gebhart/patrepeval huggingface dataset:
Domain Interactions between Streptokinase and Human Plasminogen (2001)

Plasmin (Pm), the main fibrinolytic protease in the plasma, is derived from its zymogen plasminogen (Plg) by cleavage of a peptide bond at Arg(561)-Val(562). Streptokinase (SK), a widely used thrombolytic agent, is an efficient activator of human Plg. Both are multiple-domain proteins that form a tight 1:1 complex. The Plg moiety gains catalytic activity, without peptide bond cleavage, allowing the complex to activate other Plg molecules to Pm by conventional proteolysis. We report here studies on the interactions between individual domains of the two proteins and their roles in Plg activation. Individually, all three SK domains activated native Plg. While the SK alpha domain was the most active, its activity was uniquely dependent on the presence of Pm. The SK gamma domain also induced the formation of an active site in Plg(R561A), a mutant that resists proteolytic activation. The alpha and gamma domains together yielded synergistic activity, both in Plg activation and in Plg(R561A) active site formation. However, the synergistic activity of the latter was dependent on the correct N-terminal isoleucine in the alpha domain. Binding studies using surface plasmon resonance indicated that all three domains of SK interact with the Plg catalytic domain and that the beta domain additionally interacts with Plg kringle 5. These results suggest mechanistic steps in SK-mediated Plg activation. In the case of free Plg, complex formation is initiated by the rapid and obligatory interaction between the SK beta domain and Plg kringle 5. After binding of all SK domains to the catalytic domain of Plg, the SK alpha and gamma domains cooperatively induce the formation of an active site within the Plg moiety of the activator complex. Substrate Plg is then recognized by the activator complex through interactions predominately mediated by the SK alpha domain.
An extended Intelligent Water Drops algorithm for workflow scheduling in cloud computing environment (2017)

Cloud computing is emerging as a high performance computing environment with a large scale, heterogeneous collection of autonomous systems and flexible computational architecture. Many resource management methods may enhance the efficiency of the whole cloud computing system. The key part of cloud computing resource management is resource scheduling. Optimized scheduling of tasks on the cloud virtual machines is an NP-hard problem and many algorithms have been presented to solve it. The variations among these schedulers are due to the fact that the scheduling strategies of the schedulers are adapted to the changing environment and the types of tasks. The focus of this paper is on workflows scheduling in cloud computing, which is gaining a lot of attention recently because workflows have emerged as a paradigm to represent complex computing problems. We proposed a novel algorithm extending the natural-based Intelligent Water Drops (IWD) algorithm that optimizes the scheduling of workflows on the cloud. The proposed algorithm is implemented and embedded within the workflows simulation toolkit and tested in different simulated cloud environments with different cost models. Our algorithm showed noticeable enhancements over the classical workflow scheduling algorithms. We made a comparison between the proposed IWD-based algorithm with other well-known scheduling algorithms, including MIN-MIN, MAX-MIN, Round Robin, FCFS, and MCT, PSO and C-PSO, where the proposed algorithm presented noticeable enhancements in the performance and cost in most situations.
Gas Optimization at the Kuparuk River Field (1994)

Abstract The Kuparuk River Field is located on the North Slope of Alaska, original oil in place was approximately 6.4 billion barrels of oil. Total cumulative production to date is approximately 1.2 billion barrels, and current average daily production is 300,000 barrels of oil. The total number of wells in the field is 750, approximately half of these are producers and half are injectors. A number of enhanced recovery processes including; waterflood, water alternating immiscible gas, and water alternating miscible gas are underway. Oil, water, and gas are separated at three Central Processing Facilities (CPFs). Production can be routed between the various CPFs to more efficiently utilize facility processing capacity. Gas is compressed at each facility for use in gas lift operations and for miscible and immiscible water alternating gas pressure support projects. Currently the central processing facilities are gas handling limited; therefore, a gas optimization strategy is vital to the efficient operation of the field. The objective of the optimization strategy is to maximize oil production by; efficient allocation of lift gas to the producing wells, non-gas lifted production well selection, allocation of production to the various CPFs, load balancing between centrifugal and reciprocal compressors. If Kuparuk had no compression limitations then all wells would be on production and all gas lifted wells would be operated at maximum rate. The limited compression capacity requires Kuparuk to optimize formation gas and recycled lift gas in order to optimize field oil production. A computer program has been developed to facilitate optimization. This program may be run in lift gas allocation and production well selection mode or in system analysis mode. In the lift gas allocation/producer well selection mode, lift gas rates for wells are determined based on the facility incremental gas oil ratio (IGOR), for a given set of facility operating conditions. The formation gas oil ratio (FGOR) cutoff for wells not on gas lift is set at the IGOR. These two criteria provide starting points for the optimization. The program then performs an iterative search technique to converge on the optimum IGOR and FGOR for each CPF. In the system analysis mode, thousands of simulations are run to explore the system response to a variety of operating conditions. Optimal facility operating parameters are determined from the result of the system analysis simulations. The lift gas allocation/producing well selection processing is done on the field data acquisition system, and the system analysis simulations are implemented via parallel distributed processing on a network of workstations. Surface line hydraulics effects are modeled using nonlinear adaptive models (neural nets) based on rigorous hydraulic simulations. The distributed processing and adaptive models implementation minimizes processing time and cost.
Dimers of β2-Glycoprotein I Increase Platelet Deposition to Collagen via Interaction with Phospholipids and the Apolipoprotein E Receptor 2′ (2003)

Patients with prolonged clotting times caused by lupus anticoagulant (LAC) are at risk for thrombosis. This paradoxal association is not understood. LAC is frequently caused by anti-beta2-glycoprotein I (beta 2GPI) antibodies. Antibody-induced dimerization of beta 2GPI increases the affinity of beta 2GPI for phospholipids, explaining the observed prolonged clotting times. We constructed dimers of beta 2GPI that mimic effects of beta 2GPI-anti-beta 2GPI antibody complexes, and we studied their effects on platelet adhesion and thrombus formation in a flow system. Dimeric beta 2GPI increased platelet adhesion to collagen by 150% and increased the number of large aggregates. We also observed increased platelet adhesion to collagen when whole blood was spiked with patient-derived polyclonal anti-beta 2GPI or some, but not all, monoclonal anti-beta 2GPI antibodies with LAC activity. These effects could be abrogated by inhibition of thromboxane synthesis. A LAC-positive monoclonal anti-beta 2GPI antibody, which did not affect platelet adhesion, prevented the induced increase in platelet adhesion by beta 2GPI dimers. Furthermore, increased platelet adhesion disappeared after preincubation with receptor-associated protein, a universal inhibitor of interaction of ligands with members of the low density lipoprotein receptor family. Using co-immunoprecipitation, it was shown that dimeric beta 2GPI can interact with apolipoprotein E receptor 2 (apoER2'), a member of the low density lipoprotein receptor family present on platelets. These results demonstrate that dimeric beta 2GPI induces increased platelet adhesion and thrombus formation, which depends on activation via apoER2'.
Half is Great the Rest Only Good (2005)

A book review of Good to Great by Jim Collins.
Mn-Metalloporphyrin Conjugated with Gd-DTPA (Gd-ATN10): Tumor Enhancement Agent for Magnetic Resonance Imaging (1997)

A conjugate of manganese-metalloporphyrin and gadolinium (Gd)-diethylenetriaminepenta-acetic acid (Gd-ATN10) was developed as a tumor-specific enhancement agent for magnetic resonance (MR) imaging. Gd-ATN10 was evaluated in an experimental 9L gliosarcoma rat tumor model. T1-weighted MR imaging showed enhancement of the tumor which persisted for up to 24 hours. Gd concentration measurement by inductively coupled plasma atomic emission spectroscopy revealed the peak Gd concentration was reached after 30 minutes and Gd was retained in the blood and tumor up to 24 hours. There was no uptake of Gd in the normal brain and little in the skin. Gd-porphyrin derivatives are potentially useful agents for tumor diagnosis on MR imaging and for neutron capture therapy.
Development of a Radiolabeled Probe for Detecting Membrane Type-1 Matrix Metalloproteinase on Malignant Tumors (2009)

Membrane type-1 matrix metalloproteinase (MT1-MMP) expressed on the tumor cell surface activates pro-MMP-2 and pro-MMP-13 to exacerbate the malignancy, suggesting its suitability as a target molecule for diagnosis by in vivo molecular imaging. Thus, we prepared radiolabeled anti-MT1-MMP monoclonal antibody (mAb) as a novel radiolabeled probe for detecting MT1-MMP in vivo and evaluated its usefulness in breast tumor-bearing rodents. (99m)Tc-anti-MT1-MMP mAb was prepared using HYNIC as a bifunctional chelating agent and immunoreactivity was evaluated by flow cytometry. MT1-MMP expression in breast carcinoma cells (rat: Walker-256 and MRMT-1, mouse: FM3A) was measured by Western blotting. In vivo biodistribution was examined for 48 h using tumor-implanted rodents followed by estimation of radiation absorbed by a standard quantitation platform Organ Level Internal Dose Assessment (OLINDA). (99m)Tc-anti-MT1-MMP mAb was obtained with 84% immunoreactivity to MT1-MMP and more than 92% radiochemical purity. MT1-MMP was highly expressed in all malignant cells. Tumor radioactivity increased with time after administration and reached 3 to 5 times higher values at 24 h post-injection than those at 1 h. Other organs, including the stomach, showed decreasing values over time. Tumor to blood ratios increased with time and reached more than 1.3 at 48 h. The effective dose was <5.0 muSv/MBq. The results suggest that (99m)Tc-anti-MT1-MMP mAb is a promising probe for future diagnosis of breast tumors by in vivo nuclear medical imaging.
Proteasome Inhibition with Bortezomib Depletes Plasma Cells and Autoantibodies in Experimental Autoimmune Myasthenia Gravis (2011)

Bortezomib, an inhibitor of proteasomes, has been reported to reduce autoantibody titers and to improve clinical condition in mice suffering from lupus-like disease. Bortezomib depletes both short- and long-lived plasma cells; the latter normally survive the standard immunosuppressant treatments targeting T and B cells. These findings encouraged us to test whether bortezomib is effective for alleviating the symptoms in the experimental autoimmune myasthenia gravis (EAMG) model for myasthenia gravis, a disease that is characterized by autoantibodies against the acetylcholine receptor (AChR) of skeletal muscle. Lewis rats were immunized with saline (control, n = 36) or Torpedo AChR (EAMG, n = 54) in CFA in the first week of an experimental period of 8 wk. After immunization, rats received twice a week s.c. injections of bortezomib (0.2 mg/kg in saline) or saline injections. Bortezomib induced apoptosis in bone marrow cells and reduced the amount of plasma cells in the bone marrow by up to 81%. In the EAMG animals, bortezomib efficiently reduced the rise of anti-AChR autoantibody titers, prevented ultrastructural damage of the postsynaptic membrane, improved neuromuscular transmission, and decreased myasthenic symptoms. This study thus underscores the potential of the therapeutic use of proteasome inhibitors to target plasma cells in Ab-mediated autoimmune diseases.
Characterization of piezoceramics (1991)

A 3-D approach to piezoelectric material characterization, based on the assumption that the coordinate axes are pure mode propagation directions, is described. In this case the general equations simplify and an analytical solution can be achieved. For two geometrical shapes (rectangular and cylindrical), stress and strain tensor components and the electrical impedance of the sample are obtained. These 3-D equations show that the wave velocities and permittivity are intrinsic parameters of the medium and do not depend on either the sample geometry or the mode that is considered. This was not true for the 1-D models where the wave velocities and permittivity are different for each of the modes or geometries.
Offshore Value Chain Optimization (2009)

The paper addresses the major points in the offshore value chain and describes a market maturing as it gains more global acceptance, allowing segments of the industry to transition from typical land-based upstream and downstream services with conventional LNG carriers providing point to point transportation solutions to nontypical offshore based systems providing added value to operational and commercial considerations through increased flexibility, reduced costs and a major shift from the traditional concept of fixed land-based assets. As the number of offshore and dockside regasification facilities continue to grow, the ability to cost effectively open new seasonal and year-round markets utilizing regasification capable LNG vessels as floating terminals in conjunction with ship to ship transfer capabilities to maximize the utilization of these assets, continues to demonstrate a global appeal. Applying the valuable lessons learned in taking LNG transfer and regasification operations offshore will allow offshore LNG participants to
Stack Attack (1997)

People who are in a constant state of readiness usually end up diagnosed with some sort of clinical disorder, dubbed anxiety, paranoia, manic psychosis, or whatever. Yet for years, business authors have been urging readers to put themselves and their corporations in a perpetual state of preparedness for change. It doesn't take a genius to make the connection between people so hyper‐vigilant they're of little use to us in the real world and corporations so focused on embracing change with enthusiasm that they in some ways are just not “here” with us in this more practical dimension.
Drugs for Autoimmune Inflammatory Diseases: From Small Molecule Compounds to Anti-TNF Biologics (2017)

Although initially described as an anti-tumor mediator, tumor necrosis factor-alpha (TNF) is generally considered as the master pro-inflammatory cytokine. It plays a crucial role in the pathogenesis of inflammatory diseases, such as rheumatoid arthritis (RA), inflammatory bowel disease, ankylosing spondylitis (AS), and psoriasis. Consequently, anti-TNF therapy has become mainstay treatment for autoimmune diseases. Historically, anti-inflammatory agents were developed before the identification of TNF. Salicylates, the active components of <i>Willow</i> spp., were identified in the mid-19th century for the alleviation of pain, fever, and inflammatory responses. Study of this naturally occurring compound led to the discovery of aspirin, which was followed by the development of non-steroidal anti-inflammatory drugs (NSAIDs) due to the chemical advances in the 19th-20th centuries. Initially, the most of NSAIDs were organic acid, but the non-acidic compounds were also identified as NSAIDs. Although effective in the treatment of inflammatory diseases, NSAIDs have some undesirable and adverse effect, such as ulcers, kidney injury, and bleeding in the gastrointestinal tract. In the past two decades, anti-TNF biologics were developed. Drugs belong to this class include soluble TNF receptor 2 fusion protein and anti-TNF antibodies. The introduction of anti-TNF therapeutics has revolutionized the management of autoimmune diseases, such as RA, psoriatic arthritis (PsA), plaque psoriasis (PP), AS, CD and ulcerative colitis (UC). Nevertheless, up to 40% of patients have no response to anti-TNF treatment. Furthermore, this treatment is associated with some adverse effects such as increased risk of infection, and even triggered the <i>de novo</i> development of autoimmune diseases. Such harmful effect of anti-TNF treatment is likely caused by the global inhibition of TNF biological functions. Therefore, specific inhibition of TNF receptor (TNFR1 or TNFR2) may represent a safer and more effective treatment, as proposed by some recent studies. In this review article, the historical development of anti-inflammatory drugs after World War II as briefly described above will be reviewed and analyzed. The future trend in the development of novel TNF receptor-targeting therapeutics will be discussed in the context of latest progress in the research of TNF biology.
Towards holonomic electro-elastomer actuators with six degrees of freedom (2012)

Functionally efficient six degrees of freedom (DOF) actuators have not yet been developed in a scale-invariant and inherently compliant unified form. This has primarily been due to the use of conventional serial or parallel kinema°tical configurations and electro-magnetic motors, pneumatics and hydraulics. Contrary to traditional technologies, utilizing electro-active elastomers enables multi-DOF actuation and holonomic operation with minimal structural complexity. Conical dielectric elastomer actuators (DEAs) are compact multi-DOF actuator-sensors that are scalable and can be entirely polymeric, making them suitable for a variety of applications including minimally invasive medical devices. In this paper, cone DEAs are developed towards integrated 6-DOF actuation with muscle-like performance from a single structure. This is achieved by demonstrating the feasibility of holonomic 6-DOF actuation and through experimental characterization a 5-DOF prototype. The 5-DOF prototype (50 mm length, 60 mm diameter) produced rotational actuation outputs of ±21.7 degrees and ±9.42 mNm and linear actuation outputs of ±4.45 mm (±9.1%) and ±0.55 N. Finally, combined multi-DOF actuation is demonstrated as part of development towards scalable holonomic electro-active elastomer actuators.
Ocular Injury in Cosmetic Laser Treatments of the Face. (2018)

<b>BACKGROUND:</b> The eye is a vulnerable and commonly injured organ in cosmetic laser procedures of the face. Treatment of the eyelids and periorbital areas increases this risk, especially when ocular protection devices are not used or are removed during the procedure. A study has shown that injury from laser epilation of the periocular areas is one of the most common causes of litigation in cutaneous laser surgery. <b>OBJECTIVE:</b> The goal of this review is to determine the causes of ocular injury in cosmetic laser procedures and derive lessons on critical safety elements to prevent future injury. <b>METHODS:</b> We conducted a review of the current literature through a PubMed search on case reports of ocular injury in cosmetic laser treatments of the face. Twenty-one cases are examined. <b>RESULTS:</b> In more than 62 percent of cases, ocular protection was not used or protection was used but removed during the procedure to treat areas close to the eye. However, despite the proper use of intraocular corneal shields and wavelength-specific goggles, accidents occurred in 33 percent of cases. <b>CONCLUSION:</b> Ocular protection devices are essential to prevent most cases of laser-induced eye injury. Use of high fluence and long wavelength lasers increases the risk of ocular injury due to deeper penetration of the organ by radiation. Inadequate cooling between pulses also predisposes to injury by cosmetic lasers.
Absorbed-Dose Computations For Inhomogeneous Media In Radiation-Treatment Planning Using Differential Scatter-Air Ratios (2005)

Abstract
In clinical radiotherapy, the presently available methods of dose computation in the presence of inhomogeneities are approximate and their applicability to actual situations is therefore limited. Recent developments in computed tomography have given a new level of precision in internal structure localization and tissue characterization in terms of electron density. Motivated by these new advances, we have developed a method for calculating dose distributions in three dimensions in the presence of inhomogeneities of arbitrary shapes and sizes. Our method, applicable for treatment planning in megavoltage therapy, can perform well for beams of either regular or irregular cross-section. Unlike most current treatment-planning schemes, our proposed method appeals directly to established physical principles governing the interaction of electromagnetic radiations with matter at the atomic level.

In our approach, dose at a point is separated into primary and scatter components. The scatter component at any point is obtained by summing contributions from small volume elements. We present some computed results for absorbed dose obtained with our method, and compare them with published experimental data for a 60Co beam in the presence of inhomogeneities such as air, aluminum, foamed plastic and carbon.
SoK: Shining Light on Shadow Stacks (2019)

Control-Flow Hijacking attacks are the dominant attack vector against C/C++ programs. Control-Flow Integrity (CFI) solutions mitigate these attacks on the forward edge, i.e., indirect calls through function pointers and virtual calls. Protecting the backward edge is left to stack canaries, which are easily bypassed through information leaks. Shadow Stacks are a fully precise mechanism for protecting backwards edges, and should be deployed with CFI mitigations. We present a comprehensive analysis of all possible shadow stack mechanisms along three axes: performance, compatibility, and security. For performance comparisons we use SPEC CPU2006, while security and compatibility are qualitatively analyzed. Based on our study, we renew calls for a shadow stack design that leverages a dedicated register, resulting in low performance overhead, and minimal memory overhead, but sacrifices compatibility. We present case studies of our implementation of such a design, Shadesmar, on Phoronix and Apache to demonstrate the feasibility of dedicating a general purpose register to a security monitor on modern architectures, and Shadesmar's deployability. Our comprehensive analysis, including detailed case studies for our novel design, allows compiler designers and practitioners to select the correct shadow stack design for different usage scenarios. Shadow stacks belong to the class of defense mechanisms that require metadata about the program's state to enforce their defense policies. Protecting this metadata for deployed mitigations requires in-process isolation of a segment of the virtual address space. Prior work on defenses in this class has relied on information hiding to protect metadata. We show that stronger guarantees are possible by repurposing two new Intel x86 extensions for memory protection (MPX), and page table control (MPK). Building on our isolation efforts with MPX and MPK, we present the design requirements for a dedicated hardware mechanism to support intra-process memory isolation, and discuss how such a mechanism can empower the next wave of highly precise software security mitigations that rely on partially isolated information in a process.