gebhart/patrepeval huggingface dataset:
Technology vital for horizontal well success (1995)

Union Pacific Resources Co. (UPRC) has drilled more than 1,100 horizontal wells since 1987 and continues to operate about 15--20 rigs drilling horizontal wells. Technology has advanced the drilling, completion, formation evaluation, stimulation, and production of horizontal wells. Drilling break-throughs include dual-powerhead mud motors, retrievable whipstocks, and routine multiple lateral wells. Cost improvements have enabled UPRC to extend activity into deeper zones, which are hotter and more hostile. State-of-the-art drilling includes as many as four, 4,000+ ft horizontal laterals, horizontal wells at TVDs greater than 16,000 ft, and mud weights in excess of 15 ppg. In the Austin chalk, UPRC operates properties producing more than 480 MMcfd, 40,000 bo/d, and over 100,000 bw/d. The paper uses the wells of the Austin chalk to describe the technology used for formation evaluation, geological steering, muds, top drives, bit selection, mud motors, multiple laterals, retrievable whipstocks, water fracs, vapor-recovery units, artificial lift, automation, and surface facilities. Organizations, alliances, and corrosion problems are also discussed.
In vitro Biological Characterization of a Novel, Synthetic Diaryl Pyrazole Resorcinol Class of Heat Shock Protein 90 Inhibitors (2007)

The molecular chaperone heat shock protein 90 (HSP90) has emerged as an exciting molecular target. Derivatives of the natural product geldanamycin, such as 17-allylamino-17-demethoxy-geldanamycin (17-AAG), were the first HSP90 ATPase inhibitors to enter clinical trial. Synthetic small-molecule HSP90 inhibitors have potential advantages. Here, we describe the biological properties of the lead compound of a new class of 3,4-diaryl pyrazole resorcinol HSP90 inhibitor (CCT018159), which we identified by high-throughput screening. CCT018159 inhibited human HSP90beta with comparable potency to 17-AAG and with similar ATP-competitive kinetics. X-ray crystallographic structures of the NH(2)-terminal domain of yeast Hsp90 complexed with CCT018159 or its analogues showed binding properties similar to radicicol. The mean cellular GI(50) value of CCT018159 across a panel of human cancer cell lines, including melanoma, was 5.3 mumol/L. Unlike 17-AAG, the in vitro antitumor activity of the pyrazole resorcinol analogues is independent of NQO1/DT-diaphorase and P-glycoprotein expression. The molecular signature of HSP90 inhibition, comprising increased expression of HSP72 protein and depletion of ERBB2, CDK4, C-RAF, and mutant B-RAF, was shown by Western blotting and quantified by time-resolved fluorescent-Cellisa in human cancer cell lines treated with CCT018159. CCT018159 caused cell cytostasis associated with a G(1) arrest and induced apoptosis. CCT018159 also inhibited key endothelial and tumor cell functions implicated in invasion and angiogenesis. Overall, we have shown that diaryl pyrazole resorcinols exhibited similar cellular properties to 17-AAG with potential advantages (e.g., aqueous solubility, independence from NQO1 and P-glycoprotein). These compounds form the basis for further structure-based optimization to identify more potent inhibitors suitable for clinical development.
Novel cerebroprotective agents with central nervous system stimulating activity. 1. Synthesis and pharmacology of the 1-amino-7-hydroxyindan derivatives (1991)

In a continuous search for a novel cerebroprotective drug with a central nervous system (CNS) stimulating activity, a series of 1-(acylamino)-7-hydroxyindan derivatives has been synthesized and tested for its dual activities. The cerebroprotective activities of the compounds in this series were evaluated in terms of their effect on the survival of mice in hypoxic conditions (210 mmHg), and their CNS stimulating activities were examined by evaluating their promotional effects on the recovery from coma induced by cerebral concussion in mice. Several compounds prolonged the survival of mice in the hypoxic conditions at a dose of 30 mg/kg po. Four compounds in this series showed the CNS-stimulating effect at the same dose. Among them, 7-hydroxy-1-[4-(3-methoxyphenyl)-1-piperazinyl]acetyl]amino]-2,2,4, 6-tetramethylindan (18, OPC-14117), which was active in the two tests with no side effect up to 500 mg/kg po daily for 2 weeks of administration to rats, was selected for preclinical investigations.
Location verification using secure distance bounding protocols (2005)

Authentication in conventional networks (like the Internet) is usually based upon something you know (e.g., a password), something you have (e.g., a smartcard) or something you are (biometrics). In mobile ad-hoc networks, location information can also be used to authenticate devices and users. We focus on how a provers can securely show that (s)he is within a certain distance to a verifier. Brands and Chaum proposed the distance bounding protocol as a secure solution for this problem. However, this protocol is vulnerable to a so-called "terrorist fraud attack". In this paper, we explain how to modify the distance bounding protocol to make it resistant to this kind of attacks. Recently, two other secure distance bounding protocols were published. We discuss the properties of these protocols and show how to use it as a building block in a location verification scheme
D-Amino Acid Oxidase (1968)

Abstract A variety of anionic compounds was studied as inhibitors of d-amino acid oxidase by means of a recently described spectrophotometric assay for the enzyme. Several phosphorus- and sulfur-containing acids were shown not to be effective inhibitors of the enzyme. A series of meta- and para-substituted benzoic acid derivatives was studied as inhibitors and the σρ relationship obtained indicated the binding of these compounds to be facilitated by electron-withdrawing substituent groups. A variety of saturated and unsaturated carboxylic acids was evaluated as substrate-competitive inhibitors of the enzyme. It is indicated that these inhibitors interact with a positively charged group of the enzyme that is a critical distance from an aromatic residue contained in a limited nonpolar region of the enzyme. It is suggested that the aromatic residue of the protein interacts with the inhibitors through electron donation. Steric interactions involved in the binding of inhibitors were also observed.
Local linear estimators for the bioelectromagnetic inverse problem (2005)

Linear estimators have been used widely in the bioelectromagnetic inverse problem, but their properties and relationships have not been fully characterized. Here, we show that the most widely used linear estimators may be characterized by a choice of norms on signal space and on source space. These norms depend, in part, on assumptions about the signal space and source space covariances. We demonstrate that two estimator classes (standardized and weight vector normalized) yield unbiased estimators of source location for simple source models (including only the noise-free case) but biased estimators of source magnitude. In the presence of instrumental (white) noise, we show that the nonadaptive standardized estimator is a biased estimator of source location, while the adaptive weight vector normalized estimator remains unbiased. A third class (distortionless) is an unbiased estimator of source magnitude but a biased estimator of source location.
Long-term Treatment of Malignant Gliomas with Intramuscularly Administered Polyinosinic-Polycytidylic Acid Stabilized with Polylysine and Carboxymethylcellulose: An Open Pilot Study (1996)

POLYINOSINIC-POLYCYTIDYLIC ACID STABILIZED with polylysine and carboxymethylcellulose (poly-ICLC) (10-50 mcg/kg, administered intramuscularly one to three times weekly) was given for ≤56 months to 38 patients with malignant gliomas. There was minimal or no toxicity. Twenty of 30 patients(66%) receiving at least twice weekly poly-ICLC showed regression or stabilization of gadolinium-enhancing tumor, as revealed by magnetic resonance imaging (median = 65% volume decrease). All but one patient with anaplastic astrocytomas who received continuous poly-ICLC remain alive, with a median progression-free survival of 54 months from diagnosis. Median Kaplan-Meier survival is 19 months for patients with glioblastomas who receive at least twice weekly poly-ICLC treatments. Tumor response was associated with 2′,5′-oligoadenylate synthetase activation (P = 0.03) but not with serum interferon. We hypothesize clinical activation by poly-ICLC of a basic host tumor suppressor system. Prolonged, quality survival with tumor stabilization or regression confirmed by magnetic resonance imaging for most patients with anaplastic astrocytomas and glioblastomas suggests that more extensive laboratory and controlled clinical studies are warranted. The concept of long-term, broad spectrum stimulation of host defenses with nontoxic, inexpensive double-stranded ribonucleic acids, such as low-dose poly-ICLC, may be applicable to the treatment of other malignancies.
Intravaginal Metronidazole/Miconazole for the Treatment of Vaginal Trichomoniasis (2013)

High-dose intravaginal metronidazole combined with miconazole offers the possibility of a well-tolerated treatment that avoids the systemic adverse effects of nitroimidazoles for the treatment of trichomoniasis.
In situ tuning of omnidirectional microelectromechanical-systems microphones to improve performance fit in hearing aids (2008)

Hearing aids are not a one-size-fits-all solution to hearing problems; they must be uniquely tuned for each wearer. There are currently no low-cost and/or effective methods for in situ tuning. This paper describes a microelectromechanical-systems (MEMS)-based dual omnidirectional microphone that can be tuned by growing metallic nanostructures. The nanostructures are grown on integrated solid electrolyte layers on a suspended parylene diaphragm using an external bias and tune the MEMS microphones in situ thereby limiting mismatch. In our tests, this tuning improved the directivity index from 3.5 (fair directionality) to 4.6 dB (excellent directionality) in normal (room temperature) operating environments.
Tumor Stem Cell Antigens as Consolidative Active Specific Immunotherapy (2012)

Only 10% of metastatic melanoma patients survive 5 years, even though many can achieve substantial tumor reduction by surgical resection and/or radiation therapy and/or systemic therapy. An effective, nontoxic, consolidation immunotherapy could benefit such patients. We initiated a randomized trial to compare 2 promising patient-specific immunotherapy cell products. Patients had to have a diagnosis of metastatic melanoma and availability of an autologous melanoma cell line. Patients were stratified by whether their most advanced stage had been regional or distant metastases, and by whether they had measurable disease at the time of treatment, then they were randomized to receive irradiated autologous proliferating tumor cells or autologous dendritic cells (DC) loaded with antigens from such cells. Both products were injected subcutaneously in 500 µg of granulocyte-macrophage colony stimulating factor, weekly for 3 weeks and then monthly for 5 months. Patients in the 2 arms did not differ in baseline characteristics. All patients received prescribed therapy. Treatment was well tolerated. At the time of initial analysis, with no patients lost to follow-up, 50% of patients deceased, and all surviving patients followed for at least 6 months after randomization, survival is superior in the DC arm (hazard ratio, 0.27; 95% confidence interval, 0.098-0.729) with median survival not reached versus 15.9 months, and 2-year survival rates of 72% versus 31% (P=0.007). This trial provides evidence that a DC vaccine is associated with longer survival compared with a tumor cell vaccine, and is consistent with previous data suggesting a survival benefit from this patient-specific immunotherapy.
Of Mice, Men and Elephants: The Relation between Articular Cartilage Thickness and Body Mass (2013)

Mammalian articular cartilage serves diverse functions, including shock absorption, force transmission and enabling low-friction joint motion. These challenging requirements are met by the tissue's thickness combined with its highly specific extracellular matrix, consisting of a glycosaminoglycan-interspersed collagen fiber network that provides a unique combination of resilience and high compressive and shear resistance. It is unknown how this critical tissue deals with the challenges posed by increases in body mass. For this study, osteochondral cores were harvested post-mortem from the central sites of both medial and lateral femoral condyles of 58 different mammalian species ranging from 25 g (mouse) to 4000 kg (African elephant). Joint size and cartilage thickness were measured and biochemical composition (glycosaminoclycan, collagen and DNA content) and collagen cross-links densities were analyzed. Here, we show that cartilage thickness at the femoral condyle in the mammalian species investigated varies between 90 µm and 3000 µm and bears a negative allometric relationship to body mass, unlike the isometric scaling of the skeleton. Cellular density (as determined by DNA content) decreases with increasing body mass, but gross biochemical composition is remarkably constant. This however need not affect life-long performance of the tissue in heavier mammals, due to relatively constant static compressive stresses, the zonal organization of the tissue and additional compensation by joint congruence, posture and activity pattern of larger mammals. These findings provide insight in the scaling of articular cartilage thickness with body weight, as well as in cartilage biochemical composition and cellularity across mammalian species. They underscore the need for the use of appropriate in vivo models in translational research aiming at human applications.
东南亚地区古生代-中生代地质演化：生物地理的各种约束及意义 (2011)

东亚和东南亚是一个巨型的由大陆地体形成的锯齿状拼合图，各个地体以断层、狭窄的活动带或代表以前洋盆位置的缝合带为界，各个地体的构造地层、古生物学和古地磁的比较研究表明，它们都直接或间接来自冈瓦纳大陆，曾经构成“大冈瓦纳大陆”的一部分。冈瓦纳大陆北缘在泥盆纪、早一中二叠世和晚三叠世一晚侏罗世出现了三次大陆地体的裂离。这些地体的向北漂移伴随着三个连续的大洋的张开和闭合，即古特提斯、中特提斯和新特提斯。晚泥盆世和白垩纪期间不断发生的亚洲地体的拼贴和增生，开始是晚泥盆世-早石炭世时特提斯内华南和印支的拼贴，形成华夏陆块，紧接着是二叠纪塔里木地体增生到哈萨克斯坦／西伯利亚之上。二叠一三叠纪，中缅马苏和羌塘与华夏陆块缝合，然后这个超级地体又与华北拼贴。到晚三叠世-早侏罗世增生到劳亚大陆上。高度变形的日本黑濑川地体可能来自澳大利亚冈瓦纳，晚侏罗世增生到日本欧亚大陆之上。拉萨、西缅甸和Woyla地体在晚三叠世一晚侏罗世期间从冈瓦纳的西北澳大利亚裂离出来，在白垩纪增生到古东南亚之上。西南婆罗洲和塞米陶地体来自华南／印支陆缘，该陆缘在白垩纪时发生边缘海盆地扩张，接着南海张开，礼乐滩-南沙地体从华南分离出来并向南俯冲，对西南婆罗洲和塞米陶地体造成破坏。接着发生了冈瓦纳大陆最后破裂，印度迅速向北移动，在白垩纪末与欧亚发生初始接触。重建显了古生代和中生代期间各个地体推测的位置和陆海分布。
Homology Requirements for Targeting Heterologous Sequences During P-Induced Gap Repair in Drosophila melanogaster 1 (1997)

The effect of homology on gene targeting was studied in the context of P-element-induced double-strand breaks at the white locus of Drosophila melanogaster. Double-strand breaks were made by excision of P-w(hd), a P-element insertion in the white gene. A nested set of repair templates was generated that contained the 8 kilobase (kb) yellow gene embedded within varying amounts of white gene sequence. Repair with unlimited homology was also analyzed. Files were scored phenotypically for conversion of the yellow gene to the white locus. Targeting of the yellow gene was abolished when all of the 3' homology was removed. Increases in template homology up to 51 base pairs (bp) did not significantly promote targeting. Maximum conversion was observed with a construct containing 493 bp of homology, without a significant increase in frequency when homology extended to the tips of the chromosome. These results demonstrate that the homology requirements for targeting a large heterologous insertion are quite different than those for a point mutation. Furthermore, heterologous insertions strongly affect the homology requirements for the conversion of distal point mutations. Several aberrant conversion tracts, which arose from templates that contained reduced homology, also were examined and characterized.
Diffusion‐based process for carbon dioxide uptake and isoprene emission in gaseous/aqueous two‐phase photobioreactors by photosynthetic microorganisms (2011)

Photosynthesis for the generation of fuels and chemicals from cyanobacteria and microalgae offers the promise of a single host organism acting both as photocatalyst and processor, performing sunlight absorption and utilization, as well as CO(2) assimilation and conversion into product. However, there is a need to develop methods for generating, sequestering, and trapping such bio-products in an efficient and cost-effective manner that is suitable for industrial scale-up and exploitation. A sealed gaseous/aqueous two-phase photobioreactor was designed and applied for the photosynthetic generation of volatile isoprene (C(5)H(8)) hydrocarbons, which operates on the principle of spontaneous diffusion of CO(2) from the gaseous headspace into the microalgal or cyanobacterial-containing aqueous phase, followed by photosynthetic CO(2) assimilation and isoprene production by the transgenic microorganisms. Volatile isoprene hydrocarbons were emitted from the aqueous phase and were sequestered into the gaseous headspace. Periodic replacement (flushing) of the isoprene (C(5)H(8)) and oxygen (O(2)) content of the gaseous headspace with CO(2) allowed for the simultaneous harvesting of the photoproducts and replenishment of the CO(2) supply in the gaseous headspace. Reduction in practice of the gaseous/aqueous two-phase photobioreactor is offered in this work with a fed-batch and a semi-continuous culturing system using Synechocystis sp. PCC 6803 heterologously expressing the Pueraria montana (kudzu) isoprene synthase (IspS) gene. Constitutive isoprene production was observed over 192 h of experimentation, coupled with cyanobacterial biomass accumulation. The diffusion-based process in gaseous/aqueous two-phase photobioreactors has the potential to be applied to other high-value photosynthetically derived volatile molecules, emanating from a variety of photosynthetic microorganisms.
Phase II trial of docetaxel in patients with advanced cutaneous malignant melanoma previously untreated with chemotherapy. (1995)

PURPOSE A phase II study was undertaken to determine the efficacy of docetaxel in patients with metastatic malignant melanoma. PATIENTS AND METHODS Between June 1992 and March 1994, 40 patients with metastatic malignant melanoma and no prior chemotherapy were treated with docetaxel 100 mg/m2 administered intravenously over 1 hour every 21 days. None of the patients had brain metastasis. Toxicity and follow-up data are provided. RESULTS One patient had a histologically confirmed complete response that lasted for 14+ months. Four patients had partial responses, bringing the overall response rate to 12.5% (95% confidence interval [CI], 6% to 30%). A patient with a partial response had a single chest-wall metastasis and was rendered free of disease surgically after a maximal response to docetaxel and remained free of tumor recurrence after 18+ months. Tumor was stabilized in 22 patients. The overall median survival time was 13 months. The main hematologic toxicity was neutropenia, which was severe but transient. Peripheral neuropathy was the limiting nonhematologic toxicity in three patients. Other important toxicities included cutaneous toxicity, fluid retention, oral mucositis, and hypersensitivity reactions. Preadministration of dexamethasone and diphenhydramine reduced the incidence of hypersensitivity reactions, cutaneous toxicities, and fluid retention. CONCLUSION Docetaxel has definite but low-level activity against malignant melanoma. Further investigation of this drug should be conducted in multidrug combination programs.
Multiple cyclin-dependent kinases signals are critical mediators of ischemia/hypoxic neuronal death in vitro and in vivo (2005)

The mechanisms involving neuronal death after ischemic/hypoxic insult are complex, involving both rapid (excitotoxic) and delayed (apoptotic-like) processes. Recent evidence suggests that cell cycle regulators such as cyclin-dependent kinases are abnormally activated in neuropathological conditions, including stroke. However, the function of this activation is unclear. Here, we provide evidence that inhibition of the cell cycle regulator, Cdk4, and its activator, cyclinD1, plays critical roles in the delayed death component of ischemic/hypoxic stress by regulating the tumor suppressor retinoblastoma protein. In contrast, the excitotoxic component of ischemia/hypoxia is predominately regulated by Cdk5 and its activator p35, components of a cyclin-dependent kinase complex associated with neuronal development. Hence, our data both characterize the functional significance of the cell cycle Cdk4 and neuronal Cdk5 signals as well as define the pathways and circumstances by which they act to control ischemic/hypoxic damage.
Sepsis-associated encephalopathy: not just delirium (2011)

Sepsis is a major cause of mortality and morbidity in intensive care units. Organ dysfunction is triggered by inflammatory insults and tissue hypoperfusion. The brain plays a pivotal role in sepsis, acting as both a mediator of the immune response and a target for the pathologic process. The measurement of brain dysfunction is difficult because there are no specific biomarkers of neuronal injury, and bedside evaluation of cognitive performance is difficult in an intensive care unit. Although sepsis-associated encephalopathy was described decades ago, it has only recently been subjected to scientific scrutiny and is not yet completely understood. The pathophysiology of sepsis-associated encephalopathy involves direct cellular damage to the brain, mitochondrial and endothelial dysfunction and disturbances in neurotransmission. This review describes the most recent findings in the pathophysiology, diagnosis, and management of sepsis-associated encephalopathy and focuses on its many presentations.
Micromachined CMOS LNA and VCO by CMOS-compatible ICP deep trench technology (2006)

Selective removal of the silicon underneath the inductors in RF integrated circuits based on inductively coupled plasma (ICP) deep trench technology is demonstrated by a complementary metal-oxide-semiconductor (CMOS) 5-GHz low-noise amplifier (LNA) and a 4-GHz voltage-controlled oscillator (VCO). Design principles of a multistandard LNA with flat and low noise figures (NFs) within a specific frequency range are also presented. A 2-dB increase in peak gain (from 21 to 23 dB) and a 0.5-dB (from 2.28 to 1.78 dB) decrease in minimum NF are achieved in the LNA while a 3-dB suppression of phase noise is obtained in the VCO after the ICP backside dry etching. These results show that the CMOS-process-compatible backside ICP etching technique is very promising for system-on-a-chip applications.
The Polycomb-Group GeneEzh2 Is Required for Early Mouse Development (2001)

Polycomb-group (Pc-G) genes are required for the stable repression of the homeotic selector genes and other developmentally regulated genes, presumably through the modulation of chromatin domains. Among the Drosophila Pc-G genes, Enhancer of zeste [E(z)] merits special consideration since it represents one of the Pc-G genes most conserved through evolution. In addition, the E(Z) protein family contains the SET domain, which has recently been linked with histone methyltransferase (HMTase) activity. Although E(Z)-related proteins have not (yet) been directly associated with HMTase activity, mammalian Ezh2 is a member of a histone deacetylase complex. To investigate its in vivo function, we generated mice deficient for Ezh2. The Ezh2 null mutation results in lethality at early stages of mouse development. Ezh2 mutant mice either cease developing after implantation or initiate but fail to complete gastrulation. Moreover, Ezh2-deficient blastocysts display an impaired potential for outgrowth, preventing the establishment of Ezh2-null embryonic stem cells. Interestingly, Ezh2 is up-regulated upon fertilization and remains highly expressed at the preimplantation stages of mouse development. Together, these data suggest an essential role for Ezh2 during early mouse development and genetically link Ezh2 with eed and YY1, the only other early-acting Pc-G genes.