gebhart/patrepeval huggingface dataset:
Simultaneous analysis of DNA and cell surface immunoglobulin in human B-cell lymphomas by flow cytometry. (1981)

Cell suspensions prepared from human B-cell lymphomas were analyzed for cellular DNA and cell surface immunoglobulin (SIg) by flow cytometry. In addition to SIg-bearing neoplastic B-lymphocytes, these tumors contain nonneoplastic cells. Flow cytometry permitted selective analysis of DNA in subpopulations defined by the membrane antigen SIg and also permitted analysis of SIg of subpopulations defined by DNA content. Because measurements of DNA and SIg were made simultaneously on each cell, physical separation of cells was not required. Using propidium iodide as a fluorescent DNA probe and fluorescein isothiocyanate-labeled antibodies to stain SIg, differences in cellular DNA between SIg-bearing neoplastic cells and nonneoplastic cells from the same tissues could be demonstrated. Additionally, this simultaneous correlated analysis allowed assessment of the cell cycle dependence of SIg expression. Mean fluorescein isothiocyanate (Slg) fluorescence was greater in S- than G1-phase cells, but the ratio of mean fluorescein isothiocyanate fluorescence of cells in S phase to that of cells in G1 phase varied for different tumors.
Phase 1 safety of ICOS agonist antibody JTX-2011 alone and with nivolumab (nivo) in advanced solid tumors; predicted vs observed pharmacokinetics (PK) in ICONIC. (2017)

3033 Background: JTX-2011 is an agonist monoclonal antibody that targets ICOS, Inducible CO-Stimulator of T cells. A dual mechanism of action is intended to activate antigen-specific CD4 T effector cells and selectively deplete intratumoral T regulatory cells. JTX-2011 is equally potent across human, rodent, and non-human primate species. Methods: A quantitative systems pharmacology (QSP) model describing target binding by JTX-2011 and target mediated drug disposition in blood, tumor and non-tumor tissues was based on preclinical potency and non-linear PK data across species. The model was translated to predict PK and target engagement (TE) in humans to facilitate dose selection. The QSP model predicts &gt; 95% TE for 21 days at the top planned dose. We present safety and actual/predicted PK from a Phase 1 study of JTX-2011 alone (Part A) and safety in combination with nivo (Part B). Results: 25 subjects have been dosed, 19 in 4 cohorts of JTX-2011 alone at .003, .01, .03, and .1 mg/kg IV q 21 days, and 6 in 2 cohorts of JTX-2011 .01 mg/kg and .03 mg/kg IV plus nivo 240 mg IV q21 days. Safety data from ≥ 1 cycle is available for 12 subjects in Part A (7 ≥ 3 cycles), and 3 in Part B (all ≥ 3 cycles). PK data is available for cycle 1 of Part A. Mean age (±SD) is 60 (±10.6). Mean prior systemic therapies is &gt; 5 (range 1-11). Tumor types include endometrial, triple negative breast, melanoma, lung, pancreatic and colorectal cancers. No dose limiting toxicities have been reported. 3 Grade 3 adverse events (AEs) were reported in 2 Part A subjects: anemia and hypoxia (unrelated SAE) at .003 mg/kg and JTX-2011 related diarrhea at .1 mg/kg. Grade 1-2 AEs in ≥2 subjects are chills, pyrexia, neck pain, dizziness, and nausea. 5 subjects had JTX-2011 related Grade 1-2 infusion reactions up to 6 hours post infusion. Non-linear exposure increase was observed. While PK at lower doses is consistent with model predictions, AUC and t 1/2 at 0.03 and 0.1 mg/kg doses are higher than predicted, suggesting higher than predicted TE. Conclusions: JTX-2011 has been well tolerated up to 0.1 mg/kg and with nivo at .01 mg/kg IV q 21 days. Greater than linear exposure increase was observed and TE may be higher than QSP model prediction. Clinical trial information: NCT02904226.
Evaluation of Acellular Dermal Graft in Sheet (AlloDerm) and Injectable (Micronized AlloDerm) Forms for Soft Tissue Augmentation (2000)

The macroscopic and microscopic behavior of subdermally implanted AlloDerm sheets and subdermally and intradermally injected micronized AlloDerm was compared with intradermally injected Zyplast. AlloDerm sheet volume persisted to a significantly (P < .001) greater degree than bovine collagen during the first 3 months after placement. Clinically, intradermally injected micronized AlloDerm volume persisted to a significantly (P = .01, .04, and .01, respectively) greater degree than intradermal Zyplast or subdermal micronized AlloDerm or Zyplast. Histologically, micronized AlloDerm and AlloDerm are well tolerated at 1 and 3 months, respectively. Host tissue incorporation with fibroblast in-growth and collagen deposition is seen in both materials. AlloDerm and micronized AlloDerm hold promise for use in facial soft tissue augmentation.
Hemodynamic effects of continuous urodilatin infusion: A dose-finding study* (1998)

Continuous infusion of 7.5 ng/kg/min and 15 ng/kg/min urodilatin exerts a significant increase in systemic and renal vascular resistance. Results of our experiments suggested that the therapeutic window for continuous urodilatin infusion is small and that doses higher than approximately 20 ng/kg/min urodilatin carry high risk for adverse drug reactions.
Low-power radio-frequency IC's for portable communications (1995)

The contributions of integrated circuits to the RF front-end of wireless receivers and transmitters operating in broadcast and personnal communications bands are surveyed. It is seen from this that when 1C's enable a rethinking of the RF architecture, the wireless device can sometimes become significantly smaller, and consume much less power. Examples are taken from FM broadcast receiver, pagers, and cellular telephone handsets. Many semiconductor technologies are competing today to supply RF-1C's to cellular telephones. The various design styles and levels of integration are compared, with the conclusion that single-chip silicon transceivers, combined with architectures which substantially reduce off-chip passive components, will likely dominate digital cellular telephones in the near future. The survey also projects future trends for 1C's for miniature spread-spectrum transceivers offering robust operation in the crowded spectrum. With sophistication in baseband digital signal processing, its increasing interaction with the RF sections, and with increasing experience in simolified radio architectures, all-CMOS radios appear promising in the 900 MH z to 2 GH z bands. A specific CMOS spread-spectrum transceiver project underway at the author's institution is discussed by way of example
A supported epoxidation catalyst for nucleophilic olefins (1988)

A polystyrene-supported peptide-linked epoxidation catalyst is described and its utility for the discovery of new epoxidants is discussed.
Amplified expression and large-scale purification of protein G'. (1992)

PCR was used to isolate the gene fragment coding for Protein G' (SpG'), a truncated bacterial cell surface protein from Streptococcus G148 which binds to the Fc region of IgG and expressed in E. coli [Goward et al. (1990) Biochem. J. 267: 171-177]. The PCR primer was designed to change the TTG initiation triplet to ATG and to incorporate it into an NdeI restriction site (CATATG), allowing the gene to be cloned in frame into an NdeI restriction site immediately downstream of a trp promoter. Expression of SpG' was estimated as about 30% total soluble cell protein which compares very favourably to the less than 1% total soluble cell protein obtained from the original system [Goward, et al. (1990) Biochem. J. 267: 171-177]. Homogeneous SpG' was recovered by a single anion-exchange chromatography step on Q-Sepharose FF in a process which avoided use of an affinity adsorbent. Even though SpG' consists of almost identical repetitive domains from amino acid sequence analysis, different proteolytic sensitivity of each domain was observed indicating their structural dissimilarity.
RNase H-independent antisense activity of oligonucleotide N3'->P5' phosphoramidates (1997)

Oligonucleotide N3'-->P5'phosphoramidates are a new and promising class of antisense agents. Here we report biological properties of phosphoramidate oligonucleotides targeted against the human T cell leukemia virus type-I Tax protein, the major transcriptional transactivator of this human retrovirus. Isosequential phosphorothioate oligodeoxynucleotides and uniformly modified and chimeric phosphoramidate oligodeoxynucleotides containing six central phosphodiester linkages are all quite stable in cell nuclei. The uniformly modified anti-tax phosphoramidate oligodeoxynucleotide does not activate nuclear RNase H, as was shown by RNase protection assay. In contrast, the chimeric phosphoramidate-phosphodiester oligodeoxynucleotide is an efficient activator of RNase H. The presence of one or two mismatched nucleotides in the phosphodiester portion of oligonucleotides affected this activation only negligibly. When introduced into tax-transformed fibroblasts ex vivo, only the uniformly modified anti-tax phosphoramidate oligodeoxynucleotide caused a sequence-dependent reduction in the Tax protein level. Neither the chimeric phosphoramidate nor the phosphorothioate oligodeoxynucleotides significantly reduced tax expression under similar experimental conditions.
The user programmability of a multimedia workstation for fast packet networks (2003)

The authors describe a user interface and nonprocedural language (NPL) designed for multimedia services and implemented on experimental multimedia workstations connected via a fast packet network. The window-based user interface contains a set of databases that represent calls in progress and NPL programs; the user initiates calls based on these NPL programs, including simple voice calls, image transfers, or interactive editing. Menus let the user place new calls and easily browse or modify existing calls. Any conventional program using the standard character I/O interface of UNIX can be involved in a multimedia call.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Tear fluid biomarkers in ocular and systemic disease: potential use for predictive, preventive and personalised medicine (2016)

In the field of predictive, preventive and personalised medicine, researchers are keen to identify novel and reliable ways to predict and diagnose disease, as well as to monitor patient response to therapeutic agents. In the last decade alone, the sensitivity of profiling technologies has undergone huge improvements in detection sensitivity, thus allowing quantification of minute samples, for example body fluids that were previously difficult to assay. As a consequence, there has been a huge increase in tear fluid investigation, predominantly in the field of ocular surface disease. As tears are a more accessible and less complex body fluid (than serum or plasma) and sampling is much less invasive, research is starting to focus on how disease processes affect the proteomic, lipidomic and metabolomic composition of the tear film. By determining compositional changes to tear profiles, crucial pathways in disease progression may be identified, allowing for more predictive and personalised therapy of the individual. This article will provide an overview of the various putative tear fluid biomarkers that have been identified to date, ranging from ocular surface disease and retinopathies to cancer and multiple sclerosis. Putative tear fluid biomarkers of ocular disorders, as well as the more recent field of systemic disease biomarkers, will be shown.
Connectivity Analysis of Somatosensory Evoked Potentials in Patients with Major Depression (2010)

These data support the suggestion that pain processing in response to noxious stimulation in MD patients is different compared to healthy controls, suggesting aberrant functional connectivity. Generalized partial directed coherence is shown to be a promising method to detect changes in connectivity in both within- and between-subject designs.
Use of fibrin glue as a substrate for in vitro endothelialization of PTFE vascular grafts. (1989)

The shear stress resistance of cultured human endothelium was investigated on 6 mm polytetrafluoroethylene vascular grafts. Endothelial cell attachment was promoted by precoating the grafts with fibrin glue, which contained human fibronectin and inhibitors of fibrinolysis (aprotinin and tranexam acid). To evaluate the possible effect of fibrinolysis on cell detachment, seven grafts were lined with adult human saphenous vein endothelial cells (AHSVEC) and 11 with fibrinolytically almost inactive human umbilical vein endothelial cells (HUVEC). Endothelial cell seeding was performed in a microprocessor-controlled rotation device, allowing a low inoculum of 12 X 10(4) endothelial cells/cm2. Grafts were then cultivated for 9 days to enable the maturation of the cytoskeleton, before they were exposed to pulsatile shear stress for 48 hours. A mock circulation simulated the flow patterns and the wall shear forces of the femoral artery. After a 3-hour seeding process, 45% of AHSVEC and 43% of HUVEC were attached to the fibrin matrix, forming a confluent monolayer. After 24 hours of perfusion, a cell loss of 23% in AHSVEC- and of 42% in HUVEC-lined grafts was encountered. In spite of a further cell loss during the following 24 hours of perfusion, the majority of the graft surface was still covered by endothelial cells. Therefore we conclude that fibrin glue is a suitable substrate for the formation of a shear stress-resistant endothelial cell monolayer on polytetrafluoroethylene vascular grafts.
MODELING OF GROWTH RATES OF SELECTIVE EPITAXIAL GROWTH (SEG) AND EPITAXIAL LATERAL OVERGROWTH (ELO) OF SILICON IN THE SIH2CL2-HCL- H2 SYSTEM (1994)

A semi-empirical model for the growth rate of selective epitaxial silicon(SEG) in the Dichlorosilane-HC1-Hz system that represents the experimenltal data has been presented. All epitaxy runs were done using a Gemini-I LPCVD pancake reactor. Dichlorosilane was used as the source gas and hydrogen as the carrier gas. Hydrogen Cllloride(HC1) was used to ensure that no nucleation took place on the oxide. The growth rate expression was considered to be the sum of a growth term dependent on the partial pressures of Dichlorosilane and hydrogen, and an etch berm that varies as the partial pressure of HC1. The growth and etch terms were found to have an Arrhenius relation with temperature, with activation energies of 52kcal/mol and 36kcal/mol respectively. Good agreement was obtained with experimental data. The variation of the selectivity threshold was correctly predicted, which had been a problem with earlier models for SEG growth rates. SEG/ELO Silicon was grown from 920-970°C at 40 and 150 torr pressures for a variety of HCI concentrations. In addition previous data collected by our research group at 820-1020°C and 40-150torr were used in the model.
Automated generation of nonlinear system characterization for sensor failure detection (1988)

Independent estimation of critical signals is required for use in consistency checking of instrument outputs and for isolating common-mode failures. When measurement redundancy is not available, this method can be used for monitoring sensor degradation or sensor drift by on-line prediction of the sensor output. A methodology is developed to characterize a given critical signal as a function of other related variables in a process by a nonlinear minimum-term model. This steady-state characterization is fully automated and implemented in a VAX workstation and is applied for sensor failure monitoring in a power plant. 5 refs., 4 figs.
Echo state networks as an alternative to traditional artificial neural networks in rainfall–runoff modelling (2013)

Abstract. Despite theoretical benefits of recurrent artificial neural networks over their feedforward counterparts, it is still unclear whether the former offer practical advantages as rainfall–runoff models. The main drawback of recurrent networks is the increased complexity of the training procedure due to their architecture. This work uses the recently introduced and conceptually simple echo state networks for streamflow forecasts on twelve river basins in the Eastern United States, and compares them to a variety of traditional feedforward and recurrent approaches. Two modifications on the echo state network models are made that increase the hydrologically relevant information content of their internal state. The results show that the echo state networks outperform feedforward networks and are competitive with state-of-the-art recurrent networks, across a range of performance measures. This, along with their simplicity and ease of training, suggests that they can be considered promising alternatives to traditional artificial neural networks in rainfall–runoff modelling.
Cyclodextrins as Emerging Therapeutic Tools in the Treatment of Cholesterol-Associated Vascular and Neurodegenerative Diseases (2016)

Cardiovascular diseases, like atherosclerosis, and neurodegenerative diseases affecting the central nervous system (CNS) are closely linked to alterations of cholesterol metabolism. Therefore, innovative pharmacological approaches aiming at counteracting cholesterol imbalance display promising therapeutic potential. However, these approaches need to take into account the existence of biological barriers such as intestinal and blood-brain barriers which participate in the organ homeostasis and are major defense systems against xenobiotics. Interest in cyclodextrins (CDs) as medicinal agents has increased continuously based on their ability to actively extract lipids from cell membranes and to provide suitable carrier system for drug delivery. Many novel CD derivatives are constantly generated with the objective to improve CD bioavailability, biocompatibility and therapeutic outcomes. Newly designed drug formulation complexes incorporating CDs as drug carriers have demonstrated better efficiency in treating cardiovascular and neurodegenerative diseases. CD-based therapies as cholesterol-sequestrating agent have recently demonstrated promising advances with KLEPTOSE® CRYSMEB in atherosclerosis as well as with the 2-hydroxypropyl-β-cyclodextrin (HPβCD) in clinical trials for Niemann-Pick type C disease. Based on this success, many investigations evaluating the therapeutical beneficial of CDs in Alzheimer’s, Parkinson’s and Huntington’s diseases are currently on-going.
Partially Degraded Fibrin(ogen) Stimulates Fibroblast Proliferation In Vitro (1995)

The conversion by thrombin of soluble plasma fibrinogen to an insoluble fibrin matrix is central to hemostasis and subsequent wound healing. Fibroblasts adhere to and rapidly grow into fibrin clots, resulting in collagen deposition and, ultimately, scar formation. Although a number of soluble mediators have been implicated in this process, a role for fibrin(ogen) itself has not been described. The present study further investigated the nature of mitogenic activity remaining in solution after in vitro fibrin clot formation. Liquid expressed from a fibrin clot (clot supernatant) elicited a mitogenic response of up to 83 +/- 4.7% above media control. Upon addition of a polyclonal fibrinogen antibody, this activity was reduced by 50%. The remaining activity was attributed to the presence of thrombin and was neutralized by the addition of a specific thrombin inhibitor. Fibrinogen cleavage products were separated by molecular sieve chromatography and the mitogenic potential of each fraction assessed. A peak of activity was observed in fractions containing proteins with apparent molecular weights of 200 to 300 kD. Enhanced chemiluminescence Western blotting of these fractions established the presence of several fibrin(ogen)-derived protein bands. It is therefore proposed that thrombin cleavage of fibrinogen, in addition to producing fibrin, generates high-molecular-weight soluble cleavage products that may play an important role during normal wound healing and in the pathogenesis of disease states associated with vascular leakage and fibrosis.
Experimental and Theoretical Studies of Serpentine Microstructures Bonded To Prestrained Elastomers for Stretchable Electronics (2013)

Stretchable electronic devices that exploit inorganic materials are attractive due to their combination of high performance with mechanical deformability, particularly for applications in biomedical devices that require intimate integration with human body. Several mechanics and materials schemes have been devised for this type of technology, many of which exploit deformable interconnects. When such interconnects are fully bonded to the substrate and/or encapsulated in a solid material, useful but modest levels of deformation (&lt;30–40%) are possible, with reversible and repeatable mechanics. Here, the use of prestrain in the substrate is introduced, together with interconnects in narrow, serpentine shapes, to yield significantly enhanced (more than two times) stretchability, to more than 100%. Fracture and cyclic fatigue testing on structures formed with and without prestrain quantitatively demonstrate the possible enhancements. Finite element analyses (FEA) illustrates the effects of various material and geometric parameters. A drastic decrease in the elastic stretchability is observed with increasing metal thickness, due to changes in the buckling mode, that is, from local wrinkling at small thicknesses to absence of such wrinkling at large thicknesses, as revealed by experiment. An analytic model quantitatively predicts the wavelength of this wrinkling, and explains the thickness dependence of the buckling behaviors.
CAVER: a new tool to explore routes from protein clefts, pockets and cavities (2006)

The algorithm developed automatically finds the path from a starting point located within the interior of a protein. The algorithm is sufficiently rapid and robust to enable routine analysis of molecular dynamics trajectories containing thousands of snapshots. The algorithm is based on reciprocal metrics and provides an easy method to find a centerline, i.e. the spine, of complicated objects such as a protein tunnel. It can also be applied to many other molecules. CAVER is freely available from the web site http://loschmidt.chemi.muni.cz/caver/.
MaxNet: a congestion control architecture (2002)

On the Internet all the bottlenecked links of a source to destination path contribute to the aggregate congestion signal that controls the source rate. We introduce an architecture, MaxNet, in which only one link, the most severely bottlenecked link on the end-to-end path, controls the source rate. We prove that MaxNet results in MaxMin fairness for sources with general homogenous utility functions and the current architecture may not. MaxNet is distributed and requires no global information or per-flow state in the link.
Diversity and Active Mechanism of Fengycin-Type Cyclopeptides from Bacillus subtilis XF-1 Against Plasmodiophora brassicae (2013)

Bacillus subtilis XF-1, a strain with demonstrated ability to control clubroot disease caused by Plasmodiophora brassicae, was studied to elucidate its mechanism of antifungal activity against P. brassicae. Fengycin-type cyclopeptides (FTCPs), a well-known class of compounds with strong fungitoxic activity, were purified by acid precipitation, methanol extraction, and chromatographic separation. Eight homologs of fengycin, seven homologs of dehydroxyfengycin, and six unknown FTCPs were characterized with LC/ESI-MS, LC/ESI-MS/MS, and NMR. FTCPs (250 microg/ml) were used to treat the resting spores of P. brassicae (10(7)/ml) by detecting leakage of the cytoplasm components and cell destruction. After 12 h treatment, the absorbencies at 260 nm (A(260)) and at 280 nm (A(280)) increased gradually to approaching the maximum of absorbance, accompanying the collapse of P. brassicae resting spores, and nearly no complete cells were observed at 24 h treatment. The results suggested that the cells could be cleaved by the FTCPs of B. subtilis XF-1, and the diversity of FTCPs was mainly attributed to a mechanism of clubroot disease biocontrol.