gebhart/patrepeval huggingface dataset:
Association of acute myeloid leukemias most immature phenotype with risk groups and outcomes (2016)

The precise phenotype and biology of acute myeloid leukemia stem cells remain controversial, in part because the "gold standard" immunodeficient mouse engraftment assay fails in a significant fraction of patients and identifies multiple cell-types in others. We sought to analyze the clinical utility of a novel assay for putative leukemia stem cells in a large prospective cohort. The leukemic clone's most primitive hematopoietic cellular phenotype was prospectively identified in 109 newly-diagnosed acute myeloid leukemia patients, and analyzed against clinical risk groups and outcomes. Most (80/109) patients harbored CD34(+)CD38(-) leukemia cells. The CD34(+)CD38(-) leukemia cells in 47 of the 80 patients displayed intermediate aldehyde dehydrogenase expression, while normal CD34(+)CD38(-) hematopoietic stem cells expressed high levels of aldehyde dehydrogenase. In the other 33/80 patients, the CD34(+)CD38(-) leukemia cells exhibited high aldehyde dehydrogenase activity, and most (28/33, 85%) harbored poor-risk cytogenetics or FMS-like tyrosine kinase 3 internal tandem translocations. No CD34(+) leukemia cells could be detected in 28/109 patients, including 14/21 patients with nucleophosmin-1 mutations and 6/7 acute promyelocytic leukemia patients. The patients with CD34(+)CD38(-) leukemia cells with high aldehyde dehydrogenase activity manifested a significantly lower complete remission rate, as well as poorer event-free and overall survivals. The leukemic clone's most immature phenotype was heterogeneous with respect to CD34, CD38, and ALDH expression, but correlated with acute myeloid leukemia risk groups and outcomes. The strong clinical correlations suggest that the most immature phenotype detectable in the leukemia might serve as a biomarker for "clinically-relevant" leukemia stem cells. ClinicalTrials.gov: NCT01349972.
Discovery of adrenomedullin in rat ischemic cortex and evidence for its role in exacerbating focal brain ischemic damage. (1995)

Focal brain ischemia is the most common event leading to stroke in humans. To understand the molecular mechanisms associated with brain ischemia, we applied the technique of mRNA differential display and isolated a gene that encodes a recently discovered peptide, adrenomedullin (AM), which is a member of the calcitonin gene-related peptide (CGRP) family. Using the rat focal stroke model of middle cerebral artery occlusion (MCAO), we determined that AM mRNA expression was significantly increased in the ischemic cortex up to 17.4-fold at 3 h post-MCAO (P < 0.05) and 21.7-fold at 6 h post-MCAO (P < 0.05) and remained elevated for up to 15 days (9.6-fold increase; P < 0.05). Immunohistochemical studies localized AM to ischemic neuronal processes, and radioligand (125I-labeled CGRP) displacement revealed high-affinity (IC50 = 80.3 nmol) binding of AM to CGRP receptors in brain cortex. The cerebrovascular function of AM was studied using synthetic AM microinjected onto rat pial vessels using a cranial window or applied to canine basilar arteries in vitro. AM, applied abluminally, produced dose-dependent relaxation of preconstricted pial vessels (P < 0.05). Intracerebroventricular (but not systemic) AM administration at a high dose (8 nmol), prior to and after MCAO, increased the degree of focal ischemic injury (P < 0.05). The ischemia-induced expression of both AM mRNA and peptide in ischemic cortical neurons, the demonstration of the direct vasodilating effects of the peptide on cerebral vessels, and the ability of AM to exacerbate ischemic brain damage suggests that AM plays a significant role in focal ischemic brain injury.
CMOS image sensors-recent advances and device scaling considerations (2002)

This paper reviews the industry trend and the recent advances in CMOS image sensor technology, covering advances in technology, devices, pixel architecture, as well as on-chip circuit integration. Compatibility with "standard" CMOS technology is an important consideration for CMOS image sensors. We therefore explore the question: "will the image sensing performance of CMOS imagers get better or get worse as CMOS technologies are scaled?" We project that "standard" CMOS technologies cannot be used for imaging in the deep sub-micron regime without some process modifications.
HBME-1 immunostaining in thyroid fine-needle aspirations: a useful marker in the diagnosis of carcinoma. (1997)

The monoclonal antibody, HBME-1, generated against the microvillous surface of mesothelial cells, has been shown to have significant reactivity in histologic sections of follicular-derived thyroid malignancies. We examined the diagnostic utility of HBME-1 in thyroid fine-needle aspiration (FNA) specimens. Twenty-four aspirates from 23 patients were evaluated. Only cases with adequate cell blocks and tissue follow-up were studied. Immunocytochemical analysis was performed on air-dried, direct smears and on sections from Bouin's-fixed, paraffin-embedded cell blocks with a standard avidin-biotin peroxidase complex method with epitope retrieval. The same immunostaining technique was applied to the corresponding formalin-fixed tissue sections. Eight (57%) of the 14 malignant aspirates showed strong cytoplasmic and/or membrane immunoreactivity for HBME-1. The cell-block and direct-smear preparations were positive in five of seven papillary carcinomas (one follicular variant), one of one minimally invasive follicular carcinoma, and one of four hybrid tumors with mixed papillary and follicular features. An additional hybrid tumor case was focally positive only in the smear slide. The eighth positive case was an adenosquamous carcinoma of the larynx that invaded into the thyroid (smear preparation was negative for this case). The 10 benign lesions were negative. All of the malignant-tumor tissue sections were positive for HBME-1, and focal positivity was seen in 5 of 10 benign resection specimens. We conclude that a positive immunostain for HBME-1 on a thyroid FNA is supportive evidence that the lesion is a carcinoma, that a negative result for HBME-1 does not preclude the diagnosis of thyroid carcinoma, and that HBME-1 can be effectively applied to thyroid FNA specimens and can be a valuable adjunct in the cytologic diagnosis of thyroid malignancies.
In-line optical amplification for Si waveguides on 1×8 splitter and selector by flip-chip bonded InP-SOAs (2016)

We investigated hybrid-integration of InP semiconductor optical amplifier on silicon photonics chip using flip-chip bonding, and achieved in-line optical amplification of 10 dB. Silicon 1×8 splitter and selector are fabricated and operated with on-chip loss-compensation.
Import of Agrobacterium T-DNA into Plant Nuclei: Two Distinct Functions of VirD2 and VirE2 Proteins (2001)

To study the mechanism of nuclear import of T-DNA, complexes consisting of the virulence proteins VirD2 and VirE2 as well as single-stranded DNA (ssDNA) were tested for import into plant nuclei in vitro. Import of these complexes was fast and efficient and could be inhibited by a competitor, a nuclear localization signal (NLS) coupled to BSA. For import of short ssDNA, VirD2 was sufficient, whereas import of long ssDNA additionally required VirE2. A VirD2 mutant lacking its C-terminal NLS was unable to mediate import of the T-DNA complexes into nuclei. Although free VirE2 molecules were imported into nuclei, once bound to ssDNA they were not imported, implying that when complexed to DNA, the NLSs of VirE2 are not exposed and thus do not function. RecA, another ssDNA binding protein, could substitute for VirE2 in the nuclear import of T-DNA but not in earlier events of T-DNA transfer to plant cells. We propose that VirD2 directs the T-DNA complex to the nuclear pore, whereas both proteins mediate its passage through the pore. Therefore, by binding to ssDNA, VirE2 may shape the T-DNA complex such that it is accepted for translocation into the nucleus.
Water Use Features of Sunflower (Helianthus annuus L.) Hybrids Irrigated at Different Growth Stages (2011)

The response of some sunflower hybrids to seven irrigation treatments was studied in the field experiments during 2002 and 2003 seasons. Sunflower hybrids of Sanbro, Tarsan-1018 and Özdemirbey were used as material. A rainfed (non-irrigated) treatment as the control (I0) and I1= irrigation at vegetative growth stage, I2= irrigation at heading stage, I3= irrigation at flowering stage, I4= I1 + I3 two irrigations, I5= I1 + I2 + I3, three irrigations, and I6= I1 + I2 + I3 + irrigation at milking stage were applied. Research revealed that average seed yield of all sunflower hybrids peaked with irrigations at all growing stages (I6). Increased water amount and irrigation frequency caused a decreasing in irrigation water use efficiency (IWUE) and an increase in irrigation efficiency (IE). Higher IWUE and lower IE were obtained from non-irrigated or one irrigation treatments. The highest IWUE (35.6 kg ha−1 mm−1) was obtained from Tarsan-1018 irrigated at vegetative stage (I1). Özdemirbey irrigated with I6 gave the highest irrigation efficiency (IE) with 186%.
Amplification and Expression of Genes Associated with Multidrug Resistance in Mammalian Cells (1986)

In multidrug resistance, which is observed clinically and in tissue culture, cells that are challenged with certain cytotoxic drugs develop resistance not only to the selective agent but also to other, seemingly unrelated, agents. The multidrug-resistant phenotype is associated with DNA sequence amplification and with the overproduction of a number of cytosolic and membrane glycoproteins. The differential amplification and altered expression of at least two related genes, termed multidrug-resistant associated genes has been shown in multidrug-resistant Chinese hamster cells. In multidrug-resistant mouse and human cells, genes homologous to those in Chinese hamster cells are also amplified. The level of expression of these genes varied and did not correlate with their copy number. Furthermore, in Chinese hamster cells, the development of resistance to a single drug and multidrug resistance were closely related, but uncoupled, events. The overexpression of the multidrug-resistant genes was better correlated with the degree of resistance to the selective agent than it was with the extent of multidrug resistance.
Disconnected operation in the Coda File System (1992)

Disconnected operation is a mode of operation that enables a client to continue accessing critical data during temporary failures of a shared data repository. An important, though not exclusive, application of disconnected operation is in supporting portable computers. In this paper, we show that disconnected operation is feasible, efficient and usable by describing its design and implementation in the Coda File System. The central idea behind our work is that caching of data , now widely used for performance, can also be exploited to improve availability.
Tumor Necrosis Factor α (TNFα) Stimulates Map4k4 Expression through TNFα Receptor 1 Signaling to c-Jun and Activating Transcription Factor 2 (2007)

Tumor necrosis factor alpha (TNFalpha) is a cytokine secreted by macrophages and adipocytes that contributes to the low grade inflammation and insulin resistance observed in obesity. TNFalpha signaling decreases peroxisome proliferator-activated receptor gamma and glucose transporter isoform 4 (GLUT4) expression in adipocytes, impairing insulin action, and this is mediated in part by the yeast Ste20 protein kinase ortholog Map4k4. Here we show that Map4k4 expression is selectively up-regulated by TNFalpha, whereas the expression of the protein kinases JNK1/2, ERK1/2, p38 stress-activated protein kinase, and mitogen-activated protein kinase kinases 4/7 shows little or no response. Furthermore, the cytokines interleukin 1beta (IL-1beta) and IL-6 as well as lipopolysaccharide fail to increase Map4k4 mRNA levels in cultured adipocytes under conditions where TNFalpha elicits a 3-fold effect. Using agonistic and antagonistic antibodies and small interfering RNA (siRNA) against TNFalpha receptor 1 (TNFR1) and TNFalpha receptor 2 (TNFR2), we show that TNFR1, but not TNFR2, mediates the increase in Map4k4 expression. TNFR1, but not TNFR2, also mediates a potent effect of TNFalpha on the phosphorylation of JNK1/2 and p38 stress-activated protein kinase and their downstream transcription factor substrates c-Jun and activating transcription factor 2 (ATF2). siRNA-based depletion of c-Jun and ATF2 attenuated TNFalpha action on Map4k4 mRNA expression. Consistent with this concept, the phosphorylation of ATF2 along with the expression and phosphorylation of c-Jun by TNFalpha signaling was more robust and prolonged compared with that of IL-1beta, which failed to modulate Map4k4. These data reveal that TNFalpha selectively stimulates the expression of a key component of its own signaling pathway, Map4k4, through a TNFR1-dependent mechanism that targets the transcription factors c-Jun and ATF2.
Irreconcilable differences: The fundamental incompatibility of science and religion (2003)

James Lett argues passionately that science and religion are not non-overlapping ‘magesteria’, and explains why he believes appeals to religious faith over scientific reason are highly dangerous.
Unconventional Myosins (1995)

Myosins are molecular motors that upon interaction with actin filaments convert energy from ATP hydrolysis into mechanical force. Evidence has emerged for the existence of a large, widely expressed and evolutionarily ancient superfamily of myosin genes. In addition to the well-catheterized conventional, filament-forming, two-headed myosin-II of muscle and nonmuscle cells, at least ten additional classes of myosins have been identified. In vertebrates, at least seven of the eleven classes are expressed, and many myosins can be expressed in a single cell type. This review summarizes known structural and functional features of these novel unconventional myosins.
Calreticulin Is Essential for Cardiac Development (1999)

Calreticulin is a ubiquitous Ca2+ binding protein, located in the endoplasmic reticulum lumen, which has been implicated in many diverse functions including: regulation of intracellular Ca2+ homeostasis, chaperone activity, steroid-mediated gene regulation, and cell adhesion. To understand the physiological function of calreticulin we used gene targeting to create a knockout mouse for calreticulin. Mice homozygous for the calreticulin gene disruption developed omphalocele (failure of absorption of the umbilical hernia) and showed a marked decrease in ventricular wall thickness and deep intertrabecular recesses in the ventricular walls. Transgenic mice expressing a green fluorescent protein reporter gene under the control of the calreticulin promoter were used to show that the calreticulin gene is highly activated in the cardiovascular system during the early stages of cardiac development. Calreticulin protein is also highly expressed in the developing heart, but it is only a minor component of the mature heart. Bradykinin-induced Ca2+ release by the InsP3-dependent pathway was inhibited in crt-/- cells, suggesting that calreticulin plays a role in Ca2+ homeostasis. Calreticulin-deficient cells also exhibited impaired nuclear import of nuclear factor of activated T cell (NF-AT3) transcription factor indicating that calreticulin plays a role in cardiac development as a component of the Ca2+/calcineurin/NF-AT/GATA-4 transcription pathway.
Structure and spectral properties of β-carbolines. Part 4. Synthesis of the new ring system: 9,10,15,15b-tetrahydroindolo[1′,2′ : 4,3]pyrazino[2,1-a]-carbolin-7(6H)-one (1991)

1-Indol-2-yl-1,2,3,4-tetrahydro-β-carboline and its 5-methoxy derivative were synthesized by the Pictet-Spengler reaction between tryptamine or 5-methoxytryptamine and indole-2-carbaldehyde, with a high yield. A step-by-step oxidation of the indolyl carbolines led to formation of the appropriate dihydrocarboline derivatives and two analogues of neoeudistomine, the fully unsaturated carbolines. Condensation of the indolyltetrahydrocarbolines with bromoacetyl chloride yielded the appropriate 2-substituted derivatives, which were cyctized to yield the new ring system compounds 9,10,15,15b-tetrahydroindolo[1′,2′ : 4,3]pyrazino[2,1-a]carbolin-7(6H)-ones, the structures of which were determined by using a high-resolution 1H NMR technique.
Origins of the anomalous stress behavior in charged colloidal suspensions under shear (2010)

Numerical simulations are conducted to determine microstructure and rheology of sheared suspensions of charged colloidal particles at a volume fraction of ϕ=0.33. Over broad ranges of repulsive force strength F0 and Péclet number Pe, dynamic simulations show coexistence of ordered and disordered stable states with the state dependent on the initial condition. In contrast to the common view, at low shear rates, the disordered phase exhibits a lower viscosity (μ(r)) than the ordered phase, while this behavior is reversed at higher shear rates. Analysis shows the stress reversal is associated with different shear induced microstructural distortions in the ordered and disordered systems. Viscosity vs shear rate data over a wide range of F0 and Pe collapses well upon rescaling with the long-time self-diffusivity. Shear thinning viscosity in the ordered phase scaled as μ(r)∼Pe(-0.81) at low shear rates. The microstructural dynamics revealed in these studies explains the anomalous behavior and hysteresis loops in stress data reported in the literature.
Ultrastructural Observations in the Myocardium Beyond the Region of Acute Coagulation Necrosis Following Radiofrequency Catheter Ablation (1994)

RF catheter ablation results in ultrastructural damage to the myocardium extending up to 6 mm beyond the acute pathologic RF lesion border as defined by NBT histochemical staining.
Peptide-induced rescue of serologic epitopes on class I MHC molecules. (1995)

To monitor conformational changes in MHC class I structure induced by interaction with peptide or beta 2-microglobulin (beta 2-m), we have taken a serologic approach. Previous studies by us and others have defined circumstances wherein specific peptides can decrease serologic recognition of class I molecules. However, such blocking of serologic epitopes has often been interpreted as steric hindrance by peptide side chains. In this paper, we describe peptide-induced gains in recognition by mAbs 30-5-7, 34-1-2, and B22/249. In experiments with mAb 30-5-7, impaired reactivity, which resulted from an Ld loop mutation, was specifically rescued by the binding of a beta-galactosidase-derived peptide to the Ld mutant. In studies with mAb 34-1-2, poor Ld detection was enhanced by mutations in Ld at beta 2-m interaction sites or by changes within the peptide-binding groove. To evaluate whether known peptides in the Ld groove could influence 34-1-2 recognition, we tested six peptide ligands, four of which increased the reactivity of 34-1-2 with the Ld-expressing cell to various degrees (up to 14-fold). It is of interest that Ld mutations at position 9 and 95/97 made significant differences in the ranking of the peptides in regard to their ability to increase recognition by 34-1-2 and B22/249. This finding suggests that mutations in the binding groove can alter peptide conformation and result in secondary changes in class I structure. On the basis of the cumulative serologic data, we propose that the class I molecule displays considerable fluidity, and is structurally influenced by both beta 2-m and peptide.
Iterative Polar Quantization-Based Modulation to Achieve Channel Capacity in Ultrahigh-Speed Optical Communication Systems (2010)

In this paper, we propose a nonuniform coded-modulation format based on iterative polar quantization (IPQ) as a scheme to enable achieving channel capacity in ultrahigh-speed optical communication systems. The proposed modulation format is coded with structured low-density parity-check (LDPC) codes optimized for Gaussian channels and, in combination with polarization-multiplexing, can achieve 800 Gb/s per wavelength aggregate rate and beyond utilizing the currently available components operating at 50 GS/s. Using coded IPQ, we show that we can achieve capacity for signal-to-noise ratios (SNRs) of up to 25 dB and increase the total propagation distance over optical transmission systems by 275 km over coded star-quadrature amplitude modulation (QAM).
Peripheral Muscle Wasting in Chronic Obstructive Pulmonary Disease (2001)

Peripheral muscle wasting is a common finding in advanced chronic obstructive pulmonary disease (COPD) and several other chronic diseases. Although muscle wasting has long been recognized by clinicians (1), its relevance to patients' outcome and management has been overlooked. There is a renewed interest in this problem in respiratory and other chronic diseases as recent advances in clinical research have confirmed the negative impact of muscle wasting on patient survival (2, 3). At the same time, exciting and innovative research in molecular biology is improving our understanding of how muscle mass is maintained (4, 5). Effective treatment for muscle wasting has yet to be developed, but there is now evidence, from animal and human studies, that muscle mass may he manipulated with success in wasting disorders (4). As a result of this research, new molecules specifically targeted at maintaining or increasing muscle mass in patients with COPD or other chronic conditions should become available in the future. In this pulmonary perspective, the clinical significance of muscle wasting associated with COPD will he briefly reviewed, taking into account the knowledge obtained from the study of other chronic diseases. Based upon new developments in molecular biology, possible mechanisms leading to muscle wasting and potential therapeutic strategies will be presented as well as suggestions for future research. It is not the scope of the present study to provide a complete review of the literature on peripheral muscle function in COPD, which can be found elsewhere (6, 7).
Combinatorial Libraries by Portioning and Mixing (1999)

Abstract: Combinatorial chemistry - due to its radically new synthetic methods - can be considered a forerunner of chemistry in the next century. One of the most important methods is the portioning-mixing (split-mix) synthesis which embodies the combinatorial principle. It is easily realized. Both manual and automatic devices have been described. Some features that contribute to its popularity include: it produces all possible structural combinations of the monomers, it has outstanding productivity, it leads to the formation of individual compounds in nearly equimolar quantities (affected by statistics and incomplete reactions), and it can be applied to all classes of organic compounds. Since an enormously large number of compounds can be produced in principle in a relatively short time, some practical considerations are discussed that can be useful in library design. Encoding organic libraries by peptide or nucleotide sequences or with binary tags are also described together with methods for tagging macroscopic support units with electronic chips, two dimensional bar codes or colored resin and capsule caps. Among the deconvolution strategies, the iteration method, positional scanning, omission libraries, the Selectide and the Pharmacopeia methods are mentioned. A collection of libraries prepared by portioning-mixing is also included in graphical format.