Miracle-dz/UniFAR-FTUs huggingface dataset:
Increased levels of copper efflux transporter ATP7B are associated with poor outcome in colorectal cancer patients receiving oxaliplatin‐based chemotherapy

Recently, the copper efflux transporters ATP7B and ATP7A have been implicated in the transport of and resistance to platinum drugs in breast and ovarian cancers. Because of the extensive use of oxaliplatin in colorectal cancer (CRC), we examined the expression of both transporters in tumors from CRC patients treated with oxaliplatin/5FU and sought to determine whether their expression can predict clinical outcome in these patients. ATP7B and ATP7A levels were determined by quantitative real‐time PCR in 50 primary tumors of previously untreated patients with advanced colorectal adenocarcinoma who were subsequently treated with oxaliplatin/5FU. Additionally, ATP7B protein expression was assessed by immunohistochemical staining using a tissue microarray. Patients with the lowest mRNA expression levels of ATP7B had a significantly longer time to progression (TTP) (p = 0.0009) than patients with the highest levels (12.14 months vs. 6.43 months) who also had an increased risk of progression (HR = 3.56; 95% CI, 1.6–7.9; p = 0.002). Furthermore, patients with low levels of both protein and mRNA of ATP7B derived the maximum benefit from oxaliplatin/5FU with the longest TTP as compared with patients with high levels of ATP7B protein and mRNA (14.64 months vs. 4.63 months, respectively, p = 0.01) and showed a nonsignificant trend toward a lower response rate (37.5% and 75%, respectively). In conclusion, ATP7B mRNA and protein expression in colorectal tumors is associated with clinical outcome to oxaliplatin/5FU. Prospective studies are required to evaluate the role of this marker in tailoring chemotherapy. © 2009 UICC
Segregation analysis of cutaneous melanoma in Queensland

To investigate whether the familial clustering of cutaneous melanoma is consistent with Mendelian inheritance of a major autosomal gene, maximum likelihood segregation analyses were performed in a population‐based sample of 1,912 families ascertained through a proband with melanoma diagnosed in Queensland between 1982 and 1990. Analyses were performed with the S.A. G.E. statistical package, using the REGTL program for a binary trait with a variable age of onset. We sought medical confirmation for all family members reported to have had melanoma, and only medically verified cases among relatives were included in the analyses. The hypothesis of codominant Mendelian inheritance gave a significantly better fit to the data than either dominant or recessive Mendelian inheritance, or environmental transmission. Overall, both Mendelian inheritance of a single major gene, and purely environmental transmission were rejected (P < 0.001). In both the single major gene and environmental models, there was strong evidence of familial dependence in melanoma occurrence (P < 0.001). These results are consistent with reported genetic heterogeneity in melanoma inheritance and suggest that other familial factors, such as pigmentation, skin type, and sun exposure habits, may play an important role in the familial clustering of melanoma. Genet. Epidemiol. 15:391–401,1998. © 1998 Wiley‐Liss, Inc.
Recognition Time Measured by Verbal Reaction to Figures and Words

Five Ss were required to recognise as quickly as possible four words (square, triangle, hexagon, octagon) and the four corresponding figures. Ss were acquainted with the eight stimuli, for the present experiment was preceded by one in which tachistoscopic perceptual thresholds were obtained. The stimuli were presented in random order for an unlimited time and the whole list was shown five times. Verbal reaction time was recorded by means of a vocal key. S's median for each stimulus was calculated, and then the mean of medians for words and figures. Results are given in . O1 sec.
Halothane‐Relaxant Anaesthesia in Elderly Patients

Twenty‐three elderly patients, scheduled for elective cholecystectomy, were studied during halothane‐relaxant anaesthesia. Anaesthesia was induced with thiopentone and maintained with halothane in 12 patients, six of whom had also received premedication. Eleven patients were anaesthetized with halothane, without thiopentone induction and with no premedication. Measurements of central haemodynamics were performed awake and during anaesthesia at end‐tidal halothane concentrations of 0.5 and 1.0%; at the lower concentration, measurements were also made after addition of nitrous oxide. Premedication and thiopentone had no influence on the subsequent halothane anaesthesia. Halothane caused reductions of cardiac index, mean arterial blood pressure and oxygen uptake. However, neither right atrial nor pulmonary capillary venous pressure increased and the arterio‐venous oxygen content difference decreased. These findings differ from those made by others in younger subjects and are probably attributable to a dose‐dependent reduction in systemic vascular resistance. The addition of nitrous oxide had only minor effects on central circulation. The results suggest that the age of the patients influences their reaction to halothane anaesthesia.
A Novel Approach to a Robust a Priori SNR Estimator in Speech Enhancement

SUMMARY This paper presents a novel approach to single channel speech enhancement in noisy environments. Widely adopted noise reduction techniques based on the spectral subtraction are generally expressed as a spectral gain depending on the signal-to-noise ratio (SNR) [1]–[4]. As the estimation method of the SNR, the well-known decision-directed (DD) estimator of Ephraim and Malah efficiently is known to reduces musical noise in noise frames, but the ap rioriSNR, which is a crucial parameter of the spectral gain, follows the a posteriori SNR with a delay of one frame in speech frames [5]. Therefore, the noise suppression gain using the delayed ap rioriSNR, which is estimated by the DD algorithm matches the previous frame rather than the current one, so after noise suppression, this degrades the performance of a noise reduction during abrupt transient parts. To overcome this artifact, we propose a computationally simple but effective speech enhancement technique based on the sigmoid type function to adaptively determine the weighting factor of the DD algorithm. Actually, the proposed approach avoids the delay problem of the ap rioriSNR while maintaining the advantage of the DD algorithm. The performance of the proposed enhancement algorithm is evaluated by the objective and subjective test under various environments and yields better results compared with the conventional DD scheme based approach.
A New Method to Measure the Performance of Leveraged Exchange‐Traded Funds

We examine the effects of daily return compounding, financing costs, and management factors on the performance of leveraged exchange-traded funds (LETFs) over various holding periods. We propose a new method to measure LETFs’ tracking errors that allows us to disentangle these effects. Our results show that the compounding effect generally has more influence on tracking errors than other factors, especially for long holding periods and in a “sideways” market. The explicit costs (i.e., the expense ratios) and other factors (e.g., financing costs) can materially affect the performance of LETFs, especially for those with high leverage ratios and bear funds.
KU: Word Sense Disambiguation by Substitution

Data sparsity is one of the main factors that make word sense disambiguation (WSD) difficult. To overcome this problem we need to find effective ways to use resources other than sense labeled data. In this paper I describe a WSD system that uses a statistical language model based on a large unannotated corpus. The model is used to evaluate the likelihood of various substitutes for a word in a given context. These likelihoods are then used to determine the best sense for the word in novel contexts. The resulting system participated in three tasks in the SemEval 2007 workshop. The WSD of prepositions task proved to be challenging for the system, possibly illustrating some of its limitations: e.g. not all words have good substitutes. The system achieved promising results for the English lexical sample and English lexical substitution tasks.
Selective Pressures of HLA Genotypes and Antiviral Therapy on Human Immunodeficiency Virus Type 1 Sequence Mutation at a Population Level

ABSTRACT The objective of this study was a comprehensive analysis of the immune-driven evolution of viruses of human immunodeficiency virus type 1 (HIV-1) clade B in a large patient cohort treated at a single hospital in Germany and its implications for antiretroviral therapy. We examined the association of the HLA-A, HLA-B, and HLA-DRB1 alleles with the emergence of mutations in the complete protease gene and the first 330 codons of the reverse transcriptase (RT) gene of HIV-1, studying their distribution and persistence and their impact on antiviral drug therapy. The clinical data for 179 HIV-infected patients, the results of HLA genotyping, and virus sequences were analyzed using a variety of statistical approaches. We describe new HLA-associated mutations in both viral protease and RT, several of which are associated with HLA-DRB1. The mutations reported are remarkably persistent within our cohort, developing more slowly in a minority of patients. Interestingly, several HLA-associated mutations occur at the same positions as drug resistance mutations in patient viruses, where the viral sequence was acquired before exposure to these drugs. The influence of HLA on thymidine analogue mutation pathways was not observed. We were able to confirm immune-driven selection pressure by major histocompatibility complex (MHC) class I and II alleles through the identification of HLA-associated mutations. HLA-B alleles were involved in more associations (68%) than either HLA-A (23%) or HLA-DRB1 (9%). As several of the HLA-associated mutations lie at positions associated with drug resistance, our results indicate possible negative effects of HLA genotypes on the development of HIV-1 drug resistance.
Role of the AP2 β-Appendage Hub in Recruiting Partners for Clathrin-Coated Vesicle Assembly

Adaptor protein complex 2 α and β-appendage domains act as hubs for the assembly of accessory protein networks involved in clathrin-coated vesicle formation. We identify a large repertoire of β-appendage interactors by mass spectrometry. These interact with two distinct ligand interaction sites on the β-appendage (the “top” and “side” sites) that bind motifs distinct from those previously identified on the α-appendage. We solved the structure of the β-appendage with a peptide from the accessory protein Eps15 bound to the side site and with a peptide from the accessory cargo adaptor β-arrestin bound to the top site. We show that accessory proteins can bind simultaneously to multiple appendages, allowing these to cooperate in enhancing ligand avidities that appear to be irreversible in vitro. We now propose that clathrin, which interacts with the β-appendage, achieves ligand displacement in vivo by self-polymerisation as the coated pit matures. This changes the interaction environment from liquid-phase, affinity-driven interactions, to interactions driven by solid-phase stability (“matricity”). Accessory proteins that interact solely with the appendages are thereby displaced to areas of the coated pit where clathrin has not yet polymerised. However, proteins such as β-arrestin (non-visual arrestin) and autosomal recessive hypercholesterolemia protein, which have direct clathrin interactions, will remain in the coated pits with their interacting receptors.
Our Children Can't Do That!: The Under-Estimation of Ability: Implications for Software Design

Abstract This paper discusses the development of a suite of educational software intended for use by children with severe learning difficulties. The software deals with conceptual, communicative and problem solving activities, commonly found to be problematic for such children. The use of such software is described, and it is argued that appropriately structured computer‐mediated interaction can result in the development and expression of cognitive skills previously unrevealed in conventional classroom settings. Specific influences on this process come from the interface of cognitive and developmental psychology and the discipline of instructional design.
Human action recognition based on Self Organizing Map

This paper proposes a novel neural network approach for human action recognition based on Self Organizing Map (SOM). The SOM acts as a tool to cluster feature data and to reduce data dimensionality. The key poses in action sequences are extracted by the trained SOM. After the mapping of SOM, a human action sequence is represented as a trajectory of map units. For action recognition, a longest common subsequence algorithm is utilized to match action trajectories on the map robustly. The experiments are carried out on a well known human action dataset, viz.: the Weizmann dataset. We obtain promising results which show the potential of this SOM based action recognition method.
A cost utility analysis of simeprevir used with peginterferon + ribavirin in the management of genotype 1 hepatitis C virus infection, from the perspective of the UK National Health Service

Abstract Introduction: Triple therapy using a protease inhibitor (PI) with peginterferon and ribavirin (PR) is increasingly used in patients with chronic hepatitis C virus (HCV) infection. The most recently introduced PI, simeprevir (SMV), offers high levels of viral eradication combined with a reduced overall duration of therapy. The objective of this study was to compare the cost-effectiveness of SMV + PR vs PR alone or in combination with telaprevir (TVR) or boceprevir (BOC) in patients infected with genotype 1 HCV Method: A cost-utility model was constructed, incorporating two phases, capturing the efficacy of therapy in an initial treatment phase, followed by a long-term post-treatment Markov phase, capturing lifetime outcomes according to whether a sustained viral response (SVR) had been achieved on treatment. Dosage regimens were based on the EMA approved label for each treatment. SVR estimates and adverse event rates were derived from a mixed treatment comparison. Baseline characteristics were drawn from an analysis of a UK HCV data-set and clinician opinion. Health state transition probabilities, utilities, and health state costs were drawn from previously published economic analyses. The model considered direct health costs only, and the perspective was that of the UK National Health Service. Results: The model yielded an ICER for SMV + PR vs PR alone of £9725/QALY for treatment-naïve and £7819/QALY for treatment-experienced. Benefit was driven by increased likelihood of achieving SVR, with consequent long-term utility gains. SMV + PR dominated TVR + PR and BOC + PR in both patient groups. This principally reflected the QALY benefit of an increased likelihood of SVR with SMV, combined with lower overall drug costs, due to reduced mean treatment duration. Conclusion: Compared to other currently licensed treatment options, SMV + PR represents a cost effective treatment option for patients with chronic genotype 1 HCV infection.
Security Analysis of Shim's Authenticated Key Agreement Protocols from Pairings

Recently, Shim proposed a tripartite authenticated key agreement protocol from Weil pairing to overcome the security flaw in Joux’s protocol. Later, Shim also proposed an ID-based authenticated key agreement protocol which is an improvement of Smart’s protocol in order to provide the forward secrecy. In this paper, we show that these two protocols are insecure against the key-compromise impersonation attack and the manin-the-middle attack respectively.
Advanced squamous cell carcinoma of the oropharynx: Efficacy of positron emission tomography and computed tomography for determining primary tumor response during induction chemotherapy

To evaluate the efficacy of fluorine‐18‐fluorodeoxyglucose emission tomography (FDG‐PET) and CT versus endoscopy with biopsy under general anesthesia for estimating tumor volume reduction among patients treated with induction chemotherapy for advanced squamous cell carcinoma (SCC) of the oropharynx.
The Elementary Operations of Human Vision Are Not Reducible to Template-Matching

It is generally acknowledged that biological vision presents nonlinear characteristics, yet linear filtering accounts of visual processing are ubiquitous. The template-matching operation implemented by the linear-nonlinear cascade (linear filter followed by static nonlinearity) is the most widely adopted computational tool in systems neuroscience. This simple model achieves remarkable explanatory power while retaining analytical tractability, potentially extending its reach to a wide range of systems and levels in sensory processing. The extent of its applicability to human behaviour, however, remains unclear. Because sensory stimuli possess multiple attributes (e.g. position, orientation, size), the issue of applicability may be asked by considering each attribute one at a time in relation to a family of linear-nonlinear models, or by considering all attributes collectively in relation to a specified implementation of the linear-nonlinear cascade. We demonstrate that human visual processing can operate under conditions that are indistinguishable from linear-nonlinear transduction with respect to substantially different stimulus attributes of a uniquely specified target signal with associated behavioural task. However, no specific implementation of a linear-nonlinear cascade is able to account for the entire collection of results across attributes; a satisfactory account at this level requires the introduction of a small gain-control circuit, resulting in a model that no longer belongs to the linear-nonlinear family. Our results inform and constrain efforts at obtaining and interpreting comprehensive characterizations of the human sensory process by demonstrating its inescapably nonlinear nature, even under conditions that have been painstakingly fine-tuned to facilitate template-matching behaviour and to produce results that, at some level of inspection, do conform to linear filtering predictions. They also suggest that compliance with linear transduction may be the targeted outcome of carefully crafted nonlinear circuits, rather than default behaviour exhibited by basic components.
Design Strategies for Bivalent Ligands Targeting GPCRs

Specifically designed bivalent ligands targeting G protein‐coupled receptor (GPCR) dimeric structures have become increasingly popular in recent literature. The advantages of the bivalent approach are numerous, including enhanced potency and receptor subtype specificity. However, the use of bivalent ligands as potential pharmacotherapeutics is limited by problematic molecular properties, such as high molecular weight and lipophilicity. This Minireview focuses on the design of bivalent ligands recently described in the literature; discussing the choice of lead pharmacophore, the position and nature of the attachment point for linking the two pharmacophore units, and the length and composition of the spacer group. Furthermore, this Minireview distils the molecular descriptors of the bivalent ligands that exhibit in vivo activity, as well as highlights their ability to access the central nervous system.
Geriatric assessment in multiple myeloma patients: validation of the International Myeloma Working Group (IMWG) score and comparison with other common comorbidity scores

This first validation of the International Myeloma Working Group geriatric assessment in 125 newly diagnosed multiple myeloma patients was performed using the International Myeloma Working Group score based on age, the Charlson Comorbidity Index and cognitive and physical conditions (Activities of Daily Living / Instrumental Activities of Daily Living) to classify patients as fit, intermediate-fit or frail. We verified the International Myeloma Working Group score’s impact on outcome, and whether additional tools complement it. Since our prior analyses determined renal, lung and Karnofsky performance impairment as multivariate risks, and the inclusion of frailty, age and cytogenetics complements this, we included the revised myeloma comorbidity index, the Charlson Comorbidity Index, the Hematopoietic Cell Transplantation-Comorbidity Index and the Kaplan-Feinstein Index in this assessment. Multivariate analysis confirmed cytogenetics, Activities of Daily Living, Instrumental Activities of Daily Living and the Charlson Comorbidity Index as risks: 3-year overall survival for fit, intermediate-fit and frail patients was 91%, 77% and 47%, respectively. Using the Charlson Comorbidity Index, the Hematopoietic Cell Transplantation-Comorbidity Index, the Kaplan-Feinstein Index and the revised Myeloma Comorbidity Index allowed us to define fit and frail patients with distinct progression-free and overall survival rates, with the most pronounced differences evidenced via the International Myeloma Working Group score, the Charlson Comorbidity Index and the revised Myeloma Comorbidity Index. Since the Charlson Comorbidity Index is included in the International Myeloma Working Group score, we propose the latter and the revised Myeloma Comorbidity Index for future frailty measurements. Both are useful instruments for identifying myeloma patients with a geriatric risk profile and have a strong prognostic value for functional decline and overall survival. The study was registered as: (clinicaltrials.gov Identifier: 00003686).
Applying Universal Schemas for Domain Specific Ontology Expansion

Manually created large scale ontologies are useful for organizing, searching, and repur-posing content ranging from scientiﬁc papers and medical guidelines to images. However, maintenance of such ontologies is expensive. In this paper, we investigate the use of universal schemas (Riedel et al., 2013) as a mechanism for ontology maintenance. We apply this approach on top of two unique data sources: 14 million full-text scientiﬁc articles and chapters, plus a 1 million concept hand-curated medical ontology. We show that using a straightforward matrix factorization algo-rithm one can achieve 0.7 F1 measure on a link prediction task in this environment. Link prediction results can be used to suggest new relation types and relation type synonyms coming from the literature as well as predict speciﬁc new relation instances in the ontology.
Behind the Seen

Face perception and emotion recognition have been extensively studied in the past decade; however, the relation between them is still poorly understood. A traditional view is that successful emotional categorization requires categorization of the stimulus as a ‘face’, at least at the basic level. Here we tested whether without explicit categorization of a stimulus as a face emotional information could still be recognized accurately. For this purpose we created a stimulus set in which facial stimuli expressing a range of happy‐to‐fear emotions were morphed into another object category (shoe). Interestingly, participants categorized emotions with great accuracy in stimuli that contained so little face information that they were explicitly categorized as shoes. Hence, our results show that accurate emotion categorization can take place in stimuli that contain surprisingly little face information. This finding raises interesting questions about the extent to which processes leading to emotion recognition and categorical face perception might be separable.