gebhart/patrepeval huggingface dataset:
Face validity study of the ProMIS augmented reality laparoscopic suturing simulator. (2008)

To prevent unnecessary mistakes and avoidable complications in laparoscopic surgery, there has to be proper training. A safe way to train surgeons for laparoscopy is simulation. This study addresses the face validity of ProMIS, an Augmented Reality laparoscopic simulator, as a tool for training suturing skills in laparoscopic surgery. A two-paged, 12-item structured questionnaire, using a five-point-Likert scale, was presented to 50 surgeons/surgical interns. The participants were allotted to two groups: an "expert" (>50 procedures; N=23) and a referent group (<50 procedures; N=27). Non-parametric statistics were used to determine statistical differences. General consensus existed in both expert and referent groups, delineating ProMIS as a useful tool in teaching suturing skills surgeons/surgical interns (mean + or - st dev, resp, score 4.91 + or - 0.42 and 4.93 + or - 0.38) with regard to realism, tactile feedback, and suturing techniques. Significant differences in opinion regarding the ergonomics and design of ProMIS between the expert and referent groups existed. The ProMIS Augmented Reality laparoscopic simulator is regarded as a useful tool in laparoscopic training in both expert and referent groups. Although significant differences in opinion existed with regards to ergonomics and design of ProMIS, they were present between experts and novices.
Current Treatment of Retinal Vein Occlusion (2011)

Retinal vein occlusion (RVO) was first described more than 150 years ago. Even though much has been written about this frequent condition, the aetiopathology appears to be multifactorial with many unclear aspects and varied expression, making it difficult to define treatment guidelines. The management of the patient with RVO is complex and a multidisciplinary approach is required in order to identify and correct the associated risk factors. In the past, laser therapy was the gold standard in RVO, but only modest functional improvement has been shown in branch retinal occlusion forms. Current multicentre studies of intravitreal drugs present them as an option to combine with laser. Anti-vascular endothelial growth factor, corticosteroids and sustained-release implants are attractive options to halt disease progression and achieve a better visual outcome. Consequently, it is useful to clarify some aspects of the pathology that allow better patient management.
Stimulation of CD8+T Cells following Diphtheria Toxin-Mediated Antigen Delivery into Dendritic Cells (2006)

Recognition and clearance of many intracellular pathogens requires the activation and subsequent effector functions of CD8+ T lymphocytes. To stimulate CD8+ T cells by immunization, the target antigens must be delivered into the cytosol of host cells. There they can be processed into peptides and presented in the context of major histocompatibility complex class I molecules to antigen-specific CD8+ T cells. One method of delivering antigens into the cytosol is to fuse them to modified bacterial toxins that are able to enter mammalian cells. The expression pattern of the toxin receptors in the host will determine the cell population that the toxin fusion protein targets and will thus restrict antigen-specific T-cell recognition to the same population. In this study we describe the development and characterization of a diphtheria toxin (DT)-based antigen delivery system. Using CD11c-DTR transgenic mice that express the DT receptor in dendritic cells (DC), this system allows for targeted delivery of CD8+ T-cell antigen to DC. We show that antigen-specific CD8+ T cells proliferate in CD11c-DTR mice following immunization with catalytically inactive DT-antigen fusion proteins. We also show that a toxin-based system that restricts antigen delivery to DC results in more robust antigen-specific CD8+ T-cell proliferation than a toxin-based system that does not restrict delivery to a particular cell type. These results have implications for vaccine design, and they suggest that use of a toxin-based vector to target antigen to DC may be an effective way to induce a CD8+ T-cell response.
CAL-101, a Specific Inhibitor of the p110δ Isoform of Phosphatidylinositide 3-Kinase Induces Cytotoxicity in Multiple Myeloma (MM) (2008)

Abstract The phosphatidylinositide 3-kinase (PI3K)/Akt pathway mediates cell proliferation, cell cycle regulation, apoptosis, and autophagy. Of the 8 distinct mammalian isoforms of PI3K, it is the class I PI3Ks (p110α, p110β, p110δ, and p110γ) that are responsible for Akt activation. Recently, p110δ expression has been shown in colon and bladder carcinoma, glioblastoma, and acute myeloid leukemia cells. In this study, we demonstrate expression and examined biologic sequelae of p110δ signaling in MM using a novel specific inhibitor CAL-101. Overexpression of p110δ protein was observed in 24/24 primary tumor cells from MM patients. High level of p110δ expression was detected in two (INA-6 and LB) of the 11 MM cell lines examined. Treatment of INA-6 and LB cells with CAL-101 (1.0 μM for 1.5, 3, 6 hr) significantly inhibited phosphorylation of Akt at serine 473 and threonine 308, suggesting that p110δ is the isoform responsible for PI3K signaling in these cells. Furthermore, CAL-101 induced cytotoxicity in INA-6 cells in a dose-dependent fashion, with an IC50 of 0.625 μM-1.25 μM at 48 h. In contrast, minimal cytotoxicity was observed in p110δ-negative cell lines. Importantly, CAL-101 (0.625 μM) triggered cytotoxicity against tumor cells from MM patients without affecting the survival of normal peripheral blood mononuclear cells at concentrations as high as 20 μM. The specificity of CAL-101 towards p110δ was confirmed by the observation that p110δ small interfering RNA knock-down, but not control, caused inhibition of cell growth and cytotoxicity that was consistent with CAL-101 treatment, further confirming the key role of p110δ in MM cells. Interleukin 6 (IL-6) and insulin-like growth factor I (IGF-I) and cell-cell contact with stromal cells have been shown to induce proliferative and anti-apoptotic responses in MM cells that abrogate cytotoxic effects of conventional therapies. Importantly, neither either IL-6 and IGF-1 treatment nor co-culture of MM cells with bone marrow stromal cells abrogated CAL-101-induced MM cell growth inhibition. Moreover, CAL-101 inhibited adherence of MM cells to bone marrow stromal cells. Since the PI3K/Akt pathway is involved in autophagy, we also examined whether CAL-101 induced autophagic cell death in MM cells. CAL-101 (6 hr treatment) significantly increased LC3-II expression, assessed by western blot and immunofluorescent analyses; conversely, autophagy inhibitor 3-MA (100 μM) blocked LC3-II expression induced by CAL-101. Acridine orange staining and electron microscopic analysis to assess the relative number of autolysosomes further confirmed induction of autophagy by CAL-101. Finally, combined CAL-101 with bortezomib showed synergistic cytotoxicity against MM cells (combination index = 0.64). In conclusion, our studies showed that p110δ is a novel therapeutic target in MM and provide the basis for clinical evaluation of CAL-101 in ongoing Phase 1/2 trial in hematologic malignancies including MM.
A Bayesian method for long AR spectral estimation: a comparative study (1996)

We address the problem of smooth power spectral density estimation of zero-mean stationary Gaussian processes when only a short observation set is available for analysis. The spectra are described by a long autoregressive model whose coefficients are estimated in a Bayesian regularized least squares (RLS) framework accounting the spectral smoothness prior. The critical computation of the tradeoff parameters is addressed using both maximum likelihood (ML) and generalized cross-validation (GCV) criteria in order to automatically tune the spectral smoothness. The practical interest of the method is demonstrated by a computed simulation study in the field of Doppler spectral analysis. In a Monte Carlo simulation study with a known spectral shape, investigation of quantitative indexes such as bias and variance, but also quadratic, logarithmic, and Kullback distances shows interesting improvements with respect to the usual least squares method, whatever the window data length and the signal-to-noise ratio (SNR).
Regulation of Insulin-Gene Expression (1987)

DURING the past decade, the focus of mammalian molecular biology has evolved from the characterization of gene structure to the regulation of gene expression. In parallel, the ability to manipulate isolated DNA in vitro has led to the development of methods for the modification of the genomes of both individual cells and whole animals. These technological leaps have now made it worthwhile to consider new remedies for human genetic diseases as well as for some deficiency states that are not genetically determined. In this review, we examine the regulation of mammalian gene expression and several approaches to gene therapy, using . . .
Quadriceps strength and fatigue assessed by magnetic stimulation of the femoral nerve in man (1996)

There is no nonvolitional method of assessing quadriceps strength which both supramaximally activates the muscle and is acceptable to subjects. In 10 normal subjects and 10 patients with suspected muscle weakness we used magnetic stimulation of the femoral nerve to elicit an isometric twitch and measured twitch tension (TwQ), surface electromyogram in addition to the maximum voluntary contraction force (MVC). Supramaximality was achieved in all subjects at a mean of 83% of maximum stimulator output. When supramaximal, TwQ was reproducible (mean coefficient of variation 3.6%, range 0.7–10.9) and correlated well with MVC (r2 = 0.83, P < 0.001). In 7 normal subjects we measured TwQ before and after a fatiguing protocol; after 20 min TwQ was a mean of 55% (range 29–77%) of baseline and remained substantially reduced at 90 min. Magnetic femoral nerve stimulation is a painless, supramaximal method of assessing quadriceps strength and fatigue which is likely to be of value in clinical and physiological studies. © 1996 John Wiley & Sons, Inc.
Elevated plasma factor VIII in a mouse model of low-density lipoprotein receptor–related protein deficiency (2003)

It has been established that low-density lipoprotein receptor-related protein (LRP) is involved in the cellular uptake and degradation of coagulation factor VIII (FVIII) in vitro. To address the physiologic role of LRP in regulating plasma FVIII in vivo, we used cre/loxP-mediated conditional LRP- deficient mice (MX1cre(+)LRP(flox/flox)). Upon inactivation of the LRP gene, MX1cre(+)LRP(flox/flox) mice had significantly higher plasma FVIII as compared with control LRP(flox/flox) mice (3.4 and 2.0 U/mL, respectively; P <.001). Elevated plasma FVIII levels in MX1cre(+)LRP(flox/flox) mice coincided with increased plasma von Willebrand factor (VWF) (2.0 and 1.6 U/mL for MX1cre(+)LRP(flox/flox) and control LRP(flox/flox) mice, respectively; P <.05). Elevation of plasma FVIII and VWF persisted for at least 6 weeks after inactivation of the LRP gene. Upon comparing plasma FVIII and VWF in individual mice, we observed an increase of the FVIII/VWF ratio in MX1cre(+)LRP(flox/flox) mice as compared with control LRP(flox/flox) mice. Administration of either a vasopressin analog or an endotoxin resulted in increased plasma VWF, but not FVIII. In clearance experiments, MX1cre(+)LRP(flox/flox) mice displayed a 1.5-fold prolongation of FVIII mean residence time. Adenovirus-mediated overexpression of the 39-kDa receptor-associated protein (RAP) in normal mice resulted in a 3.5-fold increase of plasma FVIII. These data confirm that the regulation of plasma FVIII in vivo involves a RAP-sensitive mechanism. Surprisingly, plasma FVIII in MX1cre(+)LRP(flox/flox) mice increased 2-fold after RAP gene transfer. We propose that RAP-sensitive determinants other than hepatic LRP contribute to the regulation of plasma FVIII in vivo.
A C‐terminal skeletal muscle sodium channel mutation associated with myotonia disrupts fast inactivation (2005)

Missense mutations in the skeletal muscle sodium channel α‐subunit gene ( SCN4A ) are associated with a group of clinically overlapping diseases caused by alterations in the excitability of the sarcolemma. Sodium channel defects may increase excitability and cause myotonic stiffness or may render fibres transiently inexcitable to produce periodic paralysis. A patient with cold‐aggravated myotonia did not harbour any of the common SCN4A mutations. We therefore screened all 24 exons by denaturing high‐performance liquid chromatography, followed by direct sequencing. Two novel missense changes were found with predicted amino acid substitutions: T323M in the DIS5‐S6 loop and F1705I in the intracellular C‐terminus. The functional impact of these substitutions was assessed by recording whole‐cell Na + currents from transiently transfected HEK293 cells. T323M currents were indistinguishable from wild‐type (WT). Fast inactivation was impaired for F1705I channels, as demonstrated by an 8.6‐mV rightwards shift in voltage dependence and a two‐fold slowing in the rate of inactivation. Recovery from fast inactivation was not altered, nor was there an increase in the persistent current after a 50‐ ms depolarization. Activation and slow inactivation were not appreciably affected. These data suggest that T323M is a benign polymorphism, whereas F1705I results in fast inactivation defects, which are often observed for myotonia. This is the first example of a C‐terminal mutation in SCN4A associated with human disease. Like the cardiac disorders (long QT syndrome type 3 or Brugada syndrome) and generalized epilepsy with febrile seizures plus (GEFS+) associated with C‐terminal mutations in other Na V channels, the primary effect of F1705I was a partial disruption of fast inactivation.
Radiosynthesis, in vitro validation, and in vivo evaluation of 18F-labeled COX-1 and COX-2 inhibitors. (2002)

We have developed a radiosynthetic route that can yield 18F-labeled selective inhibitors of COX-1 or COX-2. Both compounds have been fully characterized in vitro and in vivo. Our results indicate that 18F-SC58125 has potential as a marker of COX-2 activity but that, because of high nonspecific binding, 18F-SC63217 was not a good choice as a marker of COX-1.
Asymmetric Azidation−Cycloaddition with Open-Chain Peptide-Based Catalysts. A Sequential Enantioselective Route to Triazoles (2002)

A family of beta-substituted histidine-containing peptides has been synthesized to probe the effect of noncovalent conformational rigidification on catalyst enantioselectivity. Unambiguous enhancement of enantioselectivity in the conjugate addition of azide to alpha,beta-unsaturated carboxylate derivatives has been achieved, enabling application to a sequential asymmetric azidation/cycloaddition for the synthesis of optically enriched triazoles and triazolines.
Molecular cloning and characterization of a 35.5-kilodalton lipoprotein of Treponema pallidum (1991)

A clone expressing a 35.5-kDa recombinant treponemal protein was isolated from a genomic DNA library constructed from Treponema pallidum street strain 14. Polyclonal antiserum raised against the recombinant protein reacted with a corresponding native protein of comparable size in T. pallidum that is specific to the pathogenic treponemes. Radiolabeling of the recombinant protein with [3H]palmitate demonstrated that it is lipid modified. Like other recently characterized T. pallidum lipoproteins, the 35.5-kDa lipoprotein partitioned into the detergent phase from T. pallidum cells fractionated with Triton X-114, suggesting that it is an integral membrane protein. Processing of the recombinant 35.5-kDa lipoprotein from a precursor form to a smaller mature form was not evident in pulse-chase experiments. However, pretreatment of Escherichia coli cells expressing the 35.5-kDa lipoprotein with inhibitors of protein processing or translocation revealed the existence of a higher-molecular-mass precursor. Gene fusion studies with the transposon TnphoA demonstrated the presence of an export signal in the 35.5-kDa lipoprotein that promotes the extracytoplasmic localization of a 35.5-kDa lipoprotein-PhoA hybrid.
Iron Supplementation in Suckling Piglets: How to Correct Iron Deficiency Anemia without Affecting Plasma Hepcidin Levels (2013)

The aim of the study was to establish an optimized protocol of iron dextran administration to pig neonates, which better meets the iron demand for erythropoiesis. Here, we monitored development of red blood cell indices, plasma iron parameters during a 28-day period after birth (till the weaning), following intramuscular administration of different concentrations of iron dextran to suckling piglets. To better assess the iron status we developed a novel mass spectrometry assay to quantify pig plasma levels of the iron-regulatory peptide hormone hepcidin-25. This hormone is predominantly secreted by the liver and acts as a negative regulator of iron absorption and reutilization. The routinely used protocol with high amount of iron resulted in the recovery of piglets from iron deficiency but also in strongly elevated plasma hepcidin-25 levels. A similar protocol with reduced amounts of iron improved hematological status of piglets to the same level while plasma hepcidin-25 levels remained low. These data show that plasma hepcidin-25 levels can guide optimal dosing of iron treatment and pave the way for mixed supplementation of piglets starting with intramuscular injection of iron dextran followed by dietary supplementation, which could be efficient under condition of very low plasma hepcidin-25 level.
Embryonic and hematopoietic stem cells express a novel SH2–containing inositol 5′-phosphatase isoform that partners with the Grb2 adapter protein (2001)

SH2-containing inositol 5'-phosphatase (SHIP) modulates the activation of immune cells after recruitment to the membrane by Shc and the cytoplasmic tails of receptors. A novel SHIP isoform of approximately 104 kd expressed in primitive stem cell populations (s-SHIP) is described. It was found that s-SHIP is expressed in totipotent embryonic stem cells to the exclusion of the 145-kd SHIP isoform expressed in differentiated hematopoietic cells. s-SHIP is also expressed in primitive hematopoietic stem cells, but not in lineage-committed hematopoietic cells. In embryonic stem cells, s-SHIP partners with the adapter protein Grb2 without tyrosine phosphorylation and is present constitutively at the cell membrane. It is postulated that s-SHIP modulates the activation threshold of primitive stem cell populations.
Foiling the wiley hacker: more than analysis and containment (2005)

This paper will look at the methods and tools used by system Intruders. It will analyze the development of the hacker, his motivation, his environment and the burglar tools used for system intrusion. It will also probe the nature of the vulnerable networking environments that are the target of intrusions. More important, it will address turning the tables on these Intruders with their own tools and techniques. Besides reacting to attacks, there are many opportunities to learn from the intruders and design that knowledge into now defensive solutions for securing computer based systems. Having presented the problem, the paper will present a strategy to defend and thwart such intrusions in our Increasingly networked and distributed computing and telecommunications environments.
The Psycholinguistic Dimension in Second Language Writing: Opportunities for Research and Pedagogy Using Computer Keystroke Logging (2008)

This article discusses the use of computer logging as a means of investigating aspects of the second language (L2) writing process as writers are engaged in producing text at the keyboard. The observation of writing by means of this method provides researchers with detailed information concerning aspects of the planning, formulation, and revision processes. This function is illustrated by reference to a study in Sweden of school‐age learners of English as an additional language whose written production was recorded as part of a longitudinal study, and findings from the study are presented. The discussion highlights the potential uses of logging, not only not in relation to researching writers' processes, but also as a pedagogic tool given that its replay facility allows access to information about aspects of the writers' attention and strategies as they write.
Potential of Pectins to Beneficially Modulate the Gut Microbiota Depends on Their Structural Properties (2019)

Pectins are plant cell-wall polysaccharides which can be utilized by commensal bacteria in the gut, exhibiting beneficial properties for the host. Knowledge of the impact of pectins on intestinal bacterial communities is insufficient and limited to a few types of pectins. This study characterized the relationship between the structural properties of pectins and their potential to modulate composition and activity of the gut microbiota in a beneficial way. For this purpose we performed <i>in vitro</i> fermentations of nine structurally diverse pectins from citrus fruits and sugar beet, and a pectic derivative, rhamnogalacturonan I (RGI), using a TIM-2 colon model. The composition of microbiota during TIM-2 fermentations was assessed by 16S rRNA gene amplicon sequencing. Both general and pectin-specific changes were observed in relative abundances of numerous bacterial taxa in a time-dependent way. Bacterial populations associated with human health, such as <i>Faecalibacterium prausnitzii</i>, <i>Coprococcus</i>, <i>Ruminococcus</i>, <i>Dorea</i>, <i>Blautia</i>, <i>Oscillospira</i>, <i>Sutterella</i>, <i>Bifidobacterium</i>, <i>Christensenellaceae</i>, <i>Prevotella copri</i>, and <i>Bacteroides</i> spp. were either increased or decreased depending on the substrate, suggesting that these bacteria can be controlled using structurally different pectins. The main structural features linked to the pectin-mediated shifts in microbiota included degree of esterification, composition of neutral sugars, distribution of homogalacturonan and rhamnogalacturonan fractions, degree of branching, and the presence of amide groups. Cumulative production of the total short chain fatty acids and propionate was largest in fermentations of the high methoxyl pectins. Thus, this study indicates that microbial communities in the gut can be specifically modulated by pectins and identifies the features in pectin molecules linked to microbial alterations. This knowledge can be used to define preferred dietary pectins, targeting beneficial bacteria, and favoring more balanced microbiota communities in the gut.
Microstrain and Capacity Fade in Spinel Manganese Oxides (2002)

With an objective of understanding the differences in the capacity retention behavior of and the cation-substituted Co, and Ni) spinel oxides, the peak broadening in the X-ray diffraction patterns on extracting lithium has been analyzed. An analysis of the and samples before and after treating at room temperature with acid or an oxidizing agent or at 55°C with electrolyte reveals that the system experiences a larger amount of microstrain during these treatments (lithium extraction) compared to the systems. Additionally, the two cubic phases formed at lower lithium contents have a larger difference in lattice parameters in compared to The observation of nearly the same amount of manganese dissolution in and suggests that the faster capacity fade in the former is due to the development of microstrain and the larger difference in lattice parameters between the two cubic phases. © 2002 The Electrochemical Society. All rights reserved.