gebhart/patrepeval huggingface dataset:
FINCH: Fresnel Incoherent Correlation Hologram (2011)

Holographic imaging offers a reliable and fast method to capture the complete threedimensional (3D) information of the scene from a single perspective. However, holography is not widely applied to the regime of white-light imaging, because white-light is incoherent and in general creating holograms requires a coherent interferometer system. In this chapter we describe our recently invented method of acquiring incoherent digital holograms. The term incoherent digital hologram means that incoherent light beams reflected or emitted from real existing objects interfere with each other. The resulting interferogram is recorded by a digital camera and digitally processed to yield a hologram. This hologram is reconstructed in the computer so that 3D images appear on the computer's screen. The coherent optical recording is not applicable for the incoherent optics because interference between reference and object incoherent beams cannot occur. Therefore, different holographic acquisition methods should be employed for generating an incoherent digital hologram. The oldest methods of recording incoherent holograms have made use of the property that every incoherent object is composed of many source points, each of which is self-spatial coherent and therefore can create an interference pattern with light coming from the point’s mirrored image. Under this general principle, there are various types of holograms, including Fourier (Stroke & Restrick, 1965; Breckinridge, 1974) and Fresnel holograms (Lohmann, 1965; Cochran, 1966; Peters, 1966; Marathay, 1987; Mugnier et al., 1993). The process of beam interfering demands high levels of light intensity, extreme stability of the optical setup, and relatively narrow bandwidth light source. These limitations have prevented holograms from becoming widely used for many practical applications. More recently, three groups of researchers have proposed computing holograms of 3D incoherently illuminated objects from a set of images taken from different points of view
Three-dimensional transcranial microbubble imaging for guiding volumetric ultrasound-mediated blood-brain barrier opening (2018)

Focused ultrasound (FUS)-mediated blood-brain barrier (BBB) opening recently entered clinical testing for targeted drug delivery to the brain. Sources of variability exist in the current procedures, motivating the development of real-time monitoring and control techniques to improve treatment safety and efficacy. Here we used three-dimensional (3D) transcranial microbubble imaging to calibrate FUS exposure levels for volumetric BBB opening. <b>Methods:</b> Using a sparse hemispherical transmit/receive ultrasound phased array, pulsed ultrasound was focused transcranially into the thalamus of rabbits during microbubble infusion and multi-channel 3D beamforming was performed online with receiver signals captured at the subharmonic frequency. Pressures were increased pulse-by-pulse until subharmonic activity was detected on acoustic imaging (<b>p</b><sub>sub</sub>), and tissue volumes surrounding the calibration point were exposed at 50-100%<b>p</b><sub>sub</sub> via rapid electronic beam steering. <b>Results:</b> Spatially-coherent subharmonic microbubble activity was successfully reconstructed transcranially <i>in vivo</i> during calibration sonications. Multi-point exposures induced volumetric regions of elevated BBB permeability assessed via contrast-enhanced magnetic resonance imaging (MRI). At exposure levels ≥75%<b>p</b><sub>sub</sub>, MRI and histological examination occasionally revealed tissue damage, whereas sonications at 50%<b>p</b><sub>sub</sub> were performed safely. Substantial intra-grid variability of FUS-induced bioeffects was observed via MRI, prompting future development of multi-point calibration schemes for improved treatment consistency. Receiver array sparsity and sensor configuration had substantial impacts on subharmonic detection sensitivity, and are factors that should be considered when designing next-generation clinical FUS brain therapy systems. <b>Conclusion:</b> Our findings suggest that 3D subharmonic imaging can be used to calibrate exposure levels for safe FUS-induced volumetric BBB opening, and should be explored further as a method for cavitation-mediated treatment guidance.
Vibriobactin Antibodies: A Vaccine Strategy (2009)

A new target strategy in the development of bacterial vaccines, the induction of antibodies to microbial outer membrane ferrisiderophore complexes, is explored. A vibriobactin (VIB) analogue, with a thiol tether, 1-(2,3-dihydroxybenzoyl)-5,9-bis[[(4S,5R)-2-(2,3-dihydroxyphenyl)-4,5-dihydro-5-methyl-4-oxazolyl]carbonyl]-14-(3-mercaptopropanoyl)-1,5,9,14-tetraazatetradecane, was synthesized and linked to ovalbumin (OVA) and bovine serum albumin (BSA). The antigenicity of the VIB microbial iron chelator conjugates and their iron complexes was evaluated. When mice were immunized with the resulting OVA-VIB conjugate, a selective and unequivocal antigenic response to the VIB hapten was observed; IgG monoclonal antibodies specific to the vibriobactin fragment of the BSA and OVA conjugates were isolated. The results are consistent with the idea that the isolated adducts of siderophores covalently linked to their bacterial outer membrane receptors represent a credible target for vaccine development.
Temporal Changes in Outer Surface Proteins A and C of the Lyme Disease-Associated Spirochete, Borrelia burgdorferi , during the Chain of Infection in Ticks and Mice (2000)

The Lyme disease-associated spirochete, Borrelia burgdorferi, is maintained in enzootic cycles involving Ixodes ticks and small mammals. Previous studies demonstrated that B. burgdorferi expresses outer surface protein A (OspA) but not OspC when residing in the midgut of unfed ticks. However, after ticks feed on blood, some spirochetes stop making OspA and express OspC. Our current work examined the timing and frequency of OspA and OspC expression by B. burgdorferi in infected Ixodes scapularis nymphs as they fed on uninfected mice and in uninfected I. scapularis larvae and nymphs as they first acquired spirochetes from infected mice. Smears of midguts from previously infected ticks were prepared at 12- or 24-h intervals following attachment through repletion at 96 h, and spirochetes were stained for immunofluorescence for detection of antibodies to OspA and OspC. As shown previously, prior to feeding spirochetes in nymphs expressed OspA but not OspC. During nymphal feeding, however, the proportion of spirochetes expressing OspA decreased, while spirochetes expressing OspC became detectable. In fact, spirochetes rapidly began to express OspC, with the greatest proportion of spirochetes having this protein at 48 h of attachment and then with the proportion decreasing significantly by the time that the ticks had completed feeding. In vitro cultivation of the spirochete at different temperatures showed OspC to be most abundant when the spirochetes were grown at 37 degrees C. Yet, the synthesis of this protein waned with continuous passage at this temperature. Immunofluorescence staining of spirochetes in smears of midguts from larvae and nymphs still attached or having completed feeding on infected mice demonstrated that OspA but not OspC was produced by these spirochetes recently acquired from mice. Therefore, the temporal synthesis of OspC by spirochetes only in feeding ticks that were infected prior to the blood meal suggests that this surface protein is involved in transmission from tick to mammal but not from mammal to tick.
Concise Review: Crosstalk of Mesenchymal Stroma/Stem-Like Cells with Cancer Cells Provides Therapeutic Potential (2018)

Various direct and indirect cellular interactions between multi-functional mesenchymal stroma/stem-like cells (MSCs) and cancer cells contribute to increasing plasticity within the tumor tissue and its microenvironment. Direct and tight communication between MSC and cancer cells is based on membrane protein interactions and the exchange of large plasma membrane fragments also known as trogocytosis. An ultimate but rare direct interaction resumes in fusion of these two cellular partners resulting in the formation of new cancer hybrid cell populations. Alternatively, indirect interactions are displayed by the release of membranous vesicle-encapsulated microRNAs and proteins or soluble components such as molecular growth factors, hormones, chemo-/cytokines, and metabolites. Released single molecules as well as multivesicular bodies including exosomes and microvesicles can form local concentration gradients within the tumor microenvironment and are incorporated not only by adjacent neighboring cells but also affect distant target cells. The present Review will focus on vesicle-mediated indirect communication and on cancer cell fusion with direct contact between MSC and cancer cells. These different types of interaction are accompanied by functional interference and mutual acquisition of new cellular properties. Consequently, alterations in cancer cell functionalities paralleled by the capability to reorganize the tumor stroma can trigger changes in metastatic behavior and promote retrodifferentiation to develop new cancer stem-like cells. However, exosomes and microvesicles acting over long distances may also provide a tool with therapeutic potential when loaded with anti-tumor cargo. Stem Cells 2018;36:951-968.
A genetic etiology for DiGeorge syndrome: consistent deletions and microdeletions of 22q11. (1992)

DiGeorge syndrome (DGS), a developmental field defect of the third and fourth pharyngeal pouches, is characterized by aplasia or hypoplasia of the thymus and parathyroid glands and by conotruncal cardiac malformations. Cytogenetic studies support the presence of a DGS critical region in band 22q11. In the present study, we report the results of clinical, cytogenetic, and molecular studies of 14 patients with DGS. Chromosome analysis, utilizing high-resolution banding techniques, detected interstitial deletions in five probands and was inconclusive for a deletion in three probands. The remaining six patients had normal karyotypes. In contrast, molecular analysis detected DNA deletions in all 14 probands. Two of 10 loci tested, D22S75 and D22S259, are deleted in all 14 patients. A third locus, D22S66, is deleted in the eight DGS probands tested. Physical mapping using somatic cell hybrids places D22S66 between D22S75 and D22S259, suggesting that it should be deleted in the remaining six cases. Parent-of-origin studies were performed in five families. Four probands failed to inherit a maternal allele, and one failed to inherit a paternal allele. On the basis of these families, and of six maternally and five paternally derived unbalanced-translocation DGS probands in the literature, parent of origin or imprinting does not appear to play an important role in the pathogenesis of DGS. Deletion of the same three loci in all 14 DGS probands begins to delineate the region of chromosome 22 critical for DGS and confirms the hypothesis that submicroscopic deletions of 22q11 are etiologic in the vast majority of cases.
Information Age Challenge for Metropolitan Universities (1995)

The purpose of this article is first to elaborate on the premise that technology is merely the metaphor for more significant changes that we are undergoing; second, to suggest ways to involve faculty as learners in the process of understanding those changes; and, third, to explore how they might capitalize on the information age technology in order to transform learning and thus the role of the faculty itself in the process. There is no more important role for the university in the information age.
Luminescence studies of a Si/SiO2 superlattice (2002)

Photoluminescence and electroluminescence from a Si/SiO2 superlattice have been measured. They show similar characteristics and exhibit an inhomogeneously broadened photoluminescence band peaked at 2.06 eV. The excitation spectrum indicates that excitations occur in the Si layers. The insensitivity of the luminescence spectrum and decay to temperature and excitation wavelength suggests that luminescence originates from transitions between localized defect states. These localized states are most likely defect states residing at the Si/SiO2 interfaces, because there should be a significant concentration of defects at the interface and SiO2 due to the large lattice mismatch and the amorphous state. The close proximity of these states offers a more rapid transition path for the excited electrons. An energy band diagram of the superlattice is constructed based on our results.
Use of polynucleotide/polyacrylamide-gel electrophoresis as a sensitive technique for the detection and comparison of ribonuclease activities (1980)

A technique is described in which the incorporation of a polynucleotide substrate into the matrix of a polyacrylamide gel allows the use of electrophoresis for the detection of polycationic ribonuclease activity rather than simply the presence of protein. Because use is made of the catalytic properties of ribonucleases, polynucleotide/polyacrylamide-gel electrophoresis is apparoximately 10(5) times more sensitive for the detection of these enzymes than conventional gel electrophoresis with the use of protein-staining dyes. Initial studies showed that the poor migration, in the gels, of highly charged polycationic ribonucleases in the presence of negatively charged synthetic polynucleotides could be overcome by high concentrations of spermine. The positively charged polyamine, by neutralizing the polyanionic polynucleotide, enabled these basic enzymes to migrate considerable distances in the gel. Electrophoresis of the RNAases under conditions of low pH, and incubation of the gel at neutral pH followed by staining for polynucleotide, resulted in coloured gels containing clear bands that define regions of enzyme activity. Alterations in spermine concentration or substrate identity caused changes in the positions of these bands, suggesting a dynamic interaction among the enzyme, polyamine and polynucleotide. Because of the advantages, in terms of selectivity and sensitivity of polynucleotide/polyacrylamide-gel electrophoresis, this technique was used to demonstrate the nuclease homogenity of three purified bovine muscle enzymes, and to compare these enzymes with each other, as well as with bovine pancreatic ribonuclease A.
Magnesium(II) Is a Crucial Constituent of the Blood Coagulation Cascade (1996)

We recently showed that not only Ca2+ ions but also Mg2+ ions play a crucial role in stabilizing the native conformation of coagulation factor IX. We here report that Mg2+ ions at physiological concentrations greatly augment the biological activities of factor IX. In clotting assays with dialyzed plasma, addition of Mg2+ ions enhanced the apparent coagulant activity of factor IXa, while that of factor Xa was scarcely affected. Activation of factor X by factor IXa in the presence of factor VIIIa, phospholipids, and Ca2+ ions was accelerated by Mg2+ ions. It appeared that the cation increased the affinity between factor IXa and factor VIIIa, thereby increasing the apparent catalytic efficacy of the enzyme. We also evaluated the effect of Mg2+ ions in the coagulation pathway initiated by tissue factor and found that activation of factor IX by factor VIIa*tissue factor was accelerated by the cation. Consequently, clotting of normal plasma induced by factor VIIa*tissue factor was shortened by the cation, while no such effect was observed in plasma deficient in factor IX or VIII. These results indicate that the previously unrecognized plasma component, Mg2+ ions, plays crucial roles in blood coagulation and, moreover, that contributions of factors IX and VIII in the coagulation cascade have been seriously underestimated in previous investigations.
Identification and Optimization of Inhibitors of Trypanosomal Cysteine Proteases: Cruzain, Rhodesain, and TbCatB (2009)

Trypanosoma cruzi and Trypanosoma brucei are parasites that cause Chagas' disease and African sleeping sickness, respectively. Both parasites rely on essential cysteine proteases for survival: cruzain for T. cruzi and TbCatB/rhodesain for T. brucei. A recent quantitative high-throughput screen of cruzain identified triazine nitriles, which are known inhibitors of other cysteine proteases, as reversible inhibitors of the enzyme. Structural modifications detailed herein, including core scaffold modification from triazine to purine, improved the in vitro potency against both cruzain and rhodesain by 350-fold, while also gaining activity against T. brucei parasites. Selected compounds were screened against a panel of human cysteine and serine proteases to determine selectivity, and a cocrystal was obtained of our most potent analogue bound to cruzain.
Vagal Stimulation for Heart Diseases: From Animals to Men - An Example of Translational Cardiology - (2010)

An autonomic imbalance with a reduction in vagal activity and an increase in sympathetic activity is present in heart failure. The same type of imbalance, when present in patients with a myocardial infarction, is associated with increased risk for cardiac mortality. Experimental studies have demonstrated that vagal stimulation has an antifibrillatory effect and has proven to be beneficial in animal models of heart failure. Given this background, the potential value of chronic vagal stimulation was explored in humans with an implantable neuro-stimulator capable of delivering low current pulses with adjustable parameters to stimulate the right vagus. A small multicenter feasibility and safety study exploring efficacy has recently been completed. A total of 32 patients with left ventricular ejection fraction (LVEF) <35% and a history of chronic heart failure in symptomatic NYHA class II-III were included in the study. The results indicate feasibility and safety. Interestingly, there are also very encouraging results for the efficacy on the NYHA class, quality of life, 6-min walk test, left ventricular end-systolic volume and LVEF. The latter, at the 1-year follow up, had increased from 21 ± 7% to 34 ± 12% (P<0.0001). Finally, vagal stimulation in heart failure patients has a strong rationale and the preliminary data suggests that it is likely to be of value to these patients. It is now appropriate to move toward a randomized controlled clinical trial of adequate size.
Novel Lipid Modifications of Secreted Protein Signals (2004)

Secreted signaling proteins function in a diverse array of essential patterning events during metazoan development, ranging from embryonic segmentation in insects to neural tube differentiation in vertebrates. These proteins generally are expressed in a localized manner, and they may elicit distinct concentration-dependent responses in the cells of surrounding tissues and structures, thus functioning as morphogens that specify the pattern of cellular responses by their tissue distribution. Given the importance of signal distribution, it is notable that the Hedgehog (Hh) and Wnt proteins, two of the most important families of such signals, are known to be covalently modified by lipid moieties, the membrane-anchoring properties of which are not consistent with passive models of protein mobilization within tissues. This review focuses on the mechanisms underlying biogenesis of the mature Hh proteins, which are dually modified by cholesteryl and palmitoyl adducts, as well as on the relationship between Hh proteins and the self-splicing proteins (i.e., proteins containing inteins) and the Hh-like proteins of nematodes. We further discuss the cellular mechanisms that have evolved to handle lipidated Hh proteins in the spatial deployment of the signal in developing tissues and the more recent findings that implicate palmitate modification as an important feature of Wnt signaling proteins.
Of Yuppies and Housing: Gentrification, Social Restructuring, and the Urban Dream (1987)

The question of whether gentrification can and should be explained as the result of contemporary processes of social restructuring is considered. It has been proposed, in particular, that gentrification is caused by the rise of a ‘new middle class’, and this argument is evaluated in theoretical and empirical terms. There is, in fact, better evidence for the significance of women in the gentrification process, because of changing work patterns, changing patterns of reproduction, and the changing relationship between work and reproduction. In light of these arguments, issue is taken with the claim that gentrification is a ‘chaotic conception’ and it is suggested how, instead, the social restructuring that is currently being observed is closely related to an economic restructuring, and that both together involve a dramatic spatial restructuring of which ‘gentrification’ is one part. The new urban patterns now unfolding do involve the construction of ‘consumption landscapes’ in the city, and the emergence of an incipient ‘urban dream’ parallel to the suburban dream of the last decade, but this docs not imply that urban geographical change is now somehow demand led.
Structure-activity relationships of arylimidazopyridine cardiotonics: discovery and inotropic activity of 2-[2-methoxy-4-(methylsulfinyl)phenyl]-1H-imidazo[4,5-c]pyridine (1985)

Recently several noncatecholamine, nonglycoside cardiotonic drugs have been discovered that possess both inotropic and vasodilator activities in experimental animals and man. Prototypical compounds include amrinone, sulmazole, and fenoximone. We investigated the structural requirements necessary for optimal inotropic activity in a series of molecules containing a heterocyclic ring fused to 2-phenylimidazole and discovered that 2-phenylimidazo[4,5-c]pyridines were generally 5-10-fold more potent than analogous 2-phenylimidazo[4,5-b]pyridines (e.g., sulmazole) or 8-phenylpurines. Furthermore, all imidazo[4,5-c]pyridine analogues we tested were orally active; in contrast, only one of the imidazo[4,5-b]pyridine derivatives, sulmazole, was significantly active. One of several highly active compounds in the [4,5-c] series was 50 (LY175326, 2-[2-methoxy-4-(methylsulfinyl)phenyl]-1H-imidazo[4,5-c]pyridine hydrochloride). The structure-activity relationship of this series is presented and compared to that of the imidazo[4,5-b]pyridine and purine series.
Local Radiation Therapy Inhibits Tumor Growth through the Generation of Tumor-Specific CTL: Its Potentiation by Combination with Th1 Cell Therapy (2010)

Radiation therapy is one of the primary treatment modalities for cancer along with chemotherapy and surgical therapy. The main mechanism of the tumor reduction after irradiation has been considered to be damage to the tumor DNA. However, we found that tumor-specific CTL, which were induced in the draining lymph nodes (DLN) and tumor tissue of tumor-bearing mice, play a crucial role in the inhibition of tumor growth by radiation. Indeed, the therapeutic effect of irradiation was almost completely abolished in tumor-bearing mice by depleting CD8(+) T cells through anti-CD8 monoclonal antibody administration. In mice whose DLN were surgically ablated or genetically defective (Aly/Aly mice), the generation of tetramer(+) tumor-specific CTL at the tumor site was greatly reduced in parallel with the attenuation of the radiation-induced therapeutic effect against the tumor. This indicates that DLN are essential for the activation and accumulation of radiation-induced CTL, which are essential for inhibition of the tumor. A combined therapy of local radiation with Th1 cell therapy augmented the generation of tumor-specific CTL at the tumor site and induced a complete regression of the tumor, although radiation therapy alone did not exhibit such a pronounced therapeutic effect. Thus, we conclude that the combination treatment of local radiation therapy and Th1 cell therapy is a rational strategy to augment antitumor activity mediated by tumor-specific CTL.