152 research outputs found
Lessons from Women Leaders: The Impact of Professional Development
Professional development is learner-centered, where the responsibility to engage in further educational experiences belongs to the individual and is a critical way to prepare for career advancement. In higher education, cisgender women do not hold the majority of chief student affairs officers (CSAO) positions, which is unexpected given their representation in entry and mid-level positions (Shea Gasser, 2014). This article reviews a grounded theory study conducted to better understand the phenomenon of professional development experiences of women CSAOs and how professional development impacts career ascension of women in student affairs
Exploration of 1,2-phenylenediboronic esters as potential bidentate catalysts for organic synthesis
Recently, we described the first inverse electron demand Diels-Alder reaction of 1,2-diazene catalyzed by a bidentate Lewis acid. Herein we investigate 1,2-phenylenediboronic esters as potential catalysts for this transformation offering higher stability and easier handling than the currently used boranthracene derivatives. Different 1,2-phenylenediboronic esters were prepared and their ability to form bidentate coordination complexes with phthalazine was analyzed. Although a 1:1 complex was observed, X-ray analysis revealed binding only in a monodentate fashion. Graphical abstrac
Pharmaceutical distribution networks in China: analysis of benefits and challenges of entering the Chinese market
Entering foreign markets is aligned with objectives related to and influenced by the market entered. Operationalisation of objectives as well as the given environment of the host country influence setup of distribution activities which demands for joint analysis of both topics.
The objective of this dissertation is to contribute to research by exploration and expansion of the current thinking through identification of motivations and strategies for entering the Chinese pharmaceutical market and for distributing pharmaceuticals within this market.
China reveals positive forecasts and progress in regard to market size, growth, governmental stabilisation and technological development. But, foreign companies operating in China are challenged by the current status of institutional development, economic, geographic and governmental disparities, cultural differences and complex, fragmented distribution networks.
This master dissertation follows an exploratory case study approach based on desktop research as well as information received by an interview with a distribution manager of AstraZeneca in Shanghai. AstraZeneca is a global, vertically integrated bio-pharmaceutical company which entered the Chinese market in 1993.
One conclusion of this dissertation is that entering the Chinese pharmaceutical market as pioneer in a particular market segment or therapeutic area may be beneficial. In terms of location decision, settlement in Eastern regions by joint venture and later development of a wholly-owned venture as well as expansion towards central regions such as Sichuan by greenfield investment is recommended.
Major competitive advantages of prominent pharmaceutical companies which are proposed to be followed are (1) own, innovative research facilities, (2) wholesaler and distributor networks, (3) globally spread production networks, (4) branding regarding sales but also to increase the company reputation to enhance recruiting, (5) common marketing for all facilities but with local adaption to China also considering regional disparities and with special regards to compliance in sales and marketing, (6) mix flexibility in terms of product portfolio adaption and (7) targeting of diverse market segments.
In terms of market positioning differentiation by innovation, branding and distribution channels while reaching a broad customer base is proposed. Early commitment to the Chinese market and related knowledge on local customer preferences, government policies and business practices linked with existent Guanxi provide a sustainable competitive advantage.
Regarding distribution no optimal solution was found. Outsourcing as well as in-house execution reveal significant advantages in the Chinese pharmaceutical environment. In any case particular regards should be given to partner networks, securing of pharmaceutical distribution channels, temperature and humidity management in transportation as well as warehousing and shelf-life tracing
Interactive cohort exploration for spinocerebellar ataxias using synthetic cohort data for visualization
Motivation: Visualization of data is a crucial step to understanding and
deriving hypotheses from clinical data. However, for clinicians, visualization
often comes with great effort due to the lack of technical knowledge about data
handling and visualization. The application offers an easy-to-use solution with
an intuitive design that enables various kinds of plotting functions. The aim
was to provide an intuitive solution with a low entrance barrier for clinical
users. Little to no onboarding is required before creating plots, while the
complexity of questions can grow up to specific corner cases. To allow for an
easy start and testing with SCAview, we incorporated a synthetic cohort dataset
based on real data of rare neurological movement disorders: the most common
autosomal-dominantly inherited spinocerebellar ataxias (SCAs) type 1, 2, 3, and
6 (SCA1, 2, 3 and 6). Methods: We created a Django-based backend application
that serves the data to a React-based frontend that uses Plotly for plotting. A
synthetic cohort was created to deploy a version of SCAview without violating
any data protection guidelines. Here, we added normal distributed noise to the
data and therefore prevent re-identification while keeping distributions and
general correlations. Results: This work presents SCAview, an user-friendly,
interactive web-based service that enables data visualization in a clickable
interface allowing intuitive graphical handling that aims to enable data
visualization in a clickable interface. The service is deployed and can be
tested with a synthetic cohort created based on a large, longitudinal dataset
from observational studies in the most common SCAs
Grxcr1 promotes hair bundle development by destabilizing the physical interaction between Harmonin and Sans usher syndrome proteins
© The Author(s), 2018. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Cell Reports 25 (2018): 1281–1291, doi:10.1016/j.celrep.2018.10.005.Morphogenesis and mechanoelectrical transduction
of the hair cell mechanoreceptor depend on the correct
assembly of Usher syndrome (USH) proteins
into highly organized macromolecular complexes.
Defects in these proteins lead to deafness and
vestibular areflexia in USH patients. Mutations in a
non-USH protein, glutaredoxin domain-containing
cysteine-rich 1 (GRXCR1), cause non-syndromic
sensorineural deafness. To understand the deglutathionylating
enzyme function of GRXCR1 in deafness,
we generated two grxcr1 zebrafish mutant
alleles. We found that hair bundles are thinner in
homozygous grxcr1 mutants, similar to the USH1
mutants ush1c (Harmonin) and ush1ga (Sans).
In vitro assays showed that glutathionylation promotes
the interaction between Ush1c and Ush1ga
and that Grxcr1 regulates mechanoreceptor development
by preventing physical interaction between
these proteins without affecting the assembly
of another USH1 protein complex, the Ush1c-
Cadherin23-Myosin7aa tripartite complex. By elucidating
the molecular mechanism through which
Grxcr1 functions, we also identify a mechanism that
dynamically regulates the formation of Usher protein
complexes.This work was supported by grants from the NIH (DC004186, OD011195, and HD22486)
Whole-genome and long-read sequencing identify a novel mechanism in RFC1 resulting in CANVAS syndrome
OBJECTIVES: Cerebellar ataxia with neuropathy and bilateral vestibular areflexia syndrome (CANVAS) results from biallelic intronic pentanucleotide repeats in
METHODS: We performed whole-genome sequencing (WGS) on peripheral blood DNA samples from the proband and his unaffected mother. We performed DNA long-read sequencing and synthesized complementary DNA from RNA using peripheral blood from the proband.
RESULTS: WGS confirmed the maternally inherited
DISCUSSION: We report an adult with CANVAS due to compound heterozygous pathogeni
Respiratory Capacity Is Twice as Important as Temperature in Explaining Patterns of Metabolic Rate Across the Vertebrate Tree of Life
Metabolic rate underlies a wide range of phenomena from cellular dynamics to ecosystem structure and function. Models seeking to statistically explain variation in metabolic rate across vertebrates are largely based on body size and temperature. Unexpectedly, these models overlook variation in the size of gills and lungs that acquire the oxygen needed to fuel aerobic processes. Here, we assess the importance of respiratory surface area in explaining patterns of metabolic rate across the vertebrate tree of life using a novel phylogenetic Bayesian multilevel modeling framework coupled with a species-paired dataset of metabolic rate and respiratory surface area. We reveal that respiratory surface area explains twice as much variation in metabolic rate, compared to temperature, across the vertebrate tree of life. Understanding the combination of oxygen acquisition and transport provides opportunity to understand the evolutionary history of metabolic rate and improve models that quantify the impacts of climate change
Discovery of a novel CHD7 CHARGE syndrome variant by integrated omics analyses
Chromodomain helicase DNA-binding protein 7 (CHD7) pathogenic variants are identified in more than 90% of infants and children with CHARGE (Coloboma of the iris, retina, and/or optic disk; congenital Heart defects, choanal Atresia, Retardation of growth and development, Genital hypoplasia, and characteristic outer and inner Ear anomalies and deafness) syndrome. Approximately, 10% of cases have no known genetic cause identified. We report a male child with clinical features of CHARGE syndrome and nondiagnostic genetic testing that included chromosomal microarray, CHD7 sequencing and deletion/duplication analysis, SEMA3E sequencing, and trio exome and whole-genome sequencing (WGS). We used a comprehensive clinical assessment, genome-wide methylation analysis (GMA), reanalysis of WGS data, and CHD7 RNA studies to discover a novel variant that causes CHD7 haploinsufficiency. The 7-year-old Hispanic male proband has typical phenotypic features of CHARGE syndrome. GMA revealed a CHD7-associated epigenetic signature. Reanalysis of the WGS data with focused bioinformatic analysis of CHD7 detected a novel, de novo 15 base pair deletion in Intron 4 of CHD7 (c.2239-20_2239-6delGTCTTGGGTTTTTGT [NM_017780.3]). Using proband RNA, we confirmed that this novel deletion causes CHD7 haploinsufficiency by disrupting the canonical 3′ splice site and introducing a premature stop codon. Integrated genomic, epigenomic, and transcriptome analyses discovered a novel CHD7 variant that causes CHARGE syndrome
A Radial Velocity Survey of the Cygnus OB2 Association
We conducted a radial velocity survey of the Cygnus OB2 Association over a 6
year (1999 - 2005) time interval to search for massive close binaries. During
this time we obtained 1139 spectra on 146 OB stars to measure mean systemic
radial velocities and radial velocity variations. We spectroscopically identify
73 new OB stars for the first time, the majority of which are likely to be
Association members. Spectroscopic evidence is also presented for a B3Iae
classification and temperature class variation (B3 - B8) on the order of 1 year
for Cygnus OB2 No. 12. Calculations of the intial mass function with the
current spectroscopic sample yield Gamma = -2.2 +/- 0.1. Of the 120 stars with
the most reliable data, 36 are probable and 9 are possible single-lined
spectroscopic binaries. We also identify 3 new and 8 candidate double-lined
spectroscopic binaries. These data imply a lower limit on the massive binary
fraction of 30% - 42%. The calculated velocity dispersion for Cygnus OB2 is
2.44 +/- km/s, which is typical of open clusters. No runaway OB stars were
found.Comment: 56 pages, 23 figures, 5 tables, accepted for publication in the
Astrophysical Journa
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