Miracle-dz/UniFAR-FTUs huggingface dataset:
Natural mutations in a Staphylococcus aureus virulence regulator attenuate cytotoxicity but permit bacteremia and abscess formation

Significance Staphylococcus aureus is a major cause of life-threatening bacterial infection. A significant risk factor for infection is nasal carriage. Previously, we reported spontaneous mutations during carriage associated with infection, including loss-of-function of the gene repressor of surface proteins (rsp). Here we use genomic screens, experimental assays, and molecular examination of rsp mutants from patients to understand how rsp is involved in infection; we find it has far-reaching effects on gene regulation. Paradoxically, rsp mutants exhibited attenuated toxicity and reduced disease severity early in experimental infection, without sacrificing the ability to cause abscesses and bloodstream infection. This work reveals a complex relationship between correlates of disease in the laboratory and in patients, demonstrating that life-threatening disease can be associated with reduced severity early in infection. Staphylococcus aureus is a major bacterial pathogen, which causes severe blood and tissue infections that frequently emerge by autoinfection with asymptomatically carried nose and skin populations. However, recent studies report that bloodstream isolates differ systematically from those found in the nose and skin, exhibiting reduced toxicity toward leukocytes. In two patients, an attenuated toxicity bloodstream infection evolved from an asymptomatically carried high-toxicity nasal strain by loss-of-function mutations in the gene encoding the transcription factor repressor of surface proteins (rsp). Here, we report that rsp knockout mutants lead to global transcriptional and proteomic reprofiling, and they exhibit the greatest signal in a genome-wide screen for genes influencing S. aureus survival in human cells. This effect is likely to be mediated in part via SSR42, a long-noncoding RNA. We show that rsp controls SSR42 expression, is induced by hydrogen peroxide, and is required for normal cytotoxicity and hemolytic activity. Rsp inactivation in laboratory- and bacteremia-derived mutants attenuates toxin production, but up-regulates other immune subversion proteins and reduces lethality during experimental infection. Crucially, inactivation of rsp preserves bacterial dissemination, because it affects neither formation of deep abscesses in mice nor survival in human blood. Thus, we have identified a spontaneously evolving, attenuated-cytotoxicity, nonhemolytic S. aureus phenotype, controlled by a pleiotropic transcriptional regulator/noncoding RNA virulence regulatory system, capable of causing S. aureus bloodstream infections. Such a phenotype could promote deep infection with limited early clinical manifestations, raising concerns that bacterial evolution within the human body may contribute to severe infection.
Different actions of protein kinase C isoforms alpha and epsilon on gastric acid secretion.

1. The phorbol ester TPA, an activator of protein kinase C (PKC), inhibits cholinergic stimulation of gastric acid secretion but increases basal H(+) secretion. 2. Since these contradictory findings suggest the action of different PKC isozymes we analysed the role of calcium-dependent PKC-alpha, and calcium-independent PKC-epsilon in gastric acid secretion. 3. Inhibition of PKC-alpha by the indolocarbazole Gö 6976 revealed that about 28% of carbachol-induced acid secretion was inhibited by PKC-alpha. In the presence of Gö 6976 approximately 64% of the carbachol-induced signal transduction is mediated by Ca(2+)/calmodulin-dependent protein kinase II (CaMKII), and 14% is conveyed by PKC-epsilon as deduced from the inhibition with the bisindolylmaleimide Ro 31-8220. 4. Inhibition of carbachol-induced acid secretion by TPA was accompanied by a decrease in CaMKII activity. 5. The stimulation of basal acid secretion by TPA was biphasic with a peak at a very low concentration (10 pM), resulting in an activation of the calcium-sensor CaMKII. The activation was determined with a phosphospecific polyclonal antibody against active CaMKII. The TPA-induced increase of H(+) secretion was sensitive to the cell-permeable Ca(2+)-chelator BAPTA/AM, Ro 31-8220, and the CaMKII-inhibitor KN-62, but not to Gö 6976. 6. Since TPA induced the translocation of PKC-epsilon but not of PKC-alpha in resting parietal cells, PKC-epsilon seems to be at least responsible for an initial elevation of free intracellular calcium to initiate TPA-induced acid secretion. 7. Our data indicate the different roles of two PKC isoforms: PKC-epsilon activation appears to facilitate cholinergic stimulation of H(+)-secretion likely by increasing intracellular calcium. In contrast, PKC-alpha activation attenuates acid secretion accompanied by a down-regulation of CaMKII activity.
Contributions of Mathematical Modeling of Beta Cells to the Understanding of Beta-Cell Oscillations and Insulin Secretion

Mathematical modeling of pancreatic beta cells has contributed significantly to the understanding of the mechanisms involved in glucose-stimulated insulin secretion (GSIS). Early models of insulin secretion built in the 1970s were phenomenological with little biological foundation for the proposed mechanisms. In the 1980s, models focused on identifying the regulation of bursting electrical activity known to be important for insulin secretion. The main result was to reject proposed mechanisms as new data emerged, but important results of the role of cell-to-cell coupling were also established. New models have been proposed that provide possible explanations for the occurrence of various patterns of bursting and calcium oscillations. In addition, modeling has played an important role in comparing competing effects of calcium on both NADH and adenosine 3′-5′-cyclic monophosphate levels. Models including modern cell biological results of the regulation of insulin containing granules and cell heterogeneity have appeared, providing updated versions of the early models proposed in the 1970s. These models, when coupled to electrophysiological- and calcium-based ones, have the prospect to aid in understanding the overall picture of GSIS. In addition, they might be useful for estimating in vivo beta-cell functioning. Beta-cell modeling will likely move closer to clinical applications, where it can be expected to play an important role, as it has and will, in understanding the complex oscillatory phenomena observed in beta cells and islets.
Degradation of the Alzheimer's Amyloid β Peptide by Endothelin-converting Enzyme*

Deposition of β-amyloid (Aβ) peptides in the brain is an early and invariant feature of all forms of Alzheimer's disease. As with any secreted protein, the extracellular concentration of Aβ is determined not only by its production but also by its catabolism. A major focus of Alzheimer's research has been the elucidation of the mechanisms responsible for the generation of Aβ. Much less, however, is known about the mechanisms responsible for Aβ removal in the brain. In this report, we describe the identification of endothelin-converting enzyme-1 (ECE-1) as a novel Aβ-degrading enzyme. We show that treatment of endogenous ECE-expressing cell lines with the metalloprotease inhibitor phosphoramidon causes a 2–3-fold elevation in extracellular Aβ concentration that appears to be due to inhibition of intracellular Aβ degradation. Furthermore, we show that overexpression of ECE-1 in Chinese hamster ovary cells, which lack endogenous ECE activity, reduces extracellular Aβ concentration by up to 90% and that this effect is completely reversed by treatment of the cells with phosphoramidon. Finally, we show that recombinant soluble ECE-1 is capable of hydrolyzing synthetic Aβ40 and Aβ42 in vitro at multiple sites.
6-(2-Hydroxyphenyl)-5,6-dihydrobenzimidazolo[1,2-c]quinazolin-12-ium bromide ethanol solvate

In the title compound, C20H16N3O+·Br−·C2H6O, the phenol ring forms dihedral angles of 84.5 (1) and 89.3 (1)° with the benzimidazole system and the quinazoline benzene ring, respectively. The two N—H groups act as donors in hydrogen bonds with the bromide ion as acceptor, leading to infinite eight-membered chains along [100]. According to graph-set theory the descriptor on the binary level is C 2 1(8). O—H⋯O and O—H⋯Br hydrogen bonds also occur.
Holistic Wellness in Older Adulthood: Group Differences Based on Age and Mental Health

Purpose: To understand how demographic variables and depression symptoms relate to the prevalence of wellness, resilience, and age perception within a sample of community-dwelling older adults. Design: In all, 200 residents across 12 senior housing sites were surveyed. Research questions included the following: (1) Do group differences exist in wellness, resilience, and age perception based on age, sex, race, education, and depression symptoms? (2) Which profile of variables is most strongly associated with self-rated depression among older adults? Method: Multivariate analyses of variance were used to examine group differences. A discriminant analysis demonstrated which variables comprised the profile of individuals who ascribed to depression symptoms. Findings: Younger respondents (i.e., age 55-70) had significantly lower levels of wellness (η2 = .034) and resilience (η2 = .052). Respondents suffering from depression symptoms had lower levels of wellness (η2 = .155), resilience (η2 = .163), and positive age perception (η2 = .067) and higher rates of negative age perception (η2 = .052). The discriminant analysis correctly categorized 75.3% of the cases related to depression symptoms, and resilience and certain forms of wellness were most relevant. Conclusions: The current study sheds light into within-group differences in wellness, resilience, and age perception that depend on variables such as age and depression.
Control system performance monitoring: New developments and practical issues

Abstract This paper reviews some of the techniques and measures used in control loop performance monitoring systems. Basic tools are briefly reviewed. The Harris index, which for a single-input, single-output loop quantifies the distance from minimum variance, requires knowledge of the process dead time. Recently developed techniques for dead time estimation from operating data are discussed. A novel model invalidation technique is illustrated via an industrial example. Finally, issues of data quality are touched upon.
HIV replication elicits little cytopathic effects in vivo: Analysis of surrogate markers for virus production, cytotoxic T cell response and infected cell death

Several potential mechanisms for viral destruction of HIV‐infected cells have been described. The hypothesis was examined that if HIV were cytopathic, a positive relation between the in vivo virus production or CTL activity and infected cell death should be observed. In a regression analysis no significant relation was found between surrogate markers for in vivo virus production or the virus‐specific CTL response and death rates of productively infected cells. In a subgroup of patients the hypothesis is rejected that HIV replication elicits a large (R2 > 0.25) cytopathic effect (P < 0.05, N = 36). It is concluded that HIV replication elicits little cytopathic effect in productively infected cells and that CD4+ T lymphocytes are eroded by other mechanisms. J. Med. Virol. 78:1141–1146, 2006. © 2006 Wiley‐Liss, Inc.
Bivariate C 1 Quadratic Finite Elements and Vertex Splines

Following work of Heindl and of Powell and Sabin, each triangle of an arbitrary (regular) triangulation A of a polygonal region ii in R is subdi- vided into twelve triangles, using the three medians, yielding the refinement A of A , so that C quadratic finite elements can be constructed. In this paper, we derive the Bezier nets of these elements in terms of the parameters that de- scribe function and first partial derivative values at the vertices and values of the normal derivatives at the midpoints of the edges of A. Consequently, bivariate C quadratic (generalized) vertex splines on A have an explicit formulation. Here, a generalized vertex spline is one which is a piecewise polynomial on the refined grid partition A and has support that contains at most one vertex of the original partition A in its interior. The collection of all C quadratic general- ized vertex splines on A so constructed is shown to form a basis of S2 (A), the vector space of all functions on C (I2) whose restrictions to each triangular cell of the partition A are quadratic polynomials. A subspace with the basis given by appropriately chosen generalized vertex splines with exactly one vertex of A in the interior of their supports, that reproduces all quadratic polynomials, is identified, and hence, has approximation order three. Quasi-interpolation for- mulas using this subspace are obtained. In addition, a constructive procedure that yields a locally supported basis of yet another subspace with dimension given by the number of vertices of A, that has approximation order three, is given.
Epidemic spreading on dualistic social networks

The rapid development of modern society continually transforms the social structure which leads to an increasing distinct dualistic social structure pattern that more people gather to large cities, resulting high population density area, and less people remain in the rural area, resulting low population density area. We study the epidemic spreading on such dualistic structure where the infectious disease could be described by SIRS model. We find that distinct from other disease model, the SIRS model has two epidemic threshold. A disease could not persist the spreading when the population density is too high or too low, which is verified both on theoretical analysis and numerical simulations. Moreover, we find that for two areas, one has high population density and the other has low population density such that a disease could not survive in each of them, when they are connected the disease could however spread over the whole system. This phenomenon indicates that the connection of the two areas could radically change the capability of the whole system to resist an infectious disease. Our finding may provide new understanding of epidemic spreading on dualistic structure of modern society and the corresponding immunization strategies.
Curative effect analysis of different treatments for gefitinib-resistance advanced non-small cell lung cancer patients.

OBJECTIVE Gefitinib is effective epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKI) for advanced non-small cell lung cancer (NSCLC) patients, but with the drug use, inevitable gefitinib-resistance and severe complications were observed and resulted in failure treatments. The purpose of the present study was to investigate the curative effect of different treatment of navelbine plus cisplatin in combination with gefitinib and gefitinib single on gefitinib-resistance advanced NSCLC patients. METHODS Total Of 120 patients acquired gefitinib-resistance NSCLC patients treated in Taian City Central Hospital of Shandong province from May, 2010 to June, 2014 were incorporated in our study according to the inclusion and exclusion criteria. The patients were divided into chemotherapeutical group and gefitinib group and the mean follow-up was 12 months (6-39 months), the information of patients was recorded as gender, age, smoking, complications, hepatic metastasis, bone metastasis, brain metastasis and acquired chemotherapy or not. Chi-square test and t-test were performed to analyzed collection data, Log-rank was analyzed significance of survival time among groups and Cox regression was evaluated independent risk factors of survival analysis. RESULTS The survival time of chemotherapy group was significantly longer than gefitinib group; the survival time among the two groups was 29.06 and 15.23 months (P<0.05), respectively. Multivariate Cox regression analyzed that lesion's metastasis (hepatic metastasis, bone metastasis and brain metastasis) and acquired chemotherapy were independent risk factors influence on patients overall survival time; gender, age, smoking, complications had no significance influence on survival time between the two groups. CONCLUSION Lesion's metastasis and acquired chemotherapy were independent risk factors influence on patients' overall survival time and the survival time of chemotherapy group was significantly longer than gefitinib group.
Comparison of Dexamethasone Intravitreal Implant with Conventional Triamcinolone in Patients with Postoperative Cystoid Macular Edema

ABSTRACT Aims: To evaluate the efficacy of the treatment with intravitreal triamcinolone acetonide or dexamethasone intravitreal implant in patients with postoperative cystoid macular edema (PCME). Materials and Methods: Thirty eyes of 29 patients with PCME were randomized into two groups: one group initially received an injection of 4 mg triamcinolone; retreatment after 3 months was dependent on functional and anatomic outcome in a PRN regimen. The second group received a single injection of the dexamethasone intravitreal implant (Ozurdex). Patients were followed for 6 months. The main outcomes were best-corrected visual acuity (BCVA) and central millimeter retinal thickness (CMMT). Results: Mean BCVA improved significantly in both groups at 3 months (p ≤ 0.05) and 6 months (p ≤ 0.05) after treatment. There was no statistically significant difference between the two groups in visual acuity improvement at 3 months (p > 0.05) or 6 months (p > 0.05). Mean CMMT of both groups also decreased significantly after treatment at 3 and 6 months (both p ≤ 0.05) and the reduction was significantly superior in the triamcinolone group compared to ozurdex group at 1 week and 6 months (p ≤ 0.05). All cases with intraocular hypertension were managed with IOP-lowering medication and no surgery was required during the study. One patient was excluded because of endophthalmitis in the triamcinolone group. Conclusion: Intravitreal triamcinolone and dexamethasone implant are both equally effective in increasing visual acuity in patients with PCME at a 6-month follow-up. However, macular edema seems to respond more rapidly with intravitreal triamcinolone, and 3-monthly repetitive injections maintain the reduction in retinal thickness better than a single dexamethasone implant at the first 6 months of follow-up period.
MicroRNA-214 Suppresses Osteogenic Differentiation of Human Periodontal Ligament Stem Cells by Targeting ATF4

Periodontitis is the main cause of adult tooth loss. Stem cell-based tissue engineering has become a promising therapy for periodontitis treatment. To date, human periodontal ligament stem cells (hPDLSCs) have been shown to be a favorable source for tissue engineering, but modulatory mechanisms of hPDLSCs remain unclear. Approximately 60% of mammalian genes are the targets of over 2000 miRNAs in multiple human cell types, and miRNAs are able to influence various biological processes in the human body, including bone formation. In this study, we found that after osteogenic induction, miR-214 was significantly decreased in hPDLSCs; therefore, we examined the effects of miR-214 on osteogenic differentiation. Computational miRNA target prediction analyses and luciferase reporter assays revealed that activating transcription factor 4 (ATF4) is a direct target of miR-214. We prepared cells overexpressing miR-214 and found that miR-214 negatively regulates osteogenic differentiation of hPDLSCs. For the target of miR-214, ATF4 protein expression level was decreased after induction. In conclusion, we found that miR-214-ATF4 axis is a novel pathway for regulating hPDLSC osteogenic differentiation.
Dynamic output feedback control of multi-agent systems over signed graphs

We study bipartite consensus of multi-agent systems over signed directed graphs, where both cooperative and antagonistic interactions exist within the group. Each agent is modeled by a general linear time-invariant system. A dynamic output feedback control law is proposed, leading to a bipartition of two subgroups, moving individually towards opposite directions. Moreover, we show that a proper graph topology, i.e., having a spanning tree and being structurally balanced, is crucial for achieving bipartite consensus.
The validity of clinic-based samples in approximating out-of-care HIV-infected populations

Tremendous strides have been made in the diagnosis and treatment of human immunodeficiency virus (HIV); perhaps now the largest barrier to controlling HIV is retaining those diagnosed in care. Data on out-of-care populations are needed to develop effective retention methods, yet obtaining these remains methodologically challenging due to inherent difficulties in sampling. The purpose of this study was to evaluate whether individuals identified by two sampling methods commonly used to approximate out-of-care populations were significantly different from a sample of newly identified out-of-care persons. We compared medical records of 345 out-of-care persons identified by a novel population-based health information exchange who had not received CD4 or viral load monitoring in >1 year with: medical records from a randomly selected, time-matched sample of 488 HIV-infected persons with at least one HIV care visit in the past 5 years, and interviews with 382 participants from a time-matched clinic-based convenience sample. Newly identified out-of-care persons were significantly different from both proxies with respect to demographic, clinical, and utilization characteristics, suggesting that samples of in-care proxy persons are inadequate to describe those not engaged in care. Novel approaches to sampling out-of care populations are urgently needed in order to better understand these populations and ways to improve retention and slow the HIV/AIDS epidemic.
Matrix Factorization for Fast DCT Algorithms

Two principles to produce new possibilities for the radix-2 discrete cosine transform (DCT) have been presented in this paper. One is to employ matrix factorization through revealing the intrinsic relationship among several existing famous algorithms, which is regarded as an effective guide for exploring new algorithms. The other is to make use of the orthogonal property of the DCT matrix. As long as the recursive kernel of an algorithm is orthogonal, there must be a twin fast DCT algorithm of it. Matrix factorization is applied through the research and can be used to show how data flows and compute the computational complexity easily. At the end of this paper, we also present a new fast algorithm for DCT. It enjoys the parallel structure which is simpler for programming and hardware implementation and keeps the same numbers of the additions and multiplications as the fastest algorithms
Comparison of three cytologic preparation methods and immunocytochemistries to distinguish adenocarcinoma cells from reactive mesothelial cells in serous effusion

We assessed whether a panel of seven antibodies is useful in the differentiation of adenocarcinoma cells (ACCs) from reactive mesothelial cells (RMCs) in effusion samples and to determine optimal specimen preparation conditions for immunocytochemical analysis of effusion samples. Immunocytochemistry (ICC) was performed on three types of effusion preparations from the same effusion specimens: ethanol‐fixed smears, ethanol‐fixed cell ‐blocks, and formalin‐fixed cell‐blocks. Commercially available antibodies MOC‐31, Ber‐EP4, CA19‐9, CEA, EMA, CA125, and HBME‐1 were tested on RMCs from four samples of various etiology and 15 samples of adenocarcinoma from various primary sites. Ethanol‐fixed smears showed strong immunoreactivity to all antibodies tested. The immunoreactivity of ethanol‐fixed and formalin‐fixed cell‐blocks was significantly lower with all antibodies except CA19‐9. Smear preparations are more sensitive than cell‐blocks for immunocytochemical study. A panel of antibodies MOC‐31, Ber‐EP4, CA19‐9, and CEA appears to be suitable to distinguish between ACCs and RMCs. Diagn. Cytopathol. 2006;34:6–10. © 2005 Wiley‐Liss, Inc.