Miracle-dz/UniFAR-FTUs huggingface dataset:
Ibrutinib interferes with the cell-mediated anti-tumor activities of therapeutic CD20 antibodies: implications for combination therapy

The novel Bruton tyrosine kinase inhibitor ibrutinib and phosphatidyl-4-5-biphosphate 3-kinase-δ inhibitor idelalisib are promising drugs for the treatment of chronic lymphocytic leukemia and B-cell non-Hodgkin lymphoma, either alone or in combination with anti-CD20 antibodies. We investigated the possible positive or negative impact of these drugs on all known mechanisms of action of both type I and type II anti-CD20 antibodies. Pretreatment with ibrutinib for 1 hour did not increase direct cell death of cell lines or chronic lymphocytic leukemia samples mediated by anti-CD20 antibodies. Pre-treatment with ibrutinib did not inhibit complement activation or complement-mediated lysis. In contrast, ibrutinib strongly inhibited all cell-mediated mechanisms induced by anti-CD20 antibodies rituximab, ofatumumab or obinutuzumab, either in purified systems or whole blood assays. Activation of natural killer cells, and antibody-dependent cellular cytotoxicity by these cells, as well as phagocytosis by macrophages or neutrophils were inhibited by ibrutinib with a half maximal effective concentration of 0.3–3 μM. Analysis of anti-CD20 mediated activation of natural killer cells isolated from patients on continued oral ibrutinib treatment suggested that repeated drug dosing inhibits these cells in vivo. Finally we show that the phosphatidyl-4-5-biphosphate 3-kinase-δ inhibitor idelalisib similarly inhibited the immune cell-mediated mechanisms induced by anti-CD20 antibodies, although the effects of this drug at 10 μM were weaker than those observed with ibrutinib at the same concentration. We conclude that the design of combined treatment schedules of anti-CD20 antibodies with these kinase inhibitors should consider the multiple negative interactions between these two classes of drugs.
Working memory in children and adolescents with Down syndrome: evidence from a colour memory experiment.

BACKGROUND This paper reports information on the visual and verbal short-term memory of individuals with Down syndrome. METHODS Colour memory in 16 children and adolescents with Down syndrome was compared with that of 16 typically developing children matched for receptive vocabulary. It was suggested that focal colours should be remembered more successfully than non-focal colours on the basis that the former could be remembered using a verbal recoding strategy. However, children with Down syndrome, for whom a deficit in verbal short-term memory makes the use of such a strategy unlikely, should remember focal and non-focal colours equally well. More importantly, if individuals with Down syndrome have more developed visual memory abilities than control children, they should outperform them in recognising non-focal colours. RESULTS Although the group with Down syndrome demonstrated significantly better Corsi blocks performance than controls, and displayed similar levels of colour knowledge, no advantage for colour memory was found. Non-focal colours were remembered by individuals with Down syndrome as successfully as focal colours but there was no indication of a visual memory advantage over controls. Focal colours were remembered significantly more successfully than non-focal colours by the typically developing children. CONCLUSION Their focal colour memory was significantly related to digit span, but only Corsi span was related to focal colour memory in the group with Down syndrome.
Fostering Resilience with Students with Learning Disabilities: An Ecological Approach

This qualitative study explored the educational journeys of five post-secondary students with learning disabilities from the perspectives of the students and their families. Guided by Ungar’s (2012) ecological conceptualization of resilience and Bronfenbrenner’s (2007) bio-ecological theory of development, this study sought to identify the challenges that these students faced and the capacities and resources within their environments that helped them along their journeys. Data collected through in-depth, semi-structured interviews with the students and their families and analyzed inductively revealed that while each student’s educational journey was unique, most of the participants followed a similar path. Common themes that emerged in the participants’ journeys included: early academic or socio-emotional challenges, early diagnosis and intervention, common family characteristics and parent support, development of selfawareness and self-advocacy in the students over time, goal setting and determination, the important yet complex role of peers, and the impact, both positive and negative, of teachers. The participants identified a number of interactions at both the microsystem and mesosystem levels that helped the students through their educational journeys. The ongoing interactions that occurred between the students and their parents, teachers, and peers at the microsystem level helped shape and develop the capacities they needed in order to negotiate for the supports and resources that sustained their well-being. These capacities included an awareness and understanding of their learning disabilities and themselves as learners, the self-advocacy skills they needed in order to seek out and negotiate for the supports and accommodations that would help them succeed, the ability to set lofty, yet attainable goals and the perseverance to work towards these goals in spite of setbacks and challenges, and the willingness to use the supports and resources that were available to them. The interactions that occurred among the students’ Fostering Resilience in Students with LD 3 environments at the mesosystem were important as well, as they helped ensure that the resources they needed would be provided for them. The mesosystem level interactions included open and honest communication between the home and school environments as well as a solid link between the home and community environments so that the parents were able to seek out the appropriate supports in the community. These findings give voice to students with learning disabilities and their families and inform educators in how they can help other families navigate their way to the resources and supports within their environments that can sustain their wellbeing and support them through their educational journeys. Fostering Resilience in Students with LD 4
Nearly Optimal Deterministic Algorithm for Sparse Walsh-Hadamard Transform

For every fixed constant α > 0, we design an algorithm for computing the k-sparse Walsh-Hadamard transform (i.e., Discrete Fourier Transform over the Boolean cube) of an N-dimensional vector x ∈ RN in time k1 + α(log N)O(1). Specifically, the algorithm is given query access to x and computes a k-sparse x˜ ∈ RN satisfying ‖ x˜− xˆ‖1 ≤ c ‖ xˆ− Hk(xˆ)‖‖‖‖‖‖‖‖1 for an absolute constant c > 0, where xˆ is the transform of x and Hk(xˆ) is its best k-sparse approximation. Our algorithm is fully deterministic and only uses nonadaptive queries to x (i.e., all queries are determined and performed in parallel when the algorithm starts). An important technical tool that we use is a construction of nearly optimal and linear lossless condensers, which is a careful instantiation of the GUV condenser (Guruswami et al. [2009]). Moreover, we design a deterministic and nonadaptive ℓ1/ℓ1 compressed sensing scheme based on general lossless condensers that is equipped with a fast reconstruction algorithm running in time k1 + α(log N)O(1) (for the GUV-based condenser) and is of independent interest. Our scheme significantly simplifies and improves an earlier expander-based construction due to Berinde, Gilbert, Indyk, Karloff, and Strauss [Berinde et al. 2008]. Our methods use linear lossless condensers in a black box fashion; therefore, any future improvement on explicit constructions of such condensers would immediately translate to improved parameters in our framework (potentially leading to k(log N)O(1) reconstruction time with a reduced exponent in the poly-logarithmic factor, and eliminating the extra parameter α). By allowing the algorithm to use randomness while still using nonadaptive queries, the runtime of the algorithm can be improved to õ(k log3 N).
LDL Particle Size and Reactive Oxygen Metabolites in Dyslipidemic Patients

Objectives: Small dense low-density lipoprotein (sdLDL) which has a small LDL particle size with greater susceptibility to oxidation is regarded as a risk marker for cardiovascular disease. The diacron reactive oxygen metabolites (d-ROMs) test has recently been introduced as an oxidative stress-related marker in the clinic. The aim of the present study was to investigate the correlation between the mean LDL particle size and the oxidative stress status as evaluated by the d-ROMs in dyslipidemic patients. Methods: The study included 278 dyslipidemic patients (121 male and 157 female, mean age, 60 years). Clinical data including the conventional atherosclerotic risk factors in addition to the mean LDL particle size measured with the gel electrophoresis and the d-ROMs were collected. Results: Male patients had a significantly smaller mean LDL particle size than females (262.2 ± 7.5 [SD] vs. 264.3 ± 6.7 Å, P<0.05), while female patients had a significantly higher d-ROMs level than males (318 ± 68 vs. 350 ± 72 U. Carr., P<0.01). A multiple regression analysis revealed that there was an independent, significant, and inverse correlation between the mean LDL particle size and the d-ROMs (β=−0.19, P<0.05). Conclusions: These findings of the co-existence of both markers suggest that sdLDL and oxidative stress can be cooperative in atherogenesis, possibly leading to the incidence of CVD, in dyslipidemic patients.
Development of the Korean Version of the Sleep Apnea Quality of Life Index

Objectives Obstructive sleep apnea (OSA) is a disorder characterized by repetitive partial or complete occlusion of the upper airway during sleep that affects quality of life. The aim of this study was to develop the Korean version of the sleep apnea quality of life index (K-SAQLI) and apply it in Korean patients with OSA. Methods Ninety-three patients with OSA completed the K-SAQLI. Its construct validity and responsiveness were tested by comparing the baseline and change scores obtained in each domain (i.e., daily functioning, social interactions, emotional functioning, and symptoms) using the medical outcome survey-short form 36 (SF-36). Results The Cronbach α coefficients of internal reliability exceeded 0.60 in all the domains (daily functioning, 0.89; social interactions, 0.88; emotional functioning, 0.92; symptoms, 0.67; and total, 0.94). The K-SAQLI had a high test-retest correlation coefficient of 0.73 in the 20 randomized selected patients. The construct validity was confirmed by significant correlations with SF-36 subscale scores. Conclusion The results of this study demonstrate that the K-SAQLI may be applicable for clinical purposes.
Freeze‐drying of proteins: some emerging concerns

Freeze‐drying (lyophilization) removes water from a frozen sample by sublimation and desorption. It can be viewed as a three‐step process consisting of freezing, primary drying and secondary drying. While cryoprotectants can protect the protein from denaturation during early stages, lyoprotectants are needed to prevent protein inactivation during drying. The structural changes as a result of freeze‐drying have been investigated, especially by FTIR (Fourier‐transform IR) spectroscopy. In general, drying results in a decrease of α‐helix and random structure and an increase in β‐sheet structure. In the case of basic fibroblast growth factor and γ‐interferon, enhanced FTIR showed large conformational changes and aggregation during freeze‐drying, which could be prevented by using sucrose as a lyoprotectant. It is now well established that structural changes during freeze‐drying are responsible for low activity of freeze‐dried powders in nearly anhydrous media. Strategies such as salt activation can give ‘activated’ enzyme powders, e.g. salt‐activated thermolysin‐catalysed regioselective acylation of taxol to give a more soluble derivative for therapeutic use. In the presence of moisture, freeze‐dried proteins can undergo disulphide interchange and other reactions which lead to inactivation. Such molecular changes during storage have been described for human insulin, tetanus toxoid and interleukin‐2. Some successful preventive strategies in these cases have also been mentioned as illustrations. Finally, it is emphasized that freeze‐drying is not an innocuous process and needs to be understood and used carefully.
Renal Sympathetic Denervation Suppresses Postapneic Blood Pressure Rises and Atrial Fibrillation in a Model for Sleep Apnea

The aim of this study was to identify the relative impact of adrenergic and cholinergic activity on atrial fibrillation (AF) inducibility and blood pressure (BP) in a model for obstructive sleep apnea. Obstructive sleep apnea is associated with sympathovagal disbalance, AF, and postapneic BP rises. Renal denervation (RDN) reduces renal efferent and possibly also afferent sympathetic activity and BP in resistant hypertension. The effects of RDN compared with &bgr;-blockade by atenolol on atrial electrophysiological changes, AF inducibility, and BP during obstructive events and on shortening of atrial effective refractory period (AERP) induced by high-frequency stimulation of ganglionated plexi were investigated in 20 anesthetized pigs. Tracheal occlusion with applied negative tracheal pressure (NTP; at −80 mbar) induced pronounced AERP shortening and increased AF inducibility in all of the pigs. RDN but not atenolol reduced NTP-induced AF-inducibility (20% versus 100% at baseline; P=0.0001) and attenuated NTP-induced AERP shortening more than atenolol (27±5 versus 43±3 ms after atenolol; P=0.0272). Administration of atropine after RDN or atenolol completely inhibited NTP-induced AERP shortening. AERP shortening induced by high-frequency stimulation of ganglionated plexi was not influenced by RDN, suggesting that changes in sensitivity of ganglionated plexi do not play a role in the antiarrhythmic effect of RDN. Postapneic BP rise was inhibited by RDN and not modified by atenolol. We showed that vagally mediated NTP-induced AERP shortening is modulated by RDN or atenolol, which emphasizes the importance of autonomic disbalance in obstructive sleep apnea-associated AF. Renal denervation displays antiarrhythmic effects by reducing NTP-induced AERP shortening and inhibits postapneic BP rises associated with obstructive events.
BEYOND AUTONOMY AND CONTROL : AN IDENTITY-BASED VIEW OF INFORMATION PRIVACY ON SOCIAL MEDIA Research in Progress

This paper proposes an identity-based conceptualization of information privacy and suggests that privacy should be understood against the backdrop of self-identity formation. The researcher argues that the so-called “privacy paradox” the baffling contradiction between grave privacy concerns in society and the prevalence of information sharing on social media is not a paradox per se; rather, privacy concerns reflect the ideology of autonomous self, whereas social construction of identity explains voluntary information disclosure. The researcher first unpacks the mainstream conception of autonomycentric privacy in the IS literature, and then present a research model that illustrates a theorization of the relationship between privacy and self-identity. The paper also reports a pilot study that validates the constructs for future research.
Image analysis by Krawtchouk moments

In this paper, a new set of orthogonal moments based on the discrete classical Krawtchouk polynomials is introduced. The Krawtchouk polynomials are scaled to ensure numerical stability, thus creating a set of weighted Krawtchouk polynomials. The set of proposed Krawtchouk moments is then derived from the weighted Krawtchouk polynomials. The orthogonality of the proposed moments ensures minimal information redundancy. No numerical approximation is involved in deriving the moments, since the weighted Krawtchouk polynomials are discrete. These properties make the Krawtchouk moments well suited as pattern features in the analysis of two-dimensional images. It is shown that the Krawtchouk moments can be employed to extract local features of an image, unlike other orthogonal moments, which generally capture the global features. The computational aspects of the moments using the recursive and symmetry properties are discussed. The theoretical framework is validated by an experiment on image reconstruction using Krawtchouk moments and the results are compared to that of Zernike, pseudo-Zernike, Legendre, and Tchebyscheff moments. Krawtchouk moment invariants are constructed using a linear combination of geometric moment invariants; an object recognition experiment shows Krawtchouk moment invariants perform significantly better than Hu's moment invariants in both noise-free and noisy conditions.
Effect of Ventilation on Mechanical Properties and Pressure-Flow Relationships of Immature Airways

ABSTRACT: Ventilation of immature airways has been shown to result in pressure-induced deformation and alteration of mechanical properties. These changes in mechanical properties may alter the effect of compressive pressures on pressure-flow relationships. To test this hypothesis, unventilated (Group I, n = 8) and ventilated (group II, n = 8; mean pressures of 8–12 cm H2O for 2 h duration) tracheal segments were excised from preterm lambs approximately 118 days gestation and mounted in a Krebs-filled chamber for determination of compliances and pressure-flow relationships. Compliance data were obtained for both the inflation loop (inflation compliance) and the collapsing loop (collapsing compliance) of the pressure-volume curve for each segment. Flow (V = 2–10 liter/min.) was introduced through the lumen of each segment at different chamber pressures (Pc = 5–30 mm Hg). Driving pressure (Pd) was recorded for each V and Pc. Airway resistance (R) was calculated as Pd/V. Group II had significantly greater (p < 0.005) radii than Group I, suggesting ventilation-induced deformation. Group II had significantly lower (p < 0.05) inflation compliance but significantly greater (p < 0.05) collapsing compliance than group I. Two-factor analysis of variance demonstrated significantly greater (p < 0.05) R in group II at each value of V and each Pc. These data may help to explain the flow limitation and gas-trapping observed in preterm infants who have been mechanically ventilated.
Drug interactions during therapy with three major groups of antimicrobial agents

This review focuses on drug–drug interactions with three major groups of antimicrobial agents: macrolides (including azalides and ketolides), quinolones, which are widely used for the treatment of bacterial infections, and azoles, which are used for antifungal therapy. Macrolides and the ketolide telithromycin are potent inhibitors of CYP3A4 and thus interfere with the pharmacokinetics of many other drugs that are metabolised by this enzyme. In contrast, although closely related, azithromycin is not a cytochrome inhibitor. All quinolones form complexes with di- and trivalent cations and, therefore, the absorption of quinolones can be dramatically reduced when given concomitantly with mineral antacids, zinc or iron preparations. Ciprofloxacin exhibits an inhibitory potential for the cytochrome isoenzyme 1A2, resulting in an inhibition of theophylline metabolism. Other quinolones, such as levofloxacin or moxifloxacin, do not interfere with theophylline metabolism. The systemic azoles, such as ketoconazole, itraconazole, fluconazole and voriconazole, are inhibitors of CYP isoenzymes, such as CYP3A4, CYP2C9 and CYP2C19, to varying degrees. In addition, some are substrates of the MDR-1 gene product, P-glycoprotein. These features are the basis for most of the interactions occurring during azole therapy (e.g., in severely ill patients in the hospital who are treated with multiple drugs).
Types for Deadlock-freedom: The Synchronous Case

Many di erent notions of \program property", and many di erent methods of verifying such properties, arise naturally in programming. We present a general framework of Speci cation Structures for combining di erent notions and methods in a coherent fashion. We then apply the idea of speci cation structures to concurrency in the setting of Interaction Categories. As a speci c example, a certain speci cation structure de ned over the interaction category SProc yields a new category SProcD whose type system is strong enough to guarantee deadlock-freedom of concurrent processes. We present some techniques for manipulating typed processes in this category, and show that they allow us to reason about deadlock-freedom in synchronous networks, a class of concurrent systems which incorporates both synchronous data ow programs and systolic algorithms.
Bronchoprotection by Olodaterol Is Synergistically Enhanced by Tiotropium in a Guinea Pig Model of Allergic Asthma

The novel once-daily β2-agonist bronchodilator drug olodaterol has recently been shown to be effective in patients with allergic asthma for >24 hours. An increased cholinergic tone common to these patients may decrease the effectiveness of β2-agonists. This could provide a rationale for combination therapy with olodaterol and the long-acting anticholinergic tiotropium to aim for a once-daily treatment regimen. In guinea pigs, we evaluated the protective effects of olodaterol, alone and in combination with tiotropium, on airway responsiveness to histamine, which is partially mediated by a cholinergic reflex mechanism. In addition, using a guinea pig model of acute allergic asthma, we examined the cooperative effects of these bronchodilators on allergen-induced early (EAR) and late (LAR) asthmatic reactions, airway hyper-responsiveness (AHR) to histamine, and airway inflammation. It was demonstrated that the protective effect of olodaterol against histamine-induced bronchoconstriction was synergistically enhanced and prolonged in the presence of tiotropium. In addition, tiotropium synergistically augmented both the reversal of and the protection against the allergen-induced AHR after the EAR by olodaterol. Olodaterol and tiotropium were highly effective in inhibiting the magnitude of the allergen-induced EAR and LAR, and both reactions were fully inhibited by the combination of these drugs. It is remarkable that these effects were not associated with an effect on inflammatory cell infiltration in the airways. In conclusion, the results indicate that combination therapy with olodaterol and tiotropium may be highly effective in the treatment of allergen-induced asthmatic reactions and AHR.
Strategies and Benefits of Fusion of 2D and 3D Face Recognition

The extension of 2D image-based face recognition methods with respect to 3D shape information and the fusion of both modalities is one of the main topics in the recent development of facial recognition. In this paper we discuss different strategies and their expected benefit for the fusion of 2D and 3D face recognition. The face recognition grand challenge (FRGC) provides for the first time ever a public benchmark dataset of a suitable size to evaluate the accuracy of both 2D and 3D face recognition. We use this benchmark to evaluate hierarchical graph matching (HGM), an universal approach to 2D and 3D face recognition, and demonstrate the benefit of different fusion strategies. The results show that HGM yields the best results presented at the recent FRGC workshop, that 2D face recognition is significantly more accurate than 3D face recognition and that the fusion of both modalities leads to a further improvement of the 2D results.