Wolf\u27s Neck : the Gem of Casco Bay : the Charming Suburb of Freeport, Maine, with its Many Important Industries and Superior Granite Productions

https://digitalmaine.com/books/1015/thumbnail.jp

The State of Maine in 1893 by George H. Haynes

As this is the book to be distributed by the Board of World\u27s Fair Managers of Maine, to the thousands who will visit the Columbian Exposition at Chicago, in 1893, we preface the descriptions and illustrations of the many beautiful attractions and industries, by fine portraits of Governor Edwin C. Hurleigh, who was foremost in advocating and approved the appropriation to enable Maine to erect a building and exhibit her manufactures, minerals, metals, and all specimens of her handiwork. Also, that of our present Governor, who is heartily in favor of same. Following these are portraits of all the members of the Commission, with short biographical sketches. The remainder of the book will be devoted to our beautiful summer resorts, mineral springs, unexcelled system of railroads, steamer lines, manufactures, and all our industries. Also the pride of the state our fish and game. Elegant illustrations of all will adorn the book.https://digicom.bpl.lib.me.us/books_pubs/1354/thumbnail.jp

Ellsworth, Maine, the Picturesque City of the East, and Green Lake, the Tourists\u27, Anglers\u27, and Hunters\u27 Paradise

A pamphlet highlighting historic homes and outdoor recreation opportunities in the area of Ellsworth, Maine. Includes several illustrations

A Signature in HIV-1 Envelope Leader Peptide Associated with Transition from Acute to Chronic Infection Impacts Envelope Processing and Infectivity

Mucosal transmission of the human immunodeficiency virus (HIV) results in a bottleneck in viral genetic diversity. Gnanakaran and colleagues used a computational strategy to identify signature amino acids at particular positions in Envelope that were associated either with transmitted sequences sampled very early in infection, or sequences sampled during chronic infection. Among the strongest signatures observed was an enrichment for the stable presence of histidine at position 12 at transmission and in early infection, and a recurrent loss of histidine at position 12 in chronic infection. This amino acid lies within the leader peptide of Envelope, a region of the protein that has been shown to influence envelope glycoprotein expression and virion infectivity. We show a strong association between a positively charged amino acid like histidine at position 12 in transmitted/founder viruses with more efficient trafficking of the nascent envelope polypeptide to the endoplasmic reticulum and higher steady-state glycoprotein expression compared to viruses that have a non-basic position 12 residue, a substitution that was enriched among viruses sampled from chronically infected individuals. When expressed in the context of other viral proteins, transmitted envelopes with a basic amino acid position 12 were incorporated at higher density into the virus and exhibited higher infectious titers than did non-signature envelopes. These results support the potential utility of using a computational approach to examine large viral sequence data sets for functional signatures and indicate the importance of Envelope expression levels for efficient HIV transmission

Molecular identification, cloning and characterization of transmitted/founder HIV-1 subtype A, D and A/D infectious molecular clones

AbstractWe report the molecular identification, cloning and initial biological characterization of 12 full-length HIV-1 subtype A, D and A/D recombinant transmitted/founder (T/F) genomes. T/F genomes contained intact canonical open reading frames and all T/F viruses were replication competent in primary human T-cells, although subtype D virus replication was more efficient (p<0.05). All 12 viruses utilized CCR5 but not CXCR4 as a co-receptor for entry and exhibited a neutralization profile typical of tier 2 primary virus strains, with significant differences observed between subtype A and D viruses with respect to sensitivity to monoclonal antibodies VRC01, PG9 and PG16 and polyclonal subtype C anti-HIV IgG (p<0.05 for each). The present report doubles the number of T/F HIV-1 clones available for pathogenesis and vaccine research and extends their representation to include subtypes A, B, C and D

High Multiplicity Infection by HIV-1 in Men Who Have Sex with Men

Elucidating virus-host interactions responsible for HIV-1 transmission is important for advancing HIV-1 prevention strategies. To this end, single genome amplification (SGA) and sequencing of HIV-1 within the context of a model of random virus evolution has made possible for the first time an unambiguous identification of transmitted/founder viruses and a precise estimation of their numbers. Here, we applied this approach to HIV-1 env analyses in a cohort of acutely infected men who have sex with men (MSM) and found that a high proportion (10 of 28; 36%) had been productively infected by more than one virus. In subjects with multivariant transmission, the minimum number of transmitted viruses ranged from 2 to 10 with viral recombination leading to rapid and extensive genetic shuffling among virus lineages. A combined analysis of these results, together with recently published findings based on identical SGA methods in largely heterosexual (HSX) cohorts, revealed a significantly higher frequency of multivariant transmission in MSM than in HSX [19 of 50 subjects (38%) versus 34 of 175 subjects (19%); Fisher's exact p = 0.008]. To further evaluate the SGA strategy for identifying transmitted/founder viruses, we analyzed 239 overlapping 5′ and 3′ half genome or env-only sequences from plasma viral RNA (vRNA) and blood mononuclear cell DNA in an MSM subject who had a particularly well-documented virus exposure history 3–6 days before symptom onset and 14–17 days before peak plasma viremia (47,600,000 vRNA molecules/ml). All 239 sequences coalesced to a single transmitted/founder virus genome in a time frame consistent with the clinical history, and a molecular clone of this genome encoded replication competent virus in accord with model predictions. Higher multiplicity of HIV-1 infection in MSM compared with HSX is consistent with the demonstrably higher epidemiological risk of virus acquisition in MSM and could indicate a greater challenge for HIV-1 vaccines than previously recognized

Transmission of Single HIV-1 Genomes and Dynamics of Early Immune Escape Revealed by Ultra-Deep Sequencing

We used ultra-deep sequencing to obtain tens of thousands of HIV-1 sequences from regions targeted by CD8+ T lymphocytes from longitudinal samples from three acutely infected subjects, and modeled viral evolution during the critical first weeks of infection. Previous studies suggested that a single virus established productive infection, but these conclusions were tempered because of limited sampling; now, we have greatly increased our confidence in this observation through modeling the observed earliest sample diversity based on vastly more extensive sampling. Conventional sequencing of HIV-1 from acute/early infection has shown different patterns of escape at different epitopes; we investigated the earliest escapes in exquisite detail. Over 3–6 weeks, ultradeep sequencing revealed that the virus explored an extraordinary array of potential escape routes in the process of evading the earliest CD8 T-lymphocyte responses – using 454 sequencing, we identified over 50 variant forms of each targeted epitope during early immune escape, while only 2–7 variants were detected in the same samples via conventional sequencing. In contrast to the diversity seen within epitopes, non-epitope regions, including the Envelope V3 region, which was sequenced as a control in each subject, displayed very low levels of variation. In early infection, in the regions sequenced, the consensus forms did not have a fitness advantage large enough to trigger reversion to consensus amino acids in the absence of immune pressure. In one subject, a genetic bottleneck was observed, with extensive diversity at the second time point narrowing to two dominant escape forms by the third time point, all within two months of infection. Traces of immune escape were observed in the earliest samples, suggesting that immune pressure is present and effective earlier than previously reported; quantifying the loss rate of the founder virus suggests a direct role for CD8 T-lymphocyte responses in viral containment after peak viremia. Dramatic shifts in the frequencies of epitope variants during the first weeks of infection revealed a complex interplay between viral fitness and immune escape

Efficacy and safety of a multifactor intervention to improve therapeutic adherence in patients with chronic obstructive pulmonary disease (COPD): protocol for the ICEPOC study

<p>Abstract</p> <p>Background</p> <p>Low therapeutic adherence to medication is very common. Clinical effectiveness is related to dose rate and route of administration and so poor therapeutic adherence can reduce the clinical benefit of treatment. The therapeutic adherence of patients with chronic obstructive pulmonary disease (COPD) is extremely poor according to most studies. The research about COPD adherence has mainly focussed on quantifying its effect, and few studies have researched factors that affect non-adherence. Our study will evaluate the effectiveness of a multifactor intervention to improve the therapeutic adherence of COPD patients.</p> <p>Methods/Design</p> <p>A randomized controlled clinical trial with 140 COPD diagnosed patients selected by a non-probabilistic method of sampling. Subjects will be randomly allocated into two groups, using the block randomization technique. Every patient in each group will be visited four times during the year of the study. Intervention: Motivational aspects related to adherence (beliefs and behaviour): group and individual interviews; cognitive aspects: information about illness; skills: inhaled technique training. Reinforcement of the cognitive-emotional aspects and inhaled technique training will be carried out in all visits of the intervention group.</p> <p>Discussion</p> <p>Adherence to a prescribed treatment involves a behavioural change. Cognitive, emotional and motivational aspects influence this change and so we consider the best intervention procedure to improve adherence would be a cognitive and emotional strategy which could be applied in daily clinical practice. Our hypothesis is that the application of a multifactor intervention (COPD information, dose reminders and reinforcing audiovisual material, motivational aspects and inhalation technique training) to COPD patients taking inhaled treatment will give a 25% increase in the number of patients showing therapeutic adherence in this group compared to the control group.</p> <p>We will evaluate the effectiveness of this multifactor intervention on patient adherence to inhaled drugs considering that it will be right and feasible to the clinical practice context.</p> <p>Trial registration</p> <p>Current Controlled Trials <a href="http://www.controlled-trials.com/ISCTN18841601">ISCTN18841601</a></p

South Pacific Paleogene Climate

International Ocean Discovery Program (IODP) Expedition 378 was designed to recover the first comprehensive set of Paleogene sedimentary sections from a transect of sites strategically positioned in the South Pacific to reconstruct key changes in oceanic and atmospheric circulation. These sites would have provided an unparalleled opportunity to add crucial new data and geographic coverage to existing reconstructions of Paleogene climate. In addition to the ~15 month postponement of Expedition 378 and subsequent port changes resulting in a reduction of the number of primary sites, testing and evaluation of the R/V JOIDES Resolution derrick in the weeks preceding the expedition determined that it would not support deployment of drill strings in excess of 2 km. Because of this determination, only 1 of the originally approved 7 primary sites was drilled. Expedition 378 recovered the first continuously cored, multiple-hole Paleogene sedimentary section from the southern Campbell Plateau at Site U1553. This high–southern latitude site builds on the legacy of Deep Sea Drilling Project (DSDP) Site 277, a single, partially spot cored hole, providing a unique opportunity to refine and augment existing reconstructions of the past ~66 My of climate history. This also includes the discovery of a new siliciclastic unit that had never been drilled before. As the world’s largest ocean, the Pacific Ocean is intricately linked to major changes in the global climate system. Previous drilling in the low-latitude Pacific Ocean during Ocean Drilling Program (ODP) Legs 138 and 199 and Integrated Ocean Drilling Program Expeditions 320 and 321 provided new insights into climate and carbon system dynamics, productivity changes across the zone of divergence, time-dependent calcium carbonate dissolution, bio- and magnetostratigraphy, the location of the Intertropical Convergence Zone, and evolutionary patterns for times of climatic change and upheaval. Expedition 378 in the South Pacific Ocean uniquely complements this work with a high-latitude perspective, especially because appropriate high-latitude records are unobtainable in the Northern Hemisphere of the Pacific Ocean. Site U1553 and the entire corpus of shore-based investigations will significantly contribute to the challenges of the “Climate and Ocean Change: Reading the Past, Informing the Future” theme of the IODP Science Plan (How does Earth’s climate system respond to elevated levels of atmospheric CO2? How resilient is the ocean to chemical perturbations?). Furthermore, Expedition 378 will provide material from the South Pacific Ocean in an area critical for high-latitude climate reconstructions spanning the Paleocene to late Oligocene