gebhart/patrepeval huggingface dataset:
Mitotic mechanisms in Alzheimer's disease? (1996)

The mechanism(s) leading to widespread hyper-phosphorylation of proteins in Alzheimer's disease (AD) are unknown. We have characterized seven new monoclonal antibodies recognizing independent phospho-epitopes in the paired helical filament proteins (PHF) found in AD brain. These antibodies show pronounced immunoreactivity with cultured human neuroblastoma cells that are in the M phase of cell division, but have no discernible reactivity with interphase cells. Immunoreactivity with these antibodies does not localize to the microtubule spindles or chromosomes in M phase, but is confined to the surrounding cytoplasm. Similar staining in M phase is observed with cultured cells of various tissue types and species. Cells arrested in M phase with the microtubule depolymerizing agent, nocodazole, show marked increases in immunoreactivity with the antibodies by immunofluorescence staining, ELISA, and immunoblotting. In neuroblastoma cells, the appearance of the TG/MC phospho-epitopes coincides with activation of mitotic protein kinases, but not with the activity of the neuronal specific cyclin-dependent kinase, cdk5. These data suggest that the TG/MC epitopes are conserved mitotic phospho-epitopes produced as a result of increased mitotic kinase activity. To investigate this possibility in AD, we examined the staining of human brain tissue with MPM-2, a marker antibody for mitotic phospho-epitopes. It was found that MPM-2 reacts strongly with neurofibrillary tangles, neuritic processes, and neurons in AD but has no staining in normal human brain. Our data suggest that accumulation of phospho-epitopes in AD may result from activation of mitotic posttranslational mechanisms which do not normally operate in mature neurons of brain.
Recovery of Intrinsic and Extrinsic Camera Parameters using Perspective Views of Rectangles. (1995)

This paper concerns the recovery of intrinsic and extrinsic camera parameters using perspective views of rectangles. Several algorithms are described. The intrinsic parameters (aspect ratio, effective focal length, and the principal point) are determined in closed-form using a minimum of four views. The recovery of the intrinsic parameters and the rotation angles is independent of the size of the rectangles. The absolute translation is recovered by knowing either the length of one side of the rectangle or the area of the rectangle or any other absolute information. The new method for recovering extrinsic parameters is shown to be significantly more robust than the widely used method based on vanishing points. Experiments with both synthetic and real images are presented.
ViCRO: An Interactive and Cooperative VideoRecording on-demand System over MBone. (2000)

This paper presents an interactive and cooperative VideoConference Recording On-demand system (ViCRO) designed for remote playback, recording and browsing multimedia sessions over the Internet MBone. It consists of Media Servers, possibly cluster-based, and Media Clients. The interaction multiclient/multi-server is based on the RTSP protocol for streaming control, on the RTP protocol for multimedia data streaming, on the LRMP protocol for reliable messaging and on the SAP protocol for group rendezvous. The time-critical and continuous components of the media clients and media servers are built by using Java and Actor based Framework (JAF), i.e., a variant of the Actor model specialized to multimedia requirements. JAF centres on timing predictability, customizable scheduling and a modular specification of QoS constraints. The main goal is to integrate MBone and WWW technologies towards media-on-demand and virtual collaborative work in heterogeneous environments. The paper introduces the Java-enabled ViCRO system and describes its application in several scenarios ranging from teleteaching to videoconferencing.
Phenotypic knockout of the high-affinity human interleukin 2 receptor by intracellular single-chain antibodies against the alpha subunit of the receptor. (1995)

The experimental manipulation of peptide growth hormones and their cellular receptors is central to understanding the pathways governing cellular signaling and growth control. Previous work has shown that intracellular antibodies targeted to the endoplasmic reticulum (ER) can be used to capture specific proteins as they enter the ER, preventing their transport to the cell surface. Here we have used this technology to inhibit the cell surface expression of the alpha subunit of the high-affinity interleukin 2 receptor (IL-2R alpha). A single-chain variable-region fragment of the anti-Tac monoclonal antibody was constructed with a signal peptide and a C-terminal ER retention signal. Intracellular expression of the single-chain antibody was found to completely abrogate cell surface expression of IL-2R alpha in stimulated Jurkat T cells. IL-2R alpha was detectable within the Jurkat cells as an immature 40-kDa form that was sensitive to endoglycosidase H, consistent with its retention in a pre- or early Golgi compartment. A single-chain antibody lacking the ER retention signal was also able to inhibit cell surface expression of IL-2R alpha although the mechanism appeared to involve rapid degradation of the receptor chain within the ER. These intracellular antibodies will provide a valuable tool for examining the role of IL-2R alpha in T-cell activation, IL-2 signal transduction, and the deregulated growth of leukemic cells which overexpress IL-2R alpha.
A bulged lin-4/lin-14 RNA duplex is sufficient for Caenorhabditis elegans lin-14 temporal gradient formation. (1996)

The Caenorhabditis elegans heterochronic gene lin-14 generates a temporal gradient of the LIN-14 proteins to control stage-specific patterns of cell lineage during development. Down-regulation of LIN-14 is mediated by the lin-14 3' untranslated region (UTR), which bears seven sites that are complementary to the regulatory lin-4 RNA. Here we report molecular and genetic evidence that RNA duplexes between the lin-4 and lin-14 RNAs form in vivo and are necessary for LIN-14 temporal gradient generation. lin-4 RNA binds in vitro to a lin-14 mRNA bearing the seven lin-4 complementary sites but not to a lin-14 mRNA bearing point mutations in these sites. In vivo, the lin-4 complementary regions are necessary for lin-14 3' UTR-mediated temporal gradient formation. Based on lin-14 3' UTR sequence comparisons between C. elegans and C. briggsae, four of the seven lin-4/lin-14 RNA duplexes are predicted to bulge a lin-4 C residue, and three sites are predicted to form nonbulged RNA duplexes. Reporter genes bearing multimerized bulged C lin-4 binding sites show almost wild-type temporal gradient formation, whereas those bearing multimerized nonbulged lin-4 binding sites do not form a temporal gradient. Paradoxically, lin-4 RNA binds in vitro to nonbulged lin-14 RNA more avidly than to the bulged lin-14 RNA. This suggests that a specific secondary structure of lin-4/lin-14 RNA duplex that may be recognized by an accessory protein, rather than an RNA duplex per se, is required in vivo for the generation of the LIN-14 temporal gradient.
Irregularity of Airway Branching in a Mouse Bronchial Tree: A 3-D Morphometric Study. (2001)

Limited information on the degree of irregularity of branching patterns of a bronchial tree may obscure the cause of heterogeneous distribution of the lesions in a variety of lung diseases. We reconstructed three dimensional (3-D) images from hilum to terminal bronchioles of a mouse lung, and defined the irregularity of airway branching by diameter-based morphometric analysis. The relative diameter ratios of a daughter to the parent branch (D1/D0) and those of a minor to major daughter branches (D1/D2) were calculated, and irregular dichotomies were found to be distributed in 48% of bifurcations. D1/D0 is well correlated with D1/D2, and is proved to indicate regular and irregular branching, as well as D1/D2. Irregular branches with D1/D0 smaller than 0.4 correspond to typical lateral branches, taking off from major bronchi. Our novel 3-D morphometric analysis showed the first portrayal of the 3-D structures of mouse bronchial airways, which provides a quantitative description of branching patterns leading to the correlation with distribution of lesions in the diseased lung.
Sleep quality in mechanically ventilated patients: Comparison of three ventilatory modes (2008)

In conscious, mechanically ventilated patients, sleep architecture was highly abnormal, with a short REM stage and a high degree of fragmentation. The ventilatory mode did not influence sleep pattern, arousals, awakenings, and ineffective efforts.
Augmentation of osseous phenotypes in vivo with a synthetic peptide (2006)

The synthetic peptide B2A2-K-NS augmented the in vitro expression of osseous phenotypes when cells were stimulated with BMP-2, an osteoinductive growth factor. B2A2-K-NS significantly enhanced the effects of BMP-2-induced alkaline phosphatase activity and mineralization. In the absence of BMP-2, B2A2-K-NS did not have an effect on these endpoints. Based on these observations, in vivo studies were conducted to evaluate if B2A2-K-NS could augment osseous phenotypes in an osteoinductive environment in which BMP-2 should be present. In one study, human demineralized bone matrix (DBM) was used to generate an osteoinductive environment and the effects of B2A2-K-NS on ectopic mineralization of subcutaneous implants evaluated. In the second study, a noncritical sized defect in rabbit ulnas with inherent reparative capacity was used as the osteoinductive environment and was treated with or without B2A2-K-NS. In the DBM studies, B2A2-K-NS augmented mineralization as determined using a combination of radiographic analysis and von Kossa staining at 4 weeks postimplant. In the rabbit ulna model, B2A2-K-NS significantly increased the radiographic bone density in the defects compared to carrier-only or no-treatment controls after 6 weeks. Histological staining confirmed that B2A2-K-NS generated a pronounced bone repair response. The results are consistent with the hypothesis that B2A2-K-NS augments osseous phenotypes in an osteoinductive environment, and suggests that B2A2-K-NS may have clinical utility.
SB 207499 (Ariflo), a second generation phosphodiesterase 4 inhibitor, reduces tumor necrosis factor alpha and interleukin-4 production in vivo. (1998)

The ability of the second generation phosphodiesterase 4 inhibitor SB 207499 (Ariflo), [c-4-cyano-4-(3-cyclopentyloxy-4-methoxyphenyl)-r-l-cyclohexane carboxylic acid], to inhibit inflammatory cytokine production in vivo was evaluated and compared to that of rolipram, a first generation phosphodiesterase 4 inhibitor. To examine human tumor necrosis factor alpha (TNFalpha) production, human monocytes were adoptively transferred into Balb/c mice and challenged with lipopolysaccharide (LPS). In this model, SB 207499 inhibited human TNFalpha production with oral ED50 of 4.9 mg/kg. Similarly, R-rolipram inhibited human TNFalpha production with an ED50 of 5.1 mg/kg, p.o. In contrast to their equipotent activity against TNFalpha production, SB 207499 (ED50 = 2.3 mg/kg, p.o.) was 10-fold less potent than R-rolipram (ED50 = 0.23 mg/kg, p.o.) in reversing reserpine-induced hypothermia, a model of antidepressant activity. In time course studies, SB 207499 (30 mg/kg, p.o.) inhibited TNFalpha production for at least 10 hr; substantial plasma concentrations of SB 207499 were detected over the same interval. The ability of SB 207499 to modulate interleukin-4 production in vivo was assessed in a chronic oxazolone-induced contact sensitivity model in Balb/c mice. In this model, topical administration of SB 207499 (1000 microgram) inhibited intralesional concentrations of interleukin-4 (55%; P <.01). The results demonstrate that SB 207499 is a potent inhibitor of inflammatory cytokine production in a variety of settings in vivo. Moreover, although it is as potent as R-rolipram in inhibiting TNFalpha production, it has substantially less central nervous system activity. Thus SB 207499 represents an excellent candidate with which to evaluate the antiinflammatory potential of PDE4 inhibitors.
Antimicrobial susceptibility of Bordetella avium and Bordetella bronchiseptica isolates (1989)

Two veterinary pathogens, Bordetella bronchiseptica and Bordetella avium, were tested for their antimicrobial susceptibilities. Of the 20 antimicrobial agents tested, both species were consistently resistant to penicillin and cefuroxime but susceptible to mezlocillin, piperacillin, gentamicin, amikacin, and cefoperazone.
Single-fed dual band circularly polarised microstrip patch antennas (1996)

Over the past years several attempts have been made to widen the bandwidth of single-fed circularly polarised patch antennas. This paper presents a novel structure to accomplish circularly polarised dual frequency operation by using two spur-line band-stop filters. This circularly polarised dual frequency operation can be obtained without increasing either the size or the thickness of the patch. Furthermore, through several experiments this paper also demonstrates that the location of the feed point establishes and controls a trade-off between axial ratio and impedance bandwidth.
Experimental demonstration of a broadband all-dielectric metamaterial perfect reflector (2014)

All-dielectric metamaterials utilizing Mie resonances in high-permittivity dielectric resonators offer a low-loss alternative to plasmonic metamaterials. Here we present the demonstration of a single-negative all-dielectric metamaterial, comprised of a single layer of cylindrical silicon resonators on a silicon-on-insulator substrate, that possesses peak reflectance over 99% and an average reflectance over 98% across a 200 nm wide bandwidth in the short-wavelength infrared region. The study is also extended to disordered metamaterials, demonstrating a correlation between the degree of disorder and the reduction in reflectance. It is shown that near-unity reflection is preserved as long as resonator interaction is avoided. Realization of near-unity reflection from disordered metamaterials opens the door to large-area implementations using low-cost self-assembly based fabrication techniques.
Catheter Technique for Closed-Chest Ablation of the Atrioventricular Conduction System (1982)

This report describes a catheter technique for ablating the His bundle and its application in nine patients with recurrent supraventricular tachycardia that was unresponsive to medical management. A tripolar electrode catheter was positioned in the region of the His bundle, and the electrode recording a large unipolar His-bundle potential was identified. In the first patient, two shocks of 25 and 50 J, respectively, were delivered by a standard cardioversion unit to the catheter electrode, resulting in an intra-His-bundle conduction defect. Subsequent delivery of 300 J resulted in complete heart block. In the next eight patients, an initial shock of 200 J was used. The His bundle was ablated by this single shock in six of these patients and by an additional shock of 300 J in one. In the remaining patient, conduction in the atrioventricular node was modified, resulting in alternating first and second-degree atrioventricular block. A stable escape rhythm was preserved in all patients. The procedure was well tolerated, without complications, and all patients have remained free of arrhythmia, without medication, for follow-up periods of two to six months.
U.S. Food and Drug Administration Approval: Ofatumumab for the Treatment of Patients with Chronic Lymphocytic Leukemia Refractory to Fludarabine and Alemtuzumab (2010)

On October 26, 2009, the FDA granted accelerated approval to ofatumumab for the treatment of patients with CLL refractory to fludarabine and alemtuzumab, on the basis of demonstration of durable tumor shrinkage.
Brain Quinolinic Acid in Huntington's Disease (1988)

Concentrations of the endogenous neurotoxic tryptophan metabolite, quinolinic acid (QA), were measured in postmortem brain tissue obtained from patients with Huntington's disease (HD) and matched controls, using a gas chromatography/mass spectrometry method. There was no significant difference in either the putamen or the frontal cortex between the HD and control groups. These results do not support the hypothesis that increased QA is responsible for neuronal degeneration in HD.
Involvement of a lysine residue in the N‐terminal Ni2+ and Cu2+ binding site of serum albumins (1994)

We report one-dimensional and two-dimensional 1H-NMR studies of the binding of Ni2+, Cu2+, Co2+, Cd2+ and Al3+ to defatted bovine and human serum albumins. The diamagnetic shifts induced by Ni2+, and paramagnetic effects due to Cu2+, were consistent with strong binding to a square-planar site formed by the three N-terminal amino acid residues (Asp-Thr-His for bovine, and Asp-Ala-His for human albumin). In contrast to previous studies on isolated 1-24 N-terminal peptide, a Lys residue also appeared to be involved in the binding site, and is assigned as Lys4. A second His residue is also close to the Cu2+/Ni2+ binding site in bovine serum albumin and is assigned to His59 (not present in human albumin). Co2+ caused specific perturbation of the resonances for the three N-terminal residues as well as those for Lys4. This is the first evidence for Co2+ binding to the N-terminal metal site of serum albumin. Neither Al3+ nor Cd2+ perturbed resonances for the N-terminal amino acids, but bind elsewhere in the protein.
Classical And Molecular Genetics Of Tomato: Highlights And Perspectives (1988)

We have made rapid progress in recent years in identifying the genetic causes of many human diseases. However, despite this recent progress, our mechanistic understanding of these diseases is often incomplete. This is a problem because it limits our ...Read More
Is Primary Biliary Cirrhosis an Autoimmune Disease? (1994)

This review summarizes the experimental and clinical support for an autoimmune origin of primary biliary cirrhosis (PBC). Direct proof is lacking, but indications in favour of an immunologic destructive mechanism include the demonstration of antibodies and T cell clones with specificity for mitochondrial autoantigens, and the lymphocytic infiltration/destruction of small bile ducts similar to that of graft-vs-host disease and rejection. There is a weak association with other autoimmune diseases, but no clear HLA linkage. Spontaneous animal models for PBC are lacking, and immunization of animals with purified autoantigen does not result in typical disease. Anti-mitochondrial antibodies (AMAs) of M2 type are diagnostic of PBC, and are mainly directed against a functional, restricted epitope on the E2 subunit of the pyruvate dehydrogenase complex (PDC). PDC-E2 shows several similarities to other classical autoantigens. The pathogenic role of AMA remains elusive. Recent studies have shown that AMAs detect an antigenic epitope expressed on the luminal surface of biliary epithelium in PBC liver. The initial triggering event might represent a microbial infection (molecular mimicry), or an aberrant surface expression of a true autoepitope.
Vesicle and Stable Monolayer Formation from Simple “Click” Chemistry Adducts in Water (2011)

Click chemistry has been successfully extended into the field of molecular design of novel amphiphatic adducts. After their syntheses and characterizations, we have studied their aggregation properties in aqueous medium. Each of these adducts forms stable suspensions in water. These suspensions have been characterized by dynamic light scattering (DLS) studies and transmission electron microscopy (TEM). The presence of inner aqueous compartments in such aggregates has been demonstrated using dye (methylene blue) entrapment studies. These aggregates have been further characterized using X-ray diffraction (XRD), which indicates the existence of bilayer structures in them. Therefore, the resulting aggregates could be described as vesicles. The temperature-induced order-to-disorder transitions of the vesicular aggregates and the accompanying changes in their packing and hydration have been examined using high-sensitivity differential scanning calorimetry, fluorescence anisotropy, and generalized polarization measurements using appropriate membrane-soluble probe, 1,6-diphenylhexatriene, and Paldan, respectively. The findings of these studies are consistent with each other in terms of the apparent phase transition temperatures. Langmuir monolayer studies confirmed that these click adducts also form stable monolayers on buffered aqueous subphase at the air-water interface.
Is defective electron transport at the hub of aging? (2003)

The bulwark of the mitochondrial theory of aging is that a defective respiratory chain initiates the death cascade. The increased production of superoxide is suggested to result in progressive oxidant damage to cellular components and particularly to mtDNA that encodes subunits assembled in respiratory complexes. Earlier studies of respiration in muscle mitochondria obtained from large cohorts of patients supported this notion by showing that either singly or in combinations, the respiratory complexes exhibited decreased activity in the elderly. The following critique of the most cited publications over the past decade points out the systematic errors that put earlier work at odds with recent findings. These later investigations indicate that aging has no overt effect on either the electron transport system or oxidative phosphorylation.
Histological Analysis of Bone-Implant Interface (2003)

The research on biomaterials for hard-tissue implantation or replacement has expanded considerably during the last ten years. To establish a load-bearing unity of implant and hard tissue, the implant must be incorporated into the bone. However, to fulfill this function, the implant material must possess certain specific properties. The required properties can be classified roughly under the headings of biocompatibility, implant construction, and biomechanics.11 Biocompatibility deals with the interfacial reactions between biomaterials and tissue. Implant construction deals with the engineering of the implant as well as its mechanical properties, such as hardness and strength. Biomechanics is concerned with the mechanical-dynamic properties of an implant and surrounding tissues. For the safe application of implants, they must be evaluated for all these properties. This chapter focuses on the biocompatibility or interfacial analysis of materials for hard-tissue implantation.
Asymmetric total synthesis of PM-toxin A, a corn host-specific pathotoxin (1997)

H. Hayakawa, M. Ohmori, K. Takamichi, F. Matsuda and M. Miyashita, Chem. Commun., 1997, 1219 DOI: 10.1039/A702208E
Structure-Guided Design of Highly Selective and Potent Covalent Inhibitors of ERK1/2 (2015)

The RAS/RAF/MEK/ERK signaling pathway has been targeted with a number of small molecule inhibitors in oncology clinical development across multiple disease indications. Importantly, cell lines with acquired resistance to B-RAF and MEK inhibitors have been shown to maintain sensitivity to ERK1/2 inhibition by small molecule inhibitors. There are a number of selective, noncovalent ERK1/2 inhibitors reported along with the promiscuous hypothemycin (and related analogues) that act via a covalent mechanism of action. This article reports the identification of multiple series of highly selective covalent ERK1/2 inhibitors informed by structure-based drug design (SBDD). As a starting point for these covalent inhibitors, reported ERK1/2 inhibitors and a chemical series identified via high-throughput screening were exploited. These approaches resulted in the identification of selective covalent tool compounds for potential in vitro and in vivo studies to assess the risks and or benefits of targeting this pathway through such a mechanism of action.