gebhart/patrepeval huggingface dataset:
Conserved Regulation of MAP Kinase Expression by PUF RNA-Binding Proteins (2007)

Mitogen-activated protein kinase (MAPK) and PUF (for Pumilio and FBF [fem-3 binding factor]) RNA-binding proteins control many cellular processes critical for animal development and tissue homeostasis. In the present work, we report that PUF proteins act directly on MAPK/ERK-encoding mRNAs to downregulate their expression in both the Caenorhabditis elegans germline and human embryonic stem cells. In C. elegans, FBF/PUF binds regulatory elements in the mpk-1 3' untranslated region (3' UTR) and coprecipitates with mpk-1 mRNA; moreover, mpk-1 expression increases dramatically in FBF mutants. In human embryonic stem cells, PUM2/PUF binds 3'UTR elements in both Erk2 and p38alpha mRNAs, and PUM2 represses reporter constructs carrying either Erk2 or p38alpha 3' UTRs. Therefore, the PUF control of MAPK expression is conserved. Its biological function was explored in nematodes, where FBF promotes the self-renewal of germline stem cells, and MPK-1 promotes oocyte maturation and germ cell apoptosis. We found that FBF acts redundantly with LIP-1, the C. elegans homolog of MAPK phosphatase (MKP), to restrict MAPK activity and prevent apoptosis. In mammals, activated MAPK can promote apoptosis of cancer cells and restrict stem cell self-renewal, and MKP is upregulated in cancer cells. We propose that the dual negative regulation of MAPK by both PUF repression and MKP inhibition may be a conserved mechanism that influences both stem cell maintenance and tumor progression.
Label-informed cardiac magnetic resonance image synthesis through conditional generative adversarial networks (2022)

Synthesis of a large set of high-quality medical images with variability in anatomical representation and image appearance has the potential to provide solutions for tackling the scarcity of properly annotated data in medical image analysis research. In this paper, we propose a novel framework consisting of image segmentation and synthesis based on mask-conditional GANs for generating high-fidelity and diverse Cardiac Magnetic Resonance (CMR) images. The framework consists of two modules: i) a segmentation module trained using a physics-based simulated database of CMR images to provide multi-tissue labels on real CMR images, and ii) a synthesis module trained using pairs of real CMR images and corresponding multi-tissue labels, to translate input segmentation masks to realistic-looking cardiac images. The anatomy of synthesized images is based on labels, whereas the appearance is learned from the training images. We investigate the effects of the number of tissue labels, quantity of training data, and multi-vendor data on the quality of the synthesized images. Furthermore, we evaluate the effectiveness and usability of the synthetic data for a downstream task of training a deep-learning model for cardiac cavity segmentation in the scenarios of data replacement and augmentation. The results of the replacement study indicate that segmentation models trained with only synthetic data can achieve comparable performance to the baseline model trained with real data, indicating that the synthetic data captures the essential characteristics of its real counterpart. Furthermore, we demonstrate that augmenting real with synthetic data during training can significantly improve both the Dice score (maximum increase of 4%) and Hausdorff Distance (maximum reduction of 40%) for cavity segmentation, suggesting a good potential to aid in tackling medical data scarcity.
Influence of platinum group metal-free catalyst synthesis on microbial fuel cell performance (2017)

Platinum group metal-free (PGM-free) ORR catalysts from the Fe-N-C family were synthesized using sacrificial support method (SSM) technique. Six experimental steps were used during the synthesis: 1) mixing the precursor, the metal salt, and the silica template; 2) first pyrolysis in hydrogen rich atmosphere; 3) ball milling; 4) etching the silica template using harsh acids environment; 5) the second pyrolysis in ammonia rich atmosphere; 6) final ball milling. Three independent batches were fabricated following the same procedure. The effect of each synthetic parameters on the surface chemistry and the electrocatalytic performance in neutral media was studied. Rotating ring disk electrode (RRDE) experiment showed an increase in half wave potential and limiting current after the pyrolysis steps. The additional improvement was observed after etching and performing the second pyrolysis. A similar trend was seen in microbial fuel cells (MFCs), in which the power output increased from 167 ± 2 μW cm<sup>-2</sup> to 214 ± 5 μW cm<sup>-2</sup>. X-ray Photoelectron Spectroscopy (XPS) was used to evaluate surface chemistry of catalysts obtained after each synthetic step. The changes in chemical composition were directly correlated with the improvements in performance. We report outstanding reproducibility in both composition and performance among the three different batches.
Fuse and Mix (2022)

Analog computing has been recognized as a promising low-power alternative to digital counterparts for neural network acceleration. However, conventional analog computing is mainly in a mixed-signal manner. Tedious analog/digital (A/D) conversion cost significantly limits the overall system's energy efficiency. In this work, we devise an efficient analog activation unit with magnetic tunnel junction (MTJ)-based analog content-addressable memory (MACAM), simultaneously realizing nonlinear activation and A/D conversion in a fused fashion. To compensate for the nascent and therefore currently limited representation capability of MACAM, we propose to mix our analog activation unit with digital activation dataflow. A fully differential framework, SuperMixer, is developed to search for an optimized activation workload assignment, adaptive to various activation energy constraints. The effectiveness of our proposed methods is evaluated on a silicon photonic accelerator. Compared to standard activation implementation, our mixed activation system with the searched assignment can achieve competitive accuracy with >60% energy saving on A/D conversion and activation.
Supplementary Material from Developing Standards for Breakthrough Therapy Designation in Oncology (2023)

&lt;p&gt;Supplementary Material: Case Studies of Recent Therapeutic Breakthroughs PDF file 98K, This describes four recent breakthroughs (3 in oncology and 1 in cystic fibrosis)&lt;/p&gt;
The Future of Lung Cancer (2010)

Current treatments for lung cancer have limited effectiveness and unfortunately, therefore, prognosis remains poor. Major insights into the molecular pathogenesis of lung cancers have led to new and exciting approaches to improve prevention, detection, staging and treatment of lung cancer. This chapter reviews recent advances and discusses the potential clinical applications of these novel strategies, in the future.
Androgen Blockade Does Not Affect Sleep-disordered Breathing or Chemosensitivity in Men with Obstructive Sleep Apnea (1992)

As sleep apnea is more prevalent in men and testosterone has known effects on sleep apnea and chemosensitivity, reduction of androgen activity may influence sleep-disordered breathing and respiratory control. We studied the effect of 1 wk of treatment with flutamide, a nonsteroidal antiandrogen, on sleep, respiration, and ventilatory control in eight men with sleep apnea. Results on flutamide were compared with two baseline studies performed before and after the drug treatment period. Although effective androgen blockade was achieved as evidenced by increased hormone levels, flutamide had no effect on sleep architecture or chemoresponsiveness to hypoxia and hypercapnia. There was a trend towards a reduction in respiratory disturbance index in both NREM and REM sleep (41 +/- 4 baseline versus 34 +/- 3 flutamide, p = 0.09 NREM; 53 +/- 4 baseline versus 48 +/- 3 flutamide, p = 0.16 REM), but this was not significant. Our results indicate that androgen blockade had no clinically significant effect on sleep, sleep-disordered breathing, or chemosensitivity in patients with moderate to severe sleep apnea. More specific blockers such as gonadotrophin-releasing hormone analogs may have more clinical effect or, alternatively, androgen blockade may be more beneficial in patients with milder sleep apnea.
Nonlinearity mitigation with carrier phase estimation for coherent receivers with higher-order modulation formats (2009)

We investigate the nonlinearity mitigation with carrier phase estimation for coherent PolMux-16QAM and PolMux-16ASK-PSK using carrier phase estimation. The performance is demonstrated for various transmission rates, neighbor channels as well as compensated and uncompensated links.
Stencil Mask Technology for Electron-Beam Projection Lithography (2003)

The development of silicon stencil masks for cell projection lithography (CPL), electron projection lithography (EPL), low-energy electron-beam-proximity-projection lithography (LEEPL), and low-energy electron-beam lithography (LEB) is described. To satisfy the required pattern accuracy of the stencil masks, such as critical dimension and image placement, we developed a high-aspect stencil pattern formation technique to achieve a side-wall angle of over 90 deg and a membrane stress control technique using a stress-correction layer. In addition, for fabricating low-magnification stencil masks, we developed a new mask substrate with a sputtered scattering silicon membrane and a sputtered intermediate stopper layer as an etching stopper. We selected CrNx as the intermediate layer material, which demonstrated high performance in stencil mask fabrication. By improving the CrNx film qualities, its durability to dry and wet etching of backside silicon was improved. In order to improve the pattern image placement accuracy caused by membrane stress changes during stencil pattern formation, we developed a new and simple technique using a stress correction layer, which also functions as a silicon deep-etching mask. By using this functional layer, the total stress change in the pattern field in a mask pattern formation process was reduced to within 5 N/m, which corresponds to less than a 10 nm pattern image placement (IP) error.
The solutions for 3D-NAND processes with Canon's latest KrF scanner (2017)

The NAND type flash-memory is now used not only on smart phones or tablet PCs, but also adopted on infrastructures such as servers, etc. To enlarge the data capacity, the planer type NAND flash memory will need further miniaturization of the circuit pattern, whereas 3D-NAND allows far more capacity growth per wafer, without stressful miniaturization, since the transistor is formed vertically. However, there are a lot of technical challenges for 3D-NAND processes. In this report, we would like to precisely share Canon's approach, on our lithography scanner system, FPA-6300ES6a, towards the above mentioned challenges, which enables low-cost 3D-NAND flash memory mass-production.
Study of OLSR for Real-time Media Streaming over 802.11 Wireless Network in Software Emulation Environment (2010)

In this paper we present a setup to study the real-time traffic carrying performance of optimized Link State Routing (OLSR) protocol using software emulation. We emulate the IEEE 802.11 MAC/PHY using the EMANE software emulator, on a cluster of machines, for different multi-hop wireless scenarios. As an instance of real-world usage scenario, we study the performance of real-time streaming media over a mesh network supported by OLSR. In particular, we study the effect of mobility and background traffic on carried load and jitter. We propose to extend this emulation setup to test the real-time performance of prototype routing protocols such as Stable Path Topology Control (SPTC) and other real-time applications.
Early and late treatment‐related morbidity following radical cystectomy (2004)

The risk of treatment-related morbidity was high and careful patient selection before cystectomy seems important. The lack of standard criteria regarding how to report morbidity makes comparison with other studies difficult.
The functional properties of DsbG, a thiol‐disulfide oxidoreductase from the periplasm of Escherichia coli (1998)

Genetic studies have recently identified DsbG, a new member of the dsb group of redox proteins, which catalyze protein disulfide bond formation in the periplasm of Escherichia coli. We now demonstrate that DsbG functions primarily as an oxidant during protein disulfide bond formation, which is consistent with the low stability of its active site disulfide bond. There are indications, however, that the substrate range of DsbG may be narrower than the other periplasmic oxidative enzymes, DsbA and DsbC. Our observations further elaborate the pathway of disulfide bond formation in E. coli.
Lipopolythiourea Transfecting Agents: Lysine Thiourea Derivatives (2007)

Synthetic vectors represent an alternative to recombinant viruses for gene transfer. We have recently explored the transfection potential of a class of noncationic lipids bearing thiourea moieties as DNA-associating headgroups. The encouraging results obtained with lipopolythioureas derived from serinol prompted us to further investigate this family of vectors. In the present study, we considered the transfection properties of a series of derivatives based on a different thiourea polar headgroup bearing a lysine scaffold. The synthesis of these compounds could be readily achieved in three steps with good yields. We found that these lipopolythioureas (LPT) might be considered as alternative systems for gene transfection since their activity reached the same magnitude range as that of cationic vectors in the presence of serum. LPT with 14-carbon length chains appeared to be more efficient as a transfecting agent than the ones with shorter chains. Toxicity studies proved that the hydration film method led to particles well tolerated both by the cells in vitro and by the mice in vivo. The ability to induce gene expression in vivo was demonstrated by intratumoral injection. Finally, biodistribution studies showed that the quantity recovered in blood circulation, 2 h after systemic injection, was improved as compared to that in cationic lipids.
Improvements to Enable the Large Scale Synthesis of 1-{[(2S,3S,4S)-3-Ethyl-4-fluoro-5-oxopyrrolidin-2-yl]methoxy}-7-methoxyisoquinoline-6-carboxamide (PF-06650833) (2018)

An improved process for the large scale synthesis of 1-{[(2S,3S,4S)-3-ethyl-4-fluoro-5-oxopyrrolidin-2-yl]methoxy}-7-methoxyisoquinoline-6-carboxamide (1), a candidate currently in clinical development, was developed. Key objectives were to eliminate chromatographic purifications, to maximize the reproducibility of each step, and to improve the yield and efficiency of each step relative to the previous discovery syntheses of 1. This work was focused on improvements to the synthesis of the stereochemically complex lactam 2. Steps of particular concern were the preparation of the unsaturated lactam 6, the cuprate conjugate addition reaction to produce 7, and the conversion of 7 to 8 with a high degree of diastereoselection. The solutions to these challenges have permitted the synthesis of 2 in excess of 100 kg, which in turn has permitted 1 to be prepared in sufficient amounts to support further development.
Better detect iron deficiency to treat it better, a realistic goal (2023)

Martial deficiency is the most common nutritional deficiency. The measurement of two biomarkers, transferrin saturation coefficient (TSC) and ferritin, makes it possible to distinguish the two etiological forms of this deficiency, absolute or functional, and to quantify it. We studied the frequency with which these two tests were prescribed in the follow-up of 96,724 patients who received iron supplementation between January 2006 and December 2015. These tests were prescribed in only one third of the treatment sequences, and even less in the post-treatment period. Patients with chronic diseases were more likely to benefit from iron supplementation, but this was still largely inadequate. Iron supplementation is therefore most often applied without identification of the etiology involved or estimation of the effectiveness of the treatment. A review of the literature is presented to compare CST and ferritin in the management of martial deficiency.
In VitroEffects of Retinoids on the Proliferation and Differentiation Features of Epstein-Barr Virus-Immortalized B Lymphocytes (1998)

Retinoids have been shown to be effective in the chemoprevention and treatment of certain human malignancies. In this review, we will summarize our recent results concerning the effects of retinoids on the proliferation and differentiation of Epstein-Barr virus (EBV)-immortalized lymphoblastoid B-cell lines (LCLs), an in vitro model of EBV-related lymphoproliferative disorders arising in immunosuppressed hosts. Retinoids proved to be powerful inhibitors of the proliferation of EBV-infected LCLs in vitro, with 13-cis-retinoic acid (RA), all-trans-RA, and 9-cis-RA being the most effective compounds. Of note, retinoid-induced growth arrest in vitro appears irreversible at drug concentrations (10(-6) mol/L) which may be reached in man after oral systemic therapy. The antiproliferative activity exerted by retinoids on LCLs is a generalized phenomenon usually associated with a progressive accumulation in G0/G1 phases of treated cells. The strong upregulation of p27Kip1 invariably observed in cells exposed to retinoids may contribute to the decreased number of cycling cells, probably by inhibiting the transition from the G1 to S phase. Moreover, we obtained evidence indicating that the antiproliferative effects of retinoids are not dependent on the induction of terminal differentiation of EBV-immortalized B lymphocytes. In fact, the modifications induced by retinoids relative to LCL morphology, phenotype (downregulation of CD19, HLA-DR, and s-Ig, and upregulation of CD38 and c-Ig), and IgM production were highly variable among the lines tested and often only slightly relevant. Finally, the antiproliferative activity exerted by retinoids on LCLs is not mediated by a direct modulation of viral latent antigens, since EBNA-2 and LMP- downregulation was a late event detected only in some cell lines. These results indicate that retinoids may be useful in the medical treatment of EBV-related lymphoproliferative disorders of immunosuppressed patients, particularly in the earlier phases of these diseases.
Multispectral optoacoustic tomography (MSOT): Monitoring neurovascular changes in a mouse repetitive traumatic brain injury model (2023)

MSOT imaging has the potential as a noninvasive in vivo imaging method to monitor neurovascular changes and assess therapeutics in mouse models of rTBI. In comparison to standard methods of tracking inflammation and BBB disruption, MSOT can be used multiple times throughout the course of injury without the need for surgery. Thus, MSOT is especially useful in research of rTBI models for screening therapeutics, and with further technological improvements may be extended for use in rTBI patients.
Efficient and Dual SIM Aware Resource Scheduler for 5G and Future Networks (2020)

5G (Fifth Generation) wireless technology introduced a paradigm shift in the way networks are designed to provide services. Unlike 4G (Fourth Generation) which is primarily focusing on achieving high data rates, 5G networks are expected to support varying uses cases as captured in [5]. In order to support these services more efficiently with the allotted spectrum capacity, the most important challenge is to design an optimal physical resource scheduling algorithms which maximizes resource utilization and minimizes resource wastage. The widely used resource scheduling algorithms like Proportional Fair (PF) and Round Robin (RR) are designed to work effectively only for single SIM (Subscriber Identity Module) mobile phones also referred as UE (User Equipment). However, large population is already using UEs that support DSDS (Dual SIM Dual Standby) feature and numbers are increasing. Hence, enhancing these algorithms only to support additional use cases defined in 5G would not suffice to solve the problem of resource wastage. As the 5G network is primarily designed to provide services to Single SIM (SS) UEs, the above mentioned algorithms allocates resources to DSDS UEs in a similar fashion to SS UEs even though DSDS UEs may not be utilizing these resources due to the nature of dual SIM operation. As the network is not aware of dual SIM operation, it continues to allocate resources leading to lot of resource wastage. To overcome this stated problem, we propose a novel network resource scheduler called DANS DANS (Dual SIM Aware Network Scheduler) which modifies the conventional PF and RR algorithms to enhance their performance. The proposed DANS detect the outage in the active communication of all DSDS UEs with network and reduce resource allocation to such DSDS UEs to negligible levels till the duration of outage. In case of DSDS UEs, this outage refers to interruption in active communication of one SIM due to usage of communication hardware by other SIM. We simulated DANS in NS-3 setup and its performance is compared with schedulers with uses conventional PF and RR algorithms.
UV Light–inactivated HSV-1 Stimulates Natural Killer Cell–induced Killing of Prostate Cancer Cells (2019)

Herein we demonstrate that ultraviolet light-inactivated Herpes Simplex Virus-1 (UV-HSV-1) stimulates peripheral blood mononuclear cells (PBMCs) to lyse both androgen-sensitive and androgen-independent prostate cancer (PrCA) cell lines, but not the benign prostatic hyperplastic epithelial cell line, BPH-1, and is 1000-10,000-fold more potent at stimulating this killing than ultraviolet light-inactivated Vesicular Stomatitis Virus, adenovirus, reovirus or cytomegalovirus. Among PBMCs, natural killer (NK) cells appear to be a major cell type involved in this killing and UV-HSV-1 appears to directly and potently stimulate NK cell expression of CD69, degranulation, cytokine production, and migration to IL-8 in PC3 conditioned medium. We also found that UV-HSV-1 stimulates glycolysis in PBMCs and NK cells, and that 2-deoxyglucose and the protein kinase C inhibitor, Go6976, and the NFκB inhibitor, Bay 11-7082, all abrogate UV-HSV-1 activated killing of PC3 cells by PBMCs and NK cells. Using neutralizing anti-Toll-like receptor 2 (TLR2) we found that UV-HSV-1, like HSV-1, activates NK cells via TLR2. Taken together, these results are consistent with Toll-like receptor 2 ligands on UV-HSV-1 stimulating TLR2 on NK cells to activate protein kinase C, leading to enhanced glycolysis and NFκB activation, both of which play a critical role in this anti-PrCA innate immune response. Importantly, UV-HSV-1 synergizes with IL-15 to increase the cytolytic activity of PBMCs against PC3 cells and there was considerable donor-to-donor variation in killing ability. These results support the preclinical development of UV-HSV-1 as an adjuvant, in combination with IL-15, for cell infusions of healthy, preselected NK cells to treat PrCA.
Modeling and Control of a 3-DOF pendulum-like manipulator (2011)

This work deals with the kinematic and dynamic modeling of a 3-DOF, under-actuated, pendulum-like manipulator and its control system. The cable-based device is capable of completing point-to-point planar motions, driving the end-effector from a starting pose to a goal pose, by means of two actuators only. The device relies on parametric excitation to control the oscillations of the variable-length pendulum. Unlike a previous work, the dynamic model introduced here is consistent with the assumption of cable-based device. Several control strategies are compared through numerical simulations.