gebhart/patrepeval huggingface dataset:
Carbohydrate−Protein Interactions by “Clicked” Carbohydrate Self-Assembled Monolayers (2006)

A Huisgen 1,3-dipolar cycloaddition "click chemistry" was employed to immobilize azido sugars (mannose, lactose, alpha-Gal) to fabricate carbohydrate self-assembled monolayers (SAMs) on gold. This fabrication was based on preformed SAM templates incorporated with alkyne terminal groups, which could further anchor the azido sugars to form well-packed, stable, and rigid sugar SAMs. The clicked mannose, lactose, and alpha-Gal trisaccharide SAMs were used in the analysis of specific carbohydrate-protein interactions (i.e., mannose-Con A; ECL-lactose, alpha-Gal-anti-Gal). The apparent affinity constant of Con A binding to mannose was (8.7 +/- 2.8) x 10(5) and (3.9 +/- 0.2) x 10(6) M(-1) measured by QCM and SPR, respectively. The apparent affinity constants of lactose binding with ECL and alpha-Gal binding with polyclonal anti-Gal antibody were determined to be (4.6 +/- 2.4) x 10(6) and (6.7 +/- 3.3) x 10(6) M(-1), respectively by QCM. SPR, QCM, AFM, and electrochemistry studies confirmed that the carbohydrate SAM sensors maintained the specificity to their corresponding lectins and nonspecific adsorption on the clicked carbohydrate surface was negligible. This study showed that the clicked carbohydrate SAMs in concert with nonlabel QCM or SPR offered a potent platform for high-throughput characterization of carbohydrate-protein interactions. Such a combination should complement other methods such as ITC and ELISA in a favorable manner and provide insightful knowledge for the corresponding complex glycobiological processes.
Mogamulizumab, an Anti-CCR4 Antibody, Targets Human T-Lymphotropic Virus Type 1–infected CD8+and CD4+T Cells to Treat Associated Myelopathy (2014)

We determined that CD8(+)CCR4(+) T cells and CD4(+)CCR4(+) T cells are prime therapeutic targets for treating HAM/TSP and propose mogamulizumab as a new treatment.
Chronic myelogenous leukemia (1978)

Chronic myelogenous leukemia (CML) is a relatively rare disease, with a number of features that make it especially suitable for observations on leukemogenesis in man. These include known etiologic agents, often a prolonged preclinical and active stage, cells with identifiable morphological and histochemical characteristics and the presence of the unique Ph' chromosome. The transition of CML to blast crisis is a catastrophic event; however, recent clinical and biochemical studies have raised important questions as to the nature and origin of blast cells in this disease. During the past 10 years, we have followed 113 cases olf CML throughout their course and results of observations on the clinical, hematological and other apsects of the disease are presented in this communication.
Genetic analysis of the mouse X inactivation center defines an 80-kb multifunction domain (1999)

Dosage compensation in mammals occurs by X inactivation, a silencing mechanism regulated in cis by the X inactivation center (Xic). In response to developmental cues, the Xic orchestrates events of X inactivation, including chromosome counting and choice, initiation, spread, and establishment of silencing. It remains unclear what elements make up the Xic. We previously showed that the Xic is contained within a 450-kb sequence that includes Xist, an RNA-encoding gene required for X inactivation. To characterize the Xic further, we performed deletional analysis across the 450-kb region by yeast-artificial-chromosome fragmentation and phage P1 cloning. We tested Xic deletions for cis inactivation potential by using a transgene (Tg)-based approach and found that an 80-kb subregion also enacted somatic X inactivation on autosomes. Xist RNA coated the autosome but skipped the Xic Tg, raising the possibility that X chromosome domains escape inactivation by excluding Xist RNA binding. The autosomes became late-replicating and hypoacetylated on histone H4. A deletion of the Xist 5' sequence resulted in the loss of somatic X inactivation without abolishing Xist expression in undifferentiated cells. Thus, Xist expression in undifferentiated cells can be separated genetically from somatic silencing. Analysis of multiple Xic constructs and insertion sites indicated that long-range Xic effects can be generalized to different autosomes, thereby supporting the feasibility of a Tg-based approach for studying X inactivation.
Degree of Arousal Is Most Correlated with Blood Pressure Reactivity During Sleep in Obstructive Sleep Apnea (2001)

We investigated blood pressure (BP) reactivity of obstructive sleep apnea (OSA) during rapid eye movement (REM) sleep and non-rapid eye movement (NREM) sleep. The influences on BP reactivity of degree of arousal, the lowest O2 saturation (SaO2), and respiratory disturbance (RD) duration were compared. Ten normotensive or borderline hypertensive patients with OSA were studied with one-night polysomnography including non-invasive beat-to-beat BP monitoring (Finapres). We compared baseline BP, pre-apneic BP, and post-apneic BP during both REM and NREM sleep. Also, relationships between delta BP (post-apneic BP minus pre-apneic BP) and degree of arousal, the lowest SaO2, and RD duration were examined. During both REM and NREM sleep, pre-apneic BP was elevated compared with baseline BP. Post-apneic BP elevation was noted compared with pre-apneic BP. The degree of arousal was more significantly correlated with delta BP than the lowest SaO2. RD duration was hardly correlated with delta BP. Pre-apneic BP elevation seems to result from cumulation of sympathetic activation and sympathetic nervous system resetting. The correlation between delta BP and degree of arousal suggests that sympathetic activation causing post-apneic BP elevation may result mainly from an arousal response regardless of hypoxia.
Enzymic analysis for rapid detection of microbial infection in human body fluids: an overview. (1981)

One possible means of rapidly detecting microorganisms in patients with suspected infectious diseases is the direct measurement of microbial enzymes in body fluids. This technique is based on the fact that bacterial, fungal, and viral organisms possess enzymes that are not produced by mammalian cells and are thus not found in uninfected human body fluids. Detection of one of these microbial enzymes in blood, cerebrospinal fluid, or other body fluids would thus be indicative of microbial infection. Potentially useful enzymes for this purpose include bacterial beta-lactamases, fungal adenine deaminases, and viral thymidine kinases. In addition, glycosidases such as neuraminidases and galactosidases can be used as markers for microbial infection, provided that the enzymic activity can be appropriately identified as being of microbial origin. The direct measurement of microbial enzymes offers great potential for the rapid diagnosis of infectious diseases.
Bone morphogenetic protein type 2 receptor gene therapy attenuates hypoxic pulmonary hypertension (2007)

Idiopathic pulmonary arterial hypertension (PAH) is characterized by proliferation of pulmonary vascular endothelial and smooth muscle cells causing increased vascular resistance and right heart failure. Mutations in the bone morphogenetic protein receptor type 2 (BMPR2) are believed to cause the familial form of the disease. Reduced expression of BMPR2 is also noted in secondary PAH. Recent advances in the therapy of PAH have improved quality of life and survival, but many patients continue to do poorly. The possibility of treating PAH via improving BMPR2 signaling is thus a rational consideration. Such an approach could be synergistic with or additive to current treatments. We developed adenoviral vectors containing the BMPR2 gene. Transfection of cells in vitro resulted in upregulation of SMAD signaling and reduced cell proliferation. Targeted delivery of vector to the pulmonary vascular endothelium of rats substantially reduced the pulmonary hypertensive response to chronic hypoxia, as reflected by reductions in pulmonary artery and right ventricular pressures, right ventricular hypertrophy, and muscularization of distal pulmonary arterioles. These data provide further evidence for a role for BMPR2 in PAH and provide a rationale for the development of therapies aimed at improving BMPR2 signaling.
Temporal Attention Model for Neural Machine Translation (2016)

Attention-based Neural Machine Translation (NMT) models suffer from attention deficiency issues as has been observed in recent research. We propose a novel mechanism to address some of these limitations and improve the NMT attention. Specifically, our approach memorizes the alignments temporally (within each sentence) and modulates the attention with the accumulated temporal memory, as the decoder generates the candidate translation. We compare our approach against the baseline NMT model and two other related approaches that address this issue either explicitly or implicitly. Large-scale experiments on two language pairs show that our approach achieves better and robust gains over the baseline and related NMT approaches. Our model further outperforms strong SMT baselines in some settings even without using ensembles.
Direct nucleic acid diagnostic tests for bacterial infectious diseases: streptococcal pharyngitis, pulmonary tuberculosis, vaginitis, chlamydial and gonococcal infections. (2004)

Partnering with a reference lab can actually help grow a referring lab's own business. The reference lab provides a hospital's physicians with access to unique tests and clinical information and broadens the scope and depth of the referring lab's menu. As medicine moves toward prescribed treatments based on a patient's individual genotype or phenotype, the reference lab will play an even bigger role in helping the hospital to educate physicians and their patients to the most efficient testing strategies consistent with good patient management.
Nanoconfinement-Enhanced Conformational Response of Single DNA Molecules to Changes in Ionic Environment (2007)

We show that the ionic environment plays a critical role in determining the configurational properties of DNA confined in silica nanochannels. The extension of DNA in the nanochannels increases as the ionic strength is reduced, almost tripling over two decades in ionic strength for channels around $100\ifmmode\times\else\texttimes\fi{}100\text{ }\text{ }\mathrm{nm}$ in dimension. Surprisingly, we find that the variation of the persistence length alone with ionic strength is not enough to explain our results. The effect is due mainly to increasing self-avoidance created by the reduced screening of electrostatic interactions at low ionic strength. To quantify the increase in self-avoidance, we introduce a new parameter into the de Gennes theory: an effective DNA width that gives the increase in the excluded volume due to electrostatic repulsion.
Clong and expression of the rat interleukin-3 gene (1986)

Genomic clones carrying the rat interleukin-3 (IL-3) gene have been isolated and the nucleotide sequence of the gene determined. Alignment of this sequence with that of the mouse IL-3 gene has allowed the structure of the rat IL-3 gene to be deduced. The intron-exon boundaries are conserved and extensive nucleotide homology (approx 90%) is present in the 5' flanking region and the portion of the gene coding for the signal peptide. Several proposed regulatory sequences are conserved and an analogous element to the tandem repeat in intron 2 of the mouse gene is also present. The predicted amino acid sequence for mature rat IL-3 shows surprisingly low homology (54%) with its murine counterpart, although all four cysteine residues are conserved. The rat IL-3 gene was expressed in monkey COS-1 cells and colony assays established that rat IL-3 is a multi-lineage haemopoietic growth regulator. There was little cross-reactivity of the respective IL-3 species on mouse and rat bone marrow cells suggesting that rat IL-3, in concert with its receptor, has evolved significantly away from the mouse IL-3/receptor system.
Role for Glycine Betaine Transport in Vibrio cholerae Osmoadaptation and Biofilm Formation within Microbial Communities (2005)

Vibrio cholerae is a halophilic facultative human pathogen found in marine and estuarine environments. Accumulation of compatible solutes is important for growth of V. cholerae at NaCl concentrations greater than 250 mM. We have identified and characterized two compatible solute transporters, OpuD and PutP, that are involved in uptake of glycine betaine and proline by V. cholerae. V. cholerae does not, however, possess the bet genes, suggesting that it is unable to synthesize glycine betaine. In contrast, many Vibrio species are able to synthesize glycine betaine from choline. It has been shown that many bacteria not only synthesize but also secrete glycine betaine. We hypothesized that sharing of compatible solutes might be a mechanism for cooperativity in microbial communities. In fact, we have demonstrated that, in high-osmolarity medium, V. cholerae growth and biofilm development are enhanced by supplementation with either glycine betaine or spent media from other bacterial species. Thus, we propose that compatible solutes provided by other microorganisms may contribute to survival of V. cholerae in the marine environment through facilitation of osmoadaptation and biofilm development.
The linear Monge-Kantorovitch linear colour mapping for example-based colour transfer (2007)

A common task in image editing is to change the colours of a picture to match the desired colour grade of another picture. Finding the correct colour mapping is tricky because it involves numerous interrelated operations, like balancing the colours, mixing the colour channels or adjusting the contrast. Recently, a number of automated tools have been proposed to find an adequate one-to-one colour mapping. The focus in this paper is on finding the best linear colour transformation. Linear transformations have been proposed in the literature but independently. The aim of this paper is thus to establish a common mathematical background to all these methods. Also, this paper proposes a novel transformation, which is derived from the Monge-Kantorovitch theory of mass transportation. The proposed solution is optimal in the sense that it minimises the amount of changes in the picture colours. It favourably compares theoretically and experimentally with other techniques for various images and under various colour spaces
Clinical implications of hedgehog signaling pathway inhibitors (2011)

Hedgehog was first described in Drosophila melanogaster by the Nobel laureates Eric Wieschaus and Christiane Nüsslein-Volhard. The hedgehog (Hh) pathway is a major regulator of cell differentiation, proliferation, tissue polarity, stem cell maintenance, and carcinogenesis. The first link of Hh signaling to cancer was established through studies of a rare familial disease, Gorlin syndrome, in 1996. Follow-up studies revealed activation of this pathway in basal cell carcinoma, medulloblastoma and, leukemia as well as in gastrointestinal, lung, ovarian, breast, and prostate cancer. Targeted inhibition of Hh signaling is now believed to be effective in the treatment and prevention of human cancer. The discovery and synthesis of specific inhibitors for this pathway are even more exciting. In this review, we summarize major advances in the understanding of Hh signaling pathway activation in human cancer, mouse models for studying Hh-mediated carcinogenesis, the roles of Hh signaling in tumor development and metastasis, antagonists for Hh signaling and their clinical implications.
Growth and Electrical Characterization of N-face AlGaN/GaN Heterostructures (2005)

We describe growth and characterization of N-face GaN-based high electron mobility structures using plasma-assisted molecular beam epitaxy (MBE) on C-face SiC substrates. A two-step buffer approach consisting of a low Ga-flux followed by high Ga-flux was used to achieve smooth morphologies and threading dislocation (TD) densities as low as 1.5×10 10 cm -2 . These TD densities are comparable to the lowest achieved on Ga-face GaN grown by MBE on Si-face SiC. Secondary ion mass spectrometry measurements were carried out to study O, C, and Si incorporation. Hall, capacitance–voltage and transfer length method measurements on GaN/AlGaN/GaN modulation-doped heterostructures were found to match simulations, and a charge of 1×10 13 cm -2 with electron mobility above 1000 cm 2 V -1 s -1 was measured.
Genetic and comparative analyses reveal an alternative secondary structure in the region of nt 912 of Escherichia coli 16S rRNA. (1995)

Mutations at position 912 of Escherichia coli 16S rRNA result in two notable phenotypes. The C-->U transition confers resistance to streptomycin, a translational-error-inducing antibiotic, while a C-->G transversion causes marked retardation of cell growth rate. Starting with the slow-growing G912 mutant, random mutagenesis was used to isolate a second site mutation that restored growth nearly to the wild-type rate. The second site mutation was identified as a G-->C transversion at position 885 in 16S rRNA. Cells containing the G912 mutation had an increased doubling time, abnormal sucrose gradient ribosome/subunit profile, increased sensitivity to spectinomycin, dependence upon streptomycin for growth in the presence of spectinomycin, and slower translation rate, whereas cells with the G912/C885 double mutation were similar to wild type in these assays. Comparative analysis showed there was significant covariation between positions 912 and 885. Thus the second-site suppressor analysis, the functional assays, and the comparative data suggest that the interaction between nt 912 and nt 885 is conserved and necessary for normal ribosome function. Furthermore, the comparative data suggest that the interaction extends to include G885-G886-G887 pairing with C912-U911-C910. An alternative secondary structure element for the central domain of 16S rRNA is proposed.
Binding of the NG2 Proteoglycan to Kringle Domains Modulates the Functional Properties of Angiostatin and Plasmin(ogen) (2000)

Interactions of the developmentally regulated chondroitin sulfate proteoglycan NG2 with human plasminogen and kringle domain-containing plasminogen fragments have been analyzed by solid-phase immunoassays and by surface plasmon resonance. In immunoassays, the core protein of NG2 binds specifically and saturably to plasminogen, which consists of five kringle domains and a serine protease domain, and to angiostatin, which contains plasminogen kringle domains 1-3. Apparent dissociation constants for these interactions range from 12 to 75 nm. Additional evidence for NG2 interaction with kringle domains comes from its binding to plasminogen kringle domain 4 and to miniplasminogen (kringle domain 5 plus the protease domain) with apparent dissociation constants in the 18-71 nm range. Inhibition of plasminogen and angiostatin binding to NG2 by 6-aminohexanoic acid suggests that lysine binding sites are involved in kringle interaction with NG2. The interaction of NG2 with plasminogen and angiostatin has very interesting functional consequences. 1) Soluble NG2 significantly enhances the activation of plasminogen by urokinase type plasminogen activator. 2) The antagonistic effect of angiostatin on endothelial cell proliferation is inhibited by soluble NG2. Both of these effects of NG2 should make the proteoglycan a positive regulator of the cell migration and proliferation required for angiogenesis.
MO-FG-BRA-06: Electromagnetic Beacon Insertion in Lung Cancer Patients and Resultant Surrogacy Errors for Dynamic MLC Tumour Tracking (2016)

Purpose: To assess endo-bronchial electromagnetic beacon insertion and to quantify the geometric accuracy of using beacons as a surrogate for tumour motion in real-time multileaf collimator (MLC) tracking of lung tumours. Methods: The LIGHT SABR trial is a world-first clinical trial in which the MLC leaves move with lung tumours in real time on a standard linear accelerator. Tracking is performed based on implanted electromagnetic beacons (CalypsoTM, Varian Medical Systems, USA) as a surrogate for tumour motion. Five patients have been treated and have each had three beacons implanted endo-bronchially under fluoroscopic guidance. The centre of mass (C.O.M) has been used to adapt the MLC in real-time. The geometric error in using the beacon C.O.M as a surrogate for tumour motion was measured by measuring the tumour and beacon C.O.M in all phases of the respiratory cycle of a 4DCT. The surrogacy error was defined as the difference in beacon and tumour C.O.M relative to the reference phase (maximum exhale). Results: All five patients have had three beacons successfully implanted with no migration between simulation and end of treatment. Beacon placement relative to tumour C.O.M varied from 14 to 74 mm and in one patient spanned two lobes. Surrogacy error was measured in each patient on the simulation 4DCT and ranged from 0 to 3 mm. Surrogacy error as measured on 4DCT was subject to artefacts in mid-ventilation phases. Surrogacy error was a function of breathing phase and was typically larger at maximum inhale. Conclusion: Beacon placement and thus surrogacy error is a major component of geometric uncertainty in MLC tracking of lung tumours. Surrogacy error must be measured on each patient and incorporated into margin calculation. Reduction of surrogacy error is limited by airway anatomy, however should be taken into consideration when performing beacon insertion and planning. This research is funded by Varian Medical Systems via a collaborative research agreement.
Fiber-optic Faraday-effect magnetic-field sensor based on flux concentrators (1996)

The principles and performance of a fiber-optic Faraday-effect magnetic-field sensor designed around an yttrium-iron-garnet (YIG) sensing element and two flux concentrators are described. The system design exploits the technique of polarization-rotated reflection in which a single polarization-maintaining optical fiber links the sensor head to the optical source and detection system. In the sensing head, ferrite flux concentrators are magnetically coupled to the YIG sensing element to achieve maximum sensitivity. The system exhibits a noise equivalent field of 6 pT/√Hz and a 3-dB bandwidth of~10 MHz.
Indoleamine 2,3-Dioxygenase Expression in Human Cancers: Clinical and Immunologic Perspectives (2011)

Indoleamine 2,3-dioxygenase (IDO) is a tryptophan-catabolizing enzyme with immune-regulating activities in many contexts, such as fetal protection, allograft protection, and cancer progression. Clinical trials are currently evaluating IDO inhibition with 1-methyltryptophan in cancer immunotherapy. However, the exact role of tryptophan catabolism by IDO in human cancers remains poorly understood. Here, we review several studies that correlate IDO expression in human cancer samples and tumor-draining lymph nodes, with relevant clinical or immunologic parameters. IDO expression in various histologic cancer types seems to decrease tumor infiltration of immune cells and to increase the proportion of regulatory T lymphocytes in the infiltrate. The impact of IDO on different immune cell infiltration leads to the conclusion that IDO negatively regulates the recruitment of antitumor immune cells. In addition, increased IDO expression correlates with diverse tumor progression parameters and shorter patient survival. In summary, in the vast majority of the reported studies, IDO expression is correlated with a less favorable prognosis. As we may see results from the first clinical trials with 1-methyltryptophan in years to come, this review brings together IDO studies from human studies and aims to help appreciate outcomes from current and future trials. Consequently, IDO inhibition seems a promising approach for cancer immunotherapy.