Miracle-dz/UniFAR-FTUs huggingface dataset:
The Phagosome Proteome: Insight into Phagosome Functions

Phagosomes are key organelles for the innate ability of macrophages to participate in tissue remodeling, clear apoptotic cells, and restrict the spread of intracellular pathogens. To understand the functions of phagosomes, we initiated the systematic identification of their proteins. Using a proteomic approach, we identified >140 proteins associated with latex bead–containing phagosomes. Among these were hydrolases, proton pump ATPase subunits, and proteins of the fusion machinery, validating our approach. A series of unexpected proteins not previously described along the endocytic/phagocytic pathways were also identified, including the apoptotic proteins galectin3, Alix, and TRAIL, the anti-apoptotic protein 14-3-3, the lipid raft-enriched flotillin-1, the anti-microbial molecule lactadherin, and the small GTPase rab14. In addition, 24 spots from which the peptide masses could not be matched to entries in any database potentially represent new phagosomal proteins. The elaboration of a two-dimensional gel database of >160 identified spots allowed us to analyze how phagosome composition is modulated during phagolysosome biogenesis. Remarkably, during this process, hydrolases are not delivered in bulk to phagosomes, but are instead acquired sequentially. The systematic characterization of phagosome proteins provided new insights into phagosome functions and the protein or groups of proteins involved in and regulating these functions.
Personalised distributed information retrieval-based agents

This paper proposes a new approach using a multi agents system for personalising the distributed information retrieval (DIR). Most prior research in DIR focused on selecting and merging information that has the most relevant content according to the query, but ignored the user's specific needs. Our approach extends the state-of-the-art in a DIR. Firstly, it develops an agent called user-agent for managing the user profile. Secondly, it develops an agent called source-agent for each information source in order to manage its information source. Finally, it develops an agent called agent-broker for cooperating between user-agent and each source-agent in order to select the best source and merge their best documents in response to the user's query. The approach has been experimented with several known information sources. The experimental results show that the approach: (1) improve the relevance of the result, (2) reduce the response times and (3) improve the system extensibility.
Response of septal cholinergic neurons to axotomy

In the present study we employed quantitative morphometric techniques to assay the response of septal cholinergic neurons following unilateral transection of the fimbria/fornix and supracallosal stria. Analysis of 50‐μm‐thick tissue sections with a Quantimet 920 image analysis system demonstrated a reduction in ChAT immunoreactivity as early as 1 day following denervation. This decrease was associated with a drop in the number of labeled cells ipsilateral to the lesion and a decrease in the area of cholinergic perikarya on the lesioned and nonlesioned side of the septum. The response at 1 day, however, was transient, and at 4 days the number of labeled neurons was not significantly different from controls. By 8 days we observed a dramatic reduction in the number and size of ChAT‐positive cells ipsilateral to the lesion and a reduction in the size of cholinergic perikarya on the contralateral (i.e., nonlesioned) side. These values persisted throughout the remainder of the study.
Extremely Stretchable Strain Sensors Based on Conductive Self‐Healing Dynamic Cross‐Links Hydrogels for Human‐Motion Detection

Extremely stretchable self‐healing strain sensors based on conductive hydrogels are successfully fabricated. The strain sensor can achieve autonomic self‐heal electrically and mechanically under ambient conditions, and can sustain extreme elastic strain (1000%) with high gauge factor of 1.51. Furthermore, the strain sensors have good response, signal stability, and repeatability under various human motion detections.
Delivery of matrix metalloproteinase-1 attenuates established liver fibrosis in the rat.

BACKGROUND & AIMS During hepatic fibrogenesis, the hepatic extracellular matrix changes to fibrillar collagens types I and III, and cirrhosis is believed to produce an irreversible scar. In this study, we investigated whether gene delivery of human matrix metalloproteinase-1, which degrades collagens types I and type III, would attenuate established hepatic fibrosis in the rat, induced by either thioacetamide or bile duct ligation. METHODS Hepatic fibrosis induced by thioacetamide for 7 weeks was persistent for at least 2 months, even after discontinuation of the treatment. The rats were infected once with a recombinant adenovirus, Ad5MMP-1, into which human pro-human matrix metalloproteinase-1 complementary DNA was packaged, or with a control adenovirus, Ad5LacZ. RESULTS In Ad5MMP-1-infected, but not in Ad5LacZ-infected, rats, the fibrosis was dramatically attenuated at 2 weeks after the infection. It is interesting to note that the number of activated hepatic stellate cells was also decreased in Ad5MMP-1-infected rats. Moreover, disorganization of the hepatic trabecula, heterogeneity in the size of hepatocytes, and increased dried liver weight were observed only in Ad5MMP-1-treated rats, suggesting that human matrix metalloproteinase-1 stimulated hepatocyte proliferation, which was confirmed by bromodeoxyuridine staining. After 4 weeks, the proliferative effect of human matrix metalloproteinase-1 almost disappeared, but the hepatic fibrosis remained attenuated, whereas the fibrosis in Ad5LacZ-treated rats persisted. Furthermore, the administration of Ad5MMP-1, but not Ad5LacZ, decreased type I collagen and generated a small collagen fragment in hepatic fibrosis induced by bile duct ligation. CONCLUSIONS Our findings show that transient human matrix metalloproteinase-1 overexpression in the liver effectively attenuates established fibrosis and induces hepatocyte proliferation.
Statins in heart failure: Retrospective cohort study using routine primary care data

Introduction. Studies suggest no benefit from statins in heart failure (HF), but many individuals in primary care are prescribed statins before HF diagnosis. This study aimed to assess the effect of a statin prescription prior to HF diagnosis on survival in an incident HF population. Material and methods. Cases of HF diagnosed between 1995 and 2004 in 315 UK primary care practices were identified from electronic case records and followed up for 2 years from diagnosis. Statin prescribing before and after HF diagnosis was assessed, and Cox regression was used to determine the contribution of statin treatment to survival. Results. A total of 10,914 cases met the inclusion criteria of whom 20% (2185/10,914) were treated with a statin prior to HF diagnosis. Two per cent (191/8729) had an initial statin prescription following diagnosis. Cases prescribed a statin before heart failure diagnosis had a lower risk of death in the subsequent 2 years (hazard ratio 0.52; 95% confidence interval 0.39–0.68), after adjustment for confounders. Discussion. Most people with heart failure prescribed statins in primary care commenced them prior to diagnosis and appeared to gain benefit, presumably through the effect of statins on cardiovascular co-morbidities. Primary care physicians should not discontinue prior statin treatment at the time of heart failure diagnosis.
CD200R1 Agonist Attenuates Mechanisms of Chronic Disease in a Murine Model of Multiple Sclerosis

To assess the effects and mechanisms of a CD200R1 agonist administered during the progressive stage of a multiple sclerosis model, we administered CD200R1 agonist (CD200Fc) or control IgG2a during the chronic phase of disease (days 10–30) in mice with experimental autoimmune encephalomyelitis (EAE), induced using myelin oligodendrocyte glycoprotein peptide 35–55 (MOG35–55) peptide. We found that administration of CD200Fc during the chronic stages of EAE reduced disease severity, demyelination, and axonal damage, through the modulation of several key disease mechanisms. CD200Fc treatment suppressed macrophage and microglial accumulation within the CNS, in part through downregulation of adhesion molecules VLA-4 and LFA-1, which are necessary for macrophage migration. Additionally, expression of activation markers MHC-II and CD80 and production of proinflammatory cytokines IL-6, tumor necrosis factor-α, and nitric oxide by CD11b+ cells were decreased in both the spleen and CNS in CD200Fc-treated animals. Antigen-presenting cell function in the spleen and CNS was suppressed in CD200Fc-treated mice, but there were no significant alterations on T cell activation or phenotype. CD200Fc increased apoptosis of CD11b+ cells but not astrocytes. In contrast, addition of CD200Fc treatment protected oligodendrocytes from apoptosis in vitro and in vivo. Our results demonstrate that CD200R1 agonists modulate both myeloid- and non-myeloid-related mechanisms of chronic disease in the EAE model and may be effective in the treatment of progressive multiple sclerosis and other neurodegenerative diseases.
Interaction between the herpes simplex virus type 1 origin-binding and DNA polymerase accessory proteins.

Interactions between the herpes simplex virus type 1 (HSV-1) origin (ori)-binding protein (UL9) and two other components of the functional DNA replication complex have been observed. However, to date, no interaction between UL9 and a component of the DNA polymerase holoenzyme has been demonstrated. In this report, we demonstrate that UL9 and the DNA polymerase accessory protein (UL42) can form a stable complex in vitro as determined by coimmunoprecipitation with specific antibodies to each protein and by affinity chromatography using glutathione S-transferase (GST) fusion proteins. Complex formation does not require the presence of other viral proteins and occurs in the presence of ethidium bromide, indicating that UL9-UL42 interaction is DNA independent. Affinity beads charged with increasing concentrations of GST-42 fusion protein up to 5 microM bound increasing amounts of UL9 expressed by in vitro transcription/translation in rabbit reticulocyte lysates. Binding of N- and C-terminal portions of UL9 to GST affinity matrices revealed that the N-terminal 533 amino acids were sufficient for binding to GST-42, albeit at approximately a four- to six-fold reduced affinity compared to the full-length protein. No binding of a polypeptide containing the remainder of the UL9 C-terminal residues was observed. Thus the ori-binding protein, UL9, can physically associate with at least one member of each of the complexes (helicase/primase, DNA polymerase holoenzyme, single-stranded DNA-binding protein) required for origin-dependent DNA replication. These specific interactions provide a means by which the ordered assembly of HSV-1 DNA replication proteins at origins of replication can occur in the infected cell for initiation of viral DNA synthesis.
Jack-like eversion by splitting the orbicularis oris muscle for reconstruction of the philtral column in secondary cleft lip

The philtrum is an important aesthetic unit that contributes hugely to the characteristics of the human face. From March 2002 to May 2006 inclusive, a total of 16 patients with unilateral cleft lip nose were operated on to form a philtral column and obtain muscular continuity. Six of the patients were female and 12 were male, age range 5 to 30 years old. We used Millard's method, so rotation and advancement flaps were planned. A full thickness incision was made down to the orbicularis oris muscle and mucosa after the scar on the philtral column had been excised. The medial and lateral muscle flaps were exposed and split into two leaves at the coronal plane. The deepest part of the muscle flaps were sutured together to create a jack-like eversion. Skin and mucosa were then closed. The follow-up period ranged from 8 to 18 months (mean 11 months). Two visual analogue scales were used to assess the outcomes. Thirteen of 16 patients were satisfied with their good result. Three had moderate results. The advantages of the technique are: ease of use; the creation of an anatomically-natural philtrum while preserving the continuity and function of the muscle; sufficient augmentation of the philtral column by the jack-like eversion; and no donor-site morbidity.
A wide-angle broadband waveplate through field transformation

We present here a wide-angle broadband waveplate based on a field transformation (FT) method. By adjusting the thickness of such a waveplate, we obtain both half-wave and quarter-wave plates which achieve polarization conversions between TE and TM, LCP and RCP, linear and circular polarizations separately for both transmission and reflection cases. Such waveplates can be realized through sub-wavelength dielectric gratings based on effect media theory, whose performances have been verified through numeric and full-wave simulations with experimentally verification carried out in microwave regime.
Use of antibiotics for sore throat and incidence of quinsy.

BACKGROUND Quinsy is the most common major suppurative complication of sore throat. Evidence on the effectiveness of antibiotics in preventing quinsy is sparse. AIM To assess the incidence of quinsy and the pattern of presentation, and to identify variables that predict the development of quinsy. DESIGN OF STUDY Case-control study. SETTING UK-wide primary care. METHOD Retrospective analysis of data from the General Practice Research Database (GPRD) for the years 1995-1997. RESULTS There were 606 recorded cases of patients with quinsy, but only 192 (31%) of these patients presented following an initially uncomplicated sore throat. Patients with quinsy were more likely to be aged 21-40 years (odds ratio [OR] = 2.5, 95% confidence interval [CI] = 1.7 to 3.6, compared with other ages), smokers (OR = 2.5, 95% CI = 1.8 to 3.5), and male (OR = 1.6, 95% CI = 1.1 to 2.2). Quinsy developed very quickly for most patients (median of 2 days after tonsillitis and 3 days after a sore throat). For cases initially labelled as tonsillitis, there was a nonsignificant trend of antibiotics preventing quinsy (OR = 0.6, 95% CI = 0.3 to 1.3), but no evidence that antibiotics prevent quinsy for cases labelled as sore throat or pharyngitis (OR = 1.2, 95% CI = 0.7 to 2.2). CONCLUSION Most patients with quinsy develop the condition rapidly, and many do not present with a respiratory tract infection to their GP first. The current low doses of antibiotics used in modern community settings may be less likely to protect against quinsy than the trial evidence suggests.
Prevalence and risk factors of retinal vein occlusion in an Asian population

Aim: To describe the prevalence and risk factors of retinal vein occlusion (RVO) in an Asian population. Methods: The Singapore Malay Eye Study is a population-based, cross-sectional study of 3280 (78.7%) Malay adults (aged 40–80 years) living in Singapore. All participants underwent retinal photography, standardised interview, clinical examinations and laboratory investigations. RVO (central or branch) was graded based on the Blue Mountains Eye Study (BMES) protocol from retinal photographs. Results: The overall prevalence of RVO was 0.7% (n = 22) (95% CI 0.4 to 1.0) (18 branch and five central RVO cases). There was no significant gender difference in RVO prevalence. RVO was associated with higher systolic blood pressure (age-adjusted odds ratio (OR) per SD increase 1.54, CI 1.02 to 2.31), ocular perfusion pressure (OR per SD increase 1.49, CI 1.03 to 2.16), a history of angina (OR 5.18, CI 1.49 to 18.0) and heart attack (OR 4.26, CI 1.47 to 12.3), and higher total cholesterol (OR per SD increase 1.55, CI 1.07 to 2.24) and LDL (OR per SD increase 1.47, CI 1.02 to 2.12) cholesterol levels. Conclusions: The prevalence of RVO in this Asian population was lower than Caucasians in the BMES, although the systemic associations of RVO were largely similar to BMES and other studies.
Variations in clinical practice patterns.

In recent years, researchers and policy makers have increasingly focused their attention on the variation in clinical practice patterns across geographic areas and practice settings. Wennberg and Gittelsohn 1-3 have identified wide variations across small geographic areas in the use of selected surgical procedures. Numerous studies of Health Maintenance Organizations (HMOs) indicate substantially lower hospitalization rates for enrollees in prepaid group practices than for enrollees with conventional insurance coverage. 4 Such studies gain more than academic interest as insurers and the government seek ways to contain medical care expenditures by choosing selected providers and medical care systems or by developing incentives for physicians to change their practice patterns. See also p 1886. While the evidence is convincing that differences exist in practice patterns, the reasons for the observed differences are not well understood and there is much more rhetoric than research. Some argue that the prepayment arrangements in HMOs encourage
Efficacy of Knee Braces and Foot Orthoses in Conservative Management of Knee Osteoarthritis: A Systematic Review

A systematic analysis was conducted on the effectiveness of knee braces and foot orthoses in conservative management of knee osteoarthritis. The methodologic quality of the randomized clinical trials, controlled clinical trials, and observational studies were systematically reviewed using the Structured Effectiveness Quality Evaluation Scale. Twenty-five studies met the inclusion criteria. The orthoses used in the studies included Generation II osteoarthritis knee brace, valgus knee braces, functional off-loading knee braces, knee sleeves, lateral-wedged insoles with subtalar strapping, medial-wedged insoles, and specialized footwear. Results suggest that knee braces and foot orthoses are effective in decreasing pain, joint stiffness, and drug dosage. They also improve proprioception, balance, Kellgren/Lawrence grading, and physical function scores in subjects with varus and valgus knee osteoarthritis. Knee braces and foot orthoses could be cautiously considered as conservative management for relief of pain and stiffness and improving physical function for persons with knee osteoarthritis. The conclusions of this review are limited by methodologic considerations like poor quality of trials and heterogeneity of interventions.
Are current species extrapolation models a good basis for ecological risk assessment?

Extrapolating the effects of toxicants with either the fixed application factor approach or one of the species sensitivity distribution models currently in widespread use presumes that toxicant effects on single, individual‐level endpoints (e.g., survival, fecundity, and growth) reflect effects at the population level. Here, we consider if extrapolations derived on the basis of individuallevel endpoints might be misleading with regard to risk assessment and, hence, risk management decisions for ecosystems. Both analytically and by simulation, we demonstrate that for populations with multiplication rates close to one, effects of toxicants at the population level likely are less than or equal to effects on individual life‐cycle traits, suggesting that risk assessments based on the latter likely are protective of population‐level impacts. We used Monte Carlo simulations to explore how both the frequency of different life‐cycle types in a community as well as their relative sensitivity to toxicants influence the toxicant sensitivity distribution of the community as a whole. We compared the output of our simulations with predicted no‐effect concentrations derived by an application factor approach and a log‐normal distribution‐based model, using no‐observed‐effect concentrations for juvenile survival as input variables in both cases. Our analyses suggest that current extrapolation approaches appear to be protective, and may often be very overprotective, but we have identified conditions in which this may not be the case. We recommend that additional consideration be given to the relative frequency of different life‐cycle types, to the proportions of sensitive and insensitive taxonomic groups in communities, and to the role of density‐dependent influences on population dynamics to ensure that we develop environmental quality criteria that are sufficiently—but not overly—protective.
Arabidopsis rbcS Genes Are Differentially Regulated by Light

Individual members of the Arabidopsis thaliana ribulose-1,5-bisphosphate carboxylase/oxygenase small subunit (rbcS) gene family are differentially regulated by light of different qualities. In 10-d-old etiolated seedlings, the expression of only three of the four genes is under inductive phytochrome control. rbcS mRNA levels reach a maximum (3- to 5-fold higher than the dark level) about 6 h after a red light pulse, but the rate of decay differs among the genes. Moreover, rbcS 2B requires a higher fluence for induction. At early stages of development, rbcS 1A, 2B, and 3B are highly expressed in the dark and cannot be further induced by red light, indicating a developmental component in the overall regulatory mechanism. Continuous light experiments indicate that high-irradiance responses may play a role in the induction of at least three of the four rbcS genes. Under conditions of phytochrome saturation, rbcS 1A is insensitive to blue pulses, whereas among the three B locus genes, at least rbcS 3B appears to respond to a blue-light photoreceptor. These results add to the data suggesting that individual members of rbcS gene families in higher plants may be subject to a variety of differing regulatory mechanisms.
Prevention of Death in Bacterium-Infected Mice by a Synthetic Antimicrobial Peptide, L5, through Activation of Host Immunity

ABSTRACT In our previous study, we found that the antibacterial peptide KLKLLLLLKLK-NH2 (L5) and its d-enantiomer (DL5) activate neutrophils to produce superoxide anions (O2−) and prevent death due to infection by methicillin-resistant Staphylococcus aureus, suggesting that these peptides may elicit in vivo antimicrobial activities through host inflammatory responses mediated by neutrophils. In this study, we investigated the mechanisms behind in vivo antimicrobial prophylaxis by the use of L5 for the treatment of bacterial infection introduced via intra-abdominal implantation. We found that the intraperitoneal treatment with L5 before bacterial infection markedly reduced rates of death due to infection. Treatments with L5 were highly effective in preventing death due to intraperitoneal inoculation of not only S. aureus Smith but also Enterococcus faecalis SR1004 and Escherichia coli EC14. The intra-abdominal administration of L5 induced accumulation of neutrophils, increased levels of reactive oxygen species, and augmented antibacterial activity in the abdominal cavity. In addition, administration of L5 upregulated the expression of the Mig/CXCL9 chemokine gene in thioglycolate-elicited peritoneal macrophages. Our results suggested that the prevention of death by treatment of infected mice with L5 might occur primarily through the activation of a host immune response.