gebhart/patrepeval huggingface dataset:
Molecular pathology of Alzheimer neurofibrillary degeneration. (1993)

The most characteristic brain lesion of Alzheimer disease is the accumulation of paired helical filaments (PHF) in the affected neurons. Based on solubility in detergents there are two general populations of PHF, the readily soluble (PHF I) and the sparingly soluble (PHF II) types. The major polypeptides of PHF are the microtubule associated protein tau. Tau in PHF is present in abnormally phosphorylated forms. In addition to the PHF, the abnormal tau is also present in unpolymerized form in the AD brain. Small amounts of ubiquitin (%) are associated with PHF II but neither with PHF I nor with the unpolymerized abnormally phosphorylated tau in AD brain. Furthermore, the pretangle neurons can readily be immunolabeled for abnormally phosphorylated tau but not for ubiquitin. The level of tau in neocortex is several-fold higher than in AD aged control cases, but this increase is in the form of the abnormally phosphorylated protein. The microtubule associated proteins from AD brain do not promote the assembly of microtubules in vitro, whereas the in vitro dephosphorylated PHF polypeptides stimulate the binding of GTP to the exchangeable site of tubulin and the assembly of microtubules. In vitro the phosphate groups in PHF are less accessible than those of tau to alkaline phosphatase. It is suggested that a defect in the protein phosphorylation/dephosphorylation system leads to hyperphosphory-lation of tau. The altered tau contributes to a microtubule assembly defect and consequently compromises the axoplasmic flow and leads to neuronal degeneration.
Extinction of Contextual Cocaine Memories Requires Cav1.2 within D1R-Expressing Cells and Recruits Hippocampal Cav1.2-Dependent Signaling Mechanisms (2017)

Exposure to cocaine-associated contextual cues contributes significantly to relapse. Extinction of these contextual associations, which involves a new form of learning, reduces cocaine-seeking behavior; however, the molecular mechanisms underlying this process remain largely unknown. We report that extinction, but not acquisition, of cocaine conditioned place preference (CPP) in male mice increased Ca<sub>v</sub>1.2 L-type Ca<sup>2+</sup> channel mRNA and protein in postsynaptic density (PSD) fractions of the hippocampus, a brain region involved in drug-context associations. Moreover, viral-mediated deletion of Ca<sub>v</sub>1.2 in the dorsal hippocampus attenuated extinction of cocaine CPP. Molecular studies examining downstream Ca<sub>v</sub>1.2 targets revealed that extinction recruited calcium/calmodulin (Ca<sup>2+</sup>/CaMK)-dependent protein kinase II (CaMKII) to the hippocampal PSD. This occurred in parallel with an increase in phosphorylation of the AMPA GluA1 receptor subunit at serine 831 (S831), a CaMKII site, along with an increase in total PSD GluA1. The necessity of S831 GluA1 was further demonstrated by the lack of extinction in S831A GluA1 phosphomutant mice. Of note hippocampal GluA1 levels remained unaltered at the PSD, but were reduced near the PSD and at perisynaptic sites of dendritic spines in extinction-resistant S831A mutant mice. Finally, conditional knock-out of Ca<sub>v</sub>1.2 in dopamine D1 receptor (D1R)-expressing cells resulted in attenuation of cocaine CPP extinction and lack of extinction-dependent changes in hippocampal PSD CaMKII expression and S831 GluA1 phosphorylation. In summary, we demonstrate an essential role for the hippocampal Ca<sub>v</sub>1.2/CaMKII/S831 GluA1 pathway in cocaine CPP extinction, with data supporting contribution of hippocampal D1R-expressing cells in this process. These findings demonstrate a novel role for Ca<sub>v</sub>1.2 channels in extinction of contextual cocaine-associated memories.<b>SIGNIFICANCE STATEMENT</b> Continued drug-seeking behavior, a defining characteristic of cocaine addiction, can be precipitated by contextual cues, yet the molecular mechanisms required for extinction of these context-specific memories remain poorly understood. Here, we have uncovered a novel and selective role of the Ca<sub>v</sub>1.2 L-type Ca<sup>2+</sup> channel and its downstream signaling pathway in the hippocampus that mediate extinction of cocaine conditioned place preference (CPP). We additionally provide evidence that supports a role of Ca<sub>v</sub>1.2 within dopamine D1 receptor-expressing cells of the hippocampus for extinction of cocaine CPP. Therefore, these findings reveal a previously unknown role of Ca<sub>v</sub>1.2 channels within the hippocampus and in D1 receptor-expressing cells in extinction of cocaine-associated memories, providing a framework for further exploration of mechanisms underlying extinction of cocaine-seeking behavior.
Subcutaneous administration of rituximab (MabThera) and trastuzumab (Herceptin) using hyaluronidase (2013)

Coformulation with rHuPH20 may enable effective, well-tolerated, cost-effective, and convenient SC administration of rituximab and trastuzumab. Additional studies are ongoing.
Governance Decisions in the R&D Process: An Integrative Framework Based on TCT and Know-ledge View of The Firm. (2007)

In this paper we analyze boundary decisions in the R&D value chain. To do so, we
develop a theoretical framework based on TCT that maintaining the assumption of minimization
of production and transaction costs integrates the contributions of other alternative paradigms.
Specifically, we argue that: (i) the main drivers of outsourcing in emerging countries would be
the R&D service labor intensity and the degree to which firm-specific knowledge is required to
perform the service, and (ii) whereas asset specificity is not necessarily an obstacle to organize
these services through alliances, firm-knowledge specificity would lead to integration of the
R&D service.
Design of an artificial skin. Part III. Control of pore structure (1980)

Abstract Several methods are compared for preparing collagen‐glycosaminoglycan (GAG) membranes of high or low porosity. Collagen‐GAG membranes have been used to cover satisfactorily large experimental full‐thickness skin wounds in guinea pigs over the past few years. Methods studies as means for controlling pore size are confined to purely physical processes which do not require use of additives or chemical reagents to form the porous membrane. We find that membranes, initially swollen in distilled water or saline, shrink linearly to no less than 94% of original dimension after freeze drying; to 75% after critical point drying (from CO 2 , following water‐ethanol exchange); and to 41% of original dimension following air drying from the swollen state. Scanning electron microscopic study of the pore structure resulting from each drying procedure confirms our major conclusion: A carefully designed freeze drying process, two variants of which are described in detail, yields membranes with the highest mean pore size, as measured by quantitative stereological procedures. Critical point drying gave significantly more shrinkage and a lower mean pore size than either one of the two freeze drying procedures used.
Bronchoscopic Evaluation of Severe Asthma (1997)

The role of inflammation in the pathogenesis of severe asthma chronically treated with high doses of glucocorticoids is poorly understood. Despite this, treatment has been aimed at advancing anti-inflammatory and immunomodulator therapy. This study was designed to evaluate both the presence and type of airway inflammation in patients with severe asthma. A prospective bronchoscopic study evaluated 14 severe, high-dose oral glucocorticoid dependent asthmatics. Bronchoalveolar lavage fluid was analyzed for cytology and inflammatory mediators. Endobronchial and transbronchial biopsies were performed in selected patients for morphometric evaluation of macrophage/monocytes, neutrophils, eosinophils and lymphocytes. These results were compared with lavage and endo- and transbronchial biopsy studies in normal controls and patients with moderate asthma. The concentration of eosinophils in bronchoalveolar lavage fluid was highest in the moderate asthmatics not on glucocorticoids, with very little difference between normal controls and severe asthmatics (significant difference among the groups, p = 0.007). In contrast, the severe asthmatics demonstrated a twofold higher concentration of neutrophils in lavage than either the mild-moderate asthmatics, or the normal controls (p = 0.032 among the groups, p < 0.05 between the severe asthmatics and both controls). Similar results were obtained in the endobronchial and transbronchial biopsy specimens, which consistently showed significantly higher numbers of neutrophils in the severe asthmatics than in the control groups. The eicosanoid mediators, thromboxane and leukotriene B4, were also highest in the severe asthma group (differences among the groups, p = 0.019 and p = 0.023, respectively). These findings suggest that inflammation remains in severe symptomatic asthmatics despite treatment with high dose glucocorticoids which may be due to the severity of disease, glucocorticoid treatment, or other as yet undefined factors.
Supercontinuum generation in submicron fibre waveguides (2004)

Submicron-diameter tapered fibres and photonic crystal fibre cores, both of which are silica-air waveguides with low dispersion at 532 nm, were made using a conventional tapering process. In just cm of either waveguide, ns pulses from a low-power 532-nm microchip laser generated a single-mode supercontinuum broad enough to fill the visible spectrum without spreading far beyond it.
Holographic artificial impedance surfaces for conformal antennas (2005)

We have developed a method for generating arbitrary radiation patterns from antennas on complex objects. The object is coated with an artificial impedance surface consisting of a lattice of sub-wavelength metal patches on a grounded dielectric substrate. The effective surface impedance depends on the size of the patches, and can be varied as a function of position. Using holography, the surface impedance is designed to generate any desired radiation pattern from currents in the surface. With this technique we can create antennas with novel properties such as radiation toward angles that would otherwise be shadowed
Induction of fetal hemoglobin production in subjects with sickle cell anemia by oral sodium phenylbutyrate (1994)

Intravenous arginine butyrate has been shown to increase fetal hemoglobin (HbF) in sickle cell and thalassemia patients. Recently, we observed that sodium 4-phenylbutyrate, a drug administered orally to treat urea cycle disorders, increases HbF production in nonanemic children and adults. We treated six subjects with sickle cell disease over a period of 14 to 179 days. All subjects received their initial therapy of 9 to 13 g/m2/day as 0.5-g tablets of sodium 4-phenylbutyrate as inpatients. All subjects showed a rapid increase in the percentage of F-reticulocytes (pretreatment, 1% to 20%; posttreatment, 10% to 44%). Four subjects were treated only 11 to 25 days as inpatients. Two of these four subjects failed to respond to the outpatient component because of their inability to maintain an intake of 30 to 40 tablets per day. One subject (C) developed a rash at day 10 and discontinued treatment at day 14. Another subject (B) was transfused for a painful crisis on day 25. Subject A, treated for 179 days, has an increased percentage of F cells, from 54% to 77%, and increased HbF levels, from 10.6% to 18%. Subject F, treated for 154 days, has an increased percentage of F cells, from 59% to 73%, and an increased percentage of HbF, from 10.4% to 16%. All subjects showed some increase in weight. Subject A developed mild transient ankle edema. Myelotoxicity was not seen in any treated patient. Oral administration of sodium 4-phenylbutyrate rapidly increases F-cell production in sickle cell disease.
Reversible Unfolding of Individual Titin Immunoglobulin Domains by AFM (1997)

Single-molecule atomic force microscopy (AFM) was used to investigate the mechanical properties of titin, the giant sarcomeric protein of striated muscle. Individual titin molecules were repeatedly stretched, and the applied force was recorded as a function of the elongation. At large extensions, the restoring force exhibited a sawtoothlike pattern, with a periodicity that varied between 25 and 28 nanometers. Measurements of recombinant titin immunoglobulin segments of two different lengths exhibited the same pattern and allowed attribution of the discontinuities to the unfolding of individual immunoglobulin domains. The forces required to unfold individual domains ranged from 150 to 300 piconewtons and depended on the pulling speed. Upon relaxation, refolding of immunoglobulin domains was observed.
High Resolution XPS of Organic Polymers: The Scienta ESCA300 Database (1992)

Description of the spectrometer x-ray source monochromator electron lens hemispherical analyser multichannel detector sample analysis chamber charge compensation performance on conducting samples performance on insulating samples performance on testing of the spectrometer experimental protocol sample mounting data acquisition correction of binding energy scale for sample charging curve fitting lineshapes shake-up structure valence bands impurities x-ray degradation organization of the database list of polymers and acronyms the database appendix 1 - primary C 1s shifts appendix 2 - secondary C 1s shifts appendix 3.1 - 0 1s binding energies in CHO polymers appendix 3.2 - 0 1s binding energies in other polymers appendix 4 - N 1s binding energies appendix 5 - F 1s binding energies appendix 6 - binding energies and spin-orbit constants for core-line doublets apendix 7 - binding energies of peaks appearing in the valence band region.
Analysis of operational speed and scaling down the pixel size of a charge modulation device (CMD) image sensor (1991)

In a previous paper, the authors (ibid., vol.38, pp.989-998, May 1991) clarified the operational mechanism of a charge modulation device (CMD) image sensor and confirmed that numerical calculations using the transistor analysis program for imagers calculating non-steady-state equations (TRINE) predicted the actual performance of a CMD imager within a 20% discrepancy. Following these results, the scaling-down of device dimensions and the inherent operational speed are estimated using TRINE in order to realize a future high-resolution CMD image sensor. The analysis shows that a device size of 5.0 mu m (H)*5.2 mu m (V) is attainable without degrading the performance of the 10.2 mu m (H)*10.4 mu m (V) CMD imager and that the operational speed of a CMD is fast enough for a high-definition TV (HDTV) application which requires a scan rate of several tens of nanoseconds.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Conversion of monocyte chemoattractant protein-1 into a neutrophil attractant by substitution of two amino acids. (1992)

The small cytokine monocyte chemoattractant protein-1 has structural similarity to the neutrophil chemoattractant interleukin-8, but each protein is specific in attracting its own target cell. To investigate the structural basis of this cell type specificity, we have developed an Escherichia coli expression system for the monocyte chemoattractant and mutagenized selected amino acid residues to ones found at the corresponding positions of interleukin-8. We find that a double mutation of tyrosine 28 and arginine 30 to leucine and valine, respectively, causes a drastic decrease in chemotactic activity toward monocytes with the appearance of a novel (interleukin-8-like) neutrophil chemotactic activity. Computer graphic analysis predicts that, with the double substitution, a putative receptor binding groove of the monocyte chemoattractant protein would become topographically similar to that of interleukin-8. We therefore postulate that one or both of these amino acid residues are part of the binding contact of these small cytokines and their receptors.
A Bacillus thuringiensis insecticidal crystal protein with a high activity against members of the family Noctuidae (1996)

The full characterization of a novel insecticidal crystal protein, named Cry9Ca1 according to the revised nomenclature for Cry proteins, from Bacillus thuringiensis serovar tolworthi is reported. The crystal protein has 1,157 amino acids and a molecular mass of 129.8 kDa. It has the typical features of the Lepidoptera-active crystal proteins such as five conserved sequence blocks. Also, it is truncated upon trypsin digestion to a toxic fragment of 68.7 kDa by removal of 43 amino acids at the N terminus and the complete C-terminal half after conserved sequence block 5. The 68.7-kDa fragment is further degraded to a nontoxic 55-kDa fragment. The crystal protein has a fairly broad spectrum of activity against lepidopteran insects, including members of the families Pyralidae, Plutellidae, Sphingidae, and Noctuidae. A 50% lethal concentration of less than 100 ng/cm2 of diet agar was found for diamondback moth, European corn borer, cotton bollworm, and beet armyworm. It is the first insecticidal crystal protein with activity against cutworms. No activity was observed against some beetles, such as Colorado potato beetle. The protein recognizes a receptor different from that recognized by Cry1Ab5 in Ostrinia nubilalis and Plutella xylostella. In Spodoptera exigua and P. xylostella, it binds to a receptor which is also recognized by Cry1Cax but with a lower affinity. In these insects, Cry1Cax probably binds with a higher affinity to an additional receptor which is not recognized by Cry9Ca1. Elimination of a trypsin cleavage site which is responsible for the degradation to a nontoxic fragment did result in protease resistance but not in increased toxicity against O. nubilalis.
Maternal immunity and infant responses to immunization: factors influencing infant responses. (1998)

The presence of maternally-derived antibodies at the time of immunization is known to interfere frequently with active immunization, with variable levels of clinical significance. Deciphering the rules as the basis of such inhibitory effects on infant vaccine responses would certainly contribute to the development of vaccination strategies for early life. These questions were addressed in murine neonatal or early life immunization models using various antigens (measles, tetanus, RSV) and antigen-presentation systems (peptides, proteins, live attenuated vaccines, live recombinant vectors or DNA plasmids) in the absence or presence of maternal antibodies. Factors identified as crucial determinants of maternal antibody-mediated effects on both live and non-live vaccines include the relative amount of maternal antibodies and of vaccine antigens present at immunization, antigenic conformation, epitope specificity and the distinct influence on B-cell and T-cell vaccine responses.
Automatically detecting action items in audio meeting recordings (2006)

Identification of action items in meeting recordings can provide immediate access to salient information in a medium notoriously difficult to search and summarize. To this end, we use a maximum entropy model to automatically detect action item-related utterances from multi-party audio meeting recordings. We compare the effect of lexical, temporal, syntactic, semantic, and prosodic features on system performance. We show that on a corpus of action item annotations on the ICSI meeting recordings, characterized by high imbalance and low inter-annotator agreement, the system performs at an F measure of 31.92%. While this is low compared to better-studied tasks on more mature corpora, the relative usefulness of the features towards this task is indicative of their usefulness on more consistent annotations, as well as to related tasks.
Monitoring free light chains in serum using mass spectrometry (2016)

The high resolution and high mass measurement accuracy provided by the mass spectrometry based methodology eliminates the need for κ/λ ratios as the method can quantitatively monitor the abundance of the κ and λ polyclonal background at the same time it measures the monoclonal FLC.
Prolonged survival of GalT‐KO swine skin on baboons (2010)

GalT-KO skin may have potential clinical benefits as an alternative to allogeneic skin as a temporary treatment for severe skin injuries.
Separation of Chiral Biodegradation Intermediates of Linear Alkylbenzenesulfonates by Capillary Electrophoresis (1998)

High-performance capillary electrophoresis (HPCE) with α-cyclodextrin as the chiral selector was applied to separate the enantiomers of p-sulfophenyl-2-butyrate (SP2B) and p-sulfophenyl-3-butyrate (SP3B), which occur as biodegradation intermediates of linear alkylbenzenesulfonates (LAS), the widely used anionic surfactants. With this analytical method, we studied the transformation of both SP3B enantiomers in a laboratory batch incubation with activated sewage sludge of a municipal wastewater treatment plant. (S)-(+)-SP3B and (R)-(-)-SP3B could be detected in mechanically treated sewage effluent. After enrichment on graphitized carbon black (Carbopack B), the extracts were analyzed by HPLC with UV diode array and fluorescence detection as well as by HPCE with UV diode array detection. Quantification of SP3B in a 24-h composite sample of primary sewage effluent yielded 34 μg/L (limit of detection, 0.1 μg/L) of the racemic mixture determined by HPLC and 18 μg/L of each enantiomer measured by HPCE (limit of detection, 1 μg/L).
Extracellularly tumor-activated prodrugs for the selective chemotherapy of cancer: application to doxorubicin and preliminary in vitro and in vivo studies. (2001)

Oligopeptidic derivatives of anthracyclines unable to penetrate cells were prepared and screened for their stability in human blood and their reactivation by peptidases secreted by cancer cells. N-beta-alanyl-L-leucyl-L-alanyl-L-leucyl-doxorubicin was selected as a new candidate prodrug. The NH2-terminal beta-alanine allows a very good blood stability. A two-step activation by peptidases found in conditioned media of cancer cells ultimately yields N-L-leucyl-doxorubicin. In vitro, when MCF-7/6 cancer cells are exposed to the prodrug, they accumulate about 14 times more doxorubicin than MRC-5 normal fibroblasts, whereas when exposed to doxorubicin the uptake is slightly higher in fibroblasts than in MCF-7/6 cells. This increased specificity of the prodrug over doxorubicin was confirmed in cytotoxicity assays using the same cell types. In vivo, the prodrug proved about nine times less toxic than doxorubicin in the normal mouse and also much more efficient in two different experimental chemotherapy models of human breast tumors.
Fluorescence Spectroscopy of Color Centers Generated in Phosphate Glasses after Exposure to Femtosecond Laser Pulses (2002)

A confocal fluorescence microscopy setup was used to observe, in situ , spectral changes in phosphate glasses which were modified using 0.3 μJ of tightly focused 800 nm, 130 fs laser pulses. On 488 nm excitation, the modified glass shows a broad fluorescence centered at roughly 600 nm, which decays with prolonged exposure to the 488 nm light. The decay behavior is dependent on the 488 nm power, with a faster decay rate for higher powers. A mechanism whereby color centers, formed by the femtosecond pulses, fluoresce when excited by the 488 nm light and are simultaneously photobleached is proposed to explain the observed behavior.