gebhart/patrepeval huggingface dataset:
Antibody-mediated stabilization of NRG1 induces behavioral and electrophysiological alterations in adult mice (2018)

Neuregulin 1 (NRG1) is required for development of the central and peripheral nervous system and regulates neurotransmission in the adult. NRG1 and the gene encoding its receptor, ERBB4, are risk genes for schizophrenia, although how alterations in these genes disrupt their function has not been fully established. Studies of knockout and transgenic mice have yielded conflicting results, with both gain and loss of function resulting in similar behavioral and electrophysiological phenotypes. Here, we used high affinity antibodies to NRG1 and ErbB4 to perturb the function of the endogenous proteins in adult mice. Treatment with NRG1 antibodies that block receptor binding caused behavioral alterations associated with schizophrenia, including, hyper-locomotion and impaired pre-pulse inhibition of startle (PPI). Electrophysiological analysis of brain slices from anti-NRG1 treated mice revealed reduced synaptic transmission and enhanced paired-pulse facilitation. In contrast, mice treated with more potent ErbB4 function blocking antibodies did not display behavioral alterations, suggesting a receptor independent mechanism of the anti-NRG1-induced phenotypes. We demonstrate that anti-NRG1 causes accumulation of the full-length transmembrane protein and increases phospho-cofilin levels, which has previously been linked to impaired synaptic transmission, indicating enhancement of non-canonical NRG1 signaling could mediate the CNS effects.
A Facile Synthesis–Fabrication Strategy for Integration of Catalytically Active Viral-Palladium Nanostructures into Polymeric Hydrogel Microparticles <i>via</i> Replica Molding (2013)

The synthesis of small, uniform, well-dispersed and active Pd nanocatalysts under mild conditions in a predictable and controlled manner is an unmet challenge. Viral nanomaterials are attractive biotemplates for the controlled synthesis of nanoparticles due to their well-defined and monodisperse structure along with abundant surface functionalities. Here, we demonstrate spontaneous formation of small (1-2 nm), uniform and highly crystalline palladium (Pd) nanoparticles along genetically modified tobacco mosaic virus (TMV1cys) biotemplates without external reducing agents. The ratio between TMV and Pd precursor plays an important role in the exclusive formation of well-dispersed Pd nanoparticles along TMV biotemplates. The as-prepared Pd-TMV complexes are then integrated into the poly(ethylene glycol) (PEG)-based microparticles via replica molding (RM) technique in a simple, robust and highly reproducible manner. High catalytic activity, recyclability and stability of the hybrid Pd-TMV-PEG microparticles are further demonstrated through dichromate reduction as a model reaction. Taken together, these findings demonstrate a significant step toward simple, robust, and scalable synthesis and fabrication of efficient biotemplate-supported Pd nanocatalysts in readily deployable polymeric scaffolds with high capacity in a controlled manner.
Hereditary common cancers: molecular and clinical genetics. (2001)

This review focuses on the functional role and structural features of the genes involved in common hereditary cancers. Most of these tumors are sporadic and the genetic alterations responsible for their genesis take place over several cell generations; nevertheless, 5 to 10% of the human tumors are hereditary, with a rapid development. Cancer susceptibility genes have been classified as "gatekeepers" (e.g. RB1, ki-ras) and "caretakers" (e.g. hMLH1 and hMSH2, BRCA1). The first step in identifying individuals at high risk of developing a specific inherited form of cancer, and who should therefore undergo genetic tests, is the detailed construction of family history (an accurate cancer family history that includes at least three generation pedigrees, an appropriate cancer risk assessment and an effective genetic counseling). At present, the most useful methods of risk assessment are those performed on the following genes: BRCA1 and BRCA2 especially for hereditary breast and ovarian cancer, hMLH1 and hMSH2 for hereditary non polyposis colorectal cancer, APC for familial adenomatous polyposis, ret for medullary thyroid carcinoma, p53 for the Li-Fraumeni syndrome, p16 for melanoma and RB1 for retinoblastoma. In conclusion, the development of new diagnostic tests will permit a more accurate assessment of risk in individuals who have not so far shown any sign or symptom of the disease.
LED Backlight Driving System for Large-Scale LCD Panels (2007)

This paper presents an LED backlight driving system for large-scale liquid crystal display panels. High efficiency, high power factor, circuit simplicity, and low cost can be achieved by using a single-stage charge-pump asymmetrical half-bridge converter. To regulate the LED current and brightness for the LED backlight system, some current sharing methods are presented and compared. The requirements for the current sharing and luminance balance among paralleled LED arrays can be satisfied while current ripple is eliminated significantly. Because of the addition of bypass diodes, an alternative current path can be offered when a single LED fails. The LED array will not be extinguished. Reliability of the LED backlight system can thus be improved effectively. A laboratory prototype has been built and tested. The simulation and experimental results are shown to verify the feasibility of the proposed method.
Rapid Quantification of Viable <i>Campylobacter</i> Bacteria on Chicken Carcasses, Using Real-Time PCR and Propidium Monoazide Treatment, as a Tool for Quantitative Risk Assessment (2010)

A number of intervention strategies against Campylobacter-contaminated poultry focus on postslaughter reduction of the number of cells, emphasizing the need for rapid and reliable quantitative detection of only viable Campylobacter bacteria. We present a new and rapid quantitative approach to the enumeration of food-borne Campylobacter bacteria that combines real-time quantitative PCR (Q-PCR) with simple propidium monoazide (PMA) sample treatment. In less than 3 h, this method generates a signal from only viable and viable but nonculturable (VBNC) Campylobacter bacteria with an intact membrane. The method's performance was evaluated by assessing the contributions to variability by individual chicken carcass rinse matrices, species of Campylobacter, and differences in efficiency of DNA extraction with differing cell inputs. The method was compared with culture-based enumeration on 50 naturally infected chickens. The cell contents correlated with cycle threshold (C(T)) values (R(2) = 0.993), with a quantification range of 1 x 10(2) to 1 x 10(7) CFU/ml. The correlation between the Campylobacter counts obtained by PMA-PCR and culture on naturally contaminated chickens was high (R(2) = 0.844). The amplification efficiency of the Q-PCR method was not affected by the chicken rinse matrix or by the species of Campylobacter. No Q-PCR signals were obtained from artificially inoculated chicken rinse when PMA sample treatment was applied. In conclusion, this study presents a rapid tool for producing reliable quantitative data on viable Campylobacter bacteria in chicken carcass rinse. The proposed method does not detect DNA from dead Campylobacter bacteria but recognizes the infectious potential of the VBNC state and is thereby able to assess the effect of control strategies and provide trustworthy data for risk assessment.
Lead(II) Complex Formation with <scp>l</scp>-Cysteine in Aqueous Solution (2015)

The lead(II) complexes formed with the multidentate chelator l-cysteine (H2Cys) in an alkaline aqueous solution were studied using 207Pb, 13C, and 1H NMR, Pb LIII-edge X-ray absorption, and UV–vis spectroscopic techniques, complemented by electrospray ion mass spectrometry (ESI-MS). The H2Cys/PbII mole ratios were varied from 2.1 to 10.0 for two sets of solutions with CPbII = 0.01 and 0.1 M, respectively, prepared at pH values (9.1–10.4) for which precipitates of lead(II) cysteine dissolved. At low H2Cys/PbII mole ratios (2.1–3.0), a mixture of the dithiolate [Pb(S,N-Cys)2]2– and [Pb(S,N,O-Cys)(S-HCys)]− complexes with average Pb–(N/O) and Pb–S distances of 2.42 ± 0.04 and 2.64 ± 0.04 Å, respectively, was found to dominate. At high concentration of free cysteinate (>0.7 M), a significant amount converts to the trithiolate [Pb(S,N-Cys)(S-HCys)2]2–, including a minor amount of a PbS3-coordinated [Pb(S-HCys)3]− complex. The coordination mode was evaluated by fitting linear combinations of EXAFS oscillations to the experimental spectra and by examining the 207Pb NMR signals in the chemical shift range δPb = 2006–2507 ppm, which became increasingly deshielded with increasing free cysteinate concentration. One-pulse magic-angle-spinning (MAS) 207Pb NMR spectra of crystalline Pb(aet)2 (Haet = 2-aminoethanethiol or cysteamine) with PbS2N2 coordination were measured for comparison (δiso = 2105 ppm). The UV–vis spectra displayed absorption maxima at 298–300 nm (S– → PbII charge transfer) for the dithiolate PbS2N(N/O) species; with increasing ligand excess, a shoulder appeared at ∼330 nm for the trithiolate PbS3N and PbS3 (minor) complexes. The results provide spectroscopic fingerprints for structural models for lead(II) coordination modes to proteins and enzymes.
Photonic DPASK/QAM signal generation at microwave/millimeter-wave band based on an electro-optic phase modulator (2008)

We have proposed and experimentally demonstrated two novel photonic architectures to generate differential-phase amplitude-shift keying and circular quadrature amplitude modulation signals at microwave/millimeter-wave band based on an electro-optic phase modulator. In our proposed schemes, the electronic driven circuits were greatly simplified by employing the photonic vector modulation technique.
A finite-element model of oxygen diffusion in the pulmonary capillaries (1997)

We determined the overall pulmonary diffusing capacity (DL) and the diffusing capacities of the alveolar membrane (Dm) and the red blood cell (RBC) segments (De) of the diffusional pathway for O2 by using a two-dimensional finite-element model developed to represent the sheet-flow characteristics of pulmonary capillaries. An axisymmetric model was also considered to assess the effect of geometric configuration. Results showed the membrane segment contributing the major resistance, with the RBC segment resistance increasing as O2 saturation (SO2) rises during the RBC transit: RBC contributed 7% of the total resistance at the capillary inlet (SO2 = 75%) and 30% toward the capillary end (SO2 = 95%) for a 45% hematocrit (Hct). Both Dm and DL increased as the Hct increased but began approaching a plateau near an Hct of 35%, due to competition between RBCs for O2 influx. Both Dm and DL were found to be relatively insensitive (2-4%) to changes in plasma protein concentration (28-45%). Axisymmetric results showed similar trends for all Hct and protein concentrations but consistently overestimated the diffusing capacities (approximately 2.2 times), primarily because of an exaggerated air-tissue barrier surface area. The two-dimensional model correlated reasonably well with experimental data and can better represent the O2 uptake of the pulmonary capillary bed.
Down modulation of tumor-associated proteolytic activity by n-butanol in cultured murine mammary adenocarcinoma cells (1996)

The extractive effects of n-butanol on the cell membrane have been extensively studied. Although shortterm effects of this alcohol were reported, a sustained action on tumor cells has not been described. It was previously shown that M3 mouse mammary adenocarcinoma cells pretreated with n-butanol exhibited a longer latency after subcutaneous inoculation into syngeneic mice. In the present study a short, 5-minute exposure of M3 cells to n-butanol (2.5% v/v) resulted in the complete inhibition of a secreted metalloproteinase activity of 105 kDa and a significant decrease in secreted urokinase (uPA) activity levels (p<0.01) measured in conditioned media after 72 hours of culture. Total cell-associated uPA activity of M3 control monolayers was composed of a membrane-bound (31%) and a cytoplasmic (69%) uPAfraction. In contrast, cell-associated uPA activity of n-butanol pretreated M3 cells was mainly composed of a cytoplasmic uPA fraction and an extremely low membrane-bound uPA fraction (<5%). Further, an impaired uPA receptor binding capacity in these monolayers was also observed (p<0.05). These findings suggest that reduced proteolysis of extracellular matrix components may lead to local changes in tumor stroma composition, resulting in an altered behavior of M3 adenocarcinoma cells when inoculated in vivo.
Efficacy and Safety of Memantine Treatment for Reduction of Changes Associated with Experimental Glaucoma in Monkey, II: Structural Measures (2004)

Histologic measurements of RGC survival as well as tomographic measurements of nerve head topography show that systemic treatment with memantine, a compound which does not lower intraocular pressure, is both safe and effective to reduce changes associated with experimental glaucoma.
Heart‐beat‐phase‐coherent Doppler optical coherence tomography for measuring pulsatile ocular blood flow (2012)

We introduce a Doppler OCT (DOCT) platform that is fully synchronized with the heart-beat via a pulse oximeter. The system allows reconstructing heart-beat-phase-coherent quantitative DOCT volumes. The method is to acquire a series of DOCT volumes and to record the pulse in parallel. The heartbeat data is used for triggering the start of each DOCT volume acquisition. The recorded volume series is registered to the level of capillaries using a cross-volume registration. The information of the pulse phase is used to rearrange the tomograms in time, to obtain a series of phase coherent DOCT volumes over a pulse. We present Doppler angle independent quantitative evaluation of the absolute pulsatile blood flow within individual retinal vessels as well as of the total retinal blood flow over a full heartbeat cycle.
Gain- and Loss-of-Function Mutations in the Breast Cancer Gene GATA3 Result in Differential Drug Sensitivity (2016)

Patterns of somatic mutations in cancer genes provide information about their functional role in tumourigenesis, and thus indicate their potential for therapeutic exploitation. Yet, the classical distinction between oncogene and tumour suppressor may not always apply. For instance, TP53 has been simultaneously associated with tumour suppressing and promoting activities. Here, we uncover a similar phenomenon for GATA3, a frequently mutated, yet poorly understood, breast cancer gene. We identify two functional classes of frameshift mutations that are associated with distinct expression profiles in tumours, differential disease-free patient survival and gain- and loss-of-function activities in a cell line model. Furthermore, we find an estrogen receptor-independent synthetic lethal interaction between a GATA3 frameshift mutant with an extended C-terminus and the histone methyltransferases G9A and GLP, indicating perturbed epigenetic regulation. Our findings reveal important insights into mutant GATA3 function and breast cancer, provide the first potential therapeutic strategy and suggest that dual tumour suppressive and oncogenic activities are more widespread than previously appreciated.
A method for the comparison of biomechanical breast models (2002)

Biomechanical models of the breast are being developed for a wide range of applications including image alignment tasks to improve diagnosis and therapy monitoring, imaging related studies of the biomechanical properties of lesions, and image guided interventions. In this paper we present a method to evaluate the accuracy with which biomechanical breast models based on finite element methods (FEM) can predict the displacements of tissue within the breast. Our experimental data was obtained by compressing the breast of a volunteer in a controlled manner, and the acquisition of MR images of the breast before and after compression. Non-rigid registration of these two MR volumes together with interactive identification of corresponding landmarks provided an independent estimate of the displacements. In addition, the non-rigid registration provided estimates of the displacements of the surface points (skin points) of the breast. The accuracy of the FEM models was evaluated using all or a subset of these surface displacements as boundary conditions. The influence of pectoral muscle movement on the performance of the FEM models was also investigated. Our initial results indicate that the accurate setting of the boundary conditions is more important than the actual choice of elastic properties in these compression scenarios. With the complete boundary conditions, the displacements agreed to within 2.6 mm for all FEM models on average. Assuming no movement at the posterior or the medial side of the breast, the accuracy of the FEM models deteriorated to worse than 4.6 mm for all models.
Site-selective DNA hydrolysis induced by a metal-free peptide nucleic acid–cyclen conjugate (2011)

A metal-free artificial restriction DNA cutter which is composed of cyclen and classical peptide nucleic acid (PNA) was synthesized. Analysis of DNA cleavage products indicates the site-selective hydrolysis.
DCAN: Dual Channel-wise Alignment Networks for Unsupervised Scene Adaptation (2018)

Harvesting dense pixel-level annotations to train deep neural networks for semantic segmentation is extremely expensive and unwieldy at scale. While learning from synthetic data where labels are readily available sounds promising, performance degrades significantly when testing on novel realistic data due to domain discrepancies. We present Dual Channel-wise Alignment Networks (DCAN), a simple yet effective approach to reduce domain shift at both pixel-level and feature-level. Exploring statistics in each channel of CNN feature maps, our framework performs channel-wise feature alignment, which preserves spatial structures and semantic information, in both an image generator and a segmentation network. In particular, given an image from the source domain and unlabeled samples from the target domain, the generator synthesizes new images on-the-fly to resemble samples from the target domain in appearance and the segmentation network further refines high-level features before predicting semantic maps, both of which leverage feature statistics of sampled images from the target domain. Unlike much recent and concurrent work relying on adversarial training, our framework is lightweight and easy to train. Extensive experiments on adapting models trained on synthetic segmentation benchmarks to real urban scenes demonstrate the effectiveness of the proposed framework.
Striatal Direct and Indirect Pathway Output Structures Are Differentially Altered in Mouse Models of Huntington's Disease (2018)

The present study examined synaptic communication between direct and indirect output pathway striatal medium-sized spiny neurons (MSNs) and their target structures, the substantia nigra pars reticulata (SNr) and the external globus pallidus (GPe) in two mouse models of Huntington's disease (HD). Cre recombination, optogenetics, and whole-cell patch-clamp recordings were used to determine alterations in intrinsic and synaptic properties of SNr and GPe neurons from both male and female symptomatic R6/2 (>60 d) and presymptomatic (2 months) or symptomatic (10-12 months) YAC128 mice. Cell membrane capacitance was decreased, whereas input resistance was increased in SNr neurons from R6/2, but not YAC128 mice. The amplitude of GABAergic responses evoked by optogenetic stimulation of direct pathway terminals was reduced in SNr neurons of symptomatic mice of both models. A decrease in spontaneous GABA synaptic activity, in particular large-amplitude events, in SNr neurons also was observed. Passive membrane properties of GPe neurons were not different between R6/2 or YAC128 mice and their control littermates. Similarly, the amplitude of GABA responses evoked by activation of indirect pathway MSN terminals and the frequency of spontaneous GABA synaptic activity were similar in HD and control animals. In contrast, the decay time of the evoked GABA response was significantly longer in cells from HD mice. Interestingly, activation of indirect pathway MSNs within the striatum evoked larger-amplitude responses in direct pathway MSNs. Together, these results demonstrate differential alterations in responses evoked by direct and indirect pathway terminals in SNr and GPe leading to striatal output imbalance and motor dysfunction.<b>SIGNIFICANCE STATEMENT</b> Previous work on Huntington's disease (HD) focused on striatal medium-sized spiny neurons (MSNs) almost exclusively. Little is known about the effects that alterations in the striatum have on output structures of the direct and indirect pathways, the substantia nigra pars reticulata (SNr) and the external segment of the globus pallidus (GPe), respectively. We combined electrophysiological and optogenetic methods to examine responses evoked by selective activation of terminals of direct and indirect pathway MSNs in SNr and GPe neurons in two mouse models of HD. We show a differential disruption of synaptic communication between the direct and indirect output pathways of the striatum with their target regions leading to an imbalance of striatal output, which will contribute to motor dysfunction.
Probing T cell antigen recognition: use of synthetic peptides. (1992)

The availability and use of synthetic peptides have significantly enhanced our understanding of T cell recognition of antigen. This review is an attempt to chronicle applications of synthetic peptide technology to examine various aspects of T cell recognition. Specifically, a historical prospective of T cell antigen recognition precedes a description of the use of synthetic peptides to probe T cell recognition in the context of a trimolecular complex, in terms of regulatory and cytotoxic T cells, with respect to T cell tolerance and the concept of immunodominance, and its relevance to autoimmunity.
Human amylase gene copy number variation as a determinant of metabolic state (2018)

Salivary amylase may influence postprandial 'cephalic phase' insulin release, which improves glucose tolerance, while serum amylase may have insulin-sensitizing properties. This could explain the favorable metabolic status associated with higher AMY1 copy number. The association with BMI is harder to explain and is potentially mediated by increased flux of undigested starch into the ileum, with resultant effects on short-chain fatty acids (SCFAs), changes in gut microbiota and effects on appetite and energy expenditure in those with low copy number. Future research on the role of amylase as a determinant of metabolic health and BMI may lead to novel therapies to target obesity.
Novel Trifunctional Building Blocks for Fluorescent Polymers (2003)

[reaction: see text] Herein, we describe the synthesis of fluorescent 2-(arylsulfonyl)methacrylates and its polymers. These novel trifunctional monomers, possessing a fluorescent arylsulfonyl (ArSO(2)) group, an alkyl group (R), and a polymerizable olefin, serve as useful building blocks for functionalized fluorescent polymers.
Assessing Methane Emissions from Global Space-Borne Observations (2005)

In the past two centuries, atmospheric methane has more than doubled and now constitutes 20% of the anthropogenic climate forcing by greenhouse gases. Yet its sources are not well quantified, introducing uncertainties in its global budget. We retrieved the global methane distribution by using spaceborne near-infrared absorption spectroscopy. In addition to the expected latitudinal gradient, we detected large-scale patterns of anthropogenic and natural methane emissions. Furthermore, we observed unexpectedly high methane concentrations over tropical rainforests, revealing that emission inventories considerably underestimated methane sources in these regions during the time period of investigation (August through November 2003).