gebhart/patrepeval huggingface dataset:
The substantia nigra of the human brain (1999)

To achieve accuracy in studying the patterns of loss of midbrain dopamine-containing neurons in Parkinson's disease, we used compartmental patterns of calbindin D(28K) immunostaining to subdivide the substantia nigra with landmarks independent of the degenerative process. Within the substantia nigra pars compacta, we identified dopamine-containing neurons in the calbindin-rich regions ('matrix') and in five calbindin-poor pockets ('nigrosomes') defined by analysis of the three-dimensional networks formed by the calbindin-poor zones. These zones were recognizable in all of the brains, despite severe loss of dopamine-containing neurons. The degree of loss of dopamine-containing neurons in the substantia nigra pars compacta was related to the duration of the disease, and the cell loss followed a strict order. The degree of neuronal loss was significantly higher in the nigrosomes than in the matrix. Depletion was maximum (98%) in the main pocket (nigrosome 1), located in the caudal and mediolateral part of the substantia nigra pars compacta. Progressively less cell loss was detectable in more medial and more rostral nigrosomes, following the stereotyped order of nigrosome 1 > nigrosome 2 > nigrosome 4 > nigrosome 3 > nigrosome 5. A parallel, but lesser, caudorostral gradient of cell loss was observed for dopamine-containing neurons included in the matrix. This pattern of neuronal loss was consistent from one parkinsonian substantia nigra pars compacta to another. The spatiotemporal progression of neuronal loss related to disease duration can thus be drawn in the substantia nigra pars compacta for each Parkinson's disease patient: depletion begins in the main pocket (nigrosome 1) and then spreads to other nigrosomes and the matrix along rostral, medial and dorsal axes of progression.
<title>Multispot scanning exposure system for excimer laser stepper</title> (1991)

A new type of spot scanning exposure system has been developed for an excimer laser stepper. To optimize exposure parameters, the authors developed a SIPSE (Simulator for Spot Scanning Exposure) and performed experiments with a He-Cd laser and a g-line lens. Applying the results, a prototype of an excimer laser exposure system was developed. A lens evaluation system has also been developed to adjust the lens elements in the projection lens. Using these systems, 0.35 micron line and space patterns were clearly resolved. SIPSE will be usable to optimize a phase-shifting exposure system with a potential for 0.25 micron patterns.
South Sandwich slices reveal much about arc structure, geodynamics, and composition (1998)

The simple tectonic history of the South Sandwich island arc, a classic intra‐oceanic arc lying in the South Atlantic Ocean, provided excellent opportunities for the Sandwich Lithospheric and Crustal Experiment (SLICE), conducted early in 1997, to investigate how, and at what rates, the Earth's crust is modified by subduction processes. The SLICE investigations of the South Sandwich island arc and the East Scotia Sea back‐arc basin (Figure 1) included onshore and offshore recording of controlled‐source and earthquake seismic data, establishment of geodetic GPS monuments on two islands, a new geological survey of the islands, and sampling of the islands and sea floor. Knowledge of the structure, geodynamics, and composition of this arc system is important because its simple tectonic history will allow estimation of the rates at which subduction processes modify the crust, and because its intra‐oceanic setting makes it ideal for studying the timing and compositions of fluxes from the subducting slab.
Ultra low-leakage power strategies for sub-1 V VLSI: novel circuit styles and design methodologies for partially depleted silicon-on-insulator (PD-SOI) CMOS technology (2003)

As supply voltage is scaled to below 1 V, leakage power becomes significant in CMOS ICs. This paper proposes novel circuit techniques in PD-SOI technology to reduce standby power in the sub-1 V regime by over three orders of magnitude while maintaining circuit speed and with minimal overhead. Simulation results obtained using process parameters from an IBM 0.13 /spl mu/m PD-SOI technology show considerable improvement over previously proposed methods as supply voltage is scaled to 0.5 V. A new design algorithm for efficient implementation of these PD-SOI standby power reduction schemes is also described.
Routine Part-per-Million Mass Accuracy for High- Mass Ions:  Space-Charge Effects in MALDI FT-ICR (1998)

The effect of ion space-charge on mass accuracy in Fourier transform ion cyclotron resonance mass spectrometry is examined. Matrix-assisted laser desorption/ionization is used to form a population of high-molecular-weight polymer ions with a wide mass distribution. The density of the ions in the analyzer cell is varied using ion remeasurement and suspended trapping techniques to allow the effect of ion space charge to be examined independently of other experimental influences. Observed cyclotron frequency exhibits a linear correlation with ion population. Mass errors of 100 ppm or more in externally calibrated mass spectra result when ion number is not taken into account. By matching the total ion intensities of calibrant and analyte mass spectra, the protonated ion of insulin B-chain, 3494.6513 Da, is measured with an accuracy of 0.07 ppm (average of 10 measurements, σ = 2.3 ppm, average absolute error 1.6 ppm) using a polymer sample as an external calibrant. Alternatively, the correction for space charge can be made by using a calibration equation that accounts for the total ion intensity of the mass spectrum. A calibration procedure is proposed and is tested with the measurement of the mass of insulin B-chain. A mass accuracy of 2.0 ppm (average of 20 measurements, σ = 4.2 ppm, average absolute error 3.5 ppm) is achieved. Space-charge-induced mass errors are more significant for samples with many components, such as a polymer, than for single-component samples such as purified peptides or proteins.
RNA interference therapy for the Spinocerebellar ataxias (2014)

25 Introduction 26 Results 27 Silencing ataxin-7 expression 27 miS4 improves motor phenotypes 29 Reduction of ataxin-7 in the pcs does not induce toxicity 30 miS4 has a therapeutic impact on the SCA7 cerebellum 30 Discussion 32 Materials and methods 35
Detection and quantification of rare mutations with massively parallel sequencing (2011)

The identification of mutations that are present in a small fraction of DNA templates is essential for progress in several areas of biomedical research. Although massively parallel sequencing instruments are in principle well suited to this task, the error rates in such instruments are generally too high to allow confident identification of rare variants. We here describe an approach that can substantially increase the sensitivity of massively parallel sequencing instruments for this purpose. The keys to this approach, called the Safe-Sequencing System ("Safe-SeqS"), are (i) assignment of a unique identifier (UID) to each template molecule, (ii) amplification of each uniquely tagged template molecule to create UID families, and (iii) redundant sequencing of the amplification products. PCR fragments with the same UID are considered mutant ("supermutants") only if ≥95% of them contain the identical mutation. We illustrate the utility of this approach for determining the fidelity of a polymerase, the accuracy of oligonucleotides synthesized in vitro, and the prevalence of mutations in the nuclear and mitochondrial genomes of normal cells.
Raw-starch-digesting and thermostable α-amylase from the yeast Cryptococcus sp. S-2: purification, characterization, cloning and sequencing (1996)

A starch-degrading enzyme produced by the yeast Cryptococcus sp. S-2 was purified in only one step by using an alpha-cyclodextrin-Sepharose 6B column, and was characterized as an alpha-amylase (EC 3.2.1.1). The molecular mass and isoelectric point of purified alpha-amylase (AMY-CS2) were estimated to be 66 kDa and 4.2 respectively. AMY-CS2 has raw-starch-digesting and raw-starch-absorbing activities. Furthermore it was shown to be thermostable. An open reading frame of the cDNA specified 611 amino acids, including a putative signal peptide of 20 amino acids. The N-terminal region of AMY-CS2 (from the N-terminus to position 496) had 49.7% similarity with the whole region of alpha-amylase from Aspergillus oryzae (Taka-amylase), whereas the C-terminal region had a sequence that was similar to the C-terminal region of glucoamylase G1 from A. niger. In addition, putative raw-starch-binding motifs exist in some amylolytic enzymes. A mutant AMY-CS2 that lacks the C-terminal domain lost not only its ability to bind or digest raw starch, but also its thermostability. Consequently it is possible that the putative raw-starch-binding domain of AMY-CS2 plays a role not only in the molecule's raw-starch-digesting ability but also in its thermostability.
Mice, Men and Math: Finding Novel Drugs for Organ Transplantation (2012)

To ensure long term allograft function, immunosuppressive drugs are needed that target the immune responses which up to date lead to the development of clinical and subclinical acute allograft rejection (AR) despite immunosuppression. In a novel drug discovery approach we investigated, whether already FDA approved drugs exist that target biologically relevant pathways with significant enrichment in AR development. We performed quantitative microarray gene set analyses (GSA) using 3307 publicly available and manually created biologically functional gene-sets in 33 pre-transplant donor biopsies (D0) and matched 33 post renal transplant protocol biopsies with increasing AR (no significant abnormalities STA, n=16; borderline AR, ARIA, ARIB, n=17). To identify FDA approved drugs data for 7200 compounds were screened for drugs interacting with selected target genes with an existing PubMed entry in GeneGo Metacore. An in-vitro PBMC based inhibitory assay and an interventional in-vivo murine cardiac AR model were subsequently applied to test the potential of a selected drug to attenuate AR and prolong graft survival. The IL17 pathway was significantly enriched in patients with increasing grades of AR (GSA; FDR< 5%, D0>STA>BL>ARIA>ARIB). IL17 genes segregated patients into AR and STA and reflected AR subset segregation. Target-drug alignment studies identified Fenofibrate (FF) currently approved for hypertriglyceridemia as IL17 inhibitor. In antigen stimulated PBMC, FF inhibited not only IL17, but also IFNG, TNF, IL1B, IL6 gene expression which was confirmed in vivo in allografts from cardiac transplanted mice treated with FF for 7days. The number of graft infiltrating CD4+, CD8+ T-cells, as well as neutrophils, DC, NK and macrophages in mice at POD7 was reduced compared to non-treated animals (FACS of graft infiltrating cells; n=6 mice/group). Intracellular cytokine staining for IFNG and TNF producing graft infiltrating cells confirmed these results. Most importantly, FF significantly prolonged allograft survival (30-day graft survival study: n=10; median graft survival time: FF=21days; No treatment=9.5). This study represents a novel approach for the identification of alternative drug targets opening the window for novel treatment options in transplantation.
β-Amyloid Activates the Mitogen-Activated Protein Kinase Cascade via Hippocampal α7 Nicotinic Acetylcholine Receptors:In VitroandIn VivoMechanisms Related to Alzheimer's Disease (2001)

Alzheimer's Disease (AD) is the most common of the senile dementias, the prevalence of which is increasing rapidly, with a projected 14 million affected worldwide by 2025. The signal transduction mechanisms that underlie the learning and memory derangements in AD are poorly understood. β-Amyloid (Aβ) peptides are elevated in brain tissue of AD patients and are the principal component of amyloid plaques, a major criterion for postmortem diagnosis of the disease. Using acute and organotypic hippocampal slice preparations, we demonstrate that Aβ peptide 1-42 (Aβ42) couples to the mitogen-activated protein kinase (MAPK) cascade via α7 nicotinic acetylcholine receptors (nAChRs). In vivo elevation of Aβ, such as that exhibited in an animal model for AD, leads to the upregulation of α7 nAChR protein. α7 nAChR upregulation occurs concomitantly with the downregulation of the 42 kDa isoform of extracellular signal-regulated kinase (ERK2) MAPK in hippocampi of aged animals. The phosphorylation state of a transcriptional mediator of long-term potentiation and a downstream target of the ERK MAPK cascade, the cAMP-regulatory element binding (CREB) protein, were affected also. These findings support the model that derangement of hippocampus signal transduction cascades in AD arises as a consequence of increased Aβ burden and chronic activation of the ERK MAPK cascade in an α7 nAChR-dependent manner that eventually leads to the downregulation of ERK2 MAPK and decreased phosphorylation of CREB protein.
Live and Inactivated Influenza Vaccines Induce Similar Humoral Responses, but Only Live Vaccines Induce Diverse T-Cell Responses in Young Children (2011)

NCT00231907.
Imaging Biological Compounds Using The Coherent Anti-Stokes Raman Scattering Microscope (1985)

The microscopic spatial distribution of biological compounds can be imaged using a coherent anti-Stokes Raman scattering (CARS) microscope. Spatial resolution of less than one micrometer has been achieved, and excellent molecular discrimination using chemically similar molecular species has been obtained using digital image processing techniques.
Synthesis of functional ‘polyolefins’: state of the art and remaining challenges (2013)

Functional polyolefins (i.e., polyethene or polypropene bearing functional groups) are highly desired materials, due to their beneficial surface properties. Many different pathways exist for the synthesis of these materials, each with its own advantages and drawbacks. This review focuses on those synthetic pathways that build up a polymer chain from ethene/propene and functionalised polar vinyl monomers. Despite many recent advances in the various fields of olefin polymerisation, it still remains a challenge to synthesise high molecular-weight copolymers with tuneable amounts of functional groups, preferably with consecutive insertions of polar monomers occurring in a stereoselective way. To overcome some of these challenges, polymerisation of alternative functionalised monomers is explored as well.
Image annotation by large-scale content-based image retrieval (2006)

Image annotation has been an active research topic in recent years due to its potentially large impact on both image understanding and Web image search. In this paper, we target at solving the automatic image annotation problem in a novel search and mining framework. Given an uncaptioned image, first in the search stage, we perform content-based image retrieval (CBIR) facilitated by high-dimensional indexing to find a set of visually similar images from a large-scale image database. The database consists of images crawled from the World Wide Web with rich annotations, e.g. titles and surrounding text. Then in the mining stage, a search result clustering technique is utilized to find most representative keywords from the annotations of the retrieved image subset. These keywords, after salience ranking, are finally used to annotate the uncaptioned image. Based on search technologies, this framework does not impose an explicit training stage, but efficiently leverages large-scale and well-annotated images, and is potentially capable of dealing with unlimited vocabulary. Based on 2.4 million real Web images, comprehensive evaluation of image annotation on Corel and U. Washington image databases show the effectiveness and efficiency of the proposed approach.
Application of imaging to the laproscopic surgery (2002)

One of the main components which facilitated the success of Minimally Invasive Surgery (MIS), e.g. laparoscopic surgery, is the utilization of a scope which can be fed through small incision hole. As a result, this offered the surgeon a two-dimensional view of the surgical site. In general, the (laparo)scope is held by the assistance surgeon which may not offer an steady images of the viewing area. Another main difficulty in performing laparoscopic surgery is the lack of three-dimension perception of the surgical site. This perception includes the lack visual information about the relative position of the surgical tools and the lack of volumetric perception of the abdominal cavity. This paper presents some preliminary results on application of image processing and imaging technique to the field of laparoscopic surgery. In particular the paper presents (a) models for the lens distortion which can be used for diagnostics purposes; (b) a method for tracking surgical tools; (c) sensing system for determining the size of the abdominal volume.
Parkinsonianlike Signs and Risk of Incident Alzheimer Disease in Older Persons (2003)

Progression of parkinsonianlike signs in old age is associated with decline in cognitive function and the development of AD.
Growth of continuous bonelike mineral within porous poly(lactide-co-glycolide) scaffolds in vitro (2000)

Strategies to engineer bone have focused on the use of natural or synthetic degradable materials as scaffolds for cell transplantation or as substrates to guide bone regeneration. The basic requirements of the scaffold material are biocompatibility, degradability, mechanical integrity, and osteoconductivity. A major design problem is satisfying each of these requirements with a single scaffold material. This study addresses this problem by describing an approach to combine the biocompatibility and degradability of a polymer scaffold with the osteoconductivity and mechanical reinforcement of a bonelike mineral film. We report the nucleation and growth of a continuous carbonated apatite mineral on the interior pore surfaces of a porous, degradable polymer scaffold via a one step, room temperature incubation process. A 3-dimensional, porous scaffold of the copolymer 85:15 poly(lactide-co-glycolide) was fabricated by a solvent casting, particulate leaching process. Fourier transform IR spectroscopy and scanning electron microscopy (SEM) analysis after different incubation times in a simulated body fluid (SBF) demonstrate the growth of a continuous bonelike apatite layer within the pores of the polymer scaffold. Quantification of phosphate on the scaffold displays the growth and development of the mineral film over time with an incorporation of 0.43 mg of phosphate (equivalent to 0.76 mg of hydroxyapatite) per scaffold after 14 days in SBF. The compressive moduli of polymer scaffolds increased fivefold with formation of a mineral film after a 16-day incubation time as compared to control scaffolds. In summary, this biomimetic treatment provides a simple, one step, room temperature method for surface functionalization and subsequent mineral nucleation and growth on biodegradable polymer scaffolds for tissue engineering. © 2000 John Wiley & Sons, Inc. J Biomed Mater Res, 50, 50–58, 2000.
Transforming growth factor beta inhibits the antigen-presenting functions and antitumor activity of dendritic cell vaccines. (2003)

Dendritic cell (DC)-based vaccines have exhibited minimal effectiveness in treating established tumors, likely because of factors present in the tumor microenvironment. One such factor is transforming growth factor beta (TGF-beta), a cytokine that is produced by numerous tumor types and has been demonstrated to impair DC functions in vitro. We have evaluated the effect of TGF-beta on the immunostimulatory activities of DCs. We demonstrate that TGF-beta exposure inhibits the ability of DCs to present antigen, stimulate tumor-sensitized T lymphocytes, and migrate to draining lymph nodes. Neutralization of TGF-beta using the TGF-beta-neutralizing monoclonal antibody 2G7 enhanced the ability of DC vaccines to inhibit the growth of established 4T1 murine mammary tumors. Treatment of 4T1 tumors transduced with the antisense TGF-beta transgene (4T1-asT) with the combination of DC and 2G7 monoclonal antibody inhibited tumor growth and resulted in complete regression of tumors in 40% of the mice. These results demonstrate that neutralization of TGF-beta in tumor-bearing mice enhances the efficacy of DC-based vaccines.
Genetically engineered tetravalent single-chain Fv of the pancarcinoma monoclonal antibody CC49: improved biodistribution and potential for therapeutic application. (2000)

Failure of radiolabeled monoclonal antibodies (MAbs) in the treatment of solid tumors, for the most part, is a result of undesirable pharmacokinetics that lead to significant radiation exposure of normal tissues and an inadequate delivery of radiation doses to tumors. Using genetic engineering, antitumor MAbs can be optimized for desirable clinical applications. In the present study, we report the generation of a tetravalent single-chain Fv [[sc(Fv)2]2] of the murine MAb CC49 that recognizes the tumor-associated glycoprotein, TAG-72. [Sc(Fv)2]2 was expressed as a secreted soluble protein in Pichia pastoris under the regulation of alcohol oxidase 1 promoter. The in vitro binding properties of the tetravalent construct were analyzed by solid-phase RIA and surface plasmon resonance studies using BIAcore. The binding affinity constant (K(A)) for the [sc(Fv)2]2 and CC49 IgG were similar, i.e., 1.02 x 10(8) M(-1) and 1.14 x 10(8) M(-1), respectively, and were 4-fold higher than its divalent scFv [sc(Fv)2; 2.75 x 10(7) M(-1)]. At 6 h postadministration, the percentage of injected dose accumulated/g of LS-174T colon carcinoma xenografts was 21.3+/-1.3, 9.8+/-1.3, and 17.3+/-1.1 for radioiodinated [sc(Fv)2]2, sc(Fv)2, and IgG, respectively. Pharmacokinetic analysis of blood clearance studies showed the elimination half-life for [sc(Fv)2]2, sc(Fv)2, and IgG as 170, 80, and 330 min, respectively. The gain in avidity resulting from multivalency along with an improved biological half-life makes the tetravalent construct an important reagent for cancer therapy and diagnosis in MAb-based radiopharmaceuticals.
Clinical and Immunologic Effects of Component Peptides in Allervax<sup>®</sup> Cat (1997)

Peptides have been designed to be T cell tolerogenic for the principal allergens of the cat. These have been administered in several dosage programs to cat-sensitive patients in multicenter blinded studies. In contrast to proteins in standard extracts, IgE sensitization to peptides is an uncommon event. Pretreatment prick tests with peptides will identify the occasional sensitized patient. Other side reactions consist of allergic symptoms occurring on the day of injections. These become less severe with subsequent injections and are easily treatable with antihistamines or bronchodilators, depending on the symptoms. Treatment with cat peptides ameliorated symptoms that occur upon exposure to cats 1-6 or more weeks later. A 2-week course of 4 injections is the most effective of the regimens so far tried. T-cell-active peptides offer a promising low-risk alternative for specific treatment of respiratory allergies.
Predictors of bone mass in healthy older men in the community (2000)

These data indicate that measures of body composition, such as weight and lean mass, are the main predictors of bone mass in healthy, community-dwelling older men.
Mode multi/demultiplexer based on cascaded asymmetric Y-junctions (2013)

A mode-(de)multiplexer with low loss and large spectral bandwidth is proposed. The device is designed by utilizing a structure with cascaded asymmetric Y-junctions. By carefully controlling the widths of the wide and narrow arms of the Y-junctions, the fundamental mode of a narrow arm excites the higher-order mode of its stem in the multiplexing case, and a high-order mode of the stem separated from other lower-order modes evolves into the fundamental mode of the narrow arm in the demultiplexing case. As an example, a 1 × 4 mode-(de)multiplexer is analyzed by using the beam propagation method. Simulation results show the demultiplexed crosstalk is lower than -21.8 dB, under a common spectral bandwidth of 140 nm. The insertion loss is negligible.