gebhart/patrepeval huggingface dataset:
KIFC1 is a novel potential therapeutic target for breast cancer (2015)

Kinesin-like protein KIFC1, a normally nonessential kinesin motor, plays a critical role in centrosome clustering in cancer cells and is essential for the survival of cancer cells. Herein, we reported that KIFC1 expression is up-regulated in breast cancer, particularly in estrogen receptor negative, progesterone receptor negative and triple negative breast cancer, and is not associated with epidermal growth factor receptor 2 status. In addition, KIFC1 is highly expressed in all 8 tested human breast cancer cell lines, but is absent in normal human mammary epithelial cells and weakly expressed in 2 human lung fibroblast lines. Moreover, KIFC1 silencing significantly reduced breast cancer cell viability. Finally, we found that PJ34, a potent small molecule inhibitor of poly(ADP-ribose) polymerase, suppressed KIFC1 expression and induced multipolar spindle formation in breast cancer cells, and inhibited cell viability and colony formation within the same concentration range, suggesting that KIFC1 suppression by PJ34 contributes to its anti-breast cancer activity. Together, these results suggest that KIFC1 is a novel promising therapeutic target for breast cancer.
Magnetic versus electrical stimulation in the interpolation twitch technique of elbow flexors. (2012)

The study compared peripheral magnetic with electrical stimulation of the biceps brachii m. (BB) in the single pulse Interpolation Twitch Technique (ITT). 14 healthy participants (31±7 years) participated in a within-subjects repeated-measures design study. Single, constant-current electrical and magnetic stimuli were delivered over the motor point of BB with supramaximal intensity (20% above maximum) at rest and at various levels of voluntary contraction. Force measurements from right elbow isometric flexion and muscle electromyograms (EMG) from the BB, the triceps brachii m. (TB) and the abductor pollicis brevis m. (APB) were obtained. The twitch forces at rest and maximal contractions, the twitch force-voluntary force relationship, the M-waves and the voluntary activation (VA) of BB between magnetic and electrical stimulation were compared. The mean amplitude of the twitches evoked at MVC was not significantly different between electrical (0.62 ± 0.49 N) and magnetic (0.81 ± 0.49 N) stimulation (p > 0.05), and the maximum VA of BB was comparable between electrical (95%) and magnetic (93%) stimulation (p > 0. 05). No differences (p >0.05) were revealed in the BB M-waves between electrical (13.47 ± 0.49 mV.ms) and magnetic (12.61 ± 0.58 mV.ms) stimulation. The TB M-waves were also similar (p > 0.05) but electrically evoked APB M-waves were significantly larger than those evoked by magnetic stimulation (p < 0.05). The twitch-voluntary force relationship over the range of MVCs was best described by non-linear functions for both electrical and magnetic stimulation. The electrically evoked resting twitches were consistently larger in amplitude than the magnetically evoked ones (mean difference 3.1 ± 3.34 N, p < 0.05). Reduction of the inter-electrodes distance reduced the twitch amplitude by 6.5 ± 6.2 N (p < 0.05). The fundamental similarities in voluntary activation assessment of BB with peripheral electrical and magnetic stimulation point towards a promising new application of peripheral magnetic stimulation as an alternative to the conventional ITT for the assessment of BB voluntary activation.
Recent developments in ambient ionization techniques for analytical mass spectrometry (2008)

Ambient ionization techniques enable the interrogation of a variety of samples in their native state by mass spectrometry, and are rapidly advancing all fields where screening for the presence of various analytes in a broadband and/or high-throughput fashion is desirable. This Highlight article provides an introduction to the field, and showcases the different ionization approaches reported since 2004, with an emphasis on the most recent developments.
Distribution of acid stable trypsin inhibitor immunoreactivity in normal and malignant human tissues (1989)

The distribution and localization of acid stable trypsin inhibitor (ASTI) in normal and malignant human tissues from various organs were examined using immunohistochemical techniques that used goat antibody raised against highly purified ASTI from human urine. Tissues were assessed as positive only when they were stained by both the biotin-avidin-peroxidase complex system and biotin-streptavidin-beta-galactosidase complex system, and the staining was abolished by absorption with purified ASTI. Under normal conditions, ASTI immunoreactivity was observed in only a few organs. Positive tissues for ASTI immunoreactivity included the kidney proximal tubules, glial cells of the cerebrum, fibrillar structures of the lamina propria of the stomach and colon, and bronchial epithelial cells. No ASTI immunoreactivity was observed in the cardiovascular system, reproductive system, or other tissues examined. As is not the case for normal tissues, ASTI immunoreactivity was found to be widely distributed in malignant tumors. Staining was observed in the extracellular space, i.e., in the stroma of the tumor and in connective tissues around the tumor invasion, whereas no ASTI immunoreactivity was detected in the malignant cells. Considering the identity of the first 36 NH2-terminal residues of ASTI purified from plasma or urine with a recently reported endothelial cell growth factor, the present findings suggest that ASTI could play an important role, not limited to its function as a protease inhibitor, in the invasive growth of malignant neoplasms.
Frequency domain measurement of timing jitter in ATE (2004)

The objective of this paper is to provide a framework by which jitter phenomena, which are encountered at the output signals of a head board in an automatic test equipment (ATE), can be studied. In this paper, the jitter refers to the one caused by radiated electromagnetic interference (EMI) noise, which is present in the head of all ATE due to DC-DC converter activity. An initial analysis of the areas of the head board most sensitive to EMI noise has been made. It identifies a sensitive part in the loop filler of a phase locked loop which is used to obtain a high frequency clock for the timing generator. Different H-fields are then applied externally at the loop filter to verify the behavior of the output signal of the head board in terms of RMS jitter. As for RMS jitter measurements, a frequency domain methodology has been employed. A trend for RMS jitter variation with respect to radiated EMI magnitude as well as frequency has been obtained. Also the orientation of the external H-field source with respect to the target board and its effects on the measured RMS jitter has been investigated. For measuring the RMS value, a proper circuitry has been designed on a daughter board to circumvent ground noise and connectivity problems arising from the head environment.
Effect of two paradigms of chronic intermittent hypoxia on carotid body sensory activity (2004)

Reflexes arising from the carotid bodies may play an important role in cardiorespiratory changes evoked by chronic intermittent hypoxia (CIH). In the present study, we examined whether CIH affects the hypoxic sensing ability of the carotid bodies and, if so, by what mechanisms. Experiments were performed on adult male rats (Sprague-Dawley, 250-300 g) exposed to two paradigms of CIH for 10 days: 1) multiple exposures to short durations of intermittent hypoxia per day (SDIH; 15 s of 5% O(2) + 5 min of 21% O(2), 9 episodes/h, 8 h/day) and 2) single exposure to longer durations of intermittent hypoxia per day [LDIH; 4 h of hypobaric hypoxia (0.4 atm/day) + 20 h of normoxia]. Carotid body sensory response to graded isocapnic hypoxia was examined in both groups of animals under anesthetized conditions. Hypoxic sensory response was significantly enhanced in SDIH but not in LDIH animals. Similar enhancement in hypoxic sensory response was also elicited in ex vivo carotid bodies from SDIH animals, suggesting that the effects were not secondary to cardiovascular changes. SDIH, however, had no significant effect on the hypercapnic sensory response. The effects of SDIH on the hypoxic sensory response completely reversed after SDIH animals were placed in a normoxic environment for an additional 10 days. Previous treatment with systemic administration of O(2)(-)* radical scavenger prevented SDIH-induced augmentation of the hypoxic sensory response. These results demonstrate that SDIH but not LDIH results in selective augmentation of the hypoxic response of the carotid body and O(2)(-)* radicals play an important role in SDIH-induced sensitization of the carotid body.
Effects of porosity and pore size on in vitro degradation of three‐dimensional porous poly(D,L‐lactide‐co‐glycolide) scaffolds for tissue engineering (2005)

In vitro degradation of seven three-dimensional porous scaffolds composed of PLGA85/15, a very useful poly(D,L-lactide-co-glycolide), was performed in phosphate-buffered saline solution at 37 degrees C up to 26 weeks, and effects of porosity (80-95%) and pore size (50-450 mum) on the degradation of the scaffolds were investigated. A series of quantities were measured during the degradation processes: molecular weight and its distribution of PLGA; compressive strength and modulus; and weight, dimension, and porosity of scaffolds. In all of cases with different pore morphologies, the degradation processes obeyed a three-stage model. Scaffolds with a higher porosity or a smaller pore size degraded more slowly than and thus outlasted those with a lower porosity or a larger pore size. The effects are both attributed to a wall effect and a surface area effect because the scaffolds with lower porosities or larger pores possess thicker pore walls and smaller surface area, which depress the diffusion of acidic degradation products and thus results in a stronger acid-catalyzed hydrolysis. This work suggests that, in designing a tissue-engineering scaffold composed of PLGA and adjusting its degradation rate, the effects of pore morphologies should be taken into consideration in addition to those of chemical composition and condensed state of raw materials.
Characterization of antigenic peptides presented by HLA‐B44 molecules on tumor cells expressing the gene MAGE3 (1996)

The amino acid sequence of the protein encoded by the gene MAGE-3was screened for peptides containing the binding motif for HLA-B44. Nine peptides were synthesized, and their binding affinity for HLA-B*4402 and -B*4403 was analyzed in an HLA class I α-chain refolding assay. Four peptides with binding affinity for HLA-B*4403 were chosen for in vitro cytotoxic T-lymphocyte induction assays using as antigen-presenting cells peptide-pulsed, autologous activated B lymphoblasts from a healthy, B*4403+ donor. Peptide-specific effectors could be raised only against one peptide, M3-167. Cytotoxic T lymphocytes specific for this peptide were also able to recognize melanoma cell lines expressing HLA-B44 and the gene MAGE-3, strongly suggesting that M3-167is a naturally processed MAGE-3-encoded epitope presented by HLA-B44.M3-167 is a 1 amino acid N-terminal extension of M3-168, a naturally processed epitope MAGE-3-encoded epitope presented by HLA-A1 that has been previously described. TAP binding studies of these 2 peptides revealed that the TAP affinity of M3-167 is about 9-fold higher than that of M3-168. M3-167 or a longer precursor could be transported into the endoplasmatic reticulum, where it could be trimmed for presentation by HLA-A1 or -B44 molecules. Taken together, our data suggest that M3-167 could be an immunodominant peptide encoded by the gene MAGE-3. © 1996 Wiley-Liss, Inc.
New hydrazone derivatives of Adriamycin and their immunoconjugates - a correlation between acid stability and cytotoxicity (1991)

New N-substituted hydrazine linkers were synthesized and their hydrazone derivatives of adriamycin were prepared. These functionalized adriamycin derivatives were conjugated with a monoclonal antibody, 5E9. The release rate of adriamycin from the hydrazones and from some of the conjugates was studied, and their relationship to the IC50's of the conjugate against 5E9-positive Daudi cells was investigated.
Experimental study of the antithrombogenic behavior of Dacron vascular grafts coated with hydrophilic acrylic copolymers bearing salicylic acid residues (1996)

The objective of the present work was study of the behavior of active coatings of hydrophilic acrylic polymers bearing salicylic acid residues linked covalently to the macromolecular chains, after their application to woven and knitted Dacron vascular grafts. In vitro tests were carried out under dynamic flow conditions using equipment especially designed to reproduce physiologic conditions, to determine the retention of the coating using a saline solution. Ex vivo tests were carried out in an extracorporeal circuit using the dog as an animal model. The study of the deposition of platelets was followed by labeling of autologous platelets with 111In-oxine, as well as by analysis of the surfaces of the prostheses by scanning electron microscopy. An application of thin coatings of hydrophilic acrylic copolymers improves the antithrombogenicity of the vascular grafts with respect to the uncoated prosthesis. The presence of relatively small amounts of units bearing salicylic acid residues in the copolymer chains (5-20 wt %) gives good results when they are applied to woven and knitten Dacron meshes which have been quantified by analysis of the percentage of radiotracer on the surface of the vascular grafts tested in ex vivo experiments. The salicylic acid residues are released slowly to the medium by hydrolysis of the reversible covalent bonds of this compound to the acrylic macromolecular chains, which provides an additional antiaggregating effect for platelets. The polymeric coating forms a thin active film which improves the antithrombogenic properties of the surface of woven or knitted Dacron vascular grafts in ex vivo experiments.
A software-oriented approach to the design of media processing environments (1994)

The ViewStation architecture embodies a software-oriented approach to the support of interactive media-based applications. Starting from the premise that the raw media data, e.g., the video pixels themselves, must eventually be made accessible to the application, we have derived a set of architectural guidelines for the design of media processing environments. The resultant ViewStation architecture, as described in this paper, consists of the VuSystem, a complete media programming environment, and the VuNet, a substrate for the acquisition communication and rendering of video and closed caption text. We describe a set of computer-participative applications that demonstrate the present day viability of applications that participate in, i.e., actively process, live media-based information. Early performance results illustrate the affordability and benefits of our software-oriented approach.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Role of the methylcitrate cycle in propionate metabolism and detoxification in Mycobacterium smegmatis (2007)

Catabolism of odd-chain-length fatty acids yields acetyl-CoA and propionyl-CoA. A common pathway of propionyl-CoA metabolism in micro-organisms is the methylcitrate cycle, which includes the dedicated enzymes methylcitrate synthase (MCS), methylcitrate dehydratase (MCD) and methylisocitrate lyase (MCL). The methylcitrate cycle is essential for propionate metabolism in Mycobacterium tuberculosis. Unusually, M. tuberculosis lacks an MCL orthologue and this activity is provided instead by two isoforms of the glyoxylate cycle enzyme isocitrate lyase (ICL1 and ICL2). These bifunctional (ICL/MCL) enzymes are jointly required for propionate metabolism and for growth and survival in mice. In contrast, the non-pathogenic species Mycobacterium smegmatis encodes a canonical MCL enzyme in addition to ICL1 and ICL2. The M. smegmatis gene encoding MCL (prpB) is clustered with genes encoding MCS (prpC) and MCD (prpD). Here we show that deletion of the M. smegmatis prpDBC locus reduced but did not eliminate MCL activity in cell-free extracts. The residual MCL activity was abolished by deletion of icl1 and icl2 in the DeltaprpDBC background, suggesting that these genes encode bifunctional ICL/MCL enzymes. A DeltaprpB Deltaicl1 Deltaicl2 mutant was unable to grow on propionate or mixtures of propionate and glucose. We hypothesize that incomplete propionyl-CoA metabolism might cause toxic metabolites to accumulate. Consistent with this idea, deletion of prpC and prpD in the DeltaprpB Deltaicl1 Deltaicl2 background paradoxically restored growth on propionate-containing media. These observations suggest that the marked attenuation of ICL1/ICL2-deficient M. tuberculosis in mice could be due to the accumulation of toxic propionyl-CoA metabolites, rather than inability to utilize fatty acids per se.
Control of lymphocyte recirculation in man. II. Differential regulation of the cutaneous lymphocyte-associated antigen, a tissue-selective homing receptor for skin-homing T cells (1993)

Recent work indicates that a novel homing receptor (HR)/endothelial ligand pair--the cutaneous lymphocyte-associated Ag (CLA) and E-selectin--is involved in targeting a unique skin-associated subpopulation of memory T cells to cutaneous sites of chronic inflammation. To investigate the regulatory mechanisms responsible for the generation of a memory T cell subset with skin-selective homing capability, we used multiparameter flow cytometry to assess the expression of CLA on T cells during initial T cell activation in secondary lymphoid tissues (the virgin to memory transition), and upon reactivation in skin. Our analyses indicate that in vivo induction of CLA (and E-selectin-binding ability) first occurs during the virgin to memory transition, and is regulated in a highly tissue-selective manner. The frequency of CLA expression on CD45RA+/RO+ transitional T cells within skin-associated peripheral lymph nodes was > fivefold higher than within the mucosal microenvironment of the appendix. In keeping with its role as a skin-selective homing receptor, levels of cell-surface CLA on T cells obtained from cutaneous blisters overlying delayed-type hypersensitivity sites were a mean 23-fold higher than on corresponding peripheral blood T cells, including all time points of lesional evolution. However, comparisons of CLA expression on resting vs activated skin blister T cells (HLA-DR - vs +, respectively) indicated that CLA expression, which is already quite high on the resting subset, appeared to be further up-regulated upon activation in skin. The critical involvement of local microenvironments in the regulation of CLA expression was also supported by in vitro studies demonstrating the necessity of specific secondary signals for the induction of CLA glycoproteins on mitogen-activated T cells. CLA up-regulation on both the virgin and memory T cell subsets was dependent on the presence of TGF-beta 1 (or, to a lesser extent, IL-6), but not a wide variety of other cytokines. Thus, the development of the CLA+ memory T cell subset is likely a product of the cumulative experience of those T cells with respect to local microenvironments at previous sites of activation, perhaps involving differential availability of bioactive TGF-beta 1 and/or IL-6 (both cytokines produced in skin). Repeated activation in skin or skin-associated peripheral lymph nodes may act to reinforce CLA expression on T cells functionally-associated with skin, and thus enhance the functional efficiency of these cells by preferentially focusing their recirculation to the skin or related sites.
Genotype × Environment Interactions, Stability, and Agronomic Performance of Soybean with Altered Fatty Acid Profiles (2002)

There has been a major effort to produce soybean [Glycine max (L.) Merr.] lines with modified fatty acid profiles in order to improve quality and develop new uses for soybean oil. Utilization of the lines depends on their agronomic traits and stability of the fatty acid profiles in diverse environments. The objectives of this study were to (i) evaluate the influence of years and locations on the fatty acid composition of soybean genotypes with unique fatty acid profiles, (ii) determine which fatty acids and fatty acid profiles are the most stable, and (iii) evaluate agronomic and seed quality traits of mutant soybean lines. Genotypes were evaluated over three years (1996, 1997, and 1998) at four locations in Southern Ontario, Canada. Year effects had the largest impact on all fatty acid levels. Location effects were significant only for oleic and linolenic acids. Genotype x year interaction effect was significant for all fatty acids whereas genotype x location and genotype x year x location interaction effects were significant only for oleic, linoleic, and linolenic acids. Mutants with reduced or elevated palmitic, elevated oleic, or reduced linolenic acid concentrations exhibited average or higher stability than lines with normal levels of these fatty acids. Therefore, these lines may be suitable for growing in a wide range of environments. Maturity, plant height, lodging, seed size, and seed quality were significantly different between mutants and cultivars. Seed yield was significantly reduced in mutants compared to cultivars.
Intravenous Tissue-Type Plasminogen Activator for Treatment of Acute Stroke (2000)

This study, conducted at multiple institutions throughout the United States, suggests that favorable clinical outcomes and low rates of symptomatic intracerebral hemorrhage can be achieved using tPA for stroke treatment.
Accuracy of MRI in the Detection of Residual Breast Cancer After Neoadjuvant Chemotherapy (2003)

MRI can show residual malignancy after neoadjuvant chemotherapy better than physical examination, particularly in patients who have not had a complete clinical response to therapy.
First Transformation of Unsaturated Fatty Esters Involving Enyne Cross‐Metathesis (2009)

Abstract magnified image The ruthenium‐catalysed enyne cross‐metathesis of several alkyne derivatives with terminal olefins was performed. These reactions were efficiently achieved under mild conditions in dimethyl carbonate, an eco‐friendly solvent. A unique one‐pot reaction based on an ethenolysis step followed by an enyne cross‐metathesis allowed the efficient transformation of renewable unsaturated fatty esters into valuable conjugated 1,3‐dienes of interest for further transformations.
CD38 expressed on human monocytes: A coaccessory molecule in the superantigen-induced proliferation (2000)

This work analyzes the hypothesis that human CD38 may cooperate with MHC Class II by acting as coreceptor in a superantigen-induced activation. The initial evidence is that CD38 ligation by specific monoclonal antibodies inhibits superantigen-induced T lymphocyte proliferation. Inhibitory effects become apparent after engagement of CD38 expressed by monocytes, whereas ligation of CD38 expressed by T lymphocytes does not apparently affect activation. The inhibition requires a cell-to-cell interaction, followed by the relevant transmembrane signaling that is reproduced by CD38 ligation. Indeed, CD38 ligation on monocytes induces tyrosine phosphorylation of several intracellular proteins including the protooncogene product c-cbl and the fgr and hck tyrosine kinases. The receptorial nature of the CD38-mediated events is confirmed by the observation of an intracellular calcium flux in monocytes secondary to CD38 ligation. These effects are additive with the similar events elicited by MHC Class II ligation, a likely indication that CD38 and MHC Class II share a common activation pathway. This conclusion is strengthened by results of comodulation experiments, indicating that CD38 and MHC Class II display lateral associations on monocytes. These results attribute to CD38 expressed by monocytes a role in the transduction of signal(s) involved in superantigen-induced activation, operating in synergy with MHC Class II.