gebhart/patrepeval huggingface dataset:
A pyramid approach to subpixel registration based on intensity (1998)

We present an automatic subpixel registration algorithm that minimizes the mean square intensity difference between a reference and a test data set, which can be either images (two-dimensional) or volumes (three-dimensional). It uses an explicit spline representation of the images in conjunction with spline processing, and is based on a coarse-to-fine iterative strategy (pyramid approach). The minimization is performed according to a new variation (ML*) of the Marquardt-Levenberg algorithm for nonlinear least-square optimization. The geometric deformation model is a global three-dimensional (3-D) affine transformation that can be optionally restricted to rigid-body motion (rotation and translation), combined with isometric scaling. It also includes an optional adjustment of image contrast differences. We obtain excellent results for the registration of intramodality positron emission tomography (PET) and functional magnetic resonance imaging (fMRI) data. We conclude that the multiresolution refinement strategy is more robust than a comparable single-stage method, being less likely to be trapped into a false local optimum. In addition, our improved version of the Marquardt-Levenberg algorithm is faster.
Buffer Design to Minimize Current Collapse in GaN/AlGaN HFETs (2012)

The bulk trap-induced component of current collapse (CC) in GaN/AlGaN heterojunction field-effect transistors is studied in drift diffusion simulations, distinguishing between acceptor traps situated in the top and the bottom half of the bandgap, with Fe and C used as specific examples. It is shown that Fe doping results in an inherent but relatively minor contribution to dispersion under pulse conditions. This simulation is in reasonable quantitative agreement with double pulse experiments. Simulations using deep-level intrinsic growth defects produced a similar result. By contrast, carbon can induce a strong CC which is dependent on doping density. The difference is attributed to whether the trap levels, whether intrinsic or extrinsic dopants, result in a resistive n-type buffer or a p-type floating buffer with bias-dependent depletion regions. This insight provides a key design concept for compensation schemes needed to ensure semi-insulating buffer doping for either RF or power applications.
A Genetically Encoded Fluorescent Amino Acid (2006)

The fluorescent amino acid l-(7-hydroxycoumarin-4-yl) ethylglycine 1 has been genetically encoded in E. coli in response to the amber TAG codon. Because of its high fluorescence quantum yield, relatively large Stoke's shift, and sensitivity to both pH and polarity, this amino acid should provide a useful probe of protein localization and trafficking, protein conformation changes, and protein-protein interactions.
Corneal penetration of levofloxacin into the human aqueous humour: a comparison with ciprofloxacin (2003)

Levofloxacin achieves 9.1 times the aqueous humour concentration of ciprofloxacin. It could be considered a better choice than ofloxacin or ciprofloxacin for topical ophthalmic use.
Immunohistochemical Localization of Klotho Protein in Brain, Kidney, and Reproductive Organs of Mice (2004)

Klotho mutant mouse (kl-/-), a mouse model for human aging, exhibits various phenotypes in a wide range of organs including arteriosclerosis, neural degeneration, skin and gonadal atrophy, pulmonary emphysema, calcification of soft tissues, and cognition impairment. Klotho mRNA, however, is expressed only in brain, kidney, reproductive organs, pituitary gland, and parathyroid gland. Therefore it remains to be elucidated how lack of Klotho protein in these limited organs leads to the variety of phenotypes. To shed light on mechanisms by which Klotho protein acts on distant targets, we examined localization of Klotho protein in brain, kidney, and reproductive organs, and analyzed brain and kidney in kl-/- mice searching for changes in target regions in these organs. In brain, Klotho proteins were localized at choroid plexus, where the proteins were dominantly localized at the apical plasma membrane of ependymal cells. In kl-/- brain, reduction of synapses was evident in hippocampus, suggesting a role of Klotho as a humoral factor in cerebrospinal fluid. Klotho proteins in kidney localized at distal renal tubules. Interestingly, in kl-/-mice, type IIa Na/phosphate (Pi) cotransporters, which function at the proximal renal tubules in reabsorption of phosphate ions, were translocated. This suggests that Klotho protein in kidney is implicated in calcium homeostasis which regulates localization of type IIa Na/Pi cotransporters via parathyroid hormone (PTH). Klotho proteins in reproductive organs were expressed only in mature germ cells, although in kl-/- mice germ cell maturation was arrested at earlier stages. Thus, Klotho proteins not only function as a humoral factor, but also are implicated in hormonal regulation, which may explain why mutation of klotho gene results in a variety of phenotypes.
A dual-fluorescence reporter system for high-throughput clone characterization and selection by cell sorting (2005)

Molecular biology critically depends upon the isolation of desired DNA sequences. Flow cytometry, with its capacity to interrogate and sort more than 50,000 cells/s, shows great potential to expedite clone characterization and isolation. Intrinsic heterogeneity of protein expression levels in cells limits the utility of single fluorescent reporters for cell-sorting. Here, we report a novel dual-fluorescence strategy that overcomes the inherent limitations of single reporter systems by controlling for expression variability. We demonstrate a dual-reporter system using the green fluorescent protein (GFP) gene fused to the Discosoma red fluorescent protein (DsRed) gene. The system reports the successful insertion of foreign DNA with the loss of DsRed fluorescence and the maintenance of GFP fluorescence. Single cells containing inserts are readily recognized by their altered ratios of green to red fluorescence and separated using a high-speed cell-sorter for further processing. This novel reporter system and vector were successfully validated by shotgun library construction, cloned sequence isolation, PCR amplification and DNA sequencing of cloned inserts from bacteria after cell-sorting. This simple, robust system can also be adapted for diverse biosensor assays and is amenable to miniaturization. We demonstrated that dual-fluorescence reporting coupled with high-speed cell-sorting provides a more efficient alternative to traditional methods of clone isolation.
Calcitonin gene-related peptide receptors in rat trigeminal ganglion do not control spinal trigeminal activity (2012)

Calcitonin gene-related peptide (CGRP) is regarded as a key mediator in the generation of primary headaches. CGRP receptor antagonists reduce migraine pain in clinical trials and spinal trigeminal activity in animal experiments. The site of CGRP receptor inhibition causing these effects is debated. Activation and inhibition of CGRP receptors in the trigeminal ganglion may influence the activity of trigeminal afferents and hence of spinal trigeminal neurons. In anesthetized rats extracellular activity was recorded from neurons with meningeal afferent input in the spinal trigeminal nucleus caudalis. Mechanical stimuli were applied at regular intervals to receptive fields located in the exposed cranial dura mater. α-CGRP (10(-5) M), the CGRP receptor antagonist olcegepant (10(-3) M), or vehicle was injected through the infraorbital canal into the trigeminal ganglion. The injection of volumes caused transient discharges, but vehicle, CGRP, or olcegepant injection was not followed by significant changes in ongoing or mechanically evoked activity. In animals pretreated intravenously with the nitric oxide donor glyceryl trinitrate (GTN, 250 μg/kg) the mechanically evoked activity decreased after injection of CGRP and increased after injection of olcegepant. In conclusion, the activity of spinal trigeminal neurons with meningeal afferent input is normally not controlled by CGRP receptor activation or inhibition in the trigeminal ganglion. CGRP receptors in the trigeminal ganglion may influence neuronal activity evoked by mechanical stimulation of meningeal afferents only after pretreatment with GTN. Since it has previously been shown that olcegepant applied to the cranial dura mater is ineffective, trigeminal activity driven by meningeal afferent input is more likely to be controlled by CGRP receptors located centrally to the trigeminal ganglion.
Direct and Continuous Production of Hydrogen Peroxide with 93 % Selectivity Using a Fuel‐Cell System (2003)

Avoiding a bang! Electrochemical reduction of O2 in an H2/O2 fuel cell with a three-phase boundary (gaseous O2, aqueous electrolyte, solid cathode) produces concentrated aqueous solutions of H2O2. Even air can serve as the oxygen source.
Beta cell antigens in type 1 diabetes: triggers in pathogenesis and therapeutic targets (2010)

Recognition of pancreatic beta cell antigens by autoreactive T lymphocytes plays a central role in the pathogenesis of insulin-dependent type 1 diabetes. Recent results suggest that non-conventional antigenic epitope processing and presentation may contribute to triggering and maintaining autoreactive responses. Moreover, promising results raise hope that autoantigens may become safe and specific therapeutics for type 1 diabetes in the future.
A Major Locus Influencing Plasma High-Density Lipoprotein Cholesterol Levels in the San Antonio Family Heart Study (1995)

To detect and measure the effects of a single locus on quantitative variation in plasma concentrations of HDL cholesterol (HDL-C), we conducted statistical genetic analyses on data from 526 Mexican American individuals in 25 randomly ascertained pedigrees. By using maximum-likelihood complex segregation analysis, we found evidence for a major locus with a codominant mixture model that included the phenotypic means, standard deviations, relative frequency of a low HDL-C allele, and heritability for plasma HDL-C levels, plus the effects of sex (genotype specific), age-by-sex, age2-by-sex, plasma concentrations of apolipoprotein (apo)AI and triglycerides (genotype specific), exogenous sex hormone use, and menopausal status under an unrestricted general model. Inclusion of the four covariates (in addition to the sex and age-by-sex effects) accounted for nearly 79% of the variance in total plasma HDL-C levels. Of the remaining 21% of the variance, the detected major locus accounted for approximately 55% in men and 21% in women; the total genetic contributions to the variance by genes were approximately 82% in men and 69% in women. Linkage analyses with penetrance parameter estimates from the segregation analysis excluded tight linkage between the detected major locus and markers for the following candidate loci: the apoAI/apoCIII genomic region (P < .05), apoB (P < .01), hepatic lipase (P < .001), lipoprotein lipase (P < .001), and the LDL receptor (P < .001). While not excluding the apoE locus (LOD = -0.348, P < .21), the analysis provided no support for tight linkage between it and the detected major locus.
Subretinal injection of amyloid-β peptide accelerates RPE cell senescence and retinal degeneration (2014)

Drusen are considered a hallmark characteristic of age-related macular degeneration (AMD). In our previous study, we found that amyloid-β (Aβ) peptide, a component of drusen, induced the cells of the retinal pigment epithelium (RPE; RPE cells) to enter senescence; however, its effects in vivo remain unknown. Thus, the present study was carried out to explore the in vivo effects of Aβ peptide on RPE cell senescence and senescence-associated inflammation in C57BL/6 mice. C57BL/6 mice received a subretinal injection of Aβ(1-42) peptide; on day 7 post-injection, the mice were anesthetized and subjected to whole-body perfusion with 4% paraformaldehyde (PFA) in PBS and the whole eyes were then enucleated. Retinal function was assessed by electroretinography (ERG), and the morphological characteristics of the retina were examined by light and electron microscopy. Fundus autofluorescence (FAF) was examined by confocal scanning laser ophthalmoscopy (cSLO). The expression of p16INK4a, a marker of cellular senescence, was examined by immunofluorescence staining and western blot analysis. The RPE-choroid was analyzed for cytokine expression by RT-PCR. In Aβ(1-42)-injected mice, scotopic ERG responses declined. Degenerative alterations, including the disruption of the inner segment (IS)/outer segment (OS) junction and extensive vacuolation and thickness of Bruch's membrane (BrM) were observed under a a light microscope. The accumulation of vacuoles and the loss of basal infoldings in the RPE were identified using an electron microscope. FAF and p16INK4a expression increased in Aβ(1-42)-injected mice. In addition, Aβ(1-42) upregulated interleukin (IL)-6 and IL-8 gene expression in the RPE-choroid. In conclusion, our results confirm the effects of Aβ(1-42) peptide on RPE senescence in vivo. The Aβ-injected mice developed AMD-like ocular pathology. It is thus suggested that RPE cell senescence is a potential mechanistic link between inflammation and retinal degeneration.
Infrastructure design of a picture archiving and communication system. (1992)

A picture archiving and communication system (PACS) infrastructure is the necessary framework to integrate distributed and heterogeneous imaging systems, provide intelligent data-base management of all radiology-related information, arrange an efficient means of viewing, analyzing, and documenting study results, and furnish a mechanism for effectively communicating study results to the referring physician. The PACS infrastructure consists of a basic skeleton of hardware components integrated by standardized, flexible software subsystems. This review describes these concepts and basic building blocks drawn from our original investigation, past experience, and the current clinical system in our radiology department.
Weight pushing and binarization for fixed-grammar parsing (2009)

We apply the idea of weight pushing (Mohri, 1997) to CKY parsing with fixed context-free grammars. Applied after rule binarization, weight pushing takes the weight from the original grammar rule and pushes it down across its binarized pieces, allowing the parser to make better pruning decisions earlier in the parsing process. This process can be viewed as generalizing weight pushing from transducers to hypergraphs. We examine its effect on parsing efficiency with various binarization schemes applied to tree substitution grammars from previous work. We find that weight pushing produces dramatic improvements in efficiency, especially with small amounts of time and with large grammars.
Nuclear Hormone Receptor NHR-49 Controls Fat Consumption and Fatty Acid Composition in C. elegans (2005)

Mammalian nuclear hormone receptors (NHRs), such as liver X receptor, farnesoid X receptor, and peroxisome proliferator-activated receptors (PPARs), precisely control energy metabolism. Consequently, these receptors are important targets for the treatment of metabolic diseases, including diabetes and obesity. A thorough understanding of NHR fat regulatory networks has been limited, however, by a lack of genetically tractable experimental systems. Here we show that deletion of the Caenorhabditis elegans NHR gene nhr-49 yielded worms with elevated fat content and shortened life span. Employing a quantitative RT-PCR screen, we found that nhr-49 influenced the expression of 13 genes involved in energy metabolism. Indeed, nhr-49 served as a key regulator of fat usage, modulating pathways that control the consumption of fat and maintain a normal balance of fatty acid saturation. We found that the two phenotypes of the nhr-49 knockout were linked to distinct pathways and were separable: The high-fat phenotype was due to reduced expression of enzymes in fatty acid beta-oxidation, and the shortened adult life span resulted from impaired expression of a stearoyl-CoA desaturase. Despite its sequence relationship with the mammalian hepatocyte nuclear factor 4 receptor, the biological activities of nhr-49 were most similar to those of the mammalian PPARs, implying an evolutionarily conserved role for NHRs in modulating fat consumption and composition. Our findings in C. elegans provide novel insights into how NHR regulatory networks are coordinated to govern fat metabolism.
Nucleic Acid for the Treatment of Cancer: Genetic Vaccines and DNA Adjuvants (2001)

Despite some interesting pilot experiments more than a century ago, nucleic acid has only recently been added to the list of agents used for the prevention and therapy of cancer. Two distinct features of nucleic acids are used for this purpose: in DNA and RNA vaccines, genetic information for pathogen- or tumor-derived antigens is delivered to the host who then produces the encoded antigen and initiates an immune response. In DNA adjuvants, immunostimulatory sequences (CpG motifs) present in DNA of bacterial origin are used. Such sequences are delivered in the form of oligonucleotides or within the sequence of DNA vaccine. In addition, CpG oligonucleotides by themselves have successfully been used to stimulate the immune system in an antigen-independent manner for the treatment of experimental tumors. DNA and RNA vaccines for the treatment and prevention of cancer and other diseases suffer from two some shortcomings: insufficient immunogenicity and--in the case of RNA--low stability. A variety of strategies are being explored to improve the efficacy of nucleic acid vaccines (genetic vaccines) especially for self-antigens in the case of cancer. Among the most recent improvements are self-replicating RNA vaccines and replicase-based DNA-vaccines in which antigen expression is under the control of an alphaviral replicase. Despite highly promising results in many animal tumor models the efficacy of nucleic acid vaccines and adjuvants in the clinic remains to be seen.
Silicon light-emitting transistor for on-chip optical interconnection (2006)

The authors propose a light-emitting field-effect transistor with the active layer made of the ultrathin single crystal silicon with the (100) surface orientation. The ambipolar carrier injections from the highly impurity doped regions to the ultrathin silicon are achieved in complementary-metal-oxide-semiconductor compatible planar structures and the optical intensities are controlled by the gate voltage. By using the device, they have demonstrated that a simple electrical signal can be transferred by light and detected on the same silicon chip as photocurrents controlled by the gate bias.
Monodisperse Enantiomeric Lactic Acid Oligomers:  Preparation, Characterization, and Stereocomplex Formation (1998)

d- and l-lactic acid oligomers were synthesized by polymerization of d- or l-lactide using 2-(2-methoxyethoxy)ethanol (MEE) and stannous octoate as initiator and catalyst, respectively. The average degree of polymerization (DPav) of the oligomers could be tailored by the monomer/initiator ratio. HPLC and GPC analysis showed that the oligomers had a Mw/Mn ratio of around 1.5. Mass spectroscopic analysis revealed that products contained besides MEE−(lactate)n=2,4,6,etc. also MEE−(lactate)n=1,3,5,etc.. The latter products are most likely formed due to transesterification reactions. Monodisperse lactic acid oligomers (DP 1−16) were obtained from the polydisperse oligomers by preparative HPLC and characterized by NMR and mass spectrometry. DSC analysis showed that crystallinity was present in d- or l-oligomers with DP ≥ 11. On the other hand, in blends of d- and l-oligomers of lactic acid crystallinity (stereocomplexation) was observed at a DP ≥ 7.
Type 1 Diabetes: Etiology, Immunology, and Therapeutic Strategies (2011)

Type 1 diabetes (T1D) is a chronic autoimmune disease in which destruction or damaging of the beta-cells in the islets of Langerhans results in insulin deficiency and hyperglycemia. We only know for sure that autoimmunity is the predominant effector mechanism of T1D, but may not be its primary cause. T1D precipitates in genetically susceptible individuals, very likely as a result of an environmental trigger. Current genetic data point towards the following genes as susceptibility genes: HLA, insulin, PTPN22, IL2Ra, and CTLA4. Epidemiological and other studies suggest a triggering role for enteroviruses, while other microorganisms might provide protection. Efficacious prevention of T1D will require detection of the earliest events in the process. So far, autoantibodies are most widely used as serum biomarker, but T-cell readouts and metabolome studies might strengthen and bring forward diagnosis. Current preventive clinical trials mostly focus on environmental triggers. Therapeutic trials test the efficacy of antigen-specific and antigen-nonspecific immune interventions, but also include restoration of the affected beta-cell mass by islet transplantation, neogenesis and regeneration, and combinations thereof. In this comprehensive review, we explain the genetic, environmental, and immunological data underlying the prevention and intervention strategies to constrain T1D.
Low proliferation and differentiation capacities of adult hippocampal stem cells correlate with memory dysfunction in humans (2010)

The hippocampal dentate gyrus maintains its capacity to generate new neurons throughout life. In animal models, hippocampal neurogenesis is increased by cognitive tasks, and experimental ablation of neurogenesis disrupts specific modalities of learning and memory. In humans, the impact of neurogenesis on cognition remains unclear. Here, we assessed the neurogenic potential in the human hippocampal dentate gyrus by isolating adult human neural stem cells from 23 surgical en bloc hippocampus resections. After proliferation of the progenitor cell pool in vitro we identified two distinct patterns. Adult human neural stem cells with a high proliferation capacity were obtained in 11 patients. Most of the cells in the high proliferation capacity cultures were capable of neuronal differentiation (53 ± 13% of in vitro cell population). A low proliferation capacity was observed in 12 specimens, and only few cells differentiated into neurons (4 ± 2%). This was reflected by reduced numbers of proliferating cells in vivo as well as granule cells immunoreactive for doublecortin, brain-derived neurotrophic factor and cyclin-dependent kinase 5 in the low proliferation capacity group. High and low proliferation capacity groups differed dramatically in declarative memory tasks. Patients with high proliferation capacity stem cells had a normal memory performance prior to epilepsy surgery, while patients with low proliferation capacity stem cells showed severe learning and memory impairment. Histopathological examination revealed a highly significant correlation between granule cell loss in the dentate gyrus and the same patient's regenerative capacity in vitro (r = 0.813; P < 0.001; linear regression: R²(adjusted) = 0.635), as well as the same patient's ability to store and recall new memories (r = 0.966; P = 0.001; linear regression: R²(adjusted) = 0.9). Our results suggest that encoding new memories is related to the regenerative capacity of the hippocampus in the human brain.