gebhart/patrepeval huggingface dataset:
Tuberculosis Drug Discovery: Challenges and New Horizons (2022)

Over the past 2000 years, tuberculosis (TB) has claimed more lives than any other infectious disease. In 2020 alone, TB was responsible for 1.5 million deaths worldwide, comparable to the 1.8 million deaths caused by COVID-19. The World Health Organization has stated that new TB drugs must be developed to end this pandemic. After decades of neglect in this field, a renaissance era of TB drug discovery has arrived, in which many novel candidates have entered clinical trials. However, while hundreds of molecules are reported annually as promising anti-TB agents, very few successfully progress to clinical development. In this Perspective, we critically review those anti-TB compounds published in the last 6 years that demonstrate good <i>in vivo</i> efficacy against <i>Mycobacterium tuberculosis</i>. Additionally, we highlight the main challenges and strategies for developing new TB drugs and the current global pipeline of drug candidates in clinical studies to foment fresh research perspectives.
Fully automated prostate magnetic resonance imaging and transrectal ultrasound fusion via a probabilistic registration metric (2013)

In this work, we present a novel, automated, registration method to fuse magnetic resonance imaging (MRI) and transrectal ultrasound (TRUS) images of the prostate. Our methodology consists of: (1) delineating the prostate on MRI, (2) building a probabilistic model of prostate location on TRUS, and (3) aligning the MRI prostate segmentation to the TRUS probabilistic model. TRUS-guided needle biopsy is the current gold standard for prostate cancer (CaP) diagnosis. Up to 40% of CaP lesions appear isoechoic on TRUS, hence TRUS-guided biopsy cannot reliably target CaP lesions and is associated with a high false negative rate. MRI is better able to distinguish CaP from benign prostatic tissue, but requires special equipment and training. MRI-TRUS fusion, whereby MRI is acquired pre-operatively and aligned to TRUS during the biopsy procedure, allows for information from both modalities to be used to help guide the biopsy. The use of MRI and TRUS in combination to guide biopsy at least doubles the yield of positive biopsies. Previous work on MRI-TRUS fusion has involved aligning manually determined fiducials or prostate surfaces to achieve image registration. The accuracy of these methods is dependent on the reader's ability to determine fiducials or prostate surfaces with minimal error, which is a difficult and time-consuming task. Our novel, fully automated MRI-TRUS fusion method represents a significant advance over the current state-of-the-art because it does not require manual intervention after TRUS acquisition. All necessary preprocessing steps (i.e. delineation of the prostate on MRI) can be performed offline prior to the biopsy procedure. We evaluated our method on seven patient studies, with B-mode TRUS and a 1.5 T surface coil MRI. Our method has a root mean square error (RMSE) for expertly selected fiducials (consisting of the urethra, calcifications, and the centroids of CaP nodules) of 3.39 ± 0.85 mm.
SR120819A, an orally‐active and selective neuropeptide Y Y1 receptor antagonist (1995)

An orally-active antagonist of neuropeptide Y (NPY) Y1 receptors, SR 120819A, has been characterized. This compound displays highly selective and competitive affinity for rat, guinea-pig and human (Ki = 15 nM) NPY Y1 receptors. In vitro, SR 120819A blocks the inhibitory effect of NPY on adenylyl cyclase activity in human SK-N-MC cells and that of the selective Y1 agonist, [Leu31,Pro34]NPY, on rabbit vas deferens contraction (pA2 = 7.20 +/- 0.07). In vivo, by intravenous route, this compound acts as an antagonist in anesthetized guinea-pigs and, notably, after oral administration, SR 120819A counteracts the pressor response of [Leu31,Pro34]NPY (5 micrograms/kg i.v.) with a long duration of action (> 4 h at 5 mg/kg p.o.). Thus, SR 120819A is the first orally-effective NPY Y1 receptor antagonist yet described. It could be a useful tool for exploring the role of NPY and the therapeutic relevance of an antagonist at NPY Y1 receptors.
Coordinated Pulses of mRNA and of Protein Translation or Degradation Produce EGF-Induced Protein Bursts (2017)

Protein responses to extracellular cues are governed by gene transcription, mRNA degradation and translation, and protein degradation. In order to understand how these time-dependent processes cooperate to generate dynamic responses, we analyzed the response of human mammary cells to the epidermal growth factor (EGF). Integrating time-dependent transcript and protein data into a mathematical model, we inferred for several proteins their pre-and post-stimulus translation and degradation coefficients and found that they exhibit complex, time-dependent variation. Specifically, we identified strategies of protein production and degradation acting in concert to generate rapid, transient protein bursts in response to EGF. Remarkably, for some proteins, for which the response necessitates rapidly decreased abundance, cells exhibit a transient increase in the corresponding degradation coefficient. Our model and analysis allow inference of the kinetics of mRNA translation and protein degradation, without perturbing cells, and open a way to understanding the fundamental processes governing time-dependent protein abundance profiles.
Proceedings of the adjunct publication of the 26th annual ACM symposium on User interface software and technology (2013)

It is our pleasure to welcome you to the 26th Annual ACM Symposium on User Interface Software and Technology (UIST) 2013, held from October 8-11th, in the historic town and University of St Andrews, Scotland, United Kingdom.

UIST is the premier forum for the presentation of research innovations in the software and technology of human-computer interfaces. Sponsored by ACM's special interest groups on computer-human interaction (SIGCHI) and computer graphics (SIGGRAPH), UIST brings together researchers and practitioners from many areas, including web and graphical interfaces, new input and output devices, information visualization, sensing technologies, interactive displays, tabletop and tangible computing, interaction techniques, augmented and virtual reality, ubiquitous computing, and computer supported cooperative work. The single-track program and intimate size, makes UIST 2013 an ideal place to exchange results at the cutting edge of user interfaces research, to meet friends and colleagues, and to forge future collaborations.

We received a record 317 paper submissions from more than 30 countries. After a thorough review process, the program committee accepted 62 papers (19.5%). Each anonymous submission was first reviewed by three external reviewers, and meta-reviews were provided by two program committee members. If any of the five reviewers deemed a submission to pass a rejection threshold we asked the authors to submit a short rebuttal addressing the reviewers' concerns. The program committee met in person in Pittsburgh, PA, on May 30-31, 2013, to select the papers for the conference. Submissions were finally accepted only after the authors provided a final revision addressing the committee's comments.

In addition to the presentations of accepted papers, this year's program includes a keynote by Raffaello D'Andrea (ETH Zurich) on feedback control systems for autonomous machines. A great line up of posters, demos, (the ninth) annual Doctoral Symposium, and (the fifth) annual Student Innovation Contest (this year focusing on programmable water pumps called Pumpspark) complete the program. We hope you enjoy all aspects of the UIST 2013 program, and that you get to enjoy our wonderful venues and that your discussions and interactions prove fruitful.
Gold(I) Biscarbene Complexes Derived from Vascular‐Disrupting Combretastatin A‐4 Address Different Targets and Show Antimetastatic Potential (2014)

Gold N-heterocyclic carbene (NHC) complexes are an emerging class of anticancer drugs. We present a series of gold(I) biscarbene complexes with NHC ligands derived from the plant metabolite combretastatin A-4 (CA-4) that retain its vascular-disrupting effect, yet address different cellular and protein targets. Unlike CA-4, these complexes did not interfere with tubulin, but with the actin cytoskeleton of endothelial and cancer cells. For the highly metastatic 518A2 melanoma cell line this effect was accompanied by a marked accumulation of cells in the G1 phase of the cell cycle and a suppression of active prometastatic matrix metalloproteinase-2. Despite these mechanistic differences the complexes were as strongly antivascular as CA-4 both in vitro in tube formation assays with human umbilical vein endothelial cells, and in vivo as to blood vessel disruption in the chorioallantoic membrane of chicken eggs. The antiproliferative effect of the new gold biscarbene complexes in a panel of six human cancer cell lines was impressive, with low sub-micromolar IC50 values (72 h) even against CA-4-refractory HT-29 colon and multidrug-resistant MCF-7 breast carcinoma cells. In preliminary studies with a mouse melanoma xenograft model the complexes led to significant decreases in tumor volume while being very well tolerated.
The Regulation of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone-Induced Lung Tumor Promotion by Estradiol in Female A/J Mice (2014)

Epidemiological studies indicate that women are at a higher risk developing lung cancer than men are. It is suggested that estrogen is one of the most important factors in lung cancer development in females. Additionally, cigarette smoke, and environmental pollutants, such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), may play salient roles in female lung carcinogenesis. However, the mechanisms responsible for the interaction of these factors in the promotion of lung cancer are still poorly understood. The present study was designed to explore two ideas: first, the synergistic lung tumorigenic effects of 4-(methylnitrosamino)-1-(3-pyridyl)-butanol (NNK) combined with TCDD, 17β-estradiol (E2) or both through a long-term treatment experiment, and second, to identify early changes in the inflammatory and signaling pathways through short-term treatment experiments. The results indicate that A/J mice given E2 had strong effects in potentiating NNK-induced activation of MAPK signaling, NFκB, and COX-2 expression. In the long-term exposure model, E2 had a strong tumor promoting effect, whereas TCDD antagonized this effect in A/J mice. We conclude that treatment with NNK combined with either E2 or TCDD induces lung carcinogenesis and the promotion effects could be correlated with lung inflammation. E2 was shown to potentiate NNK-induced inflammation, cell proliferation, thereby leading to lung tumorigenesis.
ELECTRONIC HOLOGRAPHY FOR IMAGING THROUGH TISSUE USING FEMTOSECOND GATED PULSES (1991)

Get PDF Email Share Share with Facebook Tweet This Post on reddit Share with LinkedIn Add to CiteULike Add to Mendeley Add to BibSonomy Get Citation Copy Citation Text E. LEITH, H. CHEN, Y. CHEN, D. DILWORTH, J. LOPEZ, R. MASRI, J. RUDD, and J. VALDMANIS, "ELECTRONIC HOLOGRAPHY FOR IMAGING THROUGH TISSUE USING FEMTOSECOND GATED PULSES," Optics & Photonics News 2(12), 39-40 (1991) Export Citation BibTex Endnote (RIS) HTML Plain Text Citation alert Save article
Efficient technology for wavelength stabilization and spectrum narrowing of high-power multimode laser diodes and arrays (2004)

We present a technology for achieving a significant line narrowing (by approximately an order of magnitude) and stabilization of the emission wavelength of multimode high-power laser diodes and arrays.
Present and future durability challenges for reinforced concrete structures (2012)

Abstract This paper sums up the International RILEM Workshop on Present and Future Durability Challenges for Reinforced Concrete Structures, held at ETH Zurich in Switzerland on 17–18 April 2012. Major focus is put on the discussions. During the latter it was revealed that one of the key durability challenges lies in predicting the performance of new materials, where the increasing diversity of cement and concrete plays a major role. As most current engineering models are not capable of predicting actual field performance adequately, a knowledge‐based approach to durability will become more important than ever. Only a scientific approach on a multi‐scale and interdisciplinary level will allow predicting the performance of new materials (where no long‐term experience is available for fitting purposes). This will facilitate the use of more performance‐based durability design that is urgently needed to promote innovative, long‐lasting solutions.
Abstract 5199: Microenvironmental control of breast cancer subtype elicited by paracrine platelet-derived growth factor-CC signaling (2018)

Abstract Aim: Breast tumors of the basal-like, hormone receptor-negative subtype, remain an unmet clinical challenge, as patients exhibit the highest recurrence rate, the shortest time to recurrence and the worst overall survival rate due to a paucity of therapeutic targets. Also, as tumors develop, the surrounding microenvironment co-evolves into an activated state through continuous paracrine communication, creating a dynamic signaling circuitry that promotes malignant progression. Thus, novel treatment approaches that also include the targeting of stromal components are urgently required. Methods: We used experimental mouse models of cancer (transgenic, syngeneic, human cell lines and patient-derived xenografts) for knockout studies and preclinical trials, immunostaining, in vitro assays, western-blot, gene expression analysis and RNA-sequencing, patient cohorts, data mining and bioinformatics analysis. Results and discussion: We identified a paracrine crosstalk between cancer cells expressing platelet-derived growth factor (PDGF)-CC and cancer-associated fibroblasts (CAFs) expressing the cognate receptors in human basal-like mammary carcinomas. In translational efforts, we found that PDGF-CC expression in the malignant epithelium of breast cancer was associated with a hormone receptor-negative state. We then generated a mouse model to characterise the functional role of PDGF-CC in tumorigenesis. Moreover, we identified and validated factors secreted by CAFs to maintain a basal-like phenotype, e.g. Stanniocalcin (STC)-1, Hepatocyte Growth Factor (HGF) and Insulin Growth Factor Binding Protein (IGFBP)-3. Genetic or pharmacological targeting of PDGF-CC in experimental mouse models resulted in the transcriptional reprogramming and conversion of basal-like breast tumors into a luminal-like state characterised by Estrogen Receptor (ER)-α positivity, that conferred sensitivity to endocrine therapy in previously intrinsically unresponsive tumors. Conclusions: Specification of the basal-like subtype of breast cancer is under microenvironmental control and therapeutically actionable in order to achieve sensitivity to endocrine therapy. Our work sheds light on previously unknown mechanisms that define breast cancer subtype and has significant therapeutic implications for patients with basal-like breast tumors. Citation Format: Matteo Bocci, Michael Bartoschek, Pernilla Roswall, Kristian Pietras. Microenvironmental control of breast cancer subtype elicited by paracrine platelet-derived growth factor-CC signaling [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5199.
Genome Sequence of Listeria monocytogenes Strain F4244, a 4b Serotype (2017)

<i>Listeria monocytogenes</i> is an opportunistic invasive foodborne pathogen. Here, we performed whole-genome sequencing of <i>L. monocytogenes</i> strain F4244 (serotype 4b) using Illumina sequencing. The sequence showed 94.5% identity with strain F2365, serotype 4b, and 90.6% with EGD-e, serotype 1/2a.
On minimum detectable velocity (2019)

In comparing system performance for ground moving target indicator (GMTI) radar systems, various metrics are used. It is highly desirable that the metric be simple and powerful. Ideally it is a single number, or a plot. It is often the case that a single number is not sufficient to describe the radar performance under all operational conditions. In spite of this, it is still common to attempt to use a simple metric, such as the minimum detectable velocity (MDV). This paper discusses the concept of minimum detectable velocity with the goal of showing what this metric attempts to communicate, and what may not be properly communicated by this metric without careful attention. Basic parameters that affect the minimum detectable velocity are presented.
Antenna Booster Versus a Spiral Monopole Antenna for Single-Band Operation at 900 MHz (2023)

The number of devices connected to the internet has grown exponentially through the last decade, making IoT and connection worldwide more possible every year, enabling an incredible number of applications. This calls for better and more efficient methods for designing wireless devices. An efficient and small antenna is needed to ensure connectivity, range, and battery life. Under these circumstances, antenna booster technology is proposed, which uses a tiny component called an antenna booster to excite currents in the ground plane of the IoT device. This allows the antenna booster to be as small as 12 mm × 3 mm × 2.4 mm, representing only ~λ/30 at 863 MHz. The antenna booster is matched across the frequency range using a matching network. The paper compares an antenna booster and a monopole antenna regarding bandwidth for a design using a 120 mm × 60 mm ground plane in the 863 MHz to 928 MHz frequency range. Afterwards, the same designs are analysed when the ground plane size changes from 20 mm × 30 mm to 200 mm × 200 mm using steps of 10 mm to determine which approach can be reused across 53.8% of the ground planes with S11 &lt; −6 dB without making any changes to the antenna system; for contrast, the monopole antenna can be reused only 4.6%. In addition, the antenna booster features better total efficiencies of up to 2.3 dB. A physical prototype with the antenna booster validates the numerical analysis.
Hemoxygenase-1 as a key mediator of acute radiation pneumonitis revealed in a human lung alveolus-on-a-chip (2023)

ABSTRACT Exposure to gamma radiation either due to environmental disasters or cancer radiotherapy can result in development of acute radiation syndrome (ARS), characterized by pneumonitis and lung fibrosis. We leveraged a microfluidic organ-on-a-chip lined by human lung alveolar epithelium interfaced with pulmonary endothelium to model acute radiation-induced lung injury in vitro . Both lung epithelium and endothelium exhibited DNA damage, cellular hypertrophy, upregulation of inflammatory cytokines, and loss of barrier function within 6 h of radiation exposure, although greater damage was observed in the endothelium. Transcriptomic analysis revealed increased expression of the cytoprotective gene, hemoxygenase-1 (HMOX-1) and gene network analysis identified it as a central mediator of radiation-induced injury. Pharmacological stimulation of HMOX-1 activity also significantly reduced acute radiation-induced lung injury, although it enhanced damage at later times. Thus, this human lung chip offers a new platform to study ARS and these results suggest that HMOX-1 may be mechanistically involved in this injury response.
Reader preferences and behavior on Wikipedia (2014)

Wikipedia is a collaboratively-edited online encyclopaedia that relies on thousands of editors to both contribute articles and maintain their quality. Over the last years, research has extensively investigated this group of users while another group of Wikipedia users, the readers, their preferences and their behavior have not been much studied. This paper makes this group and its %their activities visible and valuable to Wikipedia's editor community. We carried out a study on two datasets covering a 13-months period to obtain insights on users preferences and reading behavior in Wikipedia. We show that the most read articles do not necessarily correspond to those frequently edited, suggesting some degree of non-alignment between user reading preferences and author editing preferences. We also identified that popular and often edited articles are read according to four main patterns, and that how an article is read may change over time. We illustrate how this information can provide valuable insights to Wikipedia's editor community.
Performance evaluation of automated segmentation software on optical coherence tomography volume data (2016)

Over the past two decades a significant number of OCT segmentation approaches have been proposed in the literature. Each methodology has been conceived for and/or evaluated using specific datasets that do not reflect the complexities of the majority of widely available retinal features observed in clinical settings. In addition, there does not exist an appropriate OCT dataset with ground truth that reflects the realities of everyday retinal features observed in clinical settings. While the need for unbiased performance evaluation of automated segmentation algorithms is obvious, the validation process of segmentation algorithms have been usually performed by comparing with manual labelings from each study and there has been a lack of common ground truth. Therefore, a performance comparison of different algorithms using the same ground truth has never been performed. This paper reviews research-oriented tools for automated segmentation of the retinal tissue on OCT images. It also evaluates and compares the performance of these software tools with a common ground truth.
Western Blot Analysis of Human IgG Reactive with the Collagenous Portion of C1q: Evidence of Distinct Binding Specificities (1992)

An enzyme-linked immunosorbent assay (ELISA) with purified collagenous C1q fragments in the solid phase was used for detection of C1q-specific immunoglobulins in the sera of twelve patients with systemic lupus erythematosus (SLE) or the SLE-like disease hypocomplementemic urticarial vasculitis syndrome (HUVS). By clinical criteria, four patients had SLE, and three HUVS. Five patients had overlap syndromes. All patients demonstrated high concentrations of C1q-specific IgG and markedly low concentrations of circulating C1q. Detection of C1q-specific IgG in SLE sera was facilitated by employment of saturating concentrations of collagenous C1q fragments in the solid-phase ELISA. When added to SLE serum, immune complex-fixed C1q inhibited binding of IgG to the C1q fragments, whereas addition of C1q alone had limited inhibitory effects. Under similar conditions, using approximately equimolar amounts of C1q relative to solid-phase C1q fragments, no ELISA inhibition was obtained after addition of C1q or immune complex-fixed C1q to a HUVS serum. Even in large excess, purified C1q did not inhibit binding of HUVS-IgG to solid-phase C1q fragments. Thus, possible interactions between HUVS-IgG and native Clq are probably of low affinity. By Western blot analysis, IgG reactive with the B and C chains of C1q was found in the eight patients with evidence of HUVS, five of whom also showed IgG binding to C'-C' and A'-B' dimers of collagenous C1q fragments. Sera from SLE patients were negative by Western blot analysis. It seems likely that C1q-specific IgG in SLE primarily recognizes assembled C1q molecules or collagenous C1q fragments expressing conformational epitopes of bound C1q. Interestingly, patients with evidence of HUVS fairly consistently had zymogen (C1r-C1s)2 complexes in their serum, while patients with SLE showed high concentrations of complexes containing Cl inhibitor, C1r and C1s. Different binding specificities of C1q-reactive IgG could be of importance with regard to pathogenetic mechanisms in SLE and HUVS. There was no correlation between findings of C1q-specific IgG and a variety of autoantibodies associated with SLE and SLE-like disease.