Miracle-dz/UniFAR-FTUs huggingface dataset:
Parenteral and Oral Administration of Tolerogens: Protein‐IgG Conjugates

Interest in immunologic tolerance, discovered by Medawar almost half a century ago,' has increased for two main reasons: (1) Several of its mechanisms, such as clonal deletion,2 an erg^,^ and regulatory T cells4 have been uncovered. (2) Both systemic and oral tolerance,5B6 the topic of this volume, can be induced to, it is hoped, prevent either autoimmune or allergic diseases. For example, several strategies have been used in trying to prevent allergy, including administration of modified allergen,' allergen linked to nonimmunogenic carriers,8 single peptides? or an allergen-antibody complex.Lo It is known that antigen presentation can influence the type of immune response. Not only haptens,". '* but also proteins covalently linked to a carrier molecule naturally tolerated by the host, such as isologous immunoglobulin, can induce unresponsiveness to these protein^. '^. '^ In this paper. the results from the parenteral administration in rats of tolerogens made of either P-lactoglobulin (PLG) or ovalbumin (OVA) linked to isologous immunoglobulin will be briefly revie~ed. '~ . ~ ' In addition, new data on the administration of OVAIgG conjugates given either intraperitoneally or orally to neonatal rats will be shown. The results suggest that tolerogenic conjugates given either parenterally or orally could provide a way to prevent certain diseases.
Minimal Deviation Endometrioid Adenocarcinoma of the Uterine Cervix - A Case Report -

first described by Gusserow in 1870 as a well differentiated adenocarcinoma in which most of the glands are impossible to be distinguished from the normal endocervical mucosa, although the MDA invades deep into the cervical stroma. At first, MDA was restricted to the mucinous type, but the definition of MDA has been expanded to other cell types, including the endometrioid, clear cell and nonspecific cellular types of differentiation. Minimal deviation endometrioid adenocarcinoma (MDEA) is a variant of MDA, and it is characterized by the proliferation of infiltrative, mildly atypical endometrioid glands with no or minimal stromal reaction. Only 17 cases of cervical MDEA have been reported in the English literature. In this current report, we describe our recent experience of a patient with MDEA and we compare this case with the previous reports.
Volcanic Ash from Mount Mazama (Crater Lake) and from Glacier Peak

New petrographic and chemical data indicate that the great Mount Mazama eruption at Crater Lake, Oregon, about 6600 years ago was the source of most ash which has been called "Glacier Peak" and of some ash called "Galata. " Glacier Peak volcano in Washington was itself the source of an older ash deposit, perhaps very late glacial or early postglacial in age.
Glycogen Synthase Kinase-3β (GSK-3β) Inhibition Enhances Dendritic Cell-based Cancer Vaccine Potency via Suppression of Interferon-γ-induced Indoleamine 2,3-Dioxygenase Expression*

Background: IDO functions as a crucial mediator of tumor-mediated immune tolerance. Results: Here, we found that GSK-3β-dependent IDO expression in the dendritic cell plays a role in anti-tumor activity via the regulation of CD8+ T-cell proliferation and CTL activity. Conclusion: GSK-3β activity functions in the immune enhancement-mediated anti-tumor response via IDO regulation. Significance: We proved the effectiveness of the GSK-3β-dependent IDO regulatory mechanism in DC-based cancer vaccination. Indoleamine 2,3-dioxygenase (IDO) functions as a crucial mediator of tumor-mediated immune tolerance by causing T-cell suppression via tryptophan starvation in a tumor environment. Glycogen synthase kinase-3β (GSK-3β) is also involved in immune and anti-tumor responses. However, the relativity of these proteins has not been as well defined. Here, we found that GSK-3β-dependent IDO expression in the dendritic cell (DC) plays a role in anti-tumor activity via the regulation of CD8+ T-cell polarization and cytotoxic T lymphocyte activity. By the inhibition of GSK-3β, attenuated IDO expression and impaired JAK1/2-Stat signaling crucial for IDO expression were observed. Protein kinase Cδ (PKCδ) activity and the interaction between JAK1/2 and Stat3, which are important for IDO expression, were also reduced by GSK-3β inhibition. CD8+ T-cell proliferation mediated by OVA-pulsed DC was blocked by interferon (IFN)-γ-induced IDO expression via GSK-3β activity. Specific cytotoxic T lymphocyte activity mediated by OVA-pulsed DC against OVA-expressing EG7 thymoma cells but not OVA-nonexpressing EL4 thymoma cells was also attenuated by the expressed IDO via IFN-γ-induced activation of GSK-3β. Furthermore, tumor growth that was suppressed with OVA-pulsed DC vaccination was restored by IDO-expressing DC via IFN-γ-induced activation of GSK-3β in an OVA-expressing murine EG7 thymoma model. Taken together, DC-based immune response mediated by interferon-γ-induced IDO expression via GSK-3β activity not only regulates CD8+ T-cell proliferation and cytotoxic T lymphocyte activity but also modulates OVA-pulsed DC vaccination against EG7 thymoma.
Identifying opportunities to bridge disparity gaps in curing childhood cancer in Malawi: Malignancies with excellent curative potential account for the majority of diagnoses

ABSTRACT The majority of African children with cancer die without access to resources. We describe efforts to build a public treatment program with curative intent for childhood cancer in Lilongwe, Malawi despite severe limitations in diagnostic and therapeutic resources. We retrospectively analyzed a cohort of childhood cancer patients at Kamuzu Central Hospital from 12/2011–6/2013. Consistently available chemotherapeutic agents were limited to cyclophosphamide, vincristine, doxorubicin, bleomycin, methotrexate, and prednisone. Of 258 newly diagnosed childhood malignancies, 17 patients with retinoblastoma were excluded from clinical analyses due to insufficient clinical data. Among the remainder of the cohort (n = 241), 42% were female with median age 8.4 years (range 0.6–17.9). Forty-six (19%) were HIV-infected (42 Kaposi sarcoma, 3 Burkitt lymphoma, 1 Hodgkin lymphoma). The most common clinical presentations were palpable abdominal mass (41%), peripheral lymphadenopathy (33%), and jaw mass (17%). Nearly two-thirds of total diagnoses were accounted for by Burkitt lymphoma (n = 74), Kaposi sarcoma (n = 52), Hodgkin lymphoma (n = 21), and Wilms tumor (n = 19). Twelve-month overall survival for these 4 most common diagnoses was 54% (95% confidence interval 46–61) versus 19% (95% confidence interval 11–30) for all other diagnoses (median follow-up 19 months). Treatment-related mortality was highest in patients with non-Wilms solid tumors of the abdomen (48% versus 10% for the overall cohort, p < 0.001), while treatment abandonment was highest in patients with bone and soft-tissue sarcomas (29% versus 14% overall, p = 0.05). Childhood cancers with excellent curative potential accounted for the majority of patients, establishing an opportunity to build treatment programs with curative intent despite severe limitations.
Integration of the nuclear receptor REV-ERBα linked with circadian oscillators in the expressions of Alas1, Ppargc1a, and Il6 genes in rat granulosa cells

The nuclear receptor REV-ERBα links circadian rhythms and numerous physiological processes, but its physiological role in ovaries remains largely unknown. The aim of this study was to determine the potential role of REV-ERBα in the regulation of the transcription of its putative target genes in granulosa cells (GCs) prepared from Per2-destablized luciferase (dLuc) reporter gene transgenic rats. Alas1, Ppargc1a, and Il6 were chosen as representatives for genes analysis. A real-time monitoring system of Per2 promoter activity was performed to detect Per2-dLuc circadian oscillations. Two agonists (GSK4112, heme) and an antagonist (SR8278) of REV-ERBα as well as Rev-erbα siRNA knockdown were used to identify its target genes. Clear Per2-dLuc circadian oscillations were generated in matured GCs after synchronization with GSK4112 or SR8278. GSK4112 treatment lengthened and SR8278 treatment shortened the period of circadian oscillations in matured GCs stimulated with or without luteinizing hormone (LH). GSK4112 showed an inhibitory effect on the amplitude of circadian oscillations and caused an arrhythmic expression of canonical clock genes. SR8278 also had a subtle effect on their daily expression profiles, but the treatment resulted only in the arrhythmic expression of Rev-erbα. These findings indicate the functional biological activity of REV-ERBα in response to its ligands. Its natural ligand heme further elongated the period of circadian oscillations and alleviated their amplitudes in GCs cultured with LH. Heme treatment also repressed the expressions of clock genes, Alas1, Il6, and Ppargc1a. Rev-erbα knockdown up-regulated these transcript levels. Collectively, these data extend the recent finding to rat GCs and demonstrate that REV-ERBα represses the expressions of Alas1, Ppargc1a, and Il6, providing novel insights into the physiological significance of REV-ERBα in ovarian circadian oscillators.
Stability studies of selected polycyclic aromatic hydrocarbons in different organic solvents and identification of their transformation products

o ne of the problems in an hPlC laboratory is the preservation of samples and extracts prior to analysis without any changes. It has been found that degradation processes cannot be eliminated entirely, but they can be slowed down considerably. Photodegradation kinetics of fluorene, anthracene and benzo(a)pyrene were studied in various organic solvents. Solvents known as good media to store PA hs for a long time were selected with respect to avoid degradation. in the case of fluorene, 9-fluorenone and 9-hydroxyfluorene were detected as main photoproducts. Formation of anthraquinone and 1,8-dihydroxyanthraquinone during the degradation of anthracene was observed. Benzo(a)pyrene-4,5-dihydrodiol and one of the isomers of hydroxy-BaP-dione as products of benzo(a)pyrene photodegradation have been identified.
Quantile-Optimal Treatment Regimes

ABSTRACT Finding the optimal treatment regime (or a series of sequential treatment regimes) based on individual characteristics has important applications in areas such as precision medicine, government policies, and active labor market interventions. In the current literature, the optimal treatment regime is usually defined as the one that maximizes the average benefit in the potential population. This article studies a general framework for estimating the quantile-optimal treatment regime, which is of importance in many real-world applications. Given a collection of treatment regimes, we consider robust estimation of the quantile-optimal treatment regime, which does not require the analyst to specify an outcome regression model. We propose an alternative formulation of the estimator as a solution of an optimization problem with an estimated nuisance parameter. This novel representation allows us to investigate the asymptotic theory of the estimated optimal treatment regime using empirical process techniques. We derive theory involving a nonstandard convergence rate and a nonnormal limiting distribution. The same nonstandard convergence rate would also occur if the mean optimality criterion is applied, but this has not been studied. Thus, our results fill an important theoretical gap for a general class of policy search methods in the literature. The article investigates both static and dynamic treatment regimes. In addition, doubly robust estimation and alternative optimality criterion such as that based on Gini’s mean difference or weighted quantiles are investigated. Numerical simulations demonstrate the performance of the proposed estimator. A data example from a trial in HIV+ patients is used to illustrate the application. Supplementary materials for this article are available online.
Escolha de carreira: o Dark Triad revela interesses de estudantes de Contabilidade

Três traços de personalidades socialmente sombrios, mas não patológicos, compõem o chamado Dark Triad: Narcisismo, o Maquiavelismo e a Psicopatia. Analisamos a influência do Dark Triad sobre os interesses da carreira profissional pretendida por estudantes de graduação em Ciências Contábeis. Foi aplicado questionário em cursos de graduação em contabilidade de universidades brasileiras públicas e privadas. Os mais de 1400 estudantes que participaram têm preferência pela carreira de Auditoria e Contabilidade em organizações privadas. A satisfação profissional, seguida da remuneração são os interesses que mais impulsionam os estudantes na escolha de carreira. O Dark Triad para estes estudantes impulsiona interesses e objetivos associados a manipulação, superioridade, exibicionismo e poder.
Pattern Search Algorithms for Surface Wave Analysis

In recent years Rayleigh waves have been used increasingly as a nondestructive tool to obtain near-surface S-wave velocity, one of the key parameters in environmental and engineering applications (Miller et al., 1999a, 1999b; Park et al., 1998, 1999; Xia et al., 1999, 2003; Foti et al., 2002; Beaty and Schmitt, 2003; Tian et al., 2003; Zhang and Chan, 2003; Lin and Chang, 2004; O’Neill et al., 2003; Ryden et al., 2004; and Song et al., 2006). Utilization of surface wave dispersive properties may be roughly divided into three steps: field data acquisition, dispersion-curve picking, and inversion of phase velocities (Xia et al., 2004). Inversion of Rayleigh wave dispersion curves is one of the key steps in surface wave analysis to obtain a shallow subsurface S-wave velocity profile (Rix, 1988; Lai et al., 2002). However, inversion of high-frequency Rayleigh wave dispersion curves, as with most other geophysical optimization problems, is typically a nonlinear, multiparameter inversion problem. Dal Moro et al. (2007) have demonstrated the high nonlinearity and multimodality by a synthetic model. Consequently, local optimization methods, e.g. matrix inversion, steepest descent, conjugate gradients, are prone to being trapped by local minima, and their success depends heavily on the choice of a good starting model (Boschetti et al., 1996) and the accuracy of the partial derivatives. Thus, global optimization methods that can overcome this limitation are particularly attractive for surface wave analysis (e.g., Meier and Rix, 1993; Yamanaka and Ishida, 1996; and Beaty et al., 2002). Pattern search algorithms are a direct search method well suitable for the global optimization of highly nonlinear, multimodal objective functions (Lewis and Torczon, 1999). Pattern search algorithms have recently been used and tested to optimize complex mathematical problems characterized by the large numbers of local minima and/or maxima (Lewis and Torczon, 2000). However, few attempts have been made to address real-world geophysical problems, especially for the inversion of surface wave data. In this chapter, In this chapter, I first implemented and tested a Rayleigh wave dispersion curve inversion scheme based on GPS Positive Basis 2N, a commonly used pattern search algorithm. Incorporating complete poll and complete search strategies based on GPS Positive Basis 2N into the inverse procedure greatly enhances the performance of pattern search algorithms because the two steps can effectively locate the promising areas in the solution space containing the global minima and significantly reduce the computation cost, respectively. The calculation efficiency and stability of the inversion scheme are tested on three synthetic models. Secondly, effects of the number of data points, the reduction of the frequency range
Blind image restoration based on wavelet analysis

Blind image restoration is important and full of challenge as an issue of image processing. Many conventional approaches have been developed to restore the original image at present. But since there are two unknown things: the original image and the point spread function (PSF), in many case it is difficult to reach the expected results, especially when the image is heavily degraded. In this paper, blind image restoration approach based on wavelet analysis is proposed. The key of the approach is the wavelet analysis implemented before the restoration with conventional approaches. Wavelet analysis returns some useful information about the degraded image as well as the restored image, and the information can help further restoration. The experimental results prove that the approach is satisfactory.
'Will you help me with my research?' Gaining access to primary care settings and subjects.

This paper is concerned with the negotiation of agreement to carry out research in primary care settings. It is argued that this is a key part of any research project, and that careful handling of this process will not only improve response rates, but will also often enhance the quality of the data obtained. A number of strategies for negotiating access are proposed which have been developed and applied in primary care settings. These strategies depend on creating a sense of collective ownership of projects between researchers and participants which contributes to the successful completion of the projects and provides a positive atmosphere for further collaboration.
The potentiation of platelet aggregation and adhesion by heparin in vitro and in vivo.

1. Heparin has been shown to increase platelet aggregation by ADP and adrenaline and to enhance the platelet release reaction when tested in citrated platelet-rich plasma (P.R.P.). This activity is present when heparin is added to P.R. P. or when P.R. P. is prepared after intravenous injection of heparin, and when heparin is added to non-anticoagulated native P.R. P. 2. Retention of platelets by cellophane membranes within a specially designed test-cell was significantly increased when heparin was added to citrated whole blood. 3. Though aspirin blocks the release reaction with and without heparin, it does not prevent the potentiation of initial ADP or first wave adrenaline aggregation caused by heparin.
SINGLE‐DONOR COLD STORAGE VERSUS MACHINE PERFUSION IN CADAVER KIDNEY PRESERVATION

Preservation of thirty-eight consecutive renal allograft donors was studied in a prospective, randomized protocol. Procurement was in-situ cooled, en-bloc nephrectomy accomplished by a single program. Nine pairs were deleted because of nonutilization of one kidney or change in mode of preservation. The remaining twenty nine pairs were implanted by twenty two institutions through usual organ sharing policies. Results showed that posttransplantation dialysis was required in 17% of machine-perfused and 63% of cold-stored allografts, which reached statistical significance (P<0.01). This increased number of dialyses in patients receiving the cold-stored kidneys offsets cost savings achieved through transporting cold stored allografts. This study shows machine-perfused renal allografts to be superior to paired, cold-stored allografts when analyzed with respect to early graft function.
Anti‐HSP60 Immunity Is Already Associated with Atherosclerosis Early in Life

Abstract: In this review, we first briefly introduce the reader to our autoimmune hypothesis for the development of atherosclerosis based on experimental and clinical data. This hypothesis postulates that humoral and cellular immunity against heat‐shock protein 60 (HSP60), a phylogenetically highly conserved stress protein, is the mechanism that initiates atherogenesis. We then turn to our investigations of arterial specimens from children and young adults. These clearly show that mononuclear cell infiltrations of the intimal layer already occur before the emergence of clear‐cut atherosclerotic lesions, a phenomenon we have termed vascular‐associated lymphoid tissue (VALT). In early lesions analyzed within the framework of the Pathological Determinants of Atherosclerosis in Youth (PDAY) study, T lymphocytes proved to be a major cellular constituent. In the Bruneck Study, a large, prospective atherosclerosis‐prevention study in adults aged 40 years and older, we found a highly significant correlation between serum anti‐HSP60 antibody titers and the occurrence and extent of sonographically demonstrable atherosclerotic lesions. However, no such correlation emerged with respect to HSP60‐reactive T cells in the peripheral blood. In contrast, the similar Atherosclerosis Risk‐Factors in Male Youngsters (ARMY) study, performed on 17‐ to 18‐year‐old volunteers, showed a highly statistically significant correlation between arterial intima‐media thickening and HSP60 reactivity among peripheral T cells and (less pronounced) anti‐HSP60 antibodies, even at this young age. We take this as indirect evidence that both T cell and B cell immunity against HSP60 plays a major role in the earliest stages of the disease. Because VALT can already be observed in healthy children and young adults, we hypothesize that T cells initiate the disease and that humoral antibodies play a facilitating, accelerating role. Finally, we provide initial evidence that smoking, as the most important risk factor for atherogenesis, also exerts its disease‐inducing and disease‐promoting effects by inducing HSP60 expression by vascular endothelial cells.
To what Extent May Botulinum Toxin Type A Injections be an Alternative Choice to Surgery in Infantile Esotropia?

Introduction Evaluation of a single injection of botulinum toxin A in infantile esotropia as an alternative choice to surgery in a retrospective cases serie. Methods Patients (65 consecutive children aged 9 to 26 months with infantile strabismus) underwent botulinum toxin A injection in both medial recti Botulinum toxin A injection. Clinical datas including measurement of angle of deviation before and after injection. visual acuity, stereoscopy and side effects were observed in a 24 months period of follow-up. Results Stable satisfactory result (angle equal to or less than 8 dioptres) was obtained in 33 cases (50.7%). Excellent result (-2 to + 4 dioptres) were obtained in 17 children (26%). Additional surgery was required in 32 cases for a residual (albeit smaller angle than the initial deviation) or recurrent deviation and/or DVD (49,2%). Conclusions Botulinum toxin A reduces the tonic spastic motor component of strabismus and, should additional surgery be required (49% in our series), allows the procedure to be carried out on a smaller angle. A reduction in the maximum angle of deviation is thus achieved sooner, and allows the development of anomalous binocularity in a stable microtropia.
Comparative effects of schizophrenia and temporal lobe epilepsy on memory

The goal of this study was to further characterize episodic memory functioning in schizophrenia. This study compared verbal and visual learning and memory performance in (1) patients with schizophrenia (N = 35), (2) patients with temporal lobe epilepsy (TLE; N = 30), and (3) normal controls (N = 25). Results indicated significant memory impairments in patients with schizophrenia and TLE. “Savings” score measures of memory decay showed that the loss of information in schizophrenia and TLE was approximately equal, and quantitatively mild compared to that found in most neurologic groups with memory disorders. The severe difficulty shown by the schizophrenia group on a task of incidental recall suggested that the absence of instructional set added to a vulnerability to memory deficit. In contrast, relatively mildly impaired performance on paired associate learning suggested that patients with schizophrenia benefited from retrieval cues, multiple trials, and short (nonsupraspan) informational loads. Because patients with schizophrenia consisted of a relatively nonchronic sample with a mean IQ of 99.7, their memory disorder could not be attributed to schizophrenic dementia, nor was it accounted for by other potential confounds. Patients with schizophrenia, even those relatively early in the course of illness, have a mild episodic memory disorder. (JINS, 1998, 4, 342–352.)