gebhart/patrepeval huggingface dataset:
Engineering of a TrpR-Based Biosensor for Altered Dynamic Range and Ligand Preference (2022)

Transcriptional factors play a crucial role in regulating cellular functions. Understanding and altering the dynamic behavior of the transcriptional factor-based biosensors will expand our knowledge in investigating biomolecular interactions and facilitating biosynthetic applications. In this study, we characterized and engineered a TrpR-based tryptophan repressor system in <i>Escherichia coli</i>. We found that the reconstructed TrpR1-<i>PtrpO1</i> biosensor system exhibited low basal expression and narrow dynamic range in the presence of tryptophan or its analogue 5-hydroxytryptophan (5-HTP). Given the application potential of the biosensor, we introduced engineering approaches in multiple levels to optimize its dynamic behavior. First, the I57 and V58 residues in the ligand-binding pocket were rationally mutated in search of variants with altered ligand specificity. Two TrpR1 variants, V58E and V58K, successfully acquired ligand preference toward tryptophan and 5-HTP, respectively. The biosensor-induced expression levels were increased up to 10-fold with those variants. Furthermore, to pursue broader operational range, we tuned the regulator-operator binding affinity by mutating the binding box of TrpR1. Collectively, we demonstrated that the biosynthesis-significant biosensor TrpR1-<i>PtrpO1</i> can be engineered to acquire extended dynamic ranges and improved ligand preference. The engineered biosensor variants with remarkable dynamic behavior can serve as key genetic elements in high-throughput screening and dynamic regulation in biosynthetic scenarios.
Abstract PO-031: MetMap: A map of metastatic potential of human cancer cell lines (2020)

Abstract Most deaths from cancer are explained by metastasis, and yet large-scale metastasis research has been impractical due to the complexity of in vivo models. Here, we introduce an in vivo barcoding strategy capable of determining the metastatic potential of human cancer cell lines in murine xenografts at scale. We validated the robustness, scalability and reproducibility of the method, and applied it to 500 cell lines spanning 21 solid cancer types. We created a first-generation Metastasis Map (MetMap) that reveals organ-specific patterns of metastasis and allows relating those patterns to clinical and genomic features. We demonstrated the utility of MetMap by exploring the molecular basis of breast cancers capable of metastasizing to the brain – a principal cause of death in these patients. We found that breast cancers capable of metastasizing to the brain had unexpected evidence of altered lipid metabolism. Perturbing lipid metabolism curbed brain metastasis development, suggesting a therapeutic strategy to combat the disease and demonstrating the utility of MetMap as a public resource to support metastasis research. Citation Format: Xin Jin, Zelalem Demere, Karthik Nair, Ahmed Ali, Gino B. Ferraro, Ted Natoli, Amy Deik, Lia Petronio, Andrew A. Tang, Cong Zhu, Li Wang, Danny Rosenberg, Vamsi Mangena, Jennifer Roth, Kwanghun Chung, Rakesh K. Jain, Clary B. Clish, Matthew G. Vander Heiden, Todd R. Golub. MetMap: A map of metastatic potential of human cancer cell lines [abstract]. In: Abstracts: AACR Special Virtual Conference on Epigenetics and Metabolism; October 15-16, 2020; 2020 Oct 15-16. Philadelphia (PA): AACR; Cancer Res 2020;80(23 Suppl):Abstract nr PO-031.
Volatile Biomarkers in Clinical Decision Support Systems (2022)

This chapter offers a brief overview of the integration of medical instruments and sensors with artificial intelligence (AI) for advanced clinical decision support systems, which could help decision makers and healthcare systems to improve in the approach to information, insights and surrounding contexts of health, as well as to promote the uptake of personalized medicine. Relying on these systems, volatile organic compound (VOC) sensing devices could enable interactive and evolving clinical decisions for use in evidence-based analysis and recommendations as well as for personalized monitoring of disease progress and treatment. The ongoing challenges and future opportunities associated with VOC-enabled medical sensors in clinical decisions are presented and discussed.
AIMS EUV: the actinic aerial image review platform for EUV masks (2011)

EUV mask infrastructure is of key importance for the introduction of the 13.5nm extreme ultraviolet (EUV) wavelength into volume production. In particular, the manufacturing of defect free masks is essential and requires a printability analysis ("review") of potential defect sites. For this purpose, Carl Zeiss and the SEMATECH EUVL Mask Infrastructure consortium have performed a concept and feasibility study for an actinic aerial image metrology system (AIMS&trade;). In this paper, we discuss the main results of this study. We explain the system concept, discuss the expected performance and show simulations of the capability to find minimum sized defects. We demonstrate that our EUV AIMS concept is technically feasible and supports the defect review requirements for the 22nm and 16nm half-pitch (hp) node.
Quantum Pairwise Symmetry: Applications in 2D Shape Analysis (2015)

A pair of rooted tangents -- defining a quantum triangle -- with an associated quantum wave of spin 1/2 is proposed as the primitive to represent and compute symmetry. Measures of the spin characterize how "isosceles" or how "degenerate" these triangles are -- which corresponds to their mirror or parallel symmetry. We also introduce a complex-valued kernel to model probability errors in the parameter space, which is more robust to noise and clutter than the classical model.
Optimisation de la cellule élémentaire d'un réseau réflecteur large bande pour application spatiale (2002)

International audience
Developmental barcoding of whole mouse via homing CRISPR (2018)

In vivo barcoding using nuclease-induced mutations is a powerful approach for recording biological information, including developmental lineages; however, its application in mammalian systems has been limited. We present in vivo barcoding in the mouse with multiple homing guide RNAs that each generate hundreds of mutant alleles and combine to produce an exponential diversity of barcodes. Activation upon conception and continued mutagenesis through gestation resulted in developmentally barcoded mice wherein information is recorded in lineage-specific mutations. We used these recordings for reliable post hoc reconstruction of the earliest lineages and investigation of axis development in the brain. Our results provide an enabling and versatile platform for in vivo barcoding and lineage tracing in a mammalian model system.
Development of subtype-specific and heterosubtypic antibodies to the influenza A virus hemagglutinin after primary infection in children (1985)

Children undergoing primary infection with an H1N1 or H3N2 influenza A virus developed subtype-specific hemagglutination inhibition antibodies and enzyme-linked immunosorbent assay antibodies to purified hemagglutinin (HA) of the infecting virus subtype. They also developed lower titered ELISA antibodies to the noninfecting H1 or H3 HA and to H8 (an avian strain) HA. Thus, after primary infection with an influenza A virus, children develop enzyme-linked immunosorbent assay, but not hemagglutination inhibition, antibodies reactive with heterosubtypic HAs. These heterosubtypic antibodies could influence the response to infection with other wild-type or attenuated vaccine strains of influenza A virus.
Gene expression in Lucilia sericata ( Diptera : Calliphoridae ) larvae exposed to Pseudomonas aeruginosa and Acinetobacter baumannii identifies shared and microbe‐specific induction of immune genes (2021)

Antibiotic resistance is a continuing challenge in medicine. There are various strategies for expanding antibiotic therapeutic repertoires, including the use of blow flies. Their larvae exhibit strong antibiotic and antibiofilm properties that alter microbiome communities. One species, Lucilia sericata, is used to treat problematic wounds due to its debridement capabilities and its excretions and secretions that kill some pathogenic bacteria. There is much to be learned about how L. sericata interacts with microbiomes at the molecular level. To address this deficiency, gene expression was assessed after feeding exposure (1 h or 4 h) to two clinically problematic pathogens: Pseudomonas aeruginosa and Acinetobacter baumannii. The results identified immunity-related genes that were differentially expressed when exposed to these pathogens, as well as non-immune genes possibly involved in gut responses to bacterial infection. There was a greater response to P. aeruginosa that increased over time, while few genes responded to A. baumannii exposure, and expression was not time-dependent. The response to feeding on pathogens indicates a few common responses and features distinct to each pathogen, which is useful in improving the wound debridement therapy and helps to develop biomimetic alternatives.
Experimental Investigation of a Multiplex Fuel Injector Module with Discrete Jet Swirlers for Low Emission Combustors (2004)

A low-NOx emissions combustor concept has been demonstrated in flame-tube tests. A lean-direct injection (LDI) concept was used where the fuel is injected directly into the flame zone and the overall equivalence ratio of the mixture is lean. The LDI concept described in this report is a multiplex fuel injector module containing multipoint fuel injection tips and multi-burning zones. The injector module comprises 25 equally spaced injection tips within a 76 by 76 mm area that fits into the flame-tube duct. The air swirlers were made from a concave plate on the axis of the fuel injector using drilled holes at an angle to the axis of the fuel injector. The NOx levels were quite low and are greater than 70 percent lower than the 1996 ICAO standard. At an inlet temperature of 810 K, inlet pressure of 2760 kPa, pressure drop of 4 percent and a flame temperature of 1900 K with JP8 fuel, the NOx emission index was 9. The 25-point injector module exhibited the most uniform radial distribution of fuel-air mixture and NOx emissions in the flame tube when compared to other multipoint injection devices. A correlation is developed relating the NOx emissions to inlet temperature, inlet pressure, equivalence ratio and pressure drop.
Lack of Immune Responses to Mycobacterium tuberculosis DosR Regulon Proteins following Mycobacterium bovis BCG Vaccination (2007)

Mycobacterium bovis BCG is widely used as a vaccine against tuberculosis (TB), despite its variable protective efficacy. Relatively little is known about the immune response profiles following BCG vaccination in relation to protection against TB. Here we tested whether BCG vaccination results in immune responses to DosR (Rv3133c) regulon-encoded proteins. These so-called TB latency antigens are targeted by the immune system during persistent Mycobacterium tuberculosis infection and have been associated with immunity against latent M. tuberculosis infection. In silico analysis of the DosR regulon in BCG and M. tuberculosis showed at least 97% amino acid sequence homology, with 41 out of 48 genes being identical. Transcriptional profiling of 14 different BCG strains, under hypoxia and nitric oxide exposure in vitro, revealed a functional DosR regulon similar to that observed in M. tuberculosis. Next, we assessed human immune responses to a series of immunodominant TB latency antigens and found that BCG vaccination fails to induce significant responses to latency antigens. Similar results were obtained with BCG-vaccinated BALB/c mice. In contrast, responses to latency antigens were observed in individuals with suspected exposure to TB (as indicated by positive gamma interferon responses to TB-specific antigens ESAT-6 and CFP-10) and in mice vaccinated with plasmid DNA encoding selected latency antigens. Since immune responses to TB latency antigens have been associated with control of latent M. tuberculosis infection, our findings support the development of vaccination strategies incorporating DosR regulon antigens to complement and improve the current BCG vaccine.
10-kJ Status and 100-kJ Future for NIF PetaWatt Technology (2007)

We discuss the status of the NIF ARC, an 8-beam 10-kJ class high-energy petawatt laser, and the future upgrade path of this and similar systems to 100-kJ-class with coherent phasing of multiple apertures.
Mapping of the basal forebrain cholinergic system of the dog: A choline acetyltransferase immunohistochemical study (1996)

In an effort to produce a canine model of basal forebrain ischemia with memory deficits, we have shown that dogs possess a medial striate artery that perfuses basal forebrain territory, homologous to the human recurrent artery of Heubner. In the present study, we set out to delineate the precise topography of the cholinergic neurons in the canine forebrain, a neuronal system implicated in cognitive and memory functions. Floating coronal sections, derived from the head of the caudate nucleus to the rostral border of the hippocampus, were stained for choline acetyltransferase using a monoclonal antibody. Representative sections from one dog brain were drawn. These outlines were used for measurement of cell density, cell size, number of processes, and cell roundness. Choline acetyltransferase-positive neurons constituted four major subdivisions within the basal forebrain. A relatively dense population of cholinergic neurons was present in the medial septal nucleus (Ch1). A continuum of densely packed cells was also delineated within the vertical (Ch2) and horizontal (Ch3) nuclei of the diagonal band of Broca. A fourth group of heterogeneously packed cholinergic neurons represented the nucleus basalis magnocellularis (Ch4). Except for the caudal component of the Ch4 population, the forebrain cholinergic corticopetal system was located within the perfusion territory of the medial striate arteries. The Ch4 cell group in dogs is better defined than that of rodents but is not as sharply demarcated as in human and nonhuman primates. Our findings indicate that the dog may serve as an excellent model for assessing neurological and memory deficits, which, in humans, results from hypoperfusion of the recurrent artery of Heubner. © 1996 Wiley-Liss, Inc.
Immunotherapy in HER2-positive breast cancer: state of the art and future perspectives (2019)

Breast cancer (BC) is a complex disease with primary or acquired incurability characteristics in a significant part of patients. Immunotherapeutical agents represent an emerging option for breast cancer treatment, including the human epidermal growth factor 2 positive (HER2+) subtype. The immune system holds the ability to spontaneously implement a defensive response against HER2+ BC cells through complex mechanisms which can be exploited to modulate this response for obtaining a clinical benefit. Initial immune system modulating strategies consisted mostly in vaccine therapies, which are still being investigated and improved. However, the entrance of trastuzumab into the scenery of HER2+ BC treatment was the real game changing event, which embodied a dominant immune-mediated mechanism. More recently, the advent of the immune checkpoint inhibitors has caused a new paradigm shift for immuno-oncology, with promising initial results also for HER2+ BC. Breast cancer has been traditionally considered poorly immunogenic, being characterized by relatively low tumor mutation burden (TMB). Nevertheless, recent evidence has revealed high tumor infiltrating lymphocytes (TILs) and programmed cell death-ligand 1 (PD-L1) expression in a considerable proportion of HER2+ BC patients. This may translate into a higher potential to elicit anti-cancer response and, therefore, wider possibilities for the use and implementation of immunotherapy in this subset of BC patients. We are herein presenting and critically discussing the most representative evidence concerning immunotherapy in HER2+ BC cancer, both singularly and in combination with therapeutic agents acting throughout HER2-block, immune checkpoint inhibition and anti-cancer vaccines. The reader will be also provided with hints concerning potential future projection of the most promising immutherapeutic agents and approaches for the disease of interest.
Supplementary Methods, Table 1, Figures 1-5 from Anti–Placental Growth Factor Reduces Bone Metastasis by Blocking Tumor Cell Engraftment and Osteoclast Differentiation (2023)

Supplementary Methods, Table 1, Figures 1-5 from Anti–Placental Growth Factor Reduces Bone Metastasis by Blocking Tumor Cell Engraftment and Osteoclast Differentiation
Novel photoresist thin films with in-situ photoacid generator by molecular layer deposition (2013)

Current photoresist materials are facing many challenges introduced by advanced lithographies, particularly the need for excellent compositional homogeneity and ultrathin film thickness. Traditional spin-on polymeric resists have inherent limitations in achieving a high level of control over the chemical composition, leading to interest in development of alternative methods for making photoresists. In this work, we demonstrate that molecular layer deposition (MLD) is a potential method for synthesizing photoresists because it allows for precise control over organic film thickness and composition. MLD utilizes sequential, self-limiting reactions of organic precursors to build a thin film directly on a substrate surface and grows organic films by depositing only one molecular layer at each precursor dose, which in turn allows for fine-tuning of the position and concentration of various functionalities in the deposited film. In this study, we use bifunctional precursors, diamine and diisocyanate, to build polyurea resist films via urea coupling reaction between the amine and isocyanate groups. Acid-labile groups and photoacid generators (PAGs) are embedded in the backbone of the resist films with a highly uniform distribution. The resist films were successfully deposited and characterized for both materials properties and resist response. E-beam patterning was achieved with the resist films. Cross-linking behavior of the resist films was observed, likely due to the aromatic rings in the films, which is undesirable for application as a positive-tone photoresist. Moreover, the in-situ polymer-bound PAGs had low sensitivity. It is suggested that this effect may arise because the PAG is cation-bound, leading to lower efficiency of sulfur-carbon bond cleavage in the sulfonium cation, which is needed to produce the photoacid, and consequently a lower photoacid yield. Further work is needed to improve the performance of the MLD resist films.
α→γ→α Transformation Texture Formation at Cold-Rolled Ultra Low Carbon Steel Surfaces (2005)

The influence of Mn on the surface texture formation through a®g®a transformation was investigated. After the a®g®a transformation, a weak texture was formed at the surface of ultra low carbon cold-rolled sheet steel without Mn. In contrast, a sharp &lt;100&gt;//ND cube texture was observed in Mn alloyed ultra low carbon steel. In order to interpret the effect of Mn two alternative mechanisms were considered : (i) one assumption attributes the occurrence of the specific surface texture to the effect of outer-surface energy (ii) and according to an alternative hypothesis the release of elastic work parallel to ND in the surface area is responsible for the observed &lt;100&gt;//ND surface texture.
Interbody Fusion Cage Design Using Integrated Global Layout and Local Microstructure Topology Optimization (2004)

The new design approach using integrated topology optimization demonstrated comparable or better stability by limited displacement and reduced localized deformation related to the risk of subsidence. Less shielding of newly formed bone was predicted inside the new designed cage. Using the present approach, it is also possible to tailor cage design for specific materials, either titanium or polymer, that can attain the desired balance between stability, reduced stress shielding, and porosity for biofactor delivery.
Enhanced mobilization of hematopoietic progenitor cells by mouse MIP-2 and granulocyte colony-stimulating factor in mice (1997)

Human interleukin-8 (IL-8) induces a rapid mobilization of hematopoietic progenitor cells (HPCs) into peripheral blood in mice and primates. Because an exact homologue of human IL-8 does not exist in mice, a chemokine, macrophage inflammatory protein-2 (MIP-2), is supposed to substitute the function of IL-8 in mice. Hence, we investigated the capacity of mouse MIP-2 to induce HPC mobilization in mice. Mouse MIP-2 induced, in either untreated or splenectomized mice, a rapid HPC mobilization, as evidenced by increased numbers of colony-forming unit granulocyte-macrophage (CFU-GM) and lineage marker (Lin)-c-kit+Sca-1+ cells. Although release of elastase from activated neutrophils was proposed to be involved in IL-8-induced HPC mobilization, mouse MIP-2 induced similar levels of HPC mobilization in elastase-deficient beige mice at a similar level to normal ones. This HPC mobilization by MIP-2 was markedly enhanced by pretreatment with granulocyte-colony-stimulating factor (G-CSF). Moreover, the combination of G-CSF and MIP-2 apparently down-regulated L-selectin expression on Lin-Sca-1+ cells in peripheral blood as well as bone marrow. Thus, MIP-2 may down-modulate the interaction between HPCs and bone marrow stroma by reducing L-selectin expression on HPCs and cause rapid mobilization of HPCs into peripheral blood.
Update on infections involving permanent pacemakers. Characterization and management. (1985)

From January, 1974, to December, 1983, 75 patients with infections related to permanent pacemakers were successfully treated. Demographic characterization, mode of presentation, types of infecting organisms, potential predisposing factors, significance of a retained infected pacemaker lead, and various medical and surgical treatment methods were analyzed. Likely infecting organisms depended on the mode of presentation and the time of the infection. Dermatologic diseases accounted for a significant number of secondary infections. Removal of the entire infected pacing system was required for eradication of infection in 74 of 75 patients. In 31 patients, the infected system was removed at the same time that the new system was implanted. In 26 patients, a two-stage procedure was used that included a period of temporary pacing between explantation of the old system and implantation of the new. No difference in complications or incidence of reinfection was found between these two groups. Infections occurring within 2 weeks after operation accounted for 15% of the cases. In these patients, Staphylococcus aureus was the most common organism. In patients with later infections, Staphylococcus epidermidis was the most common.
Inhibition of rat tissue kallikrein gene family members by rat kallikrein‐binding protein and α1‐proteinase inhibitor (1992)

The regulation of tissue kallikrein activity by plasma serine proteinase inhibitors (serpins) was investigated by measuring the association rate constants of six tissue-kallikrein family members isolated from the rat submandibular gland, with rat kallikrein-binding protein (rKBP) and alpha 1-proteinase inhibitor (alpha 1-PI). Both these serpins inhibited kallikreins rK2, rK7, rK8, rK9 and rK10 with association rate constants in the 10(3)-10(4) M-1.s-1 range, whereas only 'true' tissue kallikrein rK1 was not susceptible to alpha 1-PI. This results in slow inhibition of rK1 by plasma serpins, which could explain why this kallikrein is the only member of the gene family identified so far that induces a transient decrease in blood pressure when injected in minute amounts into the circulation.