Miracle-dz/UniFAR-FTUs huggingface dataset:
Delineation of a Conserved Arrestin-Biased Signaling Repertoire In Vivo

Biased G protein–coupled receptor agonists engender a restricted repertoire of downstream events from their cognate receptors, permitting them to produce mixed agonist-antagonist effects in vivo. While this opens the possibility of novel therapeutics, it complicates rational drug design, since the in vivo response to a biased agonist cannot be reliably predicted from its in cellula efficacy. We have employed novel informatic approaches to characterize the in vivo transcriptomic signature of the arrestin pathway-selective parathyroid hormone analog [d-Trp12, Tyr34]bovine PTH(7-34) in six different murine tissues after chronic drug exposure. We find that [d-Trp12, Tyr34]bovine PTH(7-34) elicits a distinctive arrestin-signaling focused transcriptomic response that is more coherently regulated across tissues than that of the pluripotent agonist, human PTH(1-34). This arrestin-focused network is closely associated with transcriptional control of cell growth and development. Our demonstration of a conserved arrestin-dependent transcriptomic signature suggests a framework within which the in vivo outcomes of arrestin-biased signaling may be generalized.
Verteporfin PDT for subfoveal occult CNV in AMD: two-year results of a randomized trial

ABSTRACT Objective: To determine whether verteporfin photodynamic therapy (PDT) can safely reduce the risk of vision loss in patients with subfoveal occult with no classic choroidal neovascularization (CNV) due to age-related macular degeneration. Research design and methods: Eligible patients were ≥50 years of age with lesion size ≤6 disc areas and best-corrected vision 20/40–20/200. A total of 364 patients with occult with no classic CNV were randomly assigned 2 : 1 to verteporfin PDT (n = 244) or placebo (n = 120). The primary outcome measures were loss of ≥15 and ≥30 letters of visual acuity (VA) from baseline at 12 and 24 months. Results: A total of 37% and 47% of verteporfin-treated patients versus 45% and 53% of placebo recipients lost ≥15 letters of VA at month 12 and month 24, respectively; 16% and 23% of verteporfin-treated patients versus 17% and 25% of placebo recipients lost ≥30 letters at month 12 and month 24, respectively. These differences were not statistically significant. Four (1.6%) verteporfin-treated patients and one placebo patient (who received verteporfin in error) experienced an acute severe VA decrease; all five patients recovered some degree of vision. No unexpected ocular or systemic adverse events were identified. Conclusions: Verteporfin PDT in the treatment of occult with no classic CNV was safe and well-tolerated. The differences between the two groups in the primary efficacy variables were not significant. Baseline characteristics and patient selection methods may have contributed to the small treatment effect. Trial registration: ClinicalTrials.gov identifier: NCT00121407.
Design of 2x2 Mimo OFDM Architecture for Fixed Wimax

Input Multiple Output Orthogonal Frequency Division Multiplexing technology is an advanced transmission technique for wireless communication systems. In this paper, the 64 point pipeline FFT/IFFT processor is introduced for efficient implementation of OFDM architecture. The IFFT processor is used to modulate the subcarrier in transmitter section and FFT processor demodulate the subcarrier in receiver section in the architecture. Our design adopts a single-path delay feedback style requiring less memory space and reconfigurable complex constant multiplier and bit parallel multiplier used in pipeline FFT/IFFT processor, instead of using ROM's to store twiddle factors that consuming lower power. The design of ROM-less FFT/IFFT processor is applied to OFDM architecture in the IEEE 802.16d communication standard. The result shows overall architecture design using the FFT/IFFT processor that gives efficient power, area and timing specifications considerably. Index Terms
CAR-modified T-cell therapy for cancer: an updated review

The use of chimeric antigen receptor (CAR)-modified T cells is a promising approach for cancer immunotherapy. These genetically modified receptors contain an antigen-binding moiety, a hinge region, a transmembrane domain, and an intracellular costimulatory domain resulting in T-cell activation subsequent to antigen binding. Optimal tumor removal through CAR-modified T cells requires suitable target antigen selection, co-stimulatory signaling domain, and the ability of CAR T cells to traffic, persist, and retain antitumor function after adoptive transfer. There are several elements which can improve antitumor function of CAR T cells, including signaling, conditioning chemotherapy and irradiation, tumor burden of the disease, T-cell phenotype, and supplementary cytokine usage. This review outlines four generations of CAR. The pre-clinical and clinical studies showed that this technique has a great potential for treatment of solid and hematological malignancies. The main purpose of the current review is to focus on the pre-clinical and clinical developments of CAR-based immunotherapy.
Using GUI Run-Time State as Feedback to Generate Test Cases

This paper presents a new automated model-driven technique to generate test cases by using feedback from the execution of a "seed test suite" on an application under test (AUT). The test cases in the seed suite are designed to be generated automatically and executed very quickly. During their execution, feedback obtained from the AUT's run-time state is used to generate new, "improved" test cases. The new test cases subsequently become part of the seed suite. This "anytime technique" continues iteratively, generating and executing additional test cases until resources are exhausted or testing goals have been met. The feedback-based technique is demonstrated for automated testing of graphical user interfaces (GUIs). An existing abstract model of the GUI is used to automatically generate the seed test suite. It is executed; during its execution, state changes in the GUI pinpoint important relationships between GUI events, which evolve the model and help to generate new test cases. Together with a reverse- engineering algorithm used to obtain the initial model and seed suite, the feedback-based technique yields a fully automatic, end-to-end GUI testing process. A feasibility study on four large fielded open-source software (OSS) applications demonstrates that this process is able to significantly improve existing techniques and help identify/report serious problems in the OSS. In response, these problems have been fixed by the developers of the OSS in subsequent versions.
MUC (Memory, Unification, Control) and beyond

A neurobiological model of language is discussed that overcomes the shortcomings of the classical Wernicke-Lichtheim-Geschwind model. It is based on a subdivision of language processing into three components: Memory, Unification, and Control. The functional components as well as the neurobiological underpinnings of the model are discussed. In addition, the need for extension of the model beyond the classical core regions for language is shown. The attention network and the network for inferential processing are crucial to realize language comprehension beyond single word processing and beyond decoding propositional content. It is shown that this requires the dynamic interaction between multiple brain regions.
Ready, Set, Go.

Kommen Kinder mit zwei Fremdsprachen zurecht? Das kann man vorbehaltlos bejahen. Kinder, auch solche, deren Muttersprache nicht Englisch ist, kommen auf der Primarstufe mit zwei und gar noch mehr Fremdsprachen zurecht. Erwarten wir von ihnen, dass sie diese Sprachen nach der beschränkten Unterrichtszeit, die ihnen dafür auf der Primarstufe zur Verfügung steht, beherrschen? Sicher nicht. Wir können jedoch von der Motivation der Kinder in diesem Alter profitieren und erwarten, dass sie sich, wenn sie früh mit Englisch anfangen, ihrer eigenen Sprache bewusster werden und für Sprachen allgemein sensibilisiert werden. Um die englische Sprache wirklich gut zu beherrschen, werden sie sich aber nach wie vor über längere Zeit damit beschäftigen müssen.
On the Role of Discourse Markers for Discriminating Claims and Premises in Argumentative Discourse

This paper presents a study on the role of discourse markers in argumentative discourse. We annotated a German corpus with arguments according to the common claim-premise model of argumentation and performed various statistical analyses regarding the discriminative nature of discourse markers for claims and premises. Our experiments show that particular semantic groups of discourse markers are indicative of either claims or premises and constitute highly predictive features for discriminating between them.
Optimization of Multimodal Imaging of Mesenchymal Stem Cells Using the Human Sodium Iodide Symporter for PET and Cerenkov Luminescence Imaging

Purpose The use of stably integrated reporter gene imaging provides a manner to monitor the in vivo fate of engrafted cells over time in a non-invasive manner. Here, we optimized multimodal imaging (small-animal PET, Cerenkov luminescence imaging (CLI) and bioluminescence imaging (BLI)) of mesenchymal stem cells (MSCs), by means of the human sodium iodide symporter (hNIS) and firefly luciferase (Fluc) as reporters. Methods First, two multicistronic lentiviral vectors (LV) were generated for multimodal imaging: BLI, 124I PET/SPECT and CLI. Expression of the imaging reporter genes was validated in vitro using 99mTcO4 − radioligand uptake experiments and BLI. Uptake kinetics, specificity and tracer elution were determined as well as the effect of the transduction process on the cell's differentiation capacity. MSCs expressing the LV were injected intravenously or subcutaneously and imaged using small-animal PET, CLI and BLI. Results The expression of both imaging reporter genes was functional and specific. An elution of 99mTcO4 − from the cells was observed, with 31% retention after 3 h. After labeling cells with 124I in vitro, a significantly higher CLI signal was noted in hNIS expressing murine MSCs. Furthermore, it was possible to visualize cells injected intravenously using BLI or subcutaneously in mice, using 124I small-animal PET, CLI and BLI. Conclusions This study identifies hNIS as a suitable reporter gene for molecular imaging with PET and CLI, as confirmed with BLI through the expression of Fluc. It supports the potential for a wider application of hNIS reporter gene imaging and future clinical applications.
Developing thai economic model to study cost-effectiveness of switching to bupropion compared to combination with bupropion after the failure of an SSRI for major depressive disorder.

OBJECTIVE To present an economic model and cost-effectiveness estimates of switching to bupropion compared to combination with bupropion after failure of an SSRI for major depressive disorder (MDD). MATERIAL AND METHOD An economic model was developed to simulate the transitions of Thai outpatients with nonpsychotic MDD who had no remission or could not tolerate the SSRI citalopram and received either sustained-release bupropion monotherapy as switching strategy or sustained-release bupropion plus citalopram as combination strategy. Clinical data were obtained form 2 trials of the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study. The four event probabilities: remission rates, rates of non-remission, discontinuation rates due to intolerance, and incidence of serious adverse events were estimated. Direct costs included drug cost, hospitalizations, and electroconvulsive therapy (ECT). The primary outcome considered in the model was a remission of symptoms. Outputs were measured in terms of costs per remission and costs per quality-adjusted life-years (QALYs). RESULTS In the base-case analysis, the total direct costs with a bupropion switch were 22,937 THB per remission and 29,346 THB per remission with a bupropion combination. Compared with combination option, switching to bupropion also had lower total cost per QALY (28,672 THB vs. 36,682 THB) and had cost saving of 21.8%. The incremental cost-effectiveness of the combination regimen compared with the switching regimen was 6,409 THB per remission gained and 8,011 THB per QALY gained. In a sensitivity analysis, combination strategy dominated switching strategy if the value of the transitional probability of remission changed to a value of greater than 0.547. CONCLUSION The economic model indicated that treatment of MDD patients who fail to achieve remission from an SSRI with a switch to bupropion is a cost-effectiveness treatment option compared with a combination of SSRI with bupropion.
On Characterizations of Large Language Models and Creativity Evaluation

Incredible as they may be, Large Language Models (LLMs) have their limitations. While they generate high-quality texts, excel at stylistic reproduction, and tap into an immense pool of information, they can produce wildly inaccurate responses. The hype around LLMs led to them being characterized as “reasoning”, “sentient”, or “knowing” like humans. We examine these characterizations and discuss what LLMs can’t do and what they are surprisingly good at. LLMs are still susceptible to traditional issues with AI, probabilities are not knowledge, and they are not in the world. Nonetheless, LLMs, despite not being human, have great potential to perform various creative tasks. We conclude that LLMs are beyond “mere generation” and perceivable as creative, but we may need to reassess some frameworks for creativity evaluation.
Different Conceptualizations of IS Post-Adoptive Behavior

This paper proposes the examination of IS post-adoptive behavior from four different perspectives: 1) the traditional perspective grounded in TAM and research on habit, 2) the ecological perspective which emphasizes the interaction of users with IT without the necessity of cognition, 3) the affect-object perspective which highlights the role of emotion in determining behavior, and 4) the sensemaking perspective which states that cognition occurs after users are confronted with unexpected outcomes while using IT. In order to explore these different conceptualizations of IS post-adoptive behavior, a methodology based on case-studies and experiments is proposed. Thus, the proposed research goes beyond TAM to consider other theoretical perspectives in IS post-adoptive behaviors from disparate disciplines that will provide an enriching understanding of the phenomena under study.
Impact of Multi-Micronutrient Fortified Rice on Hemoglobin, Iron and Vitamin A Status of Cambodian Schoolchildren: a Double-Blind Cluster-Randomized Controlled Trial

In Cambodia, micronutrient deficiencies remain a critical public health problem. Our objective was to evaluate the impact of multi-micronutrient fortified rice (MMFR) formulations, distributed through a World Food Program school-meals program (WFP-SMP), on the hemoglobin concentrations and iron and vitamin A (VA) status of Cambodian schoolchildren. The FORISCA-UltraRice+NutriRice study was a double-blind, cluster-randomized, placebo-controlled trial. Sixteen schools participating in WFP-SMP were randomly assigned to receive extrusion-fortified rice (UltraRice Original, UltraRice New (URN), or NutriRice) or unfortified rice (placebo) six days a week for six months. Four additional schools not participating in WFP-SMP were randomly selected as controls. A total of 2440 schoolchildren (6–16 years old) participated in the biochemical study. Hemoglobin, iron status, estimated using inflammation-adjusted ferritin and transferrin receptors concentrations, and VA status, assessed using inflammation-adjusted retinol-binding protein concentration, were measured at the baseline, as well as at three and six months. Baseline prevalence of anemia, depleted iron stores, tissue iron deficiency, marginal VA status and VA deficiency were 15.6%, 1.4%, 51.0%, 7.9%, and 0.7%, respectively. The strongest risk factors for anemia were hemoglobinopathy, VA deficiency, and depleted iron stores (all p < 0.01). After six months, children receiving NutriRice and URN had 4 and 5 times less risk of low VA status, respectively, in comparison to the placebo group. Hemoglobin significantly increased (+0.8 g/L) after three months for the URN group in comparison to the placebo group; however, this difference was no longer significant after six months, except for children without inflammation. MMFR containing VA effectively improved the VA status of schoolchildren. The impact on hemoglobin and iron status was limited, partly by sub-clinical inflammation. MMFR combined with non-nutritional approaches addressing anemia and inflammation should be further investigated.
Exploring geodynamics at different depths with shear wave splitting

Dynamic processes in the Earth's interior are the dominant driving forces behind the continuous deformation-related reworking of its surface. The characterization of deformation caused by past tectonic events near the Earth's surface as well as mapping of ongoing dynamic-driven processes deep inside the Earth are therefore major objectives to understand the dynamics of our planet. Seismic anisotropy, the direction-dependence of seismic wave speed, is directly related to deformation processes and can be "felt" by passing seismic waves. Although seismic anisotropy is a well-known phenomenon, the individual contributions from different depth ranges are still debated. However, recordings available from dense and large-aperture seismic station networks, provide the opportunity for resolving both, small-scale variations relatively close to the surface as well as so far unknown structures at greater depth. In 2012, an international seismological field experiment, called ScanArray, was initiated. The combination of 72 temporary broadband stations with long-running national permanent stations and arrays resulted in a recording network consisting of 266 seismic stations in total that were distributed across the Fennoscandian peninsula in northern Europe. Fennoscandia opens the opportunity to study the (past) geodynamical evolution of crustal and upper mantle structures far away from currently active plate tectonics. The main goal of this study is to characterize the anisotropic structure beneath the Fennoscandian peninsula as well as in the Earth's lowermost mantle based on a uniformly processed data set provided by the ScanArray network. For this purpose single-event shear wave splitting analysis was performed using core-refracted shear waves (SKS, SKKS, PKS) of around 3000 globally distributed teleseismic earthquakes (1998-2017). In order to improve the data coverage at a recording station, a new plugin (StackSplit) for a widely applied analysis software (SplitLab) is introduced allowing efficient and flexible handling of multi-event splitting measurements. Based on the massive seismic data set, this study provides a comprehensive characterization of the distinct lateral and backazimuthal variations of the shear wave splitting pattern at individual stations and across the ScanArray network. These variations partly correlate well with different tectonic regimes related to past large-scale lithospheric deformation due to ancient collision events. Detailed forward modeling allowed to explore different anisotropic structural geometries including anisotropy with a dipping axis of symmetry. Although, the majority of the shear wave splitting observations can be explained with high reliability, for a small number of recording stations non-unique anisotropy models were found which fit the observed data equally well. Furthermore, this study sheds light on lowermost mantle anisotropy located in the so-called D" layer just atop the core-mantle boundary in ~ 2900 km depth. This unexpected discovery is…
UvA-DARE (

In this paper we describe our participation in INEX 2010 in the Ad Hoc Track and the Book Track. In the Ad Hoc track we investigate the impact of propagated anchor-text on article level precision and the impact of an element length prior on the within-document precision and recall. Using the article ranking of an document level run for both document and focused retrieval techniques, we ﬁnd that focused retrieval techniques clearly outperform document retrieval, especially for the Focused and Restricted Relevant in Context Tasks, which limit the amount of text than can be returned per topic and per article respectively. Somewhat surprisingly, an element length prior increases within-document precision even when we restrict the amount of retrieved text to only 1000 characters per topic. The query-independent evidence of the length prior can help locate elements with a large fraction of relevant text. For the Book Track we look at the relative impact of retrieval units based on whole books, individual pages and multiple pages.
in Applications with MicroGuards

Application compartmentalization and privilege separation are our primary weapons against ever-increasing security threats and privacy concerns on connected devices. Despite signiﬁcant progress, it is still challenging to privilege separate inside an application address space and in multithreaded environments, particularly on resource-constrained and mobile devices. We propose MicroGuards, a lightweight kernel modi-ﬁcation and set of security primitives and APIs aimed at ﬂexible and ﬁne-grained in-process memory protection and privilege separation in multi-threaded applications. MicroGuards take advantage of hardware support in modern CPUs and are high-level enough to be adaptable to various architectures. This paper focuses on enabling MicroGuards on embedded and mobile devices running Linux kernel and utilizes tagged memory support to achieve good performance. Our evaluation show that Micro-Guards add small runtime overhead (less than 3.5%), minimal memory footprint, and are practical to get integrated with existing applications to enable ﬁne-grained privilege separation.
Predicting depth , surface normals and semantic labels with a common multi-scale convolutional architecture

This paper presents a special CNN architecture which set the state-of-the-art of three different computer vision tasks at the same time, notably depth and surface normal prediction in monocular images as well as semantic labeling of RGB(-D) data. The CNN architecture operates at multiple scales, each of which also incorporates the output from the previous scale for progressive prediction refinements. This paper embeds the approach into the context of related work, presents the proposed architecture and shows selected results.
Solving Totally Unimodular LPs with the Shadow Vertex Algorithm

We show that the shadow vertex simplex algorithm can be used to solve linear programs in strongly polynomial time with respect to the number $n$ of variables, the number $m$ of constraints, and $1/\delta$, where $\delta$ is a parameter that measures the flatness of the vertices of the polyhedron. This extends our recent result that the shadow vertex algorithm finds paths of polynomial length (w.r.t. $n$, $m$, and $1/\delta$) between two given vertices of a polyhedron. Our result also complements a recent result due to Eisenbrand and Vempala who have shown that a certain version of the random edge pivot rule solves linear programs with a running time that is strongly polynomial in the number of variables $n$ and $1/\delta$, but independent of the number $m$ of constraints. Even though the running time of our algorithm depends on $m$, it is significantly faster for the important special case of totally unimodular linear programs, for which $1/\delta\le n$ and which have only $O(n^2)$ constraints.