gebhart/patrepeval huggingface dataset:
A double-blind, placebo-controlled pilot study of carbamazepine for the treatment of alcohol dependence. (1997)

Carbamazepine, chemically related to the tricyclic antidepressants, has multiple clinical actions. It is a potent anticonvulsant, mild sedative, and mood stabilizer. It is nonaddictive and has little toxicity when clinical and laboratory monitoring is performed. It has proven efficacy in the treatment of acute alcohol withdrawal. Kindling and protracted withdrawal are the theoretical rationale for the mechanism of its action in the treatment of alcohol dependence. This 12-month double-blind placebo-controlled pilot study of 29 subjects evaluated the efficacy of carbamazepine for the treatment of alcohol dependence. Subjects were randomly assigned to either placebo or carbamazepine. A baseline assessment and bimonthly follow-up for 12 months assessed demographic variables, mood and functioning, treatment compliance, drinking behaviors, biological markers of drinking, and medication toxicity. Despite the small sample size, compliance difficulties after 4 months and a sizable drop-out rate, there were treatment effects favoring carbamazepine. Univariate analyses showed a decrease in drinks per drinking day and maximum number of heavy drinking days in a row at 2 and 4 months of follow-up. Survival analysis revealed a significant delay in time to first episode of heavy drinking, and close to a trend level of significance for time to first drink. There were significant time, but not time by treatment group, effects on multiple measures of mood. These pilot results are encouraging and support carbamazepine as a possible pharmacologic tool in the treatment of alcohol dependence.
Human Kallikrein 8 Protein Is a Favorable Prognostic Marker in Ovarian Cancer (2006)

Human kallikrein 8 (hK8/neuropsin/ovasin; encoded by KLK8) is a steroid hormone-regulated secreted serine protease differentially expressed in ovarian carcinoma. KLK8 mRNA levels are associated with a favorable patient prognosis and hK8 protein levels are elevated in the sera of 62% ovarian cancer patients, suggesting that KLK8/hK8 is a prospective biomarker. Given the above, the aim of the present study was to determine if tissue hK8 bears any prognostic significance in ovarian cancer. Using a newly developed ELISA, hK8 was quantified in 136 ovarian tumor extracts and correlated with clinicopathologic variables and outcome [progression-free survival (PFS); overall survival (OS)] over a median follow-up period of 42 months. hK8 levels in ovarian tumor cytosols ranged from 0 to 478 ng/mg total protein, with a median of 30 ng/mg. An optimal cutoff value of 25.8 ng/mg total protein (74th percentile) was selected based on the ability of hK8 values to predict the PFS of the study population and to categorize tumors as hK8 positive or negative. Women with hK8-positive tumors most often had lower-grade tumors (G1), no residual tumor after surgery, and optimal debulking success (P < 0.05). Univariate and multivariate analyses revealed that patients with hK8-positive tumors had a significantly longer PFS and OS than hK8-negative patients (P < 0.05). Kaplan-Meier survival curves further confirmed a reduced risk of relapse and death in women with hK8-positive tumors (P = 0.001 and P = 0.014, respectively). These results indicate that hK8 is an independent marker of favorable prognosis in ovarian cancer.
High-density data storage using proximal probe techniques (1995)

We describe some of the achievements and problems associated with proximal probe-based approaches to high-density data storage. While STM-based methods have demonstrated spectacular areal densities dwarfing anything achievable with today's storage technologies, reliability and data rate issues present serious obstacles. These problems have led us to focus on techniques based on AFM and near-field optics. First, we have developed a thermomechanical writing scheme using an AFM tip. We have addressed many of the practical issues involved, including data rate. With custom low-mass cantilevers, we have demonstrated readback on real data with a data rate of 1.2 Mb/s. We have also pursued nontopographic storage techniques based on charge storage in nitride-oxide semiconductor structures and near-field optical storage. These techniques should be able to achieve densities comparable to those reached with the AFM scheme, with the added advantage that they are fast and reversible. Although it is not yet clear whether any of these probe-based approaches can ever be made practical, they do represent potential pathways to the higher densities that will be needed in the decades ahead.
Spreading dynamics and wetting transition of cellular aggregates (2011)

We study the spreading of spheroidal aggregates of cells, expressing a tunable level of E-cadherin molecules, on glass substrates decorated with mixed fibronectin and polyethylene glycol. We observe the contact area by optical interferometry and the profile by side-view microscopy. We find a universal law of aggregate spreading at short times, which we interpret through an analogy with the spreading of viscoelastic droplets. At long times, we observe either partial wetting or complete wetting, with a precursor film of cells spreading around the aggregate with two possible states. In strongly cohesive aggregates this film is a cellular monolayer in the liquid state, whereas in weakly cohesive aggregates, cells escape from the aggregate, forming a 2D gas. The escape of isolated cells is a physical mechanism that appears also to be present in the progression of a noninvasive tumor into a metastatic malignant carcinoma, known as the epithelial-mesenchymal transition.
Fundamentals of Biomechanics in Tissue Engineering of Bone (2000)

The objective of this review is to provide basic information pertaining to biomechanical aspects of bone as they relate to tissue engineering. The review is written for the general tissue engineering reader, who may not have a biomechanical engineering background. To this end, biomechanical characteristics and properties of normal and repair cortical and cancellous bone are presented. Also, this chapter intends to describe basic structure-function relationships of these two types of bone. Special emphasis is placed on salient classical and modern testing methods, with both material and structural properties described.
Three distinct stages of B-cell defects in common varied immunodeficiency. (1982)

B-lymphocyte function of 15 patients with primary common varied immunodeficiency or related disease were examined. All patients had low serum levels of IgM, IgG, and IgA, but 12 of 15 patients had nearly normal numbers of peripheral blood B lymphocytes. Mononuclear cells and B cells from peripheral blood were assayed for B-cell mitogenic responses to anti-Ig mu chain antibodies or to Staphylococcus aureus strain Cowan I (referred to as Cowan I), and for differentiation to Ig-secreting cells of IgM, IgG, and IgA classes in the presence of Cowan I and pokeweed mitogen or T-cell factor. The patients all showed profound B-cell defects in one or more of the assays and could be divided into three approximately equal groups based on their responses. The first group showed normal proliferation in response to the two B-cell mitogens and near normal numbers of IgM-secreting cells but no IgG- or IgA-secreting cells. B cells in the second group showed proliferative responses to Cowan I or anti-mu, but no differentiation to Ig-secreting cells. The third group had no B-cell proliferative responses or differentiation in our assays. In several patients from each group, (i) helper T cells were functional in Ig-secreting-cell responses with purified normal B cells, (ii) patient T cells did not significantly suppress formation of Ig-secreting cells by normal cells in coculture, and (iii) removal of T cells with addition of T-cell-replacing factor, or partial removal of monocytes, did not alleviate any of the defects. These studies show that primary B-cell defects in common varied immunodeficiency occur at several levels, probably representing blocks at different stages of differentiation.
Effects of recombinant insulin-like growth factor I on insulin secretion and renal function in normal human subjects. (1989)

Insulin-like growth factor I (IGF-I) is an important mediator of growth hormone (GH) action and it appeared tempting to evaluate possible clinical applications. Recombinant IGF-I was infused s.c. at a dose of 20 micrograms/kg of body weight per hour during 6 days in two healthy adult subjects. Blood glucose and fasting insulin levels remained within normal limits and IGF-II levels were suppressed. In contrast to insulin, fasting C peptide levels were decreased. GH secretion was also suppressed by IGF-I. Our preliminary data allow us to distinguish between the effects of GH per se and those of IGF-I: GH causes hyperinsulinism, whereas IGF-I leads to decreased insulin secretion. Glomerular filtration rate, as estimated by creatinine clearance, increased to 130% of preinfusion values during the IGF-I infusion. Total creatinine and urea excretion remained unchanged. We conclude that IGF-I influences kidney function and, in contrast to GH, exerts an insulin-sparing effect. It may be speculated that the therapeutic spectrum of IGF-I is quite different from that of GH.
Interface properties for GaAs/InGaAlP heterojunctions by the capacitance-voltage profiling technique (1987)

The conduction-band discontinuity ΔEc and interface charge density σ have been studied for GaAs/In0.5(Ga1−xAlx)0.5P heterojunctions, prepared by metalorganic chemical vapor deposition. The dependences of ΔEc and σ on Al composition x were investigated for x from 0 to 1. The In0.5Al0.5P/ In0.5Ga0.5P heterojunction was also examined. The results suggest that the valence-band discontinuity ΔEv for GaAs/In0.5(Ga1−xAlx)0.5P is a linear function of x and is larger than ΔEc, being in reasonable agreement with results on the InAlP/InGaP heterojunction. The σ values for GaAs/InGaAlP were found to be one order of magnitude larger than those for GaAs/AlGaAs and InAlP/InGaP heterojunctions.
Analyses of phosphoenolpyruvate carboxylase gene structure and expression in alfalfa nodules (1997)

Phosphoenolpyruvate carboxylase (PEPC) plays a crucial role in the assimilation of CO2 during symbiotic N2 fixation in legume root nodules. In this study, an alfalfa PEPC gene (PEPC-7), whose transcripts are found at elevated levels in nodules relative to either leaves or roots, has been isolated and characterized. The intron/exon structure of this gene is identical to that of most other plant PEPC genes except for the presence of an additional intron in the 5' untranslated region. In situ RNA hybridization studies showed that PEPC transcripts were present in the nodule meristem, the infection zone, the nitrogen-fixing zone, and the parenchyma. PEPC transcripts were also found in vascular tissue of roots and nodules and in the pulvinus of petioles. In transgenic alfalfa, a chimeric reporter gene was expressed in these same regions except that little expression was found in the nodule meristem. Analyses of promoter deletions suggest that the region between -634 and -536 is of particular importance in directing transcriptional activity to the infected zone of nodules. Within this region is a mirror repeat sequence that is potentially capable of forming an H-DNA structure. These results indicate that PEPC-7 has a central role in nitrogen-fixing nodules and that regulation of transcription is an important determinant of its activity.
In vitro selection of active hairpin ribozymes by sequential RNA-catalyzed cleavage and ligation reactions. (1992)

In vitro selection methods provide rapid and extremely powerful tools for elucidating interactions within and between macromolecules. Here, we describe the development of an in vitro selection procedure that permits the rapid isolation and evaluation of functional hairpin ribozymes from a complex pool of sequence variants containing an extremely low frequency of catalytically proficient molecules. We have used this method to analyze the sequence requirements of two regions of the ribozyme-substrate complex: a 7-nucleotide internal loop within the ribozyme that is essential for catalytic function and substrate sequences surrounding the cleavage-ligation site. Results indicate that only 3 of the 16,384 internal loop variants examined have high cleavage and ligation activity and that the ribozyme has a strong requirement for guanosine immediately 3' to the cleavage-ligation site.
Role of vascular endothelial growth factor C expression in the development of lymph node metastasis in gastric cancer. (1999)

Neogenesis of lymphatic vessel and lymphatic invasion is frequently found in the stroma of cancers, but the mechanisms of this phenomenon remain unclear. Vascular endothelial growth factor C (VEGF-C) is known to be the only growth factor for the lymphatic vascular system, and its receptor has been identified as Flt4. To clarify the mechanism of lymphatic invasion in cancer, we studied the expression of VEGF-C and flt4 genes in gastric cancer tissues. VEGF-C mRNA was mainly expressed in primary tumors (15 of 32; 47%), but the frequency of VEGF-C mRNA expression was low in normal mucosa (4 of 32; 13%). In primary tumors, there was a significant relationship between VEGF-C and flt4 mRNA expression. In contrast, Flt4 was mainly expressed on the lymphatic endothelial cells but not in cancer cells. A strong correlation was found between VEGF-C expression and lymph node status, lymphatic invasion, venous invasion, and tumor infiltrating patterns. Cancer cells in the lymphatic vessels frequently showed intracytoplasmic VEGF-C immunoreactivity. Furthermore, there was a close correlation between VEGF-C tissue status and the grade of lymph node metastasis. Patients with high expression of VEGF-C protein had a significantly poorer prognosis than did those in low VEGF-C expression group. By the Cox regression model, depth of wall invasion, lymph node metastasis, and VEGF-C tissue status emerged as independent prognostic parameters, and the VEGF-C tissue status was ranked third as an independent risk factor for death. These results strongly suggest that cancer cells producing VEGF-C may induce the proliferation and dilation of lymphatic vessels, resulting in the development of invasion of cancer cells into the lymphatic vessel and lymph node metastasis.
Vitamin E analogues as inducers of apoptosis: implications for their potential antineoplastic role (2001)

Recent evidence suggests that vitamin E and its analogues, which have been used for many years as antioxidants, may not only protect cells from free radical damage but also induce apoptotic cell death in various cell types. While alpha-tocopherol (alpha-TOH) is mainly known as an anti-apoptotic agent, its redox-silent analogues either have no influence on cell survival (alpha-tocopheryl acetate, alpha-TOA), or induce apoptosis (alpha-tocopheryl succinate, alpha-TOS). Although precise mechanisms of apoptosis induction by alpha-TOS remain to be elucidated, there is evidence that this process involves both the antiproliferative and membrane destabilising activities of the agent. Alpha-TOS has been shown to induce apoptosis in malignant cell lines but not, in general, in normal cells, and to inhibit tumorigenesis in vivo. These features suggest that this semi-synthetic analogue of vitamin E could be a promising antineoplastic agent.
Transcriptional regulation of epidermal cell fate in theArabidopsisembryo (2007)

How distinct cell fates are specified at correct positions within the plant embryo is unknown. In Arabidopsis, different cell fates are generated early on, starting with the two daughter cells of the zygote. To address mechanisms of position-dependent gene activation and cell fate specification, we analyzed the regulatory region of the Arabidopsis thaliana MERISTEM LAYER 1 (ATML1) gene, which is already expressed at the one-cell stage and whose expression is later restricted to the outermost, epidermal cell layer from its inception. A sensitive, multiple GFP reporter revealed a modular organization to the ATML1 promoter. Each region contributes positively to specific spatial and temporal aspects of the overall expression pattern, including position-dependent but auxin-independent regulation along the apical-basal axis of the embryo. A 101 bp fragment that conferred all aspects of ATML1 expression contained known binding sites for homeodomain transcription factors and other regulatory sequences. Our results suggest that expression patterns associated with cell fate determination in the plant embryo result from positional signals targeting different regulatory sequences in complex promoters.
Impacts of fiber length distribution on market value and yarn quality: Implications for U.S. cotton (2005)

The shrinking U.S. textile manufacturing industry has created an increased reliance on the international market for selling U.S. cotton. In turn, this process is transforming the requirements on fiber properties.
Fluorine-18-α-Methyltyrosine Positron Emission Tomography for Diagnosis and Staging of Lung Cancer: A Clinicopathologic Study (2007)

[(18)F]FMT PET had no false-positives in the detection of primary tumor and lymph node metastasis and could improve the diagnostic performance in NSCLC. Uptake of [(18)F]FMT correlated with the expression of LAT1 that showed a significant association with cellular proliferation.
Structural and functional properties of ras proteins (1989)

The ras proteins belong to a family of related polypeptides that are present in all eukaryotic organisms from yeast to human. Their extraordinary evolutionary conservation suggests that they have essential cellular functions, although their exact role remains unknown. Mutations in specific amino acids and overexpression of normal proteins have been linked to altered proliferation and/or differentiation and, particularly, to neoplastic processes. Mature ras proteins are located on the inner side of the plasma membrane, and their biochemical properties include binding and exchange of guanine nucleotides and GTPase activity. The favored hypothesis for ras function is that these proteins exist in an equilibrium between an inactive conformation (p21.GDP) and an active conformation (p21. GTP) in which they are able to interact with their as yet unknown cellular target or targets. Similarities in cellular location, structure, and biochemistry with other known regulatory (G) proteins suggest that they play a role in transduction of signals from the cell surface. The elucidation of the crystal structure of normal and transforming ras proteins and the identification of cellular proteins that interact directly with them (GAP, CDC25) or suppress some of their biological effects (Krev-1) have opened new avenues in the search for their elusive cellular targets and in the elucidation of the functional role of ras gene products.
Reproduction of motion artifacts for performance analysis of prospective motion correction in MRI (2013)

Precise reproduction of motion artifacts assists qualification of prospective motion correction strategies. The presented method provides an important tool to investigate the effects of rigid body motion on a wide range of sequences, and to quantify the improvement in image quality through prospective motion correction.
Immune tolerance induction to enzyme-replacement therapy by co-administration of short-term, low-dose methotrexate in a murine Pompe disease model (2008)

Summary Clinical investigations of recombinant human acid α-glucosidase for the treatment of Pompe disease often reveal the appearance of therapy-specific antibodies. These antibodies could potentially interfere with recombinant human acid α-glucosidase efficacy and induce immunological consequences. Several immunosuppressive agents, including methotrexate, mycophenolate mofetil and cyclosporin A with azathioprine, were evaluated for their potential to induce immune tolerance to recombinant human acid α-glucosidase. Methotrexate was the only agent that reduced recombinant human acid α-glucosidase-specific antibody responses in acid α-glucosidase knock-out mice. A 3-week, low-dose methotrexate regimen controlled recombinant human acid α-glucosidase-specific antibody levels throughout 8 months of weekly recombinant human acid α-glucosidase treatment. The success of this methotrexate regimen appears to require methotrexate administration within the first 24 h of recombinant human acid α-glucosidase treatment. In an attempt to understand the benefit of methotrexate within the first day of recombinant human acid α-glucosidase administration, the immune response 24 h following intravenous recombinant human acid α-glucosidase treatment was investigated. A consistent expansion of peritoneal B1 B cells was observed. Control over this B1 B cell response may be part of the complex mechanism of action of methotrexate-induced immune tolerance.
Dominant-negative polo-like kinase 1 induces mitotic catastrophe independent of cdc25C function. (2000)

Polo-like kinase 1 (PLK1), which has been shown to have a critical role in mitosis, is one possible target for cancer therapeutic intervention. PLK1, at least in Xenopus, starts the mitotic cascade by phosphorylating and activating cdc25C phosphatase. Also, loss of PLK1 function has been shown to induce mitotic catastrophe in a HeLa cervical carcinoma cell line but not in normal Hs68 fibroblasts. We wanted to understand whether the selective mitotic catastrophe in HeLa cells could be extended to other tumor types, and, if so, whether it could be attributable to a tumor-specific loss of dependence on PLK1 for cdc25C activation. When PLK1 function was blocked through adenovirus delivery of a dominant-negative gene, we observed tumor-selective apoptosis in most tumor cell lines. In some lines, dominant-negative PLK1 induced a mitotic catastrophe similar to that published in HeLa cells (K. E. Mundt et al., Biochem. Biophys Res. Commun., 239: 377-385, 1997). Normal human mammary epithelial cells, although arrested in mitosis, appeared to escape the loss of centrosome maturation and mitotic catastrophe seen in tumor lines. Mitotic phosphorylation of cdc25C and activation of cdk1 was blocked by dominant-negative PLK1 in human mammary epithelial cells as well as in the tumor lines regardless of whether they underwent mitotic catastrophe. These data strongly argue that the mitotic catastrophe is not attributable to a lack of dependence for PLK1 in activating cdc25C.