Miracle-dz/UniFAR-FTUs huggingface dataset:
APG350 Induces Superior Clustering of TRAIL Receptors and Shows Therapeutic Antitumor Efficacy Independent of Cross-Linking via Fcγ Receptors

Cancer cells can be specifically driven into apoptosis by activating Death-receptor-4 (DR4; TRAIL-R1) and/or Death-receptor-5 (DR5; TRAIL-R2). Albeit showing promising preclinical efficacy, first-generation protein therapeutics addressing this pathway, especially agonistic anti-DR4/DR5-monoclonal antibodies, have not been clinically successful to date. Due to their bivalent binding mode, effective apoptosis induction by agonistic TRAIL-R antibodies is achieved only upon additional events leading to antibody-multimer formation. The binding of these multimers to their target subsequently leads to effective receptor-clustering on cancer cells. The research results presented here report on a new class of TRAIL-receptor agonists overcoming this intrinsic limitation observed for antibodies in general. The main feature of these agonists is a TRAIL-mimic consisting of three TRAIL-protomer subsequences combined in one polypeptide chain, termed the single-chain TRAIL-receptor–binding domain (scTRAIL-RBD). In the active compounds, two scTRAIL-RBDs with three receptor binding sites each are brought molecularly in close proximity resulting in a fusion protein with a hexavalent binding mode. In the case of APG350—the prototype of this engineering concept—this is achieved by fusing the Fc-part of a human immunoglobulin G1 (IgG1)-mutein C-terminally to the scTRAIL–RBD polypeptide, thereby creating six receptor binding sites per drug molecule. In vitro, APG350 is a potent inducer of apoptosis on human tumor cell lines and primary tumor cells. In vivo, treatment of mice bearing Colo205-xenograft tumors with APG350 showed a dose-dependent antitumor efficacy. By dedicated muteins, we confirmed that the observed in vivo efficacy of the hexavalent scTRAIL–RBD fusion proteins is—in contrast to agonistic antibodies—independent of FcγR-based cross-linking events. Mol Cancer Ther; 12(12); 2735–47. ©2013 AACR.
Physical and mechanical characterizations of oil palm fruit bunch fiber filled polypropylene composites

Pulverized oil palm fruit bunch (OPFB) fiber was used as filler in Polypropylene (PP). Pulverized OPFB was added at various sizes (250 μm, 180 μm, 125 μm, and 100 μm) to study its effect on the physical and mechanical properties of OPFB filled PP. OPFB powder was mixed with polypropylene at 20 wt% and maleic anhydride polypropylene (MAPP) was also added as coupling agent at 2 wt%. Water absorption behavior of composites followed the normal trend where the water uptake increases with the increasing of OPFB size due to its hydrophilic characteristic. The incorporation of OPFB also decreases the thermal stability of composites at initial stage. Tensile and flexural properties were enhanced with the addition of OPFB powder and further increased with the increase of OPFB size. Meanwhile elongation at break and impact strength were decreased with the increase of OPFB size. SEM observation on the fracture surface of tensile, flexural, and impact tested samples provide further understanding on the effect of OPFB as filler in the matrix.
Presence and The Sixth Sense

This paper discusses the notion that presence may be considered as a selection mechanism that organizes the stream of sensory data into an environmental gestalt or perceptual hypothesis about current environment. A par ticular environmental gestalt results in scan-sensing of the world in a particular pattern reminiscent of saccades and fixations in eye scan paths. The environment hypothesis is continually reverified or else a break in presence oc curs. Presence is therefore compared to visual hypothe sis selection in the work of Richard Gregory and Law rence Stark. The implications for measurement are discussed, and it is concluded that physiological measures indicating breaks in presence are worthy of study, and that the study of presence is also the study of what maintains an environmental gestalt.
PTCH1 and SMO Gene Alterations in Keratocystic Odontogenic Tumors

Keratocystic odontogenic tumors (KCOTs, previously known as odontogenic keratocysts) are aggressive jaw lesions that may occur in isolation or in association with nevoid basal cell carcinoma syndrome (NBCCS). Mutations in the PTCH1 (PTCH) gene are responsible for NBCCS and are related in tumors associated with this syndrome. Mutations in the SMO gene have been identified in basal cell carcinoma and in medulloblastoma, both of which are features of NBCCS. To clarify the role of PTCH1 and SMO in KCOTs, we undertook mutational analysis of PTCH1 and SMO in 20 sporadic and 10 NBCCS-associated KCOTs, and for SMO, 20 additional cases of KCOTs with known PTCH1 status were also included. Eleven novel (1 of which occurred twice) and 5 known PTCH1 mutations were identified. However, no pathogenic mutation was detected in SMO. Our findings suggest that mutations are rare in SMO, but frequent in PTCH1 in sporadic and NBCCS-associated KCOTs. Abbreviations: NBCCS, nevoid basal cell carcinoma syndrome; KCOTs, keratocystic odontogenic tumors; BCCs, basal cell carcinomas.
A Computer Game Based Approach for Increasing Fluency in the Speech of the Autistic Children

Autism is a complex developmental disability that typically appears during the first three years of life. This is the result of a neurological disorder that affects the functioning of human brain. Children diagnosed with autism often are self-absorbed and seem to exist in a private world where they are unable to successfully communicate and interact with others. Sometimes they have difficulties in developing speaking skills and understanding what others say to them. Lack of fluency in the speech is one of the most frequently found problems with autistic children. The traditional methods for increasing fluency were found to be monotonous and hence, not much successful during our three months of observations over the participants of Autism Welfare Foundation (AWF) at Dhaka. Therefore, we developed an interactive computer game for the autistic children for improving the fluency in their speech. Our game produced encouraging results over a participant during three months of observation. In this paper, we describe our project and the outcomes.
Wnt Signaling Exerts an Antiproliferative Effect on Adult Cardiac Progenitor Cells Through IGFBP3

Rationale: Recent work in animal models and humans has demonstrated the presence of organ-specific progenitor cells required for the regenerative capacity of the adult heart. In response to tissue injury, progenitor cells differentiate into specialized cells, while their numbers are maintained through mechanisms of self-renewal. The molecular cues that dictate the self-renewal of adult progenitor cells in the heart, however, remain unclear. Objective: We investigate the role of canonical Wnt signaling on adult cardiac side population (CSP) cells under physiological and disease conditions. Methods and Results: CSP cells isolated from C57BL/6J mice were used to study the effects of canonical Wnt signaling on their proliferative capacity. The proliferative capacity of CSP cells was also tested after injection of recombinant Wnt3a protein (r-Wnt3a) in the left ventricular free wall. Wnt signaling was found to decrease the proliferation of adult CSP cells, both in vitro and in vivo, through suppression of cell cycle progression. Wnt stimulation exerted its antiproliferative effects through a previously unappreciated activation of insulin-like growth factor binding protein 3 (IGFBP3), which requires intact IGF binding site for its action. Moreover, injection of r-Wnt3a after myocardial infarction in mice showed that Wnt signaling limits CSP cell renewal, blocks endogenous cardiac regeneration and impairs cardiac performance, highlighting the importance of progenitor cells in maintaining tissue function after injury. Conclusions: Our study identifies canonical Wnt signaling and the novel downstream mediator, IGFBP3, as key regulators of adult cardiac progenitor self-renewal in physiological and pathological states.
Early dumping syndrome is not a complication but a desirable feature of Roux‐en‐Y gastric bypass surgery

Early dumping syndrome after gastric bypass surgery due to rapid delivery of hyperosmolar nutrients into the bowel causing intense symptoms is often described as a complication. Twelve patients, mean age 47 years, were interviewed approximately 9 years post‐operation. The interviews were audiotaped and transcribed verbatim, followed by an inductive content analysis to reveal patients' experience of the dumping syndrome. The core category ‘Dumping syndrome is a positive consequence of Roux‐en‐Y gastric bypass surgery and a tool to control food intake’ was identified based on the following four sub‐categories: (i) ‘The multidimensional emergence and effects of dumping syndrome’, (ii) ‘Dumping syndrome as something positive although unpleasant’, (iii) ‘Developing coping mechanisms and ingenious strategies’ and (iv) ‘My own fault if I expose myself to dumping syndrome’. From the patients' perspective, dumping syndrome gives control over food intake; although the symptoms were unpleasant, patients considered dumping syndrome as a positive protection against over‐consumption. Hence, healthcare professionals should not present dumping syndrome as a complication but rather as an aid to control eating behaviour and excessive food intake.
Time and concentration dependency of P-gp, MRP1 and MRP5 induction in response to gemcitabine uptake in Capan-2 pancreatic cancer cells

Abstract 1. Influx and efflux proteins play a major role in the overall uptake and efficacy of chemotherapeutic agents and cellular chemo-resistance. 2. The present study investigated the time course and dose dependency of the induction of three efflux proteins, P-gp, MRP1 and MRP5, in response to gemcitabine exposure in Capan-2 pancreatic cancer cell line at transcriptional and translational levels. The influence of exposure on the influx protein (ENT1), the net cellular uptake of the gemcitabine, the overall ATPase activity and the cell death rate were also measured. 3. The time course of the expression exhibited an initial rise, toward a plateau level. The estimated Km and Vmax confirmed that MRP5 and to a lesser extent MRP1 are the prominent proteins for efflux of gemcitabine. Both mRNA and protein expression demonstrated the time and concentration dependency of the induction; and the elevated ATPase activity validated that the induced efflux proteins are functionally active. 4. The results of the study revealed that the efficacy window of gemcitabine as it relates to the function of the efflux proteins is concentration and temporal dependent and is well correlated to the first 60 min of exposure.
Characterizing nanoscale changes in the activity of VEGFR-2 on glioma microvascular endothelial cell membranes using atomic force microscopy

The aim of the current study was to demonstrate the distribution of VEGFR-2 on glioma microvascular endothelial cells on a nanoscale and investigate changes in VEGFR-2 activity following treatment with the VEGFR-2 inhibitor and agonist sorafenib and bradykinin, respectively. Three groups were evaluated in this study: Control glioma microvascular endothelial cells, sorafenib-treated glioma microvascular endothelial cells and bradykinin-treated glioma microvascular endothelial cells. Changes in the activity of VEGFR-2 on the glioma microvascular endothelial cell membranes following treatment with sorafenib and bradykinin were characterized by atomic force microscopy (AFM). Colloidal gold-labeled immune complexes and AFM were used to visualize the distribution of VEGFR-2 on the cell membranes. In the control group, VEGFR-2, which was observed as numerous globular structures, was evenly distributed on the cell surface membranes. The majority of the receptors were active. In the sorafenib group, only a few globular structures were observed on the cell membranes, with a density significantly lower than that in the control group (P<0.01). Furthermore, compared with the control group, fewer of the receptors were active. In the bradykinin group, numerous globular structures were densely distributed on the cell membranes, with a density significantly higher than that in the control group (P<0.01). The distribution and activity of VEGFR-2 on glioma microvascular endothelial cell membranes treated with sorafenib and bradykinin suggested that the activity of VEGFR-2 could be regulated by its inhibitor or agonist.
Effect of Inhaled Iloprost Plus Oral Sildenafil in Patients With Primary Pulmonary Hypertension

Background—The application of iloprost, a stable prostacyclin analogue, by inhalation has been shown to improve hemodynamic variables in patients with primary pulmonary hypertension. However, repetitive inhalations are required due to its short-term effects. One potential approach to prolong and increase the vasorelaxant effects of aerosolized iloprost might be to combine use with phosphodiesterase inhibitors. Methods and Results—The short-term effects of 8.4 to 10.5 &mgr;g of aerosolized iloprost, the phosphodiesterase type 5 inhibitor sildenafil, and the combination thereof were compared in 5 patients with primary pulmonary hypertension. Aerosolized iloprost resulted in a more pronounced decrease in mean pulmonary arterial pressure (PAP) than sildenafil alone (9.4±1.3 versus 6.4±1.1 mm Hg;P <0.05). The reduction in mean PAP after sildenafil was maximal after the first dose (25 mg). The combination of sildenafil plus iloprost lowered mean PAP significantly more than iloprost alone (13.8±1.4 versus 9.4±1.3 mm Hg;P <0.009). No significant changes in heart rate or systemic arterial pressure were observed during any treatment. The treatments were well tolerated, without major adverse effects. Conclusions—Sildenafil caused a long-lasting reduction in mean PAP and pulmonary vascular resistance, with a further additional improvement after iloprost inhalation. These data suggest that small doses of a phosphodiesterase type 5 inhibitor may be a useful adjunct to inhaled iloprost in the management of pulmonary hypertension.
Science for the Twenty‐First Century: From Social Contract to the Scientific Core

The article addresses the need, posed by the challenges of sustainable development and the changing context at the beginning of the 21st century, for changes in the method and practice of science. The major challenges for a “sustainability science” arise from increasing complexification at the ontological, epistemological and political levels, calling for an integrated science going far beyond an interdisciplinary style of research. The requirement is for the development, adoption, and dissemination of a truly complex-systems scientific research model. Complex socio-ecological systems share a number of fundamental properties that require changes in scientific methods, criteria of truth and quality, and conceptual frameworks. These properties include non-linearity, plurality of perspectives, emergence of properties, self-organization, multiplicity of scales, and irreducible uncertainty. Some implications of the analysis are pointed out, in the form of practical recommendations. The authors argue for the involvement of both natural and social scientists in the investigation of the necessary steps to develop a sustainability science.
Use of Replicating Oncolytic Adenoviruses in Combination Therapy for Cancer

Oncolytic virotherapy is the use of genetically engineered viruses that specifically target and destroy tumor cells via their cytolytic replication cycle. Viral-mediated tumor destruction is propagated through infection of nearby tumor cells by the newly released progeny. Each cycle should amplify the number of oncolytic viruses available for infection. Our understanding of the life cycles of cytolytic viruses has allowed manipulation of their genome to selectively kill tumor cells over normal tissue. Because the mechanism of tumor destruction is different, oncolytic virotherapy should work synergistically with current modes of treatment such as chemotherapy and radiation therapy. This article focuses on oncolytic adenoviruses that have been created and tested in preclinical and clinical trials in combination with chemotherapy, radiation therapy, and gene therapy.
Mining Consumer Dialog in Online Forums

Purpose – The paper's aim is to mine and analyze opinion formation on the basis of consumer dialogs in online forums.Design/methodology/approach – The study identifies opinions, communication relationships, and dialog acts of forum users using different text mining methods. Utilizing this data, social networks can be derived and analyzed to detect influential users and opinion tendencies. The approach is applied to sample online forums discussing the iPhone.Findings – Combining text mining and social network analysis enables the study of opinion formation and yields encouraging results. Out of the four methods employed for text mining, support vector machines performed best.Research limitations/implications – The data set applied here is fairly small. More threads on different products will be considered in future work to improve validation.Practical implications – The approach represents a valuable instrument for online market research. It enables companies to recognize opportunities and risks and to ini.
Transjugular intrahepatic portal‐systemic shunt in the treatment of refractory ascites: Effect on clinical, renal, humoral, and hemodynamic parameters

Seventeen cirrhotics with refractory ascites were treated with transjugular intrahepatic portosystemic shunt (TIPS) and followed for 15.5 ± 3.4 months. Five patients died, four within 3 months after TIPS (hepatocellular failure) and one after 22 months (cholangiocarcinoma). Six patients received transplants 1 to 10 months after the procedure. Actuarial survival at 6, 12, and 24 months was 75%, 75%, and 63%, respectively. Portosystemic venous pressure gradient decreased by 46% at 1 month and by 38% at 7 to 12 months. Eight patients presented 18 stenoses 1 to 18 months after TIPS. Twelve stenoses required balloon dilatation. Tense ascites was present before TIPS in 100% of the patients, whereas it was mild or absent in 56% at 1 month, in 66% at 3 to 6 months, in 57% at 7 to 12 months, and in 100% at 24 months after TIPS. Requirements for diuretics and paracentesis decreased after TIPS (P < .001, both). One month after TIPS, urinary and fractional sodium excretion increased (P < .001, both), plasma renin activity, plasma aldosterone (P < .005, both), and plasma norepinephrine (P < .05) decreased and cardiac output (P < .01) increased, systemic vascular resistances (P < .005) decreased, and arterial pressure did not change. Acute hepatic encephalopathy was frequent early after TIPS but was responsive to treatment and caused no long‐term disability. In conclusion, TIPS is useful in the treatment of refractory ascites through lowering portal pressure and improving renal sodium excretion. This effect could be attributable to an increase in effective blood volume causing deactivation of vasopressor systems. (HEPATOLOGY 1995; 21:986–994.)
Vivos Voco: A survey of recent research on voice transformation at IRCAM

IRCAM has a long experience in analysis, synthesis and transformation of voice. Natural voice transformations are of great interest for many applications and can be combine with text-to-speech system, leading to a powerful creation tool. We present research conducted at IRCAM on voice transformations for the last few years. Transformations can be achieved in a global way by modifying pitch, spectral envelope, durations etc. While it sacrifices the possibility to attain a specific target voice, the approach allows the production of new voices of a high degree of naturalness with different gender and age, modified vocal quality, or another speech style. These transformations can be applied in realtime using ircamTools TRAX. Transformation can also be done in a more specific way in order to transform a voice towards the voice of a target speaker. Finally, we present some recent research on the transformation of expressivity.
Borrelia burgdorferi Population Dynamics and Prototype Gene Expression during Infection of Immunocompetent and Immunodeficient Mice

ABSTRACT The population dynamics of Borrelia burgdorferi were quantified by real-time PCR targeting the flaB gene in skin (inoculation site, noninoculation site, and ear), heart (heart base and ventricle), quadriceps muscle, and the tibiotarsal joint at 1, 2, 4, 6, and 8 weeks after intradermal inoculation in C3H and C3H-scid mice. In addition, RNA transcription was assessed for several prototype genes, including flaB, ospA, ospC, dbpA, arp, vlsE, fbp, oppA-2, and p37-42. Spirochete numbers were equivalent in C3H and C3H-scid mice at 1 or 2 weeks and then declined in C3H mice, but they continued to rise and then plateaued in C3H-scid mice. Gene transcription was likewise higher in C3H-scid mice than in C3H mice, particularly at 4 or more weeks of infection. Gene transcription showed variation among tissues, with the highest levels of transcription in heart and joint tissue, which are sites of inflammation.
Absorption and Sorptivity of Cover Concrete

The absorption characteristics and sorptivity of cover concrete obtained by the initial surface absorption test (ISAT), the covercrete absorption test (CAT), and the sorptivity test have been studied and compared. Two types of concrete, namely ordinary portland cement (OPC) control and low water concrete (LWC) of grade 35 have been tested. The laboratory work has shown close agreement between the ISAT and sorption results but the CAT yields higher results. An analytical model has been developed based on the mechanisms of capillary suction and pressure-driven flow. In this model water entering concrete during the tests is assumed to be concentrated in a well-defined volume. This volume is fully saturated and is separated from the surrounding concrete by a wetting front at which capillary suction occurs. By applying the physical equations for capillary suction pressures and permeability the experimental results are explained in terms of the basic properties of the concrete. The model gives good agreement with the experimental results.
Generalization for Adaptively-chosen Estimators via Stable Median

Datasets are often reused to perform multiple statistical analyses in an adaptive way, in which each analysis may depend on the outcomes of previous analyses on the same dataset. Standard statistical guarantees do not account for these dependencies and little is known about how to provably avoid overfitting and false discovery in the adaptive setting. We consider a natural formalization of this problem in which the goal is to design an algorithm that, given a limited number of i.i. d. ~samples from an unknown distribution, can answer adaptively-chosen queries about that distribution. We present an algorithm that estimates the expectations of $k$ arbitrary adaptively-chosen real-valued estimators using a number of samples that scales as $\sqrt{k}$. The answers given by our algorithm are essentially as accurate as if fresh samples were used to evaluate each estimator. In contrast, prior work yields error guarantees that scale with the worst-case sensitivity of each estimator. We also give a version of our algorithm that can be used to verify answers to such queries where the sample complexity depends logarithmically on the number of queries $k$ (as in the reusable holdout technique). Our algorithm is based on a simple approximate median algorithm that satisfies the strong stability guarantees of differential privacy. Our techniques provide a new approach for analyzing the generalization guarantees of differentially private algorithms.