gebhart/patrepeval huggingface dataset:
Abstract 4171: Tumor suppressive microRNA-218 mediated focal adhesion pathways in cervical squamous cell carcinoma. (2013)

Abstract Background: MicroRNAs (miRNAs), a class of small non-coding RNAs, regulate protein-coding gene expression by repressing translation or cleaving RNA transcripts in a sequence-specific manner. A growing body of evidence suggests that miRNAs contribute to cervical squamous cell carcinoma (cervical-SCC) progression, development, and metastasis. Recent our miRNA expression signature of SCC (hypopharyngeal-SCC and esophageal-SCC) revealed that microRNA-218 (miR-218) was significantly reduced in cancer tissues. The study of the aim was to investigate the functional significance of miR-218 and its mediated molecular pathways in cervical-SCC. Methods: Gain-of-function studies were performed to investigate cancer cell proliferation, migration and invasion by restoration of mature miRNAs into HPV positive or negative cervical-SCC cell lines (CaSKi, HeLa, ME180 and YUMOTO). To identify the biological processes or pathways potentially regulated by the miRNAs, we applied genome-wide gene expression analysis and in silico study. The GENECODIS software assigned a number of the putative miRNA targets to known pathways in KEGG [http://www.genome.jp/kegg/pathway.html]. Gene expression analyses of all candidate genes involved in each of the pathways using GEO (http://www.ncbi.nlm.nih.gov/geo/) database. Results: Expression levels of miR-218 were significantly reduced in cervical-SCC clinical specimens compared to adjacent non-cancerous tissues (P&lt;0.0001). Restoration of miR-218 significantly inhibited cancer cell migration and invasion in all cervical-SCC cell lines. These data indicated that miR-218 act as a tumor suppressor in cervical-SCC. Our in silico analysis showed that miR-218 appeared to be an important modulator of tumor cell processes through suppression of many targets, particularly those involved in “focal adhesion” signaling pathways (P&lt;0.05). Gene expression data indicated that LAMB3 and LAMC1 were up-regulated in cervical-SCC clinical specimens. The laminins are an important and biologically active part of the basal lamina, the function of that are various such as influencing cell differentiation, migration and adhesion as well as proliferation and cell survival. Conclusions: Aberrant expression of miRNAs has shed light on recent miRNA signatures and identification of tumor suppressive miRNA mediated novel molecular pathways in cervical-SCC. Tumor suppressive miR-218-mediated novel molecular pathways provide a new insight of cervical-SCC oncogenesis and metastasis. Citation Format: Noriko Yamamoto, Takashi Kinosita, Nijiro Nohata, Toshihiko Idesako, Hirofumi Yoshino, Hideki Enokida, Masayuki Nakagawa, Makio Syozu, Naohiko Seki. Tumor suppressive microRNA-218 mediated focal adhesion pathways in cervical squamous cell carcinoma. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4171. doi:10.1158/1538-7445.AM2013-4171
HybCache: Hybrid Side-Channel-Resilient Caches for Trusted Execution Environments (2019)

Modern multi-core processors share cache resources for maximum cache utilization and performance gains. However, this leaves the cache vulnerable to side-channel attacks, where timing differences in shared cache behavior are exploited to infer information on the victim's execution patterns, ultimately leaking private information. The root cause for these attacks is mutually distrusting processes sharing cache entries and accessing them in a deterministic manner. Various defenses against cache side-channel attacks have been proposed. However, they either degrade performance significantly, impose impractical restrictions, or can only defeat certain classes of these attacks. More importantly, they assume that side-channel-resilient caches are required for the entire execution workload and do not allow to selectively enable the mitigation only for the security-critical portion of the workload. We present a generic mechanism for a flexible and soft partitioning of set-associative caches and propose a hybrid cache architecture, called HybCache. HybCache can be configured to selectively apply side-channel-resilient cache behavior only for isolated execution domains, while providing the non-isolated execution with conventional cache behavior, capacity and performance. An isolation domain can include one or more processes, specific portions of code, or a Trusted Execution Environment. We show that, with minimal hardware modifications and kernel support, HybCache can provide side-channel-resilient cache only for isolated execution with a performance overhead of 3.5-5%, while incurring no performance overhead for the remaining execution workload. We provide a simulator-based and hardware implementation of HybCache to evaluate the performance and area overheads, and show how it mitigates typical access-based and contention-based cache attacks.
Experimental and numerical studies in the evaluation of epoxy-cured fiber optic connectors (2002)

The fiber optic connector (FOC) is a passive optical component that is used in many applications and whose function is to physically and optically link two fiber joints. It is important for the reliability of fiber optic infrastructure to identify the mechanisms of degradation and failure of these components. This paper reviews work at the University of Maryland CALCE Center to accomplish this, including experimental strain analysis utilizing fiber sensors and calculations and models to predict the stresses in FOCs and their effect on the response of the sensors used. In-fiber Bragg grating sensors have been used to study the mechanical strain state in optical fibers that have been terminated in ST connectors. Our findings indicate that terminated sensors experience a compressive strain whose magnitude depends on the cure profile of the epoxy encapsulant used in these connectors. Specifically, we have found that room temperature cures result in lower strain as compared to thermally cured samples. The measured strain magnitude is also believed to be sensitive to the position of the sensor along the axis of the connector. It is believed that to adequately account for such phenomena to occur and predict failure and degradation of the connector, the behavior and response of the epoxy encapsulant is a key consideration.
Impact-echo : (1986)

To develop a basis for a nondestructive test method for heterogenous solids such as concrete, analytical, numerical, and laboratory studies of transient stress wave propagation in solid plates and in plates containing flaws are presented. The technique, which is referred to as the impact-echo method, involves introducing transient stress waves into a test object by mechanical point impact and monitoring reflections of the waves from internal defects and external boundaries using a point receiver located close to the impact point .
Integrated design of AES (Advanced Encryption Standard) encrypter and decrypter (2003)

This paper proposed a method of integrating the AES encrypter and the AES decrypter into a full functional AES crypto-engine. This method can make it a very low-complexity architecture, especially in saving the hardware resource in implementing the AES (Inv)SubBytes module and (Inv)Mixcolumns module, etc. Most designed modules can be used for both AES encryption and decryption. Besides, the architecture can still deliver a high data rate in both encryption/decryption operations. The proposed architecture is suited for hardware-critical applications, such as smart cards, PDAs, and mobile phones, etc.
Epigenetics of Drug Abuse: Predisposition or Response (2012)

Drug addiction continues to be a serious medical and social problem. Vulnerability to develop an addiction to drugs is dependent on genetic, environmental, social and biological factors. In particular, the interactions of environmental and genetic factors indicate the significance of epigenetic mechanisms, which have been found to occur in response to illicit drug use or as underlying factors in chronic substance abuse and relapse. Epigenetics is defined as the heritable and possibly reversible modifications in gene expression that do not involve alterations in the DNA sequence. This review discusses the various types of epigenetic modifications and their relevance to drug addiction to elucidate whether epigenetics is a predisposing factor, or a response to, developing an addiction to drugs of abuse.
MUSTANG: A multiple structural alignment algorithm (2006)

Multiple structural alignment is a fundamental problem in structural genomics. In this article, we define a reliable and robust algorithm, MUSTANG (MUltiple STructural AligNment AlGorithm), for the alignment of multiple protein structures. Given a set of protein structures, the program constructs a multiple alignment using the spatial information of the C(alpha) atoms in the set. Broadly based on the progressive pairwise heuristic, this algorithm gains accuracy through novel and effective refinement phases. MUSTANG reports the multiple sequence alignment and the corresponding superposition of structures. Alignments generated by MUSTANG are compared with several handcurated alignments in the literature as well as with the benchmark alignments of 1033 alignment families from the HOMSTRAD database. The performance of MUSTANG was compared with DALI at a pairwise level, and with other multiple structural alignment tools such as POSA, CE-MC, MALECON, and MultiProt. MUSTANG performs comparably to popular pairwise and multiple structural alignment tools for closely related proteins, and performs more reliably than other multiple structural alignment methods on hard data sets containing distantly related proteins or proteins that show conformational changes.
Structure-function study of maize ribosome-inactivating protein: implications for the internal inactivation region and the sole glutamate in the active site (2007)

Maize ribosome-inactivating protein is classified as a class III or an atypical RNA N-glycosidase. It is synthesized as an inactive precursor with a 25-amino acid internal inactivation region, which is removed in the active form. As the first structural example of this class of proteins, crystals of the precursor and the active form were diffracted to 2.4 and 2.5 A, respectively. The two proteins are similar, with main chain root mean square deviation (RMSD) of 0.519. In the precursor, the inactivation region is found on the protein surface and consists of a flexible loop followed by a long alpha-helix. This region diminished both the interaction with ribosome and cytotoxicity, but not cellular uptake. Like bacterial ribosome-inactivating proteins, maize ribosome-inactivating protein does not have a back-up glutamate in the active site, which helps the protein to retain some activity if the catalytic glutamate is mutated. The structure reveals that the active site is too small to accommodate two glutamate residues. Our structure suggests that maize ribosome-inactivating protein may represent an intermediate product in the evolution of ribosome-inactivating proteins.
Morrison and Parry Seals for Water Pressures up to 345 MPa (1980)

The use of water in high-pressure jet cutting and machining requires seals capable of sealing reciprocating and rotating shafts with minimal leakage. Both Morrison and Parry seals are studied analytically to determine the geometric parameters influencing their behavior in water. Limited experimental evidence supports the findings. In particular, the Morrison seal is most appropriate for use with oil, while the Parry seal shows greater potential for sealing water.
Register allocation for irregular architectures (2002)

For irregular architectures global register allocation is still a challenging problem that has not been successfully solved so far. The graph-coloring analogy of traditional approaches does not match the needs of register allocation for such architectures which feature non-orthogonal instruction sets and small register files. This work proposes a fundamentally new approach to global register allocation for irregular architectures. Our approach formulates global allocation as a partitioned boolean quadratic optimization problem (PBQP) that allows generic modeling of processors peculiarities. Because PBQP is NP-complete we present a heuristic that exhibits a nearly linear run-time complexity.We integrated our register allocator with the Infineon Carmel C Compiler which is based on the Open Compiler Environment from Atair Software. A DSP benchmark suite was used to compare the performance of our register allocator with a graph-coloring approach and with an optimal allocation. The experiments show that our new approach performs better than a traditional graph coloring approach for irregular architectures.
Structural and functional characterisation of cardiac fibroblasts (2004)

Cardiac fibroblasts form one of the largest cell populations, in terms of cell numbers, in the heart. They contribute to structural, biochemical, mechanical and electrical properties of the myocardium. Nonetheless, they are often disregarded by in vivo and in vitro studies into cardiac function. This review summarizes our understanding of fibroblast origin and identity, their structural organization and role in myocardial architecture, as well as functional aspects related to cell signalling and electro-mechanical function in the heart.
High-dynamic range imaging techniques based on both color-separation algorithms used in conventional graphic arts and the human visual perception modeling (2009)

The aim of this research is to derive illuminant-independent type of HDR imaging modules which can optimally multispectrally reconstruct of every color concerned in high-dynamic-range of original images for preferable cross-media color reproduction applications. Each module, based on either of broadband and multispectral approach, would be incorporated models of perceptual HDR tone-mapping, device characterization. In this study, an xvYCC format of HDR digital camera was used to capture HDR scene images for test. A tone-mapping module was derived based on a multiscale representation of the human visual system and used equations similar to a photoreceptor adaptation equation, proposed by Michaelis-Menten. Additionally, an adaptive bilateral type of gamut mapping algorithm, using approach of a multiple conversing-points (previously derived), was incorporated with or without adaptive Un-sharp Masking (USM) to carry out the optimization of HDR image rendering. An LCD with standard color space of Adobe RGB (D65) was used as a soft-proofing platform to display/represent HDR original RGB images, and also evaluate both renditionquality and prediction-performance of modules derived. Also, another LCD with standard color space of sRGB was used to test gamut-mapping algorithms, used to be integrated with tone-mapping module derived.
Central Nervous System Delivery of Interleukin 4 by a Nonreplicative Herpes Simplex Type 1 Viral Vector Ameliorates Autoimmune Demyelination (1998)

Multiple sclerosis (MS) is a T cell-mediated organ-specific inflammatory disease leading to central nervous system (CNS) demyelination. On the basis of results obtained in experimental autoimmune encephalomyelitis (EAE) models, MS treatment by administration of antiinflammatory cytokines such as interleukin 4 (IL-4) is promising but is hampered by the limited access of the cytokines to the CNS and by the pleiotropic effects of systemically administered cytokines. We established a cytokine delivery system within the CNS using non-replicative herpes simplex type 1 (HSV-1) viral vectors engineered with cytokine genes. These vectors injected into the cisterna magna (i.c.) of mice diffuse in all ventricular and subarachnoid spaces and infect with high efficiency the ependymal and leptomeningeal cell layers surrounding these areas, without obvious toxic effects. Heterologous genes contained in the vectors are efficiently transcribed in infected ependymal cells, leading to the production of high amounts of the coded proteins. For example, 4.5 ng of interferon gamma (IFN-gamma) per milliliter is secreted into the cerebrospinal fluid (CSF) up to day 28 postinjection (p.i.) and reaches the CNS parenchyma in bioactive form, as demonstrated by upregulation of MHC class I expression on CNS-resident cells. We then exploited the therapeutic potential of the vectors in EAE mice. An HSV-1-derived vector containing the IL-4 gene was injected i.c. in Biozzi AB/H mice at the time of EAE induction. We found the following in treated mice: (1) delayed EAE onset, (2) a significant decrease in clinical score, (3) a significant decrease in perivascular inflammatory infiltrates and in the number of macrophages infiltrating the CNS parenchyma and the submeningeal spaces, and (4) a reduction in demyelinated areas and axonal loss. Peripheral T cells from IL-4-treated mice were not affected either in their antigen-specific proliferative response or in cytokine secretion pattern. Our results indicate that CNS cytokine delivery with HSV-1 vectors is feasible and might represent an approach for the treatment of demyelinating diseases. Advantages of this approach over systemic cytokine administration are the high cytokine level reached in the CNS, the absence of effects on the peripheral immune system, and the long-lasting cytokine production in the CNS after a single vector administration.
The Ubiquitin-Conjugating DNA Repair Enzyme HR6A Is a Maternal Factor Essential for Early Embryonic Development in Mice (2004)

The Saccharomyces cerevisiae RAD6 protein is required for a surprising diversity of cellular processes, including sporulation and replicational damage bypass of DNA lesions. In mammals, two RAD6-related genes, HR6A and HR6B, encode highly homologous proteins. Here, we describe the phenotype of cells and mice deficient for the mHR6A gene. Just like mHR6B knockout mouse embryonic fibroblasts, mHR6A-deficient cells appear to have normal DNA damage resistance properties, but mHR6A knockout male and female mice display a small decrease in body weight. The necessity for at least one functional mHR6A (X-chromosomal) or mHR6B (autosomal) allele in all somatic cell types is supported by the fact that neither animals lacking both proteins nor females with only one intact mHR6A allele are viable. In striking contrast to mHR6B knockout males, which show a severe spermatogenic defect, mHR6A knockout males are normally fertile. However, mHR6A knockout females fail to produce offspring despite a normal ovarian histology and ovulation. The absence of mHR6A in oocytes prevents development beyond the embryonic two-cell stage but does not result in an aberrant methylation pattern of histone H3 at this early stage of mouse embryonic development. These observations support redundant but dose-dependent roles for HR6A and HR6B in somatic cell types and germ line cells in mammals.
ProtEST: protein multiple sequence alignments from expressed sequence tags (2000)

geoff@ebi.ac.uk
Stomatal Development and Pattern Controlled by a MAPKK Kinase (2004)

Stomata are epidermal structures that modulate gas exchange between a plant and its environment. During development, stomata are specified and positioned nonrandomly by the integration of asymmetric cell divisions and intercellular signaling. The Arabidopsis mitogen-activated protein kinase kinase kinase gene, YODA, acts as part of a molecular switch controlling cell identities in the epidermis. Null mutations in YODA lead to excess stomata, whereas constitutive activation of YODA eliminated stomata. Transcriptome analysis of seedlings with altered YODA activity was used to identify potential stomatal regulatory genes. A putative transcription factor from this set was shown to regulate the developmental behavior of stomatal precursors.
E2A and IRF-4/Pip Promote Chromatin Modification and Transcription of the Immunoglobulin κ Locus in Pre-B Cells (2006)

The immunoglobulin kappa light chain (Igkappa) locus is regulated in a lineage- and stage-specific manner during B-cell development. The highly restricted timing of V to J gene recombination at the pre-B-cell stage is under the control of two enhancers, the intronic enhancer (kappaEi) and the 3' enhancer (kappaE3'), flanking the constant exon. E2A transcription factors have been indicated to be directly involved in the regulation of Igkappa locus activation. In this study, we utilize E2A-deficient pre-B cells to directly investigate the mechanism of E2A-mediated Igkappa activation. We demonstrate that Igkappa germ line transcription is severely impaired and recombination is blocked in the absence of E2A. Reconstitution of E2A-/- pre-B cells with inducible human E2A (E47R) is sufficient to promote chromatin modification of Igkappa and rescue Igkappa germ line transcription and Jkappa gene recombinase accessibility. Furthermore, we show that increased E2A recruitment to kappaEi and kappaE3' correlates with activation of Igkappa in pre-B cells and that recruitment of E2A to kappaE3' is in part dependent on the transcription factor IRF-4. Inhibition of IRF-4 expression in pre-B cells leads to a significant reduction of Igkappa germ line transcription and enhancer acetylation. In the absence of E2A, increased IRF-4 expression is not sufficient to promote Igkappa enhancer chromatin modification or transcription, suggesting that the sequential involvement of IRF-4 and E2A is necessary for the activation of the Igkappa locus. Finally, we provide genetic evidence in the mouse that E2A gene dosage can influence the development of pre-B cells during the phase of Igkappa gene activation.
Human Cardiac Fibroblast Number and Activation State Modulate Electromechanical Function of hiPSC-Cardiomyocytes in Engineered Myocardium (2020)

Cardiac tissue engineering using hiPSC-derived cardiomyocytes is a promising avenue for cardiovascular regeneration, pharmaceutical drug development, cardiotoxicity evaluation, and disease modeling. Limitations to these applications still exist due in part to the need for more robust structural support, organization, and electromechanical function of engineered cardiac tissues. It is well accepted that heterotypic cellular interactions impact the phenotype of cardiomyocytes. The current study evaluates the functional effects of coculturing adult human cardiac fibroblasts (hCFs) in 3D engineered tissues on excitation and contraction with the goal of recapitulating healthy, nonarrhythmogenic myocardium in vitro. A small population (5% of total cell number) of hCFs in tissues improves tissue formation, material properties, and contractile function. However, two perturbations to the hCF population create disease-like phenotypes in engineered cardiac tissues. First, increasing the percentage of hCFs to 15% resulted in tissues with increased ectopic activity and spontaneous excitation rate. Second, hCFs undergo myofibroblast activation in traditional two-dimensional culture, and this altered phenotype ablated the functional benefits of hCFs when incorporated into engineered cardiac tissues. Taken together, the results of this study demonstrate that human cardiac fibroblast number and activation state modulate electromechanical function of hiPSC-cardiomyocytes and that a low percentage of quiescent hCFs are a valuable cell source to advance a healthy electromechanical response of engineered cardiac tissue for regenerative medicine applications.