Miracle-dz/UniFAR-FTUs huggingface dataset:
Baseline Peripheral Blood Biomarkers Associated with Clinical Outcome of Advanced Melanoma Patients Treated with Ipilimumab

Purpose: To identify baseline peripheral blood biomarkers associated with clinical outcome following ipilimumab treatment in advanced melanoma patients. Experimental Design: Frequencies of myeloid-derived suppressor cells (MDSC) and regulatory T cells (Treg), serum lactate dehydrogenase (LDH), routine blood counts, and clinical characteristics were assessed in 209 patients. Endpoints were overall survival (OS) and best overall response. Statistical calculations were done by Kaplan–Meier and Cox regression analysis, including calibration and discrimination by C-statistics. Results: Low baseline LDH, absolute monocyte counts (AMC), Lin−CD14+HLA-DR−/low-MDSC frequencies, and high absolute eosinophil counts (AEC), relative lymphocyte counts (RLC), and CD4+CD25+FoxP3+-Treg frequencies were significantly associated with better survival, and were considered in a combination model. Patients (43.5%) presenting with the best biomarker signature had a 30% response rate and median survival of 16 months. In contrast, patients with the worst biomarkers (27.5%) had only a 3% response rate and median survival of 4 months. The occurrence of adverse events correlated with neither baseline biomarker signatures nor the clinical benefit of ipilimumab. In another model, limited to the routine parameters LDH, AMC, AEC, and RLC, the number of favorable factors (4 vs. 3 vs. 2–0) was also associated with OS (P < 0.001 for all pairwise comparisons) in the main study and additionally in an independent validation cohort. Conclusions: A baseline signature of low LDH, AMC, and MDSCs as well as high AEC, Tregs, and RLC is associated with favorable outcome following ipilimumab. Prospective investigation of the predictive impact of these markers following ipilimumab and other treatments, e.g., PD-1 antibodies, is warranted. Clin Cancer Res; 22(12); 2908–18. ©2016 AACR.
Nanomanipulation of a single carbon nanotube for the fabrication of a field-effect transistor

Field-effect transistors (FETs) have been developed from silicon based to carbon nanotubes (CNTs) based, and the fabrication space became three-dimensionl (3D). Such fabrication process requires to accurately assemble a single CNT in 3D. However, most of the current assembly technologies were used for planar structures but not for 3D structures. In this study, we aim to use nanomanipulation based on a scanning electron microscopy (SEM) to realize the 3D assembly. To achieve this goal, we first proposed a novel 3D structure named Tri-gate CNT-FET. The Tri-gate CNT-FET has three cuboid micro-electrodes and it is wrapped by CNTs with front, top and back sides. After fabrication of the electrodes, a single CNT was picked up by an Au-coated probe and placed on the front side of the three micro-electrodes by suspending over a substrate to a certain height. The CNT pick-up and placement highly depended on attractive interactions at a CNT-metal contact interface by van der Waals force. Electron beam induced deposition (EBID) technique was then used to deposit Tungsten at the interface to fix CNT. Mechanical cutting was finally carried out to release the probe from the assembled structure. The whole assembly was achieved by using only one nanomanipulator. Experiment results validated our proposed 3D assembly method for the fabrication of Tri-gate CNT-FET.
The NCI/CIT MicroArray Database (mAdb) System -Bioinformatics for the Management and Analysis of Affymetrix and Spotted Gene Expression Microarrays

A scalable, modular, enterprise-level system for both microarray databasing and analysis over the Internet has been developed over the past four years by the National Cancer Institute's Center for Cancer Research in collaboration with NIH's Center for Information Technology. This completely Web-based system, called mAdb (for microArray database), is currently supporting over 810 registered users and collaborators at NIH and contains over 22,000 microarray experiments, making it one of the largest collections of microarray data in existence. In addition, the mAdb system has been ported for the Netherlands Cancer Institute, the Genome Institute of Singapore, and the CDC. This system has been used for a wide variety of scientific experiments spanning the range from cancer to studies of early development, and for human, mouse, rat, yeast, and numerous microbial organisms.
Innervation of the human tooth

The purpose of this investigation is to add to our knowledge and to clarify the conflicting literature concerning the innervation of the human tooth. Studies of the teeth of animals and man have so far failed to demonstrate satisfactorily the terminal distribution of nerves within the teeth. Our knowledge at the present time is inadequate and controversial. The descriptions found in anatomical texts, dental texts, and current references are incomplete and in disagreement. The general course of the nerves in the pulp have been described adequately. There is no controversy concerning the fact that the main nerve enters the apical foramina and that it accompanies the pulpal vessels in their course parallel with the long axis of the tooth. The mode of branching and the terminations of the fibers are the principal points of the disagreement, that is, do the fibers enter the dentin or do they terminate solely in the pulp?
Analysis of Gamma-Band Activity from Human EEG Using Empirical Mode Decomposition

The purpose of this paper is to determine whether gamma-band activity detection is improved when a filter, based on empirical mode decomposition (EMD), is added to the pre-processing block of single-channel electroencephalography (EEG) signals. EMD decomposes the original signal into a finite number of intrinsic mode functions (IMFs). EEGs from 25 control subjects were registered in basal and motor activity (hand movements) using only one EEG channel. Over the basic signal, IMF signals are computed. Gamma-band activity is computed using power spectrum density in the 30–60 Hz range. Event-related synchronization (ERS) was defined as the ratio of motor and basal activity. To evaluate the performance of the new EMD based method, ERS was computed from the basic and IMF signals. The ERS obtained using IMFs improves, from 31.00% to 73.86%, on the original ERS for the right hand, and from 22.17% to 47.69% for the left hand. As EEG processing is improved, the clinical applications of gamma-band activity will expand.
PHYSIOLOGICALLY BASED PHARMACOKINETIC MODELING OF STYRENE AND STYRENE OXIDE RESPIRATORY-TRACT DOSIMETRY IN RODENTS AND HUMANS

Styrene (ST) is widely used to manufacture resins, glass-reinforced plastics, and a number of commercially important polymers (Miller et al., 1994). Chronic ST inhalation studies in rodents have demonstrated unique species specificity in the resulting pulmonary toxicity and carcinogenicity. Increased incidences of pulmonary bronchioloalveolar tumors have been observed in mice, but not in rats. No other tumor type was increased significantly in either species. Clara cells lining the respiratory epithelium metabolize ST to styrene 7,8-oxide (SO), which is cytotoxic and weakly genotoxic. Rodent species show marked differences in the distribution and regional density of Clara cells within the respiratory tract, as well as in their capacity to produce and eliminate SO. A mode of action-based physiologically based pharmacokinetic (PBPK) model was developed to predict the concentration of ST and SO in blood, liver, and the respiratory-tract tissues, particularly in terminal bronchioles (target tisue), in order to conduct interspecies extrapolations and determine the extent to which there is a pharmacokinetic basis for the observed species specificity. This PBPK model has a multicompartment description of the respiratory tract and incorporates species-specific quantitative information on respiratory-tract physiology, cellular composition, and metabolic capacity. The model is validated against multiple data sets, including blood, liver, and whole lung tissue concentration of ST and SO following multiple routes of exposure. The trend in neoplastic incidences in mice correlated well with model-estimated SO concentration in the terminal bronchioles. The PBPK model predicts a 10-fold lower SO concentration in the terminal bronchioles in rats compared to mice, which is consistent with the observed species sensitivity to the development of respiratory-tract neoplasms. The model-based analysis suggests that humans would be expected to be 100-fold less sensitive to ST-inducted lung tumors than mice, based on pharmacokinetic differences. Pharmacodynamic factors are also expected to contribute to species sensitivity, potentially augmenting pharmacokinetics-based differences.
Local Feature Detection by Higher Order Riesz Transforms on Images

An important issue in image analysis is the detection of features in images. Problems occur, when the images contain noise or are rotated. An example for a rotation invariant feature is the apex angle. However, apex angle detection is only expedient, on a special class of images, therefore in this thesis only images with up to two overlaid intrinsically one dimensional structures are considered. Images belonging to this class also allow the calculation of the local main orientation. Together, local main orientation and apex angle provide access to the computation of both orientations and vice versa. The estimation of the local main orientation and apex angle are done by applying Riesz transforms up to third order to a local neighborhood of the image. In order to accomplish that, a new interpretation of the Riesz transform is studied, which in turn provides a new interpretation of the monogenic signal and the monogenic curvature tensor. Another direct result of the new interpretation of the Riesz transform is the ability to detect the rotation angle between two otherwise identical images. In order to implement Riesz transforms up to the third order they need to be combined with a suitable bandpass filter. The Laplacian of Poisson allows the development of new filter kernels for the second and third order Riesz transforms. The implementation of this method is compared to an implementation of a well-known method using image gradients and computing the orientations of up to two overlaid structures that has been developed in Lübeck.
Controlled, systematic, and efficient code replacement for running java programs

In this paper we present PROSE, a system that performs reversible and systematic changes to running Java applications without requiring them to be shut down. PROSE is motivated by scenarios such as hotfixes, online program instrumentation and debugging, and evolution of critical legacy applications. In PROSE, changes to running applications are performed by replacing method bodies. To select which code to replace, PROSE supports matching based on both type information and regular expressions. New code can invoke the method it replaces, facilitating code evolution. Changes are composable, and may be reordered or selectively withdrawn at any time. Furthermore, the dynamic changes are expressed as Java classes rather than through an additional programming language. We describe the architecture of PROSE, the challenges of using aggressive inlining to achieve performance, and use standard benchmarks to demonstrate code performance comparable with, or better than, compile-time systems from the Aspect-Oriented Programming community.
Efficient Multicast Packet Authentication

Providing authentication mechanisms for IP-Multicast streams is paramount for the development of large scale commercial multicast content delivery applications. This need is particularly strong for the delivery of real time content, such as live video/audio news events or financial stock quote distribution. However, this turns out to be a quite challenging problem for many reasons. First, the authentication of the multicast data must be verifiable by a potentially very large number of untrusted recipients. Second, since multicast communication protocols are almost always best effort, the authentication mechanisms needs to authenticate received content despite the potential loss of some packets. Finally, the authentication mechanism needs to be efficient enough to cope with real time data and should have a small communication overhead. We propose a new multicast authentication scheme designed to authenticate real time multicast packet streams with a potentially unlimited number of recipients. This scheme provides both integrity and nonrepudiation of origin, and in a majority of situations, it performs with less overhead in bytes per packet than previously proposed practical real time stream authentication schemes.
A Whole-Body Systems Approach to ASD

Although autism is defi ned at the level of behavior, it is becoming clear that there is much more than behavior impairments to autism. For a long time, the focus of autism research has been on genetics and neurobiology. The high heritability factor has supported a strong interest in genetics, while the brain basis of behavior, combined with fi ndings documenting brain differences in autism, has supported a neurobiological focus. In recent years, a growing amount of attention has been devoted to a range of somatic features in autism. Prominent among these are disturbances in gastrointestinal, immune, and metabolic functioning. Understanding the role these features play in autism is complicated by the fact that they do not present in any one uniform fashion, nor are abnormalities in these domains measurable in every autistic individual. While somatic features have often been classifi ed as “secondary” in comparison to the “core” features of autism, this classifi cation is increasingly challenged by advances in peer-reviewed scientifi c research, and more generally, in our understanding of gut-brain and immune-brain relationships, and of metabolic infl uences on brain functioning. Going forward, it will be important to develop awareness of these whole-body and systems issues in autism, in order both to include them in thorough appreciation and documentation of clinical history, and to more fully appreciate scientifi c and clinical advances in these autism-relevant domains.
Secretion and processing of insulin precursors in yeast.

A series of dibasic insulin precursors including proinsulin was expressed and secreted from Saccharomyces cerevisiae. Recombinant plasmids were constructed to encode fusion proteins consisting of a modified mating factor alpha 1 leader sequence and an insulin precursor. The leader sequence serves to direct the fusion protein into the secretory pathway of the cell and to expose it to the Lys-Arg processing enzyme system. The secreted peptides were purified from the fermentation broth and characterized by sequencing and amino acid analysis. Processing at one or both dibasic sequences was shown in proinsulin and in other insulin precursors containing a short spacer peptide in place of the C peptide. In contrast, no processing was observed in the absence of a spacer peptide in the insulin precursor molecule, e.g., B-Lys-Arg-A (where A and B are the A and B chain of human proinsulin, respectively). This type of single-chain insulin precursors isolated from such constructions could be enzymatically converted into insulin by treatment with trypsin and carboxypeptidase B. The above results suggest that the C-peptide region of proinsulin serves to direct the trypsin-like converting enzyme to process at the two dibasic sequences. We propose that in hormone precursors in general the spacer peptides serve to expose dibasic sequences for processing.
Automatic Design of Scheduling Policies for Dynamic Multi-objective Job Shop Scheduling via Cooperative Coevolution Genetic Programming

A scheduling policy strongly influences the performance of a manufacturing system. However, the design of an effective scheduling policy is complicated and time consuming due to the complexity of each scheduling decision, as well as the interactions among these decisions. This paper develops four new multi-objective genetic programming-based hyperheuristic (MO-GPHH) methods for automatic design of scheduling policies, including dispatching rules and due-date assignment rules in job shop environments. In addition to using three existing search strategies, nondominated sorting genetic algorithm II, strength Pareto evolutionary algorithm 2, and harmonic distance-based multi-objective evolutionary algorithm, to develop new MO-GPHH methods, a new approach called diversified multi-objective cooperative evolution (DMOCC) is also proposed. The novelty of these MO-GPHH methods is that they are able to handle multiple scheduling decisions simultaneously. The experimental results show that the evolved Pareto fronts represent effective scheduling policies that can dominate scheduling policies from combinations of existing dispatching rules with dynamic/regression-based due-date assignment rules. The evolved scheduling policies also show dominating performance on unseen simulation scenarios with different shop settings. In addition, the uniformity of the scheduling policies obtained from the proposed method of DMOCC is better than those evolved by other evolutionary approaches.
Assessing and Teaching Scope, Mutation, and Aliasing in Upper-Level Undergraduates

Scope, aliasing, mutation, and parameter passing are fundamental programming concepts that interact in subtle ways, especially in complex programs. Research has shown that students have substantial misconceptions on these topics. But this research has been done largely in CS1 courses, when students' programming experience is limited and problems are necessarily simple. What happens later in the curriculum? Does more programming experience iron out these misconceptions naturally, or are interventions required? This paper explores students' understanding of these topics in the context of a programming languages class for third- and fourth-year CS majors. Our pre- and post-tests pose questions in two programming languages to gauge whether upper-level students transfer knowledge between languages. Many students held misconceptions about these concepts at the start of the course. Students made progress in only some languages and topics, and cross-language transfer does not occur naturally. We also discuss various pedagogic activities we used to engage students with these concepts, and provide data and student opinion on their effectiveness.
Multiple Intelligences as predictors Cognitive and Metacognitive Self-regulated Learning

The present study aimed to investigate the relationship between multiple intelligences and self-regulated learning components of Iranian EFL university students majoring in Teaching English and English Translation. To this end, a sample of 150 intermediate level students from Imam Khomeini International University in Qazvin and Islamic Azad University in Takestan were selected. Data were gathered by means of questionnaires and were analyzed using stepwise multiple regression procedures. Results indicated that in relation to the first research question, verbal and existential intelligences were predictors of cognitive self-regulated learning. About second research question related to the field of study, findings revealed that visual and verbal intelligences made significant contributions to predicting metacognitive self-regulated learning. Likewise, there was a negative relationship between visual intelligences and metacognitive selfregulation. The findings have implications for teachers, learners, and material developers.
A Randomised Controlled Trial of a Social Support Intervention

Background: Much evidence has accumulated over the last three decades that low social support is related to both mental and physical health. Despite this large and convincing literature, reviewers have noted that there exists remarkably little evidence that social support can be increased by an appropriate intervention. This study reports on the development and evaluation of a new intervention for social support which takes account of the stress-buffering and direct effect models. Method: Eighty-one individuals scoring low on social support were randomly allocated to the intervention or a waiting-list control condition. Treatment consisted of 10 weekly sessions administered in a group format, and 49 participants (nine males) completed assessments at the beginning and end of a 10-week period, and at 10-week follow-up (intervention condition only). Results: The intervention proved to be successful at increasing functional support but not structural support. The intervention was also successful in increasing the social skill of self-disclosure, and decreasing depression. Gains made between pre- and post-treatment were maintained at 10-week follow-up. Conclusions: Based on published analyses of the effects of social support on health, the results imply that the intervention would be useful for stress-buffering purposes, but not for the general health-promoting effects that are associated with good social integration.
Long-Standing Nonkin Relationships of Older Adults in the Netherlands and the United States

The main research questions of this study were (1) How long have adults in the Netherlands and the United States known members of their nonkin networks? (2) What are the predictors of long-standing nonkin relationships? and (3) Which predictors are recognizable in both societies? The data came from the NESTOR-LSN survey (3,229 adults aged 55 to 89 years in the Netherlands) and from the Northern California Community Study (n = 1,050, with 225 respondents aged 55 to 91 years in the United States). In both countries, the duration of nonkin relationships was related to the absence of network-disturbing variables (e.g., the number of years since the last move), network-sustaining variables (e.g., distance to nonkin), and other network properties (e.g., homogeneity). Nationally based differences were also observed (e.g., having a car was related to stable relationships only in the United States, and the special integrative functions of exclusive friendships were elicited only in Europe).
Artificial noise design for discriminatory channel estimation in wireless MIMO systems

Discriminatory channel estimation (DCE) is a secrecy-enhancing training and channel estimation technique previously proposed in the literature to enhance the effective channel quality difference between the main and the eavesdropper channels (i.e., the channels experienced by the legitimate receiver and the eavesdropper, respectively) in the channel estimation phase. In the past, this was achieved by developing techniques to first provide the transmitter with preliminary estimates of the main channel and by then emitting training signals that embed AN in the null space of the estimated main channel to disrupt the channel estimation at the eavesdropper. Extending upon previous works on DCE, this work proposes a general AN design that does not rely on the availability of the null space of the estimated main channel and, thus, does not require the transmitter to have more antennas than the receiver. In particular, the AN covariance matrix, the pilot signal power, and the linear estimator are jointly determined to minimize the channel estimation error at the receiver subject to a constraint below on the channel estimation error at the eavesdropper. The design is obtained by adopting an alternating optimization approach where the AN and pilot signals at the transmitter and the estimator at the receiver are optimized in turn until no further decrease in channel estimation error is observed. The effectiveness of the proposed scheme is demonstrated through computer simulations.