Miracle-dz/UniFAR-FTUs huggingface dataset:
Overexpression of E2F5/p130, but not E2F5 alone, can inhibit E2F-induced cell cycle entry in transgenic mice

Purpose The retinoblastoma (Rb) gene family member p130 binds preferentially to the E2F5 transcription factor and forms a repressive E2F5/p130 complex that inhibits cell cycle progression and tumor growth. It is unclear whether E2F5, either alone or in combination with p130, can interfere with the transcriptional activity of other E2F family members, such as E2F1 and E2F3a, in vivo. In this study, we used transgenic mice to test whether overexpression of E2F5 with/without p130 would be sufficient to inhibit E2F1 or E2F3a induced cell cycle reentry. Methods Transgenic mice were generated by microinjection of constructs containing different E2F cDNAs (E2F1, E2F3a, and E2F5) or the p130 cDNA linked to the mouse αA-crystallin promoter. The E2F5 single and E2F5/p130 double transgenic mice were cross-mated with E2F1 or E2F3a transgenic mice. The resulting double or triple transgenic mouse embryos were characterized by histology, in situ hybridization, immunohistochemistry, and BrdU incorporation assays. Results Overexpression of E2F5 alone was not sufficient to inhibit E2F1 or E2F3a induced cell cycle reentry in lens fiber cells. Transgenic mice coexpressing E2F5 and p130 in lens fiber cells did not show lens defects. However, coexpression of E2F5/p130 with E2F1 or E2F3a in lens fiber cells decreased the number of BrdU positive fiber cells induced by the E2F1 or E2F3a alone. Therefore, overexpression of E2F5/p130, but not E2F5 alone, can inhibit activator E2F-mediated cell proliferation in vivo, confirming that p130 plays a critical role in the repressive activity of E2F5/p130 complex. Conclusions Overexpression of E2F5/p130 in post-mitotic lens fiber cells does not affect their normal differentiation program, but can inhibit inappropriate cell cycle reentry induced by the activator E2Fs. Since E2F5 alone cannot interfere with these E2F activities, we conclude that p130 is a key player in the inhibitory process.
The one loop UV divergent structure of U(1) Yang-Mills theory on noncommutative R**4

We show that U(1) Yang-Mills theory on noncommutative R^4 can be renormalized at the one-loop level by multiplicative dimensional renormalization of the coupling constant and fields of the theory. We compute the beta function of the theory and conclude that the theory is asymptotically free. We also show that the Weyl-Moyal matrix defining the deformed product over the space of functions on R^4 is not renormalized at the one-loop level.
Genetic Ablation of Luteinizing Hormone Receptor Improves the Amyloid Pathology in a Mouse Model of Alzheimer Disease

Amyloid-&bgr; peptide (A&bgr;) plays an essential pathophysiologic role in Alzheimer disease, and elevation of luteinizing hormone (LH) levels during aging has been implicated in its pathogenesis. To assess the effect of LH receptor deficiency on A&bgr; accumulation, we generated a bigenic mouse model, APPsw+/Lhr−/−, which expresses human amyloid precursor protein (APPsw) in the background of LH receptor (Lhr) knockout. Genetic ablation of Lhr resulted in a significant decrease in the number of A&bgr; plaques and protein content in the hippocampus and cerebral cortex in both male and female mice. Accordingly, several A&bgr; deposition-related neuropathologic features and functionally relevant molecules were markedly improved, including decreased astrogliosis, reductions of elevated phosphorylated tau, c-fos, &agr;7-nicotinic acetylcholine receptor, and restoration of the altered neuropeptide Y receptors Y1 and Y2. Diminution of A&bgr; accumulation in the absence of LH receptor supports the contention that dysregulation of LH may impact the pathogenesis of Alzheimer disease. The APPsw+/Lhr−/− mouse may be a useful tool for advancing understanding of the role of LH-mediated events in Alzheimer disease and a model in which to test therapeutic interventions.
On the translation of relational queries into iterative programs

This paper investigates the problem of translating set-oriented query specifications into iterative programs. The translation uses techniques of functional programming and program transformation. We present two algorithms that generate iterative programs from algebra-based query specifications. The first algorithm translates query specifications into recursive programs. Those are simplified by sets of transformation rules before the algorithm generates the final iterative form. The second algorithm uses a two-level translation that generates iterative programs faster than the first algorithm. On the first level a small set of transformation rules performs structural simplification before the functional combination on the second level yields the final iterative form.
Response of Staphylococcus aureus to subinhibitory concentrations of a sequence-selective, DNA minor groove cross-linking pyrrolobenzodiazepine dimer.

OBJECTIVES ELB-21 is a pyrrolo[2,1-c][1,4]benzodiazepine dimer with potent antistaphylococcal activity; it binds covalently to guanine residues on opposing strands of duplex DNA, interfering with regulatory proteins and transcription elongation in a sequence-selective manner. Transcriptional and proteomic alterations induced by exposure of Staphylococcus aureus clinical isolate EMRSA-16 to ELB-21 were determined in order to define more precisely the bactericidal mechanism of the drug. METHODS DNase I footprinting was used to identify high-affinity DNA binding sites. Microarrays and gel electrophoresis were used to assess the ELB-21-induced phenotype. RESULTS High-affinity interstrand binding sites in which guanine residues were separated by 4 bp, and also some intrastrand cross-linking sites of variable length were identified. Exposure of EMRSA-16 to 0.015 mg/L ELB-21 elicited a 2-fold or greater up-regulation of 168 genes in logarithmic phase and 181 genes in stationary phase; the majority of genes affected were associated with resident prophages Sa2 and Sa3, pathogenicity island SaPI4 and DNA damage repair. ELB-21 induced a marked increase in the number of viable phage particles in culture supernatants. The expression of only a limited number of genes showed a >50% reduction. Sixteen extracellular and four intracellular proteins were differentially expressed during logarithmic and stationary phases, including RecA, proteins associated with staphylococcal pathogenesis (IsaA, CspA), cell division and wall synthesis. CONCLUSIONS ELB-21 kills S. aureus by forming multiple interstrand and intrastrand DNA cross-links, resulting in induction of the DNA damage response, derepression of resident prophages and modulation of a limited number of genes involved with cell wall synthesis.
Language, memory, and aging: Capacity theory and the processing of inferences

The study of adult age differences in comprehension of and memory for text is a now burgeoning enterprise in cognitive gerontology, in part because of the potential for direct application of the findings to everyday life. To date, the work on discourse processing suggests the existence of age deficits of varying magnitudes, deficits that are largely quantitative rather than qualitative in nature. The work thus suggests that older adults use the same processing mechanisms as younger adults but with poorer results (e.g., Mandel & Johnson, 1984; Zelinski, Light, & Gilewski, 1984). Beyond this summary the literature yields few simple generalizations; indeed, the findings on any given variable (e.g., educational level) tend to be complex and inconsistent. Consider the literature on the recall of ideas that differ in their importance to the meaning structure of the text. The usual finding with young adults (called the "levels effect") is that the probability of recalling information from text is directly related to the information's importance level in the text as defined by a model (e.g., Kintsch's, 1974) of the hierarchical structure of that text. When young and elderly adults have been compared, different experiments have produced
Imaging Cyclic AMP Changes in Pancreatic Islets of Transgenic Reporter Mice

Cyclic AMP (cAMP) and Ca2+ are two ubiquitous second messengers in transduction pathways downstream of receptors for hormones, neurotransmitters and local signals. The availability of fluorescent Ca2+ reporter dyes that are easily introduced into cells and tissues has facilitated analysis of the dynamics and spatial patterns for Ca2+ signaling pathways. A similar dissection of the role of cAMP has lagged because indicator dyes do not exist. Genetically encoded reporters for cAMP are available but they must be introduced by transient transfection in cell culture, which limits their utility. We report here that we have produced a strain of transgenic mice in which an enhanced cAMP reporter is integrated in the genome and can be expressed in any targeted tissue and with tetracycline induction. We have expressed the cAMP reporter in β-cells of pancreatic islets and conducted an analysis of intracellular cAMP levels in relation to glucose stimulation, Ca2+ levels, and membrane depolarization. Pancreatic function in transgenic mice was normal. In induced transgenic islets, glucose evoked an increase in cAMP in β-cells in a dose-dependent manner. The cAMP response is independent of (in fact, precedes) the Ca2+ influx that results from glucose stimulation of islets. Glucose-evoked cAMP responses are synchronous in cells throughout the islet and occur in 2 phases suggestive of the time course of insulin secretion. Insofar as cAMP in islets is known to potentiate insulin secretion, the novel transgenic mouse model will for the first time permit detailed analyses of cAMP signals in β-cells within islets, i.e. in their native physiological context. Reporter expression in other tissues (such as the heart) where cAMP plays a critical regulatory role, will permit novel biomedical approaches.
Case management of childhood pneumonia in developing countries.

BACKGROUND Pneumonia is a leading cause of morbidity and mortality in children worldwide. Appropriate management depends on accurate assessment of disease severity, and for the majority of children in developing countries the assessment is based on clinical signs alone. This article reviews recent evidence on clinical assessment and severity classification of pneumonia and reported results on the effectiveness of currently recommended treatments. METHODS Potential studies for inclusion were identified by Medline (1990-2006) search. The Oxford Center for Evidence Based Medicine criteria were used to describe the methodologic quality of selected studies. RESULTS In the included studies the sensitivity of current definitions of tachypnea for diagnosing radiologic pneumonia ranged from 72% to 94% with specificities between 38% and 99%; chest indrawing had reported sensitivities of between 46% and 78%. Data provide some support for the value of current clinical criteria for classifying pneumonia severity, with those meeting severe or very severe criteria being at considerably increased risk of death, hypoxemia or bacteremia. Results of randomized controlled trials report clinically defined improvement at 48 hours in at least 80% of children treated using recommended antibiotics. However, a limitation of these data may include inappropriate definitions of treatment failure. CONCLUSION Particularly with regard to severe pneumonia, issues that specifically need to be addressed are the adequacy of penicillin monotherapy, or oral amoxicillin or alternative antibiotics; the timing of introduction of high-dose trimethoprim-sulfamethoxazole in children at risk for or known to be infected by HIV and the value of pulse oximetry.
A Preliminary Assessment of Ethiopian Sacred Grove Status at the Landscape and Ecosystem Scales.

The northern Ethiopian landscape is dotted with small patches of church forests that are religious centers for the Ethiopian Orthodox Tewahido Church (EOTC). These sacred groves are what remain of the once vast tropical Afromontane dry forest. Herein we review the landscape pattern of sacred groves in the Amhara region of Ethiopia, and their local scale nutrient status at two sites, Zahara and Debresena. A total of 1,488 sacred groves were inventoried within the study area, yielding an overall density of one sacred grove for every twenty square kilometers. Sacred groves averaged a little over five hectares and were separated from one another by more than two kilometers. At the local scale we found that soil carbon and nitrogen stocks have decreased significantly between the forest interior and the clearing indicating decreased soil fertility. Together our data indicate that these sacred groves are vulnerable to loss because of their small average size, isolation from seed sources, and decreasing soil status.
Ramanujan Graphs

In the last two decades, the theory of Ramanujan graphs has gained prominence primarily for two reasons. First, from a practical viewpoint, these graphs resolve an extremal problem in communication network theory (see for example [2]). Second, from a more aesthetic viewpoint, they fuse diverse branches of pure mathematics, namely, number theory, representation theory and algebraic geometry. The purpose of this survey is to unify some of the recent developments and expose certain open problems in the area. This survey is by no means an exhaustive one and demonstrates a highly number-theoretic bias. For more comprehensive surveys, we refer the reader to [27], [9] or [13]. For a more up-to-date survey highlighting the connection between graph theory and automorphic representations, we refer the reader to Winnie Li’s recent survey article [11]. A is a triple consisting of avertex (X), an and a map that associates to each edge two vertices (not necessarily distinct) called itsendpoints. A is an edge whose endpoints are equal. Multiple edges are edges having the same pair of endpoints. A is one having no loops or multiple edges. If a graph has loops or multiple edges, we will call it a multigraph. When two verticesu andv are endpoints of an edge, we say they are and (sometimes) write to indicate this. To any graph, we may associate the which is ann matrix (wheren |) with rows and columns indexed by the elements of the vertex set and the y)-th entry is the number of edges connecting and y. Since our graphs are undirected, the matrix is symmetric. Consequently, all of its eigenvalues are real. The convention regarding terminology is not clear in the literature. Most use the term ‘graph’ to mean a simple graph as we have defined it above. Thus, the
Dark Rims: Novel Sequence Enhances Diagnostic Specificity in Multiple Sclerosis

The authors compared WM lesions in a group of patients with multiple sclerosis and in a second group of positive controls with white matter lesions who did not have a diagnosis of MS. The presence of a rim on the gray matter-double inversion recovery MR imaging sequence was combined with the 2001 and 2010 McDonald disseminated-in-space criteria. Multiple MR imaging markers, including lesion location, size, and the presence of a rim, were compared between groups as well as a quantitative measure of lesion T1 hypointensity. MR images from 107 patients with relapsing-remitting MS and 36 positive control subjects were analyzed. In patients with MS, 1120/3211 lesions (35%) had a rim on GM-double inversion recovery; the positive control group had only 9/893 rim lesions (1%). The addition of a novel GM-double inversion recovery technique enhanced specificity for diagnosing MS compared with established MR imaging criteria. BACKGROUND AND PURPOSE: The 2010 McDonald criteria are designed to sensitively detect MS; however, the low specificity of these criteria can occasionally lead to the misdiagnosis of MS. The purpose of this study was to determine whether a novel double inversion recovery MR imaging technique has the potential to increase the specificity of diagnostic criteria distinguishing MS from non-MS white matter lesions. MATERIALS AND METHODS: This was a cross-sectional observational study. MR imaging data were acquired between 2011 and 2016. A novel double inversion recovery sequence that suppresses CSF and GM signal was used (GM-double inversion recovery). We compared WM lesions in a group of patients with multiple sclerosis and in a second group of positive controls with white matter lesions who did not have a diagnosis of MS. The presence of a rim on the GM-double inversion recovery MR imaging sequence was combined with the 2001 and 2010 McDonald disseminated-in-space criteria. Multiple MR imaging markers, including lesion location, size, and the presence of a rim, were compared between groups as well as a quantitative measure of lesion T1 hypointensity. RESULTS: MR images from 107 patients with relapsing-remitting MS (median age, 32 years) and 36 positive control (median age, 39 years) subjects were analyzed. No significant differences were found in age and sex. In patients with MS, 1120/3211 lesions (35%) had a rim on GM-double inversion recovery; the positive control group had only 9/893 rim lesions (1%). Rims were associated with a decrease in the lesion T1 ratio. Using the 2010 MR imaging criteria plus the presence of rims on GM-double inversion recovery, we achieved 78% and 97% specificity in subjects with ≥1 and ≥2 rim lesions, respectively. CONCLUSIONS: The addition of a novel GM-double inversion recovery technique enhanced specificity for diagnosing MS compared with established MR imaging criteria.
Risk of Severe Non AIDS Events Is Increased among Patients Unable to Increase their CD4+ T-Cell Counts >200+/μl Despite Effective HAART

Background Immunological non-response (INR) despite virological suppression is associated with AIDS-defining events/death (ADE). Little is known about its association with serious non-AIDS-defining events (nADE). Methods Patients highly-active antiretroviral therapy (HAART) with <200 CD4+/μl and achieving HIV-RNA <50 copies/ml within 12 (±3) months were categorized as INR if CD4+ T-cell count at year 1 was <200/μl. Predictors of nADE (malignancies, severe infections, renal failure—ie, estimated glomerular filtration rate <30 ml/min, cardiovascular events and liver decompensation) were assessed using multivariable Cox models. Follow-up was right-censored in case of HAART discontinuation or confirmed HIV-RNA>50. Results 1221 patients were observed for a median of 3 (IQR: 1.3-6.1) years. Pre-HAART CD4+ were 77/μl (IQR: 28-142) and 56% of patients had experienced an ADE. After 1 year, CD4+ increased to 286 (IQR: 197-387), but 26.1% of patients were INR. Thereafter, 86 nADE (30.2% malignancies, 27.9% infectious, 17.4% renal, 17.4% cardiovascular, 7% hepatic) were observed, accounting for an incidence of 1.83 events (95%CI: 1.73-2.61) per 100 PYFU. After adjusting for measurable confounders, INR had a significantly greater risk of nADE (HR 1.65; 95%CI: 1.06-2.56). Older age (per year, HR 1.03; 95%CI: 1.01-1.05), hepatitis C co-infection (HR 2.09; 95%CI: 1.19-3.7), a history of previous nADE (HR 2.16; 95%CI: 1.06-4.4) and the occurrence of ADE during the follow-up (HR 2.2; 95%CI: 1.15-4.21) were other independent predictors of newly diagnosed nADE. Conclusions Patients failing to restore CD4+ to >200 cells/μl run a greater risk of serious nADE, which is intertwined or predicted by AIDS progression. Improved management of this fragile population and innovative therapy able to induce immune-reconstitution are urgently needed. Also, our results strengthen the importance of earlier diagnosis and HAART introduction.
An Exon-Capture System for the Entire Class Ophiuroidea

We present an exon-capture system for an entire class of marine invertebrates, the Ophiuroidea, built upon a phylogenetically diverse transcriptome foundation. The system captures ~90 percent of the 1552 exon target, across all major lineages of the quarter-billion year old extant crown group. Key features of our system are: 1) basing the target on an alignment of orthologous genes determined from 52 transcriptomes spanning the phylogenetic diversity and trimmed to remove anything difficult to capture, map or align, 2) use of multiple artificial representatives based on ancestral states rather than exemplars to improve capture and mapping of the target, 3) mapping reads to a multi-reference alignment, and 4) using patterns of site polymorphism to distinguish among paralogy, polyploidy, allelic differences and sample contamination. The resulting data gives a well-resolved tree (currently standing at 417 samples, 275,352 bp, 91% data-complete) that will transform our understanding of ophiuroid evolution and biogeography.
Observation of the halo of the edge-on galaxy IC5249

We report optical photometry and HI synthesis observations of the southern edge-on S_c,d galaxy IC5249. The observations were carried out primarily to determine if IC5249 has a red halo surrounding it similar to the halo that has been recently found surrounding the northern edge-on galaxy NGC5907. The galaxy IC5249 is almost perfectly edge-on, and it shows no direct sign of warping or flaring out to its optical radius. It has a low luminosity and a slow rotation velocity. We find that it has a remarkably similar halo to NGC5907. The halo is visible at a distance of 3kpc from the disk of the galaxy, and at 6kpc the surface brightness is ~ 28 mag arcsec^-2. The measured distribution of halo light is similar to the distribution expected for dark matter. Red dwarfs and red giants are possible sources of the halo light. If red dwarfs are the source, and if they are distributed like dark matter, then their density at galactocentric radius r = 8.5 kpc is (7+/-3) times the the local Galactic density of halo red dwarfs. Their total contribution to the mass of IC5249 would be about 10% of the mass of the galaxy. If red giants are the dominant source of the observed halo light, and if they are distributed like Galactic gobular clusters, then their density at r = 8.5 kpc is 1.0 +1.0-0.5 times the local Galactic density of halo giants, and they provide a gravitationally insignificant fraction of the mass of the galaxy. Further optical measurements are required to identify the source of the halo light in IC5249, and also to determine more precisely its distribution. Further radio measurements are required to examine the HI distribution and rotation velocity beyond the optical radius of the galaxy.
Facilitating phoneme awareness development in 3- and 4-year-old children with speech impairment.

PURPOSE This study investigated the phonological awareness and early literacy development of 12 children who presented at 3 years of age with moderate or severe speech impairment. The children's response to early intervention that included specific activities to facilitate phoneme awareness and letter knowledge, in addition to improving speech intelligibility, was examined. METHOD Using a 3-year longitudinal design, the children's development in phonological awareness was monitored and compared to that of a group of 19 children without speech impairment. During the monitoring period from 3 to 5 years of age, the children with speech impairment received, on average, 25.5 intervention sessions. At 6 years of age, the children's performance on phonological awareness, reading, and spelling measures was also compared to that of the 19 children without impairment as well as to a matched control group of children with speech impairment who had not received any specific instruction in phonological awareness. RESULTS The results indicated that (a) phoneme awareness can be stimulated in children with speech impairment as young as 3 and 4 years of age, (b) facilitating phoneme awareness development can be achieved concurrently with improvement in speech intelligibility, and (c) enhancing phoneme awareness and letter knowledge during the preschool years is associated with successful early reading and spelling experiences for children with speech impairment. CLINICAL IMPLICATIONS The data provide evidence to support the clinical practice of integrating activities to develop phoneme awareness and letter knowledge into therapy for 3- and 4-year-old children with moderate or severe speech impairment.