gebhart/patrepeval huggingface dataset:
Locked Nucleic Acid: A Potent Nucleic Acid Analog in Therapeutics and Biotechnology (2004)

Locked nucleic acid (LNA) is a class of nucleic acid analogs possessing very high affinity and excellent specificity toward complementary DNA and RNA, and LNA oligonucleotides have been applied as antisense molecules both in vitro and in vivo. In this review, we briefly describe the basic physiochemical properties of LNA and some of the difficulties that may be encountered when applying LNA technology. The central part of the review focuses on the use of LNA molecules in regulation of gene expression, including delivery to cells, stability, unspecific effects, toxicity, pharmacokinetics, and design of LNA oligonucleotides. The last part evaluates LNA as a diagnostic tool in genotyping.
Selective deficits in the expression of striatal‐enriched mRNAs in Huntington's disease (2006)

We have identified and cataloged 54 genes that exhibit predominant expression in the striatum. Our hypothesis is that such mRNA molecules are likely to encode proteins that are preferentially associated with particular physiological processes intrinsic to striatal neurons, and therefore might contribute to the regional specificity of neurodegeneration observed in striatal disorders such as Huntington's disease (HD). Expression of these genes was measured simultaneously in the striatum of HD R6/1 transgenic mice using Affymetrix oligonucleotide arrays. We found a decrease in expression of 81% of striatum-enriched genes in HD transgenic mice. Changes in expression of genes associated with G-protein signaling and calcium homeostasis were highlighted. The most striking decrement was observed for a newly identified subunit of the sodium channel, beta 4, with dramatic decreases in expression beginning at 8 weeks of age. A subset of striatal genes was tested by real-time PCR in caudate samples from human HD patients. Similar alterations in expression were observed in human HD and the R6/1 model for the striatal genes tested. Expression of 15 of the striatum-enriched genes was measured in 6-hydroxydopamine-lesioned rats to determine their dependence on dopamine innervation. No changes in expression were observed for any of these genes. These findings demonstrate that mutant huntingtin protein causes selective deficits in the expression of mRNAs responsible for striatum-specific physiology and these may contribute to the regional specificity of degeneration observed in HD.
Rab Proteins, Connecting Transport and Vesicle Fusion (2005)

Small GTPases of the Rab family control timing of vesicle fusion. Fusion of two vesicles can only occur when they have been brought into close contact. Transport by microtubule- or actin-based motor proteins will facilitate this process in vivo. Ideally, transport and vesicle fusion are linked activities. Active, GTP-bound Rab proteins dock on specific compartments and are therefore perfect candidates to control transport of the different compartments. Recently, a number of Rab proteins were identified that control motor protein recruitment to their specific target membranes. By cycling through inactive and active states, Rab proteins are able to control motor protein-mediated transport and subsequent fusion of intracellular structures in both spatial and timed manners.
Catheter ablation of tachyarrhythmias in small children. (2005)

An estimated 80,000-100,000 radiofrequency ablation (RFA) procedures are performed in the United States each year.1 Approximately 1% of these are performed on pediatric patients at centers that contribute data to the Pediatric Radiofrequency Registry.2 Previous reports from this registry have demonstrated that RFA can safely and effectively be performed in pediatric patients.3,4 However, patients weighing less than 15 kg have been identified as being at greater risk for complications.3,4 Consequently, there has been great reluctance to perform RFA in small children such that children weighing less than 15 kg only represent approximately 6% of the pediatric RFA experience2 despite the fact that this age group carries the highest incidence of tachycardia, particularly supraventricular tachycardia (SVT).5 Factors other than the risk of complications contribute to the lower incidence of RFA in this group, including the natural history of the most common tachycardias (SVT), technical issues with RFA in small hearts, and the potential unknown long-term effects of RF applications in the maturing myocardium. Conversely, there are several reasons why ablation may be desirable in small children, including greater difficulties with medical management,6,7,8 the higher risk for hemodynamic compromise during tachycardia in infants with congenital heart disease (CHD), and the inability of these small children to effectively communicate their symptoms thereby making it more likely that their symptoms may go unnoticed until the children become more seriously ill. Before ultimately deciding that catheter ablation is indicated in small children, one must consider which tachycardias are likely to be ablated, the clinical presentation of these tachycardias, alternatives to ablation, the relative potential for success or complications, and modifications of the procedure that might reduce the risk of ablation in this group.
Evaluation of the Effects of DNase Treatment on Signal Specificity in RT-PCR and In Situ RT-PCR (1998)

In this study, the effects of DNase treatment on the specificity of reverse transcription (RT)-PCR have been investigated on different samples, containing RNA, DNA, DNA/RNA and DNA/cDNA. This was to evaluate the possibilities of getting specific results in a direct in situ RT-PCR. All DNA targets in the samples were eliminated after 1 h of DNase treatment. However, some DNA fragments still remained after both 1 h and overnight DNase treatment. When these fragments served as primers for amplification, nonspecific smears resulted. In samples containing small amounts of RNA, the RNA was affected by overnight treatment with DNase. Our conclusion is that the direct in situ RT-PCR is an unreliable method because the necessary DNase treatment induces nonspecific amplification, and no size-separation is possible. We conclude that the best way to perform an in situ RT-PCR is to hybridize with a labeled specific probe after amplification is completed.
An improved approach to the hidden Markov model decomposition of speech and noise (1992)

The author addresses the problem of automatic speech recognition in the presence of interfering noise. The novel approach described decomposes the contaminated speech signal using a generalization of standard hidden Markov modeling, while utilizing a compact and effective parametrization of the speech signal. The technique is compared to some existing noise compensation techniques, using data recorded in noise, and is found to have improved performance compared to existing model decomposition techniques. Performance is comparable to existing noise subtraction techniques, but the technique is applicable to a wider range of noise environments and is not dependent on an accurate endpointing of the speech.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Photoluminescence in porous sputtered polysilicon films formed by chemical etching (1997)

We have investigated the materials and photoluminescence properties of porous polysilicon films formed by chemical etching. The polysilicon samples were prepared by furnace crystallization of r.f. sputtered silicon films on a crystalline silicon substrate. The materials properties were observed by SEM, TEM, XRD and FTIR. XRD showed that the grains with (111) orientation have the highest etching rate and are probably most efficient in forming porous regions. The photoluminescence intensity depends on the annealing temperature of the sputtered Si film, and has a maximum value at a temperature around . This temperature dependence can be explained from the relative peak intensities of grains of different orientation measured by XRD. Rapid thermal oxidation of porous polysilicon films was found to degrade the photoluminescence intensity.
Efficient Monte Carlo and greedy heuristic for the inference of stochastic block models (2014)

We present an efficient algorithm for the inference of stochastic block models in large networks. The algorithm can be used as an optimized Markov chain Monte Carlo (MCMC) method, with a fast mixing time and a much reduced susceptibility to getting trapped in metastable states, or as a greedy agglomerative heuristic, with an almost linear O(Nln2N) complexity, where N is the number of nodes in the network, independent of the number of blocks being inferred. We show that the heuristic is capable of delivering results which are indistinguishable from the more exact and numerically expensive MCMC method in many artificial and empirical networks, despite being much faster. The method is entirely unbiased towards any specific mixing pattern, and in particular it does not favor assortative community structures.
Endoderm and heart development (2000)

Since the first half of the 20th century, experimental embryologists have noted a relationship between endoderm cells and the development of cardiac tissue from mesoderm. During the past decade, the accumulation of evidence for an obligatory interaction between endoderm and mesoderm during the specification and terminal differentiation of myocardial, and more recently endocardial, cells has markedly accelerated. Moreover, the endoderm-derived molecules that may regulate these processes are being identified. It now appears that endoderm-derived growth factors regulate the formation of both myocardial and endocardial cells during specification, terminal differentiation, and perhaps morphogenesis of cells in the developing embryonic heart.
The retinoblastoma gene in breast cancer: allele loss is not correlated with loss of gene protein expression. (1992)

The significance of the retinoblastoma gene (RB) in the development of human breast cancer remains unclear. In the present study, loss of heterozygosity (LOH) in RB was found in 26% of 90 informative primary breast tumors and was correlated to DNA nondiploidy, a high S-phase fraction, and LOH at chromosome 17p13.3. However, allele loss was not associated with loss of RB protein (pRB) expression. Low to absent levels of pRB were found in 15% of 73 immunoblot analyzed tumors, most of which manifested retained heterozygosity in RB. Conversely, tumors exhibiting LOH showed often high pRB expression. Our data suggest that RB may be involved in the pathogenesis of some breast tumors, as evidenced by the absence of pRB, but that this alteration is acquired by mechanisms other than the unmasking of a recessive mutation by allele loss. LOH in RB may be merely a stochastic event in the unstable genome of aneuploid, rapidly proliferating cells or, alternatively, reflect the presence of an adjacent tumor suppressor gene.
Tools for Protecting the Privacy of Specific Individuals in Video (2007)

This paper presents a system for protecting the privacy of specific individuals in video recordings. We address the following two problems: automatic people identification with limited labeled data, and human body obscuring with preserved structure and motion information. In order to address the first problem, we propose a new discriminative learning algorithm to improve people identification accuracy using limited training data labeled from the original video and imperfect pairwise constraints labeled from face obscured video data. We employ a robust face detection and tracking algorithm to obscure human faces in the video. Our experiments in a nursing home environment show that the system can obtain a high accuracy of people identification using limited labeled data and noisy pairwise constraints. The study result indicates that human subjects can perform reasonably well in labeling pairwise constraints with the face masked data. For the second problem, we propose a novel method of body obscuring, which removes the appearance information of the people while preserving rich structure and motion information. The proposed approach provides a way to minimize the risk of exposing the identities of the protected people while maximizing the use of the captured data for activity/behavior analysis.
Structural determinants for ERK5 (MAPK7) and leucine rich repeat kinase 2 activities of benzo[e]pyrimido-[5,4-b]diazepine-6(11H)-ones (2013)

The benzo[e]pyrimido-[5,4-b]diazepine-6(11H)-one core was discovered as a novel ERK5 (also known as MAPK7 and BMK1) inhibitor scaffold, previously. Further structure-activity relationship studies of this scaffold led to the discovery of ERK5-IN-1 (26) as the most selective and potent ERK5 inhibitor reported to date. 26 potently inhibits ERK5 biochemically with an IC₅₀ of 0.162 ± 0.006 μM and in cells with a cellular EC₅₀ for inhibiting epidermal growth factor induced ERK5 autophosphorylation of 0.09 ± 0.03 μM. Furthermore, 26 displays excellent selectivity over other kinases with a KINOMEscan selectivity score (S₁₀) of 0.007, and exhibits exceptional bioavailability (F%) of 90% in mice. 26 will serve as a valuable tool compound to investigate the ERK5 signaling pathway and as a starting point for developing an ERK5 directed therapeutic agent.
Common Variants in Glutamine:Fructose-6-Phosphate Amidotransferase 2 (GFPT2) Gene Are Associated with Type 2 Diabetes, Diabetic Nephropathy, and Increased GFPT2 mRNA Levels (2004)

Increased flux of glucose through the hexosamine biosynthetic pathway has been implicated in insulin resistance, altered insulin secretion, and diabetic nephropathy. Glutamine:fructose-6-phosphate amidotransferase (GFPT), the rate limiting enzyme in hexosamine biosynthesis, is encoded by the unlinked but highly homologous genes GFPT1 and GFPT2. We tested the hypothesis that GFPT2 sequence variation contributed to the susceptibility to type 2 diabetes mellitus (T2DM) and diabetic nephropathy in Caucasian and African-American individuals. We identified 11 single nucleotide polymorphisms (SNPs), of which seven were common. A single variant in exon 14, I471V, altered the amino acid sequence, is conserved between human and mouse genes, and was associated with T2DM among Caucasians (P = 0.05). A trend to an association was noted with diabetic nephropathy among African-American individuals (P = 0.15). Several variants in the 3' untranslated region (UTR) and exon 18 were also associated with T2DM in Caucasian individuals (P < 0.05), and the SNP in the 3' UTR was associated with diabetic nephropathy in African-American subjects (P = 0.047). GFPT2 mRNA levels in transformed lymphocytes from study subjects were significantly increased among African-American subjects compared with Caucasian individuals, regardless of diagnosis. Furthermore, the associated allele of the 3' UTR SNP was approximately 2-fold overexpressed. We propose that the 3' UTR variant results in increased GFPT2 mRNA levels with resultant increased hexosamine flux. The I471V variant may contribute to altered protein function or may simply be in linkage disequilibrium with the 3' UTR.
Synthesis of continuous mesoporous silica thin films with three-dimensional accessible pore structures (1998)

Continuous mesoporous silica thin films with three-dimensional (3-D) accessible pore structures (Pm3n, P63/mmc space groups) have been prepared by a dip-coating technique using cationic surfactants as the structure-directing agents in nonaqueous media under acidic conditions.
Beyond 1 Tb/s Intra-Data Center Interconnect Technology: IM-DD OR Coherent? (2019)

We discuss technology options and challenges for scaling intra-datacenter interconnects beyond 1 Tb/s bandwidths, with focus on two possible approaches: pulse amplitude modulation (PAM)-based intensity modulation-direct detection (IM-DD) and baud-rate sampled coherent technology. In our studies, we compare the performance of various orders of PAM modulation (PAM4 to 8). In addition to these fixed PAM signaling options, a flexible PAM (FlexPAM) technique leveraging granularity in spectral efficiency (SE) is proposed to maximize link margin. For baud-rate sampled coherent technology, we propose a simplified digital signal processing (DSP) architecture to bring down power consumption of the coherent approach closer to that of IM-DD PAM. We also propose two new phase noise tolerant 2D coherent modulation formats to relax the laser linewidth requirement. In closing, a comparative study of fixed IM-DD PAM versus coherent polarization multiplexed-quadrature amplitude modulation (PM-QAM) is presented for a 1.6 Tb/s solution (200 Gb/s per dimension), with consideration of link loss/reach budget, power consumption, implementation complexity, as well as fan-out granularity.
Micronization: A method of improving the bioavailability of poorlysoluble drugs (1998)

For poorly soluble drugs, the digestive absorption depends on their rate of dissolution. Decreasing the particle size of these drugs improves their rate of dissolution. Fine grinding mills are use to micronize powders: either jar mills or fluid energy mills. Theses processes were applied to griseofulvin, progesterone, spironolactone and diosmin. For each drug, micronization improved their digestive absorption, and consequently their bioavailability and clinical efficacy.
Mechanism of action of regulatory proteins encoded by complex retroviruses (1992)

Complex retroviruses are distinguished by their ability to control the expression of their gene products through the action of virally encoded regulatory proteins. These viral gene products modulate both the quantity and the quality of viral gene expression through regulation at both the transcriptional and posttranscriptional levels. The most intensely studied retroviral regulatory proteins, termed Tat and Rev, are encoded by the prototypic complex retrovirus human immunodeficiency virus type 1. However, considerable information also exists on regulatory proteins encoded by human T-cell leukemia virus type I, as well as several other human and animal complex retroviruses. In general, these data demonstrate that retrovirally encoded transcriptional trans-activators can exert a similar effect by several very different mechanisms. In contrast, posttranscriptional regulation of retroviral gene expression appears to occur via a single pathway that is probably dependent on the recruitment of a highly conserved cellular cofactor. These two shared regulatory pathways are proposed to be critical to the ability of complex retroviruses to establish chronic infections in the face of an ongoing host immune response.
Identification and characterization of a “biomarker of toxicity” from the proteome of the paralytic shellfish toxin‐producing dinoflagellate Alexandrium tamarense (Dinophyceae) (2005)

The objective of this study was to identify and characterize a "biomarker of toxicity" from the proteome of Alexandrium tamarense, a paralytic shellfish toxin (PST)-producing dinoflagellate. A combination of 2-DE and MS approaches was employed to identify proteins of interest in the vegetative cells of several strains of A. tamarense with different toxin compositions and from different geographical locations. The electrophoretic analysis of the total water-soluble proteins from these toxic strains by 2-DE showed that several abundant proteins, namely AT-T1, AT-T2 and AT-T3, differing slightly in apparent Mr and pIs, were consistently present in all toxic strains of A. tamarense. Further analysis by MALDI-TOF MS and N-terminal amino acid sequencing revealed that they are isoforms of the same protein. Even more intriguing is that these proteins in A. tamarense have similar amino acid sequences and are closely related to a "biomarker of toxicity" previously reported in A. minutum. Unambiguous and highly species-specific identification was later achieved by comparing the PMFs of proteins in these two species. An initial attempt to characterize these proteins by generation of murine polyclonal antibodies against the AT-T1 protein was successful. Western blot analysis using the murine AT-T1-polycolonal antibodies identified all the toxic strains of A. tamarense and A. minutum, but not the nontoxic strain of A. tamarense. These results indicate that these protein characteristics for toxic strains are species-specific and that they are stable properties of the tested algae which are clearly distinguishable irrespective of geographical location and toxin composition. To our knowledge, this is the first study to demonstrate the use of polyclonal antibodies against marker proteins purified from 2-DE gels to distinguish different strains and species of the PST-producing dinoflagellate Alexandrium. It provides the basis for the production of monoclonal antibody probes against the "biomarkers of toxicity" for those dinoflagellates whose genome is incompletely characterized. Potentially, immunoassays could be developed to detect the presence of toxic algae in routine monitoring programs as well as to predict bloom development and movement.
The p53 tumor suppressor gene and gene product. (1989)

Three lines of evidence suggest that the p53 gene and gene product may act as a negative regulator of growth or a tumor suppressor gene: (1) in several tumors of mice and humans, both of the p53 alleles have suffered mutations and in some cases large or complete deletions demonstrating a loss of function mutation. (2) The murine wild-type p53 gene can suppress transformation of rat embryo fibroblasts in cell culture by other oncogenes such as the adenovirus E1A plus ras genes. In rat embryo fibroblast cells transfected with the wild-type p53 gene, E1A and ras, the wild-type p53 gene either fails to express any RNA or only a mutant form of this p53 gene is selected for in culture. This is analogous (in cell culture) to the observations made in tumors (in vivo) discussed above. (3) Both the tumor suppressor gene, the retinoblastoma sensitivity gene or Rb and p53 are found in oligomeric protein complexes with the oncogene products of the DNA tumor viruses. Both the SV40 large T antigen and the adenovirus E1A plus E1B-55Kd proteins bind to, and presumably inactivate, these tumor suppressor activities which in turn contributes to cellular transformation. A set of point mutations, deletions or insertion mutations in the murine p53 gene localized between amino acid residues 120-270 (out of 390 amino acids) activate the p53 gene and gene product for cooperation with ras in transforming rat embryo fibroblast cells. The mutant p53 proteins produced by these transformed cells all have several properties in common; (1) a prolonged half-life, which is 20 min for the wild-type gene product to greater than 2 hr for the mutant proteins, (2) very high levels of p53 protein in these transformed cells, (3) a conformational change in the mutant p53 proteins, and (4) the binding of mutant p53 protein to the rat cellular heat shock protein, hsc70. These transformation activating mutations apparently act in a trans-dominant manner with the murine mutant p53, forming an oligomeric protein complex with the wild-type rat p53 proteins, resulting in the inactivation of the wild-type p53 function (rat p53).