Miracle-dz/UniFAR-FTUs huggingface dataset:
Prothymosin α in Vivo Contains Phosphorylated Glutamic Acid Residues*

Human and monkey prothymosin α contain activated carbonyl groups on glutamic acid residues. Three lines of evidence indicate the existence of unusual phosphates. 1) Prothymosin α continued to be metabolically labeled with [32P]orthophosphoric acid despite a mutation at Ser1, the sole site of phosphate in purified bovine prothymosin α (Sburlati, A. R., De La Rosa, A., Batey, D. W., Kurys, G. L., Manrow, R. E., Pannell, L. K., Martin, B. M., Sheeley, D. M., and Berger, S. L. (1993)Biochemistry 32, 4587–4596). 2) Immediately upon cell lysis, the pH stability curves of metabolically labeled native [32P]prothymosin α or a [32P]histidine-tagged variant resembled the pH stability curve of acetyl phosphate. 3) After a brief incubation at pH 7, these curves changed from a pattern diagnostic for an acyl phosphate to that characteristic of a serine or threonine phosphate, an observation consistent with transfer of phosphate in vitro. Our data indicate that most of prothymosin α’s phosphates are subject instantaneously to hydrolysis, based on the observation that greater than 90% of the phosphate initially found at pH 7 disappeared at the extremes of pH. Rapid loss of phosphate was not affected by the presence of phosphatase inhibitors including 50 mm sodium fluoride, 1 mm okadaic acid, and 0.5 mmcalyculin A. The amount of phosphate missing could not be ascertained, but the trifling amount recovered on Ser or Thr depended heavily on conditions favoring the transient survival of labile phosphate. Further analysis using COS cells lysed in the presence of sodium borohydride showed that: 1) phosphate recovered on prothymosin α decreased 8-fold when lysates were treated with borohydride; 2) the reagent caused 4–8 glutamic acid residues/molecule to vanish; 3) using [3H]NaBH4, label was introduced into proline, a product derived from reductive cleavage of phosphoglutamate; and 4) [3H]proline was localized almost exclusively to a peptide with pronounced homology to the histone binding site of nucleoplasmin, a chromatin remodeling protein found in Xenopus laevis. Our data demonstrate that prothymosin α is energy-rich by virtue of stoichiometric amounts of glutamyl phosphate.
Clefting, amniotic bands, and polydactyly: A distinct phenotype that supports an intrinsic mechanism for amniotic band sequence

Amniotic band sequence (ABS) is a well‐described condition involving a variety of congenital anomalies in association with fibrous bands. However, many cases are associated with birth defects that are not readily explained by the mechanism of fibrous strings entangling body parts and causing disruption of the fetal structures. The most common of these is typical cleft lip and palate (CLP). Here we describe such a case, with typical ABS limb defects and constriction bands, along with CLP, supernumerary left nipple, polydactyly, and a skin papilla. This case is nearly identical to a child previously described by Guion‐Almieda and Richieri‐Costa [ 2000 ] and may, therefore, represent a previously unrecognized syndrome that overlaps with ABS. Furthermore it may be that cases with ABS‐like anomalies associated with CLP represent a different condition, possibly caused by mutations in the genes Disorganization, p63, or IRF6. © 2005 Wiley‐Liss, Inc.
Small‐molecule inhibitors of bone morphogenic protein and activin/nodal signals promote highly efficient neural induction from human pluripotent stem cells

The balance of bone morphogenic protein (BMP), transforming growth factor‐β (TGFβ)/activin/nodal, and Wnt signals regulates the early lineage segregation of human embryonic stem cells (ESCs). Here we demonstrate that a combination of small‐molecule inhibitors of BMP (Dorsomorphin) and TGFβ/activin/nodal (SB431542) signals promotes highly efficient neural induction from both human ESCs and induced pluripotent stem cells (iPSCs). The combination of small molecules had effects on both cell survival and purity of neural differentiation, under conditions of stromal (PA6) cell coculture and feeder‐free floating aggregation culture, for all seven pluripotent stem cell lines that we studied, including three ESC and four iPSC lines. Small molecule compounds are stable and cost effective, so our findings provide a promising strategy for controlled production of neurons in regenerative medicine. © 2010 Wiley‐Liss, Inc.
Repair of Dihydrouracil Supported by Base Excision Repair in mNTH1 Knock-out Cell Extracts*

In mammalian cells, thymine glycols and other oxidized pyrimidines such as 5,6-dihydrouracil are removed from DNA by the NTH1 protein, a bifunctional DNA-N-glycosylase. However, mNTH1 knock-out mice in common with other DNA glycosylase-deficient mice do not show any severe abnormalities associated with accumulation of DNA damage and mutations. In the present study we used an in vitro repair system to investigate the mechanism for the removal of 5,6-dihydrouracil from DNA by mNTH1-deficient cell-free extracts derived from testes of mNTH1 knock-out mice. We found that these extracts are able to support the removal of 5,6-dihydrouracil from DNA at about 20% of the efficiency of normal extracts. Furthermore, we also found that single-nucleotide patch base excision repair is the major pathway for removal of 5,6-dihydrouracil in mNTH1-deficient cell extracts, suggesting the involvement of other DNA glycosylase(s) in the removal of oxidized pyrimidines.
Administración de fondos de pensiones y multifondos en Colombia

Este documento evalua la regulacion vigente relacionada con la inversion de los recursos de los Fondos de Pensiones Obligatorios (FPO), para lo cual se analiza el perfil de eficiencia del sistema dadas sus actuales restricciones. De acuerdo con los resultados obtenidos, se observa que el marco regulatorio de las inversiones de los FPO restringen el retorno esperado y hace que los administradores de portafolios no accedan a niveles superiores de retorno por unidad de riesgo con 05res beneficios de diversificacion. Las propuestas apuntan hacia la flexibilizacion de las restricciones a las inversiones y a su adecuacion al perfil de riesgo de los cotizantes, utilizando para ello el esquema de multifondos implementado en otros paises de la region.
Diagnostic Performance of DWI With Multiple Parameters for Assessment and Characterization of Pulmonary Lesions: A Meta-Analysis.

OBJECTIVE The objective of our study was to evaluate the diagnostic performance of DWI using a 5-point rank scale, lesion-to-spinal cord signal intensity ratio, which we refer to as "LSR," and apparent diffusion coefficient (ADC) for the characterization of pulmonary lesions. MATERIALS AND METHODS After a literature search in several databases, two investigators independently selected studies, assessed methodologic quality, and extracted data. On a per-lesion basis, we pooled and compared the three parameters for malignant and benign lesions. Also, we determined pooled sensitivity and specificity with individual 95% CIs. RESULTS In total, 31 articles involving 2368 lesions were included. The mean scores of malignant and benign lesions on the 5-point scale were 3.83 (95% CI, 3.71-3.96) and 2.36 (95% CI, 2.18-2.54), respectively. The mean LSRs of malignant and benign lesions were 1.15 (95% CI, 1.07-1.24) and 0.71 (95% CI, 0.62-0.79). The mean ADC values of malignant and benign lesions were 1.23 (95% CI, 1.21-1.24) and 1.72 (95% CI, 1.68-1.77). All three parameters differed significantly between malignant and benign lesions (p < 0.05). On the basis of these parameters, the pooled sensitivity and specificity were 0.88 (95% CI, 0.84-0.91) and 0.75 (95% CI, 0.68-0.80) for the 5-point scale, 0.80 (95% CI, 0.75-0.85) and 0.85 (95% CI, 0.76-0.92) for LSR, and 0.84 (95% CI, 0.82-0.86) and 0.84 (95% CI, 0.81-0.87) for ADC. CONCLUSION Three DWI parameters-a visual parameter (score on a 5-point scale), semiquantitative parameter (LSR), and quantitative parameter (ADC)-can help to distinguish malignant from benign pulmonary lesions.
Substance P and Renshaw cells: a new concept of inhibitory synaptic interactions.

1. The actions of microelectrophoretically administered substance P on Renshaw cells in pentobarbitone anaesthetized cats were investigated. 2. The effects on spontaneous and synaptic firing and interactions with a number of other agents including acetylcholine, acetyl‐beta‐methylcholine, acidic amino acids, morphine, dihydro‐beta‐erythroidine and strychnine were studied in attempts to elucidate the mechanism of action of substance P. 3. Substance P usually selectively depressed the excitation by ACh, and also reduced submaximal synaptically evoked discharges which activate nicotinic receptors, but failed to modify excitation caused either by acetyl‐beta‐methylcholine, which activates muscarinic receptors, or excitation caused by glutamate or homocysteate. Substance P also depressed excitation by morphine which acted via the nicotinic receptors. 4. The inhibitory effect was not blocked by strychinine and was considered to be unlikely to be due to interaction between the polypeptide and either glycine or GABA receptors. 5. On some cells substance P caused excitation which was blocked by dihydro‐beta‐erythroidine. Mixed excitatory‐inhibitory effects were observed on some of these neurones. 6. The results are discussed in relation to the possibility that substance P could function as a synaptic inhibitory mediator with an unusual selectivity of action.
Thromboelastographic assessment of the impact of mexiletine on coagulation abnormalities induced by air or normal saline intravenous injections in conscious rats.

BACKGROUND Thromboelastography (TEG) in venous air embolism (VAE) has been poorly studied. We induced coagulation abnormalities by VAE in a rat model, assessed by TEG with and without mexiletine, a lidocaine analogue local anesthetic. METHODS Twenty-three Sprague Dawley rats instrumented under isoflurane anesthesia and allowed to recover five days prior to the experiments were randomized into three experimental groups: 1) VAE (n = 6); 2) VAE and mexiletine (n = 9); and 3) normal saline (NS) alone (control group, n = 8). Blood samples were collected at baseline, one hour (h) and 24 h in all groups and analyzed by TEG to record the R, K, angle α and MA parameters. RESULTS In Group 1, VAE decreased significantly R at 1 h (31%), K at 1 h (59%) and 24 h (34%); α increased significantly at 1 h (30%) and 24 h (22%). While R returned to baseline values within 24 h, K, MA and α did not. In group-2 (Mexiletine + VAE), K and R decreased at 1 h (48% and 29%, respectively) and at 24 h the changes were non-significant. Angle α increased at 1 h (28%) and remained increased for 24 h (25%). In group 3 (NS), only R was temporarily affected. MA increased significantly at 24 h only in the VAE alone group. CONCLUSION As expected, VAE produced a consistent and significant hypercoagulable response diagnosed/confirmed by TEG. Mexiletine prevented the MA elevation seen with VAE and corrected R and K time at 24 h, whereas angle α remained unchanged. Mexiletine seemed to attenuate the hypercoagulability associated with VAE in this experiment. These results may have potential clinical applications and deserve further investigation.
Cluster differentiation antigen expression, proliferative activity and clinical stage in centroblastic centrocytic lymphomas

Using a panel of B‐cell antibodies recognizing clusters of leucocyte differentiation antigens, immunostaining patterns of eight reactive lymph nodes and 28 centroblastic/centrocytic and centrocytic lymphomas have been studied. Centroblastic/centrocytic and centrocytic lymphomas retained many of the B‐cell differentiation antigens and neoplastic follicles partially recapitulated the staining patterns observed in reactive follicles. Centrocytic lymphomas usually expressed a heavy chain mantle zone‐like phenotype. Nearly one‐half of follicular lymphomas showed extension of neoplastic cells into interfollicular areas as evidenced by positivity for CD 10 (common acute lymphoblastic leukaemia) and/or CD9 (immature B‐cell) and CD23 (B‐blast cell) antigens. Cases showing interfollicular involvement also manifested considerable phenotypic heterogeneity. Light chain restriction could not be used to determine interfollicular involvement because of the presence of many non‐neoplastic cells. Most follicular lymphomas retained a polyclonal mantle around at least some neoplastic follicles and in no case was a monoclonal mantle seen. Most lymphomas (16/21) were diploid when examined by flow cytometry. Diploid tumours exhibiting interfollicular lymphomatous involvement had high proliferation (S + G2) fractions and these lymph nodes were usually derived from patients with widespread disease. Tumours containing a high percentage of cells in the G0/G1 phases displayed fewer B‐cell differentiation antigens than tumours with low G0/G1 fractions.
Differences in income distributions for men and women in the European Union countries

Research background: Recently there has been an increase in interest in the studies of income inequalities. The findings of numerous empirical studies show that males earn higher wages than females. A variety of techniques of income inequalities decomposition are becoming popular. New procedures go far beyond the Oaxaca-Blinder decomposition. They allow to study differences of income distributions for various groups of people and to decompose them at various quantile points. Purpose of the article: The aim of the paper is to compare personal income distributions in selected countries of the European Union, taking into account gender differences. Methods: First, we examined the income inequalities between men and women in each country using the Oaxaca-Blinder decomposition procedure. The unexplained part of the gender pay gap gave us information about the wage discrimination. Second, we extended the decomposition procedure to different quantile points along the whole income distribution. To describe differences between the incomes of men and women, we constructed the so-called counterfactual distribution, which is a mixture of a conditional distribution of the dependent variable (income) and a distribution of the explanatory variables (individual people’s characteristics). Then, we utilized the residual imputation approach (JMP-approach). Findings & Value added: In the article data from EU-SILC (Statistics on Income and Living Conditions) were used. We found that there exists an important diversity in the size of the gender pay gap across members of the European Union. The results obtained for these countries allowed us to group them into clusters. In general, there are two types of countries in Europe: the countries, where the bulk of the observed income differences cannot be explained by observed characteristics, and the countries, where the explained and the unexplained effects are both positive, with even a bigger explained effect for the lower income ranges.
Common carotid intima-media thickness in cardiovascular risk stratification of older people: the Rotterdam Study

Aim: Non-invasive measures of atherosclerosis, such as carotid intima-media thickness (cIMT), may improve global cardiovascular risk prediction. The aim of this study was to determine whether common carotid IMT in addition to traditional risk factors improves risk classification in a general population of older people. Methods and results: A group of 3580 non-diabetic people aged 55–75 years and free of cardiovascular disease at baseline were followed for a median time of 12.2 years. Compared to models based on Framingham risk factors, we studied the ability of common cIMT measurement to better classify people into categories of low (<10%), intermediate (10–20%) and high (>20%) 10-year risk of hard coronary heart disease (CHD) and stroke. In older men, addition of cIMT to Framingham risk factors did not improve prediction of hard CHD or stroke. In older women, addition of cIMT to Framingham risk factors significantly improved risk classification. cIMT improved the C-statistic of the model for hard CHD from 0.711 to 0.719 and for stroke from 0.712 to 0.721, at good calibration. Reclassification was least in the majority of women classified as low risk (4% (n = 76) for hard CHD and 3% (n = 62) for stroke) and most substantial in women at intermediate risk (43% (n = 70) for hard CHD and 28% (n = 76) for stroke). The net reclassification improvement in women was 8.2% (p = 0.03) for hard CHD and 8.0% (p = 0.06) for stroke. Conclusion: cIMT had some additional value beyond traditional risk factors in the cardiovascular risk stratification of older women, but not of older men.
Hierarchical control of a renewable hybrid energy system

This study deals with system integration and controller design for power management of a stand-alone renewable energy (RE) hybrid system, which is in its construction stage in Lambton College (Sarnia, Ontario, Canada). The system consists of five main components: photovoltaic (PV) arrays, wind turbine, electrolyzer, hydrogen storage tanks, and fuel cell. The model for each process component is developed and all the hybrid energy system components are integrated in a MATLAB/Simulink environment. A hierarchical control system is implemented, comprising of a supervisory controller, which ensures the power balance between intermittent renewable energy generation, energy storage and dynamic load demand, and local controllers for the PV, wind, electrolyzer and fuel cell units. A decentralized model predictive control (MPC) was designed and implemented on the electrolyzer and fuel cell to ensure optimal power flow.
Is GPR119 agonism an appropriate treatment modality for the safe amelioration of metabolic diseases?

Introduction: GPR119 is a recently deorphanised G-protein coupled receptor which has been suggested to be important in mediating systemic metabolic homeostasis. Research to date has primarily focused on the ability of GPR119 to promote euglycaemia and thus as a therapeutic target for the treatment of type 2 diabetes mellitus (T2DM). Indeed, previous studies have shown that GPR119 promotes glucose-stimulated insulin secretion, pancreatic β-cell function and glucagon-like peptide-1 release, all of which provide valid mechanisms through which GPR119 may improve systemic glucose homeostasis. Areas covered: In the current review, the authors provide a brief overview of the known functions of GPR119 and then discuss the novel potential for GPR119 to regulate metabolic function in skeletal and cardiac muscle and how this may translate to improvements or impairments in systemic health. Expert opinion: GPR119 is largely purported as being anti-diabetic and has been rapidly progressed to clinical trials, mainly as anti-diabetic agents. However, emerging data suggest that this class of agonists may have a detrimental effect at the level of the muscle. This may potentiate the development and progression of metabolic diseases such as T2DM. Therefore, further research is required before GPR119 receptor agonists can be prescribed with confidence as an anti-diabetic agent.
Utility of acid-fast staining for detection of mycobacteria in cutaneous granulomatous tissue reactions.

OBJECTIVES Ancillary molecular testing on tissue is available for mycobacterial disease; however, judicious use of highly sensitive tests, such as polymerase chain reaction (PCR) and sequencing, should be guided by histologic parameters. We sought to investigate the utility of performing acid-fast stains (AFS) on skin biopsy specimens with granulomatous inflammation without an otherwise obvious histologic or clinical explanation. METHODS Our retrospective review identified 31 patients with biopsy specimens showing granulomatous inflammation that had simultaneous AFS and mycobacterial culture or PCR performed. RESULTS Biopsy specimens from eight (25.8%) patients had AFS interpreted as positive or suspicious for acid-fast bacilli. Eight had positive cultures and one had positive PCR. One biopsy specimen with AFS that showed occasional acid-fast structures that were interpreted as "suspicious" for mycobacteria was associated with a negative culture and negative PCR. Three (9.7%) biopsy specimens with negative AFS had positive cultures, and 19 (61.3%) biopsy specimens with negative AFS also had negative culture results. In our biopsy specimens, sensitivity of AFS was 72.7% and specificity was 95.0%. Positive predictive value of AFS was 88.9%, and negative predictive value was 86.4%. CONCLUSIONS AFS has good sensitivity and excellent specificity and should be performed on all unexplained granulomatous tissue reactions of skin in conjunction with mycobacterial culture.
Energy Resolution of Calcium Co-Doped LSO:Ce Scintillators

Co-doping Lu2SiO5:Ce (LSO:Ce) with Ca divalent cations changes the scintillation properties of the crystal. In the present work an influence of Ca2+ co-doping on energy resolution, light output and non-proportionality was investigated for samples with 0, 0.1, 0.2, 0.3, and 0.4 atomic percent Ca with respect to Lu. A substantial improvement of energy resolution in the co-doped crystals was found and higher light output by about 10% was observed. The best energy resolution of 7.35 plusmn 0.15% was measured for LSO with 0.2% Ca. Contrary to our expectations, the change in the measured energy resolution of Ca2+ co-doped LSO samples is not reflected in the non-proportional characteristic of the studied crystals as the non-proportionality curves are independent of Ca concentration. Possible explanations of the underlying mechanism of improving the energy resolution include afterglow suppression via Ca co-doping. Earlier studies showed that calcium co-doping significantly reduces the trap population, hence the decay time of LSO is shortened and the afterglow is substantially quenched. In the current work, the integrated afterglow intensities as well as the afterglow effective decay times correlate with the concentration of Ca2+. Since the afterglow was measured about 30 ms after the crystal was irradiated by a strong X-ray source, the integral intensity does not include the faster components of afterglow. Hence, the correlation between afterglow intensity and energy resolution treated in this work is very preliminary.
Positive peritoneal cytology in endometrial cancer: enhancement of other prognostic indicators.

OBJECTIVE The goal of this study was to investigate the prognostic significance of positive peritoneal cytology in endometrial cancer. METHODS A clinicocytopathological study was performed in 534 patients with endometrial cancer to assess the prognostic value of positive peritoneal cytology. The study population was divided into three groups: a low-risk group (disease limited to the uterus, grade 1, and depth of invasion < or =1/2), a moderate-risk group (disease limited to the uterus, grade 2 or 3, and/or depth of invasion >1/2), and a high-risk group (extrauterine disease). In each group, disease-free survival was compared in the patients who were positive or negative for malignant cells. RESULTS The overall incidence of positive peritoneal cytology was 22.3% (119/534). The 5-year disease-free survival of patients positive or negative for malignant cells was 98.1% versus 100% in the low-risk group (n = 250), 77.5% versus 91.3% in the moderate-risk group (n = 211), and 42.9% versus 72.1% in the high-risk group (n = 73). A significant difference was noted in the moderate-risk (P = 0.044) and high-risk (P = 0.015) groups, but not in the low-risk group (P = 0.56). CONCLUSIONS Positive peritoneal cytology is not a negative prognostic indicator itself, but it potentiates other prognostic indicators for endometrial cancer. Our findings also suggest that patients with positive peritoneal cytology in the absence of other adverse prognostic factors do not need upstaging.