Miracle-dz/UniFAR-FTUs huggingface dataset:
A Possible Role of ER-60 Protease in the Degradation of Misfolded Proteins in the Endoplasmic Reticulum (*)

Wild-type human lysozyme (hLZM) is secreted when expressed in mouse L cells, whereas misfolded mutant hLZMs are retained and eventually degraded in a pre-Golgi compartment (Omura, F., Otsu, M., Yoshimori, T., Tashiro, Y., and Kikuchi, M.(1992) Eur. J. Biochem. 210, 591-599). These misfolded mutant hLZMs are associated with protein disulfide isomerase (Otsu, M., Omura, F., Yoshimori, T., and Kikuchi, M.(1994) J. Biol. Chem. 269, 6874-6877). From the observation that this degradation is sensitive to cysteine protease inhibitors, such as N-acetyl-leucyl-leucyl-norleucinal and N-acetyl-leucyl-leucyl-methioninal, but not to the serine protease inhibitors, 1-chloro-3-tosylamido-7-amino-2-heptanone and (p-amidinophenyl)methanesulfonyl fluoride, it was suggested that some cysteine proteases are likely responsible for the degradation of abnormal proteins in the endoplasmic reticulum (ER). ER-60 protease (ER-60), an ER resident protein with cysteine protease activity (Urade, R., Nasu, M., Moriyama, T., Wada, K., and Kito, M.(1992) J. Biol. Chem. 267, 15152-15159), was found to associate with misfolded hLZMs, but not with the wild-type protein, in mouse L cells. Furthermore, denatured hLZM is degraded by ER-60 in vitro, whereas native hLZM is not. These results suggest that ER-60 could be a component of the proteolytic machinery for the degradation of misfolded mutant hLZMs in the ER.
Identifying key enablers to improve business performance in Taiwanese electronic manufacturing companies

Purpose – Integrated supplier management (ISM), new product development (NPD) and knowledge sharing (KS) practices are three primary business activities utilised to enhance manufacturers' business performance (BP). The purpose of this paper is to empirically investigate the relationships between these three business activities (i.e. ISM, NPD, KS) and BP in a Taiwanese electronics manufacturing context.Design/methodology/approach – A questionnaire survey is first administered to a sample of electronic manufacturing companies operating in Taiwan to elicit the opinions of technical and managerial professionals regarding business activities and BP within their companies. A total of 170 respondents from 83 companies respond to the survey. Factor, correlation and path analysis are undertaken on this quantitative data set to derive the key factors which leverage business outcomes in these companies. Following empirical analysis, six semi‐structured interviews are undertaken with manufacturing executives to provi.
An Improved TCP Migrate Scheme with DNS Handover Assistant for End-to-End Mobility

As a transport layer mobility solution, the TCP migrate allows mobile nodes to remain reachable and retain existing connections while changing their point of attachment to the Internet. However, our study shows that the referenced TCP migrate has to face a challenge of simultaneous movement which is specific for the end-to-end mobility solution. In this paper we extend the transport layer mobility work by resolving issues that the existing approaches lack off and propose a novel improved TCP migrate scheme with DNS handover assistant for handover redirection and transmission resuming. The handover performance of the proposed scheme is evaluated by simulation.
Sign and the lambda-term

Abstract We examine lambda calculus as a sign system and show that it explains important properties of language. First, we verify that a lambda-term has two essential functionalities of signs — articulation and naming — and argue that a lambda-term can thus be regarded as a sign model. Then, when signs are defined by self-reference, we show that these two functionalities become tightly coupled and that dyadic/triadic sign models become equivalent. Last, we show that the difference of structuralism is explained in relation to the undecidability of the equivalence of two arbitrary lambda-terms.
Design of a V-band low sidelobe and wideband linear DRA array

In this paper, a V-band low sidelobe and wideband series fed linear dielectric resonator antenna (DRA) array is proposed. Among many kinds of DRAs, the perforated rectangular dielectric resonator antenna (RDRA) is chosen as the antenna element in our design, which can enhance the impedance bandwidth by lowering down the quality factor. By optimizing the size of the slots and distance between adjacent slots, the fundamental TE111 mode of the RDRA is preserved. Besides enhancement of impedance bandwidth, such structure can also miniaturize the antenna elements, which can light the weight of the array and reduce the mutual coupling between antenna elements. To get a low sidelobe level (SLL), the Chebyshev current distribution is used in our design, which is achieved by a series feeding network. A ground plane separates the arrays and the feeding network, which avoids the parasitic radiation from feeding network affecting the radiation pattern of the array. The structure of the proposed DRA array is optimized, simulation results are also presented. The impedance bandwidth of the proposed antenna array is of 36.1% (56.3 ~ 81.1 GHz), which completely covers the 57 ~ 66 GHz unlicensed frequency band. The antenna gain is of 15.7dBi in 60GHz, and is higher than 13dBi over the 57 ~ 66 GHz frequency band, which can meet the IEEE 802.15 and ECMA 384 standards in the 60GHz wireless communication systems. The SLL is of -27.7dB in 60GHz, and the low sidelobe level bandwidth (SLL <; -20dB) is of 9.05% (57.0 ~ 62.4GHz). All these features make the proposed antenna array good potential applications in V-band system, especially in the 60 GHz wireless communication systems.
Prevalence of diabetic retinopathy and maculopathy in Northland, New Zealand: 2011-2012.

AIM To determine the prevalence of diabetic retinopathy and maculopathy in the Northland Diabetic Retinopathy Screening Programme. METHOD Retrospective analysis of the latest and most severe retinopathy and maculopathy grades from each patient in the programme. RESULTS Data from 7098 screenings from 5647 diabetics were obtained, which represented approximately 77% of the total number of diagnosed diabetics in Northland. The two main ethnic groups in our study were New Zealand European (56.5%) and Maori (39.3%). Retinopathy was present in 19% of the Northland diabetic screening population: 13.6% had minimal non-proliferative diabetic retinopathy (NPDR), 5.4% had NPDR and 0.4% had Proliferative Diabetic Retinopathy (PDR). Ethnicity data for NPDR was 57% Maori, 38% European, and PDR 50% Maori, 45% European. Maculopathy was present in 11%. Maculopathy requiring treatment was present in 1.4% (Maori 48%, European 44%). The mean failure-to-attend rate was 31%. CONCLUSION Rates of retinopathy and maculopathy detected by the Northland screening programme were comparable to rates reported in Waikato, lower than Wellington rates and lower than international averages. Maori were over-represented in patients with retinopathy and maculopathy, but underrepresented within the screening population. The success of this programme was undermined by the high failure-to-attend rate despite attempts to improve access.
The Economic Burden of Posttransplant Events in Renal Transplant Recipients in Europe

Background This study aims to describe the healthcare resource utilization and costs of managing renal posttransplant patients over 3 years posttransplant in nine European countries and to stratify them by year 1 glomerular filtration rate (GFR). Methods A retrospective observational and database analysis of renal transplant patients and a physician questionnaire study were conducted to collect recipient and donor characteristics, posttransplant events, and healthcare resource utilization related to these posttransplant events. In each country, local published costs were applied to the resource use identified. The results were stratified by the patient GFR reading at a time point 1 year after renal transplant. Results The database study identified 3,181 patients who met the inclusion criteria, along with 2,818 transplants carried out in the centers surveyed by questionnaire. Total 3-year costs derived from the questionnaire analysis vary depending on local treatment practices, from a minimum of &OV0556;33,602 per patient in the Czech Republic to &OV0556;77,461 per patient in the Netherlands. Consistently across countries, estimated costs appear to decrease with improved graft functioning status (increased GFR) at 1 year. The average 3-year costs, discounting immunosuppresion therapy and certain posttransplant events, per patient with a GFR greater than or equal to 60 at 1 year are estimated to be around 35% lower than those with 15⩽GFR<30. Conclusion This study demonstrates that in Europe, worsening posttransplant renal function may contribute to substantive increases in resource use, with some variation across regions. Therefore, management strategies that promote renal function after transplantation have the potential to provide important resource savings.
Glutamate‐Mediated Injury in Focal Cerebral Ischemia: The Excitotoxin Hypothesis Revised

Neuronal injury following focal cerebral ischemia is widely attributed to the excitotoxic effects of gluta‐mate. However, critical analysis of published data on glutamate toxicity in vitro and the comparison of these data with in vivo release of glutamate and the therapeutic effect of glutamate antagonists raises doubts about a neurtoxic mechamism. An alternative explanation for glutamate‐mediated injury is hypoxia due to peri‐infarct spreading depression‐like depolarizations. These depolarizations are triggered in the core of the ischemic infarct and spread at irregular intervals into the peri‐infarct surrounding. In ischemically uncompromised tissue, the metabolic workload associated with spreading depression is coupled to an increase in blood flow and oxygen supply, assuring maintenance of oxidative respiration. In the penumbra region of focal ischemia, the hemodynamic constraints of collateral blood circulation prevail the adequate adjustment of oxygen delivery, leading to transient episodes of relative tissue hypoxia. The hypoxic episodes cause a suppression of protein synthesis, a gradual deterioration of energy metabolism and a progression of irreversibly damaged tissue into the penumbra zone.
ACTGGCCTCA ATGGCTCAGC AGTGAACTCA TCGACATTTT CCAAGGCTTG GCATCCAGCG 761 CCCGTGGTTG CACCAGGTCC AAGCGGCGAA TCTCATCCAC GAAGGCCAGC ATACGATGGT 821 GTCTACCGGC ACCGCTTCCG GCAAGTCCAT GGCCTACCTC ATGCCGAGTT TGGATGCCCT 881 ATTCAGGTCA CGCGATAGCC TTTAATGATG CCGATTCCGG CGCCTCAATT CTCTACATTT

Arthrobacter strain N.R. R.L. B3728 superproduces a D-xylose isomerase that is also a useful industrial D-glucose isomerase. The gene (xylA) that encodes it has been cloned by complementing a xylA mutant of the ancestral strain, with the use of a shuttle vector. The 5' region shows strong sequence similarity to Escherichia coli consensus promoters and ribosome-binding sequences and allows high levels of expression in E. coli. The coding sequence shows similarity to those for other D-xylose isomerases and is followed by 22 nucleotide residues with stop codons in each reading frame, a good 'consensus' ribosome-binding site and an open reading frame showing similarity to those of known D-xylulokinases (xylB). Studies on the expression of the cloned gene in Arthrobacter and in E. coli suggest that the two genes are part of
Simulação numérica de fluidos viscoelásticos com superfície livre utilizando o modelo integral K-BKZ

Esse trabalho tem por objetivo apresentar um metodo numerico para resolver as equacoes governantes para escoamentos viscoelasticos, com superficies livres em movimento, governados pela equacao constitutiva integral K-BKZ. Considera-se escoamentos bidimensionais e um algoritmo para resolver as equacoes governantes, utilizando o metodo de diferencas finitas, e apresentado. A metodologia proposta e verificada comparando-se a solucao numerica do escoamento totalmente desenvolvido em um canal. Resultados provenientes da simulacao do problema conhecido como ‘jet-buckling’ sao apresentados.
PSY 3 , a New Member of the Phytoene Synthase Gene Family Conserved in the Poaceae and Regulator of Abiotic Stress-Induced Root Carotenogenesis 1 [ W ] [ OA ]

Abscisic acid (ABA) plays a vital role in mediating abiotic stress responses in plants. De novo ABA biosynthesis involves cleavage of carotenoid precursors by 9-cis-epoxycarotenoid dioxygenase (NCED), which is rate controlling in leaves and roots; however, additional bottlenecks in roots must be overcome, such as biosynthesis of upstream carotenoid precursors. Phytoene synthase (PSY) mediates the first committed step in carotenoid biosynthesis; with PSY3 described here, maize (Zea mays) and other members of the Poaceae have three paralogous genes, in contrast to only one in Arabidopsis thaliana. PSY gene duplication has led to subfunctionalization, with each paralog exhibiting differential gene expression. We showed that PSY3 encodes a functional enzyme for which maize transcript levels are regulated in response to abiotic stresses, drought, salt, and ABA. Drought-stressed roots showed elevated PSY3 transcripts and ABA, responses reversed by rehydration. By blocking root carotenoid biosynthesis with the maize y9 mutation, we demonstrated that PSY3 mRNA elevation correlates with carotenoid accumulation and that blocking carotenoid biosynthesis interferes with stress-induced ABA accumulation. In parallel, we observed elevated NCED transcripts and showed that, in contrast to dicots, root zeaxanthin epoxidase transcripts were unchanged. PSY3 was the only paralog for which transcripts were induced in roots and abiotic stress also affected leaf PSY2 transcript levels; PSY1 mRNA was not elevated in any tissues tested. Our results suggest that PSY3 expression influences root carotenogenesis and defines a potential bottleneck upstream of NCED; further examination of PSY3 in the grasses is of value for better understanding root-specific stress responses that impact plant yield.
Borrelia burgdorferi, the Causative Agent of Lyme Disease, Forms Drug-Tolerant Persister Cells

ABSTRACT Borrelia burgdorferi is the causative agent of Lyme disease, which affects an estimated 300,000 people annually in the United States. When treated early, the disease usually resolves, but when left untreated, it can result in symptoms such as arthritis and encephalopathy. Treatment of the late-stage disease may require multiple courses of antibiotic therapy. Given that antibiotic resistance has not been observed for B. burgdorferi, the reason for the recalcitrance of late-stage disease to antibiotics is unclear. In other chronic infections, the presence of drug-tolerant persisters has been linked to recalcitrance of the disease. In this study, we examined the ability of B. burgdorferi to form persisters. Killing growing cultures of B. burgdorferi with antibiotics used to treat the disease was distinctly biphasic, with a small subpopulation of surviving cells. Upon regrowth, these cells formed a new subpopulation of antibiotic-tolerant cells, indicating that these are persisters rather than resistant mutants. The level of persisters increased sharply as the culture transitioned from the exponential to stationary phase. Combinations of antibiotics did not improve killing. Daptomycin, a membrane-active bactericidal antibiotic, killed stationary-phase cells but not persisters. Mitomycin C, an anticancer agent that forms adducts with DNA, killed persisters and eradicated growing and stationary cultures of B. burgdorferi. Finally, we examined the ability of pulse dosing an antibiotic to eliminate persisters. After addition of ceftriaxone, the antibiotic was washed away, surviving persisters were allowed to resuscitate, and the antibiotic was added again. Four pulse doses of ceftriaxone killed persisters, eradicating all live bacteria in the culture.
Knowledge Representation for an Automated Normalized Answers Assessment System, Based on Text Comprehension Theories

In the present work, a knowledge representation of Computer Networks technical text, according to the Denhiere-Baudet text comprehension model, is presented. The semantic relations among units and events of a technical text can be expressed by structures, as microstructure and macrostructure. Furthermore, the explicit and implicit knowledge representation, and the micro and macrostructure representation of the functional system operations, depicted in this text, is provided. The presented methodology can support automated reasoning, through the knowledge representation, which leads to automated knowledge extraction from a technical text, and, subsequentially, to automated normalized answers assessment.
Prognostic factor analysis of the survival of elderly patients with AML in the MRC AML11 and LRF AML14 trials

This analysis, of 2483 patients with acute myeloid leukaemia (AML) aged 60+ years entered into two UK trials, was performed to determine the baseline parameters related to survival and to develop a risk index. The Medical Research Council (MRC) AML11 trial (n = 1071) was used to develop the index; this was validated using data from the Leukaemia Research fund (LRF) AML14 trial on 1137 intensively (AML14I) and 275 non‐intensively (AML14NI) treated patients. In AML11, cytogenetic group, age, white blood count, performance status and type of AML (de novo, secondary) were all highly significantly related to prognosis in multivariate analysis. The regression coefficients were used to define good, standard and poor risk groups, with 1‐year survival of 53%, 43% and 16% respectively (P < 0·0001). The risk index showed very good discrimination in both AML14I and AML14NI (both P < 0·0001), thereby providing validation, although survival in all groups was very poor in AML14NI. The risk factors for survival in older AML patients were similar to those in younger ones and discrimination of patient groups with relatively good to very poor prognosis was possible. These risk groups apply to both intensively and non‐intensively treated patients. Randomized trials of intensive versus non‐intensive therapy are needed to determine which types of patient should be given which type of treatment.
Modelado Semántico y Centrado en el Usuario de Servicios Adaptados al Contexto de Uso

Cuando los usuarios acceden a servicios telematicos, esperan obtener experiencias cada vez mas adaptadas a su contexto especifico, en especial, ante la gran cantidad de contenidos en linea a su alcance a traves de dichos servicios. Para que estos servicios proporcionen funcionalidades centradas en el usuario –por ejemplo, busquedas relevantes, adaptacion de contenidos, personalizacion y recomendacion– es necesario que los contenidos esten anotados semanticamente y disponer de un modelo preciso que represente al usuario y su contexto de uso. En este escenario, presentamos un marco generico de servicios centrados en el usuario basado en la caracterizacion semantica de los usuarios y su mapeo con los contenidos. En concreto, aplicamos dicho marco a un buscador semantico que caracteriza automaticamente tanto los contenidos a los que los usuarios pueden acceder como el contexto de uso desde el que se accede. La solucion propuesta incluye modelos de usuario dinamicos y adaptativos, con informacion explicita e implicita; asi como descriptores de los contenidos que pueden utilizarse para determinar cuales son mas adecuados para cada usuario.
Virtues and Vices and Other Essays in Moral Philosophy

Preface to 2002 Edition Preface Introduction Acknowledgements 1. Virtues and Vices 2. The Problem of Abortion and the Doctrine of Double Effect 3. Euthanasia 4. Free Will as Involving Determinism 5. Hume on Moral Judgement 6. Nietzsche: The Revaluation of Values 7. Moral Arguments 8. Moral Beliefs 9. Goodness and Choice 10. Reasons for Actions and Desires 11. Morality as a System for Hypothetical Imperatives 12. A Reply to Professor Frankena 13. Are Moral Considerations Overriding? 14. Approval and Disapproval Index
COLÁGENO: UMA ABORDAGEM PARA A ESTÉTICA

O colageno ganhou espaco nas ultimas decadas devido a suas inumeras aplicacoes. A area em que mais teve destaque e a estetica e cosmetica, devido as suas atividades reparadoras dos tecidos cutâneos. Muito se pode avancar em relacao ao retardo do envelhecimento e o colageno e um dos fatores que prometem retardar o envelhecimento celular. Os radicais livres produzidos em excesso pelo organismo como resposta ao fumo, bebidas alcoolicas, exposicao solar sem protecao, estresse, consumo de drogas, falta de atividade fisica e ma alimentacao aceleram o processo de envelhecimento do organismo. O objetivo da pesquisa foi fazer uma revisao bibliografica sobre o colageno e as vitaminas antioxidantes e sua influencia no envelhecimento cutâneo. A metodologia do presente artigo foi elaborada atraves de pesquisa bibliografica em bases de dados nacionais e internacionais, atraves dos periodicos da CAPES e pesquisas realizadas on-line e em bibliotecas atraves de livros e artigos, publicados preferencialmente nos ultimos 10 anos. Envelhecer e inevitavel, e um processo natural, que engloba todas as classes de seres vivos. O que a ciencia tem buscado sao maneiras de esses sinais ficarem menos evidentes. Em estudos, pode-se verificar que apenas o colageno nao e o suficiente para atingir resultados beneficos. Inumeros fatores interferem no processo de envelhecimento celular, alguns fatores beneficos como a alimentacao saudavel, balanceada, que supra as demandas energeticas necessarias diariamente de vitaminas e minerais. Vitaminas como a vitamina C, E sao excelentes antioxidantes que, juntamente com o colageno, podem desacelerar o processo de envelhecimento.
Simultaneous Platelet P2Y12 and P2Y1 ADP Receptor Blockade: Are Two Better Than One?

Human platelets possess 3 purinergic receptors (P2Y12, P2Y1, and P2X1), which collectively orchestrate key steps leading to platelet activation and aggregation (Figure). Until now, the selective blockade of the platelet P2Y12 ADP receptor, combined with the inhibition of thromboxane production by aspirin, has remained the backbone of pharmacotherapy for patients presenting with acute coronary syndrome or undergoing percutaneous coronary intervention.1 Figure. The investigational modified diadenosine tetraphosphate (Ap4A) derivative, GLS-409, in the context of major classes of currently approved antiplatelet therapies and their respective pharmacologic targets. COX indicates cyclooxygenase; F, fibrinogen; GP, glycoprotein; PAR, protease-activated receptor; and T, thrombin. See accompanying article on page 501 Despite significant progress in the attenuation of excess platelet activity in these high-risk settings, percutaneous coronary intervention–related thrombotic complications, including stent thrombosis, and severe bleeding continue to be major sources of morbidity and mortality. Early after acute coronary syndrome, patients may …