gebhart/patrepeval huggingface dataset:
Anti-CD166 single chain antibody-mediated intracellular delivery of liposomal drugs to prostate cancer cells (2007)

Targeted delivery of small-molecule drugs has the potential to enhance selective killing of tumor cells. We have identified previously an internalizing single chain [single chain variable fragment (scFv)] antibody that targets prostate cancer cells and identified the target antigen as CD166. We report here the development of immunoliposomes using this anti-CD166 scFv (H3). We studied the effects of a panel of intracellularly delivered, anti-CD166 immunoliposomal small-molecule drugs on prostate cancer cells. Immunoliposomal formulations of topotecan, vinorelbine, and doxorubicin each showed efficient and targeted uptake by three prostate cancer cell lines (Du-145, PC3, and LNCaP). H3-immunoliposomal topotecan was the most effective in cytotoxicity assays on all three tumor cell lines, showing improved cytotoxic activity compared with nontargeted liposomal topotecan. Other drugs such as liposomal doxorubicin were highly effective against LNCaP but not PC3 or Du-145 cells, despite efficient intracellular delivery. Post-internalization events thus modulate the overall efficacy of intracellularly delivered liposomal drugs, contributing in some cases to the lower than expected activity in a cell line-dependent manner. Further studies on intracellular tracking of endocytosed liposomal drugs will help identify and overcome the barriers limiting the potency of liposomal drugs.
The Duty to Rescue: A Reexamination and Proposal (1985)

From time to time, national attention is drawn to the issue of a legal duty to assist those in distress.In 1964, accounts of the murder of Kitty Genovese on a New York City street horrified the nation.Over the course of thirty-five interminable minutes, the young woman was repeatedly stabbed as she cried for help and crawled toward the door of her apartment building.Thirty-eight of her neighbors looked on from the safety of their own apartments above the well-lighted street, but none summoned help.Well after her attacker had fled, a single caller notified the police, who were on the scene within two minutes. 1 A stunned public learned that Ms. Genovese's neighbors had violated no law.Legal commentators called for legislative reform, but within a few years the issue had faded from view.Recently, a series of incidents involving callous bystanders has rekindled interest in creating a "rescue" duty.The most notorious incident, in which patrons of a bar near Boston cheered for over an hour as four men raped a female customer, 2 has already spurred passage of a public rescue duty in Minnesota and, in Massachusetts and Rhode Island, a duty on the part of witnesses to report certain crimes.'As similar legislation is introduced in other states, 4 the legal community and the public will sharpen their focus on the issue.
Synthesis and characterization of a multiarm star polymer (2004)

Abstract A multiarm star polymer was synthesized through the grafting of oligo polyglycol with urethane chain end units onto the core of hyperbranched polyglycerol (HPG), which was obtained through the cationic ring‐opening polymerization of glycidol. Samples were characterized with 13 C NMR, liquid chromatography/mass spectrometry, vapor pressure osmometry, and Raman spectroscopy. The degree of branching of HPG was 0.54, and the number of arms grafting onto HPG was 4. The urethane of the arms mainly reacted with the terminal hydroxy groups of HPG. The differences between the spin–spin relaxation times indicated that the terminal segments of the star were more flexible than those of the core. Grafting polyglycol polyurethane (soft segments of polyurethane is polyglycol) onto HPG improved its dimensional stability. © 2004 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 42: 2356–2364, 2004
Chromosomal transformation of Escherichia coli recD strains with linearized plasmids (1989)

Wild-type Escherichia coli are resistant to genetic transformation by purified linear DNA, probably in part because of exonuclease activity. We demonstrate that E. coli containing a recD mutation could be easily transformed by linearized plasmids containing a selectable marker. The marker was transferred to the chromosome by homologous recombination, whereas plasmid markers not in the region of homology were lost.
Characterization of Immobilization of an Enzyme in a Modified Y Zeolite Matrix and Its Application to an Amperometric Glucose Biosensor (1997)

A new approach to construct an amperometric biosensor is described. Without using bovine serum albumin-glutaraldehyde, glucose oxidase (GOx) was immobilized on a dealuminized Y zeolite (DAY)-modified platinum electrode to construct a glucose sensor. The large specific surface area of the zeolite substrate resulted in high enzyme loading. The immobilized GOx in this manner was stable and could maintain its high activity for at least 3 months. The interactions between the zeolite and the enzyme were investigated by means of Fourier transform infrared spectra, and the pore distribution and the surface acid property of DAY were preliminarily studied. The results showed that the hydrophilic property and the existing mesopores of DAY played important roles in the enzyme immobilization. This resulting biosensor exhibited good reproducibility and selectivity, owing to the uniform pore structure and unique ion-exchange property of the zeolite. The biosensor responded rapidly to glucose in the linear range from 2.0 x 10(-6) to 3.0 x 10(-3) M, with a detection limit of 0.5 microM.
Sympatho‐renal interactions in the determination of arterial pressure: role in hypertension (2004)

Renal mechanisms and the sympathetic nervous system contribute to the development of arterial hypertension. Renal transplantation experiments in spontaneously hypertensive rats (SHRs) were performed to investigate how the sympathetic nervous system and the kidneys interact during the development and maintenance of hypertension. Our findings indicate that the rise in arterial pressure that occurs after transplantation of a kidney from a SHR into normotensive recipients is not mediated by elevations in sympathetic activity. However, chronic reductions in sympathetic tone reduce the rise in arterial pressure which can be induced by SHR renal grafts in normotensive recipients. Untreated SHRs transplanted with a kidney from sympathectomized donors have lower arterial pressure and reduced sodium sensitivity of arterial pressure compared to SHRs transplanted with a kidney from hydralazine-treated donors. It is concluded that chronic non-adapting changes in sympathetic activity modulate the degree to which renal mechanisms can cause hypertension in SHRs. Severe reduction in sympathetic tone during early ontogeny causes long-term changes in renal function that mitigate hypertension development in SHRs even when the extrarenal neuro-hormonal environment is restored.
Stem cells in inflammatory demyelinating disorders: a dual role for immunosuppression and neuroprotection (2005)

In recent years much excitement has been generated over the possibility that adult stem cells may attempt repair of the injured central nervous system (CNS), thus setting the stage for their utilisation in the treatment of neurodegenerative disorders. Recent studies have shown that some subsets of stem cells can also modulate the (auto)immune response, thus providing a rationale for their use as therapy for experimental autoimmune encephalomyelitis (EAE), an animal model for multiple sclerosis (MS). This article reviews the scientific evidence supporting the possible use of neural stem cells (NSCs) and mesenchymal stem cells (MSCs) for the treatment of MS. In addition, possible mechanisms sustaining the beneficial mode of action of haematopoietic stem cells (HSCs) following transplantation in MS individuals are discussed. Overall, it is proposed that limited subsets of adult stem cells may have a dual function that may be effective for the treatment of MS, an autoimmune disease of the CNS where degeneration of neural cells follows inflammation.
Molecular classification of human endometrial cycle stages by transcriptional profiling (2004)

Endometrium is a dynamic tissue that undergoes cyclic changes each month, under the overall control of estrogen and progesterone. The aims of this study were to investigate the changing global gene expression profile of human endometrium during the menstrual cycle using microarray technology and to determine the correlation between histopathological evaluation and molecular profile of the samples. Standard two-colour cDNA microarrays were performed on the 43 samples against a common reference, using a 10.5 K cDNA glass slide microarray. The results were validated using real-time PCR. Analysis of expression data was carried out using parametric analysis of variance with Benjamini-Hochberg correction. Hierarchical clustering reveals a strong relationship between histopathology and transcriptional profile of the samples. The study identified 1452 genes that showed significant changes in expression (P< or =0.05) across the menstrual cycle, with 425 genes having changes that are at least 2-fold. The data were also independently analysed by a CSIRO algorithm called GeneRaVE that identified a small subset of genes whose expression profiles could be used to classify nearly all the biopsies into their correct cycle stage. We also identified and validated three genes [(natural cytotoxicity triggering receptor (NCR)3, fucosyl transferase (FUT)4 and Fyn-binding protein (FYB)] that had not been shown to have significant cyclic changes in the human endometrium, previously. We have shown for the first time that endometrial cycle stage prediction is possible based on global gene expression profile.
ChemInform Abstract: Novel 1,2,3,4‐Tetrahydroisoquinolines with High Affinity and Selectivity for the Dopamine D3 Receptor (1999)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Presence of the μ3 Opiate Receptor in Endothelial Cells (1995)

Initial confinement of opiate receptors to the nervous system has recently been broadened to several other cell types. Based on the well established hypotensive effect of morphine, we hypothesized that endothelial cells may represent a target for this opiate substance. Endothelial cells (human arterial and rat microvascular) contain a high affinity, saturable opiate binding site presumed to mediate the morphine effects that is stereoselectively and characteristically antagonized by naloxone. This opiate alkaloid-specific binding site is insensitive to opioid peptides. It is, therefore, considered to be the same subtype of opiate receptor (designated mu3) used in the mediation of morphine in other cell types exhibiting the same binding profile. Experiments with endothelial cultures and the aortic ring of rats cultured in vitro demonstrate that morphine exerts direct modulatory control over the activities of endothelial cells, which leads to vasodilation. It induces the production of nitric oxide, a process that is sensitive to naloxone antagonism and nitric oxide synthase inhibition. In contrast with that of opiates, the administration of opioid peptides does not induce nitric oxide production by endothelial cells. In conclusion, the data presented above reveal a novel site of morphine action, endothelial cells, where a mu3 receptor is coupled to nitric oxide release and vasodilation.
Full-Length Genome Sequence of a Plaque-Cloned Virulent Porcine Epidemic Diarrhea Virus Isolate (USA/Iowa/18984/2013) from a Midwestern U.S. Swine Herd (2013)

Porcine epidemic diarrhea (PED) was recognized in U.S. swine for the first time in early 2013. A plaque-purified PED virus (PEDV) isolate (USA/Iowa/18984/2013) was obtained from a diarrheic piglet. The isolate is genetically close to other previously reported U.S. PEDVs and recent Chinese PEDVs and was virulent when inoculated into neonatal pigs.
The mechanism of inactivation of human factor V and human factor Va by activated protein C. (1994)

The cleavage of human factor V and human factor Va by human activated protein C (APC) was analyzed in the absence and presence of phospholipid vesicles containing 75% phosphatidylcholine (PC) and 25% phosphatidylserine (PS). Membrane-bound human factor V (250 nM) is cleaved by APC (2.5 nM) to give M(r) = 200,000, 70,000, 45,000, and 30,000 fragments and an M(r) = 22/20,000 doublet. These fragments are released after four sequential cleavages of the membrane-bound procofactor at Arg306, Arg506, Arg679, and Lys994. No cofactor activity is observed following thrombin treatment of the membrane-bound APC-cleaved procofactor. In the absence of a membrane surface, no cleavage of factor V by APC is observed, and following thrombin activation factor Va retains full cofactor activity. Membrane-bound human factor Va (600 nM) loses more than 90% of its initial cofactor activity after 10 min of incubation with APC (10.9 nM), and virtually no cofactor activity is observed after 1 h of incubation. Under similar conditions but in the absence of PCPS vesicles, factor Va is cleaved but retains approximately 80% of its initial cofactor activity after 2 h of incubation with APC. In the presence of PCPS vesicles, the APC related loss of activity is correlated with cleavage of the heavy chain and appearance of fragments of M(r) = 45,000, 30,000, and of 28/26,000, and 22/20,000 doublets. These products correspond to three cleavages of the heavy chain (at Arg306, Arg506, and Arg679). Cleavage at Arg506 of factor Va precedes and appears to be required for cleavage at Arg306 and Arg679. In the absence of membrane, proteolysis at Arg506 produces an M(r) = 75,000 fragment which corresponds to the NH2-terminal portion of the human factor Va heavy chain (residues 1-506), and a carboxyl-terminal doublet of M(r) = 28/26,000 (residues 507-709) which is cleaved by APC at Arg679 to generate an M(r) = 22/20,000 doublet and an M(r) = 6,000 peptide. No cleavage of the light chain of the human cofactor is observed in the presence or absence of PCPS vesicles following 2 h of incubation with APC. Our data demonstrate that inactivation of human factor V and human factor Va only occurs in the presence of a membrane surface after cleavage at Arg306. However, while this cleavage site is exposed on membrane-bound human factor V, cleavage at Arg506 on the heavy chain of factor Va appears necessary for complete exposure of the cleavage site at Arg306.
Mechanically Strained Strained-Si NMOSFETs (2004)

The drain-current enhancement of the mechanically strained strained-Si NMOSFET device is investigated for the first time. The improvements of the drain current are found to be /spl sim/3.4% and /spl sim/6.5% for the strained-Si and control Si devices, respectively, with the channel length of 25 μm at the external biaxial tensile strain of 0.037%, while the drain-current enhancements are /spl sim/2.0% and /spl sim/4.5% for strained-Si and control Si devices, respectively, with the channel length of 0.6 μm. Beside the strain caused by lattice mismatch, the mechanical strain can further enhance the current drive of the strained-Si NMOSFET. The strain distribution due to the mechanical stress has different effect on the current enhancement depending on the strain magnitude and channel direction. The smaller current enhancement for strained-Si device as compared to the control device can be explained by the saturation of mobility enhancement at large strain.
Hearing Loss in Syndromic Craniosynostoses: Introduction and Consideration of Mechanisms (2014)

The variable auditory phenotypes seen in individuals with Muenke syndrome may have a genetic basis, likely due to multiple interacting factors in the genetic environment or modifying factors. Further analysis and studies of mouse models of Muenke syndrome, in particular, may provide clues to the specific effects of the defining mutation in FGFR3 in the inner ear not only at birth but also into adulthood. In particular, investigations into these models may give insight into the variable expression and incomplete penetrance of this phenotype.
Computationally Efficient Convolved Multiple Output Gaussian Processes (2011)

Recently there has been an increasing interest in regression methods that deal with multiple outputs. This has been motivated partly by frameworks like multitask learning, multisensor networks or structured output data. From a Gaussian processes perspective, the problem reduces to specifying an appropriate covariance function that, whilst being positive semi-definite, captures the dependencies between all the data points and across all the outputs. One approach to account for non-trivial correlations between outputs employs convolution processes. Under a latent function interpretation of the convolution transform we establish dependencies between output variables. The main drawbacks of this approach are the associated computational and storage demands. In this paper we address these issues. We present different efficient approximations for dependent output Gaussian processes constructed through the convolution formalism. We exploit the conditional independencies present naturally in the model. This leads to a form of the covariance similar in spirit to the so called PITC and FITC approximations for a single output. We show experimental results with synthetic and real data, in particular, we show results in school exams score prediction, pollution prediction and gene expression data.
Characterizing mobility and network usage in a corporate wireless local-area network (2003)

Wireless local-area networks are becoming increasingly popular. They are commonplace on university campuses and inside corporations, and they have started to appear in public areas [17]. It is thus becoming increasingly important to understand user mobility patterns and network usage characteristics on wireless networks. Such an understanding would guide the design of applications geared toward mobile environments (e.g., pervasive computing applications), would help improve simulation tools by providing a more representative workload and better user mobility models, and could result in a more effective deployment of wireless network components.Several studies have recently been performed on wire-less university campus networks and public networks. In this paper, we complement previous research by presenting results from a four week trace collected in a large corporate environment. We study user mobility patterns and introduce new metrics to model user mobility. We also analyze user and load distribution across access points. We compare our results with those from previous studies to extract and explain several network usage and mobility characteristics.We find that average user transfer-rates follow a power law. Load is unevenly distributed across access points and is influenced more by which users are present than by the number of users. We model user mobility with persistence and prevalence. Persistence reflects session durations whereas prevalence reflects the frequency with which users visit various locations. We find that the probability distributions of both measures follow power laws.
Suppression of O-Methyltransferase Gene by Homologous Sense Transgene in Quaking Aspen Causes Red-Brown Wood Phenotypes1 (1998)

Homologous sense suppression of a gene encoding lignin pathway caffeic acid O-methyltransferase (CAOMT) in the xylem of quaking aspen (Populus tremuloides Michx.) resulted in transgenic plants exhibiting novel phenotypes with either mottled or complete red-brown coloration in their woody stems. These phenotypes appeared in all independent transgenic lines regenerated with a sense CAOMT construct but were absent from all plants produced with antisense CAOMT. The CAOMT sense transgene expression was undetectable, and the endogenous CAOMT transcript levels and enzyme activity were reduced in the xylem of some transgenic lines. In contrast, the sense transgene conferred overexpression of CAOMT and significant CAOMT activity in all of the transgenic plants' leaves and sclerenchyma, where normally the expression of the endogenous CAOMT gene is negligible. Thus, our results support the notion that the occurrence of sense cosuppression depends on the degree of sequence homology and endogene expression. Furthermore, the suppression of CAOMT in the xylem resulted in the incorporation of a higher amount of coniferyl aldehyde residues into the lignin in the wood of the sense plants. Characterization of the lignins isolated from these transgenic plants revealed that a high amount of coniferyl aldehyde is the origin of the red-brown coloration-a phenotype correlated with CAOMT-deficient maize (Zea mays L.) brown-midrib mutants.
Hepatitis C virus entry: an intriguing challenge for drug discovery. (2006)

The entry of hepatitis C virus (HCV) into host cells is an obligatory step in virus replication that presents a multi-faceted opportunity for drug discovery. However, the current understanding of HCV entry is rudimentary at best, with insights to date obtained by examining the fusion of pseudoparticles that express the HCV surface glycoproteins E1 and E2. The absence of an infectious virus replication system capable of replicating through a full virus life-cycle has hampered progress in determining the events involved in viral entry, resulting in considerable ambiguity surrounding the process. The recent development of an infectious HCV virus replication system provides a method with which to examine HCV entry in detail in a setting that promises greater authenticity and with the potential to increase understanding of this process. Weak inhibitors of the interactions between the HCV glycoproteins and potential host cell receptors have been identified, but their mechanism of action, in the context of virus infectivity, is not understood, and these inhibitors remain to be validated with infectious virus in cell culture. The advent of an infectious virus replication system holds considerable promise for developing a detailed understanding of HCV entry, but while mechanistic insights developed with other viruses may provide useful paradigms for experimental design, it is likely that HCV entry will be characterized by several unique biochemical events. Developing a deeper understanding of HCV entry will clearly take some time given the complexity of the process and the current state of affairs. Nevertheless, interfering with HCV entry holds promise for drug design and discovery as the mechanistic insights emerge and coalesce into a coherent biochemical description of the process.
Discrete Logarithms and Factoring (1984)

This note discusses the relationship between the two problems of the title. We present probabilistic polynomial-time reductions that show: &lt;br /&gt;1) To factor &lt;i&gt;n&lt;/i&gt;, it suffices to be able to compute discrete logarithms modulo &lt;i&gt;n&lt;/i&gt;. &lt;br /&gt;2) To compute a discrete logarithm modulo a prime power &lt;i&gt;p^(e)&lt;/i&gt;, it suffices to know it mod &lt;i&gt;p&lt;/i&gt;. &lt;br /&gt;3) To compute a discrete logarithm modulo any &lt;i&gt;n&lt;/i&gt;, it suffices to be able to factor and compute discrete logarithms modulo primes. &lt;p&gt;To summarize: solving the discrete logarithm problem for a composite modulus is exactly as hard as factoring and solving it modulo primes