Miracle-dz/UniFAR-FTUs huggingface dataset:
Antisense radiotherapy: targeting full‐size mdr1 mRNA with 125I‐labelled oligonucleotides

Purpose: Antisense radiotherapy is an approach based on the targeting of mRNA of specific genes by complementary oligonucleotide probes labelled with an Auger‐electron‐emitting radioisotope. Decay of the Auger emitter should specifically destroy the targeted mRNA while producing minimal damage to the rest of mRNA pool and the nuclear DNA. The feasibility of this approach was investigated by using full‐length human multidrug‐resistance gene (mdr1) mRNA as a target. Materials and methods: Antisense oligonucleotides were labelled with [125I] I‐dCTP by primer extension and annealed to target mRNA. Breaks in the target mRNA were analysed by denaturing polyacrylamide gel electriphoresis. Results: The efficiency of 125I‐labelled antisense oligonucleotides in producing RNA strand breaks was tested on short synthetic RNA and DNA targets. The position and specificity of 125I‐induced breaks in the full‐length mRNA were then tested and compared with the cleavage of the target by RNase H. The distribution of the breaks in the longer mRNA is different from that in the short RNA targets, most likely due to a complex folding of RNA strands in the full‐length mRNA. Conclusions: The authors posit that 125I‐labelled antisense probes could be useful not only for targeting mRNA, but also as probes for mRNA folding in vivo.
Lifestyles, social background and eating patterns of 15‐year‐old boys and girls in Finland

The aim was to investigate whether lifestyles or social background have stronger impact on eating patterns among young people. A school‐based survey carried out in 1998 among 15‐year‐old pupils (n=2388) in Helsinki was used as data. The lifestyle dimensions of leisure‐time activities used were street‐oriented lifestyle, commercialised lifestyle, home‐oriented lifestyle, and arts‐oriented and hobby‐oriented lifestyle. Social background was indicated by father's educational level. Three family‐related and school‐related eating measures (eating school lunch, having dinner at home and consumption of recommended foods) and two peer‐related eating measures (consumption of fast food and consumption of sweets) were analysed. Those from households with higher educational level more often took part in meals at home (boys) and at school (all), and also consumed recommended food items more often. A more street‐oriented lifestyle and a more commercialised leisure time were associated with higher intake of fast food and sweets. The results suggest that structural factors such as social background continue to have more influence than lifestyles on young people's daily diet
Electronegative Low-Density Lipoprotein Increases C-Reactive Protein Expression in Vascular Endothelial Cells through the LOX-1 Receptor

Objectives Increased plasma C-reactive protein (CRP) levels are associated with the occurrence and severity of acute coronary syndrome. We investigated whether CRP can be generated in vascular endothelial cells (ECs) after exposure to the most electronegative subfraction of low-density lipoprotein (LDL), L5, which is atherogenic to ECs. Because L5 and CRP are both ligands for the lectin-like oxidized LDL receptor-1 (LOX-1), we also examined the role of LOX-1. Methods and Results Plasma LDL samples isolated from asymptomatic hypercholesterolemic (LDL cholesterol [LDL-C] levels, 154.6±20 mg/dL; n = 7) patients and normocholesterolemic (LDL-C levels, 86.1±21 mg/dL; P<0.001; n = 7) control individuals were chromatographically resolved into 5 subfractions, L1-L5. The L5 percentage (L5%) and the plasma L5 concentration ([L5] = L5% × LDL-C) in the patient and control groups were 8.1±2% vs. 2.3±1% (P<0.001) and 12.6±4 mg/dL vs. 1.9±1 mg/dL (P<0.001), respectively. In hypercholesterolemic patients treated with atorvastatin for 6 months (10 mg/day), [L5] decreased from 12.6±4 mg/dL to 4.5±1.1 mg/dL (P = 0.011; n = 5), whereas both [L5] and L5% returned to baseline levels in 2 noncompliant patients 3 months after discontinuation. In cultured human aortic ECs (HAECs), L5 upregulated CRP expression in a dose- and time-dependent manner up to 2.5-fold (P<0.01), whereas the least electronegative subfraction, L1, had no effect. DiI-labeled L1, internalized through the LDL receptor, became visible inside HAECs within 30 seconds. In contrast, DiI-labeled L5, internalized through LOX-1, became apparent after 5 minutes. L5-induced CRP expression manifested at 30 minutes and was attenuated by neutralizing LOX-1. After 30 minutes, L5 but not L1 induced reactive oxygen species (ROS) production. Both L5-induced ROS and CRP production were attenuated by ROS inhibitor N-acetyl cysteine. Conclusions Our results suggest that CRP, L5, and LOX-1 form a cyclic mechanism in atherogenesis and that reducing plasma L5 levels with atorvastatin disrupts the vascular toxicity of L5.
A Call for the Renewal of Adventism's Communal Consciousness.

It was my first registration as an academic dean. The auditorium had already begun to fill with students who had come to register for a new academic year. Then I was given a dose of reality in my new context. The registrar pulled me over to the side and said it was the academic dean’s job, at the beginning of every academic year, to announce our nojewelry policy to the students. In fact, part of the message was to inform them that non-compliant students would not be allowed to complete their registration. And sure enough, each student was receiving an external inspection to see if he/she was wearing jewelry. Those who wore jewelry either had to take it off or wait to register at a later time. I was literally shocked at the news. The thought of keeping students from registering because they were wearing earrings, bracelets, or necklaces seemed foreign and not very welcoming to me. But, as the new dean, I wasn’t about to enter into a discussion about how we should enforce the university standards. Grudgingly, I made the announcement, gave my warning, and prayed inwardly that the students would cooperate and not walk out and select another school. Not a happy prospect for a tuitiondriven institution. I also figured that as soon as the students were registered, they would put their jewelry back on, which, of course, they did. Let us illustrate from another angle. Often my colleagues in the administration and I attended pastors’ meetings to promote the institution and get the support of the church leaders. I’ll never forget the reaction of one pastor at one of these meetings. The pastor publicly expressed his dismay for what, in his mind, was a declining situation with respect to the standards of the church at the university. He had recently visited the cam
The RACK1 signal anchor protein from Trypanosoma brucei associates with eukaryotic elongation factor 1A: a role for translational control in cytokinesis

RACK1 is a WD‐repeat protein that forms signal complexes at appropriate locations in the cell. RACK1 homologues are core components of ribosomes from yeast, plants and mammals. In contrast, a cryo‐EM analysis of trypanosome ribosomes failed to detect RACK1, thus eliminating an important translational regulatory mechanism. Here we report that TbRACK1 from Trypanosoma brucei associates with eukaryotic translation elongation factor‐1a (eEF1A) as determined by tandem MS of TAP‐TbRACK1 affinity eluates, co‐sedimentation in a sucrose gradient, and co‐precipitation assays. Consistent with these observations, sucrose gradient purified 80S monosomes and translating polysomes each contained TbRACK1. When RNAi was used to deplete cells of TbRACK1, a shift in the polysome profile was observed, while the phosphorylation of a ribosomal protein increased. Under these conditions, cell growth became hypersensitive to the translational inhibitor anisomycin. The kinetoplasts and nuclei were misaligned in the postmitotic cells, resulting in partial cleavage furrow ingression during cytokinesis. Overall, these findings identify eEF1A as a novel TbRACK1 binding partner and establish TbRACK1 as a component of the trypanosome translational apparatus. The synergy between anisomycin and TbRACK1 RNAi suggests that continued translation is required for complete ingression of the cleavage furrow.
Real Time Freeway Incident Detection

The US Department of Transportation (US-DOT) estimates that over half of all congestion events are caused by highway incidents rather than by rush-hour traffic in big cities. Real-time incident detection on freeways is an important part of any modern traffic control center operation because it offers an opportunity to maximize road system performance. An effective incident detection and management operation cannot prevent incidents, however, it can diminish the impacts of non-recurring congestion problems. The main purpose of real-time incident detection is to reduce delay and the number of secondary accidents, and to improve safety and travel information during unusual traffic conditions. The purpose of this project is to evaluate two recently developed automatic incident detection algorithms. The majority of automatic incident detection algorithms are focused on identifying traffic incident patterns but may not adequately investigate possible similarities in patterns observed under incident-free conditions. When traffic demand exceeds road capacity, the traffic speed decreases significantly and the traffic enters a highly unstable regime often referred to as “stop-and-go” conditions. The most challenging part of real-time incident detection is recognition of traffic pattern changes when incidents happen during stop-and-go conditions. This work describes a case study evaluation of two recently evolved incident detection methods using data from the Dallas, Texas traffic control center.
Superantigen-reactive CD4+ T cells are required to stimulate B cells after infection with mouse mammary tumor virus

Superantigens are defined by their ability to stimulate a large fraction of T cells via interaction with the T cell receptor (TCR) V beta domain. Endogenous superantigens, classically termed minor lymphocyte-stimulating (Mls) antigens, were recently identified as products of open reading frames (ORF) in integrated proviral copies of mouse mammary tumor virus (MMTV). We have described an infectious MMTV homologue of the classical endogenous superantigen Mls-1a (Mtv-7). The ORF molecules of both the endogenous Mtv-7 and the infectious MMTV(SW) interact with T cells expressing the TCR V beta 6, 7, 8.1, and 9 domains. Furthermore, the COOH termini of their ORF molecules, thought to confer TCR specificity, are very similar. Since successful transport of MMTV from the site of infection in the gut to the mammary gland depends on a functional immune system, we were interested in determining the early events after and requirements for MMTV infection. We show that MMTV(SW) infection induces a massive response of V beta 6+ CDC4+ T cells, which interact with the viral ORF. Concomitantly, we observed a B cell response and differentiation that depends on both the presence and stimulation of the superantigen-reactive T cells. Furthermore, we show that B cells are the main target of the initial MMTV infection as judged by the presence of the reverse-transcribed viral genome and ORF transcripts. Thus, we suggest that MMTV infection of B cells leads to ORF-mediated B-T cell interaction, which maintains and possibly amplifies viral infection.
Poverty and Mortality Disparities in Central Appalachia: Mountaintop Mining and Environmental Justice

Objectives. This study investigated the associations between poverty rates, Appalachian mountaintop coal mining, and age-adjusted total mortality rates to determine if persons exposed to this form of mining experience greater poverty and higher death rates compared to other types of mining or other areas of Appalachia. Methods. Mortality rates, poverty rates, Appalachian designation and mining activity were examined for counties in Kentucky, Tennessee, Virginia and West Virginia (N=403). Linear least squares models tested for annual group differences from 2000-2007 in total and child poverty, and total mortality, based on mining type and Appalachian location. Nested linear models accounting for state-level effects were used to determine whether mountaintop mining and poverty were associated with mortality rates controlling for other risks. Results. Mountaintop mining areas had significantly higher mortality rates, total poverty rates and child poverty rates every year compared to other referent counties of these states. Both poverty and mountaintop mining were independently associated with age-adjusted mortality rates in nested models. Conclusions. Persons living in MTM areas experience persistently elevated poverty and mortality rates. Higher mortality is independently associated with both poverty and MTM, the latter effect suggestive of a possible environmental contribution from mining activities. Efforts to reduce longstanding health disparities in Appalachia must focus on those areas where disparities are concentrated: the Appalachian coalfields.
Chromium-51 Ethylenediaminetetraacetate for Estimation of Glomerular Filtration Rate

Renal clearances of inulin and chromium-51 ethylenediaminetetraacetate were compared in sheep. In 41 clearance periods from five animals the mean clearance ratio of the chelate to inulin was 0.95 � 0.03 (S.D.). Part of the difference between the two sets of results may have been due to binding of the metal chelate by plasma protein since 1.5 to 2 percent of chromium-51 ethylenediaminetetraacetate in plasma could not be removed by dialysis.
Determination of Stromal Signatures in Breast Carcinoma

Many soft tissue tumors recapitulate features of normal connective tissue. We hypothesize that different types of fibroblastic tumors are representative of different populations of fibroblastic cells or different activation states of these cells. We examined two tumors with fibroblastic features, solitary fibrous tumor (SFT) and desmoid-type fibromatosis (DTF), by DNA microarray analysis and found that they have very different expression profiles, including significant differences in their patterns of expression of extracellular matrix genes and growth factors. Using immunohistochemistry and in situ hybridization on a tissue microarray, we found that genes specific for these two tumors have mutually specific expression in the stroma of nonneoplastic tissues. We defined a set of 786 gene spots whose pattern of expression distinguishes SFT from DTF. In an analysis of DNA microarray gene expression data from 295 previously published breast carcinomas, we found that expression of this gene set defined two groups of breast carcinomas with significant differences in overall survival. One of the groups had a favorable outcome and was defined by the expression of DTF genes. The other group of tumors had a poor prognosis and showed variable expression of genes enriched for SFT type. Our findings suggest that the host stromal response varies significantly among carcinomas and that gene expression patterns characteristic of soft tissue tumors can be used to discover new markers for normal connective tissue cells.
Single neuron responses in amygdala of alert monkey during complex sensory stimulation with affective significance

Among other deficits, amygdalectomy impairs the ability of the animal to recognize the affective significance of a stimulus. In the present study, neuronal activity in the amygdala (AM) was recorded from alert monkeys while they performed tasks leading to the presentation of rewarding or aversive stimuli. Of 585 AM neurons tested, 312 (53.3%) responded to at least one stimulus in one or more of 5 major groups: 40 vision related, 26 audition related, 41 ingestion related, 117 multimodal, and 14 selective. Ingestion-related neurons were subdivided according to their responses to other stimuli: oral sensory, oral sensory plus vision, and oral sensory plus audition. Depending upon their responsiveness to the affective significance of the stimuli, neurons in the vision- and audition-related categories were divided into 2 subclasses: vis-I (26/40), vis-II (14/40), aud-I (8/26), and aud- II (18/26). All 4 subtypes usually responded to unfamiliar stimuli but seldom responded to neutral familiar stimuli. Types vis-I and aud-I responded to both positive and negative familiar stimuli. Types vis-II and aud-II responded to certain familiar negative stimuli but not to familiar positive stimuli. In vis-I neurons, responses were stronger for palatable foods than for less palatable foods. No neurons within vision-related, audition-related, and multimodal categories responded solely to positive or to negative stimuli. Of the 27 oral sensory neurons 9 were tested with saline or salted food, and 8 responded to normally aversive oral sensory stimuli in the same manner as they did to normal food or liquid (water or juice). In contrast to oral sensory neurons, all responses of 4 oral sensory-plus-vision and all of 4 selective neurons tested, as well as bar pressing behavior, were modulated by altering the affective significance of the food. These results suggest that the AM is one of the candidates for stimulus- affective association based on associative learning and memory.
In Search of Excellence: Fads, Success Stories, and Adaptive Emulation1

The faddishness of the business community is often noted and lamented but not well understood by standard models of innovation and diffusion. We combine arguments about organizational cognition and institutional mimicry to develop a model of adaptive emulation, where firms respond to perceived failure by imitating their most successful peers. Computational experiments show that this process generates empirically plausible cascades of adoption, even if innovations are entirely worthless. Faddish cycles are most robust across alternative treatments of managerial decision making where innovations have modest positive effects on outcomes. These results have broad implications for the faddishness of a business community increasingly marked by media‐driven accounts of success, and for the properties of organizational practices that are hot one day and cold the next.
Altruism and Gender in the Trust Game

This paper analyses gender differences in the trust game. Our experiment implements the triadic design proposed by Cox (2004) to discriminate between transfers resulting from trust or trustworthiness and transfers resulting from altruistic preferences. We observe that women exhibit a higher degree of altruism than men for both trust and trustworthiness but relatively more for trustworthiness. This result provides an explanation to the experimental finding that women reciprocate more than men.
Five-Year Cervical (Pre)Cancer Risk of Women Screened by HPV and Cytology Testing

Primary human papillomavirus (HPV)–based cervical screening will be introduced in the Netherlands in 2016. We assessed the 5-year cervical (pre)cancer risk of women with different combinations of HPV and cytology test results. Special attention was paid to risks for cervical intraepithelial neoplasia grade 3 and 2 or more (CIN3+/2+) of HPV-positive women with a negative triage test, because this determines the safety of a 5-year screening interval for HPV-positive, triage test–negative women. In addition, age-related effects were studied. A total of 25,553 women were screened by HPV testing and cytology in a screening setting. Women were managed on the presence of HPV and/or abnormal cytology. Five-year cumulative incidences for CIN3+/2+ were calculated. Five-year CIN3+(2+) risk was 10.0% (17.7%) among HPV-positive women. When stratified by cytology, the CIN3+(CIN2+) risk was 7.9% (12.9%) for women with normal cytology and 22.2% (45.3%) for women with equivocal or mildly abnormal (i.e., BMD) cytology. For HPV-negative women, the 5-year CIN3+(2+) risk was 0.09% (0.21%). Additional triage of HPV-positive women with normal cytology by repeat cytology at 12 months showed a 5-year CIN3+(2+) risk of 4.1% (7.0%). HPV-non 16/18-positive women with normal cytology at baseline had comparable risks of 3.5% (7.9%). HPV-non 16/18-positive women with normal baseline cytology and normal repeat cytology had a 5-year CIN3+ risk of 0.42%. No age-related effects were detected. In conclusion, HPV-positive women with normal cytology and a negative triage test, either repeat cytology after 12 months or baseline HPV 16/18 genotyping, develop a non-negligible CIN3+ risk over 5 years. Therefore, extension of the screening interval over 5 years only seems possible for HPV screen–negative women. Cancer Prev Res; 8(6); 502–8. ©2015 AACR.
The dasycladalean algae of the Plassen Carbonate Platform ( Kimmeridgian-Early Berriasian ) : taxonomic inventory and palaeogeographical implications within the platform-basin-system of the Northern Calcareous Alps ( Austria , p . p . Germany )

The present paper compiles an up-to-date taxonomic inventory of dasycladalean green algae of the KimmeridgianEarly Berriasian Plassen Carbonate Platform and their resediments in basinal sediments (e.g., Barmstein Limestone, Sillenkopf Formation) of the Northern Calcareous Alps of Austria (p.p. Germany). Today, the Plassen Carbonate Platform sensu lato (or Plassen Group) is divided into three independent carbonate platforms with radiolarite deepwater basins between: the Wolfgangsee Carbonate Platform to the north, the Plassen Carbonate Platform sensu stricto in a central position and the Lärchberg Carbonate Platform to the south. All together 42 taxa are reported from these platforms and associated resediments, each shortly commented and illustrated. Amongst these, there are taxa common in all three platforms, others exhibit restricted distributions. These peculiarities can be explained by the different lithostratigraphic and overall geodynamic evolution of the three platforms. In many cases, it allows the assignment of resediments in basinal series to a certain platform as a helpful palaeobiogeographical tool when other data are lacking.