gebhart/patrepeval huggingface dataset:
Simulation of 3D image depth perception in a 3D display using two stereoscopic displays at different depths (2006)

We studied a new 3-D display that uses two stereoscopic displays instead of two 2-D displays in a depth-fused 3D display. We found that two 3-D images with the same shape displayed at different depths by the two stereoscopic displays were fused into one 3-D image when they were viewed as overlapping. Moreover, we found that the perceived depth of the fused 3-D image depends on both the luminance ratio of the two 3-D images and their original perceived depth. This paper presents the simulation results for the perceived depth of the fused 3-D image on the new 3-D display. We applied a model in which the human visual system uses a low-pass filter to perceive the fused image, the same as that used for a conventional DFD display. The simulation results revealed that the perceived depth of the fused image changed depending on both the luminance ratio of the two 3-D images and their original perceived depth, as in the subjective test results, and the low-pass filter model accurately presented the perception of a 3-D image on our 3-D display.
A Cell-Penetrating Bispecific Antibody for Therapeutic Regulation of Intracellular Targets (2012)

The therapeutic use of antibodies is restricted by the limited access of antibodies to intracellular compartments. To overcome this limitation, we developed a cell-penetrating monoclonal antibody, mAb 3E10, as an intracellular delivery vehicle for the intracellular and intranuclear delivery of antibodies constructed as bispecific single-chain Fv fragments. Because MDM2 is an important target in cancer therapy, we selected monoclonal antibody (mAb) 3G5 for intracellular transport. mAb 3G5 binds MDM2 and blocks binding of MDM2 to p53. Here, we show that the resulting 3E10-3G5 bispecific antibody retains cell-penetrating and MDM2-binding activity, increases tumor p53 levels, and inhibits growth of MDM2-addicted tumors. The use of cell-penetrating bispecific antibodies in targeted molecular therapy will significantly broaden the spectrum of accessible intracellular targets and may have a profound impact in cancer therapy.
Identification and Characterization of a New Family of Cell-penetrating Peptides (2011)

Cell-penetrating peptides can translocate across the plasma membrane of living cells and thus are potentially useful agents in drug delivery applications. Disulfide-rich cyclic peptides also have promise in drug design because of their exceptional stability, but to date only one cyclic peptide has been reported to penetrate cells, the Momordica cochinchinensis trypsin inhibitor II (MCoTI-II). MCoTI-II belongs to the cyclotide family of plant-derived cyclic peptides that are characterized by a cyclic cystine knot motif. Previous studies in fixed cells showed that MCoTI-II could penetrate cells but kalata B1, a prototypic cyclotide from a separate subfamily of cyclotides, was bound to the plasma membrane and did not translocate into cells. Here, we show by live cell imaging that both MCoTI-II and kalata B1 can enter cells. Kalata B1 has the same cyclic cystine knot structural motif as MCoTI-II but differs significantly in sequence, and the mechanism by which these two peptides enter cells also differs. MCoTI-II appears to enter via macropinocytosis, presumably mediated by interaction of positively charged residues with phosphoinositides in the cell membrane, whereas kalata B1 interacts directly with the membrane by targeting phosphatidylethanolamine phospholipids, probably leading to membrane bending and vesicle formation. We also show that another plant-derived cyclic peptide, SFTI-1, can penetrate cells. SFTI-1 includes just 14 amino acids and, with the exception of its cyclic backbone, is structurally very different from the cyclotides, which are twice the size. Intriguingly, SFTI-1 does not interact with any of the phospholipids tested, and its mechanism of penetration appears to be distinct from MCoTI-II and kalata B1. The ability of diverse disulfide-rich cyclic peptides to penetrate cells enhances their potential in drug design, and we propose a new classification for them, i.e. cyclic cell-penetrating peptides.
Effective Orthotic Therapy for the Painful Cavus Foot (2006)

Patients with a cavus or high-arched foot frequently experience foot pain, which can lead to significant limitation in function. Custom foot orthoses are widely prescribed to treat cavus foot pain. However, no clear guidelines for their construction exist, and there is limited evidence of their efficacy. In a randomized, single-blind, sham-controlled trial, the effect of custom foot orthoses on foot pain, function, quality of life, and plantar pressure loading in people with a cavus foot type was investigated. One hundred fifty-four participants with chronic musculoskeletal foot pain and bilateral cavus feet were randomly assigned to a treatment group receiving custom foot orthoses (n = 75) or to a control group receiving simple sham insoles (n = 79). At 3 months, 99% of the participants provided follow-up data using the Foot Health Status Questionnaire. Foot pain scores improved more with custom foot orthoses than with the control (difference, 8.3 points; 95% confidence interval [CI], 1.2 to 15.3 points; P = .022). Function scores also improved more with custom foot orthoses than with the control (difference, 9.5 points; 95% CI, 2.9 to 16.1 points; P = .005). Quality-of-life data favored custom foot orthoses, although differences reached statistical significance only for physical functioning (difference, 7.0 points; 95% CI, 1.9 to 12.1 points; P = .008). Plantar pressure improved considerably more with custom foot orthoses than with the control for all regions of the foot (difference, -3.0 N . s/cm(2); 95% CI, -3.7 to -2.4 N . s/cm(2); P < .001). In conclusion, custom foot orthoses are more effective than a control for the treatment of cavus foot pain and its associated limitation in function.
A novel tumor-associated antigen expressed in human uterine and ovarian carcinomas (1996)

The 22-1-1 MoAb reactive to a novel tumor-associated antigen was generated. This Ag was expressed in cancer cells derived mainly from the uterus and ovary. Moreover, 22-1-1 Ag was associated in the vaginal discharges of uterine cervical carcinoma patients. 22-1-1 MoAb is a potential tool for the study of oncogenesis and the management of cancer patients.
Activation of alpha7 nicotinic acetylcholine receptor by nicotine selectively up-regulates cyclooxygenase-2 and prostaglandin E2 in rat microglial cultures. (2005)

BACKGROUND: Nicotinic acetylcholine (Ach) receptors are ligand-gated pentameric ion channels whose main function is to transmit signals for the neurotransmitter Ach in peripheral and central nervous system. However, the alpha7 nicotinic receptor has been recently found in several non-neuronal cells and described as an important regulator of cellular function. Nicotine and ACh have been recently reported to inhibit tumor necrosis factor-alpha (TNF-alpha) production in human macrophages as well as in mouse microglial cultures. In the present study, we investigated whether the stimulation of alpha7 nicotinic receptor by the specific agonist nicotine could affect the functional state of activated microglia by promoting and/or inhibiting the release of other important pro-inflammatory and lipid mediator such as prostaglandin E2. METHODS: Expression of alpha7 nicotinic receptor in rat microglial cell was examined by RT-PCR, immunofluorescence staining and Western blot. The functional effects of alpha7 receptor activation were analyzed in resting or lipopolysaccharide (LPS) stimulated microglial cells pre-treated with nicotine. Culture media were assayed for the levels of tumor necrosis factor, interleukin-1beta, nitric oxide, interleukin-10 and prostaglandin E2. Total RNA was assayed by RT-PCR for the expression of COX-2 mRNA. RESULTS: Rat microglial cells express alpha7 nicotinic receptor, and its activation by nicotine dose-dependently reduces the LPS-induced release of TNF-alpha, but has little or no effect on nitric oxide, interleukin-10 and interleukin-1beta. By contrast, nicotine enhances the expression of cyclooxygenase-2 and the synthesis of one of its major products, prostaglandin E2. CONCLUSIONS: Since prostaglandin E2 modulates several macrophage and lymphocyte functions, which are instrumental for inflammatory resolution, our study further supports the existence of a brain cholinergic anti-inflammatory pathway mediated by alpha7 nicotinic receptor that could be potentially exploited for novel treatments of several neuropathologies in which local inflammation, sustained by activated microglia, plays a crucial role.
Do surfaces with mixed hydrophilic and hydrophobic areas enhance pool boiling? (2010)

We demonstrate that smooth and flat surfaces combining hydrophilic and hydrophobic patterns improve pool boiling performance. Compared to a hydrophilic surface with 7° wetting angle, the measured critical heat flux and heat transfer coefficients of the enhanced surfaces are, up to respectively, 65% and 100% higher. Different networks combining hydrophilic and hydrophobic regions are characterized. While all tested networks enhance the heat transfer coefficient, large enhancements of critical heat flux are typically found for hydrophilic networks featuring hydrophobic islands. Hydrophilic networks indeed are shown to prevent the formation of an insulating vapor layer.
Development of Lymphoid Hyperplasia in Transgenic Mice Expressing the HIV tat Gene (1995)

During HIV infection, individuals experience multiorgan disorders such as adenopathy, splenomegaly, and lung and brain diseases. There is an increasing body of evidence that the HIV trans-activating tat gene product possesses multiple activities. First, it can activate several cellular genes; second, in its extracellular soluble form, it plays the role of growth factor in some cells such as Kaposi's sarcoma cells. Thus, we introduced the HIV tat gene, under the control of the cellular proteolipoprotein promoter, into the germline of mice and demonstrate that, when expressed, the tat gene product induces lymphoid hyperplasia in spleen, lymph nodes, and lung, as is observed in AIDS patients, but not in the brain or testes. Our findings indicate that HIV, through some of its genes, directly participates in the pathogenesis of AIDS.
Structure-Function Relationships in the Neuropeptide S Receptor (2006)

Neuropeptide S (NPS) and its receptor (NPSR) are thought to have a role in asthma pathogenesis; a number of single nucleotide polymorphisms within NPSR have been shown to be associated with an increased prevalance of asthma. One such single nucleotide polymorphism leads to the missense mutation N107I, which results in an increase in the potency of NPS for NPSR. To gain insight into structure-function relationships within NPS and NPSR, we first carried out a limited structural characterization of NPS and subjected the peptide to extensive mutagenesis studies. Our results show that the NH(2)-terminal third of NPS, in particular residues Phe-2, Arg-3, Asn-4, and Val-6, are necessary and sufficient for activation of NPSR. Furthermore, part of a nascent helix within the peptide, spanning residues 5 through 13, acts as a regulatory region that inhibits receptor activation. Notably, this inhibition is absent in the asthma-linked N107I variant of NPSR, suggesting that residue 107 interacts with the aforementioned regulatory region of NPS. Whereas this interaction may be at the root of the increase in potency associated with the N107I variant, we show here that the mutation also causes an increase in cell-surface expression of the mutant receptor, leading to a concomitant increase in the maximal efficacy (E(max)) of NPS. Our results identify the key residues of NPS involved in NPSR activation and suggest a molecular basis for the functional effects of the N107I mutation and for its putative pathophysiological link with asthma.
Dihydropyridine Ca 2+ Channel Blockers Increase Cytosolic [Ca 2+ ] by Activating Ca 2+ -sensing Receptors in Pulmonary Arterial Smooth Muscle Cells (2013)

The dihydropyridine derivatives increase [Ca(2+)](cyt) by potentiating the activity of CaSR in PASMC independently of their blocking (or activating) effect on Ca(2+) channels; therefore, it is possible that the use of dihydropyridine Ca(2+) channel blockers (eg, nifedipine) to treat IPAH patients with upregulated CaSR in PASMC may exacerbate pulmonary hypertension.
Characterization of Human Immunodeficiency Virus Gag-Specific Gamma Interferon-Expressing Cells following Protective Mucosal Immunization with Alphavirus Replicon Particles (2005)

A safe, replication-defective viral vector that can induce mucosal and systemic immune responses and confer protection against many infectious pathogens, such as human immunodeficiency virus type 1 (HIV-1), may be an ideal vaccine platform. Accordingly, we have generated and tested alphavirus replicon particles encoding HIV-1 Gag from Sindbis virus (SIN-Gag) and Venezuelan equine encephalitis virus (VEE-Gag), as well as chimeras between the two (VEE/SIN-Gag). Following intramuscular (i.m.), intranasal (i.n.), or intravaginal (IVAG) immunization with VEE/SIN-Gag and an IVAG challenge with vaccinia virus encoding HIV Gag (VV-Gag), a larger number of Gag-specific CD8+ intracellular gamma interferon-expressing cells (iIFNEC) were detected in iliac lymph nodes (ILN), which drain the vaginal/uterine mucosa (VUM), than were observed after immunizations with SIN-Gag. Moreover, a single i.n. or IVAG immunization with VEE/SIN-Gag induced a larger number of cells expressing HIV Gag in ILN, and immunizations with VEE/SIN-Gag through any route induced better protective responses than immunizations with SIN-Gag. In VUM, a larger percentage of iIFNEC expressed alpha4beta7 or alpha(Ebeta)7 integrin than expressed CD62L integrin. However, in spleens (SP), a larger percentage of iIFNEC expressed alpha4beta7 or CD62L than expressed alpha(Ebeta)7. Moreover, a larger percentage of iIFNEC expressed the chemokine receptor CCR5 in VUM and ILN than in SP. These results demonstrate a better induction of cellular and protective responses following immunizations with VEE/SIN-Gag than that following immunizations with SIN-Gag and also indicate a differential expression of homing and chemokine receptors on iIFNEC in mucosal effector and inductive sites versus systemic lymphoid tissues.
Role of PD-1 and its ligand, B7-H1, in early fate decisions of CD8 T cells (2007)

Expression of the PD-1 receptor on T cells has been shown to provide an important inhibitory signal that down-modulates peripheral effector responses in normal tissues and tumors. Furthermore, PD-1 up-regulation on chronically activated T cells can maintain them in a partially reversible inactive state. The function of PD-1 in the very early stages of T-cell response to antigen in vivo has not been fully explored. In this study, we evaluate the role of PD-1 and its 2 B7 family ligands, B7-H1 (PD-L1) and B7-DC (PD-L2), in early fate decisions of CD8 T cells. We show that CD8 T cells specific for influenza hemagglutinin (HA) expressed as a self-antigen become functionally tolerized and express high levels of surface PD-1 by the time of their first cell division. Blockade of PD-1 or B7-H1, but not B7-DC, at the time of self-antigen encounter mitigates tolerance induction and results in CD8 T-cell differentiation into functional cytolytic T lymphocytes (CTLs). These findings demonstrate that, in addition to modulating effector functions in the periphery, B7-H1:PD-1 interactions regulate early T-cell-fate decisions.
A new cobalt salicide technology for 0.15-μm CMOS devices (1998)

A new cobalt (Co) salicide technology for sub-quarter micron CMOS transistors has been developed using high-temperature sputtering and in situ vacuum annealing. Sheet resistance of 11 /spl Omega///spl square/ for both gate electrode and diffusion layer was obtained with 5-nm-thick Co film. No line width dependence of sheet resistance was observed down to 0.15-/spl mu/m-wide gate electrode and 0.33-/spl mu/m-wide diffusion layer. The high temperature sputtering process led to the growth of epitaxial CoSi/sub 2/ layers with high thermal stability. By using this technology 0.15 /spl mu/m CMOS devices which have shallow junctions were successfully fabricated.
Cap-dependent RNA splicing in a HeLa nuclear extract. (1985)

We have studied the involvement of the 5' cap structure in the splicing of precursor mRNAs in a HeLa nuclear extract. We show that precursor mRNAs are spliced efficiently only when they possess a cap structure and that preincubation of a HeLa nuclear extract rendered the splicing reaction highly sensitive to inhibition by cap analogues. This sensitization was dependent on exogenous Mg2+ but not exogenous ATP or GTP. These results demonstrate that splicing in a nuclear extract is highly dependent on the cap structure, as was demonstrated for the splicing process in a HeLa whole-cell extract [Konarska, M. M., Padget, R. A. & Sharp, P. A. (1984) Cell 38, 731-736], and thus support the contention that cap recognition is an important feature of eukaryotic mRNA biogenesis.
The conformation of single‐stranded nucleic acids (1990)

Conformational analyses using the single-strand-specific nuclease from mung bean and restriction endonucleases have been performed on a series of DNA fragments related to the sequence of the yeast initiator tRNA(Met). Mung bean nuclease cleaves DNA fragments exclusively in some, but not all, single-stranded regions as predicted by RNA secondary structural rules. Comparison of cleavage patterns of yeast initiator tRNA(Met), tDNA(Met) (a DNA oligomer having the sequence of tRNA(Met] and the anti-tDNA(Met) (the complement of tDNA(Met] suggests that the conformation of the three molecules is very similar. Furthermore, both tDNA and anti-tDNA are cleaved by HhaI and CfoI restriction endonucleases at two GCG/C sites which would be in double-stranded regions (the acceptor and dihydrouridine stem), if the two molecules adopt the tRNA cloverleaf structure. On the other hand, minor cleavage products show that the core region, i.e. the extra loop area, is slightly more exposed in tDNA and in anti-tDNA than in tRNA. Therefore, we submit that the global conformation of nucleic acids is primarily dictated by the interaction of purine and pyrimidine bases with atoms and functional groups common to both RNA and DNA. In this view the 2'-hydroxyl group, in tRNA at least, is an auxiliary structural feature whose role is limited to fostering local interactions, which increase the stability of a given conformation.
Systematic Construction of Cyclically Permutable Code Words (1975)

A numerical procedure for determining the cyclically permutable code of any length over an arbitrary alphabet is outlined. This method is easily programmed on a digital computer. A formula for the Hamming weight distribution of the code is also given. The results for the 12 bit binary cyclically permutable code are presented along with the weight distribution of the binary codes through length 14.
Comparative and Library Epidemiological Typing Systems: Outbreak Investigations versus Surveillance Systems (1998)

A number of high-resolution molecular typing systems have been developed in recent years. Their availability raises the new issues of selecting the method (s) best suited for a particular purpose and interpreting and communicating typing results. Most of the currently available methods are comparative only: they allow testing of a sample of isolates for delineation of those closely related from those markedly different in genomic backgrounds. This approach is adequate for outbreak investigation, allowing determination of clonal spread in a microenvironment and identification of the source of infection. Comparative methods with sufficient resolution for most pathogens include restriction fragment-length polymorphism (RFLP), pulsed-field gel electrophoresis (PFGE), and arbitrarily primed and randomly amplified polymorphic DNA-polymerase chain reaction (PCR) analysis. For surveillance systems, monitoring clonal spread and prevalence in populations over extended periods of time requires library typing systems. These must be standardized, must have a high throughput, and must use a uniform nomenclature. Promising or validated methods include serotyping, insertion sequence fingerprinting, ribotyping, PFGE, amplified fragment-length polymorphism (AFLP), infrequent-restriction-site amplification PCR, interrepetitive element PCR typing (rep-PCR) and PCR-RFLP of polymorphic loci. PCR methods generating arrays of size-specific amplicons (AFLP, rep-PCR) can be more reproducibly analyzed by using denaturing polyacrylamide gel or capillary electrophoresis with automated laser detection. Binary probe typing systems appear optimal and should be enhanced further through use of DNA chip technology. In these systems, amplification of polymorphic regions is followed by solid-phase hybridization with a reference panel of sequence-variant specific probes. The resulting binary type results allow determination of reproducible, numeric profiles. However, interpretation and nomenclature of typing results for large-scale surveillance purposes still require a better understanding of population structure and microevolution of most microbial pathogens.
rsmC of the Soft-Rotting Bacterium Erwinia carotovora subsp. carotovora Negatively Controls Extracellular Enzyme and Harpin Ecc Production and Virulence by Modulating Levels of Regulatory RNA ( rsmB ) and RNA-Binding Protein (RsmA) (1999)

Previous studies have shown that the production of extracellular enzymes (pectate lyase [Pel], polygalacturonase [Peh], cellulase [Cel], and protease [Prt]) and harpin(Ecc) (the elicitor of hypersensitive reaction) in Erwinia carotovora subsp. carotovora is regulated by RsmA, an RNA-binding protein, and rsmB, a regulatory RNA (Rsm stands for regulator of secondary metabolites) (Y. Liu et al., Mol. Microbiol. 29:219-234, 1998). We have cloned and characterized a novel regulatory gene, rsmC, that activates RsmA production and represses extracellular enzyme and harpin(Ecc) production, rsmB transcription, and virulence in E. carotovora subsp. carotovora. In an rsmC knockout mutant of E. carotovora subsp. carotovora Ecc71 carrying the chromosomal copy of the wild-type rsmA(+) allele, the basal levels of Pel, Peh, Cel, Prt, and harpin(Ecc) as well as the amounts of rsmB, pel-1, peh-1, celV, and hrpN(Ecc) transcripts are high, whereas the levels of rsmA transcripts and RsmA protein are low. Furthermore, the expression of an rsmA-lacZ gene fusion is lower in the RsmC(-) mutant than in the RsmC(+) parent. Conversely, the expression of an rsmB-lacZ operon fusion is higher in the RsmC(-) mutant than in the RsmC(+) parent. These observations establish that RsmC negatively regulates rsmB transcription but positively affects RsmA production. Indeed, comparative studies with an RsmC(-) mutant, an RsmA(-) mutant, and an RsmA(-) RsmC(-) double mutant have revealed that the negative effects on exoprotein production and virulence are due to the cumulative regulatory effects of RsmC on rsmA and rsmB. Exoprotein production by the RsmC(-) mutant is partially dependent on the quorum sensing signal, N-(3-oxohexanoyl)-L-homoserine lactone. Southern blot data and analysis of PCR products disclosed the presence of rsmC sequences in E. carotovora subsp. atroseptica, E. carotovora subsp. betavasculorum, and E. carotovora subsp. carotovora. These findings collectively support the idea that rsmA and rsmB expression in these plant pathogenic Erwinia species is controlled by RsmC or a functional homolog of RsmC.