gebhart/patrepeval huggingface dataset:
Distribution of Liposomes into Brain and Rat Brain Tumor Models by Convection-Enhanced Delivery Monitored with Magnetic Resonance Imaging (2004)

Although liposomes have been used as a vehicle for delivery of therapeutic agents in oncology, their efficacy in targeting brain tumors has been limited due to poor penetration through the blood-brain barrier. Because convection-enhanced delivery (CED) of liposomes may improve the therapeutic index for targeting brain tumors, we conducted a three-stage study: stage 1 established the feasibility of using in vivo magnetic resonance imaging (MRI) to confirm adequate liposomal distribution within targeted regions in normal rat brain. Liposomes colabeled with gadolinium (Gd) and a fluorescent indicator, 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine-5,5'-disulfonic acid [DiI-DS; formally DiIC(18)(3)-DS], were administered by CED into striatal regions. The minimum concentration of Gd needed for monitoring, correlation of infused volume with distribution volume, clearance of infused liposome containing Gd and DiI-DS (Lip/Gd/DiI-DS), and potential local toxicity were evaluated. After determination of adequate conditions for MRI detection in normal brain, stage 2 evaluated the feasibility of in vivo MRI monitoring of liposomal distribution in C6 and 9L-2 rat glioma models. In both models, the distribution of Lip/Gd/DiI-DS covering the tumor mass was well defined and monitored with MRI. Stage 3 was designed to develop a clinically relevant treatment strategy in the 9L-2 model by infusing liposome containing Gd (Lip/Gd), prepared in the same size as Lip/Gd/DiI-DS, with Doxil, a liposomal drug of similar size used to treat several cancers. MRI detection of Lip/Gd coadministered with Doxil provided optimum CED parameters for complete coverage of 9L-2 tumors. By permitting in vivo monitoring of therapeutic distribution in brain tumors, this technique optimizes local drug delivery and may provide a basis for clinical applications in the treatment of malignant glioma.
Tandem mass spectrometry acquisition approaches to enhance identification of protein‐protein interactions using low‐energy collision‐induced dissociative chemical crosslinking reagents (2007)

Chemical crosslinking combined with mass spectrometry is a useful tool for studying the topological organization of multiprotein interactions, but it is technically challenging to identify peptides involved in a crosslink using tandem mass spectrometry (MS/MS) due to the presence of product ions originating from both peptides within the same crosslink. We have previously developed a novel set of collision-induced dissociative chemical crosslinking reagents (CID-CXL reagents) that incorporate a labile bond within the linker which readily dissociates at a single site under low-energy collision-induced dissociation (CID) to enable independent isolation and sequencing of the crosslinked peptides by traditional MS/MS and database searching. Alternative low-energy CID events were developed within the in-source region by increasing the multipole DC offset voltage (ISCID) or within the ion trap by increasing the collisional excitation (ITCID). Both dissociation events, each having their unique advantages, occur without significant backbone fragmentation to the peptides, thus permitting subsequent CID to be applied to these distinct peptide ions for generation of suitable product ion spectra for database searching. Each approach was developed and applied to a chemical crosslinking study involving the N-terminal DNA-binding domain of AbrB (AbrBN), a transition-state regulator in Bacillus subtilis. A total of thirteen unique crosslinks were identified using the ITCID approach which represented a significant improvement over the eight unique crosslinks identified using the ISCID approach. The ability to segregate intrapeptide and interpeptide crosslinks using ITCID represents the first step towards high-throughput analysis of protein-protein crosslinks using our CID-CXL reagents.
Expression and immunogenicity of an Echinococcus granulosus fatty acid-binding protein in live attenuated Salmonella vaccine strains (1997)

Fatty acid-binding proteins (FABPs) are candidate molecules for vaccines against several parasitic platyhelminths. A FABP from the cestode Echinococcus granulosus (EgDf1) was expressed in Salmonella vaccine strains as a C-terminal fusion to fragment C of tetanus toxin (TetC) by using expression vector pTECH. The fusion protein was equally expressed in several attenuated vaccine strains derived from bacteria with different genetic backgrounds and different attenuating mutations. Single-dose immunization experiments with the aroA Salmonella typhimurium strain SL3261 carrying the pTECH-EgDf1 construct were conducted with mice, using both the intravenous and the oral routes. Surprisingly, the antibody response to EgDf1 and the antigen-specific cytokine production in spleen cells were stronger in mice immunized orally. Furthermore, immune mouse sera strongly reacted with fixed sections of the worm's larval stage. Analysis of the isotype distribution of the specific anti-EgDf1 antibodies showed similar production of immunoglobulin G1 (IgG1) and IgG2a together with specific IgA antibodies. In addition, stimulation of spleen cells from mice immunized with the different constructs with either Salmonella lysate, TetC, or EgDf1 showed that, together with Th1-related cytokines (gamma interferon and interleukin 2 [IL-2]), significant levels of a Th2 cytokine (IL-5) were produced specifically, indicating a Th2 component to the response to the Salmonella carrier and to the recombinant antigens. Salmonellae expressing the TetC-rEgDfl fusion are currently under evaluation as potential vaccines against E. granulosus.
Resistance-associated point mutations in insecticide-insensitive acetylcholinesterase. (1994)

Extensive utilization of pesticides against insects provides us with a good model for studying the adaptation of a eukaryotic genome to a strong selective pressure. One mechanism of resistance is the alteration of acetylcholinesterase (EC 3.1.1.7), the molecular target for organophosphates and carbamates. Here, we report the sequence analysis of the Ace gene in several resistant field strains of Drosophila melanogaster. This analysis resulted in the identification of five point mutations associated with reduced sensitivities to insecticides. In some cases, several of these mutations were found to be combined in the same protein, leading to different resistance patterns. Our results suggest that recombination between resistant alleles preexisting in natural populations is a mechanism by which insects rapidly adapt to new selective pressures.
The Oct-1 POU domain mediates interactions between Oct-1 and other POU proteins. (1992)

The POU domain is the conserved DNA binding domain of a family of gene regulatory proteins. It consists of a POU-specific domain and a POU homeodomain, connected by a variable linker region. Oct-1 is a ubiquitously expressed POU domain transcription factor. It binds to the canonical octamer sequence (ATGCAAAT) as a monomer. Here we show by chemical cross-linking and protein affinity chromatography that the Oct-1 POU domain monomers can interact in solution. This association requires both the POU homeodomain and the POU-specific domain. The interaction is transient in solution and can be stabilized by binding to the heptamer-octamer sequence in the immunoglobulin heavy-chain promoter. This correlates with cooperative DNA binding to this site. POU proteins from different subclasses, including Oct-1, Oct-2A, Oct-6, and a chimeric Oct-1 protein containing the Pit-1 POU domain, can bind cooperatively to a double binding site and form a heteromeric complex.
Molecular Characterization of the Acute Inflammatory Response to Infections with Gram-Negative versus Gram-Positive Bacteria (2003)

Sepsis caused by gram-negative bacteria and that caused by gram-positive bacteria often manifest similar clinical features. We investigated plasma proinflammatory cytokine profiles in patients with sepsis due to gram-positive and gram-negative bacteria and studied the cytokine production and differential gene regulation of leukocytes stimulated ex vivo with Escherichia coli lipopolysaccharide or heat-killed Staphylococcus aureus. Concentrations of tumor necrosis factor alpha, interleukin 1 receptor antagonist (IL-1Ra), IL-8, IL-10, IL-18 binding protein, procalcitonin, and protein C in plasma did not differ between patients with sepsis due to gram-negative and gram-positive bacteria. However, plasma IL-1beta, IL-6, and IL-18 concentrations were significantly higher in patients with sepsis due to gram-positive bacteria. Ex vivo stimulation of whole blood with heat-killed S. aureus markedly increased IL-1beta and IL-18 levels more than E. coli lipopolysaccharide stimulation. Microarray analysis revealed at least 359 cross-validated probe sets (genes) significant at the P < 0.001 level whose expression discriminated among gram-negative-organism-stimulated, gram-positive-organism-stimulated, and unstimulated whole-blood leukocytes. The host inflammatory responses to gram-negative and gram-positive stimuli share some common response elements but also exhibit distinct patterns of cytokine appearance and leukocyte gene expression.
Porous silicon microcavities as optical chemical sensors (2000)

The optical properties of porous silicon microcavities are strongly dependent on the environment. For highly luminescent samples, both the luminescence intensity and the peak position are affected by organic substances, giving the possibility to obtain dual-parameter optical sensors. While the peak position depends on the organic compound refractive index, luminescence intensity depends on its low-frequency dielectric constant. This allows the discrimination between different organic substances. This sensor is particularly interesting for solvents with low dielectric constant, where the response of electrical sensors is very weak.
Dynamic Traffic Grooming in Elastic Optical Networks (2013)

Spectrum elastic optical networks support flexible central frequency and spectrum assignment for lightpaths. When provisioning a new connection in an elastic optical network that allows traffic grooming, the control plane has to solve two problems: the electrical-layer routing and optical-layer routing and spectrum assignment (RSA). The electrical-layer routing determines how to route the new connection through a combination of new and existing lightpaths, while the optical-layer RSA decides how to establish new lightpaths under the spectrum-continuity constraint. The flexibility (e.g., bandwidth variability of lightpaths) provided by elastic optical networks makes it suitable for accommodating dynamic traffic. It is important and challenging to exploit the full potential of the flexibility when dealing with the above two problems. In this study, we propose a multi-layer auxiliary graph to jointly solve the electrical-layer routing and optical-layer RSA. Various traffic-grooming policies (objectives) can be achieved by properly adjusting the edge weights in the auxiliary graph. Also, we propose a spectrum reservation scheme that can efficiently utilize the bandwidth variability of lightpaths by reserving bandwidth for non-fully utilized lightpaths and grooming future connections onto them. We show that there is a tradeoff among different traffic-grooming policies, and the spectrum reservation scheme can be easily incorporated into various traffic-grooming policies and lead to a significant reduction in operational expenditure (OPEX) and better spectrum efficiency.
Precomputing Geometry-Based Reverberation Effects for Games (2009)

Current video games either pre-render reverberation effects into the sound effects or implement them at run-time using artificial reverberation filters. While interactive geometrical approaches can be used for more accurate acoustical modeling, the increased authoring complexity and the additional cost of geometrical calculations still appears to overshadow their potential benefits. This paper presents solutions to integrate off-line geometrical acoustic modeling in game environments. By pre-computing image-source gradients for early reflections and directional decay profiles, we can generate location dependent reverberation effects without storing or accessing the actual geometry at run-time. We render such reverberation effects using a frequency-domain scalable processing approach. In this context, we introduce an efficient prioritization scheme and evaluate alternative transforms for late reverberation processing. Our pipeline enables fine-grain rendering of distance and surface proximity effects and modeling of both outdoor and coupled indoor spaces with arbitrary reverberation decay profiles. 1.
Pathogenesis and Pharmacological Strategies for Mitigating Secondary Damage in Acute Spinal Cord Injury (1999)

Pharmacological agents must be given within a narrow window of opportunity to be effective. Although many therapeutic agents show potential promise in animal models, only methylprednisolone has been shown in large, randomized, double-blinded human studies to enhance the functional recovery of neural elements after acute SCI. Future therapy is likely to involve various combinations of these agents.
Hybrid proteins of the transglycosylase and the transpeptidase domains of PBP1B and PBP3 of Escherichia coli (1995)

The construction of hybrid proteins of PBP1B and PBP3 has been described. One hybrid protein (PBP1B/3) contained the transglycosylase domain of PBP1B and the transpeptidase domain of PBP3. In the other hybrid protein, the putative transglycosylase domain of PBP3 was coupled to the transpeptidase domain of PBP1B (PBP3/1B). The hybrid proteins were localized in the cell envelope in a similar way as the wild-type PBP1B. In vitro isolates of the strains containing the hybrid proteins had a transglycosylase activity intermediate between that of wild-type PBP1B-producing strain and that of a PBP1B overproducer. Analysis with specific antibiotics against PBP1A/1B and PBP3 and mutant analysis in strains containing PBP3/1B revealed no detectable effects in vivo compared with wild-type strains. The same was shown for PBP1B/3 when the experiments were performed in a recA background. The data indicate that the hybrid proteins cannot replace native penicillin-binding proteins. This finding suggests that functional high-molecular-weight penicillin-binding protein specificity is at least in part determined by the unique combination of the two functional domains.
Neuropathic Pain in Animal Models of Nervous System Autoimmune Diseases (2013)

Neuropathic pain is a frequent chronic presentation in autoimmune diseases of the nervous system, such as multiple sclerosis (MS) and Guillain-Barre syndrome (GBS), causing significant individual disablement and suffering. Animal models of experimental autoimmune encephalomyelitis (EAE) and experimental autoimmune neuritis (EAN) mimic many aspects of MS and GBS, respectively, and are well suited to study the pathophysiology of these autoimmune diseases. However, while much attention has been devoted to curative options, research into neuropathic pain mechanisms and relief has been somewhat lacking. Recent studies have demonstrated a variety of sensory abnormalities in different EAE and EAN models, which enable investigations of behavioural changes, underlying mechanisms, and potential pharmacotherapies for neuropathic pain associated with these diseases. This review examines the symptoms, mechanisms, and clinical therapeutic options in these conditions and highlights the value of EAE and EAN animal models for the study of neuropathic pain in MS and GBS.
Common genetic variants of microsomal epoxide hydrolase affect warfarin dose requirements beyond the effect of cytochrome P450 2C9 (2005)

Variant mEH T 612 C genotypes are associated with warfarin doses of greater than 50 mg/wk beyond the effect of CYP2C9.
NADPH oxidase 4 limits bone mass by promoting osteoclastogenesis (2013)

ROS are implicated in bone diseases. NADPH oxidase 4 (NOX4), a constitutively active enzymatic source of ROS, may contribute to the development of such disorders. Therefore, we studied the role of NOX4 in bone homeostasis. Nox4(-/-) mice displayed higher bone density and reduced numbers and markers of osteoclasts. Ex vivo, differentiation of monocytes into osteoclasts with RANKL and M-CSF induced Nox4 expression. Loss of NOX4 activity attenuated osteoclastogenesis, which was accompanied by impaired activation of RANKL-induced NFATc1 and c-JUN. In an in vivo model of murine ovariectomy–induced osteoporosis, pharmacological inhibition or acute genetic knockdown of Nox4 mitigated loss of trabecular bone. Human bone obtained from patients with increased osteoclast activity exhibited increased NOX4 expression. Moreover, a SNP of NOX4 was associated with elevated circulating markers of bone turnover and reduced bone density in women. Thus, NOX4 is involved in bone loss and represents a potential therapeutic target for the treatment of osteoporosis.
Adaptive-VNE: A flexible resource allocation for virtual network embedding algorithm (2012)

In this paper, we propose a new dynamic adaptive virtual network resource allocation strategy named Adaptive-VNE to deal with the complexity and the inefficiency of resource allocation. The proposal coordinates virtual node and virtual link mapping stages. The main idea behind the proposal is take advantage of unused bandwidth with respect to the occupancy rate of embedded virtual links. Hence, the unused bandwidth will be reassigned to incoming virtual network requests. To do so, Adaptive-VNE adopts the “divide and conquer” strategy. It divides the virtual network request topology into many star topologies. Then, the mapping of each piece within the whole topology is formulated as a K-supplier problem and resolved by an approximation bottleneck algorithm. To generate the global virtual network topology, Adaptive-VNE uses a backtracking algorithm in order to minimise the global mapping cost. Note that the proposal forecasts usage rate of virtual links and adapts their bandwidth reservation. Adaptive-VNE was validated by simulations and compared to the related strategies found in literature. The results obtained show that, contrarily to static bandwidth allocation approaches, the adaptive strategy maximises substrate bandwidth usage while the virtual links' bottleneck rate is minimised. Moreover, the congestion periods are minimised and during the bottleneck the bandwidth satisfaction is maximised. Finally, Adaptive-VNE improves performances in terms of acceptance rate of virtual networks and revenue of infrastructure providers.
Diagnosis using hierarchical design models (1982)

This paper presents a new algorithm for the diagnosis of computer hardware faults. The algorithm uses a general inference procedure to compute suspect components and generate discriminatory tests from information about the design of the device being diagnosed. In the current implementation this procedure is linear-input resolution, guided by explicit meta-level control rules. The algorithm exploits the hierarchy inherent in most computer system designs to diagnose systems a level at a time. In this way the number of parts under consideration at any one time is kept small, and the cost of test generation remains manageable.
3D FULL TENSOR GRADIENT METHOD IMPROVES SUBSALT INTERPRETATION (1998)

Imagine you`re working the deepwater Gulf of Mexico, looking for potential subsalt prospects to guide your company`s bidding in an upcoming lease sale. There are no speculative 3D surveys in the area, just 2D seismic and a few well logs. So you obtain some regional 2D lines across a number of promising salt features and begin your initial structural interpretation. The top of salt is pretty easy to pick. But, not surprisingly, the base is fuzzy in many areas. Large shadow zones wipe out the image, making it difficult to tell how thick the salt may be and whether sediments continue beneath the salt or truncate at the edges. With the limited data you have available, you could pick the base of salt in several different places, all of them reasonable. How do you decide? One option is an expensive reprocessing job. But it would be nice to have another choice--a way to independently test your salt interpretation against high-quality data not derived from seismic. Three-dimensional full tensor gradient (FTG) data can provide such an alternative. This article focuses on an actual test study done on a regional 2D seismic line across the Green Canyon area of the Gulf ofmore » Mexico. The purpose of the study was to determine how well 3D FTG data could identify the base of salt, where standard seismic interpretation was ambiguous.« less
Treatment with Inhaled Steroids in Asthma and Chronic Bronchitis: Long-term Compliance and Inhaler Technique (1992)

We investigated compliance and inhaler technique in 50 patients with airway obstruction (26 asthma, 24 chronic bronchitis) being treated with inhaled steroid (beclomethasone dipropionate, BDP) via a dry powder inhaler (Rotahaler omega). Patients had already participated for one year in a 2-year trial of BDP in general practice. They were treated daily with two dry powder inhalations of 400 micrograms BDP in combination with a bronchodilator. Compliance with BDP was measured by counting capsules (single-blind) at the end of a 4-month period and through a questionnaire. Counting capsules revealed non-compliance in 46% of the patients. Compliance was not related to age, sex, diagnosis or side-effects of BDP. In chronic bronchitis, but not in asthma, compliance was related to the outcome parameters of steroid treatment (pulmonary symptoms, change in lung function and non-specific bronchial responsiveness). The inhaler technique was judged insufficient in 27% of the patients. This study stresses the importance of regular instruction in inhaler technique and proper information about prophylactic steroid treatment by the general practitioner during the treatment of asthma and chronic bronchitis.