gebhart/patrepeval huggingface dataset:
Properties of Bispecific Single Chain Antibodies Expressed in Escherichia coli (1995)

Single chain bispecific antibodies, in which the genes that encode the VH and VL regions are linked in tandem, may offer some advantages over other methods of bispecific antibody preparation. To begin to evaluate the potential of this system, a single chain bispecific antibody (scFv2) that binds to the T cell receptor of a cytotoxic T cell clone and to the hapten fluorescein was constructed. The individual scFv regions were joined by a 25 amino acid linker, and the scFv2 protein was obtained from insoluble inclusion bodies after guanidine solubilization and refolding. Fluorescein-purified scFv2 is active at concentrations of approximately 10 nM (approximately 1 microgram/ml) and above in mediating lysis of fluorescein-coupled tumor cells by the cytotoxic T lymphocytes (CTL). This system has now been used to evaluate various features of the scFv2 approach: (a) affinities of the scFv2 for the TCR and fluorescein, (b) yields of the scFv2 from several different purification schemes, (c) relationship of antigen density (i.e., fluorescein density on tumor cells) to the ability to redirect lysis of the tumor cell, and (d) relationship of scFv2 affinity for the tumor antigen to the ability to redirect lysis. This study was performed by using several analogs of fluorescein for which the scFv2 had different affinities. Results showed that it should be possible to select antibodies with appropriate affinities such that tumor cells with typical antigen densities of 10(4)-10(5) molecules per cell will be lysed and normal cells that have lower levels of the antigen will be spared.
Parallel frequency-domain optical coherence tomography scatter-mode imaging of the hamster cheek pouch using a thermal light source (2008)

We use a parallel frequency-domain optical coherence tomography (FDOCT) system to generate a scatter-mode image of the hamster cheek pouch epithelium. To our knowledge, this is the first optical coherence tomography (OCT) image of a biological sample obtained using a thermal light source in the frequency domain. The system employs an imaging spectrometer to acquire depth-resolved profiles from adjacent spatial points without the need for any scanning. To enable this imaging modality, we have considered that signals originating from multiple depths combine in a different manner in FDOCT compared to time-domain optical coherence tomography (TDOCT). Because a multicomponent FDOCT signal is a coherent sum, it is necessary to limit the number of modes that contribute to the detected signal. Conversely, multicomponent TDOCT signals can be represented as incoherent sums, where increasing the number of modes improves the signal.
Use-dependent block of excitatory amino acid currents in cultured neurons by ketamine (1987)

1. Mouse hippocampal neurons grown in dissociated cell culture were patch clamped using a whole cell voltage clamp (discontinuous switching clamp) technique. The currents generated by pressure applications of excitatory amino acids were studied over a wide range of holding potentials, and current-voltage curves were plotted. Excitatory amino acids that activated the N-methyl-D-aspartic acid (NMDA) receptor demonstrated some degree of desensitization with repeated applications, whereas the currents observed in response to kainic acid (KAI) did not. Desensitization could be minimized by keeping the frequency of application sufficiently low (i.e., less than 0.1 Hz). 2. The short-acting dissociative anaesthetic, ketamine (2-50 microM), selectively blocked L-aspartic acid (L-Asp), NMDA, and L-glutamic acid (L-Glu) currents while sparing those in response to KAI. Therefore, ketamine is a relatively selective blocker of the NMDA response versus that (those) activated by KAI. 3. The block by ketamine of excitatory amino acid currents is highly voltage dependent. Concentrations of ketamine that had little effect on outward current responses at depolarized potentials were quite effective at blocking inward current responses at hyperpolarized potentials. In contrast, DL-2-amino-5-phosphonovaleric acid (APV) was equally effective at blocking both inward and outward currents (voltage independent). The voltage dependence of ketamine (a positively charged molecule) could be accounted for if ketamine blocked the NMDA response by binding to a site that experienced 55% of the membrane field. 4. In the presence of ketamine, peak inward currents evoked by repeated applications of NMDA, L-Asp, or L-Glu progressively declined to a steady-state level of block (use-dependent block). This decrement occurred at frequencies much lower than those that were employed to demonstrate desensitization (in the absence of ketamine). Moving the membrane potential to depolarized values did not, in itself, relieve the ketamine block. However, if the appropriate excitatory amino acid (L-Asp, NMDA, L-Glu) was applied during the period of depolarization, a relief of the block could be demonstrated. No recovery from the blockade occurred with periods of rest (no amino acid application) as long as 5 min. Furthermore, no recovery was observed even when ketamine was washed out of the bathing solution until the appropriate agonist was applied. Thus recovery from blockade, like development of blockade, was use dependent.(ABSTRACT TRUNCATED AT 400 WORDS)
Nanoparticles as Nonviral Gene Delivery Vectors (2007)

Gene therapy, as therapeutic treatment to genetic or acquired diseases, is attracting much interest in the research community, leading to noteworthy developments over the past two decades. Although this field is still dominated by viral vectors, nonviral vectors have recently received an ever increasing attention in order to overcome the safety problems of their viral counterpart. This review presents the biological aspects involved in the gene delivery process and explores the recent developments and achievements of nonviral gene carriers.
Simplified Protocol of Solid-Phase cDNA Libraries for Multiple PCR Amplification (1996)

International audience
A Mild, Convenient Synthesis of Sulfinic Acid Salts and Sulfonamides from Alkyl and Aryl Halides. (2003)

Abstract For Abstract see ChemInform Abstract in Full Text.
Structure-Based Design of Inhibitors of Purine Nucleoside Phosphorylase. 4. A Study of Phosphate Mimics (1994)

9-(3,3-Dimethyl-5-phosphonopentyl)guanine was synthesized and found to be a potent inhibitor of purine nucleoside phosphorylase (PNP) (IC50 = 44 nM). A number of other functional end groups were investigated as phosphate mimics attached to the 9-position of guanine by this same alkyl side chain, which provided a sensitive method for the detection of any interaction of these groups with the phosphate binding site of PNP. Both the sulfonic acid (compound 13) and the carboxylic acid (compound 15) end groups interact significantly with the phosphate binding site, but in different ways, as determined by X-ray crystallographic analysis of the complexes. The sulfonic acid of 13, which binds about one-fourth as tightly as the phosphonate 12, binds in the phosphate subsite much like the phosphonic acid. The carboxylic acid, the interaction of which is much weaker, turns away from the center of the phosphate binding site to form hydrogen bonds with Ser 200 and Met 219. Thus, the only phosphate mimics that bind like phosphate itself are themselves highly ionic, probably with limited ability to penetrate cell membranes.
C-end rule peptides mediate neuropilin-1-dependent cell, vascular, and tissue penetration (2009)

Screening of phage libraries expressing random peptides for binding to prostate cancer cells primarily yielded peptides that had a C-terminal arginine (or rarely lysine) residue, usually in a consensus context R/KXXR/K. Phage expressing these sequences and synthetic nanoparticles coated with them bound to and were internalized into cells. The C-terminal arginine (or lysine) was essential to the activity; adding another amino acid, or even blocking the free carboxyl group of this arginine residue by amidation, eliminated the binding and internalizing activity. An internal R/KXXR/K can be exposed and switched on by a cleavage by a protease. The strict requirement for C-terminal exposure of the motif prompted us to term the phenomenon the C-end rule (CendR). Affinity chromatography showed that the CendR peptides bind to neuropilin-1 (NRP-1) on the target cells. NRP-1 is a cell-surface receptor that plays an essential role in angiogenesis, regulation of vascular permeability, and the development of the nervous system. VEGF-A165 and other ligands of NRP-1 possess a C-terminal CendR sequence that interacts with the b1 domain of NRP-1 and causes cellular internalization and vascular leakage. Our CendR peptides have similar effects, particularly when made multivalent through coupling to a particle. We also noted a unique and important activity of these peptides: penetration and transportation through tissues. The peptides were able to take payloads up to the nanoparticle size scale deep into extravascular tissue. Our observations have implications in drug delivery and penetration of tissue barriers and tumors.
CELL SURFACE INTERACTIONS WITH EXTRACELLULAR MATERIALS (1983)

The Hippo pathway was initially discovered in Drosophila melanogaster as a key regulator of tissue growth. It is an evolutionarily conserved signaling cascade regulating numerous biological processes, including cell growth and fate decision, organ size ...Read More
Enhanced synthesis of neutrophil-activating peptide-I/interleukin-8 in active ulcerative colitis (1992)

1. We studied neutrophil-activating peptide-1/interleukin-8 in inflammatory bowel disease. 2. Mucosal levels of neutrophil-activating peptide-1/interleukin-8 were significantly higher in patients with active ulcerative colitis [median 74.5 (range 17.7-450.8) pg/mg] than in patients with active Crohn's disease [10.4 (4-46.9) pg/mg; P less than 0.002] or in normal control subjects [10.4 (4-16.6) pg/mg; P less than 0.002]. 3. Circulating neutrophil-activating peptide-1/interleukin-8 was generally undetectable but there were higher levels of anti-neutrophil-activating peptide-1/interleukin-8 antibodies in patients with active ulcerative colitis [62.9 (3.4-239) ng/ml] than in patients with active Crohn's disease [5.9 (2.1-18.10) ng/ml; P less than 0.001] or in control subjects [6.1 (3.2-15.8) ng/ml; P less than 0.001]. 4. Neutrophil-activating peptide-1/interleukin-8 may be of specific functional importance in mediating inflammation in ulcerative colitis.
Effects of Celecoxib, a Novel Cyclooxygenase‐2 Inhibitor, on Platelet Function in Healthy Adults: A Randomized, Controlled Trial (2000)

Conventional nonsteroidal anti-inflammatory drugs (NSAIDs) nonspecifically inhibit cyclooxygenase-1 (COX-1), an enzyme critical to normal platelet function, and COX-2, which mediates inflammatory response mechanisms. Celecoxib, an antiarthritic agent that inhibits COX-2 but spares COX-1 at therapeutic doses, is expected to have minimal effects on platelet function. A double-blind, randomized, placebo-controlled study of 10 days' duration was conducted in 24 healthy adults to compare the effects on platelet function of a supratherapeutic dose of celecoxib (600 mg bid) with a standard dose of naproxen (500 mg bid), a conventional NSAID. Ex vivo platelet aggregation in response to standard agonists (collagen, arachidonate, or U46619 [a thromboxane A2 receptor agonist]), bleeding time, and serum thromboxane B2 (TxB2) level were measured. Unlike celecoxib or placebo, naproxen produced statistically significant reductions in platelet aggregation and serum TxB2 levels and increased bleeding time. The results indicate that even at supratherapeutic doses, celecoxib will not interfere with normal mechanisms of platelet aggregation and hemostasis, supporting the premise that celecoxib is COX-1 sparing relative to conventional NSAIDs.
Thermal response of skin to cyclic pressure and pressure with shear: a technical note. (2001)

The thermal response of skin to pressure alone and to pressure with shear was compared under cyclic loading conditions. Stresses were applied to the anterior aspect of the leg of three healthy subjects for time intervals up to 10 min, and the difference in temperature between the stressed site and a contralateral control site was assessed after load release. The thermal recovery time (TRT), the time interval between load release and either a maximum or a stabilization in the temperature difference vs. time record was determined. Results demonstrated that for a resultant stress of 142.9 kPa, TRTs were longer for combined pressure and shear than for pressure alone. For Subjects A, B, and C, TRT increases were 1.5 min, 5.5 min, and 2.0 min respectively. For a resultant stress magnitude of 71.4 kPa, increases were 1.5 min, 3.5 min, and -0.5 min respectively. Comparing responses for different resultant stress magnitudes for pressure-only application, TRTs were 1.5 min, 1.5 min, and 5.5 min longer for the 142.9-kPa condition than for the 71.4-kPa condition for Subjects A, B, and C. For combined pressure and shear, increases were 1.5 min, 3.5 min, and 8.0 min respectively. A next step will be to determine if the TRT differences measured here are physiologically relevant and have clinical meaning. The thermal response assessment method could then potentially be used to quantitatively evaluate the effects of different interface design features in lower-limb prosthetics on tissue response.
InAs-based heterojunction bipolar transistors (2002)

The first InAlAs/InAs heterojunction bipolar transistors are reported. A current gain of 100 at room temperature is measured. The base-collector junction is an InAs pn homojunction, which is optimised to have low reverse leakage at room temperature. The emitter is pseudomorphic AlInAs, linearly graded to increase the barrier which inhibits hole injection into the emitter.
Endogenous tumor-reactive CD8+T cells are differentiated effector cells expressing high levels of CD11a and PD-1 but are unable to control tumor growth (2013)

Immunotherapies aimed at enhancing natural or endogenous antitumor T-cell immunity in patients affected by advanced malignancies are currently being implemented in the clinic with promising results. In order to optimize therapeutic protocols and monitor the effectiveness of such therapies, reliable biomarkers are needed. We used CD11a, an integrin that is upregulated on the surface of effector and memory CD8<sup>+</sup> T cells, and PD-1, an immunoregulatory receptor expressed by activated T cells, as biomarkers to identify, quantify and monitor endogenous tumor-reactive cytotoxic T lymphocytes (CTLs) in two mouse tumor models and in the peripheral blood of 12 patients affected by Stage IV melanoma. High expression levels of CD11a and PD-1 were detected among CD8<sup>+</sup> T cells residing within primary and metastatic murine tumor sites, as well as in spontaneous murine breast cancer tissues. In the peripheral blood of melanoma patients, tumor antigen-specific CD8<sup>+</sup> T cells were associated with a population of CD11a<sup>high</sup> CD8<sup>+</sup> T cells that co-expressed high levels of PD-1. Healthy donors exhibited a comparatively much lower frequency of such PD-1<sup>+</sup>CD11a<sup>high</sup>CD8<sup>+</sup> T cells. Phenotypic analyses demonstrated that CD11a<sup>high</sup>CD8<sup>+</sup> T cells are proliferating (Ki67<sup>+</sup>) and activated (CD62L<sup>-</sup>CD69<sup>+</sup>). Increased CD11a<sup>high</sup>CD8<sup>+</sup> T cells and delayed tumor growth were observed in PD-1 deficient mice, suggesting that the antitumor effector functions of CD8<sup>+</sup> T cells is compromised by an elevated expression of PD-1. The CD11a<sup>high</sup>CD8<sup>+</sup> T-cell population expresses high levels of PD-1 and presumably constitutes the cellular target of PD-1 blockade therapy. The expression level of CD11a and PD-1 by CD8<sup>+</sup> T cells may therefore represent a novel biomarker to identify and monitor endogenous tumor-reactive CTLs. This may not only provide an immunological readout for evaluating the efficacy of immunotherapy but also contribute to the selection of cancer patients who are likely to benefit from anti-PD-1 therapy.
View-Independent Action Recognition from Temporal Self-Similarities (2010)

This paper addresses recognition of human actions under view changes. We explore self-similarities of action sequences over time and observe the striking stability of such measures across views. Building upon this key observation, we develop an action descriptor that captures the structure of temporal similarities and dissimilarities within an action sequence. Despite this temporal self-similarity descriptor not being strictly view-invariant, we provide intuition and experimental validation demonstrating its high stability under view changes. Self-similarity descriptors are also shown to be stable under performance variations within a class of actions when individual speed fluctuations are ignored. If required, such fluctuations between two different instances of the same action class can be explicitly recovered with dynamic time warping, as will be demonstrated, to achieve cross-view action synchronization. More central to the current work, temporal ordering of local self-similarity descriptors can simply be ignored within a bag-of-features type of approach. Sufficient action discrimination is still retained in this way to build a view-independent action recognition system. Interestingly, self-similarities computed from different image features possess similar properties and can be used in a complementary fashion. Our method is simple and requires neither structure recovery nor multiview correspondence estimation. Instead, it relies on weak geometric properties and combines them with machine learning for efficient cross-view action recognition. The method is validated on three public data sets. It has similar or superior performance compared to related methods and it performs well even in extreme conditions, such as when recognizing actions from top views while using side views only for training.
Cell cycle checkpoints, genetic instability and cancer. (1993)

During the cell cycle, the order of events is maintained by controls termed checkpoints. Two checkpoints are sensitive to DNA damage, one that acts before mitosis and a second that acts before DNA replication. This is relevant to cancer because checkpoint mutants show genetic instability, and such instability is characteristic of many cancers. Studies of checkpoints in normal and cancer cells suggest a mechanistic relationship to the central cell cycle control p34CDC2 and its regulators. We suggest how mutations in these genes and those with a role in DNA metabolism may affect the function of checkpoints. A further link between checkpoints and cancer may be the p53 protein, which appears to function at the G1-S checkpoint. Consideration of checkpoints may provide more effective means for cancer treatment.
Molecular characterization of Hor v 9. Conservation of a T-cell epitope among group IX pollen allergens and human VCAM and CD2. (1996)

We have cloned, sequenced and expressed a recombinant group IX pollen allergen from barley (Hordeum vulgare). Hor v 9 is a polypeptide of 313 amino acids. The Hor v 9 cDNA clone was engineered into the E. coli protein expression vector pMAL and expressed as a fusion of maltose binding protein and truncated Hor v 9. Polyclonal antibodies to the fusion protein were raised in mice. Cross-reactive proteins, RNA and DNA homologues were found in many agricultural species including wheat, rye, triticale, oats, maize, sunflower and flax. The presence of group IX-like proteins in a variety of agricultural crops may represent a previously uncharacterized aeroallergenic occupational hazard. Sequence comparisons of the barley allergen, Hor v 9, with Poa p 9 and other cloned group IX pollen allergens revealed putative structural domains common to all. These include a signal peptide, two conserved immunoglobulin-like motifs, a 150 amino acid highly conserved carboxyterminal domain and a carboxyterminal transmembrane helix. This structural arrangement is also found in cell adhesion molecules. The highly conserved T-cell epitope previously characterized and mapped in group IX allergens (and present in Hor v 9) was found in several human cell adhesion molecule sequences (VCAM, NCAM and CD2). This T-cell epitope corresponded to the most highly conserved amino acid residues common to all group IX homologues sequenced to date. CD2 and VCAM are known to play a role in allergic inflammation: VCAM is involved in the recruitment of lymphocytes to sites of inflammation, and cross-linking CD2 leads to T-cell activation. We anticipate that the similar structural arrangement of group IX allergens and human cell adhesion molecules, as well as the presence of a T-cell epitope common to group IX pollen allergens and cell adhesion molecules, will have important consequences in the natural history of the atopic immune response.
DNMT3L Stimulates the DNA Methylation Activity of Dnmt3a and Dnmt3b through a Direct Interaction (2004)

In mammals, the resetting of DNA methylation patterns in early embryos and germ cells is crucial for development. Two DNA methyltransferases, Dnmt3a and Dnmt3b, are responsible for the creation of DNA methylation patterns. Dnmt3L, a member of the Dnmt3 family, has been reported to be necessary for maternal methylation imprinting, possibly by interacting with Dnmt3a and/or Dnmt3b (Hata, K., Okano, M., Lei, H., and Li, E. (2002) Development 129, 1983-1993). In the present study, the effect of DNMT3L, a human homologue of Dnmt3L, on the DNA methylation activity of mouse Dnmt3a and Dnmt3b was examined in vitro. DNMT3L enhanced the DNA methylation activity of Dnmt3a and Dnmt3b about 1.5-3-fold in a dose-dependent manner but did not enhance the DNA methylation activity of Dnmt1. Although the extents of stimulation were different, a stimulatory effect on the DNA methylation activity was observed for all of the substrate DNA sequences examined, such as those of the maternally methylated SNRPN and Lit-1 imprinting genes, the paternally methylated H19 imprinting gene, the CpG island of the myoD gene, the 5 S ribosomal RNA gene, an artificial 28-bp DNA, poly(dG-dC)-poly(dG-dC), and poly(dI-dC)-poly(dI-dC). DNMT3L could not bind to DNA but could bind to Dnmt3a and Dnmt3b, indicating that the stimulatory effect of DNMT3L on the DNA methylation activity may not be due to the guiding of Dnmt3a and Dnmt3b to the targeting DNA sequence but may comprise a direct effect on their catalytic activity. The carboxyl-terminal half of DNMT3L was found to be responsible for the enhancement of the enzyme activity.
Leukocyte Responses to Injury (1993)

Injury elicits a response from all cells of the immune system in which cytokines and other metabolic products of activated leukocytes can act either beneficially to provide for enhanced host resistance or deleteriously to depress the function of remote organs and cause what has been termed systemic inflammation. These at times antithecal responses of leukocytes that appear to integrate postinjury changes in the neuroendocrine, immune, and coagulation systems have been implicated as principal causative factors in multiple systems organ failure. Numerous investigators have evaluated a variety of therapeutic agents to prevent and control infection by restoring leukocyte function, while others have evaluated antagonists and monoclonal antibodies as a means of controlling the exaggerated and persistent actions of leukocytes and cytokines caused by systemic inflammation. The redundancies of the cell populations and the cytokines and other metabolites produced by the cells predictably limit the effectiveness of any single agent and make clinical evaluation of such agents difficult.