gebhart/patrepeval huggingface dataset:
Dual Vulnerability of Tau to Calpains and Caspase-3 Proteolysis Under Neurotoxic and Neurodegenerative Conditions (2010)

Axonally specific microtubule-associated protein tau is an important component of neurofibrillary tangles found in AD (Alzheimer's disease) and other tauopathy diseases such as CTE (chronic traumatic encephalopathy). Such tau aggregate is found to be hyperphosphorylated and often proteolytically fragmented. Similarly, tau is degraded following TBI (traumatic brain injury). In the present study, we examined the dual vulnerability of tau to calpain and caspase-3 under neurotoxic and neurodegenerative conditions. We first identified three novel calpain cleavage sites in rat tau (four-repeat isoform) as Ser130↓Lys131, Gly157↓Ala158 and Arg380↓Glu381. Fragment-specific antibodies to target the major calpain-mediated TauBDP-35K (35 kDa tau-breakdown product) and the caspase-mediated TauBDP-45K respectively were developed. In rat cerebrocortical cultures treated with excitotoxin [NMDA (N-methyl-D-aspartate)], tau is significantly degraded into multiple fragments, including a dominant signal of calpain-mediated TauBDP-35K with minimal caspase-mediated TauBDP-45K. Following apoptosis-inducing EDTA treatment, tau was truncated only to TauBDP-48K/45K-exclusively by caspase. Cultures treated with another apoptosis inducer STS (staurosporine), dual fragmentation by calpain (TauBDP-35K) and caspase-3 (TauBDP-45K) was observed. Tau was also fragmented in injured rat cortex following TBI in vivo to BDPs of 45-42 kDa (minor), 35 kDa and 15 kDa, followed by TauBDP-25K. Calpain-mediated TauBDP-35K-specific antibody confirmed robust signals in the injured cortex, while caspase-mediated TauBDP-45K-specific antibody only detected faint signals. Furthermore, intravenous administration of a calpain-specific inhibitor SNJ-1945 strongly suppressed the TauBDP-35K formation. Taken together, these results suggest that tau protein is dually vulnerable to calpain and caspase-3 proteolysis under different neurotoxic and injury conditions.
Thwarting Attacks in Malcode-Bearing Documents by Altering Data Sector Values (2009)

Embedding malcode within documents provides a convenient means of attacking systems. Such attacks can be very targeted and difficult to detect to stop due to the multitude of document-exchange vectors and the vulnerabilities in modern document processing applications. Detecting malcode embedded in a document is difficult owing to the complexity of modern document formats that provide ample opportunity to embed code in a myriad of ways. We focus on Microsoft Word documents as malcode carriers as a case study in this paper. To detect stealthy embedded malcode in documents, we develop an arbitrary data transformation technique that changes the value of data segments in documents in such a way as to purposely damage any hidden malcode that may be embedded in those sections. Consequently, the embedded malcode will not only fail but also introduce a system exception that would be easily detected. The method is intended to be applied in a safe sandbox, the transformation is reversible after testing a document, and does not require any learning phase. The method depends upon knowledge of the structure of the document binary format to parse a document and identify the specific sectors to which the method can be safely applied for malcode detection. The method can be implemented in MS Word as a security feature to enhance the safety of Word documents.
High mobility group protein HMGA1 expression in breast cancer reveals a positive correlation with tumour grade. (2003)

Members of the HMGA protein (high mobility group protein A) family act as master switches of the chromatin structure by bending DNA and thus modulating the formation of transcription factor complexes of a number of target genes. Accordingly, HMGA proteins have been shown to be associated with the development and/or progression of a variety of benign and malignant tumours. Nevertheless, the HMGA1 expression studies published so far have not included primary breast cancer samples. In this study we have investigated the HMGA1 expression patterns in a series of 170 breast cancer samples by immunohistochemistry. We have found a strong variation in HMGA1 expression between the tumours. Based on an immunoreactive score (IRS) 14.1% of the tumour samples were scored to IRS 8-12 (strong positivity for HMGA1), 24.7% were scored to IRS 4-6 (moderate positivity), 25.3% were scored to IRS 1-3 (weak positivity), and 35.9% showed no positivity at all. Immunoreaction could be detected in all histological types of breast cancers analysed with the exception of invasive papillary and cribriform carcinoma. Statistical analysis revealed a strong correlation between tumour grade and HMGA1 expression (rs=0.3516, p<0.0001). Thus, the HMGA1 expression level can be considered a potential prognostic marker for breast cancer.
Docetaxel Associated Pathways in Cisplatin Resistant Head and Neck Squamous Cell Carcinoma: A Pilot Study (2005)

Gene and protein expression are different and distinct between cells treated with docetaxel and cells treated with cisplatin. This finding provides evidence that different molecular pathways leading to cell death are targeted by docetaxel and cisplatin. Future studies focusing on these differentially expressed genes and proteins may improve our understanding, at the molecular level, of the mechanisms responsible for docetaxel-induced apoptosis in cisplatin-resistant HNSCC. Furthermore, these differentially expressed genes and proteins can be exploited as useful surrogate endpoint biomarkers in future clinical trials using docetaxel.
Expression of MMP-2 and TIMP-1 in Renal Tissue of Patients with Chronic Active Antibody-mediated Renal Graft Rejection (2012)

The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1128474926172838.
Proton Block and Voltage Gating Are Potassium-dependent in the Cardiac Leak Channel Kcnk3 (2000)

Potassium leak conductances were recently revealed to exist as independent molecular entities. Here, the genomic structure, cardiac localization, and biophysical properties of a murine example are considered. Kcnk3 subunits have two pore-forming P domains and unique functional attributes. At steady state, Kcnk3 channels behave like open, potassium-selective, transmembrane holes that are inhibited by physiological levels of proton. With voltage steps, Kcnk3 channels open and close in two phases, one appears to be immediate and one is time-dependent (tau = approximately 5 ms). Both proton block and gating are potassium-sensitive; this produces an anomalous increase in outward flux as external potassium levels rise because of decreased proton block. Single Kcnk3 channels open across the physiological voltage range; hence they are "leak" conductances; however, they open only briefly and rarely even after exposure to agents that activate other potassium channels.
A 1.2V, 140GHz receiver with on-die antenna in 65nm CMOS (2008)

This paper presents a 1.2 V, 100 mW, 140 GHz receiver with on-die antenna in a 65 nm General Purpose (GP) CMOS process with digital back-end. The receiver has a conversion loss of 15-19 dB in the 100-140 GHz range with 102 GHz LO, and occupies a die area of only 580 mum times 700 mum including pads. The LNA achieves 8 dB gain at 140 GHz, 10 GHz bandwidth, at least -1.8 dBm of saturated output power, and maintains 3 dB gain at 125 degC. The on-chip antenna, which meets all density fill requirements of 65 nm CMOS, has -25 dB gain, and occupies 180 mum times 100 mum of die area. Additionally, design techniques which maximize the millimeter-wave performance of CMOS devices are discussed.
Microarray-Based Study of Carbohydrate−Protein Binding by Gold Nanoparticle Probes (2008)

In order to develop a novel high-throughput tool for monitoring carbohydrate-protein interactions, we prepared carbohydrate or glycoprotein microarrays by immobilizing amino modified carbohydrates on aldehyde-derivatized glass slides or glycoprotein on epoxide-derivatized glass slides and carried out lectin binding experiments by using these microarrays, respectively. The interaction events are marked by attachment of gold nanoparticles followed by silver deposition for signal enhancement. The attachment of the gold nanoparticles is achieved by standard avidin-biotin chemistry. The detection principle is resonance light scattering (RLS). The well-defined recognition systems, namely, three monosaccharides (Man-alpha, Glc-beta and Gal-beta) or three glycoproteins (Asf, RNase A and RNase B) with two lectins (ConA and RCA120), were chosen here to establish the RLS assay, respectively. Highly selective recognition of carbohydrate-protein down to 25.6 pg/mL for RCA120 in solution and 8 microM for Gal-beta and 32 ng/mL for Asf on the microarray spots is demonstrated.
Activated Ras interacts with the Ral guanine nucleotide dissociation stimulator. (1994)

The yeast two-hybrid system was used to identify proteins that interact with Ras. The H-Ras protein was found to interact with a guanine nucleotide dissociation stimulator (GDS) that has been previously shown to regulate guanine nucleotide exchange on another member of the Ras protein family, Ral. The interaction is mediated by the C-terminal, noncatalytic segment of the RalGDS and can be detected both in vivo, using the two-hybrid system, and in vitro, with purified recombinant proteins. The interaction of the RalGDS C-terminal segment with Ras is specific, dependent on activation of Ras by GTP, and blocked by a mutation that affects Ras effector function. These characteristics are similar to those previously demonstrated for the interaction between Ras and its putative effector, Raf, suggesting that the RalGDS may also be a Ras effector. Consistent with this idea, the RalGDS was found to inhibit the binding of Raf to Ras.
The structure of the gene for the large subunit of ribulose 1,5-bisphosphate carboxylase from spinach chloroplast DNA (1981)

A cloned fragment of spinach chloroplast DNA carrying the gene for the large subunit of ribulose bisphosphate (RuBP) carboxylase has been analysed by electron microscopy of R-loops, by hybridization to Northern blots of chloroplast RNA, by S1 nuclease mapping and by DNA sequencing. The transcribed region of the gene is 1690 +/- 3 nucleotides long and co-linear with its mRNA. It comprises a 178-179 bp 5' untranslated sequence, a 1425 bp coding region and an 85-88 bp 3' untranslated region. The deduced sequence of the 475 amino acids of the spinach large subunit protein shows 10% divergence from that of the maize large subunit protein (1). The nucleotide sequence divergence between spinach and maize over the same coding region is 16% but in the transcribed flanking regions it is 35%. Features of the spinach chloroplast gene which resemble those of bacterial genes include a 5-base Shine-Dalgarno sequence complementary to a sequence near the 3' end of chloroplast and bacterial 16S rRNA, a promoter region partially homologous to a consensus sequence of bacterial promoters, and a transcription termination region capable of forming a typical stem and loop structure.
Spontaneous Partition of Carbon Nanotubes in Polymer-Modified Aqueous Phases (2013)

The distribution of nanoparticles in different aqueous environments is a fundamental problem underlying a number of processes, ranging from biomedical applications of nanoparticles to their effects on the environment, health, and safety. Here, we study distribution of carbon nanotubes (CNTs) in two immiscible aqueous phases formed by the addition of polyethylene glycol (PEG) and dextran. This well-defined model system exhibits a strikingly robust phenomenon: CNTs spontaneously partition between the PEG- and the dextran-rich phases according to nanotube's diameter and metallicity. Thermodynamic analysis suggests that this chirality-dependent partition is determined by nanotube's intrinsic hydrophobicity and reveals two distinct regimes in hydrophobicity-chirality relation: a small diameter (<1 nm) regime, where curvature effect makes larger diameter tubes more hydrophobic than small diameter ones, and a large diameter (>1.2 nm) regime, where nanotube's polarizability renders semiconducting tubes more hydrophobic than metallic ones. These findings reveal a general rule governing CNT behaviors in aqueous phase and provide an extremely simple way to achieve spatial separation of CNTs by their electronic structures.
Real-time power control of data centers for providing Regulation Service (2013)

Data centers account for 3% of the national electricity consumption today. Recent advances in power capping enable data centers to provide Regulation Service (RS) reserves to power markets. RS reserve requirements are expected to increase with the integration of substantial environmentally sustainable, albeit volatile and intermittent, renewable generation. We investigate the ability of server clusters to provide RS reserves while meeting contractual Quality-of-Service (QoS) guarantees for user applications running on the cluster. We propose a dynamic server power regulation policy for processing randomly arriving applications within probabilistic QoS constraints while tracking dynamically broadcasted RS requests by the power market Independent System Operator (ISO). Numerical results demonstrate the ability to select optimal RS reserve and average energy consumption levels that allow data centers to both deliver probabilistic QoS guarantees to customers and track real time ISO RS requests. Finally, we argue that simulated optimal policy performance statistics can enable data centers to bid for energy and to offer RS reserves in the the hour-ahead power markets.
Perturbation of the secondary structure of the scrapie prion protein under conditions that alter infectivity. (1993)

Limited proteolysis of the scrapie prion protein (PrPSc) generates PrP 27-30, which polymerizes into amyloid. By attenuated total reflection-Fourier transform infrared spectroscopy, PrP 27-30 polymers contained 54% beta-sheet, 25% alpha-helix, 10% turns, and 11% random coil; dispersion into detergent-lipid-protein-complexes preserved infectivity and secondary structure. Almost 60% of the beta-sheet was low-frequency infrared-absorbing, reflecting intermolecular aggregation. Decreased low-frequency beta-sheet and increased turn content were found after SDS/PAGE, which disassembled the amyloid polymers, denatured PrP 27-30, and diminished scrapie infectivity. Acid-induced transitions were reversible, whereas alkali produced an irreversible transition centered at pH 10 under conditions that diminished infectivity. Whether PrPSc synthesis involves a transition in the secondary structure of one or more domains of the cellular prion protein from alpha-helical, random coil, or turn into beta-sheet remains to be established.
Asynchronous wrapper for heterogeneous systems (1997)

We propose a new method for creating globally asynchronous locally synchronous (GALS) circuits. Each locally synchronous module is surrounded by an "asynchronous wrapper" which provides an asynchronous interface to an otherwise synchronous circuit. Every locally synchronous (LS) region operates independently, minimising problems of clock skew and enabling regions to run at different clock speeds if desired. Metastability can never cause the system to fail because an asynchronous handshake "stretches" or "pauses" the local clock until data has stabilised. When new data is not available for processing, the local clock stretches, automatically preventing the LS block from consuming power. Once new data does arrive, the block responds directly in phase with the handshake without wasted synchronisation time. The LS modules can be designed using typical synchronous techniques. However, since the external interface to each LS block uses asynchronous handshaking, we can now freely mix synchronous and asynchronous circuits.
A Practical Synthesis of (−)‐Oseltamivir (2007)

So einfach wie möglich: Das immer noch stark nachgefragte Grippemedikament (−)-Oseltamivir-Phosphat (Tamiflu; siehe Schema) wurde ausgehend von Pyridin mithilfe billiger Reagentien synthetisiert, wobei die Zahl an Reinigungsschritten konsequent gering gehalten wurde. Die Syntheseroute umfasst eine asymmetrische Diels-Alder-Reaktion, eine Bromlactonisierung, eine Hofmann-Umlagerung und eine Dominoreaktion eines Bicyclo[2.2.2]-Systems in ein Aziridinintermediat. Supporting information for this article is available on the WWW under http://www.wiley-vch.de/contents/jc_2001/2007/z701754_s.pdf or from the author. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
De novo assembly of the pepper transcriptome (Capsicum annuum): a benchmark for in silico discovery of SNPs, SSRs and candidate genes (2012)

Before availability of pepper genome sequence, assembling transcriptomes of this economically important crop was required to generate thousands of high-quality molecular markers that could be used in breeding programs. In order to have a better understanding of the assembled sequences and to identify candidate genes underlying QTLs, we annotated the contigs of Sanger-EST and Illumina transcriptome assemblies. These and other information have been curated in a database that we have dedicated for pepper project.
β-Amyloid peptide blocks the response of α7-containing nicotinic receptors on hippocampal neurons (2001)

Alzheimer's disease produces a devastating decline in mental function, with profound effects on learning and memory. Early consequences of the disease include the specific loss of cholinergic neurons in brain, diminished cholinergic signaling, and the accumulation of β-amyloid peptide in neuritic plaques. Of the nicotinic acetylcholine receptors at risk, the most critical may be those containing the α7 gene product (α7-nAChRs), because they are widespread, have a high relative permeability to calcium, and regulate numerous cellular events in the nervous system. With the use of whole-cell patch–clamp recording we show here that nanomolar concentrations of β-amyloid peptides specifically and reversibly block α7-nAChRs on rat hippocampal neurons in culture. The block is noncompetitive, voltage-independent, and use-independent and is mediated through the N-terminal extracellular domain of the receptor. It does not appear to require either calcium influx or G protein activation. β-Amyloid blockade is likely to be a common feature of α7-nAChRs because it applies to the receptors at both somato-dendritic and presynaptic locations on rat hippocampal neurons and extends to homologous receptors on chick ciliary ganglion neurons as well. Because α7-nAChRs in the central nervous system are thought to have numerous functions and recently have been implicated in learning and memory, impaired receptor function in this case may contribute to cognitive deficits associated with Alzheimer's disease.
Toward comprehensive nursing care of the total artificial heart patient. (1990)

At this time, heart transplantation is the only form of intervention for some end-stage cardiac diseases. The use of the artificial heart has been adopted at the Ottawa Institute as a bridge to transplant when a heart is needed, and there are no suitable donors available. The patient is maintained with this technology until a donor heart can be found and transplanted. This article chronicles the steps that were taken by the nursing staff in preparation for these unique patients. The nursing process was the main framework around which we developed our plan of action, assessed and evaluated our interventions and modified nursing care accordingly. The basic functioning of the system that operates the heart is described, as well as nursing care specific to the Total Artificial Heart patient.
Poliovirus vaccine vectors elicit antigen-specific cytotoxic T cells and protect mice against lethal challenge with malignant melanoma cells expressing a model antigen (1998)

Recombinant polioviruses expressing foreign antigens may provide a convenient vaccine vector system to induce protective immunity against diverse pathogens. Replication-competent chimeric viruses can be constructed by inserting foreign antigenic sequences within the poliovirus polyprotein. When inserted sequences are flanked by poliovirus protease recognition sites the recombinant polyprotein is processed to mature and functional viral proteins plus the exogenous antigen. It previously has been shown that poliovirus recombinants can induce antibody responses against the inserted sequences but it is not known whether poliovirus or vaccine vectors derived from it can elicit effective cytotoxic T lymphocyte (CTL) responses. To examine the ability of the recombinant poliovirus to induce CTL responses, a segment of the chicken ovalbumin gene, which includes the H2-Kb-restricted CTL epitope SIINFEKL, was cloned at the junction of the P1 and P2 regions. This recombinant virus replicated with near wild-type efficiency in culture and stably expressed high levels of the ovalbumin antigen. Murine and primate cells infected with the recombinant virus appropriately processed the SIINFEKL epitope and presented it within major histocompatibility complex class I molecules. Inoculation of mice with recombinant poliovirus that expresses ovalbumin elicits an effective specific CTL response. Furthermore, vaccination with these recombinant poliovirus induced protective immunity against challenge with lethal doses of a malignant melanoma cell line expressing ovalbumin.
Properties of Human Trabecular Bone Cells from Elderly Women: Implications for Cell-Based Bone Engraftment (2004)

Tissue-engineered bone regeneration offers new therapeutic options in the treatment of patients with fractures. Due to the changes in the hormone levels, elderly women are most affected by bone fractures and thus constitute one of the future target groups of cell-based bone therapy. For designing cell-based therapy approaches, a better understanding of individual-dependent variations in bone-derived cells of the host is required. In this study, a simple, high-yield procedure is described for the collection of cells from bone tissue of a high number of elderly women. The cultured cells display stem cell characteristics indicated by the presence of a CD13+, CD44+, CD90+, CD147+, CD14-, CD34-, CD45- and CD144- cell populations and by a stable undifferentiated phenotype as well as by the ability to proliferate extensively while retaining the potential to differentiate along the osteoblastic lineage even after 27 cell doublings. A high variability in the number of cell-forming units (CFUs) within a donor population of 34 samples, in the morphology within 50 donors, in the expression of alkaline phosphatase within 15 samples and in the responsiveness to BMP-2 was evident, but no age-related correlation could be found. In conclusion, the data indicate that individual variations in cell number, cell morphology and in the osteogenic potential of progenitor cells of the patient may be relevant for a successful treatment of bone fractures in the elderly by cell-based therapy approaches.