gebhart/patrepeval huggingface dataset:
Lint‐O cooperates with L(3)mbt in target gene suppression to maintain homeostasis in fly ovary and brain (2022)

Loss-of-function mutations in Drosophila lethal(3)malignant brain tumor [l(3)mbt] cause ectopic expression of germline genes and brain tumors. Loss of L(3)mbt function in ovarian somatic cells (OSCs) aberrantly activates germ-specific piRNA amplification and leads to infertility. However, the underlying mechanism remains unclear. Here, ChIP-seq for L(3)mbt in cultured OSCs and RNA-seq before and after L(3)mbt depletion shows that L(3)mbt genomic binding is not necessarily linked to gene regulation and that L(3)mbt controls piRNA pathway genes in multiple ways. Lack of known L(3)mbt co-repressors, such as Lint-1, has little effect on the levels of piRNA amplifiers. Identification of L(3)mbt interactors in OSCs and subsequent analysis reveals CG2662 as a novel co-regulator of L(3)mbt, termed "L(3)mbt interactor in OSCs" (Lint-O). Most of the L(3)mbt-bound piRNA amplifier genes are also bound by Lint-O in a similar fashion. Loss of Lint-O impacts the levels of piRNA amplifiers, similar to the lack of L(3)mbt. The lint-O-deficient flies exhibit female sterility and tumorous brains. Thus, L(3)mbt and its novel co-suppressor Lint-O cooperate in suppressing target genes to maintain homeostasis in the ovary and brain.
An enantioselective tandem reduction/nitro-Mannich reaction of nitroalkenes using a simple thiourea organocatalyst (2013)

There is a continual need for ever more effective and operationally simpler methods for the asymmetric synthesis of nitrogen containing molecules. We report here a generally efficient synthesis of stereochemically defined β-nitroamine building blocks which, through the combination of two catalytic transformations into one tandem process, results in the use of a simpler asymmetric catalyst, less reaction materials, shorter reaction times, circumvents the need for moisture sensitive reaction partners and leads to a wider substrate scope. Using para-methoxy-phenyl (PMP) protected imines, a Hantzsch ester as hydride source and a simple and economic thiourea organocatalyst, we have promoted the nitro-Mannich reaction with a nitroalkene to form anti-β-nitroamines. After protection as their trifluoroacetamides the products can be isolated in good yields (32–83%), high diastereomeric ratios (90 : 10 to >95 : 5) and excellent enantioselectivity (73–99% ee).
Wearable Woven Electrochemical Biosensor Patch for Non‐invasive Diagnostics (2016)

Abstract In this paper, we demonstrate a woven electrochemical biosensor patch as a low cost, robust wearable sensor for non‐invasive diagnostics. The critical requirement for wearable sensors is their robustness which necessitates the output signal to be independent of the deformation that the sensor system could potentially undergo. In this work, the performance of woven electrode patch post standard deformations such as bending and twisting were analysed using chronoamperometric detection of lactate, a sweat borne analyte, as a model system. In spite of rigorous deformation, the CV was well within 13 %, indicating the applicability of woven electrode patch as a low cost, robust, wearable, non‐invasive electrochemical biosensor platform.
Early graft failure of xenogeneic islets in NOD mice is accompanied by high levels of interleukin-1 and low levels of transforming growth factor-beta mRNA in the grafts. (2000)

Early graft failure, graft rejection, and autoimmune recurrence remain unresolved issues in islet xenotransplantation in type 1 diabetes. The first aim of this study was to examine the existence of early graft failure in spontaneously diabetic autoimmune NOD mice after rat islet transplantation under technically controlled circumstances. The second aim was to examine the mediators of this early xenograft dysfunction. First, we demonstrated a higher percentage of early xenograft failure (48%) in spontaneously diabetic NOD mice as compared with chemically diabetic old NOD (13%, P < 0.05) and C57Bl/6 (7%, P < 0.01) mice. In addition, in spontaneously diabetic NOD mice, xenogeneic islets displayed early graft failure more frequently than allogeneic (23%, P < or = 0.05) or isogeneic islets (7%, P < 0.01). No early graft failure was observed in allotransplantation or isotransplantation in chemically diabetic mice. Reverse transcriptase-polymerase chain reaction analysis of cytokine mRNA in islet xenografts 8 h after transplantation showed higher levels of interleukin (IL)-1 mRNA in autoimmune diabetic mice compared with chemically diabetic old NOD mice (1.40 +/- 0.32 vs. 0.90 +/- 0.14 IL-1 copies/beta-actin copies, P < 0.05). In contrast, mRNA levels of transforming growth factor (TGF)-beta were lower in spontaneously diabetic NOD mice than in chemically diabetic old NOD mice (0.67 +/- 0.16 vs. 1.36 +/- 0.50 TGF-beta copies/beta-actin copies, P < 0.05). No differences in tumor necrosis factor-alpha, IL-6, and inducible nitric oxide synthase were seen between autoimmune and nonautoimmune diabetic mice. T-cell cytokines (IL-2, IL-4, IL-10, and gamma-interferon) were absent in all mice until 48 h after transplantation. These data suggest that early islet xenograft failure is more common in spontaneously diabetic NOD mice and could be due to a nonspecific inflammatory reaction locally in the grafts.
Structure, sequence and function of a marsupial LIF gene: Conservation of IL-6 family cytokines (2001)

Leukaemia Inhibitory Factor (LIF) is a multifunctional cytokine with an obligate role in the mouse in embryonic implantation. In this paper we demonstrate the existence of a functional LIF gene in the marsupial Sminthopsis crassicaudata, and the presence of LIF-related sequences in the monotreme Tachyglossus aculeatus (Australian echidna). Isolation of genomic and cDNA clones from S. crassicaudata, indicated that the LIF gene is highly conserved between marsupials and monotremes in terms of sequence and genomic organisation. Critical functional residues within the LIF sequence were also conserved including residues implicated in intracellular LIF activity, and in interaction with the receptor subunits LIFR and gp130. These findings suggest that the structure and biochemical function of the protein is likely to be conserved. Consistent with this, purified recombinant S. crassicaudata LIF interacted functionally with mouse receptor components and was sufficient for maintenance of mouse embryonic stem (ES) cells in the undifferentiated state. Conservation of LIF outside eutherians is intriguing given the markedly divergent reproductive strategies which include, for some marsupial species, embryonic diapause, and in monotremes, the absence of implantation. The availability of marsupial LIF probes provides an opportunity to investigate conservation of expression and function in these mammals.
Rapid electron density decay observed by surface-wave probe in afterglow of pulsed fluorocarbon-based plasma (2016)

Abstract To elucidate the pulsed fluorocarbon plasma behavior, a surface-wave probe with high time resolution was used to measure the electron density n e in the afterglow of plasma. In a dual-frequency capacitively coupled plasma of fluorocarbon chemistry, e.g., an O 2 -based C 4 F 6 and Ar mixture, n e vanished rapidly in a short time (∼5 µs), whilst the dc current flowing onto the top electrode biased at −300 V decreased very slowly (decay time ∼70 µs). This observation is clear evidence of ion–ion plasma formation by electron attachment in the afterglow. We point out that the electron attachment rates for fluorocarbon radicals significantly affect the electrons and ion–ion plasma behaviors observed at the afterglow phase.
Kinesthetics eXtreme: an external infrastructure for monitoring distributed legacy systems (2003)

Autonomic computing - self-configuring, self-healing, self-optimizing applications, systems and networks - is widely believed to be a promising solution to ever-increasing system complexity and the spiraling costs of human system management as systems scale to global proportions. Most results to date, however, suggest ways to architect new software constructed from the ground up as autonomic systems, whereas in the real world organizations continue to use stovepipe legacy systems and/or build ''systems of systems'' that draw from a gamut of new and legacy components involving disparate technologies from numerous vendors. Our goal is to retrofit autonomic computing onto such systems, externally, without any need to understand or modify the code, and in many cases even when it is impossible to recompile. We present a meta-architecture implemented as active middleware infrastructure to explicitly add autonomic services via an attached feedback loop that provides continual monitoring and, as needed, reconfiguration and/or repair. Our lightweight design and separation of concerns enables easy adoption of individual components, as well as the full infrastructure, for use with a large variety of legacy, new systems, and systems of systems. We summarize several experiments spanning multiple domains.
Metabolic engineering for Escherichia coli BW25113 for the production of 5-Aminolevulinic Acid based on CRISPR/Cas9 mediated gene knockout and metabolic pathway modification (2022)

Abstract 5-Aminolevulinic acid (ALA) recently received much attention due to its potential application in many fields. In this study, an ALA production strain of Escherichia coli was constructed by rational metabolic engineering and stepwise improvement based on known regulatory and metabolic information and CRISPR/Cas9 mediated gene knockout. A metabolic strategy to produce ALA directly from glucose in this recombinant E. coli via the C5 pathway was applied herein. The rational metabolic engineering by gene knockouts significantly improved ALA production from 662.3 to 1601.7 mg/L. In addition, we tried to synergistically produce ALA via the C4 pathway in recombinant strain. The expression of a modified hemA gene, encoding an ALA synthase from Rhodobacter sphaeroides , improved ALA production from 1601.7 to 2099.7 mg/L. After 24 h cultivation, a yield of 0.210 g ALA per g glucose was achieved by constructed E. coli D5:FYABD. These results suggest that an industrially competitive strain can be efficiently developed by metabolic engineering based on combined rational modification and optimization of gene expression.
Exegetai (2016)

Abstract The exegetai were, in Athens, the interpreters of the “sacred laws and ancestral customs” ( patria kai hiera ), offering their advice on various matters such as purification rituals after homicides, as well as in funerary rites. These specialists are first described in detail by Plato, though the exegetic tradition of the “unwritten laws” probably originates during the Archaic period. There are three types of (known) exegetai : the pythochrestoi , the Eumolpid exegetai , and the Eupatrid exegetai .
Mechanism of Hydroxyl Radical Attack to Chemical Structure of PFSA Ionomer: A Solid State Q-NMR Study (2013)

Abstract not Available.
An Overview of Codes Tailor-made for Better Repairability in Networked Distributed Storage Systems (2011)

The continuously increasing amount of digital data generated by today's society asks for better storage solutions. This survey looks at a new generation of coding techniques designed specifically for the needs of distributed networked storage systems, trying to reach the best compromise among storage space efficiency, fault tolerance, and maintenance overheads. Four families of codes tailor-made for distributed settings, namely - pyramid, hierarchical, regenerating and self-repairing codes - are presented at a high level, emphasizing the main ideas behind each of these codes, and discussing their pros and cons, before concluding with a quantitative comparison among them. This survey deliberately excluded technical details for the codes, nor does it provide an exhaustive summary of the numerous works. Instead, it provides an overview of the major code families in a manner easily accessible to a broad audience, by presenting the big picture of advances in coding techniques for distributed storage solutions.
IFITM3 incorporation sensitizes influenza A virus to antibody-mediated neutralization (2021)

The disease severity of influenza is highly variable in humans, and one genetic determinant behind these differences is the IFITM3 gene. As an effector of the interferon response, IFITM3 potently blocks cytosolic entry of influenza A virus (IAV). Here, we reveal a novel level of inhibition by IFITM3 in vivo: We show that incorporation of IFITM3 into IAV particles competes with incorporation of viral hemagglutinin (HA). Decreased virion HA levels did not reduce infectivity, suggesting that high HA density on IAV virions may be an antagonistic strategy used by the virus to prevent direct inhibition. However, we found that IFITM3-mediated reduction in HA content sensitizes IAV to antibody-mediated neutralization. Mathematical modeling predicted that this effect decreases and delays peak IAV titers, and we show that, indeed, IFITM3-mediated sensitization of IAV to antibody-mediated neutralization impacts infection outcome in an in vivo mouse model. Overall, our data describe a previously unappreciated interplay between the innate effector IFITM3 and the adaptive immune response.
Sars-cov-2 vaccines induce durable neutralizing antibodies in infant rhesus macaques (2021)

Background: SARS-CoV-2 vaccines have shown promising efficacy in human adult trials, but immunogenicity and efficacy studies in the pediatric population are lagging behind. Here we evaluated the immunogenicity of two prefusion stabilized Spike protein (S-2P) vaccine platforms in infant Rhesus Macaques (RM): an adjuvanted S-P2 subunit and mRNA vaccine. Methods: Infant RMs (2.5 months-old) were immunized intramuscularly at weeks (wks) 0 & 4 with 15 μg S-P2 adjuvanted with the toll-like receptor 7/8 agonist 3M-052 in stable emulsion (n=8), or 30 μg of S-P2 mRNA in lipid nanoparticles (mRNA-LNP, Moderna) (n=8). Blood was collected at wks 0, 4, 6, 8, & 14. Plasma (Spike[S]) and salivary (receptor binding domain [RBD]) IgG responses were measured by ELISA and epitope specificity by multiparameter bead array. Antibody function was assessed by an ACE2 blocking assay and neutralization by pseudovirus (PSVA) and whole virus neutralization assays, both with D614G. Flow cytometry was applied to measure S-specific memory B cells using fluorochrome-conjugated recombinant S, and S-specific IL-2, IL-17, TNF-α, or IFN-γ producing T cells after stimulation with overlapping peptides of full-length S. Results: No adverse effects were observed with either vaccine. Plasma S-specific IgG responses were induced by both vaccines at wk 4, increased after the second dose, and persisted through wk 14 (Fig 1A). All S regions were targeted by plasma IgG (Fig 1B), and RBD-specific IgG was also detected in saliva. Serum antibodies achieved >95% ACE2 blocking by wk 6 (1:10 dilution), remaining >90% at wk 14. Geometric mean ID50 titers of neutralizing antibodies in the PSVA exceeded 10[3] from wk 6 through wk 14 (Fig 1C) and strongly correlated with whole virion neutralization (p<0.0001). In the protein vaccine group, S-specific CD27+ memory B cells peaked at 3.1% (mean) of total memory B cells;and S-specific CD4+ T cell responses were dominated by IL-17 and IFN-γ Mean S-specific CD27+ B cells peaked at 0.9% total memory B cells in mRNA vaccinees and S-specific CD4+ T cells produced IL-2, IFN-γ, IL-17, or TNF-α. Conclusion: The S-2P-3M-052-SE and mRNA-LNP vaccines were well-tolerated and highly immunogenic in infant Rhesus Macaques, with persistent IgG binding and neutralization responses that are comparable to those reported for adult RMs and humans. Our results provide proof-of-concept that a pediatric SARS-CoV-2 vaccine could induce long term protection against SARS-CoV-2.
Safety and activity of a first-in-class oral HIF2-alpha inhibitor, PT2385, in patients with first recurrent glioblastoma (GBM). (2019)

2027 Background: Hypoxia inducible factor 2-alpha (HIF2a) mediates cellular responses to hypoxia and is overexpressed in GBM. PT2385 is an oral HIF2a inhibitor with in vivo activity against GBM. Methods: A two-stage single-arm open-label phase II study of adults with first recurrent GBM following chemoradiation with measurable disease was conducted through the Adult Brain Tumor Consortium. PT2385 was administered at the phase II dose (800 mg b.i.d.). The primary outcome was objective radiographic response (CR+PR); secondary outcomes were safety and survival. Exploratory objectives included PK (day 15 Cmin), PD, and pH-weighted amine-CEST MRI to quantify tumor acidity at baseline and explore associations with drug response. Stage 1 enrolled 24 patients with early stoppage for ≤1 response. Results: Of the 24 patients, mean age was 61±11 years, median KPS 80, MGMT promoter methylated in 46%. PT2385 was well tolerated. Grade ≥3 drug-related AEs were hypoxia (n = 2), anemia (1), hyperglycemia (1), hyponatremia (2) and lymphopenia (2). No objective radiographic responses were observed; median PFS was 1.8 months (95%CI 1.6-3.1). Drug exposure varied widely (Table) and did not differ by corticosteroid use (p = 0.12), antiepileptics (p = 0.09), or sex (p = 0.37). Patients with high systemic exposure had significantly longer PFS (6.7 vs 1.8 months, 0.009). Non-enhancing infiltrative disease with high acidity gave rise to recurrence. Baseline acidity correlated significantly with treatment duration (R 2 = 0.49, p = 0.017). Conclusions: Drug exposure to PT2385 was variable. Signals of activity were observed in GBM patients with high systemic exposure and acidic (e.g. hypoxic) lesions on baseline imaging. A second-generation HIF2a inhibitor is being studied. Clinical trial information: NCT03216499. [Table: see text]
Topographie des Elektroenzephalogramms: Endotracheale Intubation unter Narkose mit Propofol und Fentanyl (2005)

Individual titration of the dose of propofol and fentanyl as done during routine clinical practice is not sufficient to block the strong noxious stimulation of intubation. Tracheal intubation resulted in "classical" cortical arousal. It remains open whether this cortical wake-up phenomenon has a clinical impact.
A novel ion selective PVC membrane electrode for determination of propranolol in pharmaceutical formulation (2000)

A novel ion selective PVC membrane electrode for determination of propranolol is developed. Silicotungstic acid is used as the counter ion and diisononyl phthalate (DNP) used as the plastizer. The electrode exhibits excellent potential response properties, showing a Nernstian response in the concentration of $3.0 \times 10^{-6} \sim 2.6 \times 10^{-2}$ M with the slope of 54.7 mV per decade, shorter conditioning time (~ 3 h), fast response time (40 s), a lower limit of detection ($1.0 \times 10^{-7}$ M). The electrode is successfully used for the analysis of propranolol in pharmaceutical formulation with the recoveries of 99.2 ~ 102.6%, by using a direct potentiometric method and which does not require tedious sample preparation.
A Case of Aconite Intoxication and Recurrent Ventricular Arrhythmia without Apparent Myocardial Damage after 20,680 Joules DC Shock (1997)

The aconite root has been used in oriental medicine to improve metabolism of debilitated patient and to cure acute dysuria, cardiac weakness, gout, neuralgias and rheumatism. The crude drug “ bu-shi” or “ cho-oh” , which is obtained from the Aconitum roots, contains the potent poisons aconitine, mesaconitine, jesaconitine, and hypaconitine, which are C19 diterpenoid ester alkaloids. These alkaloids have been known to induce fatal cardiac arrhythmias, such as ventricular tachycardia, and ventricular fibrillation. In ventricular tachycardia or fibrillation, cardioversion/defibrillation are the most effective treatment of choice to terminate reentrant arrhythmias. Through animal experiments, it has been known that repeated delivery of high energy DC shocks cause some myocardial damage, and the severity of myocardial damage is proportional to the delivered energy. The paddle size, defibrillation interval and total delivered energy have also been known to be associated with the severity of injury. But in humans, the amount of energy that causes myocardial damage or dysfunction has not been studied. Therefore it is necessary that a quantitative study on this issue in conjunction with the amount of each delivered energy and the interval between electrical shocks should be done. We experienced a 36 year old man who complained nausea, vomiting, dizziness and generalized weakness and showed hemodynamic compromise with recurrent ventricular tachyarrhythmias such as bidirectional ventricular tachycardia, Torsades de pointes and ventricular fibrillation. This patient was resuscitated with repeated cardioversion/defibrillation of 20,680 Joules for 8 hours and 30 minutes, but did not show significant myocardial damage.
Discovery of (R)-4-(8-Fluoro-2-oxo-1,2-dihydroquinazolin-3(4H)-yl)-N-(3-(7-methyl-1H-indazol-5-yl)-1-oxo-1-(4-(piperidin-1-yl)piperidin-1-yl)propan-2-yl)piperidine-1-carboxamide (BMS-694153): A Potent Antagonist of the Human Calcitonin Gene-Related Peptide Receptor for Migraine with Rapid and Efficient Intranasal Exposure (2008)

Calcitonin gene-related peptide (CGRP) has been implicated in the pathogenesis of migraine. Early chemistry leads suffered from modest potency, significant CYP3A4 inhibition, and poor aqueous solubility. Herein, we describe the optimization of these leads to give 4 (BMS-694153), a molecule with outstanding potency, a favorable predictive toxicology profile, and remarkable aqueous solubility. Compound 4 has good intranasal bioavailability in rabbits and shows dose-dependent activity in validated in vivo and ex vivo migraine models.
Radiosensitization of Serratia marcescens by nitropyridinium compounds. (1978)

The two nitropyridinium compounds tested sensitize hypoxic Serratia marcescens to irradiation up to the oxygen enhancement level by two components which can be separated as a function of compound concentration. Sensitization above the initial plateau level is in order of their determined one-electron reduction potentials, Ro 03-5580 (E 7 1 = -335 mV) being more efficient than Ro 03-5637 (E 7 1 = -358 mV). Additivity in sensitization up to a maximum enhancement level of 2.1 +/- 0.1 is found on combining these hydrophilic compounds at concentrations to give sensitization at the plateau level, with the hydrophobic sensitizer paranitroacetophenone (PNAP). It is concluded that the nitropyridinium compounds and PNAP sensitize the same site.
The Space Group Visualizer (2013)

A new free interactive OpenGL software tool is demonstrated, that visualizes all monoclinic, and so far part of the orthorhombic, triclinic and hexagonal space group symmetries. The software computes with Clifford (geometric) algebra. The space group visualizer originated as a script for the open source visual CLUCalc, which fully supports geometric algebra computation. This paper briefly describes the historical and scientific developments leading to the space group visualizer project. Then we step by step demonstrate space group selection and the powerful set of interactive tools, including continuous free interactive 3D rotations, repositioning and resizing of the crystal domain in view. The most prominent feature of the space group visualizer is the full visualization of all spatial symmetries of a crystal domain. Beyond this the user can reduce the view to single symmetry operations or to certain classes of symmetries.