gebhart/patrepeval huggingface dataset:
Rational optimization of tumor epitopes using <i>in silico</i> analysis‐assisted substitution of TCR contact residues (2009)

Altered peptide ligands with increased affinity of the peptide-MHC complex for the TCR provide an alternative strategy to natural T-cell epitopes for cancer immunotherapy, as they can recruit and stimulate stronger T-cell repertoires. However, it remains unclear how alterations of the TCR contact residues improve the interaction between the peptide-MHC complex and the TCR molecule. In this study, we introduced a molecular simulation strategy to optimize a tumor immunodominant epitope NY-ESO-1(157-165) by the substitution of the potential TCR contact residues. We correlated molecule simulation with T-cell activation capacity assay and detected the effect of modifications of TCR contact residues on T-cell recognition. An agonist peptide W5F with substitution at Trp5 with Phe was identified and it exhibits a stronger ability to induce a cross-reactive CTL response with the WT peptide. Additionally, the W5F-induced CTL could be maintained with the WT peptide and possess higher capacity in lysing native NY-ESO-1-expressing tumor cells. These results provide important insights into the enhanced immunogenicity of epitopes through substitution at the TCR contact sites and revealed a novel molecular simulation approach for rational therapeutic peptide vaccine design.
Expression and regulation of golli products of myelin basic protein gene during in vitro development of oligodendrocytes (2001)

The myelin basic protein (MBP) gene produces two families of proteins, the classic MBPs, important for myelination of the CNS, and the golli proteins, whose biological role in oligodendrocytes (OLs) is still unknown. The goals of this work were to study the in vitro pattern of expression of the golli products during OL differentiation and to compare it with that of the classic MBP products of the gene. Mouse primary glial cultures were analyzed at the mRNA and protein levels with an array of techniques. We found that OLs express golli mRNA primarily during intermediate stages of differentiation, which was confirmed by immunocytochemical analysis. Golli expression was low in proliferating OL progenitors as well as in terminally mature OLs. Golli proteins were found associated with the OL cell soma and nuclei and, to a lesser extent, with the cellular processes. We also found that golli proteins are not targeted to myelin in vitro and in vivo, in contrast to the classic MBPs. Finally, we found that golli expression is regulated during OL development and can be manipulated by growth factors such as basic fibroblast growth factor, neurotrophin-3, and retinoic acid.
X-LINKED RECESSIVE BULBOSPINAL NEURONOPATHY (1989)

A clinicopathological study on X-linked recessive bulbospinal neuronopathy was undertaken on 9 cases, with morphological observations on 3 autopsied cases and sural nerve biopsies from 6 patients. Both lower motor and primary sensory neurons were involved. Lower motor neurons were markedly depleted through all spinal segments and in brainstem motor nuclei except for the third, fourth and sixth cranial nerves. Primary sensory neurons were less severely affected. A quantitative study of primary sensory axons at several levels in the peripheral nervous system suggested that a distally accentuated axonopathy was the salient pathological process. Segmental demyelination and remyelination clustered on individual fibres, and g ratios (axon diameter: total fibre diameter) in the sural nerve showed an increased scatter in some cases. Evidence of regeneration was inconspicuous. Unmyelinated fibres were well preserved throughout all the nerves examined. Neurons in the Onufrowicz nuclei, in the intermediolateral columns and in Clarke's columns of the spinal cord were generally well preserved. These observations indicate that a lower motor and primary sensory neuronopathy is a major neurological manifestation in this disease.
ENHANCED ROSETTING OF SHEEP ERYTHROCYTES BY HUMAN PERIPHERAL BLOOD T CELLS IN THE PRESENCE OF DEXTRAN (1975)

In part 1 of this review, published last month, literature exploring the psychological bereavement theories and the health consequences of bereavement are summarized. The second part builds on this to outline the debate surrounding the characteristics of abnormal bereavement, while also focusing on risk factors for this morbidity. This leads on to a summary of the literature on bereavement care, particularly from a general practice point of view. Finally, areas for further research are highlighted.
Validity of newborn oscillometric blood pressure. (1995)

The objective of this study was to determine the validity of oscillometric blood pressure in relation to arterial blood pressure. Thirty-one newborns were studied. Clinical characteristics, complications, and treatment interventions were documented. Arterial pressure (every 2 sec) and oscillometric pressure (every 3 min) were concurrently recorded for 1-2 h. Serial observations of oscillometric pressure followed the trend of arterial pressure in the individual newborn. However, the study averaged oscillometric pressures were lower than the arterial pressures: systolic, by 1 mmHg; mean, by 5.3 mmHg (p < 0.0001); and diastolic, by 4.6 mmHg (p < 0.0001). The variance of individual, 15-min averaged, and 1-h averaged observations of oscillometric pressure in relation to arterial pressure was examined. Variance for individual observations may be large. The least variance of oscillometric pressure was in the 1-h averaged mean pressure, in which the difference was +/- 2 mmHg in 77% and +/- 4 mmHg in 95% of observations. Clinical characteristics, with the exception of birth weight and treatment interventions, did not affect the variance of oscillometric pressure. This study implies that the offset in relation to arterial pressure should be established for each oscillometric pressure monitoring system. Hourly averaged mean oscillometric pressure is satisfactory for many newborn assessments and management circumstances. However, arterial pressure may be necessary to accurately document transient hypertension or hypotension or an unstable blood pressure.
The Yale cTAKES extensions for document classification: architecture and application (2011)

The F(1)-Score of the system for the retrieval of abdominal radiology reports was 96%, and was 79%, 91%, and 95% for the presence of liver masses, ascites, and varices, respectively. The authors released YTEX as open source, available at http://code.google.com/p/ytex.
Reduction Expansion Synthesis for Magnetic Alloy Powders (2015)

In this work submicron scale ferromagnetic and magnetic rare-earth alloys were produced using Reduction Expansion Synthesis (RES), a technique in which metal particles are the product of the rapid heating to approximately 800 degrees Celsius, in inert atmosphere, of physical mixtures of urea, or similar molecules, and metal oxide, hydroxide or nitrates. As shown by scanning electron microscopy and x-ray diffraction, RES produced submicron magnetic particles. Essential to both 3D printing and metal injection molding (MIM) is the availability of fine powders to manufacture small, complex, metal parts. There are technological limits to the minimum particle size that can be produced using available low cost techniques, which is approximately 10 microns. This minimum particle size in turn limits the size of features on MIM and 3D printed metal parts. The demonstrated ability of RES to produce sub-micron particle sizes indicates this technology could enable the manufacture of finer features using either 3D printing or MIM.
Isomer-specific actions of conjugated linoleic acid on muscle glucose transport in the obese Zucker rat (2003)

The fatty acid-conjugated linoleic acid (CLA) enhances glucose tolerance and insulin action on skeletal muscle glucose transport in rodent models of insulin resistance. However, no study has directly compared the metabolic effects of the two primary CLA isomers, cis-9,trans-11-CLA (c9,t11-CLA) and trans-10,cis-12-CLA (t10,c12-CLA). Therefore, we assessed the effects of a 50:50 mixture of these two CLA isomers (M-CLA) and of preparations enriched in either c9,t11-CLA (76% enriched) or t10,c12-CLA (90% enriched) on glucose tolerance and insulin-stimulated glucose transport in skeletal muscle of the insulin-resistant obese Zucker (fa/fa) rat. Animals were treated daily by gavage with either vehicle (corn oil), M-CLA, c9,t11-CLA, or t10,c12-CLA (all CLA treatments at 1.5 g total CLA/kg body wt) for 21 consecutive days. During an oral glucose tolerance test, glucose responses were reduced (P < 0.05) by 10 and 16%, respectively, in the M-CLA and t10,c12-CLA animals, respectively, whereas insulin responses were diminished by 21 and 19% in these same groups. There were no significant alterations in these responses in the c9,t11-CLA group. Insulin-mediated glucose transport activity was enhanced by M-CLA treatment in both type I soleus (32%) and type IIb epitrochlearis (58%) muscles and by 36 and 48%, respectively, with t10,c12-CLA. In the soleus, these increases were associated with decreases in protein carbonyls (index of oxidative stress, r = -0.616, P = 0.0038) and intramuscular triglycerides (r = -0.631, P = 0.0028). Treatment with c9,t11-CLA was without effect on these variables. These results suggest that the ability of CLA treatment to improve glucose tolerance and insulin-stimulated glucose transport activity in insulin-resistant skeletal muscle of the obese Zucker rat are associated with a reduction in oxidative stress and muscle lipid levels and can be specifically ascribed to the actions of the t10,c12 isomer. In the obese Zucker rat, the c9,t11 isomer of CLA is metabolically neutral.
Cholinergic modulation of memory in the basolateral amygdala involves activation of both m1 and m2 receptors (2003)

Muscarinic cholinergic activation is a critical component of basolateral amygdala (BLA)-mediated modulation of memory consolidation. The receptor(s) mediating this activation during consolidation have not been elucidated. This study investigated the roles of muscarinic subtype 1 (m1) and subtype 2 (m2) receptors in memory enhancement, by post-training intra-BLA infusions of the non-selective muscarinic agonist oxotremorine. Rats received intra-BLA infusions of either oxotremorine alone (10 microg in 0.2 microl per side), oxotremorine together with the selective m1 antagonist telenzipine (1.7, 5.0, 17 or 50 nmol/side), oxotremorine with the selective m2 antagonist methoctramine (1.7, 5.0, 17 or 50 nmol/side), oxotremorine with a combination of the above doses of telenzipine and methoctramine, or only vehicle, immediately after inhibitory avoidance training. Performance on a 48-hour retention test was significantly enhanced in oxotremorine-treated rats relative to vehicle-infused controls. Intra-BLA co-infusion of oxotremorine with either telenzipine (5, 17 or 50 nmol/side) or methoctramine (17 or 50 nmol/side) blocked the oxotremorine-induced enhancement. Combinations of these antagonists did not act additively to block memory enhancement by oxotremorine. These findings indicate that modulation of memory consolidation induced by cholinergic influences within the BLA requires activation of both m1 and m2 receptor synapses. Plausible mechanisms for m1- and m2-mediated influences on BLA circuitry are discussed.
Effects of ground electrode on signal transmission of human body communication using human body as transmission medium (2006)

In this paper, the measurement results on the effects of ground electrode according to the transmission distance are presented. A biological tissue-equivalent phantom has been used in the measurement of a previous paper, but a real human body is used in this paper. Also, the measurement results are analyzed by EM simulation. In the previous papers K. Fujii et al. (2003)-(2002), the simulation model for human body has been composed of only muscle tissue. In this paper, a more accurate model composed of muscle and other tissues is used during the simulation. Finally, the method by which a ground electrode can be used more efficiently is proposed based on the measurement results
A unifying concept in vascular health and disease (2018)

Interventions to restore blood vessel stability could improve health outcomes
Gender differences in chronic headache in a treatment-seeking population. (2001)

Treatment recommendations for chronic headache should be similar for men and women. However, evaluation of disability and exercise as headache triggers should be actively sought in male patients, while women should be educated about dietary adjustments and avoidance of eating irregularities.
Performance evaluation of space-frequency coded OFDM systems over frequency selective fading channels (2004)

In this paper, closed-form expressions of bit error rate (BER) performance of space-frequency block coded OFDM (SFBC-OFDM) systems are derived and evaluated over frequency selective fading channels. In the performance evaluation both M-ary phase shift keying (MPSK) and M-ary quadrature amplitude modulation (MQAM) are considered. Numerical results are provided for analysis and simulations. In addition performance of several forms of SFBC-OFDM system are also evaluated and compared.
Stability and Safety of an AAV Vector for Treating <i>RPGR-ORF15</i> X-Linked Retinitis Pigmentosa (2015)

Our collaborative successful gene replacement therapy using AAV vectors expressing a variant of human RPGR-ORF15 in two canine models provided therapeutic proof of concept for translation into human treatment. The ORF15 sequence contained within this AAV vector, however, has ORF15 DNA sequence variations compared to the published sequence that are likely due to its unusual composition of repetitive purine nucleotides. This mutability is a concern for AAV vector production and safety when contemplating a human trial. In this study, we establish the safety profile of AAV-hIRBP-hRPGR and AAV-hGRK1-hRPGR vectors used in the initial canine proof-of-principle experiments by demonstrating hRPGR-ORF15 sequence stability during all phases of manipulation, from plasmid propagation to vector production to its stability in vivo after subretinal administration to animals. We also evaluate potential toxicity in vivo by investigating protein expression, retinal structure and function, and vector biodistribution. Expression of hRPGR is detected in the inner segments and synaptic terminals of photoreceptors and is restricted to the connecting cilium when the vector is further diluted. Treated eyes exhibit no toxicity as assessed by retinal histopathology, immunocytochemistry, optical coherence tomography, fundoscopy, electroretinogram, and vector biodistribution. Therefore, the hRPGR-ORF15 variant in our AAV vectors appears to be a more stable form than the endogenous hRPGR cDNA when propagated in vitro. Its safety profile presented here in combination with its proven efficacy supports future gene therapy clinical trials.
A Robust Kolmogorov-Smirnov Detector for Misbehavior in IEEE 802.11 DCF (2007)

The CSMA/CA protocols are designed under the assumption that all participant nodes would abide to the protocol rules. This is of particular importance in distributed protocols such as the IEEE 802.11 distributed coordinating function (DCF), in which nodes control their own backoff parameters. A selfish node may deliberately modify its random assignment and gain unfair access to the network resources. This would result in an increased observed collision probability for the rest of the nodes, that would increase their backoff windows as a result, further increasing the benefit of the selfish nodes. In this work, we develop of a robust non parametric batch detector based on the Kolmogorov-Smirnov (K-S) statistics that does not require any modification on the existing CSMA/CA protocols, and we apply it to detect misbehaviors in an IEEE 802.11 DCF network using the ns-2 simulator. We show that our method has a performance comparable to the optimum detectors with perfect information for the majority of misbehaviors, and it is able to detect any deviation from the protocol after just a few transmissions from the offending terminal.
Photoacoustic technique to measure temperature effects on microbubble viscoelastic properties (2018)

Phospholipid-coated microbubbles are being developed for several biomedical applications, but little is known about the effect of temperature on the viscoelastic properties of the shell. Here, we report on the use of a photoacoustic technique to study the shell properties of individual microbubbles as a function of temperature. The microbubbles were driven into small-amplitude oscillations by ultrasound waves generated from the absorption of an intensity-modulated infrared laser, and these oscillations were detected by forward-light scattering of a second blue laser. The drive laser modulation frequency was swept to determine the resonant response of 2-4 <i>μ</i>m radius microbubbles. Lipid shell elasticity and viscosity were determined by modeling the microbubble response as a linear harmonic oscillator. The results from slow heating showed a linear decrease in elasticity and viscosity between 21 and 53 °C and a corresponding increase in the maximum oscillation amplitude. Rapid heating to 38 °C, on the other hand, showed a transient response in the viscoelastic properties, suggesting shell rupture and reformation during microbubble growth and subsequent dissolution. These effects are important for biomedical applications, which require warming of the microbubbles to body temperature.
Incidence of circulating tumor cells (CTCs) in peripheral blood of breast cancer patients at primary diagnosis—A potential tool for risk stratification (2006)

20053 Background: In metastatic breast cancer, CTCs have been proven an independent predictor for progression-free and overall survival (Cristofanilli, NEJM 2004). Therefore, we evaluated the role of CTCs in peripheral blood of breast cancer patients at primary diagnosis and during adjuvant systemic treatment within the Success-Trial (n = 3,658 pts). First results of the incidence of CTCs prior to chemotherapy will be presented here. Methods: The CellSearchSystem (Veridex) was used for isolation and enumeration of CTCs from 23 ml of peripheral blood. Briefly, after immunomagnetic enrichment with an anti-Epcam-antibody, cells were labelled with anti-cytokeratin (8,18,19) and anti-CD45 antibodies to distinguish epithelial cells and leukocytes. Patients had been accrued between September and December 2005. Results: We analyzed 124 breast cancer patients at the time of primary diagnosis. The majority of patients presented with small tumors (41% T1, 55% T2, 4% T3), and 32% were node-negative (45% N1, 14% N2, 9% N3). While a positive hormone receptor status was observed in 74% of patients and 31% were her2/neu positive, most tumors showed an intermediate or unfavourable grading (2% G1, 98% G2–3). In this patient group, 32% of patients (n = 40) presented with ≥1CTC in peripheral blood. In patients with the detection of CTCs, the mean number of cells was 5 (range 1–38). In 11 healthy individuals we found 1 CTC in one blood sample. The presence of CTCs did not correlated with tumor size (p = .39), presence of lymph node metastases (p = .25), histopathological grading (p = .33), hormone receptor status (p = .56) or her2/neu status of the primary tumor (p = .14). Conclusions: The isolation of CTCs from peripheral blood of primary breast cancer patients is feasible and might prove as an easy applicable and convenient technique to give further insight into the spread of the disease. The Success-Trial will investigate, whether CTCs can be used for risk stratification to more tailored treatment approaches and for the monitoring of treatment efficacy in individual patients. [Table: see text]
Human XCR1+ Dendritic Cells Derived In Vitro from CD34+ Progenitors Closely Resemble Blood Dendritic Cells, Including Their Adjuvant Responsiveness, Contrary to Monocyte-Derived Dendritic Cells (2014)

Human monocyte-derived dendritic cell (MoDC) have been used in the clinic with moderately encouraging results. Mouse XCR1(+) DC excel at cross-presentation, can be targeted in vivo to induce protective immunity, and share characteristics with XCR1(+) human DC. Assessment of the immunoactivation potential of XCR1(+) human DC is hindered by their paucity in vivo and by their lack of a well-defined in vitro counterpart. We report in this study a protocol generating both XCR1(+) and XCR1(-) human DC in CD34(+) progenitor cultures (CD34-DC). Gene expression profiling, phenotypic characterization, and functional studies demonstrated that XCR1(-) CD34-DC are similar to canonical MoDC, whereas XCR1(+) CD34-DC resemble XCR1(+) blood DC (bDC). XCR1(+) DC were strongly activated by polyinosinic-polycytidylic acid but not LPS, and conversely for MoDC. XCR1(+) DC and MoDC expressed strikingly different patterns of molecules involved in inflammation and in cross-talk with NK or T cells. XCR1(+) CD34-DC but not MoDC efficiently cross-presented a cell-associated Ag upon stimulation by polyinosinic-polycytidylic acid or R848, likewise to what was reported for XCR1(+) bDC. Hence, it is feasible to generate high numbers of bona fide XCR1(+) human DC in vitro as a model to decipher the functions of XCR1(+) bDC and as a potential source of XCR1(+) DC for clinical use.
Urinary interleukins in patients receiving intravesical bacillus calmette-guerin therapy for superficial bladder cancer (1989)

Intravesical administration of Bacillus Calmette-Guerin (BCG) causes a localized cell-mediated immune response. The intensity of this inflammatory response may be gauged by measuring the levels of both interleukin-2 (IL-2) and an inhibitor of interleukin-2 (IL-2-IN) activity in the urine during the hours after a BCG instillation. The levels of urinary IL-2 and IL-2-IN in the sixth week of BCG therapy predicted the subsequent clinical course in a group of 25 patients (P less than 0.01). Measurement of urinary IL-2 and IL-2-IN activity may be used to identify accurately those patients likely to develop a tumor recurrence, thereby sparing them the risk associated with inadequately treated bladder cancer. Since IL-2 and IL-2-IN are competitive with respect to biologic activity, and since relatively high urinary levels of either IL-2 or IL-2-IN activity correlated with a favorable clinical course, the authors conclude that the presence of bioactive IL-2 in urine is not required for the prevention of recurrent superficial bladder cancer.
A New Ruthenium Sensitizer Containing Benzo[1,9]quinolizino(acridin-2-yl)vinyl-2,2′-bipyridine Ligand for Effective Nanocrystalline Dye-Sensitized Solar Cells (2012)

Novel ruthenium bipyridyl sensitizer incorporating conjugated benzo[1,9]quinolizino-(acridin-2-yl)vinyl-2,2′-bipyridine ligand [ JJ-12 ] has been synthesized and demonstrated as efficient sensitizer in dye-sensitized solar cells. A mesoporous titania film stained with JJ-12 exhibits a remarkable incident monochromatic photon-to-current conversion efficiency of 82%. Under standard AM 1.5 sunlight, the solar cell using a liquid-based electrolyte consisting of 0.6 M 1,2-dimethyl-3-propylimidazolium iodide (DMPII), 0.05 M I 2 , 0.1 M LiI, and 0.5 M tert -butylpyridine in acetonitrile exhibits a short-circuit photocurrent density of 16.47 mA/cm 2 , an open-circuit voltage of 0.71 V, and a fill factor of 0.71, corresponding to an overall conversion efficiency of 8.34 %.
旅美华侨在一九○五至一九○六年中国抵制美货运动中的作用 (1991)

1905年■月13日,美国船王 R·p·施沃林就中国商人决定联合抵制美货输入中国一事致函西奥多·罗斯福总统说:“当这颗球已经开始向山下滚的时候,很难讲它何时才会停下来。”三个星期后,忧心忡忡的范约翰牧士——上海著名的长老会传教士——写信给总统说,这次抵制运动“必定会把每一个美国人,并且随后把每一个外国人赶出中国”。然而这对于一位兴高采