trimming on behavior and barrel cortex of rat].

OBJECTIVE To investigate the change of behavior, as well as the plasticity of somatosensory cortex after whisker trimming. METHODS SD rats were divided into 4 groups. Group A is the normal control group; group B: bilateral vibrissotomy on the second postnatal day; group C: unilateral right vibrissotomy on the second postnatal day; group D: right unilateral whisker trimmed during 1-5 days after birth, and leave untreated after the 5th postnatal day. Their body weight, length of the left D2 whiskers was measured on the 30th postnatal day. At the same time, the changes of their behavior (including the slit-detection test, the home exploring behavior and thigmotaxis test) were also recorded on the 30th postnatal day. Cytochrome oxydase histochemistry (CO reaction)was applied to study the development and arrangement of barrel cortex. RESULTS In the slit-detection test, control rats could find and get into the right slit very quickly. The rats in group B could get into the slit only if their noses touched the slit. The rats in group C couldn't identify the slit by right face, but if they turned their body and touched the slit with the left whiskers, they could get into the slit very quickly. The behavior of rats in group D was similar to that in group C. The time spent for finding out the right slit of the rats in group A, B, C was obviously longer than that of group A (P < 0.01, P < 0.05, P < 0.01). In the exploring behavior and thigmotaxis test, the time for left thigmotaxis, right thigmotaxis and total thigmotaxis of rats in group B was longer than that of control animals. The time for right thigmotaxis of group C was significantly shorter than that of group A (P < 0.05). Both the weight of the rats and the length of left D2 whiskers of rats in all the four groups had no significant difference. CO reaction showed that the barrels became smaller, the septum was not clear, the arrangement of the barrels was not tidy in the mice whose right whiskers were trimmed from 2-30 days after birth. CONCLUSION Deafferentation doesn't change the body weight and length of the whiskers left. But the stimulation of whiskers is important for rodent especially in thigmotaxis and exploring behavior. Deafferentation can also induce the plastic change of barrel cortex.
Visualizing metabolite distribution and enzymatic conversion in plant tissues by desorption electrospray ionization mass spectrometry imaging.

In comparison with the technology platforms developed to localize transcripts and proteins, imaging tools for visualization of metabolite distributions in plant tissues are less well developed and lack versatility. This hampers our understanding of plant metabolism and dynamics. In this study, we demonstrate that desorption electrospray ionization mass spectrometry imaging (DESI-MSI) of tissue imprints on porous Teflon may be used to accurately image the distribution of even labile plant metabolites such as hydroxynitrile glucosides, which normally undergo enzymatic hydrolysis by specific β-glucosidases upon cell disruption. This fast and simple sample preparation resulted in no substantial differences in the distribution and ratios of all hydroxynitrile glucosides between leaves from wild-type Lotus japonicus and a β-glucosidase mutant plant that lacks the ability to hydrolyze certain hydroxynitrile glucosides. In wild-type, the enzymatic conversion of hydroxynitrile glucosides and the concomitant release of glucose were easily visualized when a restricted area of the leaf tissue was damaged prior to sample preparation. The gene encoding the first enzyme in hydroxynitrile glucoside biosynthesis in L. japonicus leaves, CYP79D3, was found to be highly expressed during the early stages of leaf development, and the hydroxynitrile glucoside distribution in mature leaves reflected this early expression pattern. The utility of direct DESI-MSI of plant tissue was demonstrated using cryo-sections of cassava (Manihot esculenta) tubers. The hydroxynitrile glucoside levels were highest in the outer cell layers, as verified by LC-MS analyses. The unexpected discovery of a hydroxynitrile-derived di-glycoside shows the potential of DESI-MSI to discover and guide investigations into new metabolic routes.
Crystallography of Precipitates in Metals and Alloys: (1) Analysis of Crystallography

This chapter and the following chapters describe crystallography of second-phase precipitate particles in metals and alloys. The focus of this chapter is placed on technical aspects in the analysis of their crystal structure, composition, and crystal orientation relationship with the matrix. Characterization of fine precipitates embedded in solid matrix is technically rather difficult; the signal from the matrix always hinders the signal from the precipitates. Although even state-of-the-art characterization techniques are still incomplete, it is becoming possible to assess the validity of assumptions involved in classic theories related to the crystallography of precipitates. For instance, recent experimental studies demonstrated that evolution of their crystal structure during nucleation seems to contradict the so-called classical nucleation theory, in terms of fluctuations in size and composition. Recent studies also demonstrated that their crystal orientation relationship with the matrix is often different from the one predicted by energy considerations related to the interfacial lattice mismatch. Furthermore, crystal orientation relationship with the matrix was found to be a factor controlling the magnitude of precipitation hardening, contrary to the conventional Orowan ’ s hardening model based on continuum elasticity theory calculations without considering crystallography. nucleate solute structurally indistinguishable followed structural change. Their crystal structure changes at a critical size with a critical composition.
Transmit power allocation for successive interference cancellation in multicode MIMO systems

Multiple-input multiple-output (MIMO) system with multicode transmission can provide high speed data services by transmitting independent parallel substreams from multiple antennas and through multicode channelization. In this paper, we first introduce an iterative two-stage successive interference cancellation (SIC) detection scheme for a multicode MIMO system. The proposed technique cancels the interference signals successively in the space domain followed by the code domain. Next, we develop various transmit power allocation schemes over different data substreams for the proposed detection process to improve error rate performance. The joint transmit power allocation is derived to make the post-detection signal-to-interference-plus-noise ratio (SINR) become the same for all substreams in both the space and code domains. As a computationally efficient scheme, we propose a two-stage power allocation scheme, which allocates the total transmit power to the substreams in the code domain at the first stage, and allocates this code domain power to the substreams in the space domain at the second stage. Furthermore, variable and constant power ratio (PR) schemes are derived to reduce the feedback overhead. In particular, the constant PR scheme utilizes the transmit power ratio determined by the long-term statistical properties of the fading channel amplitudes, and achieves significantly reduced feedback rate. Numerical results show that the proposed transmit power allocation schemes for the two-stage SIC significantly outperform the equal power allocation scheme.
Altered endochondral bone development in matrix metalloproteinase 13-deficient mice

The assembly and degradation of extracellular matrix (ECM) molecules are crucial processes during bone development. In this study, we show that ECM remodeling is a critical rate-limiting step in endochondral bone formation. Matrix metalloproteinase (MMP) 13 (collagenase 3) is poised to play a crucial role in bone formation and remodeling because of its expression both in terminal hypertrophic chondrocytes in the growth plate and in osteoblasts. Moreover, a mutation in the human MMP13 gene causes the Missouri variant of spondyloepimetaphyseal dysplasia. Inactivation of Mmp13 in mice through homologous recombination led to abnormal skeletal growth plate development. Chondrocytes differentiated normally but their exit from the growth plate was delayed. The severity of the Mmp13- null growth plate phenotype increased until about 5 weeks and completely resolved by 12 weeks of age. Mmp13-null mice had increased trabecular bone, which persisted for months. Conditional inactivation of Mmp13 in chondrocytes and osteoblasts showed that increases in trabecular bone occur independently of the improper cartilage ECM degradation caused by Mmp13 deficiency in late hypertrophic chondrocytes. Our studies identified the two major components of the cartilage ECM, collagen type II and aggrecan, as in vivo substrates for MMP13. We found that degradation of cartilage collagen and aggrecan is a coordinated process in which MMP13 works synergistically with MMP9. Mice lacking both MMP13 and MMP9 had severely impaired endochondral bone, characterized by diminished ECM remodeling, prolonged chondrocyte survival, delayed vascular recruitment and defective trabecular bone formation (resulting in drastically shortened bones). These data support the hypothesis that proper ECM remodeling is the dominant rate-limiting process for programmed cell death, angiogenesis and osteoblast recruitment during normal skeletal morphogenesis.
Designing System-Level Defenses against Cellphone Malware

Cellphones are increasingly becoming attractive targets of various malware, which not only cause privacy leakage, extra charges, and depletion of battery power, but also introduce malicious traffic into networks. In this work, we seek system-level solutions to handle these security threats. Specifically, we propose a mandatory access control–based defense to blocking malware that launch attacks through creating new processes for execution. To combat more elaborated malware which redirect program flows of normal applications to execute malicious code within a legitimate security domain, we further propose using artificial intelligence (AI) techniques such as Graphic Turing test. Through extensive experiments based on both Symbian and Linux smartphones, we show that both our system-level countermeasures effectively detect and block cellphone malware with low false positives, and can be easily deployed on existing smartphone hardware.
An Algorithmic Trading Agent Based on a Neural Network Ensemble: A Case of Study in North American and Brazilian Stock Markets

In recent years, double auctions have become a topic of much interest in both economics and computer science literature, and automated trading has become very popular in stock markets. In this context, although many time series prediction studies are focused in the prediction of exact values in the future, evidences show that this kind of problem perform better when we transform it into a classification problem. In this work we propose a trading agent based on a neural network ensemble that predicts if one stock is going to raise or fall instead of predicting its future values. To show the efficiency of our method in different situations, we evaluate our model in two different datasets: the North American and the Brazilian stock markets. Real operations were simulated in these markets and we were able to profit in all tested time series.
Teleoperation system with hybrid pneumatic-piezoelectric actuation for MRI-guided needle insertion with haptic feedback

This paper presents a surgical master-slave tele-operation system for percutaneous interventional procedures under continuous magnetic resonance imaging (MRI) guidance. This system consists of a piezoelectrically actuated slave robot for needle placement with integrated fiber optic force sensor utilizing Fabry-Perot interferometry (FPI) sensing principle. The sensor flexure is optimized and embedded to the slave robot for measuring needle insertion force. A novel, compact opto-mechanical FPI sensor interface is integrated into an MRI robot control system. By leveraging the complementary features of pneumatic and piezoelectric actuation, a pneumatically actuated haptic master robot is also developed to render force associated with needle placement interventions to the clinician. An aluminum load cell is implemented and calibrated to close the impedance control loop of the master robot. A force-position control algorithm is developed to control the hybrid actuated system. Teleoperated needle insertion is demonstrated under live MR imaging, where the slave robot resides in the scanner bore and the user manipulates the master beside the patient outside the bore. Force and position tracking results of the master-slave robot are demonstrated to validate the tracking performance of the integrated system. It has a position tracking error of 0.318mm and sine wave force tracking error of 2.227N.
Signaling and Regulation KRASG 12 Dand BRAFV 600 E-Induced Transformation of Murine Pancreatic Epithelial Cells Requires MEK / ERK-Stimulated IGF 1 R Signaling

Mutation of KRAS is a common initiating event in pancreatic ductal adenocarcinoma (PDAC). Yet, the specific roles of KRAS-stimulated signaling pathways in the transformation of pancreatic ductal epithelial cells (PDEC), putative cells of origin for PDAC, remain unclear. Here, we show that KRAS and BRAF enhance PDEC proliferation and increase survival after exposure to apoptotic stimuli in a manner dependent on MEK/ERK and PI3K/AKT signaling. Interestingly, we find that activation of PI3K/AKT signaling occurs downstream of MAP– ERK kinase (MEK), and is dependent on the autocrine activation of the insulin-like growth factor (IGF) receptor (IGF1R) by IGF2. Importantly, IGF1R inhibition impairs KRASand BRAF-induced survival, whereas ectopic IGF2 expression rescues KRASand BRAF-mediated survival downstream of MEK inhibition. Moreover, we show that KRASand BRAF-induced tumor formation in an orthotopic model requires IGF1R. Interestingly, we show that while individual inhibition ofMEK or IGF1R does not sensitize PDAC cells to apoptosis, their concomitant inhibition reduces survival. Our findings identify a novel mechanism of PI3K/AKT activation downstream of activated KRAS, illustrate the importance of MEK/ERK, PI3K/AKT, and IGF1R signaling in pancreatic tumor initiation, and suggest potential therapeutic strategies for this malignancy.Mol Cancer Res; 10(9); 1228–39. 2012 AACR.
MobiCom poster: optimized fast-handoff schemes for application layer mobility management

In order to ensure proper quality of service for real-time communication in a mobile wireless Internet environment, it is essential to minimize the transient packet loss when the mobile host (MH) is moving between different cells (subnets) within a domain. This paper introduces application layer techniques to achieve fast handoff for real-time (RTP/UDP) multimedia traffic in a SIP-based signaling environment. These techniques are based on standard SIP components such as user agents and proxies and provide a network-independent solution suitable for application service providers.