gebhart/patrepeval huggingface dataset:
The PI3K Pathway As Drug Target in Human Cancer (2010)

The phosphatidylinositol 3-kinase (PI3K) signaling axis impacts on cancer cell growth, survival, motility, and metabolism. This pathway is activated by several different mechanisms in cancers, including somatic mutation and amplification of genes encoding key components. In addition, PI3K signaling may serve integral functions for noncancerous cells in the tumor microenvironment. Consequently, therapeutics targeting the PI3K pathway are being developed at a rapid pace, and preclinical and early clinical studies are beginning to suggest specific strategies to effectively use them. However, the central role of PI3K signaling in a large array of diverse biologic processes raises concerns about its use in therapeutics and increases the need to develop sophisticated strategies for its use. In this review, we will discuss how PI3K signaling affects the growth and survival of tumor cells. From this vantage, we will consider how inhibitors of the PI3K signaling cascade, either alone or in combination with other therapeutics, can most effectively be used for the treatment of cancer.
HYRISE (2010)

In this paper, we describe a main memory hybrid database system called HYRISE, which automatically partitions tables into vertical partitions of varying widths depending on how the columns of the table are accessed. For columns accessed as a part of analytical queries (e.g., via sequential scans), narrow partitions perform better, because, when scanning a single column, cache locality is improved if the values of that column are stored contiguously. In contrast, for columns accessed as a part of OLTP-style queries, wider partitions perform better, because such transactions frequently insert, delete, update, or access many of the fields of a row, and co-locating those fields leads to better cache locality. Using a highly accurate model of cache misses, HYRISE is able to predict the performance of different partitionings, and to automatically select the best partitioning using an automated database design algorithm. We show that, on a realistic workload derived from customer applications, HYRISE can achieve a 20% to 400% performance improvement over pure all-column or all-row designs, and that it is both more scalable and produces better designs than previous vertical partitioning approaches for main memory systems.
Increased Lectin-Like Oxidized Low-Density Lipoprotein Receptor-1 Expression in the Maternal Vasculature of Women With Preeclampsia (2008)

Preeclampsia is a hypertensive disorder unique to pregnancy, in which the placenta may release factors into the maternal circulation resulting in systemic effects. Small dense low-density lipoprotein (LDL; which is susceptible for oxidation) is increased in preeclampsia. Lectin-like oxidized LDL receptor-1 (LOX-1) is a receptor for oxidized LDL. However, the expression levels and the regulation of LOX-1 in the maternal vasculature of women with preeclampsia are unknown. We hypothesized that there is an increased LOX-1 expression in arteries from women with preeclampsia. We further hypothesized that circulating factors in the plasma of women with preeclampsia would upregulate the LOX-1 expression in vascular endothelial cells and contribute to vascular endothelial oxidative stress. We observed abundant LOX-1 expression and the presence of oxidized LDL in arteries from women with preeclampsia, which was negligible in arteries from normotensive pregnant women. Human umbilical vein endothelial cells treated for 24 hours with 2% plasma from preeclamptic women increased LOX-1 expression and oxidized LDL uptake, as well as induced oxidative stress, as evidenced by increased NADPH oxidase activity and superoxide and peroxynitrite levels. These effects were significantly reduced by pretreatment with blocking antibody or small interfering RNA to LOX-1, as well as 5,10,15,20-tetrakis(4-sulfonatophenyl)porphyrinato iron (III), chloride (FeTPPS), a peroxynitrite scavenger. Exogenous peroxynitrite and 3-morpholino sydnonimine (SIN-1) increased LOX-1 protein and mRNA expression. In conclusion, increased LOX-1 expression in the systemic vasculature of preeclampsia women provides a fundamental insight into the pathology of preeclampsia and likely contributes to the induction and maintenance of vascular oxidative stress.
LOH in the HLA Class I Region at 6p21 Is Associated with Shorter Survival in Newly Diagnosed Adult Glioblastoma (2013)

LOH in the HLA class I region is frequent in adult GBMs. The association of shorter survival with LOH in this region suggests a crucial role for these genes in immunosurveillance.
Distribution of glutamate transporters in the hippocampus of patients with pharmaco‐resistant temporal lobe epilepsy (2002)

In patients suffering from temporal lobe epilepsy (TLE), increased extracellular glutamate levels in the epileptogenic hippocampus both during and after clinical seizures have been reported. These increased glutamate levels could be the result of malfunctioning and/or downregulation of glutamate transporters (also known as EAATs; excitatory amino acid transporters). In this study, the distribution of protein and mRNA of EAAT subtypes was examined in the hippocampus of TLE patients with hippocampal sclerosis (HS group) and without hippocampal sclerosis (non-HS group), and in autopsy controls without neurological disorders. EAAT protein localization was studied by immunohistochemistry on paraffin sections using specific poly- and monoclonal antibodies against the glial glutamate transporters EAAT1 and EAAT2 and the neuronal glutamate transporter EAAT3. Antibody specificity was shown by immunoblotting. In the HS group, a small decrease in EAAT1-immunoreactivity (IR) was observed in CA4 and in the polymorphic and supragranular layer of the dentate gyrus, compared with the control group. The strongest changes were found for EAAT2 levels. In the non-HS group, increased EAAT2-IR was detected in the CA1 and CA2 field, compared with non-epileptic controls. EAAT2-IR was decreased in the HS compared with the non-HS group. Fewer EAAT3-positive cells were found in the HS group than in the non-HS and control group. In both TLE groups, increased EAAT3 levels were observed in individual neurones. In the HS group, the percentage of EAAT3-IR neurones was increased in CA2 and in the granule cell layer of the dentate gyrus. Radioactive in situ hybridization for EAAT1-3 confirmed our immunohistochemical results. Non-radioactive in situ hybridization showed that not only astrocytes, but also neurones express EAAT2 mRNA. Taken together, differences in both mRNA and protein levels of glutamate transporter subtypes were found in specific regions in the TLE hippocampus, with most severe changes found for EAAT2 and EAAT3 levels. The results indicate an upregulation of EAAT2 protein expression in CA1 and CA2 in neurones in the non-HS group. This is in line with decreased EAAT2 protein levels in the HS group, since these hippocampi are characterized by severe neuronal cell loss. The functional consequences (glutamate transport capacity) of the reported changes in EAAT2 and EAAT3 remain to be determined.
Toxicologic Effects of an Oligodeoxynucleotide Phosphorothioate and Its Analogs Following Intravenous Administration in Rats (1997)

The aim of the present study is to evaluate the in vivo toxicologic effects of a phosphorothioate oligodeoxynucleotide (PS oligo) and three of its analogs [PS oligo containing four methylphosphonate linkages at the 3' and 5'-ends (MBO 1), PS oligo containing four 2'-O-methylribonucleosides at both the 3'- and 5'-ends (MBO 2), and PS oligo containing an 8 bp loop region at the 3'-end (self-stabilized oligo)]. Oligodeoxynucleotides were administrated intravenously to male and female rats at doses of 3, 10, and 30 mg/kg/day for 14 days. Rats were killed on day 15, blood samples were collected for hematology and clinical chemistry determinations, and tissues, including lymph nodes, spleens, livers, and kidneys, were subjected to pathologic examinations. The toxicity profiles of the four oligodeoxynucleotides were very similar, but differed in magnitude. In terms of the severity of the abnormalities caused by the oligodeoxynucleotides, the order was MBO 2 > PS oligo > self-stabilized oligo > MBO 1. Alterations in hematology parameters included thrombocytopenia, anemia, and neutropenia. Abnormalities in clinical chemistry parameters observed with PS oligo or MBO 2 were dose-dependent elevation of liver transaminases and reduction of the levels of alkaline phosphatase, albumin, and total protein. In addition, MBO 2 caused elevation of the total bilirubin level in male rats at the 30 mg/kg dose. No major alterations in hematology or clinical chemistry were observed in rats receiving MBO 1 or self-stabilized oligo. Dose-dependent enlargements of spleen, liver, and kidney were observed, especially in rats receiving PS oligo and MBO 2. Pathologic studies showed a generalized hyperplasia of the reticuloendothelial (RE) system in the tissues examined. Alterations in the spleen were mainly RE cell hyperplasia and hematopoietic cell proliferation. In addition to RE cell hyperplasia, lymph nodes showed necrosis, hepatocytes showed cytologic alterations and necrosis, and kidneys showed renal tubule regeneration. The severity of pathologic changes observed was oligodeoxynucleotide dependent, in the order of MBO 2 > PS oligo > self-stabilized oligo > MBO 1.
Fibril assembly and carotenoid overaccumulation in chromoplasts: a model for supramolecular lipoprotein structures. (1994)

Chromoplast development in ripening bell pepper fruits is characterized by a massive synthesis of carotenoid pigments, resulting in their distinctive red color. We have shown that 95% of these pigments accumulate in chromoplasts in specific lipoprotein fibrils. In addition to carotenoids, purified fibrils contain galactolipids, phospholipids, and a single, 32-kD protein, designated fibrillin, which has antigenically related counterparts in other species. Fibrils were reconstituted in vitro when purified fibrillin was combined with carotenoids and polar lipids in the same stoichiometric ratio found in fibrils in vivo. Antibodies directed against fibrillin were used to isolate a fibrillin cDNA clone and, in immunological studies, to follow its accumulation during the chloroplast-to-chromoplast transition under different conditions. A model for fibril architecture is proposed wherein carotenoids accumulate in the center of the fibrils and are surrounded by a layer of polar lipids, which in turn are surrounded by an outer layer of fibrillin. Topological analysis of purified fibrils verified this structure. Collectively, these results suggest that the process of fibril self-assembly in chromoplasts is an example of a general phenomenon shared among cells that target excess membrane lipids into deposit structures to avoid their destabilizing or toxic effects. In addition, we have shown that abscisic acid stimulates this phenomenon in chromoplasts, whereas gibberellic acid and auxin delay it.
Aminoglycoside 2′‐N‐acetyltransferase genes are universally present in mycobacteria: characterization of the aac(2 ′)‐Ic gene from Mycobacterium tuberculosis and the aac(2 ′)‐Id gene from Mycobacterium smegmatis (1997)

The genus Mycobacterium comprises clinically important pathogens such as M. tuberculosis, which has reemerged as a major cause of morbidity and mortality world-wide especially with the emergence of multidrug-resistant strains. The use of fast-growing species such as Mycobacterium smegmatis has allowed important advances to be made in the field of mycobacterial genetics and in the study of the mechanisms of resistance in mycobacteria. The isolation of an aminoglycoside-resistance gene from Mycobacterium fortuitum has recently been described. The aac(2')-Ib gene is chromosomally encoded and is present in all isolates of M. fortuitum. The presence of this gene in other mycobacterial species is studied here and genes homologous to that of M. fortuitum have been found in all mycobacterial species studied. In this report, the cloning of the aac(2')-Ic gene from M. tuberculosis H37Rv and the aac(2')-Id gene from M. smegmatis mc(2)155 is described. Southern blot hybridizations have shown that both genes are present in all strains of this species studied to date. In addition, the putative aac(2')-Ie gene has been located in a recent release of the Mycobacterium leprae genome. The expression of the aac(2')-Ic and aac(2')-Id genes has been studied in M. smegmatis and only aac(2')-Id is correlated with aminoglycoside resistance. In order to elucidate the role of the aminoglycoside 2'-N-acetyltransferase genes in mycobacteria and to determine whether they are silent resistance genes or whether they have a secondary role in mycobacterial metabolism, the aac(2')-Id gene from M. smegmatis has been disrupted in the chromosome of M. smegmatis mc(2)155. The disruptant shows an increase in aminoglycoside susceptibility along with a slight increase in the susceptibility to lysozyme.
Multiple approaches to robust speech recognition (1992)

This paper compares several different approaches to robust speechWe have found that two major factors degrading the performance of recognition.We review CMU's ongoing research in the use of speech recognition systems using desktop microphones in normal acoustical pre-processing to achieve robust speech recognition, inoffice environments are additive noise and unknown linear filtering.cluding the first evaluation of pre-processing in the context of the We showed in [2, 6] that simultaneous joint compensation for the DARPA standard ATIS domain for spoken language systems.We effects of additive noise and linear filtering is needed to achieve also describe and compare the effectiveness of three complementary maximal robustness with respect to acoustical differences between the methods of signal processing for robust speech recognition: acoustical training and testing environments of a speech recognition system.pre-processing, microphone array processing, and the use of We described in [2, 6] two algorithms that perform such joint comphysiologically-motivated models of peripheral signal processing.pensation, based on additive corrections to the cepstral coefficients of Recognition error rates are presented using these three approaches in the speech waveform.The more effective and adaptive of these isolation and in combination with each other for the speakeralgorithms, Codeword-Dependent Cepstral Normalization (CDCN) independent continuous alphanumeric census speech recognition task.[2], uses EM techniques to compute ML estimates of the additive noise and linear filtering that corrupt "clean" speech signals.The CDCN algorithm adapts automatically to new testing environments,
Verification of a closed-loop shaped-input controller for a five-bar-linkage manipulator (2002)

A closed-loop control strategy is verified experimentally for a five-bar-linkage manipulator with one flexible link. The prototype, a highly nonlinear system, is a prominent candidate of a class of manipulators with one flexible link. The controller combines a closed-loop shaped-input filter with conventional control techniques. Experimental results show that this technique is effective and robust enough to reduce vibrations, even for the nonlinear system. The implementation methodology and the experimental results are discussed with future research issues.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Screening and preoperative imaging of candidates for conventional repair of abdominal aortic aneurysm. (1999)

This article summarizes considerations in screening for abdominal aortic aneurysm (AAA) and preoperative imaging before conventional surgical repair. Because death of this relatively common disease can be prevented by an effective treatment, there is great interest in early detection and elective repair. The prevalence of AAA in older adults (65 to 80 years of age) varies from 4% to 7%. Factors associated with AAA include smoking, age, coronary artery disease, high serum cholesterol level, family history, and hypertension. A higher prevalence of AAA has been found among first-degree relatives of AAA patients, particularly in men, and smoking is an important factor in the development and progression of AAA. Screening for AAA may be appropriate in male patients older than 65 years with a smoking history, particularly current smokers, who have carotid occlusive disease, coronary artery disease, or lower extremity occlusive disease. Ultrasound is the screening method of choice and has the benefit of being inexpensive and noninvasive. Preoperative imaging serves mainly to establish the indication for operation. The vascular surgeon comfortable with discovering potentially confusing anatomic configurations or adverse extensions of pathology at the time of operation may not require any imaging beyond ultrasound. Specific indications for arteriography include suggestion of juxtarenal aneurysm by ultrasound or physical examination, clinical evidence of lower extremity arterial occlusive disease, uncontrolled hypertension or unexplained creatinine elevation, or prior arterial reconstruction. Spiral computed tomography (CT) scan with 3-dimensional reconstruction and gadolinium magnetic resonance (MR) angiography are increasingly useful alternatives to contrast arteriography.
ES cells have only a limited lymphopoietic potential after adoptive transfer into mouse recipients (1993)

While hematopoietic stem cells from adult and fetal stages of murine development are capable of long term reconstitution of all mature blood lineages in vivo, embryonic hematopoietic stem cell repopulation in vivo has proved difficult. It is thought that there are many fewer hematopoietic stem cells in the embryo than in the fetal/adult stages of mouse development and that these cells possess a different developmental potential. One source of such cells are embryonic stem (ES) cells which can differentiate into most mature blood lineages in vitro. We have therefore used transplantation of differentiated ES cells to assess the hematopoietic potential of embryonic hematopoietic cells in vivo. We demonstrate here that precursors obtained from in vitro cultures of normal ES cells can contribute only to restricted and limited hematopoiesis in a mouse without leading to tumour formation. Repopulation occurs for greater than 6.5 months at levels ranging from 0.1% to 6% in B and T cell lineages in peripheral blood. In contrast to in vitro colony data demonstrating the myeloid lineage developmental potential of ES cells, no donor-derived myeloid repopulation was observed in CFU-S assays and no macrophage and mast cells were found in long term repopulated recipients. Thus, the hematopoietic potential of ES cells in vivo is limited to low levels of repopulation and is restricted to the lymphoid lineage.
Development of Micro-Array Biochip Using Photo-Immobilization Method (2004)

マイクロアレイ型バイオチップの新しい作製方法として筆者らの開発してきた光固定化法を用いる方法をまとめた. 光固定化法を用いることによりさまざまな有機分子を同一の方法で容易に固定化でき, 固定化に用いるマトリックスに非特異的相互作用を抑制する高分子を用いることによりS/N比の高い測定が可能となった. さまざまなタンパク質・抗体や細胞を固定化して, タンパク質・抗体や細胞との相互作用を検討した. マイクロアレイ・チップは, 今後はゲノム, プロテオーム, セローム解析のような学術的な使用ばかりでなく, 臨床分析においても重要になるものと期待できる.
Airframe Life Extension through Cold Expansion Techniques (1991)

Techniques designed to increase the fatigue life of aircraft structures are discussed. A detailed survey of repair methods developed by Fatigue Technology, Inc. based on the cold expansion process is presented.
A Bispecific HER2-Targeting FynomAb with Superior Antitumor Activity and Novel Mode of Action (2014)

Upregulation of HER2 is a hallmark of 20% to 30% of invasive breast cancers, rendering this receptor an attractive target for cancer therapy. Although HER2-targeting agents have provided substantial clinical benefit as cancer therapeutics, there is a need for the development of new agents aiming at circumventing anti-HER2 resistance. On the basis of the approved antibody pertuzumab, we have created a panel of bispecific FynomAbs, which target two epitopes on HER2. FynomAbs are fusion proteins of an antibody and a Fyn SH3-derived binding protein. One bispecific FynomAb, COVA208, was characterized in detail and showed a remarkable ability to induce rapid HER2 internalization and apoptosis in vitro. Moreover, it elicited a strong inhibition of downstream HER2 signaling by reducing HER2, HER3, and EGFR levels in vitro and in vivo. Importantly, COVA208 demonstrated superior activity in four different xenograft models as compared with the approved antibodies trastuzumab and pertuzumab. The bispecific FynomAb COVA208 has the potential to enhance the clinical efficacy and expand the scope of HER2-directed therapies, and delineates a paradigm for designing a new class of antibody-based therapeutics for other receptor targets.
A multipage cell architecture for high-speed programming multilevel NAND flash memories (1998)

To realize low-cost, highly reliable, high-speed programming, and high-density multilevel flash memories, a multipage cell architecture has been proposed. This architecture enables both precise control of the V/sub th/ of a memory cell and fast programming without any area penalty. In the case of a four-level cell, a high programming speed of 236 /spl mu/s/512 bytes or 2.2 Mbytes/s can be obtained, which is 2.3 times faster than the conventional method. A small die size can be achieved with the newly developed compact four-level column latch circuit. A preferential page select method has also been proposed so as to improve the data retention characteristics. The IC error rate can be decreased by as much as 33%, and a highly reliable operation can be realized.
Structural Studies of Impatiens balsamina Antimicrobial Protein (Ib-AMP1) (1998)

Structural studies of Ib-AMP1, a small antimicrobial peptide derived from the seeds of Impatiens balsamina have been performed using circular dichroism (CD) and two-dimensional proton nuclear magnetic resonance (1H NMR). This 20-residue peptide is highly basic with five arginine residues and contains four cysteines which form two intramolecular disulfide bonds. CD results reveal that the peptide may include a beta-turn but do not show evidence for either helical or beta-sheet structure over a range of temperature and pH. Structural information from NMR was obtained in the form of proton-proton internuclear distances inferred from NOEs and dihedral angle restraints from spin-spin coupling constants, which were used for distance geometry calculations. Owing to the difficulty in obtaining the correct disulfide connectivities by chemical methods, three separate calculations were performed; with no disulfides and with the two possible alternate disulfide connectivities. Results from distance geometry calculations reveal that although the peptide is small, the cysteines constrain part of it to adopt a well-defined main chain conformation. From residue 6 to 20, the backbone is well defined, whilst the N-terminal region, residues 1-5, has very few constraints and appears to be very flexible. In the defined core region, there are three beta-turns at residues 9-12, 10-13, and 12-15. The side chains show no strong interactions in the NMR spectra and are therefore thought to adopt multiple conformations. Superposition of the structures generated shows that the peptide has two hydrophilic patches which are at opposite ends of the molecule separated by a large hydrophobic patch. Little is known about the mode of action of this protein, but it is thought to interact with a membrane-bound receptor, and possible sites of interaction are discussed. The structures determined are compared with those of the alpha-conotoxins, which are also highly basic proteins with similar disulfide connectivities.