Miracle-dz/UniFAR-FTUs huggingface dataset:
Major histocompatibility complex class I presentation of ovalbumin peptide 257–264 from exogenous sources: protein context influences the degree of TAP‐independent presentation

Peritoneal macrophages from C57BL/6 mice process antigens from bacteria or coated on polystyrene beads for presentation by major histocompatibility complex (MHC) class I molecules. To investigate this antigen processing pathway, peritoneal macrophages from homozygous TAP1−/− mice, which lack the transporter associated with antigen processing (TAP) and are defective in presenting endogenous antigens on MHC class I, were used. TAP1−/− or C57BL/6 macrophages were co‐incubated with either bacteria or polystyrene beads containing the 257–264 epitope from ovalbumin [OVA(257–264)], which binds the mouse class I molecule Kb. The source of the OVA(257–264) epitope was either the Crl‐OVA(257–264) (Crl‐OVA) fusion protein, the maltose binding protein (MBP)‐Crl‐OVA fusion protein, native OVA or bacterial recombinant OVA (rOVA); Crl‐OVA, MBP‐Crl‐OVA and rOVA were each expressed in bacteria, and Crl‐OVA and MBP‐Crl‐OVA purified from bacterial lysates and native egg OVA were coated onto polystyrene beads. The data reveal that peritoneal macrophages from C57BL/6 and TAP1−/− mice can process bacteria expressing Crl‐OVA, MBP‐Crl‐OVA and rOVA as well as beads coated with native OVA, purified Crl‐OVA, and purified MBP‐Crl‐OVA and present OVA(257–264) for recognition by OVA(257–264)/Kb‐specific T hybridoma cells, albeit with different relative processing efficiencies. The processing efficiency of TAP1−/− macrophages co‐incubated with bacteria or beads containing Crl‐OVA or MBP‐Crl‐OVA was reduced approximately three to five times compared to C57BL/6 macrophages, but OVA(257–264) was presented 100 times less efficiently when the source of OVA(257–264) was full‐length OVA. Chloroquine inhibition studies showed a differential requirement for acidic compartments in C57BL/6 versus TAP1−/− macrophages, which also depended upon the source of the OVA (257–264) epitope (Crl‐OVA versus full‐length OVA). These data suggest that TAP1−/− and C57BL/6 macrophages may process Crl‐OVA and full‐length OVA in different cellular compartments and that the protein context of the OVA(257–264) epitope influences the extent of TAP‐independent processing for MHC class I presentation.
Non-Member Participation in Political Parties: A Framework for Analysis and Selected Empirical Examples from Scandinavia

Non-member participants have become an increasingly important resource that helps modern parties sustain a representational bond between citizens and the state. However, the emerging literature on non-member participation still lacks a theoretical–analytical framework for the analysis of non-member participation that allows for both the study of individual parties and comparative studies of non-member participation. Only with such a framework at hand to measure the actual extent of non-member participation may we begin to gauge fully the potential of non-members to aid parties in sustaining a representational bond between citizens and the state. This article therefore develops a theoretically informed framework for assessing parties' permission of non-member participation that comprises five categories: No, Basic, Midrange, Full participation and finally Full membership, which denotes the threshold where non-members effectively become members. While systematic empirical analysis is beyond the scope of the article, evidence from seven Scandinavian parties exemplifies the framework's applicability.
Effect of rapid viral diagnosis on the management of children hospitalized with lower respiratory tract infection.

BACKGROUND Although rapid viral tests are commonly used in children with lower respiratory tract infection, their effect on patient management has not been studied. OBJECTIVES To examine how physicians utilize an enzyme immunoassay for respiratory syncytial virus (RSV EIA) and a centrifugation-enhanced cellular immunofluorescence assay for multiple viral pathogens [viral respiratory panel (VRP)] in children hospitalized with respiratory illness; to determine the effect of testing on length of stay, antibiotic use and costs; and to determine physician attitudes toward RSV testing. DESIGN AND SETTING Prospective study and survey at a large children's hospital. PATIENTS Previously healthy children < 24 months of age consecutively admitted between January 1 and February 11, 1995, with symptoms of lower respiratory tract infection. RESULTS Of 200 patients 160 were tested by RSV EIA; 92 were positive and 68 were negative. Tested children were younger, more tachypneic and more likely to require oxygen than those not tested. Overall the length of stay was similar in RSV-positive and -negative patients. Although equal proportions of each group were given antibiotic therapy, RSV-positive children received antibiotic therapy for fewer days than RSV-negative children (median 2 vs. 3 days; P = 0.0387). However, a crude cost analysis did not support a strategy of testing all bronchiolitis patients for RSV. Sixty-five of the 68 RSV-negative children were tested for RSV and other pathogens by VRP. In 55 cases the results were not available until after patient discharge and could not have influenced their management. One hundred three physicians caring for children in the study were surveyed. Of 75 respondents almost all thought that RSV EIA results influenced their management of patients and were important to parents. CONCLUSIONS Most children hospitalized with symptoms of lower respiratory tract infection were tested for viral pathogens. The VRP provided little clinically useful information. In contrast RSV EIA results may have been used by clinicians to make antibiotic decisions. Physicians felt that rapid testing for RSV was important.
“Complex” Attention-Deficit Hyperactivity Disorder, More Norm Than Exception? Diagnoses and Comorbidities in a Developmental Clinic

Objective: Current recommendations for evaluation and diagnosis of attention-deficit hyperactivity disorder (ADHD) are meant for primary care settings and may not adequately address the needs of children seen in subspecialty developmental-behavioral pediatric settings who may have higher rates of comorbid developmental, learning, and psychiatric disorders. The authors sought to characterize the diagnostic complexity of school-aged children diagnosed with ADHD after comprehensive multidisciplinary evaluation in a subspecialty developmental-behavioral pediatric clinic. Methods: The authors conducted a retrospective medical record review of 144 patients aged 7 to 11 years who were consecutively evaluated by an interdisciplinary team (developmental-behavioral pediatrician, psychologist, educator) in a school-age clinic within a developmental-behavioral pediatrics tertiary care center from January 1, 2009 to December 31, 2009. Results: After comprehensive evaluation, rates of ADHD diagnosis increased from 32.6% (n = 47) preevaluation to 54.2% (n = 78) postevaluation (p < .0001). Rates of learning disorders among children receiving a final diagnosis of ADHD increased from 2.6% (n = 2) preevaluation to 50% (n = 39) postevaluation. (p < .0001). Among children receiving a final diagnosis of ADHD, 73.1% (n = 57) were diagnosed with at least 1 comorbid psychiatric, developmental, or learning disorder. Conclusions: Among school-aged children diagnosed with ADHD in a developmental-behavioral pediatric subspecialty setting, a comprehensive evaluation including developmental, neuropsychological, and educational assessments yielded high rates of comorbid psychiatric, developmental, and learning disorders. This supports the need to provide comprehensive interdisciplinary assessment for such children to ensure the identification and treatment of not only the core symptoms of ADHD but also the comorbidities that may otherwise go unrecognized and therefore not optimally treated.
Expression of functional Toll-like receptors and nucleotide-binding oligomerization domain proteins in murine cementoblasts and their upregulation during cell differentiation.

BACKGROUND AND OBJECTIVE While the primary role of cementoblasts is to synthesize the components of cementum, we have reported that immortalized murine cementoblasts (OCCM-30) express functional Toll-like receptor (TLR)-2 and -4, and these receptors are involved in the alteration of gene expression associated with cementum formation and in the upregulation of osteoclastogenesis-associated molecules, such as receptor activator of nuclear factor-kappaB (NF-kappaB) ligand. We hypothesized that cementoblasts express a wide range of pattern recognition receptors in a manner comparable to osteoblasts, which are known to express various functional TLRs and nucleotide-binding oligomerization domain (NOD) proteins. MATERIAL AND METHODS Murine cementoblasts and pre-osteoblasts were used. The gene and protein levels of TLRs/NODs were analyzed using real-time polymerase chain reaction and flow cytometry. Interleukin-6 (IL-6) and activated NF-kappaB were measured using enzyme-linked immunosorbent assay. RESULTS The expressions of TLR-1, -2, -4, -6 and -9, CD14, NOD-1 and -2 were detected in cementoblasts and were upregulated upon differentiation induced by ascorbic acid. Similar patterns were observed in the mouse MC3T3-E1 osteoblast cell line. Synthetic ligands, Pam3CSK4 (TLR-1/2 agonist), Pam2CGDPKHPKSF (TLR-2/6 agonist), lipid A (TLR4 agonist), CpG DNA (TLR-9 agonist), FK565 (NOD1 agonist) and muramyldipeptide (NOD2 agonist), effectively induced NF-kappaB activation in cementoblasts and/or ascorbic acid-treated cementoblasts. Furthermore, these ligands induced IL-6 production in a NF-kappaB-dependent manner in cementoblasts and/or ascorbic acid-treated cementoblasts. CONCLUSION These results indicate that cementoblasts possess functional TLR and NOD signaling systems and have a similar capacity to osteoblasts in responding to a wide variety of pathogens.
Expression of Stress Response Protein Grp78 Is Associated with the Development of Castration-Resistant Prostate Cancer

Background: Induction of molecular chaperone Grp78 (78-kDa glucose-regulated protein) occurs in stress conditions that often characterize tumor microenvironments. We investigated the role of Grp78 in prostate cancer progression and the development of castration resistance, where cancer cells continue to survive despite the stress of an androgen-starved environment. Experimental Design: Immunohistochemistry was done to examine Grp78 expression in 219 prostate cancers from patients with pathologic stage T3N0M0 disease [androgen ablation naive (untreated) and androgen ablation exposed (treated)] and castration-resistant prostate cancer. Classification of tumors was based on intensity of Grp78 cytoplasmic immunoreactivity and percentage of immunoreactive tumor cells. The associations of Grp78 expression with prostate cancer recurrence (clinical and/or serum prostate-specific antigen) and survival were examined in the untreated stage T3N0M0 group. Grp78 expression was also analyzed in the androgen-dependent LNCaP and castration-resistant C42B cell lines. Results: The percentage of tumor cells expressing Grp78 was strongly associated with castration-resistant status (P = 0.005). Increased Grp78 expression was consistently associated with greater risk of prostate cancer recurrence and worse overall survival in patients who had not undergone prior hormonal manipulation. Grp78 expression was also increased in the castration-resistant LNCaP-derived cell line C42B and in LNCaP cells grown in androgen-deprived conditions compared with LNCaP cells grown in androgen-rich media. Conclusion: Our findings show that up-regulation of Grp78 is associated with the development of castration resistance, possibly in part by augmenting cell survival as previously suggested, and may serve as an important prognostic indicator of recurrence in a subset of patients with T3N0M0 disease.
VAD chemotherapy for refractory multiple myeloma

Thirty‐four patients with refractory multiple myeloma were treated with 4‐d continuous infusions of vincristine and adriamycin in combination with 4‐d pulsed high‐dose dexamethasone (VAD). Of 31 evaluable patients, 16 entered a complete remission (50%) and three a partial remission (10%). No difference in response rate was observed between primary refractory and relapsed patients. The median response duration was 9 months and the median survival of the responding patients was 12 months versus 4 months for the non‐responders. Ten patients have currently survived longer than 360 d, of which six are stable in complete remission without therapy. All responding patients showed a remarkable improvement of their performance status and 70% of these patients became pain‐free. Bacterial infection was the major complication and was probably due to the intensive corticosteroid programme. Severe myelosuppression was rarely observed. Irrespective of the response to VAD, a high β‐microglobulin of 4 μg/ml or more was a bad prognostic parameter. As early relapses were seen especially in this group of patients, in the patients with a plasma‐cell LI% of 3 or more, and in patients with previous anthracyclin treatment, early consolidation, with, for instance, high dose melphalan, might improve the prognosis for these patients.
Voluntary Informed Consent in Research and Clinical Care: An Update

Informed consent is important: in research, it allows subjects to make an informed and voluntary choice to participate—or refuse to participate—in a project where they will be asked to take risks for the benefit of others. In both research and clinical care, informed consent represents a permission to intervene on a person's private sphere. The elements of informed consent are usually described as disclosure, understanding, decision‐making capacity, and voluntariness. Each poses distinct difficulties, and can be amenable to improvements. However, research on the quality of informed consent and on strategies intended to improve it have only become the object of research relatively recently. In this article, we describe some results of this research, and outline how they can be relevant to informed consent in research and clinical care. Although much of the data suffers from limitations, it does suggest that disclosure has improved, but is still uneven, comprehension is often poor, for both patients and research subjects. Moreover, trust is a motivating factor for research participation, and thus we run risks if we allow false expectations and prove ourselves unworthy of this trust. Although improving consent forms does not have a clear effect on understanding, improving the consent process may help. Finally, better information may decrease anxiety and seems to have at most a small negative effect on research recruitment.
Reflective Journal Writing and the First-Year Experience

In recent years, great emphasis has been placed on student success and retention in higher education. To address this issue, many universities’ strategic retention programs include first-year seminars. A variety of pedagogical strategies have been employed in these seminars to help students succeed personally, socially and academically. This article reports findings from a qualitative study that explored the teaching/learning outcomes and benefits derived from the experience of reflective journal writing during a first-year seminar from the perspectives of students and the instructor. The findings document how journaling in a first-year seminar can be used to support institutional action to improve the quality of the undergraduate experience and student success.
The MurC Ligase Essential for Peptidoglycan Biosynthesis Is Regulated by the Serine/Threonine Protein Kinase PknA in Corynebacterium glutamicum*

The Mur ligases play an essential role in the biosynthesis of bacterial cell-wall peptidoglycan and thus represent attractive targets for the design of novel antibacterials. These enzymes catalyze the stepwise formation of the peptide moiety of the peptidoglycan disaccharide peptide monomer unit. MurC is responsible of the addition of the first residue (l-alanine) onto the nucleotide precursor UDP-MurNAc. Phosphorylation of proteins by Ser/Thr protein kinases has recently emerged as a major physiological mechanism of regulation in prokaryotes. Herein, the hypothesis of a phosphorylation-dependent mechanism of regulation of the MurC activity was investigated in Corynebacterium glutamicum. We showed that MurC was phosphorylated in vitro by the PknA protein kinase. An analysis of the phosphoamino acid content indicated that phosphorylation exclusively occurred on threonine residues. Six phosphoacceptor residues were identified by mass spectrometry analysis, and we confirmed that mutagenesis to alanine residues totally abolished PknA-dependent phosphorylation of MurC. In vitro and in vivo ligase activity assays showed that the catalytic activity of MurC was impaired following mutation of these threonine residues. Further in vitro assays revealed that the activity of the MurC-phosphorylated isoform was severely decreased compared with the non-phosphorylated protein. To our knowledge, this is the first demonstration of a MurC ligase phosphorylation in vitro. The finding that phosphorylation is correlated with a decrease in MurC enzymatic activity could have significant consequences in the regulation of peptidoglycan biosynthesis.
Spectrum of Endoscopic Findings in Patients of Upper Gastrointestinal Bleeding at a Tertiary Care Hospital

Background & aims Upper gastrointestinal bleeding (UGIB) is a common medical emergency that results in high patient morbidity and mortality. There are numerous causes of UGIB. The aim of our study was to evaluate the endoscopic findings in patients of UGIB in this part of the world. Methods This retrospective study was conducted at the Department of Gastroenterology Nishtar Medical University & Hospital Multan from June 2018 to March 2019. Record of all patients undergoing esophagogastroduodenoscopy (EGD) for evaluation of UGIB was reviewed. Data was entered and analyzed using SPSS version 20 (IBM, Armonk, NY, USA). Results Record of 730 (464 male and 266 females) patients undergoing EGD for UGIB was reviewed. Mean age of study population was 49.38 years with standard deviation of 14.86 years. Age of the youngest patient was 14 years while the oldest patient was 99 years of age. More than half of the patients (53%) belonged to the 41-60 years age group. The most common endoscopic finding was esophageal varices in 371 (50.8%) patients, followed by gastropathy (114, 15.6%), gastritis (68, 9.3%), cardio-fundal varices (58, 7.9%) and duodenal ulcer (26, 3.6%). Esophageal varices, gastritis, duodenal ulcers and gastric carcinomas were more likely to be found in male UGIB patients as compared to female patients (p = 0.039). Gastropathy, esophageal ulcer and gastric ulcer were more likely to be found in female UGIB patients. Esophageal varices and cardio-fundal varices were more likely to be found in UGIB patients from middle age group (p = 0.000). Whereas gastritis, duodenal ulcer, gastric erosions and duodenitis were more likely to be found in older (>60 years) UGIB patients (p = 0.000). Conclusion UGIB was more likely to occur in male gender. In our study, bleeding from esophageal varices was the most important cause of UGIB in this part of the world and bleeding from duodenal ulcer was quite uncommon as compared to the western world. Variceal bleeding had a significant association with male gender and middle age group patients. While duodenal ulcer bleed had a significant association with older age.
Deficiency of T-regulatory cells exaggerates angiotensin II-induced microvascular injury by enhancing immune responses

Aims: T-regulatory lymphocyte (Treg) adoptive transfer prevented angiotensin (Ang) II-induced hypertension and microvascular injury. Scurfy mice are deficient in Treg because of a mutation in the transcription factor forkhead box P3 (Foxp3) gene. Enhanced Ang II effects in the absence of Treg would unambiguously demonstrate their vascular protective role. We hypothesized that adoptive transfer of Scurfy vs. wild-type T cells will exacerbate Ang II-induced microvascular damage in T and B-cell-deficient recombination-activating gene 1 (Rag1) knockout mice. Methods and results: Rag1 knockout mice were injected with vehicle, 107 T cells from wild-type or Scurfy mice or 106 wild-type Treg alone or in combination with Scurfy T cells, and then infused or not with Ang II (490 ng/kg per min, subcutaneous) for 14 days. Ang II increased SBP in all the groups, but DBP only in wild-type and Scurfy T-cell groups. Ang II-induced endothelial dysfunction and oxidative stress in perivascular adipose tissue (PVAT) of mesenteric arteries of the wild-type T-cell group, whereas these were exaggerated in the Scurfy T-cell group. Ang II enhanced microvascular remodeling and stiffness in vehicle and Scurfy T-cell groups. Ang II increased monocyte chemotactic protein-1 expression in the vascular wall and PVAT, monocyte/macrophage infiltration and proinflammatory polarization in PVAT and the renal cortex, and T-cell infiltration in the renal cortex only in the Scurfy T-cell group. Treg coinjection in the vehicle and Scurfy T-cell groups prevented or reduced the effects of Ang II. Conclusion: FOXP3+ Treg deficiency exaggerates Ang II-induced microvascular injury by modulating innate and adaptive immune responses.
Benchmarking sustainability performance: the next step in building sustainable business models

Developing sustainable business models incorporating effects on people, profit, and planet is becoming an increasingly important strategic issue. Benchmarking with peer companies can assist a company in setting goals of improving its performance. As such, developing a methodology for effectively benchmarking sustainable business practices is an important step in the evolution of sustainability management. However, a company's sustainability performance is composed of many elements that may involve difficult tradeoffs, and its performance may vary over time. In this paper, we propose a data-driven approach of innovatively adapting statistical process control charts, conventionally used in quality control, to simultaneously compare multiple performance measures and analyze variation in both trend and performance among companies in a given industry. We apply this approach to benchmarking the sustainability performance of companies in the US utility industry and demonstrate it is robust and reliable for benchmarking the performance of companies in virtually all industries. Copyright © 2016 John Wiley & Sons, Ltd.