Miracle-dz/UniFAR-FTUs huggingface dataset:
Phospholipase D2 Mediates Survival Signaling through Direct Regulation of Akt in Glioblastoma Cells*♦

Background: Phospholipase D (PLD) and phosphatidic acid regulate fundamental cellular processes that contribute to cancer cell proliferation and survival. Results: Inhibition of PLD2 decreases activation of the pro-survival kinase Akt leading to cell death through inhibition of autophagic flux. Conclusion: PLD2 promotes autophagy through regulation of Akt in glioblastoma cells. Significance: PLD presents a novel opportunity for Akt inhibition without directly targeting the kinase. The lack of innovative drug targets for glioblastoma multiforme (GBM) limits patient survival to approximately 1 year following diagnosis. The pro-survival kinase Akt provides an ideal target for the treatment of GBM as Akt signaling is frequently activated in this cancer type. However, the central role of Akt in physiological processes limits its potential as a therapeutic target. In this report, we show that the lipid-metabolizing enzyme phospholipase D (PLD) is a novel regulator of Akt in GBM. Studies using a combination of small molecule PLD inhibitors and siRNA knockdowns establish phosphatidic acid, the product of the PLD reaction, as an essential component for the membrane recruitment and activation of Akt. Inhibition of PLD enzymatic activity and subsequent Akt activation decreases GBM cell viability by specifically inhibiting autophagic flux. We propose a mechanism whereby phosphorylation of beclin1 by Akt prevents binding of Rubicon (RUN domain cysteine-rich domain containing beclin1-interacting protein), an interaction known to inhibit autophagic flux. These findings provide a novel framework through which Akt inhibition can be achieved without directly targeting the kinase.
Multi-Gaussian Schell-model beams.

In a recent publication [Opt. Lett.37, 2970 (2012)10.1364/OL.37. 002970], a novel class of planar stochastic sources, generating far fields with flat intensity profiles, was introduced. In this paper we examine the behavior of the spectral density and the state of coherence of beamlike fields generated by such sources on propagation in free space and linear isotropic random media. In particular, we find that at sufficiently large distances from the source, the medium destroys the flat intensity profile, even if it remains such for intermediate distances from the source.
Strategies for joint venture success

List of Tables. List of Figures. Preface. 1. The Joint Venture Paradox. 2. How Joint Should a Venture Be? 3. Comparative Case Studies: Dominant and Shared Ventures on the Seabed. 4. How to Design a Share Management Joint Venture. 5. The Art of Managing Share Joint Ventures. 6. Options for Technology-seeking Firms: Joint Ventures as a Mechanism for Technology Transfer. 7. Bringing Technology to North America. 8. A Managerial Perspective. Bibliography. Index.
Intelligent Routing T echniques for Mobile Ad hoc Networks using Swarm Intelligence

A Mobile Ad hoc Network (MANET) is a collection of autonomous self-organized nodes. They use wireless medium for communicat ion, thus two nodes can communicate directly if and only if they are within each other‟s transmission radius in a multi-hop fashion. Many conventional routing algorithms have been proposed for MANETs. An emerg ing area that has recently captured much attention in network routing researches is Swarm Intelligence (SI). Besides conventional approaches, many new researches have proposed the adoption of Swarm Intelligence for MANET routing. Swarm Intelligence (SI) refers to complex behaviors that arise from very simple individual behaviors and interactions, which is often observed in nature, especially among social insects such as ants, bees, fishes etc. Although each individual has little intelligence and simply follows basic rules using local in formation obtained from the environment. Ants routing resembles basic mechanisms from distributed Swarm Intelligence (SI) in b iological systems and turns out to become an interesting solution where routing is a problem. Ants based routing is gaining more popularity because of its adaptive and dynamic nature. A number of Swarm Intelligence (SI) based algorithms were p roposed by researchers. In this paper, we study bio-inspired routing protocols for MANETs.
Surgical removal of the carotid body for bronchial asthma.

Introduction Because of the existence of a wide variety of implied etiologic factors and obscurity concerning its pathogenesis, a definitive form of therapy for bronchial asthma has not been forthcoming. Surgical treatment”7”4 has been predicted on a presumed imbalance of autonomic nervous system function. K#{252}mmell,6’7 in 1923, advocated resection of the superior cervical sympathetic ganglion, but Homer’s syndrome and parotid pain were frequent distressing complications. In 1924, Kappis4’5 assumed a predominant parasympathetic role and sectioned the vagus nerve. Short term results with both procedures were encouraging, but a complete cure was rare beyond three years. ”” ”4 G#{246}bell2 combined both of these procedures and in 1928 he performed bilateral superior cervical ganglionectomy and severed the right vagus nerve. The results1’1’ were no better than for either procedure alone and the combined operation was attended by a significantly increased mortality rate. Carotid body excision, first reported by the author in 1942,#{176} is a simple and often effective method of treatment. Residual symptoms and operative mortality are negligible.
An Examination of Organizational Factors Influencing New Product Success in Internal and Alliance-Based Processes

New products provide increased sales, profits, and competitive strength for most organizations. However, nearly 50% of the new products that are introduced each year fail. Organizations thus find themselves in a double bind. On the one hand they must innovate consistently to remain competitive, but on the other hand innovation is risky and expensive. Many organizations are forming business alliances to quicken the pace of and reduce risks associated with innovation. Yet by some estimates, 70% of these alliances fail. Many of the prescriptions for successful alliance management clash with recommendations for effective innovation management. The authors develop testable hypotheses by integrating the new products and alliance literature. A construct—cooperative competency—derived from related concepts of mutual adjustment, absorptive capacity, and relational capability is posited as the key factor affecting new product development success, regardless of whether it is an intra- or interfirm endeavor. The authors test the model with data from a sample survey in the semiconductor manufacturing context and replicate it in the health care sector. The antecedents of cooperative competency—formalized and clannish administration, mutual dependence, and institutional support—are revealed empirically and substantiated. The authors identify the importance and means of developing interfirm cooperation.
Temporomandibular Dysfunction and Headache Disorder

It has been well established that primary headaches (especially migraine, chronic migraine, and tension‐type headache) and temporomandibular dysfunction (TMD) are comorbid diseases, with the presence of one of them in a patient increasing the prevalence of the others. The relationship between the 2 diseases may involve the sharing of common physiopathological aspects. Studies about the treatment of this disease association have shown that a simultaneous therapeutic approach to the 2 diseases is more effective than the separate treatment of each. As a consequence, specialists in orofacial pain are now required to know the criteria for the diagnosis of headaches, and headache physicians are required to know the semiologic aspects of orofacial pain. Nevertheless, a headache may be attributed to TMD, instead be an association of 2 problems – TMD and primary headaches – in these cases a secondary headache, described in item 11.7 of the International Classification of Headache Disorders, is still a controversial topic. Attempts to determine the existence of this secondary headache with a specific or suggestive phenotype have been frustrated. The conclusion that can be reached based on the few studies published thus far is that this headache has a preferential unilateral or bilateral temporal location and migraine‐like or tension‐type headache‐like clinical characteristics. In the present review, we will consider the main aspects of the TMD‐headache relationship, that is, comorbidity of primary headaches and TMD and clinical aspects of the headaches attributed to TMD from the viewpoint of the International Headache Society and of a group of specialists in orofacial pain. This paper aims to explore our understanding of the association between TMD and headaches in general and migraine in particular.
Physiologic functions of activating natural killer (NK) complex‐encoded receptors on NK cells

Summary: Natural killer (NK) cells express a superfamily of surface proteins that share common structural features: dimeric type II integral membrane proteins with extracellular domains resembling C‐type lectins. These receptors are encoded by a single genetic region called the NK complex (NKC). The NKC encompasses several families of genes including NKR‐P1, Ly‐49, CD94/NKG2, and NKG2D. Different NKC‐encoded receptors have been shown to activate or to inhibit NK‐cell function, and different receptors within the same family can have opposing functions. Within an individual NK cell, inhibitory receptors typically predominate over stimulatory receptors, calling into question the teleologic requirement or physiologic significance of lectin‐like activating receptors in NK cells. Despite the widespread expression of inhibitory receptors, however, subtle features of activating receptor biology enable them to stimulate effector functions in vivo and in vitro. Activating receptors and inhibitory receptors differ in their subset expression, in their structural constraints for binding to common ligands, in their ligand repertoires, and in that divergent families of activating receptors utilize different signaling pathways. These subset, binding, repertoire, and signaling diversities may allow activating receptors to manifest their effects in spite of inhibitory receptor functions during pathologic conditions in vivo. In this review, we will present a detailed analysis of the data supporting this hypothesis with particular relevance toward physiologic NK‐cell functions.
Prescribing for the Elderly: Part II Prescribing Patterns: Differences Due to Age

or a variety of reasons, the extent of drug prescribing for patients of all ages is an important issue. Overprescribing can lead to increased F morbidity rather than an improvement in the quality of life. Furthermore, concurrent prescription of several drugs increases the risk of adverse reactions and drug interactions,2 and multiple drug therapy with complex drug regimens can lead to poor ~ompliance. ~ Finally, the financial cost of drugs is a significant component of health expenditure. Because of alterations in pharmacokinetics and pharmacodynamics with age and the increased prevalence of ill health, these problems may be accentuated in elderly patients. Indeed numerous reports and reviews have been published on the putative hazards of drug therapy in this age group4-l1 Again cost is an important factor since the elderly as a group are responsible for a disproportionate amount of the health bill in developed countries.5 While the consequences of extensive drug therapy have attracted much attention, few definitive studies have been carried out to examine the number and types of drugs prescribed for patients in different age groups. A detailed examination of the evidence reveals that our concept of extensive, inappropriate drug use in the elderly may be based on assumption rather than scientific fact. Analysis and interpretation of the data is facilitated by examination of the pattern of prescribing in the various health care settings and by taking into account the population samples studied. To this end, we classify
An ontology-based hierarchical clustering approach for decision support in mass customization environments

The shift from mass production to mass customization has led many manufacturers to diversify their product portfolio by making their products highly configurable. This diversification often results in higher production costs. Through standardization this costs can be reduced. Clustering of sold product configurations can help identify configurations that can be standardized without dissatisfying the customers. Many clustering algorithms are developed for different applications, but often the results are not self-describing. In this paper an ontology-based hierarchical clustering approach with a linkage method particularly designed to return reasonable clusters is proposed. An experimental evaluation with historic sales data supplied by a truck manufacturer shows that the approach is able to find meaningful insights in mass customization contexts. The introduced linkage method shows advantages to the single linkage method in semantic clustering.
Clearance mechanisms of von Willebrand factor and factor VIII

Coagulation factor (F) VIII and vonWillebrand factor (VWF) are known for their crucial roles in hemostasis. The functional absence of either VWF or FVIII is associated with severe bleeding disorders, known respectively as von Willebrand disease (VWD) and hemophilia A [1,2]. In contrast, epidemiological studies have revealed that elevated levels of VWF and/ or FVIII predispose to thrombotic complications like venous thrombosis and stroke [3]. Both proteins circulate in plasma as a tight, non-covalently linked complex that is of major physiological relevance, as exemplified by the markedly reduced FVIII plasma levels observed in patients with no detectable VWF protein (VWD type 3) or with a defect in VWF–FVIII complex assembly (e.g. VWD type 2 N) [4–6]. Several mechanisms may explain this necessity for complex formation: (i) VWF stabilizes the heterodimeric structure of FVIII; (ii) VWF protects FVIII from proteolytic degradation by phospholipid-binding proteases like activated protein C and activated FX (FXa); (iii) VWF interferes with binding of FVIII to negatively charged phospholipid surfaces, which are for example exposed within activated platelets; (iv) VWF inhibits binding of FVIII to activated FIX (FIXa), thereby denying FVIII access to the FXactivating complex; and (v) VWF prevents the cellular uptake of FVIII. The intricate linkage between VWF and FVIII and its effect on the survival of these proteins has drawn considerable attention, not only because of its impact on hemophilia treatment via FVIII-replacement therapy, but also in view of the finding that abnormal clearance of VWF contributes to the pathogenesis of VWD. Being present as a complex complicates the assessment of how the VWF–FVIII complex or its individual components are removed from the circulation. It is only in the last few years that insight into the molecular basis of VWF–FVIII clearance has been obtained. The present review will address these recent findings.
Kinetics of the Association/Dissociation Cycle of an ATP-binding Cassette Nucleotide-binding Domain*

Background: ATP induces dimerization of the nucleotide-binding domains (NBD) of ATP-binding cassette proteins, followed by ATP hydrolysis and dimer dissociation. Results: The rate of dimerization induced by MgATP is faster than previously thought. Conclusion: During the hydrolysis cycle, there is a dynamic equilibrium where neither monomers nor dimers are favored. Significance: Knowledge of the mechanism of hydrolysis by NBDs will help us understand the function of ATP-binding cassette proteins. Most ATP binding cassette (ABC) proteins are pumps that transport substrates across biological membranes using the energy of ATP hydrolysis. Functional ABC proteins have two nucleotide-binding domains (NBDs) that bind and hydrolyze ATP, but the molecular mechanism of nucleotide hydrolysis is unresolved. This is due in part to the limited kinetic information on NBD association and dissociation. Here, we show dimerization of a catalytically active NBD and follow in real time the association and dissociation of NBDs from the changes in fluorescence emission of a tryptophan strategically located at the center of the dimer interface. Spectroscopic and structural studies demonstrated that the tryptophan can be used as dimerization probe, and we showed that under hydrolysis conditions (millimolar MgATP), not only the dimer dissociation rate increases, but also the dimerization rate. Neither dimer formation or dissociation are clearly favored, and the end result is a dynamic equilibrium where the concentrations of monomer and dimer are very similar. We proposed that based on their variable rates of hydrolysis, the rate-limiting step of the hydrolysis cycle may differ among full-length ABC proteins.
Parity-time–symmetric optoelectronic oscillator

A parity-time–symmetric optoelectronic oscillator was demonstrated without the use of a narrowband microwave or optical filter. An optoelectronic oscillator (OEO) is a hybrid microwave and photonic system incorporating an amplified positive feedback loop to enable microwave oscillation to generate a high-frequency and low–phase noise microwave signal. The low phase noise is ensured by the high Q factor of the feedback loop enabled by the use of a long and low-loss optical fiber. However, an OEO with a long fiber loop would have a small free spectral range, leading to a large number of closely spaced oscillation modes. To ensure single-mode oscillation, an ultranarrowband optical filter must be used, but such an optical filter is hard to implement and the stability is poor. Here, we use a novel concept to achieve single-mode oscillation without using an ultranarrowband optical filter. The single-mode operation is achieved based on parity-time (PT) symmetry by using two identical feedback loops, with one having a gain and the other having a loss of the same magnitude. The operation is analyzed theoretically and verified by an experiment. Stable single-mode oscillation at an ultralow phase noise is achieved without the use of an ultranarrowband optical filter. The use of PT symmetry in an OEO overcomes the long-existing mode-selection challenge that would greatly simplify the implementation of OEOs for ultralow–phase noise microwave generation.
Neuroprotective Effects of Antenatal Magnesium Sulfate in Very Premature and Extremely Premature Infants

Infants born very prematurely have a greatly increased risk of suffering permanent neurologic sequelae such as cerebral palsy (CP), a leading cause of physical disability in childhood (Doyle, Crowther, Middleton, Marrett, and Rouse, 2010; Stanley and Crowther, 2008). The risk of developing CP increases exponentially as gestational age at birth decreases (Ancel, Livinec, Larroque, et al., 2006). Observational studies conducted during the 1980s and 1990s found pre-term infants exposed in utero to magnesium sulfate (MgSo4) had decreased incidence of CP (Cahill, Stout, and Caughey, 2010). This paper compares data from several randomized trials as well as meta-analyses to determine whether a relationship exists between antenatal MgSo4 exposure and decreased incidence of CP. Defining the Problem CP is defined by O'Shea (2008, pg 35), as "a disorder in posture and movement due to a defect in or lesion of the immature brain. " This disorder results in permanent, non-progressive symptoms ranging from mild tremor to quadriplegia (Hayes, 2010). Sensation of the hands is impaired in about half of all cases and chronic pain is reported by more than 25% of adults. Up to 80% of affected individuals have at least some impairment of speech (Odding, Roebroeck , and Stam, 2006). Low visual acuity is reported in almost 75% of all affected children (Odding et sl., 2006). 50% of all children have gastrointestinal and feeding problems, and stunted growth occurs in 25% (Odding et al., 2006). Significant monetary costs are also associated with CP, both for affected persons, and society in general. A 2004 report by the United States Center for Disease Control and Prevention estimated lifetime costs, including medical, non-medical, and 3 Running head Running Head: NEUROPROTECTIVE EFFECTS productivity losses, for CP patients born in the year 2000 to reach 11.5 billion dollars (Honeycut, Dunlap, Chen, al Homsi, Grosse et al., 2003).
Chronic irradiation with 222-nm UVC light induces neither DNA damage nor epidermal lesions in mouse skin, even at high doses

Surgical site infections (SSIs) represent an important clinical problem associated with increased levels of surgical morbidity and mortality. UVC irradiation during surgery has been considered to represent a possible strategy to prevent the development of SSI. 254-nm UVC induces marked levels of DNA damage by generating cyclobutyl pyrimidine dimers (CPD) in microorganisms. However, this effect is elicited not only in microorganisms, but also in human cells, and chronic exposure to 254-nm UVC has been established to represent a human health hazard. In contrast, despite short wavelength-UVC light, especially 222-nm UVC, having been demonstrated to elicit a bactericidal effect, single irradiation with a high dose of 222-nm UVC energy has been reported to not induce mutagenic or cytotoxic DNA lesions in mammalian cells. However, the effect of chronic irradiation with a high dose of 222-nm UVC to mammalian cells has not been determined. In this study, it was demonstrated that large numbers of CPD-expressing cells were induced in the epidermis of mice following treatment with a small amount of single exposure 254-nm UVC, and then less than half of these cells reduced within 24 h. Chronic 254-nm UVC irradiation was revealed to induce sunburn and desquamation in mouse skin. Histological analysis demonstrated that small numbers of CPD-expressing cells were detected only in hyperkeratotic stratum corneum after chronic irradiation with a high dose of 254-nm UVC, and that significant hyperplasia and intercellular edema were also induced in the epidermis of mice. In contrast, chronic irradiation with 222-nm UVC light was revealed not to induce mutagenic or cytotoxic effects in the epidermis of mice. These results indicated that 222-nm UVC light emitted from the lamp apparatus (or device), which was designed to attenuate harmful light present in wavelengths of more than 230 nm, represents a promising tool for the reduction of SSI incidence in patients and hospital staff.