gebhart/patrepeval huggingface dataset:
Highly Selective Glycosylated Prodrugs of Cytostatic CC-1065 Analogues for Antibody-Directed Enzyme Tumor Therapy (2001)

Novel prodrugs of the cytotoxic antibiotic CC-1065 for an antibody-directed enzyme prodrug therapy (ADEPT) were prepared that show an excellent selectivity with a high toxicity of the corresponding drug. In particular, the seco-CBI analogue of CC-1065, 1-chloromethyl-5-hydroxy-1,2-dihydro-3H-benz[e]indole, as well as the novel methyl-seco-CBI analogue 1-(1'-chloroethyl)-5-hydroxy-1,2-dihydro-3H-benz[e]indole, were synthesized and transformed into their galactosides 10 a and 10 b, respectively. These galactosides can be cleaved with beta-D-galactosidase to give the free cytotoxic compounds. They were tested in in vitro cytotoxicity assays by using human bronchial carcinoma cells of line A549 in the presence and in the absence of beta-D-galactosidase. While the seco-CBI prodrugs revealed only modest selectivity, prodrugs of the methyl-seco-CBI analogue bearing an anti orientation of the substituents at the two stereogenic centers of the N-heterocycle displayed an excellent selectivity with an ED(50) quotient of about 750. The cytotoxicity of the corresponding phenol was rather high, with an ED(50) of 1.3 nM. The diastereomer with a syn orientation at the stereogenic centers was much less toxic.
Toward cost-sensitive modeling for intrusion detection and response (2002)

Intrusion detection systems (IDSs) must maximize the realization of security goals while minimizing costs. In this paper, we study the problem of building cost-sensitive intrusion detection models. We examine the major cost factors associated with an IDS, which include development cost, operational cost, damage cost due to successful intrusions, and the cost of manual and automated response to intrusions. These cost factors can be qualified according to a defined attack taxonomy and site-specific security policies and priorities. We define cost models to formulate the total expected cost of an IDS, and present cost-sensitive machine learning techniques that can produce detection models that are optimized for user-defined cost metrics. Empirical experiments show that our cost-sensitive modeling and deployment techniques are effective in reducing the overall cost of intrusion detection.
Carriage of Mycoplasma pneumoniae in the Upper Respiratory Tract of Symptomatic and Asymptomatic Children: An Observational Study (2013)

Although our study has limitations, such as a single study site and limited sample size, our data indicate that the presence of M. pneumoniae in the URT is common in asymptomatic children. The current diagnostic tests for M. pneumoniae are unable to differentiate between asymptomatic carriage and symptomatic infection.
Queue locks on cache coherent multiprocessors (2002)

Large-scale shared-memory multiprocessors typically have long latencies for remote data accesses. A key issue for execution performance of many common applications is the synchronization cost. The communication scalability of synchronization has been improved by the introduction of queue-based spin-locks instead of Test&(Test&Set). For architectures with long access latencies for global data, attention should also be paid to the number of global accesses that are involved in synchronization. We present a method to characterize the performance of proposed queue lock algorithms, and apply it to previously published algorithms. We also present two new queue locks, the LH lock and the M lock. We compare the locks in terms of performance, memory requirements, code size and required hardware support. The LH lock is the simplest of all the locks, yet requires only an atomic swap operation. The M lock is superior in terms of global accesses needed to perform synchronization and still competitive in all other criteria. We conclude that the M lock is the best overall queue lock for the class of architectures studied.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Antitachyphylactic effects of progesterone and oxytocin on term human myometrial contractile activity in vitro. (1993)

Progesterone stimulated the frequency of contractions and tonus of strips from the lower uterine segment of term human myometrium. A lasting increase in the frequency of contractions was observed with superfusion of progesterone plus oxytocin, suggesting that progesterone counteracted the reaction of tachyphylaxis to oxytocin.
A highly sensitive strategy for SCID-repopulating cell assay by direct injection of primitive human hematopoietic cells into NOD/SCID mice bone marrow (2003)

To measure the ability of human hematopoietic stem cells (HSCs), the SCID-repopulating cell (SRC) assay has been widely used. Conventionally, human HSCs are transplanted into a nonobese diabetic/severe combined immunodeficient (NOD/SCID) mouse via a tail vein. However, those cells must go through various obstacles until they reach the mouse marrow environment, which could explain the generally low homing efficiency in this system. Thus, the capability of HSCs may not be studied accurately by this intravenous transplantation method. In our attempt to reveal actual SRC potential, ie, self-renewal and multilineage differentiation in recipient bone marrow, we introduced cells into mouse marrow directly (intrabone marrow [iBM]) to minimize the effect of factors that may interfere with the homing of HSCs and compared the results obtained by intravenous and iBM methods. When cord blood CD34(+)CD38(-) cells were transplanted in NOD/SCID mice by iBM, a 15-fold higher frequency of SRC, 1 in 44 CD34(+)CD38(-) cells, was achieved compared with 1 in 660 by the intravenous method. Furthermore, the iBM transplant showed high levels of engraftment in the secondary transplantation. Pretreatment of CD34(+) cells with antibodies that block either very late antigen 4 (VLA-4) or VLA-5 reduced engraftment partially, whereas blockage of both molecules resulted in complete inhibition of engraftment, which suggests that VLA-4 and VLA-5 are involved in different processes in engraftment or have complementary roles. Our results indicate that the iBM injection strategy is a more sensitive and direct way to measure the capability of human SRCs and is useful to investigate the interaction of HSCs and marrow environment in vivo.
The fabrication of thin-film bulk acoustic wave resonators employing a ZnO/Si composite diaphragm structure using porous silicon layer etching (1999)

Thin-film bulk acoustic wave resonators (FBARs) are used in monolithic microwave integrated circuits (MMICs) for semiconductor devices. FBARs are more attractive than surface acoustic wave resonators since they have the advantages of small size, low cost, and mass-production ability. An FBAR with an air gap is fabricated by a surface micromachining technique which utilizes porous silicon layer (PSL) etching. This FBAR has a forward reflection coefficient of -18.912 dB when the thickness of the ZnO thin film measures 1 μm. The FBAR is composed of a piezoelectric zinc oxide (ZnO) thin film and top and bottom electrode thin films of Au(1000 /spl Aring/)/Ni-Cr(50 /spl Aring/). The ZnO thin film is deposited by RF magnetron sputtering. This fabrication process is compatible with conventional IC processes, thereby enabling the development of monolithic-integrated FBAR's on Si or GaAs substrates.
The Wisconsin Epidemiologic Study of Diabetic Retinopathy (1989)

The four-year incidence and progression of retinopathy were investigated in a population-based sample of people with diabetes diagnosed at 30 years of age or older. For insulin users, 73 (47%) of the 154 who did not have any retinopathy at the first visit developed it in the four-year interval, and 31 (7%) of the 418 free of proliferative retinopathy developed it. Worsening of retinopathy occurred in a total of 34% (142/418). For nonusers of insulin, corresponding rates were 34% (110/320) for incidence of any retinopathy, 2% (11/486) for developing proliferative retinopathy, and 25% (121/486) for worsening. These population-based data clearly indicate the risk of retinopathy worsening in a short interval (four years) in a large proportion of people with older-onset diabetes, a group previously thought to be relatively protected from retinopathy. Such patients who make up the largest proportion of diabetic patients in the United States need examination when diabetes is first diagnosed and regular follow-up.
Persistent Structural Modifications in Nucleus Accumbens and Prefrontal Cortex Neurons Produced by Previous Experience with Amphetamine (1997)

Experience-dependent changes in behavior are thought to involve structural modifications in the nervous system, especially alterations in patterns of synaptic connectivity. Repeated experience with drugs of abuse can result in very long-lasting changes in behavior, including a persistent hypersensitivity (sensitization) to their psychomotor activating and rewarding effects. It was hypothesized, therefore, that repeated treatment with the psychomotor stimulant drug amphetamine, which produces robust sensitization, would produce structural adaptations in brain regions that mediate its psychomotor activating and rewarding effects. Consistent with this hypothesis, it was found that amphetamine treatment altered the morphology of neurons in the nucleus accumbens and prefrontal cortex. Exposure to amphetamine produced a long-lasting (>1 month) increase in the length of dendrites, in the density of dendritic spines, and in the number of branched spines on the major output cells of the nucleus accumbens, the medium spiny neurons, as indicated by analysis of Golgi-stained material. Amphetamine treatment produced similar effects on the apical (but not basilar) dendrites of layer III pyramidal neurons in the prefrontal cortex. The ability of amphetamine to alter patterns of synaptic connectivity in these structures may contribute to some of the long-term behavioral consequences of repeated amphetamine use, including amphetamine psychosis and addiction.
Total Synthesis of Escherichia coli Lipid A, the Endotoxically Active Principle of Cell-Surface Lipopolysaccharide (1987)

Abstract Chemical syntheses are described of polyacylated β(1→6) glucosamine disaccharide 1,4′-bis(phosphate), which corresponds to the proposed structure of E. coli lipid A, and of its dephospho derivatives. The synthetic bisphosphate proved to be identical with the corresponding natural specimen. The chemical structure of lipid A was thus established.
Profiling receptor tyrosine kinase activation by using Ab microarrays (2003)

Signal transduction in mammalian cells is mediated by complex networks of interacting proteins. Understanding these networks at a circuit level requires devices to measure the amounts and activities of multiple proteins in a rapid and accurate manner. Ab microarrays have previously been applied to the quantification of labeled recombinant proteins and proteins in serum. The development of methods to analyze intracellular signaling molecules on microarrays would make Ab arrays widely useful in systems biology. Here we describe the fabrication of multiplex Ab arrays sensitive to the amounts and modification states of signal transduction proteins in crude cell lysates and the integration of these arrays with 96-well microtiter plate technology to create microarrays in microplates. We apply the Ab arrays to monitoring the activation, uptake, and signaling of ErbB receptor tyrosine kinases in human tumor cell lines. Data obtained from multicolor ratiometric microarrays correlate well with data obtained by using traditional approaches, but the arrays are faster and simpler to use. The integration of microplate and microarray methods for crude cell lysates should make it possible to identify and analyze small molecule inhibitors of signal transduction processes with unprecedented speed and precision. We demonstrate the future potential of this approach by characterizing the action of the epidermal growth factor receptor inhibitor PD153035 on cells by using Ab arrays; direct scale-up to array-based screening in 96- and 384-well plates should allow small molecules to be identified with specific inhibitory profiles against a signaling network.
Studies on the Reduction and Re-formation of Protein Disulfide Bonds (1961)

The information contained in the amino acid sequence of a protein is linear, such as it is in DNA, but proteins function by
 virtue of the arrangement of their linear structure into a well-defined three-dimensional conformation. In this article,
 Anfinsen and Haber sought to determine how the two-dimensional data of DNA were translated into the three-dimensional information
 that was characteristic of globular proteins. This simple and elegant experiment was designed to determine what would happen
 when reduced, unfolded, and enzymatically inactive ribonuclease was allowed simply to refold in the presence of only neutral
 aqueous buffer and air. They found that most of the activity of the enzyme was regained.
HBT Modeling (2008)

III-V heterojunction bipolar transistors (HBTs) enjoy several advantages over their conventional silicon cousins. These include: (1) a thinner base and lower base resistance which yields higher gain and f <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">max</sub> ; (2) high breakdown voltage; (3) low parasitics; (4) high power density. The combination of a thin base (higher f <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">T</sub> ), low base resistance (higher f <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">max</sub> ), and low parasitics in particular make HBTs a suitable choice for high- frequency applications.
Polymorphisms in the hANP (Human Atrial Natriuretic Peptide) Gene, Albuminuria, and Hypertension (2001)

Atrial natriuretic peptide (ANP) jointly affects kidney function and blood pressure homeostasis and is a candidate susceptibility gene for both essential hypertension and kidney disease. We evaluated the relation between the ScaI and BstXI polymorphisms of the human ANP (hANP) gene, hypertension, and albuminuria in a clinical cohort of 1033 subjects, including type 1 and type 2 diabetic patients, nondiabetic subjects with essential hypertension, and nondiabetic normotensive control subjects. Microalbuminuria was present in 15%, 29%, and 2%, respectively, of type 1 diabetic, type 2 diabetic, and nondiabetic patients. Macroalbuminuria was present in 9% of type 1 diabetics, 21% of type 2 diabetics, and 31% of nondiabetics. Prevalence of hypertension was 31%, 58%, and 61% in normoalbuminuric, microalbuminuric, and macroalbuminuric subjects, respectively (P<0.0001). Genotype distributions were in Hardy-Weinberg equilibrium in all 4 patient subgroups. The frequency of the ScaI mutated allele (A(1)) was significantly lower in hypertensive than in control subjects (11% versus 19%, P=0.018) and in patients with macroalbuminuria (5%) as compared with normoalbuminuric subjects (16%; P<0.0001). In a nominal logistic model adjusting for gender, age, obesity, diabetes, micro/macroalbuminuria, and hypertension, the A(1) allele was independently associated with macroalbuminuria (odds ratio, 0.57; confidence interval, 1.39 to 3.59; P=0.003) but not with hypertension. In the same model, the frequency of the BstXI mutated allele (T(708)) was increased in the presence of microalbuminuria (odds ratio, 2.25; confidence interval, 1.39 to 3.59; P<0.001). We conclude that the mutated genotypes of the ScaI polymorphism are negatively associated with overt nephropathy, whereas the mutated genotypes of BstXI polymorphism are positively associated with microalbuminuria. hANP gene variants may exert a protective effect against the development and progression of kidney damage in diabetes.
That-clauses in NP (1995)

The aim of this paper is to discuss aspects of the grammar of the (non-relative) that-clauses which follow head nouns. Specifically, two aspects will be discussed here. The first has to do with the different types of expansions of head nouns wich can appear under the form of (non-relative) that- clauses. The second concerns the nature of the evidence for positing distinct types of that-clauses in NP structure. In essence, this paper focuses on the complement/modifier divide, as this applies to that-clauses in NP. Central to this discussion will be our attempt to sustain the thesis that that-clause complements to nouns do not exist.
Pathology of the Gaucher cell. (1982)

The Gaucher cell results from the accumulation of excessive glucocerebroside in cells of the monocyte-macrophage system. It is characterized ultrastructurally by the presence of cytoplasmic inclusions which consist of tubule-like structures measuring 130 to 150 Ao in diameter. Utilizing freeze fracture and x-ray diffraction techniques these structures appear to be bilayers measuring 6 nm in thickness, 40 to 60 nm wide and up to 600 nm in length. The Gaucher cell contains isoenzyme 5 of acid phosphatase which is resistant to prior incubation in tartaric acid. The bone marrow smears from patients with Gaucher's disease contain monocytes and monocytoid cells which contain inclusions which are acid phosphatase positive and resemble the acid phosphatase positive inclusions in the Gaucher cells. Ultrastructural studies of monocytes from Gaucher patients demonstrated membrane-bound inclusions containing tubule-like structures identical to those in Gaucher cells. These monocytic cells appear to represent precursors of Gaucher cells.
EphA2 receptor tyrosine kinase regulates endothelial cell migration and vascular assembly through phosphoinositide 3-kinase-mediated Rac1 GTPase activation (2004)

Angiogenesis is critical for vascular remodeling during development and contributes to the pathogenesis of diseases such as cancer. Targeted disruption of several EphB class receptor tyrosine kinases results in vascular remodeling defects during embryogenesis. The role of EphA class receptors in vascular remodeling, however, is not well-characterized. We recently demonstrated that global inhibition of EphA receptors disrupts endothelial migration induced by ephrin, VEGF or tumor-derived signals, though the specific target remained undefined. Here, we report that EphA2 regulates endothelial cell assembly and migration through phosphoinositide (PI) 3-kinase-mediated activation of Rac1 GTPase in two model systems: primary bovine and murine pulmonary microvascular endothelial cells. EphA2-deficient endothelial cells fail to undergo vascular assembly and migration in response to ephrin-A1 in vitro. Ephrin-A1 stimulation induces PI3-kinase-dependent activation of Rac1 in wild-type endothelial cells, whereas EphA2-deficient cells fail to activate Rac1 upon stimulation. Expression of dominant negative PI3-kinase or Rac1 inhibits ephrin-A1-induced endothelial cell migration. Consistent with in vitro data, EphA2-deficient mice show a diminished angiogenic response to ephrin-A1 in vivo. Moreover, EphA2-deficient endothelial cells fail to assemble in vivo when transplanted into recipient mice. These data suggest that EphA2 is an essential regulator of post-natal angiogenesis.
Visualization of the Stomach's Arterial Networks During Esophageal Surgery Using the HyperEye Medical System. (2015)

The HEMS-LMM is safe and feasible for visualizing the blood supply border of the right gastroepiploic artery and the ANS before GT creation during esophageal surgery, and it might reduce leakage in esophageal surgery.
Efficiency and sensitivity of techniques for recovering nematode eggs from bovine feces. (1981)

Haemonchus contortus eggs were extracted from sheep feces and known numbers were added to helminthologically sterile bovine feces to provide samples with seven, 30 and 60 eggs per gram (epg). At 60 epg, dilution techniques (modified Cornell-McMaster and modified McMaster) tended to overestimate the number of eggs and more eggs were recovered (mean of 121 and 88% respectively) with these techniques than with centrifugal concentration procedures (modified Cornell—63% and Wisconsin— 69%). At 30 epg, all techniques were comparable (modified Cornell-McMaster 67%, modified McMaster 63%, modified Cornell and Wisconsin 64%). At 7 epg, the Wisconsin (61%), modified Cornell (60%) and Cornell-McMaster (94%) techniques were comparable and better than the modified McMaster technique (16%). At all levels of epg, the modified Cornell and Wisconsin techniques recovered eggs from 100% of the samples. The Cornell-McMaster and modified McMaster techniques recovered eggs from 90 and 100% of samples at 60 epg; 40 and 100% at 30 epg; and 21 and 11% at 7 epg. With a gravitational concentration procedure, the Standard Vial, no more than 16% of the eggs at any level of epg were recovered and at 7 epg eggs were recovered from only one-half of the samples. Five gravitational concentration techniques were assessed over 66 to 490 epg. The Ovassay, Fecalyzer and modified Standard Vial techniques were comparable in efficiency (28%, 25% and 24% respectively), but the Standard Vial technique was less efficient (11%).
Abnormal gene expression in skin fibroblasts from a Hutchinson-Gilford patient. (1991)

We had the opportunity to investigate a new case of Hutchinson-Gilford progeria, a rare disease commonly regarded as a model in the study of aging. Two strains of fibroblasts (strains 1 and 2) were derived from two pieces of a skin biopsy. These two populations multiplied as normal cells at low population doubling level but senesced rapidly and stopped proliferating after 14 or 15 population doubling levels. Interestingly, an unusual pattern of growth in clusters was observed for strain 1. The level of collagen and noncollagen protein synthesis of both strains of affected fibroblasts was similar to that of normal fibroblasts as determined by [3H]proline incorporation measurement and was similarly affected by varying serum concentrations. The pattern of the main types of newly synthesized collagen polypeptides analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis was similar in normal and progeria cells. The steady-state level of mRNAs coding for macromolecules of the extracellular matrix did not provide any differences between affected and control fibroblasts except for a strong increase of elastin and of alpha 1 and alpha 2 type IV procollagen mRNA mainly in strain 1 and less marked in strain 2. Interestingly, senescent progeria fibroblasts exhibited a reduced level of all the tested mRNAs, whereas collagen type IV and elastin mRNAs remained elevated. As suggested by immunofluorescence and immunoblotting studies, the increased amount of type IV mRNAs was paralleled by an enhanced production of type IV collagen by fibroblasts in vitro. Histologic examination of the skin revealed a superabundant network of abnormal elastic fibers in the reticular dermis and a thickening of basement membranes. The relationship between these alterations and aging in progeria is discussed.