gebhart/patrepeval huggingface dataset:
Discovery of VNRX-7145 (VNRX-5236 Etzadroxil): An Orally Bioavailable β-Lactamase Inhibitor for Enterobacterales Expressing Ambler Class A, C, and D Enzymes (2021)

A major antimicrobial resistance mechanism in Gram-negative bacteria is the production of β-lactamase enzymes. The increasing emergence of β-lactamase-producing multi-drug-resistant "superbugs" has resulted in increases in costly hospital Emergency Department (ED) visits and hospitalizations due to the requirement for parenteral antibiotic therapy for infections caused by these difficult-to-treat bacteria. To address the lack of outpatient treatment, we initiated an iterative program combining medicinal chemistry, biochemical testing, microbiological profiling, and evaluation of oral pharmacokinetics. Lead optimization focusing on multiple smaller, more lipophilic active compounds, followed by an exploration of oral bioavailability of a variety of their respective prodrugs, provided <b>36</b> (VNRX-7145/VNRX-5236 etzadroxil), the prodrug of the boronic acid-containing β-lactamase inhibitor <b>5</b> (VNRX-5236). <i>In vitro</i> and <i>in vivo</i> studies demonstrated that <b>5</b> restored the activity of the oral cephalosporin antibiotic ceftibuten against Enterobacterales expressing Ambler class A extended-spectrum β-lactamases, class A carbapenemases, class C cephalosporinases, and class D oxacillinases.
Determination of Rac inhibitor Ehop‐016 in mouse plasma by ultra‐performance liquid chromatography tandem mass spectrometry (987.2) (2014)

The Rho GTPase Rac is an important regulator of cancer cell migration and cell invasion; processes required for metastatic progression. We previously characterized the small molecule Ehop‐016 as a novel Rac inhibitor in metastatic breast cancer cells in‐vitro (Montalvo‐Ortiz, et al., 2012). To investigate the efficacy of EHop‐016 in‐vivo, we used a mouse model of experimental metastasis, where mice with MDA‐MB‐435 mammary fat pad tumors were treated with intraperitoneal EHop‐016. At 25 and 40 mg/kg BW, EHop‐016 significantly inhibited mammary tumor growth and metastasis. In order to characterize the pharmacokinetics of Ehop‐016, we developed a rapid and sensitive method for the quantitation of Ehop‐016 in mouse plasma by ultra high performance liquid chromatography coupled with electrospray ionization tandem mass spectrometry (UPLC/MS/MS). Plasma samples were pretreated with acetonitrile (ACN) to extract matrix proteins prior to injection into UPLC/MS/MS. Separation was carried out on an Agilent Poroshell 120 EC‐C18 column (3.0 x 50) mm using a mobile phase of 50% ACN/50% methanol/0.1% formic acid and 1mM ammonium fluoride. Ehop‐016 was identified from its accurate mass and retention times from the acquired full‐scan chromatogram and quantified by its peak areas. The linear range for the determination of analytes was 5 ‐ 1000 ng/mL. Ehop‐016 was quantified in samples from the in‐vivo study using this method.
Development of a microfluidic perfusion 3D cell culture system (2018)

Recently, 3-dimensional in vitro cell cultures have gained much attention in biomedical sciences because of the closer relevance between in vitro cell cultures and in vivo environments. This paper presents a microfluidic perfusion 3D cell culture system with consistent control of long-term culture conditions to mimic an in vivo microenvironment. It consists of two sudden expansion reservoirs to trap incoming air bubbles, gradient generators to provide a linear concentration, and microchannel mixers. Specifically, the air bubbles disturb a flow in the microfluidic channel resulting in the instability of the perfusion cell culture conditions. For long-term stable operation, the sudden expansion reservoir is designed to trap air bubbles by using buoyancy before they enter the culture system. The performance of the developed microfluidic perfusion 3D cell culture system was examined experimentally and compared with analytical results. Finally, it was applied to test the cytotoxicity of cells infected with Ewing's sarcoma. Cell death was observed for different concentrations of H2O2. For future work, the developed microfluidic perfusion 3D cell culture system can be used to examine the behavior of cells treated with various drugs and concentrations for high-throughput drug screening.
Physical Layer Cryptographic Key Generation by Exploiting PMD of an Optical Fiber Link (2018)

We present a symmetric physical layer based secret key generation scheme for Point-to-Point Optical Link (PPOL) communication by exploiting Polarization Mode Dispersion (PMD) as a random and inimitable channel characteristic. The randomness and security strength of generated cryptographic keys based on PMD is significantly high. In this paper, we present that random modulation of a probe signal caused by PMD in a high-speed data communication network (40Gb/s and 60Gb/s) is reciprocal with average Pearson correlation coefficient of 0.862, despite the presence of optical nonlinearities, dispersion, and noise in the system. 128-bit symmetric cryptographic key has been successfully generated using the proposed scheme. Moreover, PMD based encryption keys passed the National Institute of Standards and Technology (NIST) tests. We have shown through simulations with a 50km link that, with optimal key generation settings, symmetric keys can be generated with high randomness (high P-values for NIST randomness tests) and with sufficient generation rates (>50%). Furthermore, we considered an attack model of a non-invasive adversary intercepting at 10km into the link and found that the generated keys have high average key bit mismatch rates (>40%).
Boron selective thin film composite nanofiltration membrane fabricated <i>via</i> a self-assembled trimesic acid layer at a liquid–liquid interface on an ultrafiltration support (2019)

A negatively charged nanofiltration membrane was prepared with a high selectivity for the rejection of both multivalent and monovalent ions during seawater pre-treatment.
Data from Highly Potent, Anthracycline-based Antibody–Drug Conjugates Generated by Enzymatic, Site-specific Conjugation (2023)

<div>Abstract<p>Antibody–drug conjugates (ADC) are highly potent and specific antitumor drugs, combining the specific targeting of mAbs with the potency of small-molecule toxic payloads. ADCs generated by conventional chemical conjugation yield heterogeneous mixtures with variable pharmacokinetics, stability, safety, and efficacy profiles. To address these issues, numerous site-specific conjugation technologies are currently being developed allowing the manufacturing of homogeneous ADCs with predetermined drug-to-antibody ratios. Here, we used sortase-mediated antibody conjugation (SMAC) technology to generate homogeneous ADCs based on a derivative of the highly potent anthracycline toxin PNU-159682 and a noncleavable peptide linker, using the anti-HER2 antibody trastuzumab (part of Kadcyla) and the anti-CD30 antibody cAC10 (part of Adcetris). Characterization of the resulting ADCs <i>in vitro</i> and <i>in vivo</i> showed that they were highly stable and exhibited potencies exceeding those of ADCs based on conventional tubulin-targeting payloads, such as Kadcyla and Adcetris. The data presented here suggest that such novel and highly potent ADC formats may help to increase the number of targets available to ADC approaches, by reducing the threshold levels of target expression required. <i>Mol Cancer Ther; 16(5); 879–92. ©2017 AACR</i>.</p></div>
Laser photochemical etching of molybdenum and tungsten thin films by surface halogenation (1986)

Laser direct-write etching of the refractory metals Mo and W has been developed using reactions in Cl2 and NF3 vapors. Rates and high spatial resolution are simultaneously optimized using a two-vapor halogenation/development sequence, based on surface modification. Local-area laser chlorination of the metal surface is used to predispose areas to subsequent bulk etching.
A novel neural-network-based image resolution enhancement (2004)

In this paper, a novel HVS-directed neural-network-based adaptive interpolation scheme for natural image is proposed. A fuzzy decision system built from the characteristics of the human visual system (HVS) is proposed to classify pixels of the input image into human perception non-sensitive class and sensitive class. High-resolution digital images along with supervised learning algorithms are used to automatically train the proposed neural network. Simulation results demonstrate that the proposed new resolution enhancement algorithm can produce higher visual quality of the interpolated image than the conventional interpolation methods.
Measurement of nanomechanical resonant structures in single-crystal silicon (1998)

We have used electron beam lithography to make very small (&lt;30 nm linewidth) mechanical structures in single-crystal silicon. These structures can be driven capacitively by applying a voltage between the suspended portion and the underlying substrate. Optical interference techniques are used to detect and measure the motion of the structures with resonant frequencies above 40 MHz. We employed a design consisting of a square mesh with a 315 nm period, which results in a low mass (∼1×10−13 g) and large relative surface area (10−6 cm2). Also, by making suboptical-wavelength features, the optical properties can be altered, leading to an improved measurement sensitivity. We measured the oscillations at small amplitudes where the detected change in the optical reflection is proportional to the drive amplitude.
Ultraviolet and visible light spectrophotometric approach to blood typing: objective analysis by agglutination index (1999)

The method accurately predicted A, B, and O blood groups, and D type in over 275 samples. Scattering theory-based calculations of relative volumes of red cells before and after agglutination show a direct correlation with the agglutination index and provide the theoretical basis of the analysis. This quantitative technique is reproducible and has the potential for automation.
A Lossless Beam-Forming Network for Linear Arrays Based on Overlapped Sub-Arrays (2013)

A novel lossless beam-forming network (BFN) architecture for limited field of view and multi-beam linear arrays is introduced. The BFN, which is based on the overlapped sub-array technique, presents a number of advantages if compared to previous architectures. The most attractive feature consists in a substantial reduction of the number of control elements and associated active devices (i.e., amplifiers, variable phase shifters, etc.). This advantage is achieved adopting a lossless topology with reduced implementation complexity together with a rigorous and analytical design methodology which allows to fully define the BFN at architectural level and to optimize the sub-array radiation pattern in a least mean square error sense.
Genome-wide Screening Reveals the Genetic Determinants of an Antibiotic Insecticide in Bacillus thuringiensis (2010)

Thuringiensin is a thermostable secondary metabolite in Bacillus thuringiensis and has insecticidal activity against a wide range of insects. Until now, the regulatory mechanisms and genetic determinants involved in thuringiensin production have remained unclear. Here, we successfully used heterologous expression-guided screening in an Escherichia coli-Bacillus thuringiensis shuttle bacterial artificial chromosome library, to clone the intact thuringiensin synthesis (thu) cluster. Then the thu cluster was located on a 110-kb endogenous plasmid bearing insecticide crystal protein gene cry1Ba in strain CT-43. Furthermore, the plasmid, named pBMB0558, was indirectly cloned and sequenced. The gene functions on pBMB0558 were annotated by BLAST based on the GenBank(TM) and KEGG databases. The genes on pBMB0558 could be classified into three functional modules: a thuringiensin synthesis cluster, a type IV secretion system-like module, and mobile genetic elements. By HPLC coupling mass spectrometer, atmospheric pressure ionization with ion trap, and TOF technologies, biosynthetic intermediates of thuringiensin were detected. The thuE gene is proved to be responsible for the phosphorylation of thuringiensin at the last step by vivo and vitro activity assays. The thuringiensin biosynthesis pathway was deduced and clarified. We propose that thuringiensin is an adenine nucleoside oligosaccharide rather than an adenine nucleotide analog, as is traditionally believed, based on the predicted functions of the key enzymes, glycosyltransferase (ThuF) and exopolysaccharide polymerization protein (Thu1).
Whole-chip ESD protection design verification by CAD (2009)

CAD is essential to simulation, design and synthesis of on-chip ESD protection circuitry to ensure design prediction and verification at whole-chip level. This paper reviews a new function-based ESD CAD platform and design methodology, including arbitrary ESD protection device extraction algorithm, smart parametric ESD checking mechanism, smart ESD zapping simulation flow and new CAD tools enabling whole-chip ESD protection design verification. Practical design examples are presented.
Molecular mechanisms of Plasmodium falciparum placental adhesion . Microreview (2001)

In natural Plasmodium falciparum infections, parasitized erythrocytes (PEs) circulate in the peripheral blood for a period corresponding roughly to the first part of the erythrocytic life cycle (ring stage). Later, in blood-stage development, parasite-encoded adhesion molecules are inserted into the erythrocyte membrane, preventing the circulation of the PEs. The principal molecule mediating PE adhesion is P. falciparum erythrocyte membrane protein 1 (PfEMP1), encoded by the polymorphic var gene family. The population of parasites is subject to clonal antigenic variation through changes in var expression, and a single PfEMP1 variant is expressed at the PE surface in a mutually exclusive manner. In addition to its role in immune evasion, switches in PfEMP1 expression may be associated with fundamental changes in parasite tissue tropism in malaria patients. A switch from CD36 binding to chondroitin sulphate A (CSA) binding may lead to extensive sequestration of PEs in placenta syncytiotrophoblasts. This is probably a key event in malaria pathogenesis during pregnancy. The CSA-binding phenotype of mature PEs is linked to another distinct adhesive phenotype: the recently described CSA-independent cytoadhesion of ring-stage PEs. Thus, a subpopulation of PEs that sequentially displays these two different phenotypes may bind to an individual endothelial cell or syncytiotrophoblast throughout the asexual blood-stage cycle. This suggests that non-circulating (cryptic) parasite subpopulations are present in malaria patients.
Integrating context information into enterprise applications for the mobile workforce - a case study (2001)

The integration of context information (especially location information) into mobile applications and services is one of the most crucial requirements to achieve a broader usability and hence acceptance of these. So far location information is used for typical business-to-consumer applications such as mobile-MapQuest or ATM-finder. The application of location awareness in typical enterprise or business applications, such as logistics or Customer Relationship Management (CRM), is currently addressed rather poor.
Optimal traffic aggregation in multi-RAT heterogeneous wireless networks (2016)

Traffic load balancing and radio resource management is key to harness the dense and increasingly heterogeneous deployment of next generation “5G” wireless infrastructure. Strategies for aggregating user traffic from across multiple radio access technologies (RATs) and/or access points (APs) would be crucial in such heterogeneous networks (HetNets), but are not well investigated. In this paper, we develop a low complexity solution for maximizing an α-optimal network utility leveraging the multi-link aggregation (simultaneous connectivity to multiple RATs/APs) capability of users in the network. The network utility maximization formulation has maximization of sum rate (α = 0), maximization of minimum rate (α → ∞), and proportional fair (α = 1) as its special cases. A closed form is also developed for the special case where a user aggregates traffic from at most two APs/RATs, and hence can be applied to practical scenarios like LTE-WLAN aggregation (LWA) and LTE dual-connectivity solutions. It is shown that the required objective may also be realized through a decentralized implementation requiring a series of message exchanges between the users and network. Using comprehensive system level simulations, it is shown that optimal leveraging of multi-link aggregation leads to substantial throughput gains over single RAT/AP selection techniques.
Design and experimental evaluation of an electromechanical engine valve drive (2004)

In conventional internal combustion (IC) engines, engine valve timing is fixed with respect to crankshaft angle. Flexibly controlled valve timing offers significant improvements in fuel efficiency, engine performance and emissions. One way to achieve variable valve timing (VVT) is by using an electromechanical valve drive (EMVD). In this paper, we describe the design and experimental evaluation of a new EMVD comprising an electric motor coupled by a nonlinear mechanical transformer to a resonant valve-spring system. Experimental results demonstrate that a 3.3 ms transition time adequate for 6 krpm engine speed, reasonable power consumption, and low valve seating velocity are obtained with the design.
Optimal MU-MIMO precoder with MISO decomposition approach (2010)

This paper proposes a new iterative implementation algorithm for sum-rate maximization in a Multiuser MIMO system (MU-MIMO). The proposed algorithm is based on joint precoder and decoder optimization. For that we considered the best existing precoder design algorithm for a MISO multiuser system proposed in . This algorithm is based on the Lagrangian sum-rate maximization procedure. For the receiving part, an optimal receiver is designed based on the system throughput maximization derived in the general case from the sum-rate expression given for a MU-MIMO broadcast channel. To link these two optimal algorithms, we use an iterative procedure transforming the MU-MIMO channel for each iteration into a MU-MISO channel trough virtual channel calculations. Finally to validate our prosed solution we compare it with an existing MMSE based iterative optimization algorithm. This algorithm proposed in is based on an MMSE as well at the transmission side than at the receiving side. The obtained results demonstrate significant gains without introducing neither supplementary complexity nor resource needs.
Simple Fairness Protocols for Daisy Chain Interconnects (2009)

In this paper, we focus on fair access to bandwidth in daisy-chained interconnects. We first analyze the original HyperTransport fairness protocol and show that it is not perfectly fair. We then propose a new, fair scheme whose complexity is similar to that of the HyperTransport protocol.
Crystallophore: a versatile lanthanide complex for protein crystallography combining nucleating effects, phasing properties, and luminescence (2017)

Macromolecular crystallography suffers from two major issues: getting well-diffracting crystals and solving the phase problem inherent to large macromolecules. Here, we describe the first example of a lanthanide complex family named "crystallophore" (Xo4), which contributes to tackling both bottlenecks. This terbium complex, Tb-Xo4, is an appealing agent for biocrystallography, combining the exceptional phasing power of the Tb(iii) heavy atom with powerful nucleating properties, providing ready-to-use crystals for structure determination. Furthermore, protein/Tb-Xo4 co-crystals can be easily detected and discriminated from other crystalline by-products using luminescence. We demonstrate the potential of this additive for the crystallisation and structure determination of eight proteins, two of whose structures were unknown.
Coherence characteristics of electrically excited tandem organic light-emitting diodes (2005)

A tandem organic light-emitting diode structure, excited electrically in the pulsed domain and confined within a double spatial filter configuration, is observed to emit a low-divergence beam (deltatheta approximately 2.53 mrad, or approximately 1.1 times the diffraction limit) with a near-Gaussian spatial distribution. The emission originates from the laser dye Coumarin 545 T, which is used as a dopant. Spectral coherence was determined by use of a double-slit interferometer. The interferometric distribution from our device approximates the interferometric pattern obtained from well-known lasers emitting at lambda approximately 540 nm.
Local quality assessment for optical coherence tomography (2008)

Optical coherence tomography (OCT) is a non-invasive tool for visualizing the retina. It is increasingly used to diagnose eye diseases such as glaucoma and diabetic maculopa- thy. However, diagnosis is only possible when the layers of the retina can be easily distinguished, which is when the images are evenly illuminated. Automated OCT quality assessment (i.e. signal strength) is only available for images as a whole. In this work, we present an automated method for local quality assessment. For training data, three OCT experts label the quality of each individual a-scan line in 270 OCT images. We extract features that are insensitive to pathology, and employ a hierarchy of support vector machines and histogram-based metrics. Our trained classifier is able to determine not only when signal strength is low, but also when it will affect doctors' diagnostic ability. Our results improve over the state of the art in OCT quality assessment.
Two Dimensional Code Based on Low Density Parity Check and Reed–Solomon Codes for the Terrestrial Cloud Transmission System (2014)

In this paper, we propose a two dimensional (2-D) code based on a vertical low-density parity check (LDPC) code and a horizontal Reed-Solomon code for the cloud transmission system. The proposed 2-D code shows superior performance under fading channels due to its inherent block-type interleaving feature. Furthermore, the proposed 2-D code can be adaptively decoded to reduce decoding latency and complexity because the vertical LDPC code has raptor-like rate-compatible feature.
Selecting for lactic acid producing and utilising bacteria in anaerobic enrichment cultures (2020)

Lactic acid-producing bacteria are important in many fermentations, such as the production of biobased plastics. Insight in the competitive advantage of lactic acid bacteria over other fermentative bacteria in a mixed culture enables ecology-based process design and can aid the development of sustainable and energy-efficient bioprocesses. Here we demonstrate the enrichment of lactic acid bacteria in a controlled sequencing batch bioreactor environment using a glucose-based medium supplemented with peptides and B vitamins. A mineral medium enrichment operated in parallel was dominated by Ethanoligenens species and fermented glucose to acetate, butyrate and hydrogen. The complex medium enrichment was populated by Lactococcus, Lactobacillus and Megasphaera species and showed a product spectrum of acetate, ethanol, propionate, butyrate and valerate. An intermediate peak of lactate was observed, showing the simultaneous production and consumption of lactate, which is of concern for lactic acid production purposes. This study underlines that the competitive advantage for lactic acid-producing bacteria primarily lies in their ability to attain a high biomass specific uptake rate of glucose, which was two times higher for the complex medium enrichment when compared to the mineral medium enrichment. The competitive advantage of lactic acid production in rich media can be explained using a resource allocation theory for microbial growth processes.