gebhart/patrepeval huggingface dataset:
Dissection of the Neonatal Fc Receptor (FcRn)-Albumin Interface Using Mutagenesis and Anti-FcRn Albumin-blocking Antibodies (2014)

Albumin is the most abundant protein in blood and plays a pivotal role as a multitransporter of a wide range of molecules such as fatty acids, metabolites, hormones, and toxins. In addition, it binds a variety of drugs. Its role as distributor is supported by its extraordinary serum half-life of 3 weeks. This is related to its size and binding to the cellular receptor FcRn, which rescues albumin from intracellular degradation. Furthermore, the long half-life has fostered a great and increasing interest in utilization of albumin as a carrier of protein therapeutics and chemical drugs. However, to fully understand how FcRn acts as a regulator of albumin homeostasis and to take advantage of the FcRn-albumin interaction in drug design, the interaction interface needs to be dissected. Here, we used a panel of monoclonal antibodies directed towards human FcRn in combination with site-directed mutagenesis and structural modeling to unmask the binding sites for albumin blocking antibodies and albumin on the receptor, which revealed that the interaction is not only strictly pH-dependent, but predominantly hydrophobic in nature. Specifically, we provide mechanistic evidence for a crucial role of a cluster of conserved tryptophan residues that expose a pH-sensitive loop of FcRn, and identify structural differences in proximity to these hot spot residues that explain divergent cross-species binding properties of FcRn. Our findings expand our knowledge of how FcRn is controlling albumin homeostasis at a molecular level, which will guide design and engineering of novel albumin variants with altered transport properties.
Glycoconjugate profile and cd44 expression in human melanoma cell lines with different metastatic capacity (1995)

Changes in glycoconjugate production have been reported for tumor cells. In this study, we investigated the glycoconjugate expression pattern in normal human melanocytes and in a panel of 6 human melanoma cell lines with different metastatic capacity after s.c. inoculation into nude mice. Glycoconjugates were labeled in vitro with [35S] sulphate and [3H] glucosamine, purified from cells and culture medium by column chromatography and identified by treatment with specific glycosidases. Characterization of the purified glycoconjugate fractions as well as alcian-blue staining of xenograft lesions revealed that hyaluronic acid (HA) is the main glycoconjugate produced by all cell lines. Highly metastatic cell lines expressed higher levels of HA than melanocytes and than weakly metastatic or non-metastatic cell lines. In addition, a shift in dominance from chondroitin-sulphate proteoglycan to heparan-sulphate proteoglycan was observed with increasing metastatic capacity. We also studied the expression and binding activity of the HA receptor CD44. Immunoprecipitation experiments indicated high CD44 synthesis only in highly metastatic cell lines, but FACS analysis demonstrated approximately the same surface expression in melanocytes as in all cell lines. Adhesion assays to immobilized HA showed that CD44 can be present in an inactive or an active conformation. Our data suggest that a combination of increased HA production and the expression of CD44 on the cell surface may be associated with high metastatic potential of human melanoma cell lines in nude mice.
VELOCITY‐STACK PROCESSING1 (1989)

A bstract A conventional velocity‐stack gather consists of constant‐velocity CMP‐stacked traces. It emphasizes the energy associated with the events that follow hyperbolic traveltime trajectories in the CMP gather. Amplitudes along a hyperbola on a CMP gather ideally map onto a point on a velocity‐stack gather. Because a CMP gather only includes a cable‐length portion of a hyperbolic traveltime trajectory, this mapping is not exact. The finite cable length, discrete sampling along the offset axis and the closeness of hyperbolic summation paths at near‐offsets cause smearing of the stacked amplitudes along the velocity axis. Unless this smearing is removed, inverse mapping from velocity space (the plane of stacking velocity versus two‐way zero‐offset time) back to offset space (the plane of offset versus two‐way traveltime) does not reproduce the amplitudes in the original CMP gather. The gather resulting from the inverse mapping can be considered as the model CMP gather that contains only the hyperbolic events from the actual CMP gather. A least‐squares minimization of the energy contained in the difference between the actual CMP gather and the model CMP gather removes smearing of amplitudes on the velocity‐stack gather and increases velocity resolution. A practical application of this procedure is in separation of multiples from primaries. A method is described to obtain proper velocity‐stack gathers with reduced amplitude smearing. The method involves a t 2 ‐stretching in the offset space. This stretching maps reflection amplitudes along hyperbolic moveout curves to those along parabolic moveout curves. The CMP gather is Fourier transformed along the stretched axis. Each Fourier component is then used in the least‐squares minimization to compute the corresponding Fourier component of the proper velocity‐stack gather. Finally, inverse transforming and undoing the stretching yield the proper velocity‐stack gather, which can then be inverse mapped back to the offset space. During this inverse mapping, multiples, primaries or all of the hyperbolic events can be modelled. An application of velocity‐stack processing to multiple suppression is demonstrated with a field data example.
A Role for β-Cell-Expressed G Protein-Coupled Receptor 119 in Glycemic Control by Enhancing Glucose-Dependent Insulin Release (2007)

Pancreatic beta-cell dysfunction is a hallmark event in the pathogenesis of type 2 diabetes. Injectable peptide agonists of the glucagon-like peptide 1 (GLP-1) receptor have shown significant promise as antidiabetic agents by virtue of their ability to amplify glucose-dependent insulin release and preserve pancreatic beta-cell mass. These effects are mediated via stimulation of cAMP through beta-cell GLP-1 receptors. We report that the Galpha(s)-coupled receptor GPR119 is largely restricted to insulin-producing beta-cells of pancreatic islets. Additionally, we show here that GPR119 functions as a glucose-dependent insulinotropic receptor. Unlike receptors for GLP-1 and other peptides that mediate enhanced glucose-dependent insulin release, GPR119 was suitable for the development of potent, orally active, small-molecule agonists. The GPR119-specific agonist AR231453 significantly increased cAMP accumulation and insulin release in both HIT-T15 cells and rodent islets. In both cases, loss of GPR119 rendered AR231453 inactive. AR231453 also enhanced glucose-dependent insulin release in vivo and improved oral glucose tolerance in wild-type mice but not in GPR119-deficient mice. Diabetic KK/A(y) mice were also highly responsive to AR231453. Orally active GPR119 agonists may offer significant promise as novel antihyperglycemic agents acting in a glucose-dependent fashion.
Human Seminal Vesicle-Specific Antigen during Semen Liquefaction1 (1987)

Binding of monoclonal antibody MHS-5 to western blots of human seminal plasma was employed to follow the fate of a seminal vesicle-specific antigen (SVSA) during semen liquefaction. Ejaculates from four vasectomized donors were collected in a manner to inhibit liquefaction or to allow liquefaction to proceed at room temperature. Aliquots of the liquefying seminal fluid were removed at specific time points and further liquefaction inhibited with sodium dodecyl sulfate (SDS). Western blot analysis using monoclonal antibody MHS-5 demonstrated that the SVSA epitope in all donors was located on multiple bands ranging in mass from 15-92 kDa in unliquefied ejaculates; immunoreactive peptides below 15 kDa were not detected. As early as 5 min post ejaculation, immunoreactive bands below 15 kDa were identified in liquefying samples. During the same time period (5 min), immunoreactive bands of 69-71 and 58 kDa could not be immunologically detected in liquefying samples. A decrease in immunoreactive staining of components higher molecular mass was accompanied by a concomitant increase in immunoreactive staining of intermediate and small molecular mass molecules during the first 2 h of liquefaction. After 8-24 h of liquefaction, two immunoreactive bands of 10.9 and 12.5 kDa predominated. Between 24 and 48 h, each donor's ejaculate demonstrated a common single immunoreactive band of 10.9 kDa. These results indicate that there is a rapid transformation in mass of the SVSA with major 69-71 and 58 kDa bands being converted to forms of lower mass within 5 min of ejaculation.
Cytosolic Viral Sensor RIG-I Is a 5'-Triphosphate–Dependent Translocase on Double-Stranded RNA (2009)

Retinoic acid inducible-gene I (RIG-I) is a cytosolic multidomain protein that detects viral RNA and elicits an antiviral immune response. Two N-terminal caspase activation and recruitment domains (CARDs) transmit the signal, and the regulatory domain prevents signaling in the absence of viral RNA. 5'-triphosphate and double-stranded RNA (dsRNA) are two molecular patterns that enable RIG-I to discriminate pathogenic from self-RNA. However, the function of the DExH box helicase domain that is also required for activity is less clear. Using single-molecule protein-induced fluorescence enhancement, we discovered a robust adenosine 5'-triphosphate-powered dsRNA translocation activity of RIG-I. The CARDs dramatically suppress translocation in the absence of 5'-triphosphate, and the activation by 5'-triphosphate triggers RIG-I to translocate preferentially on dsRNA in cis. This functional integration of two RNA molecular patterns may provide a means to specifically sense and counteract replicating viruses.
Cisplatin-Induced Ototoxicity (2008)

IT dexamethasone protected the mouse ear against cisplatin-induced ototoxicity in a frequency-dependent manner. The present results suggest that IT dexamethasone may be a safe, simple, and effective intervention that minimizes cisplatin ototoxicity without interfering with the chemotherapeutic actions of cisplatin.
Target Directed Drug Synthesis: The Aminoacyl‐tRNA Synthetases as Possible Targets (1981)

Abstract The “tailor‐made” pharmaceutical has been an old dream ever since Paracelsus ' days. His saying “ Dosis sola facit venenum ” is still valid. The ideal pharmacon should inhibit the pathological process or the parasitical organism to a maximum while causing as little harm as possible to the human organism. In order to achieve this goal one must try to make use of metabolic differences between the metabolism of the pathological organism and normal human metabolism in a rational way. With today's improved knowledge of enzymatic processes this seems to be a possible and highly promising approach. The pharmaceutical should act upon a process of central importance, such as the process of protein biosynthesis, where the required highly accurate construction of the macromolecules is achieved by a “proofreading” process. It is shown that this “proofreading” mechanism exhibits specific difference in different species.
Conformational studies of a bicyclic, lactam-constrained parathyroid hormone-related protein-derived agonist (1999)

The N-terminal 1-34 segments of both parathyroid hormone (PTH) and parathyroid hormone-related protein (PTHrP) bind and activate the same membrane receptor in spite of major differences in their amino acid sequence. The hypothesis was made that they share the same bioactive conformation when bound to the receptor. A common structural motif in all bioactive fragments of the hormone in water/trifluoroethanol mixtures or in aqueous solution containing detergent micelles is the presence of two helical segments at the N- and C-termini of the sequence. In order to stabilize the helical structures, we have recently synthesized and studied the PTHrP(1-34) analog [(Lys13-Asp17, Lys26-Asp30)]PTHrP(1-34)NH2, which contains lactam-constrained Lys-Asp side chains at positions i, i+4. This very potent agonist exhibits enhanced helix stability with respect to the corresponding linear peptide and also two flexible sites at positions 12 and 19 in 1:1 trifluoroethanol/water. These structural elements have been suggested to play a critical role in bioactivity. In the present work we have extended our conformational studies on the bicyclic lactam-constrained analog to aqueous solution. By CD, 2D-NMR and structure calculations we have shown that in water two helical segments are present in the region of the lactam bridges (13-18, and 26-31) with high flexibility around Gly12 and Arg19. Thus, the essential structural features observed in the aqueous-organic medium are maintained in water even if, in this solvent, the overall structure is more flexible. Our findings confirm the stabilizing effect of side-chain lactam constraints on the alpha-helical structure.
A metering rotary nanopump for microfluidic systems (2010)

We describe the design, fabrication, and testing of a microfabricated metering rotary nanopump for the purpose of driving fluid flow in microfluidic devices. The miniature peristaltic pump is composed of a set of microfluidic channels wrapped in a helix around a central camshaft in which a non-cylindrical cam rotates. The cam compresses the helical channels to induce peristaltic flow as it is rotated. The polydimethylsiloxane (PDMS) nanopump design is able to produce intermittent delivery or removal of several nanolitres of fluid per revolution as well as consistent continuous flow rates ranging from as low as 15 nL min−1 to above 1.0 µL min−1. At back pressures encountered in typical microfluidic devices, the pump acts as a high impedance flow source. The durability, biocompatibility, ease of integration with soft-lithographic fabrication, the use of a simple rotary motor instead of multiple synchronized pneumatic or mechanical actuators, and the absence of power consumption or fluidic conductance in the resting state all contribute to a compact pump with a low cost of fabrication and versatile implementation. This suggests that the pump design may be useful for a wide variety of biological experiments and point of care devices.
Fluorescence Resonance Energy Transfer-Based Near-Infrared Fluorescence Sensor for Glucose Monitoring (2004)

A novel near-infrared (NIR) fluorescence affinity sensor for continuous glucose monitoring was developed and characterized. The sensor operates by fluorescence resonance energy transfer between a NIR chromophore linked to concanavalin A (ConA) and an NIR fluorophore linked to free dextran. The binding of dextran with ConA in the absence of glucose results in low fluorescence due to quenching; however, the quenching is reversed by competitive displacement of dextran from ConA by glucose. In order to increase thermodynamic stability and the lifetime of the sensor, ConA was immobilized within a macroporous bead matrix. The sensor was contained within a sealed hollow dialysis fiber (o.d. 215 microm, wall thickness 20 microm), preventing the macromolecules from leaking out and enabling glucose to rapidly enter the fiber lumen. A glucose-insensitive reference fluorophore was also incorporated to allow for ratiometric measurements, resulting in a robust sensor output that is independent of positional and/or light intensity changes. The response of the fluorescence affinity sensor to glucose was tested continuously in an automated test chamber at 37 degrees C. The sensor showed good dynamic range within physiologically relevant glucose concentration range (15% change over 2.5-30 mM, no hysteresis), fast response time (2-4 min), and a remarkable long-term stability (6 months). We interpret the improved longevity of this sensor to be the result of an optimized photo exposure regime and immobilization of ConA to the matrix. Its small size, ratiometric output, and NIR fluorescence make this sensor well suited for dermal implantation and continuous transdermal monitoring.
Analysis of Biomass Blend Co-Firing for Post Combustion CO2 Capture (2018)

The correct conduction of the CO2 capture process in coal-fired power plants with the use of monoethanolamine (MEA) requires constant process parameter monitoring and ensuring a specific flue gas chemical composition. One of the most common problems in these types of installations is the progressive corrosion and degradation of the valuable solvent. Despite the established reduction levels of oxygen and impurities entering into irreversible reactions with the absorber, the flue gas composition may change as a daily and annual function of time. The article presents a detailed analysis of the flue gas components that have the greatest influence on carbon dioxide capture installation technical safety, i.e., SOx, NOx, O2, and fly ash. The analysis was based on the results of experiments conducted at the Jaworzno III Tauron Wytwarzanie SA Polish coal power plant. The results show a significant influence of the flue gas desulfurization (FGD) process on MEA oxidative degradation. The amount of oxygen in flue gas during biomass and coal blend co-firing was nearly twice as low compared to pure coal combustion. Differences were also observed in the amounts of gas impurities with relation to the time of year and time of day of power plant operation.
Histone deacetylase inhibitors in Hodgkin lymphoma (2010)

Although Hodgkin lymphoma (HL) is considered one of the most curable human cancers, the treatment of patients with relapsed and refractory disease, especially those who relapse after autologous stem cell transplantation, remains challenging. Furthermore, because of the young age of these patients, the impact of early mortality on the number of years lost from productive life is remarkable. Patients with relapsed HL post stem cell transplantation currently have no curative therapy, and are in need for new drugs and novel treatment strategies. While no new drugs have been approved for the treatment of patients with HL in more than three decades, several new agents are demonstrating promising results in early clinical trials. This review will focus on the emerging role of histone deacetylase inhibitors in patients with relapsed HL.
FILLING THE GAPS BETWEEN TOOLS AND USERS: A TOOL COMPARATOR, USING PROTEIN-PROTEIN INTERACTION AS AN EXAMPLE (2007)

Recently, several text mining programs have reached a near-practical level of performance. Some systems are already being used by biologists and database curators. However, it has also been recognized that current Natural Language Processing (NLP) and Text Mining (TM) technology is not easy to deploy, since research groups tend to develop systems that cater specifically to their own requirements. One of the major reasons for the difficulty of deployment of NLP/TM technology is that re-usability and interoperability of software tools are typically not considered during development. While some effort has been invested in making interoperable NLP/TM toolkits, the developers of end-to-end systems still often struggle to reuse NLP/TM tools, and often opt to develop similar programs from scratch instead. This is particularly the case in BioNLP, since the requirements of biologists are so diverse that NLP tools have to be adapted and re-organized in a much more extensive manner than was originally expected. Although generic frameworks like UIMA (Unstructured Information Management Architecture) provide promising ways to solve this problem, the solution that they provide is only partial. In order for truly interoperable toolkits to become a reality, we also need sharable type systems and a developer-friendly environment for software integration that includes functionality for systematic comparisons of available tools, a simple I/O interface, and visualization tools. In this paper, we describe such an environment that was developed based on UIMA, and we show its feasibility through our experience in developing a protein-protein interaction (PPI) extraction system.
Amyloid β-peptide stimulates nitric oxide production in astrocytes through an NFκB-dependent mechanism (1998)

The major pathological features of Alzheimer's disease (AD) include amyloid plaques composed primarily of the beta-amyloid (Abeta) peptide, degenerating neurons and neurofibrillary tangles, and the presence of numerous activated astrocytes and microglia. Although extensive genetic data implicate Abeta in the neurodegenerative cascade of AD, the molecular mechanisms underlying its effects on neurons and glia and the relationship between glial activation and neuronal death are not well defined. Abeta has been shown to induce glial activation, and a growing body of evidence suggests that activated glia contribute to neurotoxicity through generation of inflammatory cytokines and neurotoxic free radicals, such as nitric oxide (NO), potent sources of oxidative stress known to occur in AD. It is therefore crucial to identify specific Abeta-induced molecular pathways mediating these responses in activated glia. We report that Abeta stimulates the activation of the transcription factor NFkappaB in rat astrocytes, that NFkappaB activation occurs selectively from p65 transactivation domain 2, and that Abeta-induced NO synthase expression and NO production occur through an NFkappaB-dependent mechanism. This demonstration of how Abeta couples an intracellular signal transduction pathway involving NFkappaB to a potentially neurotoxic response provides a key mechanistic link between Abeta and the generation of oxidative damage. Our results also suggest possible molecular targets upon which to focus future drug discovery efforts for AD.
Adenovirus Preterminal Protein Binds to the CAD Enzyme at Active Sites of Viral DNA Replication on the Nuclear Matrix (1998)

Adenovirus (Ad) replicative complexes form at discrete sites on the nuclear matrix (NM) via an interaction mediated by the precursor of the terminal protein (pTP). The identities of cellular proteins involved in these complexes have remained obscure. We present evidence that pTP binds to a multifunctional pyrimidine biosynthesis enzyme found at replication domains on the NM. Far-Western blotting identified proteins of 150 and 240 kDa that had pTP binding activity. Amino acid sequencing of the 150-kDa band revealed sequence identity to carbamyl phosphate synthetase I (CPS I) and a high degree of homology to the related trifunctional enzyme known as CAD (for carbamyl phosphate synthetase, aspartate transcarbamylase, and dihydroorotase). Western blotting with an antibody directed against CAD detected a 240-kDa band that comigrated with that detected by pTP far-Western blotting. Binding experiments showed that a pTP-CAD complex was immunoprecipitable from cell extracts in which pTP was expressed by a vaccinia virus recombinant. Additionally, in vitro-translated epitope-tagged pTP and CAD were immunoprecipitable as a complex, indicating the occurrence of a protein-protein interaction. Confocal fluorescence microscopy of Ad-infected NM showed that pTP and CAD colocalized in nuclear foci. Both pTP and CAD were confirmed to colocalize with active sites of replication detected by bromodeoxyuridine incorporation. These data support the concept that the pTP-CAD interaction may allow anchorage of Ad replication complexes in the proximity of required cellular factors and may help to segregate replicated and unreplicated viral DNA.