gebhart/patrepeval huggingface dataset:
The role of surgery for patients with metastatic melanoma (2002)

When deciding to perform a resection for metastatic melanoma one should first decide whether the intent of the procedure is curative or palliative. When the resection is palliative, the success of surgical treatment will depend on the presence of identifiable symptoms, the morbidity of the procedure, the course of the disease, and the ability to communicate the treatment goals among surgeon, patient, and family. When the resection is curative, survival will depend on the ability of the surgeon to select patients with a pattern of recurrence suggestive of less aggressive tumor biology. Factors generally found predictive of improved survival, and therefore reflective of tumor biology, include longer disease-free interval, fewer numbers of metastases, and the ability to obtain a complete resection. Resection of metastases in patients who recur within one-year, who present with multiple lesions, and who present with disease that cannot be completely resected, will not result in long-term survival.
Copper,zinc superoxide dismutase is primarily a cytosolic protein in human cells. (1992)

The intracellular localization of human copper,zinc superoxide dismutase (Cu,Zn-SOD; superoxide:superoxide oxidoreductase, EC 1.15.1.1) was evaluated by using EM immunocytochemistry and both isolated human cell lines and human tissues. Eight monoclonal antibodies raised against either native or recombinant human Cu,Zn-SOD and two polyclonal antibodies raised against either native or recombinant human Cu,Zn-SOD were used. Fixation with 2% paraformaldehyde/0.2% glutaraldehyde was found necessary to preserve normal distribution of the protein. Monoclonal antibodies were less effective than polyclonal antibodies in recognizing the antigen after adequate fixation of tissue. Cu,Zn-SOD was found widely distributed in the cell cytosol and in the cell nucleus, consistent with it being a soluble cytosolic protein. Mitochondria and secretory compartments did not label for this protein. In human cells, peroxisomes showed a labeling density slightly less than that of cytoplasm.
Inhibition of experimental metastasis of murine Lewis lung carcinoma by an inhibitor of glucosylceramide synthase and its possible mechanism of action. (1990)

In view of the increasing evidence that glucosphingolipids (GSLs) on tumor cell surfaces play an important role in tumor metastasis, an inhibitor of glucosylceramide synthase, D-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol (D-PDMP) was used to evaluate the role of GSLs in this respect. Treatment of Lewis lung carcinoma cells with 5 microM D-PDMP resulted in a time-dependent marked decrease in levels of all cellular GSLs (glucosylceramide, lactosylceramide, ceramide trihexoside, globoside, and ganglioside GM3). By 6 days, the total GSL content was reduced to approximately 20% of the level in the untreated control cells and at the same time the lung-colonizing capacity of the PDMP-treated cells in inoculated mice was greatly reduced. Closely associated with the degree of GSL depletion, the ability of the cells to invade reconstituted basement membranes in vitro was also reduced, suggesting that GSLs in tumor cell membranes modulate the cell surface interaction with basement membrane components. In order to assess a possible contribution of the defective capacities to drug-induced suppression of experimental metastasis and invasion, we tested the effect of D-PDMP on attachment and migration to laminin and fibronectin and found that the inhibitor specifically reduced the laminin-mediated attachment and migration, whereas it had no effect on fibronectin-mediated attachment and migration. These effects of the inhibitor on lung colonizing capacity in vivo and the invasion, adhesion, and migration properties of the cells in vitro were reversible within 24 h after removal of the drug. By contrast, L-PDMP (the enantiomeric form of D-PDMP), which has no inhibitory activity on glucosylceramide synthesis, did not cause any of the changes produced by D-PDMP. Together, these results suggest that GSLs in tumor cell membranes are essential for the metastatic spread of tumor cells through basement membranes, modulating the interaction of laminin and its receptors.
Tandem reporter assay for myristoylated proteins post‐translationally (TRAMPP) identifies novel substrates for post‐translational myristoylation: PKC∊, a case study (2011)

Myristoylation, the addition of a 14-carbon fatty acid to the N-terminal glycine of a protein, is key to protein-membrane and protein-protein interactions. Typically, myristoylation occurs cotranslationally; however, post-translational myristoylation of caspase-cleaved proteins is now emerging as a well-established protein modification and as a novel regulator of apoptosis. To identify additional post-translationally myristoylated proteins, we engineered a plasmid vector encoding for a caspase-cleavable reporter protein named tandem reporter assay for myristoylation of proteins post-translationally (TRAMPP). pTRAMPP consists of tdTomato-DEVD-"test myristoylation sequence"-enhanced green fluorescent protein (EGFP). After induction of apoptosis, the reporter protein is cleaved by caspases, which frees a new N-terminal glycine residue attached to EGFP that can be myristoylated. We used pTRAMPP in appropriately transfected cells to identify 7 post-translationally myristoylated proteins. First, we confirmed the post-translational myristoylation of two previously identified putative substrates, cytoplasmic dynein intermediate chain 2A and PKCε (ctPKCε), and identified 5 more caspase-cleaved potential substrates for myristoylation that include the antiapoptotic regulator of apoptosis, Mcl-1, and the causative agent of Huntington's disease, huntingtin protein. Further investigation revealed that post-translationally myristoylated ctPKCε localized to membranes and increased Erk signaling and degradation of the proapoptotic protein Bim, which prevented a significant loss of mitochondrial potential of 17% over nonmyristoylated ctPKCε in HeLa cells in the presence of apoptotic stimuli. Taken together, these findings suggest a possible antiapoptotic role for post-translationally myristoylated caspase-cleaved ctPKCε.
Plasma Gelsolin and Circulating Actin Correlate with Hemodialysis Mortality (2009)

Plasma gelsolin (pGSN) binds actin and bioactive mediators to localize inflammation. Low pGSN correlates with adverse outcomes in acute injury, whereas administration of recombinant pGSN reduces mortality in experimental sepsis. We found that mean pGSN levels of 150 patients randomly selected from 10,044 starting chronic hemodialysis were 140 +/- 42 mg/L, 30 to 50% lower than levels reported for healthy individuals. In a larger sample, we performed a case-control analysis to evaluate the relationship of pGSN and circulating actin with mortality; pGSN levels were significantly lower in 114 patients who died within 1 yr of dialysis initiation than in 109 survivors (117 +/- 38 mg/L versus 147 +/- 42 mg/L, P < 0.001). pGSN levels had a graded, inverse relationship with 1-yr mortality, such that patients with pGSN < 130 mg/L experienced a > 3-fold risk for mortality compared with those with pGSN > or = 150 mg/L. The 69% of patients with detectable circulating actin had lower pGSN levels than those without (127 +/- 45 mg/L versus 141 +/- 36 mg/L, P = 0.026). Compared with patients who had elevated pGSN and no detectable actin, those with low pGSN levels and detectable actin had markedly increased mortality (odds ratio 9.8, 95% confidence interval 2.9 to 33.5). Worsening renal function correlated with pGSN decline in 53 subjects with CKD not on dialysis. In summary, low pGSN and detectable circulating actin identify chronic hemodialysis patients at highest risk for 1-yr mortality.
Multicolor quantum dots for molecular diagnostics of cancer (2006)

In the pursuit of sensitive and quantitative methods to detect and diagnose cancer, nanotechnology has been identified as a field of great promise. Semiconductor quantum dots are nanoparticles with intense, stable fluorescence, and could enable the detection of tens to hundreds of cancer biomarkers in blood assays, on cancer tissue biopsies, or as contrast agents for medical imaging. With the emergence of gene and protein profiling and microarray technology, high-throughput screening of biomarkers has generated databases of genomic and expression data for certain cancer types, and has identified new cancer-specific markers. Quantum dots have the potential to expand this in vitro analysis, and extend it to cellular, tissue and whole-body multiplexed cancer biomarker imaging.
Screening for known good die (KGD) based on defect clustering: an experimental study (2002)

Die screening based on the locality of defects has long been informally practised in the industry whereby dice from wafers, or parts of the wafer, that display high defect levels are discarded. More recently this approach has been refined such that test results for neighbouring dice on the wafer are also considered in evaluating test results for a particular die. It has been shown in principle, using negative binomial statistics for defect distributions on wafers, that such an approach can much better optimize test costs and screen for low defect levels in bare dice and packaged chips. In this paper we present, for the first time, experimental test data to demonstrate the effectiveness of this new approach. Our results are based on extensive testing of 4784 dice on 23 wafers from an IBM process. We show that bare die screening based on defect clustering considerations can significantly reduce defect levels in dice that pass wafer probe tests. This approach also has the potential to screen out burn-in failures. Thus it offers new low cost strategies for delivering high quality "known- good" die (KGD) for MCM applications.
Statistical Analysis of the Effects of Common Chemical Substituents on Ligand Potency (2008)

The results of a statistical analysis of more than 84,000 compounds from lead optimization programs against 30 different protein targets is presented, with a focus on the effects that different chemical substituents have on compound potency. It is observed that the potency changes induced by most chemical groups follows a nearly normal distribution centered near zero (i.e., no effect on potency). However, the widths of the distributions vary significantly between different substituents, and these effects cannot be rationalized by simple physicochemical parameters. In addition, certain substituents consistently bias the distribution toward higher or lower potency, suggesting the existence of preferred and nonpreferred chemical groups for lead optimization. The implications of these results for understanding protein-ligand recognition and for enhancing the efficiency and speed of lead optimization will be discussed.
What's up CAPTCHA? (2009)

We present a new CAPTCHA which is based on identifying an image's upright orientation. This task requires analysis of the often complex contents of an image, a task which humans usually perform well and machines generally do not. Given a large repository of images, such as those from a web search result, we use a suite of automated orientation detectors to prune those images that can be automatically set upright easily. We then apply a social feedback mechanism to verify that the remaining images have a human-recognizable upright orientation. The main advantages of our CAPTCHA technique over the traditional text recognition techniques are that it is language-independent, does not require text-entry (e.g. for a mobile device), and employs another domain for CAPTCHA generation beyond character obfuscation. This CAPTCHA lends itself to rapid implementation and has an almost limitless supply of images. We conducted extensive experiments to measure the viability of this technique.
Oral immunization with PspA elicits protective humoral immunity against Streptococcus pneumoniae infection (1997)

Streptococcus pneumoniae is a major respiratory mucosal pathogen affecting infants and children. Although a polysaccharide-based vaccine has been useful in adult populations, it does not elicit protective immunity in infants and young children. Pneumococcal surface protein A (PspA) is a highly immunogenic surface protein produced by all strains of Streptococcus pneumoniae. Previous studies have shown that systemic immunization of mice with PspA can elicit protective immunity against fatal pneumococcal infection. In this study, we demonstrated that oral immunization with PspA could elicit protective immune responses against pneumococcal infection. When mice were orally immunized with PspA alone, low levels of PspA-specific immunoglobulin G (IgG) responses were induced in serum; none was induced in secretion. On the other hand, when PspA was given orally with the mucosal adjuvant cholera toxin (CT), significant levels of IgG and IgA anti-PspA responses were induced in serum. The major IgG subclass was IgG1, followed by IgG2b, a profile of antibody response supported by Th2-type cells. In addition, all mice orally immunized with PspA and CT were protected from the lethal challenge with capsular serotype 3 S. pneumoniae A66. These results suggested that an oral PspA vaccine may be a useful means of preventing pneumococcal disease.
A modal approach to hyper-redundant manipulator kinematics (1994)

This paper presents novel and efficient kinematic modeling techniques for "hyper-redundant" robots. This approach is based on a "backbone curve" that captures the robot's macroscopic geometric features. The inverse kinematic, or "hyper-redundancy resolution," problem reduces to determining the time varying backbone curve behavior. To efficiently solve the inverse kinematics problem, the authors introduce a "modal" approach, in which a set of intrinsic backbone curve shape functions are restricted to a modal form. The singularities of the modal approach, modal non-degeneracy conditions, and modal switching are considered. For discretely segmented morphologies, the authors introduce "fitting" algorithms that determine the actuator displacements that cause the discrete manipulator to adhere to the backbone curve. These techniques are demonstrated with planar and spatial mechanism examples. They have also been implemented on a 30 degree-of-freedom robot prototype.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Ion Channels in Microbes (2008)

Studies of ion channels have for long been dominated by the animalcentric, if not anthropocentric, view of physiology. The structures and activities of ion channels had, however, evolved long before the appearance of complex multicellular organisms on earth. The diversity of ion channels existing in cellular membranes of prokaryotes is a good example. Although at first it may appear as a paradox that most of what we know about the structure of eukaryotic ion channels is based on the structure of bacterial channels, this should not be surprising given the evolutionary relatedness of all living organisms and suitability of microbial cells for structural studies of biological macromolecules in a laboratory environment. Genome sequences of the human as well as various microbial, plant, and animal organisms unambiguously established the evolutionary links, whereas crystallographic studies of the structures of major types of ion channels published over the last decade clearly demonstrated the advantage of using microbes as experimental organisms. The purpose of this review is not only to provide an account of acquired knowledge on microbial ion channels but also to show that the study of microbes and their ion channels may also hold a key to solving unresolved molecular mysteries in the future.
Predicting Fluid Responsiveness by Passive Leg Raising (2016)

Passive leg raising retains a high diagnostic performance in various clinical settings and patient groups. The predictive value of a change in pulse pressure on passive leg raising is inferior to a passive leg raising-induced change in a flow variable.
Testing the statistical similarity of discrete observations using Dirichlet priors (2002)

In this paper the combined Bayes test, which uses a Dirichlet (noninformative) prior, is used to determine if the underlying statistics of two data populations are the same. Results demonstrate that the combined Bayes test performs better than the more conventional Kolmogorov-Smirnov test.
Wide field fluorescence imaging in narrow passageways using scanning fiber endoscope technology (2010)

An ultrathin scanning fiber endoscope (SFE) has been developed for high resolution imaging of regions in the body that are commonly inaccessible. The SFE produces 500 line color images at 30 <i>Hz</i> frame rate while maintaining a 1.2-1.7 <i>mm</i> outer diameter. The distal tip of the SFE houses a 9 mm rigid scan engine attached to a highly flexible tether (minimum bend radius &lt; 8 <i>mm</i>) comprised of optical fibers and electrical wires within a protective sheath. Unlike other ultrathin technologies, the unique characteristics of this system have allowed the SFE to navigate narrow passages without sacrificing image quality. To date, the SFE has been used for <i>in vivo</i> imaging of the bile duct, esophagus and peripheral airways. In this study, the standard SFE operation was tailored to capture wide field fluorescence images and spectra. Green (523 <i>nm</i>) and blue (440 <i>nm</i>) lasers were used as illumination sources, while the white balance gain values were adjusted to accentuate red fluorescence signal. To demonstrate wide field fluorescence imaging of small lumens, the SFE was inserted into a phantom model of a human pancreatobiliary tract and navigated to a custom fluorescent target. Both wide field fluorescence and standard color images of the target were captured to demonstrate multimodal imaging.
Development of small-sized 3 DOF finger module in micro hand for micro manipulation (2003)

A dexterous micro manipulation system was developed for applications such as assembling micro machines, manipulating cells, and micro surgery. We have proposed a concept of a two-fingered microhand, and designed and built a prototype. We succeeded in performing basic micro manipulations, including the grasp, release, and rotation of a microscopic object. The two-fingered micro hand prototype should be more miniaturized for higher accuracy and combination in small chamber of SEM. In this paper, we will propose a small-sized 3-DOF finger module with a parallel mechanism. An optimized link mechanism for miniaturization is used to the finger module. A photo fabrication system is used to fabrication of the finger module. Basic experiment shows excellent micro capability.
Increase in S-adenosylhomocysteine concentration in interferon-treated HeLa cells and inhibition of methylation of vesicular stomatitis virus mRNA. (1983)

A fraction of the viral mRNA synthesized in interferon-treated HeLa cells infected with vesicular stomatitis virus (VSV) lacks the 7-methyl group in the 5'-terminal guanosine of the cap; this mRNA is not associated with polyribosomes and does not bind to ribosomes in an assay for initiation of protein synthesis (de Ferra, F., and Baglioni, C. (1981) Virology 112, 426-435). To establish whether this defect in methylation is due to changes in the level of the methyl donor S-adenosylmethionine (AdoMet) and of its competitive inhibitor S-adenosylhomocysteine (AdoHcy), we measured the concentration of these compounds in HeLa cells treated with interferon. An increase in both AdoMet and AdoHcy was detected 3 to 6 h after addition of interferon. The level of these compounds increased gradually and in proportion to the interferon concentration used. With 125 reference units/ml of beta interferon, for example, the AdoHcy concentration increased more than 3-fold and that of AdoMet about 1.5-fold with a consequent change in the AdoHcy/AdoMet ratio. An increased AdoHcy/AdoMet ratio was also found in HeLa cells treated with pure alpha 2 interferon produced in Escherichia coli by recombinant DNA techniques. When the methylation of VSV mRNA was measured in assays carried out with permeabilized virions at the AdoHcy and AdoMet concentrations found in interferon-treated cells, a preferential inhibition of the viral (guanine-7-)methyltransferase activity was observed. Such an inhibition may account for the synthesis of VSV mRNA lacking the 7-methyl group of guanosine in the cap.
[Clinical problems of optimum bioavailability, in particular in cytostatic therapy (author's transl)]. (1976)

The clinical application of cytostatic drugs requires knowledge of their biochemistry, pharmacology, pharmacokinetics as well as their action at the cellular level within the generation cycle. The principles apply to tumor cells as well as to normal, rapidly proliferating tissues. The intensive research on cancer treatment all over the world is leading to a rapid accumulation of experimental data about the action of single cytostatic drugs in tissue culture and on transplantable animal tumor systems, especially in rodents. Clinical chemotherapy in human malignancies today preferentially uses combinations of different cytostatics. Inumerable combinations of drugs are available, especially if variations in respect to drug dose and intervals of drug application are taken into consideration. The experimental basis for such combinations of drugs and drug interactions is scanty. Using the pyrimidine analog cytosine arabinoside and the two antibiotics daunorubicin and doxyrubicin (adriamycin) as examples, it is demonstrated that information on the pharmacolinetic behaviour of cytostatic drugs is a prerequisite for their success in clinical application, but is on its own insufficient to predict the tumor response.
Semantics-driven portrait cartoon stylization (2010)

This paper proposes an efficient framework for transforming an input human portrait image into an artistic cartoon style. Compared to the previous work of non-photorealistic rendering (NPR), our method exploits the portrait semantics for enriching and manipulating the cartooning style, based on a semantic grammar model. The proposed framework consists of two phases: a portrait parsing phase to localize and recognize facial components in a hierarchic manner, and further calculate the portrait saliency with the facial components; a cartoon stylizing phase to abstract and cartoonize the portrait according to the parsed semantics and saliency, in which the regions and structure (edges/boundaries) of the portrait are rendered in two layers. In the experiments, we test our method with different types of human portraits: daily photos, identification photos, and studio photos, and find satisfactory results; a quantitative evaluation of subjective preference is presented as well.
Maneuver-based motion planning for nonlinear systems with symmetries (2005)

In this paper, we introduce an approach for the efficient solution of motion-planning problems for time-invariant dynamical control systems with symmetries, such as mobile robots and autonomous vehicles, under a variety of differential and algebraic constraints on the state and on the control inputs. Motion plans are described as the concatenation of a number of well-defined motion primitives, selected from a finite library. Rules for the concatenation of primitives are given in the form of a regular language, defined through a finite-state machine called a Maneuver Automaton. We analyze the reachability properties of the language, and present algorithms for the solution of a class of motion-planning problems. In particular, it is shown that the solution of steering problems for nonlinear dynamical systems with symmetries and invariant constraints can be reduced to the solution of a sequence of kinematic inversion problems. A detailed example of the application of the proposed approach to motion planning for a small aerobatic helicopter is presented.