gebhart/patrepeval huggingface dataset:
Effect of extraction methods on yield, phytochemical constituents and antioxidant activity of Withania somnifera (2013)

Withnaia somnifera (L.) is a wonder herb with multiple medicinal properties. Its root is used in the preparation of many Ayurvedic medicines. Withanolides, steroidal lactones, present in the root are active chemical markers, however, phenolics, and flavonoids have also been reported in the root of this plant. In most of the herbal preparations, water extraction is carried out using the infusion or decoction preparation process. In the present study, extract yield, phytochemical constituents such as total phenol and withanolide content of water and water-alcohol extracts prepared using two most commonly used extraction techniques, also known as “Green Extraction” techniques, ultrasound and microwave assisted solvent extraction were compared with the conventional extraction method. Antioxidant activity of the extracts was also determined using DPPH and ABTS methods of antioxidant assay. Extract yield, chemical composition of the extracts (total phenol and withanolide content) and antioxidant activity of the extracts varied with the extraction process as well as solvent composition.
Hypoglycemic Neuronal Death and Cognitive Impairment Are Prevented by Poly(ADP-Ribose) Polymerase Inhibitors Administered after Hypoglycemia (2003)

Severe hypoglycemia causes neuronal death and cognitive impairment. Evidence suggests that hypoglycemic neuronal death involves excitotoxicity and DNA damage. Poly(ADP-ribose) polymerase-1 (PARP-1) normally functions in DNA repair, but promotes cell death when extensively activated by DNA damage. Cortical neuron cultures were subjected to glucose deprivation to assess the role of PARP-1 in hypoglycemic neuronal death. PARP-1-/- neurons and wild-type, PARP-1+/+ neurons treated with the PARP inhibitor 3,4-dihydro-5-[4-(1-piperidinyl)butoxy]-1(2H)-isoquinolinone both showed increased resistance to glucose deprivation. A rat model of insulin-induced hypoglycemia was used to assess the therapeutic potential of PARP inhibitors after hypoglycemia. Rats subjected to severe hypoglycemia (30 min EEG isoelectricity) accumulated both nitrotyrosine and the PARP-1 product, poly(ADP-ribose), in vulnerable neurons. Treatment with PARP inhibitors immediately after hypoglycemia blocked production of poly(ADP-ribose) and reduced neuronal death by >80% in most brain regions examined. Increased neuronal survival was also achieved when PARP inhibitors were administered up to 2 hr after blood glucose correction. Behavioral and histological assessments performed 6 weeks after hypoglycemia confirmed a sustained salutary effect of PARP inhibition. These results suggest that PARP-1 activation is a major factor mediating hypoglycemic neuronal death and that PARP-1 inhibitors can rescue neurons that would otherwise die after severe hypoglycemia.
Fc Engineering for Developing Therapeutic Bispecific Antibodies and Novel Scaffolds (2017)

Therapeutic monoclonal antibodies have become molecules of choice to treat autoimmune disorders, inflammatory diseases, and cancer. Moreover, bispecific/multispecific antibodies that target more than one antigen or epitope on a target cell or recruit effector cells (T cell, natural killer cell, or macrophage cell) toward target cells have shown great potential to maximize the benefits of antibody therapy. In the past decade, many novel concepts to generate bispecific and multispecific antibodies have evolved successfully into a range of formats from full bispecific immunoglobulin gammas to antibody fragments. Impressively, antibody fragments such as bispecific T-cell engager, bispecific killer cell engager, trispecific killer cell engager, tandem diabody, and dual-affinity-retargeting are showing exciting results in terms of recruiting and activating self-immune effector cells to target and lyse tumor cells. Promisingly, crystallizable fragment (Fc) antigen-binding fragment and monomeric antibody or half antibody may be particularly advantageous to target solid tumors owing to their small size and thus good tissue penetration potential while, on the other hand, keeping Fc-related effector functions such as antibody-dependent cellular cytotoxicity, complement-dependent cytotoxicity, antibody-dependent cell-mediated phagocytosis, and extended serum half-life <i>via</i> interaction with neonatal Fc receptor. This review, therefore, focuses on the progress of Fc engineering in generating bispecific molecules and on the use of small antibody fragment as scaffolds for therapeutic development.
The Caenorhabditis elegans Orthologue of Mammalian Puromycin-sensitive Aminopeptidase Has Roles in Embryogenesis and Reproduction (2003)

Mammals possess membrane-associated and cytosolic forms of the puromycin-sensitive aminopeptidase (PSA; EC 3.4.11.14). Increasing evidence suggests the membrane PSA is involved in neuromodulation within the central nervous system and in reproductive biology. The functional roles of the cytosolic PSA are less clear. The genome of the nematode Caenorhabditis elegans encodes an aminopeptidase, F49E8.3 (PAM-1), that is orthologous to PSA, and sequence analysis predicts it to be cytosolic. We have determined the spatio/temporal gene expression pattern of pam-1 by using the promoter region of F49E8.3 to control expression in the nematode of a second exon translational fusion of the aminopeptidase to green fluorescent protein. Cytosolic fluorescence was observed throughout development in the intestine and nerve cells of the head. Neuronal expression was also observed in the tail of adult males. Recombinant PAM-1, expressed and purified from Escherichia coli, hydrolyzed the N-terminal amino acid from peptide substrates. Favored substrates had positively charged or small neutral amino acids in the N-terminal position. Peptide hydrolysis was inhibited by the metal-chelating agent 1,10-phenanthroline and by the aminopeptidase inhibitors actinonin, amastatin, and leuhistin. However, the enzyme was approximately 100-fold less sensitive toward puromycin (IC50, 135 mum) than other PSA homologues. Following inactivation of the enzyme, aminopeptidase activity was recovered with Zn2+, Co2+, and Ni2+. Silencing expression of pam-1 by RNA interference resulted in 30% embryonic lethality. Surviving adult hermaphrodites deposited large numbers of oocytes throughout the self-fertile period. The overall brood size was, however, unaffected. We conclude that pam-1 encodes an aminopeptidase that clusters phylogenetically with the PSAs, despite attenuated sensitivity toward puromycin, and that it functions in embryo development and reproduction of the nematode.
The urinary bladder, a consistent source of Borrelia burgdorferi in experimentally infected white-footed mice (Peromyscus leucopus) (1988)

White-footed mice, Peromyscus leucopus, were experimentally infected in the laboratory with Borrelia burgdorferi, the causative agent of Lyme disease. After mice were infected by intraperitoneal or subcutaneous inoculation or by tick bite, attempts were made to culture spirochetes from the urinary bladder, spleen, kidney, blood, and urine. Spirochetes were most frequently isolated from the bladder (94%), followed by the kidney (75%), spleen (61%), and blood (13%). No spirochetes were isolated from the urine. Tissue sectioning and immunofluorescence staining of the urinary bladder demonstrated spirochetes within the bladder wall. The results demonstrate that cultivation of the urinary bladder is very effective at isolating B. burgdorferi from experimentally infected white-footed mice and that culturing this organ may be productive when surveying wild rodents for infection with this spirochete.
Endosomal Trafficking of Nanoformulated Antiretroviral Therapy Facilitates Drug Particle Carriage and HIV Clearance (2014)

The need for long-acting ART is significant and highlighted by limitations in drug access, toxicity, adherence, and reservoir penetrance. We propose that targeting nanoformulated drugs to infected tissues, cells, and subcellular sites of viral replication may improve clinical outcomes. Endosomes are sites for human immunodeficiency virus assembly, and increasing ART concentrations in such sites enhances viral clearance. The current work uncovers a new mechanism by which nanoART can enhance viral clearance over native drug formulations.
Higher order nuclear organization: three-dimensional distribution of small nuclear ribonucleoprotein particles. (1990)

The structural and functional organization of the cell nucleus has been investigated using three-dimensional reconstruction, immunoelectron microscopy, and high-resolution in situ autoradiography. Nuclear regions enriched in small nuclear ribonucleoprotein particles (snRNPs) form a reticular network within the nucleoplasm that extends between the nucleolar surface and the nuclear envelope. The snRNPs occupy approximately 18% of the volume of CHOC 400 cell nuclei. The in situ sites of DNA replication and transcription are complementary to, rather than coincident with, the nuclear regions concentrated in snRNPs. Based on these data a three-dimensional model of the organization of the mammalian cell nucleus is presented.
Finding Related Pages Using the Link Structure of the WWW (2005)

Most of the current algorithms for finding related pages are exclusively based on text corpora of the WWW or incorporate only authority or hub values of pages. In this paper, we present HubFinder, a new fast algorithm for finding related pages exploring the link structure of the Web graph. Its criterion for filtering output pages is "pluggable", depending on the user's interests, and may vary from global page ranks to text content, etc. We also introduce HubRank, a new ranking algorithm which gives a more complete view of page "importance" by biasing the authority measure of PageRank towards hub values of pages. Finally, we present an evaluation of these algorithms in order to prove their qualities experimentally.
TLR5-Deficient Mice Lack Basal Inflammatory and Metabolic Defects but Exhibit Impaired CD4 T Cell Responses to a Flagellated Pathogen (2011)

TLR5-deficient mice have been reported to develop spontaneous intestinal inflammation and metabolic abnormalities. However, we report that TLR5-deficient mice from two different animal colonies display no evidence of basal inflammatory disease, metabolic abnormalities, or enhanced resistance to Salmonella infection. In contrast, the absence of TLR5 hindered the initial activation and clonal expansion of intestinal flagellin-specific CD4 T cells following oral Salmonella infection. Together, these data demonstrate that a basal inflammatory phenotype is not a consistent feature of TLR5-deficient mice and document a novel role for TLR5 in the rapid targeting of flagellin by intestinal pathogen-specific CD4 T cells.
Contrast-Induced Nephropathy (CIN) Consensus Working Panel: executive summary. (2006)

With the advances made in radiology and cardiology, greater numbers of patients are expected to undergo exposure to iodinated contrast media in the years to come. Contrast-induced nephropathy (CIN) accounts for a significant number of cases of hospital-acquired renal failure, with adverse effects on prognosis and healthcare costs. The CIN Consensus Working Panel is an international multidisciplinary group convened to address the challenges of CIN. The group reviewed 865 published papers, chosen for potential relevance from a comprehensive literature search that identified over 4000 references. The results were used to compile reviews covering the epidemiology and pathogenesis of CIN, baseline renal function measurement, risk assessment, identification of high-risk patients, contrast medium use, and preventive strategies. In this executive summary, consensus statements and an algorithm for the risk stratification and management of CIN are presented.
Human histocompatibility leukocyte antigen-binding supermotifs predict broadly cross-reactive cytotoxic T lymphocyte responses in patients with acute hepatitis. (1997)

The present study was designed to determine if highly conserved hepatitis B virus (HBV)-derived peptides that bind multiple HLA class I alleles with high affinity are recognized as cytotoxic T lymphocyte (CTL) epitopes in acutely infected patients. Peripheral blood mononuclear cells from 67 patients with acute hepatitis B, and 12 patients convalescent from acute hepatitis B, were stimulated with three panels of peptides, each of which bind with high affinity to several class I alleles from the HLA-A2-, HLA-A3-, or HLA-B7-supertypes. In these patients, 8 of the 19 peptides tested were found to represent CTL epitopes recognized by two or more alleles in each supertype. Two sets of nested peptides were recognized in the context of alleles with completely unrelated peptide binding specificities. Finally, promiscuous recognition by the same CTL of a given peptide presented by target cells expressing different A2 subtypes was also commonly observed. In conclusion, several HBV-specific CTL epitopes, recognized by acutely infected or convalescent patients in the context of a wide range of HLA alleles have been identified. These results demonstrate the functional relevance of the supertype grouping of HLA class I molecules in a human viral disease setting. Furthermore, they represent a significant advance in the development of a totally synthetic vaccine to terminate chronic HBV infection and support the feasibility of a systematic approach to development of similar vaccines for prevention and treatment of other chronic viral infections.
IMPACT-IONIZATION MASS SPECTROMETRY OF COSMIC DUST (2003)

In situ characterization of cosmic dust grains typically involves impact-ionization time-of-flight mass spectrometry. Considering the performance and limitations of previous instruments, I designed and tested a novel, compact time-of-flight mass spectrometer for cosmic dust analysis. The instrument, Dustbuster, incorporates a large target area with a reflectron, simultaneously optimizing mass resolution, particle detection, and ion collection. Dust particles hit the 65-cm2 target plate and are partially ionized by the impact. The resulting ions, with broad energy and angular distributions, are accelerated through the modified reflectron, focusing ions spatially and temporally to produce high-resolution spectra.

Initial performance tests of the Dustbuster used laser desorption ionization of embedded metal and mineral samples to simulate particle impacts. Mass resolution (mass/peakwidth) in these experiments ranged from 60 to 180, permitting resolution of isotopes. Subsequent experiments included hypervelocity microparticle impacts. Charged iron and copper microparticles, accelerated to 2-20 km/s in a 2 MV van de Graaff accelerator, impacted the Dustbuster. Mass resolution in these experiments ranged from 150 to 300 for iron and copper. Hydrogen, carbon, and oxygen ions appeared in many spectra. Field-induced emission of electrons immediately before impact is a possible cause of ion formation from species with high ionization potentials. The implications of this ionization effect are discussed in relation to interpretation of mass spectra from other in situ dust analyzers.

Another time-of-flight instrument, originally designed as an energy analyzer, shows promise as a high-resolution mass spectrometer for high-flux cosmic dust environments.

Ice is an important component of particulates ejected from comets and other icy bodies in the solar system. Due to limited experimental data on ice particle impacts, I built an ice particle source based on a vibrating orifice aerosol generator connected directly to vacuum. Ice particles produced in this manner can be electrostatically accelerated for impact ionization studies.

Hypervelocity impact vaporization may have played a key role in the mass extinction that occurred at the Cretaceous-Tertiary (K-T) boundary. In order to study the speciation of gases that may have been produced in such an asteroid impact, I designed a specialized orthogonal extraction mass spectrometer for future laboratory impact experiments.
64Cu-MM-302 Positron Emission Tomography Quantifies Variability of Enhanced Permeability and Retention of Nanoparticles in Relation to Treatment Response in Patients with Metastatic Breast Cancer (2017)

<b>Purpose:</b> Therapeutic nanoparticles are designed to deliver their drug payloads through enhanced permeability and retention (EPR) in solid tumors. The extent of EPR and its variability in human tumors is highly debated and has been proposed as an explanation for variable responses to therapeutic nanoparticles in clinical studies.<b>Experimental Design:</b> We assessed the EPR effect in patients using a <sup>64</sup>Cu-labeled nanoparticle, <sup>64</sup>Cu-MM-302 (<sup>64</sup>Cu-labeled HER2-targeted PEGylated liposomal doxorubicin), and imaging by PET/CT. Nineteen patients with HER2-positive metastatic breast cancer underwent 2 to 3 PET/CT scans postadministration of <sup>64</sup>Cu-MM-302 as part of a clinical trial of MM-302 plus trastuzumab with and without cyclophosphamide (NCT01304797).<b>Results:</b> Significant background uptake of <sup>64</sup>Cu-MM-302 was observed in liver and spleen. Tumor accumulation of <sup>64</sup>Cu-MM-302 at 24 to 48 hours varied 35-fold (0.52-18.5 %ID/kg), including deposition in bone and brain lesions, and was independent of systemic plasma exposure. Computational analysis quantified rates of deposition and washout, indicating peak liposome deposition at 24 to 48 hours. Patients were classified on the basis of <sup>64</sup>Cu-MM-302 lesion deposition using a cut-off point that is comparable with a response threshold in preclinical studies. In a retrospective exploratory analysis of patient outcomes relating to drug levels in tumor lesions, high <sup>64</sup>Cu-MM-302 deposition was associated with more favorable treatment outcomes (HR = 0.42).<b>Conclusions:</b> These findings provide important evidence and quantification of the EPR effect in human metastatic tumors and support imaging nanoparticle deposition in tumors as a potential means to identify patients well suited for treatment with therapeutic nanoparticles. <i>Clin Cancer Res; 23(15); 4190-202. ©2017 AACR</i>.
Templated Photochemistry:  Toward Catalysts Enhancing the Efficiency and Selectivity of Photoreactions in Homogeneous Solutions (2006)

ADVERTISEMENT RETURN TO ISSUEPREVArticleTemplated Photochemistry: Toward Catalysts Enhancing the Efficiency and Selectivity of Photoreactions in Homogeneous SolutionsJiří Svoboda and Burkhard KönigView Author Information Institut für Organische Chemie, Universität Regensburg, Universitätsstrasse 31, 93053 Regensburg, Germany Cite this: Chem. Rev. 2006, 106, 12, 5413–5430Publication Date (Web):November 22, 2006Publication History Received14 February 2006Published online22 November 2006Published inissue 1 December 2006https://pubs.acs.org/doi/10.1021/cr050568whttps://doi.org/10.1021/cr050568wresearch-articleACS PublicationsCopyright © 2006 American Chemical SocietyRequest reuse permissionsArticle Views2841Altmetric-Citations125LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose SUBJECTS:Genetics,Ions,Irradiation,Oligomers,Photochemical reactions Get e-Alerts
Simultaneously ensuring privacy and authenticity in digital communication (2002)

Practice-oriented provable security is a modern approach in cryptography to concretely reduce security of a cryptographic construct to the computational hardness of an underlying problem. This dissertation studies a construct called authenticated encryption scheme, a set of algorithms whose collective purpose is to simultaneously guarantee both privacy and authenticity of the data being transmitted between two parties. First, we focus on the symmetric settings. We define precise security notions for authenticated encryption schemes, show relative strengths among our notions and existing standard notions, and investigate the effectiveness of one of the most popular design methodologies for authenticated encryption schemes, namely the generic composition paradigm. In this paradigm, one combines a standard encryption scheme—a construct whose goal is privacy—and a MAC scheme—a construct whose goal is authenticity—in a modular fashion to obtain an authenticated encryption scheme. The methods we study are Encrypt-and-MAC, MAC-then-Encrypt, and Encrypt-then-MAC . As a case study, we analyze the popular SSH Internet protocol suite, find that its current design yields insecure authenticated encryption schemes, then suggest provably secure fixes. Our proofs model SSH's authenticated encryption mechanism as a case of what we call the Encode-then-Encrypt-and-MAC composition method. Our proofs can thus be generically applied to other schemes employing this composition method. 
In real applications, symmetric-key cryptography is often used in combination with public-key cryptography. We focus on the most common way to combine public-key cryptography with authenticated encryption schemes. First, two parties run an authenticated key-exchange protocol to obtain a shared session key. Then, they secure successive data transmissions via an authenticated encryption scheme based on the session key. We show that such a communication session meets the notion of a secure channel proposed by Canetti and Krawczyk if and only if the underlying authenticated encryption scheme meets two new, simple definitions of security that we introduce, and the key-exchange protocol is secure. This reduces the secure channel requirements of Canetti and Krawczyk to easier to use, stand-alone security requirements on the underlying authenticated encryption scheme.
Second-order sampling of wideband signals (2002)

Second-order sampling based digital demodulation technique is discussed and analyzed. Using a fractional delay filter, the modest image rejection of the basic second-order sampling scheme is improved to provide sufficient demodulation performance also for wideband receivers. Furthermore, a closed-form expression explicitly characterizing the obtainable image attenuation is derived. As illustrated by a design example, image attenuations in the order of 100 dB are theoretically achievable.