gebhart/patrepeval huggingface dataset:
A novel cell type responsible for marrow graft rejection in mice. T cells with NK phenotype cause acute rejection of marrow grafts. (1989)

Acute rejection of allogeneic and semiallogeneic marrow grafts has long been considered to be a function of the natural immune system because it shares many features with NK activity in mice. With the use of a recently developed in vivo adoptive transfer assay in which spleen cells are transferred from mice able to reject a particular marrow graft into mice that fail to do so, we show that the cells responsible for induction of marrow graft rejection indeed display the phenotype of NK cells: they lack the T cell Ag CD4 and CD8 but express the NK Ag NK1 and ASGM1. The rejection induced by adoptively transferred cells is exquisitely specific--a feature that points to a specific recognition process by the transferred cells. To elucidate what the recognition structure on these cells may be we found that they express CD3 and most likely the beta-chain of the TCR. Highly purified responder cells with the NK1+, CD3+, CD4-, CD8- phenotype, when transferred into nonresponder recipients, cause specific marrow graft rejection. We conclude that the acute rejection of bone marrow grafts is caused by a cell that expresses NK phenotype but is of T cell lineage. This may suggest the specificity of acute marrow graft rejection is caused by a specific recognition process that involves TCR.
Versatile effects of sildenafil: recent pharmacological applications. (2008)

Sildenafil is a phosphodiesterase-5 (PDE5) inhibitor and is predominantly used in the treatment of erectile dysfunction. While maintaining an excellent safety and tolerability profile in the management of erectile dysfunction, sildenafil also provides a prolonged benefit in various other diseases. Sildenafil has been shown to have a potential therapeutic efficacy for disorders related to the central nervous system and pulmonary system. In the central nervous system, it exerts its neuroprotective effects in multiple sclerosis and has a significant memory enhancing action. Sildenafil also significantly enhances neurogenesis. Several lines of evidence indicate that targeting PDE5 with sildenafil offers novel strategies in the treatment of age-related memory impairment. Guanylate cyclase/cGMP/protein kinase G pathway or glutamate/nitric oxide/cGMP pathway appears to mediate memory enhancing effects. Some of the positive cognitive features of sildenafil therapy are likely attributable to the mechanisms reviewed here. Sildenafil has been shown to reduce pulmonary hypertension and alleviate pain in animals and humans. The present review primarily focuses on the various pharmacological effects of sildenafil with regard to its influence on the nervous and pulmonary system.
Tonotopic Organization in Human Auditory Cortex Revealed by Progressions of Frequency Sensitivity (2004)

Functional neuroimaging experiments have revealed an organization of frequency-dependent responses in human auditory cortex suggestive of multiple tonotopically organized areas. Numerous studies have sampled cortical responses to isolated narrow-band stimuli, revealing multiple locations in auditory cortex at which the position of response varies systematically with frequency content. Because appropriate anatomical or functional grouping of these distinct frequency-dependent responses is uncertain, the number and location of tonotopic mappings within human auditory cortex remains unclear. Further, sampling does not address whether the observed mappings exhibit continuity as a function of position. This functional magnetic resonance imaging study used frequency-swept stimuli to identify progressions of frequency sensitivity across the cortical surface. The center-frequency of narrow-band, amplitude-modulated noise was slowly swept between 125 and 8,000 Hz. The latency of response relative to sweep onset was determined for each cortical surface location. Because frequency varied systematically with time, response latency indicated the frequency to which a location was maximally sensitive. Areas of cortex exhibiting a progressive change in response latency with position were considered tonotopically organized. There exist two main findings. First, six progressions of frequency sensitivity (i.e., tonotopic mappings) were repeatably observed in the superior temporal plane. Second, the locations of the higher- and lower-frequency endpoints of these progressions were approximately congruent with regions reported to be most responsive to discrete higher- and lower-frequency stimuli. Based on these findings and previous anatomical work, we propose a correspondence between these progressions and anatomically defined cortical areas, suggesting that five areas in human auditory cortex exhibit at least six tonotopic organizations.
Cycloaddition Reactions of Chiral 2-Amino-1,3-butadienes with Nitroalkenes:  Synthesis of Enantiomerically Pure 4-Nitrocyclohexanones1 (1997)

2-Amino-1,3-butadienes bearing commercially available S-(+)-2-(methoxymethyl)pyrrolidine as chiral auxiliary undergo a [4 + 2] cycloaddition reaction with nitroalkenes to furnish 4-nitrocyclohexanones upon hydrolysis of the resulting enamine. The cycloadducts are obtained with good yields and very high enantiomeric excesses. The reaction has been performed with aromatic and aliphatic conjugated nitroalkenes. Moreover, a 2-amino diene which features a (Z) double bond undergoes a Michael addition reaction with nitroalkenes, which gives rise to open chain compounds with high enantioselectivity. After acidic hydrolysis, the open chain compounds cyclize to form chiral substituted furans.
Prolonged Residence Time of a Noncovalent Molecular Adapter, β-Cyclodextrin, within the Lumen of Mutant α-Hemolysin Pores (2001)

Noncovalent molecular adapters, such as cyclodextrins, act as binding sites for channel blockers when lodged in the lumen of the alpha-hemolysin (alphaHL) pore, thereby offering a basis for the detection of a variety of organic molecules with alphaHL as a sensor element. beta-Cyclodextrin (betaCD) resides in the wild-type alphaHL pore for several hundred microseconds. The residence time can be extended to several milliseconds by the manipulation of pH and transmembrane potential. Here, we describe mutant homoheptameric alphaHL pores that are capable of accommodating betaCD for tens of seconds. The mutants were obtained by site-directed mutagenesis at position 113, which is a residue that lies near a constriction in the lumen of the transmembrane beta barrel, and fall into two classes. Members of the tight-binding class, M113D, M113N, M113V, M113H, M113F and M113Y, bind betaCD approximately 10(4)-fold more avidly than the remaining alphaHL pores, including WT-alphaHL. The lower K(d) values of these mutants are dominated by reduced values of k(off). The major effect of the mutations is most likely a remodeling of the binding site for betaCD in the vicinity of position 113. In addition, there is a smaller voltage-sensitive component of the binding, which is also affected by the residue at 113 and may result from transport of the neutral betaCD molecule by electroosmotic flow. The mutant pores for which the dwell time of betaCD is prolonged can serve as improved components for stochastic sensors.
Database mining: a performance perspective (1993)

The authors' perspective of database mining as the confluence of machine learning techniques and the performance emphasis of database technology is presented. Three classes of database mining problems involving classification, associations, and sequences are described. It is argued that these problems can be uniformly viewed as requiring discovery of rules embedded in massive amounts of data. A model and some basic operations for the process of rule discovery are described. It is shown how the database mining problems considered map to this model, and how they can be solved by using the basic operations proposed. An example is given of an algorithm for classification obtained by combining the basic rule discovery operations. This algorithm is efficient in discovering classification rules and has accuracy comparable to ID3, one of the best current classifiers.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Contact Lens Transmissibility: Effects on Delivery of Oxygen to the Cornea (1996)

The purpose of this study was to determine the effects of rigid contact lens materials of various permeabilities and identical design on the oxygen shortfall of the human cornea and to explore differences in oxygen delivery to the cornea associated with contact lens materials of different modulus of elasticity values. Measurement of corneal oxygen uptake was performed for six human subjects under three conditions: (1) normal open eye; (2) after the static wear of six materials; and (3) after the dynamic wear of the same six materials. The 6 materials had Dk values that ranged from 0.02 to 127 (cm2/s)(ml O2/ml x mm Hg) and modulus of elasticity values from 1300 to 2200 MPa. Major results include: (1) that the oxygen shortfall of the cornea decreased with increasing lens transmissibility under both static and dynamic conditions, with significant differences (p < 0.001) being demonstrated among materials; and (2) significantly larger differences (p < 0.001) between the static and dynamic condition data were seen for materials of low Dk but were not predictable by lens modulus (p = 0.43, r2 = 0.018). The corneal demand differences between high and low Dk materials are possibly related to changes in corneal oxygen dynamics rather than to differences in tear exchange.
Rapid Image Analysis Screening Procedure for Identifying Chloroplast Number Mutants in Mesophyll Cells of Arabidopsis thaliana (L.) Heynh. (1991)

To analyze the genetic control of the process of chloroplast division, a direct image analysis screening procedure has been developed in which mutants of Arabidopsis thaliana (L.) Heynh. var Landsberg erecta are selected on the basis of abnormal chloroplast number. The selection procedure is based on image analysis thresholding after iodine staining, which facilitates the automatic counting of chloroplasts in isolated mesophyll cells. M2 seedlings are screened for significant deviation from the wild type relationship between mesophyll cell size and chloroplast number. Mutants with both abnormally high and abnormally low chloroplast numbers were identified. Of 3500 individual M2 seedlings screened, 18 mutant lines have been isolated and shown to be stably inherited in three subsequent generations. The most extreme phenotypes show an 80% reduction or a 50% increase in chloroplast number per mesophyll cell.
On reducing the bit rate of a CELP-based speech coder (1992)

For a code excited linear prediction (CELP)-based coder, coarse quantization usually results in the degradation of speech quality. Spectrum and gain were found to have the least sensitivity to quantization errors and were efficiently quantized. The frame period and number of subframes per frame were also appropriately selected for the purpose of bit-rate reduction. The performance of four possible excitations, namely, stochastic excitation, binary pulse excitation, self-excitation and repeat excitation were investigated. Using signal-to-noise ratio as a quality measure, the coder at 3076 b/s was found to have a performance very close to that of the federal standard at 4800 b/s.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Interdomain Conformational Changes in Akt Activation Revealed by Chemical Cross-linking and Tandem Mass Spectrometry (2006)

Akt, a serine/threonine kinase, plays a critical role in cell survival. Upon growth factor receptor stimulation, cytosolic Akt is recruited to the plasma membrane by phospholipid binding and activated through phosphorylation at Thr(308) and Ser(473). Although crystal structures for the parts of Akt have been reported, neither the three-dimensional structure of the whole molecule nor sequential conformational changes during activation have been demonstrated. In this study, we demonstrated that Akt undergoes dramatic interdomain conformational changes during activation processes by probing the three-dimensional structure of full-length Akt in solution using chemical cross-linking and tandem mass spectrometry. The cross-linking results not only provided new structural information but also revealed distinctive spatial arrangements of individual domains in the Akt molecule in resting, membrane-interacted, phosphorylated, and substrate-bound states. Our data allowed a new model for stepwise interdomain conformational changes in Akt activation sequence, setting a stage for the further investigation on Akt-membrane, Akt-protein, and/or Akt-drug interactions in solution to understand molecular mechanisms involved in physiological and pathophysiological processes of cell survival.
Analytical treatment of polarization-mode dispersion in single-mode fibers by means of the backscattered signal (1999)

We present analytical results on the polarization-mode dispersion characteristics of single-mode birefringent fibers based on statistical properties of the backscattered signal. In particular, we calculate exactly the relationship between polarization-mode dispersion characteristics in forward propagation with respect to round-trip propagation in terms of dynamical equations, differential group delays, correlation lengths, and second-order effects. The theory applies to fibers affected by superposition of linear and circular birefringence in both the short-length and the long-length regimes.
TAM receptor tyrosine kinases as emerging targets of innate immune checkpoint blockade for cancer therapy (2017)

Cancer immunotherapy utilizing T-cell checkpoint inhibitors has shown tremendous clinical success. Yet, this mode of treatment is effective in only a subset of patients. Unresponsive patients tend to have non-T-cell-inflamed tumors that lack markers associated with the activation of adaptive anti-tumor immune responses. Notably, elimination of cancer cells by T cells is critically dependent on the optimal activity of innate immune cells. Therefore, identifying new targets that regulate innate immune cell function and promote the engagement of adaptive tumoricidal responses is likely to lead to the development of improved therapies against cancer. Here, we review the TAM receptor tyrosine kinases-TYRO3, AXL, and MERTK-as an emerging class of innate immune checkpoints that participate in key steps of anti-tumoral immunity. Namely, TAM-mediated efferocytosis, negative regulation of dendritic cell activity, and dysregulated production of chemokines collectively favor the escape of malignant cells. Hence, disabling TAM signaling may promote engagement of adaptive immunity and complement T-cell checkpoint blockade.
Identification of differentially methylated sequences in colorectal cancer by methylated CpG island amplification. (1999)

CpG island methylation has been linked to tumor suppressor gene inactivation in neoplasia and may serve as a useful marker to clone novel cancer-related genes. We have developed a novel PCR-based method, methylated CpG island amplification (MCA), which is useful for both methylation analysis and cloning differentially methylated genes. Using restriction enzymes that have differential sensitivity to 5-methyl-cytosine, followed by adaptor ligation and PCR amplification, methylated CpG rich sequences can be preferentially amplified. In a model experiment using a probe from exon 1 of the p16 gene, signal was detected from MCA products of a colorectal cancer cell line but not in normal colon mucosa. To identify novel CpG islands differentially methylated in colorectal cancer, we have applied MCA coupled with representational difference analysis to the colon cancer cell line Caco2 as a tester and normal colon mucosa as a driver. Using this strategy, we isolated 33 differentially methylated DNA sequences, including fragments identical to several known genes (PAX6, Versican, alpha-tubulin, CSX, OPT, and rRNA gene). The association of hypermethylation of the clones obtained and transcriptional suppression in colorectal cancer was confirmed by examining the Versican gene, which we found to be silenced in methylated cell lines and reactivated by the methylation inhibitor 5-aza-2'-deoxycytidine. We therefore propose that MCA is a useful technique to study methylation and to isolate CpG islands differentially methylated in cancer.
Layered video multicast with retransmissions (LVMR): evaluation of hierarchical rate control (2002)

Layered video multicast with retransmissions (LVMR) is a system for distributing video using layered coding over the Internet. The two key contributions of the system are: (1) improving the quality of reception within each layer by retransmitting lost packets given an upper bound on recovery time and applying an adaptive playback point scheme to help achieve more successful retransmission, and (2) adapting to network congestion and heterogeneity using hierarchical rate control mechanism. This paper concentrates on the rate control aspects of LVMR. In contrast to the existing sender-based and receiver-based rate control in which the entire information about network congestion is either available at the sender (in sender-based approach) or replicated at the receivers (in receiver-based approach), the hierarchical rate control mechanism distributes the information between the sender, receivers, and some agents in the network in such a way that each entity maintains only the information relevant to itself. In addition to that, the hierarchical approach enables intelligent decisions to be made in terms of conducting concurrent experiments and choosing one of several possible experiments at any instant of time based on minimal state information at the agents in the network. Protocol details are presented in the paper together with experimental and simulation results to back our claims.
The evolving role of sirolimus in renal transplantation (2003)

Sirolimus (rapamycin) is a macrolide antibiotic isolated from the fungus Streptomyces hygroscopicus 1 first identified in soil samples from Easter Island. Structurally similar to the calcineurin inhibitor (CNI) tacrolimus (Figure 1), it shares its potent immunosuppressive properties, but with a novel mechanism of action (Figure 2). Initial clinical trials have focussed on its use as adjunctive therapy, substituting for the anti-metabolite azathioprine. However, given that it lacks the nephrotoxicity of the CNIs (cyclosporin and tacrolimus), it has the potential to supplant these agents as baseline immunosuppressive therapy following renal transplantation, and offers the added potential benefit of promoting immunological tolerance. Figure 1. 
Structure of sirolimus. Sirolimus (rapamycin) is a macrocyclic lactone structurally similar to tacrolimus (FK506).





 Figure 2. 
Mechanism of action of sirolimus (rapamycin). CD4-positive T cells recognize a complex of class II MHC and peptide present on the surface of antigen-presenting cells (APCs). This results in signalling via the T cell receptor (TCR) and activation of calcineurin, a phosphatase. Calcineurin dephosphorylates NFAT (nuclear factor of activated T cells) facilitating its transfer into the nucleus where it acts as a transcription factor regulating IL-2 production. IL-2, and other cytokines, in turn promote further T-cell activation and proliferation, following interaction with its cell surface receptor (IL-2R). Of note, T-cell receptor engagement alone is insufficient to produce an immune response. Co-stimulatory signals (prototypically via CD28) are also necessary to produce and sustain a T-cell response. T-cell receptor engagement in the absence of co-stimulatory signals is thought to produce tolerance by inducing non-responsiveness to specific antigens and promoting apoptotic deletion of the activated cells (activation-induced cell death, AICD). Cyclosporin and tacrolimus (FK506) act by binding to their respective immunophilins (cyclophilin/FK-binding protein, FKBP-12) with the resultant complexes producing calcineurin inhibition. The net effect is blockade of IL-2 production, resulting in inhibition of T-cell activation. Sirolimus (SRL) also binds … 



Address correspondence to: Dr A.N Warrens, Department of Immunology, Commonwealth Building, Hammersmith Hospital, Ducane Road, London W12 0NN. e-mail: a.warrens{at}ic.ac.uk
Highly Luminescent Water-Soluble CdTe Quantum Dots (2003)

Colloidal CdTe quantum dots prepared in TOP/DDA (trioctylphosphine/dodecylamine) are transferred into water by the use of aminoethanethiol.HCl (AET) or mercaptopropionic acid (MPA). This results in an increase in the photoluminescence quantum efficiency and a longer exciton lifetime. For the first time, water-soluble semiconductor nanocrystals presenting simultaneously high band-edge photoluminescence quantum efficiencies (as high as 60% at room temperature), monoexponential exciton decays, and no observable defect-related emission are obtained.
Study of FC<sup>M</sup>BGA with low CTE core substrate (2009)

Amkor's FC <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">M</sup> BGA, flip chip package based on transfer molding for high performance device was developed and introduced to industry in 2008[1,2]. During the molding process, bump deformation was not significant, and voids were not observed under flip chip die. Coplanarity with a low Coefficient of Thermal Expansion, CTE, substrate construction was similar to a single piece lidded package construction. Coplanarity at high temperature did not change significantly with low CTE substrate compared to standard substrates. The flip chip package with molding passed reliability test such as Moisture Resistance Testing, MRT, and Thermal Cycling, TC 1500 cycles. No delamination or cracks were observed.
Successful Treatment of Adult's Langerhans Cell Histiocytosis With Thalidomide (1993)

<h3>REPORT OF A CASE</h3><h3>CASE 1</h3> A 59-year-old woman treated for diabetes insipidus by desmopressin (Minirin) for 8 years was seen with large granulomatous ulcerations and infiltrated papules of the perianal region that were present for 3 years (<b>Figure 1</b>). A few papular lesions were seen in the submammary region. Histopathologic examination of a skin biopsy specimen taken from the perianal lesions disclosed a thick dermal infiltrate with lymphocytes, eosinophils, and large histiocytes (<b>Figure 2</b>). Immunohistopathologic study showed that the histiocytes stained positive for S100 and CD la. Electron microscopy confirmed the diagnosis of Langerhans cell histiocytosis, showing 20% of the cells in the infiltrate contained Birbeck's granules (<b>Figure 3</b>). The patient's clinical examination showed negative findings, and no pulmonary involvement was seen on a chest roentgenogram and a thoracic computed tomographic scan. The bone marrow biopsy specimen showed normal findings. Endocrine tests revealed deficiences in corticotropin, gondatropin, and somatotropin
End-labeled amino terminated monotelechelic glycopolymers generated by ROMP and Cu(I)-catalyzed azide–alkyne cycloaddition (2013)

Functionalizable monotelechelic polymers are useful materials for chemical biology and materials science. We report here the synthesis of a capping agent that can be used to terminate polymers prepared by ring-opening metathesis polymerization of norbornenes bearing an activated ester. The terminating agent is a cis-butene derivative bearing a Teoc (2-trimethylsilylethyl carbamate) protected primary amine. Post-polymerization modification of the polymer was accomplished by amidation with an azido-amine linker followed by Cu(I)-catalyzed azide-alkyne cycloaddition with propargyl sugars. Subsequent Teoc deprotection and conjugation with pyrenyl isothiocyanates afforded well-defined end-labeled glycopolymers.