gebhart/patrepeval huggingface dataset:
The effect of benzylation or sequential amidinationand benzylation on the ability of rabbit gamma-G-antibody to fix complement. (1968)

Summary Benzylation of rabbit γG-antibody results in a partial loss of complement-fixing ability, as has been described by others. The greater part of this loss is due to the conjugation of only one or two tryptophan groups. The tryptophan groups which contribute most to the antibody9s ability to fix complement are most susceptible to benzylation. Double conjugation of rabbit γG-antibody, by means of sequential amidination and benzylation, results in an antibody preparation which shows no significant loss in its ability to combine with and precipitate antigen, but which has suffered a 92% reduction in complement-fixing ability. This reduction is probably due to the specific inactivation of complement-fixing sites on the antibody molecule. Moreover, amidination and benzylation affect the same population of complement-fixing sites. The doubly conjugated antibodies show a diminution in the rate at which they aggregate with antigen. However, double conjugation is more effective at maximizing changes in complement fixation and minimizing alterations in reaction with antigen than either amidination or benzylation alone.
Nomadic radio (2000)

Mobile workers need seamless access to communication and information services while on the move. However, current solutions overwhelm users with intrusive interfaces and ambiguous notifications. This article discusses the interaction techniques developed for Nomadic Radio, a wearable computing platform for managing voice and text-based messages in a nomadic environment. Nomadic Radio employs an auditory user interface, which synchronizes speech recognition, speech synthesis, nonspeech audio, and spatial presentation of digital audio, for navigating among messages as well as asynchonous notific ation of nely arrived messages. Emphasis is placed on an auditory modality as Nomadic Radio is designed to be used while performing other tasks in a user's everyday environment; a range of auditory cues provides peripheral awareness of incoming messages. Notification is adaptive and cntext sensitive; messages are presented as more or less obtrsive based on importance inferred from content filtering, whether the user is engaged in conversation and his or her own recent responses to prior messages. Auditory notifications are dynamically scaled from ambient sound through recorded voice cues up to message summaries. Iterative design and a preliminary user evaluation suggest that audio is an appropriate medium for mobile messaging, but that care must be taken to minimally intrude on the wearer's social and physical environment.
Levels of CSF prostaglandin E2, cognitive decline, and survival in Alzheimer's disease (2005)

COX activity in Alzheimer's disease varies with stage of the disease. PGE2 levels correlate positively with patient survival. These findings suggest that inhibition of COX activity does not represent a major target for the pharmacological treatment of Alzheimer's disease.
Complete set of ORF clones of Escherichia coli ASKA library (A Complete Set of E. coli K-12 ORF Archive): Unique Resources for Biological Research (2006)

Based on the genomic sequence data of Escherichia coli K-12 strain, we have constructed a complete set of cloned individual genes encoding Histidine-tagged proteins with or without GFP fused for functional genomic analysis. Each clone encodes a protein of predicted ORF attached by Histidines and seven spacer amino acids at the N-terminal end, and five spacer amino acids and GFP at the C-terminal end. SfiI restriction sites are generated at both the N- and C-terminal boundaries of ORF upon cloning, which enables easy transfer of ORF to other vector systems by cutting with SfiI. Expression of cloned ORF is under the control of an IPTG-inducible promoter, which is strictly repressed by lacI(q) repressor gene product. The set of cloned ORFs described here should provide unique resources for systematic functional genomic approaches including (i) construction of DNA microarray, (ii) production and purification of proteins, (iii) analysis of protein localization by monitoring GFP fluorescence and (iv) analysis of protein-protein interaction.
Transcriptional Regulation of the p67 Gene (2001)

We have investigated the myeloid-specific transcriptional regulation of p67(phox), an essential component of phagocyte respiratory burst NADPH oxidase. Analysis was carried out on the p67(phox) 5'-flanking region from -3669 to -4 (relative to ATG), including the first exon and intron and part of the second exon. The construct extending from -985 to -4 produced the highest luciferase activity in myeloid HL-60 cells but was not active in HeLa or Jurkat cells, indicating myeloid-specific expression. Four active elements were identified: Sp1/Sp3 at -694, PU.1 at -289, AP-1 at -210, and PU.1/HAF1 at -182, the latter three being in the first intron. These cis elements bound their cognate transacting factors both in vitro and in vivo. Mutation of the Sp1, PU.1, or PU.1/HAF1 site each decreased promoter activity by 35-50%. Mutations in all three sites reduced promoter activity by 90%. However, mutation of the AP-1 site alone nearly abolished promoter activity. The AP-1 site bound Jun and Fos proteins from HL-60 cell nuclear extract. Co-expression with Jun B in AP-1-deficient cells increased promoter activity by 3-fold. These data show that full p67(phox) promoter activity requires cooperation between myeloid-specific and nonmyeloid transcription factors, with AP-1 being the most critical for function.
Reactive oxygen species‐induced molecular damage and its application in pathology (1999)

Recent studies have clarified that reactive oxygen species (ROS) are involved in a diversity of biological phenomena including radiation damage, carcinogenesis, ischemia-reperfusion injury, diabetes mellitus and neurodegenerative diseases. The breakthrough of these fruitful accomplishments was the discovery of an enzyme, superoxide dismutase, by McCord and Fridovich in 1968. In the 1970s and 80s, biochemists and radiation biologists were attracted by the role of ROS in its irreversible damage to biological molecules. In the 1990s, ROS were further found to be a reversible modulator of protein structure as well, and this led to a recent rapid data accumulation on the association of ROS and transcription factors. At the same time, methods to localize ROS-induced damage in paraffin-embedded tissues have been established. This owes to a successful production of antibodies against covalently modified structures specific for ROS-induced damage. The epitopes include 8-hydroxy-2'-deoxyguanosine and 4-hydroxy-2-nonenal-modified proteins. The present article reviews histochemical and immunohistochemical methods to localize ROS-induced damage in tissues and cells, further comments on the association of ROS with transcription factors, and shows a prospective view of ROS-induced carcinogenesis.
FC-Receptors (1991)

Exhausted CD8 T (Tex) cells are a distinct cell lineage that arise during chronic infections and cancers in animal models and humans. Tex cells are characterized by progressive loss of effector functions, high and sustained inhibitory receptor expression, ...Read More
Preclinical Validation of the Utility of BLZ-100 in Providing Fluorescence Contrast for Imaging Spontaneous Solid Tumors (2015)

There is a need in surgical oncology for contrast agents that can enable real-time intraoperative visualization of solid tumors that can enable complete resections while sparing normal surrounding tissues. The Tumor Paint agent BLZ-100 is a peptide-fluorophore conjugate that can specifically bind solid tumors and fluoresce in the near-infrared range, minimizing light scatter and signal attenuation. In this study, we provide a preclinical proof of concept for use of this imaging contrast agent as administered before surgery to dogs with a variety of naturally occurring spontaneous tumors. Imaging was performed on excised tissues as well as intraoperatively in a subset of cases. Actionable contrast was achieved between tumor tissue and surrounding normal tissues in adenocarcinomas, squamous cell carcinomas, mast cell tumors, and soft tissue sarcomas. Subcutaneous soft tissue sarcomas were labeled with the highest fluorescence intensity and greatest tumor-to-background signal ratio. Our results establish a foundation that rationalizes clinical studies in humans with soft tissue sarcoma, an indication with a notably high unmet need.
IGFs and IGF-binding proteins as diagnostic markers and biological modulators in brain tumors (2002)

The insulin-like growth factors (IGFs) play a pivotal role in brain tumor growth and inhibition of apoptosis. Specific IGF binding proteins (IGFBPs) may enhance or inhibit tumor growth. Moreover, IGFBPs represent tumor markers and their expression correlates with tumor grading and patient survival. Understanding the role IGFs play for the proliferation of brain tumors is a prerequisite for modulating the biology of tumorigenesis. Novel antisense strategies targeting IGF-I or the Type I IGF receptor may offer additional options to patients suffering from malignant gliomas and other CNS malignancies. Clinical trials are currently underway that should demonstrate whether a beneficial effect is achievable in these patients.
Modulation doping in Ge(x)Si(1−x)/Si strained layer heterostructures: Effects of alloy layer thickness, doping setback, and cladding layer dopant concentration (1985)

Selectively doped GexSi1−x/Si strained layer heterostructures have been grown in a single quantum well configuration on 〈001〉-Si substrate using molecular beam epitaxy. The modulation doping effect has been observed in p-type structures only; although both n- and p-type double heterostructures were grown. We have investigated the effects of: (i) alloy layer thickness (well width), (ii) doping setback, and (iii) cladding layer dopant concentration, on the hole mobilities. At present, optimum structures show peak hole mobilities in excess of 3300 cm2V−1s−1 at 4.2 K, sheet charge densities of 3.0–14×1011 cm−2, and hole effective mass m*h =0.32±0.03 m0. It is found that the low temperature (T∼10 K) hole mobility, in structure having x=0.2 is relatively insensitive to alloy layer (well) thickness in the range 100 Å≲Lw≲Lc; where Lc is the critical thickness marking the transition from strained layer to relaxed, misfit accommodated, alloy growth. For Lw&amp;gt;Lc, misfit dislocation scattering dramatically decreases μh at T≲100 K; whereas for Lw≲100 Å the hole mobility is uniformly lowered over the entire range of measurement temperatures. Doping setback and cladding layer dopant concentration affect the mobility via changes in sheet charge density, in a manner consistent with theoretical expectations. The absence of the modulation doping effect in n-type heterostructure is taken as an indication that ΔEv≫ΔEc.
Real-time interferometric synthetic aperture microscopy (2008)

An interferometric synthetic aperture microscopy (ISAM) system design with real-time 2D cross-sectional processing is described in detail. The system can acquire, process, and display the ISAM reconstructed images at frame rates of 2.25 frames per second for 512 X 1024 pixel images. This system provides quantitatively meaningful structural information from previously indistinguishable scattering intensities and provides proof of feasibility for future real-time ISAM systems.
Diversity of core antigen epitopes of hepatitis B virus (2003)

Core antigen (cAg), the viral capsid, is one of the three major clinical antigens of hepatitis B virus. cAg has been described as presenting either one or two conformational epitopes involving the "immunodominant loop." We have investigated cAg antigenicity by cryo-electron microscopy at approximately 11-A resolution of capsids labeled with monoclonal Fabs, combined with molecular modeling, and describe here two conformational epitopes. Both Fabs bind to the dimeric external spikes, and each epitope has contributions from the loops on both subunits, explaining their discontinuous nature: however, their binding aspects and epitopes differ markedly. To date, four cAg epitopes have been characterized: all are distinct. Although only two regions of the capsid surface are accessible to antibodies, local clustering of the limited number of exposed peptide loops generates a potentially extensive set of discontinuous epitopes. This diversity has not been evident from competition experiments because of steric interference effects. These observations suggest an explanation for the distinction between cAg and e-antigen (an unassembled form of capsid protein) and an approach to immunodiagnosis, exploiting the diversity of cAg epitopes.
Design, Synthesis, and Testing of Difluoroboron-Derivatized Curcumins as Near-Infrared Probes for in Vivo Detection of Amyloid-β Deposits (2009)

Amyloid-beta (Abeta) deposits have been identified as key players in the progression of Alzheimer's disease (AD). Recent evidence indicates that the deposits probably precede and induce the neuronal atrophy. Therefore, methods that enable monitoring the pathology before clinical symptoms are observed would be beneficial for early AD detection. Here, we report the design, synthesis, and testing of a curcumin-derivatized near-infrared (NIR) probe, CRANAD-2. Upon interacting with Abeta aggregates, CRANAD-2 undergoes a range of changes, which include a 70-fold fluorescence intensity increase, a 90 nm blue shift (from 805 to 715 nm), and a large increase in quantum yield. Moreover, this probe also shows a high affinity for Abeta aggregates (K(d) = 38.0 nM), a reasonable log P value (log P = 3), considerable stability in serum, and a weak interaction with albumin. After intravenous injection of this probe, 19-month-old Tg2576 mice exhibited significantly higher relative signal than that of the control mice over the same period of time. In summary, CRANAD-2 meets all the requirements for a NIR contrast agent for the detection of Abeta plaques both in vitro and in vivo. Our data point toward the feasibility of monitoring the progress of the disease by NIR imaging with CRANAD-2. In addition, we believe that our probe could be potentially used as a tool for drug screening.
No lung toxicity after repeated aerosol or intravenous delivery of plasmid-cationic liposome complexes (1994)

The safety aspects of human gene therapy are of paramount importance in developing an ideal system for gene transfer. Lipofection using DNA in the form of a plasmid has been shown to successfully transfect the lungs when administered either intravenously or by aerosol. We have shown that repeated intravenous or aerosol administration of a plasmid containing the recombinant human alpha 1-antitrypsin gene and a cytomegalovirus promoter complexed to cationic liposomes results in no adverse effects on pulmonary histology, lung compliance, lung resistance, or alveolar-arterial oxygen gradient. Immunohistochemistry and Western blot analysis confirm successful gene transfer using this delivery system. We conclude that plasmids complexed to cationic liposomes may be a safe and efficacious delivery system for in vivo gene transfer to the lungs. Using this delivery system, in vivo gene therapy to the lungs can be achieved by either intravenous or aerosol administration of the transgene.
Type-of-service routing in dynamic datagram networks (2002)

The authors propose a new approach to achieving type-of-service (TOS) with adaptive next-hop routing in wide-area networks such as the Internet. They consider two traffic classes, namely delay-sensitive and throughput-sensitive. Their approach attempts to isolate the two traffic classes by using two FCFS queues at each out-going link, one for each TOS; the link is shared cyclicly between the two TOS queues. The next-hops for the delay-sensitive traffic adapts to link delays of that traffic. The next-hops for the throughput-sensitive traffic adapts to overall link utilizations. They compare their approach with a traditional approach using discrete-event simulation and Lyapunov analysis (for stability of routes). Because of the isolation feature, the proposed approach offers lower end-to-end delays for both traffic classes.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
The role of exon sequences in splice site selection. (1993)

Using mouse immunoglobulin mu (IgM) pre-mRNA as the model substrate for in vitro splicing, we have explored the role of exon sequences in splicing. We have found that deletion of the 5' portion of exon M2 of the IgM gene abolishes the splicing of its immediately upstream intron. Splicing was restored when a purine-rich sequence found within the deleted region was reinserted into the deletion construct. This M2 exon sequence was able to stimulate the splicing of a heterologous intron of the Drosophila doublesex pre-mRNA that contains a suboptimal 3' splice site sequence. These results show that the IgM M2 exon sequence functions as a splicing enhancer. We found that the assembly of the early splicing complex is stimulated by the M2 exon sequence. In vitro competition experiments show that this stimulatory effect is mediated by the interaction of some trans-acting factors. Our results suggest that the U1 snRNP is one such factor. We propose that recognition of an enhancer exon sequence by the components of splicing machinery plays a vital role in the selection of splice sites, not only for the IgM pre-mRNA but for other pre-mRNAs. We designate such a sequence as exon recognition sequence (ERS).
Is Instructional Design Becoming a Commodity (2003)

The ascension of Learning Content Management Systems (LCMS) and their increasingly automated authoring processes may be marginalizing the craft, if not the science, of instructional design. All the templates, wizards, and other productivity tools that come bundled into the leading LCMS platforms have certainly made it easier to assemble and deploy structured learning content.
Local Anesthetic Neurotoxicity Does Not Result from Blockade of Voltage-Gated Sodium Channels (1995)

To investigate whether local anesthetic neurotoxicity results from sodium channel blockade, we compared the effects of intrathecally administered lidocaine, bupivacaine, and tetrodotoxin (TTX), the latter a highly selective sodium channel blocker, on sensory function and spinal cord morphology in a rat model.First, to determine relative anesthetic potency, 25 rats implanted with intrathecal catheters were subjected to infusions of lidocaine (n = 8), bupivacaine (n = 8), or TTX (n = 9). The three drugs produced parallel dose-effect curves that differed significantly from one another: the EC50 values for lidocaine, bupivacaine, and TTX were 28.2 mM (0.66%), 6.6 mM (0.19%), and 462 nM, respectively. Twenty-five additional rats were then given intrathecal lidocaine (n = 8), bupivacaine (n = 8), or TTX (n = 9) at concentrations 10 times the calculated EC50 for sensory block. Lidocaine and bupivacaine induced persistent sensory impairment, whereas TTX did not. Finally, 28 rats were given either intrathecal bupivacaine (n = 10) or TTX (n = 9) at 10 times the EC50, or normal saline (n = 9). Significant sensory impairment again occurred after infusion of bupivacaine, but not after infusion of TTX or saline. Neuropathologic evaluation revealed moderate to severe nerve root injury in bupivacaine-treated animals; histologic changes in TTX- and saline-treated animals were minimal, similar, and restricted to the area adjacent to the catheter. These results indicate that local anesthetic neurotoxicity does not result from blockade of the sodium channel, and suggest that development of a safer anesthetic is a realistic goal. (Anesth Analg 1995;81:338-46)
Transforming growth factor beta inhibits bone resorption in fetal rat long bone cultures. (1988)

TGF-beta 1 is a polypeptide that is abundant in bone matrix, is produced by bone cells, and modulates proliferation and differentiated functions of osteoblastic cells in vitro. TGF-beta 2 is a closely related polypeptide that was originally isolated from bone matrix. TGF-beta 1 has been shown previously to stimulate prostaglandin production in cultures of neonatal mouse calvariae, which causes these bones to resorb. We found similar effects with TGF-beta 2. In comparison, TGF-beta 1 and TGF-beta 2 failed to stimulate bone resorption in fetal rat long bone cultures during a 3-d incubation period in concentrations up to 50-100 times greater than those capable of inducing bone resorption in calvariae. Incubation with TGF-beta 1 for a further 3 d decreased bone resorption up to 30%. Moreover, bone resorption induced by the bone-resorbing agents IL 1 and 1,25-dihydroxyvitamin D3 was partially or completely inhibited by TGF-beta 1 and TGF-beta 2 during the second half of the 6-d incubation period. Inhibition of DNA synthesis with hydroxyurea inhibited bone resorption in long bones in a similar pattern to that seen with TGF-beta 1. The inhibitory effects of TGF-beta 1 and TGF-beta 2 on bone resorption in long bone cultures may therefore be due to inhibition of osteoclast precursor proliferation.
Selective and Rapid Nuclear Translocation of a c-Myc-Containing Complex after Fertilization of Xenopus laevis Eggs (1995)

We report here unusual features of c-Myc specific to early embryonic development in Xenopus laevis, a period characterized by generalized transcriptional quiescence and rapid biphasic cell cycles. Two c-Myc protein forms, p61 and p64, are present in large amounts in the oocyte as well as during early development. In contrast, only p64 c-Myc is present in Xenopus somatic cells. p61 c-Myc is the direct translation product from both endogenous c-myc mRNAs and c-myc recombinant DNA. It is converted to the p64 c-Myc form after introduction into an egg extract, in the presence of phosphatase inhibitors. p61 and p64 belong to two distinct complexes localized in the cytoplasm of the oocyte. A 15S complex contains p64 c-Myc, and a 17.4S complex contains p61 c-Myc. Fertilization triggers the selective and total entry of only p64 c-Myc into the nucleus. This translocation occurs in a nonprogressive manner and is completed during the first cell cycles. This phenomenon results in an exceptionally high level of c-Myc in the nucleus, which returns to a somatic cell-like level only at the end of the blastulation period. During early development, when the entire embryonic genome is transcriptionally inactive, c-Myc does not exhibit a DNA binding activity with Max. Moreover, embryonic nuclei not only prevent the formation of c-Myc/Max complexes but also dissociate such preformed complexes. These peculiar aspects of c-Myc behavior suggest a function that could be linked to the rapid DNA replication cycles occurring during the early cell cycles rather than a function involving transcriptional activity.