Tikhonov Regularization Within Ensemble Kalman Inversion

Ensemble Kalman inversion is a parallelizable methodology for solving inverse or parameter estimation problems. Although it is based on ideas from Kalman filtering, it may be viewed as a derivative-free optimization method. In its most basic form it regularizes ill-posed inverse problems through the subspace property: the solution found is in the linear span of the initial ensemble employed. In this work we demonstrate how further regularization can be imposed, incorporating prior information about the underlying unknown. In particular we study how to impose Tikhonov-like Sobolev penalties. As well as introducing this modified ensemble Kalman inversion methodology, we also study its continuous-time limit, proving ensemble collapse; in the language of multi-agent optimization this may be viewed as reaching consensus. We also conduct a suite of numerical experiments to highlight the benefits of Tikhonov regularization in the ensemble inversion context.Comment: 39 page

Fallopian tube origin of supposed ovarian high‐grade serous carcinomas

INTRODUCTION: Serous carcinomas are the most frequent histologic type of ovarian and peritoneal cancers, and can also be detected in the endometrium and fallopian tubes. Serous carcinomas are usually high-grade neoplasms when diagnosed, yet the identification of an associated precursor lesion remains challenging. Pathological examination of specimens obtained from prophylactic bilateral salpingo-oophorectomies that were performed for patients harboring BRCA1/2 mutations suggests that high-grade serous carcinomas may arise in the fallopian tubes rather than in the ovaries. OBJECTIVE: To investigate the presence and extent of fallopian tube involvement in cases of serous pelvic carcinomas. METHODS: Thirty-four cases of serous pelvic carcinoma with clinical presentations suggesting an ovarian origin were analyzed retrospectively. Histologic samples of fallopian tube tissues were available for these cases and were analyzed. Probable primary site, type of tubal involvement, tissues involved in the neoplasia and vascular involvement were evaluated. RESULTS: Fallopian tube involvement was observed in 24/34 (70.6%) cases. In 4 (11.8%) of these cases, an intraepithelial neoplasia was present, and therefore these cases were hypothesized to be primary from fallopian tubes. For an additional 7/34 (20.6%) cases, a fallopian tube origin was considered a possible primary. CONCLUSIONS: Fallopian tubes can be the primary site for a subset of pelvic high-grade serous carcinomas

Single-molecule observation of nucleotide induced conformational changes in basal SecA-ATP hydrolysis

11 pages ; illustrationsSecA is the critical adenosine triphosphatase that drives preprotein transport through the translocon, SecYEG, in Escherichia coli. This process is thought to be regulated by conformational changes of specific domains of SecA, but real-time, real-space measurement of these changes is lacking. We use single-molecule atomic force microscopy (AFM) to visualize nucleotide-dependent conformations and conformational dynamics of SecA. Distinct topographical populations were observed in the presence of specific nucleotides. AFM investigations during basal adenosine triphosphate (ATP) hydrolysis revealed rapid, reversible transitions between a compact and an extended state at the ~100-ms time scale. A SecA mutant lacking the precursor-binding domain (PBD) aided interpretation. Further, the biochemical activity of SecA prepared for AFM was confirmed by tracking inorganic phosphate release. We conclude that ATP-driven dynamics are largely due to PBD motion but that other segments of SecA contribute to this motion during the transition state of the ATP hydrolysis cycle.Funding: This work was supported by the National Science Foundation (CAREER award number 1054832 to G.M.K.) and a Burroughs Wellcome Fund Career Award at the Scientific Interface (to G.M.K.)Nagaraju Chada1*, Kanokporn Chattrakun1, Brendan P. Marsh1†, Chunfeng Mao2, Priya Bariya2, Gavin M. King1,2‡: 1Department of Physics and Astronomy, University of Missouri–Columbia, Columbia, MO 65211, USA. 2Department of Biochemistry, University of Missouri–Columbia, Columbia, MO 65211, USA. *Present address: Department of Biology, Johns Hopkins University, 3400 North Charles Street, Baltimore, MD 21218, USA. †Present address: Department of Applied Physics, Stanford University, Stanford, CA 94305 USA. ‡Corresponding author.Nagaraju Chada (1*), Kanokporn Chattrakun (1), Brendan P. Marsh (1†), Chunfeng Mao (2), Priya Bariya (2), Gavin M. King (1,2‡) -- References: 1) Department of Physics and Astronomy, University of Missouri–Columbia, Columbia,MO 65211, USA ; 2) Department of Biochemistry, University of Missouri–Columbia, Columbia, MO 65211, USA ; *) Present address: Department of Biology, Johns Hopkins University, 3400 North Charles Street, Baltimore, MD 21218, USA ; †) Present address: Department of Applied Physics, Stanford University, Stanford, CA 94305 USA ; ‡) Corresponding author

The hessian blob algorithm : precise particle detection in atomic force microscopy imagery

"Received: 20 October 2017; Accepted: 29 December 2017; Published online: 17 January 2018."Imaging by atomic force microscopy (AFM) offers high-resolution descriptions of many biological systems; however, regardless of resolution, conclusions drawn from AFM images are only as robust as the analysis leading to those conclusions. Vital to the analysis of biomolecules in AFM imagery is the initial detection of individual particles from large-scale images. Threshold and watershed algorithms are conventional for automatic particle detection but demand manual image preprocessing and produce particle boundaries which deform as a function of user-defined parameters, producing imprecise results subject to bias. Here, we introduce the Hessian blob to address these shortcomings. Combining a scalespace framework with measures of local image curvature, the Hessian blob formally defines particle centers and their boundaries, both to subpixel precision. Resulting particle boundaries are independent of user defined parameters, with no image preprocessing required. We demonstrate through direct comparison that the Hessian blob algorithm more accurately detects biomolecules than conventional AFM particle detection techniques. Furthermore, the algorithm proves largely insensitive to common imaging artifacts and noise, delivering a stable framework for particle analysis in AFM

MEDIDA PROVISÓRIA Nº 948 DE 8 DE ABRIL DE 2020 E OS IMPACTOS SOBRE OS DIREITOS SOCIAIS E ECONÔMICOS NAS RELAÇÕES DE CONSUMO

O presente trabalho tratou do tema da Medida Provisória nº 948, de 8 de abril de 2020, com foco nos impactos que sua edição causou nos direitos sociais e nas relações de consumo. O objetivo central do trabalho foi responder as perguntas: “quais consequências a Medida Provisória em questão trouxe para os direitos dos consumidores? Como harmonizar e equilibrar as relações de consumo em meio a uma pandemia que provocou uma grave crise econômica mundial?”. Adotou-se como metodologia de pesquisa o método de abordagem indutivo e o método de procedimento de análise de jurisprudência e análise bibliográfica. Os objetivos específicos do trabalho foram: compreender a Medida Provisória a partir de premissas constitucionais; analisar o impacto do referido ato normativo nos direitos sociais e econômicos dos consumidores e realizar a análise crítica da medida editad

MEDIDA PROVISÓRIA Nº 948 DE 8 DE ABRIL DE 2020 E OS IMPACTOS SOBRE OS DIREITOS SOCIAIS E ECONÔMICOS NAS RELAÇÕES DE CONSUMO

O presente trabalho tratou do tema da Medida Provisória nº 948, de 8 de abril de 2020, com foco nos impactos que sua edição causou nos direitos sociais e nas relações de consumo. O objetivo central do trabalho foi responder as perguntas: “quais consequências a Medida Provisória em questão trouxe para os direitos dos consumidores? Como harmonizar e equilibrar as relações de consumo em meio a uma pandemia que provocou uma grave crise econômica mundial?”. Adotou-se como metodologia de pesquisa o método de abordagem indutivo e o método de procedimento de análise de jurisprudência e análise bibliográfica. Os objetivos específicos do trabalho foram: compreender a Medida Provisória a partir de premissas constitucionais; analisar o impacto do referido ato normativo nos direitos sociais e econômicos dos consumidores e realizar a análise crítica da medida editad

Glass is a viable substrate for precision force microscopy of membrane proteins

Scientific Reports ; 5:12550 ; DOI: 10.1038/srep12550.Chada, N. et al. Glass is a Viable Substrate for Precision Force Microscopy of Membrane Proteins. Sci. Rep. 5, 12550; doi: 10.1038/srep12550 (2015).8 pages.Received: 01 April 2015 ; Accepted: 02 July 2015 ; Published: 31 July 2015.Though ubiquitous in optical microscopy, glass has long been overlooked as a specimen supporting surface for high resolution atomic force microscopy (AFM) investigations due to its roughness. Using bacteriorhodopsin from Halobacterium salinarum and the translocon SecYEG from Escherichia coli, we demonstrate that faithful images of 2D crystalline and non-crystalline membrane proteins in lipid bilayers can be obtained on microscope cover glass following a straight-forward cleaning procedure. Direct comparison between AFM data obtained on glass and on mica substrates show no major differences in image fidelity. Repeated association of the ATPase SecA with the cytoplasmic protrusion of SecYEG demonstrates that the translocon remains competent for binding after tens of minutes of continuous AFM imaging. This opens the door for precision long-timescale investigations of the active translocase in near-native conditions and, more generally, for integration of high resolution biological AFM with many powerful optical techniques that require non-birefringent substrates.Includes bibliographical references

Adherence to cervical and breast cancer programs is crucial to improving screening performance

Publicado onlineINTRODUCTION: Cervical and breast cancer are the most common malignancies among women worldwide. Effective screening can facilitate early detection and dramatically reduce mortality rates. The interface between those screening patients and patients most needing screening is complex, and women in remote areas of rural counties face additional barriers that limit the effectiveness of cancer prevention programs. This study compared various methods to improve compliance with mass screening for breast and cervical cancer among women in a remote, rural region of Brazil. METHODS: In 2003, a mobile unit was used to perform 10,156 mammograms and Papanicolaou smear tests for women living in the Barretos County region of São Paulo state, Brazil (consisting of 19 neighbouring cities). To reach the women, the following community outreach strategies were used: distribution of flyers and pamphlets; media broadcasts (via radio and car loudspeakers); and community healthcare agents (CHCAs) making home visits. RESULTS: The most useful intervention appeared to be the home visits by healthcare agents or CHCAs. These agents of the Family Health Programme of the Brazilian Ministry of Health reached an average of 45.6% of those screened, with radio advertisements reaching a further 11.9%. The great majority of the screened women were illiterate or had elementary level schooling (80.9%) and were of 'poor' or 'very poor' socioeconomic class (67.2%). CONCLUSIONS: Use of a mobile screening unit is a useful strategy in developing countries where local health systems have inadequate facilities for cancer screening in underserved populations. A multimodal approach to community outreach strategies, especially using CHCAs and radio advertisements, can improve the uptake of mass screening in low-income, low-educational background female populations

Glass is a viable substrate for atomic force microscopy of membrane proteins : [abstract]

Abstract only."2314-Pos Board B6.""Page 458a, Tuesday, February 18, 2014."--At top of page.Abstract in program book: Since its invention in the mid-1980s, the atomic force microscope (AFM) has become an invaluable complementary tool for studying membrane proteins in near-native environments. Historically, mica is the most common substrate utilized for biological AFM. Glass being amorphous, transparent, and optically homogeneous has its own set of advantages over mica and has the potential to broaden the use the AFM into fields that require high quality non-birefringent optical access. The use of silanized glass as AFM substrates has been reported as a means to fine tune surface chemistry. However, such coatings usually require hours of additional preparation time and can lead to increased surface roughness. In this work, we present a simple technique for preparing borosilicate glass as a substrate for two membrane systems: non-crystalline translocons (SecYEG) of the general secretary system from E. coli, and bacteriorhodopsin (BR) from H. salinarum. For both these membrane proteins, quantitative comparisons of the measured protein structures on glass versus mica substrates show agreement. An additional advantage of glass is that lipid coverage is rapid (< 10 minutes) and complete (occupying the entire surface). A goal is to study the bacterial export system using recently developed precision measurement techniques such as ultra-stable AFM