Miracle-dz/UniFAR-FTUs huggingface dataset:
Activation of a dendritic cell–T cell axis by Ad5 immune complexes creates an improved environment for replication of HIV in T cells

The STEP HIV vaccine trial, which evaluated a replication-defective adenovirus type 5 (Ad5) vector vaccine, was recently stopped. The reasons for this included lack of efficacy of the vaccine and a twofold increase in the incidence of HIV acquisition among vaccinated recipients with increased Ad5-neutralizing antibody titers compared with placebo recipients. To model the events that might be occurring in vivo, the effect on dendritic cells (DCs) of Ad5 vector alone or treated with neutralizing antiserum (Ad5 immune complexes [IC]) was compared. Ad5 IC induced more notable DC maturation, as indicated by increased CD86 expression, decreased endocytosis, and production of tumor necrosis factor and type I interferons. We found that DC stimulation by Ad5 IC was mediated by the Fcγ receptor IIa and Toll-like receptor 9 interactions. DCs treated with Ad5 IC also induced significantly higher stimulation of Ad5-specific CD8 T cells equipped with cytolytic machinery. In contrast to Ad5 vectors alone, Ad5 IC caused significantly enhanced HIV infection in DC–T cell cocultures. The present results indicate that Ad5 IC activates a DC–T cell axis that, together with the possible persistence of the Ad5 vaccine in seropositive individuals, may set up a permissive environment for HIV-1 infection, which could account for the increased acquisition of HIV-1 infection among Ad5 seropositive vaccine recipients.
The clinical significance of small copy number variants in neurodevelopmental disorders

Background Despite abundant evidence for pathogenicity of large copy number variants (CNVs) in neurodevelopmental disorders (NDDs), the individual significance of genome-wide rare CNVs <500 kb has not been well elucidated in a clinical context. Methods By high-resolution chromosomal microarray analysis, we investigated the clinical significance of all rare non-polymorphic exonic CNVs sizing 1–500 kb in a cohort of 714 patients with undiagnosed NDDs. Results We detected 96 rare CNVs <500 kb affecting coding regions, of which 58 (60.4%) were confirmed. 6 of 14 confirmed de novo, one of two homozygous and four heterozygous inherited CNVs affected the known microdeletion regions 17q21.31, 16p11.2 and 2p21 or OMIM morbid genes (CASK, CREBBP, PAFAH1B1, SATB2; AUTS2, NRXN3, GRM8). Two further de novo CNVs affecting single genes (MED13L, CTNND2) were instrumental in delineating novel recurrent conditions. For the first time, we here report exonic deletions of CTNND2 causing low normal IQ with learning difficulties with or without autism spectrum disorder. Additionally, we discovered a homozygous out-of-frame deletion of ACOT7 associated with features comparable to the published mouse model. In total, 24.1% of the confirmed small CNVs were categorised as pathogenic or likely pathogenic (median size 130 kb), 17.2% as likely benign, 3.4% represented incidental findings and 55.2% remained unclear. Conclusions These results verify the diagnostic relevance of genome-wide rare CNVs <500 kb, which were found pathogenic in ∼2% (14/714) of cases (1.1% de novo, 0.3% homozygous, 0.6% inherited) and highlight their inherent potential for discovery of new conditions.
Design of a Robust Active Queue Management Altorithm Based on Adaptive Neuron Pid

The paper designs a new AQM algorithm called ANPID, which applies the theory of adaptive linear neuron to AQM controller in congestion control. ANPID can adjust the queue length to the desired value, revise its weights online by LMS learning rule, and tune the coefficients of PID controller. The weighted factors are regulated continuously according to the system errors, as well as eliminate the sensitivity to the parameter. The result of simulation shows that the presented ANPID controller can effectively avoid network congestion, stabilize queue length to the desire value quickly, and have good performances in respect to robustness to variation of system parameters
Ethanol pretreatment enhances NMDA excitotoxicity in biogenic amine neurons: protection by brain derived neurotrophic factor.

BACKGROUND Biogenic amine neurons are involved in a number of mental diseases including addiction and alcohol dependence. Because chronic ethanol is known to cause supersensitivity to NMDA excitotoxicity in cortical neurons, this study sought to determine the effect of ethanol treatment on biogenic amine neurons. METHODS To determine if ethanol exposure alters the vitality of biogenic amine neurons, cultures were prepared from E14 rat brain. After 24 hr in culture, cells were divided into control or ethanol (100 mM) treatment groups, cultured an additional 48 hr, and then half of them exposed to NMDA for 25 min. The NMDA was then removed and cells cultured in fresh media for an additional 24 hr to allow for excitotoxic delayed neuronal death. Cultures were then stained with antibodies to 5-hydroxytryptamine or tyrosine hydroxylase to identify serotonin and dopamine neurons, respectively. Cultures were analyzed for cell number and neuronal morphology. RESULTS Ethanol treatment alone had no effect on biogenic amine cell number, soma area, number of neurites, or terminal segments, although the field area of dopamine neurons was decreased. Treatment with 30 microM NMDA had no effect on controls, but significantly decreased dopamine neurons in ethanol-treated cultures as well as reduced soma area, field area, number of neurites and number of terminal segments. Treatment with higher concentrations of NMDA reduced dopamine and serotonin neurons in both controls and ethanol-treated groups, and ethanol treatment significantly enhanced NMDA excitotoxic effects. Treatment with Brain Derived Neurotrophic Factor (BDNF) prevented ethanol sensitization to NMDA excitotoxicity. CONCLUSIONS These studies suggest that ethanol treatment sensitizes biogenic amine neurons to excitotoxic insults. Ethanol sensitization of biogenic amine neurons to insults could contribute to the development of mental disease.
METAPHORS, NARRATIVE AND ‘TRUTH’: SOUTH AFRICA'S TRC

THE INTERNATIONAL EDITION OF the draft report of the Truth and Reconciliation Commission of South Africa (TRC) documents the infringement of human rights in apartheid South Africa through the testimony of both victims and perpetrators. The documentation of the arbitrary, shocking and violent nature of apartheid in all areas of South African life in government and the private sector, in urban and rural areas stands, according to the Report, in contradistinction to the 'lies and deception that were at the heart of apartheid'. Narrative truths (discussed below) imply an individual narrator and this fact alone guarantees that, in any future contemplation of the consequences of apartheid as a system, individual acts of oppression and individual oppressed people cannot be ignored. The fact that over 20,000 black people told their stories illustrates the value that was placed upon the opportunity to explore personal experiences in public as well as upon their altered relationship with the State. Archbishop Tutu, in his autobiographical book written out of his experiences of the TRC and of the indignities and absurdities of apartheid No Future Without Forgiveness puts the case against collective amnesia in the following way: 'Accepting that option would have victimised the victims of apartheid a second time round. It would have meant denying their experience, a vital part of their identity' (p. 32). Tutu's view on dealing with the past, influenced by the consequences of the Anglo-Boer War, is that 'the past, far from disappearing or lying down and being quiet, is embarrassingly persistent, and will return and haunt us unless it has been dealt with adequately' (p. 31). He also states that, as a result of the work
Research Issues

The purpose of this article is to review the state of the science of nursing research on Therapeutic Touch and imagery framed within a nursing theoretical model or theory. The criteria for review were nursing studies on Therapeutic Touch and imagery published in peer-reviewed journals between 1990 and 2000. Studies were critiqued on the use of a nursing theoretical model or theory, not on the basis of study design or findings. An increasing number of consumers are seeking health patterning modalities that are noninvasive and self-healing. The nursing profession’s phenomenon of concern is human beings and their environment. In their quest to promote human betterment, nurses have been creative and innovative in developing and using health patterning, integrative modalities in practice. Barrett (1998) defined health patterning as the process of assisting people with their knowing participation in change. Health patterning facilitates power enhancement. Health patterning modalities, such as Therapeutic Touch and imagery, are tools that operationalize the health patterning process. Rogers (1990), envisioning the health changes that will occur in the future, stated that “the practice of nursing will be characterized primarily by non-invasive modalities” (p. 10). Therapeutic Touch and imagery are two modalities used by many nurses in their practice. As the demand for the use of health patterning modalities increases, there is also a demand, as well as a need, to advance the science of nursing by conducting research on these modalities. It is the authors’ contention that if research is to advance nursing as a basic science, it Editor’s Note: Send manuscripts concerning research using nursing theories and models, new research methods, or research issues pertinent to nursing’s epistemology to Violet M. Malinski, RN, PhD, Associate Professor, Hunter-Bellevue School of Nursing, Hunter College, City University of New York, 425 E. 25th Street, Box 945, New York, NY 10010-2590; work phone: (212) 481-5102; fax: (212) 481-4427; home phone: (914) 793-4145; E-mail: ViMM@ aol.com
In Vitro Synthesis of Cross-linked Murein and Its Attachment to Sacculi by PBP1A from Escherichia coli*

The penicillin-binding protein (PBP) 1A is a major murein (peptidoglycan) synthase in Escherichia coli. The murein synthesis activity of PBP1A was studied in vitro with radioactive lipid II substrate. PBP1A produced murein glycan strands by transglycosylation and formed peptide cross-links by transpeptidation. Time course experiments revealed that PBP1A, unlike PBP1B, required the presence of polymerized glycan strands carrying monomeric peptides for cross-linking activity. PBP1A was capable of attaching nascent murein synthesized from radioactive lipid II to nonlabeled murein sacculi. The attachment of the new material occurred by transpeptidation reactions in which monomeric triand tetrapeptides in the sacculi were the acceptors.
Assessing the need for a protocol in monitoring weight loss and nutritional status in orthognathic surgery based on patients experiences

Background To investigate retrospectively the orthognathic surgery (OGS) patients experience in weight loss and the influence of gender, age, duration of the surgical procedure, length of hospital stay, location of surgery and use of intermaxillary fixation (IMF) or without IMF on postoperative weight loss. Material and Methods A total of 4487 patients treated by OGS where all patients visited the outpatient clinic one, three and six weeks after the surgical procedure. After six weeks, patients filled out a questionnaire in which weight loss was addressed. The patients were asked to give an estimate of their experiences weight loss. The population was first divided in two groups weight loss and no weight loss. Results In the weight loss group there is no significant difference in weight loss between patients with IMF and patients without IMF. In the weight loss group there were significantly more females then males. Further, in the subgroup IMF the operation time was significantly longer compared with the subgroup without IMF. The other parameters including age and hospital stay were not different in the groups. Conclusions IMF in orthognathic treatment does not result in a difference self-reported loss of body weight compared to patients without IMF. Treatment protocols should include pre- and post-operative dietician consultations and possible indications for medical nutrition and vitamins. Key words:Assessing, protocol, weight loss, experiences, orthognathic surgery.
The fissure: interlobar collateral ventilation and implications for endoscopic therapy in emphysema

In patients with severe emphysema, bronchoscopic lung volume reduction using one-way valves is a promising therapeutic option to improve lung function and quality of life. The goal of this treatment is to achieve a complete lobar atelectasis. In a significant proportion of patients, this atelectasis cannot be achieved due to interlobar collateral ventilation. This collateral ventilation is generated through incomplete lobar fissures. Therefore, only patients with complete fissures and no collateral ventilation can be selected for endobronchial therapy with one-way valves. Incomplete fissures are very common and exhibit a great variation in anatomy. The reported prevalence is 17%–85% for the right major fissure, 19%–74% for the left major fissure, and 20%–90% for the minor fissure. There are several methods of measuring or predicting the presence of collateral ventilation, with computed tomography (CT)-fissure analysis and the Chartis measurement being the most important. CT-fissure analysis is an indirect method to measure the completeness of fissures as a surrogate for collateral ventilation. The Chartis system is an endobronchial method to directly measure the presence of collateral ventilation. Both methods have unique value, and the combination of both can accurately predict the treatment response to the bronchoscopic placement of endobronchial valves. This review provides an in-depth view of lung fissure and collateral ventilation to help understand its importance in selecting the appropriate patients for new emphysema treatments and thus avoid useless treatment in unsuitable patients.
Communicative efficiency in severe aphasia

The communicative efficiency of three severely aphasic clients was assessed with a 10-item message exchange task. The three clients demonstrated distinctively different communication profiles. Client M.D. communicated verbally; B.D. relied on drawing and writing; J.S. employed elaborate gestures. Three groups of eight raters assessed the communicative efficiency (CE) and degree of communicative burden (CB) assumed by the partner for each message exchange using a visual analogue scale. One group was aware of the content of the message exchanges (Full Content); a second received partial information about message contents in the form of a cue (Partial Content); a third received no information (No Content). Mean ratings of CE and CB differed significantly for the three clients. Many of these differences can be explained in relation to the client's severity of aphasia and abilities to effectively employ output modalities available to them to convey messages. CE ratings were higher and CB ratings were lower in the No Content viewing condition than the Partial and Full Content conditions. Several possible explanations are offered for this surprising result.
Adaptive Environment Supporting Understanding and Learning from Texts in Informatics (ADULT)

The aim of this paper is to present the design of an adaptive environment supporting understanding and learning from texts in informatics (ADULT). It is a three-stage system. In the first stage examines studentspsila background knowledge using a questionnaire concerning the knowledge in the general domain of the current text. In the second stage the system proposes to the reader the appropriate text according to his score in the background knowledge questionnaire. ADULT uses four versions of a text, orthogonally varying local and global coherence. In the third stage, participantspsila comprehension is assessed through free-recall measure, text-based, bridging-inference and problem solving questions and a sorting task. The system suggests the previous learning sequence; however the student can set his own sequence. The design of such an environment is appropriate for personalized learning and is based on the results of previous studies which demonstrated that high and low knowledge readers benefit from low- and high coherence texts respectively.
Cellular NAD Replenishment Confers Marked Neuroprotection Against Ischemic Cell Death: Role of Enhanced DNA Repair

Background and Purpose— NAD+ is an essential cofactor for cellular energy production and participates in various signaling pathways that have an impact on cell survival. After cerebral ischemia, oxidative DNA lesions accumulate in neurons because of increased attacks by ROS and diminished DNA repair activity, leading to PARP-1 activation, NAD+ depletion, and cell death. The objective of this study was to determine the neuroprotective effects of NAD+ repletion against ischemic injury and the underlying mechanism. Methods— In vitro ischemic injury was induced in rat primary neuronal cultures by oxygen-glucose deprivation (OGD) for 1 to 2 hours. NAD+ was replenished by adding NAD+ directly to the culture medium before or after OGD. Cell viability, oxidative DNA damage, and DNA base-excision repair (BER) activity were measured quantitatively up to 72 hours after OGD with or without NAD+ repletion. Knockdown of BER enzymes was achieved in cultures using AAV-mediated transfection of shRNA. Results— Direct NAD+ repletion in neurons either before or after OGD markedly reduced cell death and OGD-induced accumulation of DNA damage (AP sites, single and double strand breaks) in a concentration- and time-dependent manner. NAD+ repletion restored nDNA repair activity by inhibiting serine-specific phosphorylation of the essential BER enzymes AP endonuclease and DNA polymerase-β. Knocking down AP endonuclease expression significantly reduced the prosurvival effect of NAD+ repletion. Conclusion— Cellular NAD+ replenishment is a novel and potent approach to reduce ischemic injury in neuronal cultures. Restoration of DNA repair activity via the BER pathway is a key signaling event mediating the neuroprotective effect of NAD+ replenishment.
Translesional synthesis past acetylaminofluorene-derived DNA adducts catalyzed by human DNA polymerase kappa and Escherichia coli DNA polymerase IV.

Human DNA polymerase kappa (pol kappa) has a sequence significantly homologous with that of Escherichia coli DNA polymerase IV (pol IV). We used a truncated form of human pol kappa (pol kappaDeltaC) and full-length pol IV to explore the miscoding properties of these enzymes. Oligodeoxynucleotides, modified site-specifically with N-(deoxyguanosin-8-yl)-2-acetylaminofluorene (dG-AAF) and N-(deoxyguanosin-8-yl)-2-aminofluorene (dG-AF), were used as DNA templates in primer extension reactions that included all four dNTPs. Reactions catalyzed by pol kappaDeltaC were partially blocked one base prior to dG-AAF or dG-AF, and also opposite both lesions. At higher enzyme concentrations, a significant fraction of primer was extended. Analysis of the fully extended reaction product revealed incorporation of dTMP opposite dG-AAF, accompanied by much smaller amounts of dCMP, dAMP, and dGMP and some one- and two-base deletions. The product terminating 3' to the adduct site contained AMP misincorporated opposite dC. On templates containing dG-AF, dAMP, dTMP, and dCMP were incorporated opposite the lesion in approximately equal amounts, together with some one-base and two-base deletions. Steady-state kinetics analysis confirmed the results obtained from primer extension reactions catalyzed by pol kappa. In contract, primer extension reactions catalyzed by pol IV were blocked effectively by dG-AAF and dG-AF. At high concentrations of pol IV, full-length products were formed containing primarily one- or two-base deletions with dCMP, the correct base, incorporated opposite dG-AF. The miscoding properties of pol kappa observed in this study are consistent with mutational spectra observed when plasmid vectors containing dG-AAF or dG-AF are introduced into simian kidney cells [Shibutani, S. , et al. (2001) Biochemistry 40, 3717-3722], supporting a model in which pol kappa plays a role in translesion synthesis past acetylaminofluorene-derived lesions in mammalian cells.
Determinants of progressive vascular calcification in haemodialysis patients.

BACKGROUND We determined recently that targeted treatment with calcium-based phosphate binders (calcium acetate and carbonate) led to progressive coronary artery and aortic calcification by electron beam tomography (EBT), while treatment with the non-calcium-containing phosphate binder, sevelamer, did not. Aside from the provision of calcium, we hypothesized that other factors might be related to the likelihood of progressive calcification in both or either treatment groups. METHODS We explored potential determinants of progressive vascular calcification in 150 randomized study subjects who underwent EBT at baseline and at least once during follow-up (week 26 or 52). RESULTS Among calcium-treated subjects, higher time-averaged concentrations of calcium, phosphorus and the calcium-phosphorus product were associated with more pronounced increases in EBT scores; no such associations were demonstrated in sevelamer-treated subjects. The relation between parathyroid hormone (PTH) and the progression of calcification was more complex. Lower PTH was associated with more extensive calcification in calcium-treated subjects, whereas higher PTH was associated with calcification in sevelamer-treated subjects. Serum albumin was inversely correlated with progression in aortic calcification. Sevelamer was associated with favourable effects on lipids, although the link between these effects and the observed attenuation in vascular calcification remains to be elucidated. CONCLUSION Calcium-based phosphate binders are associated with progressive coronary artery and aortic calcification, especially when mineral metabolism is not well controlled. Calcium may directly or indirectly (via PTH) adversely influence the balance of skeletal and extraskeletal calcification in haemodialysis patients.
Analysis of features contributing to activity of the single-stranded origin of Bacillus plasmid pBAA1

The features which contribute to the activity of the single-stranded origin of the Bacillus plasmid pBAA1 were investigated. This origin is contained on a DNA fragment greater than 116 but less than 191 bases in size. There is the potential to form three stem-loop structures within this fragment. Comparison of the sequence of this origin from pBAA1 with the sequence of a homologous fragment from the Bacillus thuringiensis plasmid pGI2 indicates that both the structure and the relative positioning of the predicted stem-loops are important for origin activity. Deletion analysis suggests that it is the structure of stem-loop III which is important, because it can be replaced by a nonrelated dyad element without significant loss of origin activity. Three sequence motifs are conserved between the origins from pBAA1 and pGI2. Mutation of motif 1 leads to attenuation of single-stranded origin activity. A second motif (motif 3) shares significant homology with a group of single-strand initiation (ssi) sites found on plasmids isolated from Escherichia coli, suggesting that it also contributes to single-stranded origin activity. Our results also indicate that RNA polymerase is utilized to synthesize the RNA primer at the pBAA1 single-stranded origin and that this origin can function in both Bacillus subtilis and Staphylococcus aureus.