866 research outputs found
Microarray evidence of glutaminyl cyclase gene expression in melanoma: implications for tumor antigen specific immunotherapy
BACKGROUND: In recent years encouraging progress has been made in developing vaccine treatments for cancer, particularly with melanoma. However, the overall rate of clinically significant results has remained low. The present research used microarray datasets from previous investigations to examine gene expression patterns in cancer cell lines with the goal of better understanding the tumor microenvironment. METHODS: Principal Components Analyses with Promax rotational transformations were carried out with 90 cancer cell lines from 3 microarray datasets, which had been made available on the internet as supplementary information from prior publications. RESULTS: In each of the analyses a well defined melanoma component was identified that contained a gene coding for the enzyme, glutaminyl cyclase, which was as highly expressed as genes from a variety of well established biomarkers for melanoma, such as MAGE-3 and MART-1, which have frequently been used in clinical trials of melanoma vaccines. CONCLUSION: Since glutaminyl cyclase converts glutamine and glutamic acid into a pyroglutamic form, it may interfere with the tumor destructive process of vaccines using peptides having glutamine or glutamic acid at their N-terminals. Finding ways of inhibiting the activity of glutaminyl cyclase in the tumor microenvironment may help to increase the effectiveness of some melanoma vaccines
Targeting uracil-DNA glycosylases for therapeutic outcomes using insights from virus evolution
Ung-type uracil-DNA glycosylases are frontline defenders of DNA sequence fidelity in bacteria, plants, and animals; Ungs also directly assist both innate and humoral immunity. Critically important in viral pathogenesis, whether acting for or against viral DNA persistence, Ungs also have therapeutic relevance to cancer, microbial, and parasitic diseases. Ung catalytic specificity is uniquely conserved, yet selective antiviral drugging of the Ung catalytic pocket is tractable. However, more promising precision therapy approaches present themselves via insights from viral strategies, including sequestration or adaptation of Ung for non-canonical roles. A universal Ung inhibition mechanism, converged upon by unrelated viruses, could also inform design of compounds to inhibit specific distinct Ungs. Extrapolating current developments, the character of such novel chemical entities is proposed
Thermodynamic analysis of inverted bifurcation
We present a thermodynamic analysis of inverted bifurcation
in binary mixtures heated from below. From this analysis it
follows that an inverted bifurcation is caused by the competition
between a stabilizing effect with a long relaxation time and a
destabilizing effect with a short relaxation time. These
conditions are precisely the same as those that give rise to
overstability. This might explain why overstability and inverted
bifurcation occur in the same systems
Use of a Javid™ shunt in the management of axillary artery injury as a complication of fracture of the surgical neck of the humerus: a case report
<p>Abstract</p> <p>Introduction</p> <p>Axillary artery injury is a rare but severe complication of fractures of the surgical neck of the humerus.</p> <p>Case presentation</p> <p>We present a case of axillary artery pseudoaneurysm secondary to such a fracture, in a 82-year-old white woman, presenting 10 weeks after the initial injury, successfully treated with subclavian to brachial reversed vein bypass together with simultaneous open reduction and internal fixation of the fracture. We discuss the use of a Javid™ shunt during combined upper limb revascularisation and open reduction and internal fixation of the fractured humerus.</p> <p>Conclusion</p> <p>This case highlights the usefulness of a Javid™ shunt, over other forms of vascular shunts, in prompt restoration of blood flow to effect limb salvage. It can be considered as a temporary measure whilst awaiting definitive revascularisation which can be performed following fracture fixation.</p
Motif Minang Kaluak Paku Kacang Balimbiang pada Busana Kasual
Minangkabau sebagai salah satu suku bangsa yang mengisi kekhasan
budaya Indonesia memiliki warisan budaya yang terpencar dalam berbagai aspek
kehidupannya. Salah satu warisan budaya adalah seni ukir. Seni ukir yang
dikembangkan dengan mengambil ide dari alam memiliki makna-makna filosofi
bagi kehidupan masyarakat Minangkabau. Semua jenis ukiran yang dipahatkan di
Rumah Gadang menunjukkan unsur penting pembentuk budaya Minangkabau
bercerminkan kepada apa yang ada di alam. Salah satu ukiran pada rumah gadang
yaitu kaluak paku. Kaluak paku adalah nama salah satu motif ukiran dalam adat
Minangkabau. Berasal dari motif gulungan (kelukan/kaluak) pada ujung tanaman
pakis (paku) yang masih muda. Ukiran kaluak paku rumah gadang melambangkan
tanggung jawab seorang lelaki dalam adat Minangkabau kepada generasi penerus,
sebagai ayah dari anak-anaknya dan sebagai mamak dari kemenakan (keponakan).
Ukiran rumah gadang kaluak paku minangkabau inilah yang menjadi sumber ide
penciptaan busana pada tugas akhir ini.
Pada Penciptaan karya ini menggunakan beberapa metode, yaitu metode
pendekatan estetis dan ergonomis, metode pengumpulan data dengan studi
pustaka, dan motode penciptaan dengan teori Gustami Sp 3 tahap 6 Langkah.
Dalam proses pembuatan karya dibutuhkan beberapa data, cara pengumpulan data
acuan berdasarkan pengumpulan data pustaka yaitu berupa buku, jurnal pada
media sosial, serta aplikasi pada smartphone seperti pinterest. Data yang
dikumpulkan yang paling utama adalah gambar bentuk visual dari ukiran tanaman
kaluak paku minangkabau dan busana kasual.
Penciptaan karya yang dihasilkan yaitu berupa 8 busana kasual. Siluet pada
kesuluruhan hasil karya yaitu memiliki siluet A yang mengembang pada bagian
bawah. Pada penciptaan karya ini menggunakan bahan utama primisima.
Perpaduan warna yang diterapkan menggunakan warna khas minangkabau yang
diambil dari warna bendera adatnya “marawa” yaitu merah, hitam, dan kuning.
Karya- karya yang dihasilkan dengan penggunaan warna tersebut sangat sesuai
dengan tema yang mengangkat ukiran rumah gadang kaluak paku minangkabau.
Kata Kunci : Minang, Kaluak Paku Kacang Balimbiang, Kasua
Applied Interventions in the Prevention and Treatment of Obesity Through the Research of Professor Jane Wardle
Purpose of Review
Obesity presents a challenge for practitioners, policy makers, researchers and for those with obesity themselves. This review focuses on psychological approaches to its management and prevention in children and adults.
Recent Findings
Through exploring the work of the late Professor Jane Wardle, we look at the earliest behavioural treatment approaches and how psychological theory has been used to develop more contemporary approaches, for example incorporating genetic feedback and habit formation theory into interventions. We also explore how Jane has challenged thinking about the causal pathways of obesity in relation to eating behaviour. Beyond academic work, Jane was an advocate of developing interventions which had real-world applications.
Summary
Therefore, we discuss how she not only developed new interventions but also made these widely available and the charity that she established
Using Expression and Genotype to Predict Drug Response in Yeast
Personalized, or genomic, medicine entails tailoring pharmacological therapies according to individual genetic variation at genomic loci encoding proteins in drug-response pathways. It has been previously shown that steady-state mRNA expression can be used to predict the drug response (i.e., sensitivity or resistance) of non-genotyped mammalian cancer cell lines to chemotherapeutic agents. In a real-world setting, clinicians would have access to both steady-state expression levels of patient tissue(s) and a patient's genotypic profile, and yet the predictive power of transcripts versus markers is not well understood. We have previously shown that a collection of genotyped and expression-profiled yeast strains can provide a model for personalized medicine. Here we compare the predictive power of 6,229 steady-state mRNA transcript levels and 2,894 genotyped markers using a pattern recognition algorithm. We were able to predict with over 70% accuracy the drug sensitivity of 104 individual genotyped yeast strains derived from a cross between a laboratory strain and a wild isolate. We observe that, independently of drug mechanism of action, both transcripts and markers can accurately predict drug response. Marker-based prediction is usually more accurate than transcript-based prediction, likely reflecting the genetic determination of gene expression in this cross
Compliance and persistence with osteoporosis medications: A critical review of the literature
It is widely acknowledged that compliance and persistence with oral osteoporosis medications, particularly with bisphosphonates, is poor. Several excellent reviews have been written on compliance and persistence with osteoporosis medications and have discussed improvements seen with extended dosing intervals. This review begins with studies on extended dosing intervals to examine the limitations of administrative claims data. It also looks at compliance and persistence across multiple medical conditions, examining the importance of prescription fulfillment, intentional choice, causation and possible interventions
Abrolhos Bank Reef Health Evaluated by Means of Water Quality, Microbial Diversity, Benthic Cover, and Fish Biomass Data
The health of the coral reefs of the Abrolhos Bank (southwestern Atlantic) was characterized with a holistic approach using measurements of four ecosystem components: (i) inorganic and organic nutrient concentrations, [1] fish biomass, [1] macroalgal and coral cover and (iv) microbial community composition and abundance. The possible benefits of protection from fishing were particularly evaluated by comparing sites with varying levels of protection. Two reefs within the well-enforced no-take area of the National Marine Park of Abrolhos (Parcel dos Abrolhos and California) were compared with two unprotected coastal reefs (Sebastião Gomes and Pedra de Leste) and one legally protected but poorly enforced coastal reef (the “paper park” of Timbebas Reef). The fish biomass was lower and the fleshy macroalgal cover was higher in the unprotected reefs compared with the protected areas. The unprotected and protected reefs had similar seawater chemistry. Lower vibrio CFU counts were observed in the fully protected area of California Reef. Metagenome analysis showed that the unprotected reefs had a higher abundance of archaeal and viral sequences and more bacterial pathogens, while the protected reefs had a higher abundance of genes related to photosynthesis. Similar to other reef systems in the world, there was evidence that reductions in the biomass of herbivorous fishes and the consequent increase in macroalgal cover in the Abrolhos Bank may be affecting microbial diversity and abundance. Through the integration of different types of ecological data, the present study showed that protection from fishing may lead to greater reef health. The data presented herein suggest that protected coral reefs have higher microbial diversity, with the most degraded reef (Sebastião Gomes) showing a marked reduction in microbial species richness. It is concluded that ecological conditions in unprotected reefs may promote the growth and rapid evolution of opportunistic microbial pathogens
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