Neutral Hydrogen Mapping of Virgo Cluster Blue Compact Dwarf Galaxies

A new installment of neutral hydrogen mappings of Blue Compact Dwarf galaxies, as defined by optical morphology, in and near the Virgo cluster is presented. The primary motivation was to search for outlying clouds of HI as potential interactive triggers of the enhanced star formation, and therefore the mapped galaxies were selected for large HI} mass, large optical diameter, and large velocity profile width. Approximately half the sample proved to have one or more small, low column density star-free companion clouds, either detached or appearing as an appendage in our maps, at resolution of order 4 kpc. Comparison is made to a sample of similarly mapped field BCD galaxies drawn from the literature; however, the Virgo cluster sample of mapped BCDs is still too small for conclusive comparisons to be made. We found, on the one hand, little or no evidence for ram pressure stripping nor, on the other, for extremely extended low column density HI envelopes. The HI rotation curves in most cases rise approximately linearly, and slowly, as far out as we can trace the gas.Comment: To appear in AJ, Dec. 200

A Novel, Multifunctional c-Cbl Binding Protein in Insulin Receptor Signaling in 3T3-L1 Adipocytes

The protein product of the c-Cbl proto-oncogene is prominently tyrosine phosphorylated in response to insulin in 3T3-L1 adipocytes and not in 3T3-L1 fibroblasts. After insulin-dependent tyrosine phosphorylation, c-Cbl specifically associates with endogenous c-Crk and Fyn. These results suggest a role for tyrosine-phosphorylated c-Cbl in 3T3-L1 adipocyte activation by insulin. A yeast two-hybrid cDNA library prepared from fully differentiated 3T3-L1 adipocytes was screened with full-length c-Cbl as the target protein in an attempt to identify adipose-specific signaling proteins that interact with c-Cbl and potentially are involved in its tyrosine phosphorylation in 3T3-L1 adipocytes. Here we describe the isolation and the characterization of a novel protein that we termed CAP for c-Cbl-associated protein. CAP contains a unique structure with three adjacent Src homology 3 (SH3) domains in the C terminus and a region showing significant sequence similarity with the peptide hormone sorbin. Both CAP mRNA and proteins are expressed predominately in 3T3-L1 adipocytes and not in 3T3-L1 fibroblasts. CAP associates with c-Cbl in 3T3-L1 adipocytes independently of insulin stimulation in vivo and in vitro in an SH3-domain-mediated manner. Furthermore, we detected the association of CAP with the insulin receptor. Insulin stimulation resulted in the dissociation of CAP from the insulin receptor. Taken together, these data suggest that CAP represents a novel c-Cbl binding protein in 3T3-L1 adipocytes likely to participate in insulin signaling

Organizational preparedness for the use of large language models in pathology informatics

In this paper, we consider the current and potential role of the latest generation of Large Language Models (LLMs) in medical informatics, particularly within the realms of clinical and anatomic pathology. We aim to provide a thorough understanding of the considerations that arise when employing LLMs in healthcare settings, such as determining appropriate use cases and evaluating the advantages and limitations of these models. Furthermore, this paper will consider the infrastructural and organizational requirements necessary for the successful implementation and utilization of LLMs in healthcare environments. We will discuss the importance of addressing education, security, bias, and privacy concerns associated with LLMs in clinical informatics, as well as the need for a robust framework to overcome regulatory, compliance, and legal challenges

A format for phylogenetic placements

We have developed a unified format for phylogenetic placements, that is, mappings of environmental sequence data (e.g. short reads) into a phylogenetic tree. We are motivated to do so by the growing number of tools for computing and post-processing phylogenetic placements, and the lack of an established standard for storing them. The format is lightweight, versatile, extensible, and is based on the JSON format which can be parsed by most modern programming languages. Our format is already implemented in several tools for computing and post-processing parsimony- and likelihood-based phylogenetic placements, and has worked well in practice. We believe that establishing a standard format for analyzing read placements at this early stage will lead to a more efficient development of powerful and portable post-analysis tools for the growing applications of phylogenetic placement.Comment: Documents version 3 of the forma

Bacterial Communities in Women with Bacterial Vaginosis: High Resolution Phylogenetic Analyses Reveal Relationships of Microbiota to Clinical Criteria

Bacterial vaginosis (BV) is a common condition that is associated with numerous adverse health outcomes and is characterized by poorly understood changes in the vaginal microbiota. We sought to describe the composition and diversity of the vaginal bacterial biota in women with BV using deep sequencing of the 16S rRNA gene coupled with species-level taxonomic identification. We investigated the associations between the presence of individual bacterial species and clinical diagnostic characteristics of BV.Broad-range 16S rRNA gene PCR and pyrosequencing were performed on vaginal swabs from 220 women with and without BV. BV was assessed by Amsel's clinical criteria and confirmed by Gram stain. Taxonomic classification was performed using phylogenetic placement tools that assigned 99% of query sequence reads to the species level. Women with BV had heterogeneous vaginal bacterial communities that were usually not dominated by a single taxon. In the absence of BV, vaginal bacterial communities were dominated by either Lactobacillus crispatus or Lactobacillus iners. Leptotrichia amnionii and Eggerthella sp. were the only two BV-associated bacteria (BVABs) significantly associated with each of the four Amsel's criteria. Co-occurrence analysis revealed the presence of several sub-groups of BVABs suggesting metabolic co-dependencies. Greater abundance of several BVABs was observed in Black women without BV.The human vaginal bacterial biota is heterogeneous and marked by greater species richness and diversity in women with BV; no species is universally present. Different bacterial species have different associations with the four clinical criteria, which may account for discrepancies often observed between Amsel and Nugent (Gram stain) diagnostic criteria. Several BVABs exhibited race-dependent prevalence when analyzed in separate groups by BV status which may contribute to increased incidence of BV in Black women. Tools developed in this project can be used to study microbial ecology in diverse settings at high resolution

Intersectin, a Novel Adaptor Protein with Two Eps15 Homology and Five Src Homology 3 Domains

We screened a Xenopus laevis oocyte cDNA expression library with a Src homology 3 (SH3) class II peptide ligand and identified a 1270-amino acid-long protein containing two Eps15 homology (EH) domains, a central coiled-coil region, and five SH3 domains. We named this protein Intersectin, because it potentially brings together EH and SH3 domain-binding proteins into a macromolecular complex. The ligand preference of the EH domains were deduced to be asparajine-proline-phenylalanine (NPF) or cyclized NPF (CX1-2NPFXXC), depending on the type of phage-displayed combinatorial peptide library used. Screens of a mouse embryo cDNA library with the EH domains of Intersectin yielded clones for the Rev-associated binding/Rev-interacting protein (RAB/Rip) and two novel proteins, which we named Intersectin-binding proteins (Ibps) 1 and 2. All three proteins contain internal and C-terminal NPF peptide sequences, and Ibp1 and Ibp2 also contain putative clathrin-binding sites. Deletion of the C-terminal sequence, NPFL-COOH, from RAB/Rip eliminated EH domain binding, whereas fusion of the same peptide sequence to glutathione S-transferase generated strong binding to the EH domains of Intersectin. Several experiments support the conclusion that the free carboxylate group contributes to binding of the NPFL motif at the C terminus of RAB/Rip to the EH domains of Intersectin. Finally, affinity selection experiments with the SH3 domains of Intersectin identified two endocytic proteins, dynamin and synaptojanin, as potential interacting proteins. We propose that Intersectin is a component of the endocytic machinery

The Arecibo Legacy Fast ALFA Survey: II. Results of Precursor Observations

In preparation for the full Arecibo Legacy Fast ALFA extragalactic HI survey, precursor observations were carried out in Aug--Sep 2004 with the 7-beam Arecibo L-band feed array (ALFA) receiver system and the WAPP spectral processors. While these observations were geared mainly at testing and debugging survey strategy, hardware and software, approximately 36 hours of telescope time yielded science--quality data. From those observations, an initial list of 730 tentative detections of varying degree of reliability was extracted. Ninety--eight high signal-to-noise candidates were deemed to be bona fide HI line detections. To test our ability to discriminate cosmic signals from RFI and noise, 165 candidates ranging in reliability likelihood were re--observed with the single beam L--band wide system at Arecibo in Jan--Feb 2005. Of those, 41% were confirmed as real. We present the results of both the ALFA and single beam observations for the sample of 166 confirmed HI sources, as well as our assessment of their optical counterparts. Of the 166 sources, 62 coincide with previously known HI sources, while optical redshifts were available for an additional 18 galaxies; thus, 52% of the redshifts reported here were previously unknown. Of the 166 HI detections, 115 are identified with previously cataloged galaxies, of either known or unknown redshift, leaving 51 objects identified for the first time. Because of the higher sensitivity of the Arecibo system, fewer than 10% of the 166 HI sources would have been detected by a HIPASS--like survey of the same region. Three of the objects have HI masses less than 10^7 solar masses. The full ALFALFA survey which commenced in February 2005 should detect more than 100 times as many objects of similarly low HI mass over the next 5 years.Comment: 40 pages, including 4 tables and 8 figures; to appear in Astron. J.; see http://egg.astro.cornell.edu/alfalfa/pubs.ph

The Arecibo Legacy Fast ALFA Survey: III. HI Source Catalog of the Northern Virgo Cluster Region

We present the first installment of HI sources extracted from the Arecibo Legacy Fast ALFA (ALFALFA) extragalactic survey, initiated in 2005. Sources have been extracted from 3-D spectral data cubes and then examined interactively to yield global HI parameters. A total of 730 HI detections are catalogued within the solid angle 11h44m < R.A.(J2000) < 14h00m and +12deg < Dec.(J2000) < +16deg, and redshift range -1600 \kms < cz < 18000 \kms. In comparison, the HI Parkes All-Sky Survey (HIPASS) detected 40 HI signals in the same region. Optical counterparts are assigned via examination of digital optical imaging databases. ALFALFA HI detections are reported for three distinct classes of signals: (a) detections, typically with S/N > 6.5; (b) high velocity clouds in the Milky Way or its periphery; and (c) signals of lower S/N (to ~ 4.5) which coincide spatially with an optical object of known similar redshift. Although this region of the sky has been heavily surveyed by previous targeted observations based on optical flux-- or size-- limited samples, 69% of the extracted sources are newly reported HI detections. The resultant positional accuracy of HI sources is 20" (median). The median redshift of the sample is ~7000 \kms and its distribution reflects the known local large scale structure including the Virgo cluster. Several extended HI features are found in the vicinity of the Virgo cluster. A small percentage (6%) of HI detections have no identifiable optical counterpart, more than half of which are high velocity clouds in the Milky Way vicinity; the remaining 17 objects do not appear connected to or associated with any known galaxy.Comment: Astronomical Journal, in pres

Contraceptive adherence among HIV-infected women in Malawi: a randomized controlled trial of the copper intrauterine device and depot medroxyprogesterone acetate

To evaluate contraceptive adherence to the copper intrauterine device (Cu-IUD) and the injectable depot medroxyprogesterone acetate (DMPA) among women with HIV in Lilongwe, Malawi

Antibiotic strategies for eradicating Pseudomonas aeruginosa in people with cystic fibrosis

Background: Respiratory tract infection with Pseudomonas aeruginosa occurs inmost people with cystic fibrosis. Once chronic infection is established, Pseudomonas aeruginosa is virtually impossible to eradicate and is associated with increased mortality and morbidity. Early infection may be easier to eradicate. This is an update of a Cochrane review first published in 2003, and previously updated in 2006 and 2009. Objectives: To determine whether antibiotic treatment of early Pseudomonas aeruginosa infection in children and adults with cystic fibrosis eradicates the organism, delays the onset of chronic infection, and results in clinical improvement. To evaluate whether there is evidence that a particular antibiotic strategy is superior to or more cost-effective than other strategies and to compare the adverse effects of different antibiotic strategies (including respiratory infection with other micro-organisms). Search methods: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register comprising references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings. Most recent search: 08 September 2014. Selection criteria: We included randomised controlled trials of people with cystic fibrosis, in whom Pseudomonas aeruginosa had recently been isolated from respiratory secretions. We compared combinations of inhaled, oral or intravenous antibiotics with placebo, usual treatment or other combinations of inhaled, oral or intravenous antibiotics. We excluded non-randomised trials, cross-over trials, and those utilising historical controls. Data collection and analysis: Both authors independently selected trials, assessed risk of bias and extracted data. Main results: The search identified 49 trials; seven trials (744 participants) with a duration between 28 days and 27 months were eligible for inclusion. Three of the trials are over 10 years old and their results may be less applicable today given the changes in standard treatment. Some of the trials had low numbers of participants and most had relatively short follow-up periods; however, there was generally a low risk of bias from missing data. In most trials it was difficult to blind participants and clinicians to treatment given the interventions and comparators used. Two trials were supported by the manufacturers of the antibiotic used. Evidence from two trials (38 participants) at the two-month time-point showed treatment of early Pseudomonas aeruginosa infection with inhaled tobramycin results in microbiological eradication of the organism from respiratory secretions more often than placebo, odds ratio 0.15 (95% confidence interval 0.03 to 0.65) and data from one of these trials, with longer follow up, suggested that this effect may persist for up to 12 months. One randomised controlled trial (26 participants) compared oral ciprofloxacin and nebulised colistin versus usual treatment. Results after two years suggested treatment of early infection results in microbiological eradication of Pseudomonas aeruginosa more often than no anti-pseudomonal treatment, odds ratio 0.12 (95% confidence interval 0.02 to 0.79). One trial comparing 28 days to 56 days treatment with nebulised tobramycin solution for inhalation in 88 participants showed that both treatments were effective and well-tolerated, with no notable additional improvement with longer over shorter duration of therapy. However, this trial was not powered to detect non- inferiority or equivalence. A trial of oral ciprofloxacin with inhaled colistin versus nebulised tobramycin solution for inhalation alone (223 participants) failed to show a difference between the two strategies, although it was underpowered to show this. A further trial of inhaled colistin with oral ciprofloxacin versus nebulised tobramycin solution for inhalation with oral ciprofloxacin also showed no superiority of the former, with increased isolation of Stenotrophomonas maltophilia in both groups. A recent, large trial in 306 children aged between one and 12 years compared cycled nebulised tobramycin solution for inhalation to culture-based therapy and also ciprofloxacin to placebo. The primary analysis showed no difference in time to pulmonary exacerbation or proportion of Pseudomonas aeruginosa positive cultures. An analysis performed in this review (not adjusted for age) showed fewer participants in the cycled therapy group with one or more isolates of Pseudomonas aeruginosa, odds ratio 0.51 (95% CI 0.31 to 0.28). Authors’ conclusions: We found that nebulised antibiotics, alone or in combination with oral antibiotics, were better than no treatment for early infection with Pseudomonas aeruginosa. Eradication may be sustained for up to two years. There is insufficient evidence to determine whether antibiotic strategies for the eradication of early Pseudomonas aeruginosa decrease mortality or morbidity, improve quality of life, or are associated with adverse effects compared to placebo or standard treatment. Four trials of two active treatments have failed to show differences in rates of eradication of Pseudomonas aeruginosa. There have been no published randomised controlled trials that investigate the efficacy of intravenous antibiotics to eradicate Pseudomonas aeruginosa in cystic fibrosis. Overall, there is still insufficient evidence from this review to state which antibiotic strategy should be used for the eradication of early Pseudomonas aeruginosa infection in cystic fibrosis