gebhart/patrepeval huggingface dataset:
Antibacterial Activities of Amphiphilic Cyclic Cell-Penetrating Peptides against Multidrug-Resistant Pathogens (2014)

Multidrug-resistant pathogens have become a major public health concern. There is a great need for the development of novel antibiotics with alternative mechanisms of action for the treatment of life-threatening bacterial infections. Antimicrobial peptides, a major class of antibacterial agents, share amphiphilicity and cationic structural properties with cell-penetrating peptides (CPPs). Herein, several amphiphilic cyclic CPPs and their analogues were synthesized and exhibited potent antibacterial activities against multidrug-resistant pathogens. Among all the peptides, cyclic peptide [R4W4] (1) showed the most potent antibacterial activity against methicillin-resistant Staphylococcus aureus [MRSA, exhibiting a minimal inhibitory concentration (MIC) of 2.67 μg/mL]. Cyclic [R4W4] and the linear counterpart R4W4 exhibited MIC values of 42.8 and 21.7 μg/mL, respectively, against Pseudomonas aeruginosa. In eukaryotic cells, peptide 1 exhibited the expected cell penetrating properties and showed >84% cell viability at a concentration of 15 μM (20.5 μg/mL) in three different human cell lines. Twenty-four hour time-kill studies evaluating [R4W4] with 2 times the MIC in combination with tetracycline demonstrated bactericidal activity at 4 and 8 times the MIC of tetracycline against MRSA (MIC = 0.5 μg/mL) and 2-8 times the MIC against Escherichia coli (MIC = 2 μg/mL). This study suggests that when amphiphilic cyclic CPPs are used in combination with an antibiotic such as tetracycline, they provide significant benefit against multidrug-resistant pathogens when compared with the antibiotic alone.
Stimulation of Osteoprotegerin Ligand and Inhibition of Osteoprotegerin Production by Glucocorticoids in Human Osteoblastic Lineage Cells: Potential Paracrine Mechanisms of Glucocorticoid-Induced Osteoporosis1 (1999)

Osteoporosis is a serious complication of systemic glucocorticoid use. However, while glucocorticoids increase bone resorption in vitro and in vivo, the mechanism(s) of this effect are at present unclear. Recent studies have identified the osteoprotegerin (OPG) ligand (OPG-L) as the final effector of osteoclastogenesis, an action that is opposed by the soluble neutralizing receptor, OPG. Thus, we assessed glucocorticoid regulation of OPG and OPG-L in various human osteoblastic lineage cells using Northern analysis, RT-PCR, and ELISA. Dexamethasone inhibited constitutive OPG messenger RNA (mRNA) steady-state levels by 70-90% in primary (MS) and immortalized stromal cells (hMS), primary trabecular osteoblasts (hOB), immortalized fetal osteoblasts (hFOB), and osteosarcoma cells (MG-63). In hFOB cells, dexamethasone inhibited constitutive OPG mRNA steady-state levels in a dose- and time-dependent fashion by 90%, and also suppressed cytokine-stimulated OPG mRNA steady-state levels. Dexamethasone-induced inhibition of OPG mRNA levels was not affected by the protein synthesis inhibitor, cycloheximide, and was shown to be due to inhibition of OPG gene transcription using a nuclear run-on assay. Moreover, dexamethasone also dose dependently (10(-10) M-10(-7) M) inhibited constitutive OPG protein concentrations in the conditioned medium of hFOB cells from 2.59 +/- 0.02 ng/ml (control) to 0.30 +/- 0.01 ng/ml (88% inhibition; P < 0.001 by ANOVA). Concurrently, dexamethasone stimulated OPG-L mRNA steady-state levels in MS and hFOB cells by 2- and 4-fold, respectively. Treatment of murine marrow cultures with conditioned medium harvested from dexamethasone-treated MG-63 cells increased tartrate-resistant acid phosphatase (TRAP) activity by 54% (P < 0.005) compared with medium harvested from control-treated cells (in the presence of OPG-L and macrophage colony-stimulating factor). Moreover, dexamethasone (10(-8) M) promoted osteoclast formation in vitro, as assessed by a 2.5-fold increase of TRAP activity in cell lysates (P < 0.001) and the appearance of TRAP-positive multinucleated cells. Our data are thus consistent with the hypothesis that glucocorticoids promote osteoclastogenesis by inhibiting OPG and concurrently stimulating OPG-L production by osteoblastic lineage cells, thereby enhancing bone resorption.
Time-averaged quantum dynamics and the validity of the effective Hamiltonian model (2010)

We develop a technique for finding the dynamical evolution in time of an averaged density matrix. The result is an equation of evolution that includes an effective Hamiltonian, as well as decoherence terms in Lindblad form. Applying the general equation to harmonic Hamiltonians, we confirm a previous formula for the effective Hamiltonian together with a additional decoherence term which should, in general, be included and whose vanishing provides the criteria for validity of the effective Hamiltonian approach. Finally, we apply the theory to examples of the ac Stark shift and three-level Raman transitions, recovering a decoherence effect in the latter.
HER-2/neu is expressed in human renal cell carcinoma at heterogeneous levels independently of tumor grading and staging and can be recognized by HLA-A2.1-restricted cytotoxic T lymphocytes (2000)

The HER-2/neu oncoprotein, a 185 kDa membrane-associated tyrosine kinase with extensive homology to the epidermal growth factor receptor (EGF-R), is overexpressed in breast and ovarian carcinomas. Its overexpression is closely associated with poor prognosis in the course of disease. Here we demonstrate HER-2/neu overexpression in both established cell lines and biopsy material obtained from renal epithelial tumors. Immunohistochemical analysis of human kidney tumor lesions using 2 HER-2/neu-specific antibodies revealed HER-2/neu expression in more than 40% of primary epithelial renal tumors and more than 30% of primary renal cell carcinoma (RCC) specimens. A distinctive HER-2/neu expression pattern was found in different subtypes of kidney tumors with the highest frequency in chromophilic and chromophobic RCC, but neither associated with disease stage nor tumor grade. Eight of 10 RCC cell lines expressed significant levels of HER-2/neu mRNA and protein, but at a lower level compared with HER-2/neu overexpressing ovarian carcinoma cells. To evaluate the immune response against HER-2/neu expressing HLA-A2-positive (HLA-A2(+)) RCC cells, allogeneic HLA-A2-restricted cytotoxic T-lymphocyte (CTL) lines generated by pulsing dendritic cells with 3 different HER-2/neu-derived peptides, (HER-2(9.369), HER-2(9.435) and HER-2(9.689), were utilized in chromium-release assays. Specific lysis of HER-2/neu expressing HLA-A2(+) RCC cell lines was mediated by CTL lines specific for each of these 3 HER-2/neu-derived epitopes. The fine specificity of 2 CTL clones was defined to the epitopes HER-2(9.435) and HER-2(9.689). Their specificity was then confirmed by cold target inhibition assays. In addition, CTL-mediated lysis was enhanced by pulsing tumor cells with exogenous HER-2/neu-specific peptides. Our data suggest that (i) HER-2/neu is heterogeneously expressed in different subtypes of RCC, (ii) HER-2/neu is naturally processed by RCC and (iii) HER-2/neu epitopes presented by RCC can be recognized by HLA-A2-restricted, HER-2/neu-specific CTL.
Fast personalized PageRank on MapReduce (2011)

In this paper, we design a fast MapReduce algorithm for Monte Carlo approximation of personalized PageRank vectors of all the nodes in a graph. The basic idea is very efficiently doing single random walks of a given length starting at each node in the graph. More precisely, we design a MapReduce algorithm, which given a graph G and a length », outputs a single random walk of length » starting at each node in G. We will show that the number of MapReduce iterations used by our algorithm is optimal among a broad family of algorithms for the problem, and its I/O efficiency is much better than the existing candidates. We will then show how we can use this algorithm to very efficiently approximate all the personalized PageRank vectors. Our empirical evaluation on real-life graph data and in production MapReduce environment shows that our algorithm is significantly more efficient than all the existing algorithms in the MapReduce setting.
A Genome-wide Map of CTCF Multivalency Redefines the CTCF Code (2013)

The "CTCF code" hypothesis posits that CTCF pleiotropic functions are driven by recognition of diverse sequences through combinatorial use of its 11 zinc fingers (ZFs). This model, however, is supported by in vitro binding studies of a limited number of sequences. To study CTCF multivalency in vivo, we define ZF binding requirements at ∼50,000 genomic sites in primary lymphocytes. We find that CTCF reads sequence diversity through ZF clustering. ZFs 4-7 anchor CTCF to ∼80% of targets containing the core motif. Nonconserved flanking sequences are recognized by ZFs 1-2 and ZFs 8-11 clusters, which also stabilize CTCF broadly. Alternatively, ZFs 9-11 associate with a second phylogenetically conserved upstream motif at ∼15% of its sites. Individually, ZFs increase overall binding and chromatin residence time. Unexpectedly, we also uncovered a conserved downstream DNA motif that destabilizes CTCF occupancy. Thus, CTCF associates with a wide array of DNA modules via combinatorial clustering of its 11 ZFs.
Browsing within time-driven multimedia documents (1988)

We present the software design and the interfaces of an interactive browser for time-driven multimedia objects. Time-driven multimedia objects may have as their main resource voice or animation sequences. Several important application environments such as training systems, home entertainment systems, do-it-yourself manuals may involve time-driven multimedia objects and they may be implemented with such browsing interfaces. Such applications may be implemented using easy to replicate optical disks such as CD-ROMs, and distributed to a large user community.
Activation of human complement by IgG antisperm antibody and the demonstration of C3 and C5b-9-mediated immune injury to human sperm (1991)

To investigate the role of C in the pathogenesis of antisperm antibody (ASA)-mediated infertility, we evaluated the binding and biologic effects of antisperm IgG and autologous C on human sperm. A flow cytometric assay using motile sperm as a target for IgG ASA+ (n = 30) and ASA- (n = 5) sera was developed for the concomitant detection of sperm-bound IgG and the initial (C3d) and terminal (C5b-9) C components on the surface of human sperm. Of the 30 IgG ASA+ sera evaluated by flow cytometry, 15 (50%) and 22 (73.3%) sera were also positive for sperm-bound C3d and C5b-9, respectively. Monomeric IgG purified from C-fixing ASA+ serum was able to bind to sperm and induced deposition of C3 on the sperm surface in the presence of human C. Incubation of motile sperm with C-fixing immune sera resulted in a significant loss (43 to 87%) of motility associated with characteristic C5b-9-induced alterations in sperm morphology leading ultimately to sperm lysis. When motile sperm were cocultured with purified polymorphonuclear leukocytes (PMN) in the presence of C-fixing immune sera, the binding of sperm heads to the PMN resulted in the formation of sperm rosettes, whereas non C-fixing or control sera had no such effect. Transmission electron microscopy of thin sections of the rosettes revealed ingestion of the sperm by the human PMN. These data suggested that 1) antibody bound to sperm is capable of activating autologous C by the classical pathway; 2) binding of both IgG and C proteins initiates C3-mediated sperm binding to PMN and sperm inactivation by deposition of membrane attack complex (MC5b-9) of C; and 3) concomitant detection of sperm-bound IgG, C3d, and C5b-9 may serve as an indicator of C-fixing cytotoxic ASA in the sera of infertile couples.
Total Synthesis of Eleutherobin and Eleuthosides A and B (1998)

The total synthesis of the cytotoxic marine natural products eleutherobin (1) and eleuthosides A (2) and B (3) is described. The strategy involves glycosidation of the (+)-carvone-derived intermediate 7 with the arabinose-derived trichloroacetimidate 9 followed by base-induced ring closure and elaboration to afford the dihydroxy eneynone 19. Selective hydrogenation of 19 led to the generation and intramolecular collapse of dienone 20 furnishing 21 and thence 22 with the required structural framework of the target molecules. Finally, esterification with mixed anhydride 24 followed by deprotection gave eleutherobin (1) which served as a precursor to eleuthosides A (2) and B (3). The α-glycoside anomer of eleutherobin, compound 27, was also synthesized by application of the developed chemistry, demonstrating the flexibility of the sequence in generating designed analogues for biological screening.
Pyroglutamate‐modified amyloid β‐peptides – AβN3(pE) – strongly affect cultured neuron and astrocyte survival (2002)

N-terminally truncated amyloid-beta (Abeta) peptides are present in early and diffuse plaques of individuals with Alzheimer's disease (AD), are overproduced in early onset familial AD and their amount seems to be directly correlated to the severity and the progression of the disease in AD and Down's syndrome (DS). The pyroglutamate-containing isoforms at position 3 [AbetaN3(pE)-40/42] represent the prominent form among the N-truncated species, and may account for more than 50% of Abeta accumulated in plaques. In this study, we compared the toxic properties, fibrillogenic capabilities, and in vitro degradation profile of Abeta1-40, Abeta1-42, AbetaN3(pE)-40 and AbetaN3(pE)-42. Our data show that fibre morphology of Abeta peptides is greatly influenced by the C-terminus while toxicity, interaction with cell membranes and degradation are influenced by the N-terminus. AbetaN3(pE)-40 induced significantly more cell loss than the other species both in neuronal and glial cell cultures. Aggregated AbetaN3(pE) peptides were heavily distributed on plasma membrane and within the cytoplasm of treated cells. AbetaN3(pE)-40/42 peptides showed a significant resistance to degradation by cultured astrocytes, while full-length peptides resulted partially degraded. These findings suggest that formation of N-terminally modified peptides may enhance beta-amyloid aggregation and toxicity, likely worsening the onset and progression of the disease.
Cold storage of pooled, buffy‐coat‐derived, leucoreduced platelets in plasma (2008)

Several assays, both in vitro and in vivo, were able to detect differences in platelet-storage characteristics and in vivo recovery and survival in a model system. Galactosylation did not correct these cold-induced changes.
Immunoglobulin E and systemic lupus erythematosus (2004)

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by intense polyclonal production of autoantibodies and circulating immune complexes. Some reports have associated SLE with a Th2 immune response and allergy. In the present study 21 female patients with SLE were investigated for total IgE and IgE antibodies to dust house aeroallergens by an automated enzyme-linked fluorescent assay, and were also evaluated for antinuclear IgE autoantibodies by a modified indirect immunofluorescence test using HEp-2 cells as antigen substrate. Additionally, immunocapture ELISA was used to investigate serum anti-IgE IgG autoantibodies. Serum IgE above 150 IU/ml, ranging from 152 to 609 IU/ml (median = 394 IU IgE/ml), was observed in 7 of 21 SLE patients (33%), 5 of them presenting proteinuria, urinary cellular casts and augmented production of anti-dsDNA antibodies. While only 2 of 21 SLE patients (9.5%) were positive for IgE antibodies to aeroallergens, all 10 patients with respiratory allergy (100%) from the atopic control group (3 males and 7 females), had these immunoglobulins. SLE patients and healthy controls presented similar anti-IgE IgG autoantibody titers (X = 0.37 +/- 0.20 and 0.34 +/- 0.18, respectively), differing from atopic controls (0.94 +/- 0.26). Antinuclear IgE autoantibodies were detected in 17 of 21 (81%) sera from SLE patients, predominating the fine speckled pattern of fluorescence, that was also observed in IgG-ANA. Concluding, SLE patients can present increased IgE levels and antinuclear IgE autoantibodies without specific clinical signs of allergy or production of antiallergen IgE antibodies, excluding a possible association between SLE and allergy.
Computer assisted spine surgery: A first step toward clinical, application in orthopaedics (1992)

A system based on medical imaging and robot has been designed. It is intended to increase accuracy and security of surgical interventions, especially in surgery of the spine. To plan and perform the intervention multi-modal images and a guiding system are involved. A robot aligns a light beam with the previously defined surgical trajectory in order to assist the surgeon.
Acyloxymethyl as a drug protecting group. Part 5.1 Kinetics and mechanism of the hydrolysis of tertiary N-acyloxymethylsulfonamides (1999)

Tertiary acyloxymethylsulfonamides undergo hydrolysis via pH-independent and acid- and base-catalysed processes. Reactions are also buffer catalysed for buffer species with pKa values > ca. 10.5. For the pH-independent pathway, hydrolysis takes place via formation of an N-sulfonyl iminium ion. There is no general-base or nucleophilic catalysis in this region. The mechanism of the acid-catalysed process involves pre-equilibrium protonation of the substrate followed by iminium ion formation. General-acid catalysis is not observed. The base-catalysed pathway involves the normal BAc2 mechanism of ester hydrolysis. The buffer-catalysed reaction gives rise to a curved Brønsted plot, with β values of 1.6 and 0.25 for nucleophiles with pKa values <12.5 and >13, respectively. This is indicative of nucleophilic catalysis associated with a change in rate-limiting step from formation of the tetrahedral intermediate for buffer species with pKa > 13 to decomposition of the tetrahedral intermediate for buffer species with pKa < 12.5.Acyloxymethylsulfonamides have similar reactivity to, and follow similar reaction mechanisms as, the corresponding carboxamide derivatives. Semi-empirical PM3 SCF-MO calculations of the heats of formation, ΔHf, and atomic charges, q, for acyloxymethyl- and chloromethyl-sulfonamides and amides and their derived iminium ions were performed. These reveal that (1) iminium formation from the sulfonamide series is thermodynamically slightly favoured, and (2) the charge difference at the nitrogen atom, ΔqN, between the neutral molecule and the iminium ion is similar for both sulfonamides and amides.
Textbook of gastroenterology: Volume 1 and 2. (1999)

Our previous study demonstrated IL-17-mediated induction of MIP-1α through its binding to the cognate IL-17RA and MIP-1α was involved in astrocyte activation. Transient receptor potential canonical (TRPC) channel was involved in astrocyte activation, however, whether TRPC channel regulates MIP-1α expression in the context of multiple sclerosis (MS) remains largely unknown. In this study we identify the essential role of TRPC channel in IL-17-mediated MIP-1α expression and astrocyte activation. Moreover, treatment of astrocytes with IL-17 activated MAPKs and PI3K/Akt signaling pathways with downstream NF-κB pathways. Interestingly, the TRPC blocker-SKF96365 (10 μM) and Norgestimate (10 μM) significantly inhibited the increased expression of MIP-1α via suppression of IL-17-mediated ERK, p38 and JNK MAPKs and PI3K/Akt pathway activation, thereby underscoring the role of TRPC channel in this process. Together these data underpin the role of TRPC channel as a novel target that regulates MIP-1α expression and cell activation-mediated by IL-17 with implications for therapeutic intervention for reversal of neuroinflammation inflicted by IL-17. Understanding the regulation of MIP-1α expression may provide insights into the development of potential therapeutic targets for neuroinflammation associated with MS.
Indirect inhibition of in vivo and in vitro T-cell responses by intravenous immunoglobulins due to impaired antigen presentation (2009)

Several clinical studies done with intravenous immunoglobulin (IVIg)-treated autoimmune patients as well as several in vitro studies have revealed that IVIg can reduce polyclonal T-cell activation and modify their cytokine secretion pattern. However, their effect on (auto)antigen-specific T-cell responses has never been addressed directly. In the present work, we used an in vivo model of induction of antigen-specific T-cell responses and an in vitro antigen presentation system to study the effects of IVIg on T-cell responses. The results obtained showed that IVIg inhibited both the in vivo and in vitro antigen-specific T-cell responses but that this effect was the indirect consequence of a reduction in the antigen presentation ability of antigen-presenting cells. The inhibitory effect of IVIg was FcgammaRIIb-independent, suggesting that IVIg must interfere with activating FcgammaRs expressed on antigen-presenting cells to reduce their ability to present antigens. Such inhibition of T-cell responses by reducing antigen presentation may therefore contribute to the well-known anti-inflammatory effects of IVIg in autoimmune diseases.
Splenic afferents and some of their reflex responses (1982)

Afferent nerve activity was recorded from the distal ends of cut splenic nerves in pentobarbital- (35 mg/kg) anesthetized mongrel dogs (15-20 kg). Increases in splenic venous pressure (SVP) produced either by manual compression of discrete portions of the spleen or splenic contraction produced by injection of epinephrine (100 micrograms) into the splenic artery or vein of an occluded spleen produced significant increases in SVP and splenic afferent nerve activity. Increases in splenic afferent nerve activity were linearly related to increases in SVP. Histological sections of nerves from which afferent recordings were obtained demonstrated that all afferents were unmyelinated C-fibers. Electrical stimulation of the cut central end of splenic nerves resulted in marked reflex increases in both renal and cardiopulmonary sympathetic efferent nerve activity that remained elevated throughout the stimulation period. Reflex increase in cardiopulmonary sympathetic efferent nerve activity was associated with increases in right (22-45%) and left (11-19%) ventricular contractile force measured with Brodie-Walton strain gauge transducers, in heart rate (5-15 beats/min), and in blood pressure (5-10 mmHg). This study is the first to demonstrate both the existence of low-pressure baroreceptors in the spleen and that these splenic afferents can reflexly alter cardiopulmonary and renal sympathetic efferent nerve activity, heart rate, ventricular contractile force, and systemic blood pressure.
Pregnancy after uterine artery embolization to control haemorrhage from gestational trophoblastic tumour (1996)

Gestational trophoblastic tumour (GTT) of the uterus can cause severe and even life threatening haemorrhage in patients who may be contemplating future pregnancy. Three cases of successful pregnancy after uterine artery embolization to control severe haemorrhage from uterine GTT are reported. Both uterine arteries had been selectively catheterized and embolized in these patients. The areas of pathological circulation measured on the pre- and post-embolization films had been reduced by over 80%. Embolization failed to control haemorrhage in another four patients in whom the uterine arteries had not been selectively catheterized and embolized and where the embolization procedures had reduced the areas of pathological circulation by less than 65%. The conclusions are that control of severe haemorrhage from uterine GTT is likely if both uterine arteries are selectively catheterized and embolized. Patients thus treated can become pregnant.