Miracle-dz/UniFAR-FTUs huggingface dataset:
Superior Antitumor Activity of a Novel Bispecific Antibody Cotargeting Human Epidermal Growth Factor Receptor 2 and Type I Insulin-like Growth Factor Receptor

The humanized anti-HER2 monoclonal antibody (mAb) trastuzumab (Herceptin; Genentech) effectively inhibits human epidermal growth factor receptor 2 (HER2)-positive breast tumors. However, many patients responding to treatment often develop resistance. Cross-talk between type I insulin–like growth factor receptor (IGF-IR) and HER2 and elevated IGF-IR signaling have been implicated in tumor cell resistance to trastuzumab therapy. Previously, we reported that the anti-IGF-IR mAb m590 inhibits proliferation and migration of breast cancer MCF-7 cells in vitro. Here, we generated a “knobs-into-holes” bispecific antibody (Bi-Ab) against HER2 and IGF-IR by engineering trastuzumab and m590. We compared the effects of Bi-Ab treatment in vitro and in SKOV-3 HER2- and IGF-IR–overexpressing cancer xenograft mouse model with those of m590 and trastuzumab treatment alone or in combination. Bi-Ab effectively inhibited proliferation of HER2- and IGF-IR–overexpressing ovarian cancer SKOV-3 cells in vitro by ablating receptor phosphorylation and downstream PI3K/Akt and mitogen-activated protein kinase signaling. Bi-Ab more effectively inhibited cancer growth in SKOV-3 HER2- and IGF-IR–overexpressing cancer xenograft mouse model than m590 and trastuzumab alone or in combination. Mice bearing SKOV-3 HER2- and IGF-IR–overexpressing xenografts showed extensive and sustainable tumor regression when treated with Bi-Ab. Our results suggest that Bi-Ab has superior antitumor activity compared with monospecific antibodies, and cotargeting HER2 and IGF-IR may be clinically beneficial in minimizing the acquired resistance to trastuzumab therapy. Mol Cancer Ther; 13(1); 90–100. ©2013 AACR.
Did Montaigne Love His Children? Demography and the Hypothesis of Parental Indifference

Philippe Aries' hypothesis that parental indifference is inversely related to infant and child survival has proved to be particularly influential during the last four decades. Aries uses Montaigne's apparent indifference to the deaths of his own infant children as an example to support his case. But it can be argued on the basis of firmer supporting evidence not only that Montaigne was a caring father but also that infant and childhood mortality were not universally high in modern Europe.
Scaffold/Matrix Attachment Region Elements Interact with a p300-Scaffold Attachment Factor A Complex and Are Bound by Acetylated Nucleosomes

ABSTRACT The transcriptional coactivator p300 regulates transcription by binding to proteins involved in transcription and by acetylating histones and other proteins. These transcriptional effects are mainly at promoter and enhancer elements. Regulation of transcription also occurs through scaffold/matrix attachment regions (S/MARs), the chromatin regions that bind the nuclear matrix. Here we show that p300 binds to the S/MAR binding protein scaffold attachment factor A (SAF-A), a major constituent of the nuclear matrix. Using chromatin immunoprecipitations, we established that both p300 and SAF-A bind to S/MAR elements in the transiently silent topoisomerase I gene prior to its activation at G1 during cell cycle. This binding is accompanied by local acetylation of nucleosomes, suggesting that p300-SAF-A interactions at S/MAR elements of nontranscribed genes might poise these genes for transcription.
An Obligatory Role of NF-κB in Mediating Bone Marrow Derived Endothelial Progenitor Cell Recruitment and Proliferation Following Endotoxemic Multiple Organ Injury in Mice

Background Recruitment of bone marrow derived endothelial progenitor cells (BMDEPCs) alleviates multiple organ injury (MOI) and improves outcomes. However, mechanisms mediating BMDEPC recruitment following septic MOI remain largely unknown. This study characterized the kinetics of BMDEPC recruitment and proliferation and defined the role of NF-κB in regulating BMDEPC recruitment and proliferation. Methods and Main Findings Chimeric mice with an intact or disrupted NF-κB p50 gene and BMDEPC-restricted expression of green fluorescent protein were created and injected with LPS (2 mg/kg, i.p.). BMDEPC recruitment and proliferation in multiple organs were quantified. BMDEPC recruitment and proliferation are highly organ-dependent. Lungs had the highest number of BMDEPC recruitment, whereas heart, liver and kidney had only a small fraction of the number of BMDEPCs in lungs. Number of proliferating BMDEPCs was several-fold higher in lungs than in other 3 organs. Kinetically, BMDEPC recruitment into different organs showed different time course profiles. NF-κB plays obligatory roles in mediating BMDEPC recruitment and proliferation. Universal deletion of NF-κB p50 gene inhibited LPS-induced BMDEPC recruitment and proliferation by 95% and 69% in heart. However, the contribution of NF-κB to these regulations varies significantly between organs. In liver, universal p50 gene deletion reduced LPS-induced BMDEPC recruitment and proliferation only by 49% and 35%. NF-κB activities in different tissue compartments play distinct roles. Selective p50 gene deletion either in stromal/parenchymal cells or in BM/blood cells inhibited BMDEPC recruitment by a similar extent. However, selective p50 gene deletion in BM/blood cells inhibited, but in stromal/parenchymal cells augmented BMDEPC proliferation. Conclusions BMDEPC recruitment and proliferation display different kinetics in different organs following endotoxemic MOI. NF-κB plays obligatory and organ-dependent roles in regulating BMDEPC recruitment and proliferation. NF-κB activities in different tissue compartments play distinct roles in regulating BMDEPC proliferation.
Real-Time Program Execution on NAND Flash Memory for Portable Media Players

NAND flash memory has been widely used as a non-volatile storage for storing data. However, it requires a large amount of SRAM for executing program codes stored in it since it only supports page-based reads, not byte-level random reads. This paper proposes a new paging mechanism called RT-PLRU (real-time constrained combination of pinning and LRU) that allows program codes stored in NAND flash memory to be executed satisfying real-time requirements with minimal usage of SRAM. Moreover, the RT-PLRU is optimally configured in a developer-transparent way without giving any burden to the program developer. The developed technique is specifically applied to a media player program targeting a PMP (portable medial player). To the best of our knowledge, this is the first effort to use NAND flash memory as a code storage for storing and executing real-time programs with minimal usage of SRAM.
Moving People and Knowledge: Scientific Mobility in the European Union1

This paper considers the relationship between highly skilled scientific migration (HSM) and the transfer of knowledge within the European Union (EU). To understand these processes we need to conceptualize the phenomenon and then develop appropriate operational tools. HSM engages two key concepts: (1) the concept of skill or knowledge; and (2) the concept of migration. nalysing the impact of HSM requires an understanding of who is moving (and the quality of their skills) and the nature of their migration. This might include consideration of the direction of flows; their frequency, duration, and permanency; and the propensity to return. In order to evaluate the impact of these processes on the regions concerned and develop appropriate policy responses, we need to examine the relationship between scientific mobility and the transfer of knowledge. Much existing literature focuses on the size and direction of migratory flows assuming a clear correlation between human mobility and the transfer of knowledge to identify the “winning” and “losing” regions. More recent work emphasizing “circulation”. questions these assumptions and suggests that flows may not be unidirectional, homogenous, or permanent and may be mitigated by certain “compensatory” mechanisms This article considers some of the issues raised in the literature and the ways in which the variables identified may interact to shape these relationships with important implications for sending and receiving countries and individual scientists. This article does not endeavour to present new conclusions. Drawing on a pilot project concerned with the mobility of Italian scientists, it begins to map out a research agenda capable of informing a new study of scientific migration in the context of EU enlargement that may potentially inform other research in this field.
Query-sensitive ray shooting

Ray (segment) shooting is the problem of determining the first intersection between a ray (directed line segment) and a collection of polygonal or polyhedral obstacles. In order to process queries efficiently, the set of obstacle polyhedra is usually preprocessed into a data structure. In this paper we propose a query-sensitive data structure for ray shooting, which means that the performance of our data structure depends on the local geometry of obstacles near the query segment. We measure the complexity of the local geometry near the segment by a parameter called the simple cover complexity, denoted by scc(s) for a segment s. Our data structure consists of a subdivision that partitions the space into a collection of polyhedral cells, each of O(1) complexity. We answer a segment shooting query by wallking along the segment through the subdivision. Our first result is that, for any fixed dimension d, there exists a simple hierarchical subdivision in which no query segment s intersects more than O(scc(s)) cells. Our second result shows that in two dimensions such a subdivision of size O(n) can be constructed in time O(nlogn), where n is the total number of vertices in all the obstacles.
The role of stress and articulatory difficulty in children's early productions

Interactions between stress level and articulatory difficulty as influences on children's early words were investigated in an elicited imitation task. Thirty-two 26-month-old children were asked to imitate nonsense-word stimuli containing target syllables that varied in articulatory difficulty and level of stress. Both factors had significant effects on aspects of the children's imitations, although the relative contributions of each differed for whole word avoidance, syllable omissions, and accuracy of production. Implications of these differential effects for accounts of children's early productions are discussed.
New Trends in Diagnosis and Control Strategies for Implant Infections

In implant infections, a quick and reliable identification of the etiological agent is crucial to realizing efficacious therapies. Among molecular methods, automated ribotyping has proven to be an accurate and rapid technique. More recently, MALDI-TOF/MS and PCR-electrospray ionization (ESI)/ MS have been applied successfully to microbiological diagnosis. In implant infections, biofilm is still the major problem for bacterial persistence and recalcitrance to antibiotic therapy. Among biofilm-disrupting agents, enzymes promise the greatest therapeutic possibilities. DNase I degrades biofilm extracellular DNA and has been shown to sensitize biofilm to various biocides and anionic detergents, while dispersin B acts on biofilm exopolysaccharide and, combined with antiseptic, gives a broad-spectrum antibiofilm and antimicrobial activity. The novel antimicrobial approach based on photodynamic treatment (PDT) applies, in combination with antibiotics, to the implant or medical devices reachable by optical fibers. Better progress could be gained by the development of infection-resistant biomaterials able to both inhibit bacterial adhesion and promote tissue integration. New knowledge regarding the fibronectin-mediated internalization of Staphylococcus aureus by osteoblasts, and on its role in the pathogenesis of implant-related osteomyelitis, paves the way for the development of vaccines against staphylococcal adhesins, to prevent both adhesion on biomaterials and bacterial invasion of bone cells.
Prognostic significance of total metabolic tumor volume on 18F-fluorodeoxyglucose positron emission tomography/ computed tomography in patients with diffuse large B-cell lymphoma receiving rituximab-containing chemotherapy

Purpose The purpose of this study was to determine the prognostic significance of metabolic parameters on pre-treatment 18F-fluorodeoxyglucose positron emission tomography/ computed tomography (FDG PET/CT), in patients with diffuse large B-cell lymphoma (DLBCL) receiving rituximab-containing therapy. Materials and Methods From September 2009 to December 2014, DLBCL patients who had received FDG PET/CT scans for staging were enrolled. The maximal standardized uptake value of tumor (SUVt) was recorded. The metabolic tumor volume (MTV) was the volume of lesion with an elevated SUV greater than 2.5. The total lesion glycolysis (TLG) was the sum of the products of MTV and mean SUV in all measured lesions. Univariate and multivariate analyses were used to assess the prognostic significance of maximal SUVt, total MTV, TLG and other clinical parameters. Results There were 118 patients enrolled in this study. The median follow-up time was 28.7 months. The 5-year progression-free survival (PFS) for patients with higher and lower total MTV was 32.3% and 66.0% respectively (p = 0.0001). The 5-year overall survival (OS) for patients with higher and lower total MTV was 34.3% and 69.9% respectively (p < 0.0001). Multivariate analysis revealed, besides IPI, that total MTV was independently predictive for PFS (HR: 2.31, 95% CI: 1.16 – 4.60, p = 0.0180) and OS (HR: 2.38, 95% CI: 1.12 – 5.04, p = 0.024). TLG and maximal SUV of tumor were not independent prognostic factors. Conclusions An elevated total MTV was a predictor for shorter PFS and OS in patients with DLBCL receiving rituximab-containing therapy, independent of IPI.
DSP-Based Intelligent Adaptive Control System Using Recurrent Functional-Link-Based Petri Fuzzy-Neural-Network for Servo Motor Drive

This paper presents an intelligent adaptive control system (IACS) using a recurrent functional-linkbased Petri fuzzy-neural-network (RFLPFNN) for induction motor (IM) servo drive to achieve high dynamic performance. The proposed IACS comprises a RFLPFNN controller and a robust controller. The RFLPFNN controller is used as the main tracking controller to mimic an optimal control law while the robust controller is proposed to compensate the difference between the optimal control law and the RFLPFNN controller. Moreover, the structure and parameter-learning of the RFLPFNN are performed concurrently. Furthermore, an on-line parameter training methodology, which is derived based on the Lyapunov stability analysis and the back propagation method, is proposed to guarantee the asymptotic stability of the IACS for the IM servo drive. In addition, to relax the requirement for the bound of minimum approximation error and Taylor higher-order terms, an adaptive control law is utilized to estimate the mentioned bounds. A computer simulation is developed and an experimental system is established to validate the effectiveness of the proposed IACS. All control algorithms are implemented in a TMS320C31 DSP-based control computer. The simulation and experimental results confirm that the IACS grants robust performance and precise response regardless of load disturbances and IM parameters uncertainties. Key-Words: Functional-link neural-networks (FLNNs), intelligent control, indirect field-orientation control (IFOC), induction motor, Lyapunov satiability theorem, Petri net (PN), fuzzy-neural-network, robust control.
Making Components Fit: SPINing

The more popular it is to build an application from reusable software components, the more desperate is the need for showing correctness of such a composition. This requires on one hand, being able to formally specify behavior of software components, while, on the other hand, providing appropriate tool support for verification of correctness of the composition. In this paper, we suggest use of the formalism of extended behavior protocols and present a tool chain for verification of composition correctness of component applications. The advantage of the proposed approach is using a well-tested and supported model checker Spin as a backend. As a proof of the concept, we share our experience with application of the method.
Supervisor selection or allocation and continuity of supervision: Ph.D. students’ progress and outcomes

This article reports part of an Australian longitudinal study which examined the patterns evident in the relationships Ph.D. students and supervisors developed and the ways they worked together. The participants were 21 Ph.D. students and their main supervisors. Data were collected via interviews conducted between 1995 and 1998. Three interviews were conducted separately for each student and supervisor. This report focuses on the allocation of supervisors to students and continuity of supervision in relation to students’ progress and satisfaction with supervision. From this small sample it appears students who felt involved in supervisor selection, whose topics were matched with their supervisor’s expertise and who developed good interpersonal working relationships with supervisors were more likely to make good progress and be satisfied. This was more likely when supervisors were experienced and senior academics or the student had two active supervisors. Disruptions caused by a temporary change of supervisor created problems and delays. Suggestions to overcome this are made.
Family Environment and Adolescent Depressive Symptoms and Antisocial Behavior: A Multivariate Genetic Analysis.

Measures of family environment often show substantial differences between children in the same family and are thus nonshared environment candidates. A key question is whether differential environments are related to differential outcomes when genetic differences between children in the same family are controlled. Parent and child reports and observations of family interactions were used to assess familial negativity and adolescents' depressive symptoms and antisocial behavior in a genetically informative sample of 719 same-sex sibling pairs ranging from 10 to 18 years old. Analyses revealed that parental and sibling negativity is significantly related to adolescent adjustment through nonshared environmental processes, although genetic factors account for most of the association between parental negativity and adolescent adjustment.
Epstein-Barr Virus Thymidine Kinase Is a Centrosomal Resident Precisely Localized to the Periphery of Centrioles

ABSTRACT The thymidine kinase (TK) encoded by Epstein-Barr virus (EBV) differs not only from that of the alphaherpesviruses but also from that of the gamma-2 herpesvirus subfamily. Because cellular location is frequently a determinant of regulatory function, to gain insight into additional role(s) of EBV TK and to uncover how the lymphocryptovirus and rhadinovirus enzymes differ, the subcellular localizations of EBV TK and the related cercopithecine herpesvirus-15 TK were investigated. We show that in contrast to those of the other family members, the gamma-1 herpesvirus TKs localize to the centrosome and even more precisely to the periphery of the centriole, tightly encircling the tubulin-rich centrioles in a microtubule-independent fashion. Centrosomal localization is observed in diverse cell types and occurs whether the protein is expressed independently or in the context of lytic EBV infection. Surprisingly, analysis of mutants revealed that the unique N-terminal domain was not critical for targeting to the centrosome, but rather, peptide sequences located C terminal to this domain were key. This is the first herpesvirus protein documented to reside in the centrosome, or microtubule-organizing center, an amembranous organelle that regulates the structural biology of the cell cycle through control of chromosome separation and cytokinesis. More recently, proteasome-mediated degradation of cell cycle regulatory proteins, production and loading of antigenic peptides onto HLA molecules, and transient homing of diverse virion proteins required for entry and/or egress have been shown to be coordinated at the centrosome. Potential implications of centrosomal localization for EBV TK function are discussed.
Towards joint attention for a domestic service robot - person awareness and gesture recognition using Time-of-Flight cameras

Joint attention between a human user and a robot is essential for effective human-robot interaction. In this work, we propose an approach to person awareness and to the perception of showing and pointing gestures for a domestic service robot. In contrast to previous work, we do not require the person to be at a predefined position, but instead actively approach and orient towards the communication partner. For perceiving showing and pointing gestures and for estimating the pointing direction a Time-of-Flight camera is used. Estimated pointing directions and shown objects are matched to objects in the robot's environment. Both the perception of showing and pointing gestures as well as the accurary of estimated pointing directions have been evaluated in a set of different experiments. The results show that both gestures are adequatly perceived by the robot. Furthermore, our system achieves a higher accuracy in estimating the pointing direction than is reported in the literature for a stereo-based system. In addition, the overall system has been successfully tested in two international RoboCup@Home competitions and the 2010 ICRA Mobile Manipulation Challenge
Phenomenology and classification of dystonia: A consensus update

This report describes the consensus outcome of an international panel consisting of investigators with years of experience in this field that reviewed the definition and classification of dystonia. Agreement was obtained based on a consensus development methodology during 3 in‐person meetings and manuscript review by mail. Dystonia is defined as a movement disorder characterized by sustained or intermittent muscle contractions causing abnormal, often repetitive, movements, postures, or both. Dystonic movements are typically patterned and twisting, and may be tremulous. Dystonia is often initiated or worsened by voluntary action and associated with overflow muscle activation. Dystonia is classified along 2 axes: clinical characteristics, including age at onset, body distribution, temporal pattern and associated features (additional movement disorders or neurological features); and etiology, which includes nervous system pathology and inheritance. The clinical characteristics fall into several specific dystonia syndromes that help to guide diagnosis and treatment. We provide here a new general definition of dystonia and propose a new classification. We encourage clinicians and researchers to use these innovative definition and classification and test them in the clinical setting on a variety of patients with dystonia. © 2013 Movement Disorder Society