gebhart/patrepeval huggingface dataset:
Integration of semiconductor quantum dots into nano-bio-chip systems for enumeration of CD4+ T cell counts at the point-of-need (2008)

Recent humanitarian efforts have led to the widespread release of antiretroviral drugs for the treatment of the more than 33 million HIV afflicted people living in resource-scarce settings. Here, the enumeration of CD4+ T lymphocytes is required to establish the level at which the immune system has been compromised. The gold standard method used in developed countries, based on flow cytometry, though widely accepted and accurate, is precluded from widespread use in resource-scarce settings due to its high expense, high technical requirements, difficulty in operation-maintenance and the lack of portability for these sophisticated laboratory-confined systems. As part of continuing efforts to develop practical diagnostic instrumentation, the integration of semiconductor nanocrystals (quantum dots, QDs) into a portable microfluidic-based lymphocyte capture and detection device is completed. This integrated system is capable of isolating and counting selected lymphocyte sub-populations (CD3+CD4+) from whole blood samples. By combining the unique optical properties of the QDs with the sample handling capabilities and cost effectiveness of novel microfluidic systems, a practical, portable lymphocyte measurement modality that correlates nicely with flow cytometry (R2 = 0.97) has been developed. This QD-based system reduces the optical requirements significantly relative to molecular fluorophores and the mini-CD4 counting device is projected to be suitable for use in both point-of-need and resource-scarce settings.
Data Warehouse Configuration (1997)

In the data warehousing approach to the integration of data from multiple information sources, selected information is extracted in advance and stored in a repository. A data warehouse (DW) can therefore be seen as a set of materialized views defined over the sources. When a query is posed, it is evaluated locally, using the materialized views, without accessing the original information sources. The applications using DWs require high query performance. This requirement is in conflict with the need to maintain in the DW updated information. The DW configuration problem is the problem of selecting a set of views to materialize in the DW that answers all the queries of interest while minimizing the total query evaluation and view maintenance cost. In this paper we provide a theoretical framework for this problem in terms of the relational model. We develop a method for dealing with it by formulating it as a state space optimization problem and then solving it using a...
Systematic Comparison of Fractionation Methods for In-depth Analysis of Plasma Proteomes (2012)

Discovery and validation of plasma biomarkers are quite challenging because of the high complexity and wide dynamic range of the plasma proteome. Current plasma protein profiling strategies usually use major protein immunodepletion and nanoLC-MS/MS as the first and final analytical steps, respectively, but additional fractionation is needed to detect and quantify low-abundance disease biomarkers. In this study, the performances of 1-D SDS-PAGE, peptide isoelectrofocusing, and peptide high pH reverse-phase chromatography for fractionation of immunodepleted human plasma were systematically compared by evaluating protein coverage, peptide resolution, and capacity to detect known low-abundance proteins. Trade-offs between increasing the number of fractions to improve proteome coverage and resulting decreases in throughput also were assessed. High pH reverse-phase HPLC exhibited the highest peptide resolution and yielded the best depth of analysis with detection of the largest number of known low-abundance proteins for a given level of fractionation. Another advantage of using high pH reverse-phase fractionation rather than 1-D SDS gels is that all fractionation steps except for abundant protein depletion occur at the peptide level, making this strategy more compatible with quantitative biomarker validation methods such as stable isotope dilution multiple reaction monitoring.
Focal Adhesions: Transmembrane Junctions Between The Extracellular Matrix And The Cytoskeleton (1988)

Cells organize many of their biochemical reactions in non-membrane compartments. Recent evidence has shown that many of these compartments are liquids that form by phase separation from the cytoplasm. Here we discuss the basic physical concepts necessary ...Read More
Ways to Enhance Lymphocyte Trafficking into Tumors and Fitness of Tumor Infiltrating Lymphocytes (2013)

The tumor is a hostile microenvironment for T lymphocytes. Indeed, irregular blood flow, and endothelial cell (EC) anergy that characterize most solid tumors hamper leukocyte adhesion, extravasation, and infiltration. In addition, hypoxia and reprograming of energy metabolism within cancer cells transform the tumor mass in a harsh environment that limits survival and effector functions of T cells, regardless of being induced in vivo by vaccination or adoptively transferred. In this review, we will summarize on recent advances in our understanding of the characteristics of tumor-associated neo-angiogenic vessels as well as of the tumor metabolism that may impact on T cell trafficking and fitness of tumor infiltrating lymphocytes. In particular, we will focus on how advances in knowledge of the characteristics of tumor ECs have enabled identifying strategies to normalize the tumor-vasculature and/or overcome EC anergy, thus increasing leukocyte-vessel wall interactions and lymphocyte infiltration in tumors. We will also focus on drugs acting on cells and their released molecules to transiently render the tumor microenvironment more suitable for tumor infiltrating T lymphocytes, thus increasing the therapeutic effectiveness of both active and adoptive immunotherapies.
Anterior cruciate ligament graft positioning, tensioning and twisting (1998)

This paper reports on a scientific workshop to study anterior cruciate ligament (ACL) reconstruction. The aim is to present recommendations for ACL reconstruction methods that will be of use for surgeons. A study of knee anatomy and graft placement concluded that the tibial attachment must be posterior enough to avoid graft impingement against the femur, and methods to attain this were presented. On the femur, poor graft placement leads to excessive changes of the graft attachment site separation distance as the knee flexes, and the worst case corresponds to the attachment being too far anterior. It was agreed that there were typical patterns of graft tension changes as the knee flexes, and that grafts should be tensioned close to full knee extension. A typical tensioning protocol would be 60 N tension applied at 10 degrees of flexion. It was recognised that graft remodelling caused uncontrollable tension changes post-operation. Graft twisting, to recreate the anatomical spiral of ACL fibres seen in the flexed knee, was also discussed.
Protective role of magnesium in the neutralization by antibodies of Chlamydia trachomatis infectivity (1988)

Neutralization of the infectivity of Chlamydia trachomatis was assessed by using polyclonal antisera and monoclonal antibodies (MAbs). Polyclonal antisera and a species-reactive MAb as well as a subspecies-specific MAb, both of which were directed toward the major outer membrane protein of C. trachomatis, reduced the number of chlamydial inclusion-forming units in an in vitro assay. Neutralization was dependent on the presence of complement. The species-specific MAb reacted with all 15 serovars by a microimmunofluorescence assay and a dot blot enzyme-linked immunosorbent assay with heat-treated elementary bodies. On the other hand, this same MAb reacted with all serovars, except those in the C complex, by the dot blot enzyme-linked immunosorbent assay with viable organisms and neutralized in vitro all 10 serovars tested, except those in the C complex. When neutralization assays were performed in a solution containing Mg2+, neutralization by both polyclonal antisera and MAbs was significantly reduced. A dose response to Mg2+ supplied as MgSO4 revealed that all concentrations tested from 50 to 800 microM had some effect. Concentrations of greater than or equal to 400 microM MgSO4 completely abolished neutralization at the lowest dilution of polyclonal antisera and species-reactive MAb tested. Although Mg2+ also blocked the neutralization effect of the subspecies-specific MAb, this neutralization was not as complete as that observed with the species-reactive MAb. Addition of Mg2+ to the assay over the initial 45 min of incubation of C. trachomatis with MAb and complement showed that the organisms could be rescued to some extent over the first 30 min of incubation, after which time neutralization of infectivity could not be reversed. C. trachomatis treated with Mg2+, the species-reactive MAb, and complement were lethal to mice in an in vivo toxicity and infectivity assay, whereas mice injected with organisms incubated with the same MAb and complement without Mg2+ survived.
Multihop lightwave networks: a new approach to achieve terabit capabilities (2003)

A multihop approach for achieving concurrency in distributed lightwave networks with hundreds or thousands of Gb/s throughput, even while the users are limited to rates of 1 Gb/s or lower, is described. Multihop networks avoid two serious drawbacks of standard multichannel approaches: the requirement of wavelength-agile transmitters or receivers, and pretransmission coordination between users wishing to communicate. Although transmitting a packet from one user to another may require routing the packet through intermediate network interface units, the approach's connectivity is specifically designed to achieve efficient use of the channel bandwidth, allow modular growth of the network from small to large configurations, and provide a degree of network reliability.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Insig-dependent Ubiquitination and Degradation of Mammalian 3-Hydroxy-3-methylglutaryl-CoA Reductase Stimulated by Sterols and Geranylgeraniol (2003)

The endoplasmic reticulum enzyme 3-hydroxy-3-methylglutaryl-CoA reductase produces mevalonate, which is converted to sterols and to other products, including geranylgeraniol groups attached to proteins. The enzyme is known to be ubiquitinated and rapidly degraded when sterols and nonsterol end products of mevalonate metabolism accumulate in cells. Here, we use RNA interference to show that sterol-accelerated ubiquitination of reductase requires Insig-1 and Insig-2, membrane-bound proteins of the endoplasmic reticulum that were shown previously to accelerate degradation of reductase when overexpressed by transfection. Alanine substitution experiments reveal that binding of reductase to Insigs and subsequent ubiquitination require the tetrapeptide sequence YIYF in the second membrane-spanning helix of reductase. The YIYF peptide is also found in the sterol-sensing domain of SCAP, another protein that binds to Insigs in a sterol-stimulated fashion. When lysine 248 of reductase is substituted with arginine, Insig binding persists, but the reductase is no longer ubiquitinated and degradation is markedly slowed. Lysine 248 is predicted to lie immediately adjacent to a membrane-spanning helix, suggesting that a membrane-bound ubiquitin transferase is responsible. Finally, we show that Insig-dependent, sterol-stimulated degradation of reductase is further accelerated when cells are also supplied with the 20-carbon isoprenoid geranylgeraniol, but not the 15-carbon farnesol, raising the possibility that the nonsterol potentiator of reductase regulation is a geranylgeranylated protein.
Effect of Adhesive Type and Thickness on the Lap Shear Strength (2006)

The effect of the adhesive thickness on the bond strength of single-lap adhesive joints is still not perfectly understood. The classical elastic analyses predict that the strength increases with the adhesive thickness, whereas experimental results show the opposite. Various theories have been proposed to explain this discrepancy, but more experimental tests are necessary to understand all the variables. The objective of the present study was to assess the effect of the adhesive thickness on the strength of single-lap joints for different kinds of adhesives. Three different adhesives were selected and tested in bulk. The strain to failure in tension ranged from 1.3% for the most brittle adhesive to 44% for the most ductile adhesive. The adherend selected was a high-strength steel to keep the adherends in the elastic range and simplify the analysis. Three thicknesses were studied for each adhesive: 0.2, 0.5, and 1 mm. A statistical analysis of the experimental results shows that the lap shear strength increases as the bondline gets thinner and the adhesive gets tougher.
Opportunities with combined modality therapy for selective organ preservation in muscle‐invasive bladder cancer (1996)

Combined-modality therapy for organ preservation represents an appropriate alternative to radical surgery in the management of several malignant diseases. The standard therapy for muscle-invasive bladder cancer in the United States has been radical cystectomy. Although the sequelae of radical surgery have been ameliorated somewhat by techniques for the construction of orthotopic bladders, the ideal therapy should both cure the patient of cancer and maintain a functioning natural bladder. Years of experience in Europe and Canada with bladder preservation using radiation therapy are documented. Advances in transurethral surgery technique and in the combination of radiation and chemotherapy have led to safe and effective regimens for patients with bladder cancer. Several recent trials with combined-modality therapy have established this treatment as a viable alternative to radical cystectomy in selected patients. © 1996 Wiley-Liss, Inc.
Effect of Duodenal Distension on the Pyloric Sphincter and Antrum and the Gastric Corpus: Duodenopyloric Reflex (1998)

The mechanical effect of balloon distension of the duodenum on the stomach was studied in 10 mongrel dogs with a mean weight of 14.8 +/- 3.2 kg. The response of the pyloric sphincter and antrum as well as of the corpus of the stomach to duodenal distension by a balloon filled with water in increments of 2 ml, up to 6 ml, was determined. The test was repeated after anesthetizing the pyloric sphincter and antrum and the duodenum, each at a separate time. In 5 of 10 dogs the effect of duodenal distension on the vagotomized stomach was studied. Duodenal distension with 2 ml of water produced an increase in the pyloric sphincter pressure (p < 0.05) and a decrease in the antral pressure (p < 0.05); it had no effect on corporeal pressure (p > 0.05). Distension with 4 ml and 6 ml produced the same effect as 2 ml (p > 0.05). The anesthetized pyloric sphincter and antrum did not respond to duodenal distension. Likewise, the pyloric sphincter and antrum showed no response to distension of the anesthetized duodenum or of the duodenum after vagotomy. Pyloric sphincter contraction and antral dilatation upon duodenal distension suggest a reflex relation we call the duodenopyloric reflex. This reflex appears to prevent duodenopyloric reflux. Moreover, the antrum dilates probably to accommodate more gastric contents.
Androgen Replacement in Women: A Commentary (1999)

There is increasing evidence to suggest that many postmenopausal women experience symptoms alleviated by androgen therapy and that such symptoms may be secondary to androgen deficiency. Affected women complain of fatigue, low libido, and diminished well-being, symptoms easily and frequently attributed to psychosocial and environmental factors. When such symptoms occur in the setting of low circulating bioavailable testosterone, testosterone replacement results in significant improvement in symptomatology and, hence, quality of life for the majority of women. Whether the apparent therapeutic effects of testosterone replacement are mediated by testosterone and its metabolite 5alpha- dihydrotestosterone or are a consequence of aromatization to estrogen is not known. Despite the paucity of data regarding its effects, inclusion of testosterone in postmenopausal hormone replacement regimens is not uncommon and is likely to become more widespread with the availability of preparations developed specifically for women. Other novel and even more controversial potential indications for androgen therapy in women are currently being evaluated. These include use in women with premature ovarian failure, premenopausal androgen deficiency symptoms, postmenopausal and glucocorticosteroid-related bone loss, alleviation of wasting syndrome secondary to human immunodeficiency virus infection, and management of premenstrual syndrome. The aim of this commentary is to very briefly review the rationale for the use of testosterone in women, create awareness of some of the therapeutic options available in various countries, and stimulate discussion of this important aspect of women's health.
Tumor Treating Fields Perturb the Localization of Septins and Cause Aberrant Mitotic Exit (2015)

The anti-tumor effects of chemotherapy and radiation are thought to be mediated by triggering G1/S or G2/M cell cycle checkpoints, while spindle poisons, such as paclitaxel, block metaphase exit by initiating the spindle assembly checkpoint. In contrast, we have found that 150 kilohertz (kHz) alternating electric fields, also known as Tumor Treating Fields (TTFields), perturbed cells at the transition from metaphase to anaphase. Cells exposed to the TTFields during mitosis showed normal progression to this point, but exhibited uncontrolled membrane blebbing that coincided with metaphase exit. The ability of such alternating electric fields to affect cellular physiology is likely to be dependent on their interactions with proteins possessing high dipole moments. The mitotic Septin complex consisting of Septin 2, 6 and 7, possesses a high calculated dipole moment of 2711 Debyes (D) and plays a central role in positioning the cytokinetic cleavage furrow, and governing its contraction during ingression. We showed that during anaphase, TTFields inhibited Septin localization to the anaphase spindle midline and cytokinetic furrow, as well as its association with microtubules during cell attachment and spreading on fibronectin. After aberrant metaphase exit as a consequence of TTFields exposure, cells exhibited aberrant nuclear architecture and signs of cellular stress including an overall decrease in cellular proliferation, followed by apoptosis that was strongly influenced by the p53 mutational status. Thus, TTFields are able to diminish cell proliferation by specifically perturbing key proteins involved in cell division, leading to mitotic catastrophe and subsequent cell death.
Insulin-induced activation of glycerol-3-phosphate acyltransferase by a chiro-inositol-containing insulin mediator is defective in adipocytes of insulin-resistant, type II diabetic, Goto-Kakizaki rats. (1994)

Type II diabetic Goto-Kakizaki (GK) rats were insulin-resistant in euglycemic-hyperinsulinemic clamp studies. We therefore examined insulin signaling systems in control Wistar and diabetic GK rats. Glycerol-3-phosphate acyltransferase (G3PAT), which is activated by headgroup mediators released from glycosyl-phosphatidylinositol (GPI), was activated by insulin in intact and cell-free adipocyte preparations of control, but not diabetic, rats. A specific chiro-inositol-containing inositol phosphoglycan (IPG) mediator, prepared from beef liver, bypassed this defect and comparably activated G3PAT in cell-free adipocyte preparations of both diabetic GK and control rats. A myo-inositol-containing IPG mediator did not activate G3PAT. Relative to control adipocytes, labeling of GPI by [3H]glucosamine was diminished by 50% and insulin failed to stimulate GPI hydrolysis in GK adipocytes. In contrast to GPI-dependent G3PAT activation, insulin-stimulated hexose transport was intact in adipocytes and soleus and gastrocnemius muscles of the GK rat, as was insulin-induced activation of mitogen-activated protein kinase and protein kinase C. We conclude that (i) chiro-inositol-containing IPG mediator activates G3PAT during insulin action, (ii) diabetic GK rats have a defect in synthesizing or releasing functional chiro-inositol-containing IPG, and (iii) defective IPG-regulated intracellular glucose metabolism contributes importantly to insulin resistance in diabetic GK rats.
Isomers of Metal–Organic Complex Arrays (2012)

Three metal-organic complex arrays (MOCAs) with a specific sequence of metal centers as well as that of amino acid units were synthesized. These MOCAs are also isomers exhibiting a gelation capability dependent on the location of the metal complexes in the arrays.
Lambda YES: a multifunctional cDNA expression vector for the isolation of genes by complementation of yeast and Escherichia coli mutations. (1991)

This work describes a multifunctional phage lambda expression vector system, lambda YES, designed to facilitate gene isolation from eukaryotes by complementation of Escherichia coli and Saccharomyces cerevisiae mutations. lambda YES vectors have a selection for cDNA inserts using an oligo adaptor strategy and are capable of expressing genes in both E. coli and S. cerevisiae. They also allow conversion from phage lambda to plasmid clones by using the cre-lox site-specific recombination system, referred to here as automatic subcloning. A simple method has been developed for the conversion of any plasmid into a phage lambda cDNA cloning vector with automatic subcloning capability. cDNA libraries constructed in these vectors were used to isolate genes from humans and Arabidopsis thaliana by complementation of yeast and bacterial mutations, respectively.
The effects of lead time and visual aids in TTO valuation: a study of the EQ-VT framework (2013)

Different lead-time time trade-off variants should be carefully studied in order to achieve the best measurement of health-state values using this new method.
Transcription Factor Binding and Induced Transcription Alter Chromosomal c- myc Replicator Activity (2004)

The observation that transcriptionally active genes generally replicate early in S phase and observations of the interaction between transcription factors and replication proteins support the thesis that promoter elements may have a role in DNA replication. To test the relationship between transcription and replication we constructed HeLa cell lines in which inducible green fluorescent protein (GFP)-encoding genes replaced the proximal approximately 820-bp promoter region of the c-myc gene. Without the presence of an inducer, basal expression occurred from the GFP gene in either orientation and origin activity was restored to the mutant c-myc replicator. In contrast, replication initiation was repressed upon induction of transcription. When basal or induced transcription complexes were slowed by the presence of alpha-amanitin, origin activity depended on the orientation of the transcription unit. To test mechanistically whether basal transcription or transcription factor binding was sufficient for replication rescue by the uninduced GFP genes, a GAL4p binding cassette was used to replace all regulatory sequences within approximately 1,400 bp 5' to the c-myc gene. In these cells, expression of a CREB-GAL4 fusion protein restored replication origin activity. These results suggest that transcription factor binding can enhance replication origin activity and that high levels of expression or the persistence of transcription complexes can repress it.