Miracle-dz/UniFAR-FTUs huggingface dataset:
Pathophysiologie Senescent CD 4 + CD 28 – T Cells Are a Possible Trigger of Primary Osteoporosis 01

s der Posterpräsentationen pathophysiology. CD4+FoxP3+ Treg, on the other hand, are important for maintaining peripheral tolerance to self-antigens. In human SLE, however, both the absolute numbers and the functionality of these cells are reduced and correlate inversely with disease activity, but direct evidence for a central role of Treg malfunction in SLE pathophysiology is still missing. Objective We therefore analyzed if Treg-deficient scurfy mice share typical features of SLE. Methods Scurfy mice have dysfunctional Treg due to a genetic defect in the transcription factor foxP3 which is crucial for their development and function. 9 scurfy mice and 9 matched controls (C57Bl/6 mice) were analyzed at 4–5 weeks of age. By immunofluorescence, immunoblotting, and ELISA, we screened for autoantibodies and also performed haematological workup. Specimen of skin and inner organs were stained with H/E and screened for inflammation by a blinded pathologist; kidneys were also stained with PAS and by direct immunofluorescence. We analyzed joint pathology after staining with H/E (overview), tolloidin blue (cartilage), and TRAP (osteoclasts). Immunohistochemistry allowed for further analysis of the cellular composition of the inflammatory infiltrate, which was finally quantified by image analysis systems (Osteomeasure and HistoQuest, respectively). Results We confirmed previous reports that scurfy mice spontaneously develop severe systemic autoimmune disease which includes pneumonitis and haematological abnormalities (anaemia, lymphopenia) similar to those seen in SLE. We here show that scurfy, but not control mice, exhibit various additional features typical for SLE: They tested positive for ANA (100 %) as well as for anti-dsDNAabs (100 %), anti-Sm (80 %), anti-RNP (90 %) – but not for anti-Ro, -La, or -Scl70-abs; immunoblot – and had elevated anti-histone-ab levels (145 ± 58 vs 66 ± 36 U/ml, p = 0.003, ELISA); scurfy also developed severe interface dermatitis and mesangial glomerulonephritis resembling lupus nephritis WHO2 (seen in 8 out of 9 scurfy [88.9 %] vs 0/6 [0 %] of controls, respectively, p = 0.0014). In contrast to controls, scurfy mice showed increased cartilage degradation (destained/normal cartilage area 0.050 ± 0.009 vs 0.018 ± 0.003, p = 0.004) and developed inflammatory arthritic infiltrates (mean area 0.38 ± 0.25 mm2). There were no osteoclasts within the joint space and, consecutively, no erosions. Besides fibroblasts, the inflammatory infiltrate consisted mainly of CD3+ T lymphocytes (13 %), with 7 % B cells and < 3 % neutrophils and macrophages. In transfer experiments, CD4+ T cells from scurfy, but not from controls, induced production of ANA and dsDNA-abs in athymic nude mice. Conclusion Our observations support the hypothesis that lupuslike disease develops in the absence of functional Treg. The Role of CD11c+ Dendritic Cells in Inflammatory
ON THE GENERATION OF AN OPTIMIZED FRACTIONAL CLOUDINESS TIME SERIES USING A MULTI-SENSOR APPROACH

Five active and passive remote sensing techniques that observe clouds are operated nearly continuously at the Cabauw Experimental Site for Atmospheric Research [CESAR]. The instruments involved are: 2 types of ceilometers, including the sensor that is used operationally by KNMI for generating the automated cloud observations; a cloud radar; an infrared pyrgeometer; a scanning pyrometer and a total sky imager. The total cloud cover has been determined for each of these techniques at 10-minute intervals and their characteristics have been investigated. Next an algorithm was designed to derive a continuous and optimized record of fractional cloudiness that takes into account the strength and weaknesses of the individual observational techniques. The algorithm accounts for breaks in instrumental availability and assigns an error to the data. The fractional cloudiness characteristics of the individual instruments and the synthetic algorithm have also been evaluated against a climatology of human cloud observations. The paper presents details and the challenges encountered in the evaluation of the cloudiness obtained with the individual instruments and the construction of the optimized fractional cloudiness series. Particularly the lack of a reference is a serious issue. The measure of uncertainty of the resulting series and the relative contribution of each instrument will be discussed.
Parametric yield optimization with mesh adaptive direct search

Random manufacturing process variations can affect the performance of an integrated circuit to the extent that a significant number of the manufactured circuits must be discarded because they fail to satisfy the specifications. To increase the yield, random variations must be taken into account in the design phase. This can be achieved by choosing appropriate values for the parameters accessible to the circuit designer. This process (circuit sizing) can be automated by means of parametric optimization. As simulators do not compute sensitivities, derivative-free optimization algorithms, like mesh adaptive direct search (MADS), are well suited for optimizing circuits. We propose an MADS-based approach for finding a circuit that satisfies the minimum yield requirement. The approach is tested on two integrated circuit-sizing problems. The results demonstrate its effectiveness and speed.
Inverter Dynamic Electro-Thermal Simulation with Experimental Verification

A full electro-thermal simulation of a three-phase space-vector-modulated (SVM) inverter is performed and validated with measurements. Electrical parameters are extracted over temperature for the insulated gate bipolar transistor (IGBT) and diode electro-thermal models. A thermal network methodology that includes thermal coupling between devices is applied to a six-pack module package containing multiple IGBT and diode chips. The electro-thermal device models and six-pack module thermal model are used to simulate SVM inverter operation at several power levels. Good agreement between model and measurement is obtained for steady state operation of the three-phase inverter. In addition, transient heating of a single IGBT in the six-pack module is modeled and validated, yielding good agreement. Acknowledgements I want to thank my three advisors Dr. Jason Lai (Virginia Tech), Dr. Allen Hefner (National Institute of Standard Technology), and Dr. Ty McNutt (Northrop Grumman). Dr. Lai provided me with a strong background in power electronic systems and provided guidance with the system level simulation. Dr. Allen Hefner helped with IGBT parameter extraction and device characterization. He also provided guidance in creating the thermal model methodology used in this work. Dr. McNutt helped with Diode parameter extraction and provided assistance on the system level simulation and actual writing of the thesis. A special thanks to Dave Berning (National Institute of Standard Technology) for providing the test circuits and methodology for measurements. I want to thank Chris Smith (Virginia Tech) for helping take thermal measurements using system hardware. I also want to thank my family. Thank you, Mom, Dad, Shelly and Ruthie for your continued support, understanding and patience. I also want to thank my good friend Ali Hajjiah for our countless discussion sessions on all class related material. A special mention to my other colleagues while in school: Doug Sterk, Arthur Ball, Sean Finnigan, Sean Blackburn and Andrew Hutchinson. A special thanks to my girlfriend Lori who has been very patient and supportive of me.
Mobile augmented reality: enhance visualization skills in learning abstract concept in chemistry

For the last few decades, integrating technology in teaching and learning in the classroom has been an important issue. According to Lee et al. (2013), there are several meta-analyses have been conducted in order to examine the specific modes or educational practices that can enhances the effectiveness of student learning and teaching with technology. The digital technologies that being used is now not limited to the usage of computer only. There are others digital technologies also arise which are the mobile devices, digital media creation and distribution tools, video games and social networking sites (Collins & Halversont, 2010).
Chapter 13 Consumer Generated Advertising in Blogs

Of the various online media available to marketers, “Blogs” are the newest and potentially the most attractive. They have become a part of what Deighton and Kornfeld (2007) describes as a “digital interactive transformation in marketing. ” This revolution shows no signs of slowing down and according to a report by Universal-McCann (2009) on the impact of social media, 71 percent of active internet users read blogs. Blog participation has also increased with more people leaving comments (an increase to over 50 percent in 2009). The AbstrAct
Modelling our cities in weather forecasting

Urban weather forecasting within an operational model presents an interesting yet challenging problem. An increasing number of customers require accurate forecasts within these areas and many people are aware of how the cities can be warmer than the surrounding rural areas. However, within an operational weather prediction model, these urban areas are poorly resolved, so it is difficult to be able to model these urban-rural differences well.
The Npro product of classical swine fever virus interacts with I k B a , the NFk B inhibitor

Received 6 December 2007 Accepted 8 April 2008 Classical swine fever virus (CSFV) belongs to the genus Pestivirus and is the causative agent of classical swine fever, a haemorrhagic disease of pigs. The virus replicates in host cells without activating interferon (IFN) production and has been reported to be an antagonist of doublestranded RNA-induced apoptosis. The N-terminal protease (N) of CSFV is responsible for this evasion of the host innate immune response. In order to identify cellular proteins that interact with the N product of CSFV, a yeast two-hybrid screen of a human library was carried out, which identified IkBa, the inhibitor of NF-kB, a transcription factor involved in the control of apoptosis, the immune response and IFN production. The N–IkBa interaction was confirmed using yeast two-hybrid analysis and additional co-precipitation assays. It was also shown that N localizes to both the cytoplasmic and nuclear compartments in stably transfected cells and in CSFVinfected cells. Following stimulation by tumour necrosis factor alpha, PK-15 cell lines expressing N exhibited transient nuclear accumulation of pIkBa, but no effect of CSFV infection on IkBa localization or NF-kB p65 activation was observed.
Miniaturized Micro strip band pass filter for lower UWB applications

-This paper proposes a miniaturized micro strip band pass filter for lower UWB applications, which is designed by using open and short circuited stubs. The filter has pass band from 3.1GHz to 5 GHz having the insertion loss of >-2dB. The return loss of <-10dB has been achieved in the pass band with the maximum of -40dB at 3.23 GHz. The sharp roll-offsat lower and upper cut-off frequencies have been computed. The insertion loss of -33dB has been generated in stop band. The filter is designed on FR 4 dielectric substrate (εr = 4.3) which is available at low cost. The group delay is also a very flat in the pass band. So, this filter will be an important key component in the lower UWB wireless communication.
Jozef Zurada

Credit scoring is the term used by the credit industry to describe methods used for classifying applicants for credit into risk classes according to their likely repayment behavior (e.g. “default” and “non-default”). The credit industry has been using such methods as logistic regression, discriminant analysis, and various machine learning techniques to more precisely identify creditworthy applicants who are granted credit, and non-creditworthy applicants who are denied credit. Accurate classification is of benefit both to the creditor (in terms of increased profit or reduced loss) and to the loan applicant (avoiding overcommitment). This paper examines historical data from consumer loans issued by a financial institution to individuals that the financial institution deemed to be qualified customers. The data set consists of the financial attributes of each customer and includes a mixture of loans that the customers paid off or defaulted upon. The paper uses rule induction methods (decision trees) to predict whether a particular applicant paid off or defaulted upon his/her loan. The main advantage of decision trees is their ability to generate if-then classification rules which are intuitive and easy to understand. Rules could be explained to business managers who would need to approve their implementation as well as loan applicants as the reason for denying a loan. The paper compares the correct classification accuracy rates of several decision tree algorithms with other data mining methods proposed in earlier works.
Controlling Data-Flow in the Cloud

A big obstacle for using cloud services is that users have no control over the locations where their data are stored or processed, respectively. This paper presents a program analysis approach that enables clients to negotiate services with undesired locations. Clients may only use services that guarantee not to use (directly or indirectly) services on undesired locations for processing or storing the clients’ data. In order to increase trust in the answers given by services during the negotiation process, a cryptographic approach similar to Web page certification is proposed. We show that a static data-flow analysis combined with a cryptographic approach ensures that clients’ data do not reach undesired locations in the cloud. Keywordsdata-flow; service-level agreement; cloud security.
Biocompatibility of Nanocellulose-Reinforced PVA Hydrogel with Human Corneal Epithelial Cells for Ophthalmic Applications

Transparent composite hydrogel in the form of a contact lens made from poly(vinyl alcohol) (PVA) and cellulose nanocrystals (CNCs) was subjected to in vitro biocompatibility evaluation with human corneal epithelial cells (HCE-2 cells). The cell response to direct contact with the hydrogels was investigated by placing the samples on top of confluent cell layers and evaluating cell viability, morphology, and cell layer integrity subsequent to 24 h culture and removal of the hydrogels. To further characterize the lens–cell interactions, HCE-2 cells were seeded on the hydrogels, with and without simulated tear fluid (STF) pre-conditioning, and cell viability and morphology were evaluated. Furthermore, protein adsorption on the hydrogel surface was investigated by incubating the materials with STF, followed by protein elution and quantification. The hydrogel material was found to have affinity towards protein adsorption, most probably due to the interactions between the positively charged lysozyme and the negatively charged CNCs embedded in the PVA matrix. The direct contact experiment demonstrated that the physical presence of the lenses did not affect corneal epithelial cell monolayers in terms of integrity nor cell metabolic activity. Moreover, it was found that viable corneal cells adhered to the hydrogel, showing the typical morphology of epithelial cells and that such response was not influenced by the STF pre-conditioning of the hydrogel surface. The results of the study confirm that PVA-CNC hydrogel is a promising ophthalmic biomaterial, motivating future in vitro and in vivo biocompatibility studies.
Time to viral rebound and safety after antiretroviral treatment interruption in postpartum women compared to men.

OBJECTIVE(S) The short-term safety of treatment interruptions, a necessary part of cure studies, is not well-established, particularly in women. We explored viral rebound kinetics and safety in a group of postpartum women discontinuing ART and compared results to males in historical interruption trials. DESIGN Prospective evaluation of time to virologic rebound. METHODS 1,076 asymptomatic, virally suppressed, postpartum women living with HIV enrolled in the PROMISE trial with baseline CD4 cell counts ≥ 350/mm underwent antiretroviral treatment (ART) discontinuation. Proportion with virologic suppression at weeks 4 and 12 were compared to participants in ACTG treatment interruption trials (91% male population). RESULTS In PROMISE, using interval censored methods, the estimated median time to HIV viral rebound was two weeks. An estimated 6% of women would remain virally suppressed at 30 weeks. Of those who had viral rebound by 30 weeks (N = 993), <4% experienced grade 3 or higher laboratory events, and 1% experienced WHO stage 2 or higher clinical events. Overall, <1% of participants progressed from WHO Stage 1 to Stage 2 or higher after discontinuation of ART, and 3.9% experienced a decline in CD4 cell count to < 350/mm or local treatment guidelines. A significantly higher proportion of women in PROMISE (25.4%) were virologically suppressed (<400 copies/mL) at 12 weeks compared to ACTG NWCS 371 participants (6.4%). CONCLUSION Temporary treatment interruptions in healthy, HIV-infected women with high CD4 cell counts can be safe. Potential sex differences need to be considered in cure studies examining time to virologic rebound.
Immuno-PET identifies the myeloid compartment as a key contributor to the outcome of the antitumor response under PD-1 blockade

Significance Immunotherapy, especially blockade of the PD-1/PD-L1 and CTLA-4 axes, has resulted in durable responses in a range of cancers. However, responses remain heterogeneous among patients. Treatment outcome results from changes in the tumor microenvironment imposed by such blockade. Here, we use immuno-PET and single-cell RNA sequencing to increase our understanding of the dynamics of immune cells and their functional status in the tumor microenvironment in response to PD-1 blockade. Our data provide insights into the dynamics of CD8+ T cells and the functional status of the myeloid compartment in response to PD-1 blockade. Immunotherapy using checkpoint-blocking antibodies against PD-1 has produced impressive results in a wide range of cancers. However, the response remains heterogeneous among patients. We used noninvasive immuno-positron emission tomography (PET), using 89Zr-labeled PEGylated single-domain antibody fragments (nanobodies or VHHs), to explore the dynamics and distribution of intratumoral CD8+ T cells and CD11b+ myeloid cells in response to anti–PD-1 treatment in the MC38 colorectal mouse adenocarcinoma model. Responding and nonresponding tumors showed consistent differences in the distribution of CD8+ and CD11b+ cells. Anti–PD-1 treatment mobilized CD8+ T cells from the tumor periphery to a more central location. Only those tumors fully infiltrated by CD8+ T cells went on to complete resolution. All tumors contained CD11b+ myeloid cells from the outset of treatment, with later recruitment of additional CD11b+ cells. As tumors grew, the distribution of intratumoral CD11b+ cells became more heterogeneous. Shrinkage of tumors in responders correlated with an increase in the CD11b+ population in the center of the tumors. The changes in distribution of CD8+ and CD11b+ cells, as assessed by PET, served as biomarkers to gauge the efficacy of anti–PD-1 treatment. Single-cell RNA sequencing of RNA from intratumoral CD45+ cells showed that CD11b+ cells in responders and nonresponders were markedly different. The responders exhibited a dominant population of macrophages with an M1-like signature, while the CD45+ population in the nonresponders displayed an M2-like transcriptional signature. Thus, by using immuno-PET and single-cell RNA sequencing, we show that anti–PD-1 treatment not only affects interactions of CD8+ T cells with the tumor but also impacts the intratumoral myeloid compartment.
Heterochronic regulation of lung development via the Lin28‐Let‐7 pathway

The heterochronic gene Lin28 regulates diverse developmental processes. It was shown previously that global Lin28A overexpression during mouse embryogenesis results in perinatal lethality. However, the reason for this early lethality has not been elucidated. Here, we showed that Lin28A overexpression prevents normal lung development via the inhibition of the Let‐7 micro RNAs, thus causing the perinatal lethality. We further found that Lin28A overexpression in lung mesenchymal cells, but not epithelial cells, is sufficient to recapitulate the lung phenotype. Moreover, we defined the specific time window wherein Lin28A expression exerts its effect. Deep characterization of the transgenic lungs suggests that the Lin28A‐Let‐7 pathway delays the transition from one developmental stage to another but does not completely abrogate the differentiation capacity of the lung progenitor cells. Finally, we suggested that the effect of Lin28A‐Let‐7 on embryonic lung development is mediated at least in part through the TGF‐p1‐signaling pathway. Altogether, these findings define for the first time the Lin28‐Let‐7 pathway as a critical heterochronic regulator of lung development. —Komarovsky Gulman, N. , Armon, L. , Shalit, T. , Urbach, A. Heterochronic regulation of lung development via the Lin28‐Let‐7 pathway. FASEB J. 33, 12008‐12018 (2019). www.fasebj. org
Recent Advances in Coarse-Grained Models for Biomolecules and Their Applications

Molecular dynamics simulations have emerged as a powerful tool to study biological systems at varied length and timescales. The conventional all-atom molecular dynamics simulations are being used by the wider scientific community in routine to capture the conformational dynamics and local motions. In addition, recent developments in coarse-grained models have opened the way to study the macromolecular complexes for time scales up to milliseconds. In this review, we have discussed the principle, applicability and recent development in coarse-grained models for biological systems. The potential of coarse-grained simulation has been reviewed through state-of-the-art examples of protein folding and structure prediction, self-assembly of complexes, membrane systems and carbohydrates fiber models. The multiscale simulation approaches have also been discussed in the context of their emerging role in unravelling hierarchical level information of biosystems. We conclude this review with the future scope of coarse-grained simulations as a constantly evolving tool to capture the dynamics of biosystems.