gebhart/patrepeval huggingface dataset:
Repertoire of Computationally Designed Peroxygenases for Enantiodivergent C−H Oxyfunctionalization Reactions (2023)

The generation of enantiodivergent biocatalysts for C−H oxyfunctionalizations is ever more important in modern synthetic chemistry. Here, we have applied the FuncLib algorithm based on phylogenetic and Rosetta calculations to design a diverse repertoire of active, stable, and enantiodivergent fungal peroxygenases. 24 designs, each carrying 4−5 mutations in the catalytic core, were expressed functionally in yeast and benchmarked against characteristic model compounds. Several designs were active and stable in a range of temperature and pH, displaying unprecedented enantiodivergence, changing regioselectivity from alkyl to aromatic hydroxylation, and increasing catalytic efficiencies up to 10-fold, with 15-fold improvements in total turnover numbers over the parental enzyme. We find that this dramatic functional divergence stems from beneficial epistasis among the mutations and an extensive reorganization of the heme channel. Our work demonstrates that FuncLib can rapidly design highly functional libraries enriched in enantioselective peroxygenases not seen in nature for a range of biotechnological applications.
Everolimus in combination with Exemestane in hormone receptor-positive, locally advanced or metastatic breast cancer patients progressing on prior non-steroidal aromatase inhibitors (NSAIs) : BALLET study (CRAD001YIC04) (2015)

peer reviewed
Obstructive Uropathy Secondary to Uretero-inguinal Hernia (2015)

Uretero-inguinal hernia in patients with native kidneys is rare. We report a case of an 84-year-old man who was diagnosed with obstructive uropathy secondary to uretero-inguinal hernia, with no past history of herniorrhaphy or congenital genitourinary malformation. Uretero-inguinal hernias are predominantly indirect inguinal hernias and may be paraperitoneal or extraperitoneal. Computed tomography (CT) is a non-invasive diagnostic tool for uretero-inguinal hernia. Herniorrhaphy is indicated in all cases of uretero-inguinal hernia to prevent obstructive uropathy.
LEAP: Learnable Pruning for Transformer-based Models (2021)

Pruning is an effective method to reduce the memory footprint and computational cost associated with large natural language processing models. However, current pruning algorithms either only focus on one pruning category, e.g., structured pruning and unstructured, or need extensive hyperparameter tuning in order to get reasonable accuracy performance. To address these challenges, we propose LEArnable Pruning (LEAP), an effective method to gradually prune the model based on thresholds learned by gradient descent. Different than previous learnable pruning methods, which utilize $L_0$ or $L_1$ penalty to indirectly affect the final pruning ratio, LEAP introduces a novel regularization function, that directly interacts with the preset target pruning ratio. Moreover, in order to reduce hyperparameter tuning, a novel adaptive regularization coefficient is deployed to control the regularization penalty adaptively. With the new regularization term and its associated adaptive regularization coefficient, LEAP is able to be applied for different pruning granularity, including unstructured pruning, structured pruning, and hybrid pruning, with minimal hyperparameter tuning. We apply LEAP for BERT models on QQP/MNLI/SQuAD for different pruning settings. Our result shows that for all datasets, pruning granularity, and pruning ratios, LEAP achieves on-par or better results as compared to previous heavily hand-tuned methods.
Current Methods of Pharmacologic Stress Testing and the Potential Advantages of New Agents (2009)

This article presents the exciting advances made and ongoing in the area of pharmacologic cardiac stress testing. In particular, new A(2A)-specific receptor agonists work like adenosine but promise the delivery of uncomplicated vasodilator stress testing or the diagnosis and prognosis of coronary disease. These agents, although not perfect, do likely present a level of protection against the complications of bronchospasm and heart block. Phase III studies have shown that these agents promise a reduced symptom intensity and greater patient tolerance. One of these agents, regadenoson, is now Food and Drug Administration approved and will be delivered as the same single-dose bolus in all patients, regardless of weight, greatly simplifying the method and increasing its acceptability. Most widely applied with myocardial perfusion SPECT, these agents will find application with PET myocardial perfusion studies and likely MRI studies. Because of their effect on coronary supply rather than demand, they will not be applied with stress echocardiography. Before considering these agents, we will consider the principles and methods of stress testing, and particularly pharmacologic stress testing. The learning objectives of this article are to familiarize the reader with the methods and choices in stress testing for coronary disease diagnosis and prognosis, to present the advantages and disadvantages of pharmacologic stress testing, to review current pharmacologic stress-testing methods and their specific combination with imaging methods, to present the chemistry and effects of the new A(2a)-specific receptor agonists and their advantages compared with existing nonspecific agents, and to help the reader better understand the clinical role of the A(2a)-specific receptor agonists and their application.
Clinical, genetic, and pathologic determinants of prostate cancer brain metastasis. (2020)

5536 Background: Prostate cancer (PCa) brain metastasis (BM) is a rare event occurring in 0.16-0.63% of PCa patients. Current clinical data on this phenomenon is limited to small retrospective cohorts and our understanding of it is incomplete. We sought to identify clinical and molecular predictors of PCa BM in a large retrospective cohort treated at our institution. Methods: Men diagnosed with Pca from 1995-2017 with ≥6 months of follow-up were included. Data was collected on clinical and tumor characteristics at diagnosis, PCa treatment, brain and bone metastasis, and tumor genetic profile based on Integrated Mutation Profiling of Actionable Cancer Targets (IMPACT) analysis. Results were examined using Kyoto Encyclopedia of Genes and Genome (KEGG) pathway. Genes altered in ≥5% of patients were included. Time to brain metastasis (TTBM) and overall survival (OS) were analyzed with univariable (UVA) Fine-Gray competing risks regression and Cox proportional hazards. TTBM and OS were landmarked at 6 months after PCa diagnosis. False discovery rate (FDR) adjustment accounted for multiple comparisons. Results: 27,887 men met inclusion criteria; 74 developed BM. Clinical variables associated with increased hazard of TTBM in UVA were high-clinical and pathologic-* (p&lt;.001) T stage, node-positive disease* (p&lt;.001), primary* and total* Gleason (p&lt;.001), receipt of abiraterone* (HR 52.51 (95% CI 7.1-389.8), p&lt;.001), and receipt of leuprolide* (HR 3.0 (95% CI 1.7-5.4), p&lt;.001). Tumor alterations associated with BM include mutations in BRCA2 (HR 2.94 (95% CI 1.1-8.0), p=.04), MYC (HR 3.41 (95% CI 1.2-9.5), p=.02), PTEN (HR 2.90 (95% CI 1.2-6.9), p=.02), RB1 (HR 3.09 (95% CI 1.2-8.0), p=.02), and pathways involving homologous recombination (HR 2.70 (95% CI 1.1-6.4), p=.02), Fanconi anemia* (HR 4.22 (95% CI 1.8-10.0), p&lt;.001), Ras signaling* (HR 4.6 (95% CI 1.5-13.9), p=.006), mTOR signaling (HR 2.88 (95% CI 1.1-7.9), p=.04), VEGF signaling* (HR 3.60 (95% CI 1.5-8.8), p=.005), and GnRH signaling* genes (HR 3.93 (95% CI 1.6-9.6), p0.003). Variables associated with increased hazard of BM after FDR adjustment are denoted with an asterisk. Variables associated with reduced OS after FDR adjustment were neuroendocrine or blastoma histology, node-positive disease, high-T stage, high initial PSA, receipt of leuprolide, and alterations in AR, TP53, and CDK12 genes. Conclusions: PCa BM is significantly associated with high-stage and grade disease, receipt of androgen deprivation agents such as abiraterone and leuprolide, and alterations in the Fanconi anemia, Ras, VEGF, and GnRH pathways.
Bridgeless ZETA PFC converter for low voltage high current LED driver (2017)

This paper deals with power factor correction (PFC) in low voltage high current (LVHC) multi-string light emitting diode (LED) using a bridgeless (BL) ZETA. This application is designed for large area LED lighting with illumination control. A multi-mode LED dimming technique is used for lighting control. The BL-ZETA PFC converter feeds power to isolated flyback DC-DC converter. The regulated low voltage from flyback converter is a source power to the synchronous buck converters for multi-string LED driver and forced cooling system for LED junction. The BL-ZETA PFC converter inductor design is based on discontinuous inductor current modes (DICM) which provide good PFC at low cost. The proposed LED driver is designed and developed with hardware test results. The critical parameter of the LED driver is tested and measured at full load with dimming control capability for universal input AC (90–265 V). The total harmonic distortion (THD) is observed lesser than the IEC 61000-3-2 Class C harmonic limits.
High efficiency pure blue thermally activated delayed fluorescence molecules having 10H-phenoxaborin and acridan units (2015)

Highly efficient blue thermally activated delayed fluorescence molecules having 10H-phenoxaborin and acridan units were reported. Pure blue emission peaking at around 450 nm with a high external electroluminescence quantum efficiency of around 20% was demonstrated.
Deinococcus citri sp. nov., isolated from citrus leaf canker lesions (2014)

A Gram-stain-positive, strictly aerobic, non-motile, coccoid bacterium, designated NCCP-154(T), was isolated from citrus leaf canker lesions and was subjected to a polyphasic taxonomic study. Strain NCCP-154(T) grew at 10-37 °C (optimum 30 °C) and at pH 7.0-8.0 (optimum pH 7.0). The novel strain exhibited tolerance of UV irradiation (>1000 J m(-2)). Based on 16S rRNA gene sequence analysis, strain NCCP-154(T) showed the highest similarity to Deinococcus gobiensis CGMCC 1.7299(T) (98.8 %), and less than 94 % similarity to other closely related taxa. The chemotaxonomic data [major menaquinone, MK-8; cell-wall peptidoglycan type, A3β (Orn-Gly2); major fatty acids, summed feature 3 (C16 : 1ω7c/iso-C15 : 0 2-OH; 35.3 %) followed by C16 : 0 (12.7 %), iso-C17 : 1ω9c (9.2 %), C17 : 1ω8c (7.4 %) and iso-C17 : 0 (6.9 %); major polar lipids made up of several unidentified phosphoglycolipids and glycolipids and an aminophospholipid, and mannose as the predominant whole-cell sugar] also supported the affiliation of strain NCCP-154(T) to the genus Deinococcus. The level of DNA-DNA relatedness between strain NCCP-154(T) and D. gobiensis JCM 16679(T) was 63.3±3.7 %. The DNA G+C content of strain NCCP-154(T) was 70.0 mol%. Based on the phylogenetic analyses, DNA-DNA hybridization and physiological and biochemical characteristics, strain NCCP-154(T) can be differentiated from species with validly published names. Therefore, it represents a novel species of the genus Deinococcus. The name Deinococcus citri sp. nov. is proposed, with the type strain NCCP-154(T) ( = JCM 19024(T) = DSM 24791(T) = KCTC 13793(T)).
Evoked bursting in injured Aβ dorsal root ganglion neurons: A mechanism underlying tactile allodynia (2012)

Chronic compression of rat dorsal root ganglion (CCD) produced tactile allodynia accompanied with hyperexcitability of the myelinated Aβ dorsal root ganglion (DRG) neurons. The Aβ DRG neuron hyperexcitability exhibits as bursting discharges in response to peripherally evoked action potentials (evoked bursting [EB]). The incidence of EB was significantly increased after chronic compression of DRG (CCD) (43.3%) vs control (13.3%). EB was maintained by oscillation of the membrane potential, and its duration was increased when the membrane potential was depolarized. EB was found to coexist in some neurons with spontaneous bursting (SB), but EB always occurred at a more negative membrane potential than SB. Afterdischarges of the wide dynamic range neurons of the dorsal horn in the spinal cord in response to electrical stimulation of Aβ afferent nerve fibers were suppressed by blocking EB of the DRG neurons. CCD neurons with EB exhibited increased current density of persistent sodium current (I(Nap)) and hyperpolarization-activated cation current (I(h)) and decreased α-dendrotoxin (α-DTX) sensitive current (I(DTX)). The increased I(h) activated by afterhyperpolarization of peripheral afferent action potential was necessary for EB generation and a balance between I(DTX) and I(Nap) might be necessary for EB maintenance. This study may suggest a role of EB of myelinated DRG neurons in development of allodynia after nerve injury and a potential pharmaceutical therapy in treating neuropathic allodynia.
Real-Time Caustics in Dynamic Scenes with Multiple Directional Lights (2010)

We present a real-time GPU caustics rendering technique in dynamic scenes under multiple directional lights taking into account light occlusion. Our technique renders caustics cast on receiver objects as well as volumetric caustics. We precompute caustic patterns of caustic objects for several directional lights and store them in caustic images. During the rendering, we interpolate the precomputed caustic patterns based on a given light direction. One of the applications of our technique is to render approximate caustics under environment illumination. To achieve this, we propose an environment cube map segmentation technique which divides cube maps into several light regions with each region is represented using one directional light.
High Density - HD Using ERTMS: The Italian Solution for the Railway Traffic Management (2018)

The HD ERTMS solution for railway traffic management is presented. It allows to achieve “high density” railway traffic, increasing the number of trains on the existing railway lines. The proposed solution is based on the ERTMS technological standard and can be integrated with existing signaling systems minimizing field intervention: HD ERTMS trains do not interfere with trains equipped by other signaling and train separation systems. The railway traffic simulation software RFI NET has been upgraded to verify HD ERTMS potentiality and to optimize rail traffic on lines, nodes and stations. Finally, results of the first HD ERTMS application to the Italian railway node of Florence are presented.
Visualization of Field Distributions of Waveform-Selective Metasurface (2015)

We demonstrate numerical simulations of recently reported waveform-selective metasurfaces by developing a new electromagnetic (EM) simulation method based on the Transmission Line Modeling (TLM) method. As opposed to a conventional method integrating an EM simulator with a circuit simulator, this simulation method allows us to fully visualize electromagnetic fields around the metasurfaces. Therefore, this demonstrates how the waveform selectivity varies the surrounding fields in response to the pulse width of the incoming wave even at the same frequency. This simulation method is expected to be useful for testing other kinds of circuit-based metasurfaces and metamaterials as well.
The unconventional geminivirus Beet curly top Iran virus: satisfying Koch's postulates and determining vector and host range (2012)

Abstract Beet curly top Iran virus ( BCTIRV ) is a geminivirus with unusual genomic organisation, recently reported in Iran, infecting sugarbeet and a few other plant species. Although three BCTIRV sequences have been reported, demonstration that BCTIRV DNA is the causal agent of the disease was missing. A full‐length genomic DNA was obtained from symptomatic leaves of sugarbeet collected in the Sivand area of Iran, and its nucleotide sequence was determined ( BCTIRV ‐Siv, 2845 nt). To satisfy Koch's postulates, an infectivity assay was developed by inserting a 1.4‐mer of BCTIRV ‐Siv DNA in Agrobacterium tumefaciens and using it in agroinoculation experiments. The cloned viral DNA was capable of infecting sugarbeets, reproducing the leaf curling and vein enations observed in the field. These results demonstrate that the single DNA component of BCTIRV is sufficient for infectivity. Host range studies indicated that some economically important crops can be affected, such as spinach, tomato and sweet pepper, as well as important laboratory plants including Nicotiana benthamiana , Arabidopsis thaliana and Jimson weed. Circulifer haematoceps , the dominant leafhopper species present in sugarbeet fields in Iran, was successfully used to transmit the disease. The availability of an infectious clone will facilitate extended host range studies, to determine the potential risks to other crops, as well as genetic studies on this unusual member of the family Geminiviridae .
Doppelt und dreifach funktionalisierte, enantiomerenreine C4‐Synthesebausteine aus β‐Hydroxybuttersäure, Äpfelsäure und Weinsäure (1981)

Enantiomerically Pure Synthetic Building Blocks with Four C‐Atoms and Two or Three Functional Groups from β‐Hydroxy‐butanoic, Malic, and Tartaric Acid The pool of chiral, non‐racemic electrophilic building blocks, which are available from simple natural products in both enantiomeric forms is enlarged by the epoxides 3, 5 , and 10 , by the tosylate 12a , and by the aldehydes 18 ( cf. symbols A‐D , 14 , and Scheme 1 ). Key steps of the conversions leading from hydroxyacids to the building blocks are: epoxide‐opening by triethylborohydride ( 1 → 2a ) and tosylate reduction ( 12a → 12b ); the Mitsunobu inversion ( 2a → 4a ); the reduction of ( R, R )‐tartaric ester to ( R )‐malic ester by NBS ( N ‐bromosuccinimide) opening of the benzaldehyde acetal 8 and tin hydride reduction ( 6c → 7c ); the enantiomer enrichment of optically active ethyl β‐hydroxy‐butanoate through the crystalline dinitrobenzoate 21b . Detailed procedures are given for large scale preparations of the key intermediates. The enantiomeric purities of the building blocks are secured by correlations.
Large-field scanning laser ablation system (1997)

A large-field scanning imaging system has been developed to perform imaging ablation using 308-nm excimer laser light. A 1× Dyson-like lens images a portion of the mask onto a portion of the substrate to be ablated. The lens has a field of 12 mm and a numerical aperture of 0.05, providing a resolution of about 6 µm. A mirror system comprising a roof and a plane mirror, with all three surfaces mutually orthogonal, ensures that the mask and the substrate have identical orientations. A common stage is used to hold the mask and the substrate. The stage is scanned in a serpentine manner to transfer the entire image. The illuminated region is diamond-shaped, and adjacent scans overlap by half its width to ensure uniformity. Illumination uniformity is provided by a light tunnel in the illumination system. Alignment is performed by optically combining images of mask marks and substrate marks formed by a pair of microscope objectives, one viewing the mask and the other viewing the substrate. The substrate is leveled, focused, and registered relative to the image of the mask by a stage with six degrees of freedom.
Indications for gadolinium-DTPA in magnetic resonance evaluation of extracranial head and neck mass lesions: review of experience with 27 patients examined with a 2 tesla imager. (1992)

The authors review their experience with 27 patients who underwent gadolinium-enhanced magnetic resonance imaging (MRI) at 2 tesla. The contribution of the contrast agent was evaluated with respect to three properties--lesion conspicuity, margins and characterization. Gadolinium enhancement contributed most to the characterization of the lesion and helped to better define lesion margins in relationship to nonfatty tissues. It is concluded that gadolinium-enhanced MR images frequently give significant additional information in the evaluation of head and neck mass lesions.
Wearable Monitoring and Interpretable Machine Learning Can Objectively Track Progression in Patients during Cardiac Rehabilitation (2020)

Cardiovascular diseases (CVD) are often characterized by their multifactorial complexity. This makes remote monitoring and ambulatory cardiac rehabilitation (CR) therapy challenging. Current wearable multimodal devices enable remote monitoring. Machine learning (ML) and artificial intelligence (AI) can help in tackling multifaceted datasets. However, for clinical acceptance, easy interpretability of the AI models is crucial. The goal of the present study was to investigate whether a multi-parameter sensor could be used during a standardized activity test to interpret functional capacity in the longitudinal follow-up of CR patients. A total of 129 patients were followed for 3 months during CR using 6-min walking tests (6MWT) equipped with a wearable ECG and accelerometer device. Functional capacity was assessed based on 6MWT distance (6MWD). Linear and nonlinear interpretable models were explored to predict 6MWD. The t-distributed stochastic neighboring embedding (t-SNE) technique was exploited to embed and visualize high dimensional data. The performance of support vector machine (SVM) models, combining different features and using different kernel types, to predict functional capacity was evaluated. The SVM model, using chronotropic response and effort as input features, showed a mean absolute error of 42.8 m (±36.8 m). The 3D-maps derived using the t-SNE technique visualized the relationship between sensor-derived biomarkers and functional capacity, which enables tracking of the evolution of patients throughout the CR program. The current study showed that wearable monitoring combined with interpretable ML can objectively track clinical progression in a CR population. These results pave the road towards ambulatory CR.
Identification of paraoxonase 3 in rat liver microsomes: purification and biochemical properties (2003)

Three paraoxonase genes (PON1, PON2 and PON3) have been described so far in mammals. Although considerable information is available regarding PON1, little is known about PON2 and PON3. PON3 has been isolated recently from rabbit serum [Draganov, Stetson, Watson, Billecke and La Du (2000) J. Biol. Chem. 275, 33435-33442] and liver [Ozols (1999) Biochem. J. 338, 265-275]. In the present study, we have identified the presence of PON3 in rat liver microsomes and a method for the purification to homogeneity is presented. PON3 has been purified 177-fold to apparent homogeneity with a final specific activity of 461 units/mg using a method consisting of seven steps: solubilization of the microsomal fraction, hydroxyapatite adsorption, chromatography on DEAE-Sepharose CL-6B, non-specific affinity chromatography on Cibacron Blue 3GA, two DEAE-cellulose steps and a final affinity chromatography on concanavalin A-Sepharose. SDS/PAGE of the final preparation indicated a single protein-staining band with an apparent molecular mass of 43 kDa. The isolated protein was identified by nanoelectrospray MS. Internal amino acid sequences of several peptides were determined and compared with those of human, rabbit and mouse PON3, showing a high similarity. Some biochemical properties of PON3 were also studied, including optimum pH, K(m) and heat and pH stability.
ChemInform Abstract: Metalation Reactions of 1‐Silacyclo‐3‐pentenes. (1988)

Abstract Treatment of the silacyclopentenes (I) with tert‐butyllithium and subsequent quenching with electrophiles such as MeI (II) give a mixture of the 2‐ or the 4‐substituted isomers such as (III) and (IV).