gebhart/patrepeval huggingface dataset:
X-ray crystal structure of the protease inhibitor domain of Alzheimer's amyloid .beta.-protein precursor (1990)

Alzheimer's amyloid beta-protein precursor contains a Kunitz protease inhibitor domain (APPI) potentially involved in proteolytic events leading to cerebral amyloid deposition. To facilitate the identification of the physiological target of the inhibitor, the crystal structure of APPI has been determined and refined to 1.5-A resolution. Sequences in the inhibitor-protease interface of the correct protease target will reflect the molecular details of the APPI structure. While the overall tertiary fold of APPI is very similar to that of the Kunitz inhibitor BPTI, a significant rearrangement occurs in the backbone conformation of one of the two protease binding loops. A number of Kunitz inhibitors have similar loop sequences, indicating the structural alteration is conserved and potentially an important determinant of inhibitor specificity. In a separate region of the protease binding loops, APPI side chains Met-17 and Phe-34 create an exposed hydrophobic surface in place of Arg-17 and Val-34 in BPTI. The restriction this change places on protease target sequences is seen when the structure of APPI is superimposed on BPTI complexed to serine proteases, where the hydrophobic surface of APPI faces a complementary group of nonpolar side chains on kallikrein A versus polar side chains on trypsin.
Familial Aggregation of Common Sequence Variants on 15q24-25.1 in Lung Cancer (2008)

Three recent genome-wide association studies identified associations between markers in the chromosomal region 15q24-25.1 and the risk of lung cancer. We conducted a genome-wide association analysis to investigate associations between single-nucleotide polymorphisms (SNPs) and the risk of lung cancer, in which we used blood DNA from 194 case patients with familial lung cancer and 219 cancer-free control subjects. We identified associations between common sequence variants at 15q24-25.1 (that spanned LOC123688 [a hypothetical gene], PSMA4, CHRNA3, CHRNA5, and CHRNB4) and lung cancer. The risk of lung cancer was more than fivefold higher among those subjects who had both a family history of lung cancer and two copies of high-risk alleles rs8034191 (odds ratio [OR] = 7.20, 95% confidence interval [CI] = 2.21 to 23.37) or rs1051730 (OR = 5.67, CI = 2.21 to 14.60, both of which were located in the 15q24-25.1 locus, than among control subjects. Thus, further research to elucidate causal variants in the 15q24-25.1 locus that are associated with lung cancer is warranted.
Clostridium difficile Recombinant Toxin A Repeating Units as a Carrier Protein for Conjugate Vaccines: Studies of Pneumococcal Type 14, Escherichia coli K1, and Shigella flexneri Type 2a Polysaccharides in Mice (2000)

Unlike the native protein, a nontoxic peptide (repeating unit of the native toxin designated rARU) from Clostridium difficile toxin A (CDTA) afforded an antigen that could be bound covalently to the surface polysaccharides of pneumococcus type 14, Shigella flexneri type 2a, and Escherichia coli K1. The yields of these polysaccharide-protein conjugates were significantly increased by prior treatment of rARU with succinic anhydride. Conjugates, prepared with rARU or succinylated (rARUsucc), were administered to mice by a clinically relevant dosage and immunization scheme. All conjugates elicited high levels of serum immunoglobulin G both to the polysaccharides and to CDTA. Conjugate-induced anti-CDTA had neutralizing activity in vitro and protected mice challenged with CDTA, similar to the rARU alone. Conjugates prepared with succinylated rARU, therefore, have potential for serving both as effective carrier proteins for polysaccharides and for preventing enteric disease caused by C. difficile.
Review of Pseudobulbar Affect Including a Novel and Potential Therapy (2005)

Pseudobulbar affect (PBA) is an affective disinhibition syndrome associated with various neuropathologies, which is characterized by involuntary and inappropriate outbursts of laughter and/or crying. The PBA syndrome can be socially and occupationally disabling, and it is largely unrecognized in clinical settings. Validated instruments to distinguish PBA from other disorders of affective regulation exist and could be used to improve recognition of the disorder. There is no pharmacological therapy with a Food and Drug Administration indication for PBA, although antidepressants and dopaminergic agents have been reported to show varying levels of treatment success. Recent evidence suggests that treatment with a fixed combination of dextromethorphan and the cytochrome P450 2D6 enzyme inhibitor, quinidine, can improve PBA. This review describes the clinical and neuropathological features of PBA, and presents an overview of current and future treatment approaches.
Circulating Tumor Cells and Circulating Tumor DNA: Challenges and Opportunities on the Path to Clinical Utility (2015)

Recent technological advances have enabled the detection and detailed characterization of circulating tumor cells (CTC) and circulating tumor DNA (ctDNA) in blood samples from patients with cancer. Often referred to as a "liquid biopsy," CTCs and ctDNA are expected to provide real-time monitoring of tumor evolution and therapeutic efficacy, with the potential for improved cancer diagnosis and treatment. In this review, we focus on these opportunities as well as the challenges that should be addressed so that these tools may eventually be implemented into routine clinical care.
BULK ISOLATION OF MOUSE HEPATOCYTE GAP JUNCTIONS (1974)

A method is reported for isolating a preparation of hepatic gap junctions from the mouse. The method involves a collagenase digestion, treatment with the detergent Sarkosyl NL-97, and ultrasonication, followed by sucrose gradient ultracentrifugation. A run with 36 animals yields 0.1–0.5 mg protein. Electron microscopy with thin-sectioning and negative staining techniques reveals that the final pellet is a very pure preparation of gap junctions, accompanied by a small amount of amorphous contamination. Polyacrylamide-gel electrophoresis of sodium dodecyl sulfate (SDS)-solubilized material shows one major protein in the junction, with an apparent mol wt of 20,000, and two minor components. Thin-layer chromatography demonstrates one major and one minor phospholipid, and some neutral lipid. Low-angle X-ray diffraction of wet and dried specimens show reflections which index on an 86 A center-to-center hexagonal lattice, corresponding closely to electron microscope data. Dried specimens also show a lamellar diffraction, corresponding to the total profile thickness of the junction (150 A).
Role of oxygen free radicals in shock, ischemia, and organ preservation. (1983)

Oxygen radicals appear to be involved in the microvascular and parenchymal cell injury associated with various pathologic disorders. Studies indicate that oxygen radicals increase microvascular permeability by creating large leakage sites predominantly in the small venules. The highly reactive hydroxyl radical appears to be responsible for the microvascular alterations associated with oxygen radical production. There is considerable indirect evidence implicating oxygen radicals in the pathogenesis of circulatory shock. The oxygen radicals are probably formed by the enzyme xanthine oxidase when intravascular volume is restored. Similar biochemical processes appear to be involved in reperfusion injury to the kidney and skin. Evidence is also presented that implicates oxygen radicals in the reperfusion injury associated with organ preservation and transplantation.
Counting on Cancer Registry (1991)

any cancers are avoidable and treatable. The broad purpose of cancer registration is to help assess the M impact of malignant diseases on the community 50 Counting on Cancer and the measures taken to control them. Cancer Registry registration also provides a reservoir of data which can be used for case series or analytic epidemiological studies.
Object retrieval with large vocabularies and fast spatial matching (2007)

In this paper, we present a large-scale object retrieval system. The user supplies a query object by selecting a region of a query image, and the system returns a ranked list of images that contain the same object, retrieved from a large corpus. We demonstrate the scalability and performance of our system on a dataset of over 1 million images crawled from the photo-sharing site, Flickr [3], using Oxford landmarks as queries. Building an image-feature vocabulary is a major time and performance bottleneck, due to the size of our dataset. To address this problem we compare different scalable methods for building a vocabulary and introduce a novel quantization method based on randomized trees which we show outperforms the current state-of-the-art on an extensive ground-truth. Our experiments show that the quantization has a major effect on retrieval quality. To further improve query performance, we add an efficient spatial verification stage to re-rank the results returned from our bag-of-words model and show that this consistently improves search quality, though by less of a margin when the visual vocabulary is large. We view this work as a promising step towards much larger, "web-scale" image corpora.
Synthesis of Hexagonally Packed Mesoporous TiO2 by a Modified Sol–Gel Method (1995)

Stable to surfactant removal by calcination , Ti‐TMS1 is the first hexagonally packed, mesoporous transition metal oxide. The synthesis of this new material was achieved by a modified sol–gel technique from titanium alkoxides and phosphate surfactants. The large internal surface area, narrow and controllable pore size, thermal stability, and variable oxidation states of the metal give this new material great potential as a catalyst and sorbent.
Compilation of vertebrate-encoded transcription factors (1992)

Journal Article Compilation of vertebrate-encoded transcription factors Get access Steffen Faisst, Steffen Faisst Oncologie Moléculaire, Institut Pasteur de Lille1 rue Calmette, BP 245, F-59019 Lille Cédex, France Search for other works by this author on: Oxford Academic PubMed Google Scholar Silke Meyer Silke Meyer Oncologie Moléculaire, Institut Pasteur de Lille1 rue Calmette, BP 245, F-59019 Lille Cédex, France Search for other works by this author on: Oxford Academic PubMed Google Scholar Nucleic Acids Research, Volume 20, Issue 1, 11 January 1992, Pages 3–26, https://doi.org/10.1093/nar/20.1.3 Published: 11 January 1992 Article history Received: 16 October 1991 Revision received: 02 December 1991 Accepted: 02 December 1991 Published: 11 January 1992
Biallelic germline mutations in MYH predispose to multiple colorectal adenoma and somatic G:C->T:A mutations (2002)

We have recently demonstrated that inherited defects of the base excision repair gene MYH predispose to multiple colorectal adenomas and carcinoma. Three affected siblings from a single British family were identified as Y165C/G382D compound heterozygotes and both missense mutations were shown to be functionally compromised. Here, we report the identification of seven further unrelated patients with >100 colorectal adenomas (six with colorectal cancer) and biallelic germline mutations in MYH: four were homozygous for truncating mutations, two were homozygous for Y165C and one was a Y165C/G382D compound heterozygote. As predicted from studies of the bacterial and yeast orthologues of MYH, colorectal tumours from affected individuals displayed a significant excess of somatic G:C-->T:A mutations in APC, as compared to sporadic ( chi(2)=242.96, P<10(-20)) or FAP-associated ( chi(2)=194.85, P<10(-20)) colorectal tumours. The sequence immediately downstream of the somatic G:C-->T:A mutations was predominantly AA, irrespective of the nature of the germline MYH mutations. These findings confirm the role of MYH in colorectal adenoma and carcinoma predisposition.
Formation of 17-Allylamino-Demethoxygeldanamycin (17-AAG) Hydroquinone by NAD(P)H:Quinone Oxidoreductase 1: Role of 17-AAG Hydroquinone in Heat Shock Protein 90 Inhibition (2005)

We have examined the role of NAD(P)H:quinone oxidoreductase 1 (NQO1) in the bioreductive metabolism of 17-allylamino-demethoxygeldanamycin (17-AAG). High-performance liquid chromatography (HPLC) analysis of the metabolism of 17-AAG by recombinant human NQO1 revealed the formation of a more polar metabolite 17-AAGH2. The formation of 17-AAGH2 was NQO1 dependent, and its formation could be inhibited by the addition of 5-methoxy-1,2-dimethyl-3-[(4-nitrophenoxy)methyl]indole-4,7-dione (ES936), a mechanism-based (suicide) inhibitor of NQO1. The reduction of 17-AAG to the corresponding hydroquinone 17-AAGH2 was confirmed by tandem liquid chromatography-mass spectrometry. 17-AAGH2 was relatively stable and only slowly underwent autooxidation back to 17-AAG over a period of hours. To examine the role of NQO1 in 17-AAG metabolism in cells, we used an isogenic pair of human breast cancer cell lines differing only in NQO1 levels. MDA468 cells lack NQO1 due to a genetic polymorphism, and MDA468/NQ16 cells are a stably transfected clone that express high levels of NQO1 protein. HPLC analysis of 17-AAG metabolism using cell sonicates and intact cells showed that 17-AAGH2 was formed by MDA468/NQ16 cells, and formation of 17-AAGH2 could be inhibited by ES936. No 17-AAGH2 was detected in sonicates or intact MDA468 cells. Following a 4-hour treatment with 17-AAG, the MDA468/NQ16 cells were 12-fold more sensitive to growth inhibition compared with MDA468 cells. More importantly, the increased sensitivity of MDA468/NQ16 cells to 17-AAG could be abolished if the cells were pretreated with ES936. Cellular markers of heat shock protein (Hsp) 90 inhibition, Hsp70 induction, and Raf-1 degradation were measured by immunoblot analysis. Marked Hsp70 induction and Raf-1 degradation was observed in MDA468/NQ16 cells but not in MDA468 cells. Similarly, downstream Raf-1 signaling molecules mitogen-activated protein kinase/extracellular signal-regulated kinase (ERK) kinase and ERK also showed decreased levels of phosphorylation in MDA468/NQ16 cells but not in MDA468 cells. The ability of 17-AAG and 17-AAGH2 to inhibit purified yeast and human Hsp90 ATPase activity was examined. Maximal 17-AAG-induced ATPase inhibition was observed in the presence of NQO1 and could be abrogated by ES936, showing that 17-AAGH2 was a more potent Hsp90 inhibitor compared with 17-AAG. Molecular modeling studies also showed that due to increased hydrogen bonding between the hydroquinone and the Hsp90 protein, 17-AAGH2 was bound more tightly to the ATP-binding site in both yeast and human Hsp90 models. In conclusion, these studies have shown that reduction of 17-AAG by NQO1 generates 17-AAGH2, a relatively stable hydroquinone that exhibits superior Hsp90 inhibition.
Heterodimeric DNA-binding dyes designed for energy transfer: synthesis and spectroscopic properties (1993)

Heterodimeric dyes are described which bind tightly to double-stranded (dsDNA) with large fluorescence enhancements. These dyes are designed to exploit energy transfer between donor and acceptor chromophores to tune the separation between excitation and emission wavelengths. The dyes described here absorb strongly at the 488 nm argon ion line, but emit at different wavelengths, and can be applied to multiplex detection of various targets. The chromophores in these dyes, a thiazole orange-thiazole blue heterodimer (TOTAB), two different thiazole orange-ethidium heterodimers (TOED1 and TOED2), and a fluorescein-ethidium heterodimer (FED), are in each case linked through polymethyleneamine linkers. The emission maxima of the DNA-bound dyes lie at 662 (TOTAB), 614 (TOED 2), and 610 nm (FED). The dyes showed a > 100 fold enhancement of the acceptor chromophore fluorescence on binding to dsDNA and no sequence selectivity. In comparison with direct 488 nm excitation of the constituent monomeric dyes, in the heterodimers the fluorescence of the acceptor chromophores was greatly enhanced and the emission of the donor chromophores quenched by over 90%. The acceptor emission per DNA-bound dye molecule was constant from 100 DNA bp:dye to 20 bp:dye and decreased sharply at higher dye:DNA ratios.
Double‐echo three‐point‐dixon method for fat suppression MRI (1995)

Abstract A double‐echo two‐excitation pulse sequence encoding fat and water signals for a phase‐sensitive three‐point Dixon‐type analysis (DE‐3PD) was developed and implemented on a 1.5 T MR imager. Data processing was performed using a previously developed two‐dimensional (2D) region‐growing algorithm, adapted to use double‐echo data. Density‐, T 1 , and T 2 ‐weighted fat suppression images were obtained from six volunteers using the new fat suppression method. The images were compared with corresponding images obtained using frequency‐selective excitation fat suppression (FAT‐SAT) and a single‐echo three‐point‐Dixon method (SE‐3PD). The results demonstrate that the DE‐3PD sequence shortens the imaging time by one‐third compared with the SE‐3PD method, without loss in image quality. The data also show that a 2D region‐growing algorithm effectively unwraps the phase of DE‐3PD data sets, and that results of DE‐3PD fat signal suppression are consistently better than those obtained using a standard FATSAT method. The authors conclude that the double‐echo sequence provides density‐, T 1 , and T 2 ‐weighted images that appear to be promising for routine clinical applications.
Hydrogen-atom abstraction from methane by stoichiometric early transition metal oxide cluster cations (2010)

Stoichiometric early transition metal oxide cations (TiO(2))(1-5)(+), (ZrO(2))(1-4)(+), (HfO(2))(1-2)(+), (V(2)O(5))(1-5)(+), (Nb(2)O(5))(1-3)(+), (Ta(2)O(5))(1-2)(+), (MoO(3))(1-2)(+), (WO(3))(1-3)(+), and Re(2)O(7)(+) are able to activate the C-H bond of methane under near room temperature conditions.
Effect of the H1 Antihistamine Chlorpheniramine Maleate on Histamine‐Induced Symptoms in the Human Conjunctiva (1982)

Earlier studies have shown that intranasal chlorpheniramine (0.77%) can inhibit histamine-induced tickling, sneezing, and hypersecretion by a local effect on nerve fibres. The aim of the present study was to examine whether this solution had local anaesthetic of parasympatholytic properties. If neither of these properties are present it suggests that the anti-pruritic effects of the solution are caused by inhibition of H1 receptors, which in turn is indirect evidence for the presence of H1 receptors on nerve fibers. In a double-blind design 15 normal subjects were provoked with histamine in the eye after pretreatment with chlorpheniramine or with a local anaesthetic, oxybuprocain. Both drugs inhibited itching, but the H1 antihistamine was significantly more effective than the local anaesthetic (P less than 0.01). Corneal sensitivity was measured by an esthesiometer, and pupil difference was used as a measure for atropine activity. Chlorpheniramine had neither a local anaesthetic nor a parasympatholytic effect. This study has therefore strengthened the hypothesis that there are nervous H1 receptors in the mucous membranes of the eye and airways and has extended its application in animals to also include man.
Fast Infrared Chemical Imaging with a Quantum Cascade Laser (2014)

Infrared (IR) spectroscopic imaging systems are a powerful tool for visualizing molecular microstructure of a sample without the need for dyes or stains. Table-top Fourier transform infrared (FT-IR) imaging spectrometers, the current established technology, can record broadband spectral data efficiently but requires scanning the entire spectrum with a low throughput source. The advent of high-intensity, broadly tunable quantum cascade lasers (QCL) has now accelerated IR imaging but results in a fundamentally different type of instrument and approach, namely, discrete frequency IR (DF-IR) spectral imaging. While the higher intensity of the source provides a higher signal per channel, the absence of spectral multiplexing also provides new opportunities and challenges. Here, we couple a rapidly tunable QCL with a high performance microscope equipped with a cooled focal plane array (FPA) detector. Our optical system is conceptualized to provide optimal performance based on recent theory and design rules for high-definition (HD) IR imaging. Multiple QCL units are multiplexed together to provide spectral coverage across the fingerprint region (776.9 to 1904.4 cm(-1)) in our DF-IR microscope capable of broad spectral coverage, wide-field detection, and diffraction-limited spectral imaging. We demonstrate that the spectral and spatial fidelity of this system is at least as good as the best FT-IR imaging systems. Our configuration provides a speedup for equivalent spectral signal-to-noise ratio (SNR) compared to the best spectral quality from a high-performance linear array system that has 10-fold larger pixels. Compared to the fastest available HD FT-IR imaging system, we demonstrate scanning of large tissue microarrays (TMA) in 3-orders of magnitude smaller time per essential spectral frequency. These advances offer new opportunities for high throughput IR chemical imaging, especially for the measurement of cells and tissues.
Interactive maps for a digital video library (2003)

The Informedia Digital Video Library contains over 1200 hours of video. Through automatic processing, descriptors are derived for the video to improve library access. A new extension to the video processing is the extraction of geographic references from these descriptors. The operational library interface shows the geographic entities addressed in a given story, highlighting the regions discussed at any point in the video through a map display, synchronized with the video playback. The map can also be used as a query mechanism, allowing users to search the terabyte library for stories taking place in a selected area of interest.
Discovery of APD334: Design of a Clinical Stage Functional Antagonist of the Sphingosine-1-phosphate-1 Receptor (2014)

APD334 was discovered as part of our internal effort to identify potent, centrally available, functional antagonists of the S1P1 receptor for use as next generation therapeutics for treating multiple sclerosis (MS) and other autoimmune diseases. APD334 is a potent functional antagonist of S1P1 and has a favorable PK/PD profile, producing robust lymphocyte lowering at relatively low plasma concentrations in several preclinical species. This new agent was efficacious in a mouse experimental autoimmune encephalomyelitis (EAE) model of MS and a rat collagen induced arthritis (CIA) model and was found to have appreciable central exposure.