gebhart/patrepeval huggingface dataset:
Imaging Spectrometers for Fluorescence and Raman Microscopy: Acousto-Optic and Liquid Crystal Tunable Filters (1994)

Acousto-optic tunable filters (AOTF) and liquid crystal tunable filters (LCTF) are evaluated for their suitability as fluorescence microscopy imaging spectrometers. AOTFs are solid-state birefringent crystals that provide an electronically tunable spectral notch passband in response to an applied acoustic field. LCTFs also provide a notch passband that can be controlled by incorporating liquid crystal waveplate retarders within a Lyot birefringent filter. In this paper, spectroscopic performance and imaging quality are contrasted by evaluation of model systems. Studies include transmission imaging of standard resolution targets, multispectral fluorescence emission imaging of tagged polystyrene microspheres, and immunofluorescence imaging of neurotransmitters within rat-brainstem thin sections. In addition, the first use of LCTFs for Raman microscopy is demonstrated. Raman microscopy is a noninvasive spectral imaging technique that can provide chemically significant image contrast complementary to fluorescence microscopy without the use of stains or tags.
Rate control for communication networks: shadow prices, proportional fairness and stability (1998)

This paper analyses the stability and fairness of two classes of rate control algorithm for communication networks. The algorithms provide natural generalisations to large-scale networks of simple additive increase/multiplicative decrease schemes, and are shown to be stable about a system optimum characterised by a proportional fairness criterion. Stability is established by showing that, with an appropriate formulation of the overall optimisation problem, the network's implicit objective function provides a Lyapunov function for the dynamical system defined by the rate control algorithm. The network's optimisation problem may be cast in primal or dual form: this leads naturally to two classes of algorithm, which may be interpreted in terms of either congestion indication feedback signals or explicit rates based on shadow prices. Both classes of algorithm may be generalised to include routing control, and provide natural implementations of proportionally fair pricing.
Fiber-optic add-drop device based on a silica microsphere-whispering gallery mode system (1999)

An all-optical passive four-port system including a fused silica microsphere and two tapered fibers is proposed and demonstrated for the application as a channel adding-dropping device. It is shown that channels can be selectively exchanged between two fibers by coupling to a whispering gallery mode resonance in the microsphere. Finesse in excess of 11150 is measured for the loaded whispering gallery modes.
<title>Virtual Sensors</title> (1995)

Virtual sensors are a software abstraction that permit application programs to have a simple and consistent view of input devices. Using virtual sensors we can substitute devices at any time before or during an application's execution. Additionally, virtual sensors allow an application to treat computationally constructed data as if it came from a real device. Examples of such constructed device data include data filtering, data fusion from two or more detectors, and phantom device data by combining data from real device inputs using a set of constraints.
Modulation of the leader peptide sequence of the HLA-E gene up-regulates its expression and down-regulates natural killer cell-mediated swine endothelial cell lysis1 (2002)

The co-expression of HLA-G1 and HLA-E molecules with the modified genes has potential for use in preventing xenograft rejection, as mediated by human NK cells.
Occupancy Detection from Electricity Consumption Data (2013)

Detecting when a household is occupied by its residents is fundamental to enable a number of home automation applications. Current systems for occupancy detection usually require the installation of dedicated sensors, like passive infrared sensors, magnetic reed switches, or cameras. In this paper, we investigate the suitability of digital electricity meters -- which are already available in millions of households worldwide -- to be used as occupancy sensors. To this end, we have collected fine-grained electricity consumption data along with ground-truth occupancy information for 5 households during a period of about 8 months. Our results show that using common classification methods it is possible to achieve occupancy detection accuracies of more than 80%.
QoS with differentiated services (2002)

This paper describes the fundamental components of quality of service (QoS) and how they can be supported through various solutions based on the Internet protocol (IP). We consider and contrast the QoS efforts undertaken by the Internet Engineering Task Force (IETF) in the Integrated Services and Differentiated Services working groups. We then describe the integrated services model, evaluate differentiated services, and discuss how the latter is expected to evolve.
Proteases of cell adhesion proteins in cancer. (1993)

Neoplastic cells elaborate a vast array of proteases that enable them to proteolytically digest underlying adhesion molecules. In doing this, the tumor cell disrupts the adhesive interactions holding it in place so it is free to degrade and migrate through the basement membrane and interstitial stroma resulting in invasion and ultimately metastasis. Invasive cells elaborate specialized membrane protrusions, invadopodia, that actively degrade the underlying substratum. Evidence indicates that integral membrane proteases and receptors for secreted proteases are present on these surface protrusions. All the major classes of secreted proteases are reported to associate with the plasma membrane. Interactions between proteases occurring at the plasma membrane may result in proenzyme activation. It is possible that various proteases in close proximity to each other on the plasma membrane could interact in a proteolytic cascade resulting in in vivo activation, and the subsequent degradation of adhesion proteins.
Transcatheter Closure of Atrial Septal Defects (1992)

Transcatheter closure of atrial septal defects using a double-umbrella (clamshell) device can now be performed during an overnight hospital stay with little morbidity and no mortality. The initial 2-yr experience with anesthetic care for the procedure was collected and subsequently analyzed. Primary anesthetic care was given in 118 cases and urgent anesthetic intervention was required in another four cases. Anesthesia with spontaneous ventilation in patients with unprotected airways using intravenous ketamine and midazolam (average cumulative doses 1.4 and 0.17 mg.kg-1.h-1, respectively) was used in 93 cases (77%); mean maximum PaCO2 value was 41 +/- 6 mm Hg. In 29 patients (23%) tracheal intubation and muscle paralysis were used to facilitate control of airway and ventilation. Anesthetic-related complications occurred in three patients: ventilatory compromise developed in two patients in the spontaneous ventilation group and one patient experienced awareness during endotracheal anesthesia with paralysis. Procedural complications that altered anesthetic management were more frequent, including embolization of the clamshell device requiring surgical retrieval in two of six embolizations, intracardiac air embolization (four cases), tricuspid regurgitation (one case), device malplacement requiring late operation (one case), and transient brachial plexus injury (three cases). Anesthesia for transcatheter atrial septal defect closure allows precise device placement, prompt control of hemodynamic complications, and transesophageal echocardiographic monitoring of device placement. Although general anesthesia with spontaneous ventilation using ketamine and midazolam was usually safe and effective, tracheal intubation for control of airway and ventilation was sometimes necessary for safety and for optimal operating conditions. Familiarity with transcatheter closure techniques and close communication with the catheterization team is essential to minimize and treat associated complications.(ABSTRACT TRUNCATED AT 250 WORDS)
Mutational analysis of the CD2/CD58 interaction: the binding site for CD58 lies on one face of the first domain of human CD2. (1993)

The adhesion interaction between the immunoglobulin superfamily molecules CD2 and CD58 (lymphocyte function-associated antigen 3) plays an important role in T cell and natural killer cell interaction with various antigen-presenting and target cells. Determination of the solution structure of rat CD2 domain 1 has allowed a model of human CD2 domain 1 to be generated, and a series of mutants based on this model have been made. Residues of domain 1 of human CD2 predicted to be solvent exposed were substituted with the equivalent residues present in the rat CD2 molecule. The ability of these mutants to mediate rosetting with human and sheep erythrocytes was studied. Results show that the binding site of CD2 for both human and sheep CD58 maps to the beta sheet containing beta strands CC'C"F and G. Residues K34 and E36 in beta strand C, R48 and K49 in beta strand C', and K91 and N92 in the loop connecting beta strands F and G are shown to be critical in the interaction. The data support the proposition that the interaction between CD2 and CD58 involves the major beta sheet face of CD2.
Fitness Costs Limit Viral Escape from Cytotoxic T Lymphocytes at a Structurally Constrained Epitope (2004)

The intense selection pressure exerted by virus-specific cytotoxic T lymphocytes (CTL) on replicating human immunodeficiency virus and simian immunodeficiency virus results in the accumulation of CTL epitope mutations. It has been assumed that fitness costs can limit the evolution of CTL epitope mutations. However, only a limited number of studies have carefully examined this possibility. To explore the fitness costs associated with viral escape from p11C, C-M-specific CTL, we constructed a panel of viruses encoding point mutations at each position of the entire p11C, C-M epitope. Amino acid substitutions at positions 3, 4, 5, 6, 7, and 9 of the epitope significantly impaired virus replication by altering virus production and Gag protein expression as well as by destabilizing mature cores. Amino acid substitutions at position 2 of the epitope were tolerated but required reversion or additional compensatory mutations to generate replication-competent viruses. Finally, while amino acid substitutions at positions 1 and 8 of the p11C, C-M epitope were functionally tolerated, these substitutions were recognized by p11C, C-M-specific CTL and therefore provided no selection advantage for the virus. Together, these data suggest that limited sequence variation is tolerated by the region of the capsid encoding the p11C, C-M epitope and therefore that only a very limited number of mutations can allow successful viral escape from the p11C, C-M-specific CTL response.
Modification of milk composition. (1990)

Revolutionary new opportunities for the modification of milk composition have been created by the development of methods for gene transfer and targeted mutation of genes may extend the range of opportunities still further. Exploitation of these opportunities depends upon selection and cloning of milk protein genes and identification of the sequences that govern tissue-specific hormonally induced expression in the mammary gland. Fragments of the ovine beta-lactoglobulin gene fused to cDNA for the human therapeutic proteins clotting factor IX and alpha-1 antitrypsin have directed production of these proteins in the milk of transgenic mice and sheep. Factor IX was biologically active and co-migrated with authentic proteins, but was present at too low a concentration for commercial exploitation. Recent observations suggest that fusion genes containing genomic clones direct production of higher concentrations of protein. Mouse whey acidic protein genomic sequences also directed production of low concentrations of human tissue plasminogen activator in the milk of transgenic mice. Targeted expression of this kind may be used for the production of therapeutic and industrial proteins, to increase the concentration or modify the nature of milk proteins, reduce the concentration of lactose, change the composition of fat or direct production of bacteriocidal proteins in milk in order to combat mastitis.
The phenotype of normal, reactive and malignant plasma cells. Identification of "many and multiple myelomas" and of new targets for myeloma therapy. (2006)

The aim of this review is to integrate non-exhaustive relevant data on the phenotype of human plasma cells (PC), including normal, reactive and malignant (multiple myeloma, MM) PC. This review focuses on (i) a universal marker of both normal and malignant plasma cells, CD138; (ii) markers related to malignancy i.e., CD19, CD27, CD28, and CD56; (iii) markers associated with signaling and severity of MM (CD45, CD221). Finally, this review presents data from normal PC up to human myeloma cell lines in order to: (i) define different entities of MM based on expression of CD19, CD20, CD27 and CD117; and (ii) identify new therapeutic targets.
In vivo leukemogenic potential of an interleukin 7 receptor α chain mutant in hematopoietic stem and progenitor cells (2013)

Somatic gain-of-function mutations in interleukin 7 receptor α chain (IL7Rα) have been described in pediatric T and B acute lymphoblastic leukemias (T/B-ALLs). Most of these mutations are in-frame insertions in the extracellular juxtamembrane-transmembrane region. By using a similar mutant, a heterozygous in-frame transmembrane insertional mutation (INS), we validated leukemogenic potential in murine hematopoietic stem/progenitor cells, using a syngeneic transplantation model. We found that ectopic expression of INS alone in hematopoietic stem/progenitor cells caused myeloproliferative disorders, whereas expression of INS in combination with a Notch1 mutant led to the development of much more aggressive T-ALL than with wild-type IL7Rα. Furthermore, forced expression of INS in common lymphoid progenitors led to the development of mature B-cell ALL/lymphoma. These results demonstrated that INS has significant in vivo leukemogenic activity and that the lineage of the resulting leukemia depends on the developmental stage in which INS occurs, and/or concurrent mutations.
Structures of DNA‐binding mutant zinc finger domains: Implications for DNA binding (1993)

Studies of Cys2-His2 zinc finger domains have revealed that the structures of individual finger domains in solution determined by NMR spectroscopy are strikingly similar to the structure of fingers bound to DNA determined by X-ray diffraction. Therefore, detailed structural analyses of single finger domains that contain amino acid substitutions known to affect DNA binding in the whole protein can yield information concerning the structural ramifications of such mutations. We have used this approach to study two mutants in the N-terminal finger domain of ADR1, a yeast transcription factor that contains two Cys2-His2 zinc finger sequences spanning residues 102-159. Two point mutants at position 118 in the N-terminal zinc finger (ADR1b: 102-130) that adversely affect the DNA-binding activity of ADR1 have previously been identified: H118A and H118Y. The structures of wild-type ADR1b and the two mutant zinc finger domains were determined using two-dimensional nuclear magnetic resonance spectroscopy and distance geometry and were refined using a complete relaxation matrix method approach (REPENT) to improve agreement between the models and the nuclear Overhauser effect spectroscopy data from which they were generated. The molecular architecture of the refined wild-type ADR1b domain is presented in detail. Comparisons of wild-type ADR1b and the two mutants revealed that neither mutation causes a significant structural perturbation. The structures indicate that the DNA binding properties of the His 118 mutants are dependent on the identity of the side chain at position 118, which has been postulated to make a direct DNA contact in the wild-type ADR1 protein. The results suggest that the identity of the side chain at the middle DNA contact position in Cys2-His2 zinc fingers may be changed with impunity regarding the domain structure and can affect the affinity of the protein-DNA interaction.
An in vivo analysis of the localisation and interactions of human p66 DNA polymerase δ subunit (2005)

We have defined the regions of p66 required for its interaction with PCNA and the p50 polymerase subunit. We demonstrate a functional link between PCNA interaction and localisation to replication foci and show that there is a direct interaction between p66 and PCNA in living cells during DNA replication. The dominant negative effect upon growth resulting from expression of p66 sub-domains confirms that the p66-PCNA interaction is essential in vivo.
DcE2F, a Functional Plant E2F-like Transcriptional Activator from Daucus carota (2000)

In animal cells the progression of the cell cycle through G(1)/S transition and S phase is under the control of the pRB/E2F regulatory pathway. The E2F transcription factors are key activators of genes coding for several regulatory proteins and for enzymes involved in nucleotide and DNA synthesis. In this report we have detected the presence of E2F-like DNA binding activities in carrot nuclear extracts, and we have isolated a carrot cDNA (DcE2F) encoding a plant E2F homologue. The DcE2F gene is expressed in proliferating cells and is induced during the G(1)/S transition of the cell cycle. Supershift experiments using anti-DcE2F antiserum have confirmed that the DcE2F protein is a component of the carrot E2F-like nuclear activities. DNA binding assays have demonstrated that the DcE2F protein can recognize a canonical E2F cis-element in association with a mammalian DP protein. Furthermore, transactivation assays have revealed that DcE2F is a functional transcription factor that can transactivate, together with a DP partner, an E2F-responsive reporter gene in both plant and mammalian cells.
Timed Ablation of Regulatory CD4+ T Cells Can Prevent Murine AIDS Progression (2004)

We describe successful immunotherapy of murine AIDS (MAIDS) in C57BL/6J mice based on the elimination of replicating CD4(+) regulator T cells. We demonstrate that a single injection of the antimitotic drug vinblastine (Vb) given 14 days postinfection (p.i.) with LP-BM5 can prevent MAIDS progression. Treatment with anti-CD4 mAb at 14 days p.i. is similarly able to prevent MAIDS. Treatment at other time points with Vb or anti-CD4 mAb is ineffective. The effect is based on ablation of a replicating dominantly suppressive CD4(+) T cell population, as indicated by adoptive transfer and in vivo depletion experiments using mAbs against CD4 as well as combinations of mAbs against the known regulatory cell surface markers CD25, GITR, and CTLA-4. Cell surface marker analysis shows a population of CD4(+)CD25(+) cells arising shortly before day 14 p.i. Cytokine analyses show a peak in IL-10 production from day 12 to day 16 p.i. MAIDS-infected mice also have CD4(+) T cells with significantly higher expression levels of CD38 and particularly CD69, which have been demonstrated to be regulator T cell markers in the Friend retroviral model. The immunotherapy appears to prevent disease progression, although no protection against reinfection with LP-BM5 is generated. These data define a new therapy for murine retroviral infection, which has potential for use in other diseases where T regulator cell-mediated immunosuppression plays a role in the disease process.
Identification of Catalytic Residues of Ca2+-independent 1,2-α-d-Mannosidase from Aspergillus saitoi by Site-directed Mutagenesis (2003)

The roles of six conserved active carboxylic acids in the catalytic mechanism of Aspergillus saitoi 1,2-alpha-d-mannosidase were studied by site-directed mutagenesis and kinetic analyses. We estimate that Glu-124 is a catalytic residue based on the drastic decrease of kcat values of the E124Q and E124D mutant enzyme. Glu-124 may work as an acid catalyst, since the pH dependence of its mutants affected the basic limb. D269N and E411Q were catalytically inactive, while D269E and E411D showed considerable activity. This indicated that the negative charges at these points are essential for the enzymatic activity and that none of these residues can be a base catalyst in the normal sense. Km values of E273D, E414D, and E474D mutants were greatly increased to 17-31-fold wild type enzyme, and the kcat values were decreased, suggesting that each of them is a binding site of the substrate. Ca2+, essential for the mammalian and yeast enzymes, is not required for the enzymatic activity of A. saitoi 1,2-alpha-d-mannosidase. EDTA inhibits the Ca2+-free 1,2-alpha-d-mannosidase as a competitive inhibitor, not as a chelator. We deduce that the Glu-124 residue of A. saitoi 1,2-alpha-d-mannosidase is directly involved in the catalytic mechanism as an acid catalyst, whereas no usual catalytic base is directly involved. Ca2+ is not essential for the activity. The catalytic mechanism of 1,2-alpha-d-mannosidase may deviate from that typical glycosyl hydrolase.
Correction: The Trouble with Sliding Windows and the Selective Pressure in BRCA1 (2008)

Sliding-window analysis has widely been used to uncover synonymous (silent, d S ) and nonsynonymous (replacement, d N ) rate variation along the protein sequence and to detect regions of a protein under selective constraint (indicated by d N ,d S ) or positive selection (indicated by d N .d S ). The approach compares two or more protein-coding genes and plots estimates d S and d N from each sliding window along the sequence. Here we demonstrate that the approach produces artifactual trends of synonymous and nonsynonymous rate variation, with greater variation in d S than in d N. Such trends are generated even if the true d S and d N are constant along the whole protein and different codons are evolving independently. Many published tests of negative and positive selection using sliding windows that we have examined appear to be invalid because they fail to correct for multiple testing. Instead, likelihood ratio tests provide a more rigorous framework for detecting signals of natural selection affecting protein evolution. We demonstrate that a previous finding that a particular region of the BRCA1 gene experienced a synonymous rate reduction driven by purifying selection is likely an artifact of the sliding window analysis. We evaluate various sliding-window analyses in molecular evolution, population genetics, and comparative genomics, and argue that the approach is not generally valid if it is not known a priori that a trend exists and if no correction for multiple testing is applied.
Engineering influenza viral vectors (2012)

The influenza virus is a respiratory pathogen with a negative-sense, segmented RNA genome. Construction of recombinant influenza viruses in the laboratory was reported starting in the 1980s. Within a short period of time, pioneer researchers had devised methods that made it possible to construct influenza viral vectors from cDNA plasmid systems. Herein, we discuss the evolution of influenza virus reverse genetics, from helper virus-dependent systems, to helper virus-independent 17-plasmid systems, and all the way to 3- and 1- plasmid systems. Successes in the modification of different gene segments for various applications, including vaccine and gene therapies are highlighted.