gebhart/patrepeval huggingface dataset:
Determinants of the substrate specificity of human cytochrome P-450 CYP2D6: design and construction of a mutant with testosterone hydroxylase activity (1998)

Cytochrome P-450 CYP2D6, human debrisoquine hydroxylase, metabolizes more than 30 prescribed drugs, the vast majority of which are small molecules containing a basic nitrogen atom. In contrast, the similar mouse protein Cyp2d-9 was first characterized as a testosterone 16alpha-hydroxylase. No common substrates have been reported for the two enzymes. Here we investigate the structural basis of this difference in substrate specificity. We have earlier used a combination of NMR data and homology modelling to generate a three-dimensional model of CYP2D6 [Modi, Paine, Sutcliffe, Lian, Primrose, Wolf, C.R. and Roberts (1996) Biochemistry 35, 4541-4550]. We have now generated a homology model of Cyp2d-9 and compared the two models to identify specific amino acid residues that we believe form the substrate-binding site in each protein and therefore influence catalytic selectivity. Although there are many similarities in active site structure, the most notable difference is a phenylalanine residue (Phe-483) in CYP2D6, which in the model is located such that the bulky phenyl ring is positioned across the channel mouth, thus limiting the size of substrate that can access the active site. In Cyp2d-9, the corresponding position is occupied by an isoleucine residue, which imposes fewer steric restraints on the size of substrate that can access the active site. To investigate whether the amino acid residue at this position does indeed influence the catalytic selectivity of these enzymes, site-directed mutagenesis was used to change Phe-483 in CYP2D6 to isoleucine and also to tryptophan. CYP2D6, Cyp2d-9 and both mutant CYP2D6 proteins were co-expressed with NADPH cytochrome P-450 reductase as a functional mono-oxygenase system in Escherichia coli and their relative catalytic activities towards bufuralol and testosterone were determined. All four proteins exhibited catalytic activity towards bufuralol but only Cyp2d-9 catalysed the formation of 16alpha-hydroxytesterone. Uniquely, the CYP2D6F483I mutant acquired the ability to metabolize testosterone to a novel product, which was identified by MS and proton NMR spectroscopy as 15alpha-hydroxytestosterone. NMR spin relaxation experiments were used to measure distances between the haem iron and protons of testosterone bound to the CYP2D6F483I mutant. These experiments demonstrate that very minor modifications to the active site structure of CYP2D6 can have a profound influence on the substrate specificity of the enzyme.
Fixed topical combinations in glaucomatous patients and ocular discomfort (2012)

This work shows the better tolerability of brinzolamide 1% plus timolol 0.5% suspension, compared with dorzolamide 2% plus timolol 0.5% solution. Fortunately, some of the adverse reactions induced by preserved eye drop glaucoma medication are reversible after removing the preservatives. Both the potential for added benefit and patient compliance should be considered when selecting ocular hypotensive therapy.
β1 Integrin Adhesion Enhances IL-6–Mediated STAT3 Signaling in Myeloma Cells: Implications for Microenvironment Influence on Tumor Survival and Proliferation (2009)

The bone marrow microenvironmental components interleukin (IL)-6 and fibronectin (FN) individually influence the proliferation and survival of multiple myeloma (MM) cells; however, in vivo, these effectors most likely work together. We examined signaling events, cell cycle progression, and levels of drug response in MM cells either adhered to FN via beta1 integrins, stimulated with IL-6, or treated with the two combined. Although G(1)-S cell cycle arrest associated with FN adhesion was overcome when IL-6 was added, the cell adhesion-mediated drug resistance (CAM-DR) was maintained in the presence of IL-6. Concomitant exposure of MM cells to IL-6 and FN adhesion revealed a dramatic increase in signal transducers and activators of transcription 3 (STAT3) phosphorylation, nuclear translocation, and DNA binding, compared with either IL-6 or FN adhesion alone in four MM cell lines. Importantly, this increase in STAT3 activation correlated with a novel association between STAT3 and gp130 in cells adhered to FN before stimulation with IL-6, relative to nonadherent cells. Taken together, these results suggest a mechanism by which collaborative signaling by beta1 integrin and gp130 confers an increased survival advantage to MM cells.
Analysis of GNSS Correction Data Standards for the Automotive Market (2018)

In the past few years, the number of applications for GNSS has grown dramatically. As a result of this progression, the requirements for GNSS positioning systems have also changed. One of the most relevant components in precision GNSS technology is the correction data format or standard used to transmit corrections from reference GNSS infrastructure to user GNSS receivers. These data can include corrections for GNSS satellite orbit and clocks, GNSS satellite equipment delays, and ionospheric and tropospheric refraction. With the introduction of high-precision GNSS technology into the automotive industry, it has become clear that an appropriate data correction standard does not exist, which is optimized to specifically serve this market segment. Such a standard requires low-bandwidth and at the same time must provide specific and detailed integrity measures for safety-of-life applications. In this paper, we present a new standard that has been developed by Sapcorda Services in order to target the specific requirements of the automotive sector. This new standard was created as a joint effort of several organizations and has similarities with RTCM v3; however, it has different message design rules, which allows for the use of low-bandwidth transmission. Results indicate significant reduction in bandwidth usage for the new format under various test scenarios, increased end-to-end positioning performance integrity, as well as, better flexibility for future growth of GNSS correction service technology capabilities.
Investigation of the Birt–Hogg–Dubé tumour suppressor gene (FLCN) in familial and sporadic colorectal cancer (2010)

BACKGROUND Birt-Hogg-Dubé (BHD) syndrome is an autosomal dominant multisystem disorder with skin (fibrofolliculomas or trichodiscomas), lung (cysts and pneumothorax) and kidney (renal cell carcinoma) tumours. Although colorectal neoplasia was reported initially to be part of the BHD phenotype, some recent studies have not confirmed this association. METHODS A series of clinical and laboratory studies was undertaken to investigate possible relationships between colorectal neoplasia and the BHD gene (FLCN). The studies investigated whether individuals with familial colorectal cancer of unknown cause might have unsuspected germline FLCN mutations, looked for somatic FLCN C(8) tract mutations in microsatellite unstable sporadic colorectal cancers, and assessed the risk of colorectal neoplasia and possible genotype-phenotype correlations in BHD patients. RESULTS Although it was found previously that germline FLCN mutations can be detected in approximately 5% of patients with familial renal cell carcinoma, germline FLCN mutations were not detected in 50 patients with familial non-syndromic colorectal cancer. Analysis of genotype-phenotype correlations for two recurrent FLCN mutations identified in a subset of 51 families with BHD demonstrated a significantly higher risk of colorectal neoplasia in c.1285dupC mutation (within the exon 11 C(8) mononucleotide tract) carriers than in c.610delGCinsTA mutation carriers (chi(2)=5.78, p=0.016). Somatic frameshift mutations in the FLCN exon 11 C(8) mononucleotide tract were detected in 23% of sporadic colorectal cancers with microsatellite instability, suggesting that FLCN inactivation might contribute to colorectal tumourigenesis. CONCLUSIONS These findings suggest that the previously reported clinical heterogeneity for colorectal neoplasia may reflect allelic heterogeneity and the risk of colorectal neoplasia in BHD syndrome requires further investigation.
Infant microbiota in colic: predictive associations with problem crying and subsequent child behavior (2020)

Infant colic is a condition of unknown cause which can result in carer distress and attachment difficulties. Recent studies have implicated the gut microbiota in infant colic, and certain probiotics have demonstrated possible efficacy. We aim to investigate whether the intestinal microbiota composition in infants with colic is associated with cry/fuss time at baseline, persistence of cry/fuss at 4-week follow-up, or child behavior at 2 years of age. Fecal samples from infants with colic (n = 118, 53% male) were analyzed using 16S rRNA sequencing. After examining the alpha and beta diversity of the clinical samples, we performed a differential abundance analysis of the 16S data to look for taxa that associate with baseline and future behavior, while adjusting for potential confounding variables. In addition, we used random forest classifiers to evaluate how well baseline gut microbiota can predict future crying time. Alpha diversity of the fecal microbiota was strongly influenced by birth mode, feed type, and child gender, but did not significantly associate with crying or behavioral outcomes. Several taxa within the microbiota (including Bifidobacterium, Clostridium, Lactobacillus, and Klebsiella) associate with colic severity, and the baseline microbiota composition can predict further crying at 4 weeks with up to 65% accuracy. The combination of machine learning findings with associative relationships demonstrates the potential prognostic utility of the infant fecal microbiota in predicting subsequent infant crying problems.
Variational (Gradient) Estimate of the Score Function in Energy-based Latent Variable Models (2020)

The learning and evaluation of energy-based latent variable models (EBLVMs) without any structural assumptions are highly challenging, because the true posteriors and the partition functions in such models are generally intractable. This paper presents variational estimates of the score function and its gradient with respect to the model parameters in a general EBLVM, referred to as VaES and VaGES respectively. The variational posterior is trained to minimize a certain divergence to the true model posterior and the bias in both estimates can be bounded by the divergence theoretically. With a minimal model assumption, VaES and VaGES can be applied to the kernelized Stein discrepancy (KSD) and score matching (SM)-based methods to learn EBLVMs. Besides, VaES can also be used to estimate the exact Fisher divergence between the data and general EBLVMs.
Galanin enhances systemic glucose metabolism through enteric Nitric Oxide Synthase-expressed neurons (2018)

Here, we demonstrate that oral galanin administration improves glucose homeostasis via the enteric nervous system and could be considered a therapeutic potential for the treatment of T2D.
Ohmic and degradation mechanisms of Ag contacts on p-type GaN (2005)

The electrical and optical properties of the Ag contacts have been investigated as a function of the annealing temperature. The as-deposited contact becomes good Ohmic with contact resistivity of 2.47×10−4Ωcm2 and produces reflectance of ∼84% when annealed at 330°C for 1mm in air ambient. However, annealing at 530°C results in nonlinear current–voltage behavior and degraded reflectance. The light output of InGaN∕GaN blue light emitting diodes (LEDs) fabricated with the as-deposited Ag contact shows somewhat better output performance than those of LEDs with the annealed Ag contacts. Based on the transmission electron microscopy-energy dispersive x-ray analysis, synchrotron x-ray diffraction, and x-ray photoemission spectroscopy results, possible mechanisms for the ohmic formation and degradation of the Ag contacts are described.
Comb-based photonic neural population for parallel and nonlinear processing (2021)

It is believed that neural information representation and processing relies on the neural population instead of a single neuron. In neuromorphic photonics, photonic neurons in the form of nonlinear responses have been extensively studied in single devices and temporal nodes. However, to construct a photonic neural population (PNP), the process of scaling up and massive interconnections remain challenging considering the physical complexity and response latency. Here, we propose a comb-based PNP interconnected by carrier coupling with superior scalability. Two unique properties of neural population are theoretically and experimentally demonstrated in the comb-based PNP, including nonlinear response curves and population activities coding. A classification task of three input patterns with dual radio-frequency (RF) tones is successfully implemented in a time-efficient manner, which allows the comb-based PNP to make effective use of the ultra-broad bandwidth of photonics for parallel and nonlinear processing.
Carrier recombination dynamics and temperature dependent optical properties of InAs–GaSb heterostructures (2022)

Carrier lifetimes of InAs/GaSb heterostructures probed by μ-PCD at 1800 nm wavelength.
Aromatic lithiation directed by the carboxylic acid group. Synthesis of 9-substituted dibenzodioxin-1-carboxylic acids and 6-substituted phenoxathiin-4-carboxylic acids (1990)

An efficient procedure has been developed for the regiospecific synthesis of 9-substituted dibenzo[ 1,4]diox- in-1-carboxylic acid derivatives. Lithiation of dibenzo[ 1,4]dioxin-l-carboxylic acid forms the lithium carboxylate, which directs subsequent metalation exclusively to the 9-position. Conditions for the controlled mono- and dilithiation of dibenzo[ 1,4]dioxin itself, leading to the direct synthesis of the corresponding mono- and isomeric dimethyl esters, are also described.
Evaluating the influence of 3D-printing parameters on acoustic material properties (2017)

We present a non-destructive measurement procedure to obtain material properties on parts manufactured using the Fused-Deposition-Modeling (FDM) method. This manufacturing method leads to an anisotropic structure within the part and possible degradation of the material itself due to high temperatures. Utilizing our measurement setup, we obtain the material properties from a set of samples, varying the printing temperature. The measurements show an influence of the printing temperature on the Young's modulus and Poisson's ratio. Young's modulus decreases due to a thermal degeneration by 3%. Poisson's ratio along the fiber direction increases by 7% because of better adhesion between the fibers and layers. The results can be utilized to include more design goals, such as maximum strength or maximum isotropy, when preparing a model for manufacturing in addition to already established design goals such as minimum surface roughness or maximum printing speed.
A Set of Experimentally Validated Decoys for the Human CC Chemokine Receptor 7 (CCR7) Obtained by Virtual Screening (2022)

We present a state-of-the-art virtual screening workflow aiming at the identification of novel CC chemokine receptor 7 (CCR7) antagonists. Although CCR7 is associated with a variety of human diseases, such as immunological disorders, inflammatory diseases, and cancer, this target is underexplored in drug discovery and there are no potent and selective CCR7 small molecule antagonists available today. Therefore, computer-aided ligand-based, structure-based, and joint virtual screening campaigns were performed. Hits from these virtual screenings were tested in a CCL19-induced calcium signaling assay. After careful evaluation, none of the <i>in silico</i> hits were confirmed to have an antagonistic effect on CCR7. Hence, we report here a valuable set of 287 inactive compounds that can be used as experimentally validated decoys.
CATECHOLAMINE CONTENT OF SPINAL CORD (1962)

Values for the catecholamine content of spinal cords of rats, rabbits, cats, humans, hogs, and oxen were obtained. The catecholamine content tended to decrease with increasing size of the species. Dopamine averaged 1.0 micrograms/g of wet tissue in the rat, and 0.2 micrograms/g in the ox; noradrenaline averaged 0.15 micrograms/g in the rat, and 0.10 micrograms/g in the ox. Adrenaline could not be detected with certainty. The catecholamine content of gray matter was much greater than that of white and seemed greater in the posterior than in the anterior part of cord. No segmental distribution was apparent. Dopamine and noradrenaline were both found in the free and bound state. Modifications to previous methods of catecholamine determinations are described. Recoveries in the analyses were determined by using radioactive tracers in preference to the usual method of doing parallel analyses. No deterioration in catecholamine content of tissues was apparent for the first 3 hours after death, but thereafter deterioration was evident.
Engineering Mesophase Stability and Structure via Incorporation of Cyclic Terminal Groups (2021)

We report on the characterisation of a number of liquid-crystalline materials featuring cyclic terminal groups, which lead to significant enhancements in the temperature range of the mesomorphic state. Materials with only short terminal chains are able to support lamellar mesophase formation by appending a large terminal cyclic unit at the end of a short methylene spacer. X-ray scattering experiments reveal that the layer spacings of the lamellar smectic phase are significantly larger when a cyclic end-group is present than for equivalent linear unsubstituted materials, but there is no effect on orientational order. Fully atomistic molecular dynamics simulations faithfully reproduce experimental layer spacings and orientational order parameters, and indicate that the cyclic terminal units spontaneously segregate into diffuse sub-layers and thus cause the increased layer spacing. This shape segregation predicted by molecular dynamics simulations is observed in the crystalline solid state by X-ray diffraction.
Multiplanes (2017)

Multiplanes is a virtual reality (VR) drawing system that provides users with the flexibility of freehand drawing and the ability to draw perfect shapes. Through the combination of both beautified and 2D drawing, Multiplanes addresses challenges in creating 3D VR drawings. To achieve this, the system beautifies user's strokes based on the most probable, intended shapes while the user is drawing them. It also automatically generates snapping planes and beautification trigger points based on previous and current strokes and the current controller pose. Based on geometrical relationships to previous strokes, beautification trigger points act as guides inside the virtual environment. Users can hit these points to (explicitly) trigger a stroke beautification. In contrast to other systems, when using Multiplanes, users do not need to manually set or do any kind of special gesture to activate, such guides allowing the user to focus on the creative process.
THz generation from InN films due to destructive interference between optical rectification and photocurrent surge (2009)

We have investigated the characteristics of THz generation including the dependence of the output power and polarization on the incident angle and pump polarization from two series of InN films grown by plasma-assisted molecular beam epitaxy (PAMBE) and metal organic chemical vapor deposition (MOCVD), respectively. Following the analyses of our results, we have attributed the mechanism of the THz generation from these InN samples to the destructive interference between optical rectification and photocurrent surge. Under the average intensity of 176 W cm−2 for the subpicosecond laser pulses at 782 nm, the THz output powers were measured to be as high as 2.4 µW from the 220 nm InN film, with the output frequencies spanning the band from 300 GHz to 2.5 THz.
Detection of Carbendazim by Surface-Enhanced Raman Scattering Using Cyclodextrin Inclusion Complexes on Gold Nanorods (2009)

Surface-enhanced Raman scattering (SERS) was used for the detection of carbendazim using gold nanorods derivatized with a beta-cyclodextrin derivative to bind this fungicide. Gold nanorods were synthesized with an aspect ratio of 3.3 to match the 785 nm excitation wavelength used in the SERS studies. A thiolated cyclodextrin-based sensor molecule was synthesized, and its inclusion complex with carbendazim was formed and studied using SERS spectroscopy. SERS analysis of the inclusion complex at different concentrations in the presence of gold nanorods afforded good quality Raman spectra of carbendazim at micromolar concentrations. Quantitative analysis was preformed using partial least-squares (PLS), and a calibration plot for these data was generated. Results suggest that carbendazim concentrations as low as 50 microM can be accurately detected using the described SERS assay.
Figure S1 from Tumor-Specific Inhibition of <i>In Situ</i> Vaccination by Distant Untreated Tumor Sites (2023)

&lt;p&gt;Concomitant immune tolerance prevents an immunotherapeutic response at the distant tumor site, is observed with an 8 Gy x 3 fraction RT regimen, and requires a well-established macroscopic secondary tumor.&lt;/p&gt;
Eradication of large tumors expressing human papillomavirus E7 protein by therapeutic vaccination with E7 fused to the extra domain a from fibronectin (2011)

Cervical carcinoma is one of the most common cancers in women worldwide. It is well established that chronic infection of the genital tract by various mucosatropic human papillomavirus (HPV) types causes cervical cancer. Cellular immunity to E7 protein from HPV (HPVE7) has been associated with clinical and cytologic resolution of HPV-induced lesions. Thus, we decided to test if targeting of HPVE7 to dendritic cells using a fusion protein containing the extra domain A (EDA) from fibronectin, a natural ligand for TLR4, and HPVE7 (EDA-HPVE7) might be an efficient vaccine for the treatment of cervical carcinoma. We found that EDA-HPVE7 fusion protein was efficiently captured by bone marrow derived dendritic cells in vitro and induced their maturation, with the upregulation of maturation markers and the production of IL-12. Immunization of mice with EDA-HPVE7 fusion protein induced antitumor CD8(+) T cell responses in the absence of additional adjuvants. Repeated intratumoral administration of EDA-HPVE7 in saline was able to cure established TC-1 tumors of 5-7 mm in diameter. More importantly, intravenous injection with EDA-HPVE7 in combination with the TLR ligand polyinosinic-polycytidylic acid (pIC), or with low doses of cyclophosphamide and the TLR9 ligand CpG-B complexed in cationic lipids, were able to eradicate large established TC-1 tumors (1.2 cm in diameter). Thus, therapeutic vaccination with EDA-HPVE7 fusion protein may be effective in the treatment of human cervical carcinoma.
Estimating the HEVC decoding energy using the decoder processing time (2015)

This paper presents a method to accurately estimate the required decoding energy for a given HEVC software decoding solution. We show that the decoder's processing time as returned by common C++ and UNIX functions is a highly suitable parameter to obtain valid estimations for the actual decoding energy. We verify this hypothesis by performing an exhaustive measurement series using different decoder setups and video bit streams. Our findings can be used by developers and researchers in the search for new energy saving video compression algorithms.