Miracle-dz/UniFAR-FTUs huggingface dataset:
Establishment of HIV Latency in Primary CD4+ Cells Is due to Epigenetic Transcriptional Silencing and P-TEFb Restriction

ABSTRACT The development of suitable experimental systems for studying HIV latency in primary cells that permit detailed biochemical analyses and the screening of drugs is a critical step in the effort to develop viral eradication strategies. Primary CD4+ T cells were isolated from peripheral blood and amplified by antibodies to the T-cell receptor (TCR). The cells were then infected by lentiviral vectors carrying fluorescent reporters and either the wild-type Tat gene or the attenuated H13L Tat gene. After sorting for the positive cells and reamplification, the infected cells were allowed to spontaneously enter latency by long-term cultivation on the H80 feeder cell line in the absence of TCR stimulation. By 6 weeks almost all of the cells lost fluorescent protein marker expression; however, more than 95% of these latently infected cells could be reactivated after stimulation of the TCR by α-CD3/CD28 antibodies. Chromatin immunoprecipitation assays showed that, analogously to Jurkat T cells, latent proviruses in primary CD4+ T cells are enriched in heterochromatic markers, including high levels of CBF-1, histone deacetylases, and methylated histones. Upon TCR activation, there was recruitment of NF-κB to the promoter and conversion of heterochromatin structures present on the latent provirus to active euchromatin structures containing acetylated histones. Surprisingly, latently infected primary cells cannot be induced by tumor necrosis factor alpha because of a restriction in P-TEFb levels, which can be overcome by activation of the TCR. Thus, a combination of restrictive chromatin structures at the HIV long terminal repeat and limiting P-TEFb levels contribute to transcriptional silencing leading to latency in primary CD4+ T cells.
Invariance and Inconsistency in Utility Ratings

Purpose . To assess utilities of composite health states for dependence in activities of daily living (ADLs) for invariance (i.e., when subjects provide a utility of 1 for all health states) and order inconsistency (i.e., when subjects order their utilities such that their utility for a combination of ADL dependencies is greater than their utility for any subset of the combination). Methods . Each of the 400 subjects, age 65 y and older, enrolled in one of several regional medical centers of the Kaiser Permanente Medical Care Program of Northern California and provided standard-gamble utilities for single ADL dependencies (e.g., bathing, dressing, continence) and for dependence in 8 other combinations of ADL dependencies. For order-inconsistent responses, the authors calculated the maximum magnitude of inconsistency as the maximum difference between the utility for the combined ADL dependence health state and that of its inconsistent subset. Results . A total of 76 subjects (19%) gave a utility of 1.0 for all health states presented to them; 19 (5%) gave the same utility other than 1.0 for all health states; 130 (33%) gave at least 1 utility < 1.0 and had no order inconsistencies; and 175 (44%) had at least 1 order inconsistency. Invariance was associated with a Mini-Mental Status Examination score < 28.6 (P = 0.01), with education < 12 y (P = 0.004), with race/ethnicity other than non-Hispanic White/Caucasian (P = 0.001), and with shorter time spent on the utility elicitation task (P < 0.0001). Among the inconsistent subjects, 69% had a maximal magnitude of inconsistency that was within 1 standard deviation of the mean utilities. The maximal magnitude of inconsistency was associated with longer time spent on the elicitation task (P < 0.0001) and race/ethnicity other than non-Hispanic White/Caucasian (P = 0.005). The mean (s) utility for dependence in continence among consistent subjects who were not invariant (0.88 [0.24]) was higher than among inconsistent subjects (0.80 [0.27]; P = 0.01). Conclusions . Invariance and order inconsistencies in utility ratings for complex health states occur frequently. Utilities of consistent subjects may differ from those of inconsistent subjects. Utility assessments should attempt to measure and report these patterns.
Iron modifies plasma FGF23 differently in autosomal dominant hypophosphatemic rickets and healthy humans.

CONTEXT In autosomal dominant hypophosphatemic rickets (ADHR), fibroblast growth factor 23 (FGF23) resists cleavage, causing increased plasma FGF23 levels. The clinical phenotype includes variable onset during childhood or adulthood and waxing/waning of hypophosphatemia. Delayed onset after puberty in females suggests iron status may be important. OBJECTIVE Studies were performed to test the hypothesis that plasma C-terminal and intact FGF23 concentrations are related to serum iron concentrations in ADHR. DESIGN AND SETTING Cross-sectional and longitudinal studies of ADHR and a cross-sectional study in healthy subjects were conducted at an academic medical center. PARTICIPANTS Participants included 37 subjects with ADHR mutations from four kindreds and 158 healthy adult controls. MAIN OUTCOME MEASURE The relationships of serum iron concentrations with plasma C-terminal and intact FGF23 concentrations were evaluated. RESULTS Serum phosphate and 1,25-dihydroxyvitamin D correlated negatively with C-terminal FGF23 and intact FGF23 in ADHR but not in controls. Serum iron was negatively correlated to both C-terminal FGF23 (r = -0.386; P < 0.05) and intact FGF23 (r = -0.602; P < 0.0001) in ADHR. However, control subjects also demonstrated a negative relationship of serum iron with C-terminal FGF23 (r = -0.276; P < 0.001) but no relationship with intact FGF23. Longitudinally in ADHR subjects, C-terminal FGF23 and intact FGF23 concentrations changed negatively with iron concentrations (P < 0.001 and P = 0.055, respectively), serum phosphate changed negatively with C-terminal FGF23 and intact FGF23 (P < 0.001), and there was a positive relationship between serum iron and phosphate (P < 0.001). CONCLUSIONS Low serum iron is associated with elevated FGF23 in ADHR. However, in controls, low serum iron was also associated with elevated C-terminal FGF23, but not intact FGF23, suggesting cleavage maintains homeostasis despite increased FGF23 expression.
El Principio del Máximo

En este articulo presentamos la definicion basica del principio del maximo, su aplicabilidad a las ecuaciones diferenciales, en particular a las ecuaciones diferenciales lineales ordinarias de segundo orden y la ecuacion diferencial lineal parcial parabolica llamada ecuacion del calor, ademas mostraremos este principio en su forma mas conocida utilizando una funcion auxiliar diferente.
Saccharomyces cerevisiae cell wall chitin, the Kluyveromyces lactis zymocin receptor

The exozymocin secreted by Kluyveromyces lactis causes sensitive yeast cells, including Saccharomyces cerevisiae, to arrest growth in the G1 phase of the cell cycle. Despite its heterotrimeric (αβγ) structure, intracellular expression of its smallest subunit, the γ‐toxin, is alone responsible for the G1 arrest. The α subunit, however, has a chitinase activity that is essential for holozymocin action from the cell exterior. Here we show that sensitive yeast cells can be rescued from zymocin treatment by exogenously applying crude chitin preparations, supporting the idea that chitin polymers can compete for binding to zymocin with chitin present on the surface of sensitive yeast cells. Consistent with this, holozymocin can be purified by way of affinity chromatography using an immobilized chitin matrix. PCR‐mediated deletions of chitin synthesis (CHS) genes show that most, if not all, genetic scenarios that lead to complete loss (chs3Δ), blocked export (chs7Δ) or reduced activation (chs4Δ), combined with mislocalization (chs4Δchs5Δ; chs4Δchs6Δ; chs4Δchs5Δchs6Δ) of chitin synthase III activity (CSIII), render cells refractory to the inhibitory effects of exozymocin. In contrast, deletions in CHS1 and CHS2, which code for CSI and CSII, respectively, have no effect on zymocin sensitivity. Thus, CSIII‐polymerized chitin, which amounts to almost 90% of the cell's chitin resources, appears to be the carbohydrate receptor required for the initial interaction of zymocin with sensitive cells. Copyright © 2001 John Wiley & Sons, Ltd.
Trans-Presentation of IL-15 Dictates IFN-Producing Killer Dendritic Cells Effector Functions1

IFN-producing killer dendritic cells (IKDC) were initially described as B220+CD11c+CD3−NK1.1+ tumor-infiltrating cells that mediated part of the antitumor effects of the combination therapy with imatinib mesylate and IL-2. In this study, we show their functional dependency on IL-15 during homeostasis and inflammatory processes. Trans-presentation of IL-15 by IL-15Rα allows dramatic expansion of IKDC in vitro and in vivo, licenses IKDC for TRAIL-dependent killing and endows IKDC with immunizing potential, all three biological attributes not shared by B220−NK cells. However, IL-15 down-regulates the capacity of IKDC to induce MHC class I- or II-restricted T cell activation in vitro. Trans-presentation of IL-15 by IL-15Rα allows IKDC to respond to TLR3 and TLR4 ligands for the production of CCL2, a chemokine that is critical for IKDC trafficking into tumor beds (as described recently). We conclude that IKDC represent a unique subset of innate effectors functionally distinguishable from conventional NK cells in their ability to promptly respond to IL-15-driven inflammatory processes.
Significance of CK19, TPO, and HBME-1 expression for diagnosis of papillary thyroid carcinoma.

OBJECTIVES To evaluate the expression and significance of CK19, TPO, and HBME-1 in the differential diagnosis of papillary thyroid carcinoma (PTC) and nonmalignant nodules. METHODS Tissue samples were obtained from 257 patients with PTC and 149 patients with nonmalignant thyroid specimens, and immunohistochemical staining for CK-19, TPO, and HBME-1 was performed. RESULTS The expression of CK-19, TPO, and HBME-1 was 96.3%, 12.0%, and 85.3%, respectively, for the PTC group. For nonmalignant thyroid lesions group, the expression of these markers was 40.4%, 86.2%, and 37.2%, respectively. Further, the expression of CK-19 and HBME-1 in PTCs was much higher than that in the benign thyroid lesions (P < 0.05). However, the positive expression of TPO in PTC specimens was much lower than that in the nonmalignant specimens (P < 0.05). CK-1 had the highest sensitivity (96.30%) for PTCs. The combination of the positive expression of CK-19 and negative expression of TPO had the highest sensitivity (98.50%), while that of the positive expression of HBME-1 and negative expression of TPO had the highest specificity (92.90%). CONCLUSIONS The combination of positive expression of CK-19 or HBME-1 or negative expression of TPO can improve the specificity of the diagnosis of PTC.
Aging of the Cervical Spine in Healthy Volunteers: A 10-Year Longitudinal Magnetic Resonance Imaging Study

Study Design. Prospective longitudinal study, mean follow-up period; 11.7 ± 0.8 years was conducted from 1995 to 2007. Objective. To clarify normal aging process of cervical spine and correlation between progression of disc degeneration and development of clinical symptoms. Summary of Background Data. Aging of the cervical spine can inevitably occur in anyone. Long-term longitudinal studies following the same individuals are necessary to elucidate the accurate aging processes of the cervical spine. Methods. Two hundred twenty-three subjects of 497 original cohorts (123 men, 100 women, mean age: 39.0 ± 15.0, follow-up rate: 44.9%). Subjects, who underwent MRI 10 years ago, underwent another MRI, neurologic examination, and questionnaire survey regarding symptoms related to cervical spine and life style. Following 5 MR findings representing intervertebral disc degeneration were evaluated: (1) decrease in signal intensity of disc, (2) anterior compression of dura and spinal cord, (3) posterior disc protrusion (PDP), (4) disc space narrowing (DSN), and (5) foraminal stenosis (FS). Results. Progression of degenerative findings was observed in 189 subjects (81.1%). Progression of decrease in signal intensity of disc was observed in 59.6%, anterior compression of dura and spinal cord in 61.4%, PDP in 70.0%, DSN in 26.9%, and FS in 9.0%. Logistic regression analysis revealed that incidence of progression of PDP, DSN, FS was higher in elderly subjects. There were no correlations between any degenerative MR findings and sex, smoking, alcohol, sport, or body mass index. Neck pain, shoulder stiffness, and numbness in upper extremities were recognized in 9.9%, 30.0%, and 4.0% of subjects, and 1 or more clinical symptoms have developed in 34.1% during 10 years. Conclusion. Progression of degeneration of cervical spine on MRI was frequently observed during 10-year period, with development of symptoms in 34% of subjects. No factor related to progression of degeneration of cervical spine was identified except for age.
Modeling of Human Cytomegalovirus Maternal-Fetal Transmission in a Novel Decidual Organ Culture

ABSTRACT Human cytomegalovirus (HCMV) is the leading cause of congenital infection, associated with severe birth defects and intrauterine growth retardation. The mechanism of HCMV transmission via the maternal-fetal interface is largely unknown, and there are no animal models for HCMV. The initial stages of infection are believed to occur in the maternal decidua. Here we employed a novel decidual organ culture, using both clinically derived and laboratory-derived viral strains, for the ex vivo modeling of HCMV transmission in the maternal-fetal interface. Viral spread in the tissue was demonstrated by the progression of infected-cell foci, with a 1.3- to 2-log increase in HCMV DNA and RNA levels between days 2 and 9 postinfection, the expression of immediate-early and late proteins, the appearance of typical histopathological features of natural infection, and dose-dependent inhibition of infection by ganciclovir and acyclovir. HCMV infected a wide range of cells in the decidua, including invasive cytotrophoblasts, macrophages, and endothelial, decidual, and dendritic cells. Cell-to-cell viral spread was revealed by focal extension of infected-cell clusters, inability to recover infectious extracellular virus, and high relative proportions (88 to 93%) of cell-associated viral DNA. Intriguingly, neutralizing HCMV hyperimmune globulins exhibited inhibitory activity against viral spread in the decidua even when added at 24 h postinfection—providing a mechanistic basis for their clinical use in prenatal prevention. The ex vivo-infected decidual cultures offer unique insight into patterns of viral tropism and spread, defining initial stages of congenital HCMV transmission, and can facilitate evaluation of the effects of new antiviral interventions within the maternal-fetal interface milieu.
Pricing Schemes in Cloud Computing: An Overview

Cloud Computing is one of the technologies with rapid development in recent years where there is increasing interest in industry and academia. This technology enables many services and resources for end users. With the rise of cloud services number of companies that offer various services in cloud infrastructure is increased, thus creating a competition on prices in the global market. Cloud Computing providers offer more services to their clients ranging from infrastructure as a service (IaaS), platform as a service (PaaS), software as a service (SaaS), storage as a service (STaaS), security as a service (SECaaS), test environment as a service (TEaaS). The purpose of providers is to maximize revenue by their price schemes, while the main goal of customers is to have quality of services (QoS) for a reasonable price. The purpose of this paper is to compare and discuss several models and pricing schemes from different Cloud Computing providers.
Set-based model predictive consensus under bounded additive disturbances

An efficient, model-predictive-control (MPC)-based scheme is presented for a class of consensus-related control problems involving dynamically decoupled subsystems which are required to reach a consensus condition in some optimal way. A general case of constrained subsystems with external disturbances is considered and a suitable set-based near-consensus condition is set as the target condition to achieve. The proposed scheme employs computationally efficient, closed-loop MPC policies in the subsystems together with a distributed optimization method to optimize the global consensus trajectory and the subsystem control inputs in real time. It also allows the incorporation of computational delays in the policy formulation so that the desired control performance is ensured.
Computer model of fetal-maternal heat exchange in sheep.

We constructed and used a mathematical model of maternal-fetal heat exchange in the sheep to explore the effects of changes in certain parameters on steady-state fetal temperatures and to determine whether the fetus in the model has any potential to control its own temperature. The model took into account both fetal and placental heat production and exchange of heat in the placenta, across the fetal skin, via amniotic fluid, and through the uterine wall. The maternal ewe was assumed to be a constant temperature heat sink. Changes in placental or fetal heat production were calculated to change the ratio of heat exiting across the placenta or fetal skin significantly but to have little effect on fetal core temperature, e.g., a rise of only 0.8 degrees C was predicted after a twofold increase in fetal heat production. Fetal placental blood flow was calculated to affect fetal temperature the most of any flow, a reduction to zero causing fetal temperature to rise 5.0 degrees C. Changes in heat conductances between fetal skin and amniotic fluid, or between amniotic fluid and uterine wall, had minimal effect on fetal temperature. From the model calculations here and because heat exchange within the sheep placenta has previously been calculated to be extremely efficient, we conclude that the fetal sheep has little ability to control its temperature by changes in heat dissipated through extraplacental pathways. Thus the model predicts an effective heat clamp that closely links fetal to maternal temperature.
Solitary plasmacytoma. I: Extramedullary soft tissue plasmacytoma

The details of 16 patients with extramedullary plasmacytoma are presented. All but one presented with localized disease, and all were treated successfully by radiotherapy. Only one patient developed local recurrence and only one has developed disseminated disease. Radiotherapy is recommended as the primary treatment of choice for these localized radiosensitive tumors. It is suggested that the good prognosis of plasmacytomas of the head and neck, in contrast to plasmacytomas arising at other sites, is related to the observation that a high proportion of these tumors are localized at the time of diagnosis and that very large primary tumors are uncommon.
Characterological resistances in psychotherapy supervision.

While resistance has long been discussed as an obstacle to the process of psychotherapy (Freud, S., 1912,1914; Freud, A., 1936; Fenichel, 1945; Gill, 1963; Greenson, 1967) it has been less frequently addressed in the context of psychotherapy supervision. The most frequent aspect of resistance in supervision that has been discussed in the literature is the type of resistant behavior most commonly manifested by supervisees. Among these behaviors Bauman (1972) includes: submission, turning the tables, self-depreciation, helplessness, and projection. Bauman also discusses supervisory methods for dealing with these forms of resistance including interpretation, feedback, clarification, generalization, ignoring, the alterego technique and audio taping. Kadushin (1976) also describes the forms mat supervisory resistance can take. These include flattery, redefining the supervisory relationship, reducing the supervisor's power, ensuring that uncomfortable topics won't be raised, engaging in excessive self-criticism to solicit reassurance, concealing problems and distorting what actually occurs in the therapy session. Dodge (1982) notes that supervisees may
Removal of positioned nucleosomes from the yeast PHO5 promoter upon PHO5 induction releases additional upstream activating DNA elements.

The chromatin fine structure in the promoter region of PHO5, the structural gene for a strongly regulated acid phosphatase in yeast, was analyzed. An upstream activating sequence 367 bp away from the start of the coding sequence that is essential for gene induction was found to reside in the center of a hypersensitive region under conditions of PHO5 repression. Under these conditions three related elements at positions ‐469, ‐245 and ‐185 are contained within precisely positioned nucleosomes located on both sides of the hypersensitive region. Upon PHO5 induction the chromatin structure of the promoter undergoes a defined transition, in the course of which two nucleosomes upstream and two nucleosomes downstream of the hypersensitive site are selectively removed. In this way approximately 600 bp upstream of the PHO5 coding sequence become highly accessible and all four elements are free to interact with putative regulatory proteins. These findings suggest a mechanism by which the chromatin structure participates in the functioning of a regulated promoter.
Donor-derived exosomes: the trick behind the semidirect pathway of allorecognition

Purpose of review The passenger leukocyte hypothesis predicts that after transplantation, donor antigen-presenting cells (APCs) from the graft present donor MHC molecules to directly alloreactive T cells in lymphoid organs. However, in certain transplantation models, recent evidence contradicts this long-standing concept. New findings demonstrate that host, instead of donor, APCs play a prominent role in allosensitization against donor MHC molecules via the semidirect pathway. A similar mechanism operates in development of T-cell split tolerance to noninherited maternal antigens. Recent findings Following fully mismatch skin or heart transplantation in mice, no or extremely few donor migrating APCs (i.e. conventional dendritic cells) are detected in the draining lymphoid organs. Instead, recipient dendritic cells that have captured donor extracellular vesicles (i.e. exosomes) carrying donor MHC molecules and APC costimulatory signals present donor MHC molecules to directly alloreactive T cells. This semidirect pathway can also give rise to a form of ‘split’ tolerance during chronic alloantigen exposure, as indirectly alloreactive T helper cells and directly alloreactive T-cell effectors are differentially impacted by host dendritic cells ‘cross-dressed’ with extracellular vesicles/exosomes derived from maternal microchimerism. Summary Acquisition by recipient APCs of donor exosomes (and likely other extracellular vesicles) released by passenger leukocytes or the graft explains the potent T-cell allosensitization against donor MHC molecules, in the absence or presence of few passenger leukocytes in lymphoid organs. It also provides the basic mechanism and in-vivo relevance of the elusive semidirect pathway. Its degree of coordination with the allopeptide – specific, indirect pathway of T-cell help may determine whether semidirect allopresentation results in a sustained, effective, acute rejection response, or rather, in abortive acute rejection and ‘split’ tolerance.