Miracle-dz/UniFAR-FTUs huggingface dataset:
Amphiphilic Tobramycin Analogues as Antibacterial and Antifungal Agents

ABSTRACT In this study, we investigated the in vitro antifungal activities, cytotoxicities, and membrane-disruptive actions of amphiphilic tobramycin (TOB) analogues. The antifungal activities were established by determination of MIC values and in time-kill studies. Cytotoxicity was evaluated in mammalian cell lines. The fungal membrane-disruptive action of these analogues was studied by using the membrane-impermeable dye propidium iodide. TOB analogues bearing a linear alkyl chain at their 6″-position in a thioether linkage exhibited chain length-dependent antifungal activities. Analogues with C12 and C14 chains showed promising antifungal activities against tested fungal strains, with MIC values ranging from 1.95 to 62.5 mg/liter and 1.95 to 7.8 mg/liter, respectively. However, C4, C6, and C8 TOB analogues and TOB itself exhibited little to no antifungal activity. Fifty percent inhibitory concentrations (IC50s) for the most potent TOB analogues (C12 and C14) against A549 and Beas 2B cells were 4- to 64-fold and 32- to 64-fold higher, respectively, than their antifungal MIC values against various fungi. Unlike conventional aminoglycoside antibiotics, TOB analogues with alkyl chain lengths of C12 and C14 appear to inhibit fungi by inducing apoptosis and disrupting the fungal membrane as a novel mechanism of action. Amphiphilic TOB analogues showed broad-spectrum antifungal activities with minimal mammalian cell cytotoxicity. This study provides novel lead compounds for the development of antifungal drugs.
Expression of the HPV E7 oncoprotein mimics but does not evoke a p53-dependent cellular DNA damage response pathway.

Acute expression of the human papillomavirus E7 oncoprotein in preimmortal human fibroblasts induces changes in the abundances of multiple cellular regulatory proteins. These alterations include a destabilization of the retinoblastoma tumor suppressor protein pRB, stabilization of the tumor suppressor protein p53, and increases in the level of the cyclin-dependent kinase inhibitor p21(cip1). Since the HPV E7 oncoproteins can interfere with several cell cycle checkpoints and similar alterations in the levels of pRB, p53, and p21(cip1) are also observed in a p53-dependent response to DNA damage, we investigated whether E7 expression triggers this signal transduction pathway. The results demonstrate that E7-mediated destabilization of pRB does not require p53 activity and is independent of the ability of E7 to induce apoptosis. Moreover, E7-mediated increases in p21(cip1) levels are largely p53-independent and involve stabilization of the p21(cip1) protein. In contrast the decreases in pRB expression in response to DNA damage involve transcriptional downregulation of RB gene expression.
Comparative activity of immunofluorescent antibody and complement-fixing antibody in cytomegalovirus infection

Three different tests for detection of antibodies to human cytomegalovirus (CMV), complement fixing with antigen prepared by freeze-thaw disruption (CF-FT) or with antigen prepared by extraction with alkaline glycine buffer (CF-GE) and immunofluorescent staining (FA), were compared in renal transplant recipients and their healthy donors, FA and CF-GE tests yielded positive results at an identical and significantly higher frequency than CF-FT in both donors and recipients. CF-GE and FA performed on donors and recipients predicted all virus shedding post-transplant, whereas CF-FT did not. In the individuals who developed primary infection concurrent with the transplanted kidney, FA developed earlier than other antibodies in about one-half and at the same time in the remainder. In addition, the FA test could be completed more quickly and all sera could be interpreted, which made the FA test more useful than the CF-GE, but both of these tests were clearly superior to CF-FT.
Localization of the human gene for advanced glycosylation end product-specific receptor (AGER) to chromosome 6p21.3.

Advanced glycosylation end products (AGEs), which are the result of nonenzymatic glycosylation and oxidation of proteins exposed to aldoses, are present in plasma and accumulate in the tissues during aging and at an accelerated rate in diabetes as a result of hyperglycemia. A cell surface receptor for AGE (RAGE) with homology to the immunoglobulin superfamily of receptors has been isolated, and both RAGE antigen and mRNA have been identified in the endothelium, vascular smooth muscle cells, cardiac myocytes, monocyte-derived macrophages, and neural tissue. AGEs modulate a variety of biological reactions in tissues, such as monocyte/macrophage migration and production of cytokine-growth factors in mononuclear cells, as well as permeability, growth, and thrombogenicity of endothelia cells. Although AGEs interact specifically with RAGE, it has been suggested that AGEs are accidental and potentially pathogenic ligands for this receptor. In this study, we have used fluorescence in situ hybridization (FISH) to assign the human RAGE (AGER) gene to chromosome 6p21.3. 9 refs., 1 fig.
Assessment of a New Web-Based Sexual Concurrency Measurement Tool for Men Who Have Sex With Men

Background Men who have sex with men (MSM) are the most affected risk group in the United States’ human immunodeficiency virus (HIV) epidemic. Sexual concurrency, the overlapping of partnerships in time, accelerates HIV transmission in populations and has been documented at high levels among MSM. However, concurrency is challenging to measure empirically and variations in assessment techniques used (primarily the date overlap and direct question approaches) and the outcomes derived from them have led to heterogeneity and questionable validity of estimates among MSM and other populations. Objective The aim was to evaluate a novel Web-based and interactive partnership-timing module designed for measuring concurrency among MSM, and to compare outcomes measured by the partnership-timing module to those of typical approaches in an online study of MSM. Methods In an online study of MSM aged ≥18 years, we assessed concurrency by using the direct question method and by gathering the dates of first and last sex, with enhanced programming logic, for each reported partner in the previous 6 months. From these methods, we computed multiple concurrency cumulative prevalence outcomes: direct question, day resolution / date overlap, and month resolution / date overlap including both 1-month ties and excluding ties. We additionally computed variants of the UNAIDS point prevalence outcome. The partnership-timing module was also administered. It uses an interactive month resolution calendar to improve recall and follow-up questions to resolve temporal ambiguities, combines elements of the direct question and date overlap approaches. The agreement between the partnership-timing module and other concurrency outcomes was assessed with percent agreement, kappa statistic (κ), and matched odds ratios at the individual, dyad, and triad levels of analysis. Results Among 2737 MSM who completed the partnership section of the partnership-timing module, 41.07% (1124/2737) of individuals had concurrent partners in the previous 6 months. The partnership-timing module had the highest degree of agreement with the direct question. Agreement was lower with date overlap outcomes (agreement range 79%-81%, κ range .55-.59) and lowest with the UNAIDS outcome at 5 months before interview (65% agreement, κ=.14, 95% CI .12-.16). All agreements declined after excluding individuals with 1 sex partner (always classified as not engaging in concurrency), although the highest agreement was still observed with the direct question technique (81% agreement, κ=.59, 95% CI .55-.63). Similar patterns in agreement were observed with dyad- and triad-level outcomes. Conclusions The partnership-timing module showed strong concurrency detection ability and agreement with previous measures. These levels of agreement were greater than others have reported among previous measures. The partnership-timing module may be well suited to quantifying concurrency among MSM at multiple levels of analysis.
Design, Development and Optimization of a Novel Time and pH-Dependent Colon Targeted Drug Delivery System

The aim of present study was to develop a time- and pH-dependent system for delivering mesalamine to the colon. The system consists of the core tablet of mesalamine which is compression coated with hydroxypropyl methylcellulose (HPMC K4M) (time-dependent factor). This is then coated with pH-dependent polymer Eudragit® L100. The simplex lattice design was adopted to optimize the independent variables i.e. amount of HPMC (X1), dextrose (X2) and polyvinyl pyrollidone (PVP) (X3) and to study their effect on the dependent variables i.e. lag time and time for 50% drug dissolution (t50). The results of the linear interactive model and graphical representation revealed that as the amount of HPMC increases, the lag time and t50 value also increases and as the amount of dextrose and PVP were increased the lag time and t50 value decreases.
Smart gateway diversity techniques and transport‐layer issues for future satellite networks

Next‐generation satellite networks will build on smart gateway diversity (SGD) architectures based on the large capacity offered by high‐frequency bands (Q, V, and W) in order to achieve very high system availability figures (greater than 99%). Despite the numerous studies about system design, little literature has explored the networking problems arising when switching traffic flows from one gateway, subject to feeder link outage, to an alternate one. In this regard, particularly promising multi‐path strategies are represented by multi‐path transmission control protocol (MP‐TCP) and concurrent multipath transfer‐stream control transmission protocol, which are the main aim of this paper along with the management of quality of service (QoS) requirements. This work shows the attractive advantages offered by MP‐TCP in various operative SGD scenarios and also explores how multi‐path strategies can be efficiently combined with QoS‐based scheduling strategies. Copyright © 2015 John Wiley & Sons, Ltd.
Melanomas of the mucosa in the oral cavity and the upper respiratory passages

Thirty‐eight patients with malignant melanoma of the mucosa in the nasal and oral cavity have been treated at the Radium Centres in Århus, Copenhagen and Odense in the years from 1956 to 1978. Twenty cases were localized to the nasal cavity and the nasal sinuses, and 18 cases to the oral cavity and oropharynx. Twenty‐nine patients had local tumors, eight had local lymph node metastases, and one patient had lung metastases. The primary treatment has been surgery, which was radical in 50% of the cases, whereas 14 patients received irradiation and combined treatment. Complete response was seen locally in five of six irradiated nasal tumors and in three of eight oral tumors. Only two patients with nasal and one patient with oral tumors had recurrence later. Active treatment for recurrence has had the result that 10 patients have survived for 2 additional years, and 1 patient for almost 5 additional years. Eight patients lived for more than 5 years; crude survival is 26%.
The Natural History of Soft Tissue Hypertrophy, Bony Hypertrophy, and Nodule Formation in Patients With Untreated Head and Neck Capillary Malformations

BACKGROUND A percentage of patients with capillary malformation (CM) develop soft tissue hypertrophy, bony hypertrophy, and/or nodule formation. OBJECTIVE To determine the incidence, age of onset, anatomic distribution of soft tissue/bony hypertrophy, and nodule formation in patients with untreated CM. METHODS A retrospective medical records review of head and neck CM patients presenting to a tertiary referral center over a 7-year period (2004–2011) was performed. RESULTS Of the 160 patients with CM, 96 demonstrated progression of disease to include either soft tissue/bony hypertrophy or nodule formation. Of these, 87 patients had not received previous treatment and met the inclusion criteria for analysis. On average, soft tissue hypertrophy began at 9 years of age. The V2/maxillary segment was most commonly involved with upper lip hypertrophy being the most prominent. Fourteen percent of the patients also presented with bony hypertrophy, which began at an average age of 15 years. Nodules were present in 38/87 (44%) of patients with an average age of onset of 22 years. CONCLUSION This study demonstrates the nature progression of CM and quantifies the clinical characteristics of hypertrophy and nodule formation with untreated head and neck CM. Early and continuous treatment is recommended in hopes of preventing CM progression.
The relationship of creativity to cortical activation and its operant control.

Abstract On the basis of theories and research on cognitive and perceptual processes, several hypotheses concerning psychophysiological differences between high and low creative subjects were made. Thirty male undergraduates were divided into high and low creative groups on the basis of the Remote Associates Test and a version of the Uses Test. Basal alpha index, alpha blocking in response to stimulus onset, and performance on alpha enhancement and suppression in a feedback situation were measured. High creative subjects exhibited a lower alpha index and a greater decrement in alpha due to stimulus onset. High creatives showed immediate acquisition of control in alpha enhancement trials but no improvement across trials, while low creative subjects showed continual improvements and quickly reached the level of control of high creative subjects. High creatives were much better at alpha suppression than at alpha enhancement.
Profile of the Effective Vocational Agriculture Teacher.

Educators have long desired to discover valid and reliable criteria which could be used to distinguish the effective from the less effective teacher. Research attempting to identify valid and reliable teacher effectiveness criteria has been conducted since the late 1880's. Only during the last two decades has evidence been provided which links some teacher behaviors to student achievement. Reviews of teacher effectiveness research such as those provided by Kash and Borich (1982), The School Improvement Model Project (Blackmer, Brown, Pinckney and Walker, 1981), Manatt (1982), and Medley (1979) have given researchers a solid base upon which to proceed with future teacher effectiveness studies.
Regulated Expression of the Neural Cell Adhesion Molecule L1 by Specific Patterns of Neural Impulses

Development of the mammalian nervous system is regulated by neural impulse activity, but the molecular mechanisms are not well understood. If cell recognition molecules [for example, L1 and the neural cell adhesion molecule (NCAM)] were influenced by specific patterns of impulse activity, cell-cell interactions controlling nervous system structure could be regulated by nervous system function at critical stages of development. Low-frequency electrical pulses delivered to mouse sensory neurons in culture (0.1 hertz for 5 days) down-regulated expression of L1 messenger RNA and protein (but not NCAM). Fasciculation of neurites, adhesion of neuroblastoma cells, and the number of Schwann cells on neurites was reduced after 0.1-hertz stimulation, but higher frequencies or stimulation after synaptogenesis were without effect.
Impact of cyclooxygenase-2 gene expression on tumor invasiveness in a human renal cell carcinoma cell line.

PURPOSE We have previously confirmed that cyclooxygenase-2 (COX-2) is expressed in a human renal cell carcinoma (RCC) cell line and it has an important role in cell tumorigenesis and angiogenesis. In the current study we evaluated the impact on cell adhesion and tumor invasiveness in human RCC cell lines by transfection of COX-2 sense and antisense cDNAs. MATERIALS AND METHODS A human RCC cell line that expresses COX-2 was transfected with COX-2 sense or antisense cDNA. E-cadherin expression in parental cells of OS-RC-2 and transfectants was detected by real-time polymerase chain reaction and Western blotting. The expression of beta-catenin was detected by Western blotting. Zymography was used to detect gelatinase activity. CD44 expression in parental cells and transfectants was detected by fluorescence activated cell sorting. Cell adhesion was detected by adhesion assay and cell invasive ability was detected by invasion assay. RESULTS E-cadherin expression was increased in antisense transfectants and decreased in sense transfectants compared with parental cells at the mRNA and protein levels. However, obvious consistent changes in beta-catenin expression could not be confirmed in parental cells and transfectants, nor were there any significant differences in gelatinase activity in parental cells and transfectants. CD44 expression was increased in sense transfectants and decreased in antisense transfectants compared with parental cells. Adhesion to hyaluronan coated wells was significantly enhanced in sense transfectants and inhibited in antisense transfectants compared with parental cells. Compared with parental cells invasive ability was significantly increased in sense transfectants and decreased in antisense transfectants. CONCLUSIONS The results demonstrate that COX-2 expression has a crucial role in cell invasion ability and the suppression of COX-2 expression might regulate adhesion molecule expression and inhibit invasive ability in the RCC cell line OS-RC-2.
High Incidence of Severe Influenza among Individuals over 50 Years of Age

ABSTRACT Age-specific epidemiological data on asymptomatic, symptomatic, and severe infections are essential for public health policies on combating influenza. In this study, we incorporated data on microbiologically confirmed infections and seroprevalence to comprehensively describe the epidemiology of pandemic H1N1 2009 influenza. Seroprevalence was determined from 1,795 random serum samples collected in our hospital in January 2007 (before the first wave of the pandemic) and March 2010 (after the second wave). Data on microbiologically confirmed infection and severe cases were obtained from the Centre for Health Protection in Hong Kong. Severe cases were most common in the 51- to 60-year-old age group. The microbiologically confirmed incidence rate was highest for children aged ≤10 years and dropped sharply for the adult population (ρ = −1.0; P < 0.01), but the incidence rate for severe disease was highest for the 51- to 60-year-old age group. For the 51- to 60-year-old age group, the seroprevalence was similar to that for the younger age groups, but the proportion of severe cases relative to seroprevalence was significantly higher than that for 11- to 50-year-old age groups. As judged from the percentage of specimens positive for other respiratory viruses compared with that for pandemic H1N1 virus, the impact of symptomatic disease due to pandemic H1N1 virus was higher than that for other respiratory viruses in people aged ≤50 years. In conclusion, the 51- to 60-year-old age group, which had the highest overall incidence and the highest rate of severe disease but is currently not considered by the World Health Organization to be an at-risk group, should be prioritized for influenza vaccination in areas where universal influenza vaccination is not practiced.
Immune complexes inhibit apoptosis of chronic lymphocytic leukaemia B cells

In the present study we examined the effect of immune complexes (IC) on the survival of chronic lymphocytic leukaemia (B‐CLL) B cells. Our results showed that either precipitating IC (pIC), Ab‐coated erythrocytes (E‐IgG) or heat‐aggregated IgG (aIgG) significantly inhibited spontaneous apoptosis of B‐CLL cells, as well as that induced by fludarabine, chlorambucil or dexamethasone. After depletion of T lymphocytes, monocytes and NK cells, incubation with IC was no longer able to delay B‐CLL cells apoptosis, suggesting that prevention of apoptosis depends on IC interaction with accessory leucocytes. The release of IFNγ by non‐malignant cells upon activation with IC was responsible, to some extent, for IC effects as shown by the fact that neutralizing anti‐IFNγ MoAb partially prevented their ability to inhibit B‐CLL cells apoptosis. The observation that treatment with IC resulted in increased expression of HLA‐DR on B‐CLL cells suggests that inhibition of apoptosis is associated with cellular activation.
Advance Directives in the Context of Uncertain Prognosis for Residents of Nursing Homes

This report documents the findings of a mixed-methods study focused on the advanced directives of 182 residents of three LTC facilities in southern Ontario, Canada. Although almost all had a completed advance directive within 3 months of death, most did not have a palliative designation or directive until a few days before they died. Each facility's written Progress Notes revealed staff members usually sought additional confirmation of care preferences from residents' substitute decision-makers within a few days of the death. It was thus common for advance directives to change from a more interventionist approach to the least interventionist approach near death. This change indicates that the meaning and significance of advance care planning and resulting advance directives must be considered in light of the processes and temporal factors involved in their completion and use within this distinct population. The relational nature of advance care planning and concern about ageism as a factor for withholding or withdrawing life support for LTC residents are considered as possible explanatory factors. These findings and their implications are described in relation to end-of-life care policies and practices in LTC facilities.