gebhart/patrepeval huggingface dataset:
Analog of H2 relaxin exhibits antagonistic properties and impairs prostate tumor growth (2006)

Hormone antagonists can be effective tools to delineate receptor signaling pathways and their resulting downstream physiological actions. Mutation of the receptor binding domain (RBD) of human H2 relaxin (deltaH2) impaired its biological function as measured by cAMP signaling. In a competition assay, deltaH2 exhibited antagonistic activity by blocking recombinant H2 relaxin from binding to receptors on THP-1 cells. In a flow cytometry-based binding assay, deltaH2 demonstrated weak binding to 293T cells expressing the LGR7 receptor in the presence of biotinylated H2 relaxin. When human prostate cancer cell lines (PC-3 and LNCaP) were engineered to overexpress eGFP, wild-type (WT) H2, or deltaH2, and subsequently implanted into NOD/SCID mice, tumor xenografts overexpressing deltaH2 displayed smaller volumes compared to H2 and eGFP controls. Plasma osmolality readings and microvessel density and area assessment suggest that deltaH2 modulates physiological parameters in vivo. In a second murine model, intratumoral injections of lentivectors engineered to express deltaH2/eGFP led to suppressed tumor growth compared to controls. This study provides further evidence supporting a role for H2 relaxin in prostate tumor growth. More importantly, we report how mutation of the H2 relaxin RBD confers the hormone derivative with antagonistic properties, offering a novel reagent for relaxin research.
Which interaction technique works when? (2002)

We conducted an experiment that compared three post-WIMP interaction techniques: floating palettes, marking menus and toolglasses, in a real-world Coloured Petri-Net editor, CPN2000. We created six situations in which users performed identical sets of actions with equally-complex nets, but with different cognitive contexts. We found significant differences in performance and preferences across interaction techniques. When a user is in a "copy" context, floating palettes are more efficient. If the user is problem solving, toolglasses or marking menus are preferred. No single interaction technique is clearly superior: each has strengths in different contexts. Since a single application must support different kinds of cognitive tasks, interaction designers should consider integrating multiple interaction techniques, rather than selecting only one.
Stabilization of ZnO polar plane with charged surface nanodefects (2010)

Based on in situ scanning probe microscopy/spectroscopy, this study investigates the stabilization of Zn-terminated ZnO polar plane using surface defects. O-terminated surface defects on a nanometer scale, which have two morphologies, i.e., hexagonal cavities and small pits, are observed at the submonolayer depth on the (0001)-Zn surface by applying medium-energy ${\text{Ar}}^{+}$ bombardment (2.5 keV) at a high temperature $(850\text{ }\ifmmode^\circ\else\textdegree\fi{}\text{C})$. Experimental results indicate that the local electronic structure of O-terminated surface defects exhibits upward band bending with respect to the Zn-terminated surface, which is consistent with the observations made using Kevin probe microscopy, in which the ZnO polar surface has a locally reversed electrostatic field. Moreover, pair-distribution analysis indicates that the O-terminated surface defects with diameters below 0.9 nm are charged with one electron per pit, thus helping to compensate for the internal polarization.
One-step generation of knockout pigs by zygote injection of CRISPR/Cas system (2014)

The pig is an important livestock for food supply and an ideal model for various human diseases. Efficient and precise genetic engineering in pigs holds great promise in agriculture and biomedicine1. Using currently available approach, generating specific gene modifications in pigs requires two steps. First, site-specific nucleases such as zinc finger nucleases (ZFNs) and transcription activator-like effector nucleases (TALENs) are used to generate targeted mutations in pig somatic cells. Then the engineered somatic nucleus is used to generate cloned animals using somatic cell nuclear transfer (SCNT) technology2,3. The complex design and generation of ZFNs and TALENs, as well as the technical challenges of SCNT, greatly limit the application of this method.
Transactional boosting (2008)

We describe a methodology for transforming a large class of highly-concurrent linearizable objects into highly-concurrent transactional objects. As long as the linearizable implementation satisfies certain regularity properties (informally, that every method has an inverse), we define a simple wrapper for the linearizable implementation that guarantees that concurrent transactions without inherent conflicts can synchronize at the same granularity as the original linearizable implementation.
K-Ras4A splice variant is widely expressed in cancer and uses a hybrid membrane-targeting motif (2015)

The two products of the KRAS locus, K-Ras4A and K-Ras4B, are encoded by alternative fourth exons and therefore, possess distinct membrane-targeting sequences. The common activating mutations occur in exons 1 or 2 and therefore, render both splice variants oncogenic. K-Ras4A has been understudied, because it has been considered a minor splice variant. By priming off of the splice junction, we developed a quantitative RT-PCR assay for K-Ras4A and K-Ras4B message capable of measuring absolute amounts of the two transcripts. We found that K-Ras4A was widely expressed in 30 of 30 human cancer cell lines and amounts equal to K-Ras4B in 17 human colorectal tumors. Using splice variant-specific antibodies, we detected K-Ras4A protein in several tumor cell lines at a level equal to or greater than that of K-Ras4B. In addition to the CAAX motif, the C terminus of K-Ras4A contains a site of palmitoylation as well as a bipartite polybasic region. Although both were required for maximal efficiency, each of these could independently deliver K-Ras4A to the plasma membrane. Thus, among four Ras proteins, K-Ras4A is unique in possessing a dual membrane-targeting motif. We also found that, unlike K-Ras4B, K-Ras4A does not bind to the cytosolic chaperone δ-subunit of cGMP phosphodiesterase type 6 (PDE6δ). We conclude that efforts to develop anti-K-Ras drugs that interfere with membrane trafficking will have to take into account the distinct modes of targeting of the two K-Ras splice variants.
The conformation of Alzheimer's β peptide determines the rate of amyloid formation and its resistance to proteolysis (1996)

Amyloid beta-peptide (A beta) is found in an aggregated poorly soluble form in senile or neuritic plaques deposited in the brain of individuals affected by Alzheimer's disease (AD). In addition soluble A beta (sA beta) is identified normally circulating in human body fluids. In this study we report that synthetic peptides containing the sequences 1-40 and 1-42 of A beta, and A beta analogues bearing amino acid substitutions can adopt two major conformational states in solution: (1) an amyloidogenic conformer (A beta ac) with a high content of beta-sheet and partly resistant to proteases and (2) a non-amyloidogenic conformer (A beta nac) with a random coil conformation and protease-sensitive. The differences in the fibrillogenesis rate and in the protease resistance among the several A beta peptides studied depend mainly on the relative propensity for adopting the amyloidogenic conformation, which in the absence of external factors is largely conditioned by the primary structure of the peptide. A beta nac containing the sequence 1-40, 1-42 or bearing amino acid substitutions (Dutch variant of A beta) was protease-sensitive and unable to form a significant amount of amyloid even at high concentrations or after long incubations. The finding of the simultaneous existence of different A beta conformers with distinct abilities to form amyloid may help to explain why A beta is found in both soluble and fibrillar forms in vivo.
Folate deficiency disturbs hepatic methionine metabolism and promotes liver injury in the ethanol-fed micropig (2002)

Alcoholic liver disease is associated with abnormal hepatic methionine metabolism and folate deficiency. Because folate is integral to the methionine cycle, its deficiency could promote alcoholic liver disease by enhancing ethanol-induced perturbations of hepatic methionine metabolism and DNA damage. We grouped 24 juvenile micropigs to receive folate-sufficient (FS) or folate-depleted (FD) diets or the same diets containing 40% of energy as ethanol (FSE and FDE) for 14 wk, and the significance of differences among the groups was determined by ANOVA. Plasma homocysteine levels were increased in all experimental groups from 6 wk onward and were greatest in FDE. Ethanol feeding reduced liver methionine synthase activity, S-adenosylmethionine (SAM), and glutathione, and elevated plasma malondialdehyde (MDA) and alanine transaminase. Folate deficiency decreased liver folate levels and increased global DNA hypomethylation. Ethanol feeding and folate deficiency acted together to decrease the liver SAM/S-adenosylhomocysteine (SAH) ratio and to increase liver SAH, DNA strand breaks, urinary 8-oxo-2'-deoxyguanosine [oxo(8)dG]/mg of creatinine, plasma homocysteine, and aspartate transaminase by more than 8-fold. Liver SAM correlated positively with glutathione, which correlated negatively with plasma MDA and urinary oxo(8)dG. Liver SAM/SAH correlated negatively with DNA strand breaks, which correlated with urinary oxo(8)dG. Livers from ethanol-fed animals showed increased centrilobular CYP2E1 and protein adducts with acetaldehyde and MDA. Steatohepatitis occurred in five of six pigs in FDE but not in the other groups. In summary, folate deficiency enhances perturbations in hepatic methionine metabolism and DNA damage while promoting alcoholic liver injury.
Within-patient variability of (18)F-FDG: standardized uptake values in normal tissues. (2004)

The SUVs measured in normal liver and mediastinum in cancer-free patients are stable over time, no matter which normalization is used. Correcting for blood glucose level increases the variability of the values and should therefore be avoided. Normalizing for BSA or LBM does not improve the reproducibility of the measurements.
Quantitative cerebral blood flow with Optical Coherence Tomography (2010)

Absolute measurements of cerebral blood flow (CBF) are an important endpoint in studies of cerebral pathophysiology. Currently no accepted method exists for in vivo longitudinal monitoring of CBF with high resolution in rats and mice. Using three-dimensional Doppler Optical Coherence Tomography and cranial window preparations, we present methods and algorithms for regional CBF measurements in the rat cortex. Towards this end, we develop and validate a quantitative statistical model to describe the effect of static tissue on velocity sensitivity. This model is used to design scanning protocols and algorithms for sensitive 3D flow measurements and angiography of the cortex. We also introduce a method of absolute flow calculation that does not require explicit knowledge of vessel angles. We show that OCT estimates of absolute CBF values in rats agree with prior measures by autoradiography, suggesting that Doppler OCT can perform absolute flow measurements in animal models.
Increased matrix metalloproteinase-9 (MMP-9) activity observed in chronic wound fluid is related to the clinical severity of the ulcer (2008)

In view of these results, it is hypothesized that a specific inhibitor of MMP-9 could potentially be more therapeutically effective than general MMP inhibitors in modulating chronic ulcers towards a healing state.
Comparative Evaluation of Various Human Feeders for Prolonged Undifferentiated Growth of Human Embryonic Stem Cells (2003)

Human embryonic stem (hES) cells are typically derived and serially propagated on inactivated murine embryonic fibroblast (MEF) feeders. The use of MEFs and other components of animal origin in the culture media for hES cell support substantially elevates the risk of contaminating these cell lines with infectious agents of animal origin thereby severely limiting their potential for clinical application. We have previously shown that it is possible to derive and establish new hES cell lines in a xeno-free culture system using human fetal muscle fibroblast feeders. In this report, we have comparatively evaluated a panel of 11 different human adult, fetal, and neonatal feeders for hES cell support and have ranked them as supportive and non-supportive. We report that two adult skin fibroblast cell lines established in-house from abdominal skin biopsies supported prolonged undifferentiated hES cell growth for over 30 weekly passages in culture. Furthermore, hES cell lines cultured on adult skin fibroblast feeders retain hES cell morphology and remain pluripotent. Also, differences in feeder support exist between human cell types and sources. The use of human adult skin feeders is convenient for hES cell support given the ease of obtaining skin biopsies.
Local Immunotherapy with Interleukin-2 Delivered from Biodegradable Polymer Microspheres Combined with Interstitial Chemotherapy: A Novel Treatment for Experimental Malignant Glioma (2003)

By showing synergy of IL-2 and BCNU in an animal glioma model and using a reproducible synthetic delivery system for each agent (i.e., one that did not rely on genetically engineered cells or viruses), we hope that the combination of local immunotherapy and chemotherapy can take an important step closer to clinical application in patients with malignant brain tumors.
Potentiometric Detection of Single Nucleotide Polymorphism by Using a Genetic Field‐effect transistor (2005)

Potentiometric measurement of allele-specific oligonucleotide hybridization based on the principle of detection of charge-density change at the surface of a gate insulator by using of a genetic field-effect transistor has been demonstrated. Since DNA molecules are negatively charged in aqueous solution, a hybridization event at the gate surface leads to a charge-density change in the channel of the FET and can be directly transduced into an electrical signal without any labeling of target DNA molecules. One of the unique features of our method is to utilize DNA binders such as intercalators as charged species for double-stranded DNA after hybridization, since these are ionized and carry positive charges in aqueous solution. Single-base mismatch of the target DNA could be successfully detected both with the wild-type and with the mutant genetic FETs by controlling the hybridization temperatures and introducing Hoechst 33258 as DNA binder. The genetic FET platform is suitable as a simple, accurate, and inexpensive system for SNP typing in clinical diagnostics.
Controlled delivery of proteins into bilayer lipid membranes on chip (2007)

The study and the exploitation of membrane proteins for drug screening applications requires a controllable and reliable method for their delivery into an artificial suspended membrane platform based on lab-on-a-chip technology. In this work, a polymeric device for forming lipid bilayers suitable for electrophysiology studies and biosensor applications is presented. The chip supports a single bilayer and is configured for controlled protein delivery through on-chip microfluidics. In order to demonstrate the principle of protein delivery, the potassium channel KcsA was reconstituted into proteoliposomes, which were then fused with the suspended bilayer on-chip. Fusion of single proteoliposomes with the membrane was identified electrically. Single channel conductance measurements of KcsA in the on-chip bilayer were recorded and these were compared to previously published data obtained with a conventional planar bilayer system.
Abstract 3417: Unselected Human Cardiosphere-derived Cells are Functionally Superior to c-Kit- or CD90-Purified Cardiosphere-derived Cells (2008)

Cardiosphere-derived cells (CDCs), a naturally heterogeneous mixture of cell sub-populations, were grown from percutaneous endomyocardial adult human biopsy specimens (n=6). c-Kit + and CD90 + CDCs were selected using magnetic-activated cell sorting with excellent purity as determined by flow cytometry. Immunostaining revealed that ~30% of c-Kit + CDCs expressed Nkx2.5, ~100% of CD90 + CDCs expressed procollagen type I, and ~100% of both sub-populations expressed CD105. When placed in co-culture with neonatal myocytes and fibroblasts, c-Kit + CDCs expressed cardiac troponin I, while CD90 + CDCs expressed vimentin. In order to assess the therapeutic potential of purified CDCs, acute myocardial infarcts (MIs) were created in immunodeficient mice and c-Kit + (n=16), CD90 + (n=14), or CD105 + (n=3) CDCs were injected into the border zone. Echocardiograms were performed 3 weeks post-MI to measure left ventricular ejection fraction (LVEF). CD105-injected mice were comparable to an historical control group of mixed CDC-injected mice (LVEF = 41.3±2.9% CD105 vs. 42.8±10.4% CDC [n=11], p=0.60), indicating that the sorting process did not itself impair the therapeutic potential of CDCs. c-Kit- and CD90-injected mice were indistinguishable from one another (LVEF=31.7±8.2% c-Kit vs. 32.1±11.8% CD90, p=0.92), and both groups were significantly outperformed by the CD105-injected mice (p=0.01 and p=0.03, respectively). All groups were then compared to two other historical control groups, mice treated with normal human dermal fibroblasts (NHDFs [n=7]) and mice treated with phosphate-buffered saline (PBS [n=11]). c-Kit-injected mice did significantly outperform both NHDF- (p=0.04) and PBS-injected mice (p=0.03), while more variability in the CD90-injected group resulted in nearly significant comparisons with the NHDF (p=0.08) and PBS groups (p=0.08). While the therapeutic mechanisms of action of these two distinct sub-populations are undoubtedly different, both offer similar global functional benefits in the setting of acute MI. We conclude that the spontaneously-emerging unselected CDC population serves as a therapeutic cell cocktail, and that no functional advantage is conferred by the extra step of sorting for c-Kit + or CD90 + sub-populations.
A Survey of Mobile VPN Technologies (2015)

Virtual private network (VPN) is the traditional approach for an end-to-end secure connection between two endpoints. Most existing VPN solutions are intended for wired networks with high-speed, highly reliable connections. In a mobile environment, these network connections are less reliable. This affects traditional VPN performance resulting in frequent application failure, data loss, and reduced productivity. Mobile VPN bridges the gap between what users and applications expect from a wired network and the realities of mobile computing. In this survey, we provide a taxonomy of VPN designs, present a study of existing mobile VPN solutions, and highlight the advantages and disadvantages and applications of these methods.
Fluorescence correlation spectroscopy and fluorescence cross-correlation spectroscopy reveal the cytoplasmic origination of loaded nuclear RISC in vivo in human cells (2008)

Studies of RNA interference (RNAi) provide evidence that in addition to the well-characterized cytoplasmic mechanisms, nuclear mechanisms also exist. The mechanism by which the nuclear RNA-induced silencing complex (RISC) is formed in mammalian cells, as well as the relationship between the RNA silencing pathways in nuclear and cytoplasmic compartments is still unknown. Here we show by applying fluorescence correlation and cross-correlation spectroscopy (FCS/FCCS) in vivo that two distinct RISC exist: a large approximately 3 MDa complex in the cytoplasm and a 20-fold smaller complex of approximately 158 kDa in the nucleus. We further show that nuclear RISC, consisting only of Ago2 and a short RNA, is loaded in the cytoplasm and imported into the nucleus. The loaded RISC accumulates in the nucleus depending on the presence of a target, based on an miRNA-like interaction with impaired cleavage of the cognate RNA. Together, these results suggest a new RISC shuttling mechanism between nucleus and cytoplasm ensuring concomitant gene regulation by small RNAs in both compartments.
Blood Flow, Pressure and Compliance in the Male Human Bladder (2002)

Human bladder blood flow tends to increase with increasing volume and pressure, and depends largely on local regulation. At capacity bladder blood flow is significantly decreased. Immediately after bladder drainage there is a rebound in blood flow, allowing reperfusion to occur. Decreased bladder blood flow and decreased bladder wall compliance correlated strongly, suggesting that ischemia may lead to structural changes in the bladder wall.
MIME Object Security Services (1995)

This document defines MIME Object Security Services (MOSS), a protocol that uses the multipart/signed and multipart/encrypted framework [7] to apply digital signature and encryption services to MIME objects. The services are offered through the use of end-to-end cryptography between an originator and a recipient at the application layer. Asymmetric (public key) cryptography is used in support of the digital signature service and encryption key management. Symmetric (secret key) cryptography is used in support of the encryption service. The procedures are intended to be compatible with a wide range of public key management approaches, including both ad hoc and certificate-based schemes. Mechanisms are provided to support many public key management approaches.
The growth and morphology of epitaxial multilayer graphene (2008)

The electronic properties of epitaxial graphene grown on SiC have shown its potential as a viable candidate for post-CMOS electronics. However, progress in this field requires a detailed understanding of both the structure and growth of epitaxial graphene. To that end, this review will focus on the current state of epitaxial graphene research as it relates to the structure of graphene grown on SiC. We pay particular attention to the similarity and differences between graphene growth on the two polar faces, (0001) and , of hexagonal SiC. Growth techniques, subsequent morphology and the structure of the graphene/SiC interface and graphene stacking order are reviewed and discussed. Where possible the relationship between film morphology and electronic properties will also be reviewed.
A PATTERN MATCHING MODEL FOR MISUSE INTRUSION DETECTION (1994)

This paper describes a generic model of matching that can be usefully applied to misuse intrusion detection. The model is based on Colored Petri Nets. Guards define the context in which signatures are matched. The notion of start and final states, and paths between them define the set of event sequences matched by the net. Partial order matching can also be specified in this model. The main benefits of the model are its generality, portability and flexibility. 1 Introduction Computer break-ins are becoming increasingly frequent and their detection is increasingly important. Break-ins make the data residing on computer systems vulnerable to theft and corruption. Compromised sites can also be used to launch further attacks, thus achieving another level of indirection for further break-ins. A majority of break-ins, however, are the result of a small number of known attacks, as evidenced by reports from response teams (e.g. CERT). Automating detection of these attacks should therefore res...
Infectious causes of acute flaccid paralysis (2003)

Despite the near eradication of poliomyelitis, AFP caused by viruses remains an important clinical presentation. Distinguishing direct viral causes from GBS is important for public health reasons, and to avoid inappropriate therapies.