Miracle-dz/UniFAR-FTUs huggingface dataset:
Molecular Basis for the Relative Substrate Specificity of Human Immunodeficiency Virus Type 1 and Feline Immunodeficiency Virus Proteases

ABSTRACT We have used a random hexamer phage library to delineate similarities and differences between the substrate specificities of human immunodeficiency virus type 1 (HIV-1) and feline immunodeficiency virus (FIV) proteases (PRs). Peptide sequences were identified that were specifically cleaved by each protease, as well as sequences cleaved equally well by both enzymes. Based on amino acid distinctions within the P3-P3′ region of substrates that appeared to correlate with these cleavage specificities, we prepared a series of synthetic peptides within the framework of a peptide sequence cleaved with essentially the same efficiency by both HIV-1 and FIV PRs, Ac-KSGVF↓VVNGLVK-NH2 (arrow denotes cleavage site). We used the resultant peptide set to assess the influence of specific amino acid substitutions on the cleavage characteristics of the two proteases. The findings show that when Asn is substituted for Val at the P2 position, HIV-1 PR cleaves the substrate at a much greater rate than does FIV PR. Likewise, Glu or Gln substituted for Val at the P2′ position also yields peptides specifically susceptible to HIV-1 PR. In contrast, when Ser is substituted for Val at P1′, FIV PR cleaves the substrate at a much higher rate than does HIV-1 PR. In addition, Asn or Gln at the P1 position, in combination with an appropriate P3 amino acid, Arg, also strongly favors cleavage by FIV PR over HIV PR. Structural analysis identified several protease residues likely to dictate the observed specificity differences. Interestingly, HIV PR Asp30 (Ile-35 in FIV PR), which influences specificity at the S2 and S2′ subsites, and HIV-1 PR Pro-81 and Val-82 (Ile-98 and Gln-99 in FIV PR), which influence specificity at the S1 and S1′ subsites, are residues which are often involved in development of drug resistance in HIV-1 protease. The peptide substrate KSGVF↓VVNGK, cleaved by both PRs, was used as a template for the design of a reduced amide inhibitor, Ac-GSGVFΨ(CH2NH)VVNGL-NH2. This compound inhibited both FIV and HIV-1 PRs with approximately equal efficiency. These findings establish a molecular basis for distinctions in substrate specificity between human and feline lentivirus PRs and offer a framework for development of efficient broad-based inhibitors.
Barriers to breast cancer screening in Australia: experiences of women with physical disabilities.

AIMS AND OBJECTIVES To explore the experiences of breast cancer screening for women with physical disabilities. BACKGROUND Despite women with disabilities having the same or greater risk of having breast cancer than women without disabilities, they are less likely to uptake breast cancer screening services. DESIGN Qualitative descriptive study. METHODS Twelve women with physical disabilities were recruited for the purpose of this study. Data were collected via semi-structured face to face or telephone interviews. Interviews were transcribed and data were analysed thematically. RESULTS Overwhelmingly, participants conveyed that their breast screening experiences were negative. The following four themes describe the experiences of breast cancer screening for women with physical disabilities: feeling I'm not in control; being ignored and not listened to; being helpless, alone and afraid and; experiencing pain, torture and humiliation. CONCLUSIONS Women with physical disabilities experience substantial barriers to breast cancer screening. This research highlights that the attitudes and poor communication skills of health professionals served as a deterrent to future screening for participants. RELEVANCE TO CLINICAL PRACTICE By exploring experiences of women with physical disabilities of breast cancer screening, nurses and other health-care professionals can use this to develop and implement optimal approaches, such as collaborative models of care which empower women with disabilities.
Interactive Hierarchical Task Learning via Crowdsourcing for Robot Adaptability

This paper describes the application of crowdsourcing to the problem of interactive task learning with the aim of enabling remotely-located users to effectively teach robots to perform complex tasks in real-world environments. We present a novel system that allows users to demonstrate hierarchical tasks via web-based control of a table-mounted six degree of freedom robot arm. The system employs intelligent action grouping suggestions and substitution suggestions for error recovery to assist the user in providing quality demonstrations. In addition, we describe design considerations and proposed extensions for the effective application of crowdsourcing to several human-robot interaction scenarios as motivated by this initial study.
Explaining Variation in the Effect of Floral Density on Pollinator Visitation

Pollinator responses to floral density have important implications for plant biology. In particular, a decline in pollinator visitation at low density can cause an Allee effect (a positive relation of fitness to density) in the plant population, which heightens that population’s vulnerability to extinction. Empiricists have reported a variety of relations between flower or plant density and pollinator visitation rates. Here I develop and test a model that provides explanations for this diversity. The model assumes that pollinators distribute themselves between a focal patch of flowers and the surrounding environment so as to maximize foraging success. The resulting relation of per-flower visitation rate to focal-patch floral density is nonlinear, with positive effects at low floral densities and weaker or negative effects at higher densities. The relation is influenced by floral density in the surrounding environment and traits of both the plants and their pollinators. In a field experiment, floral density of Holocarpha virgata ssp. virgata had a nonlinear effect on per-flower visitation that was largely consistent with the model’s predictions. By producing testable hypotheses based on biologically reasonable assumptions, this model serves as a starting point for explaining an important facet of plant-pollinator mutualisms.
Managing Flexible Loads in Residential Areas

Policy makers foster the use of clean, renewable electricity generators. These mainly decentralized, small units with intermittent output are in conflict with the current power grid control infrastructure. Demand response, the active participation of the demand side, is a promising option for efficient and reliable operation of future power systems. Today, demand response programs focus mainly on large industrial customers. Yet, the large number of households should also be tapped into demand response, particularly, since highly flexible loads in residential areas are expected to increase (e.g., electric vehicles or stationary batteries). Consequently, demand response potentials need to be addressed and appropriate mechanisms to coordinate a large number of small flexible units need to leverage. This work concentrates initially on building appropriate models for demand response analysis and elaborates an accurate representation of customer reactions in smart grids. The model is then used to evaluate potentials of two distinct demand response scenarios—direct load control and price-based incentives. Under direct load control an aggregator can combine flexible loads and intermittent renewable energy sources into one portfolio to increase load coverage with renewable generation. A large amount of flexible customers in a portfolio is not necessarily sufficient to balance load and generation. It turns out that for demand scheduling electric vehicles and storage heaters are the most promising devices and on the supply side an equally balanced wind and photovoltaic mix leads to the lowest procurement costs for the aggregator. Furthermore, direct load control models facilitate the determination of key properties for load flexibility. The analysis suggests that load balancing potentials are mainly influenced by electricity consumption and shifting distance of a device. Scheduling restrictions have limited effect.
Hadzihalilovic-Numanovic Genetic Variation and Relatedness of Freshwater Pearl Mussel Margaritifera margaritifera L . Populations Genetic Variation and Relatedness of Freshwater Pearl Mussel

The two papers presented in this thesis focus on the population genetics of freshwater pearl mussel populations in Sweden, using the RAPD-PCR method. Specifically, I studied genetic variation within and between 5 populations in a single drainage area in south-western Sweden. This study was followed by an investigation of evolutionary relationships and genetic variation of 14 populations of freshwater pearl mussel from different drainage areas in southcentral Sweden. In both studies, I found that genetic variation was larger than reported from previous studies using other techniques, and that variation was larger between than within populations. I did not found any correlation between geographic and genetic distance, which indicates that mussel populations have adapted to local environmental conditions in a relatively short time. I also found that genetic distance between populations from a single drainage area was greater than found in other studies, despite small geographic distances. When comparing populations from multiple drainage areas, I found that populations were highly differentiated, indicating little gene flow between them. There was no significant positive relation between genetic variation and population size or age structure but there was a significant positive relation between mean age and population size, indicating that many populations have gone through bottlenecks recently.
High-throughput measurement of pKa values in a mixed-buffer linear pH gradient system.

A procedure is described for measuring pKa values in a short time, e.g., 4 min/assay. Samples, as 10 mM solutions, are prepared in DMSO in 96-well plates. A flowing pH gradient is produced by mixing two buffer solutions containing mixtures of weak acids and bases that do not absorb significantly in the UV above 250 nm. The sample solution is diluted with water and then injected directly into the flowing gradient, which then passes through a diode array spectrophotometer measuring in the UV wavelength range. The buffer has been formulated so that its acid-base titration curve is linear over a wide pH range, such that the pH of the gradient is a linear function of time. The solution pH in the measurement flow cell is therefore proportional to the time elapsed since the start of gradient generation. The sample's pKa values are calculated from the change in UV absorbance at multiple wavelengths as a function of pH. The pKa values of 71 drugs have been measured, and results compare well with values measured by pH-metric or traditional UV methods. Rules are suggested for the rapid inspection of data and the choice of method for the calculation of pKa from the data.
The ICOS Molecule Plays a Crucial Role in the Development of Mucosal Tolerance1

The ICOS molecule stimulates production of the immunoregulatory cytokine IL-10, suggesting an important role for ICOS in controlling IL-10-producing regulatory T cells and peripheral T cell tolerance. In this study we investigate whether ICOS is required for development of oral, nasal, and high dose i.v. tolerance. Oral administration of encephalitogenic myelin oligodendrocyte glycoprotein (MOG) 35–55 peptide to ICOS-deficient (ICOS−/−) mice did not inhibit experimental autoimmune encephalomyelitis (EAE), T cell proliferation, or IFN-γ production, in striking contrast to wild-type mice. Similarly, intranasal administration of MOG35–55 before EAE induction suppressed EAE and T cell responses in wild-type, but not in ICOS−/−, mice. In contrast, ICOS−/− mice were as susceptible as wild-type mice to high dose tolerance. These results indicate that ICOS plays an essential and specific role in mucosal tolerance and that distinct costimulatory pathways differentially regulate different forms of peripheral tolerance. Surprisingly, CD4+ cells from MOG-fed wild-type and ICOS−/− mice could transfer suppression to wild-type recipients, indicating that functional regulatory CD4+ cells can develop in the absence of ICOS. However, CD4+ T cells from MOG-fed wild-type mice could not transfer suppression to ICOS−/− recipients, suggesting that ICOS may have a key role in controlling the effector functions of regulatory T cells. These results suggest that stimulating ICOS may provide an effective therapeutic approach for promoting mucosal tolerance.
BC-PROM: validation of a patient-reported outcomes measure for patients with breast cancer

Abstract Key issues of treatment for patients with breast cancer such as patient satisfaction with treatments, compliance, and some side effects are essential for evaluating quality of life by patient-reported outcomes in clinical trials. The study aimed to develop and evaluate a specific patient-reported measure which included physical, psychological, social, and therapeutic domain for assessing the survival of patients with breast cancer. The pool of items was drafted after a theoretical revision and cognitive interviews with women with breast cancer. The draft scale was formed after the adjustment of the items and dimensions, and the selected items were submitted to expert's judgments. Five statistical methods were used to select these items by 2 validation samples. The final scale was administered to a sample of 417 patients from 8 hospitals and 135 controls for reliability, validity, and responsive analyses. The final BC-PROM consisted of 52 items, 13 subdomains, and 4 domains, being developed after preexamination and formal examination. Cronbach alpha coefficient was 0.902 and 0.712 for the full scale and therapeutic domain. The structural validity results showed that the multidimensional measurement of the scale fulfilled expectations. Differences in the BC-PROM mean scores were significant between cancer patients and healthy participants in 13 subdomains (P < .05), indicating good responsiveness. Among the sample survey of patients, the scale copy acceptance rate was 98.2%, completion rate 94.6%, and average filling time 10 minutes. The new and reliable BC-PROM was developed in patients with breast cancer and applied to clinical treatment evaluation and clinical trials for such patients.
Novel BICM HARQ Algorithm Based on Adaptive Modulations

A novel type-II hybrid automatic repeat request (HARQ) algorithm using adaptive modulations and bit-interleaved coded modulation (BICM) is presented. The algorithm uses different optimized puncturing patterns for different transmissions of the same data packet. The proposed approach exploits mapping diversity through BICM with iterative decoding. The modulation order is changed in each transmission to keep the number of symbols transmitted constant. We present new bit error rate and frame error rate analytical results for the proposed technique showing good agreement with simulation results. We compare the throughput performance of our proposed HARQ technique with a reference HARQ technique that uses different mapping arrangements but keeps the modulation order fixed. By using optimized puncturing patterns and adaptive modulations, our method provides significantly better throughput performance over the reference HARQ method in the whole signalto-noise ratio (SNR) range, and achieves a gain of 12 dB in the medium SNR region.
Motion Path Planning for Mobile Robots

Potential field methods are rapidly gaining popularity in obstacle avoidance applications for mobile robots. The general principles of potential field path planning are presented first. The electrostatic potential field (EPF) path planner is then combined with a twolayered fuzzy logic inference engine and implemented for mobile robot navigation in a 2-D dynamic environment. The first layer of the fuzzy logic inference engine performs sensor fusion from sensor readings into a fuzzy variable, collision, providing information about possible collisions in four directions, front, back, left, and right. The second layer guarantees collision avoidance with dynamic obstacles while following the trajectory generated by the electrostatic potential field.
Haemoglobin F (HbF) levels in sickle‐cell anaemia patients homozygous for the Bantu haplotype

To the Editor: Sickle-cell anaemia (SCA) presents diverse clinical manifestations amongst affected persons (1). Environmental, cellular and genetic factors have been suggested as possible determinants of this variability (1). Homozygous sickle-cell anaemia (SS patients) in India (2) and in the Eastern province of Saudi Arabia (3) is, in general, clinically milder than sickle-cell anaemia of African origin (4). It is thought that very high foetal haemoglobin (HbF) levels may contribute to the mildness of the disease (5). The role of foetal haemoglobin (HbF) in ameliorating the severity of SCA has been widely investigated. Whereas several studies (6,7) suggest a beneficial role for HbF, some are less inclined to agree (8). In this paper we report the study of HbF in Congolese SS patients. 116 consecutive unrelated SS patients (61 males and 55 females) homozygous for the Bantu haplotype attending the “service de Pediatrie grands enfants” of the “Centre Hospitalier Universitaire de Brazzaville” (CHUB), were enrolled. The age was between 1 and 32 years with a mean age of 9.40k5. 3 years. None of the patients was hospitalized or transfused during the blood collection period or in the previous 3 months. Haematological data were obtained using a Coulter MD8 (Coultronics, Margency-France). Thin-layer isoelectric focusing was used to analyse haemoglobin. Abnormal haemoglobin (HbS) results were confirmed using citrate agar electrophoresis and the Itano test. Quantitation of HbA2, HbF and HbS
The Role of Factor V Leiden in Adult Patients With Venous Thromboembolism: A Meta-Analysis of Published Studies from Turkey

Factor V Leiden (FVL) is the most common inherited risk factor for venous thromboembolism (VTE). The frequency of FVL in patients with VTE has been reported from different parts of Turkey. A meta-analysis was performed to estimate the risk of VTE associated with FVL in Turkish population. Published studies were retrieved from Pubmed and Science Citation Index/Expanded. We selected studies comparing the prevalence of FVL in patients with VTE with controls. The analysis was performed by the software comprehensive meta-analysis. The analysis consisted of 10 studies including 1202 patients with VTE and 1283 controls. The pooled frequency of FVL was significantly higher in patients with VTE (22.8%) than controls (7.6%). The pooled odds ratio (OR) was 3.4 (95% confidence interval [CI], 2.6-4.5). The study showed homogeneity (Q value, 9.955). No publication bias was observed in any comparison model. Our meta-analysis showed an association of FVL with VTE in Turkey.
KUI: Self-organizing Multi-lingual WordNet Construction Tool

Abstract. This paper describes a multi-lingual WordNet construction tool, called KUI (Knowledge Unifying Initiator), which is a knowledge user interface for online collaborative knowledge construction. KUI facilitates online community in developing and discussing multi-lingual WordNet. KUI is a sort of social networking system that unifies the various discussions following the process of thinking model, i.e. initiating the topic of interest, collecting the opinions to the selected topics, localizing the opinions through the translation or customization and finally posting for public hearing to conceptualize the knowledge. The process of thinking is done under the selectional preference simulated by voting mechanism in the case that there are many alternatives. By measuring the history of participation of each member, KUI adaptively manages the reliability of each member’s opinion and vote according to the estimated ExpertScore . As a result, the multi-lingual WordNet can be created online and produce a reliable result.
patients : a systematic review versus palliative care in terminally ill Treatment targeted at underlying disease

GENERAL COMMENTS This is an important review. It is only a pity that so few source studies were available. Methodologically the work keeps strictly to the Cochrane Collaboration guidelines and techniques, with the trustworthiness that follows. There are no obvious missed opportunities for supplementary analyses. My remarks will therefore mostly deal with minor details. References px/y are to Authors‟ pg no x, pdf line no y. PC = palliative care, TTD = active treatment of disease.
The Expansion of Activity-Based Costing/Management in the Czech Republic

This paper aims to investigate the expansion of an advanced management tool - Activity-based costing/management (ABC/M) among Czech companies and to map the level of its utilization. The empirical survey was carried out among 548 Czech medium-sized and large companies from various economic sectors. The expansion of ABC/M has grown to 22% in 2013 which is comparable to neighbouring countries, but companies still use a relatively simple ABC/M model. They use only a limited extent of ABC/M and do not exploit all its possibilities.
Three Essays on Corporate Debt Financing

Three essays on corporate debt financing Mahsa Somayeh Kaviani, Ph.D. Concordia University, 2016 In the first of three essays, we study the relationship between corporate debt structures and the strength of creditor rights. Firms use a more concentrated debt-type structure as a reaction mechanism to stronger creditor rights. We show that managers form more concentrated debt structures in response to stronger creditor rights in order to first, reduce bankruptcy costs and second, to provide more monitoring incentives for creditors. Across 46 countries, we document that firms have more concentrated debt-type structures in countries with stronger creditor rights. Based on an examination of the cross-sectional heterogeneity of firms to different creditor rights regimes, we confirm our two proposed mechanisms. This study extends the literature of debt structure to an international setting and is the first to document the effect of cross-country legal and institutional determinants on the choice of debt structures. In the second essay, we investigate how uncertainty about economic policies influence corporate credit spreads. We find a large and positive association between corporate credit spreads and a news-based index of policy uncertainty. We document that a one standard deviation increase in policy uncertainty results in 25 basis points increase in the credit spreads of corporate bonds controlling for bond, firm and macro-economic variables. We find that the influence of policy uncertainty on corporate credit spreads differs across firms and is more pronounced for firms with higher investment irreversibility and dependence on government spending. We also document a larger impact of policy uncertainty during economic recessions. Our results show that not only firm-level default probabilities, but also bond-CDS bases increase in response to elevated policy uncertainty. The third and final essay empirically measures the financial and economic costs (benefits) to firm value associated with deteriorations or improvements in the firm’s credit quality. We document that firms incur economically large and statistically significant costs to their values following credit-rating deteriorations. Consistent with an asymmetric effect, we find significant but smaller firm-value benefits associated with credit-rating upgrades. The financial costs to a firm’s market value associated with each notch downgrade to the investment and speculative grade categories are 7.1% and 14.8%, respectively, and these costs are generally larger than the economic costs to the firm value from credit rating downgrades. Using a continuous KMV distance to default model, we conclude that deteriorations (improvements) in a model-generated credit rating quality can also adversely (positively) affect firm value. Our findings have implications for corporate financing and leverage decisions, and for the unresolved underleverage puzzle (Graham, 2001).