Miracle-dz/UniFAR-FTUs huggingface dataset:
The potential role of retroviruses in autoimmunity

In the last 20 years research in Immunology underwent fundamental changes. Most importantly, the identification of the key role of innate immune pattern recognition receptors (PRRs) that recognize evolutionarily conserved molecular patterns on infectious pathogens. This results in priming of innate immune cells, which in turn activate and direct the adaptive immune response. Progress in innate immune recognition instigated the current working hypothesis, that recognition of endogenous ligands by PRRs results in innate immune cell activation (autoinflammation) or activation of adaptive cells, with self‐reactive antigen receptors (autoimmunity). In particular, nucleic acid‐sensing innate immune receptors seem to be prime candidates for a mechanistic understanding of autoreactive activation of the immune system. However, it remains uncertain what the actual source of nucleic acid ligands is and what other signals are needed to drive activation of autoreactive innate immune cells and break self‐tolerance of the adaptive immune system. Here, I will review our present understanding about whether the infection with exogenous retroviruses or the reactivation of endogenous retroviruses might play an etiological role in certain autoimmune conditions of humans and murine experimental models.
New RAF kinase inhibitors in cancer therapy

Introduction: Alterations in some key components of the MAPK pathway, such as BRAF, have been found to be related to the development of several malignancies. A number of BRAF inhibitors have been developed in recent years. Two of these compounds, vemurafenib and dabrafenib, have been licensed for the treatment of BRAF-mutant advanced melanoma. Areas covered: This article reviews the antitumour activity and safety of the BRAF inhibitors, vemurafenib and dabrafenib. Moreover, early clinical data available for the most promising new members of this family of drugs as well as the novel therapeutic strategy of dual RAF-MEK inhibition is reviewed. A perspective of the potential role of MAPK inhibition in the treatment of cancer in forthcoming years is also provided. Expert opinion: Inhibition of BRAF has achieved highly successful results in patients affected by BRAF-mutated melanoma and has revolutionised their care. Its efficacy in other malignancies is currently under evaluation in monotherapy and as combination with other agents. Early clinical results of concomitant inhibition of BRAF and MEK suggest that this therapeutic approach is superior to either BRAF or MEK inhibition alone. Identification of BRAF mutations sensitive to treatment is essential for the success of these drugs.
Can Magnetic Targeting of Magnetically Labeled Circulating Cells Optimize Intramyocardial Cell Retention?

Therapeutic intracavitary stem cell infusion currently suffers from poor myocardial homing. We examined whether cardiac cell retention could be enhanced by magnetic targeting of endothelial progenitor cells (EPCs) loaded with iron oxide nanoparticles. EPCs were magnetically labeled with citrate-coated iron oxide nanoparticles. Cell proliferation, migration, and CXCR4 chemokine receptor expression were assessed in different labeling conditions and no adverse effects of the magnetic label were observed. The magnetophoretic mobility of labeled EPCs was determined in vitro, with the same magnet as that subsequently used in vivo. Coronary artery occlusion was induced for 30 min in 36 rats (31 survivors), followed by 20 min of reperfusion. The rats were randomized to receive, during brief aortic cross-clamping, direct intraventricular injection of culture medium (n = 7) or magnetically labeled EPCs (n = 24), with (n = 14) or without (n = 10) subcutaneous insertion of a magnet over the chest cavity (n = 14). The hearts were explanted 24 h later and engrafted cells were visualized by magnetic resonance imaging (MRI) of the heart at 1.5 T. Their abundance in the myocardium was also analyzed semiquantitatively by immunofluorescence, and quantitatively by real-time polymerase chain reaction (RT-PCR). Although differences in cell retention between groups failed to be statistically significant using RT-PCR quantification, due to the variability of the animal model, immunostaining showed that the average number of engrafted EPCs was significantly ten times higher with than without magnetic targeting. There was thus a consistent trend favoring the magnet-treated hearts, thereby suggesting magnetic targeting as a potentially new mean of enhancing myocardial homing of intravascularly delivered stem cells. Magnetic targeting has the potential to enhance myocardial retention of intravascularly delivered endothelial progenitor cells.
Contribution of calcium, phosphorus and 25-hydroxyvitamin D to the excessive severity of secondary hyperparathyroidism in African-Americans with CKD.

BACKGROUND Parathyroid hormone (PTH) levels in African-American (AA) chronic kidney disease (CKD) patients exceed those in patients of other races; mechanisms are unknown. METHODS We performed a cross-sectional analysis of initial laboratory data collected on 2028 CKD patients (505 AA) from US practices using a laboratory CKD service. Serum calcium (Ca), phosphorus (P), 25-hydroxyvitamin D (25-D) and plasma PTH levels were compared between the two groups. RESULTS Mean PTH for AA exceeded PTH for non-AA in Stages 2-5 (P<0.001, all four stages). 25-D levels were higher for non-AA in Stages 1-3 (P<0.001). Serum Ca and P did not differ between groups at any stage. Full adjustment for these variables using multivariable generalized linear modeling did not remove the effect of AA race: AA PTH values exceeded non-AA values in CKD Stages 2-5 (P<0.02, all four stages). Serum Ca, P and 25-D were all inversely correlated with PTH levels irrespective of race, but all factors combined accounted for ∼42% of the variance in PTH. CONCLUSIONS PTH rises with progressive CKD stage far more in AA than in non-AA patients, and only a moderate component of the rise in PTH is explained by changes in serum Ca, P and 25-D in either group. These findings concur with those from other large CKD cohorts and support the need for further study to determine other factors responsible for this racial difference.
Entrepreneurial learning and innovation: The critical role of team-level learning for the evolution of innovation capabilities in technology-based ventures

Purpose The purpose of this paper is to develop a conceptual model that explains how learning processes at the team level connect with individual and organizational levels of learning in technology-based ventures, thereby influencing the evolution of innovation capabilities in the entrepreneurial process. Design/methodology/approach The 4I organizational learning framework is used as an overarching theoretical structure to acknowledge entrepreneurial learning as a dynamic process that operate on multiple levels in technology-based ventures. Embedded in this logic, research on team learning is integrated into this theorizing to examine how learning processes at the team level bridge and connect with learning processes operating at individual and organizational levels. Findings The conceptual model identifies different sets of team learning processes critical for the routinization and evolution of innovation capabilities in technology-based ventures. In this respect, the conceptual model advances the scholarly understanding of entrepreneurial learning as a dynamic process operating across multiple levels in technology-based ventures. Originality/value By conceptualizing how individual streams of experiences over time become institutionalized via interaction, conversation and dialogue, the paper provides novel insights into the critical role of team learning for bridging individual and organizational levels of learning in the entrepreneurial learning process.
Rehabilitation of women with gynaecological cancer: the association between adult attachment, post‐traumatic stress disorder and depression

We hypothesised that being diagnosed with gynaecological cancer influences adult attachment and occurrence of depression and post‐traumatic stress disorder (PTSD). The main aim of the study was to assess changes in the attachment dimensions, PTSD and depression from baseline to 5‐month post‐treatment. Further, we evaluated the association between attachment avoidance/anxiety dimensions and PTSD/depression among women newly diagnosed with ovarian, endometrial, or cervical cancer.
The locus of knowledge externalities and the cost of knowledge

ABSTRACT The locus of knowledge externalities and the cost of knowledge. Regional Studies. This paper provides an extended Crépon–Duguet–Mairesse (CDM) approach to analyse jointly the simultaneous effects of knowledge spillovers in the knowledge-generation and technology production functions. It introduces the distinction between imitation and knowledge externalities and articulates the hypothesis that spillovers yield their effects via three well-distinct mechanisms: (1) knowledge externalities that exert positive and direct effects on the knowledge-production function and (2) indirect effects on the technology-production function via their effects on the cost of knowledge; and (3) imitation externalities that exert direct and positive effects on productivity in the technology-production function. We test our hypotheses on a large panel of Italian companies distributed in NUTS-2 regions for the period 2005–09. The econometric analysis consists of a model comprising a system of equations that test the simultaneous role of spillovers in the knowledge-generation and technology-production functions with the inclusion of endogenous knowledge costs. The results confirm that the access to external knowledge – as an input in the knowledge-generation function – plays a key role in increasing the knowledge output and – as an input in the technology-production function – has positive indirect and direct effects on the productivity of firms.
Generalized Financial Ratios to Predict the Equity Premium

Empirical evidence for the price-dividend ratio to be a predictor of the equity premium is weak. We argue that changes in the economic conditions and market composition lead to a time-varying relationship between prices, dividends and the equity premium. Exploiting the information in the rolling window log-log regression of stock prices on dividends, we obtain the Generalized Price-Dividend Ratio (GPDR), that compares the price per share with a time-varying transformation of the dividend per share. The GPDR leads to economic and statistical gains when forecasting the equity premium of the S&P 500 at the 1, 3, 6 and 12 month horizon, as compared to using the classical price-dividend ratio or the prevailing historical average excess market return. Similar improvements are obtained for Generalized Financial Ratios based on the corporate earnings and book value.
Organizational Success: How the Presence of Happiness in the Workplace Affects Employee Engagement that Leads to Organizational Success

The central focus of this quantitative, correlational study is to examine the relationship between happiness found in the work place and employees’ engagement that leads to organizational success. Employee engagement has been touted as the next frontier that will help organizations to achieve success. This is because passionate employees will ensure that they are productive in the work place. Happiness has been argued to be one of the factors that enhance employee engagement. The collected data shows a positive correlation between happiness and engagement of the employee. This is an important finding as it can be used by organizations to fast track their development by ensuring that employees are happy. The establishment of a positive correlation between these two aspects ensures that an organization can benefit greatly when it enhances employee happiness. In addition, measures can be put in place to ensure that employee happiness is enhanced, a move that would lead to a more productive organization and faster growth. Although the concept of employee engagement and its relationship to happiness has been around, this study goes further to confirm that happy employees are more engaged and this leads to organizational success. Organizational culture and environment affects the performance and approach of employees. Leadership in the organization is a vital aspect as it ensures that employees are provided with the right environment to carry out tasks and be content with the work. With this new knowledge, leaders can take measures to improve employee happiness, which will lead to employee engagement and, consequently, improve the prospects of organizational success.
Domains b′ and a′ of Protein Disulfide Isomerase Fulfill the Minimum Requirement for Function as a Subunit of Prolyl 4-Hydroxylase

Protein disulfide isomerase (PDI) is a modular polypeptide consisting of four domains, a,b, b′, and a′, plus an acidic C-terminal extension, c. PDI carries out multiple functions, acting as the β subunit in the animal prolyl 4-hydroxylases and in the microsomal triglyceride transfer protein and independently acting as a protein folding catalyst. We report here that the minimum sequence requirement for the assembly of an active prolyl 4-hydroxylase α2β2 tetramer in insect cell coexpression experiments is fulfilled by the PDI domain constructb′a′ but that the sequential addition of the band a domains greatly increases the level of enzyme activity obtained. In the assembly of active prolyl 4-hydroxylase tetramers, the a and b domains of PDI, but notb′ and a′, can in part be substituted by the corresponding domains of ERp57, a PDI isoform that functions naturally in association with the lectins calnexin and calreticulin. Thea′ domain of PDI could not be substituted by the PDIa domain, suggesting that both b′ anda′ domains contain regions critical for prolyl 4-hydroxylase assembly. All PDI domain constructs and PDI/ERp57 hybrids that contain the b′ domain can bind the 14-amino acid peptide Δ-somatostatin, as measured by cross-linking; however, binding of the misfolded protein “scrambled” RNase required the addition of domains ab or a′ of PDI. The human prolyl 4-hydroxylase α subunit has at least two isoforms, α(I) and α(II), which form with the PDI polypeptide the (α(I))2β2 and (α(II))2β2 tetramers. We report here that all the PDI domain constructs and PDI/ERp57 hybrid polypeptides tested were more effectively associated with the α(II) subunit than the α(I) subunit.
Screening for mild cognitive impairment in patients with heart failure: Montreal Cognitive Assessment versus Mini Mental State Exam

Background: Cognitive impairments occur frequently in patients with chronic heart failure (CHF), resulting in worse health outcomes than expected. These impairments can remain undetected unless specifically screened. There are limited sensitive screening measures available in nursing practice to identify mild cognitive impairment (MCI). Aim: To compare the Montreal Cognitive Assessment (MoCA) with the Mini Mental State Exam (MMSE) in screening for MCI in CHF patients. Methods: The MMSE and MoCA were administered to 93 hospitalized CHF patients (70±11 years), without a history of neurocognitive problems. Patients with low MoCA scores (<26) were compared to those with low MMSE scores (<27). Two different parameters were examined between the MoCA and the MMSE: level of MCI agreement (Kappa coefficient) and task errors on assessed cognitive domains (χ2 test). Results: Statistically more patients had low MoCA scores compared with low MMSE scores (66 vs. 30, p=0.02). The MoCA classified 38 (41%) patients as cognitively impaired that were not classified by the MMSE. A significantly low level of agreement was found (κ=0.25, p=0.001) between the MMSE and MoCA in identifying patients with scores suggestive of MCI. More task errors were observed on the MoCA cognitive domains compared with the MMSE cognitive domains. In 68% of patients with low cognitive scores, visuospatial task errors were observed on tasks from the MoCA compared with 22% on a similar task of the MMSE. Conclusion: The MoCA, a screening tool for MCI, identified subtle but potentially clinically relevant cognitive dysfunctions with greater frequency than MMSE.
Effects of in utero ethanol exposure on the developing serotonergic system.

Previous work in this laboratory demonstrated that the 19- and 35-day-old offspring of ethanol-fed rats have a significant deficiency of cortical serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA), as well as a decrease in the number of total 5-HT1 receptors in the motor and somatosensory cortex. The present studies extend our previous reports by demonstrating that there is also a deficit of 5-HT and 5-HIAA in the motor cortex but not in the somatosensory cortex. In addition, we have shown that a deficit of 5-HT1A receptors in the motor and somatosensory cortices contributes to the deficit of total 5-HT1 receptors. In contrast, we did not observe any changes in the binding to 5-HT1B receptors in these cortical regions from the 19-day-old offspring of ethanol-fed rats. The present studies also examined the effects of in utero ethanol exposure on the early development of the serotonergic system. The results of these studies demonstrated a deficit of 5-HT and/or 5-HIAA in the brain stem as early as the 15th day of gestation (G15) and in the cortex as early as G19. In addition, we demonstrated a delay in both the normal developmental decline of 5-HT1A receptors in the brain stem and in the acquisition of cortical 5-HT1A receptors. No changes were found in the binding of [125I]cyanopindolol to 5-HT1B receptors in either region of fetal or neonatal rats exposed to ethanol in utero. (ABSTRACT TRUNCATED AT 250 WORDS)
PENGARUH TINGKAT LOAN TO DEPOSIT RATIO (LDR) TERHADAP PROFITABILITAS PADA PT BANK X (PERIODE TAHUN 2008-2012)

Abstract - Bank is a financial institution that serves as a financial intermediary which means collecting funds from the public and distribute it back to the community in the form of loans. The purpose of this study was to determine whether there is a significant influence and how much influence the Loan to Deposit Ratio (LDR) to Bank Profitability expressed by Return on Assets (ROA). The method used in this research is deskriptife with the survey approach. While to analyze the data, used a quantitative approach, namely the technique of correlation analysis and simple linear regression analysis as a tool for the calculation.From the research, the regression equation is Y = 0.083 +0.706 X. Keywords : Loan to Deposit Ratio (LDR), Bank Profitability, Return on Asset (ROA) Abstrak - Bank adalah lembaga keuangan yang berfungsi sebagai financial intermediary yang berarti menghimpun dana dari masyarakat dan menyalurkannya kembali kepada masyarakat ke dalam bentuk pinjaman.Tujuan dilakukannya penelitian ini adalah untuk mengetahui apakah terdapat pengaruh yang signifikan dan seberapa besar pengaruh Loan to Deposit Ratio (LDR) terhadap Profitabilitas Bank yang dinyatakan dengan Return on Asset (ROA). Metode penelitian yang digunakan pada penelitian ini adalah metode Deskriptif dengan pendekatan survei. Sementara untuk menganalisis data, digunakan pendekatan kuantitatif, yaitu dengan teknik analisis korelasi dan analisis regresi linier sederhana sebagai alat bantu perhitungannya. Dari hasil penelitian,diperoleh persamaan regresi yaitu Y= 0,083+0,706 X. Kata kunci : Loan to Deposit Ratio (LDR), Profitabilitas Bank,Return on Asset (ROA)
Gastrointestinal Stromal Tumors and Extra-Gastrointestinal Tract Neoplasms

Objectives: Gastrointestinal stromal tumor (GIST) is a relatively uncommon and predominantly sporadic tumor of the gastrointestinal tract (GIT). Infrequently, it can be associated with other neoplasms, notably GIT carcinomas and, rarely, extra-gastrointestinal tumors. Whether this concomitant occurrence is a causal association or a coincidence is not yet resolved, nor is its clinical importance determined. We attempted to investigate the frequency and spectrum of associations between non-incidental GISTs and extra-GIT tumors. Methods: A retrospective review study was carried out over 18 years of records. All confirmed cases of GISTs were retrieved from the pathology files of our institution. Each case was investigated for any synchronous or metachronous association with GIT or extra-GIT tumors. Results: Five (24%) out of 21 cases of GISTs were found to be either synchronously or metachronously associated with extra-gastrointestinal neoplasms in 55% of the women with GISTs. Males had no such association. Conclusion: The cause of the association between non-incidental GISTs and extra-GIT tumors is difficult to determine. In the majority of cases, this association is most likely a coincidental finding. Synchronous occurrence with certain tumors, however, may suggest a nonrandom causal association. We report a case series study of the possible association of GISTs with extra-GIT tumors in female patients. Like other studies, we suggest that patients—especially women—with GISTs should be clinically investigated and followed up for the possibility of coexisting GIT and extra-GIT neoplasms.
High-power VCSEL arrays for emission in the watt regime at room temperature

Selectively oxidized InGaAs vertical-cavity surface emitting lasers (VCSELs) at an emission wavelength of /spl lambda/=980 mm are investigated for high-power applications. Densely packed arrays consisting of 19 single devices with an active diameter of 50 /spl mu/m emit 1.08 W of continuous-wave (CW) optical output power at room temperature. At 10/spl deg/C, heat sink temperature the output power increases to 1.4 W, which corresponds to a chip size averaged power density of 1 kW/spl middot/cm/sup 2/. Low divergence angle of less than 16/spl deg/ full-width at half-maximum (FWHM) and the circularly symmetric far-field pattern allow for simple focusing of the beam with power densities above 10 kW/spl middot/cm/sup 2/.
Incidence of corneal ulceration in Madurai district, South India.

OBJECTIVE To determine the incidence of corneal ulceration in Madurai District, South India. DESIGN Retrospective incidence study. SETTING General community. PATIENTS All patients who reside in Madurai District and presented to an ophthalmologist in 1993 with corneal ulceration. MAIN OUTCOME MEASURE Cases of corneal ulceration. RESULTS 1148 cases of corneal ulceration were recorded in the medical records of those ophthalmologists who maintained records. Based upon the recorded number of cases, the annual incidence per 10,000 population was 3.4. The ratio of male to female patients was 1.6:1.0. When the estimated number of cases from those without records was added to the total number of recorded cases the annual incidence was 11.3 per 10,000 population. CONCLUSION Corneal ulceration is a common occurrence in South India. While the true incidence of this problem is impossible to determine because of the lack of medical records, we believe our estimation of the incidence to be close to the true incidence in this community.