gebhart/patrepeval huggingface dataset:
Oral microbiota and host innate immune response in bisphosphonate-related osteonecrosis of the jaw (2014)

Bacterial biofilms have emerged as potential critical triggers in the pathogenesis of bisphosphonate (BP)-related osteonecrosis of the jaw (ONJ) or BRONJ. BRONJ lesions have shown to be heavily colonized by oral bacteria, most of these difficult to cultivate and presents many clinical challenges. The purpose of this study was to characterize the bacterial diversity in BRONJ lesions and to determine host immune response. We examined tissue specimens from three cohorts (n=30); patients with periodontal disease without a history of BP therapy (Control, n=10), patients with periodontal disease having history of BP therapy but without ONJ (BP, n=5) and patients with BRONJ (BRONJ, n=15). Denaturing gradient gel electrophoresis of polymerase chain reaction (PCR)-amplified 16S rRNA gene fragments revealed less bacterial diversity in BRONJ than BP and Control cohorts. Sequence analysis detected six phyla with predominant affiliation to Firmicutes in BRONJ (71.6%), BP (70.3%) and Control (59.1%). Significant differences (P<0.05) in genera were observed, between Control/BP, Control/BRONJ and BP/BRONJ cohorts. Enzyme-linked immunosorbent assay (ELISA) results indicated that the levels of myeloperoxidase were significantly lower, whereas interleukin-6 and tumor necrosis factor-alpha levels were moderately elevated in BRONJ patients as compared to Controls. PCR array showed significant changes in BRONJ patients with downregulation of host genes, such as nucleotide-binding oligomerization domain containing protein 2, and cathepsin G, the key modulators for antibacterial response and upregulation of secretory leukocyte protease inhibitor, proteinase 3 and conserved helix-loop-helix ubiquitous kinase. The results suggest that colonization of unique bacterial communities coupled with deficient innate immune response is likely to impact the pathogenesis of ONJ.
Wavelength-scale analysis of influence of chirped DBRs on optical characteristics of multinanolayer photovoltaic cells (2016)

An electromagnetic wavelength-scale numerical analysis of optical characteristics of multinanolayer photovoltaic (PV) cells based on Si p-i-n type absorber with non-periodic (chirped) distributed Bragg reflector (DBR) on the top of the structure mounted on a metallic layer and SiO <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sub> substrate is performed. Computer modelling of absorbing, reflecting and transmitting characteristics of multinanolayer PV cells with chirped DBR mirrors is performed by the method of single expression (MSE). Influence of layers of chirped DBRs on optical characteristics of multinanolayer PV cells is analysed by observing the localization of the electric component of optical field and power flow distribution within the structures. The modelling results will have a scientific and practical importance for optimization of operation of thin-film multinanolayer PV cells with broadband resonant reflectors on the subject of enhancement of their efficiency.
Efficient Solving of Large Non-linear Arithmetic Constraint Systems with Complex Boolean Structure1 (2007)

In order to facilitate automated reasoning about large Boolean combinations of non-linear arithmetic constraints involving transcendental functions, we provide a tight integration of recent SAT solving techniques with interval-based arithmetic constr
Prevention of carcinogenesis by protease inhibitors. (1994)

Protease inhibitors are very effective in their ability to suppress carcinogenesis in many different in vivo and in vitro assay systems. One particularly effective protease inhibitor, the soybean-derived Bowman-Birk inhibitor, has been extensively studied in our laboratory. Our results have indicated that Bowman-Birk inhibitor suppresses carcinogenesis 1) induced by several different types of carcinogens, 2) in three different species (mice, rats, and hamsters), 3) in several different tissues/organs [colon, liver, lung, esophagus, and cheek pouch (oral epithelium)], 4) when administered to animals by several different routes (including the diet), 5) involving several different types of tumors (squamous cell carcinomas, adenocarcinomas, angiosarcomas, etc.) and 6) in different cell types [epithelial cells (in the colon, liver, lung, esophagus, and cheek pouch) as well as connective tissue cells (fibroblasts, both in vitro and those in the liver which give rise to angiosarcomas)]. Thus, the remarkable ability of Bowman-Birk inhibitor to serve as an anticarcinogenic agent has been demonstrated in a variety of different carcinogenesis assay systems. Although the mechanism of action of protease inhibitors as anticarcinogenic agents is unknown, many hypotheses have been presented. Our results suggest that anticarcinogenic protease inhibitors are capable of reversing the initiating event in carcinogenesis, presumably by stopping an ongoing process begun by carcinogen exposure. We have observed several effects of protease inhibitors which are thought to be related to their anticarcinogenic activity; these include 1) the ability to affect the expression of certain oncogenes (e.g., c-myc and c-fos) and 2) the ability to affect the levels of certain types of proteolytic activities (e.g., N-t-butoxycarbonyl-Val-Pro-Arg-7-amino-4-methylcoumarin-hydrolyzing activity) which are elevated in carcinogen-exposed tissues. We have also observed other effects of anticarcinogenic protease inhibitors which may be related to carcinogenesis. For example, we have reported that the inhibitors can reduce the carcinogen-induced, elevated levels of gene amplification to nearly normal levels. While all of these effects of protease inhibitors may contribute to the prevention of carcinogenesis, the mechanism by which protease inhibitors prevent cancer cannot be determined with certainty until the mechanisms involved in cancer induction are known. While the mechanism remains unclear, it is clear that protease inhibitors can reverse a number of carcinogen-induced cellular changes which may play important roles in carcinogenesis.
Cleavage of oligodeoxyribonucleotides from controlled-pore glass supports and their rapid deprotection by gaseous amines (1996)

A novel method for the deprotection of oligodeoxyribonucleotides has been developed. Gaseous amines such as ammonia or methylamine were employed under pressure to achieve mild and rapid deprotection conditions. For example, oligodeoxyribonucleotides having a (tert-butyl)phenoxyacetyl group for the protection of the exocyclic amino function of cytosine, adenine and guanine were released from controlled-pore glass supports and fully deprotected by ammonia or methylamine under gas phase conditions, at room temperature, within 35 or 2 min respectively.
Writing and Erasing Barriers to Lateral Mobility into Fluid Phospholipid Bilayers (1999)

We describe a method for making and erasing barriers to the lateral diffusion of membrane components in fluid lipid bilayers supported on glass substrates. When a bilayer is mechanically partitioned by scratching the membrane-coated surface at basic pH, barriers to lateral diffusion are formed which prevent mixing between the regions separated by the scratches. Upon lowering the pH, the bilayer is observed to spread over the scratch boundary, allowing diffusive mixing between the previously separated regions. This is exploited in combination with electrophoresis within the membrane to separate fluorescently labeled charged lipid probes, partition them with a scratch, and allow remixing to occur when the scratch is healed. This method for membrane manipulation can be used to transform a homogeneous membrane into an array of corrals with different compositions while preserving the ability to allow subsequent remixing. This approach should be useful for examining the kinetics of reactions and the assembly of fluid membrane-associated components in a native setting, and for investigating the dynamics of two-dimensional fluids.
Localization of two epitopes recognized by monoclonal antibody PCG-4 on Clostridium difficile toxin A (1992)

The toxin A gene of Clostridium difficile contains a 2.5-kb region encoding a series of contiguous repeating units located at the COOH terminus of the molecule. We previously showed that the monoclonal antibody (MAb) PCG-4, which neutralizes the enterotoxic activity of toxin A, binds to epitopes located within these repeating units. In the present study, we subcloned a series of fragments from this portion of the gene. The recombinant peptides expressed from the gene fragments were examined for reactivity with MAb PCG-4 to identify the epitopes involved in binding. Our results showed that MAb PCG-4 recognizes epitopes in amino acid residues 2097 through 2141 and amino acid residues 2355 through 2398.
Design and implementation of software system of E-beam lithography based on SEM (2009)

In this paper, a newly developed software system for electron beam lithography based on SEM is introduced. This software system consists of exposure layout processing functional module, alignment control functional module and exposure control functional module. It can accomplish the microlithography and micro-nanofabrication layouts design, generate the exposure data files, detect and correct the hardware, and control the whole process of exposure. Furthermore, the software system can be used in various electron beam lithography systems based on scanning electron microscope (SEM) with its powerful functions and friendly manipulation. The software system plays an important role in the electron beam lithography system based on SEM.
Sources of the neurotoxin quinolinic acid in the brain of HIV‐1‐infected patients and retrovirus‐infected macaques (1998)

ABSTRACT This study investigated the sources of quinolinic acid, a neurotoxic tryptophan‐kynurenine pathway metabolite, in the brain and blood of HIV‐infected patients and retrovirus‐infected macaques. In brain, quinolinic acid concentrations in HIV‐infected patients were elevated by &gt;300‐fold to concentrations that exceeded cerebrospinal fluid (CSF) by 8.9‐fold. There were no significant correlations between elevated serum quinolinic acid levels with those in CSF and brain parenchyma. Because nonretrovirus‐induced encephalitis confounds the interpretation of human postmortem data, rhesus macaques infected with retrovirus were used to examine the mechanisms of increased quinolinic acid accumulations and determine the relationships of quinolinic acid to encephalitits and systemic responses. The largest kynurenine pathway responses in brain were associated with encephalitis and were independent of systemic responses. CSF quinolinic acid levels were also elevated in all infected macaques, but particularly those with retrovirus‐induced encephalitis. In contrast to the brain changes, there was no difference in any systemic measure between macaques with encephalitis vs. those without. Direct measures of the amount of quinolinic acid in brain derived from blood in a macaque with encephalitis showed that almost all quinolinic acid (&gt;98%) was synthesized locally within the brain. These results demonstrate a role for induction of indoleamine‐2,3‐dioxygenase in accelerating the local formation of quinolinic acid within the brain tissue, particularly in areas of encephalitis, rather than entry of quinolinic acid into the brain from the meninges or blood. Strategies to reduce QUIN production, targeted at intracerebral sites, are potential approaches to therapy.—Heyes, M. P., Saito, K., Lackner, A., Wiley, C. A., Achim, C. L., Markey, S. P. Sources of the neurotoxin quinolinic acid in the brain of HIV‐1‐infected patients and retrovirus‐infected macaques. FASEB J . 12, 881–896 (1998)
LYN-activating mutations mediate antiestrogen resistance in estrogen receptor–positive breast cancer (2014)

Estrogen receptor-positive (ER(+)) breast cancers adapt to hormone deprivation and become resistant to antiestrogen therapy. Here, we performed deep sequencing on ER(+) tumors that remained highly proliferative after treatment with the aromatase inhibitor letrozole and identified a D189Y mutation in the inhibitory SH2 domain of the SRC family kinase (SFK) LYN. Evaluation of 463 breast tumors in The Cancer Genome Atlas revealed four LYN mutations, two of which affected the SH2 domain. In addition, LYN was upregulated in multiple ER(+) breast cancer lines resistant to long-term estrogen deprivation (LTED). An RNAi-based kinome screen revealed that LYN is required for growth of ER(+) LTED breast cancer cells. Kinase assays and immunoblot analyses of SRC substrates in transfected cells indicated that LYN(D189Y) has higher catalytic activity than WT protein. Further, LYN(D189Y) exhibited reduced phosphorylation at the inhibitory Y507 site compared with LYN(WT). Other SH2 domain LYN mutants, E159K and K209N, also exhibited higher catalytic activity and reduced inhibitory site phosphorylation. LYN(D189Y) overexpression abrogated growth inhibition by fulvestrant and/or the PI3K inhibitor BKM120 in 3 ER(+) breast cancer cell lines. The SFK inhibitor dasatinib enhanced the antitumor effect of BKM120 and fulvestrant against estrogen-deprived ER(+) xenografts but not LYN(D189Y)-expressing xenografts. These results suggest that LYN mutations mediate escape from antiestrogens in a subset of ER(+) breast cancers.
Synthesis and Properties of Segmented Block Copolymers of Functionalised Polybenzimidazoles for High‐Temperature PEM Fuel Cells (2011)

Abstract A series of novel segmented block copolymers of sulphonated polybenzimidazole (PBI) (s‐PBI) and p ‐PBI were prepared with various polymer ratios (10–90 mol% s‐PBI; 90‐10 mol% p ‐PBI). A two‐step synthesis of oligomeric species, followed by combination and further polymerisation was used via the polyphosphoric acid (PPA) process. The membranes showed improved high‐temperature proton conductivities and fuel cell performance over previous literature reports, with moderate incorporation of s‐PBI into the copolymer showing the best results. The non‐humidified fuel cell performance was extensively studied with various fuels and oxidants and showed excellent properties. Block copolymers that incorporated 40, 50 or 60 mol% s‐PBI and the corresponding 60, 50 or 40 mol% p ‐PBI, at 0.2 A cm –2 and 160 °C, had hydrogen–air performances of 0.661–0.666 V, depending on composition. The performance was improved using hydrogen–oxygen, with voltages between 0.734 and 0.742 V at 0.2 A cm –2 and 160 °C. Fuel cells operating on a reformed hydrocarbon gas showed decreased performance (0.622–0.627 V, same conditions), especially at lower temperatures, but was significantly improved over previous literature reports of sulphonated PBI membranes operating at high temperatures.
DNA unwinding produced by site-specific intrastrand crosslinks of the antitumor drug cis-diamminedichloroplatinum(II) (1991)

The DNA unwinding produced by specific adducts of the antitumor drug cis-diamminedichloroplatinum(II) has been quantitatively determined. Synthetic DNA duplex oligonucleotides of varying lengths with two base pair cohesive ends were synthesized and characterized that contained site-specific intrastrand N7-purine/N7-purine cross-links. Included are cis-[Pt(NH3)2[d(GpG)]], cis-[Pt(NH3)2(d(ApG)]], and cis-[Pt(NH3)2[d(GpTpG)]] adducts, respectively referred to as cis-GG, cis-AG, and cis-GTG. Local DNA distortions at the site of platination were amplified by polymerization of these monomers and quantitatively evaluated by using polyacrylamide gel electrophoresis. The extent of DNA unwinding was determined by systematically varying the interplatinum distance, or phasing, in polymers containing the adducts. The multimer that migrates most slowly gives the optimal phasing for cooperative bending, from which the degree of unwinding can be obtained. We find that the cis-GG and cis-AG adducts both unwind DNA by 13 degrees, while the cis-GTG adduct unwinds DNA by 23 degrees. In addition, experiments are presented that support previous studies revealing that a hinge joint forms at the sites of platination in DNA molecules containing trans-GTG adducts. On the basis of an analysis of the present and other published studies of site-specifically modified DNA, we propose that local duplex unwinding is a major determinant in the recognition of DNA damage by the Escherichia coli (A)BC excinuclease. In addition, local duplex unwinding of 13 degrees and bending by 35 degrees are shown to correlate well with the recognition of platinated DNA by a previously identified damage recognition protein (DRP) in human cells.
Terahertz beams (1989)

We have generated freely propagating, diffraction-limited beams of single-cycle 0.5 THz electromagnetic pulses from a 5-mm-diam coherent source. After propagating 100 cm in air, there was little change in the measured subps pulse shape, even though the signal strength was reduced by 20 times compared to the strength at 10 cm.
A phase II trial of chimeric monoclonal antibody G250 for advanced renal cell carcinoma patients (2004)

Chimeric monoclonal antibody G250 (WX-G250) binds to a cell surface antigen found on >90% of renal cell carcinoma (RCC). A multicentre phase II study was performed to evaluate the safety and efficacy of WX-G250 in metastatic RCC (mRCC) patients. In all, 36 patients with mRCC were included. WX-G250 was given weekly by intravenous infusion for 12 weeks. Patients with stable disease (SD) or response were eligible to receive additional treatment for 8 weeks. None of the 36 enrolled patients experienced any drug-related grade III or IV toxicity. Only three patients had grade II toxicity possibly related to the study medication. In all, 10 patients had SD and received extended treatment. One complete response and a significant regression was observed during the follow-up of the treatment. Five patients with progressive disease at study entry were stable for more than 6 months after study entry. The median survival after treatment start was 15 months. The weekly schedule of WX-G250 was well tolerated. With a median survival of 15 months after the start of this treatment and two late clinical responses, WX-G250 seems to be able to modulate mRCC. To improve the activity of WX-G250-specific antibody-dependent cellular cytotoxicity and the clinical response rate, currently combinations of WX-G250 with cytokines are in phase II trials.
Single-agent combinatorial cancer therapy (2013)

Proceedings of the National Academy of Sciences (PNAS), a peer reviewed journal of the National Academy of Sciences (NAS) - an authoritative source of high-impact, original research that broadly spans the biological, physical, and social sciences.
Automated chip-based device for simple and fast nucleic acid amplification (2005)

A chip-based PCR device is presented that is capable of rapid temperature ramping and handling sample volumes in the microliter range. The PCR chip comprises a microchannel thermally connected to three temperature zones. Inside this microchannel, the PCR sample plug is driven and precisely positioned by a ferrofluidic actuator for more than 40 cycles within 5 min. Computer simulations predict that the sample plugs are thermally equilibrated on a time scale of some 10 ms when transported to a different temperature zone. Hence, the thermal limitations on the cycle speed of the system are considerably reduced compared with conventional cyclers. The system was developed on a modular platform suitable for handling further microfluidic tasks such as DNA extraction and preparation of the PCR mix. Thus, the aspired chip-based platform represents not only a PCR system but a complete analysis system, from the injection of a patient's blood sample to its final appraisal.
Uncoating of influenza virus in endosomes (1984)

The intracellular uncoating site of influenza virus was studied by measuring the fluorescence intensity of probes conjugated to the virus or the isolated hemagglutinin and also by assaying virus replication under various incubation conditions. Acidification of the viral environment was monitored by the decrease in the fluorescence intensity of fluorescein isothiocyanate, and transport of the virus particles into secondary lysosomes was assayed by the increase in the fluorescence intensity of fluorescein isothiocyanate diphosphate. The intracellular pH was estimated by the ratio of fluorescence intensities excited at two different wavelengths. It was found that the viral environment became acidified to a pH value of 5.1 to 5.2 within 10 min at 37 degrees C or 1 h at 20 degrees C after endocytosis. Addition of ammonium chloride to the medium rapidly raised the pH to 6.7. Transport of the virus particles into the secondary lysosomes was slower and negligibly low during those incubation periods. Virus replication occurred when the cells were incubated for 10 min at 37 degrees C or for 1 h at 20 degrees C, followed by incubation in the presence of ammonium chloride for a total of 12 h. These results indicate the uncoating of influenza virus in endosomes before reaching the secondary lysosomes.
Germination and adhesion of fungal conidia on polycarbonate membranes and on apple fruit exposed to mycoactive acetate esters (2003)

The adhesion and germination of conidia of nine fungal species were assessed on polycarbonate membranes or on the skin of apple fruit in sealed glass bottles injected or not injected with acetate esters. Adhesion was determined after dislodging conidia from surfaces using a sonication probe. Adhesion and germination of conidia of Aspergillus flavus, Aspergillus fumigatus, Aspergillus niger, Penicillium citrinum, Penicillium claviforme, or Trichoderma sp. on membranes after 48 h were not increased in a 1.84 microg mL(-1) headspace of butyl acetate (BA), ethyl acetate, hexyl acetate, 2-methylbutyl acetate, pentyl acetate, or propyl acetate. Adhesion and germination of Botrytis cinerea, Penicillium expansum, and Penicillium roquefortii conidia were stimulated by all esters. Only conidia of B. cinerea and P. expansum exhibited increased adhesion and germination on the skin of apple fruit in bottles exposed to 0.92 microg mL(-1) of BA. Only conidia of B. cinerea and P. expansum produced decay in inoculated puncture wounds on fruit. Freshly made puncture wounds or 24-h-old puncture wounds in fruit were more adhesive than the unpunctured skin of fruit to conidia of B. cinerea or P. expansum. Fresh wounds were more adhesive to both fungi than 24-h-old puncture wounds. The skin and wounds of fruit were as adhesive to B. cinerea conidia as they were to P. expansum conidia. A 4-h exposure to 1.43 microg mL(-1) of BA increased adhesion of B. cinerea and P. expansum conidia in 24-h-old wounds. Results suggest that acetate-ester stimulation most likely is not a rare phenomenon in the fungi. For nutrient-dependent decay pathogens of apple fruit, acetate esters may be an alternative chemical cue used to maintain adhesion of conidia to wound surfaces.