gebhart/patrepeval huggingface dataset:
Scaled Cortical Impact in Immature Swine: Effect of Age and Gender on Lesion Volume (2009)

The piglet scaled cortical impact model creates a focal contusion using a skull-mounted, spring-loaded blunt indentation device scaled to achieve identical tissue strains in subjects with different brain sizes. Preliminary data showed that contusion size increased proportional to subject age. This study details the results from a new, larger series of subjects of three ages, and compares the effect of age and additional host and physiologic variables on injury response. Sixty-seven subjects, including infant (5- to 7-day-old), "toddler" (1-month-old), and early adolescent (4-month-old) swine underwent scaled cortical impact under strict anesthetic protocols. Serum glucose, testosterone, and 17beta-estradiol levels were measured. Lesion size was measured at 1 week post injury, as the ratio of the lesion area over the area of the contralateral hemisphere. Adolescent subjects had lesions over eight times larger than infants (p < 0.0001). Lesion volumes were larger in toddlers than in infants, most significantly for males (p < 0.05). Adolescent subjects were warmer on average, but there was no correlation between temperature and lesion volume within any age group. Serum glucose did not differ among ages. Infant males had the highest levels of circulating sex steroids. In this model, age was the most robust predictor of lesion size. Temperature had an effect, but did not explain all the variability seen among age groups. There was an interaction among gender, hormone levels, and lesion size in younger subjects. Characterization of these variables allows use of this model for treatment trials for subjects at different stages of maturation.
Paracrine Regulation of Angiogenesis and Adipocyte Differentiation During In Vivo Adipogenesis (2003)

With an increasing incidence of obesity worldwide, rational strategies are needed to control adipogenesis. Growth of any tissue requires the formation of a functional and mature vasculature. To gain mechanistic insight into the link between active adipogenesis and angiogenesis, we developed a model to visualize noninvasively and in real time both angiogenesis and adipogenesis using intravital microscopy. Implanted murine preadipocytes induced vigorous angiogenesis and formed fat pads in a mouse dorsal skin-fold chamber. The newly formed vessels subsequently remodeled into a mature network consisting of arterioles, capillaries, and venules, whereas the preadipocytes differentiated into adipocytes as confirmed by increased aP2 expression. Inhibition of adipocyte differentiation by transfection of preadipocytes with a peroxisome proliferator-activated receptor gamma dominant-negative construct not only abrogated fat tissue formation but also reduced angiogenesis. Surprisingly, inhibition of angiogenesis by vascular endothelial growth factor receptor-2 (VEGFR2) blocking antibody not only reduced angiogenesis and tissue growth but also inhibited preadipocyte differentiation. We found that part of this inhibition stems from the paracrine interaction between endothelial cells and preadipocytes and that VEGF-VEGFR2 signaling in endothelial cells, but not preadipocytes, mediates this process. These findings reveal a reciprocal regulation of adipogenesis and angiogenesis, and suggest that blockade of VEGF signaling can inhibit in vivo adipose tissue formation. The full text of this article is available online at http://www.circresaha.org.
The environmental benefits of water recycling and reuse (2003)

The world's supply of fresh water is finite and is threatened by pollution. Rising demands for water to supply agriculture, industry and cities are leading to competition over the allocation of limited fresh water resources. This paper examines how water reuse increases the available supply of water and enables human needs to be met with less fresh water. The paper is illustrated with water reuse case studies in agriculture, urban areas, industry and water resource supplementation in Australia and other countries. The links between water reuse and sustainable water management are examined. Water conservation and water reuse produce substantial environmental benefits, arising from reductions in water diversions, and reductions in the impacts of wastewater discharges on environmental water quality. Some examples are presented demonstrating the environmental benefits in quantitative terms. The paper also describes the economic and environmental benefits identified in a number of recent integrated water cycle planning studies in Australia.
Membrane Insertion of a Potassium-Channel Voltage Sensor (2005)

The mechanism of voltage gating in K+ channels is controversial. The paddle model posits that highly charged voltage-sensor domains move relatively freely across the lipid bilayer in response to membrane depolarization; competing models picture the charged S4 voltage-sensor helix as being shielded from lipid contact by other parts of the protein. We measured the apparent free energy of membrane insertion of a K+-channel S4 helix into the endoplasmic reticulum membrane and conclude that S4 is poised very near the threshold of efficient bilayer insertion. Our results suggest that the paddle model is not inconsistent with the high charge content of S4.
High-speed CMOS I/O buffer circuits (1992)

Very high-speed off-chip data rates have been difficult to achieve in CMOS technologies. An all-CMOS set of I/O buffer circuits, which use current-mode and impedance matching techniques, capable of transmitting off-chip at 1-Gb/s data rates is described. The circuits are also compatible with voltage-mode signal levels for ECL input and MOS output circuits.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
SYNTHESIS OF 2-ALKYL AND 2-ARYL PYRIMIDINES FROM β-CHLOROVINYL KETONES OF CYCLOPENTANONE TYPE (2001)

Abstract Amidines react in the presence of NaHCO3 with β-chlorovinyl ketones, prepared regioselectively by the reaction of 2-acetylcyclo- pentanone-type diketones with PPh3-CCl4 in 73–78% yield, to afford 2-alkyl (aryl)-pyrimidines annelated with cyclopentane derivatives in 79–87% yields. ACKNOWLEDGMENTS The authors thank the Russian Foundation for Basic Research (grant no. 98-03-32910 a) and INTAS (grant # 97-0217) for the financial support of this work.
Intellectual property protection systems and digital watermarking (1998)

Adequate protection of digital copies of multimedia content - both audio and video - is a prerequisite to the distribution of this content over networks. Until recently digital audio and video content has been protected by its size: it is difficult to distribute and store without compression. Modern compression algorithms allow substantial bitrate reduction while maintaining high-fidelity reproduction. If distribution of these algorithms is controlled, cleartext uncompressed content is still protected by its size. However, once the compression algorithms are generally available cleartext content becomes extremely vulnerable to piracy. In this paper we explore the implications of this vulnerability and discuss the use of compression and watermarking in the control of piracy.
Binding of the Src SH2 Domain to Phosphopeptides is Determined by Residues in both the SH2 Domain and the Phosphopeptides (1993)

Src homology 2 (SH2) domains are found in a variety of signaling proteins and bind phosphotyrosine-containing peptide sequences. To explore the binding properties of the SH2 domain of the Src protein kinase, we used immobilized phosphopeptides to bind purified glutathione S-transferase-Src SH2 fusion proteins. With this assay, as well as a free-peptide competition assay, we have estimated the affinities of the Src SH2 domain for various phosphopeptides relative to a Src SH2-phosphopeptide interaction whose Kd has been determined previously (YEEI-P; Kd = 4 nM). Two Src-derived phosphopeptides, one containing the regulatory C-terminal Tyr-527 and another containing the autophosphorylation site Tyr-416, bind the Src SH2 domain in a specific though low-affinity manner (with about 10(4)-lower affinity than the YEEI-P peptide). A platelet-derived growth factor receptor (PDGF-R) phosphopeptide containing Tyr-857 does not bind appreciably to the Src SH2 domain, suggesting it is not the PDGF-R binding site for Src as previously reported. However, another PDGF-R-derived phosphopeptide containing Tyr-751 does bind the Src SH2 domain (with an affinity approximately 2 orders of magnitude lower than that of YEEI-P). All of the phosphopeptides which bind to the Src SH2 domain contain a glutamic acid at position -3 or -4 with respect to phosphotyrosine; changing this residue to alanine greatly diminishes binding. We have also tested Src SH2 mutants for their binding properties and have interpreted our results in light of the recent crystal structure solution for the Src SH2 domain. Mutations in various conserved and nonconserved residues (R155A, R155K, N198E, H201R, and H201L) cause slight reductions in binding, while two mutations cause severe reductions. The W148E mutant domain, which alters the invariant tryptophan that marks the N-terminal border of the SH2 domain, binds poorly to phosphopeptides. Inclusion of the SH3 domain in the fusion protein partially restores the binding by the W148E mutant. A change in the invariant arginine that coordinates twice with phosphotyrosine in the peptide (R175L) results in a nearly complete loss of binding. The R175L mutant does display high affinity for the PDGF-R peptide containing Tyr-751, via an interaction that is at least partly phosphotyrosine independent. We have used this interaction to show that the R175L mutation also disrupts the intramolecular interaction between the Src SH2 domain and the phosphorylated C terminus within the context of the entire Src protein; thus, the binding properties observed for mutant domains in an in vitro assay appear to mimic those that occur in vivo.
Epitope Analysis of a Prostate-specific Antigen (PSA) C-Terminal-specific Monoclonal Antibody and New Aspects for the Discrepancy between Equimolar and Skewed PSA Assays (1999)

The discrepancy between the values measured by equimolar and skewed assays depends on the ratio of free to total PSA in the sample.
Intracardiac impedance monitors stroke volume in resynchronization therapy patients (2010)

In HF patients, a strong correlation between changes in intracardiac impedance and LV SV was found. Typical LV lead implant positions have been tested and all appear to be suitable for this method of LV volume monitoring.
Wild-Type NRas and KRas Perform Distinct Functions during Transformation (2007)

The ras proto-oncogenes, of which there are four isoforms, are molecular switches that function in signal transduction pathways to control cell differentiation, proliferation, and survival. How the Ras isoforms orchestrate cellular processes that affect behavior is poorly understood. Further, why cells express two or more Ras isoforms is unknown. Here, using a genetically defined system, we show that the presence of both wild-type KRas and NRas isoforms is required for transformation because they perform distinct nonoverlapping functions: wild-type NRas regulates adhesion, and KRas coordinates motility. Remarkably, we find that Ras isoforms achieve functional specificity by engaging different signaling pathways to affect the same cellular processes, thereby coordinating cellular outcome. Although we find that signaling from both isoforms intersects in actin and microtubule cytoskeletons, our results suggest that KRas signals through Akt and Cdc42 while NRas signals through Raf and RhoA. Our analyses suggest a previously unappreciated convergence of different Ras isoforms on the dynamics of the processes involved in transformation.
Effect of Glucagon-Like Peptide-1(7–36) and Exendin-4 on the Vascular Reactivity in Streptozotocin/Nicotinamide-Induced Diabetic Rats (2005)

We investigated the vascular effects of glucagon-like peptide-1 (GLP-1) and Exendin-4 in type 2 diabetic rat aortae. Studies were performed in a normal control group (NC) (0.2 ml i.p. saline, n = 10), streptozotocin (STZ)/nicotinamide diabetic control group (DC) (a single dose of 80 mg/kg STZ i.p. injection 15 min after administration of 230 mg/kg nicotinamide i.p.), GLP-1 (GLPC) control group (1 microg/kg twice daily i.p. for 1 month, n = 10), Exendin-4 control group (EXC) (0.1 microg/kg twice daily i.p. for 1 month, n = 10), GLP-1-treated diabetic group (GLPT) (1 microg/kg twice daily i.p. for 1 month, n = 10), and Exendin-4-treated diabetic group (EXT) (0.1 microg/kg twice daily i.p. for 1 month, n = 10). One month of GLP-1 and Exendin-4 treatment significantly decreased the blood glucose levels of diabetic rats (113 +/- 2 mg/dl, p < 0.001, and 117 +/- 1 mg/dl, p < 0.001, respectively versus 181 +/- 9 mg/dl in the DC group). Sensitivity (pD2) and maximum response (% Max. Relax) of acetylcholine-stimulated relaxations in the DC group (pD2: 6.73 +/- 0.12 and 55 +/- 6, respectively) were decreased compared with the non-diabetic NC group (pD2: 7.41 +/- 0.25, p < 0.05, and 87 +/- 4, p < 0.01). Treating diabetic rats with GLP-1, pD2 values and with Exendin-4, Max. Relax %values of aortic strips to acetylcholine returned to near non-diabetic NC values (pD2: 7.47 +/- 0.15, p < 0.05, and 87 +/- 3, p < 0.01, respectively). Maximal contractile responses (Emax) to noradrenaline in aortic strips from the diabetic DC group (341 +/- 27 mg tension/mg wet weight) were significantly decreased compared with the non-diabetic NC (540 +/- 66 mg tension/mg wet weight, p < 0.001) and the GLPT group (490 +/- 25 mg tension/mg wet weight, p < 0.05). There were no significant differences in pD2 values of aortic strips to noradrenaline from all groups. Emax to KCl in aortic strips from the DC group (247 +/- 10 mg tension/mg wet weight, p < 0.01) was significantly decreased compared with non-diabetic NC group (327 +/- 26 mg tension/mg wet weight). Treating diabetic rats with GLP-1 (GLPT), Emax values of aortic strips to KCl returned to near non-diabetic NC values (271 +/- 12 mg tension/mg wet weight). GLP-1 and (partially) Exendin-4 treatment could improve the increased blood glucose level and normalize the altered vascular tone in type 2 diabetic rats.
Pathology of Acute and Chronic Coronary Stenting in Humans (1999)

Morphology after coronary stenting demonstrates early thrombus formation and acute inflammation followed by neointimal growth. Medial injury and lipid core penetration by struts result in increased inflammation. Neointima increases as the ratio of stent area to reference lumen area increases. Deployment strategies that reduce medial damage and avoid stent oversizing may lower the frequency of in-stent restenosis.
Interaction of the IL-2 Receptor with the src -Family Kinase p56 lck : Identification of Novel Intermolecular Association (1991)

In the interleukin-2 (IL-2) system, intracellular signal transduction is triggered by the beta chain of the IL-2 receptor (IL-2R beta); however, the responsible signaling mechanism remains unidentified. Evidence for the formation of a stable complex of IL-2R beta and the lymphocyte-specific protein tyrosine kinase p56lck is presented. Specific association sites were identified in the tyrosine kinase catalytic domain of p56lck and in the cytoplasmic domain of IL-2R beta. As a result of interaction, IL-2R beta became phosphorylated in vitro by p56lck. Treatment of T lymphocytes with IL-2 promotes p56lck kinase activity. These data suggest the participation of p56lck as a critical signaling molecule downstream of IL-2R via a novel interaction.
The biological profile of PD 0325901: A second generation analog of CI-1040 with improved pharmaceutical potential (2004)

4003 CI-1040, the first MEK inhibitor to enter clinical evaluation, was advanced into development based on promising preclinical activity. While Phase 1 data pointed to promising hints of clinical activity, efficacy in Phase 2 single agent screening studies was insufficient to warrant continued development. Target suppression in Phase 1 tumor biopsies was 50% at 24 hours post-dosing. In comparison, CI-1040 at a much higher dose (150 mg/kg) could only inhibit pERK levels for roughly 8 hours, returning to control levels by 24 hours after treatment. Oral efficacy comparisons revealed that the dose required to produce a 70% incidence of complete tumor responses (C26 model) was 25 mg/kg/day versus 900 mg/kg/day for PD0325901 and CI-1040, respectively. Anticancer activity of PD 0325901 has been demonstrated for a broad spectrum of human tumor xenografts, significantly inhibiting the growth of 6 out of 7 human tumor models tested. PD 0325901 was also shown to be highly efficacious and effective at inhibiting ERK phosphorylation when administered by the IV route. The improved anticancer activity of PD0325901 compared to CI-1040 is likely due to several contributing pharmacological factors, including longer duration and greater potency of MEK inhibition, as well as greater solubility leading to improved bioavailability, and increased metabolic stability. Based on its highly specific inhibition of MEK and its overall pharmaceutical profile, PD0325901 has the potential to provide ultimate validation of MEK as an anticancer drug target. Phase 1 trials with this agent are underway.
Ultrasensitive DNA sequence detection using nanoscale ZnO sensor arrays (2006)

We report that engineered nanoscale zinc oxide structures can be effectively used for the identification of the biothreat agent, Bacillus anthracis by successfully discriminating its DNA sequence from other genetically related species. We explore both covalent and non-covalent linking schemes in order to couple probe DNA strands to the zinc oxide nanostructures. Hybridization reactions are performed with various concentrations of target DNA strands whose sequence is unique to Bacillus anthracis. The use of zinc oxide nanomaterials greatly enhances the fluorescence signal collected after carrying out duplex formation reaction. Specifically, the covalent strategy allows detection of the target species at sample concentrations at a level as low as a few femtomolar as compared to the detection sensitivity in the tens of nanomolar range when using the non-covalent scheme. The presence of the underlying zinc oxide nanomaterials is critical in achieving increased fluorescence detection of hybridized DNA and, therefore, accomplishing rapid and extremely sensitive identification of the biothreat agent. We also demonstrate the easy integration potential of nanoscale zinc oxide into high density arrays by using various types of zinc oxide sensor prototypes in the DNA sequence detection. When combined with conventional automatic sample handling apparatus and computerized fluorescence detection equipment, our approach can greatly promote the use of zinc oxide nanomaterials as signal enhancing platforms for rapid, multiplexed, high-throughput, highly sensitive, DNA sensor arrays.
Graphics Interfaces and Sensor Actuator Extensions For the Process Trellis Software. (1995)

Abstract : We tested the new LAN-capable sensor/actuator package by developing a monitor controller for the Piranha adaptive parallelism environment. Piranha is a system that allows processes of a parallel application to be created dynamically (for example on newly idle LAN nodes) and removed dynamically (for example, when an owner resumes work at his node) while the computation as a whole continues without interruption. Overall research results of the AFOSR Grant # F49620-92-J-0240 support include development of the underlying Pirahnna system for adaptive parallelism to manage nodes of a dedicated multiprocessor efficiently specific Network Piranha and multiprocessor (CM-5) applications and implementations, and the (ongoing) development of a practical software application called 'Lifestreams,' discussed in the attached final report.
JM2, encoding a fork head–related protein, is mutated in X-linked autoimmunity–allergic disregulation syndrome (2000)

X-linked autoimmunity-allergic disregulation syndrome (XLAAD) is an X-linked recessive immunological disorder characterized by multisystem autoimmunity, particularly early-onset type 1 diabetes mellitus, associated with manifestations of severe atopy including eczema, food allergy, and eosinophilic inflammation. Consistent with the allergic phenotype, analysis of two kindreds with XLAAD revealed marked skewing of patient T lymphocytes toward the Th2 phenotype. Using a positional-candidate approach, we have identified in both kindreds mutations in JM2, a gene on Xp11.23 that encodes a fork head domain-containing protein. One point mutation at a splice junction site results in transcripts that encode a truncated protein lacking the fork head homology domain. The other mutation involves an in-frame, 3-bp deletion that is predicted to impair the function of a leucine zipper dimerization domain. Our results point to a critical role for JM2 in self tolerance and Th cell differentiation.
Hormone-refractory breast cancer remains sensitive to the antitumor activity of heat shock protein 90 inhibitors. (2003)

Based on its ability to deplete the ER as well as other critical signaling molecules in Tam-resistant breast cancer, 17AAG may provide a useful alternative treatment for patients with recurrent, hormone-refractory breast cancer that should be explored further in Phase II trials. In this context, combined treatment with 17AAG and Tam should be avoided because Tam may inhibit the ability of 17AAG to deplete the ER, potentially reducing its anticancer activity.
Spray Drying of Monoclonal Antibodies: Investigating Powder-Based Biologic Drug Substance Bulk Storage (2013)

Biologic drug substances (DSs) are stored and transported as frozen bulk in various containers, each having disadvantages. We evaluated a powder-based bulk storage approach based on spray drying and demonstrate for the first time that monoclonal antibodies (mAbs) can be spray dried with >90% powder collection yield using a laboratory-scale spray dryer, which outperformed three benchtop units in yield and water content reduction. Cyclone design was critical to collection yield, which remained sensitive to sample formulations. High yield was achieved for three mAbs formulated at a 2:1 mAb: trehalose weight ratio. Increasing the amount of trehalose beyond this ratio decreased yield by increasing the amount of powder retained in the drying chamber, apparently due to increased particle tackiness. Despite a high inlet temperature, the physical stability of spray-dried mAbs was comparable to or greater than that of freeze-dried counterparts. Water content of the spray-dried powder was affected more by gas residence time in the dryer than by outlet and inlet temperatures. The laboratory-scale unit, which allowed longer gas residence time, produced drier powders even at high liquid feed rate. Characterization of spray-dried mAb reconstitution time and reconstituted solution turbidity demonstrated that the process was suitable for powder-based biologic DS bulk storage applications.
Predicting Lack of Marketability Discounts by Use of an Econometric (Statistical Regression) Model (2002)

The Silber Model applies a multiple causal factor methodology to determine a marketability discount that is specific to the firm being valued.