gebhart/patrepeval huggingface dataset:
Principles of and Advances in Percutaneous Ablation (2011)

Image-guided tumor ablation with both thermal and nonthermal sources has received substantial attention for the treatment of many focal malignancies. Increasing interest has been accompanied by continual advances in energy delivery, application technique, and therapeutic combinations with the intent to improve the efficacy and/or specificity of ablative therapies. This review outlines clinical percutaneous tumor ablation technology, detailing the science, devices, techniques, technical obstacles, current trends, and future goals in percutaneous tumor ablation. Methods such as chemical ablation, cryoablation, high-temperature ablation (radiofrequency, microwave, laser, and ultrasound), and irreversible electroporation will be discussed. Advances in technique will also be covered, including combination therapies, tissue property modulation, and the role of computer modeling for treatment optimization.
Immunologic Characterization of CD7-Deficient Mice (1998)

Human CD7 is an Ig superfamily molecule that is expressed on mature T and NK lymphocytes. Although in vitro studies have suggested a role for CD7 in lymphoid development and function, the exact function of CD7 in vivo has remained elusive. One patient has been reported with SCID syndrome attributed to CD7 deficiency. To study in vivo functions of CD7, we have generated CD7-deficient mice and assessed their lymphoid development and function. CD7-deficient mice were viable, had normal peripheral blood and spleen lymphocyte numbers, and had normal specific Ab responses with Ag-driven Ig isotype switching. Thymocyte numbers were normal in 4-wk-old, 6-mo-old, and 1-yr-old CD7-deficient mice, but in 3-mo-old CD7-deficient mice, total thymocyte numbers were significantly increased by 60% (p < 0.02) compared with normal age-matched +/+ littermates. CD7-deficient splenocytes proliferated normally in response to various mitogens, including PHA, anti-CD3, Con A, and LPS. While NK cell numbers and cytolytic activity to YAC targets were normal, CD7-deficient mice had lower Ag-induced MHC class I-restricted CTL activity against OVA-transfected target cells than did +/+ control mice. Thus, CD7-deficient mice did not have a SCID syndrome, but rather had transient increases in thymocyte numbers at age 3 mo and altered splenocyte Ag-specific CTL effecter cell activity. These data suggest a role for CD7 in regulating intrathymic T cell development and in mediating CTL effecter function.
Identification of c-di-GMP Derivatives Resistant to an EAL Domain Phosphodiesterase (2012)

The bacterial second messenger signaling molecule bis-(3′-5′)-cyclic dimeric guanosine monophosphate (c-di-GMP) controls important biological processes such as biofilm formation, virulence response, and motility. This second messenger is sensed by macromolecular targets inside the cell, both protein and RNA, which induce specific phenotypic responses critical for bacterial survival. One class of enzymes responsible for regulating the intracellular concentration of c-di-GMP, and therefore the physiological behavior of the cell, consists of the EAL domain phosphodiesterases, which degrade the second messenger to its linear form, pGpG. Here, we investigate how base and backbone modifications of c-di-GMP affect the rate of cyclic dinucleotide degradation by an EAL domain protein (CC3396 from Caulobacter crescentus). The doubly substituted thiophosphate analogue is highly resistant to hydrolysis by this metabolizing enzyme but can still bind c-di-GMP riboswitch targets. We used these findings to develop a novel ribosyl phosphate-modified derivative of c-di-GMP containing 2′-deoxy and methylphosphonate substitutions that is charge neutral and demonstrate that this analogue is also resistant to EAL domain-catalyzed degradation. This suggests a general strategy for designing c-di-GMP derivatives with increased enzymatic stability that also possess desirable properties for development as chemical probes of c-di-GMP signaling.
What Is Multilateral Clearing and Who Cares (1994)

Clearinghouses (Banking); Futures
Expression of a Truncated ATHB17 Protein in Maize Increases Ear Weight at Silking (2014)

ATHB17 (AT2G01430) is an Arabidopsis gene encoding a member of the α-subclass of the homeodomain leucine zipper class II (HD-Zip II) family of transcription factors. The ATHB17 monomer contains four domains common to all class II HD-Zip proteins: a putative repression domain adjacent to a homeodomain, leucine zipper, and carboxy terminal domain. However, it also possesses a unique N-terminus not present in other members of the family. In this study we demonstrate that the unique 73 amino acid N-terminus is involved in regulation of cellular localization of ATHB17. The ATHB17 protein is shown to function as a transcriptional repressor and an EAR-like motif is identified within the putative repression domain of ATHB17. Transformation of maize with an ATHB17 expression construct leads to the expression of ATHB17Δ113, a truncated protein lacking the first 113 amino acids which encodes a significant portion of the repression domain. Because ATHB17Δ113 lacks the repression domain, the protein cannot directly affect the transcription of its target genes. ATHB17Δ113 can homodimerize, form heterodimers with maize endogenous HD-Zip II proteins, and bind to target DNA sequences; thus, ATHB17Δ113 may interfere with HD-Zip II mediated transcriptional activity via a dominant negative mechanism. We provide evidence that maize HD-Zip II proteins function as transcriptional repressors and that ATHB17Δ113 relieves this HD-Zip II mediated transcriptional repression activity. Expression of ATHB17Δ113 in maize leads to increased ear size at silking and, therefore, may enhance sink potential. We hypothesize that this phenotype could be a result of modulation of endogenous HD-Zip II pathways in maize.
Stat3 Isoforms, α and β, Demonstrate Distinct Intracellular Dynamics with Prolonged Nuclear Retention of Stat3β Mapping to Its Unique C-terminal End (2007)

Two isoforms of Stat3 (signal transducer and activator of transcription 3) are expressed in cells, alpha (p92) and beta (p83), both derived from a single gene by alternative mRNA splicing. The 55-residue C-terminal transactivation domain of Stat3alpha is deleted in Stat3beta and replaced by seven unique C-terminal residues (CT7) whose function remains uncertain. We subcloned the open reading frames of Stat3alpha and Stat3beta into the C terminus of green fluorescent protein (GFP). Fluorescent microscopic analysis of HEK293T cells transiently transfected with GFP-Stat3alpha or GFP-Stat3beta revealed similar kinetics and cytokine concentration dependence of nuclear accumulation; these findings were confirmed by high throughput microscope analysis of murine embryonic fibroblasts that lacked endogenous Stat3 but stably expressed either GFP-Stat3alpha or GFP-Stat3beta. However, although time to half-maximal cytoplasmic reaccumulation after cytokine withdrawal was 15 min for GFP-Stat3alpha, it was >180 min for GFP-Stat3beta. Furthermore, although the intranuclear mobility of GFP-Stat3alpha was rapid and increased with cytokine stimulation, the intranuclear mobility of GFP-Stat3beta in unstimulated cells was slower than that of GFP-Stat3alpha in unstimulated cells and was slowed further following cytokine stimulation. Deletion of the unique CT7 domain from Stat3beta eliminated prolonged nuclear retention but did not alter its intranuclear mobility. Thus, Stat3alpha and Stat3beta have distinct intracellular dynamics, with Stat3beta exhibiting prolonged nuclear retention and reduced intranuclear mobility especially following ligand stimulation. Prolonged nuclear retention, but not reduced intranuclear mobility, mapped to the CT7 domain of Stat3beta.
The role of chronic inflammation in cardiovascular disease and its regulation by nutrients. (2004)

Multiple risk markers for atherosclerosis and cardiovascular disease act in a synergistic way through inflammatory pathways. This article discusses some of the key inflammatory biochemical risk markers for cardiovascular disease; in particular, the role of three basic cell types affected by these risk markers (endothelial cells, smooth muscle cells, and immune cells), the crucial role of inflammatory mediators, nitric oxide balance in cardiovascular pathology, and the use of nutrients to circumvent several of these inflammatory pathways. Most risk markers for cardiovascular disease have a pro-inflammatory component, which stimulates the release of a number of active molecules such as inflammatory mediators, reactive oxygen species, nitric oxide, and peroxynitrite from endothelial, vascular smooth muscle, and immune cells in response to injury. Nitric oxide plays a pivotal role in preventing the progression of atherosclerosis through its ability to induce vasodilation, suppress vascular smooth muscle proliferation, and reduce vascular lesion formation. Nutrients such as arginine, antioxidants (vitamins C and E, lipoic acid, glutathione), and enzyme cofactors (vitamins B2 and B3, folate, and tetrahydrobiopterin) help to elevate nitric oxide levels and may play an important role in the management of cardiovascular disease. Other dietary components such as DHA/EPA from fish oil, tocotrienols, vitamins B6 and B12, and quercetin contribute further to mitigating the inflammatory process.
HEIGHTENED CD40 LIGAND GENE EXPRESSION IN PERIPHERAL CD4+ T CELLS FROM PATIENTS WITH KIDNEY ALLOGRAFT REJECTION (2000)

Peripheral CD4+ T cell CD40L gene expression increases significantly in acute rejection and CAN and may serve as a non-invasive method to monitor allograft function and determine the biological response to CsA and FK506.
Interleukin-1 (1984)

For the past 30 years, considerable experimentation on the mechanisms of host responses to infection has centered on soluble products derived from phagocytic cells. The biologic activities of some of these products include fever mediated by endogenous pyrogen (EP) and induction of acute-phase responses by leukocytic endogenous mediator (LEM), EP and LEM have been characterized and purified and appear to be closely related, if not identical, molecules. Lymphocyte-activating factor (LAF), a recently described polypeptide that acts on lymphocytes, shares many of the physical properties of EP and LEM; when incubated with lymphocytes, purified EP/LEM is indistinguishable from LAF. The term interleukin-1 (IL-1) is now used to describe LAF, EP, and LEM as a single molecule or as a family of closely related molecules, although at present there is no known sequence analysis of EP, LEM, or LAF. In this review, experimental and clinical data are presented that link mediation of host responses to infection and inflammation to the production and activity of IL-1. Cell sources and inducers of IL-1 are discussed, as are its chemical nature and mechanisms of action. In addition, the importance of IL-1 and its effects on host defense mechanisms are presented. For example, how IL-1-mediated responses, such as elevated temperature, lymphocyte activation, and systemic metabolic changes, alter the host as well as the invading microbe are considered. The conclusions of this review are (1) that IL-1 is a key mediator of host responses to microbial invasion, (2) that IL-1 represents a true hormone produced during infection and inflammation, and (3) that its biologic activities account for several aspects of the acute-phase reaction.
JOHNNY UPRIGHT (2013)

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Randomized Trials of Megestrol Acetate for AIDS-Associated Anorexia and Cachexia (1994)

Involuntary weight loss is a frequent complication of acquired immune deficiency syndrome (AIDS) and ultimately affects the majority of patients. The deleterious effects of weight loss on immune function and the physical and psychological sequelae of severe weight loss are well recognized. Megestrol acetate induces appetite stimulation and nonfluid weight gain in patients with advanced hormone nonresponsive cancers. In a pilot study, megestrol acetate produced nonfluid weight gain in patients with AIDS. Two double-blind randomized placebo-controlled trials of megestrol acetate for the treatment of AIDS-related anorexia and cachexia have shown improvements in body weight with treatment. In a multicenter trial reported by Flynn et al. at the 7th International Conference on AIDS (1992), 65 patients with AIDS and weight loss of > 10% of ideal body weight were randomized to placebo or megestrol acetate 800 mg/day. Megestrol acetate-treated patients had a significantly greater mean maximum weight gain (p = 0.027) and appetite stimulation (p = 0.021) than did placebo-treated patients. In a second, larger randomized placebo-controlled trial, 271 patients with AIDS, anorexia and cachexia were randomized to receive placebo or multiple doses of megestrol acetate at 100, 400 or 800 mg/day for 12 weeks. A maximum weight gain of at least 5 lb (2.25 kg) was observed in 64.2% of patients in the 800-mg megestrol acetate group compared with 21.4% in the placebo group (p < 0.0001). Mean maximum weight change from baseline to last evaluation was +8.3 lb in the 800-mg group and -1.1 lb in the placebo group (p < 0.001). Mean change in lean body mass from baseline to last evaluation was +2.5 lb in the 800-mg group versus -1.7 lb in the placebo group (p < 0.001). A significant improvement in appetite was seen in patients receiving 800 mg megestrol acetate compared with patients receiving placebo. No significant toxicity was observed with megestrol acetate therapy. Megestrol acetate is an effective treatment for some patients with AIDS-related anorexia and cachexia.
The Metabolic Network of Synechocystis sp. PCC 6803: Systemic Properties of Autotrophic Growth (2010)

Unicellular cyanobacteria have attracted growing attention as potential host organisms for the production of valuable organic products and provide an ideal model to understand oxygenic photosynthesis and phototrophic metabolism. To obtain insight into the functional properties of phototrophic growth, we present a detailed reconstruction of the primary metabolic network of the autotrophic prokaryote Synechocystis sp. PCC 6803. The reconstruction is based on multiple data sources and extensive manual curation and significantly extends currently available repositories of cyanobacterial metabolism. A systematic functional analysis, utilizing the framework of flux-balance analysis, allows the prediction of essential metabolic pathways and reactions and allows the identification of inconsistencies in the current annotation. As a counterintuitive result, our computational model indicates that photorespiration is beneficial to achieve optimal growth rates. The reconstruction process highlights several obstacles currently encountered in the context of large-scale reconstructions of metabolic networks.
Challenges for Private Equity-The Shifting Winds of Risk (2006)

The Federal Reserve System’s Private Equity and Merchant Banking Knowledge Center, formed at the Chicago Fed in 2000 after the passage of the Gramm–Leach–Bliley Act, sponsors an annual conference on new industry developments. This article summarizes the 2006 conference, “The Shifting Winds of Private Equity Risk,” held July 19–20.
Direct and Transmission Milling of Suspended Silicon Nitride Membranes With a Focused Helium Ion Beam (2012)

Helium ion milling of suspended silicon nitride thin films is explored. Milled squares patterned by scanning helium ion microscope are subsequently investigated by atomic force microscopy and the relation between ion dose and milling depth is measured for both the direct (side of ion incidence) and transmission (side opposite to ion incidence) regimes. We find that direct-milling depth varies linearly with beam dose while transmission-milling depth varies with the square of the beam dose, resulting in a straightforward method of controlling local film thickness.
Long‐term behavioral and neurochemical effects of chronic stress exposure in rats (2001)

Rats exposed to acute unavoidable stress develop a deficit in escaping avoidable aversive stimuli that lasts as long as unavoidable stress exposure is repeated. A 3-week exposure to unavoidable stress also reduces dopamine (DA) output in the nucleus accumbens shell (NAcS). This study showed that a 7-day exposure to unavoidable stress induced in rats an escape deficit and a decrease in extraneuronal DA basal concentration in the NAcS. Moreover, animals had reduced DA and serotonin (5-HT) accumulation after cocaine administration in the medial pre-frontal cortex (mPFC) and NAcS, compared with control animals. After a 3-week exposure to unavoidable stress, escape deficit and reduced DA output in the NAcS were still significant at day 14 after the last stress administration. In the mPFC we observed: (i) a short-term reduction in DA basal levels that was back to control values at day 14; (ii) a decrease in DA accumulation at day 3 followed by a significant increase beyond control values at day 14; (iii) a significant reduction in 5-HT extraneuronal basal levels at day 3, but not at day 14. Finally, a significant decrease in 5-HT accumulation following cocaine administration was present in the NAcS and mPFC at day 3, but not at day 14. In conclusion, a long-term stress exposure induced long-lasting behavioral sequelae associated with reproducible neurochemical modifications.
Preliminary nanopore cheminformatics analysis of aptamer-target binding strength (2007)

A preliminary statistical analysis using hidden Markov models (HMMs) indicates a clear change in the blockade pattern upon binding by the single captured aptamer. This is also consistent with the hypothesis that significant conformational changes occur during the annealing binding event. In further work the objective is to simply extend this ssDNA portion to be a well-studied approximately 80 base ssDNA aptamer, joined to the same bifunctional aptamer molecular platform.
[Antiphospholipid antibodies: specificity and mechanism of action]. (1990)

Circulating lupus-type anticoagulant is associated with an increased risk of arterial or venous thrombosis. The laboratory identification of lupus coagulant requires at least 2 different in vitro phospholipid-dependent coagulation techniques: immunological assessment based upon Elisa-type tests using pure phospholipids complements the coagulation procedure, but does not replace it. Circulating lupus anticoagulant is correlated with anti-phospholipid antibodies specific to phosphatidyl serine. Relationships between circulating lupus anticoagulant and anti-cardiolipin seem complex and are discussed. In fact, an entire family of anti-phospholipid antibodies exists, whose relationship with clinical manifestations remains to be determined. The effects of anti-phospholipid antibodies on human endothelial cells are described.
Monolithic nanofluid sieving structures for DNA manipulation (1998)

A new technique for fabricating two-dimensional artificial gels for DNA electrophoresis is presented. The technique differs from previous approaches in that the entire device is fabricated as a monolithic unit using exclusively planar processing techniques adapted from semiconductor electronics fabrication. The height of the fluid gap between the dielectric floor and ceiling is determined by the thickness of a sacrificial layer which is removed by a wet chemical etch. This allows precise control and excellent uniformity of the gap over an entire silicon wafer. Floor-to-ceiling height control better than 5 nm has been demonstrated over a 1.5 cm device. Electron beam lithography is used to define a square array of 100 nm obstructions in the sacrificial layer. Chemical vapor deposition silicon nitride is applied over the sacrificial layer. Reactive ion etching (RIE) is used to create access holes in the nitride layer, so that the sacrificial layer can be removed with a wet chemical etch. After the wet etch, the access holes are resealed with very low temperature oxide (VLTO) silicon dioxide. Finally, loading widows are opened with RIE at both ends of the device so that DNA in aqueous solution can be introduced and its motion under the influence of an electric field can be observed. The DNA molecules are labeled with a fluorescent dye and observed through the dielectric top layers with an optical microscope. The electrophoretic mobility is measured for two different DNA chain lengths, 43 and 7.2 kbase. The velocity for both DNA lengths is reported for an applied potential between 2 and 20 V over the 15 mm device. At some voltages the velocities differed by nearly a factor of 2.
Cytogenetic characterisation and proteomic profiling of the Imatinib-resistant cell line KCL22-R (2007)

Approximately 30% of chronic myeloid leukemia patients show initially no response to Imatinib, a potent inhibitor of BCR-ABL. This intrinsic resistance may be due to BCR-ABL-independent cell growth. Here we analysed the cytogenetic anomalies and the proteomic profiling in KCL22-S and KCL22-R, two Imatinib-sensitive and -resistant derivative cell lines of KCL22. A tetrasomy 8 and a non-reciprocal translocation +der(6)t(6;13)(p11.1;q12) were found only in KCL22-R as new evolved anomalies. Chromosome der(6)t(6;13) showed four variants differing in the chromatin content of 13q14-13qter including the retinoblastoma gene. Due to these sub-clones, approximately 65-79% of the Imatinib-treated KCL22-R cells showed a disomy and 21-35% a monosomy for 13q14. Imatinib removal reduced the main clone to approximately 20% in the benefit of the monosomic sub-clones. This was accompanied by an increased apoptosis rate and was revertible by Imatinib re-treatment. This effect may be connected with genes located in 13q14-qter. Proteomic profiling of the cell lines performed with ProteinChip technology (SELDI) revealed several differentially expressed proteins (n=45). In summary, we demonstrate here the complex changes on the cytogenetic and proteomic level which could be caused by Imatinib and the resistance resulting from it.
Sphingomyelin depletion in cultured cells blocks proteolysis of sterol regulatory element binding proteins at site 1 (1997)

The current studies explore the mechanism by which the sphingomyelin content of mammalian cells regulates transcription of genes encoding enzymes of cholesterol synthesis. Previous studies by others have shown that depletion of sphingomyelin by treatment with neutral sphingomyelinase causes a fraction of cellular cholesterol to translocate from the plasma membrane to the endoplasmic reticulum where it expands a regulatory pool that leads to down-regulation of cholesterol synthesis and up-regulation of cholesterol esterification. Here we show that sphingomyelinase treatment of cultured Chinese hamster ovary cells prevents the nuclear entry of sterol regulatory element binding protein-2 (SREBP-2), a membrane-bound transcription factor required for transcription of several genes involved in the biosynthesis and uptake of cholesterol. Nuclear entry is blocked because sphingomyelinase treatment inhibits the proteolytic cleavage of SREBP-2 at site 1, thereby preventing release of the active NH2-terminal fragments from cell membranes. Sphingomyelinase treatment thus mimics the inhibitory effect on SREBP processing that occurs when exogenous sterols are added to cells. Sphingomyelinase treatment did not block site 1 proteolysis of SREBP-2 in 25-RA cells, a line of Chinese hamster ovary cells that is resistant to the suppressive effects of sterols, owing to an activating point mutation in the gene encoding SREBP cleavage-activating protein. In 25-RA cells, sphingomyelinase treatment also failed to down-regulate the mRNA for 3-hydroxy-3-methylglutaryl CoA synthase, a cholesterol biosynthetic enzyme whose transcription depends on the cleavage of SREBPs. Considered together with previous data, the current results indicate that cells regulate the balance between cholesterol and sphingomyelin content by regulating the proteolytic cleavage of SREBPs.