gebhart/patrepeval huggingface dataset:
Extending lifetime of plastic changes in the human brain (2006)

The ability of the brain to adjust to changing environments and to recover from damage rests on its remarkable capacity to adapt through plastic changes of underlying neural networks. We show here with an eye movement paradigm that a lifetime of plastic changes can be extended to several hours by repeated applications of theta burst transcranial magnetic stimulation to the frontal eye field of the human cortex. The results suggest that repeated application of the same stimulation protocol consolidates short-lived plasticity into long-lasting changes.
Toward a Clinical Protocol for Assessing Rod, Cone, and Melanopsin Contributions to the Human Pupil Response (2011)

PURPOSE. To better understand the relative contributions of rod, cone, and melanopsin to the human pupillary light reflex (PLR) and to determine the optimal conditions for assessing the health of the rod, cone, and melanopsin pathways with a relatively brief clinical protocol. METHODS. PLR was measured with an eye tracker, and stimuli were controlled with a Ganzfeld system. In experiment 1, 2.5 log cd/m(2) red (640 ± 10 nm) and blue (467 ± 17 nm) stimuli of various durations were presented after dark adaptation. In experiments 2 and 3, 1-second red and blue stimuli were presented at different intensity levels in the dark (experiment 2) or on a 0.78 log cd/m(2) blue background (experiment 3). Based on the results of experiments 1 to 3, a clinical protocol was designed and tested on healthy control subjects and patients with retinitis pigmentosa and Leber's congenital amaurosis. RESULTS. The duration for producing the optimal melanopsin-driven sustained pupil response after termination of an intense blue stimulus was 1 second. PLR rod- and melanopsin-driven components are best studied with low- and high-intensity flashes, respectively, presented in the dark (experiment 2). A blue background suppressed rod and melanopsin responses, making it easy to assess the cone contribution with a red flash (experiment 3). With the clinical protocol, robust melanopsin responses could be seen in patients with few or no contributions from the rods and cones. CONCLUSIONS. It is possible to assess the rod, cone, and melanopsin contributions to the PLR with blue flashes at two or three intensity levels in the dark and one red flash on a blue background.
Improved quantitative PCR using nested primers. (1994)

Quantitative PCR can often be improved by conducting the amplification with nested primers. First, fewer nonspecific amplification products, which could otherwise interfere with quantitation, are produced. Often, nonspecific products can be eliminated. In these cases, relatively simple nonspecific detection techniques are suitable for quantitation. In addition, nested primer PCR provides intrinsic PCR product carryover protection and generally improves the robustness and lower limit of detection of PCR. For a nested PCR to provide useful quantitative information, it is important that the initial phase of amplification, performed with the outer pair of primers, takes place entirely in the exponential phase. This is generally achieved easily. The major consideration in designing a nested PCR protocol compatible with quantitation is to assure that the maximum concentration of PCR products produced by the outer primers does not exceed approximately 10% the molarity of the outer primers. A simple formula can be used to determine the maximum number of thermal cycles that provide this assurance. Good correspondence was obtained between initial target concentration and final PCR product yield in a nested-primer HIV-1 PCR.
SHP2 Mediates the Localized Activation of Fyn Downstream of the α6β4 Integrin To Promote Carcinoma Invasion (2010)

Src family kinase (SFK) activity is elevated in many cancers, and this activity correlates with aggressive tumor behavior. The α6β4 integrin, which is also associated with a poor prognosis in many tumor types, can stimulate SFK activation; however, the mechanism by which it does so is not known. In the current study, we provide novel mechanistic insight into how the α6β4 integrin selectively activates the Src family member Fyn in response to receptor engagement. Both catalytic and noncatalytic functions of SHP2 are required for Fyn activation by α6β4. Specifically, the tyrosine phosphatase SHP2 is recruited to α6β4 and its catalytic activity is stimulated through a specific interaction of its N-terminal SH2 domain with pY1494 in the β4 subunit. Fyn is recruited to the α6β4/SHP2 complex through an interaction with phospho-Y580 in the C terminus of SHP2. In addition to activating Fyn, this interaction with Y580-SHP2 localizes Fyn to sites of receptor engagement, which is required for α6β4-dependent invasion. Of significance for tumor progression, phosphorylation of Y580-SHP2 and SFK activation are increased in orthotopic human breast tumors that express α6β4 and activation of this pathway is dependent upon Y1494.
Impact of oxygen on Cu surface for highly reliable low-k/Cu interconnects with CuSiN and Ti-based barrier metal (2010)

A trade-off property of CuSiN between EM improvement and line resistance increase was resolved by a breakthrough that leaves oxygen at grain boundary of Cu line surface before CuSiN formation. Then, the combination of CuSiN and Ti-rich TiN (Ti(N)) barrier metal (-BM) was applied. Oxygen left by weakening process strength of CuO <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">x</sub> reduction lowered line resistance, because Si diffusion causing line resistance increase was controlled by the oxygen at grain boundary. Low-damage process of CuO <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">x</sub> reduction also improved voltage ramp dielectric breakdown (VRDB) property. Excellent EM performance brought about by CuSiN was kept by the combination with Ti(N)-BM, because the oxygen made Si and Ti distributions uniform at grain boundary of Cu surface by forming Ti-silicide. Cu atom transport that caused EM failure was suppressed throughout grain boundary of Cu surface.
Prevalence of Serum IgG and Neutralizing Factors Against Adeno-Associated Virus (AAV) Types 1, 2, 5, 6, 8, and 9 in the Healthy Population: Implications for Gene Therapy Using AAV Vectors (2010)

Adeno-associated viruses (AAVs) are small, nonenveloped single-stranded DNA viruses that require helper viruses to facilitate efficient replication. Despite the presence of humoral responses to the wild-type AAV in humans, AAV remains one of the most promising candidates for therapeutic gene transfer to treat many genetic and acquired diseases. Characterization of the IgG subclass responses to AAV and study of the prevalence of both IgG and neutralizing factors to AAV types 1, 2, 5, 6, 8, and 9 in the human population are of importance for the development of new strategies to overcome these immune responses. Natural exposure to AAV types 1, 2, 5, 6, 8, and 9 can result in the production of antibodies from all four IgG subclasses, with a predominant IgG1 response and low IgG2, IgG3, and IgG4 responses. Prevalences of anti-AAV1 and -AAV2 total IgG determined by enzyme-linked immunosorbent assay were higher (67 and 72%) than those of anti-AAV5 (40%), anti-AAV6 (46%), anti-AAV8 (38%), and anti-AAV9 (47%). Furthermore, data showed that cross-reactions are important. The two highest neutralizing factor seroprevalences were observed for AAV2 (59%) and AAV1 (50.5%) and the lowest were observed for AAV8 (19%) and AAV5 (3.2%). Vectors based on AAV5, AAV8, and AAV9 may have an advantage for gene therapy in humans. Furthermore, among individuals seropositive for AAV5, AAV8, and AAV9, about 70-100% present low titers. Better characterization of the preexisting humoral responses to the AAV capsid and cross-reactivity will allow development of new strategies to circumvent AAV acquired immune responses.
Acute IL-3 Priming Up-Regulates the Stimulus-Induced Raf-1-Mek-Erk Cascade Independently of IL-3-Induced Activation of Erk (2005)

IL-3 is a potent priming cytokine for human basophils, inducing an increase of mediator release after stimulation. The mechanism of IL-3 priming of the basophil response to FcepsilonRI aggregating stimuli remains unknown. We explored the regulation of several elements of IgE-mediated signaling by a short priming with IL-3. Early signaling events such as phosphorylation of Syk, Shc, linker for activation of T cells, and the calcium signal were not statistically affected by acute IL-3 priming. Downstream in the signaling cascade, a point of up-regulation was found at the level of Raf-1-Mek-Erk. Although the phosphorylation of Raf-1 was not changed by IL-3 priming, IL-3-primed anti-IgE-stimulated basophils showed a strong synergism for Mek and Erk phosphorylation when compared with either IL-3 or anti-IgE alone; pre-exposure to IL-3 induced a final 13-fold average increase over anti-IgE-induced Erk phosphorylation (6-fold above the sum of anti-IgE and IL-3 alone). The kinetics, dose response, and pharmacologic characteristics of the IL-3 priming of stimulus-induced Erk phosphorylation support the involvement of a yet unknown mechanism that is independent of IL-3-induced Erk and PI3K activation. This type of preactivation can be mimicked by incubation with the Ser-Thr kinase inhibitors, Ro-81-3220, or bisindoylmaleimide II.
Inhibition of growth by transforming growth factor-beta following fusion of two nonresponsive human carcinoma cell lines. Implication of the type II receptor in growth inhibitory responses. (1992)

Loss of growth regulation by transforming growth factor-beta (TGF-beta) may be an important step in carcinogenesis. We have used a cell fusion system to show that inhibition of growth by TGF-beta can be restored to carcinoma cell lines that are unresponsive to the inhibitory effects of TGF-beta. In a previous study, the EJ bladder carcinoma line was fused to the SW480 colon adenocarcinoma line and found to produce nontumorigenic hybrid cells along with one hybrid cell clone of low tumorigenicity. Here we show that the capacity of the nontumorigenic hybrid cells to respond to either TGF-beta 1 or TGF-beta 2 has been restored, while the parental or tumorigenic hybrid cells show little or no inhibition of growth following TGF-beta treatment. Cross-linking analyses with labeled TGF-beta 1 demonstrated much higher levels of the type II (85 kDa) receptor in the hybrid cells compared with the parental tumor lines. Both the parental and tumorigenic hybrid cell lines were capable of responding to TGF-beta as evidenced by increased levels of mRNA for fibronectin, type IV collagenase, and plasminogen activator inhibitor after treatment with TGF-beta 1. These results suggest that the type II receptor is necessary for mediating the effects of TGF-beta on inhibition of growth but not on gene activation of the hybrid cells.
Computed Tomography Screening and Lung Cancer Outcomes (2007)

Screening for lung cancer with low-dose CT may increase the rate of lung cancer diagnosis and treatment, but may not meaningfully reduce the risk of advanced lung cancer or death from lung cancer. Until more conclusive data are available, asymptomatic individuals should not be screened outside of clinical research studies that have a reasonable likelihood of further clarifying the potential benefits and risks.
Treating chronic total occlusions using subintimal tracking and reentry: The STAR Technique (2005)

Successful recanalization of coronary total occlusions (CTOs) remains an area where improvements are needed. We propose an approach similar to the one utilized in treating some peripheral artery occlusions and aimed to create a subintimal dissection with distal reentry. A 0.014' hydrophilic wire with a J-configuration is utilized for this purpose. We applied this technique to CTO of native coronaries in 31 patients where previous attempts failed in 21 of them (67%). The right coronary artery (RCA) was the index vessel in 87% of patients. Recanalization of the vessel and of most of distal branches was achieved in 21 patients; patency of at least one major distal branch was achieved in 9 patients. Drug-eluting stents (DESs) were implanted in 53% of patients. Three patients had intraprocedural vessel perforation without consequences. Five patients (16%) had in-hospital non-Q-wave myocardial infarction. No other adverse events occurred at a mean follow-up of 5.1 +/- 3.7 months except for one noncardiac death. Angiographic follow-up was performed in 21 (67%) patients and 53% of them developed restenosis. Reintervention on the target vessel was performed in 11 patients (52%). Complete success with the procedure was originally obtained in 8 of the 10 patients who did not develop restenosis and in 8 of them DESs were originally implanted. This technique appears a promising approach to recanalize difficult total occlusions, particularly the ones localize on the RCA, which has the most important side branches located distally.
Hepatocellular stem cells (2007)

The liver has enormous regenerative capacity. Restitution of the liver in response to different injuries involves proliferation of cells at different levels of liver lineage. Mature hepatocytes, which are normally dormant, could undergo rapid replication with a near infinite capacity to proliferate. When the replication of mature hepatocytes is inhibited, a reserve compartment of bipotential hepatic progenitor/stem cells is activated. The degree of activation appears to correlate with the degree of inflammation and stage of chronic liver disease. Deregulation of key regulatory signaling pathways such as transforming growth factor-beta, Wnt, hepatocyte growth factor, insulin-like growth factor, transforming growth factor-alpha and epidermal growth factor in this progenitor/stem cell population could give rise to HCC. Further understanding of these key signaling pathways and the molecular and genetic alterations associated with HCC could provide major advances in new therapeutic and diagnostic modalities.
Lyophilization (1999)

Finding consistent, analytical discussions of processes and principles of lyophilization can be challenging and often frustrating. The first resource to gather information about the field, Lyophilization: Introduction and Basic Principles is still the book to have on lyophilization. Presenting information in an easy-to-read style, the book comprehe
Urinary free Cortisol excretion in depression (1976)

Urinary free cortisol (UFC) excretion was determined in 60 depressed inpatients and in 35 psychiatric inpatients with other disorders. The depressed patients had high daily UFC values, while the other patients excreted normal amounts. Over 40% of the depressed patients had UFC excretions in the range seen in Cushing's disease, while only 6% of the other patients excreted such high amounts of cortisol. Age and sex differences did not account for the results. Among the depressed patients those with depressive neuroses excreted less than unipolar or bipolar depressives. Following treatment, more normal UFC excretion was found in depressed patients. The estimation of UFC and its clinical utility are discussed in detail. UFC determination is a simple and informative indicator of adrenal cortical activation and its application to psychoendocrine studies is recommended.
Demonstration of two distinct components in the early antigen complex of epstein‐barr virus‐infected cells (1971)

Abstract Examination of numerous sera from patients with infectious mononucleodis (IM), Burkitt's lymphoma (BL) or nasopharyngeal carcinoma (NPC) for antibodieh to Epstein‐Barr virus (EBV) induced early antigens (EA) revealed two distinct patterns of immunofluorescence in abortively EBV‐infected Raji cells. One showed diguse (D) staining of the nucleus and cytoplasm of invaded cells, the other (R) was restricted to masses in the cytoplasm. Although D‐ or R‐reactive Raji cells became detectable at similar times after exposure to EBV, the percentages of D‐positive cells initially exceeded R‐positive cells but ultimately both were nearly equal in number. R‐positive cells almost invariably contained also D. In EBV‐exposed RPM1 64–10 cells, frequently only D was synthesized. D antigen, in contrast to R, resisted fixation by methanol or ethanol, whereas R proved more resistant than D to proteolytic enzymes. Comparative serum titration on acetone, respectively ethanol‐fixed Raji‐EBV cell smears revealed that the transitory anti‐EA response observed in many IM patients was restricted almost exclusively to anti‐D. Anti‐EA positive sera from NPC patients also showed dominantly anti‐D activity whereas, in BL sera, anti‐R was usually, but not always, dominant, often being the only antibody to the EA complex present. Preliminary tests with pronase‐treated Raji‐EBV cell smears indicated that dominantly anti‐D reactive sera from IM patients were free of anti‐R whereas such sera from NPC or BL patients usually gave positive reactions which in part, however, failed to conform with the R pattern. The possible implications of these results have been discussed.
Blood flow: magnetic resonance imaging. (1985)

The appearance of flowing fluid has been evaluated in several clinical situations using a flow phantom, computer simulation, and clinical magnetic resonance (MR) images. Unsaturated protons just entering the imaging volume can emit a strong signal relative to the partially saturated adjacent tissue ("flow-related enhancement"). Slow laminar flow in veins can be distinguished on the basis of a stronger second echo due to rephasing effects ("even echo rephasing"). Synchronization of the cardiac cycle and the MR pulsing sequence produces increased signal in sections acquired during diastole ("diastolic pseudogating"). Intraluminal signal is shown to decrease as velocity is increased ("high velocity signal loss"). Onset of turbulence causes further loss of signal. Direction of flow oblique to the imaging plane can be predicted on the basis of decreased upstream and increased downstream signal.
Differential Killing of Human Carcinoma Cells Supplemented With n-3 and n-6 Polyunsaturated Fatty Acids<xref ref-type="fn" rid="FN2">2</xref> (1986)

The effects of essential fatty acids on cell proliferation and cell viability of 3 human tumor and 4 normal cell lines were tested in vitro. It was found that n-3 and n-6 fatty acids supplemented at 20 micrograms/ml killed human breast, lung, and prostate cancer cells selectively. Normal human fibroblasts and other normal cells were not killed, but their rate of division was lowered. The most selective cytotoxic effects were obtained with fatty acids containing 3, 4, and 5 double bonds. The degree of inhibition of growth and/or loss of viability depended on a given fatty acid, on cell density, on fatty acid concentration, and on the type of cell. When eicosapentaenoate, gammalinolenate, or arachidonate was added to cocultures made of human cancer cells with normal fibroblasts, the cancer cells were selectively eliminated. These results, combined with the observation that certain fatty acids coupled to cytotoxic agents may enhance the cytotoxic activity, suggest that treatment of cancer with polyunsaturated fatty acids containing 3, 4, and 5 double bonds has potential clinical usefulness.
Keratinocyte growth factor is a growth factor for type II pneumocytes in vivo. (1994)

Keratinocyte growth factor (KGF) administered as a single intratracheal injection causes a prominent dose-dependent proliferation of type II alveolar epithelial cells in the lungs of adult rats. The increase in mitotically active alveolar cells histologically appears as a micropapillary epithelial cell hyperplasia after 2 d and peaks after 3 d in the form of monolayers of cuboidal epithelial cells lining alveolar septae. Proliferating cell nuclear antigen immunohistochemistry confirmed the profound proliferative response induced by KGF. The hyperplastic alveolar lining cells contain immunoreactive surfactant protein B and are ultrastructurally noted to contain lamellar inclusions characteristic of surfactant-producing type II pneumocytes. Mild focal bronchiolar epithelial hyperplasia is noted but is much less striking than the proliferation of type II pneumocytes. Large airways are unaffected by KGF. Daily intravenous injection of KGF is also able to cause pneumocyte proliferation. The normal adult rat lung constitutively expresses both KGF and KGF receptor mRNA, suggesting that endogenous KGF may be implicated in the paracrine regulation of the growth of pneumocytes. In conclusion, KGF rapidly and specifically induces proliferation and differentiation of type II pneumocytes in the normal adult lung.
Expansion of Tumor-T Cell Pairs from Fine Needle Aspirates of Melanoma Metastases (2000)

Lymphocytes expanded from excised specimens can be used to characterize intratumoral T cell responses. These analyses, however, are limited to one time point in the natural history of the removed tumor. The expansion of autologous tumor cells and tumor-infiltrating lymphocytes (TIL) from fine needle aspirates (FNA) of tumors potentially allows a dynamic evaluation of T cell responses within the same lesion at moments relevant to the disease course or response to therapy. Fourteen TIL cultures and 8 tumor cell lines were generated from 18 FNA (12 patients). Five of six TIL that could be tested against autologous tumor demonstrated specific reactivity. Two additional TIL for which no autologous tumor was available demonstrated recognition of HLA-matched melanoma cell lines. Serial FNA of the same lesions were performed in five HLA-A*0201 patients vaccinated with the emulsified melanoma Ag (MA) epitopes: MART-1:27-35; tyrosinase:368-376(370D); gp100:280-288(288V); and gp100:209-217 (210M). FNA material was separately cultured for a short time in IL-2 (300 IU/ml) after stimulation with irradiated autologous PBMC pulsed with each peptide or FluM1:58-66 (1 micromol/ml). No peptide-specific TIL could be expanded from prevaccination FNA. However, after vaccination, TIL specific for gp100:280(g280), gp100:209 (g209), and MART-1:27-35 (MART-1)-related epitopes were identified in three, three, and two patients, respectively. No Flu reactivity could be elicited in TIL, whereas it was consistently present in parallel PBMC cultures. This excluded PBMC contamination of the FNA material. This analysis suggests the feasibility of TIL expansion from minimal FNA material and localization of vaccine-specific T cells at the tumor site.
Single dose oral oxycodone and oxycodone plus paracetamol (acetominophen) for acute postoperative pain in adults (2000)

Single-dose oral oxycodone, with or without paracetamol, appears to be of comparable efficacy to intramuscular morphine and non-steroidal anti-inflammatory drugs. Central nervous system adverse effects were common.
Pulse response of a high power waveguide optoelectronic switch for track and hold operation (2003)

For an analog-to-digital converter (ADC), it is important to have precise sampling time control to avoid resolution degradation. At high sampling rates, this precise sampling time control becomes increasingly difficult to achieve. To relax the stringent timing requirement of an ADC quantizer, a track-and-hold (T&H) circuit is implemented in many ADC architectures. In this work, a high power, high speed waveguide integrated photodiode (WIP) is tested as an optoelectronic switch for the T&H function. The photodiode operates with light launched into a passive waveguide before being coupled into the absorber. Using a matching layer between the passive waveguide and the absorber, the absorption profile along the absorber waveguide is modified to give small peak absorption. This reduces the effect of the charge screening effect and also the heating effect, so that the saturation power of the photodiode can be increased. Pulse measurement of an optical WIP switch is presented. The results show the peak current reaches 50 mA and the rise time is approximately 18.2 ps. These results show this switch can potentially be used for clocking an electronic T&H circuit.