gebhart/patrepeval huggingface dataset:
Loss of Bin1 Promotes the Propagation of Tau Pathology (2016)

Tau pathology propagates within synaptically connected neuronal circuits, but the underlying mechanisms are unclear. BIN1-amphiphysin2 is the second most prevalent genetic risk factor for late-onset Alzheimer's disease. In diseased brains, the BIN1-amphiphysin2 neuronal isoform is downregulated. Here, we show that lowering BIN1-amphiphysin2 levels in neurons promotes Tau pathology propagation whereas overexpression of neuronal BIN1-amphiphysin2 inhibits the process in two in vitro models. Increased Tau propagation is caused by increased endocytosis, given our finding that BIN1-amphiphysin2 negatively regulates endocytic flux. Furthermore, blocking endocytosis by inhibiting dynamin also reduces Tau pathology propagation. Using a galectin-3-binding assay, we show that internalized Tau aggregates damage the endosomal membrane, allowing internalized aggregates to leak into the cytoplasm to propagate pathology. Our work indicates that lower BIN1 levels promote the propagation of Tau pathology by efficiently increasing aggregate internalization by endocytosis and endosomal trafficking.
The effects of the mGluR5 receptor antagonist 6-methyl-2-(phenylethynyl)-pyridine (MPEP) on behavioural responses to nicotine (2010)

Previous studies have shown that blockade of metabotropic glutamate 5 receptors (mGluR5) results in inhibition of nicotine self-administration in experimental animals. However, these studies have not established the behavioural mechanisms which mediate these effects or the extent to which the effects of mGluR5 antagonism on nicotine self-administration reflect a selective attenuation of nicotine reinforcement. To investigate the effects of antagonising mGluR5 receptors on psychopharmacological responses to nicotine measured using conditioned and unconditioned behaviours. 2-Methyl-6-(phenylethynyl)-pyridine (MPEP) significantly (P < 0.01) reduced nicotine self-administration and attenuated (P < 0.01) the ability of non-contingent nicotine to enhance the reinforcing properties of a weak reinforcer (extinguishing the house light in an operant chamber). It also attenuated (P < 0.05) the much lower levels of responding for this reinforcer measured in control animals treated with saline. MPEP did not attenuate the increase in locomotor activity induced by acute and repeated nicotine in animals habituated on the test day to the test environment. Furthermore, it had no significant effects on responding for a palatable food reward. By contrast, MPEP significantly reduced (P < 0.001) conditioned locomotor stimulation evoked by pairing nicotine with a specific environment. The results are consistent with the hypothesis that mGluR5 receptors play an important role in mediating the effects of contextual cues in conditioned behavioural responses to nicotine.
On the Influence of Test-Driven Development on Software Design (2006)

Test-driven development (TDD) is an agile software development strategy that addresses both design and testing. This paper describes a controlled experiment that examines the effects of TDD on internal software design quality. The experiment was conducted with undergraduate students in a software engineering course. Students in three groups completed semester-long programming projects using either an iterative test-first (TDD), iterative test-last, or linear test-last approach. Results from this study indicate that TDD can be an effective software design approach improving both code-centric aspects such as object decomposition, test coverage, and external quality, and developer-centric aspects including productivity and confidence. In addition, iterative development approaches that include automated testing demonstrated benefits over a more traditional linear approach with manual tests. This study demonstrates the viability of teaching TDD with minimal effort in the context of a relatively traditional development approach. Potential dangers with TDD are identified regarding programmer motivation and discipline. Pedagogical implications and instructional techniques which may foster TDD adoption will also be referenced
A Hybrid Model for Identity Obfuscation by Face Replacement (2018)

As more and more personal photos are shared and tagged in social media, avoiding privacy risks such as unintended recognition becomes increasingly challenging. We propose a new hybrid approach to obfuscate identities in photos by head replacement. Our approach combines state of the art parametric face synthesis with latest advances in Generative Adversarial Networks (GAN) for data-driven image synthesis. On the one hand, the parametric part of our method gives us control over the facial parameters and allows for explicit manipulation of the identity. On the other hand, the data-driven aspects allow for adding fine details and overall realism as well as seamless blending into the scene context. In our experiments, we show highly realistic output of our system that improves over the previous state of the art in obfuscation rate while preserving a higher similarity to the original image content.
Junctional adhesion molecule 1 (JAM-1). (2004)

Junctional adhesion molecule 1 (JAM-1) was the first of a family of related proteins (JAM family) to be discovered. Two proteins with structural and sequence similarities to JAM-1, named JAM-2 and JAM-3, have been identified more recently. JAM-1 is specifically localized at the tight junctions of epithelial and endothelial cells and is involved in the regulation of junctional integrity and permeability. This function is attributed to its ability to interact in a homophilic manner. JAM-1 can also bind in a heterophilic manner as it serves as a ligand for integrin LFA-1 (CD11a/CD18), and plays a key role in the process of leukocyte transmigration. In addition, JAM-1 is also a receptor for reovirus, and is a platelet receptor involved in platelet adhesion and antibody-induced platelet aggregation. Further study of the mechanism of JAM-1 action within these diverse systems may demonstrate that JAM-1 is a key player in many different cellular functions.
Oral verapamil inhibits platelet thrombus formation in humans. (1994)

The present study demonstrates that part of the benefit of verapamil in ischemic heart disease may occur by inhibition of platelet aggregation and thrombus formation. This beneficial antithrombotic effect may be important in preventing acute coronary ischemic events resulting from thrombus formation at sites of plaque rupture.
Microtubules and microtubule-associated proteins (MAPs) in Alzheimer's disease (1985)

info:eu-repo/semantics/nonPublished
Queryable Semantics to Detect Cyber-Attacks: A Flow-Based Detection Approach (2016)

Cyber-attacks continue to increase worldwide, leading to significant loss or misuse of information assets. Most of the existing intrusion detection systems rely on per-packet inspection, a resource consuming task in today's high speed networks. A recent trend is to analyze netflows (or simply flows) instead of packets, a technique performed at a relative low level leading to high false alarm rates. Since analyzing raw data extracted from flows lacks the semantic information needed to discover attacks, a novel approach is introduced, which uses contextual information to automatically identify and query possible semantic links between different types of suspicious activities extracted from flows. Time, location, and other contextual information mined from flows is applied to generate semantic links among alerts raised in response to suspicious flows. These semantic links are identified through an inference process on probabilistic semantic link networks (SLNs), which receive an initial prediction from a classifier that analyzes incoming flows. The SLNs are then queried at run-time to retrieve other relevant predictions. We show that our approach can be extended to detect unknown attacks in flows as variations of known attacks. An extensive validation of our approach has been performed with a prototype system on several benchmark datasets yielding very promising results in detecting both known and unknown attacks.
On‐line monitoring of radiotherapy beams: Experimental results with proton beams (1999)

Proton radiotherapy is a powerful tool in the local control of cancer. The advantages of proton radiotherapy over gamma-ray therapy arise from the phenomenon known as the Bragg peak. This phenomenon enables large doses to be delivered to well-defined volumes while sparing surrounding healthy tissue. To fully realize the potential of this technique the location of the high-dose volume must be controlled very accurately. An imaging system was designed and tested to monitor the positron-emitting activity created by the beam as a means of verifying the beam's range, monitoring dose, and determining tissue composition. The prototype imaging system consists of 12 pairs of cylindrical BGO detectors shielded in lead. Each crystal was 1.9 cm in diameter, 5.0 cm long, and separated by 0.5 cm from other detectors in the row. These are arranged in two rows, 60 cm apart, with the proton beam and tissue phantoms half-way between and parallel to the detector rows. Experiments were conducted with 150 MeV continuous and macro-pulsed proton beams which had beam currents ranging from 0.14 nA to 1.75 nA. The production and decay of short-lived isotopes, 15O and 14O, was studied using 1 min irradiations with a continuous beam. These isotopes provide a significant signal on short time scales, making on-line imaging possible. Macro-pulsed beams, having a period of 10 s, were used to study on-line imaging and the production and decay of long-lived isotopes, 13N, 11C, and 18F. Decay data were acquired and on-line images were obtained between beam pulses and indicate that range verification is possible, for a 150 MeV beam, after one beam pulse, to within the 1.2 cm resolution limit of the imaging system. The dose delivered to the patient may also be monitored by observing the increase in the number of coincidence events detected between successive beam pulses. Over 80% of the initial positron-emitting activity is from 15O while the remainder is primarily 11C, 13N, 14O with traces of 18F, and 10C. Radioisotopic imaging may also be performed along the beam path by fitting decay data collected after the treatment is complete. Using this technique, it is shown that variations in elemental composition in inhomogenous treatment volumes may be identified and used to locate anatomic landmarks. Radioisotopic imaging also reveals that 14O is created well beyond the Bragg peak, apparently by secondary neutrons.
Enkephalin Degrading Enzymes: Metalloproteases with High Potential for Drug Development (2012)

Enkephalins play a great role in management of pain, blood pressure, hypertension and cardiovascular diseases. Enkephalins are short-lived molecules being rapidly hydrolyzed following their synaptic release by enkephalin degrading enzymes. The inhibitors of enkephalin degrading enzymes are able to prolong the duration of action of enkephalins. This review will focus on the inhibitors of enkephalin degrading enzymes as a novel therapeutic approach for cancer itself and also in cancer and neuropathic pain management with discussion on the present status and future directions for a new class of drugs.
Negative-index bianisotropic photonic metamaterial fabricated by direct laser writing and silver shadow evaporation (2008)

We present the blueprint for a novel negative-index metamaterial. This structure is fabricated via three-dimensional two-photon direct laser writing and silver shadow evaporation. The comparison of measured linear optical spectra with theory shows good agreement and reveals a negative real part of the refractive index at around 3.85 microm wavelength -- despite the fact that the metamaterial structure is bianisotropic owing to the lack of inversion symmetry along its surface normal.
Insights into the local residual entropy of proteins provided by NMR relaxation (1996)

A simple model is used to illustrate the relationship between the dynamics measured by NMR relaxation methods and the local residual entropy of proteins. The expected local dynamic behavior of well-packed extended amino acid side chains are described by employing a one-dimensional vibrator that encapsulates both the spatial and temporal character of the motion. This model is then related to entropy and to the generalized order parameter of the popular "model-free" treatment often used in the analysis of NMR relaxation data. Simulations indicate that order parameters observed for the methyl symmetry axes in, for example, human ubiquitin correspond to significant local entropies. These observations have obvious significance for the issue of the physical basis of protein structure, dynamics, and stability.
I/Q modulator image rejection through modulation pre-distortion (2002)

I/Q modulators have been widely used to perform digital modulation such as QPSK, QAM, GMSK and MCM. In practice, there exists a small non-90/spl deg/ phase error between the I and Q channels of an I/Q modulator. Also, the I and Q channels may not always have the same gain. The phase error and gain imbalance cause unwanted image signals that are generated in-band and consequently, degrades the system performance. This paper presents an I/Q modulator image rejection algorithm through modulation signal pre-distortion. The presented algorithm is simple and lends itself well towards a digital signal processor (DSP) implementation. Due to its simplicity, the implementation results in almost no increase in modulator complexity. Experimental results shows that for an MCM modulation system, this algorithm can reduce the image by at least 10 dB. For portable products like modems and handhelds, this feature is specially attractive because low complexity implies low cost, small product size and/or long battery life.
Ototoxicity of Antimycotics (1989)

Neither otomycoses nor defects of the tympanic membrane are rare. In cases of fungal infection when the tympanic membrane is not intact, the possibility exists that antimycotic medication could enter the middle ear and diffuse into the cochlea via the round window. Five antimycotic preparations were tested for acute ototoxic potential in guinea pigs. Those containing acetic acid or propylene glycol caused appreciable elevation of brainstem response thresholds, while little or no impairment resulted from tolnaftate or clotrimazole solutions in polyethylene glycol 400.
GaAs-AlGaAs quantum cascade lasers: physics, technology, and prospects (2002)

In recent years, the performance of GaAs-AlGaAs-based quantum cascade (QC) lasers has improved markedly. These devices are capable of pulsed room temperature operation and can deliver respectable average powers (11 mW at /spl lambda//spl sim/9 /spl mu/m) operating on a Peltier cooler. This performance has been achieved by the suppression of thermally activated carrier leakage through increases in the heterobarrier band offset. We demonstrate that QC lasers, with wavelengths /spl lambda//spl ges/9 /spl mu/m, can operate using heterostructures encompassing the entire composition range of Al/sub x/Ga/sub 1-x/As, without encountering potential problems-of the satellite X-minima for x>45%. Furthermore, we present particular characteristics of these devices, such as a phonon-limited temperature dependence, electrical and optical self-oscillations, and novel design concepts that exploit this closely lattice matched material system. Finally, we discuss improvements in device fabrication to lower the operating current through a reduction of the area of current injection. Using this technology, devices can be designed to selectively pump the fundamental lateral mode. We, therefore, observe single spatial-mode operation over the entire current range of operation.
Adipogenic and anti-adipogenic factors in the pituitary and other organs. (1981)

Adipose conversion of cultured 3T3 cells is known to depend on an adipogenic factor present in serum. In the presence of this factor, extracts of different organs were found to inhibit the adipose conversion. The most active extracts were derived from brain, uterus, and pituitary, but other organs also possessed appreciable activity. Fibroblast growth factor partially purified from both brain and pituitary was much more active in suppressing adipose conversion than were crude extracts of the corresponding organs. Purified platelet-derived growth factor was also an effective inhibitor. Of all the tissue extracts tested, only pituitary possessed, in addition to the inhibitory activity, an adipogenic factor similar to that demonstrated previously in serum. This was revealed at concentrations of extract too low for the inhibitory factor to be effective. Under these conditions the pituitary extract had a specific adipogenic activity orders of magnitude higher than that of serum. We suggest that the adipogenic factor of serum may originate in the pituitary.
Virtual screening to enrich hit lists from high‐throughput screening: A case study on small‐molecule inhibitors of angiogenin (2002)

"Hit lists" generated by high-throughput screening (HTS) typically contain a large percentage of false positives, making follow-up assays necessary to distinguish active from inactive substances. Here we present a method for improving the accuracy of HTS hit lists by computationally based virtual screening (VS) of the corresponding chemical libraries and selecting hits by HTS/VS consensus. This approach was applied in a case study on the target-enzyme angiogenin, a potent inducer of angiogenesis. In conjunction with HTS of the National Cancer Institute Diversity Set and ChemBridge DIVERSet E (approximately 18,000 compounds total), VS was performed with two flexible library docking/scoring methods, DockVision/Ludi and GOLD. Analysis of the results reveals that dramatic enrichment of the HTS hit rate can be achieved by selecting compounds in consensus with one or both of the VS functions. For example, HTS hits ranked in the top 2% by GOLD included 42% of the true hits, but only 8% of the false positives; this represents a sixfold enrichment over the HTS hit rate. Notably, the HTS/VS method was effective in selecting out inhibitors with midmicromolar dissociation constants typical of leads commonly obtained in primary screens.
Dial-to-Connect VPN System for Remote DLNA Communication (2008)

We demonstrate a prototype of Dial-to-Connect (D2C) VPN system for transmitting DLNA (Digital Living Network Alliance) protocols between home networks. Research studies implemented proxy systems over VPN so that DLNA devices could communicate remotely, but they were not designed for how to easily establish VPN tunnels. D2C VPN system uses SIP to execute an indication and authentication of the destination based on a telephone number, which is the most common information to connect two network devices. D2C VPN system enables novice PC users to establish an on-demand VPN with ease and enjoy remote DLNA communication with home appliances. D2C VPN system has two functions: SIP-VPN function and DLNA proxy function. A user requests a VPN tunnel using the SIP-VPN function by inputting a destination phone number to which he/she wants to connect, and if a gateway of the destination accepts the request based on his/her phone number successfully, the VPN tunnel is established. After that, the DLNA proxy function liaises with the SIP-VPN function. D2C VPN system can also use QoS that a SIP network provides because VPN packets are sent through a channel negotiated by the SIP.
Vision system for on-loom fabric inspection (1999)

This paper describes a vision-based fabric inspection system that accomplishes on-loom inspection of the fabric under construction with 100% coverage. The inspection system, which offers a scalable open architecture, can be manufactured at relatively low cost using off-the-shelf components. While synchronized to the motion of the loom, the developed system first acquires very high-quality vibration-free images of the fabric using either front or backlighting. Then, the acquired images are subjected to a novel defect segmentation algorithm, which is based on the concepts of wavelet transform, image fusion and the correlation dimension. The essence of this segmentation algorithm is the localization of those events (i.e., defects) in the input images that disrupt the global homogeneity of the background texture. The efficacy of this algorithm, as well as the overall inspection system, has been tested thoroughly under realistic conditions. The system was used to acquire and to analyze more than 3700 images of fabrics that were constructed with two different types of yarn. In each case, the performance of the system was evaluated as an operator introduced defects from 26 categories into the weaving process. The overall detection rate of the presented approach was found to be 89% with a localization accuracy of 0.2 in (i.e., the minimum defect size) and a false alarm rate of 2.5%.
Wavelength dependence of the degree of polarization in cloud-free skies: simulations of real environments (2012)

The visible and NIR maximum degree of polarization (DoP) of cloud-free skylight depends on many factors, including wavelength, sun zenith angle, surface reflectance, and aerosol properties. For clear-sky environments, radiative transfer models accurately estimate the sky DoP when each of these properties is well constrained. (The model used here was recently compared with full-sky polarization measurements with excellent agreement.) Using coincident Hyperion satellite observations and AERONET retrievals to provide model inputs, we simulate the maximum sky DoP for a variety of locations. Results show large variations in the wavelength dependence of sky polarization across different Earth environments. Therefore, accurate modeling of the sky DoP depends largely upon proper representation of the surface and aerosols in the model. Simple models which do not incorporate accurate aerosol and surface information have limited utility for simulating cloud-free sky DoP.
Mutations in the Yeast Mitochondrial RNA Polymerase Specificity Factor, Mtf1, Verify an Essential Role in Promoter Utilization (2002)

The yeast mitochondrial RNA polymerase (RNAP) is a two-subunit enzyme composed of a catalytic core (Rpo41) and a specificity factor (Mtf1) encoded by nuclear genes. Neither subunit on its own interacts with promoter DNA, but the combined holo-RNAP recognizes and selectively initiates from promoters related to the consensus sequence ATATAAGTA. To pursue the question of why Rpo41, which resembles the single polypeptide RNAPs from bacteriophage T7 and T3, requires a separate specificity factor, we analyzed a collection of Mtf1 point mutations that confer an in vivo petite phenotype. These mutant proteins are able to interact with Rpo41 and are capable of nearly wild type levels of initiation in vitro with a consensus promoter-containing template (14 S rRNA). However, the petite phenotype of two mutants can be explained by the fact that they exhibit dramatic transcriptional defects on non-consensus promoters. Y54F is incapable of transcribing the weak tRNA(Cys) promoter, and C192F cannot transcribe either tRNA(Cys) or the variant COX2 promoter from linear DNA templates. Transcription of the tRNA(Cys) promoter by both mutants was significantly corrected by addition of an initiating dinucleotide primer or by supercoiling the DNA template. These results establish the critical role of Mtf1 in promoter recognition and initiation of transcription.