Miracle-dz/UniFAR-FTUs huggingface dataset:
A Framework for Evaluating Replica Placement Algorithms

This paper introduces a framework for evaluating replica placement algorithms (RPA) for content delivery networks (CDN) as well as RPAs from other fields that might be applicable to current or future CDNs. First, the framework classifies and qualitatively compares RPAs using a generic set of primitives that capture problem definitions and heuristics. Second, it provides estimates for the decision times of RPAs using an analytic model. To achieve accuracy, the model takes into account disk accesses and message sizes, in addition to computational complexity and message numbers that have been considered traditionally. Third, it uses the “goodness” of produced placements to compare RPAs even when they have different problem definitions. Based on these evaluations, we identify open issues and potential areas for future research.
Abl Tyrosine Kinase Regulates Hepatitis C Virus Entry

Abl is a central regulator of multiple cellular processes controlling actin dynamics, proliferation, and differentiation. Here, we showed that knockdown of Abl impaired hepatitis C virus (HCV) propagation. Treatment of Abl tyrosine kinase-specific inhibitor, imatinib and dasatinib, also significantly decreased HCV RNA and protein levels in HCV-infected cells. We showed that both imatinib and dasatinib selectively inhibited HCV infection at the entry step of HCV life cycle, suggesting that Abl kinase activity may be necessary for HCV entry. Using HCV pseudoparticle infection assays, we verified that Abl is required for viral entry. By employing transferrin uptake and immunofluorescence assays, we further demonstrated that Abl was involved in HCV entry at a clathrin-mediated endocytosis step. These data suggest that Abl may represent a novel host factor for HCV entry.
Intracranial volume–pressure relationships during experimental brain compression in primates

In 10 anaesthetized and ventilated baboons a steady level of raised intracranial pressure was achieved by graduated inflation of an extradural balloon. Measurements were made of the ventricular fluid pressure, and of the change in this pressure after injection of 0·05 ml into the ventricle, the volume–pressure response. This response was studied at normocapnia and at hypocapnia (induced by hyperventilation), and before and after the intravenous administration of mannitol under normocapnic and hypercapnic conditions. During hypocapnia, ventricular fluid pressure and the volume–pressure response were reduced equally. Mannitol, however, caused a greater reduction in the volume–pressure response than in ventricular fluid pressure. The intravenous administration of mannitol therefore produces a beneficial effect on intracranial capacitance which is greater than observation of intracranial pressure alone indicates.
Serological response to one intradermal or intramuscular hepatitis B virus vaccine booster dose in human immunodeficiency virus-infected nonresponders to standard vaccination

Purpose: Hepatitis B virus (HBV) vaccination is recommended for all human immunodeficiency virus (HIV)-infected patients without HBV immunity. However, serological response to standard HBV vaccination is frequently suboptimal in this population and the appropriate strategy for revaccination of HIV-infected nonresponders remained controversial. We aimed to determine the serological response to one booster dose of HBV vaccine given by intradermal (ID) or intramuscular (IM) route in HIV-positive nonresponders to standard HBV vaccination. Materials and Methods: In this study, 42 HIV-infected nonresponders were enrolled. We randomized them to receive either 10 μg (0.5 mL) for ID (20 cases) or 20 μg (1 mL) for IM (22 cases) administration of HBV vaccine as a one booster dose. After 1 month, anti-HBs titer was checked in all cases. A protective antibody response (seroconversion) defined as an anti-HBs titer ≥10 IU/L. Results: Seroconversion was observed in 47.6% of subjects after 1 ID dose. A total of 30% showed antibody titers above 100 IU/L. Except one case, all responders had CD4+ >200 cells/mm3. Mean anti-HBs titer was 146.5 ± 246 IU/L. After the one IM booster dose, seroconversion was observed in 50% of cases. A total of 36.3% of subjects had anti-HBs ≥100 IU/L. All responders had CD4+ >200 cells/mm3, except one case. Mean anti-HBs titer was 416.4 ± 765.6 IU/L. Responders showed significantly higher CD4+ cell counts, in comparison to nonresponders (P < 0.001). Conclusions: One booster dose administered IM or ID to HIV-infected nonresponders resulted in similar rates of seroconversion, overall response rate 50%. However, higher anti-HBs titers observed more frequently in IM group.
Hybrid word sense disambiguation using language resources for transliteration of Arabic numerals in Korean

The high frequency of the use of Arabic numerals in informative texts and their multiple senses and readings deteriorate the accuracy of TTS systems. This paper presents a hybrid word sense disambiguation method exploiting a tagged corpus and a Korean wordnet, KorLex 1.0, for the correct and efficient conversion of Arabic numerals into Korean phonemes according to their senses. Individual contextual features are extracted from the tagged corpus and are grouped in order to determine the sense of Arabic numerals. Least upper bound synsets among common hypernyms of contextual features were obtained from the KorLex hierarchy, and they were used as semantic categories of the contextual features of Arabic numerals. The semantic classes were trained to classify the meaning and the reading of Arabic numerals using decision tree and to compose grapheme-to-phoneme rules for an automatic transliteration system for Arabic numerals. The proposed system outperforms the customized TTS systems by 3.9%--20.3%.
Introduction to Number Theory

This seems simple enough, but let’s play with this definition. The Pythagoreans, an ancient sect of mathematical mystics, said that a number is perfect if it equals the sum of its positive integral divisors, excluding itself. For example, 6 = 1 + 2 + 3 and 28 = 1 + 2 + 4 + 7 + 14 are perfect numbers. On the other hand, 10 is not perfect because 1 + 2 + 5 = 8, and 12 is not perfect because 1+2+3+4+6 = 16. Euclid characterized all the even perfect numbers around 300 BC. But is there an odd perfect number? More than two thousand years later, we still don’t know! All numbers up to about 10300 have been ruled out, but no one has proved that there isn’t an odd perfect number waiting just over the horizon.
Suspicious mind: the association between Streptococcus bovis endocarditis and carcinoma of the colon.

Sir, The association between Streptococcus bovis endocarditis and carcinoma of the colon is well documented. '-5 We report a patient in whom, following treatment of S. bovis endocarditis, a right hemicolectomy was carried out for a caecal lesion which, although biopsies had shown benign disease, the subsequent postoperative histology revealed the presence of an adenocarcinoma. An 83 year old man was admitted and treated for an infective exacerbation of his chronic obstructive airways disease. He had a past medical history of myocardial infarction, congestive cardiac failure, mitral regurgitation and pernicious anaemia. In 1989 a sigmoid colotomy had been performed for a villous adenoma found following investigation of an iron deficiency anaemia. Five days after discharge he was readmitted complaining of malaise, backache and headache. He was pyrexial. Blood culture grew S. bovis and transoesophageal echocardiogram demonstrated vegetations on the mitral valve. Following commencement on intravenous teicoplanin, the patient improved rapidly, with no recrudescence ofhis initial pyrexia. The patient denied any bowel symptoms and faecal occult bloods were negative, but at colonoscopy a large polypoid lesion of malignant appearance was seen just above the ileo-caecal valve. A number of smaller polyps were also seen. Caecal biopsies showed no malignancy. In view of the macroscopic appearance of the caecal lesion, the association of malignancy with S. bovis endocarditis, and the possibility of recurrence of the endocarditis, an elective right hemicolectomy was carried out. At operation three polyps were found in the caecum. Histological examination of the largest polyp revealed a moderately differentiated adenocarcinoma Dukes stage A. The other two polyps were tubulo-villous adenomata and three lymph nodes were free from tumour. This case emphasizes the need for a high index of suspicion of malignancy and thorough gastrointestinal investigation, even in the absence of gastrointestinal symptoms, in cases of Streptococcus bovis endocarditis or bacteraemia. Colonoscopy is the investigation of choice as barium enema failed to detect the presence of carcinoma in some reports.6'7 L.G. Copeland M.G. Malster Department of Geriatric Medicine, Royal Liverpool University Hospital, Prescot Street, Liverpool L7 8XP, UK.
Effect of antibiotic-loaded hydrophilic stent in the prevention of bacterial adherence: a study of the charge, discharge, and recharge concept using ciprofloxacin.

BACKGROUND Ciprofloxacin prophylaxis significantly prolonged stent patency in cats, but human studies produced conflicting results, possibly due to varying drug levels in bile. The uptake (charge) and release (discharge) of ciprofloxacin from a hydrophilic stent (HS) in an antibiotic solution and the effect of a ciprofloxacin-loaded stent (CHS) in inhibiting Escherichia coli adherence were tested. The adjuvant effect of ciprofloxacin perfusion (recharge) in the inhibition of E coli adherence was also tested. METHODS Uptake: segments of HS were immersed in 5 mL of ciprofloxacin solutions for 24 hours. Ciprofloxacin remaining in solution was measured to determine the uptake by the HS. Release: CHS were placed in 5 mL water for 24 hours, and released ciprofloxacin was measured. CHS were placed on culture plates with E coli and incubated; diameters of inhibited zones were measured. CHS 0.5 cm in length were incubated in separate 5 mL E coli suspension (10(7) colony forming units [CFU]/mL) in 2% ox bile for 4 hours. E coli adhered on CHS were measured and compared with control HS. An E coli (10(6) CFU/mL) suspension was perfused through a modified Robbins device (MRD)-containing CHS. Stents were removed at regular intervals and processed to determine the adherence of E coli; non-loaded HS served as controls. The experiment was repeated by using CHS together with perfusion of ciprofloxacin solution (0.3 microg/mL) into the MRD for up to 7 days; normal saline solution was used as a control in a second MRD. Stents were removed daily to determine the adherence of E coli. RESULTS Uptake and release of ciprofloxacin by HS and CHS, respectively, were related to concentration of ciprofloxacin. Between 50% to 90% of the drug was released in 24 hours. Zonal inhibition of E coli growth was proportional to the concentration of ciprofloxacin on the CHS. There was an initial 10-fold reduction in attached E coli on CHS compared with controls, but this effect diminished after 24 hours. With ciprofloxacin perfusion, there was a 100-fold reduction in adhered E coli on CHS, although there was no change in E coli concentration in bile. CONCLUSIONS There was a free exchange (uptake and release) of ciprofloxacin along a concentration gradient between the antibiotic solution and HS. CHS reduced the number of adhered E coli, but the effect was short-lived. Perfusion of ciprofloxacin offers an adjuvant benefit by enhancing inhibition of E coli adherence on CHS.
Combined chemical and genetic approach to inhibit proteolysis by the proteasome

Regulated protein destruction by the proteasome is crucial for the maintenance of normal cellular homeostasis. Much of our understanding of proteasome function stems from the use of drugs that inhibit its activity. Curiously, despite the importance of proteasomal proteolysis, previous studies have found that proliferation of the yeast Saccharomyces cerevisiae is relatively resistant to the effects of proteasome inhibitors such as MG132, even in the presence of mutations that increase inhibitor levels in cells. We reasoned that part of the resistance of S. cerevisiae to proteasome inhibitors stems from the fact that most proteasome inhibitors preferentially target the chymotryptic activity of the proteasome, and that the caspase‐like and tryptic sites within the 20S core could compensate for proteasome function under these conditions. To test this hypothesis, we generated a strain of yeast in which the gene encoding the drug efflux pump Pdr5 is deleted, and the tryptic and caspase‐like proteasome activities are inactivated by mutation. We find that this strain has dramatically increased sensitivity to the proteasome inhibitor MG132. Under these conditions, treatment of yeast with MG132 blocks progression through the cell cycle, increases the accumulation of polyubiquitylated proteins and decreases the ability to induce transcription of certain genes. These results highlight the contribution of the caspase‐like and tryptic activities of the proteasome to its function, and provide a strategy to potently block proteasomal proteolysis in yeast that has practical applications. Copyright © 2010 John Wiley & Sons, Ltd.
Transmembrane signaling in the sensor kinase DcuS of Escherichia coli: A long-range piston-type displacement of transmembrane helix 2

Significance Two-component systems represent the most common bacterial sensors for perceiving environmental stimuli. Extracytoplasmic sensing kinases of this type consist of an extracytoplasmic sensor domain, transmembrane helices (TMs), and a cytoplasmic His-kinase. Conformational changes in sensor domains upon ligand binding suggest transmembrane signal transduction by a piston-type displacement of TMs. Here, transmembrane signaling was probed for the C4-dicarboxylate sensor kinase (DcuS). Cysteine accessibility studies of TM2 showed fumarate-driven displacement of TM2 that is directly related to the activation of DcuS. TM2 repositioning is paralleled by corresponding energy optima for membrane insertion and effector-induced compaction of the corresponding binding domain. These experiments show signal transduction by a piston-type movement, which could be generally representative for bacterial sensor kinases. The C4-dicarboxylate sensor kinase DcuS is membrane integral because of the transmembrane (TM) helices TM1 and TM2. Fumarate-induced movement of the helices was probed in vivo by Cys accessibility scanning at the membrane–water interfaces after activation of DcuS by fumarate at the periplasmic binding site. TM1 was inserted with amino acid residues 21–41 in the membrane in both the fumarate-activated (ON) and inactive (OFF) states. In contrast, TM2 was inserted with residues 181–201 in the OFF state and residues 185–205 in the ON state. Replacement of Trp 185 by an Arg residue caused displacement of TM2 toward the outside of the membrane and a concomitant induction of the ON state. Results from Cys cross-linking of TM2/TM2′ in the DcuS homodimer excluded rotation; thus, data from accessibility changes of TM2 upon activation, either by ligand binding or by mutation of TM2, and cross-linking of TM2 and the connected region in the periplasm suggest a piston-type shift of TM2 by four residues to the periplasm upon activation (or fumarate binding). This mode of function is supported by the suggestion from energetic calculations of two preferred positions for TM2 insertion in the membrane. The shift of TM2 by four residues (or 4–6 Å) toward the periplasm upon activation is complementary to the periplasmic displacement of 3–4 Å of the C-terminal part of the periplasmic ligand-binding domain upon ligand occupancy in the citrate-binding domain in the homologous CitA sensor kinase.
Implicit Distortion and Fertility Models for Attention-based Encoder-Decoder NMT Model

Neural machine translation has shown very promising results lately. Most NMT models follow the encoder-decoder framework. To make encoder-decoder models more flexible, attention mechanism was introduced to machine translation and also other tasks like speech recognition and image captioning. We observe that the quality of translation by attention-based encoder-decoder can be significantly damaged when the alignment is incorrect. We attribute these problems to the lack of distortion and fertility models. Aiming to resolve these problems, we propose new variations of attention-based encoder-decoder and compare them with other models on machine translation. Our proposed method achieved an improvement of 2 BLEU points over the original attention-based encoder-decoder.
DEG: a database of essential genes.

Essential genes are genes that are indispensable to support cellular life. These genes constitute a minimal gene set required for a living cell. We have constructed a Database of Essential Genes (DEG), which contains all the essential genes that are currently available. The functions encoded by essential genes are considered a foundation of life and therefore are likely to be common to all cells. Users can BLAST the query sequences against DEG. If homologous genes are found, it is possible that the queried genes are also essential. Users can search for essential genes by their function or name. Users can also browse and extract all the records in DEG. Essential gene products comprise excellent targets for antibacterial drugs. Analysis of essential genes could help to answer the question of what are the basic functions necessary to support cellular life. DEG is freely accessible from the website http://tubic.tju. edu.cn/deg/.
Microbial Populations in Naked Neck Chicken Ceca Raised on Pasture Flock Fed with Commercial Yeast Cell Wall Prebiotics via an Illumina MiSeq Platform

Prebiotics are non-digestible carbohydrate dietary supplements that selectively stimulate the growth of one or more beneficial bacteria in the gastrointestinal tract of the host. These bacteria can inhibit colonization of pathogenic bacteria by producing antimicrobial substances such as short chain fatty acids (SCFAs) and competing for niches with pathogens within the gut. Pasture flock chickens are generally raised outdoors with fresh grass, sunlight and air, which represents different environmental growth conditions compared to conventionally raised chickens. The purpose of this study was to evaluate the difference in microbial populations from naked neck chicken ceca fed with commercial prebiotics derived from brewer’s yeast cell wall via an Illumina MiSeq platform. A total of 147 day-of-hatch naked neck chickens were distributed into 3 groups consisted of 1) C: control (no prebiotic), 2) T1: Biolex® MB40 with 0.2%, and 3) T2: Leiber® ExCel with 0.2%, consistently supplemented prebiotics during the experimental period. At 8 weeks, a total of 15 birds from each group were randomly selected and ceca removed for DNA extraction. The Illumina Miseq platform based on V4 region of 16S rRNA gene was applied for microbiome analysis. Both treatments exhibited limited impact on the microbial populations at the phylum level, with no significant differences in the OTU number of Bacteroidetes among groups and an increase of Proteobacteria OTUs for the T1 (Biolex® MB40) group. In addition there was a significant increase of genus Faecalibacterium OTU, phylum Firmicutes. According to the development of next generation sequencing (NGS), microbiome analysis based on 16S rRNA gene proved to be informative on the prebiotic impact on poultry gut microbiota in pasture-raised naked neck birds.
Pro‐Opiomelanocortin (POMC) Neurones, POMC‐Derived Peptides, Melanocortin Receptors and Obesity: How Understanding of this System has Changed Over the Last Decade

Following the cloning of the melanocortin receptor and agouti protein genes, a model was developed for the central melanocortin system with respect to the regulation of energy and glucose homeostasis. This model comprised leptin regulation of melanocortin peptides and agouti‐related peptide (AgRP) produced from central pro‐opiomelanocortin (POMC) and AgRP neurones, respectively, as well as AgRP competitive antagonism of melanocortin peptides activating melanocortin 4 receptor (MC4R) to Gαs and the cAMP signalling pathway. In the last decade, there have been paradigm shifts in our understanding of the central melanocortin system as a result of the application of advanced new technologies, including Cre‐LoxP transgenic mouse technology, pharmacogenetics and optogenetics. During this period, our understanding of G protein coupled receptor signal transduction has also dramatically changed, such that these receptors are now known to exist in the plasma membrane oscillating between various inactive and active conformational states, and the active states signal through G protein‐dependent and G protein‐independent pathways. The present review focuses on evidence obtained over the past decade that has changed our understanding of POMC gene expression and regulation in the central nervous system, POMC and AgRP neuronal circuitry, neuroanatomical functions of melanocortin receptors, melanocortin 3 receptor (MC3R) and MC4R, and signal transduction through MC3R and MC4R.
A Study of Hierarchical and Flat Classification of Proteins

Automatic classification of proteins using machine learning is an important problem that has received significant attention in the literature. One feature of this problem is that expert-defined hierarchies of protein classes exist and can potentially be exploited to improve classification performance. In this article, we investigate empirically whether this is the case for two such hierarchies. We compare multiclass classification techniques that exploit the information in those class hierarchies and those that do not, using logistic regression, decision trees, bagged decision trees, and support vector machines as the underlying base learners. In particular, we compare hierarchical and flat variants of ensembles of nested dichotomies. The latter have been shown to deliver strong classification performance in multiclass settings. We present experimental results for synthetic, fold recognition, enzyme classification, and remote homology detection data. Our results show that exploiting the class hierarchy improves performance on the synthetic data but not in the case of the protein classification problems. Based on this, we recommend that strong flat multiclass methods be used as a baseline to establish the benefit of exploiting class hierarchies in this area.