Miracle-dz/UniFAR-FTUs huggingface dataset:
Glycation of the complement regulatory protein CD59 is a novel biomarker for glucose handling in humans.

CONTEXT Human CD59, an inhibitor of the membrane attack complex of complement, is inactivated by glycation. Glycation inactivation of CD59 enhances complement-mediated injury in target organs of diabetes complications. OBJECTIVE We hypothesized that circulating soluble glycated CD59 (GCD59) represents a novel biomarker of blood glucose handling and aimed to conduct human study protocols to test this hypothesis. DESIGN, SETTING, PARTICIPANTS, AND OUTCOME MEASURES: Using a newly developed ELISA, we measured circulating soluble GCD59 in samples from 3 separate human studies evaluating acute and chronic glucose handling and glucose responses to insulin therapy. Study 1 (normal vs diabetic subjects) evaluated the cross-sectional association between GCD59 and glycated hemoglobin (HbA1c) in 400 subjects with and without type 2 diabetes. Study 2 (oral glucose tolerance test [OGTT] in nondiabetics) evaluated whether fasting GCD59 independently predicted the 2-hour glucose response to an OGTT in 109 subjects without a diagnosis of diabetes. Study 3 (intensified insulin treatment) evaluated the effect of intensification of glycemic control with insulin on GCD59 in 21 poorly controlled individuals with diabetes. RESULTS In study 1 (normal vs diabetic subjects), GCD59 was independently and positively associated with HbA1c in individuals with and without diabetes (β = 1.1, P < .0001 and β = 1.1 P < .001, respectively). In study 2 (OGTT in nondiabetics), a single GCD59 measurement independently predicted the results of the 2-hour OGTT (β = 19.8, P < .05) after multivariate modeling. In study 3 (intensified insulin treatment), intensification of glucose control with insulin resulted in a concomitant and parallel reduction of average weekly glucose and GCD59 within 2 weeks. CONCLUSIONS We observed robust relationships between a single measurement of blood levels of GCD59 and both acute (2-hour OGTT) and chronic (HbA1c) measures of glucose handling. Lowering of GCD59 levels closely reflected lowering of average weekly glucose within 2 weeks. The role of GCD59 in the diagnosis, management, and vascular risk stratification in diabetes warrants further investigation.
Pattern Search Algorithms for Bound Constrained Minimization

We present a convergence theory for pattern search methods for solving bound constrained nonlinear programs. The analysis relies on the abstract structure of pattern search methods and an understanding of how the pattern interacts with the bound constraints. This analysis makes it possible to develop pattern search methods for bound constrained problems while only slightly restricting the flexibility present in pattern search methods for unconstrained problems. We prove global convergence despite the fact that pattern search methods do not have explicit information concerning the gradient and its projection onto the feasible region and consequently are unable to enforce explicitly a notion of sufficient feasible decrease.
Effects of combined alendronate and alfacalcidol on prevention of fractures in osteoporosis patients: a network meta-analysis.

BACKGROUND Published literatures report controversial results about the effect of combined treatment with alendronate and alfacalcidol for the prevention of fractures in osteoporosis patients. METHODS Seven common databases were searched for related randomized controlled trials published up to April, 2015. Bayesian random effects network meta-analysis was used to assess the pairwise odds ratios (OR), 95% credible intervals (CI). RESULTS Thirteen randomized controlled trials were identified (3710 patients). The network meta-analysis results indicated that combining treatment with alendronate and alfacalcidol was significantly better to prevent bone fractures in osteoporosis patients than alendronate (OR=0.53, 95% CI: 0.19-0.95) and alfacalcidol (OR=0.25, 95% CI: 0.08-0.49). In addition, there was no significant difference for adverse events among the three therapeutic regimen. CONCLUSIONS Combined treatment with alendronate and alfacalcidol was more active than the monotherapies in preventing bone fractures in osteoporosis patients. Large-scale randomized, controlled trials are recommended to confirm the result.
Metamorphic Testing : Using the Properties of Sut

when testing a program, correctly executed test cases are seldom explored further, even though they may carry useful information. Metamorphic testing proposes to generate follow-up test cases to check important properties of the target function. It does not need a human oracle for output prediction and comparison. An “oracle” in software testing is a procedure by which testers can decide whether the output of the program under testing is correct. In some situations, however, the oracle is not available or too difficult to apply. This is known as the “oracle problem”. The manual prediction and verification of program output greatly decreases the efficiency and increases the cost of testing. A metamorphic testing method has been proposed to test programs without the involvement of an oracle. It employs properties of the target function, known as metamorphic relations, to generate follow-up test cases and verify the outputs automatically.
Barriers to mobile commerce adoption: an analysis framework for a country-level perspective

This research examines and categorises the country-level adoption barriers of mobile commerce services, and tests those barriers in a case study of one country. The outcomes of the research presented in this paper are a broad framework of mobile commerce barriers that might be applicable when undertaking a country-level analysis, and a case study which tests the value of this framework in helping to uncover the specific barriers of mobile commerce adoption in one example country, New Zealand.
A Domain Specific Language for Securing Distributed Systems

Distributed applications are becoming increasingly common. However, incorporating security in them remains a major challenge. There are currently few choices to express and enforce security in distributed systems. We can either use a special-purpose language which may be too limited to express security requirements, or use a general purpose language that provides the ability to make complicated security policy but makes us reimplement infrastructure code for authorization, interdiction, obligation and so on with each new security policy. In this paper, we introduce a domain-specific language approach that takes the middle road, giving a way to reuse security infrastructure for new policies while also allowing the expression of complicated security policy easily. We present our DSL approach and and apply it to a real-world scenario: specification and implementation of security policy.
Privacy Design Patterns and Anti-Patterns Patterns Misapplied and Unintended Consequences

One critique of Privacy-by-Design has focused on its lack of concrete guidance for implementation. We have proposed privacy design patterns (drawing from architectural design patterns and object-oriented programming design patterns) as documentation that can be more directly applicable and have established a site to coordinate collaborative development of such patterns. We argue that patterns — which deﬁne a problem and a solution within a certain context — can also help us understand and classify many anti -patterns as patterns misapplied. Rather than providing examples of poor or perverse user interface, we examine several design anti-pattern examples, describing: applying a pattern to a diﬀerent problem; for a diﬀerent audience; and, with unintended consequences, advantageous and not. With those models, we provide possible directions for how the community should document patterns and anti-patterns to improve future designs.
Privacy-preserving performance measurements

Internet performance is an issue of great interest, but it is not trivial to measure. A number of commercial companies try to measure this, as does RIPE, and many individual Internet Service Providers. However, all are hampered in their efforts by a fear of sharing such sensitive information. Customers make decision about "which provider" based on such measurements, and so service providers certainly do not want such data to be public (except in the case of the top provider), but at the same time, it is in everyones' interest to have good metrics in order to reduce the risk of large network problems, and to test the effect of proposed network improvements.This paper shows that it is possible to have your cake, and eat it too. Providers (and other interested parties) can make such measurements, and compute Internet-wide metrics securely in the knowledge that their private data is never shared, and so cannot be abused.
Emotion Recognition with Deep-Belief Networks

For our CS229 project, we studied the problem of reliable computerized emotion recognition in images of human faces. First, we performed a preliminary exploration using SVM classifiers, and then developed an approach based on Deep Belief Nets. Deep Belief Nets, or DBNs, are probabilistic generative models composed of multiple layers of stochastic latent variables, where each “building block” layer is a Restricted Boltzmann Machine (RBM). DBNs have a greedy layer-wise unsupervised learning algorithm as well as a discriminative fine-tuning procedure for optimizing performance on classification tasks. [1]. We trained our classifier on three databases: the Cohn-Kanade Extended Database (CK+) [2], the Japanese Female Facial Expression Database (JAFFE) [3], and the Yale Face Database (YALE) [4]. We tested several different database configurations, image pre-processing settings, and DBN parameters, and obtained test errors as low as 20% on a limited subset of the emotion labels. Finally, we created a real-time system which takes images of a single subject using a computer webcam and classifies the emotion shown by the subject.
Strong Induction Principles in the Locally Nameless Representation of Binders ( Preliminary Notes )

When using the locally nameless representation technique for binders, proofs by induction over a de nition traditionally involve a weak and strong version of this de nition, and a proof that shows both versions derive the same judgements. In these notes we demonstrate with two examples that it is often su cient to de ne just the weak version and then use the infrastructure provided by the nominal Isabelle package to derive automatically and in a uniform way a strong induction principle for this weak version. The strong induction principle o ers a similar convenience in induction proofs as the traditional approach using weak and strong versions of the de nition. From our experience with the nominal Isabelle package, we conjecture that the presented technique can be used in many rule and structural induction proofs.
Trend Detection Based Regret Minimization for Bandit Problems

We study a variation of the classical multi-armed bandits problem. In this problem, the learner has to make a sequence of decisions, picking from a fixed set of choices. In each round, she receives as feedback only the loss incurred from the chosen action. Conventionally, this problem has been studied when losses of the actions are drawn from an unknown distribution or when they are adversarial. In this paper, we study this problem when the losses of the actions also satisfy certain structural properties, and especially, do show a trend structure. When this is true, we show that using trend detection, we can achieve regret of order Õ (N √TK) with respect to a switching strategy for the version of the problem where a single action is chosen in each round and Õ (Nm √TK) when m actions are chosen each round. This guarantee is a significant improvement over the conventional benchmark. Our approach can, as a framework, be applied in combination with various well-known bandit algorithms, like Exp3. For both versions of the problem, we give regret guarantees also for the anytime setting, i.e. when length of the choice-sequence is not known in advance. Finally, we pinpoint the advantages of our method by comparing it to some well-known other strategies.
Novel Immunotherapy for Malignant Melanoma with a Monoclonal Antibody That Blocks CEACAM1 Homophilic Interactions

CEACAM1 (biliary glycoprotein-1, CD66a) was reported as a strong clinical predictor of poor prognosis in melanoma. We have previously identified CEACAM1 as a tumor escape mechanism from cytotoxic lymphocytes. Here, we present substantial evidence in vitro and in vivo that blocking of CEACAM1 function with a novel monoclonal antibody (MRG1) is a promising strategy for cancer immunotherapy. MRG1, a murine IgG1 monoclonal antibody, was raised against human CEACAM1. It recognizes the CEACAM1-specific N-domain with high affinity (KD ∼ 2 nmol/L). Furthermore, MRG1 is a potent inhibitor of CEACAM1 homophilic binding and does not induce any agonistic effect. We show using cytotoxicity assays that MRG1 renders multiple melanoma cell lines more vulnerable to T cells in a dose-dependent manner, only following antigen-restricted recognition. Accordingly, MRG1 significantly enhances the antitumor effect of adoptively transferred, melanoma-reactive human lymphocytes using human melanoma xenograft models in severe combined immunodeficient/nonobese diabetic (SCID/NOD) mice. A significant antibody-dependent cell cytotoxicity response was excluded. It is shown that MRG1 reaches the tumor and is cleared within a week. Importantly, approximately 90% of melanoma specimens are CEACAM1+, implying that the majority of patients with melanoma could be amenable to MRG1-based therapy. Normal human tissue microarray displays limited binding to luminal epithelial cells on some secretory ducts, which was weaker than the broad normal cell binding of other anticancer antibodies in clinical use. Importantly, MRG1 does not directly affect CEACAM1+ cells. CEACAM1 blockade is different from other immunomodulatory approaches, as MRG1 targets inhibitory interactions between tumor cells and late effector lymphocytes, which is thus a more specific and compartmentalized immune stimulation with potentially superior safety profile. Mol Cancer Ther; 11(6); 1300–10. ©2012 AACR.
Detection of adeno‐associated virus DNA in human genital tissue and in material from spontaneous abortion

The human helper virus‐dependent parvovirus, adeno‐associated virus (AAV) has never been associated with disease in humans [Berns et al. (1987): Advances in Virus Research 32:243–306; Siegl et al. (1985): Intervirology 23:61–73]. However, in pregnant mice, infection with AAV induces early abortion [Botquin et al. (1993): Journal of Cancer Research and Clinical Oncology 119:24]. We investigated whether this common human virus may be found in human genital tissue or in curettage material from spontaneous abortion. Using the polymerase chain reaction (PCR) AAV type 2 DNA was amplified in histological sections of 19 of 30 biopsies of the uterine mucosa. In addition, AAV‐2 DNA was detected in abortion material during the first trimester of pregnancy (12/30 cases were positive) but not in material of abortion from the second or third trimester (9 cases). Whereas in tissues from the uterus AAV DNA was found only by PCR, large amounts of viral DNA were detectable by Southern blot analysis in abortion material. In situ hybridization revealed DNA of AAV to be present in the villous moiety (trophoblast) of the placenta but not in the embryo or decidua. In the same cells, AAV proteins (including the replication‐associated rep proteins) were detected by immunofluorescence analysis. These results suggest (1) that AAV infects the uterine mucosa (possibly persistently) and (2) that it can replicate in trophoblast cells. This might disturb placenta development and may play a role in early miscarriage. To assess an immunological correlate of AAV infection of cervix uteri lesions and miscarriage, an enzyme‐linked immunosorbent assay (ELISA) was developed for detecting serum IgG‐ and IgM‐class antibodies to AAV‐2. Compared to a control population, a significantly higher prevalence of IgM type antibodies to AAV‐2 was found in women with spontaneous abortion and cervical intraepithelial neoplasia. Since about 80% of the population are seropositive for AAV‐2 the high prevalence of IgM‐class antibodies might be associated with reactivation of latent AAV or to reinfections due to a decline of IgG‐mediated immunity. In view of the presence of AAV‐2 DNA and proteins in placenta tissue, serological tests might be useful to assess further the hypothesis of a possible role of AAV infection in spontaneous abortion.
Body fat distribution and risk factors for fibrosis in patients with alcoholic liver disease.

BACKGROUND Only a small proportion of alcoholic patients develop advanced liver disease, suggesting that factors other than alcohol intake may influence alcoholic liver disease (ALD) progression. We have shown that body mass index (BMI) is an independent risk factor for fibrosis in alcohol-induced liver disease and that adipose tissue inflammation is correlated with liver lesions in alcoholic patients. The aim of this study was to determine whether visceral adipose tissue, as assessed by abdominal height measurement, affected individual susceptibility to fibrosis in alcoholic patients. METHODS We included 127 consecutive alcoholic patients with abnormal liver test findings for whom liver histology data were available. Abdominal height was measured with a Holtain-Kahn abdominal caliper. We carried out univariate comparisons followed by multivariate regression analysis, to investigate the relationship between abdominal height and fibrosis score. RESULTS Abdominal height (p < 0.005), waist circumference (p < 0.05), fasting blood glucose concentration (p < 0.05), serum triglyceride concentration (p < 0.05), serum bilirubin (p < 0.005), and BMI (p = 0.05) were higher, whereas high-density lipoprotein (HDL) cholesterol level (p < 0.01) was lower in the 72 patients with significant (F2-F4) fibrosis than in the 55 patients with F0-F1 fibrosis. In multivariate regression analysis, only abdominal height (β = 7.2, p < 0.002) was independently and positively correlated with fibrosis score, which was also negatively correlated with HDL cholesterol level (β = -1.04, p < 0.05). CONCLUSIONS We provide the first demonstration that abdominal height may be a predictor of significant fibrosis in patients with ALD. Our findings support a role for visceral fat accumulation, independent of BMI and of metabolic syndrome criteria, in the onset of alcoholic liver damage.
Preclinical Development The HSP 90 Inhibitor , AT 13387 , Is Effective against Imatinib-Sensitive and-Resistant Gastrointestinal Stromal Tumor Models

The majority of gastrointestinal stromal tumors (GIST) are characterized by activating mutations of KIT, an HSP90 client protein. Further secondary resistance mutations within KIT limit clinical responses to tyrosine kinase inhibitors, such as imatinib. The dependence of KIT and its mutated forms on HSP90 suggests that HSP90 inhibitionmight be a valuable treatment option for GIST,whichwould be equally effective on imatinibsensitive and -resistant clones. We investigated the activity of AT13387, a potent HSP90 inhibitor currently being evaluated in clinical trials, in both in vitro and in vivoGISTmodels. AT13387 inhibited the proliferation of imatinib-sensitive (GIST882, GIST-T1) and -resistant (GIST430, GIST48) cell lines, including those resistant to the geldanamycin analogueHSP90 inhibitor, 17-AAG. TreatmentwithAT13387 resulted in depletion ofHSP90 client proteins, KIT and AKT, along with their phospho-forms in imatinib-sensitive and -resistant cell lines, irrespective of KIT mutation. KIT signaling was ablated, whereas HSP70, a marker of HSP90 inhibition, was induced. In vivo, antitumor activity of AT13387 was showed in both the imatinib-sensitive, GIST-PSW, xenograft model and a newly characterized imatinib-resistant, GIST430, xenograft model. Induction of HSP70, depletion of phospho-KIT and inhibition of KIT signaling were seen in tumors from both models after treatment with AT13387. A combination of imatinib and AT13387 treatment in the imatinib-resistant GIST430 model significantly enhanced tumor growth inhibition over either of the monotherapies. Importantly, the combination of AT13387 and imatinib was well tolerated. These results suggest AT13387 is an excellent candidate for clinical testing in GIST in combination with imatinib. Mol Cancer Ther; 1–10. 2012 AACR.
Using road constraints to progress in real-time NLOS detection

Using a 3D urban model to forecast satellites visibility in urban contexts in order to monitor GPS localization is the main topic of the present article. A virtual image processing is at the core of this method. A preliminary proof of concept has been presented in IEEE ITST 2011, where the theoretically visible satellites were computed with respect to the true position of the vehicle computed off-line from the data of a much more sophisticated equipment. This article addresses now the closed-loop real-time processing of the method, i.e. using the position estimated by the navigation process itself.
CNGA3 mutations in hereditary cone photoreceptor disorders.

We recently showed that mutations in the CNGA3 gene encoding the alpha-subunit of the cone photoreceptor cGMP-gated channel cause autosomal recessive complete achromatopsia linked to chromosome 2q11. We now report the results of a first comprehensive screening for CNGA3 mutations in a cohort of 258 additional independent families with hereditary cone photoreceptor disorders. CNGA3 mutations were detected not only in patients with the complete form of achromatopsia but also in incomplete achromats with residual cone photoreceptor function and (rarely) in patients with evidence for severe progressive cone dystrophy. In total, mutations were identified in 53 independent families comprising 38 new CNGA3 mutations, in addition to the 8 mutations reported elsewhere. Apparently, both mutant alleles were identified in 47 families, including 16 families with presumed homozygous mutations and 31 families with two heterozygous mutations. Single heterozygous mutations were identified in six additional families. The majority of all known CNGA3 mutations (39/46) are amino acid substitutions compared with only four stop-codon mutations, two 1-bp insertions and one 3-bp in-frame deletion. The missense mutations mostly affect amino acids conserved among the members of the cyclic nucleotide gated (CNG) channel family and cluster at the cytoplasmic face of transmembrane domains (TM) S1 and S2, in TM S4, and in the cGMP-binding domain. Several mutations were identified recurrently (e.g., R277C, R283W, R436W, and F547L). These four mutations account for 41.8% of all detected mutant CNGA3 alleles. Haplotype analysis suggests that the R436W and F547L mutant alleles have multiple origins, whereas we found evidence that the R283W alleles, which are particularly frequent among patients from Scandinavia and northern Italy, have a common origin.