gebhart/patrepeval huggingface dataset:
ICAM‐1 and LFA‐1 on mouse epidermal Langerhans cells and spleen dendritic cells identify disparate requirements for activation of KLH‐specific CD4<sup>+</sup> Th1 and Th2 clones* (1993)

Expression of the adhesion molecules ICAM-1 and LFA-1 (CD11a/CD18) on mouse epidermal Langerhans cells (LC) and on spleen dendritic cells (DC) from BALB/c mice was examined by staining with specific mAb and was evaluated by flow cytometry. LC were shown to express both ICAM-1 and LFA-1, whereas spleen DC expressed only LFA-1. The contribution of these adhesion molecules to LC- or DC-induced activation of keyhole limpet hemocyanin (KLH)-specific, Iad-restricted, Th1 or Th2 clones was investigated in mAb blocking studies. At optimal doses, anti-CD11a or anti-CD18 mAb completely inhibited Th1 proliferation induced by either LC or DC. Anti-ICAM-1 also abrogated Th1 proliferation induced by LC, but only moderately reduced Th1 proliferation induced by DC. Inhibition in these experiments was specific, since isotype-matched control Ab against other Ag constitutively expressed on LC (NLDC 145) or DC (33D1) had no effect on Th1 proliferation. In marked contradistinction, the capacity of LC to present KLH to our Th2 clones was resistant to treatment with the same mAb against ICAM-1, CD11a or CD18. We conclude that interactions between ICAM-1 and LFA-1 on epidermal LC and LFA-1 on spleen DC with their respective ligands on our Th1 clones are required for optimal presentation of protein Ag to Th1. Our results also indicate that neither ICAM-1 nor LFA-1 is required for the analogous activation of our Th2 clones by LC.
Single Molecule Fluorescence Study of the Bacillus thuringiensis Toxin Cry1Aa Reveals Tetramerization (2011)

Pore-forming toxins constitute a class of potent virulence factors that attack their host membrane in a two- or three-step mechanism. After binding to the membrane, often aided by specific receptors, they form pores in the membrane. Pore formation either unfolds a cytolytic activity in itself or provides a pathway to introduce enzymes into the cells that act upon intracellular proteins. The elucidation of the pore-forming mechanism of many of these toxins represents a major research challenge. As the toxins often refold after entering the membrane, their structure in the membrane is unknown, and key questions such as the stoichiometry of individual pores and their mechanism of oligomerization remain unanswered. In this study, we used single subunit counting based on fluorescence spectroscopy to explore the oligomerization process of the Cry1Aa toxin of Bacillus thuringiensis. Purified Cry1Aa toxin molecules labeled at different positions in the pore-forming domain were inserted into supported lipid bilayers, and the photobleaching steps of single fluorophores in the fluorescence time traces were counted to determine the number of subunits of each oligomer. We found that toxin oligomerization is a highly dynamic process that occurs in the membrane and that tetramers represent the final form of the toxins in a lipid bilayer environment.
p<i>K</i><sub>a</sub> Coupling at the Intein Active Site: Implications for the Coordination Mechanism of Protein Splicing with a Conserved Aspartate (2011)

Protein splicing is a robust multistep posttranslational process catalyzed by inteins. In the Mtu RecA intein, a conserved block-F aspartate (D422) coordinates different steps in protein splicing, but the precise mechanism is unclear. Solution NMR shows that D422 has a strikingly high pK(a) of 6.1, two units above the normal pK(a) of aspartate. The elevated pK(a) of D422 is coupled to the depressed pK(a) of another active-site residue, the block-A cysteine (C1). A C1A mutation lowers the D422 pK(a) to normal, while a D422G mutation increases the C1 pK(a) from 7.5 to 8.5. The pK(a) coupling and NMR structure determination demonstrate that protonated D422 serves as a hydrogen bond donor to stabilize the C1 thiolate and promote the N-S acyl shift, the first step of protein splicing. Additionally, in vivo splicing assays with mutations of D422 to Glu, Cys, and Ser show that the deprotonated aspartate is essential for splicing, most likely by deprotonating and activating the downstream nucleophile in transesterification, the second step of protein splicing. We propose that the sequential protonation and deprotonation of the D422 side chain is the coordination mechanism for the first two steps of protein splicing.
Genetic Incorporation of a Small, Environmentally Sensitive, Fluorescent Probe into Proteins in <i>Saccharomyces cerevisiae</i> (2009)

Here, we report that the fluorescent amino acid, 3-(6-acetylnaphthalen-2-ylamino)-2-aminopropanoic acid (Anap), can be genetically incorporated into proteins in yeast with excellent selectivity and efficiency by means of an orthogonal tRNA/aminoacyl-tRNA synthetase pair. This small, environmentally sensitive fluorophore was site-specifically incorporated into Escherichia coli glutamine binding protein and used to directly probe local structural changes caused by ligand binding. The small size of Anap and the ability to introduce it by simple mutagenesis at defined sites in the proteome make it a useful local probe of protein structure, molecular interactions, protein folding, and localization.
Complementary lattice arrays for coded aperture imaging (2016)

In this work, we propose the concept of complementary lattice arrays in order to enable a broader range of designs for coded aperture imaging systems. We provide a general framework and methods that generate richer and more flexible designs compared to the existing techniques. Besides this, we review and interpret the state-of-the-art uniformly redundant array designs, broaden the related concepts, and propose new design methods.
Improving data ferrying by iteratively learning the radio frequency environment (2014)

A data ferry enables communication in sparse sensor networks by combining physical movement with wireless relaying of data. Optimizing an unmanned aircraft's motion and communication link scheduling, however, requires knowledge of the communication environments through which it moves. Aspects of the radio frequency environment can be opportunistically learned through the process of communicating with sensor nodes while ferrying, allowing models of the radio environment to be improved. This work analyzes the integration of ferry optimization with using a Gaussian process to learn the radio environment. The unmanned aircraft's trajectory is initially optimized with an a priori model. After flying one period of the trajectory, RF variations observed by the ferry are used to train a Gaussian process and improve the estimate of the environment. Through this iterative process, ferry performance improves rapidly, achieving 80% of optimal within 4 iterations, and 93% after 9 iterations, as the Gaussian process is able to converge rapidly to the true radio frequency environment.
An introduction to stem cells (2002)

1998 saw the publication of two papers describing the growth in vitro of human embryonic stem (ES) cells derived either from the inner cell mass (ICM) of the early blastocyst or the primitive gonadal regions of early aborted fetuses. Work on murine ES cells over many years had already established the amazing flexibility of ES cells, essentially able to differentiate into almost all cells that arise from the three germ layers. The realization of such pluripotentiality (see below) has, of course, resulted in the field of stem cell research going into overdrive, the establishment of many new biotechnology companies (http://www.stemcellresearchnew.com/catalog1677.html), and a genuine belief that stem cell research will deliver a revolution in terms of how we treat cardiovascular disease, neurodegenerative disease, cancer, diabetes, and the like. However, many people believe that early human embryos should be accorded the same status as any sentient being and thus their 'harvesting' for stem cells is morally unjustifiable. With this in mind, other sources of malleable stem cells have been sought. In the adult, organ formation and regeneration was thought to occur through the action of organ- or tissue-restricted stem cells (i.e. haematopoietic stem cells giving rise to all the cells of the blood, neural stem cells making neurons, astrocytes, and oligodendrocytes). However, it is now believed that stem cells from one organ system, for example the haematopoietic compartment can develop into the differentiated cells within another organ system, such as the liver, brain or kidney. Thus, certain adult stem cells may turn out be as malleable as ES cells and so also be useful in regenerative medicine. This brief overview summarizes the important attributes of tissue-based stem cells and clarifies the terms used.
Image processing techniques for underwater acoustic image enhancement (2003)

Underwater acoustic images are often dominated by noise, which obscures signals of interest. When the spatial character of the noise differs from that of the signal, image processing techniques can be employed to enhance the image. In underwater acoustic time-bearing displays, the signals of interest form continuous tracks, while noise often takes on the form of isolated speckle. In this case, a speckle suppression technique related to the Hough transform can be used to reduce the noise and enhance the tracks. The presentation will include a discussion of variations of the technique that are under consideration, as well as considerations of optimum values for the input parameters.
A Virulent Nonencapsulated Haemophilus influenzae (1996)

Nontypeable Haemophilus influenzae strain INT1 was isolated from the blood of a young child with clinical signs of meningitis following acute otitis media. No immunologic or anatomic predisposition of this child for invasive bacterial infection with an unusual organism was documented. Sensitive ELISA proved the absence of intra- or extracellular capsular polysaccharide production by INT1 and Southern blot analysis confirmed the lack of an intact capsulation (cap) gene locus within the chromosome. Nevertheless, INT1 established bacteremia and meningitis in infant and weanling rat models of invasive H. influenzae infection. High-molecular-weight DNA isolated from INT1 was shown to confer an invasive phenotype on transformation of a nonencapsulated, avirulent laboratory strain of H. influenzae. Together these findings imply the presence of one or more as-yet-undiscovered, noncapsular virulence factors of H. influenzae that are capable of mediating invasive disease and resistance to immunologic clearance.
Translational Research in Spinal Cord Injury: A Survey of Opinion from the SCI Community (2009)

Much like our colleagues studying neuroprotection for acute stroke, we in the spinal cord injury (SCI) community have witnessed the preclinical emergence of numerous promising neuroprotective and neuro-regenerative treatments that have then disappointingly failed to demonstrate convincing efficacy in clinical trials. In contrast to the stroke field, the SCI community lacks guidelines to steer the preclinical development of therapies and maximize their chance of success prior to translation into expensive and laborious clinical trials. We conducted a survey of the SCI research community to garner perspectives on the question of what preclinical evidence was required before translating an experimental treatment into clinical trials. The opinions of the 324 respondents about what constitutes necessary preclinical evidence before moving to human SCI trials revealed strong support for the demonstration of efficacy in large-animal models, cervical injury models, and for independent replication of promising results. Marked differences exist between the sentiments of the respondents and the translational experience of our field. A framework for guiding the preclinical development of novel therapies prior to human translation would be helpful for ensuring clinical success. Greater dialogue on this issue is necessary to improve our chances of successfully bringing effective treatments to patients with this devastating injury.
Yttrium 90 Microsphere Selective Internal Radiation Treatment of Hepatic Colorectal Metastases (2007)

Selective internal radiation treatment is a promising new modality in the treatment of patients with hepatic colorectal cancer metastases as part of a multimodality approach. A chemo-selective internal radiation treatment neoadjuvant approach has a potential to improve therapeutic outcomes. Clinical studies in neoadjuvant and salvage settings are needed for more concrete outcome data and design of optimal multimodality treatment strategies.
Constitutive expression of the granulocyte-macrophage colony-stimulating factor gene in acute myeloblastic leukemia. (1987)

Expression of the granulocyte-macrophage colony-stimulating factor (GM-CSF) gene was studied by Northern blot analysis in normal human hematopoietic cells and a series of leukemias. GM-CSF messenger (m)RNA was detected in activated T cells, but not in normal bone marrow cells, monocytes, or nonactivated T cells. In contrast, leukemic cells from 11 of 22 cases of acute myeloblastic leukemia expressed GM-CSF transcripts. Biologically active CSF was detected in supernatant conditioned by 6 of these 11 leukemias. Expression of the GM-CSF gene was not detected in "common" (pre-B cell) acute lymphoblastic leukemia (11 cases tested) or chronic myeloid leukemia (4 cases tested). These results show that the GM-CSF gene is constitutively expressed in a subset of patients with AML, and further suggest that expression of this gene could contribute to the abnormal growth properties characteristic of AML.
Technology Development of Coal-based Methanol-to-Olefins in China (2010)

The development status of coal-based methanol-to-olefins at home and abroad is discussed.Its technical feasibility and development necessity are analyzed. It is pointed out that the broad market prospects to develop coal-based methanol-to-olefins in China are promising.
An Overview of Solid-State Integrated Circuit Amplifiers in the Submillimeter-Wave and THz Regime (2011)

We present an overview of solid-state integrated circuit amplifiers approaching terahertz frequencies based on the latest device technologies which have emerged in the past several years. Highlights include the best reported data from heterojunction bipolar transistor (HBT) circuits, high electron mobility transistor (HEMT) circuits, and metamorphic HEMT (mHEMT) amplifier circuits. We discuss packaging techniques for the various technologies in waveguide modules and describe the best reported noise figures measured in these technologies. A consequence of THz transistors, namely ultra-low-noise at cryogenic temperatures, will be explored and results presented. We also present a short review of power amplifier technologies for the THz regime. Finally, we discuss emerging materials for THz amplifiers into the next decade.
A Study of Changing Trends and Patterns of Poisoning at Bangalore (2012)

A retrospective analysis of poisoning deaths was conducted at Department of forensic medicine, Kempegowda Institute of medical sciences and research centre, Bangalore over a period of five years (January2005-December 2009).Out of the total 2145 autopsies conducted in the mentioned period, deaths due to poisoning comprised 11.7% cases. The data was analyzed with respect to age, sex, marital status, motive and type of poisoning. It was observed that the incidence of poisoning was highest in the age group of 21-30years (33.7%) followed by 31-40years (22.6%). Male (67.8%) preponderance was more over female (32.1%) and married (61.1%) outnumbered the unmarried (38.9%) in both sexes. The most common type of poisons consumed were organophosphorus (53.2%) followed by over the counter medications (17%). The common reasons of consuming poison were financial constraints (21.4%) followed by ill health (15.55%). This study examines the general pattern and multiple factors associated with poisoning deaths. This rising number of deaths due to poisoning should be addressed immediately and efforts should be directed to reduce this catastrophe.
Regional haemodynamic effects of prolonged infusions of human α‐calcitonin gene‐related peptide in conscious, Long Evans rats (1991)

1. Haemodynamic measurements were made in conscious, Long Evans rats chronically instrumented for the assessment of changes in regional blood flows (renal, mesenteric and hindquarters, or internal and common carotid) and systemic arterial blood pressure and heart rate, before, during and after 3 day infusions of vehicle or human alpha-calcitonin gene-related peptide (CGRP) (1.5 or 15 nmol kg-1 h-1). 2. In animals with renal, mesenteric and hindquarters flow probes (n = 8), during the first day of infusion of human alpha-CGRP (1.5 nmol kg-1 h-1) there was sustained tachycardia and hypotension, a sustained reduction in renal flow, a transient reduction in mesenteric flow and a relatively well-maintained increase in hindquarters flow. All these effects were significantly different from the changes seen in vehicle-infused rats (n = 8), but calculation of vascular conductances showed only the late mesenteric vasodilatation and the sustained hindquarters vasodilatation were different from the changes in vehicle-infused rats. However, by the second day of infusion and thereafter cardiovascular variables in the animals receiving vehicle and those receiving human alpha-CGRP were not different. 3. Nine animals instrumented with probes to monitor changes in internal and common carotid haemodynamics initially received human alpha-CGRP infused at a rate of 1.5 nmol kg-1 h-1. Three of these animals still showed some response to the human alpha-CGRP (tachycardia, hypotension, hyperaemic vasodilatation) throughout the second day of infusion and hence were taken through the 3 day infusion protocol. When the infusion was stopped on the fourth day all these animals showed reversal of the effects of human alpha-CGRP. 4. The results indicate substantial inter-individual variation in the haemodynamic effects of prolonged infusions of human alpha-CGRP in conscious, Long Evans rats. However, since increasing the dose of human alpha-CGRP overcame the desensitization, it is feasible that, in the clinical setting, maintained increases in internal carotid blood flow could be achieved by individually-adjusted infusions of human alpha-CGRP.
Use of fat-suppressed T2 -weighted sagittal images after infusion of excess saline into the subarachnoid space as a new diagnostic modality for cerebrospinal fluid hypovolemia: technical note (2015)

The diagnosis of CSF hypovolemia remains controversial. The primary diagnostic factor relies on confirmation of leakage of the CSF based on reduced spinal fluid pressure. Determining the specific leakage site is the most important issue for effective treatment but remains a difficult task. Although CT myelography, radioisotope cisternography, and MRI are commonly performed in the diagnosis of CSF hypovolemia, these techniques can rarely identify the precise leakage site. Therefore, an epidural blood patch is performed in the lumbar spine in many cases. This study reports a new diagnostic modality that can help to confirm the leakage site. Fat-suppressed T2-weighted sagittal images were compared before and after the infusion of 20 ml of saline into the subarachnoid space of the lumbar region to detect the specific leakage site with high probability. Three patients were successfully treated by the epidural blood patch based on data obtained with the new diagnostic modality. Two patients were treated in the cervical region and 1 in the lumbar region. The use of fat-suppressed T2-weighted sagittal images after saline infusion could be a relevant diagnostic modality compared with images obtained by CT myelography, radioisotope cisternography, and ordinary MRI to achieve accurate diagnosis and effective treatment of patients with CSF hypovolemia.
Minimized response time of optical emission and mass spectrometric signals for optimized endpoint detection (1996)

The response times of optical emission spectroscopy (OES) and mass spectrometry (MS) have been measured for plasma etching of III–V heterostructures. For the Ga optical emission signal at 417.2 nm, a response time as fast as 0.2 s was obtained. The minimum response time of the 145AsCl+2 partial pressure, measured by MS, was found to be 0.9 s. The saturation times of the optical emission signal and the partial pressure signal have been shown to be related to the residence time of etch gases by varying the total gas flow rate and the chamber pressure. Decreasing residence time by reducing the pressure from 6 to 2 mTorr and maintaining a constant flow rate caused the saturation time of the Ga emission signal at 417.2 nm to decrease from 7 to 3 min. The 145AsCl+2 partial pressure signal saturated before the Ga emission signal. Endpoint detection for etching an AlInAs emitter and stopping on a GaInAs base of a heterojunction bipolar transistor was studied. Algorithms which monitor the change in Ga emission intensity have been developed to automatically stop the emitter etch with ∼2 nm of the GaInAs base layer removed. Additionally, etching of GaInAs on an InP substrate was studied and the signal from OES detected the endpoint before the MS signal did due to the faster response time.
<sup>11</sup>C-NS14492 as a Novel PET Radioligand for Imaging Cerebral α7 Nicotinic Acetylcholine Receptors: In Vivo Evaluation and Drug Occupancy Measurements (2011)

We report here that (11)C-NS14492 is the first, to our knowledge, PET radioligand for α(7)nAChR showing a dose-dependent decline in cerebral binding after receptor blockade. This compound is considered a promising PET tracer for in vivo measurements of α(7)nAChR binding in the human brain.
BET bromodomain inhibition enhances T cell persistence and function in adoptive immunotherapy models (2016)

Adoptive immunotherapy is a potentially curative therapeutic approach for patients with advanced cancer. However, the in vitro expansion of antitumor T cells prior to infusion inevitably incurs differentiation towards effector T cells and impairs persistence following adoptive transfer. Epigenetic profiles regulate gene expression of key transcription factors over the course of immune cell differentiation, proliferation, and function. Using comprehensive screening of chemical probes with defined epigenetic targets, we found that JQ1, an inhibitor of bromodomain and extra-terminal motif (BET) proteins, maintained CD8+ T cells with functional properties of stem cell-like and central memory T cells. Mechanistically, the BET protein BRD4 directly regulated expression of the transcription factor BATF in CD8+ T cells, which was associated with differentiation of T cells into an effector memory phenotype. JQ1-treated T cells showed enhanced persistence and antitumor effects in murine T cell receptor and chimeric antigen receptor gene therapy models. Furthermore, we found that histone acetyltransferase p300 supported the recruitment of BRD4 to the BATF promoter region, and p300 inhibition similarly augmented antitumor effects of the adoptively transferred T cells. These results demonstrate that targeting the BRD4-p300 signaling cascade supports the generation of superior antitumor T cell grafts for adoptive immunotherapy.