Miracle-dz/UniFAR-FTUs huggingface dataset:
Interaction of cisplatin and analogue Pt(en)Cl2 with the copper metallo-chaperone Atox1.

The human metallo-chaperone protein Atox1 features a high affinity Cu(I) binding site Cys(12)GlyGlyCys(15) (KD = 10(-17.4) M at pH 7.0) and delivers copper to the trans-Golgi network (TGN). Atox1 may participate in the metabolism of the drug cis-Pt(NH3)2Cl2 (cisplatin), either as a component of its delivery to the nucleus or of its loss via transport to the TGN and beyond. The species of stoichiometry [Pt(NH3)2(Atox1)] was the sole adduct of stoichiometry Pt : Atox1 = 1 : 1 detected by mass spectrometry under non-denaturing conditions from solutions containing cisplatin and apo-Atox1. The ions [Atox1 + Pt(NH3)2(2+) + (z - 2)H(+)](z+) (z = 3 to 7) were observed and correspond to different protonation states of the 1 : 1 adduct. Adducts of stoichiometry Pt : Atox1 = 2 : 1 were also detected but 1 : 2 adducts were not detected. The related complex Pt(en)Cl2 (en = 1,2-diaminoethane) behaved similarly. Tandem mass spectrometry experiments using top-down and bottom-up sequencing techniques were carried out, respectively, on the intact platinated protein and on platinated peptides formed from proteolysis by trypsin. A new software programme (PolyCut) designed to analyse the complex high-resolution tandem mass spectra of fragment ions derived from proteins containing transition metal ions was applied to establish the binding site(s) of the platinum atom(s). The analysis, based on the entire isotope patterns, is consistent with the cysteine residues in the Cu(I)-binding sequence Cys(12)GlyGlyCys(15) being the primary coordination site.
Selection of Shigella flexneri candidate virulence genes specifically induced in bacteria resident in host cell cytoplasm

We describe an in vivo expression technology (IVET)‐like approach, which uses antibiotic resistance for selection, to identify Shigella flexneri genes specifically activated in bacteria resident in host cell cytoplasm. This procedure required construction of a promoter‐trap vector containing a synthetic operon between the promoterless chloramphenicol acetyl transferase (cat) and lacZ genes and construction of a library of plasmids carrying transcriptional fusions between S. flexneri genomic fragments and the cat–lacZ operon. Clones exhibiting low levels (<10 µg ml−1) of chloramphenicol (Cm) resistance on laboratory media were analysed for their ability to induce a cytophatic effect – plaque – on a cell monolayer, in the presence of Cm. These clones were assumed to carry a plasmid in which the cloned fragment acted as a promoter/gene which is poorly expressed under laboratory conditions. Therefore, only strains harbouring fusion‐plasmids in which the cloned promoter was specifically activated within host cytoplasm could survive within the cell monolayer in the presence of Cm and give a positive result in the plaque assay. Pai (plaque assay induced) clones, selected following this procedure, were analysed for intracellular (i) β‐galactosidase activity, (ii) proliferation in the presence of Cm, and (iii) Cm resistance. Sequence analysis of Pai plasmids revealed genes encoding proteins of three functional classes: external layer recycling, adaptation to microaerophilic environment and gene regulation. Sequences encoding unknown functions were also trapped and selected by this new IVET‐based protocol.
Effects of cysteine-containing compounds on biosynthesis of triacylglycerol and cholesterol and anti-oxidative protection in liver from mice consuming a high-fat diet

Effects of n-acetyl cysteine (NAC), s-ethyl cysteine (SEC), s-propyl cysteine (SPC) and cysteine on enzymes participating in biosynthesis of TAG and cholesterol, and antioxidant protection in liver from mice consuming a high-saturated fat diet was examined. The high-fat diet provided 70 % fat energy, in which saturated fat was 55 % of total fat. NAC, SEC, SPC or cysteine, each agent at 1 g/l, was directly added into the drinking water as a supplement for 4 weeks. Results showed high saturated fat significantly increased hepatic TAG and total cholesterol contents (P < 0·05) via enhancing the activity and mRNA expression of malic enzyme, fatty acid synthase and 3-hydroxy-3-methylglutaryl coenzyme A reductase (P < 0·05). The intake of NAC, SEC or SPC significantly decreased TAG and total cholesterol levels (P < 0·05) via lowering the activity and mRNA expression of these three lipogenic-related enzymes (P < 0·05). NAC, SEC or SPC treatment also significantly suppressed high saturated fat-induced hepatic mRNA expression of sterol regulatory element-binding protein (SREBP)-1c and SREBP-2 (P < 0·05). High saturated fat decreased hepatic content of glutathione, and the activity of catalase and glutathione peroxidase (P < 0·05). The intake of NAC, SEC or SPC significantly increased hepatic glutathione content (P < 0·05), restored the activity and mRNA expression of glutathione peroxidase, and alleviated the high saturated fat-induced oxidative stress (P < 0·05). These results support that NAC, SEC and SPC are potent agents for affecting hepatic biosynthesis of TAG and cholesterol, and protecting liver against high saturated fat-associated oxidative damage.
Efficacy of Functional Strength Training on Restoration of Lower-Limb Motor Function Early After Stroke: Phase I Randomized Controlled Trial

After stroke, physiotherapy can promote brain reorganization and motor recovery. Combining muscle strength and functional training (functional strength training, FST) may be beneficial. The aim of the authors was to compare FST with conventional physiotherapy (CPT) while controlling for the potential confounder of therapy intensity in a multicenter, randomized controlled observer-blind trial. The mean age of the participants was 68.3 (standard deviation [SD] = 12.03) years at a mean of 34 (SD = 20) days after stroke, with mean peak paretic knee extension torque (torque) of 22 (SD = 25) Nm. The estimated sample size was 102 to detect a between-group difference of 0.2 m/s in walking speed. After baseline measures, participants were allocated randomly to CPT or CPT + CPT or CPT + FST for 6 weeks. Additional experimental therapy was provided for up to 1 hour a day, 4 times each week. Outcomes were measured 6 weeks after baseline and at follow-up 12 weeks thereafter. Measures included walking speed, knee extensor torque, and functional mobility (Rivermead). At outcome, both extraintensity groups showed greater increases in walking speed than the CPT group, but this reached significance only for the CPT + CPT group (P = .031). The CPT + CPT group also had a greater number of participants who walked at 0.8 m/s or above. No significant differences were observed for torque about the knee or for the Rivermead score. At follow-up, no significant differences were observed. These phase I results justify a subsequent trial of CPT + CPT versus CPT + FST.
A fault-tolerant architecture for ATM networks

The asynchronous transfer mode (ATM) is the transfer mode recommended for B-ISDN by CCITT. In this paper, we propose a self-routing fault-tolerant switching architecture for ATM networks. The proposed architecture uses subswitches and extra links to provide many alternative paths, and hence can tolerate multiple faults. Analytical results show that the number of redundant paths increases exponentially as the size of the network increases. A simulation model is developed to study both the reliability and She performance of the proposed architecture. Reliability analysis shows that this architecture has a much higher fault tolerance than the fault-tolerant ATM networks found in the literature. In addition, the extra paths can be used to route cells when internal cell contention occurs in switching elements. Simulation results also indicate that the proposed architecture maintains a high throughput with acceptable cell delay time, even when the number of faulty components increases.
Dimension reconstruction for visual exploration of subspace clusters in high-dimensional data

Subspace-based analysis has increasingly become the preferred method for clustering high-dimensional data. A visually interactive exploration of subspaces and clusters is a cyclic process. Every meaningful discovery will motivate users to re-search subspaces that can provide improved clustering results and reveal the relationships among clusters that can hardly coexist in the original subspaces. However, the combination of dimensions from the original subspaces is not always effective in finding the expected subspaces. In this study, we present an approach that enables users to reconstruct new dimensions from the data projections of subspaces to preserve interesting cluster information. The reconstructed dimensions are included into an analytical workflow with the original dimensions to help users construct target-oriented subspaces which clearly display informative cluster structures. We also provide a visualization tool that assists users in the exploration of subspace clusters by utilizing dimension reconstruction. Several case studies on synthetic and real-world data sets have been performed to prove the effectiveness of our approach. Lastly, further evaluation of the approach has been conducted via expert reviews.
Twittener: Listen to your Twitter Feed

Twitter is a popular social media site, as it allows users to get rapid & concise information, and to follow the latest online trends & topics. This project aims to improve user experience by proposing an alternative way to interact with Twitter, by allowing users to listen to interesting tweets, instead of the conventional way of reading them. This will allow users to get up to date with tweets from publicly-listed, categorized Twitter accounts, without needing to pay full attention to their screens. This could prove useful for populations with physical disabilities, visual impairments, the elderly and persons who multitask. A web application, called Twittener, has been developed to allow users to listen to tweets. Additionally, a console application periodically crawls through Twitter retrieving & converting tweets from text to speech, thus making up the Twittener system.
Indole‐3‐carbinol activates the ATM signaling pathway independent of DNA damage to stabilize p53 and induce G1 arrest of human mammary epithelial cells

The phytochemical indole‐3‐carbinol (I3C), from cruciferous vegetables such as broccoli, has been shown to elicit a potent anti‐proliferative response in human breast cancer cell lines. Treatment of the immortalized human mammary epithelial cell line MCF10A with I3C induced a G1 cell cycle arrest, elevated p53 tumor suppressor protein levels and stimulated expression of downstream transcriptional target, p21. I3C treatment also elevated p53 levels in several breast cancer cell lines that express mutant p53. I3C did not arrest MCF10A cells stably transfected with dominant‐negative p53, establishing a functional requirement for p53. Cell fractionation and immunolocalization studies revealed a large fraction of stabilized p53 protein in the nucleus of I3C‐treated MCF10A cells. With I3C treatment, phosphatidyl‐inositol‐3‐kinase family member ataxia telangiectasia‐mutated (ATM) was phosphorylated, as were its substrates p53, CHK2 and BRCA1. Phosphorylation of p53 at the N‐terminus has previously been shown to disrupt the interaction between p53 and its ubiquitin ligase, MDM2, and therefore stabilizing p53. Coimmunoprecipitation analysis revealed that I3C reduced by 4‐fold the level of MDM2 protein that associated with p53. The p53–MDM2 interaction and absence of p21 production were restored in cells treated with I3C and the ATM inhibitor wortmannin. Significantly, I3C does not increase the number of 53BP1 foci or H2AX phosphorylation, indicating that ATM is activated independent of DNA double‐strand breaks. Taken together, our results demonstrate that I3C activates ATM signaling through a novel pathway to stimulate p53 phosphorylation and disruption of the p53–MDM2 interaction, which releases p53 to induce the p21 CDK inhibitor and a G1 cell cycle arrest. © 2005 Wiley‐Liss, Inc.
AN APPROACH TO STATISTICAL-INFERENCE IN CROSS-SECTIONAL MODELS WITH SECURITY ABNORMAL RETURNS AS DEPENDENT VARIABLE

Several recent event studies test hypotheses about the association between event-related abnormal security returns and firm characteristics using a three-step procedure. ' First, forecast model parameters are estimated, usually parameters of a market model; second, prediction errors or residuals are computed over an event period; third, prediction errors are regressed cross-sectionally on firm characteristics hypothesized to influence the impact of the event on share values. Results of these regressions are used to draw inferences about the relation between abnormal returns and firm characteristics. Researchers who employ three-step procedures acknowledge that crosssectional (OLS) regressions lead to valid inferences if the disturbances are IID (normal) in cross-section; see, for example, Leftwich [1981, p. 23] and Lustgarten [1982, p. 138]. While sufficient assumptions to draw valid inferences from OLS regressions are clear, these assumptions are violated if there is cross-correlation and cross-sectional heteroscedasticity in the firm return processes from which the prediction errors are estimated. Assumptions about the processes generating these prediction
Hypervolume-based expected improvement: Monotonicity properties and exact computation

The expected improvement (EI) is a well established criterion in Bayesian global optimization (BGO) and metamodel-assisted evolutionary computation, both applied in optimization with costly function evaluations. Recently, it has been adopted in different ways to multiobjective optimization. A promising approach to formulate the expected improvement in this context, is to base it on the hypervolume indicator. Given the Bayesian model of the optimization landscape, the EI in hypervolume computes the expected gain in attained hypervolume for a given input point. Although a formulation of this expected improvement is relatively straightforward, its computation and mathematical properties are still to be investigated. This paper will outline and derive an algorithm for the exact computation of the proposed hypervolume-based EI. Moreover, this paper establishes monotonicity properties of the expected improvement. In particular the effect of the predictive distribution's variance on the hypervolume-based EI and elementary properties of the EI landscape are studied. The monotonicity properties will reveal regions where Pareto front approximations can be improved as well as underexplored regions that are favored by the hypervolume-based expected improvement. A first numerical example is included that illustrates the behavior of the hypervolume-based EI in the multiobjective BGO framework.
Thermal Destabilization of Non-phosphorylating Glyceraldehyde-3-phosphate Dehydrogenase from Streptococcus mutans upon Phosphate Binding in the Active Site*

Catalysis by the NADP-dependent non-phosphorylating glyceraldehyde-3-phosphate dehydrogenase (GAPN) from Streptococcus mutans, a member of the aldehyde dehydrogenase (ALDH) family, relies on a local conformational reorganization of the active site. This rearrangement is promoted by the binding of NADP and is strongly kinetically favored by the formation of the ternary complex enzyme·NADP·substrate. Adiabatic differential scanning calorimetry was used to investigate the effect of ligands on the irreversible thermal denaturation of GAPN. We showed that phosphate binds to GAPN, resulting in the formation of a GAPN·phosphate binary complex characterized by a strongly decreased thermal stability, with a difference of at least 15 °C between the maximum temperatures of the thermal transition peaks. The kinetics of phosphate association and dissociation are slow, allowing both free and GAPN·phosphate complexes to be observed by differential scanning calorimetry and to be separated by native polyacrylamide electrophoresis run in phosphate buffer. Analysis of a set of mutants of GAPN strongly suggests that phosphate is bound to the substrate C-3 subsite. In addition, the substrate analog glycerol-3-phosphate has similar effects as does phosphate on the thermal behavior of GAPN. Based on the current knowledge on the catalytic mechanism of GAPN and other ALDHs, we propose that ligand-induced thermal destabilization is a mechanism that provides to ALDHs the required flexibility for an efficient catalysis.
Miniaturization of 4×4 Butler matrix using high slow-wave factor structure

In this paper, a novel slow-wave structure with high slow-wave factor is proposed. The new structure composed of meandered-line structure, low-impedance transmission line and interdigital structure is capable of reducing the circuit size significantly due to its good slow-wave property. A miniaturized 4×4 Butler matrix resonant at 970MHz is designed using the proposed structure. The size of the proposed 4×4 Butler matrix is merely 5.8% of the conventional ones. The measured results of the manufactured are in good agreement with the simulated results.
Out of Necessity Comes Unbridled Imagination for Survival: Contributive Justice in Spanish Libraries during Economic Crisis

The call for this journal issue notes that “social justice in LIS/services involves achieving action-oriented socially relevant outcomes via information-related work. ” There is not a more fitting time and place for such action than in Spain, where the current economic crisis left more than 6 million (27 percent of the population) unemployed as of 2013. It is not just communities that are grappling with the pain of the economic downturn; libraries are also suffering from the crisis as a result of budget cuts due to reduced public funding. This article presents the case of Spanish academic and public libraries that have found solutions to keep themselves open, providing services vital to the economic and sociocultural needs of their communities. This case is an example of contributive justice, as evidenced in the actions taken by Spanish libraries and their communities as well as in the manner in which the research data were collected. Eight libraryrelated actions were found: professional, community, social, political, digital, cultural/heritage, economic, and ontological. Despite economic hardships all around, these Spanish examples reveal the impact of libraries as social justice institutions, the role of librarians as agents of change, and the value of contributive and grassroots efforts when governments fail to provide. Moreover, these contributions to social justice illustrate actions appropriate to a contributive justice framework for libraries, as proposed in this article.
Automated combination of the results of elemental and structural analysis with the help of a learning knowledgebase to identify the contained analytes: A theoretical reflection

In nature, substances mostly occur in complex matrices. For methods in analytical measurement it is important to reach a high selectivity to get the correct qualitative and quantitative results for the substances in these mixtures. Therefor the general concept of the pre-, intra- and post-sensorial selectivity is suitable. The different analytical methods of the pre- and intra-sensorial steps are used to reach the required selectivity. Since automation gain growing importance in modern laboratories the data output is increased massively. With a manual data evaluation as a post-sensorial step it is not possible to overcome this high amount of data. Modern laboratories are mostly electronic and paperless, so databases and intelligent software can be used to interpret the received data from the analytical devices. This paper shows the necessity of the combination of different methods of the pre- and intra-sensorial steps or their results to obtain a higher selectivity. Also the developed system concept for the automated combination of the results of elemental and structural analysis with the help of a learning knowledgebase to identify the contained analytes inside a complex matrix is presented. Therefor the existing infrastructure of the software Project ADE is used.
Is Fair Trade Fair for Consumers? A Hedonic Analysis of U.S. Retail Fair Trade Coffee Prices

This study aims to investigate the impact of the fair trade label on the market for coffee in the United States, a country with high public awareness regarding environmental and social matters. A revealed preference approach is adopted, using monthly Nielsen scanner sales panel data. The pricing of labelled ground and whole bean coffee is studied over the 2011-2013 period. Hedonic estimates are obtained for what consumers pay for different product characteristics. Results would provide information on the existing price differences between labelled and conventional coffee, and add to the ongoing analysis and debate over fair trade coffee.
Optimal design of a multiplying D/A converter stage with time-shifted correlated double sampling

The multiplying D/A converter stage with time-shifted correlated double sampling technique is analyzed. Comprehensive models for the residual error due to finite amplifier gain and the thermal noise power are derived; the settling behavior of such stages is presented. It is shown that the selection of the error storage/hold capacitance introduces tradeoffs with respect to noise, accuracy, and power consumption. The link between the optimal hold capacitance leading to minimum power and the converter speed is demonstrated.
Supplier strategies to compensate for knowledge asymmetries in buyer-supplier relationships: Implications for economic upgrading

This paper explores a special form of international outsourcing relationship in which suppliers make recurrent discrete transactions with the same buyers over a long period of time without the existence of any original legally binding written agreement. The study examines three research questions: (1) Can suppliers in such relationships access any of their buyers' tacit knowledge? (2) What implications does their access or the lack thereof have for their economic upgrading? (3) What strategies do suppliers adopt to compensate for existing knowledge asymmetries? The case analysis of three small Bangladeshi garment manufacturers reveals the following key findings. The studied firms only have access to their buyers' explicit/codified knowledge. Notwithstanding this, they have successfully developed relevant knowledge that has allowed them to engage in process upgrading.
Protein structure as a means to triage proposed PTM sites

PTMs such as phosphorylation are often important actors in protein regulation and recognition. These functions require both visibility and accessibility to other proteins; that the modification is located at the surface of the protein. Currently, many repositories provide information on PTMs but structural information is often lacking. This study, which focuses on phosphorylation sites available in UniProtKB/Swiss‐Prot, illustrates that most phosphorylation sites are indeed found at the surface of the protein, but that some sites are found buried in the core of the protein. Several of these identified buried phosphorylation sites can easily become accessible upon small conformational changes while others would require the whole protein to unfold and are hence most unlikely modification sites. Subsequent analysis of phosphorylation sites available in PRIDE demonstrates that taking the structure of the protein into account would be a good guide in the identification of the actual phosphorylated positions in phophoproteomics experiments. This analysis illustrates that care must be taken when simply accepting the position of a PTM without first analyzing its position within the protein structure if the latter is available.