Miracle-dz/UniFAR-FTUs huggingface dataset:
Transgenic mouse models generated by hydrodynamic transfection for genetic studies of liver cancer and preclinical testing of anti‐cancer therapy

Hepatocellular carcinoma (HCC) is one of the most lethal cancers worldwide; however, the genetic mechanisms underlying its pathogenesis are incompletely understood. Genetically engineered mouse (GEM) models of HCC have been developed to elucidate the role of individual cancer‐related genes in hepatocarcinogenesis. However, the expensive and time‐consuming processes related to generating a GEM model discourage the development of diverse genotype models. Recently, a simple and inexpensive liver‐specific transgenic approach was developed, in which a hydrodynamics‐based transfection (HT) method was coupled with the Sleeping Beauty transposase system. Various HT models in which different oncogenic pathways are activated and/or tumor‐suppressing pathways inactivated have been developed in recent years. The applicability of HT models in liver cancer research is expected to broaden and ultimately elucidate the cooperation between oncogenic signaling pathways and aid in designing molecular therapy to target altered pathways.
The Impact of Locality and Authority on Emergent Conventions: Initial Observations

In the design of systems of multiple agents, we must deal with the potential for conflict that is inherent in the interactions among agents; to ensure efficient operation, these interactions must be coordinated. We extend, in two related ways, an existing framework that allows behavioral conventions to emerge in agent societies. We first consider localizing agents, thus limiting their interactions. We then consider giving some agents authority over others by implementing asymmetric interactions. Our primary interest is to explore how locality and authority affect the emergence of conventions. Through computer simulations of agent societies of various configurations, we begin to develop an intuition about what features of a society promote or inhibit the spontaneous generation of coordinating conventions.
Coverage and costs of childhood immunizations in Cameroon.

OBJECTIVE To quantify the association between household-level and provider-level determinants and childhood immunization rates in Cameroon while also calculating the cost of childhood immunizations. METHODS This study uses multilevel regression analysis to calculate these relationships. The 1998 Cameroon Demographic and Health Survey and the 2000 Multiple Indicator Cluster Survey are the main sources of household-level data. These surveys are supplemented by data from a 2002 survey of health facilities conducted in three provinces. At the national level, immunization financing data were collected from the Ministry of Health and donors that support the national Expanded Programme on Immunization. FINDINGS The 1998 survey found that nationally 37% of children were fully immunized; the 2000 survey found that nationally 34% were fully immunized. These results are strongly correlated with both the mother's level of education and the household's economic status. Multilevel logistic regression shows that maternal education level is a stronger predictor of positive immunization status than is relative economic status. Children of mothers with secondary education or higher education were 3 times more likely to be fully vaccinated than children whose mothers had not completed primary education. At the health-facility level, both having art immunization plan and regular supervisory visits from someone at the health-district level are strongly positively associated with immunization rates. The cost of routine vaccinations for each fully immunized child is 12.73 U.S. dollars when donors' contributions are included but not the costs of immunization campaigns. CONCLUSION Studies conducted in the 1980s and 1990s found that costs per fully immunized child varied from 2.19 U.S. dollars to 26.59 U.S. dollars (not adjusted for inflation) in a range of low-income and middle-income countries. The relatively low rates of immunization coverage in Cameroon, and the strong influence of the household's socioeconomic status--particularly the mother's level of education--on immunization rates suggest that the effectiveness of the Cameroon programme could be increased by promoting immunization and directing such programmes towards households with limited resources.
Sixteen-slice multi-detector computed tomographic angiography improves the accuracy of screening for blunt cerebrovascular injury.

BACKGROUND Blunt cerebrovascular injuries (BCVI) are rare but potentially devastating injuries, particularly if the diagnosis is delayed. Only four-vessel cerebral angiography (FVCA) has been shown to be adequately sensitive and specific as a screening tool for BCVI but is resource-intensive and invasive. Computed tomography (CT) angiography has emerged as a possible alternative, but its accuracy has been poor, particularly for low-grade injuries. Recent advances in CT technology, particularly the use of a multi-detector array for image acquisition should improve the accuracy of this technique. This study is the first reported experience of the role of the 16-slice multi- detector CT scanner in screening for BCVI. METHODS From January 2, 2003 to October 31, 2004, all patients who met predefined screening criteria were screened for blunt injury to the carotid (BCI) and vertebral (BVI) arteries with a 16-slice multi-detector CT scanner with angiographic reconstruction (CTA). If CTA was positive or equivocal for BCVI, FVCA was performed as a confirmatory test. If CTA was negative, no further diagnostic studies were performed. RESULTS There were 435 patients who met criteria and were screened with CTA. Of these, 25 injuries were identified in 24 patients for an incidence of BCVI of 1.2% (24/2023) among all blunt admissions (BTA) and 5.5% (24/435) among screened patients (SP). This was increased compared with the four-slice era (0.38% BTA, 2.4% SP, p<0.01). No patient with a negative CTA was subsequently identified as having, or developed neurologic symptoms attributable to a missed BCVI. CONCLUSION Sixteen-slice multi-detector CT angiography is an excellent tool to screen for BCVI and detects all clinically significant injuries. The detected incidence of BCVI increased more than threefold with the 16-slice scanner when compared with the four-slice scanner. This demonstrates a clear technological improvement in our ability to screen for these injuries.
Linguistic, Social and Cultural Perspectives on Sign Language in South Africa.

The past decade in South Africa has seen monumental changes in practically every sphere of life. Nowhere are such changes more evident than in the celebration of the diverse and rich cultures which co-exist in South Africa, and the recognition of this diversity is one of the great resources of the nation. One aspect of this diversity that is often overlooked, however, is that which characterises the deaf community. In this article, we provide an overview of the nature and different types of signed language, and then offer a detailed discussion of the research currently available with respect to South African Sign Language (SASL), focusing on structural, lexical and lexicographical aspects of SASL. The nature of deaf culture' both in general and in the South African case, is also examined, together with issues of language policy as they are manifested in the case of SASL.
Release of 11-cis-retinal from cellular retinaldehyde-binding protein by acidic lipids

Purpose To determine molecular mechanisms for the release of 11-cis-retinal from the binding pocket of cellular retinaldehyde-binding protein (CRALBP). Methods Binding of CRALBP to lipid surfaces was assessed with a lipid-immunoblot assay. Lipids were presented to CRALBP as small unilamellar vesicles (SUVs) consisting of phosphatidylcholine (PC) plus other lipids. Release of 9-cis-retinal or 11-cis-retinal from CRALBP was measured with spectral and high performance liquid chromatography (HPLC) assays based on the protection of the protein-bound retinal carbonyl group from reaction with NH2OH. The electrostatic surface potential of CRALBP was calculated from a model of its structure using the program CCP4mg. Results Incubation of CRALBP·11-cis-retinal with lipids absorbed on nitrocellulose revealed binding to the acidic lipids, phosphatidic acid (PA)>phosphatidylinositol 3,4,5-trisphosphate [PI(3,4,5)P3]>phosphatidylserine (PS)> PI(4,5)P2 and little or no binding to PC, phosphatidylethanolamine (PE), or PI(4)P. 11-cis-retinal was released during incubation of CRALBP with SUVs consisting of PC plus 50 mol% PA but not during incubation with those composed of 100 mol% PC. The efficacy of release of 9-cis-retinal or 11-cis-retinal from CRALBP by phospholipid-containing SUVs generally paralleled that of the binding of CRALBP to the lipids (PA>PS>PI>>PC). Examination of the electrostatic surface potential of the protein structure revealed a basic recess on one face of the protein, which may bind acidic lipids. Conclusions Our results identify the first physiologic substances that release 11-cis-retinal from CRALBP. PA and PS are relatively minor membrane lipids that can be generated in the cytoplasmic leaflet of the plasma membrane in response to various signal transduction pathways, where they could interact with cytosolic CRALBP. The mechanism for release of retinal from CRALBP by acidic lipids remains to be determined but could involve binding of the acidic lipid in the 11-cis-retinal binding site or to the positive basic recess on the protein surface. These results open a new facet in our understanding of how CRALBP functions in the regeneration of visual pigments.
Situational Prevention of Child Abuse in the New Technologies

Situational prevention shifts attention from the psychological characteristics of the individual performing behaviour to the facilitating role played by the immediate environment in which the behaviour occurs. Applied to the problem of Internet child pornography, the situational approach emphasises the role of opportunity in driving consumption. It is argued that under the right environmental conditions the potential to view children as sexual objects is more widespread than sexual deviance models suggest. The Internet allows individuals to satisfy their secret desires conveniently, cheaply and relatively risk-free. Situational prevention of Internet child pornography requires strategies that reduce the opportunities for accessing child abuse images by making the activity less rewarding, more difficult, and riskier.
Epidermal or Dermal Specific Knockout of PHD-2 Enhances Wound Healing and Minimizes Ischemic Injury

Introduction Hypoxia-inducible factor (HIF)-1α, part of the heterodimeric transcription factor that mediates the cellular response to hypoxia, is critical for the expression of multiple angiogenic growth factors, cell motility, and the recruitment of endothelial progenitor cells. Inhibition of the oxygen-dependent negative regulator of HIF-1α, prolyl hydroxylase domain-2 (PHD-2), leads to increased HIF-1α and mimics various cellular and physiological responses to hypoxia. The roles of PHD-2 in the epidermis and dermis have not been clearly defined in wound healing. Methods Epidermal and dermal specific PHD-2 knockout (KO) mice were developed in a C57BL/6J (wild type) background by crossing homozygous floxed PHD-2 mice with heterozygous K14-Cre mice and heterozygous Col1A2-Cre-ER mice to get homozygous floxed PHD-2/heterozygous K14-Cre and homozygous floxed PHD-2/heterozygous floxed Col1A2-Cre-ER mice, respectively. Ten to twelve-week-old PHD-2 KO and wild type (WT) mice were subjected to wounding and ischemic pedicle flap model. The amount of healing was grossly quantified with ImageJ software. Western blot and qRT-PCR was run on protein and RNA from primary cells cultured in vitro. Results qRT-PCR demonstrated a significant decrease of PHD-2 in keratinocytes and fibroblasts derived from tissue specific KO mice relative to control mice (*p<0.05). Western blot analysis showed a significant increase in HIF-1α and VEGF protein levels in PHD-2 KO mice relative to control mice (*p<0.05). PHD-2 KO mice showed significantly accelerated wound closure relative to WT (*p<0.05). When ischemia was analyzed at day nine post-surgery in a flap model, the PHD-2 tissue specific knockout mice showed significantly more viable flaps than WT (*p<0.05). Conclusions PHD-2 plays a significant role in the rates of wound healing and response to ischemic insult in mice. Further exploration shows PHD-2 KO increases cellular levels of HIF-1α and this increase leads to the transcription of downstream angiogenic factors such as VEGF.
Activities of Daily Living Is a Critical Factor in Predicting Outcome After Carotid Endarterectomy in Asymptomatic Patients

Background and Purpose— Ability to perform basic daily activity represented by functional status (FNS) before surgery can be assessed in the clinic for determining health status of the patient. We sought to study the effect of FNS on postoperative outcomes after carotid endarterectomy (CEA) in a national data set. Methods— National Surgical Quality Improvement Project is a national data set, which includes data from >300 hospitals. Patients who underwent CEA were identified by Current Procedural Terminology code and divided into 3 categories based on FNS: independent, partially dependent, and dependent. Thirty-day postoperative stroke, death, and other postoperative complications were identified as the study end point. We used multivariate logistic regression to estimate odds ratio for outcomes while controlling for sex, race, diabetes mellitus, cardiovascular disease, smoking, and other confounders. Results— Of 19 748 CEAs, 19 348 (97.97%) were functionally independent, 377 (1.99%) were functionally partially dependent, and 23 (0.12%) were functionallydependent. In functionally independent group, there were 196 (1.01%) strokes, 84 (0.43%) deaths, and 1416 (7.17%) other complications, whereas in the functionally partially dependent group, there were 14 (3.71%) strokes, 10 (2.65%) deaths, and 80 (21.22%) other complications. In multivariable risk-adjusted model, using functionally independent as reference, functionally partially dependent was associated with death (odds ratio, 3.3; 95% confidence interval, 1.6–6.8; P<0.001), stroke (odds ratio, 3; 95% confidence interval, 1.7–5.4; P<0.001), and other complications (odds ratio, 2.5; 95% confidence interval, 1.9–3.2; P<0.001). Conclusions— In this national data set, patient’s inability to perform basic activities of independent living is associated with adverse postoperative outcomes after CEA. Hence, FNS should be vigilantly assessed in clinic for risk stratification along with other objective factors for gauging risk of adverse outcomes after CEA.
Belief Propagation in Networks of Spiking Neurons

Abstract From a theoretical point of view, statistical inference is an attractive model of brain operation. However, it is unclear how to implement these inferential processes in neuronal networks. We offer a solution to this problem by showing in detailed simulations how the belief propagation algorithm on a factor graph can be embedded in a network of spiking neurons. We use pools of spiking neurons as the function nodes of the factor graph. Each pool gathers “messages” in the form of population activities from its input nodes and combines them through its network dynamics. Each of the various output messages to be transmitted over the edges of the graph is computed by a group of readout neurons that feed in their respective destination pools. We use this approach to implement two examples of factor graphs. The first example, drawn from coding theory, models the transmission of signals through an unreliable channel and demonstrates the principles and generality of our network approach. The second, more applied example is of a psychophysical mechanism in which visual cues are used to resolve hypotheses about the interpretation of an object's shape and illumination. These two examples, and also a statistical analysis, demonstrate good agreement between the performance of our networks and the direct numerical evaluation of belief propagation.
Therapeutic Silencing of KRAS Using Systemically Delivered siRNAs

Despite being among the most common oncogenes in human cancer, to date, there are no effective clinical options for inhibiting KRAS activity. We investigated whether systemically delivered KRAS siRNAs have therapeutic potential in KRAS-mutated cancer models. We identified KRAS siRNA sequences with notable potency in knocking down KRAS expression. Using lung and colon adenocarcinoma cell lines, we assessed antiproliferative effects of KRAS silencing in vitro. For in vivo experiments, we used a nanoliposomal delivery platform, DOPC, for systemic delivery of siRNAs. Various lung and colon cancer models were used to determine efficacy of systemic KRAS siRNA based on tumor growth, development of metastasis, and downstream signaling. KRAS siRNA sequences induced >90% knockdown of KRAS expression, significantly reducing viability in mutant cell lines. In the lung cancer model, KRAS siRNA treatment demonstrated significant reductions in primary tumor growth and distant metastatic disease, while the addition of CDDP was not additive. Significant reductions in Ki-67 indices were seen in all treatment groups, whereas significant increases in caspase-3 activity were only seen in the CDDP treatment groups. In the colon cancer model, KRAS siRNA reduced tumor KRAS and pERK expression. KRAS siRNAs significantly reduced HCP1 subcutaneous tumor growth, as well as outgrowth of liver metastases. Our studies demonstrate a proof-of-concept approach to therapeutic KRAS targeting using nanoparticle delivery of siRNA. This study highlights the potential translational impact of therapeutic RNA interference, which may have broad applications in oncology, especially for traditional “undruggable” targets. Mol Cancer Ther; 13(12); 2876–85. ©2014 AACR.
Paraprofessional Proximity and Decision Making During Interactions of Students with Visual Impairments

This study examined two aspects of the use of paraprofessionals with students with visual impairments: 1) the effect of paraprofessional proximity on the students’ interactions with peers and teachers in the regular education classroom, and 2) factors that may influence a paraprofessional’s decision to interact or not interact with a student with a visual impairment. The four student/paraprofessional case studies included data collected by means of classroom observations, demographic forms, and semi-structured interviews. The classroom observation data were analyzed using the chi-square statistics to determine relationships between paraprofessional proximity and classroom activity setting, interaction participants, interaction initiators, and type of interaction that occurred. The data collected through the interviews were coded to determine themes. The data from all the case studies were cross analyzed to determine relationships and themes across cases. Proximity of paraprofessionals to students with visual impairments in the regular education classroom appears to have an effect on the interactions that occur between students with visual impairments, peers, and teachers. More interactions occurred between students and peers and between students and teachers when paraprofessionals were at a distance. Also, when paraprofessionals were at a distance, peers and teachers were more likely to initiate interactions with students with visual impairments. The decision making process for paraprofessionals is complicated. Factors that may influence how paraprofessionals make decisions concerning students with visual impairments were professional experience, personal experience, education level and type,
Interhemispheric observations of the ionospheric signature of tail reconnection during IMF-northward non-substorm intervals

This paper presents the first interhemispheric radar observations interpreted as the ionospheric response to tail reconnection during IMF-northward non-substorm in- tervals. SuperDARN measurements of plasma convection in the nightside ionospheres of both hemispheres, taken on 21-22 February and 26-27 April 2000, show bursts of flow in the midnight sector which are understood to be characteristic of such phenomena. Upstream interplanetary magnetic field data confirm that the field orientation at the dayside mag- netopause was northwards, but with a significant IMF By component (negative during the first interval, positive dur- ing the second), for many hours prior to the bursts being ob- served. During the By -negative interval the bursts were di- rected westwards in the Northern Hemisphere and eastwards in the Southern Hemisphere; during the By -positive interval their directions were reversed. These two asymmetries be- tween the different orientations of IMF By and between the two hemispheres are key to our understanding of the magne- tospheric phenomenon responsible for generating the bursts. They provide further evidence in support of the idea that the bursts are a result of reconnection in an asymmetric tail un- der the prolonged influence of IMF By . Concurrent data from ground magnetometers and geosynchronous satellites confirm that the bursts have no associated substorm charac- teristics, consistent with previous studies.
Control of the yeast telomeric senescence survival pathways of recombination by the Mec1 and Mec3 DNA damage sensors and RPA

Saccharomyces cerevisiae telomerase-negative cells undergo homologous recombination on subtelomeric or TG1–3 telomeric sequences, thus allowing Type I or Type II post-senescence survival, respectively. Here, we find that the DNA damage sensors, Mec1, Mec3 and Rad24 control Type II recombination, while the Rad9 adaptor protein and the Rad53 and Chk1 effector kinases have no effect on survivor type selection. Therefore, the Mec1 and Mec3 checkpoint complexes control telomeric recombination independently of their roles in generating and amplifying the Mec1-Rad53-Chk1 kinase cascade. rfa1-t11 mutant cells, bearing a mutation in Replication Protein A (RPA) conferring a defect in recruiting Mec1-Ddc2, were also deficient in both types of telomeric recombination. Importantly, expression of an Rfa1-t11-Ddc2 hybrid fusion protein restored checkpoint-dependent arrest, but did not rescue defective telomeric recombination. Therefore, the Rfa1-t11-associated defect in telomeric recombination is not solely due to its failure to recruit Mec1. We have also isolated novel alleles of RFA1 that were deficient in Type I but not in Type II recombination and proficient in checkpoint control. Therefore, the checkpoint and recombination functions of RPA can be genetically separated, as can the RPA-mediated control of the two types of telomeric recombination.