gebhart/patrepeval huggingface dataset:
Synthesis and antitumor activity of analogs of ifosfamide modified in the N-(2-chloroethyl) group (1988)

A series of 3-(2-chloroethyl)-N-(2-X-ethyl)tetrahydro-2H-1,3,2-oxazaphosphorin -2-amine 2-oxides with various X substituents have been prepared by cyclization of racemic ifosfamide or its enantiomers with sodium hydride and subsequent treatment of intermediary products with hydrobromic acid, diethyl hydrogen phosphate, dibenzyl hydrogen phosphate, p-toluenesulfonic acid, and acetic acid. All of these compounds were tested in vivo against L 1210 lymphoid leukemia in mice. Only bromo analogue 13 and its enantiomers were effective, exceeding the activity of racemic ifosfamide and cyclophosphamide. The therapeutic index of the racemic 13 and its levorotatory enantiomer was about 1.7 times higher than that for ifosfamide and about 2.7 times higher than that for cyclophosphamide.
Immunoregulatory Feedback Between Interleukin-1 and Glucocorticoid Hormones (1986)

The production and action of immunoregulatory cytokines, including interleukin-1 (IL-1), are inhibited by glucocorticoid hormones in vivo and in vitro. Conversely, glucocorticoid blood levels were increased by factors released by human leukocytes exposed to Newcastle disease virus preparations. This activity was neutralized by an antibody to IL-1. Therefore the capacity of IL-1 to stimulate the pituitary-adrenal axis was tested. Administration of subpyrogenic doses of homogeneous human monocyte-derived IL-1 or the pI 7 form of human recombinant IL-1 to mice and rats increased blood levels of adrenocorticotropic hormone (ACTH) and glucocorticoids. Another monokine, tumor necrosis factor, and the lymphokines IL-2 and gamma-interferon had no such effects when administered in doses equivalent to or higher than those of IL-1. The stimulatory effect of IL-1 on the pituitary-adrenal axis seemed not to be mediated by the secondary release of products from mature T lymphocytes since IL-1 was endocrinologically active when injected into athymic nude mice. These results strongly support the existence of an immunoregulatory feedback circuit in which IL-1 acts as an afferent and glucocorticoid as an efferent hormonal signal.
cDNA analysis of the mite allergen Lep d 1 identifies two different isoallergens and variants (1995)

For the first time the complete cDNA encoding two isoallergens of the non-pyroglyphid dust mite Lepidoglyphus destructor, Lep d 1, allergen has been sequenced. In addition, one of the isoallergens was found to have two variants. Oligonucleotides were designed from known amino acid sequences. The cDNA sequences were obtained by hybridizing these primers to mRNA and enhancement by the RT-PCR technique. To obtain the different complete encoding cDNA sequences and eliminate heteroduplex artifacts, we performed PCR + 1 reactions. Comparison of the amino acid sequence of the allergen shows leader sequences of 16 amino acids for both isoforms.
A Tris(ZnII−1,4,7,10-tetraazacyclododecane) Complex as a New Receptor for Phosphate Dianions in Aqueous Solution (1997)

A new tris(ZnII−cyclen) (Zn3L3), which has three ZnII−macrocyclic tetraamine (cyclen) complexes connected through a 1,3,5-trimethylbenzene spacer, has been synthesized as a novel receptor for organic phosphate dianions in aqueous solution (cyclen = 1,4,7,10-tetraazacyclododecane and L3 = 1,3,5-tris(1,4,7,10-tetraazacyclododecan-1-ylmethyl)benzene). The design of Zn3L3 was based on X-ray crystal structure analysis of the 1:3 complex of 4-nitrophenyl phosphate (NPP2-) with ZnII−cyclen (ZnL1) complex. The potentiometric pH titration of Zn3L3·3H2O revealed the deprotonation constants of the three ZnII-bound H2O molecules to be 6.1 (pK1), 7.3 (pK2), and 8.6 (pK3) at 25 °C with I = 0.1 (NaNO3). These three stepwise deprotonations and 1H NMR spectra changes at various pD values in D2O suggest that strong intramolecular hydrogen bonds link each adjacent ZnII−OH2 (or ZnII−OH-) at neutral pH in aqueous solution. At higher pH (>9), the hydrogen bond network disrupts. The 31P NMR titration of Zn3L3·3H2O with phenyl phosphate dianion (PP2-) in D2O confirmed the formation of a 1:1 complex (Zn3L3−PP2-). By potentiometric pH titrations, the 1:1 complex affinity constants, log Kaff (Kaff = [phosphate complex]/[ZnII complex][phosphate] (M-1)), were determined to be 5.8 with NPP2-, 6.6 with PP2-, 7.0 with α-d-glucose-1-phosphate, and 7.9 with phenyl phosphonate in aqueous solution. The tris(ZnII−cyclen) complex is found to be a much better host toward phosphates than the parent ZnII−cyclen (ZnL1) (log Kaff = 3.3 for ZnL1−NPP2-) or a bis(ZnII−cyclen) linked with a m-xylene spacer (Zn2L2) (log Kaff = 4.0 for Zn2L2−NPP2-).
Characterization of nuclear structures in cells infected with herpes simplex virus type 1 in the absence of viral DNA replication (1996)

Herpes simplex virus type 1 DNA replication occurs in nuclear domains termed replication compartments, which are areas of viral single-stranded DNA-binding protein (UL29) localization (M.P. Quinlan, L. B. Chen, and D. M. Knipe, Cell 36:857-868). In the presence of herpesvirus-specific polymerase inhibitors, UL29 localizes to punctate nuclear foci called prereplicative sites. Using versions of the helicase-primase complex proteins containing short peptide epitopes which can be detected in an immunofluorescence assay, we have found that the helicase-primase complex localizes to prereplicative sites and replication compartments. To determine if prereplicative site formation is dependent upon these and other essential viral replication proteins, we have studied UL29 localization in cells infected with replication-defective viruses. Cells infected with viruses that fail to express one of the three helicase-primase subunits or the origin-binding protein show a diffuse nuclear staining for UL29. However, in the presence of polymerase inhibitors, mutant-infected cells contain UL29 in prereplicative sites. Replication-defective viruses containing subtle mutations in the helicase or origin-binding proteins behaved identically to their null mutant counterparts. In contrast, cells infected with viral mutants which fail to express the polymerase protein contain prereplicative sites in the absence and presence of polymerase inhibitors. We propose that active viral polymerase prevents the formation of prereplicative sites. Models of the requirement of essential viral replication proteins in the assembly of prereplicative sites are presented.
T cell priming versus T cell tolerance induced by synthetic peptides. (1995)

It is well known that synthetic peptides are able to both induce and tolerize T cells. We have examined the parameters leading either to priming or tolerance of CD8+ cytotoxic T lymphocytes (CTL) in vivo with a major histocompatibility complex class I (H-2 Db) binding peptide derived from the glycoprotein (GP aa33-41) of lymphocytic choriomeningitis virus (LCMV). By varying dose, route, and frequency of LCMV GP peptide application, we found that a single local subcutaneous injection of 50-500 micrograms peptide emulsified in incomplete Freund's adjuvant protected mice against LCMV infection, whereas repetitive and systemic intraperitoneal application of the same dose caused tolerance of LCMV-specific CTL. The peptide-induced tolerance was transient in euthymic mice but permanent in thymectomized mice. These findings are relevant for a selective use of peptides as a therapeutic approach: peptide-induced priming of T cells for vaccination and peptide-mediated T cell tolerance for intervention in immunopathologies and autoimmune diseases.
Monolithic Rectangular Coaxial Lines and Resonators With Embedded Dielectric Support (2008)

Monolithic rectangular coaxial lines and related transmission line resonators with dielectric support embedded within the body of the inner conductor are demonstrated in this letter. Effects of dielectric straps are thoroughly studied and conclusions are verified through simulations and experiments. A very low-loss of below 0.1 dB/cm and unloaded <i xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">Q</i> -factors around 400 are measured at Ka-band. It is shown that the high-end performance is maintained for different components distributed across a 6 <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">''</sup> wafer.
Co-occurrence of boundary and resonance ejection in a multiplexed rectilinear ion trap mass spectrometer (2005)

A method is reported for evaluating ion trap mass analyzers by selection of operating conditions under which both boundary and resonance ejection peaks occur in a single mass scan. The choice of frequency and amplitude of the auxiliary waveform applied for resonance ejection can be such as to produce a resonance ejection mass spectrum with unit resolution or, under selected conditions, signals attributable to both boundary and resonance ejection in a single mass scan. The contrasting mass resolution associated with these two ejection processes is evident in these data. The co-occurrence of the two ejection phenomena is ascribed to the effects of higher-order fields; it is more marked in some rectilinear ion traps (RITs) than in other nominally identical devices, leading to the possibility of using it to compare individual mass analyzers in multiplexed instruments. The method is used to compare multiple ion traps driven by the same RF signal in a fully-multiplexed mass spectrometer, composed of parallel ion source/mass analyzer/detector channels each housed in one quadrant of a specialized vacuum chamber.
Amplification and Molecular Cloning of HTLV-I Sequences from DNA of Multiple Sclerosis Patients (1989)

Techniques of gene amplification, molecular cloning, and sequence analysis were used to test for the presence of sequences related to human T-lymphotropic virus type I (HTLV-I) in peripheral blood mononuclear cells of six patients with multiple sclerosis (MS) and 20 normal individuals. HTLV-I sequences were detected in all six MS patients and in one individual from the control group by DNA blot analysis and molecular cloning of amplified DNAs. The viral sequence in MS patients were associated with adherent cell populations consisting predominantly of monocytes and macrophages. Molecular cloning and nucleotide sequence analysis indicated that these amplified viral sequences were related to the HTLV-I proviral genome.
Novel urinary fragments from human basement membrane collagen. (1980)

Five fragments of collagen have been purified from human urine. The fragments cross-reacted with basement membrane collagen from pig kidney cortices when tested against antiserum to basement membrane collagen, type IV, from murine tumor. The concentrations of these fragments were sufficient for amino acid analysis, immunological analysis, and in one case, preliminary analytical amino acid sequencing. Compositional analysis of the fragments indicated concentrations of hydroxylysine, hydroxyproline, and glycine that are typical of collagen. High values of hexosamines and neutral sugars were also found. An NH2-terminal sequence of 18 residues was obtained for one fragment of Mr approximately 6,500. This sequence was unique among proteins reported to date, but was obviously collagen-like. A urinary source of basement membrane collagen fragments will permit molecular characterization of basement membrane in inherited or acquired diseases affecting this structure.
Femtosecond pulse generation in a laser with a nonlinear external resonator (1989)

A simple model is presented to describe mode locking in a laser coupled to a nonlinear resonator. It reveals a new mechanism for pulse shortening and shows that shortening does not rely on dispersion in the auxiliary cavity. Experimental results are given to support the basic predictions of the model.
Selective retina therapy (SRT): a review on methods, techniques, preclinical and first clinical results. (2006)

Selective retina therapy (SRT) is a new laser procedure for retinal diseases that are thought to be associated with a degradation of the retinal pigment epithelium (RPE). The aim of the irradiation is to selectively damage the RPE without affecting the neural retina, the photoreceptors and the choroid. Goal of the treatment is to stimulate RPE cell migration and proliferation into the irradiated areas in order to improve the metabolism at the diseased retinal sites. In a pilot study more than 150 patients with soft drusen, retinopathia centralis serosa (RCS) and macular edema were treated. The first 3-center international trial targets diabetic macular edema and branch vein occlusion. In this review, selective RPE effects are motivated and two modalities to achieve selective RPE effects will be introduced: a pulsed and a continuous wave scanning mode. The mechanism behind selective RPE-effects will be discussed reviewing in vitro results and temperature calculations. So far clinical SRT is performed by applying trains of 30 laser pulses from a Nd:YLF-Laser (527 nm, 1.7 micros, 100 Hz) to the diseased fundus areas. In the range of 450-800 mJ/cm(2) per pulse, RPE-defects in patients were proved angiographically by fluorescein or ICG-leakage. The selectivity with respect to surrounding highly sensitive tissue and the safety range of the treatment will be reviewed. With the laser parameters used neither bleeding nor scotoma, proved by microperimetry, were observed thus demonstrating no adverse effects to the choroid and the photoreceptors, respectively. During and after irradiation, it shows that the irradiated locations are ophthalmoscopically invisible, since the effects are very limited and confined to the RPE, thus a dosimetry control is demanded. We report on a non-invasive opto-acoustic on-line technique to monitor successful RPE-irradiation and compare the data to those achieved with standard angiography one-hour post treatment.
The Optical Resolution and Asymmetric Transformation of Dl-p-Hydroxyphenylglycine with (+)-1-Phenylethanesulfonic Acid (1987)

Abstract Optically active 1-phenylethanesulfonic acid was found to be an efficient resolving agent for the optical resolution and asymmetric transformation of Dl-p-hydroxyphenylglycine. When Dl-p-hydroxyphenylglycine was resolved by the fractional crystallization of its diastereomeric salt with (+)-1-phenylethanesulfonic acid, less soluble d-p-hydroxyphenylglycine (+)-1-phenylethanesulfonate [d-HPG·(+)-PES] was obtained in a good yield. Soluble l-HPG·(+)-PES was easily epimerized into Dl-HPG·(+)-PES by heating it at 100 °C in glacial acetic acid in the presence of a small amount of salicylaldehyde. Under such epimerizing conditions, the asymmetric transformation of Dl-HPG·(+)-PES was attempted by simultaneously combining the fractional crystallization of the less soluble d-HPG·(+)-PES and the epimerization of the soluble l-HPG·(+)-PES. This asymmetric transformation was achieved successfully; that is, 80% of the Dl-HPG used as the starting material was converted into d-HPG.
An Efficient and Convenient Synthesis of Tetrahydrocycloheptapyridines: New Precursors for CNS Agents (2005)

Development of a convenient and efficient synthetic route for functionalized tetrahydrocycloheptapyridines was accomplished by stepwise iodomethylation and subsequent radical ring expansion using a Bu3SnH/AIBN reaction system. Thus, 8- or 5-­oxotetrahydroquinolines 4a and 4d and 8- or 5-oxotetrahydroisoquinolines 4b and 4c afforded the 5,6,7,8-tetrahydrocycloheptapyridine-9-ones 3a and 3d and 6,7,8,9-tetrahydrocycloheptapyridine-5-ones 3b and 3c, respectively, in moderate total yields (37-61%). It was also found out that this reaction sequence was applicable to the preparation of other heterocyclic fused cycloheptanones.
Structure determination of human and murine beta-defensins reveals structural conservation in the absence of significant sequence similarity (2001)

Defensins are cationic and cysteine-rich peptides that play a crucial role in the host defense against microorganisms of many organisms by their capability to permeabilize bacterial membranes.The low sequence similarity among the members of the large mammalian ␤-defensin family suggests that their antimicrobial activity is largely independent of their primary structure.To investigate to what extent these defensins share a similar fold, the structures of the two human ␤-defensins, hBD-1 and hBD-2, as well as those of two novel murine defensins, termed mBD-7 and mBD-8, were determined by nuclear magnetic resonance spectroscopy.All four defensins investigated share a striking similarity on the level of secondary and tertiary structure including the lack of a distinct hydrophobic core, suggesting that the fold is mainly stabilized by the presence of three disulfide bonds.In addition to the overall shape of the molecules, the ratio of solvent-exposed polar and hydrophobic side chains is also very similar among the four defensins investigated.It is significant that ␤-defensins do not exhibit a common pattern of charged and hydrophobic residues on the protein surface and that the ␤-defensin-specific fold appears to accommodate a wide range of different amino acids at most sequence positions.In addition to the implications for the mode of biological defensin actions, these findings are of particular interest because ␤-defensins have been suggested as lead compounds for the development of novel peptide antibiotics for the therapy of infectious diseases.
Analysis of the Mechanism for Chromatin Remodeling in Embryos Reconstructed by Somatic Nuclear Transfer1 (2002)

The objective of the present study was to understand the molecular/biochemical nature of chromatin remodeling that occurs in the somatic nuclei transferred into oocytes. We produced the reconstructed mouse embryos by two different protocols of nuclear transfer. The nucleus of a cumulus cell was transferred into enucleated unfertilized oocytes (transferred before activation, TA protocol) or activated oocytes (activated before transfer, AT protocol). More than half (56.1%) of the embryos reconstructed using the TA protocol developed to the morula/blastocyst stage, whereas very few (1.0%) of the embryos reconstructed using the AT protocol reached the morula/blastocyst stage. These embryos were analyzed for the events associated with transcriptional regulation. Changes in transcriptional activity, nuclear accumulation of TATA box binding protein (TBP), and DNase I sensitivity were examined after nuclear transfer. In the embryos reconstructed by TA protocol, all of these events occurred in a manner similar to that in the control diploid parthenogenetic embryos. The transcriptional activity was silenced after nuclear transfer and resumed at the late 1-cell stage. TBP was displaced and subsequently accumulated at the early and the late 1-cell stage, respectively. DNase I sensitivity was increased and then decreased at the early and late 1-cell stage, respectively. In contrast, embryos reconstructed using the AT protocol did not show such changes in transcriptional activity, TBP accumulation, and DNase I sensitivity. These events would be necessary for differentiated nuclei to restore totipotency and are useful indices to evaluate successful chromatin remodeling.
Autoantibodies encoded by the most Jh-proximal human immunoglobulin heavy chain variable region gene. (1989)

Little is known about the utilization of human Ig heavy chain variable gene segments (VH segments) in different B-lineage cell populations or in antibodies of particular specificity and function. We now demonstrate that human antibodies with Ig VH regions encoded by the most JH-proximal human VH segment (VH6) have specificities resembling those of autoantibodies present in sera of patients with systemic lupus erythematosus (e.g., anti-DNA and anticardiolipin). These specificities appear to be encoded by the germline VH6 gene because the activity was found in multiple independent VH6 antibodies in which the light chain varied with respect to isotype and V kappa subgroup. Features of CDR3 length and somatic mutation patterns in several VH6 antibodies suggested that they were selected by the immune system.
Image Quality and Patient Acceptance of Four Regimens with Different Amounts of Mild Laxatives for CT Colonography (2008)

The mildest preparation with 20 mg of bisacodyl provided good image quality of CTC images. Increasing the amount of laxatives did not improve image quality or tagging characteristics but was associated with a lower patient acceptance.
A new applicator utilizing distributed electrodes for hyperthermia: a theoretical approach (1995)

We propose a new type of applicator for hyperthermia namely a Distributed Electrodes Applicator. Many electrodes are fixed on boli below which the patient is placed. A set of RF with optimized amplitudes and phases is supplied to the electrodes so as to minimize the ratio of SAR (specific absorption rate) in the fat layers to that in the central region of the patient. SAR patterns in a heated material were calculated using two-dimensional finite element method, and the results showed that the proposed applicator can heat the deep portions of the patient without excessive heating of the fat layers.
Dietary Sodium Loading Increases Arterial Pressure in Afferent Renal–Denervated Rats (2003)

In rats fed high sodium diet, increasing renal pelvic pressure > or =3 mm Hg activates renal mechanosensory nerves, resulting in a renorenal reflex-induced increase in urinary sodium excretion. The low activation threshold of the renal mechanosensory nerves suggests a role for natriuretic renorenal reflexes in the regulation of arterial pressure and sodium balance. If so, interruption of the afferent renal innervation by dorsal rhizotomy (DRX) at T9-L1 would impair urinary sodium excretion and/or increase arterial pressure during high dietary sodium intake. DRX and sham-DRX rats were fed either a high or a normal sodium diet for 3 weeks. Mean arterial pressure measured in conscious rats was higher in DRX than in sham-DRX rats fed a high sodium diet, 130+/-2 vs 100+/-3 mm Hg (P<0.01). However, mean arterial pressure was similar in DRX and sham-DRX rats fed a normal sodium diet, 115+/-1 and 113+/-1 mm Hg, respectively. Steady-state urinary sodium excretion was similar in DRX and sham-DRX rats on high (17.9+/-2.2 and 16.4+/-1.8 mmol/24 h, respectively) and normal (4.8+/-0.3 and 5.0+/-0.4 mmol/24 h, respectively) sodium diets. Studies in anesthetized rats showed a lack of an increase in afferent renal nerve activity in response to increased renal pelvic pressure and impaired prostaglandin E2-mediated release of substance P from the renal pelvic nerves in DRX rats fed either a high or a normal sodium diet, suggesting that DRX resulted in decreased responsiveness of peripheral renal sensory nerves. In conclusion, when the afferent limb of the renorenal reflex is interrupted, a high sodium diet results in increased arterial pressure to facilitate the natriuresis and maintenance of sodium balance.
Low V_pp, ultralow-energy, compact, high-speed silicon electro-optic modulator (2009)

We present a high-speed silicon optical modulator with a low V(pp) (peak-to-peak driving voltage) and ultralow energy consumption based on a microring resonator, with the refractive index modulation achieved by electric-field-induced carrier depletion in a reverse-biased lateral pn diode embedded in the ring structure. With a V(pp) of 2 V, we demonstrate a silicon modulator with a 3 dB bandwidth of 11 GHz, a modulation depth of 6.5 dB together with an insertion loss of 2 dB, ultralow energy consumption of 50 fJ per bit, and a small device active area of approximately 1000 microm(2).