gebhart/patrepeval huggingface dataset:
The 630-kb lung cancer homozygous deletion region on human chromosome 3p21.3: identification and evaluation of the resident candidate tumor suppressor genes. The International Lung Cancer Chromosome 3p21.3 Tumor Suppressor Gene Consortium. (2000)

We used overlapping and nested homozygous deletions, contig building, genomic sequencing, and physical and transcript mapping to further define a approximately 630-kb lung cancer homozygous deletion region harboring one or more tumor suppressor genes (TSGs) on chromosome 3p21.3. This location was identified through somatic genetic mapping in tumors, cancer cell lines, and premalignant lesions of the lung and breast, including the discovery of several homozygous deletions. The combination of molecular manual methods and computational predictions permitted us to detect, isolate, characterize, and annotate a set of 25 genes that likely constitute the complete set of protein-coding genes residing in this approximately 630-kb sequence. A subset of 19 of these genes was found within the deleted overlap region of approximately 370-kb. This region was further subdivided by a nesting 200-kb breast cancer homozygous deletion into two gene sets: 8 genes lying in the proximal approximately 120-kb segment and 11 genes lying in the distal approximately 250-kb segment. These 19 genes were analyzed extensively by computational methods and were tested by manual methods for loss of expression and mutations in lung cancers to identify candidate TSGs from within this group. Four genes showed loss-of-expression or reduced mRNA levels in non-small cell lung cancer (CACNA2D2/alpha2delta-2, SEMA3B [formerly SEMA(V), BLU, and HYAL1] or small cell lung cancer (SEMA3B, BLU, and HYAL1) cell lines. We found six of the genes to have two or more amino acid sequence-altering mutations including BLU, NPRL2/Gene21, FUS1, HYAL1, FUS2, and SEMA3B. However, none of the 19 genes tested for mutation showed a frequent (>10%) mutation rate in lung cancer samples. This led us to exclude several of the genes in the region as classical tumor suppressors for sporadic lung cancer. On the other hand, the putative lung cancer TSG in this location may either be inactivated by tumor-acquired promoter hypermethylation or belong to the novel class of haploinsufficient genes that predispose to cancer in a hemizygous (+/-) state but do not show a second mutation in the remaining wild-type allele in the tumor. We discuss the data in the context of novel and classic cancer gene models as applied to lung carcinogenesis. Further functional testing of the critical genes by gene transfer and gene disruption strategies should permit the identification of the putative lung cancer TSG(s), LUCA, Analysis of the approximately 630-kb sequence also provides an opportunity to probe and understand the genomic structure, evolution, and functional organization of this relatively gene-rich region.
Synergistic Multiresidue Substitutions of a Macrocyclic c[Pro-Arg-Phe-Phe-Asn-Ala-Phe-dPro] Agouti-Related Protein (AGRP) Scaffold Yield Potent and >600-Fold MC4R versus MC3R Selective Melanocortin Receptor Antagonists (2018)

Antagonist ligands of the melanocortin-3 and -4 receptors (MC3R, MC4R), including agouti-related protein (AGRP), are postulated to be targets for the treatment of diseases of negative energy balance. Previous studies reported the macrocyclic MC3R/MC4R antagonist c[Pro<sup>1</sup>-Arg<sup>2</sup>-Phe<sup>3</sup>-Phe<sup>4</sup>-Asn<sup>5</sup>-Ala<sup>6</sup>-Phe<sup>7</sup>-dPro<sup>8</sup>], which is 250-fold less potent at the mouse (m) mMC3R and 3-fold less potent at the mMC4R than AGRP. Previous studies explored the structure-activity relationships around individual positions in this template. Herein, a multiresidue substitution strategy is utilized, combining the lead sequence with hPhe<sup>4</sup>, Dap<sup>5</sup>, Arg<sup>5</sup>, Ser<sup>6</sup>, and Nle<sup>7</sup> substitutions previously reported. Two compounds from this study (16, 20) contain an hPhe<sup>4</sup>/Ser<sup>6</sup>/Nle<sup>7</sup> substitution pattern, are 3-6-fold more potent than AGRP at the mMC4R and are 600-800-fold selective for the mMC4R over the mMC3R. Another lead compound (21), possessing the hPhe<sup>4</sup>/Arg<sup>5</sup> substitutions, is only 5-fold less potent than AGRP at the mMC3R and is equipotent to AGRP at the mMC4R.
The mechanical properties and solubility of strontium-substituted hydroxyapatite. (1991)

The mechanical properties and solubility of sintered Sr-substituted hydroxyapatites were examined in order to investigate the influences of Sr incorporation into hydroxyapatite in bones and teeth on them. Hydroxyapatite (HAp), Sr-substituted hydroxyapatite (Ca.SrAp), and strontium-hydroxyapatite (SrAp) were synthesized and sintered. The bending strength and Young's modulus were measured. Also, solubility in isotonic NaCl solution was examined. The Young's modulus of Sr-substituted hydroxyapatite (Sr wt% = 1.0) and hydroxyapatite surface treated with Sr ion were greater than that of hydroxyapatite. The bending strengths of Sr-substituted hydroxyapatites (Sr/Ca = 4/6 and less) were reduced slightly compared to that of hydroxyapatite. The bending strength of hydroxyapatite surface treated with Sr ion was increased compared to that of hydroxyapatite. The solubility in isotonic NaCl solution at 37 degrees C was increased with an increase in Sr content. The effects of Sr on the mechanical properties and solubility of bones and/or teeth are discussed.
Algorithm for computer control of a digital plotter (1965)

The algorithm can be programmed without the use of multiplication or division. It was found that 333 core locations were sufficient for an IBM 1401 program (used to control an IBM 1627). The average computation time between successive incrementations was approximately 1.5 milliseconds.
Preparation of p-type ZnMgO thin films by Sb doping method (2007)

We report on Sb-doped p-type Zn 0.95 Mg 0.05 O thin films grown by pulsed laser deposition. The Sb-doped Zn 0.95 Mg 0.05 O films show an acceptable p-type conductivity with a resistivity of 126 cm, a Hall mobility of 1.71 cm 2 V -1 s -1 and a hole concentration of 2.90 10 16 cm -3 at room temperature. Secondary ion mass spectroscopy confirms that Sb has been incorporated into the Zn 0.95 Mg 0.05 O films. Guided by x-ray photoemission spectroscopy analysis and a model for large-size-mismatched group-V dopants in ZnO, an Sb Zn -2V Zn complex is believed to be the most possible acceptor in the Sb-doped p-type Zn 0.95 Mg 0.05 O thin films.
A class of mild surfactants that keep integral membrane proteins water-soluble for functional studies and crystallization (2011)

Mixed protein-surfactant micelles are used for in vitro studies and 3D crystallization when solutions of pure, monodisperse integral membrane proteins are required. However, many membrane proteins undergo inactivation when transferred from the biomembrane into micelles of conventional surfactants with alkyl chains as hydrophobic moieties. Here we describe the development of surfactants with rigid, saturated or aromatic hydrocarbon groups as hydrophobic parts. Their stabilizing properties are demonstrated with three different integral membrane proteins. The temperature at which 50% of the binding sites for specific ligands are lost is used as a measure of stability and dodecyl-β-D-maltoside ('C12-b-M') as a reference for conventional surfactants. One surfactant increased the stability of two different G protein-coupled receptors and the human Patched protein receptor by approximately 10°C compared to C12-b-M. Another surfactant yielded the highest stabilization of the human Patched protein receptor compared to C12-b-M (13°C) but was inferior for the G protein-coupled receptors. In addition, one of the surfactants was successfully used to stabilize and crystallize the cytochrome b(6 )f complex from Chlamydomonas reinhardtii. The structure was solved to the same resolution as previously reported in C12-b-M.
Optical technologies for cervical neoplasia: update of an NCI program project grant. (2005)

Cervical cancer is the second most common cancer in women worldwide and the leading cause of cancer mortality in women in developing countries. In the United States, over $6 billion is spent annually in the evaluation and treatment of low-grade lesions, many of which do not develop into full-blown cancer. In developing countries, however, the chief concern is that cervical cancer goes undetected because of the cost of testing and the lack of resources and trained personnel to screen and diagnose the disease. The goal of the National Cancer Institute Program Project Grant CA82710 is to assess the emerging technologies of fluorescence and reflectance spectroscopy and quantitative cytology and histopathology for the diagnosis of cervical neoplasia. All of these technologies should decrease mortality, morbidity, and the cost of treating cervical cancer.
Absorption and Metabolic Effect of Inhaled Insulin (2002)

Comparable dosing reproducibility and shorter time to peak action of INH compared with SC suggest that INH delivered via the Aerodose Insulin Inhaler can provide reliable preprandial dosing of insulin in patients with type 2 diabetes.
Consumers enter the political stage? The modernization of health care in Britain and Germany (2007)

New governance practices associated with the modernization of health systems within Europe focus on equipping health consumers with more information and power in their interactions with clinicians. This article uses material on health care reform in Britain and Germany to highlight ways in which consumerism is refracted through different institutional histories and current political projects. These give rise to different inflections on the meaning of consumerism, including the different associations of `choice', and to different forms of consumer involvement as `stakeholders' in health care systems.
Discovery and Structure−Activity Relationship of 3-Aminopyrid-2-ones as Potent and Selective Interleukin-2 Inducible T-Cell Kinase (Itk) Inhibitors (2011)

Interleukin-2 inducible T-cell kinase (Itk) plays a role in T-cell functions, and its inhibition potentially represents an attractive intervention point to treat autoimmune and allergic diseases. Herein we describe the discovery of a series of potent and selective novel inhibitors of Itk. These inhibitors were identified by structure-based design, starting from a fragment generated de novo, the 3-aminopyrid-2-one motif. Functionalization of the 3-amino group enabled rapid enhancement of the inhibitory activity against Itk, while introduction of a substituted heteroaromatic ring in position 5 of the pyridone fragment was key to achieving optimal selectivity over related kinases. A careful analysis of the hydration patterns in the kinase active site was necessary to fully explain the observed selectivity profile. The best molecule prepared in this optimization campaign, 7v, inhibits Itk with a K(i) of 7 nM and has a good selectivity profile across kinases.
High-dimensional OLAP: a minimal cubing approach (2004)

Data cube has been playing an essential role in fast OLAP (online analytical processing) in many multi-dimensional data warehouses. However, there exist data sets in applications like bioinformatics, statistics, and text pro-cessing that are characterized by high dimen-sionality, e.g., over 100 dimensions, and mod-erate size, e.g., around 106 tuples. No feasible data cube can be constructed with such data sets. In this paper we will address the problem of developing an e±cient algorithm to perform OLAP on such data sets. Experience tells us that although data analy-sis tasks may involve a high dimensional space, most OLAP operations are performed only on a small number of dimensions at a time. Based on this observation, we propose a novel method that computes a thin layer of the data cube together with associated value-list indices. This layer, while being manageable in size, will be capable of supporting °exi-ble and fast OLAP operations in the original high dimensional space. Through experiments we will show that the method has I/O costs that scale nicely with dimensionality. Further-more, the costs are comparable to that of ac-cessing an existing data cube when full mate-rialization is possible. 1
A Survey of Web Information Extraction Systems (2006)

The Internet presents a huge amount of useful information which is usually formatted for its users, which makes it difficult to extract relevant data from various sources. Therefore, the availability of robust, flexible Information Extraction (IE) systems that transform the Web pages into program-friendly structures such as a relational database will become a great necessity. Although many approaches for data extraction from Web pages have been developed, there has been limited effort to compare such tools. Unfortunately, in only a few cases can the results generated by distinct tools be directly compared since the addressed extraction tasks are different. This paper surveys the major Web data extraction approaches and compares them in three dimensions: the task domain, the automation degree, and the techniques used. The criteria of the first dimension explain why an IE system fails to handle some Web sites of particular structures. The criteria of the second dimension classify IE systems based on the techniques used. The criteria of the third dimension measure the degree of automation for IE systems. We believe these criteria provide qualitatively measures to evaluate various IE approaches.
Mechanism of ultrasonic atomization using a multipinhole plate. (1985)

Modifying ink-jet techniques used for character displays, an atomizer with a multipinhole plate is trial-made. The pinhole plate with seven pinholes of 80μm in diameter is piezoelectrically driven at 34.4 kHz by a bimorph structure. Due to the intrinsic nature of the technique, important merits such as the uniform diameter of the atomized droplets, easiness of changing the diameter and of control of the atomizing rate may be expected. Employing the trial-made atomizer, the principle and physical properties of the ultrasonic atomization are experimentally studied. The displacement amplitude distribution of the plate, threshold pressure of atomization, phase of ejection, diameter and amount of droplets as a function of applied voltage are measured to make clear the physical properties of the technique. As a result of experiments, it is made clear that the surface tension of the liquid acts as a valve and that the atomizer has a self-acting liquid supply itself and does not need any pumping apparatus.
Vertebral bone mineral analysis: an integrated approach with CT. (1987)

In the assessment of vertebral bone mineral density (BMD) with quantitative computed tomography, accuracy is limited by systematic errors caused by beam-hardening effects and unknown marrow and fat concentrations in trabecular bone. Reproducibility depends on precise repositioning of the patient, selection of the region of interest (ROI), and apparatus stability. In an integrated approach, these error sources were taken into account. Dual-energy methods are incorporated and tested to avoid systematic errors. Contour-detection algorithms for automated ROI determination that work reliably and offer improved reproducibility and efficiency are presented. A new design of reference phantom with solid tissue-equivalent materials provides calibration in BMD units and checks apparatus stability. Dual-energy methods are necessary to achieve accuracy of 5% or better. Automated ROI definition and reference phantom methods are mandatory for reproducibility of 2% or better.
Artificial Liver (1992)

Without transplantation, approximately 90% of patients with fulminant hepatic failure die. If patients receive a liver transplant, there is often a lag between the need for and the availability of a donor liver. Therefore, there is a definite need for a liver support system to support the patient's own liver function in fulminant hepatic failure and while awaiting transplantation. We have developed an artificial liver system that not only eliminates lipophilic toxins such as phenols, fatty acids, and mercaptans, but also hydrophilic ones such as ammonia. This artificial liver system consists of a monitor, an extracorporeal blood circuit that uses a hydrophilic polysulfone high-flux dialyzer to remove water-soluble metabolites, and a novel hydrophilic liquid membrane filter to remove lipophilic toxins. In more than 100 in vitro experiments using porcine (5 I) blood, the system was evaluated for its ability to remove toxins that are normally increased in hepatic failure. We found that phenol, cresol, and short- and medium-chain fatty acids can be almost completely eliminated from the blood within 5 h. In animal experiments using pigs, we also found no significant changes of blood gases, liver parameters, electrolytes, and blood cell counts.
Microbiota in health and irritable bowel syndrome: current knowledge, perspectives and therapeutic options (2013)

The gastrointestinal tract is a natural reservoir of microbiota. The gut is germ-free at birth, but rapidly becomes host to various bacteria establishing a progressively mutual relationship. The composition of gut microbiota is individual-specific and depends on the genotype of the host and environmental factors. Novel techniques have been used to characterize gastrointestinal microbiota, including genomic approaches. The bacterial profile shows that dominant and minor phyla are present in the gastrointestinal tract. From the proximal to the distal segments of the gut the bacterial density gradually increases, reaching an estimated 10(11) to 10(12) bacteria per gram of colonic content. Dynamic interactions between gut and microbiota play a physiological role in metabolic, protective and structural functions, while dysbiosis contributes to several diseases. Microbiota appear to play a role in IBS, where qualitative and quantitative changes of bacteriaoccur in IBS subtypes. Initial therapeutic approaches in IBS have focused on microbiota. The relationship between perturbations of the microbiota, mucosal inflammation and IBS remains to be further investigated.
FGF-2 controls the differentiation of resident cardiac precursors into functional cardiomyocytes (2005)

Recent evidence suggests that the heart possesses a greater regeneration capacity than previously thought. In the present study, we isolated undifferentiated precursors from the cardiac nonmyocyte cell population of neonatal hearts, expanded them in culture, and induced them to differentiate into functional cardiomyocytes. These cardiac precursors appear to express stem cell antigen-1 and demonstrate characteristics of multipotent precursors of mesodermal origin. Following infusion into normal recipients, these cells home to the heart and participate in physiological and pathophysiological cardiac remodeling. Cardiogenic differentiation in vitro and in vivo depends on FGF-2. Interestingly, this factor does not control the number of precursors but regulates the differentiation process. These findings suggest that, besides its angiogenic actions, FGF-2 could be used in vivo to facilitate the mobilization and differentiation of resident cardiac precursors in the treatment of cardiac diseases.
Effects of sulfur dioxide on pore populations of canine tracheal epithelium (1986)

The bioelectric and barrier properties of the tracheal epithelium in nose-breathing dogs and in dogs that had been exposed for 75 min to compressed air or to two high concentrations of SO2 were measured and compared. We also studied tissues that had been treated with chloroform. Based on a model of restrictive diffusion we demonstrated heteropores (6 and 250 A) in the control tissues. Bioelectric changes due to 100-ppm SO2 were minimal. After exposure to 500 ppm SO2, adverse changes in the bioelectric properties were focal; they were marked in 8 out of 12 animals but were less striking in the other 4. Nonelectrolyte permeability increased with an increase in SO2 concentrations. Small pores were still present in the tissues severely affected by SO2 but they were absent in chloroform-treated tissues. Scanning electron microscopy of tissues from animals exposed to 500 ppm SO2 showed that in the same dog tissue appearance varied from normal to one of repair (normal bioelectric properties) or one of marked exfoliation of ciliated cells (abnormal bioelectric measurements).
Breadth-first ray tracing utilizing uniform spatial subdivision (1997)

Breadth-first ray tracing is based on the idea of exchanging the roles of rays and objects. For scenes with a large number of objects, it may be profitable to form a set of rays and compare each object in turn against this set. By doing so, thrashing, due to disk access, can be minimized. We present ways to combine breadth-first methods with traditional efficient algorithms, along with new schemes to minimize accessing objects stored on disk. Experimental analysis, including comparisons with depth-first ray tracing, shows that large databases can be handled efficiently with this approach.
Plasma mediated ablation of biological tissues with nanosecond-to-femtosecond laser pulses: relative role of linear and nonlinear absorption (1996)

Plasma mediated ablation of collagen gels and porcine cornea was studied at various laser pulse durations in the range of 1 ns-300 fs at 1053-nm wavelength. It was found that pulsed laser ablation of transparent and weakly absorbing gels is always mediated by plasma. On the other hand, ablation of strongly absorbing tissues is mediated by plasma in the ultrashort-pulse range only. Ablation threshold along with plasma optical breakdown threshold decreases with increasing tissue absorbance for subnanosecond pulses. In contrast, the ablation threshold was found to be practically independent of tissue linear absorption for femtosecond laser pulses. The mechanism of optical breakdown at the tissue surface was theoretically investigated. In the nanosecond range of laser pulse duration, optical breakdown proceeds via avalanche ionization initiated by heating of electrons contributed by strongly absorbing impurities at the tissue surface. In the ultrashortpulse range, optical breakdown is initiated by multiphoton ionization of the irradiated medium (six photons in case of tissue irradiated at 1053-nm wavelength), and is less sensitive to linear absorption. High-quality ablation craters with no thermal or mechanical damage to surrounding material were obtained with subpicosecond laser pulses. Experimental results suggest that subpicosecond plasma mediated ablation can be employed as a tool for precise laser microsurgery of various tissues.