gebhart/patrepeval huggingface dataset:
Axl inhibition induces the antitumor immune response which can be further potentiated by PD-1 blockade in the mouse cancer models (2017)

Immune checkpoint blockers (ICB) have emerged as a promising new class of antitumor agents which significantly change the treatment landscape in a range of tumors; however, cancer patients benefited from ICB-based immunotherapy remains limited, scoring the need to explore the combination treatments with synergistic mechanisms of action. Axl receptor tyrosine kinase critically involves in the carcinogenesis of multiple cancers due to its dual roles in both promoting cancer invasion and metastasis and suppressing myeloid cell activation and function. Here, we found that Axl inhibition by tyrosine kinase inhibitors induces antitumor efficacy critically depending on immune effector mechanisms in two highly clinical relevant murine tumor models. Mechanistic investigation defined that Axl inhibition reprograms the immunological microenvironment leading to the increased proliferation, activation and effector function of tumor-infiltrating CD4<sup>+</sup> and CD8<sup>+</sup> T cells possibly through preferential accumulation and activation of CD103<sup>+</sup> cross-presenting dendritic cells. More importantly, we show that Axl inhibition induces an adaptive immune resistance evidenced by unregulated PD-L1 expression on tumor cells and combined Axl inhibition with PD-1 blockade mounts a potent synergistic antitumor efficacy leading to tumor eradication. Thus, Axl-directed therapy in Axl expressing tumors could hold a great potential to subvert the innate and/or adaptive resistance to and broaden the coverage of population benefited from ICB-based immunotherapy.
Modeling spatially localized photonic nanojets from phase diffraction gratings (2016)

We investigated numerically the specific spatially localized intense optical structure, a photonic nanojet (PNJ), formed in the near-field scattering of optical radiation at phase diffraction gratings. The finite-difference time-domain technique was employed to study the PNJ key parameters (length, width, focal distance, and intensity) produced by diffraction gratings with the saw-tooth, rectangle, and hemispheric line profiles. Our analysis showed that each type of diffraction gratings produces a photonic jet with unique characteristics. Based on the numerical calculations, we demonstrate that the PNJ could be manipulated in a wide range through the variation of period, duty cycle, and shape of diffraction grating rulings.
Animal models of epileptogenesis (2002)

Advances in our understanding of the molecular biology of human epileptogenesis and secondary hyperexcitability have resulted in part from the development and characterization of animal models of mesial temporal lobe epilepsy, trauma-induced epilepsy, and age-specific models of febrile seizures and neonatal hypoxia-induced seizures. Each of these models displays similarities to and differences from their human counterparts and will undoubtedly prove useful for evaluating novel therapies aimed at preventing the development, or halting the progression, of epilepsy or insult-induced secondary hyperexcitability. This article briefly reviews those models that most closely parallel human mesial temporal lobe epilepsy, trauma-induced epilepsy, febrile seizures, and hypoxia-induced seizures. Particular attention is paid to the underlying pathology, the presence or absence of a latent period, and development of spontaneous seizures.
Role of Specific Cations and Water Entropy on the Stability of Branched DNA Motif Structures (2012)

DNA three-way junctions (TWJs) are important intermediates in various cellular processes and are the simplest of a family of branched nucleic acids being considered as scaffolds for biomolecular nanotechnology. Branched nucleic acids are stabilized by divalent cations such as Mg(2+), presumably due to condensation and neutralization of the negatively charged DNA backbone. However, electrostatic screening effects point to more complex solvation dynamics and a large role of interfacial waters in thermodynamic stability. Here, we report extensive computer simulations in explicit water and salt on a model TWJ and use free energy calculations to quantify the role of ionic character and strength on stability. We find that enthalpic stabilization of the first and second hydration shells by Mg(2+) accounts for 1/3 and all of the free energy gain in 50% and pure MgCl(2) solutions, respectively. The more distorted DNA molecule is actually destabilized in pure MgCl(2) compared to pure NaCl. Notably, the first shell, interfacial waters have very low translational and rotational entropy (i.e., mobility) compared to the bulk, an entropic loss that is overcompensated by increased enthalpy from additional electrostatic interactions with Mg(2+). In contrast, the second hydration shell has anomalously high entropy as it is trapped between an immobile and bulklike layer. The nonmonotonic entropic signature and long-range perturbations of the hydration shells to Mg(2+) may have implications in the molecular recognition of these motifs. For example, we find that low salt stabilizes the parallel configuration of the three-way junction, whereas at normal salt we find antiparallel configurations deduced from the NMR. We use the 2PT analysis to follow the thermodynamics of this transition and find that the free energy barrier is dominated by entropic effects that result from the decreased surface area of the antiparallel form which has a smaller number of low entropy waters in the first monolayer.
Activity of Dendrimer−Methotrexate Conjugates on Methotrexate-Sensitive and -Resistant Cell Lines (2006)

Dendritic nanostructures can play a key role in drug delivery, due to the high density and variety of surface functional groups that can facilitate and modulate the delivery process. We have investigated the effect of dendrimer end-functionality on the activity of polyamido amine (PAMAM) dendrimer-methotrexate (MTX) conjugates in MTX-sensitive and MTX-resistant human acute lymphoblastoid leukemia (CCRF-CEM) and Chinese hamster ovary (CHO) cell lines. Two amide-bonded PAMAM dendrimer-MTX conjugates were prepared using a dicyclohexylcarbodiimide (DCC) coupling reaction: one between a carboxylic acid-terminated G2.5 dendrimer and the amine groups of the MTX (conjugate A) and another between an amine-terminated G3 dendrimer and the carboxylic acid group of the MTX (conjugate B). Our studies suggest that conjugate A showed an increased drug activity compared to an equimolar amount of free MTX toward both sensitive and resistant cell lines, whereas conjugate B did not show significant activity on any of the cell lines. Despite substantially impaired MTX transport by MTX-resistant CEM/MTX and RII cells, conjugate A showed sensitivity increases of approximately 8- and 24-fold (based on IC50 values), respectively, compared to free MTX. Co-incubation of the cells with adenosine and thymidine along with either conjugate A or MTX resulted in almost complete protection, suggesting that the conjugate achieves its effect on dihyrofolate reductase (DHFR) enzyme through the same mechanism as that of MTX. The differences in cytotoxicity of these amide-bonded conjugates may be indicative of differences in the intracellular drug release from the cationic dendrimer (conjugate B) versus the anionic dendrimer (conjugate A), perhaps due to the differences in lysosomal residence times dictated by the surface functionality. These findings demonstrate the feasibility of using dendrimers as drug delivery vehicles for achieving higher therapeutic effects in chemotherapy, especially in drug-resistant cells.
Elimination of signal distortion and crosstalk from carrier density changes in the shared semiconductor amplifier of multifrequency signal sources (1995)

The signals from multifrequency sources that utilize a shared semiconductor optical amplifier often exhibit distortion and crosstalk due to carrier density changes in the shared amplifier. We propose a technique that eliminates the signal distortion and crosstalk by keeping the carrier density in the shared amplifier constant via feedforward of the electrical drive signals. We demonstrate the technique using a waveguide grating router multifrequency laser.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Protection against experimental infection with influenza virus A/equine/Miami/63 (H3N8) provided by inactivated whole virus vaccines containing homologous virus (1988)

Thirty-one ponies immunized with inactivated virus vaccine containing A/equine/Miami/63 (H3N8) virus and six seronegative ponies were experimentally challenged with the homologous virus strain. All 6 unvaccinated ponies and 11 out of 31 vaccinated ponies became infected. A clear relationship between pre-challenge antibody, measured by single radial haemolysis (SRH), and protection was demonstrated as judged by virus excretion, febrile responses and antibody responses. Those ponies with SRH antibody levels greater than 74 mm2 were completely protected against challenge infection by the intranasal route.
Angiotensin Type 1 Receptor Blockers Induce Peroxisome Proliferator–Activated Receptor-γ Activity (2004)

The present study demonstrates that a specific subset of ARBs induces PPARgamma activity, thereby promoting PPARgamma-dependent differentiation in adipocytes. The activation of PPARgamma demonstrates new pleiotropic actions of certain ARBs, providing a potential mechanism for their insulin-sensitizing/antidiabetic effects.
Thymic stromal lymphopoietin is released by human epithelial cells in response to microbes, trauma, or inflammation and potently activates mast cells (2007)

Compelling evidence suggests that the epithelial cell-derived cytokine thymic stromal lymphopoietin (TSLP) may initiate asthma or atopic dermatitis through a dendritic cell-mediated T helper (Th)2 response. Here, we describe how TSLP might initiate and aggravate allergic inflammation in the absence of T lymphocytes and immunoglobulin E antibodies via the innate immune system. We show that TSLP, synergistically with interleukin 1 and tumor necrosis factor, stimulates the production of high levels of Th2 cytokines by human mast cells (MCs). We next report that TSLP is released by primary epithelial cells in response to certain microbial products, physical injury, or inflammatory cytokines. Direct epithelial cell-mediated, TSLP-dependent activation of MCs may play a central role in "intrinsic" forms of atopic diseases and explain the aggravating role of infection and scratching in these diseases.
Frequency of TPRMET rearrangement in patients with gastric carcinoma and in first‐degree relatives (2000)

BACKGROUND The activation of the c-met protooncogene through a rearrangement has been detected previously in gastric carcinoma tissue and precancerous lesions. In the current study the authors analyzed the rearrangement of TPR-MET in gastric carcinoma patients and in first-degree relatives to evaluate the potential role and timepoint of this genetic alteration in the process of gastric carcinogenesis and its potential value in identifying those individuals with an increased risk of developing gastric carcinoma. METHODS The presence of TPR-MET mRNA was determined in gastric tissue from 19 patients with gastric carcinoma and in the gastric mucosa of 18 first-degree relatives without gastric carcinoma and in the gastric mucosa of 18 first-degree relatives without gastric carcinoma using a nested reverse transcriptase-polymerase chain reaction (RT-PCR) and Southern blot analysis. A 205-base pair (bp) cDNA fragment and a 70-bp cDNA fragment spanning the breakpoint were amplified by nested PCR. Amplification products were hybridized with an oligonucleotide labeled at the 3′-end with DIG-11-dUTP spanning the breakpoint using Southern blot analysis. The MNNG-HOS cell line served as a positive control. RESULTS TPR-MET mRNA was detected in nine gastric carcinoma patients (47%). Among these patients, TPR-MET mRNA was present in the both tumor and tumor free tissues in 5 patients (26%), in the tumor tissue only in 2 patients (11%), and in the tumor free gastric mucosa only in 2 patients (11%). It is interesting to note that TPR-MET rearrangement also was detected in the gastric corpus mucosa of 1 first-degree relative (6%), but in none of the control subjects. CONCLUSIONS The data from the current study indicate that TPR-MET activation may be an early event in gastric carcinogenesis and may be useful for the identification of individuals with an increased risk of developing gastric carcinoma. Cancer 2000;88:1801–6. © 2000 American Cancer Society.
Development of a ceramic form for immobilization of excess plutonium (1997)

Between 8 and 50 metric tonnes of excess plutonium are currently planned to be immobilized in a glass or ceramic waste form in the US. The immobilized Pu would then be encased in HLW glass (the can-in-canister alternative), which would provide a radiation barrier to enhance the proliferation resistance of the material. Associated with the plutonium are about 15 metric tonnes of uranium primarily {sup 238}U and a variety of other impurities (primarily Ga, Mo, Al, Mg, Si, and Cl) totaling about 1 metric tonne or less. Immobilization of this material is complicated by the fact that the uranium content in the various feed streams varies widely, from 0 to about 95%. The proposed ceramic form is composed of about 90% zirconolite (CaZrTi{sub 2}O{sub 7}) and/or pyrochlore (CaPuTi{sub 2}O{sub 7}) with about 10% other phases, typically hollandite (BaAl{sub 2}Ti{sub 6}O{sub 16}) and rutile (TiO{sub 2}). The form is a variation of Synroc-C, which contains nominally 30% zirconolite, 30% perovskite, 30% hollandite, and 10% rutile and noble metal alloys. Zirconolite and perovskite are the actinide host phases in Synroc-C with zirconolite being the more durable phase. The pyrochlore structure is closely related to zirconolite and forms at higher actinide loadings. Thus, this mineral is of interest for plutonium deposition in ceramic. Pyrochlore has the advantage that it is cubic rather the monoclinic like zirconolite. Cubic mineral swell isotropically when radiation damaged. As a result, differential strain in the microstructure will be minimal, leading to significantly less microcracking of the form after thousands of years in a repository. Zirconolites and pyrochlores containing uranium and.or thorium exist in nature and have demonstrated actinide immobilizations for periods exceeding 100 million years.
Ultrathin coating by plasma polymerization applied to corneal contact lens (1975)

Plasma coating (deposition of polymer under the influence of plasma) is utilized to modify the surface properties of corneal contact lens. An ultrathin layer (thickness of roughly 200 A) of plasma polymer of acetylene/H20/N2 is applied to poly(methyl methacrylate) (PMMA) corneal contact lenses. The surface becomes highly wettable with water compared to uncoated lens. When coated and uncoated contact lenses are placed on rabbit eyes, a remarkable difference in accumulation of mucous matter is observed. With the control lenses, the accumulation of mucous matter in a week is sufficient to affect the optical clarity of the lenses, whereas the coated lenses show no change after three months continuous wearing. The comparative degree of adhesion of the corneal epithelium cells onto glass, modified glass, PMMA, and coated PMMA surfaces is studied using tissue cultures and phase contrast microscopy. The coated PMMA surface exhibits a degree of tissue adhesion lower than that of control PMMA and higher than that of glass surface, and no sign of toxicity of the coated surface is observed by the tissue cultures.
How ribosomes select initiator regions in mRNA: base pair formation between the 3' terminus of 16S rRNA and the mRNA during initiation of protein synthesis in Escherichia coli. (1975)

Initiation complexes formed by E. coli ribosomes in the presence of 32P-labeled A protein initiator region from R17 bacteriophage Rna have been treated with colicin E3 and disassembled by exposure to 1% sodium dodecyl sulfate. Electrophoresis on 9% polyacrylamide gels reveals a dissociable complex containing the 30-nucleotide-long messenger fragment and the 50-nucleotide-long colicin fragment, which arises from the 3' terminus of the 16S RNA. The complex is a pure RNA-RNA hybird; it is apparently maintained by a seven-base complementarity between the two RNA fragments. Detection of this mRNA-rRNA complex strongly supports the hypothesis that during the initiation step of protein biosynthesis the 3' end of 16S RNA base pairs with the polypurine stretch common to initiator regions in E. coli and bacteriophage mRNAs. The implications of our findings with respect to the molecular mechanism of initiation site selection and mRNA binding to ribosomes, the role of rRNA in ribosome function, and species specificity in translation are explored.
Synthetic Oligonucleotides: The Development of Antisense Therapeutics (1999)

Antisense therapeutics using synthetic oligodeoxynucleotides (ODNs) are currently being evaluated in clinical trials for cancer, inflammation, and viral diseases. These macromolecules afford a unique opportunity to treat disease at the molecular level. The specificity of these compounds is derived from the genetic code and Watson-Crick base pairing, utilizing an antisense paradigm for the inhibition of translation and the regulation of protein expression. Currently, most antisense ODNs in development contain a phosphorothioate (P=S) backbone. Additional modifications primarily involve the 2' position on the ribose or modification of the nucleotide linkages of the backbone. To date, no toxicities in animal models appear related to inhibition of the pharmacologic target, rather toxicities induced by P=S ODNs appear similar and are independent of pharmacologic target. In general, toxicities correlate well with pharmacokinetic or tissue distribution parameters. In primates, the primary acute effects are associated with complement activation and the systemic effects associated with accumulation of high concentrations of P=S ODNs in the kidneys. In rodents, the primary effect is an immune stimulation characterized by splenomegaly, lymphoid hyperplasia, and mononuclear cell infiltrates in multiple tissues. At extraordinarily high doses (15-50 times the targeted clinical doses), hepatocellular and renal tubular degeneration are evident in rodents. Second generation antisense compounds, new routes of administration, and new formulations appear to broaden and improve the application of antisense technology.
Microvessel Density as a Predictor of PSA Recurrence After Radical Prostatectomy (2000)

Whether prostate cancer recurrence can be predicted by microvessel density (MVD) measurements is controversial. One reason for the lack of agreement may be the differing antibodies used to determine MVD. We evaluated MVD using 2 different antibodies against endothelial cells, CD31 and CD34, on 102 patients who underwent radical prostatectomy without adjuvant hormonal therapy. The tumors from these cases were identified, and areas with the highest Gleason pattern were immunostained. Average MVD determined by CD31 (MVD/CD31) staining was significantly lower than that obtained by MVD/CD34 staining (60.1 vs 80.3). By using Kaplan-Meier analysis, prostate-specific antigen (PSA) recurrence was correlated with MVD/CD31 and MVD/CD34. MVD/CD34 and MVD/CD31 were associated strongly with PSA recurrence on a univariate level. However, only MVD/CD34 was an independent predictor of PSA failure. Therefore, some of the confusion about MVD value as a prognostic indicator may be due to the antibodies used.
A Comparative Study of the Analgesic Effect of Patient-Controlled Morphine, Pethidine, and Tramadol for Postoperative Pain Management After Abdominal Hysterectomy (2008)

We designed this prospective, randomized, double-blind study to compare the analgesic effectiveness and side effects of IV patient-controlled morphine, pethidine, and tramadol for postoperative pain management. One-hundred-twenty-six ASA physical status I or II patients undergoing abdominal hysterectomy were randomly allocated to receive IV-patient controlled morphine (M), pethidine (P), or tramadol (T) for postoperative analgesia. The cumulative analgesic consumption over 24 h was 25.7 +/- 9.5 mg for morphine, 266 +/- 90 mg for pethidine, and 320 +/- 10 mg for tramadol. The average supplementary fentanyl dose used was significantly higher in group T than in groups M and P (P < 0.05). In conclusion, morphine, pethidine, and tramadol resulted in equivalent pain scores and side effects, but tramadol group T required more rescue analgesic doses of fentanyl.
TheNeisseria meningitidisCapsule Is Important for Intracellular Survival in Human Cells (2007)

While much data exist in the literature about how Neisseria meningitidis adheres to and invades human cells, its behavior inside the host cell is largely unknown. One of the essential meningococcal attributes for pathogenesis is the polysaccharide capsule, which has been shown to be important for bacterial survival in extracellular fluids. To investigate the role of the meningococcal capsule in intracellular survival, we used B1940, a serogroup B strain, and its isogenic derivatives, which lack either the capsule or both the capsule and the lipooligosaccharide outer core, to infect human phagocytic and nonphagocytic cells and monitor invasion and intracellular growth. Our data indicate that the capsule, which negatively affects bacterial adhesion and, consequently, entry, is, in contrast, fundamental for the intracellular survival of this microorganism. The results of in vitro assays suggest that an increased resistance to cationic antimicrobial peptides (CAMPs), important components of the host innate defense system against microbial infections, is a possible mechanism by which the capsule protects the meningococci in the intracellular environment. Indeed, unencapsulated bacteria were more susceptible than encapsulated bacteria to defensins, cathelicidins, protegrins, and polymyxin B, which has long been used as a model compound to define the mechanism of action of CAMPs. We also demonstrate that both the capsular genes (siaD and lipA) and those encoding an efflux pump involved in resistance to CAMPs (mtrCDE) were up-regulated during the intracellular phase of the infectious cycle.
Investigation of Coronary Venous Anatomy by Retrograde Venography in Patients With Malignant Ventricular Tachycardia (2001)

The presence, diameter, angulation, and tortuosity of veins as visualized by retrograde venography determine their acceptability for the placement of a lead in a predetermined location. Despite the considerable variability of the coronary venous system among patients, a lateral vessel for lead introduction was available in 82%, and a posterior or lateral vessel was available in 99% of individuals within a patient population that could potentially benefit from a lead on the left ventricle.