gebhart/patrepeval huggingface dataset:
High tumor levels of vascular endothelial growth factor predict poor response to systemic therapy in advanced breast cancer. (2001)

Vascular endothelial growth factor (VEGF), a potent angiogenic factor, has been reported to be associated with a poor prognosis in primary breast cancer and in several other cancer types. In the present study, we have measured with ELISA the levels of VEGF in cytosolic extracts of 845 primary breast tumors of patients who developed a recurrence during follow-up. All of the patients received tamoxifen (n = 618) or cyclophosphamide, methotrexate, 5-fluorouracil (CMF) or 5-fluorouracil, Adriamycin, cyclophosphamide (FAC) chemotherapy (n = 227) as first-line systemic therapy after diagnosis of advanced disease. VEGF levels were not related to age or menopausal status but were negatively related to the cytosolic levels of estrogen receptor and progesterone receptor (P < 0.0001). In patients who relapsed within 1 year after primary surgery, tumor VEGF levels were higher than in patients who showed a longer disease-free interval (P = 0.0005). In patients with a first relapse in the viscera, VEGF levels were higher compared with those that relapsed to the bone or soft tissue (P = 0.0004). In univariate analysis for response to first-line tamoxifen therapy, patients with high or intermediate levels showed a poor rate of response, compared with patients with low tumor-VEGF levels (P = 0.0001). Similarly, in multivariate analysis for response to tamoxifen treatment, corrected for age, site of relapse, disease-free interval, and estrogen receptor and progesterone receptor status, VEGF status was an independent predictive factor (P = 0.009). In concordance, higher levels of VEGF were associated with a short progression-free survival and postrelapse overall survival (both, P < 0.0001). On first-line chemotherapy, the rate of response decreased with higher tumor levels of VEGF, both in univariate (P = 0.003) and in multivariate analysis (P = 0.004). Furthermore, higher VEGF levels were associated with a short progression-free survival (P = 0.003) and postrelapse overall survival (P = 0.001). In conclusion, the tumor VEGF level is an important independent marker that predicts a poor efficacy of both tamoxifen and chemotherapy in advanced breast cancer. Knowledge of the tumor level of VEGF might be helpful in selecting individual patients who may benefit from treatments with antiangiogenic agents combined with conventionally used drugs.
TOP: Tail Optimization Protocol For Cellular Radio Resource Allocation (2010)

In 3G cellular networks, the release of radio resources is controlled by inactivity timers. However, the timeout value itself, also known as the tail time, can last up to 15 seconds due to the necessity of trading off resource utilization efficiency for low management overhead and good stability, thus wasting considerable amount of radio resources and battery energy at user handsets. In this paper, we propose Tail Optimization Protocol (TOP), which enables cooperation between the phone and the radio access network to eliminate the tail whenever possible. Intuitively, applications can often accurately predict a long idle time. Therefore the phone can notify the cellular network on such an imminent tail, allowing the latter to immediately release radio resources. To realize TOP, we utilize a recent proposal of 3GPP specification called fast dormancy, a mechanism for a handset to notify the cellular network for immediate radio resource release. TOP thus requires no change to the cellular infrastructure and only minimal changes to smartphone applications. Our experimental results based on real traces show that with a reasonable prediction accuracy, TOP saves the overall radio energy (up to 17%) and radio resources (up to 14%) by reducing tail times by up to 60%. For applications such as multimedia streaming, TOP can achieve even more significant savings of radio energy (up to 60%) and radio resources (up to 50%).
Development of a New Generation of Thermal Power Stations Suitable for Application in New Zealand (1994)

This paper presents a review of the development of a new generation of highly efficient thermal power stations. Unlike conventional thermal power stations, these employ a binary mixture working fluid, such as hydrated ammonia, the composition of which is variable throughout the process. The most successful group of cycles of this type in terms of both efficiency and promotion are the Kalina cycles. These achieve 20% to 40% improvements in efficiency over comparable Rankine cycles in a wide range of applications. The operating principles of the Kalina technology have been proven by a test plant operating at the US Department of Energy site in Canoga Park, California. Further developments in binary fluid mixture power station technology include a condensation system similar to the absorption-vapour generator systems common in absorption refrigeration systems. In the New Zealand context, an existing proposal for a 30 MW Kalina Cycle System 11 plant to be built at Wairakei is briefly discussed.
PCR-mediated cloning of HpaII tiny fragments from microdissected human chromosomes. (1992)

Vertebrate DNA contains a small fraction of unmethylated CpG-rich DNA sequences, many of which include the 5' end of a gene. This fraction can be detected by its cleavage to tiny fragments with the methylation-sensitive restriction enzyme HpaII. Thus, the isolation of HpaII tiny fragments (HTFs) from a specific chromosome region may be a useful approach for making an inventory of the genes contained in it. Using microdissection, we have isolated DNA from human chromosome band 8q24.1. The DNA was digested with HpaII, ligated to a ClaI-cut pUC plasmid, and amplified with Taq DNA polymerase and the standard M13/pUC forward and reverse sequencing primers. The amplification products were used to construct an HTF library, which is enriched for CpG-rich single-copy clones.
Uroplakins Ia and Ib, two major differentiation products of bladder epithelium, belong to a family of four transmembrane domain (4TM) proteins. (1994)

The mammalian bladder epithelium elaborates, as a terminal differentiation product, a specialized plasma membrane called asymmetric unit membrane (AUM) which is believed to play a role in strengthening and stabilizing the urothelial apical surface through its interactions with an underlying cytoskeleton. Previous studies indicate that the outer leaflet of AUM is composed of crystalline patches of 12-nm protein particles, and that bovine AUMs contain three major proteins: the 27- to 28-kD uroplakin I, the 15-kD uroplakin II and the 47-kD uroplakin III. As a step towards elucidating the AUM structure and function, we have cloned the cDNAs of bovine uroplakin I (UPI). Our results established the existence of two isoforms of bovine uroplakin I: a 27-kD uroplakin Ia and a 28-kD uroplakin Ib. These two glycoproteins are closely related with 39% identity in their amino acid sequences. Hydropathy plot revealed that both have four potential transmembrane domains (TMDs) with connecting loops of similar length. Proteolytic digestion of UPIa inserted in vitro into microsomal vesicles suggested that its two main hydrophilic loops are exposed to the luminal space, possibly involved in interacting with the luminal domains of other uroplakins to form the 12-nm protein particles. The larger loop connecting TMD3 and TMD4 of both UPIa and UPIb contains six highly conserved cysteine residues; at least one centrally located cysteine doublet in UPIa is involved in forming intramolecular disulfide bridges. The sequences of UPIa and UPIb (the latter is almost identical to a hypothetical, TGF beta-inducible, TI-1 protein of mink lung epithelial cells) are homologous to members of a recently described family all possessing four transmembrane domains (the "4TM family"); members of this family include many important leukocyte differentiation markers such as CD9, CD37, CD53, and CD63. The tissue-specific and differentiation-dependent expression as well as the naturally occurring crystalline state of uroplakin I molecules make them uniquely suitable, as prototype members of the 4TM family, for studying the structure and function of these integral membrane proteins.
Pharmacologic Characterization of Valbenazine (NBI-98854) and Its Metabolites (2017)

The vesicular monoamine transporter 2 (VMAT2) is an integral presynaptic protein that regulates the packaging and subsequent release of dopamine and other monoamines from neuronal vesicles into the synapse. Valbenazine (NBI-98854), a novel compound that selectively inhibits VMAT2, is approved for the treatment of tardive dyskinesia. Valbenazine is converted to two significant circulating metabolites in vivo, namely, (+)-<i>α</i>-dihydrotetrabenazine (R,R,R-HTBZ) and a mono-oxy metabolite, NBI-136110. Radioligand-binding studies were conducted to assess and compare valbenazine, tetrabenazine, and their respective metabolites in their abilities to selectively and potently inhibit [<sup>3</sup>H]-HTBZ binding to VMAT2 in rat striatal, rat forebrain, and human platelet homogenates. A broad panel screen was conducted to evaluate possible off-target interactions of valbenazine, R,R,R-HTBZ, and NBI-136110 at >80 receptor, transporter, and ion channel sites. Radioligand binding showed R,R,R-HTBZ to be a potent VMAT2 inhibitor in homogenates of rat striatum (K<sub>i</sub> = 1.0-2.8 nM), rat forebrain (K<sub>i</sub> = 4.2 nM), and human platelets (K<sub>i</sub> = 2.6-3.3 nM). Valbenazine (K<sub>i</sub> = 110-190 nM) and NBI-136110 (K<sub>i</sub> = 160-220 nM) also exhibited inhibitory effects on VMAT2, but with lower potency than R,R,R-HTBZ. Neither valbenazine, R,R,R-HTBZ, nor NBI-136110 had significant off-target interactions at serotonin (5-HT<sub>1A</sub>, 5-HT<sub>2A</sub>, 5-HT<sub>2B</sub>) or dopamine (D<sub>1</sub> or D<sub>2</sub>) receptor sites. In vivo studies measuring ptosis and prolactin secretion in the rat confirmed the specific and dose-dependent interactions of tetrabenazine and R,R,R-HTBZ with VMAT2. Evaluations of potency and selectivity of tetrabenazine and its pharmacologically active metabolites were also performed. Overall, the pharmacologic characteristics of valbenazine appear consistent with the favorable efficacy and tolerability findings of recent clinical studies [KINECT 2 (NCT01733121), KINECT 3 (NCT02274558)].
Effects of free fatty acids on the growth of normal and neoplastic rat mammary epithelial cells. (1979)

Abstract To gain some understanding of the role of lipids in mammary epithelial growth and in mammary carcinogenesis, the direct effects of free fatty acids on cell growth in primary cultures of mammary epithelial cells and 7, 12-dimethylbenz[α]anthracene-induced mammary tumors from rats were studied. The epithelial nature of virgin mammary cultures was confirmed by light and electron microscopy, by association of cells with basement membrane, and by production of α-lactalbumin. In the presence of insulin, hydrocortisone, progesterone, estrogen, prolactin, and delipidized fetal calf serum, both the normal mammary and tumor cells were stimulated in their growth by the addition of unsaturated free fatty acids and inhibited by the addition of saturated free fatty acids to the growth medium. For normal cells, linoleic or linolenic acids at 1.0 and 0.1 µg/ml, respectively, and for 7,12-dimethylbenz[α]anthracene-induced tumor cells, oleic acid or linoleic acid at 0.5 and 1.0 µg/ml, respectively, resulted in greater than a doubling of the growth rate compared to cultures with no added free fatty acid. For both normal and tumor cells, saturated free fatty acids inhibited growth at all concentrations tested. The concentration optima in vitro paralleled the proportions of essential fatty acids (free and esterified) in the normal mammary gland. A state of mammary proliferation in vivo was associated with an increase of 45% in the ratio of linoleic plus oleic:palmitic acids in total mammary lipids. Lipids may play some direct role in normal and neoplastic mammary cell growth.
Amplicon profiles in ovarian serous carcinomas (2007)

Ovarian serous carcinoma is the most common and lethal type of ovarian cancer and its molecular etiology remains poorly understood. As an ongoing effort to elucidate the pathogenesis of ovarian serous carcinomas, we assessed the DNA copy number changes in 33 high-grade serous carcinomas and 10 low-grade serous tumors by using a genome-wide technique, single nucleotide polymorphism array, performed on affinity-purified tumor cells from fresh surgical specimens. Compared to low-grade tumors, high-grade serous carcinomas showed widespread DNA copy number changes. The most frequent alterations were in loci harboring candidate oncogenes: cyclin E1 (CCNE1), AKT2, Notch3 and PIK3CA as well as in novel loci, including 12p13, 8q24, 12p13 and 12q15. Seven amplicons were selected for dual color fluorescence in situ hybridization analysis in approximately 90 high-grade serous carcinomas and 26 low-grade serous tumors, and a high level of DNA copy number gain (amplification) was found in CCNE1, Notch3, HBXAP/Rsf-1, AKT2, PIK3CA and chr12p13 occurring in 36.1%, 7.8%, 15.7%, 13.6%, 10.8% and 7.3% of high-grade serous carcinomas. In contrast, we did not observe high level of ERBB2 amplification in any of the samples. Low-grade tumors did not show DNA copy number gain in any of the loci, except in 2 (8%) of 24 low-grade tumors showing low copy number gain in the Notch3 locus. Taken together, our results provide the first comprehensive analysis of DNA copy number changes in highly pure ovarian serous carcinoma. These findings may have important biological and clinical implications.
ECT: survivors in the driving seat (2000)

A former recipient of ECT, Hannah Mills, presents a research-based and personal perspective on why this therapy gives her cause for concern
Signs and symptoms versus nerve conduction studies to diagnose diabetic sensorimotor polyneuropathy: Cl vs. NPhys trial (2010)

The purpose was to test whether physicians can validly and reproducibly diagnose diabetic sensorimotor polyneuropathy (DSPN). Twelve physicians assessed 24 patients with diabetes mellitus (DM) on consecutive days (576 examinations) with physical features and voice disguised. Results were compared to gold standard 75% group diagnosis (dx) and a nerve conduction score (Sigma5 NC nds). Masking of patients was achieved. Reproducibility measured by the kappa coefficient and compared to Sigma5 NC nd varied considerably among physicians: median and ranges: signs 0.8 (0.32-1.0); symptoms 0.79 (0.36-1.0), and diagnoses 0.47 (0.33-0.84), both low and high scores indicating poor performance. There was substantial agreement between 75% group dx and confirmed NC abnormality (abn). As compared to Sigma5 NC, individual physicians' clinical dx was excessively variable and frequently inaccurate. Study physician dx from signs and symptoms were excessively variable, often overestimating DSPN. Specific approaches to improving clinical proficiency should be tested.
A memory-based high-speed digital delay line with a large adjustable length (1988)

The digital delay line concept is based on a dynamic three-transistor cell memory, with pointer access and offers high operating frequency, large maximum length, and low power dissipation. The adjustable delay requires only a small overhead for control logic. An experimental chip with 60 K transistors, which utilizes this concept, has been built in a 1.5- mu m CMOS technology. The adjustable delay ranges from 1 to 4096 clock cycles for a 4-bit-wide data word. Correct operation of the chip has been verified for clock frequencies in the range of 3 kHz to 30 MHz. Therefore the circuit is suitable for audio as well as video applications.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Thermo-optical properties of air-clad photonic crystal fiber lasers in high power operation (2003)

We report on the investigation of the thermo-optical behavior of air-clad ytterbium-doped large-mode-area photonic crystal fiber lasers. Analytical and numerical models are applied to calculate the heat distribution and induced stresses in a microstructured fiber. The results are compared to conventional double-clad fiber lasers and design guidelines are provided to ensure maximum heat dissipation and scalability to power levels of several kWs.
Gas flaring reduction projects - framework for clean development mechanism (CDM) baseline methodologies (2005)

Flaring of associated gas contributes significantly to the global emissions of greenhouse gases; flaring emissions are currently estimated to be 300 million tons of carbon dioxide equivalents per year. The clean development mechanism (CDM) can help stimulate investments in projects that reduce flaring and venting of associated gas. Pilot projects will be instrumental in defining and furthering the role of CDM in gas flaring reductions. Rules and procedures are being established to determine under what conditions such investments can earn CDM carbon credits. According to the Marrakech Accords, a CDM project activity is additional if its emissions are below those of its baseline. The baseline for a CDM project activity is the scenario that reasonably represents the anthropogenic emissions, by the sources of greenhouse gases that would occur in the absence of the proposed project activity. The business-as-usual case, in the absence of the project, typically is continued flaring. To achieve CDM designation, a project developer must use a methodology approved by the CDM Executive Board for baseline determination. To date, only one baseline methodology for flaring reduction projects has been approved, and the overall applicability of this methodology has still to be determined. Several more methodologies need to be developed and approved to cover the range of project options in this sector. Drawing on recent decisions by the CDM Executive Board, and recommendations from the Methodology Panel, this report presents a framework for constructing such methodologies, and outlines the tools that can be used to demonstrate additionality. It also presents developments and discussions that were held up to June 25, 2004 and the CDM Proposed New Methodology: Baseline (CDM-NMB), Version 01 (in effect as of July 1, 2004).
The effects of nandrolone decanoate on rarefying bone tissue (1980)

The effects of nandrolone decanoate on rarefying bone tissue were studied with the aid of microradiography and fluorescence microscopy in tetracycline-labelled preparations of the rabbit calcaneus and the long bones of old dogs. Osteoporosis was induced in the rabbit calcaneus by resecting of the Achilles tendon. In 20 of the 24 rabbits treated with nandrolone decanoate, the osteoporosis observed was less severe than in 8 untreated controls. Furthermore, in comparison with the controls, the signs of active osteogenesis in the treated groups increased systematically. In the old dogs, nandrolone decanoate caused a new opposition, identified by tetracycline labelling, to appear at the periphery of the medullary cavity. All the observations suggest that nandrolone decanoate has a favourable effect on osteogenetic phenomena and probably an inhibitory action on bone resorption. Consequently, nandrolone decanoate is capable of preventing or, at least, of partially correcting losses of bone mass.
Preparation and characterisation of nanofibrous cellulose plate as a new solid support for microbial culture (2007)

Porous plates made of nanofibrous crystalline cellulose were prepared, and used as a solid support for microbial cultures. Representative mesophilic microorganisms (, , and ) grew on the cellulose plate, just as well as they did on the conventional agar plate. optical microscopic examination revealed that the cellulose plate remained unchanged up to 280 °C at a constant pressure of 25 MPa. Due to the structural stability at high temperatures, a representative thermophile, , was cultured successfully on the cellulose plate at 80 °C. Mouse fibroblast cells did not show significant adhesion or extension on the cellulose plate.
Activated hepatic stellate cells promote liver cancer by induction of myeloid-derived suppressor cells through cyclooxygenase-2 (2016)

Hepatic stellate cells (HSCs) are critical mediators of immunosuppression and the pathogenesis of hepatocellular carcinoma (HCC). Our previous work indicates that HSCs promote HCC progression by enhancing immunosuppressive cell populations including myeloid-derived suppressor cells (MDSCs) and regulatory T cells (Tregs). MDSCs are induced by inflammatory cytokines (e.g., prostaglandins) and are important in immune suppression. However, how HSCs mediate expansion of MDSCs is uncertain. Thus, we studied activated HSCs that could induce MDSCs from bone marrow cells and noted that HSC-induced MDSCs up-regulated immunosuppressive activity via iNOS, Arg-1, and IL-4Rα. After treating cells with a COX-2 inhibitor or an EP4 antagonist, we established that HSC-induced MDSC accumulation was mediated by the COX2-PGE2-EP4 signaling. Furthermore, in vivo animal studies confirmed that inhibition of HSC-derived PGE2 could inhibit HSC-induced MDSC accumulation and HCC growth. Thus, our data show that HSCs are required for MDSC accumulation mediated by the COX2-PGE2-EP4 pathway, and these data are the first to link HSC and MDSC subsets in HCC immune microenvironment and provide a rationale for targeting PGE2 signaling for HCC therapy.
Influenza virus NS1 protein stimulates translation of the M1 protein (1994)

The influenza virus NS1 protein was shown to stimulate translation of the M1 protein. M-CAT RNA, which contains the chloramphenicol acetyltransferase (CAT) reporter gene and the terminal noncoding sequence of segment 7 (coding for the M1 and M2 proteins), was ribonucleoprotein transfected into clone 76 cells expressing the influenza virus RNA polymerase and NP proteins required for the transcription and replication of influenza virus ribonucleoproteins. When the cells were superinfected with a recombinant vaccinia virus which expresses the NS1 protein, CAT expression from the M-CAT RNA was significantly stimulated but transcription was not altered. The expression of NS-CAT RNA, which contains noncoding sequences of segment 8 (coding for the NS1 and NS2 proteins), was not altered by the NS1 protein. Site-directed mutagenesis showed that the sequence GGUAGAUA upstream of the initiation codon on segment 7 was required for stimulation.
Design of an interactive lumbar puncture simulator with tactile feedback (2002)

Lumbar puncture for purposes of administering spinal or epidural anesthesia is a complex clinical skill which requires the clinician to precisely correlate a detailed mental map of hidden three-dimensional anatomy with tactile feedback from the spinal needle as it's being inserted. At Dartmouth, a collaborative work between the engineering and medical schools is aimed at developing a computer-based simulation utilizing high-resolution 3D graphics and a force-feedback device to simulate the "feel" of inserting the needle. This paper describes the mechanical design, hardware and software issues and some of the technical challenges being addressed in this project.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>