Miracle-dz/UniFAR-FTUs huggingface dataset:
The CBP Bromodomain and Nucleosome Targeting Are Required for Zta-Directed Nucleosome Acetylation and Transcription Activation

ABSTRACT The Epstein-Barr virus (EBV)-encoded lytic activator Zta is a bZIP protein that can stimulate nucleosomal histone acetyltransferase (HAT) activity of the CREB binding protein (CBP) in vitro. We now show that deletion of the CBP bromo- and C/H3 domains eliminates stimulation of nucleosomal HAT activity in vitro and transcriptional coactivation by Zta in transfected cells. In contrast, acetylation of free histones was not affected by the addition of Zta or by deletions in the bromo or C/H3 domain of CBP. Zta stimulated acetylation of oligonucleosomes assembled on supercoiled DNA and dinucleosomes assembled on linear DNA, but Zta-stimulated acetylation was significantly reduced for mononucleosomes. Western blotting and amino-terminal protein sequencing indicated that all lysine residues in the H3 and H4 amino-terminal tails were acetylated by CBP and enhanced by the addition of Zta. Histone acetylation was also dependent upon the Zta basic DNA binding domain, which could not be substituted with the homologous basic region of c-Fos, indicating specificity in the bZIP domain nucleosome binding function. Finally, we show that Zta and CBP colocalize to viral immediate-early promoters in vivo and that overexpression of Zta leads to a robust increase in H3 and H4 acetylation at various regions of the EBV genome in vivo. Furthermore, deletion of the CBP bromodomain reduced stable CBP-Zta complex formation and histone acetylation at Zta-responsive viral promoters in vivo. These results suggest that activator- and bromodomain-dependent targeting to oligonucleosomal chromatin is required for stable promoter-bound complex formation and transcription activity.
Dentoskeletal effects of functional appliances vs bimaxillary surgery in hyperdivergent Class II patients.

OBJECTIVE To compare treatment outcomes of growing and nongrowing Class II patients characterized by mandibular retrusion and increased vertical dimension. MATERIALS AND METHODS Seventeen patients (mean age 9 years 5 months) were treated with a Bionator fabricated with posterior bite block and high-pull headgear, while 15 patients (mean age 23 years 6 months) received Le Fort I osteotomy for maxillary impaction and mandibular advancement. These groups were compared with 17 nontreated control subjects from the Bolton and Michigan growth studies. Lateral cephalograms taken for the functional group at T1 (initial records), T2 (completion of functional appliance treatment), and T3 (completion of comprehensive treatment) were compared with radiographs taken at T1 (initial records), T2 (immediate post surgery), and T3 (1 year post surgery) for the surgical patients. A null hypothesis of no difference in treatment outcomes between the functional and surgical groups was proposed. A mixed-design analysis of variance was used to compare changes within and between groups. Significance was set at P ≤ . 002. RESULTS In the functional appliance group, the mandible showed a more favorable growth direction and rotation. Both groups had stable results over time and finished treatment with similar cephalometric measurements. CONCLUSION Both the functional appliances and orthognathic surgery resulted in similar dentoskeletal treatment changes. The control groups did not self correct either in the anteroposterior or vertical dimensions.
Extreme metabolic alkalosis in intensive care

Metabolic alkalosis is a commonly seen imbalance in the intensive care unit (ICU). Extreme metabolic alkalemia, however, is less common. A pH greater than 7.65 may carry a high risk of mortality (up to 80%). We discuss the entity of life threatening metabolic alkalemia by means of two illustrative cases - both with a pH greater than 7.65 on presentation. The cause, modalities of managing and complications of this condition is discussed from the point of view of both the traditional method of Henderson and Hasselbalch and the mathematical model based on physiochemical model described by Stewart. Special mention to the pitfalls in managing patients of metabolic alkalosis with concomitant renal compromise is made.
THE EFFECT OF INSTRUMENTALIZATION OF INBORN REACTION ON ITS TRANSFORMATION INTO CONTRARY DIRECTED ESCAPE RESPONSE IN DOGS AND THE PROBLEM OF REINFORCEMENT

Transformation of inborn reaction of leg flexion into conditioned escape response of leg extension was studied. The model of the so called precise reflex was used. A dog could avoid or escape the shock applied to the paw by placing this paw in a narrow ,,safety zone" located at a definite height above the floor. When the shock is applied to the paw located below this zone, the escape response is flexion, i.e., it coincides with the inborn reaction. When the paw is lifted above this zone, the escape response is extension, i.e., it is opposite to the inborn response. Success of such extension response acquisition depended on the sequence of training conditions. The dogs of Group I at the beginning were accustomed to escape from shock by lifting the paw into the ,,safety zone", i.e., inborn reaction was instrumentalized. A subsequent formation of conditioned extension was extremely difficult and it did not became strong in spite of a very long training. Lowering the paw into the ,,safety zone" was usually slow. The dogs of group I1 were trained from the very beginning to escape from shock by leg extension. Contrary to the results obtained on group I this conditioned response was perfectly established. It was formed rapidly, only when active extension was paired regularly with termination (during extension) of the shock. It is suggested that conditioned connection from one functional center to another is formed and becomes stronger if evoked activity of the first center decreases during (or immediately after) the excitation of the second center. It is known that the transformation of a conditioned reflex into an antagonistic conditioned reflex is difficult as compared to initial conditioning (5). But is was not clear whether the transformation of inborn motor excape reflex into an antagonistic conditioned escape response was also being impeded. In the experiments of Stul (9) an escape response directly opposite to inborn reflex was formed in dogs in the course of precise avoidance reflex training i.e., lifting the paw into a narrow "safety zone" (SZ). When the subject lifted its paw above the SZ by mistake, a painful electrical stimulation (ES) was applied to it and the animal had to ldwer paw into the SZ to escape from shock. Such escape (opposite to inborn) responses (EORs) 'were formed with extreme difficulty. The purpose of the present work was to investigate the relative role of different factors which interfered with the acquisition of the EOR in the course of the precise reflex training.
Thrombospondin 2-null mice display an altered brain foreign body response to polyvinyl alcohol sponge implants

Thrombospondin (TSP)-2 is a matricellular protein that participates in the processes of tissue repair and the foreign body response. In addition, TSP2 has been shown to influence synaptogenesis and recovery of the brain following stroke. In the present study we investigated the response following the implantation of polyvinyl alcohol (PVA) sponges in the brain. PVA sponges were implanted into the brain cortex of wild type and TSP2-null mice for a period of 4 and 8 weeks and the response was analyzed by histochemistry and quantitative immunohistochemistry. TSP2 expression was detected in the interstices of the sponge and co-localized with the extracellular matrix and astrocytes. PVA sponge invasion in TSP2-null mice was characterized by dense deposition of extracellular matrix and increased invasion of reactive astrocytes and macrophages/microglia. Furthermore, the angiogenic response was elevated and the detection of mouse serum albumin (MSA) in the brain cortex indicated excessive vessel leakage, suggesting that TSP2 plays a role in the repair/maintenance of the blood brain barrier. Finally, immunostaining demonstrated an increase in the levels of matrix metalloproteinase (MMP)-2 and MMP-9. Taken together, our observations support a role for TSP2 as critical determinant of the brain response to biomaterials.
Moringa oleifera Impairs the Morphology and Functions of the Kidney in Adult Wistar Rats

Se puso a prueba la hipotesis que Moringa oleifera altera la morfologia y funcion del rinon en ratas. Fueron utilizadas 24 ratas Wistar macho adultas. El grupo control recibio suero fisiologico mientras que los Grupos II a IV recibieron 250, 500 y 750 mg/kg peso corporal del extracto metanolico de Moringa oleifera respectivamente, durante 21 dias. No se observaron anomalias en el comportamiento en ratas de los Grupos I - IV. En las ratas del grupo de control se registro un aumento de peso corporal estadisticamente significativo, mientras que las ratas de los grupos II - IV experimentaron una disminucion no significativa de peso corporal durante el procedimiento experimental (P0,05). No se observaron diferencias estadisticamente significativas (P0,05) en el analisis de los pesos relativos en rinones de las ratas de los grupos I - IV. Los examenes histologicos mostraron citoarquitectura normal de los rinones de las ratas del grupo I, mientras que en ratas de los grupos II ­ IV los espacios capsulares de los rinones aparecian mas amplios que los del Grupo I. Los analisis estadisticos mostraron niveles superiores significativos ( P 0,05 ) de la alanina y aspartato aminotransferasa, y de urea en suero en ratas de los Grupos II - IV no dependiente de la dosis, en comparacion con las ratas del Grupo I. Estos resultados coinciden con la hipotesis planteada.
Quality of Life of Stroke Survivors: A Research Synthesis

&NA; Stroke is the third leading cause of death and a major cause of disability in the United States. Individuals experiencing a completed stroke are faced with a multitude of challenges to restore their highest quality of life within the limitations of residual impairment. This research synthesis provides a summary of previous research on quality of life for stroke survivors. Research studies for inclusion in the review were identified by conducting a search of computerized databases through August 2000 and by using the ancestry method of reviewing reference lists from relevant publications. Thirty‐nine studies were identified that focused on stroke survivors' quality of life during the recovery process. Stroke survivors' overall quality of life varied based on the country where the study was implemented. Variables positively associated with stroke survivors' quality of life were independence with activities of daily living, increased functional ability, social support, and healthcare resources. Variables negatively associated with stroke survivors' quality of life were psychological impairment, severity of impairment, severity of aphasia, inappropriate reactions to illness and pessimism, and inability to return to work. Specifically, 22% to 73% of the variance in stroke survivors' quality of life was primarily explained by presence of depression; functional ability, especially the upper extremities; and socialization, in particular, leisure activities. Implications for professional nursing practice to enhance stroke survivors' quality of life include encouraging independence, managing depression, and fostering interpersonal relationships. Areas for future research include longitudinal studies, rigorous psychometric assessment of quality of life instruments, and intervention studies.
THE ALLWISE MOTION SURVEY AND THE QUEST FOR COLD SUBDWARFS

The AllWISE processing pipeline has measured motions for all objects detected on Wide-field Infrared Survey Explorer (WISE) images taken between 2010 January and 2011 February. In this paper, we discuss new capabilities made to the software pipeline in order to make motion measurements possible, and we characterize the resulting data products for use by future researchers. Using a stringent set of selection criteria, we find 22,445 objects that have significant AllWISE motions, of which 3525 have motions that can be independently confirmed from earlier Two Micron All Sky Survey (2MASS) images, yet lack any published motions in SIMBAD. Another 58 sources lack 2MASS counterparts and are presented as motion candidates only. Limited spectroscopic follow-up of this list has already revealed eight new L subdwarfs. These may provide the first hints of a “subdwarf gap” at mid-L types that would indicate the break between the stellar and substellar populations at low metallicities (i.e., old ages). Another object in the motion list—WISEA J154045.67−510139.3—is a bright (J ≈ 9 mag) object of type M6; both the spectrophotometric distance and a crude preliminary parallax place it ∼6 pc from the Sun. We also compare our list of motion objects to the recently published list of 762 WISE motion objects from Luhman. While these first large motion studies with WISE data have been very successful in revealing previously overlooked nearby dwarfs, both studies missed objects that the other found, demonstrating that many other nearby objects likely await discovery in the AllWISE data products.
Gemcitabine, oxaliplatin and dexamethasone as salvage treatment for elderly patients with refractory and relapsed peripheral T-cell lymphoma

Abstract The development of a more effective and less toxic salvage regimen remains a major challenge in elderly patients with relapsed and/or refractory peripheral T-cell lymphoma (PTCL). From April 2004 to May 2010, we used a new salvage regimen combining gemcitabine, oxaliplatin and dexamethasone (GemOD) in 24 elderly patients with relapsed (n = 11) or refractory (n = 13) PTCL unsuitable for high dose therapy. GemOD consisted of gemcitabine (1000 mg/m2 on day 1), oxaliplatin (100 mg/m2 on day 1) and dexamethasone (20 mg/day from day 1 to day 4), which was given every 3 weeks. Patients were scheduled to receive up to six courses of GemOD therapy unless there was evidence of progressive disease. The median number of GemOD courses delivered was four (range 3–6). After three courses of GemOD, the overall response rate (ORR) was 38%, with two complete responses (CRs) and seven partial responses (PRs). Among 11 patients who received three additional planned courses of therapy, there were three CRs and three PRs, for an ORR of 25% after complete treatment as per the study protocol. With a median follow-up of 18 months, the median overall survival (OS) and event-free survival (EFS) reached 14 and 10 months, respectively. Hematologic and non-hematologic toxicities were moderate in all patients. We conclude that the GemOD regimen can be administered safely and effectively in elderly patients with relapsed and refractory PTCL who are ineligible for high dose chemotherapy with stem cell transplant.
An Analysis of ISAR Image Distortion Based on the Phase Modulation Effect

Distortion in the ISAR image of a target is a result of nonuniform rotational motion of the target during the imaging period. In many of the measured ISAR images from moving targets, such as those from in-flight aircraft, the distortion can be quite severe. Often, the image integration time is only a few seconds in duration and the target's rotational displacement is only a few degrees. The conventional quadratic phase distortion effect is not adequate in explaining the severe blurring in many of these observations. A numerical model based on a time-varying target rotation rate has been developed to quantify the distortion in the ISAR image. It has successfully modelled the severe distortion observed; the model's simulated results are validated by experimental data. Results from the analysis indicate that the severe distortion is attributed to the phase modulation effect where a time-varying Doppler frequency provides the smearing mechanism. For target identification applications, an efficient method on refocusing distorted ISAR images based on time-frequency analysis has also been developed based on the insights obtained from the results of the numerical modelling and experimental investigation conducted in this study.
Children's Auditory Event-Related Potentials Index Sound Complexity and “Speechness”

Children's long-latency auditory event-related potential (LLAEP) structure differs from that of adults. Functional significance of childhood ERP components is largely unknown. In order to look for the functional correlates in adult and children's LLAEPs, stimulus-complexity effects were investigated in 8–10-year old children. To this end, auditory ERPs to vowels, acoustically matched complex tones, and sinusoidal tones were recorded. All types of stimuli elicited P100-N250-N450 ERP complex. Differences between the sinusoidal and complex tones were confined to the P100 and N250 peaks, complex tones eliciting larger responses. Vowels elicited smaller-amplitude N250 but larger-amplitude N450 than the complex tones. Some stimulus-complexity effects observed for N250 in children corresponded to those observed for the Nl in adults, whereas the N450 peak exhibited behaviour resembling that of the adult ERP components subsequent to the Nl wave.
Heterosexual Romantic Relationships Inside of Prison

This study investigated the differences in loneliness, sexual satisfaction, and quality of life among three groups of prison inmates: inmates in a heterosexual romantic relationship with a fellow prisoner, inmates with a partner outside the prison, and inmates without a partner. In-person interviews with 70 male and 70 female inmates from the Topas Penitentiary (Spain) were conducted. These inmates lived in the same facility but in gender-segregated modules. After controlling for age, nationality, total time in prison, actual sentence time served, and estimated time to parole, the results showed a lower level of romantic loneliness, and a higher level of sexual satisfaction and global, psychological, and environment quality of life for the group of inmates with a heterosexual partner inside prison. These findings highlight the positive attributes associated with heterosexual romantic relationships between inmates inside the same prison.
Effect of cooking and cold storage on biologically active antibiotic residues in meat

Summary An investigation was undertaken to see if cooking or cold storage would destroy or decrease the level of biologically active antibiotic in tissues from animals given therapeutic doses of antibiotic on three occasions prior to slaughter. The effects of cooking and cold storage on the biological activity of the residues of ampicillin, chloramphenicol, oxytetracycline, streptomycin and sulphadimidine were varied; in some instances the effects were minimal, in others nil.
Alkoxyalkyl Esters of 9-(S)-(3-Hydroxy-2-Phosphonomethoxypropyl) Adenine Are Potent and Selective Inhibitors of Hepatitis B Virus (HBV) Replication In Vitro and in HBV Transgenic Mice In Vivo

ABSTRACT Alkoxyalkyl esters of acyclic nucleoside phosphonates have previously been shown to have increased antiviral activity when they are administered orally in animal models of viral diseases, including lethal infections with vaccinia virus, cowpox virus, ectromelia virus, murine cytomegalovirus, and adenovirus. 9-(S)-(3-Hydroxy-2-phosphonomethoxypropyl)adenine [(S)-HPMPA] was previously shown to have activity against hepatitis B virus (HBV) in vitro. To assess the effect of alkoxyalkyl esterification of (S)-HPMPA, we prepared the hexadecyloxypropyl (HDP), 15-methyl-hexadecyloxypropyl (15M-HDP), and octadecyloxyethyl (ODE) esters and compared their activities with the activity of adefovir dipivoxil in vitro and in vivo. Alkoxyalkyl esters of (S)-HPMPA were 6 to 20 times more active than unmodified (S)-HPMPA on the basis of their 50% effective concentrations in 2.2. 15 cells. The increased antiviral activity appeared to be due in part to the increased uptake and conversion of HDP-(S)-HPMPA to HPMPA diphosphate observed in HepG2 cells in vitro. HDP-(S)-HPMPA retained full activity against HBV mutants resistant to lamivudine (L180M, M204V), but cross-resistance to a mutant resistant to adefovir (N236T) was detected. HDP-(S)-HPMPA is orally bioavailable and provides excellent liver exposure to the drug. Oral treatment of HBV transgenic mice with HDP-(S)-HPMPA, 15M-HDP-(S)-HPMPA, and ODE-(S)-HPMPA for 14 days reduced liver HBV DNA levels by roughly 1.5 log units, a response equivalent to that of adefovir dipivoxil.
On the development of strong ridge episodes over the eastern North Atlantic

The occurrence of strong and persistent mid‐latitude anticyclonic ridges over the Eastern North Atlantic is a major contributor to the occurrence of severe winter droughts over Western Iberia. We analyze the development of strong and persistent ridge episodes within 40–50°N; 40°W–5°E, which are defined as 300 hPa geopotential height anomalies above 50 gpm that persist for at least 10 consecutive days. Results suggest that the generation and maintenance of these episodes, with positive stratospheric geopotential anomalies over the North American continent and the adjacent North Pacific, are associated with an intensified polar jet. Such positive anomalies tend to detach from the main stratospheric anomaly and propagate eastwards and downwards as Rossby tropospheric waves. Furthermore, the Eastern North Atlantic ridge is generated and repeatedly reinforced until the stratospheric anomaly dissipates. Results also show evidence for waves breaking anticyclonically during the episodes, which is dynamically coherent with their persistency and quasi‐stationarity.
Robust continuous clustering

Significance Clustering is a fundamental experimental procedure in data analysis. It is used in virtually all natural and social sciences and has played a central role in biology, astronomy, psychology, medicine, and chemistry. Despite the importance and ubiquity of clustering, existing algorithms suffer from a variety of drawbacks and no universal solution has emerged. We present a clustering algorithm that reliably achieves high accuracy across domains, handles high data dimensionality, and scales to large datasets. The algorithm optimizes a smooth global objective, using efficient numerical methods. Experiments demonstrate that our method outperforms state-of-the-art clustering algorithms by significant factors in multiple domains. Clustering is a fundamental procedure in the analysis of scientific data. It is used ubiquitously across the sciences. Despite decades of research, existing clustering algorithms have limited effectiveness in high dimensions and often require tuning parameters for different domains and datasets. We present a clustering algorithm that achieves high accuracy across multiple domains and scales efficiently to high dimensions and large datasets. The presented algorithm optimizes a smooth continuous objective, which is based on robust statistics and allows heavily mixed clusters to be untangled. The continuous nature of the objective also allows clustering to be integrated as a module in end-to-end feature learning pipelines. We demonstrate this by extending the algorithm to perform joint clustering and dimensionality reduction by efficiently optimizing a continuous global objective. The presented approach is evaluated on large datasets of faces, hand-written digits, objects, newswire articles, sensor readings from the Space Shuttle, and protein expression levels. Our method achieves high accuracy across all datasets, outperforming the best prior algorithm by a factor of 3 in average rank.