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"Alfred, Randy"
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Mad science : Einstein's fridge, Dewar's flask, Mach's speed, and 362 other inventions and discoveries that made our world
\"365 days of inventions, discoveries, science, and technology, from the editors of Wired Magazine...Every day of the year has a rich scientific and technological heritage just waiting to be uncovered, and Wired's top-flight science-trivia book MAD SCIENCE collects them chronologically, from New Year's Day to year's end, showing just how entertaining, wonderful, bizarre, and relevant science can be. In 2010, Wired's popular \"This Day in Tech\" blog peaked with more than 700,000 page views each month, and one story in 2008 drew more than a million unique viewers. This book will collect the most intriguing anecdotes from the blog's run--one for each day of the year--and publish them in a package that will instantly appeal to hardcore techies and curious laypeople alike\"--Provided by publisher.
Assembly and function of the Escherichia coli F(1)F(o) ATPase beta and c subunits
1995
Two different aspects of the F$\\sb1$F$\\sb{\\rm o}$ ATPase complex were studied independently. First, effect of a ribosome binding site mutation on the stoichiometry of the c subunit was examined using immunoprecipitation experiments. The b:c ratios of precipitated wild-type and mutant F$\\sb1$F$\\sb{\\rm o}$, were compared. F$\\sb1$F$\\sb{\\rm o}$ was also purified from wild-type cells grown in LB, as well as minimal media with glucose or succinate. The differences between the b:c ratios in the ribosome-binding site mutant constructions and the wild-type complexes was consistently 3-5 fold. Similarly, the difference in b:c ratios between cells grown on glucose and cells grown on succinate was 1.5-2.0 fold. These results suggest that the stoichiometry of the c subunit may be variable and may also determine the functional activity of the F$\\sb1$F$\\sb{\\rm o}$ complex. The second aspect of F$\\sb1$F$\\sb{\\rm o}$ function studied was the dissection of an uncoupling phenotype in E. coli $\\beta$ mutants complemented by the $\\beta$ subunit from B. megaterium. These cells lost their ability to grow anaerobically on rich media, but were still capable of growing on succinate, a nonfermentable carbon source. Chimeric $\\beta$ subedits were constructed using different sections of the E. coli and B. megaterium $\\beta$ subunit genes. The chimeras varied in their ability to complement E. coli $\\beta$ mutants. Analyses of biochemical activities and genetic complementations suggest that the region responsible for the coupling defect is located in the last 20% of the $\\beta$ subunit. Also, the first 22% of $\\beta$ is important in the assembly of the F$\\sb1$ complex and the stabilization of the structure.
Dissertation
Resurgence of Militant Activism?
1976
A leading organization in a resurgence of militant gay activism in San Francisco, Bay Area Gay Liberation (BAGL), with goals both in the gay movement and in leftist politics and with tactics ranging from within-the-system coalitions to change-the-system confrontations, is many things to many people.
Magazine Article
BAGL, Mindshaft Agree
1975
SAN FRANCISCO, CA-- Bay Area Gay Liberation (BAGL) and the Mindshaft have reached an agreement here in a dispute over the popular disco-dance bar's alleged racial and sexual discrimination and its dress code, which barred transvestites, transsexuals, and anyone wearing floppy hats or other unconventional dress.
Magazine Article
Una solucion no muy ortodoxa
1997
Caminando por el estacionamiento del Parque Candlestick (no el 3Com), un amigo y yo dimos rienda suelta a nuestro purismo beisbolero, denigrando la regla del bateador designado y despotricando en contra del reagrupamiento. Y despues me llego como un relampago. Algun dia el beisbol tendra tres grandes ligas: La Ortodoxa, la Conservadora y la de Reforma. Esta sera su apariencia. La Ortodoxa cuenta con ocho equipos, y el equipo que termina en primer lugar es el campeon. No hay serie de campeonato de liga y solo existen playoffs cuando dos equipos empatan en el primer puesto. (Se enfrentan en una serie a ganar dos de tres). La Conservadora tiene 12 equipos, dos divisiones y una serie de campeonato de liga. La de Reforma tiene 15 equipos, comodines y playoffs.
Newspaper Article
Saturday Talk
I am becoming more and more uneasy about the trend toward radical nationalism gripping this country. It seems that anyone who attempts to criticize or speculate on the wisdom of any decision of the [George W. Bush] administration is labeled a traitor and guilty of sedition. I love my country, and I hope that every American does as well. Fervent nationalism that attacks a person's right to question authority has the potential to be as dangerous as radical Islamists. I hope Stone Mountain Park authorities will reconsider and grant permission to the Sons of Confederate Veterans and Military Order of Stars and Bars to hold their April 26 Confederate memorial on the grounds of the great Southern carving. God bless America! When Stone Mountain Park was created, it was to serve as a Confederate memorial and as a place of public recreation. The lawn in front of the carving was designated as Memorial Lawn. It appears that the private management company that now controls much of Stone Mountain Park knows a lot about creating pseudo-history in order to generate income, i.e., blacksmith shops and glass blowing shops at the base of the mountain selling high-priced souvenirs, but their spokesperson knows nothing about the true history of the park.
Newspaper Article
Multiple introductions and subsequent transmission of multidrug-resistant Candida auris in the USA: a molecular epidemiological survey
2018
Transmission of multidrug-resistant Candida auris infection has been reported in the USA. To better understand its emergence and transmission dynamics and to guide clinical and public health responses, we did a molecular epidemiological investigation of C auris cases in the USA.
In this molecular epidemiological survey, we used whole-genome sequencing to assess the genetic similarity between isolates collected from patients in ten US states (California, Connecticut, Florida, Illinois, Indiana, Maryland, Massachusetts, New Jersey, New York, and Oklahoma) and those identified in several other countries (Colombia, India, Japan, Pakistan, South Africa, South Korea, and Venezuela). We worked with state health departments, who provided us with isolates for sequencing. These isolates of C auris were collected during the normal course of clinical care (clinical cases) or as part of contact investigations or point prevalence surveys (screening cases). We integrated data from standardised case report forms and contact investigations, including travel history and epidemiological links (ie, patients that had shared a room or ward with a patient with C auris). Genetic diversity of C auris within a patient, a facility, and a state were evaluated by pairwise differences in single-nucleotide polymorphisms (SNPs).
From May 11, 2013, to Aug 31, 2017, isolates that corresponded to 133 cases (73 clinical cases and 60 screening cases) were collected. Of 73 clinical cases, 66 (90%) cases involved isolates related to south Asian isolates, five (7%) cases were related to South American isolates, one (1%) case to African isolates, and one (1%) case to east Asian isolates. Most (60 [82%]) clinical cases were identified in New York and New Jersey; these isolates, although related to south Asian isolates, were genetically distinct. Genomic data corroborated five (7%) clinical cases in which patients probably acquired C auris through health-care exposures abroad. Among clinical and screening cases, the genetic diversity of C auris isolates within a person was similar to that within a facility during an outbreak (median SNP difference three SNPs, range 0–12).
Isolates of C auris in the USA were genetically related to those from four global regions, suggesting that C auris was introduced into the USA several times. The five travel-related cases are examples of how introductions can occur. Genetic diversity among isolates from the same patients, health-care facilities, and states indicates that there is local and ongoing transmission.
US Centers for Disease Control and Prevention
Journal Article
Integration of gene mutations in risk prognostication for patients receiving first-line immunochemotherapy for follicular lymphoma: a retrospective analysis of a prospective clinical trial and validation in a population-based registry
by
Neuberg, Donna
,
Weigert, Oliver
,
Kopp, Nadja
in
Adult
,
Aged
,
Antibodies, Monoclonal, Murine-Derived - administration & dosage
2015
Follicular lymphoma is a clinically and genetically heterogeneous disease, but the prognostic value of somatic mutations has not been systematically assessed. We aimed to improve risk stratification of patients receiving first-line immunochemotherapy by integrating gene mutations into a prognostic model.
We did DNA deep sequencing to retrospectively analyse the mutation status of 74 genes in 151 follicular lymphoma biopsy specimens that were obtained from patients within 1 year before beginning immunochemotherapy consisting of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). These patients were recruited between May 4, 2000, and Oct 20, 2010, as part of a phase 3 trial (GLSG2000). Eligible patients had symptomatic, advanced stage follicular lymphoma and were previously untreated. The primary endpoints were failure-free survival (defined as less than a partial remission at the end of induction, relapse, progression, or death) and overall survival calculated from date of treatment initiation. Median follow-up was 7·7 years (IQR 5·5–9·3). Mutations and clinical factors were incorporated into a risk model for failure-free survival using multivariable L1-penalised Cox regression. We validated the risk model in an independent population-based cohort of 107 patients with symptomatic follicular lymphoma considered ineligible for curative irradiation. Pretreatment biopsies were taken between Feb 24, 2004, and Nov 24, 2009, within 1 year before beginning first-line immunochemotherapy consisting of rituximab, cyclophosphamide, vincristine, and prednisone (R-CVP). Median follow-up was 6·7 years (IQR 5·7–7·6).
We established a clinicogenetic risk model (termed m7-FLIPI) that included the mutation status of seven genes (EZH2, ARID1A, MEF2B, EP300, FOXO1, CREBBP, and CARD11), the Follicular Lymphoma International Prognostic Index (FLIPI), and Eastern Cooperative Oncology Group (ECOG) performance status. In the training cohort, m7-FLIPI defined a high-risk group (28%, 43/151) with 5-year failure-free survival of 38·29% (95% CI 25·31–57·95) versus 77·21% (95% CI 69·21–86·14) for the low-risk group (hazard ratio [HR] 4·14, 95% CI 2·47–6·93; p<0·0001; bootstrap-corrected HR 2·02), and outperformed a prognostic model of only gene mutations (HR 3·76, 95% CI 2·10–6·74; p<0·0001; bootstrap-corrected HR 1·57). The positive predictive value and negative predictive value for 5-year failure-free survival were 64% and 78%, respectively, with a C-index of 0·80 (95% CI 0·71–0·89). In the validation cohort, m7-FLIPI again defined a high-risk group (22%, 24/107) with 5-year failure-free survival of 25·00% (95% CI 12·50–49·99) versus 68·24% (58·84–79·15) in the low-risk group (HR 3·58, 95% CI 2·00–6·42; p<0.0001). The positive predictive value for 5-year failure-free survival was 72% and 68% for negative predictive value, with a C-index of 0·79 (95% CI 0·69–0·89). In the validation cohort, risk stratification by m7-FLIPI outperformed FLIPI alone (HR 2·18, 95% CI 1·21–3·92), and FLIPI combined with ECOG performance status (HR 2·03, 95% CI 1·12–3·67).
Integration of the mutational status of seven genes with clinical risk factors improves prognostication for patients with follicular lymphoma receiving first-line immunochemotherapy and is a promising approach to identify the subset at highest risk of treatment failure.
Deutsche Krebshilfe, Terry Fox Research Institute.
Journal Article