gebhart/patrepeval huggingface dataset:
Immunotoxins: current use and future prospects in bone marrow transplantation and cancer treatment. (1986)

Immunotoxins are protein toxins which have been conjugated in whole or in part to antibodies in the hope of producing cell-type-specific toxic reagents with useful properties. Such reagents hold the promise for eliminating unwanted cells both in vivo and in vitro. In practice, to date, only in vitro usage has proven clinically and experimentally useful. The design of effective immunotoxins is based on utilizing cellular entry mechanisms or entry mechanisms inherent in the parent toxins to cross the plasma membrane barrier to the cytosol compartment where the toxins exert their effects. Knowledge in the area of receptor-mediated protein transport is expanding rapidly and new immunotoxins with increased efficiencies are anticipated.
Dependence of Adenovirus Infectivity on Length of the Fiber Shaft Domain (2000)

One of the objectives in adenovirus (Ad) vector development is to target gene delivery to specific cell types. Major attention has been given to modification of the Ad fiber knob, which is thought to determine virus tropism. However, among the human Ad serotypes with different tissue tropisms, not only the knob but also the length of the fiber shaft domain varies significantly. In this study we attempted to delineate the role of fiber length in coxsackievirus-adenovirus receptor (CAR)- and non-CAR-mediated infection. A series of Ad serotype 5 (Ad5) capsid-based vectors containing long or short fibers with knob domains derived from Ad5, Ad9, or Ad35 was constructed and tested in adsorption, internalization, and transduction studies. For Ad5 or Ad9 knob-possessing vectors, a long-shafted fiber was critical for efficient adsorption/internalization and transduction of CAR/alphav integrin-expressing cells. Ad5 capids containing short CAR-recognizing fibers were affected in cell adsorption and infection. In contrast, for the chimeric vectors possessing Ad35 knobs, which enter cells by a CAR/alphav integrin-independent pathway, fiber shaft length had no significant influence on binding or infectibility on tested cells. The weak attachment of short-shafted Ad5 or Ad9 knob-possessing vectors seems to be causally associated with a charge-dependent repulsion between Ad5 capsid and acidic cell surface proteins. The differences between short- and long-shafted vectors in attachment or infection were abrogated by preincubation of cells with polycations. This study demonstrates that the fiber-CAR interaction is not the sole determinant for tropism of Ad vectors containing chimeric fibers. CAR- and alphav integrin-mediated infections are influenced by other factors, including the length of the fiber shaft.
The Repetitive Domain ofTrypanosoma cruzi trans-Sialidase Enhances the Immune Response against the Catalytic Domain (1998)

Trypanosoma cruzi trans-sialidase consists of a C-terminal domain composed essentially of immunodominant amino acid repeat units (SAPA-repeats) and an amino region responsible for the enzymatic activity (catalytic domain). To investigate the possible function(s) of SAPA-repeats, recombinant trans-sialidases either containing or lacking the C-terminal region were tested in mice. The presence of SAPA-repeats in the intravenously injected protein has two consequences. First, they enhance the persistence of the trans-sialidase activity in blood. Second, SAPA-repeats promoted the production of antibodies directed to the catalytic domain that inhibit trans-sialidase activity. These results suggest that SAPA-repeats modulate the trans-sialidase activity in blood.
Differential effects of progressive familial intrahepatic cholestasis type 1 and benign recurrent intrahepatic cholestasis type 1 mutations on canalicular localization of ATP8B1 # (2009)

These data provide an explanation for the difference in severity between the phenotypes of PFIC1 and BRIC1.
Recombinant LuIII Autonomous Parvovirus as a Transient Transducing Vector for Human Cells (1993)

Recombinants based on the genome of the autonomous parvovirus, LuIII, were constructed by replacing the viral coding sequences in an infectious clone (pGLu883) by a luciferase or beta-galactosidase reporter, which was linked to the viral P4 promoter. In cells cotransfected with either of these constructs, together with a plasmid supplying LuIII nonstructural and capsid proteins, excision and replication of the recombinant genome occurred. Transducing virions accumulated in the culture medium of the cotransfected cells, as assayed by reporter activity in recipient cells exposed to this medium. Transducing activity could be neutralized by antiserum to LuIII. Production of replicative form DNA and transducing virions were observed following cotransfection of HeLa, 293, or NB324K cells, in increasing order of efficiency. When homology existed between the recombinant genome and sequences flanking the viral genes in the helper construct, concomitant production of replication-competent, cytopathic virus was sometimes observed. This could be minimized by removal of the left end homology from the helper; by this means, preparations of luciferase transducing virus were obtained free from replication-competent virus. With such preparations, we observed luciferase expression (declining after 3 days) for up to 7 days in recipient HeLa cells. Hybridization of the recombinant viral DNA with strand-specific luciferase probes indicated packaging of both strands (as reported for LuIII), but with a several-fold excess of the (-) strand. We suggest that transducing-autonomous parvoviruses will be useful in gene transfer applications, possibly including gene therapy when only transient expression is desired.
Modern Ate Chemistry:  Applications of Synergic Mixed Alkali-Metal−Magnesium or −Zinc Reagents in Synthesis and Structure Building (2006)

The special synergic reactivity exhibited by certain heterobimetallic ate compounds in which magnesium or zinc is paired together with an alkali metal such as lithium, sodium, or potassium provides the theme of this review. The emerging concepts of alkali-metal-mediated magnesiation and alkali-metal-mediated zincation are introduced with respect to the selective deprotonation and/or polydeprotonation of a series of arene, aromatic heterocyclic, metallocene, and metal π-arene substrates. It is shown that, in accomplishing such deprotonations, alkali metal−magnesium amide based reagents can often generate “inverse crown” ring compounds. Inverse crowns display polymetallic cationic “host” rings (residue of the reacted mixed-metal base) surrounding an anionic “guest” (the deprotonated substrate) in a Lewis acidic−Lewis basic arrangement inverse to that encountered in conventional crown ether complexes. A signature feature of inverse crown ring and related mixed-metal structures is a synergic combination of Mg−C (or Zn−C) σ bonds and alkali-metal−π contacts. Also included are related inverse crown ether complexes in which the guest can be an oxo, peroxo, hydrido, alkoxo, or enolato anion and the first example of the concept of synergic nucleophilic addition involving the action of a new sodium dialkylamidozincate reagent toward benzophenone.
Cryptographic Processors-A Survey (2006)

Tamper-resistant cryptographic processors are becoming the standard way to enforce data-usage policies. Their origins lie with military cipher machines and PIN processing in banking payment networks, expanding in the 1990s into embedded applications: token vending machines for prepayment electricity and mobile phone credit. Major applications such as GSM mobile phone identification and pay TV set-top boxes have pushed low-cost cryptoprocessors toward ubiquity. In the last five years, dedicated crypto chips have been embedded in devices such as game console accessories and printer ink cartridges, to control product and accessory after markets. The "Trusted Computing" initiative will soon embed cryptoprocessors in PCs so they can identify each other remotely. This paper surveys the range of applications of tamper-resistant hardware and the array of attack and defense mechanisms which have evolved in the tamper-resistance arms race.
The motivation to manage: a study of academic librarians and library science students (1985)

ANUNDERSTANDING OF THE factors which contribute to the low proportions of women in administrative library positions can provide the library profession with a theoretical basis from which to initiate change. A number of factors previously have been suggested to explain the
Incorporating concept ontology to enable probabilistic concept reasoning for multi-level image annotation (2006)

To enable automatic multi-level image annotation, we have addressed two inter-related important issues:(1)more effective framework for image content representation and feature extraction to characterize the middle-level semantics of image contents;(2)new framework for hierarchical probabilistic image concept reasoning and detection. To address the first issue salient objects are used as the semantic building blocks to characterize the middle-level semantics of image contents effectively while reducing the image analysis cost significantly. We have proposed three approaches to designing the detection functions for automatic salient object detection,and automatic function selection is also supported to find the "right "assumptions of the principal visual properties for the corresponding salient object classes. To address the second issue wehaveproposed a novel framework to incorporate the concept ontology to achieve hierarchical probabilistic image concept reasoning for multi-level image annotation. The concept ontology for a large-scale public image database called Label Me is semi-automatically derived from the available image labels by using WordNet The image concepts at the first level of the concept ontology are used to characterize the most specific semantics of image contents with the smallest variations, and their correspondences with the semantic building blocks (i.e.,salient objects)are well-de fined and can be modeled accurately by using Bayesian networks. In addition,the predictions of the appearances of the higher-level image concepts with large variations are adopted by the underlying concept ontology or by combining the available predictions of the appearances of their children concepts through hierarchical Bayesian networks.Our experiments on a large public dataset have shown that our framework for hierarchical probabilistic image concept reasoning is scalable to diverse image contents (i.e.,large amount of salient object classes)with large within-category variations.
Total internal reflection-based biochip utilizing a polymer-filled cavity with a micromirror sidewall (2004)

A total internal reflection (TIR)-based biochip utilizing a polymer-filled cavity with a micromirror sidewall has been designed and fabricated. The implementation of the micromirror sidewall cavity facilitates precise alignment of the excitation light beam into the system. The incident angle of illumination can be easily modified by selecting polymers of different indices of refraction while optical losses are minimized. The design enables the hybrid, vertical integration of a laser diode and a CCD camera, resulting in a compact optical system. Brownian motion of fluorescent microspheres and real-time photobleaching of rhodamine 6G molecules is demonstrated. The proposed TIR-based chip simplifies current TIR optical configurations and could potentially be used as an optical-microfluidic platform for an integrated lab-on-a-chip microsystem.
Storage stability of stabilized MLV and REV liposomes containing sodium methotrexate (aqueous & lyophilized). (1998)

Multilamellar and unilamellar liposomes containing sodium methotrexate (MTX) were prepared by thin film hydration and reverse-phase evaporation methods. Encapsulation efficiency and release of MTX from liposomes at 4 degrees C, 25 degrees C and 37 degrees C were determined. When stored at 25 degrees C the liposomes lost 33% MTX after one month. To stabilize liposomes, they were freeze-dried in presence of different amounts of cryoprotectants (trehalose, PEG 10,000, PEG 20,000, and a mixture of trehalose-PEG 20,000). Measurements showed that the mixture of trehalose-PEG 20,000 imparted an MTX retention of about 70% after lyophilization. Stability tests of the lyophilized product at 4 degrees C, 25 degrees C and 37 degrees C demonstrated they were fairly stable even at 37 degrees C, indicating their potential use in commercial applications.
Incorporation and Clearance of Omega-3 Fatty Acids in Erythrocyte Membranes and Plasma Phospholipids (2006)

Erythrocyte membrane EPA+DHA increases during relatively short intervals in response to supplementation at rates related to amount of supplementation. These results may be useful to establish appropriate dosage for omega-3 fatty acid supplementation.
Neutralization of SARS-CoV-2 by destruction of the prefusion Spike (2020)

Summary There are as yet no licenced therapeutics for the COVID-19 pandemic. The causal coronavirus (SARS-CoV-2) binds host cells via a trimeric Spike whose receptor binding domain (RBD) recognizes angiotensin-converting enzyme 2 (ACE2), initiating conformational changes that drive membrane fusion. We find that monoclonal antibody CR3022 binds the RBD tightly, neutralising SARS-CoV-2 and report the crystal structure at 2.4 Å of the Fab/RBD complex. Some crystals are suitable for screening for entry-blocking inhibitors. The highly conserved, structure-stabilising, CR3022 epitope is inaccessible in the prefusion Spike, suggesting that CR3022 binding would facilitate conversion to the fusion-incompetent post-fusion state. Cryo-EM analysis confirms that incubation of Spike with CR3022 Fab leads to destruction of the prefusion trimer. Presentation of this cryptic epitope in an RBD-based vaccine might advantageously focus immune responses. Binders at this epitope may be useful therapeutically, possibly in synergy with an antibody blocking receptor attachment. Highlights CR3022 neutralises SARS-CoV-2 Neutralisation is by destroying the prefusion SPIKE conformation This antibody may have therapeutic potential alone or with one blocking receptor attachment
Expression and characterization of recombinant human acyloxyacyl hydrolase, a leukocyte enzyme that deacylates bacterial lipopolysaccharides (1991)

The molecular cloning and eukaryotic cell expression of the complementary DNA for human neutrophil acyloxyacyl hydrolase (AOAH) are described. AOAH is a leukocyte enzyme that selectively removes the secondary (acyloxyacyl-linked) fatty acyl chains from the lipid A region of bacterial lipopolysaccharides (endotoxins), thereby detoxifying the molecules. The two disulfide-linked subunits of the enzyme are encoded by a single mRNA. The amino acid sequence of the protein contains a lipase consensus sequence in the large subunit and a region in the small subunit that is similar to the saposins, cofactors for sphingolipid hydrolases. The recombinant enzyme, like native AOAH, hydrolyzes secondary acyl chains from more than one position on the lipopolysaccharide backbone. Acyloxyacyl hydrolase is a novel two-component lipase that, by deacylating lipopolysaccharides, may modulate host inflammatory responses to Gram-negative bacterial invasion.
Synthesis and Biological Activities of 2,4‐Diaminopteridine Derivatives (2009)

Substituted 2,4-diaminopteridine derivatives 10a-10l were prepared in moderate to good yield. Their structures were confirmed by 1H-NMR and MS spectroscopy, as well as by elemental analysis. Their inhibitory properties against inducible nitric oxide synthase (iNOS) were evaluated in vitro. Biological tests indicated that compound 10a, 10d, 10e, 10h, 10i, and 10l showed potent inhibitory activities similar to that of methotrexate (MTX), while the activities of compound 10b, 10c, 10f, 10g, 10j, and 10k are stronger than MTX. Two compounds, i. e., 10b (IC(50 )= 18.85 microM) and 10i (IC(50) = 24.08 microM) were further studied for their effect on septic shock in rats and immunologically liver injured mice (in vivo). The results demonstrated that 10b and 10i had the capacity to increase the blood pressure in septic shock and showed notable protective activities on immunological hepatic injury.
Salmonellavaccines for use in humans: present and future perspectives (2002)

In recent years there has been significant progress in the development of attenuated Salmonella enterica serovar Typhi strains as candidate typhoid fever vaccines. In clinical trials these vaccines have been shown to be well tolerated and immunogenic. For example, the attenuated S. enterica var. Typhi strains CVD 908-htrA (aroC aroD htrA), Ty800 (phoP phoQ) and chi4073 (cya crp cdt) are all promising candidate typhoid vaccines. In addition, clinical trials have demonstrated that S. enterica var. Typhi vaccines expressing heterologous antigens, such as the tetanus toxin fragment C, can induce immunity to the expressed antigens in human volunteers. In many cases, the problems associated with expression of antigens in Salmonella have been successfully addressed and the future of Salmonella vaccine development is very promising.
Delta-like ligand 4–Notch signaling regulates bone marrow–derived pericyte/vascular smooth muscle cell formation (2010)

Delta-like ligand 4 (DLL4) is essential for the formation of mature vasculature. However, the role of DLL4-Notch signaling in pericyte/vascular smooth muscle cell (vSMC) development is poorly understood. We sought to determine whether DLL4-Notch signaling is involved in pericyte/vSMC formation in vitro and during vasculogenesis in vivo using 2 Ewing sarcoma mouse models. Inhibition of DLL4 with the antibody YW152F inhibited pericyte/vSMC marker expression by bone marrow (BM) cells in vitro. Conversely, transfection of 10T1/2 cells with the active domains of Notch receptors led to increased expression of pericyte/vSMC markers. Furthermore, the blood vessels of Ewing sarcoma tumors from mice treated with YW152F had reduced numbers of BM-derived pericytes/vSMCs, fewer open lumens, and were less functional than the vessels in tumors of control-treated mice. Tumor growth was also inhibited. These data demonstrate a specific role for DLL4 in the formation of BM-derived pericytes/vSMCs and indicate that DLL4 may be a novel therapeutic target for the inhibition of vasculogenesis.
Pyelonephritogenic Escherichia coli and killing of cultured human renal proximal tubular epithelial cells: role of hemolysin in some strains (1990)

Acute pyelonephritis, a complication of Escherichia coli bacteriuria, must represent a bacterial invasion through the kidney epithelium. To study this process, we overlaid bacterial suspensions onto monolayers of cultured human kidney proximal tubular epithelial cells and measured cytotoxicity by release of lactate dehydrogenase (LDH). Thirty-four isolates cultured from patients with acute pyelonephritis were screened for the ability to cause pyelonephritis in CBA mice by transurethral challenge. The eight most virulent strains (greater than or equal to 70% of mice challenged developed greater than or equal to 10(3) CFU/g of kidney after 48 h) were selected for study. Each strain displayed mannose-resistant hemagglutination of human O erythrocytes; three strains were phenotypically and genotypically hemolytic. Pyelonephritogenic strains were significantly more cytotoxic (30.1 +/- 9.5% LDH release after 18 h) than eight fecal control strains (13.5 +/- 11.5% LDH release; P = 0.0068). We selected the most cytotoxic strain, CFT073, for further study. Sterile filtrate from this hemolytic strain was significantly more cytotoxic than was the filtrate of the fecal control strain, FN414. Transposon mutagenesis of CFT073 with TnphoA abolished hemolytic activity and cytotoxicity by both whole cells and sterile filtrate. Southern blot analysis revealed that the Tnphoa insertion mapped to the E. coli chromosomal hly determinant within a 12-kilobase SalI restriction fragment. Transformation of a nonhemolytic strain, CPZ005 with plasmid pSF4000, which carries a cloned hemolysin determinant, resulted in highly elevated cytotoxicity. Light micrographs of proximal tubular epithelial cell cultures demonstrated cell damage by pyelonephritogenic strains that was not induced by a fecal strain or the hemolysin-deficient mutant. Results indicate that pyelonephritogenic E. coli strains are more frequently cytotoxic for a putative target, that is, human renal tubular epithelium, than are fecal isolates. Hemolysin, in some strains, is apparently responsible for this cytotoxicity.
Discovering user-generated metaphors through usability testing (1997)

A post hoc analysis of data collected from a usability test on the Fluke ScopeMeter 97 (a diagnostic instrument for analyzing electrical signals) revealed that, in doing tasks, subjects were making use of their own internal metaphors (user generated) that were unsupported by the design of the ScopeMeter keys. We investigated the interaction of the user generated metaphors and designer generated metaphors. By examining the effects that the subjects' skill levels and their backgrounds had on employing such metaphors, we began to outline certain characteristics of user generated metaphors. We found that user generated metaphors demonstrate unyielding persistence in the minds of ScopeMeter users, particularly in the higher skilled subjects.
Fracturing Fluid Components (2013)

The materials and chemistry used to manufacture hydraulic fracture fluids are often confusing and difficult for the practicing hydraulic fracturing engineer to understand and optimize. Many times the failure of a particular fracturing treatment is blamed on the fluid because that is a major unknown from the design engineer's viewpoint. Many of the components and processes used to manufacture the fluid are held proprietary by the service company which adds to the confusion and misunderstanding. This paper makes an attempt to describe the components used in fracturing fluids at a level that the practicing frac engineer can understand and use. The paper is intended as a companion paper to the Fracturing Fluids design paper which describes how to use the fluids and viscosity generated by the fluids to design a fracturing treatment.
T cell repertoire following autologous stem cell transplantation for multiple sclerosis (2014)

Autologous hematopoietic stem cell transplantation (HSCT) is commonly employed for hematologic and non-hematologic malignancies. In clinical trials, HSCT has been evaluated for severe autoimmunity as a method to "reset" the immune system and produce a new, non-autoimmune repertoire. While the feasibility of eliminating the vast majority of mature T cells is well established, accurate and quantitative determination of the relationship of regenerated T cells to the baseline repertoire has been difficult to assess. Here, in a phase II study of HSCT for poor-prognosis multiple sclerosis, we used high-throughput deep TCRβ chain sequencing to assess millions of individual TCRs per patient sample. We found that HSCT has distinctive effects on CD4+ and CD8+ T cell repertoires. In CD4+ T cells, dominant TCR clones present before treatment were undetectable following reconstitution, and patients largely developed a new repertoire. In contrast, dominant CD8+ clones were not effectively removed, and the reconstituted CD8+ T cell repertoire was created by clonal expansion of cells present before treatment. Importantly, patients who failed to respond to treatment had less diversity in their T cell repertoire early during the reconstitution process. These results demonstrate that TCR characterization during immunomodulatory treatment is both feasible and informative, and may enable monitoring of pathogenic or protective T cell clones following HSCT and cellular therapies.