gebhart/patrepeval huggingface dataset:
ST2/T1 Protein Functionally Binds to Two Secreted Proteins from Balb/c 3T3 and Human Umbilical Vein Endothelial Cells but Does Not Bind Interleukin 1 (1995)

The ST2/T1 receptor, a homologue of the interleukin 1 receptor (IL-1R), was expressed in COS and Drosophila S2 cells as a human IgG-Fc fusion protein. While a type I IL-1RFc fusion protein bound human IL-1 in vitro, the ST2Fc fusion protein did not. Furthermore, IL-1 stimulated a synthetic interleukin-8 promoter reporter gene that was cotransfected into Jurkat cells with a full-length IL-1R type I (IL-1RI) or a chimeric receptor composed of the IL-1RI extracellular domain and ST2 intracellular domain. In contrast, IL-1 did not stimulate the interleukin-8 promoter when cotransfected with a full-length ST2 or an ST2 extracellular/IL-1R intracellular domain fusion protein. Both IL-1RI and the IL-1R/ST2R chimeric receptor also activated a receptor-associated kinase and CSBP/p38 MAP kinase. Using ST2Fc receptor, we have identified, through receptor precipitation, receptor-dot blot and surface plasmon resonance, a putative ligand of ST2 secreted from Balb/c 3T3 and human umbilical vein endothelial cells. The putative ligand was also able to stimulate CSBP/p38 MAP kinase through the ST2 receptor. These results suggest that the ST2 is not an IL-1 receptor but rather has its own cognate ligand.
Guanylate cyclase C-mediated antinociceptive effects of linaclotide in rodent models of visceral pain (2009)

BACKGROUND Linaclotide is a novel, orally administered investigational drug currently in clinical development for the treatment of constipation-predominant irritable bowel syndrome (IBS-C) and chronic idiopathic constipation. Visceral hyperalgesia is a major pathophysiological mechanism in IBS-C. Therefore, we investigated the anti-nociceptive properties of linaclotide in rodent models of inflammatory and non-inflammatory visceral pain and determined whether these pharmacological effects are linked to the activation of guanylate cyclase C (GC-C). METHODS Orally administered linaclotide was evaluated in non-inflammatory acute partial restraint stress (PRS) and acute water avoidance stress (WAS) models in Wistar rats, and in a trinitrobenzene sulfonic acid (TNBS)-induced inflammatory model in Wistar rats and GC-C null mice. KEY RESULTS In TNBS-induced colonic allodynia, linaclotide significantly decreased the number of abdominal contractions in response to colorectal distension without affecting the colonic wall elasticity change in response to distending pressures after TNBS. However, linaclotide had no effect on visceral sensitivity under basal conditions. In addition, linaclotide significantly decreased colonic hypersensitivity in the PRS and WAS models. In wild type (wt) and GC-C null mice, the instillation of TNBS induced similar hyperalgesia and allodynia. However, in post-inflammatory conditions linaclotide significantly reduced hypersensitivity only in wt mice, but not in GC-C null mice. CONCLUSIONS & INFERENCES These findings indicate that linaclotide has potent anti-nociceptive effects in several mechanistically different rodent models of visceral hypersensitivity and that these pharmacological properties of linaclotide are exerted through the activation of the GC-C receptor. Therefore, linaclotide may be capable of decreasing abdominal pain in patients suffering from IBS-C.
A crash avoidance system based upon the cockroach escape response circuit (2002)

A crash avoidance system for automobiles is developed based upon a distributed network of artificial neurons that mimic the neural organization of the escape system in the American cockroach. The cockroach escape circuit is shown to be an excellent source of inspiration for the development of a collision avoidance system. The crash avoidance system is implemented in an artificial neural network which is trained off-line, but then is shown to produce real-time performance. A collision avoidance scheme which makes use of a crash alarm strategy is developed for training the neural network. A dynamic model of a four-wheeled vehicle with front wheel steering and realistic performance constraints is used to test the crash avoidance system. Simulation results show that the well-trained neural network causes successful, reflexive crash avoidance behaviors in a dynamic environment without a priori information.
Antibody Specificities Associated with Neutralization Breadth in Plasma from Human Immunodeficiency Virus Type 1 Subtype C-Infected Blood Donors (2009)

Defining the specificities of the anti-human immunodeficiency virus type 1 (HIV-1) envelope antibodies able to mediate broad heterologous neutralization will assist in identifying targets for an HIV-1 vaccine. We screened 70 plasmas from chronically HIV-1-infected individuals for neutralization breadth. Of these, 16 (23%) were found to neutralize 80% or more of the viruses tested. Anti-CD4 binding site (CD4bs) antibodies were found in almost all plasmas independent of their neutralization breadth, but they mainly mediated neutralization of the laboratory strain HxB2 with little effect on the primary virus, Du151. Adsorption with Du151 monomeric gp120 reduced neutralizing activity to some extent in most plasma samples when tested against the matched virus, although these antibodies did not always confer cross-neutralization. For one plasma, this activity was mapped to a site overlapping the CD4-induced (CD4i) epitope and CD4bs. Anti-membrane-proximal external region (MPER) (r = 0.69; P < 0.001) and anti-CD4i (r = 0.49; P < 0.001) antibody titers were found to be correlated with the neutralization breadth. These anti-MPER antibodies were not 4E10- or 2F5-like but spanned the 4E10 epitope. Furthermore, we found that anti-cardiolipin antibodies were correlated with the neutralization breadth (r = 0.67; P < 0.001) and anti-MPER antibodies (r = 0.6; P < 0.001). Our study suggests that more than one epitope on the envelope glycoprotein is involved in the cross-reactive neutralization elicited during natural HIV-1 infection, many of which are yet to be determined, and that polyreactive antibodies are possibly involved in this phenomenon.
Indicators of prognosis after hepatic resection for colorectal secondaries. (1991)

From 1960 to 1988, 266 patients underwent resection of colorectal secondaries to the liver with curative intent. All patients were followed until April 1, 1990, or death, with a median follow-up time of 52 months. Nine patients with minimal macroscopic residual disease and 38 patients with all gross tumor removed but positive margins showed a poor prognosis with a median survival time of 13.3 months, the longest being 42 months. Of the 219 patients having potentially curative resection, 12 patients died postoperatively (5.5%). Actuarial 5, 10 and 20-year survival for the remaining 207 patients was 39%, 28%, and 18%, respectively. At April 1, 1990, 77 patients were alive with no evidence of disease for up to 24 years, and 12 patients had died without recurrence. The following factors were associated with less favorable crude survival: presence and extent of mesenteric lymph node involvement (p = 0.0003), grade III/IV primary tumor (p = 0.035), synchronous diagnosis of metastases (p = 0.017), satellite metastases (p = 0.0003), limited resection margins (p = 0.019), and nonanatomic procedures (p = 0.013). With respect to disease-free survival, grading of the primary (p = 0.055) and the extent of clear margins (p = 0.019) failed to achieve statistical significance. Two other criteria are commonly recommended as absolute contraindications to hepatic resection: extrahepatic disease and the presence of four or more independent metastases. A radical excision of all detectable disease may rarely be possible in these circumstances. Nevertheless, within the curative settings, no significant predictive value regarding either overall or disease-free survival was found in this series. Three corresponding "high risk" patients are alive without disease at 5 to 11 years from hepatic resection. These patients with more advanced intrahepatic or concomitant limited extrahepatic disease require a particularly thorough diagnostic work up. As no superior therapeutic alternative is currently available, an aggressive surgical approach may occasionally be justified, and may, in a small portion, result in definite tumor control.
The role of antibodies to PrP in the diagnosis of transmissible spongiform encephalopathies. (1993)

Transmissible spongiform encephalopathies (TSE) are progressive degenerative disorders of the central nervous system. Efficient and accurate identification of these disorders is necessitated by their transmissibility and fatal prognosis. The availability of polyclonal and monoclonal antibodies to a TSE disease-specific protein marker PrPSC affords the sensitivity and specificity for immuno-diagnostic assays. The majority of PrPSC antigenic sites are species-directed, involve non-self sites and are common to both the normal host precursor (PrPC) and the modified disease form. The availability of these antigenic sites is highly restricted by conformational influences resulting in epitope-dependent restrictions on antibody binding. Diagnostic immunoassays for TSE have relied largely on immunocytochemistry and immunoblotting. Restrictions on epitope availability have lead to the formulation by several laboratories of a variety of techniques to unmask PrP specific epitopes. In addition, diagnosis requires the ability to detect PrPSC specifically in tissue which can also contain immuno-reactive PrPC. Immuno-detection techniques are discussed relative to their range of application, ease of interpretation, specificity and sensitivity.
Phase-referenced Doppler optical coherence tomography in scattering media (2005)

We present a fiber-based, low-coherence interferometer that significantly reduces phase noise by incorporating a second, narrowband, continuous-wave light source as a phase reference. By incorporating this interferometer into a Doppler OCT system, we demonstrate significant velocity noise reduction in reflective and scattering samples using processing techniques amenable to real-time implementation. We also demonstrate 90% suppression of velocity noise in a flow phantom.
Trapping and aligning carbon nanotubes via substrate geometry engineering (2004)

We present a simple method to place pregrown carbon nanotubes at specified locations on geometrically patterned silicon devices. Following room-temperature solution deposition, the nanotubes span gaps between pairs of tooth-shaped anchors serving as mechanical and/or electrical contacts. With a single deposition step, at least 50% of the anchor pairs are spanned by nanotubes. With the simultaneous application of modest local electric fields during deposition, the yield of successfully spanned anchor pairs is increased to 100%. Our placement method may find application in the reliable fabrication of nanotube-based electronic and microelectromechanical systems (MEMS) devices.
Gene Therapy on Trial (2000)

A flurry of reports and congressional hearings, sparked by the death of a volunteer in a study at Penn, are due in the next few weeks. The Penn episode points up a central problem: The field still lacks an ideal vector
Automotive engine control and hybrid systems: challenges and opportunities (2000)

The design of engine control systems has been traditionally carried out using a mix of heuristic techniques validated by simulation and prototyping using approximate average-value models. However, the ever increasing demands on passengers' comfort, safety, emissions, and fuel consumption imposed by car manufacturers and regulations call for more robust techniques and the use of cycle-accurate models. We argue that these models must be hybrid because of the combination of time-domain and event-based behaviors. We present a hybrid model of the engine in which both continuous and discrete time-domain as well as event-based phenomena are modeled in a separate but integrated manner. Based on this model, we formalize the specification of the overall engine control by defining a number of hybrid control problems. To cope with the difficulties arising in the design of hybrid controllers, a design methodology is proposed. This methodology consists of a relaxation of the hybrid problem by simplifying some of its components to obtain a solvable problem,and then deriving a solution to the original control problem by appropriately modifying the control law so obtained to take into consideration the original specifications and models. The effectiveness of this approach is illustrated on three challenging problems: fast force-transient control, cutoff control, and idle speed control.
Catheter-implanted prosthetic heart valves. Transluminal catheter implantation of a new expandable artificial heart valve in the descending thoracic aorta in isolated vessels and closed chest pigs. (1993)

A new expandable artificial heart valve was developed for implantation by a transluminal catheter technique without using thoracotomy or extracorporeal circulation. The aim of this study was to implant the valve in isolated vessels of the descending thoracic aorta as well as in closed chest pigs, and furthermore to study the prosthesis' mechanical stability and the valve function. The artificial valve was made by mounting a porcine aortic valve on an expandable stent. Before implantation, the stent-valve was compressed on a deflated balloon catheter and mounted inside an introducer sheath. After intravascular introduction to the descending thoracic aorta the stent-valve was discharged from the sheath. Implantation was performed by balloon inflation which expanded the stent-valve to a diameter exceeding the internal vessel's diameter. After balloon deflation the stent-valve maintained an expanded configuration ensuring a stable fixation against the vessel wall. In vitro implantations were performed in 36 isolated descending thoracic aorta specimens obtained from 80 kg pigs. Mechanical stability was evaluated by applying a downing load to the prosthesis. No displacement occurred at loads < or = 1 kg when a large balloon (31 mm) was used for implantation. Transvalvular pressure differences between 11-47 mmHg (median) were obtained at antegrade flowrates between 5-8 l/min. Furthermore, only moderate leakage flows were measured during retrograde perfusion. In vivo implantations were performed in six 80 kg pigs. Implantation was safe and easy, and angiograph and haemodynamic evaluations revealed essentially no stenosis or regurgitation. No complications in migration, perforation, hemorrhage or thrombosis were observed. This study indicates a good mechanical stability and valve function of the new expandable artificial valves.
Multimedia document presentation, information extraction, and document formation in MINOS: a model and a system (1986)

MINOS is an object-oriented multimedia information system that provides integrated facilities for creating and managing complex multimedia objects. In this paper the model for multimedia documents supported by MINOS and its implementation is described. Described in particular are functions provided in MINOS that exploit the capabilities of a modern workstation equipped with image and voice input-output devices to accomplish an active multimedia document presentation and browsing within documents. These functions are powerful enough to support a variety of office applications. Also described are functions provided for the extraction of information from multimedia documents that exist in a large repository of information (multimedia document archiver) and functions that select and transform this information. Facilities for information sharing among objects of the archiver are described; an interactive multimedia editor that is used for the extraction and interactive creation of new information is outlined; finally, a multimedia document formatter that is used to synthesize a new multimedia document from extracted and interactively generated information is presented. This prototype system runs on a SUN-3 workstation running UNIX'". An Instavox, directly addressable, analog device is used to store voice segments.
Physical chemistry : principles and applications in biological sciences : solutions manual (2002)

* Includes complete solutions to all end-of-chapter problems. * Available for sale to students with instructor's permission. This edition is thoroughly revised to ensure complete, accurate answers.
Overlapping and Selective Roles of Endothelial Intercellular Adhesion Molecule-1 (ICAM-1) and ICAM-2 in Lymphocyte Trafficking (2003)

The integrin LFA-1 interacts with a variety of ligands termed ICAMs. ICAM-1 and ICAM-2 are both expressed on endothelium and serve as counterreceptors during lymphocyte trafficking. In this study, we analyzed their relative contribution to lymphocyte recirculation through lymph nodes and to recruitment into lung and inflamed skin by blocking mAbs against ICAM-1 and ICAM-2 and mice deficient for ICAM-1. The entry of lymphocytes into peripheral and mesenteric lymph nodes was found to be unaffected by the functional deletion of either ICAM-1 or ICAM-2. However, when both pathways were blocked, recirculation through lymph nodes was strongly reduced. Trapping of lymphocytes in the lung after i.v. injection is partly mediated by LFA-1/ICAM interactions; the data presented in this study show an exclusive role of ICAM-1 in LFA-1-dependent lung trapping. Similarly, ICAM-1, but not ICAM-2, was required for the migration of T effector cells into the inflamed skin. These results indicate that ICAM-1 and ICAM-2 have redundant functions in lymphocyte recirculation through lymph nodes, but ICAM-1 is unique in supporting migration into inflamed sites and trapping within the lung.
Manipulation of micrometer sized particles within a micromachined fluidic device to form two-dimensional patterns using ultrasound (2007)

Ultrasonic manipulation, which uses acoustic radiation forces, is a contactless manipulation technique. It allows the simultaneous handling of single or numerous particles (e.g., copolymer beads, biological cells) suspended in a fluid, without the need for prior localization. Here it is reported on a method for two-dimensional arraying based on the superposition of two in-plane orthogonally oriented standing pressure waves. A device has been built and the experimental results have been compared with a qualitative analytical model. A single piezoelectric transducer is used to excite the structure to vibration, which consists of a square chamber etched in silicon sealed with a glass plate. A set of orthogonally aligned electrodes have been defined on one surface of the piezoelectric. This allows either a quasi-one-dimensional standing pressure field to be excited in one of two directions or if both electrodes are activated simultaneously a two-dimensional pressure field to be generated. Two different operational modes are presented: two signals identical in amplitude and frequency were used to trap particles in oval shaped clumps; two signals with slightly different frequencies to trap particles in circular clumps. The transition between the two operational modes is also investigated.
Characterization of Human Activating Transcription Factor 4, a Transcriptional Activator That Interacts with Multiple Domains of cAMP-responsive Element-binding Protein (CREB)-binding Protein (CBP) (1997)

We demonstrate that human activating transcription factor 4 (hATF4), a member of the activating transcription factor/cAMP-responsive element-binding protein (ATF/CREB) family of transcription factors, is a potent transcriptional activator in both mammalian cells and yeast. The N-terminal 113 amino acids of hATF4 activate transcription efficiently, and unexpectedly, the C-terminal bZip DNA binding domain of hATF4 also activates transcription, albeit weakly. Our results indicate that hATF4 interacts with several general transcription factors: TATA-binding protein, TFIIB, and the RAP30 subunit of TFIIF. In addition, hATF4 interacts with the coactivator CREB-binding protein (CBP) at four regions: 1) the KIX domain, 2) a region that contains the third zinc finger and the E1A-interacting domain, 3) a C-terminal region that contains the p160/SRC-1-interacting domain, and 4) the recently identified histone acetyltransferase domain. Interestingly, both the N-terminal and C-terminal regions of hATF4 interact with the above general transcription factors and CBP, providing a mechanistic explanation for their ability to activate transcription. Consistent with its role as a coactivator, CBP potentiates the ability of hATF4 to activate transcription. The potential significance of the interaction between hATF4 and multiple factors is discussed.
Ion Solvation by Channel Carbonyls Characterized by17O Solid-State NMR at 21 T (2005)

Recently available ultrahigh magnetic fields offer new opportunities for studies of quadrupole nuclei in biological solids because of the dramatic enhancement in sensitivity and resolution associated with the reduction of second-order quadrupole interactions. Here, we present a new approach for understanding the function and energetics of ion solvation in channels using solid-state 17O NMR spectroscopy of single-site 17O-labeled gramicidin A. The chemical shift and quadrupole coupling parameters obtained in powder samples of lyophilized material are similar to those shown in the literature for carbonyl oxygens. In lipid bilayers, it is found that the carbonyl 17O anisotropic chemical shift of Leu10, one of the three carbonyl oxygens contributing to the ion binding site in gramicidin A, is altered by 40 ppm when K+ ion binds to the channel, demonstrating a high sensitivity to such interactions. Moreover, considering the large breadth of the carbonyl 17O chemical shift (>500 ppm), the recording of anisotropic 17O chemical shifts in bilayers aligned with respect to magnetic field B0 offers high-quality structural restraints similar to 15N and 13C anisotropic chemical shifts.
Site-directed integration of the cre gene mediated by Cre recombinase using a combination of mutant lox sites (2002)

The Cre-lox system is an important tool for genetic manipulation. To promote integrative reactions, two strategies using mutant lox sites have been developed. One is the left element/right element (LE/RE)-mutant strategy and the other is the cassette exchange strategy using heterospecific lox sites such as lox511 or lox2272. We compared the recombination efficiencies using these mutant lox sites in embryonic stem (ES) cells, and found that the combination of the LE/RE mutant and lox2272 showed high recombination efficiency and stability of the recombined structure. Taking advantage of this stability, we successfully integrated the cre gene into the mutant lox sites by Cre-mediated recombination. Germ line chimeric mice were produced from the cre-integrated ES cell clones, and Cre-expressing mouse lines were established. The inserted cre gene was stably maintained through the generations. This cre knock-in system using the LE/RE-lox2272 combination should be useful for the production of various cre mice for gene targeting or gene trapping.
NKTR-102 Efficacy versus irinotecan in a mouse model of brain metastases of breast cancer (2015)

Elevated and prolonged tumor SN38 exposure after NKTR-102 administration appears responsible for increased survival in this model of breast cancer brain metastasis. Further, SN38 concentrations observed in this study are clinically achieved with 145 mg/m(2) NKTR-102, such as those used in the BEACON trial, underlining translational relevance of these results.