gebhart/patrepeval huggingface dataset:
ADDITIONAL MONOCLONAL ANTIBODY (mAB) INJECTIONS CAN REPLACE THYMIC IRRADIATION TO ALLOW INDUCTION OF MIXED CHIMERISM AND TOLERANCE IN MICE RECEIVING BONE MARROW TRANSPLANTATION AFTER CONDITIONING WITH ANTI-T CELL mABs AND 3-GY WHOLE BODY IRRADIATION1 (1996)

While allogeneic bone marrow transplantation (BMT) has long been known to be capable of inducing donor-specific tolerance and hence permitting allograft acceptance without immunosuppressive pharmacotherapy, the toxicity of conditioning regimens required to achieve marrow engraftment has precluded the application of this approach to clinical organ transplantation. A relatively nontoxic method of conditioning mice that allows allogeneic bone marrow engraftment and induction of donor-specific skin allograft tolerance has recently been described. This regimen included anti-CD4 and anti-CD8 mAbs administered on day -5, followed by 3-Gy whole body irradiation (WBI) and 7-Gy thymic irradiation (TI) on day 0. To further reduce the potential toxicity of this regimen, we have now attempted to overcome the requirement for TI by administering additional mAb injections before and after BMT. Mixed chimerism and prolonged donor-specific skin graft acceptance were induced in 90% of B10 mice conditioned with anti-CD4 and -CD8 mAbs on days -6 and -1 and 3-Gy WBI on day 0 without TI. Despite long-term acceptance of donor-specific skin grafts, however, some of these animals showed a gradual decline in donor-type hematopoietic repopulation, and 2 of 10 mice regrafted with a second donor-type skin graft 5-9 months after BMT rejected the second and/or the original graft. This rejection after repeat donor-specific skin grafting correlated with a decline in the percentage of donor-type T cells between 6 and 12 weeks after BMT. In contrast, all animals receiving additional mAb injections 7 and 14 days following BMT after conditioning with mAbs on days -6 and -1 and 3-Gy WBI showed stable chimerism and accepted both primary and secondary donor-specific skin grafts. Animals receiving TI in addition to mAb and 3-Gy WBI also showed stable chimerism and long-term acceptance of initial (at 7 weeks) and later repeat donor-specific grafts. In contrast, the majority of mice receiving mAbs only on day -5 or on day -1 only, followed by 3-Gy WBI on day 0 without TI, did not accept initial donor-specific skin grafts, and showed only transient chimerism. Thus, the requirement for thymic irradiation to allow permanent mixed chimerism and donor-specific tolerance induction can be overcome by the administration of additional T cell-depleting mAb injections. These results establish a less toxic method of inducing donor-specific tolerance, thus increasing the potential clinical applicability of this approach to inducing organ allograft acceptance without chronic immunosuppressive therapy.
The Chromosomal Toxin Gene yafQ Is a Determinant of Multidrug Tolerance for Escherichia coli Growing in a Biofilm (2009)

Escherichia coli is refractory to elevated doses of antibiotics when it is growing in a biofilm, and this is potentially due to high numbers of multidrug-tolerant persister cells in the surface-adherent population. Previously, the chromosomal toxin-antitoxin loci hipBA and relBE have been linked to the frequency at which persister cells occur in E. coli populations. In the present study, we focused on the dinJ-yafQ-encoded toxin-antitoxin system and hypothesized that deletion of the toxin gene yafQ might influence cell survival in antibiotic-exposed biofilms. By using confocal laser scanning microscopy and viable cell counting, it was determined that a Delta yafQ mutant produced biofilms with a structure and a cell density equivalent to those of the parental strain. In-depth susceptibility testing identified that relative to wild-type E. coli, the Delta yafQ strain had up to a approximately 2,400-fold decrease in cell survival after the biofilms were exposed to bactericidal concentrations of cefazolin or tobramycin. Corresponding to these data, controlled overexpression of yafQ from a high-copy-number plasmid resulted in up to a approximately 10,000-fold increase in the number of biofilm cells surviving exposure to these bactericidal drugs. In contrast, neither the inactivation nor the overexpression of yafQ affected the tolerance of biofilms to doxycycline or rifampin (rifampicin). Furthermore, deletion of yafQ did not affect the tolerance of stationary-phase planktonic cells to any of the antibacterials tested. These results suggest that yafQ mediates the tolerance of E. coli biofilms to multiple but specific antibiotics; moreover, our data imply that this cellular pathway for persistence is likely different from that of multidrug-tolerant cells in stationary-phase planktonic cell cultures.
Advanced multi-contrast Jones matrix optical coherence tomography for Doppler and polarization sensitive imaging (2013)

An advanced version of Jones matrix optical coherence tomography (JMT) is demonstrated for Doppler and polarization sensitive imaging of the posterior eye. JMT is capable of providing localized flow tomography by Doppler detection and investigating the birefringence property of tissue through a three-dimensional (3-D) Jones matrix measurement. Owing to an incident polarization multiplexing scheme based on passive optical components, this system is stable, safe in a clinical environment, and cost effective. Since the properties of this version of JMT provide intrinsic compensation for system imperfection, the system is easy to calibrate. Compared with the previous version of JMT, this advanced JMT achieves a sufficiently long depth measurement range for clinical cases of posterior eye disease. Furthermore, a fine spectral shift compensation method based on the cross-correlation of calibration signals was devised for stabilizing the phase of OCT, which enables a high sensitivity Doppler OCT measurement. In addition, a new theory of JMT which integrates the Jones matrix measurement, Doppler measurement, and scattering measurement is presented. This theory enables a sensitivity-enhanced scattering OCT and high-sensitivity Doppler OCT. These new features enable the application of this system to clinical cases. A healthy subject and a geographic atrophy patient were measured in vivo, and simultaneous imaging of choroidal vasculature and birefringence structures are demonstrated.
The demonstration of serum interleukin 6–8, tumor necrosis factor-alpha, complement, and immunoglobulin levels in Behçet’s disease with ocular involvement (2004)

IgA-, C3-, C4-, IL6-, IL8-, and TNF-alpha-mediated mechanisms might be responsible for ocular lesions in BD.
Docetaxel in Combination with Dacarbazine in Patients with Advanced Melanoma (2002)

The combination of docetaxel and DTIC is active and well tolerated in patients with advanced melanoma. While this combination is at least as effective as various combination regimens, it does not differ from that reported for single-agent DTIC.
Strain-Release Rearrangement of N-Vinyl-2-Arylaziridines. Total Synthesis of the Anti-Leukemia Alkaloid (−)-Deoxyharringtonine (2006)

Deoxyharringtonine (1) is among the most potent of the anti-leukemia alkaloids isolated from the Cephalotaxus genus. A convergent total synthesis of (-)-1 is reported, involving novel synthetic methods and strategies that include (1) the strain-release rearrangement of N-aryl-2-vinylaziridines for [3]benzazepine synthesis, (2) a vinylogous amide acylation-cycloaddition cascade for spiro-pyrrolidine construction, and (3) efficient acylation of the cephalotaxine core by alpha-(beta-lactone)carboxylic acid derivatives to access the biologically active cephalotaxus esters. These innovations should allow rapid access not only to other Cephalotaxus alkaloids but also to non-natural analogues of potential therapeutic utility.
Groups of Organic Molecules That Operate Collectively (1991)

Abstract A “chemical system” is defined as an assemblage of molecules that collectively does something interesting or useful. The key word here is “collectively”, a word that implies an interdependency and a group behavior that can be quite different from that of individual molecules. Batteries, computer chips, concrete, mayonnaise, shampoo, paint, liquid crystal displays, composites, and viruses are all examples of commonly encountered systems. A host–guest or “supramolecular” complex, on the other hand, would not be considered a system (as defined here), because only two species are involved. A chemical system is multimolecular, a collection of molecules interlocked in a tangle of dependencies. The review delves into a variety of chemical systems investigated by the author, including micelles, water pools, films, vesicles, and polymers. All of them can be categorized as “self‐assembling” or “self‐organizing” in the sense that defined structures arise spontaneously owing to noncovalent forces among the component molecules. Such chemical systems are useful for many purposes, including decontamination of environmentally dangerous substances, drug delivery, and separation of organic compounds.
Characteristics of the hepatic stellate cell‐selective carrier mannose 6‐phosphate modified albumin (M6P28‐HSA) (2001)

Based on our in vivo data demonstrating the HSC-selectivity and on our in vitro data demonstrating binding and rapid internalization in activated HSC, we conclude that M6P(28)-HSA is applicable as a stellate cell-selective carrier for antifibrotic drugs that act intracellularly. This may have implications for the design of new strategies for the treatment of liver fibrosis.
Molecular dynamics simulations of human carbonic anhydrase II: Insight into experimental results and the role of solvation (1998)

In this paper, the carbonic anhydrase II (CA II) enzyme active site is modeled using ab initio calculations and molecular dynamics simulations to examine a number of important issues for the enzyme function. It is found that the Zn2+ ion is dominantly tetrahedrally coordinated, which agrees with X-ray crystallographic studies. However, a transient five-fold coordination with an extra water molecule is also found. Studies of His64 conformations upon a change in the protonation states of the Zn-bound water and the His64 residue also confirm the results of an X-ray study which suggest that the His64 conformation is quite flexible. However, the degree of water solvation is found to affect this behavior. Water bridge formation between the Zn-bound water and the His64 residue was found to involve a free energy barrier of 2-3 kcal/mol and an average lifetime of several picoseconds, which supports the concept of a proton transfer mechanism through such a bridge. Mutations of various residues around the active site provide further insight into the corresponding experimental results and, in fact, suggest an important role for the solvent water molecules in the CA II catalytic mechanism.
K-ras mutations in aberrant crypt foci, adenomas and adenocarcinomas during azoxymethane-induced colon carcinogenesis (1993)

Ras mutations are an important early event in a number of carcinogen-induced rodent tumors. Colon carcinogenesis induced in rats by azoxymethane is a useful model as it mimics the adenoma-carcinoma sequence observed in humans. In addition, aberrant crypt foci develop in the rat and these lesions appear to be potentially important precursors to adenomas in colorectal cancer. Recent studies have shown that specific K-ras codon 12 and 13 mutations are present in up to 66% of carcinogen-induced rat colon adenocarcinomas. We studied the frequency of these mutations during the aberrant crypt focus-adenoma-carcinoma sequence in azoxymethane-induced Fisher F344 rats. K-ras codon 12 GAT and codon 13 GAC mutations were detected with a sensitive assay based on the amplification of DNA using the polymerase chain reaction. No mutations were present in normal mucosa. Of 27 aberrant crypt foci, K-ras mutations were identified in 2 lesions containing 5 and 10 aberrant crypts, respectively. Mutations were present in 1 of 23 and 10 of 27 adenomas and adenocarcinomas, respectively. These data suggest that K-ras mutations play a role during the stages of carcinogenesis in azoxymethane-induced rat colon cancer. The demonstration of a genetic mutation in aberrant crypt foci provides further evidence for the significance of these lesions as precursor markers of malignant potential during colorectal tumorigenesis.
Analysis of terahertz pulse measurement with a chirped probe beam (1998)

In this letter, terahertz (THz) pulse measurements with a chirped probe pulse are analyzed. The method of stationary phase is used to explore the relation between the temporal waveform of an input THz pulse and spectral distribution of an output probe pulse on a detector array. The dependence of the temporal resolution on the chirp rate, the spectrum of the chirped probe beam, and the spectral resolution of the spectrometer is discussed. We confirm that the temporal resolution of the chirped pulse technique is equal to the square root of the product of the original unchirped probe pulse duration and the chirped pulse duration.
T cell activation-associated hepatic injury: mediation by tumor necrosis factors and protection by interleukin 6. (1994)

This study investigates the molecular mechanisms underlying the induction of and protection from T cell activation-associated hepatic injury. When BALB/c mice were given a single intravenous injection of concanavalin A (Con A) (> or = 0.3 mg/mouse), they developed acute hepatic injury as assessed by a striking increase in plasma transaminase levels within 24 h. Histopathologically, only the liver was injured while moderate infiltration of T cells and polymorphonuclear cells occurred in the portal areas and around the central veins. The induction of hepatic injury was dependent on the existence as well as the activation of T cells, as untreated BALB/c nu/nu mice or BALB/c mice pretreated with a T cell-specific immunosuppressive drug, FK506, failed to develop disease. Significant increases in the levels of various cytokines in the plasma were detected before an increase in plasma transaminase levels. Within 1 h after Con A injection, tumor necrosis factor (TNF) levels peaked, this being followed by production of two other inflammatory cytokines, interleukin 6 (IL-6) and IL-1. Passive immunization with anti-TNF but not with anti-IL-1 or anti-IL-6 antibody, conferred significant levels of protection. Moreover, administration of rIL-6 before Con A injection resulted in an IL-6 dose-dependent protection. A single administration of a given dose of rIL-6 completely inhibited the release of transaminases, whereas the same regimen induced only 40-50% inhibition of TNF production. More than 80% inhibition of TNF production required four consecutive rIL-6 injections. These results indicate that: (a) TNFs are critical cytokines for inducing T cell activation-associated (Con A-induced) hepatitis; (b) the induction of hepatitis is almost completely controlled by rIL-6; and (c) rIL-6 exerts its protective effect through multiple mechanisms including the reduction of TNF production.
A Recyclable Trinuclear Bifunctional Catalyst Derived from a Tetraoxo Bis‐Zn(salphen) Metalloligand (2013)

A tetraoxo bis-Zn(salphen) supramolecular host can bind various divalent metal salts, thereby providing access to trinuclear bifunctional systems that incorporate both Lewis acid sites and dynamically bound nucleophilic anions. The formation of these trinuclear species was investigated and their stability features were also determined. The application of these trinuclear complexes as bifunctional catalysts was evaluated in the formation of cyclic organic carbonates from epoxides and CO(2). The catalytic data, in combination with control experiments, clearly demonstrate that these trinuclear compounds show much higher recycling potential compared to various control compounds and they can be used in up to five cycles without an observable loss in activity. Furthermore, this new recyclable catalytic system does not require any additives and can be applied under solvent-free conditions.
The T helper type 17/regulatory T cell imbalance in patients with acute Kawasaki disease (2010)

The study is designed to investigate the changes and roles of T helper type 17/regulatory T cells (Th17/T(reg) ) in the immunological pathogenesis of Kawasaki disease (KD). In addition, we explore the alteration and significance of Th17 cells in patients with intravenous immune globulin-resistant KD. Real-time polymerase chain reaction (PCR) was used to evaluate the mRNA levels of interleukin (IL)-17A/F, retinoic acid-related orphan receptor (ROR)-γt and forkhead box P3 (FoxP3) in CD4-positive cells. The proportions of Th17 cells and CD4(+) CD25(+) FoxP3(high) T(regs) were analysed by flow cytometry. Plasma cytokine [IL-17A, IL-6, IL-23 and transforming growth factor (TGF)-β] concentrations were measured by sandwich enzyme-linked immunosorbent assay. Our data demonstrate that Th17 proportions and expression levels of cytokines (IL-17, IL-6 and IL-23) and transcription factors (IL-17A/F, ROR-γt) were up-regulated significantly, while T(reg) proportions and expression levels of T(reg ) transcription factor (FoxP3) were down-regulated significantly in children with acute KD (P<0·01). Compared with the sensitive group, the Th17 proportions were up-regulated significantly during the acute phase in immune globulin-resistant KD (P < 0·01). The plasma IL-17A, IL-6 and IL-23 concentrations in patients with KD were significantly higher compared with the concentrations in normal controls (NC) and infectious disease (ID). Plasma TGF-β concentrations were markedly lower in the KD group than the NC and ID groups (P < 0·05). These results suggest that Th17/T(reg) cells imbalance exists in the patients with KD. Th17/T cells imbalance may be important factors causing disturbed immunological function and resulting in immunoglobulin-resistant KD.
Effect of Acid Diffusion on Resolution of a Chemically Amplified Resist in X-Ray Lithography (1991)

The diffusion range of acids in a chemically amplified positive resist (EXP) was quantitatively evaluated using a contact replication method. The acid diffusion range reached a maximum depth of 0.4 µm. The acid diffusion range was diminished, as the temperature of prebaking was raised or the temperature of post-exposure baking (PEB) was reduced. The acid diffusion range also exerted a great influence on changing the replicated pattern width dependence on exposure dose. To clarify the effect of the acid diffusion on the characteristics of the resist, the distribution of the acid-catalyzed reaction in the resist and the acid diffusion range were calculated using the diffusion coefficient of the acid and the acid-catalyzed reaction rate constant determined by experiments. The calculated acid diffusion range coincided rather well with that obtained by the contact replication method.
Timestamps in key distribution protocols (1981)

The distribution of keys in a computer network using single key or public key encryption is discussed. We consider the possibility that communication keys may be compromised, and show that key distribution protocols with timestamps prevent replays of compromised keys. The timestamps have the additional benefit of replacing a two-step handshake.
Direct evidence that the FimH protein is the mannose-specific adhesin of Escherichia coli type 1 fimbriae (1990)

Type 1 fimbriae of Escherichia coli are surface organelles which mediate binding to D-mannose-containing structures. By direct binding of FimH to D-mannose attached to a carrier protein, we demonstrated that this protein was uniquely responsible for the receptor specificity. Furthermore, we show by receptor immunoelectron microscopy that the FimH protein is located laterally in the structure of the type 1 fimbriae.
Chemical and biomimetic total syntheses of natural and engineered MCoTI cyclotides (2008)

The naturally-occurring cyclic cystine-knot microprotein trypsin inhibitors MCoTI-I and MCoTI-II have been synthesised using both thia-zip native chemical ligation and a biomimetic strategy featuring chemoenzymatic cyclisation by an immobilised protease. Engineered analogues have been produced containing a range of substitutions at the P1 position that redirect specificity towards alternative protease targets whilst retaining excellent to moderate affinity. Furthermore, we report an MCoTI analogue that is a selective low-microM inhibitor of foot-and-mouth-disease virus (FMDV) 3C protease, the first reported peptide-based inhibitor of this important viral enzyme.
Role of inducible nitric oxide synthase in dextran sulphate sodium‐induced colitis (2000)

Inhibition of NO production by either L-NAME or AG worsened DSS-induced inflammation, suggesting a protective role for NO in acute colitis. On the other hand, a NO donor also exaggerated DSS-induced inflammatory parameters, suggesting that acute colitis may be aggravated by either too much or too little NO. These results suggest that medical treatment of ulcerative colitis must aim for maintenance of appropriate NO levels in the intestinal mucosa.
Insulin-like growth factor I mediates selective anabolic effects of parathyroid hormone in bone cultures. (1989)

PTH was studied for its effects on bone formation in cultured rat calvariae. 0.01-10 nM PTH stimulated [3H]thymidine incorporation into DNA by up to 4.8-fold. Although continuous treatment with PTH for 24-72 h inhibited [3H]proline incorporation into collagen, transient (24 h) treatment enhanced [3H]proline incorporation into collagen 24-48 h after the hormone was removed. The collagen stimulated by PTH was type I and the effect was observed in the periosteum-free bone and was not blocked by hydroxyurea. Furthermore, treatment with 1-100 nM PTH for 24 h increased insulin-like growth factor (IGF) I concentrations by two to fourfold, and an IGF I antibody prevented the PTH stimulation of collagen synthesis, but not its mitogenic effect. In conclusion, continuous treatment with PTH inhibits calvarial collagen, whereas transient treatment stimulates collagen synthesis, and the stimulatory effect is mediated by local production of IGF I.
Molecular mechanisms of UV‐induced apoptosis (2000)

Sunburn cells, single standing cells with typical morphologic features occurring in UV-exposed skin, have been recognized as keratinocytes undergoing apoptosis following UV irradiation. Induction of apoptosis following UV exposure appears to be a protective mechanism, getting rid off severely damaged cells that bear the risk of malignant transformation. UV-mediated apoptosis is a highly complex process in which different molecular pathways are involved. These include DNA damage, activation of the tumor suppressor gene p53, triggering of cell death receptors either directly by UV or by autocrine release of death ligands, mitochondrial damage and cytochrome C release. Detailed knowledge about the interplay between these pathways will increase our understanding of photocarcinogenesis. This review briefly discusses recent findings concerning the molecular mechanisms underlying UV-induced apoptosis.