Miracle-dz/UniFAR-FTUs huggingface dataset:
Tissue-specific RNA interference in postimplantation mouse embryos with endoribonuclease-prepared short interfering RNA

RNA interference (RNAi) using double-stranded RNA has been used for the systematic analysis of gene function in invertebrate organisms. Here we have explored the use of short interfering RNA (siRNA) to knock down gene expression during the development of mammalian postimplantation embryos. The developing CNS system of embryonic day 10 mouse embryos was used as a model tissue. siRNA prepared by endoribonuclease digestion (esiRNA) was injected into the lumen of the neural tube at specific regions and delivered into neuroepithelial cells by directed electroporation. Injected and electroporated embryos were grown for 1 day in whole-embryo culture and the effects of RNAi were examined. esiRNA directed against β-galactosidase (β-gal), coelectroporated into neuroepithelial cells together with reporter plasmids expressing GFP and β-gal, abolished expression of β-gal but not GFP, showing the specificity of the esiRNA-mediated RNAi. To demonstrate RNAi of endogenous gene expression, we used heterozygous embryos of a knock-in mouse line expressing GFP from the Tis21 locus, a gene turned on in neuroepithelial cells that switch from proliferation to neurogenesis. GFP-directed esiRNA electroporated into neuroepithelial cells of such embryos blocked the GFP expression normally occurring on the onset of neurogenesis. Taken together, our data indicate that esiRNA delivered in a tissue-specific manner by topical injection followed by directed electroporation can efficiently silence endogenous gene expression in mammalian postimplantation embryos.
Towards Building Deep Networks with Bayesian Factor Graphs

We propose a Multi-Layer Network based on the Bayesian framework of the Factor Graphs in Reduced Normal Form (FGrn) applied to a two-dimensional lattice. The Latent Variable Model (LVM) is the basic building block of a quadtree hierarchy built on top of a bottom layer of random variables that represent pixels of an image, a feature map, or more generally a collection of spatially distributed discrete variables. The multi-layer architecture implements a hierarchical data representation that, via belief propagation, can be used for learning and inference. Typical uses are pattern completion, correction and classification. The FGrn paradigm provides great flexibility and modularity and appears as a promising candidate for building deep networks: the system can be easily extended by introducing new and different (in cardinality and in type) variables. Prior knowledge, or supervised information, can be introduced at different scales. The FGrn paradigm provides a handy way for building all kinds of architectures by interconnecting only three types of units: Single Input Single Output (SISO) blocks, Sources and Replicators. The network is designed like a circuit diagram and the belief messages flow bidirectionally in the whole system. The learning algorithms operate only locally within each block. The framework is demonstrated in this paper in a three-layer structure applied to images extracted from a standard data set.
Impact of rotavirus vaccination in regions with low and moderate vaccine uptake in Germany

In Germany, routine RV-vaccination is not adopted into the national immunization schedule as of 2012. Because RV-vaccines were already on the market since 2006, in 2010 a moderate (58%) and low (22%) vaccine uptake was observed in the 5 eastern federal states (EFS) and the 11 western federal states (WFS), respectively. To assess the impact of RV-vaccination, we compared the incidence rates (IR) of RV-related hospitalizations before (2004‒2006) and in seasons after (2008/09–2010/11) RV-vaccine introduction in Germany by utilizing data from the national mandatory disease reporting system. In the EFS, the IR was significantly reduced in age-groups < 18 mo in 2008/09 and in age-groups < 24 mo in 2009/10–2010/11. In the WFS an IR-reduction was observed only in age-groups < 12 mo in 2008/09 and in age-groups < 18 mo in 2009/10–2010/11. Overall IR-reduction in age-groups < 24 mo comparing 2008–11 with 2004–06 was 36% and 25% in EFS and WFS, respectively. In addition, we computed IR-ratios (IRR) in the seasons after mid-2006 with negative binomial regression. The effect of vaccination was independent from the geographic region. Vaccination was associated with a significant reduction in RV-related hospitalizations in the age-groups 6–23 mo. Most prominently, vaccination of 50% of infants led to an estimated decrease in age group 6–11 mo by 42%. No significant reduction was observed in age-groups ≥ 24 mo. In conclusion, in the German setting with low to moderate vaccine uptake, RV-related hospitalization incidence decreased substantially depending on the achieved vaccination coverage, but only in the first two years of life.
Gene therapy following subretinal AAV5 vector delivery is not affected by a previous intravitreal AAV5 vector administration in the partner eye

Purpose In an earlier study we found normal adeno-associated viral vector type 2 (AAV2)-mediated GFP expression after intravitreal injection to one eye of normal C57BL/6J mice. However, GFP expression was very poor in the partner eye of the same mouse if this eye received an intravitreal injection of the same vector one month after the initial intravitreal injection. We also found both injections worked well if they were subretinal. In this study, we tested whether the efficiency of subretinal AAV vector transduction is altered by a previous intravitreal injection in the partner eye and more importantly whether therapeutic efficiency is altered in the rd12 mouse (with a recessive RPE65 mutation) after the same injection series. Methods One μl of scAAV5-smCBA-GFP (1x1013 genome containing viral particles per ml) was intravitreally injected into the right eyes of four-week-old C57BL/6J mice and 1 μl of scAAV5-smCBA-hRPE65 (1x1013 genome containing viral particles per ml) was intravitreally injected into the right eyes of four-week-old rd12 mice Four weeks later, the same vectors were subretinally injected into the left eyes of the same C57BL/6J and rd12 mice. Left eyes of another cohort of eight-week-old rd12 mice received a single subretinal injection of the same scAAV5-smCBA-hRPE65 vector as the positive control. Dark-adapted electroretinograms (ERGs) were recorded five months after the subretinal injections. AAV-mediated GFP expression in C57BL/6J mice and RPE65 expression and ERG restoration in rd12 mice were evaluated five months after the second subretinal injection. Frozen section analysis was performed for GFP fluorescence in C57BL/6J mice and immunostaining for RPE65 in rd12 eyes. Results In rd12 mice, dark-adapted ERGs were minimal following the first intravitreal injection of scAAV5-smCBA-RPE65. Following subsequent subretinal injection in the partner eye, dramatic ERG restoration was recorded in that eye. In fact, ERG b-wave amplitudes were statistically similar to those from the eyes that received the initial subretinal injection at a similar age. In C57BL/6J mice, GFP positive cells were detected in eyes following the first intravitreal injection around the injection site. Strong GFP expression in both the retinal pigment epithelium (RPE) and photoreceptor (PR) cells was detected in the partner eyes following the subsequent subretinal injection. Immunostaining of retinal sections with anti-RPE65 antibody showed strong RPE65 expression mainly in the RPE cells of subretinally injected eyes but not in the intravitreally injected eyes except minimally around the injection site. Conclusions These results show that an initial intravitreal injection of AAV vectors to one eye of a mouse does not influence AAV-mediated gene expression or related therapeutic effects in the other eye when vectors are administered to the subretinal space. This suggests that the subretinal space possesses a unique immune privilege relative to the vitreous cavity.
Dynamic Behavioral Modeling of Nonlinear Microwave Devices Using Real-Time Recurrent Neural Network

A novel real-time recurrent neural network (RTRNN) approach is presented for dynamic behavioral macromodeling of nonlinear microwave devices. A modified real-time recurrent learning algorithm is developed to train the neural network model. This proposed RTRNN model can directly be developed from input-output waveform data without having to rely on the internal details of the devices. Once trained, this model provides fast and accurate prediction on the analog behaviors of the nonlinear microwave devices under modeling, which can readily be incorporated into high-level circuit simulation and optimization. This RTRNN approach enhances the neural modeling speed and accuracy. Moreover, it also provides additional flexibility in handing diverse needs of nonlinear microwave circuit designs in the time domain, such as single-tone and multiple-tone simulations and large-signal simulations by comparison to the previously published neural models. The validity of this proposed approach is illustrated through behavioral macromodeling of two typical microwave devices: power amplifiers and pHEMTs.
Exploring the role of experience in the process of entrepreneurial learning

Researchers have recently showed an increasing interest in understanding entrepreneurship as an experiential learning process. In this article, we investigate the role of prior career experience for the development of entrepreneurial knowledge, i.e., knowledge that facilitates for individuals to recognize and act on opportunities as well as to organize and manage new ventures. Based on an analysis of 291 Swedish entrepreneurs we find links between various career experiences and the development of entrepreneurial knowledge. In addition we also find evidence that the entrepreneurs’ preference for exploring new possibilities vs. exploiting pre-existing knowledge are important to consider to explain this process. The study ends with a discussion of the findings, together with suggestions for future research.
Dual-Agent Molecular Targeting of the Epidermal Growth Factor Receptor (EGFR)

Molecular inhibition of epidermal growth factor receptor (EGFR/HER1) signaling is under active investigation as a promising cancer treatment strategy. We examined the potency of EGFR inhibition achieved by combining anti-EGFR monoclonal antibody and tyrosine kinase inhibitor, which target extracellular and intracellular domains of the receptor, respectively. We specifically studied the combination of cetuximab (Erbitux, C225; ImClone Systems, New York, NY) with either gefitinib (Iressa, ZD1839; AstraZeneca, Macclesfield, UK) or erlotinib (Tarceva, OSI-774; Genentech, South San Francisco, CA) across a variety of human cancer cells. The combination of cetuximab plus gefitinib or erlotinib enhanced growth inhibition over that observed with either agent alone. As measured by immunostaining, inhibition of EGFR phosphorylation with the combination of cetuximab plus gefitinib or erlotinib was augmented over that obtained with single-agent therapy in head and neck (H&N) cancer cell lines. Phosphorylation inhibition of downstream effector molecules [mitogen-activated protein kinase (MAPK) and AKT] also was enhanced in tumor cells treated with the combination of cetuximab plus gefitinib or erlotinib. Flow cytometry and immunoblot analysis demonstrated that treatment of H&N tumor cells with cetuximab in combination with either gefitinib or erlotinib amplified the induction of apoptosis. Following establishment of cetuximab-resistant cell lines, we observed that gefitinib or erlotinib retained the capacity to inhibit growth of lung and H&N tumor cells that were highly resistant to cetuximab. Treatment with gefitinib or erlotinib, but not cetuximab, also could further inhibit the activation of downstream effectors of EGFR signaling in cetuximab-resistant cells, including MAPK and AKT. These data suggest that tyrosine kinase inhibitors may further modulate intracellular signaling that is not fully blocked by extracellular anti-EGFR antibody treatment. Finally, animal studies confirmed that single EGFR inhibitor treatment resulted in partial and transient tumor regression in human lung cancer xenografts. In contrast, more profound tumor regression and regrowth delay were observed in mice treated with the combination of cetuximab and gefitinib or erlotinib. Immunohistochemical staining, which demonstrated significant reduction of the proliferative marker proliferating cell nuclear antigen in mice treated with dual EGFR inhibitors, further supported this in vivo observation. Together, these data suggest that combined treatment with distinct EGFR inhibitory agents can augment the potency of EGFR signaling inhibition. This approach suggests potential new strategies to maximize effective target inhibition, which may improve the therapeutic ratio for anti-EGFR-targeted therapies in developing clinical trials.
High natural prevalence of a fungal prion

Prions are infectious proteins that cause fatal diseases in mammals. Prions have also been found in fungi, but studies on their role in nature are scarce. The proposed biological function of fungal prions is debated and varies from detrimental to benign or even beneficial. [Het-s] is a prion of the fungus Podospora anserina. The het-s locus exists as two antagonistic alleles that constitute an allorecognition system: the het-s allele encoding the protein variant capable of prion formation and the het-S allele encoding a protein variant that cannot form a prion. We document here that het-s alleles, capable of prion formation, are nearly twice as frequent as het-S alleles in a natural population of 112 individuals. Then, we report a 92% prevalence of [Het-s] prion infection among the het-s isolates and find evidence of the role of the [Het-s]/het-S allorecognition system on the incidence of infection by a deleterious senescence plasmid. We explain the het-s/het-S allele ratios by the existence of two selective forces operating at different levels. We propose that during the somatic stage, the role of [Het-s]/HET-S in allorecognition leads to frequency-dependent selection for which an equilibrated frequency would be optimal. However, in the sexual cycle, the [Het-s] prion causes meiotic drive favoring the het-s allele. Our findings indicate that [Het-s] is a selected and, therefore, widespread prion whose activity as selfish genetic element is counteracted by balancing selection for allorecognition polymorphism.
What the Hell are You? An Intercategorical Analysis of Race, Ethnicity, Gender and Disability in the Australian Body Politic

Critical disability studies has examined the intersections between gender and disability. Meanwhile, feminist analyses of the intersection between race, class and gender identities have developed important insights, but failed to include dimensions of disability. A wealth of literature deals with issues of health and illness from a cross-cultural perspective, but disability has been a much-neglected area. This paper will examine why gender, race, class and disability have developed as mutually exclusive areas of research and inquiry. It will argue that an intercategorical examination between racialized groups, disability groups and gendered groups in a period of colonialism and neo-colonialism in the Australian context can bring to the fore the ways dominant cultures produce and reproduce themselves. Issues of eugenics, population control, the constitution of the normal subject and exclusion of different bodies provide evidence of these processes.
Topological properties of modular networks, with a focus on networks of functional connections in the human brain

Complex network theory offers useful approaches to analyze the structural and functional properties of real life networks. In this work, we explore some of the mathematical concepts of network theory and study real life systems from a complex network perspective. We pay particular attention to networks of connections within the human brain. We analyze weighted networks calculated from full functional magnetic resonance imaging (fMRI) data acquired during task performance. The first novelty of this study is the fact that we retain all of the connections between all of the voxels in the full brain fMRI data. We then evaluate the extent to which this rich dataset can be described by existing models of scale-free or exponentially truncated scale-free topology, comparing results across a large number of more complex topological models as well. Our results suggest that the novel model presented in this dissertation offers a significantly better fit at the voxel level. Structural characterization of the brain can also give insights into the effects of traumatic injuries. For our second study, we used brain networks to explore the topological consequences of brain damage in computational models. By simulating the effects of several traumatic brain injury (TBI) models we find a variety of disruptions in the modular structure and connectivity of the post-injury networks. In particular, we focused on the effects of focalized injuries, axonal degeneration and
2-stack 1D-1R Cross-point Structure with Oxide Diodes as Switch Elements for High Density Resistance RAM Applications

We have successfully integrated a 2-stack 8times8 array 1D- lR (one diode-one resistor) structure with 0.5 mumtimes0.5 mum cells in order to demonstrate the feasibility of high density stacked RRAM. p-CuOx/n-InZnOx heterojunction thin film was used for the first time as a oxide diode which shows increased current density of two orders over our previous p-NiOx/n-TiOx oxide diode. And Ti-doped NiO was used for the storage node. No limitation to the number of stacks has been observed from our results. Cell and device properties of our cross-point structure 8times8 array are reported. In addition, all fabrication processes were done at room temperature without other dedicated facilities or processes allowing for compatibility with current CMOS technology. Bi-stable switching for 1D-1R memory was demonstrated for our 2-stack cross-point structures showing excellent behavior for both diode and storage nodes. The forward current density for p-CuOx/n-IZOx diodes was over 104A/cm2, and the operation voltage for the storage node with diode attached was around 3 V.
Turquois: Byzantine consensus in wireless ad hoc networks

The operation of wireless ad hoc networks is intrinsically tied to the ability of nodes to coordinate their actions in a dependable and efficient manner. The failure of some nodes and momentary breakdown of communications, either of accidental or malicious nature, should not result in the failure of the entire system. This paper presents Turquois - an intrusion-tolerant consensus protocol specifically designed for resource-constrained wireless ad hoc networks. Turquois allows an efficient utilization of the broadcasting medium, avoids synchrony assumptions, and refrains from public-key cryptography during its normal operation. The protocol is safe despite the arbitrary failure of f < n over 3 processes from a total of n processes, and unrestricted message omissions. The protocol was prototyped and subject to a comparative performance evaluation against two well-known intrusion-tolerant consensus protocols. The results show that, as the system scales, Turquois outperforms the other protocols by more than an order of magnitude.
Response of milking cows fed a high concentrate, low roughage diet plus sodium bicarbonate, magnesium oxide, or magnesium hydroxide.

To determine the ability of mineral supplements to elevate depressed milk fat percent, we placed 42 Holstein cows in early to midlactation in seven blocks and assigned each to one of six treatments: control (25% corn silage and alfalfa haylage, 75% concentrate, mostly corn, dry matter); control plus magnesium oxide ground to pass a . 425-mm sieve; control plus prilled magnesium oxide sieved to between 1.70 and . 425 mm; control plus sodium bicarbonate; control plus reactive powdered magnesium oxide to pass a 45 microns sieve; and control plus powdered magnesium hydroxide. Sodium bicarbonate was 1% of diet as fed, magnesium oxide . 5%, magnesium hydroxide . 7% later reduced to . 5%. Cows were fed control ration for 3 wk to induce milk fat depression, then were changed to treatment rations for 5 wk. Five cows (unblocked) were continued on each dietary treatment for a digestibility study after the feeding trial. All mineral supplements produced greater milk fat percent and yield of milk fat per day than control and all magnesium treatments produced greater milk fat percent than sodium bicarbonate. Magnesium oxide passing a . 425-mm sieve produced the greatest increase of milk fat percent. Milk production was most for sodium bicarbonate treatment. Supplementation with magnesium increased ruminal magnesium concentration by factors of 1.26 to 3.75. Blood serum, urine, and fecal magnesium concentrations and fecal pH were more for cows fed magnesium than those fed sodium bicarbonate treatments. Kidney filtration ratios of element to creatinine increased for magnesium when diets were supplemented with magnesium and increased for phosphorus and sodium when diets were supplemented with sodium bicarbonate.
Air-Filled SIW interconnections for high performance millimeter-wave circuit and system prototyping and assembly

In this paper, the interconnection between two sections of Air-Filled Substrate Integrated Waveguide (AFSIW) transmission line is presented. AFSIW is of high interest for high performance and low-cost millimeter wave applications. It is based on multilayer Printed Circuit Board (PCB) process. For system prototyping and assembly, it is common to interconnect components and sub-circuits. However, to comply with stringent specifications, especially for space and aeronautical applications, connectors must be avoided as they directly impact the cost, the size and the loss. Also, transition from AFSIW to conventional transmission lines to implement conventional interconnect solutions will not be optimal in term of loss, size and power handling. Instead, in this paper, a direct interconnect between two AFSIW sections is studied. An experimental demonstration of the proposed interconnection shows a 0.29 dB insertion loss.
Let's Talk About Sex: Sexual Health and Communication in Romantic Partners Based on Attachment Style

Though research has explored the domain of attachment style in regards to romantic relationships and sexual behavior, little has been done to connect the two areas of study. Studies indicate that an individual's attachment style can influence their level of sexual intimacy (Hazan & Shaver, 1987; Feeney & Noller, 1990; Bogaert & Sadava, 2002; Gentzler & Kerns, 2004; Birnbaum et aI., 2006) as well as their sexual health behaviors (Gentzler & Kerns, 2004; Davis et aI., 2006; Butzer & Campbell, 2008). However, the current literature has not examined these findings in light of other variables that influence sexual satisfaction, sexual behavior, and the quality of romantic relationships: sexual communication, or conversations about sexually based matters. The present study explored the relationship between three areas of study: attachment style, sexual communication, and sexual health. Data was collected from 243 college-aged individuals in romantic relationships at a Midwestern undergraduate institution. Participants responded to an electronic questionnaire inquiring about demographic and relationship information, sexual behavior, sexual health information, and sexual communication, and completed measures to determine their communication and attachment styles. Significant relationships were found between overall communication, sexual health behavior, sexual satisfaction, and sexual communication. Participants were significantly different in their overall communication, according to their attachment style scoring. Suggestions are made for couples therapists and peer educators on how to inform therapy and wellness intervention approaches to accommodate differences in attachment style, so that individuals are empowered to improve their sexual health and improve sexual and relationship satisfaction.