Miracle-dz/UniFAR-FTUs huggingface dataset:
TSG-6 inhibits osteoclast activity via an autocrine mechanism and is functionally synergistic with osteoprotegerin.

OBJECTIVE TSG-6 (the product of tumor necrosis factor [TNF]-stimulated gene 6) has a potent inhibitory effect on RANKL-mediated bone erosion. The aim of this study was to compare the activity of TSG-6 with that of osteoprotegerin (OPG) and to investigate its role as an autocrine modulator of cytokine-mediated osteoclast formation/activation. We also determined TSG-6 expression in inflammatory joint disease. METHODS The effects of TSG-6, OPG, and the inflammation mediators TNFα, interleukin-1 (IL-1), and IL-6 on the formation of osteoclasts from peripheral blood mononuclear cells and synovial fluid (SF) macrophages were determined by tartrate-resistant acid phosphatase staining. Lacunar resorption and filamentous actin ring formation were measured as indicators of osteoclast activity. The amount of TSG-6 in culture media or SF was quantified by enzyme-linked immunosorbent assay, and expression of TSG-6 in synovial tissue was assessed by immunohistochemistry. RESULTS TSG-6 acted in synergy with OPG to inhibit RANKL-mediated bone resorption and was produced by osteoclast precursors and mature osteoclasts in response to TNFα, IL-1, and IL-6. Expression of TSG-6 correlated with inhibition of lacunar resorption; this effect was ameliorated by an anti-TSG-6 antibody. The level of TSG-6 protein was determined in SF from patients with various arthritides; it was highest in patients with inflammatory conditions such as rheumatoid arthritis, in which it correlated with the amount of TSG-6 immunostaining in the synovium. TSG-6 inhibited the activation but not the formation of osteoclasts from SF macrophages. CONCLUSION In the presence of inflammatory cytokines, osteoclasts produced TSG-6 at concentrations that are sufficient to inhibit lacunar resorption. This may represent an autocrine mechanism to limit the degree of bone erosion during joint inflammation.
Simulations and Tests of MCP-BSCCO-2212 Superconducting Fault Current Limiters

Superconducting fault current limiters (SCFCLs) represent a promising solution to the problem of increasing short- circuit currents in the grid. The SCFCL is based on the fast transition from the superconducting state to the normal state, causing a sudden increase in the impedance of the network. In this paper, we simulate the behavior of resistive-type SCFCL modules. The SCFCL modules are based on MCP-BSCCO 2212 coils. The superconductor acts as a nonlinear resistance that varies with the current and the temperature. The behavior of the simulated curves is consistent with the experimental results. Short-circuit currents as high as 37 kApeak were limited to about 10% of their peak values in the first half cycle.
Fzo1p Is a Mitochondrial Outer Membrane Protein Essential for the Biogenesis of Functional Mitochondria in Saccharomyces cerevisiae*

Fzo1p is a novel component required for the biogenesis of functional mitochondria in the yeast Saccharomyces cerevisiae. The protein is homologous to DrosophilaFzo, the first known protein mediator of mitochondrial fusion. Deletion of the FZO1 gene results in a petite phenotype, loss of mitochondrial DNA, and a fragmented mitochondrial morphology. Fzo1p is an integral protein of the mitochondrial outer membrane exposing its major part to the cytosol. It is imported into the outer membrane in a receptor-dependent manner. Fzo1p is part of a larger protein complex of 800 kDa, and presumably is the first identified component of the yeast mitochondrial fusion machinery.
Breast Milk of HIV-Positive Mothers Has Potent and Species-Specific In Vivo HIV-Inhibitory Activity

ABSTRACT Despite the nutritional and health benefits of breast milk, breast milk can serve as a vector for mother-to-child HIV transmission. Most HIV-infected infants acquire HIV through breastfeeding. Paradoxically, most infants breastfed by HIV-positive women do not become infected. This is potentially attributed to anti-HIV factors in breast milk. Breast milk of HIV-negative women can inhibit HIV infection. However, the HIV-inhibitory activity of breast milk from HIV-positive mothers has not been evaluated. In addition, while significant differences in breast milk composition between transmitting and nontransmitting HIV-positive mothers have been correlated with transmission risk, the HIV-inhibitory activity of their breast milk has not been compared. This knowledge may significantly impact the design of prevention approaches in resource-limited settings that do not deny infants of HIV-positive women the health benefits of breast milk. Here, we utilized bone marrow/liver/thymus humanized mice to evaluate the in vivo HIV-inhibitory activity of breast milk obtained from HIV-positive transmitting and nontransmitting mothers. We also assessed the species specificity and biochemical characteristics of milk's in vivo HIV-inhibitory activity and its ability to inhibit other modes of HIV infection. Our results demonstrate that breast milk of HIV-positive mothers has potent HIV-inhibitory activity and indicate that breast milk can prevent multiple routes of infection. Most importantly, this activity is unique to human milk. Our results also suggest multiple factors in breast milk may contribute to its HIV-inhibitory activity. Collectively, our results support current recommendations that HIV-positive mothers in resource-limited settings exclusively breastfeed in combination with antiretroviral therapy. IMPORTANCE Approximately 240,000 children become infected with HIV annually, the majority via breastfeeding. Despite daily exposure to virus in breast milk, most infants breastfed by HIV-positive women do not acquire HIV. The low risk of breastfeeding-associated HIV transmission is likely due to antiviral factors in breast milk. It is well documented that breast milk of HIV-negative women can inhibit HIV infection. Here, we demonstrate, for the first time, that breast milk of HIV-positive mothers (nontransmitters and transmitters) inhibits HIV transmission. We also demonstrate that breast milk can prevent multiple routes of HIV acquisition and that this activity is unique to human milk. Collectively, our results support current guidelines which recommend that HIV-positive women in resource-limited settings exclusively breastfeed in combination with infant or maternal antiretroviral therapy.
What Can Animal Models Tell Us about Human Sexual Response?

Abstract In all species, sexual behavior is directed by a complex interplay between steroid hormone actions in the brain that give rise to sexual arousability and experience with sexual reward that gives rise to expectations of competent sexual activity, including sexual arousal, desire, and performance. Sexual experience allows animals to form instrumental and Pavlovian associations that predict sexual outcome and thereby directs the strength of sexual responding. Although the study of animal sexual behavior by neuroendocrinologists has traditionally been concerned with mechanisms of copulatory responding, more recent use of conditioning and preference paradigms, and a focus on environmental circumstances and experience, has revealed behaviors and processes that resemble human sexual responses. In this paper, we review behavioral paradigms used with rodents and other species that are analogous or homologous to human sexual arousal, desire, reward, and inhibition. The extent to which these behavioral paradigms offer predictive validity and practicality as preclinical tools and models is discussed. Identification of common neurochemical and neuroanatomical substrates of sexual responding between animals and humans suggests that the evolution of sexual behavior has been highly conserved and indicates that animal models of human sexual response can be used successfully as preclinical tools.
Focal Adhesion Kinase (FAK) Binds RET Kinase via Its FERM Domain, Priming a Direct and Reciprocal RET-FAK Transactivation Mechanism*

Whether RET is able to directly phosphorylate and activate downstream targets independently of the binding of proteins that contain Src homology 2 or phosphotyrosine binding domains and whether mechanisms in trans by cytoplasmic kinases can modulate RET function and signaling remain largely unexplored. In this study, oligopeptide arrays were used to screen substrates directly phosphorylated by purified recombinant wild-type and oncogenic RET kinase domain in the presence or absence of small molecule inhibitors. The results of the peptide array were validated by enzyme kinetics, in vitro kinase, and cell-based experiments. The identification of focal adhesion kinase (FAK) as a direct substrate for RET kinase revealed (i) a RET-FAK transactivation mechanism consisting of direct phosphorylation of FAK Tyr-576/577 by RET and a reciprocal phosphorylation of RET by FAK, which crucially is able to rescue the kinase-impaired RET K758M mutant and (ii) that FAK binds RET via its FERM domain. Interestingly, this interaction is abolished upon RET phosphorylation, indicating that RET binding to the FERM domain of FAK is a priming step for RET-FAK transactivation. Finally, our data indicate that FAK inhibitors could be used as potential therapeutic agents for patients with multiple endocrine neoplasia type 2 tumors because both, treatment with the FAK kinase inhibitor NVP-TAE226 and FAK down-regulation by siRNA reduced RET phosphorylation and signaling as well as the proliferation and survival of tumor and transfected cell lines expressing oncogenic RET.
The Relationship between Inter-Arm Blood Pressure Difference and Coronary Artery Disease Severity Calculated by the SYNTAX Score

Objectives The inter-arm systolic blood pressure difference (IASBPD) is closely related to cardiovascular mortality and morbidity. The SYNTAX score indicates the extent and complexity of coronary artery disease, which are determined by coronary angiography. The aim of our study is to examine the relationship between the IASBPD (which is easily calculated in routine practice) and the SYNTAX score. Methods 104 patients were included in this cross-sectional study. The IASBPD was calculated by blood pressure measurements obtained simultaneously from both arms. The SYNTAX score was calculated by coronary angiography. Results Patients were divided into two groups: those with a high SYNTAX score (≥20) and those with a low SYNTAX score (<20). The mean IASBPD values were significantly higher in the group with a high SYNTAX score (≥20) (p<0.001). The patients with IASBPD≥10 were more likely to have a high SYNTAX score compared to the patients with IASBPD<10 (p<0.001). Multiple logistic regression analysis revealed that only the IASBPD values were found to be independently associated with high SYNTAX score (OR: 1.717 (CI: 1.307-2.257), p<0.001). Conclusion The IASBPD values obtained by only blood pressure measurements are closely related to the extent of coronary artery disease.
Human Papillomavirus 16 Non-European Variants Are Preferentially Associated with High-Grade Cervical Lesions

HPV16 accounts for 50–70% of cervical cancer cases worldwide. Characterization of HPV16 variants previously indicated that they differ in risks for viral persistence, progression to cervical precancer and malignant cancer. The aim of this study was to examine the association of severity of disease with HPV16 variants identified in specimens (n = 281) obtained from a Cervical Pathology and Colposcopy outpatient clinic in the University Hospital of Espírito Santo State, Southeastern Brazil, from April 2010 to November 2011. All cytologic and histologic diagnoses were determined prior to definitive treatment. The DNA was isolated using QIAamp DNA Mini Kit and HPV was detected by amplification with PGMY09/11 primers and positive samples were genotyped by RFLP analyses and reverse line blot. The genomes of the HPV16 positive samples were sequenced, from which variant lineages were determined. Chi2 statistics was performed to test the association of HPV16 variants between case and control groups. The prevalence of HR-HPV types in <CIN1, CIN2 and CIN3+ were 33.7%, 84.4% and 91.6%, respectively. Thirty-eight of 49 (78%) HPV16 positive samples yielded HPV16 sequence information; of which, 32 complete genomes were sequenced and an additional 6 samples were partially sequenced. Phylogenetic analysis and patterns of variations identified 65.8% (n = 25) as HPV16 European (E) and 34.2% (n = 13) as non-European (NE) variants. Classification of disease into CIN3+ vs. <CIN3 indicated that NE types were associated with high-grade disease with an OR = 4.6 (1.07–20.2, p = 0.05). The association of HPV16 NE variants with an increased risk of CIN3+ is consistent with an HPV16 genetically determined enhanced oncogenicity. The prevalence of genetic variants of HPV16 is distributed across different geographical areas and with recent population admixture, only empiric data will provide information on the highest risk HPV16 variants within a given population.
Iron Bioavailability, Storability and Sensory Evaluation of Iron Fortified Extruded Snacks Intended to Alleviate Iron Deficiency in Indian Children

Iron deficiency is one of the major health problems in India and is significantly affecting the growth and development of children. The mid day meals offered as an intervention to improve nutritional standards could not fulfill daily iron requirements of children. Iron fortified snack products were developed to supplement these daily meals, by extrusion cooking of nutritional orphan crop finger millet added with fortifying agents NaFeEDTA (sodium iron ethylenediaminetetraacetate) or ferrous fumarate and aonla (Emblica officinalis Gaertn); as a source of ascorbic acid. The extrusion variables were optimized at moisture 18%, barrel temperature 115C, screw speed 260 rpm and addition of cassava at the rate of 30 %, based on the expansion ratio. Iron bioavailability from products was assessed in terms of Haemoglobin Maintenance Efficiency (HME) through Haemoglobin regeneration assay in chicks. Overall HME was significantly different (p < 0.05) for feed fortified with ferrous fumarate (28.66 %), feed fortified with NaFeEDTA (35.26 %), and feed without fortificant (19.15%). Addition of aonla powder to chick feed significantly improved the HME in case of ferrous fumarate whereas, showed no significant effect in the case of NaFeEDTA and feeds without fortificant. Storage stability was evaluated on the basis of density, hardness, and sensory characteristics for both fresh and stored samples. Samples were fried, dusted with spice mix and were packed for storage studies in low-density polyethylene (LDPE) and aluminium foil packaging material, with or without nitrogen flushing. In conclusion, products fortified with NaFeEDTA and packed in aluminium foil with nitrogen flushing were found optimal in terms of iron bioavailability, storability and consumer acceptability.
Contribution of Chitinase A’s C-Terminal Vacuolar Sorting Determinant to the Study of Soluble Protein Compartmentation

Plant chitinases have been studied for their importance in the defense of crop plants from pathogen attacks and for their peculiar vacuolar sorting determinants. A peculiarity of the sequence of many family 19 chitinases is the presence of a C-terminal extension that seems to be important for their correct recognition by the vacuole sorting machinery. The 7 amino acids long C-terminal vacuolar sorting determinant (CtVSD) of tobacco chitinase A is necessary and sufficient for the transport to the vacuole. This VSD shares no homology with other CtVSDs such as the phaseolin’s tetrapeptide AFVY (AlaPheValTyr) and it is also sorted by different mechanisms. While a receptor for this signal has not yet been convincingly identified, the research using the chitinase CtVSD has been very informative, leading to the observation of phenomena otherwise difficult to observe such as the presence of separate vacuoles in differentiating cells and the existence of a Golgi-independent route to the vacuole. Thanks to these new insights in the endoplasmic reticulum (ER)-to-vacuole transport, GFPChi (Green Fluorescent Protein carrying the chitinase A CtVSD) and other markers based on chitinase signals will continue to help the investigation of vacuolar biogenesis in plants.
Cyclin D1 overexpression in colorectal carcinoma in vivo is dependent on β‐catenin protein dysregulation, but not k‐ras mutation

Cyclin D1 protein overexpression is commonly found in colorectal carcinomas (CRCs) and is associated with a poorer prognosis, but the mechanism underlying overexpression remains uncertain. Both dysregulation of β‐catenin protein expression and k‐ras mutation have recently been shown to promote cyclin D1 expression in human in vitro and rodent in vivo studies. In this study, 53 sporadic CRCs were examined by immunohistochemistry for cyclin D1 and β‐catenin protein expression, and with PCR and direct DNA sequencing for k‐ras gene status. The study also addressed whether cyclin D1 overexpression might associate with poorer prognosis because of a relationship with poorer response to 5‐fluorouracil (5FU) chemotherapy. Cyclin D1 overexpression was demonstrated in 34/53 (64%) CRCs, was significantly associated with higher Dukes' stage, and was particularly prominent at the invasive edges of carcinomas. Furthermore, cyclin D1 overexpression was always and only seen in association with nuclear expression of β‐catenin. There were no significant associations between cyclin D1 overexpression and k‐ras mutation or response to 5FU. Amongst 17 microsatellite unstable CRCs, a smaller proportion of tumours showed cyclin D1 overexpression (18%), but again cyclin D1 overexpression was only seen in cases showing nuclear β‐catenin expression. In conclusion, β‐catenin protein dysregulation, but not k‐ras mutation, appears to be required for cyclin D1 overexpression in colorectal carcinoma in vivo. Copyright © 2002 John Wiley & Sons, Ltd.
Flow Cytometric Immunophenotyping of Mature Lymphatic Neoplasias Using Knowledge Guided Cluster Analysis

Flow cytometry is widely used for the immunological characterization of hematopoietic malignancies. Discrimination of normal and malignant cellular immunophenotypes is the most critical step in data analysis, especially if multi‐color analysis is performed on highly heterogenous cell suspensions. We therefore investigated, whether adaptive, simultaneous multiparameter gating allowed automated, operator independent analysis of data obtained from the immunophenotyping of blood or bone marrow samples with regard to the presence of non‐Hodgkin lymphoma cells. The identification of physiological and malignant cells was achieved by predefining population boundaries, based on the expectations of the population’s location in two‐dimensional dot plots. The prospective application of these predefined region boundaries in 52 blood and bone marrow samples enabled identification of lymphoma cells with regard to their presence and immunophenotype, based on the correlation of markers as defined in multiple tubes. Our data confirm that highly standardized data analysis methods can reduce the variability of analysis and support the expert in establishing a rapid classification of the sample.
Tear Osmolarity and Ocular Changes in Pterygium

Purpose: To determine abnormalities in tear osmolarity (TO), tear function, and impression cytology in patients with pterygium and to assess the relationship between the variables. Methods: Thirty eyes from 30 patients with primary nasal pterygium and 30 eyes from 30 volunteers without ocular pathologies or dry eye symptoms were enrolled in the present study. TO test, tear ferning test, fluorescein tear breakup time, Schirmer test, and impression cytology of the conjunctiva were performed. Analysis of variance was applied for intergroup comparisons, and Pearson correlation was used to calculate the strength of relationships between the variables. A statistical significance level of P <0.05 was considered. Results: Pterygium patients had significantly higher TO, lower crystallization percentage, and lower goblet cell density (GCD) than control patients. A weak but significant negative correlation seems to exist between TO and crystallization percentage (r = −0.425, P < 0.01) and between TO and GCD (r = −0.295, P < 0.05). Conclusion: There is evidence to suggest that pterygium appears to induce unfavorable conditions of increasing TO that could trigger alterations in tear crystallization and GCD. Being aware of TO changes seems essential to understand the complex relationship among pterygium, tear film functions, and ocular surface changes.
Optimal Taxation, Marriage, Home Production, and Family Labor Supply

An empirical approach to optimal income taxation design is developed within an equilibrium collective marriage market model with imperfectly transferable utility. Taxes distort labour supply and time allocation decisions, as well as marriage market outcomes, and the within household decision process. Using data from the American Community Survey and American Time Use Survey, we structurally estimate our model and explore empirical design problems. We consider the optimal design problem when the planner is able to condition taxes on marital status, as in the U.S. tax code, but we allow the schedule for married couples to have an arbitrary form of tax jointness. Our results suggest that the optimal tax system for married couples is characterized by negative jointness, although the welfare gains from this jointness are shown to be quite modest.
HEAT KERNEL AND MODULI SPACES

In this paper we describe a proof of the formulas of Witten [W1], [W2] about the symplectic volumes and the intersection numbers of the moduli spaces of principal bundles on a compact Riemann surface. It is known that these formulas give all the information needed for the Verlinde formula. The main idea of the proof is to use the heat kernel on compact Lie groups, in a way very similar to the heat kernel proof of the Atiyah-Singer index formula and the Atiyah-Bott fixed point formula. The Reidemeister torsion comes into the picture, through a beautiful observation of Witten, as the symplectic volume of the moduli space. It plays the role similar to that played by the Ray-Singer torsion in the path-integral computations on the space of connections. The basic idea is as follows. Consider a smooth map between two compact smooth manifolds f : M → N . Let H(t, x, x0) be the heat kernel of the Laplace-Beltrami operator on N with x0 a fixed regular value of f . Because of the basic properties of the heat kernel, we know that for any continuous function a(y) on M , when t goes to zero, ∫
[5,10,15,20-Tetrakis(4-tolyl)porphyrin]zinc(II) dichloromethane solvate

In the title complex, [Zn(C48H36N4)]·CH2Cl2, the ZnII atom lies on an inversion center and the dichloromethane solvent molecule is disordered around an inversion center. The tolyl substituents are twisted compared to the central aromatic ring system of the porphyrin, similar to what is seen in previously published structures of this molecule [Dastidar & Goldberg (1996 ▶). Acta Cryst. C52, 1976–1980]. The dihedral angles between the mean planes of the tolyl rings and the central ring are 66.98 (6) and 60.40 (6)°.