Asymmetric synthesis of arylglycines, The

1992 Summer.Includes bibliographical references.The asymmetric synthesis of several arylglycines is discussed. Several methods for the coupling of an aromatic group to the chiral bromoglycinates (171, 172) were developed. It was found that the cuprate and Friedel-Crafts couplings provided the desired aryl-coupled glycinates in the greatest yield with excellent selectivity. An oxidative protocol was employed to unmask the oxazinone chiral auxiliary which provided the desired free α-amino acids. A reductive deprotection method was also employed in two unique cases which efficiently gave the arylglycine products. The % ee's ranged from 82 to 94 %. This methodology was further utilized in an approach to the asymmetric synthesis of the bis-arylglycine, actinoidic acid. This study explored the scope of the Stille biphenyl cross-coupling reaction and produced methodology for the synthesis of biphenyl amino acid precursors

Opportunities, barriers, and recommendations in down syndrome research

BACKGROUND: Recent advances in medical care have increased life expectancy and improved the quality of life for people with Down syndrome (DS). These advances are the result of both pre-clinical and clinical research but much about DS is still poorly understood. In 2020, the NIH announced their plan to update their DS research plan and requested input from the scientific and advocacy community. OBJECTIVE: The National Down Syndrome Society (NDSS) and the LuMind IDSC Foundation worked together with scientific and medical experts to develop recommendations for the NIH research plan. METHODS: NDSS and LuMind IDSC assembled over 50 experts across multiple disciplines and organized them in eleven working groups focused on specific issues for people with DS. RESULTS: This review article summarizes the research gaps and recommendations that have the potential to improve the health and quality of life for people with DS within the next decade. CONCLUSIONS: This review highlights many of the scientific gaps that exist in DS research. Based on these gaps, a multidisciplinary group of DS experts has made recommendations to advance DS research. This paper may also aid policymakers and the DS community to build a comprehensive national DS research strategy

Phosphorylation of the phosphatase modulator subunit (inhibitor-2) by casein kinase-1 Identification of the phosphorylation sites

AbstractThe isolated modulator subunit of the inactive protein phosphatase-1 is phosphorylated in vitro by casein kinase-1 at two different site Ser-86 and Ser-174. The Ser-86 site is a common target for casein kinase-1 and casein kinase-2, but is preferentially phosphorylated by the former enzyme. The Ser-174 site seems to be specific for casein kinase-1, and is phosphorylated at a slower rate. These results give a new insight into the in vitro phosphorylation pattern of the modulator subunit of the phosphatase and provides additional data on the specificity of casein kinase-1

The Stem Cell Phenotype of Aggressive Breast Cancer Cells

Aggressive cancer cells are characterized by their capacity to proliferate indefinitely and to propagate a heterogeneous tumor comprised of subpopulations with varying degrees of metastatic propensity and drug resistance properties. Particularly daunting is the challenge we face in the field of oncology of effectively targeting heterogeneous tumor cells expressing a variety of markers, especially those associated with a stem cell phenotype. This dilemma is especially relevant in breast cancer, where therapy is based on traditional classification schemes, including histological criteria, differentiation status, and classical receptor markers. However, not all patients respond in a similar manner to standard-of-care therapy, thereby necessitating the need to identify and evaluate novel biomarkers associated with the difficult-to-target stem cell phenotype and drug resistance. Findings related to the convergence of embryonic and tumorigenic signaling pathways have identified the embryonic morphogen Nodal as a promising new oncofetal target that is reactivated only in aggressive cancers, but not in normal tissues. The work presented in this paper confirms previous studies demonstrating the importance of Nodal as a cancer stem cell molecule associated with aggressive breast cancer, and advances the field by providing new findings showing that Nodal is not targeted by standard-of-care therapy in breast cancer patients. Most noteworthy is the linkage found between Nodal expression and the drug resistance marker ATP-binding cassette member 1 (ABCA1), which may provide new insights into developing combinatorial approaches to overcome drug resistance and disease recurrence

The Stem Cell Phenotype of Aggressive Breast Cancer Cells

Aggressive cancer cells are characterized by their capacity to proliferate indefinitely and to propagate a heterogeneous tumor comprised of subpopulations with varying degrees of metastatic propensity and drug resistance properties. Particularly daunting is the challenge we face in the field of oncology of effectively targeting heterogeneous tumor cells expressing a variety of markers, especially those associated with a stem cell phenotype. This dilemma is especially relevant in breast cancer, where therapy is based on traditional classification schemes, including histological criteria, differentiation status, and classical receptor markers. However, not all patients respond in a similar manner to standard-of-care therapy, thereby necessitating the need to identify and evaluate novel biomarkers associated with the difficult-to-target stem cell phenotype and drug resistance. Findings related to the convergence of embryonic and tumorigenic signaling pathways have identified the embryonic morphogen Nodal as a promising new oncofetal target that is reactivated only in aggressive cancers, but not in normal tissues. The work presented in this paper confirms previous studies demonstrating the importance of Nodal as a cancer stem cell molecule associated with aggressive breast cancer, and advances the field by providing new findings showing that Nodal is not targeted by standard-of-care therapy in breast cancer patients. Most noteworthy is the linkage found between Nodal expression and the drug resistance marker ATP-binding cassette member 1 (ABCA1), which may provide new insights into developing combinatorial approaches to overcome drug resistance and disease recurrence

Invasion of exotic earthworms into ecosystems inhabited by native earthworms

The most conspicuous biological invasions in terrestrial ecosystems have been by exotic plants, insects and vertebrates. Invasions by exotic earthworms, although not as well studied, may be increasing with global commerce in agriculture, waste management and bioremediation. A number of cases has documented where invasive earthworms have caused significant changes in soil profiles, nutrient and organic matter dynamics, other soil organisms or plant communities. Most of these cases are in areas that have been disturbed (e.g., agricultural systems) or were previously devoid of earthworms (e.g., north of Pleistocene glacial margins). It is not clear that such effects are common in ecosystems inhabited by native earthworms, especially where soils are undisturbed. We explore the idea that indigenous earthworm fauna and/or characteristics of their native habitats may resist invasion by exotic earthworms and thereby reduce the impact of exotic species on soil processes. We review data and case studies from temperate and tropical regions to test this idea. Specifically, we address the following questions: Is disturbance a prerequisite to invasion by exotic earthworms? What are the mechanisms by which exotic earthworms may succeed or fail to invade habitats occupied by native earthworms? Potential mechanisms could include (1) intensity of propagule pressure (how frequently and at what densities have exotic species been introduced and has there been adequate time for proliferation?); (2) degree of habitat matching (once introduced, are exotic species faced with unsuitable habitat conditions, unavailable resources, or unsuited feeding strategies?); and (3) degree of biotic resistance (after introduction into an otherwise suitable habitat, are exotic species exposed to biological barriers such as predation or parasitism, ‘‘unfamiliar’’ microflora, or competition by resident native species?). Once established, do exotic species coexist with native species, or are the natives eventually excluded? Do exotic species impact soil processes differently in the presence or absence of native species? We conclude that (1) exotic earthworms do invade ecosystems inhabited by indigenous earthworms, even in the absence of obvious disturbance; (2) competitive exclusion of native earthworms by exotic earthworms is not easily demonstrated and, in fact, co-existence of native and exotic species appears to be common, even if transient; and (3) resistance to exotic earthworm invasions, if it occurs, may be more a function of physical and chemical characteristics of a habitat than of biological interactions between native and exotic earthworms

The association of diabetes and obesity with prostate cancer aggressiveness among Black Americans and White Americans in a population-based study

Few studies have investigated the role of race in the association of diabetes and obesity with prostate cancer aggressiveness. Here we evaluate the independent association between diabetes and obesity with prostate cancer aggressiveness in White Americans and Black Americans

Cross-Sectional Exploration of Plasma Biomarkers of Alzheimer\u27s Disease in Down Syndrome: Early Data from the Longitudinal Investigation for Enhancing Down Syndrome Research (LIFE-DSR) Study

With improved healthcare, the Down syndrome (DS) population is both growing and aging rapidly. However, with longevity comes a very high risk of Alzheimer’s disease (AD). The LIFE-DSR study (NCT04149197) is a longitudinal natural history study recruiting 270 adults with DS over the age of 25. The study is designed to characterize trajectories of change in DS-associated AD (DS-AD). The current study reports its cross-sectional analysis of the first 90 subjects enrolled. Plasma biomarkers phosphorylated tau protein (p-tau), neurofilament light chain (NfL), amyloid β peptides (Aβ1-40, Aβ1-42), and glial fibrillary acidic protein (GFAP) were undertaken with previously published methods. The clinical data from the baseline visit include demographics as well as the cognitive measures under the Severe Impairment Battery (SIB) and Down Syndrome Mental Status Examination (DS-MSE). Biomarker distributions are described with strong statistical associations observed with participant age. The biomarker data contributes to understanding DS-AD across the spectrum of disease. Collectively, the biomarker data show evidence of DS-AD progression beginning at approximately 40 years of age. Exploring these data across the full LIFE-DSR longitudinal study population will be an important resource in understanding the onset, progression, and clinical profiles of DS-AD pathophysiology

What difference does ("good") HRM make?

The importance of human resources management (HRM) to the success or failure of health system performance has, until recently, been generally overlooked. In recent years it has been increasingly recognised that getting HR policy and management "right" has to be at the core of any sustainable solution to health system performance. In comparison to the evidence base on health care reform-related issues of health system finance and appropriate purchaser/provider incentive structures, there is very limited information on the HRM dimension or its impact. Despite the limited, but growing, evidence base on the impact of HRM on organisational performance in other sectors, there have been relatively few attempts to assess the implications of this evidence for the health sector. This paper examines this broader evidence base on HRM in other sectors and examines some of the underlying issues related to "good" HRM in the health sector. The paper considers how human resource management (HRM) has been defined and evaluated in other sectors. Essentially there are two sub-themes: how have HRM interventions been defined? and how have the effects of these interventions been measured in order to identify which interventions are most effective? In other words, what is "good" HRM? The paper argues that it is not only the organisational context that differentiates the health sector from many other sectors, in terms of HRM. Many of the measures of organisational performance are also unique. "Performance" in the health sector can be fully assessed only by means of indicators that are sector-specific. These can focus on measures of clinical activity or workload (e.g. staff per occupied bed, or patient acuity measures), on measures of output (e.g. number of patients treated) or, less frequently, on measures of outcome (e.g. mortality rates or rate of post-surgery complications). The paper also stresses the need for a "fit" between the HRM approach and the organisational characteristics, context and priorities, and for recognition that so-called "bundles" of linked and coordinated HRM interventions will be more likely to achieve sustained improvements in organisational performance than single or uncoordinated interventions

Board of Regents

This report, fifteenth of an annual series, describes 1993 mineral, oil and gas, and geothermal activities and accomplishments in Nevada: production statistics, exploration and development including drilling for petroleum and geothermal resources, discoveries of orebodies, new mines opened, and expansion and other activities of existing mines. Statistics of known gold and silver deposits, and directories of mines and mills are included. For more information contact