Miracle-dz/UniFAR-FTUs huggingface dataset:
A simulation methodology for evaluating emergency sourcing strategies of a discrete part manufacturer

Globalisation and technological evolution associated with critical socioeconomics changes altered the traditional supply chain SC nature, and the corresponding risk forms. Therefore, modern SCs are vulnerable to risks, and their effects delays and disruptions of product, money, and information flows. Whilst the nature of the overall supply disruption problem is quantitative, the vast majority of the relevant literature efforts employs a qualitative approach. In this paper we focus on the evaluation of emergency sourcing ES risk mitigation strategies for a discrete part manufacturer, employing a quantitative approach. Specifically, a discrete event simulation methodology is developed using the Arena™ simulation software for the measurement of risk impacts on the organisation's performance, and the evaluation of alternative emergency/dual sourcing policies in terms of the premium cost paid to the alternative emergency supplier. The optimal emergency capacity that should be contracted from the alternative supplier is computed along with the associated cost savings.
Emerging anti-HIV drugs

There are now exactly 20 anti-HIV drugs licenced (approved) for clinical use, and > 30 anti-HIV compounds under (pre)clinical development. The licenced anti-HIV drugs fall into five categories: nucleoside reverse transcriptase inhibitors (NRTIs: zidovudine, didanosine, zalcitabine, stavudine, lamivudine, abacavir and emtricitabine); nucleotide reverse transcriptase inhibitors (NtRTIs: tenofovir disoproxil fumarate); non-nucleoside reverse transcriptase inhibitors (NNRTIs: nevirapine, delavirdine and efavirenz); protease inhibitors (PIs: saquinavir, indinavir, ritonavir, nelfinavir, amprenavir, lopinavir, atazanavir and fosamprenavir); and fusion inhibitors (FIs: enfuvirtide). The compounds that are currently under clinical (Phase I, II or III) or preclinical investigation are either targeted at the same specific viral proteins as the licenced compounds (i.e., reverse transcriptase [NRTIs: PSI-5004, (-)-dOTC, DPC-817, elvucitabine, alovudine, MIV-210, amdoxovir, DOT; NNRTIs: thiocarboxanilide, UC-781, capravirine, dapivirine, etravirine, rilpivirine], protease [PIs: tipranavir, TMC-114]) or other specific viral proteins (i.e., gp120: cyanovirin N; attachment inhibitors: AIs, such as BMS-488043; integrase: L-870,812, PDPV-165; capsid proteins: PA-457, α-HCG); or cellular proteins (CD4 downmodulators: CADAs; CXCR4 antagonists: AMD-070, CS-3955; CCR5 antagonists: TAK-220, SCH-D, AK-602, UK-427857). Combination therapy is likely to remain the gold standard for the treatment of AIDS so as to maximise potency, minimise toxicity and diminish the risk for resistance development. Ideally, pill burden should be reduced to once-daily dosing so as to optimise the patient’s compliance and reduce the treatment costs.
Immunolocalization of carbonic anhydrase isozymes in rat and mouse salivary and exorbital lacrimal glands

Carbonic anhydrase (CA) isozyme I and isozyme II have been localized with the immunoperoxidase bridge method in cells of mouse and rat salivary glands and exorbital lacrimal glands. Immunostaining proved optimal in Carnoy fixed specimens for some sites and in Bouin fixed glands for other sites. Staining in mouse largely resembled that in rat glands, but minor species differences were observed. Serous acinar cells in the submandibular gland stained uniformly and exclusively for CA I. From 50 to 100% of the serous acinar cells in the parotid glands evidenced content of both CA I and CA II. A minor population of serous acinar cells in the mouse exorbital lacrimal gland stained for CA I and CA II, but these glands in the rat failed to stain.
Wide dynamic range pulse modulation image sensor for on-chip bioimaging applications

Image sensors with a pulse modulation measurement scheme are fabricated for bioimaging and biosensing applications. We designed pulse modulation photosensors and a 64/spl times/64-pixel image sensor. We demonstrated the feasibility of the pulse modulation measurement scheme for biosensing applications. We obtained a dynamic range of 120 dB and minimum sensing intensity level of 2 nW/cm/sup 2/. We also confirmed that 0.2% of intensity change is detectable at the minimum intensity region. An in-vitro, on-chip imaging of a mouse hippocampus was successfully demonstrated.
DDB Accumulates at DNA Damage Sites Immediately after UV Irradiation and Directly Stimulates Nucleotide Excision Repair*

Damaged DNA-binding protein, DDB, is a heterodimer of p127 and p48 with a high specificity for binding to several types of DNA damage. Mutations in the p48 gene that cause the loss of DDB activity were found in a subset of xeroderma pigmentosum complementation group E (XP-E) patients and have linked to the deficiency in global genomic repair of cyclobutane pyrimidine dimers (CPDs) in these cells. Here we show that with a highly defined system of purified repair factors, DDB can greatly stimulate the excision reaction reconstituted with XPA, RPA, XPC·HR23B, TFIIH, XPF·ERCC1 and XPG, up to 17-fold for CPDs and ∼2-fold for (6-4) photoproducts (6-4PPs), indicating that no additional factor is required for the stimulation by DDB. Transfection of thep48 cDNA into an SV40-transformed human cell line, WI38VA13, was found to enhance DDB activity and the in vivoremoval of CPDs and 6-4PPs. Furthermore, the combined technique of recently developed micropore UV irradiation and immunostaining revealed that p48 (probably in the form of DDB heterodimer) accumulates at locally damaged DNA sites immediately after UV irradiation, and this accumulation is also observed in XP-A and XP-C cells expressing exogenous p48. These results suggest that DDB can rapidly translocate to the damaged DNA sites independent of functional XPA and XPC proteins and directly enhance the excision reaction by core repair factors.
Estudio genético y funcional de NR5A2, un factor de transcripción ligado a obesidad y diabetes

RESUMEN: NR5A2 es un receptor nuclear huerfano asociado al metabolismo del colesterol, sus derivados y diferenciacion de tejidos, al que recientemente se ha implicado en el mantenimiento de la homeostasis de la glucosa. Ademas, en un estudio de asociacion previo, un SNP del promotor mostro asociacion con IMC. Partiendo de esto, realizamos un estudio de la posible implicacion de NR5A2 en el desarrollo de enfermedades metabolicas complejas, como la obesidad o la diabetes. Realizamos un secuenciado de RNA para localizar los genes del metabolismo energetico regulados por NR5A2 y empleamos como modelos lineas celulares para higado (HepG2) y mcusculo (C2C12), con expresion de NR5A2 silenciada, sobreexpresada o activada mediante un agonista sintetico. Nuestros resultados muestran que NR5A2 reduce la captacion de glucosa y la sintesis de TAGs en HepG2 y favorece la captacion y consumo de glucosa en C2C12, disminuyendo el de acidos grasos. Tomando estos resultados, NR5A2 podria actuar como un agente protector contra las patologias asociadas a la resistencia a la insulina.
The Role of MTJ-1 in Cell Surface Translocation of GRP78, a Receptor for α2-Macroglobulin-Dependent Signaling1

MTJ-1 associates with a glucose-regulated protein of Mr ∼78,000(GRP78) in the endoplasmic reticulum and modulates GRP78 activity as a chaperone. GRP78 also exists on the cell surface membrane, where it is associated with a number of functions. MHC class I Ags on the cell surface are complexed to GRP78. GRP78 also serves as the receptor for α2-macroglobulin-dependent signaling and for uptake of certain pathogenic viruses. The means by which GRP78, lacking a transmembrane domain, can fulfill such functions is unclear. In this study we have examined the question of whether MTJ-1, a transmembrane protein, is involved in the translocation of GRP78 to the cell surface. MTJ-1 and GRP78 coimmunoprecipitated from macrophage plasma membrane lysates. Silencing of MTJ-1 gene expression greatly reduced MTJ-1 mRNA and protein levels, but also abolished cell surface localization of GRP78. Consequently, binding of the activated and receptor-recognized form of α2-macroglobulin to macrophages was greatly reduced, and activated and receptor-recognized form of α2-macroglobulin-induced calcium signaling was abolished in these cells. In conclusion, we show that in addition to assisting the chaperone GRP78 in protein quality control in the endoplasmic reticulum, MTJ-1 is essential for transport of GRP78 to the cell surface, which serves a number of functions in immune regulation and signal transduction.
Animaciones interactivas para la enseñanza y aprendizaje de los protocolos de coherencia de cachés

Entre los objetivos formativos de los cursos avanzados de arquitectura de computadores suele estar el de que los estudiantes sean capaces de describir y analizar el funcionamiento de los protocolos de coherencia de caches. Aunque dichos protocolos son relativamente sencillos, es necesario analizar muchas situaciones diferentes para entender como abordan todos los detalles del problema que quieren resolver. Lo que hace que sean complejos de explicar y de comprender. Una herramienta que ilustrara graficamente el funcionamiento de dichos protocolos facilitaria enormemente su ensenanza/aprendizaje. Con objeto de mejorar la docencia de dicha materia, hemos desarrollado tres animaciones interactivas que muestran como funcionan tres de los protocolos de coherencia de cache mas frecuentemente utilizados. Para cada protocolo, una serie de operaciones de lectura/escritura ilustran todas las posibles situaciones que pueden darse. Las animaciones permiten avanzar y retroceder para poder entender/estudiar mejor las acciones que tienen lugar en cada paso.
Taxonomic distribution, repeats, and functions of the S1 domain‐containing proteins as members of the OB‐fold family

Proteins of the nucleic acid‐binding proteins superfamily perform such functions as processing, transport, storage, stretching, translation, and degradation of RNA. It is one of the 16 superfamilies containing the OB‐fold in protein structures. Here, we have analyzed the superfamily of nucleic acid‐binding proteins (the number of sequences exceeds 200,000) and obtained that this superfamily prevalently consists of proteins containing the cold shock DNA‐binding domain (ca. 131,000 protein sequences). Proteins containing the S1 domain compose 57% from the cold shock DNA‐binding domain family. Furthermore, we have found that the S1 domain was identified mainly in the bacterial proteins (ca. 83%) compared to the eukaryotic and archaeal proteins, which are available in the UniProt database. We have found that the number of multiple repeats of S1 domain in the S1 domain‐containing proteins depends on the taxonomic affiliation. All archaeal proteins contain one copy of the S1 domain, while the number of repeats in the eukaryotic proteins varies between 1 and 15 and correlates with the protein size. In the bacterial proteins, the number of repeats is no more than 6, regardless of the protein size. The large variation of the repeat number of S1 domain as one of the structural variants of the OB‐fold is a distinctive feature of S1 domain‐containing proteins. Proteins from the other families and superfamilies have either one OB‐fold or change slightly the repeat numbers. On the whole, it can be supposed that the repeat number is a vital for multifunctional activity of the S1 domain‐containing proteins. Proteins 2017; 85:602–613. © 2016 Wiley Periodicals, Inc.
A reexamination of the folding mechanism of dihydrofolate reductase from Escherichia coli: verification and refinement of a four-channel model.

The mechanism of folding of dihydrofolate reductase from Escherichia coli was reinvestigated by studying the unfolding and refolding kinetics using absorbance and fluorescence spectroscopies. The original kinetic model proposed that folding involved a series of native, intermediate, and unfolded forms which interconverted through four independent channels linked by slow cis/trans isomerization reactions at Xaa-Pro peptide bonds [Touchette, N. A. , Perry, K. M. , & Matthews, C. R. (1986) Biochemistry 25, 5445]. Recently, alternative sequential models have been proposed [Frieden, C. (1990) Proc. Natl. Acad. Sci. U.S.A. 87, 4413; Kuwajima et al. (1991) Biochemistry 30, 7693] which challenge the original proposal. Stopped-flow studies of the intrinsic tryptophan fluorescence demonstrated the presence of three (and tentatively four) kinetic phases in unfolding which correlated well with four phases previously observed in refolding experiments. By monitoring the binding of the inhibitor methotrexate during folding at varying relative concentrations of inhibitor to protein, it was found that the selective loss of the slow-folding phases at substoichiometric levels could only be explained by a four-channel folding model. Double-jump experiments (native-->unfolded-->native) showed that the four refolding channels are populated within 20 s at 15 degrees C and are not likely to be due to proline isomerization. Reverse double-jump experiments (unfolded-->native-->unfolded) demonstrated that interconversions between native conformers are more rapid than originally proposed. Interestingly, the majority of the protein folds through a channel to a native conformer that is minimally populated at equilibrium. This implies that although the folding of dihydrofolate reductase is ultimately under thermodynamic control, kinetic factors contribute to the transient populations of native species during folding.
Evaluation of hyperacute infarct volume using ASPECTS and brain CT perfusion core volume

Objective: To compare the accuracy of Alberta Stroke Program Early Computed Tomography Score (ASPECTS) and CT perfusion to detect established infarction in acute anterior circulation stroke. Methods: We performed an observational study in 59 acute anterior circulation ischemic stroke patients who underwent brain noncontrast CT, CT perfusion, and MRI within 100 minutes from CT imaging. ASPECTS scores were calculated by 4 blinded vascular neurologists. The accuracy of ASPECTS and CT perfusion core volume to detect an acute MRI diffusion lesion of ≥70 mL was evaluated using receiver operating characteristics analysis and optimum cutoff values were calculated using Youden J. Results: Median ASPECTS score was 8 (interquartile range [IQR] 5–9). Median CT perfusion core volume was 22 mL (IQR 10.4–71.9). Median MRI diffusion lesion volume was 24.5 mL (IQR 10–63.9). No significant difference was found between the accuracy of CT perfusion and ASPECTS (c statistic 0.95 vs 0.87, p value for difference = 0.17). The optimum ASPECTS cutoff score to detect a diffusion-weighted imaging lesion ≥70 mL was <7 (sensitivity 0.74, specificity 0.86, Youden J = 0.60) and the optimum CT perfusion core volume cutoff was ≥50 mL (sensitivity 0.86, specificity 0.97, Youden J = 0.84). The CT perfusion core lesion covered a median of 100% (IQR 86%–100%) of the acute MRI lesion volume (Pearson R = 0.88; R2 = 0.77). Conclusions: We found no significant difference between the accuracy of CT perfusion and ASPECTS to predict hyperacute MRI lesion volume in ischemic stroke.
Annual Ovarian Cycles in an Aseasonal Breeder, the Springbok (Antidorcas marsupialis)1

Abstract The springbok is an arid-adapted antelope inhabiting the desert and semidesert regions of southern Africa. Because it thrives in these sparsely vegetated areas, the springbok is of potential agricultural importance and the prospect of domestication has been speculated for many years. However, apart from observational studies on its breeding in the wild, suggesting it is an aseasonal breeder, little is known about the underlying reproductive endocrinology of this species. In this study, biweekly peripheral blood samples were collected from eight captive springbok ewes from October 1995 until September 1998 and analyzed for progesterone. At the start of the study, six ewes were prepubertal and cycling commenced spontaneously between November 1995 and June 1996. Cycling had already commenced in two ewes. At the end of November 1996, estrous cycles ceased abruptly in all ewes and restarted in April 1997. Cycling ceased again between December 1997 and February 1998 and restarted in June 1998 in six ewes; there was no cessation of estrous cycles in two ewes. Thus, although some individuals cycle continuously, there is a clear endocrine anestrus of between 4 and 5 mo in springbok, the timing and duration of which is synchronized between some individuals but the time of onset and cessation is variable from year to year. To ensure that the fluctuations we observed in progesterone levels were reliable indicators of changes in the estrous cycle, blood samples were collected every 6 h for 16 days in August 1998. A surge in LH secretion was observed in all ewes 55 ± 5 h after the fall in progesterone. Progesterone levels increased again 45 ± 8 h after the surge. A final study showed that the pattern of melatonin release in springbok exhibits a normal day/night profile, and thus photoperiodic information is transformed into an endocrine code to springbok but does not appear to affect reproduction. Rather, our data raise the possibility that the prevailing ambient temperature may influence the onset of ovarian activity in this species.
Microsatellite differentiation between Phillip Island and mainland Australian populations of the red fox Vulpes vulpes

Predation by the red fox Vulpes vulpes is believed to be threatening the little penguin Eudyptula minor on Phillip Island in Victoria. Polymorphism at seven microsatellite loci was examined to estimate the extent of differentiation between Phillip Island and mainland populations of V. vulpes. Loss of alleles has occurred on Phillip Island where foxes first appeared = 88 years ago compared with mainland populations. Genetic differentiation between the Phillip Island and mainland populations was high. The relatively high differentiation found between the two populations could be due to either low migration rates, the effect of the composition of founder animals or both effects. Further ecological and historical information about the populations is needed to explore the likely significance of these effects.
Clustering Tweets using Cellular Genetic Algorithm

As the popularity of Twitter continues to increase rapidly, it is extremely necessary to analyze the h uge amount of data that Twitter users generate. A popul ar method of tweet analysis is clustering. Because most tweets are textual, this study focuses on clusterin g tweets based on their textual content similarity. This study presents tweet clustering using cellular gene tic algorithm cGA. The results obtained by cGA are compared with those obtained by generational geneti c algorithm in terms of average fitness, average ti me required for execution and number of generations. E xperimental results are tested with two sets: One o f 1000 tweets and the second formed of 5000 tweets. T he results show a nearly equal performance for both algorithms in terms of the average fitness of the s olution. On the other hand, cGA shows a much faster performance than generational. These results demonstrate that cellular genetic algorithm outperforms generational genetic algorithm in tweet clustering.
Circulating fibroblast growth factor 21 is induced by peroxisome proliferator-activated receptor agonists but not ketosis in man.

CONTEXT Murine fibroblast growth factor (FGF) 21 is a nutritionally regulated hormone secreted by the liver principally in response to peroxisome proliferator-activated receptor-alpha (PPAR alpha) activation, which plays a critical role in regulating metabolism during ketosis. FGF21 is also a PPAR gamma target gene in mouse adipose tissue. Little information is available on FGF21 functions in humans. OBJECTIVE The aim of the study was to measure plasma FGF21 during fasting, ketogenic diet, and PPAR agonist treatment in humans. DESIGN AND SETTING We conducted a prospective study involving three patient groups at two university hospitals. PATIENTS Eight healthy male volunteers underwent a 48-h period of starvation followed by 24-h refeeding (group 1); seven obese individuals were allocated to a low-carbohydrate diet for 3 months (group 2); and three groups of healthy, overweight or obese male volunteers received treatment with a PPAR alpha (20 microg/d GW590735) (n=6), PPAR delta (10 mg/d GW501516) (n=6), or PPAR gamma agonist (rosiglitazone) (n=10) for 2 wk (group 3). MAIN OUTCOME MEASURES Fasting plasma FGF21 and serum 3-hydroxybutyrate were measured. RESULTS There was no significant variation in human plasma FGF21 during fasting and refeeding. A 3-month ketogenic diet was associated with a 42% decline in plasma FGF21 levels. Circulating FGF21 increased significantly in response to treatment with PPAR alpha (39%) and PPAR delta (32%), but not PPAR gamma agonists. CONCLUSION FGF21 does not play a major role in regulating the fasting response or ketosis in man. However, plasma FGF21 is elevated in response to pharmacological activation of PPAR alpha and PPAR delta and may contribute to the beneficial metabolic effects observed in response to pharmacotherapy with these compounds.
Paroxysmal complete atrioventricular block in a patient with pulmonary atresia and intact ventricular septum

Abstract Sudden death in pulmonary atresia and intact ventricular septum with right ventricular dependent coronary circulation is a well-established complication, and is thought to be caused by myocardial ischaemia. We report a case of paroxysmal complete atrioventricular block that raises the possibility of an additional mechanism of sudden death.
Un schéma aux volumes finis avec matrice signe pour les systèmes non homogènes

Cette these est consacree a l'analyse, a l'application et a l'extension bidimensionnelle, d'un nouveau schema aux volumes finis (SRNH) propose recemment pour une classe de systeme non homogene. L'analyse de stabilite du schema, d'abord dans le cas scalaire ensuite dans le cas de systemes, mene a une nouvelle formulation ou intervient le signe de la matrice Jacobienne du systeme de lois de bilan considere. Pour le systeme de Saint Venant avec terme de pente, on montre formellement que le schema SRNHS verifie la C-propriete exacte introduite pour les schemas equilibres par Bermudez et Vazquez. Les resultats numeriques 1D et 2D, en particulier du cas de rupture de barage sur un fond en forme de marche, montrent le degres d'efficacite du schema. Pour le systeme diphasiques des zones de non hyperbolicite peuvent exister, avec apparition de valeurs propres complexes dans la Jacobienne du systeme. On montre que pour les configurations faiblement non hyperboliques, on peut calculer le signe de la Jacobienne par l'algorithme de Newton-Schultz. Pour les configurations plus raides, ou la methode precedente ne fonctionne plus, on a recours a la methode de perturbation par densite. Dans les deux cas evoques, les tests numeriques montrent que l'on approche la solution exacte du probleme de Ransom avec une grande precision, et que l'on conserve la stabilite des calculs meme avec un maillage de finesse relativement elevee.
Reversible gastric and pancreatic hyposecretion after long-term total parenteral nutrition.

Total parenteral nutrition is a major advance in nutritional support, but is not without deleterious effects.1 Several animal studies have shown reversible functional and structural gastrointestinal atrophy in response to total parenteral nutrition.2 3 4 We report reversibility of gastric and pancreatic hyposecretion in a man who resumed an oral diet after two years of home parenteral nutrition as the sole source of calories. Case Report A 28-year-old man was admitted to the Philadelphia Veterans Administration Hospital because of multiple vertebral compression fractures. He had a seven-year history of Crohn's disease with extensive small-bowel involvement. Despite prolonged treatment with prednisone and sulfasalazine, .