gebhart/patrepeval huggingface dataset:
Dishevelled-1 Regulates Microtubule Stability (2000)

Dishevelled has been implicated in the regulation of cell fate decisions, cell polarity, and neuronal function. However, the mechanism of Dishevelled action remains poorly understood. Here we examine the cellular localization and function of the mouse Dishevelled protein, DVL-1. Endogenous DVL-1 colocalizes with axonal microtubules and sediments with brain microtubules. Expression of DVL-1 protects stable microtubules from depolymerization by nocodazole in both dividing cells and differentiated neuroblastoma cells. Deletion analyses reveal that the PDZ domain, but not the DEP domain, of DVL-1 is required for microtubule stabilization. The microtubule stabilizing function of DVL-1 is mimicked by lithium-mediated inhibition of glycogen synthase kinase-3beta (GSK-3beta) and blocked by expression of GSK-3beta. These findings suggest that DVL-1, through GSK-3beta, can regulate microtubule dynamics. This new function of DVL-1 in controlling microtubule stability may have important implications for Dishevelled proteins in regulating cell polarity.
Ligand-Induced Internalization of the p75 Neurotrophin Receptor: A Slow Route to the Signaling Endosome (2003)

The nerve growth factor (NGF) family of neurotrophins binds two classes of cell-surface receptors, trk receptor tyrosine kinases and the shared p75 receptor. Rapid internalization and retrograde trafficking of neurotrophin-trk complexes have been demonstrated in a number of systems and are thought to transmit trophic signals from terminals to neuronal cell bodies. In contrast, the internalization and trafficking of neurotrophin-p75 complexes are not well understood. In this study, we used biotinylated NGF and a fluorescent-labeled anti-p75 antibody to follow the kinetics and route of ligand-induced internalization of the p75 receptor in cycling and differentiated PC12 cells. Binding of neurotrophins to p75 induced internalization at a rate approximately three times slower than that of transferrin and NGF-TrkA complexes in the same cells. The ligand-p75 complex was internalized via clathrin-coated pits into early endosomes and eventually accumulated in recycling endosomes in the cell body and vesicles colabeled by the cholera toxin B-subunit in the growth cones. Both internalized ligand and p75 were protected from proteolytic degradation and accumulated in vesicles that did not undergo acidification. Finally, NGF induced endosomal association of p75 and its MAGE interactors, necdin and NRAGE. These data suggest that signaling endosomes containing activated p75 are involved in neurotrophin signaling, and that such endosomes may be temporally and spatially distinct from those containing trk receptors.
Prevention of Intractable Partial Seizures by Intermittent Vagal Stimulation in Humans: Preliminary Results (1990)

Intermittent stimulation of the vagus nerve in four patients resulted in complete seizure control in two, a 40% reduction of seizure frequency in one, and no change in seizure frequency in the other. Side effects (hoarseness, stimulation sensation in the neck, and hiccups) were transient and occurred concomitantly with stimulation. All patients tolerated increasing stimulation parameters well. The results, however, are inconclusive because of the brief duration (6-12 months) of follow-up. Vagal stimulation represents a novel approach for seizure control in patients who have intractable epilepsy, but additional studies are needed to clarify the efficacy and safety of the procedure and to define selection criteria for patients.
Recent Developments in Peptide Drug Delivery to the Brain (1992)

Peptide-based therapeutics are highly water-soluble compounds that do not readily enter brain from blood owing to poor transport through the brain capillary endothelial wall, i.e., the blood-brain barrier (BBB). Strategies available for peptide drug delivery to brain include: (a) neurosurgical-based (intraventricular drug infusion, hyperosmotic opening of the BBB); (b) pharmacological-based (peptide lipidization, liposomes); and (c) physiological-based (biochemical opening of the BBB, chimeric peptides). Chimeric peptides are formed by the covalent coupling of a pharmaceutical peptide (that is normally not transported through the BBB) to a brain transport vector that undergoes absorptive-mediated or receptor-mediated transcytosis through the BBB. The most efficient brain transport vector known to date is a monoclonal antibody to the transferrin receptor, and this vector achieves a brain volume of distribution approximately 18-fold greater than the plasma space by 5 hr after a single intravenous injection of antibody. The chimeric peptides are formed generally with chemical-based linkers. However, avidin/biotin-based linkers allow for high yield coupling of drug to vector, and for the release of biologically-active peptide following cleavage of the chimeric peptide linker. These strategies may also be used for the delivery of antisense oligonucleotide-based therapeutics to brain. In conclusion, the development of efficacious neuropharmaceuticals in the future will require the development of both drug delivery and drug discovery strategies that operate in parallel.
10-Gb/s 850-nm CMOS OEIC Receiver With a Silicon Avalanche Photodetector (2011)

We present a 10-Gb/s optoelectronic integrated circuit (OEIC) receiver fabricated with standard 0.13-μm complementary metal-oxide-semiconductor (CMOS) technology for 850-nm optical interconnect applications. The OEIC receiver consists of a CMOS-compatible avalanche photodetector (CMOS-APD), a transimpedance amplifier (TIA), an offset cancellation network, a variable equalizer (EQ), a limiting amplifier (LA), and an output buffer. The CMOS-APD provides high responsivity as well as large photodetection bandwidth. The TIA is composed of two-stage differential amplifiers with high feedback resistance of 4 kΩ. The EQ compensates high-frequency loss by controlling the boosting gain with a capacitor array. The LA consists of five-stage gain cells with active feedback and negative capacitance to achieve broadband performance. With the OEIC receiver, we successfully demonstrate transmission of 10-Gb/s optical data at 850 nm with a bit error rate of 10 <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">-12</sup> at the incident optical power of -4 dBm. The OEIC receiver has the core chip area of about 0.26 mm <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> and consumes about 66.8 mW.
The multiple-sugar metabolism (msm) gene cluster of Streptococcus mutans is transcribed as a single operon (1996)

The multiple-sugar metabolism (msm) locus of Streptococcus mutans constitutes a non-PTS sugar uptake system responsible for the transport and utilization of raffinose, melibiose and isomaltotrioses. While previous studies have used polar mutations to suggest that these genes are co-transcribed, there has not been evidence to support this. In this report we present direct evidence that the msm genes can be transcribed as a single operon.
Glucose Ingestion Selectively Amplifies ACTH and Cortisol Secretory-Burst Mass and Enhances Their Joint Synchrony in Healthy Men (2011)

Conjoint augmentation of the mass of ACTH and cortisol secreted per burst and enhancement of ACTH-cortisol synchrony underlie glucose-induced glucocorticoid secretion in healthy men. Visceral adiposity is a predictor of the glucose-stimulated increment in burst-like cortisol output, suggesting an additional possible mechanism for increased cardiovascular risk in abdominal obesity.
Function and regulation of a murine macrophage-specific IgG Fc receptor, Fc gamma R-alpha. (1988)

Ligand binding specificities of two cloned murine Fc gamma Rs (Fc gamma R-alpha, Fc gamma R-beta [9]) were determined by gene transfer into Fc gamma R negative cell lines. Both receptors were expressed as full-length molecules capable of IgG immune complex binding that was inhibitable by the mAb 2.4G2. The ligand binding profiles of these receptors were indistinguishable whereby both bound immune-complexed mouse IgG1, IgG2a, and IgG2b, but not IgG3. Neither receptor could bind monomeric IgG2a, indicating these receptors to be low-affinity IgG Fc receptors. Accumulation of the Fc gamma R-alpha mRNA can be induced with murine IFN-gamma at a concentration of 200 U/ml in the macrophage-like cell lines RAW 264.7 and J774a. The time course for induction indicates that the mRNA accumulation is transient but does not return to the uninduced level even after 50 h of treatment. Fc gamma R-beta mRNA was not induced by IFN-gamma, rather its expression was down modulated in mouse peritoneal macrophages. Both RAW and J774a cells lines exhibited increased receptor levels after IFN-gamma stimulation as measured by 125I-2.4G2 and ligand binding. In the absence of IFN-gamma, the RAW and J774a cell lines were minimally phagocytic, while P388D1 cells were actively phagocytic. In the presence of IFN-gamma, however, RAW 264.7 and J774a cells were induced to become actively phagocytic. Induction of Fc gamma R-alpha mRNA and protein by IFN-gamma may be part of the process by which macrophages become activated to engulf antibody-coated particles.
Sodium chloride assisted synthesis of silver nanowires (2011)

Silver nanowires with diameters of about 100 nm and lengths up to several micrometres have been synthesised by a developed polyol process with the assistance of polyvinyl pyrrolidone (PVP) and sodium chloride (NaCl) on a large scale. Transmission electron microscopy, high-resolution transmission electron microscopy, selected areas electron diffraction and X-ray diffraction have been employed to characterise silver nanowires. The role of NaCl for the formation of silver nanowires has been discussed by taking into account the formation of silver chloride (AgCl) to consume silver ions and reduce the rate of nucleation.
Development of ipilimumab: a novel immunotherapeutic approach for the treatment of advanced melanoma (2013)

The immunotherapeutic agent ipilimumab has helped address a significant unmet need in the treatment of advanced melanoma. Ipilimumab is a fully human monoclonal antibody that targets cytotoxic T-lymphocyte antigen-4 (CTLA-4), thereby augmenting antitumor immune responses. After decades in which a number of clinical trials were conducted, ipilimumab was the first therapy to improve overall survival in a randomized, controlled phase III trial of patients with advanced melanoma. These results led to the regulatory approval of ipilimumab at 3 mg/kg for the treatment of unresectable or metastatic melanoma. More than 17,000 patients worldwide have received ipilimumab, either as a commercial drug at 3 mg/kg or in clinical trials and expanded access programs at different doses. Consistent with its proposed mechanism of action, the most common toxicities associated with ipilimumab therapy are inflammatory in nature. These immune-related adverse events were mostly reversible when effective treatment guidelines were followed. Importantly, long-term follow-up of patients who received ipilimumab in a phase III trial showed that 24% survived at least two years, and in phase II studies, a proportion of patients survived at least five years. Evaluation of ipilimumab is ongoing in the adjuvant setting for melanoma, and for advanced disease in nonsmall cell lung, small cell lung, prostate, ovarian, and gastric cancers.
vLOD: High-Fidelity Walkthrough of Large Virtual Environments (2004)

We present visibility computation and data organization algorithms that enable high-fidelity walkthroughs of large 3D geometric data sets. A novel feature of our walkthrough system is that it performs work proportional only to the required detail in visible geometry at the rendering time. To accomplish this, we use a precomputation phase that efficiently generates per cell vLOD: the geometry visible from a view-region at the right level of detail. We encode changes between neighboring cells' vLODs, which are not required to be memory resident. At the rendering time, we incrementally construct the vLOD for the current view-cell and render it. We have a small CPU and memory requirement for rendering and are able to display models with tens of millions of polygons at interactive frame rates with less than one pixel screen-space deviation and accurate visibility.
Potency preservation following conformal radiotherapy for localized prostate cancer: impact of neoadjuvant androgen blockade, treatment technique, and patient-related factors. (1999)

Pre-EBRT partial potency, diabetes, coronary artery disease, and anti-androgen medication usage are significant predispositions to impotence in EBRT-treated prostate cancer patients. In comparing EBRT with NSRP for various age and stage groups, EBRT offers notably higher potency preservation rates than NSRP for patients older than 70 years.
Integrating proprioceptive assessment with proprioceptive training of stroke patients (2011)

Although proprioceptive impairment is likely to affect in a significant manner the capacity of stroke patients to recover functionality of the upper limb, clinical assessment methods in current use are rather crude, with a low level of reliability and a limited capacity to discriminate the relevant features of the deficits. In this paper we describe a new technique based on robot technology, with the goal of providing a reliable, accurate, quantitative evaluation of the position sense in peri-personal space. The proposed technique uses a bimanual, planar robot manipuladum (BdF device), whose handles are grasped by the blindfolded patient: the paretic hand is passively placed in one of 17 positions and the subject is asked to actively match the paretic hand position in space with the other hand. The position sense of the paretic arm and the corresponding deficit of space representation are characterized by means of 7 indicators: 1) positional error; 2) holding force; 3) medio/lateral shift; 4) antero/posterior shift; 5) medio/lateral skew; 6) antero/posterior skew; 7) shrink coefficient. We also show how the same experimental setup can be used for "proprioceptive training", i.e. for providing robot assistance to the paretic arm that may improve the position sense of the patient. A preliminary, feasibility test has been carried out with one patient and three controls.
Design, Synthesis, and Biological Studies of Efficient Multivalent Melanotropin Ligands: Tools toward Melanoma Diagnosis and Treatment (2011)

To achieve early detection and specific cancer treatment, we propose the use of multivalent interactions in which a series of binding events leads to increased affinity and consequently to selectivity. Using melanotropin (MSH) ligands, our aim is to target melanoma cells which overexpress melanocortin receptors. In this study, we report the design and efficient synthesis of new trivalent ligands bearing MSH ligands. Evaluation of these multimers on a cell model engineered to overexpress melanocortin 4 receptors (MC4R) showed up to a 350-fold increase in binding compared to the monomer, resulting in a trivalent construct with nanomolar affinity starting from a micromolar affinity ligand. Cyclic adenosine monophosphate (cAMP) production was also investigated, leading to more insights into the effects of multivalent compounds on transduction mechanisms.
Distinct microRNA expression profiles in acute myeloid leukemia with common translocations (2008)

MicroRNAs (miRNAs) are postulated to be important regulators in cancers. Here, we report a genome-wide miRNA expression analysis in 52 acute myeloid leukemia (AML) samples with common translocations, including t(8;21)/AML1(RUNX1)-ETO(RUNX1T1), inv(16)/CBFB-MYH11, t(15;17)/PML-RARA, and MLL rearrangements. Distinct miRNA expression patterns were observed for t(15;17), MLL rearrangements, and core-binding factor (CBF) AMLs including both t(8;21) and inv(16) samples. Expression signatures of a minimum of two (i.e., miR-126/126*), three (i.e., miR-224, miR-368, and miR-382), and seven (miR-17-5p and miR-20a, plus the aforementioned five) miRNAs could accurately discriminate CBF, t(15;17), and MLL-rearrangement AMLs, respectively, from each other. We further showed that the elevated expression of miR-126/126* in CBF AMLs was associated with promoter demethylation but not with amplification or mutation of the genomic locus. Our gain- and loss-of-function experiments showed that miR-126/126* inhibited apoptosis and increased the viability of AML cells and enhanced the colony-forming ability of mouse normal bone marrow progenitor cells alone and particularly, in cooperation with AML1-ETO, likely through targeting Polo-like kinase 2 (PLK2), a tumor suppressor. Our results demonstrate that specific alterations in miRNA expression distinguish AMLs with common translocations and imply that the deregulation of specific miRNAs may play a role in the development of leukemia with these associated genetic rearrangements.
Travel time data collection handbook (2010)

This Travel Time Data Collection Handbook provides guidance to transportation professionals and practitioners for the collection, reduction, and presentation of travel time data. The handbook should be a useful reference for designing travel time data collection efforts and systems, performing travel time studies, and reducing and presenting travel time data. Initial chapters of the handbook describe how to design data collection activities, including the determination of parameters such as study size and scope, data collection technique, and other critical study elements. Chapters 3 through 6 include a description of each data collection technique, major advantages and disadvantages, cost and equipment requirements, and step-by-step instructions. Related experience with the data collection techniques is included for examples of applications. Chapter 7 provides guidance for reducing travel time data and preparing tabular and graphical presentations. The handbooks opens with an interactive Table of Contents, allowing the viewer to select the desired chapter.
Generation of core-shell microcapsules with three-dimensional focusing device for efficient formation of cell spheroid (2010)

We present a microfluidic device generating three-dimensional (3D) coaxial flow by the addition of a simple hillock to produce an alginate core-shell microcapsule for the efficient formation of a cell spheroid. A hillock tapered at downstream of the two-dimensional focusing channel enables outside flow to enclose the core flow. The aqueous solution in the core flow was focused and surrounded by 1.8% alginate solution to be solidified as a shell. The double-layered coaxial flow (aqueous phase) was broken up into a droplet by the shear flow of oleic acid (oil phase) containing calcium chloride for the polymerization of the alginate shell. The droplet generated from the laminar coaxial flow maintained a double-layer structure and gelation of the alginate solution made a core-shell microcapsule. The shell-thickness of the microcapsule was adjusted from 8-21 μm by the variation of two aqueous flow rates. The inner shape of the shell was almost spherical when the ratio of the water-glycol mixture in the core flow exceeded 20%. The microcapsule was used to form a spheroid of embryonic carcinoma cells (embryoid body; EB) by injecting a cell suspension into the core flow. The cells inside the microcapsule aggregated into an EB within 2 days and the EB formation rate was more than 80% with strong compaction. The microcapsule formed single spherical EBs without small satellite clusters or a bumpy shape as observed in solid microbeads. The microfluidic chip for encapsulation of cells could generate a number of EBs with high rate of EB formation when compared with the conventional hanging drop method. The core-shell microcapsule generated by 3D focusing in the microchannel was effective in forming large number of spherical cell clusters and the encapsulation of cells in the microcapsule is expected to be useful in the transplantation of islet cells or cancer stem cell enrichment.
Development of the appendicularianOikopleura dioica: Culture, genome, and cell lineages (2008)

Appendicularians are planktonic tunicates (urochordates), and retain a swimming tadpole shape throughout their life. Together with ascidians, they are the closest relatives of the vertebrates. Oikopleura dioica is characterized by its simplified life habit and anatomical organization. It has a tiny genome, the smallest ever found in a chordate. Its life cycle is extremely short - about 5 days - and it can be maintained in the laboratory over many generations. Embryos and adults are transparent and consist of a small number of cells. The anatomy of juveniles and adults has been described in detail. Cleavage pattern, cell lineages, and morphogenetic movements during embryogenesis have also been comprehensively documented. A draft genome sequence is now available. These features make this organism a suitable experimental model animal in which genetic manipulations would be feasible, as in Drosophila and Caenorhabditis elegans. In this review, I summarize a hundred years' knowledge on the development throughout the life cycle of this organism. Oikopleura is an attractive organism for developmental and evolutionary studies of chordates. It offers considerable promise for future genetic approaches.
Mobile application for finding ATMs (2015)

This paper describes mobile application that gives Android users the ability to find ATMs quickly. Currently, the application offers locations of ATMs for various banks in Rijeka, Croatia. It also provides the possibility of finding the shortest path to the chosen ATM, as well as helpful tips where they can withdraw the money free of charge. The idea for this application was born after realizing that many people were wasting time looking for a place to withdraw money. This application saves time to inhabitants as well as to visitors of the city.
Profound functional and signaling changes in viable inflammatory neutrophils homing to cystic fibrosis airways (2008)

Blood neutrophils recruited to cystic fibrosis (CF) airways are believed to be rapidly killed by resident bacteria and to passively release elastase and other toxic by-products that promote disease progression. By single-cell analysis, we demonstrate that profound functional and signaling changes readily occur within viable neutrophils recruited to CF airways, compared with their blood counterparts. Airway neutrophils have undergone conventional activation, as shown by decreased intracellular glutathione, increased lipid raft assembly, surface mobilization of CD11b+ and CD66b+ granules, and increased levels of the cytoskeleton-associated phospho-Syk kinase. Unexpectedly, they also mobilize to the surface CD63+ elastase-rich granules, usually confined intracellularly, and lose surface expression of CD16 and CD14, both key receptors in phagocytosis. Furthermore, they express CD80, major histocompatibility complex type II, and the prostaglandin D2 receptor CD294, all normally associated with other lineages, which reflects functional reprogramming. This notion is reinforced by their decreased total phosphotyrosine levels, mirroring a postactivated stage, and increased levels of the phospho-S6 ribosomal protein, a key anabolic switch. Thus, we identified a subset of neutrophils within CF airways with a viable but dysfunctional phenotype. This subset provides a possible therapeutic target and indicates a need to revisit current paradigms of CF airway disease.