gebhart/patrepeval huggingface dataset:
Lethal Toxicity from Equimolar Infusions of Cocaine and Cocaine Metabolites in Conscious and Anesthetized Rats (1995)

We compared the lethal toxicity of cocaine with that of three of its metabolites to determine the contribution of these metabolites to the lethal potential from cocaine infusion.Equimolar quantities of cocaine, norcocaine, benzoylecgonine, and ecgonine methyl ester were infused in conscious rats to determine onset of convulsions and respiratory arrest. In addition, the convulsive and respiratory toxicity for cocaine and norcocaine were evaluated in anesthetized rats and their circulatory toxicity in anesthetized and ventilated rats. Norcocaine infusion resulted in earlier onset of convulsions and respiratory arrest in conscious rats than cocaine and earlier onset of circulatory arrest. Plasma concentrations of norcocaine and cocaine were not different at these times. Benzoylecgonine and ecgonine methyl ester were less potent convulsants and respiratory depressants than norcocaine and cocaine, with ecgonine methyl ester more respiratory depressant than benzoylecgonine. Pentobarbital anesthesia enhanced the respiratory depression and suppressed or delayed the onset of convulsions from norcocaine and cocaine infusion. Prolonged infusion of cocaine to circulatory arrest resulted in benzoylecgonine concentrations approximate 60%, and norcocaine concentrations approximate 5%, of the cocaine concentration, but no detectable ecgonine methyl ester formation. We conclude that although norcocaine, ecgonine methyl ester, and benzoylecgonine administered separately have lethal potential in massive dosages, death from cocaine overdose primarily results from the parent compound and not from metabolite formation. (Anesth Analg 1995;81:1033-8)
Quantitation of articular cartilage dimensions by computer analysis of 3D MR images of human knee joints (2002)

Loss of articular cartilage is clinically one of the most significant change associated with osteoarthritis and, at present, Magnetic Resonance Imaging (MRI) is the only modality capable of direct visualisation of articular cartilage owing to its excellent soft tissue contrast. This work demonstrates the use of three dimensional (3D) edge detection method for automatic delineation of cartilage from 3D MR images of human knee joints to produce total cartilage volume. Topographical distribution of cartilage thickness on the surface of bones is also obtained. The reproducibility of volume measurement is assessed by repeated MR scanning of a healthy volunteer at different times.
Selective Pixel Transmission for Navigating in Remote Virtual Environments (1997)

This paper presents a technique to improve the performance of a walkthrough in remote virtual environments, where a scene is rendered jointly by the server and the client, in order to reduce the network requirements as much as possible. The client generates novel views by extrapolating a reference view based on the locally available geometric model, while the server transmits data necessary to prevent an accumulation of errors. Within this concept, we show that by transmitting only a selected subset of pixels, the quality of the extrapolated views can be improved while requiring less bandwidth. We focus on the selection process in which the visibility gaps between the reference view and novel view are detected, packed and transmitted compressed to the client.
Retinal vein occlusion: pathophysiology and treatment options (2010)

This paper reviews the current thinking about retinal vein occlusion. It gives an overview of its pathophysiology and discusses the evidence behind the various established and emerging treatment paradigms.
DNA Binding by Proteins (1988)

Study of proteins that recognize specific DNA sequences has yielded much information, but the field is still in its infancy. Already two major structural motifs have been discovered, the helix-turn-helix and zinc finger, and numerous examples of DNA-binding proteins containing either of them are known. The restriction enzyme Eco RI uses yet a different motif. Additional motifs are likely to be found as well. There is a growing understanding of some of the physical chemistry involved in protein-DNA binding, but much remains to be learned before it becomes possible to engineer a protein that binds to a specific DNA sequence.
Deletion of Braun Lipoprotein and Plasminogen-Activating Protease-Encoding Genes Attenuates Yersinia pestis in Mouse Models of Bubonic and Pneumonic Plague (2014)

Currently, there is no FDA-approved vaccine against Yersinia pestis, the causative agent of bubonic and pneumonic plague. Since both humoral immunity and cell-mediated immunity are essential in providing the host with protection against plague, we developed a live-attenuated vaccine strain by deleting the Braun lipoprotein (lpp) and plasminogen-activating protease (pla) genes from Y. pestis CO92. The Δlpp Δpla double isogenic mutant was highly attenuated in evoking both bubonic and pneumonic plague in a mouse model. Further, animals immunized with the mutant by either the intranasal or the subcutaneous route were significantly protected from developing subsequent pneumonic plague. In mice, the mutant poorly disseminated to peripheral organs and the production of proinflammatory cytokines concurrently decreased. Histopathologically, reduced damage to the lungs and livers of mice infected with the Δlpp Δpla double mutant compared to the level of damage in wild-type (WT) CO92-challenged animals was observed. The Δlpp Δpla mutant-immunized mice elicited a humoral immune response to the WT bacterium, as well as to CO92-specific antigens. Moreover, T cells from mutant-immunized animals exhibited significantly higher proliferative responses, when stimulated ex vivo with heat-killed WT CO92 antigens, than mice immunized with the same sublethal dose of WT CO92. Likewise, T cells from the mutant-immunized mice produced more gamma interferon (IFN-γ) and interleukin-4. These animals had an increasing number of tumor necrosis factor alpha (TNF-α)-producing CD4(+) and CD8(+) T cells than WT CO92-infected mice. These data emphasize the role of TNF-α and IFN-γ in protecting mice against pneumonic plague. Overall, our studies provide evidence that deletion of the lpp and pla genes acts synergistically in protecting animals against pneumonic plague, and we have demonstrated an immunological basis for this protection.
Glycomic Approach for Potential Biomarkers on Prostate Cancer: Profiling of N‐Linked Glycans in Human Sera and pRNS Cell Lines (2008)

Prostate cancer is a leading cause of cancer death among men. Currently available screening test measures prostate-specific antigen (PSA) to detect prostate cancer. However, this test produces false positive values that often lead to negative biopsies. Therefore, a more reliable diagnostic tool is needed. Glycans in serum are of particular interest as around half of all proteins are glycosylated. In this study, N-linked glycans were enzymatically released by PNGase F from prostate epithelial cell lines (pRNS) expressing wild type or mutant androgen receptors and a small set of human serum samples. Released glycans were purified and partitioned into neutral and acidic components by solid phase extraction (SPE) using graphitized carbon cartridges. The SPE fractions were analyzed by matrix-assisted laser desorption/ionization Fourier transform ion cyclotron resonance mass spectrometry (MALDI FT-ICR MS). Significant changes in some high-mannose and fucosylated biantennary complex N-linked glycans were observed in the serum of prostate cancer patients.
Differential expression of voltage‐activated Na+ currents in two prostatic tumour cell lines: contribution to invasiveness in vitro (1995)

The voltage-gated ionic currents of two rodent prostatic cancer cell lines were investigated using the whole-cell patch clamp technique. The highly metastatic Mat-Ly-Lu cells expressed a transient, inward Na+ current (blocked by 600 nM tetrodotoxin), which was not found in any of the weakly metastatic AT-2 cells. Although both cell lines expressed a sustained, outward K+ current, this occurred at a significantly higher density in the AT-2 than in the Mat-Ly-Lu cells. Incubation of the Mat-Ly-Lu cell line with 600 nM tetrodotoxin significantly reduced the invasive capacity of the cells in vitro. Under identical conditions, tetrodotoxin had no effect on the invasiveness of the AT-2 cells.
Spectroscopic Characterization of the Atomic Hydrogen Energies and Densities and Carbon Species during Helium−Hydrogen−Methane Plasma CVD Synthesis of Diamond Films (2003)

Polycrystalline diamond films were synthesized on silicon substrates for the first time without diamond seeding by a very low power (38 W) microwave plasma chemical vapor deposition reaction of a mixture of helium−hydrogen−methane (48.2/48.2/3.6%). The films were characterized by time-of-flight secondary ion mass spectroscopy, X-ray photoelectron spectroscopy, Raman spectroscopy, scanning electron microscopy, and X-ray diffraction. It is proposed that He+ served as a catalyst with atomic hydrogen to form an energetic plasma. CH, C2, and C3 emissions were observed with significantly broadened H α, β, γ, and δ lines. The average hydrogen atom temperature of a helium−hydrogen−methane plasma was measured to be 120−140 eV versus ≈3 eV for pure hydrogen. Bombardment of the carbon surface by highly energetic hydrogen formed by the catalysis reaction may play a role in the formation of diamond. Then, by this novel pathway, the relevance of the CO tie line is eliminated along with other stringent conditions and complicated and inefficient techniques which limit broad application of the versatility and superiority of diamond thin film technology.
A 3-Month Course of Long-Acting Repeatable Octreotide (Sandostatin LAR) Improves Portal Hypertension in Patients With Cirrhosis: A Randomized Controlled Study (2007)

Three months of long-acting octreotide in selected cirrhotic patients with portal hypertension decreases the HVPG independent of systemic hemodynamics and liver function. The decrease in VEGF blood levels suggests an improvement in splanchnic hyperemia.
[Pharmacokinetics of dihydroqinghaosu in human volunteers and comparison with qinghaosu]. (1993)

Qinghaosu (QHS), also known as artemisinin and arteannuin, is a novel type of sesquiterpene with a peroxide linkage isolated from the Chinese herb Artemisia annua L. Since its discovery as an antimalarial with low toxicity, hundreds of derivatives have been synthesized among them artesunate (ATS), artemether (ATM) and dihydroqinghaosu (DHQHS) were found to be more active than QHS itself. A suppository of QHS, a dual-pack dosage form of ATS (artesunic acid to be dissolved in sodium bicarbonate solution just before iv injection) and an oil solution of ATM for im injection had been approved by our Ministry of Health for clinical use. However, a preparation for oral administration is still not available. We have reported that when dogs were given QHS tablets orally at the dose of 70 mg/kg, no drug was detected in the serum using the RIA method, whereas appreciable serum concentration was found by the same method when dogs were given DHQHS tablets at a dose as low as 10 mg/kg. This paper reports the pharmacokinetics of DHQHS in man studied with the RIA method and compared with QHS. When DHQHS in tablet form was given to human volunteers at doses of 1.1-2.2 mg/kg, peak serum levels of 0.13-0.71 micrograms/ml were obtained in 1.33 h with MRT of 2.26-2.36 h. When QHS tablets were given at the dose as high as 15 mg/kg, however, the peak serum level found in 1.5 h was only 0.09 microgram/ml with MRT of 1.33 h. Therefore, the bioavailability of QHS tablets is only 1.62-10.08% that of DHQHS.(ABSTRACT TRUNCATED AT 250 WORDS)
Vacuum-assisted closure for complex cranial wounds involving the loss of dura mater (2012)

The aim in this study was to describe the safety and efficacy of vacuum-assisted closure (VAC) in patients with complex cranial wounds with extensive scalp, bone, and dural defects who were not candidates for immediate free tissue transfer. Five patients (4 men and 1 woman) ages 24-73 years with complex cranial wounds were treated with VAC at Wake Forest Baptist Medical Center. Etiologies included trauma, squamous cell carcinoma, and malignant meningioma. Cutaneous wound defects measured as large as 15 cm in diameter. Four of the 5 patients had open skull defects with concomitant dural defects, and 1 patient had dural dehiscence. After surgical debridement, all 5 patients were treated with the direct application of a VAC device to a reapproximated dura mater (1 patient), to a pericranial flap (1 patient), or to a regenerative tissue matrix overlying CNS tissue (3 patients). In all cases involving open cranial wounds, the VAC device promoted granulation tissue formation over the dural substitute, prevented CSF leakage, and kept the wounds free from local infection. The duration of VAC therapy ranged from 16 to 91 days. Although VAC therapy was intended as a temporary measure until these patients could be stabilized for larger tissue transfer procedures or they succumbed to their primary pathology, 1 patient had a successful skin graft following VAC therapy. Hydrocephalus requiring shunt placement developed in 2 patients during VAC therapy. The VAC dressings applied to a tissue matrix or other barrier over brain tissue in extensive cranial wounds are safe and well tolerated, providing a functional barrier and preventing infection.
Molecular cloning and characterization of a cellular phosphoprotein that interacts with a conserved C-terminal domain of adenovirus E1A involved in negative modulation of oncogenic transformation. (1995)

The adenovirus type 2/5 E1A proteins transform primary baby rat kidney (BRK) cells in cooperation with the activated Ras (T24 ras) oncoprotein. The N-terminal half of E1A (exon 1) is essential for this transformation activity. While the C-terminal half of E1A (exon 2) is dispensable, a region located between residues 225 and 238 of the 243R E1A protein negatively modulates in vitro T24 ras cooperative transformation as well as the tumorigenic potential of E1A/T24 ras-transformed cells. The same C-terminal domain is also required for binding of a cellular 48-kDa phosphoprotein, C-terminal binding protein (CtBP). We have cloned the cDNA for CtBP via yeast two-hybrid interaction cloning. The cDNA encodes a 439-amino acid (48 kDa) protein that specifically interacts with exon 2 in yeast two-hybrid, in vitro protein binding, and in vivo coimmunoprecipitation analyses. This protein requires residues 225-238 of the 243R E1A protein for interaction. The predicted protein sequence of the isolated cDNA is identical to amino acid sequences obtained from peptides prepared from biochemically purified CtBP. Fine mapping of the CtBP-binding domain revealed that a 6-amino acid motif highly conserved among the E1A proteins of various human and animal adenoviruses is required for this interaction. These results suggest that interaction of CtBP with the E1A proteins may play a critical role in adenovirus replication and oncogenic transformation.
Switching strategy based on homotopy continuation for non-regular affine systems with application in induction motor control (2012)

In the article the problem of output setpoint tracking for affine non-linear system is considered. Presented approach combines state feedback linearization and homotopy numerical continuation in subspaces of phase space where feedback linearization fails. The method of numerical parameter continuation for solving systems of nonlinear equations is generalized to control affine non-linear dynamical systems. The illustrative example of control of MIMO system which is not static feedback linearizable is given. Application of proposed method demonstrated on the speed and rotor magnetic flux control in the three-phase asynchronous motor.
Quantitative phase analysis using the Rietveld method: towards a procedure for checking the reliability and quality of the results (2019)

The quantitative phase analysis using the Rietveld method is one of the most used analytical protocols for the characterization of several types of natural and synthetic materials, and it can be performed both on fully crystalline multiphase systems and on materials containing even an amorphous fraction. Therefore, there are several applications of this method (e.g., to natural raw materials, traditional ceramics, bricks, glass-ceramics, cementitious binders, etc.). More recently, the application of the Rietveld method has disseminated also in the chemical, pharmaceutical, and other high added-value industrial areas, where it is exploited in the operational planning, formulation analysis, and in patent protection. Nowadays, in consequence of this diffusion, several academic and private laboratories provide phase quantitative analysis using the Rietveld method as customers service, but an accreditation procedure is still pending and lacks a protocol for checking the authenticity and quality of the analytical reports.In this letter, we focus on the principal elements that an analytical report of quantitative phase analysis, based on the Rietveld method, should contain, as well as some best-practice guidelines for sample preparation and data collection procedure.
Novel steroid-linked conjugates of 17 beta-[N-[N'-(2-chloroethyl)-N'-nitroso]carbamoyl]amino acids and their antineoplastic activity against Noble Nb prostate carcinoma model in rats. (1998)

The novel steroid conjugates 17 beta-[N-[N'-(2-chloroethyl)-N'-nitroso] carbamoyl]-glycyl-19-nortestosterone (1) and 17 beta-[N-[N'-(2-chloroethyl)-N'-nitroso]carbamoyl]-L-alyanyl-19- nortestosterone (2) were synthesized and characterized with respect to affinity for steroid receptors and for androgenic efficacy. At an i.p. dosage of 50 mg/kg, conjugates 1 and 2 induced strong tumor inhibition of Nobel Nb prostate carcinoma in rats, but also a marked loss of body weight. In two further experiments, treatment with conjugate 2 at a dosage of 25 mg/kg demonstrated high antitumor activity without indication of toxicity. Conjugate 2 achieved the same tumor growth inhibition as a nearly twofold molar dose of cyclophosphamide. The results indicate reproducibly high antitumor activity of 2 in the Noble Nb model at a well tolerated dosage. A low dose equimolar mixture of unlinked N-(2-chloroethyl)-N-nitrosocarbamoyl (CNC)-alanine and 19-nortestosterone was significantly more toxic than conjugate 2, showing about the same adverse effect on the body weight as the conjugate at high dosage. CNC-L-alanine at equimolar dosage was highly toxic, causing early death of all animals.
T lymphocytes from volunteers immunized with irradiated Plasmodium falciparum sporozoites recognize liver and blood stage malaria antigens (1995)

The model of protective immunity induced by immunization with irradiated plasmodia sporozoites (SPZ) has become the prototype for a promising vaccine strategy based on Ab and CTL responses directed against pre-erythrocytic stage Ags, in particular the circumsporozoite protein (CSP) and sporozoite surface protein 2 (SSP2). However, results from recently conducted vaccine studies suggest that T cell responses directed against additional specificities might also be required for protection. We have tested this hypothesis by examining human T lymphocytes from irradiated Plasmodium falciparum SPZ-immune volunteers for proliferative reactivities to parasitized red blood cells (pRBC) and recombinant proteins and synthetic peptides representing certain liver and blood stage Ags. In this work, we report that although SPZ-induced protective immunity is stage-specific, SPZ-immune lymphocytes recognized determinants associated with erythrocytic and liver stage parasites. Thus, protective immunity induced by irradiated SPZ may depend upon responses against pre-erythrocytic Ags in addition to CSP and SSP2.
Streptococcus pyogenesactivates human plasmacytoid and myeloid dendritic cells (2007)

Abstract Human peripheral blood contains two major dendritic cell (DC) populations, namely CD11c–CD123+ plasmacytoid DCs (PDCs) and CD11c+CD123– myeloid DCs (MDCs). Although the activation of these DC types by various TLR ligands has been relatively well-characterized, less is known about the ability of whole live bacteria to induce PDC and MDC activation. In the present report, we have compared the activation of human PDCs and MDCs in response to major human bacterial pathogen Streptococcus pyogenes (group A streptococci) and influenza A virus. S. pyogenes stimulation resulted in the maturation of both DC types, as evidenced by enhanced expression of costimulatory molecules and production of proinflammatory cytokines and chemokines. Furthermore, S. pyogenes-stimulated PDCs and MDCs activated naïve CD4+ T cells and enhanced their Th1 cytokine production. Influenza A virus infection induced rapid PDC activation, whereas MDCs were extremely sensitive to influenza A virus-induced cell death. The most significant differences between DC types were seen in the production of IL-10 and IL-12, which were only produced by S. pyogenes-stimulated MDCs. Although S. pyogenes was able to induce PDC activation, only influenza A virus infection resulted in detectable IFN-α production. Our results show that depending on the infecting microbe, the functions of PDCs and MDCs may be partially overlapping, suggesting a considerable flexibility of the human DC system.
Vacuum-assisted closure: a new method for wound control and treatment: clinical experience. (1997)

Despite numerous advances, chronic and other difficult-to-manage wounds continue to be a treatment challenge. Presented is a new subatmospheric pressure technique: vacuum-assisted closure (The V.A.C.). The V.A.C. technique entails placing an open-cell foam dressing into the wound cavity and applying a controlled subatmospheric pressure (125 mmHg below ambient pressure). Three hundred wounds were treated: 175 chronic wounds, 94 subacute wounds, and 31 acute wounds. Two hundred ninety-six wounds responded favorably to subatmospheric pressure treatment, with an increased rate of granulation tissue formation. Wounds were treated until completely closed, were covered with a split-thickness skin graft, or a flap was rotated into the health, granulating would bed. The technique removes chronic edema, leading to increased localized blood flow, and the applied forces result in the enhanced formation of granulation tissue. Vacuum-assisted closure is an extremely efficacious modality for treating chronic and difficult wounds.
Commercially Available 5‘-DMT Phosphoramidites as Reagents for the Synthesis of Vinylphosphonate-Linked Oligonucleic Acids (2001)

[reaction: see text]. Commercially available cyanoethyl phosphoramidites derived from T, d(C), d(A), and d(G) were hydrolyzed (1H-tetrazole, MeCN/H2O) to give the corresponding H-phosphonates in excellent yields. Palladium(0)-catalyzed cross-coupling of each of these with the thymidine-derived vinylbromide 2 afforded the corresponding vinylphosphonate-linked dimers TT, d(C)T, d(A)T, and d(G)T in modest to good yields. The TT dimer was further elaborated to give a 5'-DMT-TT-3'-CEP building block, and this was used in the automated synthesis of the TpTTpT tetramer.
The finer things in X-ray diffraction data collection (1999)

X-ray diffraction images from two-dimensional position-sensitive detectors can be characterized as thick or thin, depending on whether the rotation-angle increment per image is greater than or less than the crystal mosaicity, respectively. The expectations and consequences of the processing of thick and thin images in terms of spatial overlap, saturated pixels, X-ray background and I/sigma(I) are discussed. The d*TREK software suite for processing diffraction images is briefly introduced, and results from d*TREK are compared with those from another popular package.