gebhart/patrepeval huggingface dataset:
Intramolecular trimerization, a novel strategy for making multispecific antibodies with controlled orientation of the antigen binding domains (2016)

Here, we describe a new strategy that allows the rapid and efficient engineering of mono and multispecific trivalent antibodies. By fusing single-domain antibodies from camelid heavy-chain-only immunoglobulins (VHHs) to the N-terminus of a human collagen XVIII trimerization domain (TIE(XVIII)) we produced monospecific trimerbodies that were efficiently secreted as soluble functional proteins by mammalian cells. The purified VHH-TIE(XVIII) trimerbodies were trimeric in solution and exhibited excellent antigen binding capacity. Furthermore, by connecting with two additional glycine-serine-based linkers three VHH-TIE(XVIII) modules on a single polypeptide chain, we present an approach for the rational design of multispecific tandem trimerbodies with defined stoichiometry and controlled orientation. Using this technology we report here the construction and characterization of a tandem VHH-based trimerbody capable of simultaneously binding to three different antigens: carcinoembryonic antigen (CEA), epidermal growth factor receptor (EGFR) and green fluorescence protein (GFP). Multispecific tandem VHH-based trimerbodies were well expressed in mammalian cells, had good biophysical properties and were capable of simultaneously binding their targeted antigens. Importantly, these antibodies were very effective in inhibiting the proliferation of human epidermoid carcinoma A431 cells. Multispecific VHH-based trimerbodies are therefore ideal candidates for future applications in various therapeutic areas.
Expression of Lymphocytes FcεRII/CD23 in Allergic Children Undergoing Hyposensitization (1993)

Owing to the proposed role of Fc epsilon RII/CD23 in allergic diseases, we analyzed the expression of this receptor on peripheral blood lymphocytes (pan-B, pan-T and CD4+ or CD8+ T cells) and its autoproteolytic product sCD23 in serum. This was done in 10 asthmatic children allergic to Dermatophagoides pteronyssinus (Dpt) before and 6 weeks after hyposensitization. FACS analysis of double, direct immunofluorescence staining of the whole blood revealed an elevated percentage of Fc epsilon RII/CD23+ lymphocytes in allergic children (10.29 +/- 5.0), a significantly higher percentage than in nonallergic children (5.7 +/- 2.4, p < 0.05). The majority of Fc epsilon RII/CD23+ were on B cells. A significant positive correlation between the percentages of CD23+ lymphocytes and serum IgE levels was found (Spearman rank = 0.63, p < 0.05). The percentage of CD20+CD23+ lymphocytes significantly decreased after 6 weeks of hyposensitization (6.2 +/- 3.6, p < 0.05), while the percentage of CD20+ lymphocytes remained unchanged. Similarly, hyposensitization was followed by a reduction of total serum IgE levels, but Dpt-specific IgG4 and IgE remained unchanged.
Wetting and dewetting of Si/SiO<sub>2</sub>-wafers by free and lipidmonolayer covered aqueous solutions under controlled humidity (1994)

The spreading and stabilization of free and lipid monolayer covered films of aqueous solutions (of NaCl, glucose, polyethylene glycol and polylysine) on Si/SiO2 were studied between 60 and 95 % relative humidity. A film balance, equipped with an ellipsometer and a closed chamber for humidity control, was used. The time evolution of the film thickness and its lateral variation was monitored by imaging ellipsometry, while high precision thickness measurements were performed by null ellipsometry. The film thickness of NaCl and glucose solutions could be reversibly varied between about 10 Å and 1 000 Å for relative humidities between 60 and 95 %. Film thicknesses were about a factor of 4 to 10 larger than reported previously. The thickness-vs.-humidity curves are explained quantitatively by the Brunauer-Emett-Teller theory (BET) of multilayer adsorption, as well as by a modified disjoining-pressure-model by accounting for the chemical potential equilibrium of water between the atmosphere and the film and with respect to Raoult's law of vapour pressure lowering. Solutions of polyethylene glycol thinned to a thickness of one adsorbed macromolecular monolayer and the thickness could be reversibly varied between 8 and 14 Å for humidities between 60 and 95 %. Non soluble fatty acid monolayers spread spontaneously on the pre-stabilized fluid films by viscous fingering, driven by the Marangoni Effect. At repulsive disjoining pressures, the composite films remained stable and could be reversibly swollen and deswollen. Dewetting occurred at attractive interactions or at negative spreading parameters either by collapse from the edges or by local hole formation. 40 mM glucose solution films covered by an arachidic acid monolayer decomposed laterally (and in a reversible way) at high humidities (> 94.8 %) into domains varying in water layer thickness by about 1 000 Å.
Cutting Force Modeling and Optimization in 3D Plane Surface Machining (1999)

Abstract The prediction and optimization of cutting forces in the finishing machining of 3D plane surfaces using ball-end milling are presented in this paper. The cutting force model is developed based on the mechanistic modeling approach. This improved model is able to accurately predict the cutting forces for non-horizontal and cross-feed cutter movements typical in 3D finishing ball-end milling. Optimization of the cutting forces is used to determine both the tool path and the maximum feed rate in 3D plane surface finishing machining. The objective is to achieve highest machining efficiency and to ensure product quality. Experimental results have shown that the cutting force model gives excellent predictions of cutting forces in 3D finishing ball-end milling. The feasibility of the integrated process planning method has been demonstrated through the establishment of optimized process plans for the finishing machining of 3D plane surfaces.
Prevention of autoimmune type I diabetes by CD4+ suppressor T cells in superantigen-treated non-obese diabetic mice. (1993)

The development of autoimmune type I diabetes in the NOD mouse appears to be controlled by both genetic and environmental factors. This investigation was initiated to determine whether exogenous superantigens, as environmental factors, can influence the development of diabetes. Several staphylococcal enterotoxins (SE) (SEA, SEC1, SEC2, or SEC3), which are known superantigens, were injected i.v. into female NOD mice at 4 and 10 wk of age. At 32 wk of age, the incidence of diabetes in the SE-treated mice ranged from 6 to 12.5%; this was significantly lower than that of mice treated with PBS--64%. There was no significant difference in effectiveness among the various SE used. SE induced a modest decrease in T lymphocytes bearing specific V beta TCR 2 wk after injection, but this effect did not persist past 4 wk. To elucidate the mechanism of the SE effect, suppressor activity in SE-treated mice was evaluated. Splenocytes from SE-treated mice inhibited the transfer of diabetes by splenocytes from acutely diabetic NOD mice when injected into irradiated young NOD mice; only 10% became diabetic. In contrast, 83% of the mice receiving splenocytes from PBS-treated control mice became diabetic. Suppressor activity of splenocytes from SE-treated mice was diminished by the depletion of CD4+ T cells, but not by the depletion of CD8+ T cells, indicating that the suppressor cells belonged to the CD4+ T class of lymphocytes. On the basis of these observations, we conclude that exogenous superantigens activate CD4+ suppressor T cells, leading to the prevention of autoimmune type I diabetes in NOD mice.
Interactions between laminin and epithelial cells in intestinal health and disease (2001)

Laminins are a multigene family of extracellular matrix molecules. Quantitatively, they are one of the most abundant glycoproteins present in basement membranes. Functionally, they can modulate several key biological activities, including cell adhesion and migration, gene expression and cell survival. Variability in the spatial and temporal expression of laminins, as well as of their specific receptors of the integrin family, in various tissues and organs, suggests that different laminins perform distinct functions. This article focuses on the human intestinal epithelium as a paradigm to illustrate the potential relationship between laminin-cell interactions and the cell state. This rapidly renewing epithelium consists of spatially separated proliferative and differentiated cell populations located in the crypts and on the villi, respectively. Differential distributions of the various laminins and laminin-binding integrins have been observed along the crypt-villus axis in both the developing and the adult intestine, and important alterations in the pattern of laminin expression have been reported in various intestinal pathologies, such as tufting enteropathy, Crohn's disease and ulcerative colitis, and colorectal cancer. More-direct approaches, including experimentation with in vitro and in vivo models, have provided evidence in support of a role for laminins in intestinal cell functions. Although further work is still needed, laminins emerge more and more as key regulators of specific cell functions important in both intestinal health and intestinal disease.
Bis-guided evaluation of dexmedetomidine vs. midazolam as anaesthetic adjuncts in off-pump coronary artery bypass surgery (OPCAB) (2009)

Background. To assess the efficacy of midazolam and dexmedetomidine as induction agents and adjuncts to anaesthesia during OPCAB surgery. Patients and Methods. 107 patients scheduled for elective OPCAB surgery between 1st of January 2005 to 31 st of December 2007 were enrolled. Patients were randomly allocated into two groups Midazolam group (Group M, n=57) and Dexmedetomidine group (Group D, n=50). Patients in Group D (Dexmedetomidine group) received dexmedetomidine as initial i.v loading dose of 1 Âµg kg -1 over 1 minute (min) before induction of anaesthesia and 60 Âµg hr -1 continuous infusion thereafter until the end of surgery. Patients in group M (Midazolam group) received midazolam 0.1 mg kg -1 over 1 min before induction of anaesthesia and 2.5mg hrÂ­ 1 continuous infusion thereafter until the end of surgery. Anaesthesia was maintained with continuous i.v infusion of sufentanil 0.2 Âµg kg -1 h -1 , study drug infusion at a rate of 10 ml h -1 , and rocuronium 0.5 mg kg-1 h -1 supplemented with sevoflurane as required. Induction doses as well as anaesthetic maintenance supplementation doses were guided by the BIS reading near 50. Data collection included haemodynamic parameters (HR, MAP, CI & SVR), BIS readings (T0-T7) and sevoflurane concentrations (T3-T7) were recorded at the following data points, T0= baseline pre-induction, T1= immediately post-induction T2= during laryngoscopy & intubation, T3= skin incision, T4= sternotomy, T5= during revascularization of the left anterior descending (LAD) artery, T6= during revascularization of the obtuse marginal (OM) artery, T7= with chest closure at conclusion of surgery. Results. 5 patients in Group M and 3 patients in group D were excluded due to diversion to on pump technique. All baseline parameters were comparable among both groups. In group M (52 patients) SVR and BP had significantly decreased following induction (T1) compared to baseline (T0, p<0.0001), while HR and CI had significantly increased during T1 compared to baseline (T0, p<0.0001). Also parameters recorded thereafter were comparable to baseline values. In Group D (47 patients) all parameters recorded were comparable to baseline values with exception of HR that decreased significantly from T1-T7 compared to T0. BIS values recorded were comparable among both groups, however sevoflurane concentrations was significantly higher in Group M compared to group D (P<0.0001). Conclusion. Midazolam can alter hemodynamic response following induction of anaesthesia; however such changes are reversible and returned to baseline. Dexmedetomidine is more haemodynamic stable and more potent anaesthetic adjuvant compared to midazolam in patients undergoing OPCAB surgery.
Multimodal flexible cystoscopy for creating co-registered panoramas of the bladder urothelium (2012)

Bladder cancer is the most expensive cancer to treat due to the high rate of recurrence. Though white light cystoscopy is the gold standard for bladder cancer surveillance, the advent of fluorescence biomarkers provides an opportunity to improve sensitivity for early detection and reduced recurrence resulting from more accurate excision. Ideally, fluorescence information could be combined with standard reflectance images to provide multimodal views of the bladder wall. The scanning fiber endoscope (SFE) of 1.2mm in diameter is able to acquire wide-field multimodal video from a bladder phantom with fluorescence cancer "hot-spots". The SFE generates images by scanning red, green, and blue (RGB) laser light and detects the backscatter signal for reflectance video of 500-line resolution at 30 frames per second. We imaged a bladder phantom with painted vessels and mimicked fluorescent lesions by applying green fluorescent microspheres to the surface. By eliminating the green laser illumination, simultaneous reflectance and fluorescence images can be acquired at the same field of view, resolution, and frame rate. Moreover, the multimodal SFE is combined with a robotic steering mechanism and image stitching software as part of a fully automated bladder surveillance system. Using this system, the SFE can be reliably articulated over the entire 360° bladder surface. Acquired images can then be stitched into a multimodal 3D panorama of the bladder using software developed in our laboratory. In each panorama, the fluorescence images are exactly co-registered with RGB reflectance.
Modulation of Tumor-host Interactions, Angiogenesis, and Tumor Growth by Tissue Inhibitor of Metalloproteinase 2 via a Novel Mechanism (2004)

Solid tumors depend on angiogenesis for sustained growth. Tissue inhibitor of metalloproteinase 2 (TIMP-2) is an angiogenesis inhibitor initially characterized for its ability to block matrix metalloproteinases; however, recent data suggest that the antiangiogenic action of TIMP-2 may rely on matrix metalloproteinase-independent mechanisms. The aim of this study was to identify molecular pathways involved in the effects of TIMP-2 on processes dependent on tumor-host interactions such as angiogenesis. Using in vitro cell culture and a syngeneic murine tumor model, we compared the effects of TIMP-2 overexpression on gene expression profiles in vitro to those observed in vivo. Validating these findings by real-time quantitative PCR and layered protein scanning, we identified up-regulation of mitogen-activated protein kinase phosphatase 1 as an effector of the antiangiogenic function of TIMP-2. Up-regulation of mitogen-activated protein kinase phosphatase 1 in tumors overexpressing TIMP-2 leads to dephosphorylation of p38 mitogen-activated protein kinase and inhibition of tumor growth and angiogenesis. Phosphatase activity appears important in regulating tumor angiogenesis, offering a promising direction for the identification of novel molecular targets and antiangiogenic compounds for the treatment of cancer.
Protective effect of oleanolic acid against chemical-induced acute necrotic liver injury in mice. (1995)

OA protects against many, but not all, hepatotoxicants, and the hepatoprotective effect of OA may involve multiple mechanisms.
Studies on the Mechanism of Action of Colloidal Bismuth Subcitrate (1993)

The effects of colloidal bismuth subcitrate (CBS) on porcine pepsin have been studied in vitro. CBS inhibited pepsin activity in a pH-dependent manner. CBS was not active at pH 4.0 but inhibited pepsin activity at pH 1.0 (IC50: 2.3 +/- 0.09 mmol/l) and pH 2.0 (IC50: 8.9 +/- 0.7 mmol/l). This inhibition was reversible. In the presence of the sulfhydryl ligand mercaptoethanol, which prevents precipitation of CBS, the inhibitory potency of CBS increased. CBS bound to both positively (Amberlite) and negatively charged (Dowex) ion exchangers in a pH-dependent manner. With increasing acidity, binding to Amberlite increased, whereas binding to Dowex decreased. From these data we conclude that negatively charged bismuth salts derived from CBS bind at pH 2.0 and 1.0 via an ionic interaction to positively charged groups of pepsin, thereby inactivating the enzyme.
Substrate-Based Cyclic Peptidomimetics of Phe-Ile-Val That Inhibit HIV-1 Protease Using a Novel Enzyme-Binding Mode (1996)

Results are presented for inhibitors of HIV-1 protease that demonstrate a new strategy for developing peptidomimetics, involving the replacement of flexible segments of peptide substrates with conformationally constrained hydrolytically-stable macrocyclic structural mimics. A 15-membered macrocycle that imitates the tripeptide Phe-Ile-Val was designed and incorporated into the C-terminus of Ac-Leu-Val-Phe-CHOHCH2-{Phe-Ile-Val}-NH2, an inhibitor of HIV-1 protease derived from a substrate sequence. Advantages of the macrocycle over the acyclic peptide include constraining its components into their bioactive conformation and protecting the amide bonds from enzymatic degradation, the cycle being stable to acid, gastric proteases, and plasma. Molecular modeling and X-ray structural studies reveal that the cyclic inhibitors have a unique enzyme-binding mode, the sterically unencumbered hydroxyethylamine isostere binds via both its hydroxyl and protonated nitrogen to the anionic Asp25 catalytic residues. The novel macrocycle superimposes well on the linear peptidic inhibitor for which it was designed as a structural mimic. Structural mimicry led to functional mimicry as shown by comparable inhibition of the protease by cyclic and acyclic molecules. Further modification of the acyclic N-terminus (Leu-Val-Phe) gave stable, water-soluble, potent inhibitors of HIV-1 protease. This approach may have general application to the development of mimetics of other bioactive peptides, including inhibitors of other enzymes.
Porphyrin-Functionalized Single-Walled Carbon Nanotube Chemiresistive Sensor Arrays for VOCs (2012)

Single-walled carbon nanotubes (SWNTs) have been used extensively for sensor fabrication due to its high surface to volume ratio, nanosized structure and interesting electronic property. Lack of selectivity is a major limitation for SWNTs-based sensors. However, surface modification of SWNTs with a suitable molecular recognition system can enhance the sensitivity. On the other hand, porphyrins have been widely investigated as functional materials for chemical sensor fabrication due to their several unique and interesting physico-chemical properties. Structural differences between free-base and metal substituted porphyrins make them suitable for improving selectivity of sensors. However, their poor conductivity is an impediment in fabrication of prophyrin-based chemiresistor sensors. The present attempt is to resolve these issues by combining freebase- and metallo-porphyrins with SWNTs to fabricate SWNTs-porphyrin hybrid chemiresistor sensor arrays for monitoring volatile organic carbons (VOCs) in air. Differences in sensing performance were noticed for porphyrin with different functional group and with different central metal atom. The mechanistic study for acetone sensing was done using field-effect transistor (FET) measurements and revealed that the sensing mechanism of ruthenium octaethyl porphyrin hybrid device was governed by electrostatic gating effect, whereas iron tetraphenyl porphyrin hybrid device was governed by electrostatic gating and Schottky barrier modulation in combination. Further, the recorded electronic responses for all hybrid sensors were analyzed using a pattern-recognition analysis tool. The pattern-recognition analysis confirmed a definite pattern in response for different hybrid material and could efficiently differentiate analytes from one another. This discriminating capability of the hybrid nanosensor devices open up the possibilities for further development of highly dense nanosensor array with suitable porphyrin for E-nose application.
Short communication: Single nucleotide polymorphisms in an intron of the ovine calpastatin gene (2000)

Calpastatin is the specific inhibitor of the ubiquitous calcium-dependent proteases mu-calpain and m-calpain. Enzyme assay data from sheep and cattle inversely correlates post-mortem muscle calpastatin levels with ultimate meat tenderness. Genetic markers of meat quality may therefore be found linked to the calpastatin gene (CAST). A three-allele system detected by polymerase chain reaction-single strand conformational polymorphism (PCR-SSCP) has been observed in the ovine CAST. The three allele amplimers have been fully nucleotide sequenced and their differences in terms of single nucleotide polymorphism (SNPs) in the intron region of the amplimer are reported and compared to a consensus sequence of the orthologous region of the cattle CAST. A PCR-RFLP for more rapid CAST genotyping of all three ovine alleles was also developed.
Defect photoluminescence from pulsed-laser-annealed ion-implanted Si (1981)

Low-temperature photoluminescence studies of pulsed-laser annealed self-ion-implanted Si are reported. Two sharp damage luminescence peaks W and G are found. The main peak W is strongest at a laser energy of 1.5 J/cm2 even though this gives good recrystallization of the amorphous surface region. Most of the W centers are created by solid-phase annealing of ion-implantation damage in a band beyond the laser-melted region. The G centers are present in the channeling tail of the implant before laser annealing.
Visualization of an extracellular mucoid layer of <i>Treponema denticola</i> ATCC 35405 and surface sugar lectin analysis of some <i>Treponema</i> species (1997)

Slime layers and capsules are common amongst medically relevant bacteria. We herein report that Treponema denticola, which has been associated with periodontitis, synthesizes or acquires an extracellular polysaccharide layer that we have observed through electron microscopy using the polysaccharide-specific dye Alcian blue and phosphotungstate. We have also visualized this extracellular layer by dark-field microscopy of Alcian blue-stained spirochete cells. A representative strain of each of the oral spirochete species T. denticola, Treponema vincentii and Treponema socranskii were differentiated by concanavalin A, phaseolus, lotus A and arachis lectins in a microtiter plate immunoassay for the detection of surface sugars.