Miracle-dz/UniFAR-FTUs huggingface dataset:
Rapid Transcriptional Pulsing Dynamics of High Expressing Retroviral Transgenes in Embryonic Stem Cells

Single cell imaging studies suggest that transcription is not continuous and occurs as discrete pulses of gene activity. To study mechanisms by which retroviral transgenes can transcribe to high levels, we used the MS2 system to visualize transcriptional dynamics of high expressing proviral integration sites in embryonic stem (ES) cells. We established two ES cell lines each bearing a single copy, self-inactivating retroviral vector with a strong ubiquitous human EF1α gene promoter directing expression of mRFP fused to an MS2-stem-loop array. Transfection of MS2-EGFP generated EGFP focal dots bound to the mRFP-MS2 stem loop mRNA. These transcription foci colocalized with the transgene integration site detected by immunoFISH. Live tracking of single cells for 20 minutes detected EGFP focal dots that displayed frequent and rapid fluctuations in transcription over periods as short as 25 seconds. Similarly rapid fluctuations were detected from focal doublet signals that colocalized with replicated proviral integration sites by immunoFISH, consistent with transcriptional pulses from sister chromatids. We concluded that retroviral transgenes experience rapid transcriptional pulses in clonal ES cell lines that exhibit high level expression. These events are directed by a constitutive housekeeping gene promoter and may provide precedence for rapid transcriptional pulsing at endogenous genes in mammalian stem cells.
p53 mutation is infrequent in clear cell carcinoma of the ovary.

OBJECTIVE p53 gene alteration has been extensively studied in epithelial ovarian cancer. However, its occurrence in clear cell carcinoma, an infrequent histologic subtype of epithelial ovarian cancer, is rarely reported. The aim of this study is to determine the status of p53 gene alteration in this distinct type of ovarian carcinoma. METHODS Paraffin blocks of tumors from 38 patients with primary or recurrent ovarian clear cell carcinoma were studied for p53 alteration. All these tumors were subjected to immunohistochemical and molecular analysis. Two monoclonal antibodies (DO-7 and PAb 1801) were used for immunohistochemical staining. Genomic DNAs extracted from paraffin blocks of the 38 tumors were subscribed for a nested polymerase chain reaction/single-strand conformation polymorphism (PCR/SSCP) analysis. Tumors showing band shift on SSCP were further prepared for DNA sequencing to determine the site of mutation. RESULTS Overexpression of p53 was observed in only one stage III clear cell carcinoma. However, focal positive p53 staining was noted in another five tumors. Of the six tumors showing positive immunohistochemistry, p53 alterations were noted in four tumors. Three tumors revealed a missense point mutation: two were in exon 7 (TCT(227) --> TTT and GGC(245) --> AGC) and one was in exon 5 (CGC(156) --> CAC). Another tumor revealed a 12-bp deletion in two possible ways: it might involve the last four codons at the 3' end of exon 4 (nucleotides 12,288-12,299) or it might cross over the splice junction between exon 4 and intron 4 (nucleotides 12,290-12,301). The former would result in a predicted protein product of 389 amino acids whereas the latter would cause a frameshift in the gene sequence and would result in a truncated protein. CONCLUSION Mutations in p53 appear to be much less frequent in clear cell carcinoma than in other histologic types of epithelial ovarian cancer. We suggest that p53 alterations may not play an important role in the development of clear cell carcinoma.
Mechanisms of Orthopnea in Stable Obese Subjects

BACKGROUND: The present study explored the role of closing volume as a determinant of orthopnea in stable obese subjects. We hypothesized that: (1) increase in closing volume in supine position would be greater in orthopneic than in non-orthopneic subjects, and (2) the relationship of change in closing volume to change in dyspnea with position would be dependent on expiratory flow limitation in the sitting position. METHODS: In stable obese subjects, in sitting and supine positions, we measured the Borg dyspnea score, static lung volumes, expiratory flow limitation during tidal breathing, and single-breath nitrogen expiration test. From the latter, we determined closing volume and closing capacity, slope of phase III, and opening capacity. Orthopnea was defined as any increase in the Borg score in the supine position from its value in the sitting position. RESULTS: Twenty-one subjects (13 women), median age (interquartile range) 55 (49–57) y and with body mass index of 39 (38–42) kg/m2 were included, of whom 12 were orthopneic and 11 had expiratory flow limitation while seated. In the sitting position, orthopneic and non-orthopneic subjects were similar for age, body mass index, and pulmonary function tests, including single-breath nitrogen expiration test-derived variables. In the orthopneic subjects, there were no changes in any respiratory variable between positions. In the non-orthopneic subjects, there was a significant decrease in slope of phase III in the supine position from 1.67 (1.33–3.60) to 1.40 (1.25–1.66)%/L (P = .008). Overall, the subjects' Borg score significantly correlated with the slope of phase III (r = 0.63, P = .002) and opening capacity (r = −0.47, P = .03). In 10 subjects without expiratory flow limitation, it correlated with slope of phase III (r = 0.68, P = .03). CONCLUSIONS: In stable obese subjects, magnitude of orthopnea correlated with an increase in the slope of phase III in subjects without expiratory flow limitation. Expiratory flow limitation should be taken into account in obese patients.
Coding-spreading tradeoff in LDPC-coded CDMA with turbo multiuser detection

We consider the problem of coding-spreading tradeoff in code-division multiple-access (CDMA) systems employing multiuser joint decoding. In particular, we assume the users employing the capacity-achieving low-density parity-check (LDPC) codes and at the receiver, turbo multiuser detection is used to implement joint decoding. We solve the coding-spreading optimization based on the extrinsic information signal-to-noise ratio (SNR) evolution curves for the soft-input soft-output (SISO) multiuser detectors and the SISO LDPC decoders. Two types of SISO multiuser detectors are treated, namely, the soft interference cancellation minimum mean-square-error (SIC-MMSE) detector and the soft interference cancellation matched filter (SIC-MF) detector. Moreover, both single-cell and multicell scenarios are considered. For each of these cases, we are able to characterize the extrinsic information SNR analytically, for both finite-size systems and for the so-called large systems where asymptotic performance results must be evoked. Our analysis indicates that the SIC-MMSE-based system offers a significant gain in spectral efficiency compared with the SIC-MF counterpart, in both single-cell and multicell scenarios. This is in contrast to the single-user decoding case, where it has been shown that the MMSE detector offers little advantage over the conventional matched-filter in terms of capacity in multicell scenario. Moreover, the results on coding-spreading tradeoff for finite-size systems and large systems match very well.
Exenatide extended-release; clinical trials, patient preference, and economic considerations

Type 2 diabetes remains an escalating problem worldwide, despite a range of treatments being available. The revelation that insulin secretion is under the control of a gut hormone, glucagon-like peptide 1, has led to a new paradigm in the management of type 2 diabetes, ie, use of medicines that directly stimulate or prolong the actions of endogenous glucagon-like peptide 1 at its receptors. Exenatide is an agonist at the glucagon-like peptide 1 receptor, and was initially developed as a subcutaneous medication twice daily (ExBID). Clinical trials with ExBID established a role for exenatide in the treatment of type 2 diabetes. Subsequently, exenatide once weekly (ExQW) was shown to have advantages over ExBID, and there is now more emphasis on the development of ExQW. ExQW alone reduces glycosylated hemoglobin (HbA1c) and body weight, and is well tolerated. ExQW has been compared with sitagliptin, pioglitazone, and metformin, and been shown to have a greater ability to reduce HbA1c than these other medicines. The only preparation of insulin with which ExQW has been compared is insulin glargine, and ExQW had some favorable properties in this comparison, notably causing weight loss compared with the weight gain on insulin glargine. ExQW has been compared with another glucagon-like peptide 1 receptor agonist, liraglutide, and was noninferior to liraglutide in reducing HbA1c. The small amount of evidence available shows that subjects with type 2 diabetes prefer ExQW to ExBID, and that adherence is high in the clinical trial setting. Health care and economic modeling suggests that ExQW will reduce diabetic complications and be cost-effective, compared with other medications, in long-term use. Little is known about whether subjects with type 2 diabetes prefer ExQW to other medicines, and whether adherence is good with ExQW in practice. These important topics require further study.
Psychometric evaluation of the Persian version of the Templer’s Death Anxiety Scale in cancer patients

ABSTRACT In this study, 398 Iranian cancer patients completed the 15-item Templer's Death Anxiety Scale (TDAS). Tests of internal consistency, principal components analysis, and confirmatory factor analysis were conducted to assess the internal consistency and factorial validity of the Persian TDAS. The construct reliability statistic and average variance extracted were also calculated to measure construct reliability, convergent validity, and discriminant validity. Principal components analysis indicated a 3-component solution, which was generally supported in the confirmatory analysis. However, acceptable cutoffs for construct reliability, convergent validity, and discriminant validity were not fulfilled for the three subscales that were derived from the principal component analysis. This study demonstrated both the advantages and potential limitations of using the TDAS with Persian-speaking cancer patients.
Spongy degeneration in the white matter of the central nervous system in the newborn: pathological findings in three infants, one with hyperglycinaemia.

Infantile spongy degeneration of the white matter of the central nervous system is a rare disorder of unknown pathogenesis. Reported cases have generally been described under the heading of spongy degeneration of van Bogaert and Bertrand type or as Canavan's type of diffuse sclerosis (see van Bogaert and Bertrand, 1967). The clinical and pathological features of the reported cases have been closely similar and a familial occurrence has been established; for these reasons it has been claimed that the disorder is a nosological entity (van Bogaert and Bertrand, 1967). However, a microscopic appearance in the central nervous system closely similar to that of van Bogaert and Bertrand's disease may be seen in association with some aminoacidurias-notably in maple syrup urine disease (Crome, Dutton, and Ross, 1961; Silberman, Dancis, and Feigin, 1961; Diezel and Martin, 1964; Menkes, Philippart, and Fiol, 1965) and in hyperglycinaemia (Donohue, 1967; Rushton, 1968). Pathologically, infantile spongy change is confined to white matter and myelinated grey masses; the vacuolation is usually associated with a considerable degree of myelin poverty, but products of myelin degeneration typical of a demyelinating disorder are not seen. These apparently incompatible findings have given rise to debate as to whether infantile spongy degeneration is primarily a myelin disease or an oedematous process with secondary myelin loss. Severe spongy change of the white matter is described here in three infants who died in the first month of life: two were born prematurely; the third, who was born at term, suffered from hyperglycinaemia. A number of pathological findings peculiar to the occurrence of the disease at an age when the nervous system is normally actively myelinating provide evidence that infantile spongy degeneration is a primary myelin disorder and indi-
Specific temperature-induced perturbations of secondary mRNA structures are associated with the cold-adapted temperature-sensitive phenotype of influenza A virus

For decades, cold-adapted, temperature-sensitive (ca/ts) strains of influenza A virus have been used as live attenuated vaccines. Due to their great public health importance it is crucial to understand the molecular mechanism(s) of cold adaptation and temperature sensitivity that are currently unknown. For instance, secondary RNA structures play important roles in influenza biology. Thus, we hypothesized that a relatively minor change in temperature (32–39°C) can lead to perturbations in influenza RNA structures and, that these structural perturbations may be different for mRNAs of the wild type (wt) and ca/ts strains. To test this hypothesis, we developed a novel in silico method that enables assessing whether two related RNA molecules would undergo (dis)similar structural perturbations upon temperature change. The proposed method allows identifying those areas within an RNA chain where dissimilarities of RNA secondary structures at two different temperatures are particularly pronounced, without knowing particular RNA shapes at either temperature. We identified such areas in the NS2, PA, PB2 and NP mRNAs. However, these areas are not identical for the wt and ca/ts mutants. Differences in temperature-induced structural changes of wt and ca/ts mRNA structures may constitute a yet unappreciated molecular mechanism of the cold adaptation/temperature sensitivity phenomena.
Multiple Peaks in the Angular Power Spectrum of the Cosmic Microwave Background: Significance and Consequences for Cosmology

Three peaks and two dips have been detected in the power spectrum of the cosmic microwave background by the BOOMERANG experiment, at l = (213), (541), (845) and l = (416), (750), respectively. Using model-independent analyses, we find that all five features are statistically significant, and we measure their location and amplitude. These are consistent with the adiabatic inflationary model. We also calculate the mean and variance of the peak and dip locations and amplitudes in a large seven-dimensional parameter space of such models, which gives good agreement with the model-independent estimates. We forecast where the next few peaks and dips should be found if the basic paradigm is correct. We test the robustness of our results by comparing Bayesian marginalization techniques on this space with likelihood maximization techniques applied to a second seven-dimensional cosmological parameter space, using an independent computational pipeline, and find excellent agreement: Ωtot = 1.02 versus 1.04 ± 0.05, Ωbh2 = 0.022 versus 0.019, and ns = 0.96 versus 0.90 ± 0.08. The determination of the best fit by the maximization procedure effectively ignores nonzero optical depth of reionization τC > 0, and the difference in primordial spectral index ns between the two methods is thus a consequence of the strong correlation of ns with the τC.
Epidemiology and clinical relevance of mutations in postpolycythemia vera and postessential thrombocythemia myelofibrosis: A study on 359 patients of the AGIMM group

Transformation to secondary myelofibrosis (MF) occurs as part of the natural history of polycythemia vera (PPV‐MF) and essential thrombocythemia (PET‐MF). Although primary (PMF) and secondary MF are considered similar diseases and managed similarly, there are few studies specifically focused on the latter. The aim of this study was to characterize the mutation landscape, and describe the main clinical correlates and prognostic implications of mutations, in a series of 359 patients with PPV‐MF and PET‐MF. Compared with PV and ET, the JAK2V617F and CALR mutated allele burden was significantly higher in PPV‐MF and/or PET‐MF, indicating a role for accumulation of mutated alleles in the process of transformation to MF. However, neither the allele burden nor the type of driver mutation influenced overall survival (OS), while absence of any driver mutation (triple negativity) was associated with significant reduction of OS in PET‐MF, similar to PMF. Of the five interrogated subclonal mutations (ASXL1, EZH2, SRSF2, IDH1, and IDH2), that comprise a prognostically detrimental high molecular risk (HMR) category in PMF, only SRSF2 mutations were associated with reduced survival in PET‐MF, and no additional mutation profile with prognostic relevance was highlighted. Overall, these data indicate that the molecular landscape of secondary forms of MF is different from PMF, suggesting that unknown mutational events might contribute to the progression from chronic phase disease to myelofibrosis. These findings also support more extended genotyping approaches aimed at identifying novel molecular abnormalities with prognostic relevance for patients with PPV‐MF and PET‐MF. Am. J. Hematol. 91:681–686, 2016. © 2016 Wiley Periodicals, Inc.
Soundness proof for a hoare logic for energy consumption analysis

Energy inefficient software implementations may cause battery drain for small systems and high energy costs for large systems. Dynamic energy analysis is often applied to mitigate these issues. However, this is often hardware-specific and requires repetitive measurements using special equipment. We present a static analysis deriving upper-bounds for energy consumption based on an introduced energy-aware Hoare logic. Software is considered together with models of the hardware it controls. The Hoare logic is parametric with respect to the hardware. Energy models of hardware components can be specified separately from the logic. Parametrised with one or more of such component models, the analysis can statically produce a sound (over-approximated) upper-bound for the energy-usage of the hardware controlled by the software.
Structure and Steroidogenesis of the Placenta in the Antarctic Minke Whale (Balaenoptera bonaerensis)

Abstract There are few reports describing the structure and function of the whale placenta with the advance of pregnancy. In this study, therefore, the placenta and nonpregnant uterus of the Antarctic minke whale were observed morphologically and immunohistochemically. Placentas and nonpregnant uteri were collected from the 15th, 16th and 18th Japanese Whale Research Programme with Special Permit in the Antarctic (JARPA) and 1st JARPA II organized by the Institute of Cetacean Research in Tokyo, Japan. In the macro- and microscopic observations, the placenta of the Antarctic minke whale was a diffuse and epitheliochorial placenta. The chorion was interdigitated to the endometrium by primary, secondary and tertiary villi, which contained no specialized trophoblast cells such as binucleate cells, and the interdigitation became complicated with the progress of gestation. Furthermore, fetal and maternal blood vessels indented deeply into the trophoblast cells and endometrial epithelium respectively with fetal growth. The minke whale placenta showed a fold-like shape as opposed to a finger-like shape. In both nonpregnant and pregnant uteri, many uterine glands were distributed. The uterine glands in the superficial layer of the pregnant endometrium had a wide lumen and large epithelial cells as compared with those in the deep layer. On the other hand, in the nonpregnant endometrium, the uterine glands had a narrower lumen and smaller epithelial cells than in the pregnant endometrium. In immunohistochemical detection, immunoreactivity for P450scc was detected in most trophoblast cells, but not in nonpregnant uteri, suggesting that trophoblast epithelial cells synthesized and secreted the sex steroid hormones and/or their precursors to maintain the pregnancy in the Antarctic minke whale.
A cytochemical study of the transcriptional and translational regulation of nuclear transition protein 1 (TP1), a major chromosomal protein of mammalian spermatids

Immunocytochemical localization and in situ hybridization techniques were used to investigate the presence of spermatid nuclear transition protein 1 (TP1) and its mRNA during the various stages of spermatogenesis in the rat. A specific antiserum to TP1 was raised in a rabbit and used to show that TP1 is immunologically crossreactive among many mammals including humans. During spermatogenesis the protein appears in spermatids as they progress from step 12 to step 13, a period in which nuclear condensation is underway. The protein is lost during step 15. An asymmetric RNA probe generated from a TP1 cDNA clone identified TP1 mRNA in late round spermatids beginning in step 7. The message could no longer be detected in spermatids of step 15 or beyond. Thus, TP1 mRNA first appears well after meiosis in haploid cells but is not translated effectively for the several days required for these cells to progress to the stage of chromatin condensation. Message and then protein disappear as the spermatids enter step 15. In agreement with a companion biochemical study (Heidaran, M.A., and W.S. Kistler. J. Biol. Chem. 1987. 262:13309-13315), these results establish that translational control is involved in synthesis of this major spermatid nuclear protein. In addition, they suggest that TP1 plays a role in the completion but not the initiation of chromatin condensation in elongated spermatids.
Total Space in Resolution

We show quadratic lower bounds on the total space used in resolution refutations of random k-CNFs over n variables, and of the graph pigeonhole principle and the bit pigeonhole principle for n holes. This answers the long-standing open problem of whether there are families of k-CNF formulas of polynomial size which require quadratic total space in resolution. The results follow from a more general theorem showing that, for formulas satisfying certain conditions, in every resolution refutation there is a memory configuration containing many clauses of large width.
Depression as a risk factor for Alzheimer disease: the MIRAGE Study.

BACKGROUND Depression symptoms may be associated with the development of Alzheimer disease (AD). OBJECTIVES To evaluate the association between depression symptoms and risk of AD, and to explore the temporal aspects of this association. SETTING Academic institutions with specialized memory clinics. DESIGN Cross-sectional, family-based, case-control study with standardized self- and proxy questionnaires to collect information on depression symptoms and other risk factors. PARTICIPANTS A total of 1953 subjects with AD and 2093 of their unaffected relatives enrolled in the Multi-institutional Research in Alzheimer's Genetic Epidemiology Study. MAIN OUTCOME MEASURES Odds ratios (ORs) of AD were estimated with and without depression symptoms, adjusted for age, sex, education, history of head trauma, and apolipoprotein E status. RESULTS There was a significant association between depression symptoms and AD (adjusted OR, 2.13; 95% confidence interval [CI], 1.71-2.67). In families where depression symptoms first occurred within 1 year before the onset of AD, the association was higher (OR, 4.57; 95% CI, 2.87-7.31), while in the families where the depression symptoms first occurred more than 1 year before the onset of AD, the association was lower (OR, 1.38; 95% CI, 1.03-1.85). In families where depression symptoms first occurred more than 25 years before the onset of AD, there was still a modest association (OR, 1.71; 95% CI, 1.03-2.82). CONCLUSIONS Depression symptoms before the onset of AD are associated with the development of AD, even in families where first depression symptoms occurred more than 25 years before the onset of AD. These data suggest that depression symptoms are a risk factor for later development of AD.