gebhart/patrepeval huggingface dataset:
In vivo imaging of nanoparticle delivery and tumor microvasculature with multimodal optical coherence tomography (2014)

Current imaging techniques capable of tracking nanoparticles in vivo supply either a large field of view or cellular resolution, but not both. Here, we demonstrate a multimodality imaging platform of optical coherence tomography (OCT) techniques for high resolution, wide field of view in vivo imaging of nanoparticles. This platform includes the first in vivo images of nanoparticle pharmacokinetics acquired with photothermal OCT (PTOCT), along with overlaying images of microvascular and tissue morphology. Gold nanorods (51.8 ± 8.1 nm by 15.2 ± 3.3 nm) were intravenously injected into mice, and their accumulation into mammary tumors was non-invasively imaged in vivo in three dimensions over 24 hours using PTOCT. Spatial frequency analysis of PTOCT images indicated that gold nanorods reached peak distribution throughout the tumors by 16 hours, and remained well-dispersed up to 24 hours post-injection. In contrast, the overall accumulation of gold nanorods within the tumors peaked around 16 hours post-injection. The accumulation of gold nanorods within the tumors was validated post-mortem with multiphoton microscopy. This shows the utility of PTOCT as part of a powerful multimodality imaging platform for the development of nanomedicines and drug delivery technologies.
Polylactide‐pine wood flour composites (2008)

Abstract Biobased and biodegradable polylactide (PLA)‐pine wood flour (PWF) composites were investigated as a means to reduce the overall material cost and tailor the material properties. The composites were prepared using a kinetic‐mixer and an injection molding machine. The tensile modulus of the PLA‐PWF composites increased with the PWF content whereas the toughness and strain‐at‐break decreased. The tensile strength remained the same irrespective of the PWF content (up to 40%). The storage modulus also increased with the PWF content. Additionally, composites containing PWF treated with silane showed higher storage modulus than those without the silane treatment. The area integration underneath the tan δ peaks decreased with increasing PWF, indicating that the PLA‐PWF composites exhibited more elastic behavior with increasing PWF. The degree of crystallinity of the PLA‐PWF composites increased significantly with the PWF content. Furthermore, the treatment of PWF with silane had a positive effect on its nucleating ability, as treated PLA‐PWF composites showed higher crystallinity compared with their untreated counterparts. The morphology of the fracture surfaces were studied using a scanning electron microscope. Finally, a Halpin‐Tsai analytical model to predict Young's modulus of PLA‐PWF composites was presented to compare the theoretical results with that of experimental results. POLYM. ENG. SCI., 2008. © 2008 Society of Plastics Engineers
Plasmonic field enhancement and SERS in the effective mode volume picture (2006)

The controlled creation of nanometric electromagnetic field confinement via surface plasmon polariton excitations in metal/insulator/metal heterostructures is described via the concept of an effective electromagnetic mode volume Veff. Extensively used for the description of dielectric microcavities, its extension to plasmonics provides a convenient figure of merit and allows comparisons with dielectric counterparts. Using a one-dimensional analytical model and three-dimensional finite-difference time-domain simulations, it is shown that plasmonic cavities with nanometric dielectric gaps indeed allow for physical as well as effective mode volumes well below the diffraction limit in the gap material, despite significant energy penetration into the metal. In this picture, matter-plasmon interactions can be quantified in terms of quality factor Q and Veff, enabling a resonant cavity description of surface enhanced Raman scattering.
<title>Technology assessment and the cost of health care</title> (1994)

The cost of health care is a major economic issue and policy concern in the United States today. It is clear that expenditures have been increasing more rapidly than the rate of growth of our gross domestic product. The escalation of costs is a result of an increase in number, intensity, and/or expense of services. The evidence forces the inescapable conclusion that this situation cannot long be maintained. Nevertheless, there is reason to believe that a greater efficiency in the system is possible, perhaps permitting the provision of higher quality care with fewer resource.demands. Some increase in efficiency may result from the proper application of technology assessment.
Impact of Immunizations with Porcine Reproductive and Respiratory Syndrome Virus on Lymphoproliferative Recall Responses of CD8 + T Cells (2004)

The objective of this study was to investigate the immune responses elicited by either a modified-live (MLV) or a killed virus (KV) porcine reproductive and respiratory syndrome virus (PRRSV) vaccine. Specifically, we investigated the effects of multiple vaccinations on antigen-specific cellular and antibody responses against PRRSV. Twelve sows were obtained from herds with either a history of repeated MLV or KV PRRSV vaccination and a non-vaccinated, PRRSV-negative herd. Within herd, sows were divided into three groups and vaccinated with MLV, KV, or injected with saline. On day 0, 27, and 38, recall responses of peripheral blood mononuclear cells (PBMC) to the parent strains of the vaccines (e.g., MLV-VR2332 or KV-ISUP) were examined. The concentrations of total PRRSV-specific and virus-neutralizing serum antibodies were determined by ELISA and serum neutralization assays. Following immunization, the antigen-specific proliferation of CD8alphabeta(+), CD4(+)CD8alphaalpha(+) T cells in the naive sows was greater than in sows repeatedly vaccinated with KV or MLV. This diminished lymphoproliferative responses of CD8alphabeta(+) and CD4(+)CD8alphaalpha(+) T cells could be partially overcome by heterologous immunization. However, B cell proliferation, PRRSV antibody concentrations and virus neutralizing antibody titers were not enhanced by heterologous immunization and only KV vaccination increased antibody levels in previously immunized (MLV or KV) sows.
Studies on 24R,25-dihydroxyvitamin D3: evidence for a nonnuclear membrane receptor in the chick tibial fracture-healing callus (1998)

The effect(s) of 24R,25-dihydroxyvitamin D3 [24R,25(OH)2D3] on fracture healing was studied in a vitamin D-depleted chick model. 24R,25(OH)2D3, together with another hormonally active vitamin D metabolite, 1alpha,25-dihydroxyvitamin D3 [1alpha,25(OH)2D3], improved bone mechanical strength parameters (torsional strength, angular deformation, and stiffness) and the ash content. The synthetic epimer 24S,25-dihydroxyvitamin D3 [24S,25(OH)2D3] was not as potent as the natural 24R,25(OH)2D3. In light of the ability of the fracture-healing callus to discriminate between 24R,25(OH)2D3 and 24S,25(OH)2D3, a search was initiated in fracture-healing callus tissue for the presence of a specific 24R,25(OH)2D3 receptor. No evidence was obtained for a classical nuclear/cytosol receptor for 24R,25(OH)2D3 in the fracture-healing callus. A specific receptor/binding protein for 24R,25(OH)2D3 was found in the callus membrane fraction, which showed different ligand binding affinities [KD = 18.3 +/- 1.9 nmol/L, Bmax = 43.9 +/- 6.0 fmol/mg; relative competitive index (RCI) for 24R,25(OH)2D3/24S,25(OH)2D3/25(OH)D3/1alpha,25(OH)2D3 = 100/37/401/2.0] compared with the ubiquitous serum vitamin D-binding protein (RCI = 100/99/219/5). Also, a callus membrane-binding protein/receptor for 1alpha,25(OH)2D3 was detected with a KD = 0.83 +/- 0.35 nmol/L and a Bmax = 35.5 +/- 5.2 fmol/mg. Thus, we have demonstrated a biological role for 24R,25(OH)2D3 in fracture healing and described the presence of its receptor/binding protein in a callus membrane fraction.
Human Cytomegalovirus Infection of Placental Cytotrophoblasts In Vitro and In Utero: Implications for Transmission and Pathogenesis (2000)

Human cytomegalovirus (CMV) is the leading cause of prenatal viral infection. Affected infants may suffer intrauterine growth retardation and serious neurologic impairment. Analysis of spontaneously aborted conceptuses shows that CMV infects the placenta before the embryo or fetus. In the human hemochorial placenta, maternal blood directly contacts syncytiotrophoblasts that cover chorionic villi and cytotrophoblasts that invade uterine vessels, suggesting possible routes for CMV transmission. To test this hypothesis, we exposed first-trimester chorionic villi and isolated cytotrophoblasts to CMV in vitro. In chorionic villi, syncytiotrophoblasts did not become infected, although clusters of underlying cytotrophoblasts expressed viral proteins. In chorionic villi that were infected with CMV in utero, syncytiotrophoblasts were often spared, whereas cytotrophoblasts and other cells of the villous core expressed viral proteins. Isolated cytotrophoblasts were also permissive for CMV replication in vitro; significantly, infection subsequently impaired the cytotrophoblasts' ability to differentiate and invade. These results suggest two possible routes of CMV transmission to the fetus: (i) across syncytiotrophoblasts with subsequent infection of the underlying cytotrophoblasts and (ii) via invasive cytotrophoblasts within the uterine wall. Furthermore, the observation that CMV infection impairs critical aspects of cytotrophoblast function offers testable hypotheses for explaining the deleterious effects of this virus on pregnancy outcome.
Bioactive Diversity and Screening Library Selection via Affinity Fingerprinting (1998)

The Similarity Principle provides the conceptual framework behind most modern approaches to library sampling and design. However, it is often the case that compounds which appear to be very similar structurally may in fact exhibit quite different activities toward a given target. Conversely, some targets recognize a wide variety of molecules and thus bind compounds that have markedly different structures. Affinity fingerprints largely overcome the difficulties associated with selecting compounds on the basis of structure alone. By describing each compound in terms of its binding affinity to a set of functionally dissimilar proteins, fundamental factors relevant to binding and biological activity are automatically encoded. We demonstrate how affinity fingerprints may be used in conjunction with simple algorithms to select active-enriched diverse training sets and to efficiently extract the most active compounds from a large library.
Accurate microfluidic sorting of droplets at 30 kHz (2014)

Fluorescence-activated droplet sorting is an important tool for droplet microfluidic workflows, but published approaches are unable to surpass throughputs of a few kilohertz. We present a new geometry that replaces the hard divider separating the outlets with a gapped divider, allowing sorting over ten times faster.
Novel Peptides Selected to Bind Vascular Endothelial Growth Factor Target the Receptor-Binding Site (1998)

Peptides that inhibit binding of vascular endothelial growth factor (VEGF) to its receptors, KDR and Flt-1, have been produced using phage display. Libraries of short disulfide-constrained peptides yielded three distinct classes of peptides that bind to the receptor-binding domain of VEGF with micromolar affinities. The highest affinity peptide was also shown to antagonize VEGF-induced proliferation of primary human umbilical vascular endothelial cells. The peptides bind to a region of VEGF known to contain the contact surface for Flt-1 and the functional determinants for KDR binding. This suggests that the receptor-binding region of VEGF is a binding "hot spot" that is readily targeted by selected peptides and supports earlier assertions that phage-derived peptides frequently target protein-protein interaction sites. Such peptides may lead to the development of pharmacologically useful VEGF antagonists.
Overlapping functions of the cell adhesion molecules Nr-CAM and L1 in cerebellar granule cell development (2001)

The structurally related cell adhesion molecules L1 and Nr-CAM have overlapping expression patterns in cerebellar granule cells. Here we analyzed their involvement in granule cell development using mutant mice. Nr-CAM-deficient cerebellar granule cells failed to extend neurites in vitro on contactin, a known ligand for Nr-CAM expressed in the cerebellum, confirming that these mice are functionally null for Nr-CAM. In vivo, Nr-CAM-null cerebella did not exhibit obvious histological defects, although a mild size reduction of several lobes was observed, most notably lobes IV and V in the vermis. Mice deficient for both L1 and Nr-CAM exhibited severe cerebellar folial defects and a reduction in the thickness of the inner granule cell layer. Additionally, anti-L1 antibodies specifically disrupted survival and maintenance of Nr-CAM-deficient granule cells in cerebellar cultures treated with antibodies. The combined results indicate that Nr-CAM and L1 play a role in cerebellar granule cell development, and suggest that closely related molecules in the L1 family have overlapping functions.
Differential activation of proliferation and cytotoxicity in human T-cell lymphotropic virus type I Tax-specific CD8 T cells by an altered peptide ligand. (1995)

Human T-cell leukemia virus type I (HTLV-I) gives rise to a neurologic disease known as HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Although the pathogenesis of the disease is unknown, the presence of a remarkably high frequency of Tax-specific, cytotoxic CD8 T cells may suggest a role of these cells in the development of HAM/TSP. Antigen-mediated signaling in a CD8 T-cell clone specific for the Tax(11-19) peptide of HTLV-I was studied using analog peptides substituted in their T-cell receptor contact residues defined by x-ray crystallographic data of the Tax(11-19) peptide in the groove of HLA-A2. CD8 T-cell stimulation with the wild-type peptide antigen led to activation of p56lck kinase activity, interleukin 2 secretion, cytotoxicity, and clonal expansion. A Tax analog peptide with an alanine substitution of the T-cell receptor contact residue tyrosine-15 induced T-cell-mediated cytolysis without activation of interleukin 2 secretion or proliferation. Induction of p56lck kinase activity correlated with T-cell-mediated cytotoxicity, whereas interleukin 2 secretion correlated with [3H]thymidine incorporation and proliferation. Moreover, Tax peptide analogs that activated the tyrosine kinase activity of p56lck could induce unresponsiveness to secondary stimulation with the wild-type peptide. These observations show that a single amino acid substitution in a T-cell receptor contact residue of Tax can differentially signal CD8 T cells and further demonstrate that primary activation has functional consequences for the secondary response of at least some Tax-specific CD8 T cells to HTLV-I-infected target cells.
Nanotaper for compact mode conversion (2003)

We propose and demonstrate an efficient coupler for compact mode conversion between a fiber and a submicrometer waveguide. The coupler is composed of high-index-contrast materials and is based on a short taper with a nanometer-sized tip. We show that the micrometer-long silicon-on-insulator-based nanotaper coupler is able to efficiently convert both the mode field profile and the effective index, with a total length as short as 40 microm. We measure an enhancement of the coupling efficiency between an optical fiber and a waveguide by 1 order of magnitude due to the coupler.
Size-Controlled Growth of CdSe Nanocrystals in Microfluidic Reactors (2003)

Cadmium selenide nanocrystals are reproducibly synthesized at high-temperature in continuous flow, chip-based microfluidic reactors and exhibit size distributions comparable to those for conventional macroscale syntheses. Nanocrystal size, probed by fluorescence, is precisely controlled by independently varying the temperature, flow rate, and concentration of precursor solution flowing through heated microchannels. These experiments demonstrate the ability to fine-tune physical properties and test wide ranges of conditions precisely and rapidly inside chip-based microreactors, enabling rational, cost-effective, and environmentally friendly development and production of novel nanostructures.
Emotions and brain function are altered up to one month after a single high dose of psilocybin (2020)

Psilocybin is a classic psychedelic compound that may have efficacy for the treatment of mood and substance use disorders. Acute psilocybin effects include reduced negative mood, increased positive mood, and reduced amygdala response to negative affective stimuli. However, no study has investigated the long-term, enduring impact of psilocybin on negative affect and associated brain function. Twelve healthy volunteers (7F/5M) completed an open-label pilot study including assessments 1-day before, 1-week after, and 1-month after receiving a 25 mg/70 kg dose of psilocybin to test the hypothesis that psilocybin administration leads to enduring changes in affect and neural correlates of affect. One-week post-psilocybin, negative affect and amygdala response to facial affect stimuli were reduced, whereas positive affect and dorsal lateral prefrontal and medial orbitofrontal cortex responses to emotionally-conflicting stimuli were increased. One-month post-psilocybin, negative affective and amygdala response to facial affect stimuli returned to baseline levels while positive affect remained elevated, and trait anxiety was reduced. Finally, the number of significant resting-state functional connections across the brain increased from baseline to 1-week and 1-month post-psilocybin. These preliminary findings suggest that psilocybin may increase emotional and brain plasticity, and the reported findings support the hypothesis that negative affect may be a therapeutic target for psilocybin.
Stage-Specific Expression of Cytokine and Receptor Messenger Ribonucleic Acids in Human Preimplantation Embryos1 (1995)

There is considerable evidence to suggest that polypeptide growth factors from either the oviduct or the endometrium can control preimplantation development of the mammalian embryo. These act directly through receptors expressed on the embryo. In addition, embryos also produce growth factors. The reverse transcriptase-polymerase chain reaction (RT-PCR) was used to determine the pattern of expression of mRNAs encoding several growth factor ligand and receptor genes throughout preimplantation development of cryopreserved human embryos. Transcripts encoding the receptor for c-fms, the receptor for colony-stimulating factor-1 (CSF-1), and c-kit (the receptor for stem cell factor [SCF]) were expressed throughout preimplantation development. Other growth factor ligand and receptor transcripts were expressed in a stage-specific manner: these included receptors for interleukin (IL)-6 (IL-6R), leukemia inhibitory factor (LIFR), tumor necrosis factor alpha (TNF alpha) (TNFRp80 and TNFRp60), and gp130. The transcripts for gp130 and the ligand SCF showed stage-specific splice variants. Blastocysts expressed a novel cDNA encoding gp130, which predicts a truncated form lacking the intracellular signaling domain. No expression of mRNAs encoding LIF, CSF-1, or the cloned receptor for platelet-activating factor was seen in any embryonic stage studied. We have shown that RT-PCR provides a sensitive and powerful method for identifying transcripts encoding growth factors and their receptors in single human embryos. The method is economical, allowing the expression pattern of many genes to be determined from a single embryo. These data are important in defining which cytokines may be involved in regulating human preimplantation development and when they may act.
Interstitial hypertension in human breast and colorectal tumors. (1992)

The efficacy of present day antineoplastic regimens depends upon the delivery and penetration of therapeutic agents through the tumor vascular and interstitial spaces to the tumor cell target. The distribution of relevant molecules or cells in a solid tumor is often poor and heterogeneous and is believed to be due to a number of pathophysiological factors, including elevated interstitial fluid pressure (IFP). Using the wick-in-needle technique, IFP was measured in primary breast and colorectal carcinomas as well as their respective metastases to the lymph nodes and liver in a total of 17 patients. IFP was also measured in one recurrent renal cell carcinoma, one melanoma metastasis to the lymph nodes, and another melanoma metastasis to the lung. IFP varied from 4 to 50 mm Hg with a mean +/- SD of 20 +/- 13 mm Hg in the neoplasms (n = 41 measurements; n = 21 tumors), while IFP in normal tissues had a mean of 2 +/- 4 mm Hg (n = 11). The mean IFPs for metastatic melanoma, primary breast carcinoma, and liver metastases from a colorectal primary were found to be 33 +/- 14, 15 +/- 9, and 21 +/- 12 mm Hg, respectively. In the renal cell carcinoma, the pressure was 38 mm Hg. These results agree with the findings of our 3 previous studies examining IFP in human superficial melanomas (14.3 +/- 12.5 mm Hg, n = 12), cervical carcinomas (15.7 +/- 5.7 mm Hg, n = 12), and head and neck tumors (13.2 +/- 8.8 mm Hg, n = 19), and indicate that in all types of human tumors studied to date, IFP was significantly elevated above that of normal tissue. This observation may be useful in localizing tumors during needle biopsy.
Self-Assembly of Aligned Tissue-Engineered Annulus Fibrosus and Intervertebral Disc Composite Via Collagen Gel Contraction (2009)

Many cartilaginous tissues such as intervertebral disc (IVD) display a heterogeneous collagen microstructure that results in mechanical anisotropy. These structures are responsible for mechanical function of the tissue and regulate cellular interactions and metabolic responses of cells embedded within these tissues. Using collagen gels seeded with ovine annulus fibrosus cells, constructs of varying structure and heterogeneity were created to mimic the circumferential alignment of the IVD. Alignment was induced within gels by contracting annular gels around an inner boundary using both a polyethylene center and alginate center to create a composite engineered IVD. Collagen alignment and heterogeneity were measured using second harmonic generation microscopy. Decreasing initial collagen density from 2.5 mg/mL to 1 mg/mL produced greater contraction of constructs, resulting in gels that were 55% and 6.2% of the original area after culture, respectively. As a result, more alignment occurred in annular-shaped 1 mg/mL gels compared with 2.5 mg/mL gels (p < 0.05). This alignment was also produced in a composite-engineered IVD with alginate nucleus pulposus. The resulting collagen alignment could promote further aligned collagen development necessary for the creation of a mechanically functional tissue-engineered IVD.