553 research outputs found
Unveiling the Impact of Human Influence on Species Distributions in Vietnam: A Case Study Using Babblers (Aves: Timaliidae)
As developing countries give priority to economic growth, the effects of development threaten natural habitats and species distributions. Over the course of two decades, Vietnam has rapidly developed, especially in the expansion of agricultural production. However, no study has quantitatively measured the effects of recent human impact on the effects of past species distributions in Vietnam. We use locality data collected from multiple natural history collections, including several in Vietnam, to infer past species distributions. We assess habitat availability of five common babbler species (Aves: Timaliidae) using distribution models with data prior to rapid development that followed political reform. Overlaying the Global Human Influence Index with predicted distributions highlights the human impact on these distributions. Three important patterns emerge: (1) human impact influences common Timaliidae distributions similarly, (2) widespread species distributions show higher fragmentation due to human influence compared to narrowly distributed species in Vietnam, and (3) less than 20% of distributions overlap with nationally declared protected areas. We emphasize that conservation efforts should not only prioritize individual species, but also focus efforts on a regional scale, and that the use of museum data can be highly informative in conservation analyses. There are current obstacles to enforcing conservation of Vietnam’s already fragmented habitats, but our results suggest there is still time to reevaluate conservation approaches
Empirical Evaluation of Pre-trained Transformers for Human-Level NLP: The Role of Sample Size and Dimensionality
In human-level NLP tasks, such as predicting mental health, personality, or
demographics, the number of observations is often smaller than the standard
768+ hidden state sizes of each layer within modern transformer-based language
models, limiting the ability to effectively leverage transformers. Here, we
provide a systematic study on the role of dimension reduction methods
(principal components analysis, factorization techniques, or multi-layer
auto-encoders) as well as the dimensionality of embedding vectors and sample
sizes as a function of predictive performance. We first find that fine-tuning
large models with a limited amount of data pose a significant difficulty which
can be overcome with a pre-trained dimension reduction regime. RoBERTa
consistently achieves top performance in human-level tasks, with PCA giving
benefit over other reduction methods in better handling users that write longer
texts. Finally, we observe that a majority of the tasks achieve results
comparable to the best performance with just of the embedding
dimensions.Comment: 2021 Annual Conference of the North American Chapter of the
Association for Computational Linguistics (NAACL-HLT
The Role of Small Satellites in the Establishment of the Gulf Region\u27s First Graduate Level Space Studies Program
Yahsat, Northrop Grumman, and Khalifa University created the Gulf region\u27s first master\u27s level advanced studies space program. To date this program has graduated three classes of master\u27s students and received accolades from the UAE Space Agency and Abu Dhabi\u27s Mubadala Investment Company. The program\u27s primary goal is to develop the resources and work force that the UAE requires to establish itself as a space-faring nation. Integral to this program are small satellites, initially used to train and educate the students and ultimately growing to accommodate new technologies and scientific payloads developed in the UAE. The first of these small satellites, a 1U CubeSat named MYSat-1 was launched in November of 2018 and deployed from the Northrop Grumman Cygnus on 13 February, 2019.
In this paper we present the role small satellites played in the establishment of this program. We discuss the challenges of establishing a satellite program at a university without a formal aerospace curriculum and how the small satellite became the anchor project for the student development. In this context, we explore the advantages of making use of the broadly established small satellite COTS component marketplace relative to the didactical benefits to be gained from having the students develop the new hardware in-house. Finally, we review the process of setting up a new small satellite lab established to be used as the primary resource for developing and testing small satellites in the country
Role of Esrrg in the Fibrate-Mediated Regulation of Lipid Metabolism Genes in Human ApoA-I Transgenic Mice
We have used a new ApoA-I transgenic mouse model to identify by global gene expression profiling, candidate genes that affect lipid and lipoprotein metabolism in response to fenofibrate treatment. Multilevel bioinformatical analysis and stringent selection criteria (2-fold change, 0% false discovery rate) identified 267 significantly changed genes involved in several molecular pathways. The fenofibrate-treated group did not have significantly altered levels of hepatic human APOA-I mRNA and plasma ApoA-I compared with the control group. However, the treatment increased cholesterol levels to 1.95-fold mainly due to the increase in high-density lipoprotein (HDL) cholesterol. The observed changes in HDL are associated with the upregulation of genes involved in phospholipid biosynthesis and lipid hydrolysis, as well as phospholipid transfer protein. Significant upregulation was observed in genes involved in fatty acid transport and β-oxidation, but not in those of fatty acid and cholesterol biosynthesis, Krebs cycle and gluconeogenesis. Fenofibrate changed significantly the expression of seven transcription factors. The estrogen receptor-related gamma gene was upregulated 2.36-fold and had a significant positive correlation with genes of lipid and lipoprotein metabolism and mitochondrial functions, indicating an important role of this orphan receptor in mediating the fenofibrate-induced activation of a specific subset of its target genes.National Institutes of Health (HL48739 and HL68216); European Union (LSHM-CT-2006-0376331, LSHG-CT-2006-037277); the Biomedical Research Foundation of the Academy of Athens; the Hellenic Cardiological Society; the John F Kostopoulos Foundatio
MAGI1 Inhibits Interferon Signaling to Promote Influenza a Infection
We have shown that membrane-associated guanylate kinase with inverted domain structure-1 (MAGI1), a scaffold protein with six PSD95/DiscLarge/ZO-1 (PDZ) domains, is involved in the regulation of endothelial cell (EC) activation and atherogenesis in mice. In addition to causing acute respiratory disease, influenza A virus (IAV) infection plays an important role in atherogenesis and triggers acute coronary syndromes and fatal myocardial infarction. Therefore, the aim of this study is to investigate the function and regulation of MAGI1 in IAV-induced EC activation. Whereas, EC infection by IAV increases MAGI1 expression, MAGI1 depletion suppresses IAV infection, suggesting that the induction of MAGI1 may promote IAV infection. Treatment of ECs with oxidized low-density lipoprotein (OxLDL) increases MAGI1 expression and IAV infection, suggesting that MAGI1 is part of the mechanistic link between serum lipid levels and patient prognosis following IAV infection. Our microarray studies suggest that MAGI1-depleted ECs increase protein expression and signaling networks involve in interferon (IFN) production. Specifically, infection of MAGI1-null ECs with IAV upregulates expression of signal transducer and activator of transcription 1 (STAT1), interferon b1 (IFNb1), myxovirus resistance protein 1 (MX1) and 2\u27-5\u27-oligoadenylate synthetase 2 (OAS2), and activate STAT5. By contrast, MAGI1 overexpression inhibits Ifnb1 mRNA and MX1 expression, again supporting the pro-viral response mediated by MAGI1. MAGI1 depletion induces the expression of MX1 and virus suppression. The data suggests that IAV suppression by MAGI1 depletion may, in part, be due to MX1 induction. Lastly, interferon regulatory factor 3 (IRF3) translocates to the nucleus in the absence of IRF3 phosphorylation, and IRF3 SUMOylation is abolished in MAGI1-depleted ECs. The data suggests that MAGI1 inhibits IRF3 activation by maintaining IRF3 SUMOylation. In summary, IAV infection occurs in ECs in a MAGI1 expression-dependent manner by inhibiting anti-viral responses including STATs and IRF3 activation and subsequent MX1 induction, and MAGI1 plays a role in EC activation, and in upregulating a pro-viral response. Therefore, the inhibition of MAGI1 is a potential therapeutic target for IAV-induced cardiovascular disease
Averaged Differential Expression for the Discovery of Biomarkers in the Blood of Patients with Prostate Cancer
<div><h3>Background</h3><p>The identification of a blood-based diagnostic marker is a goal in many areas of medicine, including the early diagnosis of prostate cancer. We describe the use of averaged differential display as an efficient mechanism for biomarker discovery in whole blood RNA. The process of averaging reduces the problem of clinical heterogeneity while simultaneously minimizing sample handling.</p> <h3>Methodology/Principal Findings</h3><p>RNA was isolated from the blood of prostate cancer patients and healthy controls. Samples were pooled and subjected to the averaged differential display process. Transcripts present at different levels between patients and controls were purified and sequenced for identification. Transcript levels in the blood of prostate cancer patients and controls were verified by quantitative RT-PCR. Means were compared using a t-test and a receiver-operating curve was generated. The Ring finger protein 19A (RNF19A) transcript was identified as having higher levels in prostate cancer patients compared to healthy men through the averaged differential display process. Quantitative RT-PCR analysis confirmed a more than 2-fold higher level of RNF19A mRNA levels in the blood of patients with prostate cancer than in healthy controls (p = 0.0066). The accuracy of distinguishing cancer patients from healthy men using RNF19A mRNA levels in blood as determined by the area under the receiving operator curve was 0.727.</p> <h3>Conclusions/Significance</h3><p>Averaged differential display offers a simplified approach for the comprehensive screening of body fluids, such as blood, to identify biomarkers in patients with prostate cancer. Furthermore, this proof-of-concept study warrants further analysis of RNF19A as a clinically relevant biomarker for prostate cancer detection.</p> </div
Alcohol Regulates Genes that Are Associated with Response to Endocrine Therapy and Attenuates the Actions of Tamoxifen in Breast Cancer Cells
Hereditary, hormonal, and behavioral factors contribute to the development of breast cancer. Alcohol consumption is a modifiable behavior that is linked to increased breast cancer risks and is associated with the development of hormone-dependent breast cancers as well as disease progression and recurrence following endocrine treatment. In this study we examined the molecular mechanisms of action of alcohol by applying molecular, genetic, and genomic approaches in characterizing its effects on estrogen receptor (ER)-positive breast cancer cells. Treatments with alcohol promoted cell proliferation, increased growth factor signaling, and up-regulated the transcription of the ER target gene GREB1 but not the canonical target TFF1/pS2. Microarray analysis following alcohol treatment identified a large number of alcohol-responsive genes, including those which function in apoptotic and cell proliferation pathways. Furthermore, expression profiles of the responsive gene sets in tumors were strongly associated with clinical outcomes in patients who received endocrine therapy. Correspondingly, alcohol treatment attenuated the anti-proliferative effects of the endocrine therapeutic drug tamoxifen in ER-positive breast cancer cells. To determine the contribution and functions of responsive genes, their differential expression in tumors were assessed between outcome groups. The proto-oncogene BRAF was identified as a novel alcohol- and estrogen-induced gene that showed higher expression in patients with poor outcomes. Knock-down of BRAF, moreover, prevented the proliferation of breast cancer cells. These findings not only highlight the mechanistic basis of the effects of alcohol on breast cancer cells and increased risks for disease incidents and recurrence, but may facilitate the discovery and characterization of novel oncogenic pathways and markers in breast cancer research and therapeutics
Comparative Analysis of Gene Regulation by the Transcription Factor PPARα between Mouse and Human
Studies in mice have shown that PPARalpha is an important regulator of hepatic lipid metabolism and the acute phase response. However, little information is available on the role of PPARalpha in human liver. Here we set out to compare the function of PPARalpha in mouse and human hepatocytes via analysis of target gene regulation
Maspin is a tumour suppressor that inhibits breast cancer tumour metastasis in vivo
Maspin is a member of the serpin family of serine proteases and functions as a tumour suppressor. A study using a new syngeneic mouse model for breast cancer suggests that maspin can inhibit metastasis in vivo
Six-membered ring systems: with O and/or S atoms
A large variety of publications have emerged in 2012 involving O- and S-6-
membered ring systems. The increasing number of reviews and other communica-
tions dedicated to natural and synthetic derivatives and their biological significance
highlights the importance of these heterocycles.
Reviews on natural products involve biosynthesis and isolation of enantiomeric
derivatives h12AGE4802i, biosynthesis, isolation, synthesis, and biological studies
on the pederin family h12NPR980i and xanthones obtained from fungi, lichens,
and bacteria h12CR3717i and on the potential chemotherapeutic value of phyto-
chemical products and plant extracts as antidiabetic h12NPR580i, antimicrobial,
and resistance-modifying agents h12NPR1007i. A more specific review covers a
structure–activity relationship of endoperoxides from marine origin and their antitry-
panosomal activity h12OBC7197i.
New synthetic routes to naturally occurring, biologically active pyran derivatives
have been the object of several papers. Different approaches have been discussed for
the total synthesis of tetrahydropyran-containing natural products (")-zampanolide
h12CEJ16868, 12EJO4130, 12OL3408i, (")-aspergillides A and B h12H(85)587,
12H(85)1255, 12TA252i, (Ăľ)-neopeltolide h12JOC2225, 12JOC9840, 12H(85)
1255i, or their macrolactone core h12OBC3689, 12OL2346i. The total synthesis
of bistramide A h12CEJ7452i and (Ăľ)-kalihinol A h12CC901i and the stereoselec-
tive synthesis of a fragment of bryostatin h12S3077, 12TL6163i have also been sur-
veyed. Other papers relate the total synthesis of naturally occurring carbocyclic and
heterocyclic-fused pyran compounds, such as (")-dysiherbaine h12CC6295i, penos-
tatin B h12OL244i, Greek tobacco lactonic products, and analogues h12TL4293i
and on the structurally intriguing limonoids andhraxylocarpins A–E h12CEJ14342i.
The stereocontrolled synthesis of fused tetrahydropyrans was used in the preparation
of blepharocalyxin D h12AGE3901i.
Polyphenolic heterocyclic compounds have also received great attention in 2012.
The biological activities and the chemistry of prenylated caged xanthones
h12PCB78i, the occurrence of sesquiterpene coumarins h12PR77i, and the medicinal properties of the xanthone mangiferin h12MRME412i have been reviewed.
An overview on the asymmetric syntheses of flavanones and chromanones
h12EJO449i, on the synthesis and reactivity of flavones h12T8523i and xanthones
h12COC2818i, on the synthesis and biosynthesis of biocoumarins h12T2553i, and on
the synthesis and applications of flavylium compounds h12CSR869i has been discussed.
The most recent developments in the synthesis and applications of sultones, a
very important class of sulfur compounds, were reported h12CR5339i.
A review on xanthene-based fluorescent probes for sensing cations, anions, bio-
logical species, and enzyme activity has described the spiro-ring-opening approach
with a focus on the major mechanisms controlling their luminescence behavior
h12CR1910i. The design and synthesis of other derivatives to be used as sensors of
gold species h12CC11229i and other specific metal cations h12PC823i have also
been described. Recent advances related to coumarin-derived fluorescent chemosen-
sors for metal ions h12COC2690i and to monitoring in vitro analysis and cellular
imaging of monoamine oxidase activity h12CC6833i have been discussed.
The study of various organic chromophores allowed the synthesis of novel dica-
tionic phloroglucinol-type bisflavylium pigments h12SL2053i, and the optical and
spectroscopic properties of several synthetic 6-aryldibenzo[b,d]pyrylium salts were
explored h12TL6433i.
Discussion of specific reactions leading to O- and S-membered heterocyclic
compounds covers intramolecular radical cyclization h12S2475i and asymmetric
enamine and dienamine catalysis h12EJO865i, oxa-Michael h12CSR988i and dom-
ino Knoevenagel–hetero-Diels–Alder (hDA) reactions h12T5693i, and the versatility
in cycloadditions as well as nucleophilic reactions using o-quinones h12CSR1050i.
The use of specific reagents relevant to this chapter includes molecular iodine
h12CEJ5460, 12COS561i, samarium diiodide–water for selective reductive transfor-
mations h12CC330i, o-quinone methides as versatile intermediates h12CEJ9160i,
InCl3 as catalyst h12T8683i, and gold and platinum p-acid mediated insertion of
alkynes into carbon–heteroatom s-bonds h12S3401i.
The remainder of this chapter discusses the most studied transformations on
O- and S-6-membered heterocycles
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