gebhart/patrepeval huggingface dataset:
A Simple Rank Test to Distinguish Extreme Pathways from Elementary Modes in Metabolic Networks (2008)

Background: Metabolic pathway analysis is a powerful tool to study the metabolic structure of a cellular metabolism that comprises an intricate network for transforming metabolites through enzyme-catalyzed reactions. The approach is based on convex analysis to solve a homogeneous system of linear equations and inequality constraints derived from the steady state operation of mass conservation of metabolites. The solutions constitute the admissible flux space known as the convex polyhedral cone. Elementary Mode and Extreme Pathway Analysis are two closely related techniques that have been developed to identify pathways spanning the admissible flux space. Both elementary modes and extreme pathways are genetically independent pathways that can support steady state operation of cellular metabolism. However, the set of extreme pathways is often a subset of elementary modes, and under certain conditions only extreme pathways are the generating edges of the polyhedral cone. Because the two techniques are closely related, it is important to develop a theoretical framework to distinguish extreme pathways from elementary modes.\nResults: We have found a simple algebraic test to distinguish extreme pathways from elementary modes which requires only the stoichiometry matrix. The method has been tested with published metabolic networks that have been characterized with Elementary Mode Analysis and Extreme Pathway Analysis. The identity and number of elementary modes are not altered in networks subjected to splitting every reversible reaction into two different irreversible reactions, other than the spurious futile cycles involving the new reactions themselves. However, the set of extreme pathways depends strongly on the specific treatment of the reversible reactions of the network. The application of this algebraic test for efficient computation of elementary modes in very large networks is discussed.\nConclusions: Elementary modes are the complete set of genetically independent pathways of a cellular metabolism that supports steady state operation. With the simple algebraic test, we can easily identify whether a given pathway is an elementary mode or an extreme pathway before computing the complete set of pathways. This test provides a convenient way to analyze and interpret network topology with Metabolic Pathway Analysis. The algebraic test is also useful for improving the efficiency of computing elementary modes in very large metabolic networks.
Tabletop coherent diffractive imaging of extended objects in transmission and reflection geometry (2013)

Recent breakthroughs in high harmonic generation have extended the reach of bright tabletop coherent light sources from a previous limit of &asymp;100 eV in the extreme ultraviolet (EUV) all the way beyond 1 keV in the soft X-ray region. Due to its intrinsically short pulse duration and spatial coherence, this light source can be used to probe the fastest physical processes at the femtosecond timescale, with nanometer-scale spatial resolution using a technique called coherent diffractive imaging (CDI). CDI is an aberration-free technique that replaces image-forming optics with a computer phase retrieval algorithm, which recovers the phase of a measured diffraction amplitude. This technique typically requires the sample of interest to be isolated; however, it is possible to loosen this constraint by imposing isolation on the illumination. Here we extend previous tabletop results, in which we demonstrated the ability to image a test object with 22 nm resolution using 13 nm light [3], to imaging of more complex samples using the keyhole CDI technique adapted to our source. We have recently demonstrated the ability to image extended objects in a transmission geometry with &asymp;100 nm resolution. Finally, we have taken preliminary CDI measurements of extended nanosystems in reflection geometry. We expect that this capability will soon allow us to image dynamic processes in nanosystems at the femtosecond and nanometer scale.
A Retrospective Look at the Impact of Binding Site Environment on the Optimization of TRPA1 Antagonists (2021)

Transient receptor potential ankyrin 1 (TRPA1) antagonists have generated broad interest in the pharmaceutical industry for the treatment of both pain and asthma. Over the past decade, multiple antagonist classes have been reported in the literature with a wide range of structural diversity. Our own work has focused on the development of proline sulfonamide and hypoxanthine-based antagonists, two antagonist classes with distinct physicochemical properties and pharmacokinetic (PK) trends. Late in our discovery program, cryogenic electron microscopy (cryoEM) studies revealed two different antagonist binding sites: a membrane-exposed proline sulfonamide transmembrane site and an intracellular hypoxanthine site near the membrane interface. A retrospective look at the discovery program reveals how the different binding sites, and their location relative to the cell membrane, influenced the optimization trajectories and overall drug profiles of each antagonist class.
Exome Sequencing Implicates SWI/SNF Chromatin Remodeling Genes in Human Congenital Hydrocephalus (2019)

INTRODUCTION: Congenital Hydrocephalus (CH) affects 1 in 1000 live births and is treated with lifelong surgical cerebrospinal fluid (CSF) diversion with substantial morbidity. Our group recently sequenced 180 probands with CH and identified 4 novel CH genes, all of which regulate neural stem cell (NSC) fate. Nonetheless, these genes account for just 10% of studied cases. METHODS: We doubled the size of our cohort through robust recruitment and exome-sequenced 361 CH probands, including 216 case-parent trios. To study the effect of novel mutations on brain development, we developed a Xenopus tropicalis model of CH using CRISPR/Cas9. Multiple, nonoverlapping CRISPR guide RNAs targeted against candidate genes were designed and injected into fertilized single cell Xenopus embryos via microinjection. Ventricular morphology and CSF flow dynamics were analyzed via optical coherence tomography (OCT) imaging. Histological sections from WT and mutant Xenopus embryos were subjected to whole-mount in Situ hybridization to assess expression of various markers of NSC growth and proliferation. RESULTS: We identified new causative mutations in both previously identified and novel genes, all of which regulate ventricular zone NSC fate. Of these, enrichment in rare, damaging variants was highest in the SWI/SNF chromatin remodeling complex genes SMARCC1 and ARID1B (P = 1.83 × 10-9). Xenopus tadpoles harboring mutations in SMARCC1 exhibited marked ventriculomegaly, aqueductal stenosis, and impaired CSF flow. In Situ hybridization of SMARCC1 knockout brain sections demonstrated decreased expression of genes regulating NSC growth and proliferation. Notably, injection of wild type SMARCC1 RNA restored normal brain development in SMARCC1 KO embryos. CONCLUSION: These findings implicate SWI/SNF complex genes in CH and validate the use of Xenopus for investigating additional candidate genes. These findings highlight the importance of NSC dysregulation in CH pathology, and suggest that in a subset of patients the risk of adverse neurodevelopmental outcomes may be unaltered whether or not shunting is performed.
Biologika: Neue Therapieoption bei schwerer chronisch polypöser Rhinosinusitis (2021)

Chronic rhinosinusitis (CRS) is defined as an inflammation of the nose and paranasal sinuses with prevalence of 10.9 % and by the presents of 2 or more symptoms, which last more than 12 weeks. The symptoms are nasal obstruction, nasal discharge (anterior/post nasal drip), facial pain or pressure and/or olfactory disorder. CRS has a high negative impact on an individual's quality of life. The pathogenesis is multifactorial and complex. CRS has been subclassiﬁed into 2 groups: CRS with nasal polyps (CRSwNP) and CRS without nasal polyps (CRSsNP). Regarding further knowledge of the inflammatory pathway the primary CRS is considered by endotype dominance, either type 2 or non-type 2. 80 % of the CRSwNP reveals a type 2 inflammation. The proteins, interleukin (IL)-4, IL-5, IL-13, and IgE were previously identified as key mediators in nasal polyp tissues pattern. CRSwNP is often refractory to medical and surgical management, especially in patients with asthma and aspirin intolerance. In most cases the control of the disease is a challenge. Patients with asthma but especially with Samter's triad are significantly more likely to have a recurrence of nasal polyps and undergo a second surgery following recurrence. In patients with severe CRSwNP, in whom the current standard of care including topical and oral corticosteroids, antibiotics and surgical procedures fail to control the disease, biologics can open new perspectives in treatment. They allow avoiding the possible adverse events resulting from repeated use of systemic corticosteroids and surgery. These biologics have a high impact on type 2 immune reaction and lead to a reduction of IgE as well as of local mucosal eosinophil migration and activation, resulting in a significant effect on nasal polyps, smell, quality of life and asthma comorbidity.
Enhanced fat suppression technique for breast imaging (2012)

DFS is a promising fat suppression technique for breast imaging even in regions with B1 (+) inhomogeneity.
10.2: Electrofluidic Displays: Multi‐stability and Display Technology Progress (2011)

Abstract Electrofluidic displays have been demonstrated with multi‐stable states that enable on, off, or grey‐scaled pixel states with zero holding power. We demonstrate operating principles and characterize optical, electrical and environmental performance. We also report other electrofluidic developments including device operation from − 30°C to 70 °C and 30 millisecond switching speeds at 25°C.
Table ST5 from ROS Induction Targets Persister Cancer Cells with Low Metabolic Activity in NRAS-Mutated Melanoma (2023)

&lt;p&gt;Table ST5: Table of the 15 most informative proteins upregulated in MEK inhibitor-resistant cell culture (ranked by log2 fold-change).&lt;/p&gt;
Clinical phase I data of the first orally available anti‐aβ‐prionic drug PRI‐002 that reverses behavioral and cognitive deficits, and decelerates neurodegeneration in AD animal models (2020)

Abstract Background More and more data suggest that the toxic protein assemblies of Aβ and TAU behave prion like. The drug candidate PRI‐002 has been developed to directly disassemble and destroy toxic Aβ oligomer prions. The anti‐prionic compound PRI‐002 (alias “RD2”) is BBB penetrable and has demonstrated target engagement in vitro and in vivo . Treatments in three different transgenic mouse models in three different laboratories yielded improved cognition and deceleration of neurodegeneration. Oral treatment of old‐aged transgenic AD mice with full‐blown pathology reversed cognitive and behavioral deficits to levels of healthy wild‐type littermates. We wanted to demonstrate safety and tolerability of PRI‐002 in healthy volunteers up to doses that are much higher than the expected therapeutic dose. Method We carried out a single (4 to 320 mg PRI‐002) and a multiple ascending dose (160 and 320 mg PRI‐002/volunteer) phase I clinical trial in 63 healthy volunteers. Result No drug‐related adverse events (AE) have been observed in the SAD study. The few possibly drug‐related AEs in the MAD study were equally distributed across groups. Already in the SAD, PRI‐002 plasma levels were reached (AUC 0‐24 104 ng h/mL) that were measured in the highest dosed animals of the successful preclinical PoC studies. Conclusion Daily administered oral doses of PRI‐002 up to 320 mg/subject/day for 28 days have been proven to be safe. PoC studies in humans for anti‐prionic compounds may be based on shorter treatment durations and do not necessarily have to be life‐long.
Surfactantgabe ohne Intubation: Multizentrische Daten zu Intubationsraten, Surfactantverbrauch und Begleitmedikation (2007)

Fragestellung: Die Gabe von Surfactant ohne Intubation (über eine beim spontan atmenden Frühgeborenen kurzfristig in der Trachea platzierten Magensonde) wird von einer zunehmenden Zahl von Neonatologen praktiziert. Wir werteten Daten einer multizentrischen Studie zu genetischen Risikofaktoren von Frühgeborenen in Bezug auf die kurzfristigen Effekte und Begleitmedikationen dieser neuen Methode der Surfactantapplikation aus.
Synthesis and Biological Activity of Phosphonate Analogs of Mannose 6-Phosphate (M6P) (1999)

Two phosphonate analogs of mannose 6-phosphate (M6P) have been synthesized. The isosteric analog 1 was obtained by a Wittig–Horner reaction at position 6 of a sugar aldehyde. The non-isosteric analog 2 was obtained by a Michaelis–Arbuzov rearrangement of a 6-bromo derivative. In contrast to the non-isosteric analog 2, the isoster 1 was shown to bind to M6P receptors as effectively as does M6P itself, thus demonstrating the considerable potential of the system in drug design.
Lattice-based training of bottleneck feature extraction neural networks (2013)

This paper investigates a method for training bottleneck (BN) features in a more targeted manner for their intended use in GMM-HMM based ASR. Our approach adds a GMM acoustic model activation layer to a standard BN feature extraction (FE) neural network and performs lattice-based MMI training on the resulting network. After training, the network is reverted back into a working BN FE network by removing the GMM activation layer, and we then train a GMM system on top of the bottleneck features in the normal way. Our results show that this approach can significantly improve recognition accuracy when compared to a baseline system that uses standard BN features. Further, we show that our approach can be used to perform unsupervised speaker adaptation, yielding significantly improved results compared to global cMLLR adaptation.
Ohm's Law + Kirchhoff's Current Law = Better AI: Neural-Network Processing Done in Memory with Analog Circuits will Save Energy (2021)

Machine learning and artificial intelligence (AI) have already penetrated so deeply into our life and work that you might have forgotten what interactions with machines used to be like. We used to ask only for precise quantitative answers to questions conveyed with numeric keypads, spreadsheets, or programming languages: “What is the square root of 10?” “At this rate of interest, what will be my gain over the next five years?”
Pro‐angiogenic Properties of Europium(III) Hydroxide Nanorods (2008)

Human umbilical vein endothelial cells (HUVECs) treated with europium(III) hydroxide nanorods (center figure) indicate the internalization of these nanorods to the cytoplasm of the cells. Chick chorioallantoic membrane (CAM) assay of HUVECS treated with the nanorods shows the formation of vascular sprouting, which supports in vivo angiogenesis.
Transactions and privatization in Delaunay triangulation (2007)

No abstract available.
Synthesis of inorganic P1‐[(S)‐16O, 17O, 18O]pyrophosphate (1989)

Abstract A novel synthetic approach has been developed for the synthesis of inorganic pyrophosphate which allows the isotopes 17 O and 18 O to be incorporated at P 1 to give chirally labelled material.
In vitro-chemosensitivity test using the collagen gel droplet embedded culture drug test (CD-DST) for malignant pleural mesothelioma: possibility of clinical application. (2008)

Although the number of tested MPM specimens was small, CD-DST data obtained by biopsy or surgical-fresh specimens of MPM marginally correlated to the disease control effect of chemotherapy for this disease. Therefore CD-DST may possibly be applied to selecting the chemotherapy regimen for MPM. To determine the possibility of a clinical application of this test to MPM, a prospective clinical study of a greater number of patients will be necessary.
Optical Cavity with Large Operational Bandwidth using Silicon-Based Slotted Micromirrors (2020)

In this paper, we report FDTD simulations and experimental results of novel silicon-based optical microcavity comprising of two slotted micromirrors. While the normal range for silicon microcavities is limited by its absorption below 1.1 μm, we demonstrate a silicon cavity that is capable of operation from the visible spectrum till the telecom C-band. Deep reactive ion etching (DRIE) is used to fabricate the deeply etched microcavity mirrors. The structure is metallized with gold to enhance mirrors' reflectivity. The slotted mirror and the cavity structure are simulated using finite difference time domain (FDTD), and the results are reported showing a quality factor of 2796 for visible TM excitation and a quality factor of 2346 for NIR TM excitation. The experimental results report the characteristics of the resonator and verify its operation in the NIR and visible ranges. The measured quality factor (Q) is 2067 around the 565 nm peak and 1922 around the 1550 nm peak. Such a microcavity would present a major step towards realizing visible laser on silicon for micro optofluidic applications.
Dielectric properties of highly c‐axis oriented chemical solution deposition derived SrBi4Ti4O15 thin films (2008)

Abstract C ‐axis oriented thin films of SrBi 4 Ti 4 O 15 were prepared by a chemical solution deposition method. The influence of precursor chemistry and processing conditions on the resulting film morphology and the dielectric properties of SrBi 4 Ti 4 O 15 thin films were investigated. By controlling the film formation process, highly c ‐axis oriented SrBi 4 Ti 4 O 15 thin films on (111)Pt/Si substrates were obtained at temperatures of 600 °C and 700 °C. The dielectric constant of the films is about 200 and it is independent of film thickness ranging from 55 to 160 nm. The dielectric constant also shows stable value with an increase in temperature from 25 °C to 200 °C. The leakage current of the film at 125 °C is in the order of 10 –7 A/cm 2 at an applied electric field of 500 kV/cm. These films exhibit stable dielectric constant and excellent insulating properties. (© 2009 WILEY‐VCH Verlag GmbH &amp; Co. KGaA, Weinheim)
Prolonged natural progression from localized to symptomatic renal cell carcinoma. (2012)

Surgical excision is the gold standard therapy for clinically localized renal masses. Nevertheless, prognostication of the natural history of untreated renal cell carcinoma (RCC) remains a clinical challenge. While active surveillance (AS) has emerged as a viable treatment option in select patients with localized tumors and significant competing mortality risks, long term follow up data to assess the risk of disease progression are limited. We present a case of a localized, clinical stage T2 renal mass progressing to regional and systemic disease over 6 years, demonstrating that kinetics of disease progression may be prolonged and are yet to be fully understood.
Silicon-based Photonic Integrated Circuits for the Mid-infrared (2016)

Silicon-based photonic integrated circuits (PICs) operating in the mid-infrared wavelength range are presented. Firstly, it is shown that the operation of the SOI-based waveguide circuits can be pushed beyond the telecom window till a wavelength of 4 μm. Ge-on-Si based PICs are demonstrated for operation beyond 4 μm wavelength. Low-loss waveguides and integrated spectrometers are reported for both the waveguide platforms. We also present our results on efficient thermo-optic phase shifters for germanium waveguide circuits.
Effect of tracer arrival time on the estimation of the myocardial perfusion in DCE-CMR (2012)

An accurate segmental myocardial blood flow (MBF) quantification can be performed by means of signal deconvolution techniques. The accuracy of MBF estimates relies on the precise identification of the tracer arrival time in the myocardium (tOnset). Voxelwise MBF quantification is likely to be more subject to such error than segmental MBF analysis due to the lower signal-to-noise ratio of myocardial signal intensity curves. Automated tOnset detection methods would be therefore warranted. The aim of this study was to assess the importance to of tOnset identification on voxelwise MBF quantification and to describe an automated algorithm to detect the optimal tOnset which minimizes the error in MBF estimates.
Wide field-of-view dual-band multispectral muzzle flash detection (2013)

Sensor technologies are undergoing revolutionary advances, as seen in the rapid growth of multispectral methodologies. Increases in spatial, spectral, and temporal resolution, and in breadth of spectral coverage, render feasible sensors that function with unprecedented performance. A system was developed that addresses many of the key hardware requirements for a practical dual-band multispectral acquisition system, including wide field of view and spectral/temporal shift between dual bands. The system was designed using a novel dichroic beam splitter and dual band-pass filter configuration that creates two side-by-side images of a scene on a single sensor. A high-speed CMOS sensor was used to simultaneously capture data from the entire scene in both spectral bands using a short focal-length lens that provided a wide field-of-view. The beam-splitter components were arranged such that the two images were maintained in optical alignment and real-time intra-band processing could be carried out using only simple arithmetic on the image halves. An experiment related to limitations of the system to address multispectral detection requirements was performed. This characterized the system’s low spectral variation across its wide field of view. This paper provides lessons learned on the general limitation of key hardware components required for multispectral muzzle flash detection, using the system as a hardware example combined with simulated multispectral muzzle flash and background signatures.
Recursive Frank-Wolfe algorithms (2020)

In the last decade there has been a resurgence of interest in Frank-Wolfe (FW) style methods for optimizing a smooth convex function over a polytope. Examples of recently developed techniques include {\em Decomposition-invariant Conditional Gradient} (DiCG), {\em Blended Condition Gradient} (BCG), and {\em Frank-Wolfe with in-face directions} (IF-FW) methods. We introduce two extensions of these techniques. First, we augment DiCG with the {\em working set} strategy, and show how to optimize over the working set using {\em shadow simplex steps}. Second, we generalize in-face Frank-Wolfe directions to polytopes in which faces cannot be efficiently computed, and also describe a generic recursive procedure that can be used in conjunction with several FW-style techniques. Experimental results indicate that these extensions are capable of speeding up original algorithms by orders of magnitude for certain applications.
Electron-Beam Resists for Lift-Off Processing with Potential Application to Josephson Integrated Circuits (1980)

Several electron-beam resists suitable for lift-off processing have been investigated with particular attention to the requirements for fabricating Pb-alloy Josephson integrated circuits. The desired resist must perform well with a baking temperature near 70°C, provide a reproducible undercut edge profile with good linewidth control, and adhere to the necessary substrates. Diazo resists as well as the commonly used PMMA and copolymer materials were studied. Initial results suggest that ®AZ-1350J soaked in chlorobenzene to enhance the undercut profile can satisfy many of these requirements. At present, the amount of undercut obtained is larger than desired, limiting the minimum separation between exposed features to about 1.5 µm.
P05-11. Yeast mannan genetics controls the molecular specificity of anti-carbohydrate antibodies cross-reactive to the HIV envelope (2009)

Immunologically carbohydrates protect the human immunodeficiency virus type -1 (HIV-1) surface glycoprotein, gp120 from antibody recognition. However, one broadly neutralising antibody, 2G12, can protect against primary viral challenge by direct recognition of these self glycans on gp120.