gebhart/patrepeval huggingface dataset:
A spacer region between the single chain antibody- and the CD3 zeta-chain domain of chimeric T cell receptor components is required for efficient ligand binding and signaling activity. (1995)

The elimination of tumor cells by cytotoxic T lymphocytes (CTLs) could become the basis of a biological cancer therapy. The recognition specificity of cytotoxic T lymphocytes (CTLs) can be genetically modified by stable introduction of chimeric T cell receptor genes and thus be directed towards tumor cells. We designed a recombinant T cell receptor (TCR) component consisting of a single chain Fv derivative of a monoclonal antibody (scFv) serving as the extracellular antigen-binding domain and the zeta-chain of the TCR/CD3 complex serving as a signal transducing domain. Three chimeric receptor constructs differing in their molecular structure were derived and their functions in transduced T cells compared. A construct in which the scFv domain, specific for the ErbB-2 receptor, was fused directly to the zeta-chain, and two constructs containing different hinge regions between the functional domains, were made. The hinge regions serve as spacers which increase the distance of the scFv moiety from the plasma membrane. Only the two scFv-zeta chimeras containing a hinge region showed ErbB-2 binding activity, when expressed in T cells. The scFv-zeta construct which lacks a spacer segment did not. Consistently, only the spacer-containing chimeras transduced T cell receptor signals following ErbB-2 mediated crosslinking. An increase in intracellular Ca2+ concentrations and cytokine secretion was observed. ErbB-2 expressing tumor cells were efficiently lysed by CTLs which expressed the spacer-containing scFv-zeta chimeras. Our results will help to optimize the design of recombinant T cell receptor components useful in the grafting of a specificity of recognition on to cytotoxic T cells and possibly the gene therapy of cancer.
Rapid Coupling of Methyl Iodide with Aryltributylstannanes Mediated by Palladium(0) Complexes: A General Protocol for the Synthesis of 11CH3‐Labeled PET Tracers (1997)

Abstract The reaction of methyl iodide and (excess) aryltributylstannane to give a methylarene has been studied with the focus on the realization of rapid coupling for incorporation of short‐lived radionuclides into bioactive organic compounds. The coupling of methyl iodide with tributylphenylstannane (40 equiv) is accomplished in &gt;90% yield within 5 min at 60°C with a tri‐ o ‐tolylphosphine‐bound, coordinatively unsaturated Pd 0 complex together with a Cu I salt and K 2 CO 3 in DMF. This protocol is applicable to a variety of homo‐ and heteroaromatic tin compounds, to give the corresponding methylated derivatives. The effects of the tri‐ o ‐tolylphosphine ligand, a Cu(I) salt, and DMF are discussed. This new protocol provides a firm chemical basis for the synthesis of 11 CH 3 ‐incorporated PET tracers.
Aminoacyl-tRNA Synthetases: Occurrence, Structure, and Function (2014)

Translation of the genetic message into proteins implies the precise correspondence between the 64 base triplets and the 20 canonical amino acids. In this process, the tRNAs play a central role by providing the nascent polypeptide with the amino acids by which they are esterified, in response to codons on the mRNA. The pairing of mRNA codon to tRNA anticodon is independent of the nature of the amino acid esterified to the tRNA. Therefore, the accuracy of the tRNA aminoacylation reaction, ensured by the aminoacyl-tRNA synthetases (aaRS), is of first importance in all living cells, since it will govern, to a large extent, the fidelity of the translation process. Much work has been done to understand how aaRS achieve high accuracy of tRNA aminoacylation while maintaining a sufficiently high rate of catalysis, generally in the order of several turnovers per second.. Since the early description of aaRS, most of the studies have focused on the kinetic mechanisms of action of the aaRS. More recently, with the availability of the three-dimensional structure of several tRNAs and synthetases and the possibility of generating variants of these macromolecules, a static picture of their specific interaction at the atomic level has emerged. Two main functions are carried out by an aaRS: the activation of the amino acid and the recognition of the tRNA molecule. In addition, association between protomers must be ensured. The present knowledge indicates that each of these functions is distributed along the aaRS polypeptide through the formation of specialized domains.
Immune Enhancing Effect of a Growth Hormone Secretagogue (2001)

Growth hormone (GH) has been known to enhance immune responses, whether directly or through the insulin like growth factor-1, induced by GH. Recently a nonpeptidyl small m.w. compound, a GH secretagogue (GHS), was found to induce the production of GH by the pituitary gland. In this study, we examined the effect of GHS in immunological functions of 5- to 6-wk-old and 16- to 24-month-old mice. In young mice, we observed a significant increase in PBLs, but T and B cell-proliferative responses were not consistently enhanced. The old mice, treated with GHS for 3 wk, did not show increases in peripheral lymphocytes, but they exhibited a statistically significant increase in thymic cellularity and differentiation. When inoculated with a transplantable lymphoma cell line, EL4, the treated old mice showed statistically significant resistance to the initiation of tumors and the subsequent metastases. Generation of CTL to EL4 cells was also enhanced in the treated mice, suggesting that GHS has a considerable immune enhancing effect, particularly in the old mice. We have also found that GHS promoted better thymic engraftment in bone marrow transplant of SCID mice. We found more cycling cells in the spleens of treated mice, suggesting that GHS may exert its immune enhancing effect by promoting cell division in lymphoid cells. These observations ascribe to GHS a novel therapy possible for aging, AIDS, and transplant individuals, whose immune functions are compromised.
Inflammatory cells in brush cytology samples correlate with the severity of corneal lesions in atopic keratoconjunctivitis (2004)

Inflammatory cells in brush cytology samples correlated with corneal damage. Evaluation of the relative percentages of inflammatory cells in brush cytology samples is a useful method of assessing disease activity in allergic conjunctival disease.
ROS and innate immunity. (2009)

Oxygen is converted into reactive oxygen (RO) by radiation, light, the electron transport system in mitochondria, or by other enzymes and is regulated by the action of antioxidative enzymes which convert RO into an inactive state. Reactive oxygen species (ROS) have a biocidal effect on invading bacteria and they can also injure the cells of the host. For this reason, RO is considered as a general cause of aging and contributes to lifestyle-related diseases and cancer. However, for any organism that uses oxygen as an energy source, RO is inevitably produced and has important biological significance. Apart from the direct activity of RO, recent studies have shown that it functions as a second messenger of signal transduction. In this review, the recent findings related to ROS/nitric oxide (NO) and especially of its relationship to innate immunity are summarized.
Leakage current: Moore's law meets static power (2003)

Off-state leakage is static power, current that leaks through transistors even when they are turned off. The other source of power dissipation in today's microprocessors, dynamic power, arises from the repeated capacitance charge and discharge on the output of the hundreds of millions of gates in today's chips. Until recently, only dynamic power has been a significant source of power consumption, and Moore's law helped control it. However, power consumption has now become a primary microprocessor design constraint; one that researchers in both industry and academia will struggle to overcome in the next few years. Microprocessor design has traditionally focused on dynamic power consumption as a limiting factor in system integration. As feature sizes shrink below 0.1 micron, static power is posing new low-power design challenges.
Linear Interpolation Revitalized (2004)

We present a simple, original method to improve piecewise-linear interpolation with uniform knots: we shift the sampling knots by a fixed amount, while enforcing the interpolation property. We determine the theoretical optimal shift that maximizes the quality of our shifted linear interpolation. Surprisingly enough, this optimal value is nonzero and close to 1/5. We confirm our theoretical findings by performing several experiments: a cumulative rotation experiment and a zoom experiment. Both show a significant increase of the quality of the shifted method with respect to the standard one. We also observe that, in these results, we get a quality that is similar to that of the computationally more costly "high-quality" cubic convolution.
Ensuring compactness, reliability, and scalability for the next generation of high-field lasers (1998)

If further developments in high-field lasers are to be accessible to universities and institutes, new laser materials and phase control techniques, which will result in compact, reliable systems with higher peak power, must be adopted. The choice of high-saturation-fluence gain material and the measurement and active control of temporal and spatial phase distortions for compact chirped-pulse amplification (CPA) systems of the future are discussed. Using the proper material and phase control a focused intensity of 10/sup 25/ W/cm/sup 2/ is theoretically possible.
Prothymosin Alpha Expression in Lymph Nodes and Tonsils: An Optical and Ultrastructural Study (1992)

Prothymosin alpha (ProT alpha) distribution in human and rat lymph nodes and human tonsils was studied by means of immunohistochemical methods, using specific antibodies raised against thymosin alpha 1. We observed ProT alpha immunoreactivity in lymphoid cells of the germinal centers both in humans and rats. In human tonsils, positive cells were also seen in the basal layer of the surface epithelium. These results support the hypothesis that ProT alpha expression is restricted to actively proliferating cells. Immunoelectron microscopy revealed that ProT alpha was located in the nucleus, mainly in the border between euchromatin and heterochromatin.
NetB, a New Toxin That Is Associated with Avian Necrotic Enteritis Caused by Clostridium perfringens (2008)

For over 30 years a phospholipase C enzyme called alpha-toxin was thought to be the key virulence factor in necrotic enteritis caused by Clostridium perfringens. However, using a gene knockout mutant we have recently shown that alpha-toxin is not essential for pathogenesis. We have now discovered a key virulence determinant. A novel toxin (NetB) was identified in a C. perfringens strain isolated from a chicken suffering from necrotic enteritis (NE). The toxin displayed limited amino acid sequence similarity to several pore forming toxins including beta-toxin from C. perfringens (38% identity) and alpha-toxin from Staphylococcus aureus (31% identity). NetB was only identified in C. perfringens type A strains isolated from chickens suffering NE. Both purified native NetB and recombinant NetB displayed cytotoxic activity against the chicken leghorn male hepatoma cell line LMH; inducing cell rounding and lysis. To determine the role of NetB in NE a netB mutant of a virulent C. perfringens chicken isolate was constructed by homologous recombination, and its virulence assessed in a chicken disease model. The netB mutant was unable to cause disease whereas the wild-type parent strain and the netB mutant complemented with a wild-type netB gene caused significant levels of NE. These data show unequivocally that in this isolate a functional NetB toxin is critical for the ability of C. perfringens to cause NE in chickens. This novel toxin is the first definitive virulence factor to be identified in avian C. perfringens strains capable of causing NE. Furthermore, the netB mutant is the first rationally attenuated strain obtained in an NE-causing isolate of C. perfringens; as such it has considerable vaccine potential.
Investigation on the Corrosion of Cu Metallization in the Focused Ion Beam System due to a low I2 Background (1999)

Abstract The corrosion effect of an I2 background during focused ion beam (FIB) analysis of Cu-metallization structures is investigated. In-situ Cu corrosion in the FIB system can occur even if the I2 gas has not been used anymore in the last 24 h before the loading of the Cu sample in the system including several vents and pump-downs of the chamber in that period. Hence the I2 can have a long-term memory effect and is not compatible with FIB analysis or modification of devices with Cu metallization. Compositional and structural analysis shows that the reaction product is CuI.
Synthesis and biological properties of (carboxyalkyl)amino-substituted bicyclic lactam inhibitors of angiotensin converting enzyme (1985)

Syntheses of the potent angiotensin converting enzyme inhibitor (3S)-1-(carboxymethyl)-3-[[(1S)-1-carboxy-3-phenylpropyl]amino]- 2,3,4,5-tetrahydro-1H-[1]benzazepin-2-one (4b; CGS 14831) and the related monoester prodrug (17a; CGS 14824A) are described together with preparative details for six- and eight-membered ring analogues. Inhibitory potencies and in vivo biological activity of the compounds are discussed. The data indicate that 17a has a biological profile comparable to that of enalapril.
Water-Soluble NaYF4:Yb,Er(Tm)/NaYF4/Polymer Core/Shell/Shell Nanoparticles with Significant Enhancement of Upconversion Fluorescence (2006)

Hexagonal phase nanoparticles of NaYF4:Yb,Er and NaYF4:Yb,Tm (∼8.5 ± 0.8 nm) were synthesized. Significant enhancements of upconversion fluorescence were observed after coating with an undoped NaYF4 shell (core/shell ∼ 11.1 ± 1.5 nm). The hydrophobic core/shell nanoparticles were rendered hydrophilic by a subsequent amphiphilic coating of PAA. These nanostructures have great potentials as bio-probes.
Ethylene/1-hexene copolymerization with Ph2C(Cp)(Flu)ZrCl2 derivatives: correlation between ligand structure and copolymerization behavior at high temperature (1999)

Ethylene homo- and copolymerization with 1-hexene were performed in the presence of diphenylmethylidene(cyclopentadienyl)(fluorenyl)zirconium dichloride (Ph2C(Cp)(Flu)ZrCl2) derivatives activated with dimethylanilinium tetrakis(pentafluorophenyl)borate (Me2PhNH·B(C6F5)4)/triisobutylaluminium (i-Bu3Al) or methylaluminoxane (MAO) to study the role of the substituent on activity, comonomer incorporation and molecular weight. C1 symmetric metallocenes which have several substituents in β-position of the cyclopentadienyl ligand produce lower molecular weight copolymers than the Ph2C(Cp)(Flu)ZrCl2 catalyst at 200°C, whereas the copolymerization reactivity is significantly influenced by the volume of the substituent: the trimethylsilyl substituted derivative produces ethylene/1-hexene copolymers with a broad chemical composition distribution. Polyethylene obtained with the diphenylmethylidene(cyclopentadienyl)(indenyl)zirconium dichloride (Ph2C(Cp)(Ind)ZrCl2) based catalyst is branched, and the molecular weight distribution and the chemical composition distribution are significantly affected by the cocatalyst. Cs symmetric metallocenes which have alkyl substituents in 2,7 position of the fluorenyl ligand produce higher molecular weight copolymers than the Ph2C(Cp)(Flu)ZrCl2 catalyst with equal copolymerization reactivity.
Association of Circulating Tumor Cells with Serum Tumor-Related Methylated DNA in Peripheral Blood of Melanoma Patients (2006)

Although previous studies have separately shown the utility of circulating tumor cells (CTC) or cell-free tumor-related DNA in blood of cancer patients, there has been no investigation of their association and/or the prognostic value of combining these assessments. To date, the true source of tumor-related DNA in serum remains unknown. We hypothesized that CTC is a possible origin of serum tumor-related methylated DNA and their combination can predict disease outcome. To test this hypothesis, we obtained matched pairs of peripheral blood lymphocytes and serum specimens simultaneously from 50 American Joint Committee on Cancer stage IV melanoma patients before administration of biochemotherapy. Peripheral blood leukocytes were analyzed for three mRNA markers of CTC: MART-1, GalNAc-T, and MAGE-A3. Sera were analyzed for two methylated DNA markers: RASSF1A and RAR-beta2. CTC were detected in 13 of 15 (86%) patients with serum tumor-related methylated DNA and only in 13 of 35 (37%) patients without methylated DNA (P = 0.001). The number of CTC markers detected significantly correlated with methylated DNA (P = 0.008). CTC and methylated DNA were significantly correlated with biochemotherapy-treated patients' outcome. Patients with both CTC and methylated DNA showed significantly poorer response to biochemotherapy (P = 0.02) and worse time to progression and overall survival (P = 0.009 and 0.02, respectively). The correlation between CTC and serum tumor-related methylated DNA and the significant effect of this correlation on disease outcome indicate that a composite molecular assessment in blood may be a useful determinant of disease status and efficacy of systemic therapy for melanoma.
Quantitative and sensitive detection of rare mutations using droplet-based microfluidics (2011)

Somatic mutations within tumoral DNA can be used as highly specific biomarkers to distinguish cancer cells from their normal counterparts. These DNA biomarkers are potentially useful for the diagnosis, prognosis, treatment and follow-up of patients. In order to have the required sensitivity and specificity to detect rare tumoral DNA in stool, blood, lymph and other patient samples, a simple, sensitive and quantitative procedure to measure the ratio of mutant to wild-type genes is required. However, techniques such as dual probe TaqMan(®) assays and pyrosequencing, while quantitative, cannot detect less than ∼1% mutant genes in a background of non-mutated DNA from normal cells. Here we describe a procedure allowing the highly sensitive detection of mutated DNA in a quantitative manner within complex mixtures of DNA. The method is based on using a droplet-based microfluidic system to perform digital PCR in millions of picolitre droplets. Genomic DNA (gDNA) is compartmentalized in droplets at a concentration of less than one genome equivalent per droplet together with two TaqMan(®) probes, one specific for the mutant and the other for the wild-type DNA, which generate green and red fluorescent signals, respectively. After thermocycling, the ratio of mutant to wild-type genes is determined by counting the ratio of green to red droplets. We demonstrate the accurate and sensitive quantification of mutated KRAS oncogene in gDNA. The technique enabled the determination of mutant allelic specific imbalance (MASI) in several cancer cell-lines and the precise quantification of a mutated KRAS gene in the presence of a 200,000-fold excess of unmutated KRAS genes. The sensitivity is only limited by the number of droplets analyzed. Furthermore, by one-to-one fusion of drops containing gDNA with any one of seven different types of droplets, each containing a TaqMan(®) probe specific for a different KRAS mutation, or wild-type KRAS, and an optical code, it was possible to screen the six common mutations in KRAS codon 12 in parallel in a single experiment.
CM101-mediated recovery of walking ability in adult mice paralyzed by spinal cord injury (1998)

CM101, an antiangiogenic polysaccharide derived from group B streptococcus, was administered by i.v. injection 1 hr post-spinal-cord crush injury in an effort to prevent inflammatory angiogenesis and gliosis (scarring) in a mouse model. We postulated that gliosis would sterically prevent the reestablishment of neuronal connectivity; thus, treatment with CM101 was repeated every other day for five more infusions for the purpose of facilitating regeneration of neuronal function. Twenty-five of 26 mice treated with CM101 survived 28 days after surgery, and 24 of 26 recovered walking ability within 2-12 days. Only 6 of 14 mice in the control groups survived 24 hr after spinal cord injury, and none recovered function in paralyzed limbs. MRI analysis of injured untreated and treated animals showed that CM101 reduced the area of damage at the site of spinal cord compression, which was corroborated by histological analysis of spinal cord sections from treated and control animals. Electrophysiologic measurements on isolated central nervous system and neurons in culture showed that CM101 protected axons from Wallerian degeneration; reversed gamma-aminobutyrate-mediated depolarization occurring in traumatized neurons; and improved recovery of neuronal conductivity of isolated central nervous system in culture.
Real-time rendering of textures with feature curves (2008)

The standard bilinear interpolation on normal maps results in visual artifacts along sharp features, which are common for surfaces with creases, wrinkles, and dents. In many cases, spatially varying features, like the normals near discontinuity curves, are best represented as functions of the distance to the curve and the position along the curve. For high-quality interactive rendering at arbitrary magnifications, one needs to interpolate the distance field preserving discontinuity curves exactly. We present a real-time, GPU-based method for distance function and distance gradient interpolation which preserves discontinuity feature curves. The feature curves are represented by a set of quadratic Bezier curves, with minimal restrictions on their intersections. We demonstrate how this technique can be used for real-time rendering of complex feature patterns and blending normal maps with procedurally defined profiles near normal discontinuities.
Antimetastatic activity of the new platinum analog [Pt(cis-dach) (DPPE).2NO3] in a metastatic model of human bladder cancer. (1998)

Surgical orthotopic implantation (SOI) of histologically intact human RT-4 bladder tumor tissue in nude mice resulted in local growth, invasion, regional extension and metastases as well as distant metastases to other organ sites and lymph nodes, thus mimicking the bladder cancer patient. This metastatic bladder tumor animal model was treated with two doses of new platinum analog ¿Pt(cis-dach)(DPPE).2NO3¿ for the evaluation of antimetastatic efficacy compared to two doses of cisplatinum. Unlike the untreated control group or the group treated with the low dose of cisplatinum, there were no metastases in either the high or low-dose platinum-analog-treated groups and the high-dose cisplatinum-treated group. The results obtained with this patient-like nude-mouse model of bladder cancer indicate that the new platinum analog appears to be a valuable lead compound with antimetastatic efficacy and clinical potential.