Miracle-dz/UniFAR-FTUs huggingface dataset:
Everolimus Augments the Effects of Sorafenib in a Syngeneic Orthotopic Model of Hepatocellular Carcinoma

Sorafenib targets the Raf/mitogen-activated protein kinase, VEGF, and platelet-derived growth factor pathways and prolongs survival patients in advanced hepatocellular carcinoma (HCC). Everolimus inhibits the mammalian target of rapamycin, a kinase overactive in HCC. To investigate whether the antitumor effects of these agents are additive, we compared a combined and sequential treatment regimen of everolimus and sorafenib with monotherapy. After hepatic implantation of Morris Hepatoma (MH) cells, rats were randomly allocated to everolimus (5 mg/kg, 2×/week), sorafenib (7.5 mg/kg/d), combined everolimus and sorafenib, sequential sorafenib (2 weeks) then everolimus (3 weeks), or control groups. MRI quantified tumor volumes. Erk1/2, 4E-BP1, and their phosphorylated forms were quantified by immunoblotting. Angiogenesis was assessed in vitro by aortic ring and tube formation assays, and in vivo with Vegf-a mRNA and vascular casts. After 35 days, tumor volumes were reduced by 60%, 85%, and 55%, relative to controls, in everolimus, the combination, and sequential groups, respectively (P < 0.01). Survival was longest in the combination group (P < 0.001). Phosphorylation of 4E-BP1 and Erk1/2 decreased after everolimus and sorafenib, respectively. Angiogenesis decreased after all treatments (P < 0.05), although sorafenib increased Vegf-a mRNA in liver tumors. Vessel sprouting was abundant in control tumors, lower after sorafenib, and absent after the combination. Intussusceptive angiogenic transluminal pillars failed to coalesce after the combination. Combined treatment with everolimus and sorafenib exerts a stronger antitumoral effect on MH tumors than monotherapy. Everolimus retains antitumoral properties when administered sequentially after sorafenib. This supports the clinical use of everolimus in HCC, both in combination with sorafenib or after sorafenib. Mol Cancer Ther; 10(6); 1007–17. ©2011 AACR.
WHO recommendations for Prevention and treatment of pre-eclampsia and eclampsia

Nearly one-tenth of maternal deaths in Asia and Africa and one-quarter of maternal deaths in Latin America are associated with hypertensive disorders of pregnancy. Among the hypertensive disorders, preeclampsia and eclampsia have the greatest impact on maternal and newborn morbidity and mortality. Yet the majority of deaths related to pre-eclampsia and eclampsia could be avoided if women received timely and effective care, delivered according to evidence-based standards.
FINITE-SNR DMT OF MIMO SYSTEM WITH ZF RECEIVER

In Multiple Input and Multiple Output (MIMO) systems, spectral efficiency can be increased when compared to single antenna systems without increasing transmit power. , A point-to-point MIMO system is considered along with a zero-forcing (ZF) linear receiver. At the receiver, perfect channel state information (CSI) is assumed. Also, at the transmitter no CSI is assumed. The diversity and multiplexing gain (DMT) is metric for comparison of multiple-antenna systems. We compute the exact closed-form expression of the DMT of this MIMO system with a ZF receiver at finite signal-to-noise ratio (SNR). We show that the asymptotic diversity gain at practical SNRs is quite optimistic and hence it is better to use DMT at finite-SNR for system analysis.
A Route Stability Based Multipath QoS Routing (SMQR) in MANETs

Providing high quality communications service among mobile wireless devices is basically a challenging task in wireless ad hoc networks. In this paper, we propose a route stability based multipath quality of service (QoS) routing (SMQR) protocol for mobile ad hoc networks (MANETs) to support throughput and delay sensitive real-time applications in MANETs. Reliability of QoS-aware path is improved through the selection of a maximum of three node-disjoint routes with higher stability. With an effective QoS violations detection and route maintenance mechanism followed, the frequency of route recovery and hence QoS disruption is reduced significantly in moderate to highly mobile scenarios. Extensive simulation studies show that SMQR can support higher level of QoS in terms of packet delivery ratio, average end-to-end delay, maximum jitter, and overall network throughput.
Aspects: passing fad or new foundation?

Aspect-oriented software development (AOSD) has a lot of interest in the research community. It has also found early adopters in application development and middleware. This panel discusses the potential expansion and use of AOP into mainstream software development.This question is not just directed to the aspect research community, but also to practicing software development teams and organizations. The panel will explore the appropriate position and awareness of aspect-orientation amidst other advances in software engineering; how to prepare organizations for adoption; and what additional research and development is necessary. The panel discussion will help the OO community to understand the appropriate use of aspect-orientation. It will also highlight areas where additional efforts by AOSD researchers and professionals are required.
Discourse Structures for Text Generation

Text generation programs need to be designed around a theory of text organization. This paper introduces Rhetorical Structure Theory, a theory of text structure in which each region of text has a central nuclear part and a number of satellites related to it. A natural text is analyzed as an example, the mechanisms of the theory are identified, and their formalization is discussed. In a comparison, Rhetorical Structure Theory is found to be more comprehensive and more informative about text function than the text organization parts of previous text generation systems.
Novel Stable Camptothecin Derivatives Replacing the E-Ring Lactone by a Ketone Function Are Potent Inhibitors of Topoisomerase I and Promising Antitumor Drugs

The E-ring lactone is the Achilles' heel of camptothecin derivatives: although it is considered necessary for the inhibition of the enzyme topoisomerase I (topo1), the opening of the lactone into a carboxylate abolishes the generation of topo1-mediated DNA breaks. S38809 is a novel camptothecin analog with a stable 5-membered E-ring ketone; therefore, it lacks the lactone function. DNA relaxation and cleavage assays revealed that S38809 functions as a typical topo1 poison by stimulating DNA cleavage at T↓G sites. The activity was strongly dependent on the stereochemistry of the C-7 carbon atom that bears the hydroxy group. S38809 proved to be a potent cytotoxic agent, with a mean IC50 of 5.4 nM versus 11.6 nM for topotecan and 3.3 nM for SN38 (the active metabolite of irinotecan) on a panel of 31 human tumor cell lines. The cytotoxicity of S38809 and its ability to stabilize cleavable complexes was considerably reduced in camptothecin-resistant cells that express a mutated topo1, confirming that topo1 is its primary target. Cell death induced by topo1 poisoning requires the conversion of DNA single-strand breaks into double-strand breaks that can be detected by the formation of phosphorylated histone H2AX. In HCT116 cells, topotecan, SN38, and S38809 induced histone H2AX phosphorylation in S phase of the cell cycle, with S38809 being as potent as SN38 and 5-fold more potent than topotecan. In vivo, S38809 showed a marked antitumor activity against HCT116 xenografts. These findings open a new route for improving the pharmacological properties of camptothecin derivatives.
Parametric Images in Assessing Bone Grafts Using Dynamic 18F-Fluoride PET

The early identification of graft failure would improve patient management. 18F-fluoride is a suitable tracer for quantifying bone metabolism. Performance of parametric images constructed by Patlak graphical analysis (PGA) with various time periods was evaluated in the analysis of dynamic 18F-fluoride PET studies of eight patients with fibula bone grafts after limb salvage surgery. The PGA parametric image approach tended to underestimate influx rate. The linear portion of PGA analysis was found to be from 10 to 50 min. It shows promise in providing a quantitative assessment of the viability of bone grafts.
Aqueous Transduction of Poly-Sige Disk Resonators

This paper demonstrates an electrostatic transducer for lateral contour-mode resonators in which the transduction gaps are filled with a liquid dielectric (water) having much higher permittivity than air ( kappawater = 80.1). Aqueous transduction is more efficient than air-gap transduction (lower motional impedance) and has a higher frequency tuning range compared than solid-dielectric transduction. We have demonstrated a 42 MHz poly-SiGe disk resonator with de-ionized (Dl) water confined to the electrode gaps. The resonator has a measured quality factor (Q) of 3,800, motional impedance (Rx) of 3.9 kOmega and 3% series frequency tuning range.
Quantitative studies on T cell diversity. II. Determination of the frequencies and Lyt phenotypes of two types of precursor cells for alloreactive cytotoxic T cells in polyclonally and specifically activated splenic T cells

Two different limiting dilution systems have been applied to compare precursor frequencies of alloreactive cytotoxic T cells (CTL-P) in the polyclonally and specifically activated lymphocyte populations and in selected Lyt T cell subsets. Both systems make use of T cell growth factor for T cell expansion but differ with respect to the activation step in that lymphocytes are either activated directly with allogenetic stimulator cells or are sensitized polyclonally with concanavalin A (Con A) in bulk culture before their expansion under limiting dilution conditions. In polyclonally activated C57BL/6 lymphocyte populations, two types of CTL-P specific for H-2d alloantigens could be identified: a frequent set with a frequency of 1/100-1/300, and a rare set with a frequency of 1/2,000-1/8,000. In contrast, only a single CTL-P set was found in specifically activated populations with a frequency similar to that of the frequent CTL-P found on Con A blasts. In Con A blasts, the frequent at higher cell concentrations by suppressor T cells, whereas rare CTL-P were insensitive to this suppressive mechanism. Whereas in specifically activated T cells, the predominant CTL-P phenotype was Lyt- 123, the predominant Lyt phenotypes for the frequent and the rare CTL-P found in Con A blasts were Lyt-123 and Lyt-123, respectively, which suggests that they represent primary and secondary CTL-P, respectively. The results are discussed with respect to previous reports on the involvement of Lyt T cell subsets in the generation of cytotoxic responses and their regulation by T suppressor cells.
Altered Sensitivity to Rewarding and Aversive Drugs in Mice with Inducible Disruption of cAMP Response Element-Binding Protein Function within the Nucleus Accumbens

The transcription factor cAMP response element-binding protein (CREB) within the nucleus accumbens (NAc) plays an important role in regulating mood. In rodents, increased CREB activity within the NAc produces depression-like signs including anhedonia, whereas disruption of CREB activity by expression of a dominant-negative CREB (mCREB, which acts as a CREB antagonist) has antidepressant-like effects. We examined how disruption of CREB activity affects brain reward processes using intracranial self-stimulation (ICSS) and inducible bitransgenic mice with enriched expression of mCREB in forebrain regions including the NAc. Mutant mice or littermate controls were prepared with lateral hypothalamic stimulating electrodes, and trained in the ICSS procedure to determine the frequency at which the stimulation becomes rewarding (threshold). Inducible expression of mCREB did not affect baseline sensitivity to brain stimulation itself. However, mCREB-expressing mice were more sensitive to the rewarding (threshold-lowering) effects of cocaine. Interestingly, mCREB mice were insensitive to the depressive-like (threshold-elevating) effects of the κ-opioid receptor agonist U50,488. These behavioral differences were accompanied by decreased mRNA expression of G-protein receptor kinase-3 (GRK3), a protein involved in opioid receptor desensitization, within the NAc of mCREB mice. Disruption of CREB or GRK3 activity within the NAc specifically by viral-mediated gene transfer enhanced the rewarding impact of brain stimulation in rats, establishing the contribution of functional changes within this region. Together with previous findings, these studies raise the possibility that disruption of CREB in the NAc influences motivation by simultaneously facilitating reward and reducing depressive-like states such as anhedonia and dysphoria.
Event-Based Decompositions for Reasoning about External Change in Planners

An increasing number of planners can handle uncertainty in the domain or in action outcomes. However, less work has addressed building plans when the planner's world can change independently of the planning agent in an uncertain manner. In this paper, I model this change with external events that concisely represent some aspects of structure in the planner's domain. This event model is given a formal semantics in terms of a Markov chain, but probabilistic computations from this chain would be intractable in real-world domains. I describe a technique, based on a reachability analysis of a graph built from the events, that allows abstractions of the Markov chain to be built to answer specific queries efficiently. I prove that the technique is correct. I have implemented a planner that uses this technique, and I show an example from a large planning domain.
Re-expression of methylation-induced tumor suppressor gene silencing is associated with the state of histone modification in gastric cancer cell lines.

AIM To identify the relationship between DNA hyper-methylation and histone modification at a hyperme-thylated, silenced tumor suppressor gene promoter in human gastric cancer cell lines and to elucidate whether alteration of DNA methylation could affect histone modification. METHODS We used chromatin immunoprecipitation (ChIP) assay to assess the status of histone acetylation and methylation in promoter regions of the p16 and mutL homolog 1 (MLH1) genes in 2 gastric cancer cell lines, SGC-7901 and MGC-803. We used methylation-specific PCR (MSP) to evaluate the effect of 5-Aza-2'-deoxycytidine (5-Aza-dC), trichostatin A (TSA) or their combination treatment on DNA methylation status. We used RT-PCR to determine whether alterations of histone modification status after 5-Aza-dC and TSA treatment are reflected in gene expression. RESULTS For the p16 and MLH1 genes in two cell lines, silenced loci associated with DNA hypermethylation were characterized by histone H3-K9 hypoacetylation and hypermethylation and histone H3-K4 hypomethylation. Treatment with TSA resulted in moderately increased histone H3-K9 acetylation at the silenced loci with no effect on histone H3-K9 methylation and minimal effects on gene expression. In contrast, treatment with 5-Aza-dC rapidly reduced histone H3-K9 methylation at the silenced loci and resulted in reactivation of the two genes. Combined treatment with 5-Aza-dC and TSA was synergistic in reactivating gene expression at the loci showing DNA hypermethylation. Similarly, histone H3-K4 methylation was not affected after TSA treatment, and increased moderately at the silenced loci after 5-Aza-dC treatment. CONCLUSION Hypermethylation of DNA in promoter CpG islands is related to transcriptional silencing of tumor suppressor genes. Histone H3-K9 methylation in different regions of the promoters studied correlates with DNA methylation status of each gene in gastric cancer cells. However, histone H3-K9 acetylation and H3-K4 methylation inversely correlate with DNA methylation status of each gene in gastric cancer cells. Alteration of DNA methylation affects histone modification.
An order flow model and a liquidity measure of financial markets

The thesis seeks a better understanding of liquidity generation process of financial markets and attempts to find a quantitative measure of market liquidity. Various statistical modeling techniques are introduced to model order flow generation, which is a liquidity generation process of the market. The order flow model successively replicates various statistical properties of price returns including fat-tailed distribution of returns, no autocorrelation of returns and strong positive autocorrelation of transaction signs. While attempting to explain how the order flow model satisfies Efficient Market Hypothesis (EMH), I discovered a method of calibrating market liquidity from order flow data. Thesis Supervisor: Tomaso Poggio Title: Eugene McDermott Professor Thesis Supervisor: Andrew W. Lo Title: Harris and Harris Group Professor Thesis Supervisor: J. Doyne Farmer Title: Professor, Santa Fe Institute
An Analysis of Visual Speech Information Applied to Voice Activity Detection

We present a new approach to the voice activity detection (VAD) problem for speech signals embedded in non-stationary noise. The method is based on automatic lipreading: the objective is to detect voice activity or non-activity by exploiting the coherence between the speech acoustic signal and the speaker's lip movements. From a comprehensive analysis of lip shape parameters during speech and non-speech events, we show that a single appropriate visual parameter, defined to characterize the lip movements, can be used for the detection of sections of voice activity or more precisely, for the detection of silence sections. Detection scores obtained on spontaneous speech confirm the efficiency of the visual voice activity detector (VVAD)
A Bimorph Multi-layer Piezoelectric Vibration Energy Harvester

This paper reports a bimorph piezoelectric vibration energy harvester incorporating multiple PZT layers. The advantage of a multi-layer generator is that it produces a higher power than a single-layer generator having the same total thickness. In addition, a lower voltage is required to polarize a multi-layer generator reducing the risk of breakdown during polarization. Moreover, the optimum resistive load of a multi-layer generator is much lower than that of a single-layer generator, which makes it easier to couple to the electrical domain. In this work, it was found, experimentally, that a double-layer generator produces 41.5% and 19.4% more power than a singlelayer generator with the same total thickness of PZT and resonant frequency. This was verified theoretically. The generators have been fabricated by screen printing which is attractive for low cost mass production.
Functional links and robustness in food webs

The robustness of ecosystems to species losses is a central question in ecology, given the current pace of extinctions and the many species threatened by human impacts, including habitat destruction and climate change. Robustness from the perspective of secondary extinctions has been addressed in the context of food webs to consider the complex network of species interactions that underlie responses to perturbations. In-silico removal experiments have examined the structural properties of food webs that enhance or hamper the robustness of ecosystems to species losses, with a focus on the role of hubs, the most connected species. Here we take a different approach and focus on the role of the connections themselves. We show that trophic links can be divided into functional and redundant based on their contribution to robustness. The analysis of empirical webs shows that hubs are not necessarily the most important species as they may hold many redundant links. Furthermore, the fraction of functional connections is high and constant across systems regardless of size and interconnectedness. The main consequence of this scaling pattern is that ecosystem robustness can be considerably reduced by species extinctions even when these do not result in any secondary extinctions. This introduces the possibility of tipping points in the collapse of ecosystems.
A cis-Acting DNA Element Located between TATA Box and Transcription Initiation Site Is Critical in Response to Regulatory Sequences in Human Angiotensinogen Gene*

The promoter of the human angiotensinogen (hAG) gene functioned in its own core promoter context but not when replaced with simian virus 40 (SV40) core promoter, suggesting the presence of a transcriptionally important cis-acting sequence. Electrophoretic mobility shift assays demonstrated that a ubiquitously expressed nuclear factor, AGCF1, bound to AGCE1 (hore promoter lement 1; positions −25 to −1) located between the TATA box and transcription initiation site. Substitution mutation in AGCE1 which disrupted AGCF1 binding affected the promoter activity more severely than a nonsense mutation of the hAG TATA sequences did. When AGCE1 was placed at the downstream of SV40 core promoter, the responsiveness to hAG upstream region was significantly restored. Furthermore, mutation and in vivo competition experiments suggested that AGCF1 acts as a critical regulator of hAG transcription by mediating the activity of the hAG upstream and downstream enhancer elements. DNase I footprinting and UV cross-linking analyses showed that AGCF1 with apparent molecular masses of 31, 33, and 43 kDa as the components protected the region from −26 to −9 which partially overlapped with the TATA box consensus sequences. These findings indicate that AGCE1 in addition to the TATA box plays a key role in mediating the hAG regulatory elements.
An integrated method of 3D garment design

Abstract We present an intuitive method that seamlessly integrates the whole process of garment design including 3D modeling, pattern development, garment simulation, and grading. Firstly, a sketch-based modeling method is proposed to design a 3D garment using editable control curves. Secondly, 2D patterns are developed by flattening 3D surface patches, then a 3D fine garment is formed directly based on the information of sewing relations and correspondence between 3D surfaces and 2D patterns. Lastly, garment templates are introduced to realize automatic design-preserving transfer of garments between human bodies with different sizes and shapes. The method is able to design 3D garments and 2D patterns efficiently and accurately. Our study provides an easy-to-learn and easy-to-use tool for both fashion designers and computer artists.