Copyright Accidents

Palgrave Macmillan is a highly respected international publisher of academic texts. But strangely, many of their books start with an apology. Open one of their recently published books and within the first pages you are likely to find the following statement: “While every care has been taken to trace and acknowledge copyright, the publishers tender their apologies for any accidental infringement where copyright has proved untraceable.” In theory, Palgrave should always obtain permission before printing copyrighted material, but in practice this is difficult. Frequently they wish to use some expressive material, but it is not clear who owns the rights or even if the work is protected by copyright at all. In these cases, they take “every care” to get the permission and avoid infringement but still sometimes accidents happen and they mistakenly print copyrighted material without authorization. Because copyright holds them responsible for these accidents regardless of how much they tried to prevent them, they offer this boilerplate apology up front. But this raises the question: Should they be legally responsible for all of these accidental infringements? The usual rule in tort law is you are only liable for accidents if you were negligent. Run someone over in your car and break their neck, spill toxic waste in a town center, or let your dog bite a neighbor, and you are only liable if you failed to take “reasonable care” to prevent the accident. So what’s so different about copyright accidents

Levodopa reverses gait asymmetries related to anhedoniaand magical ideation

Animals and men turn preferentially away from the hemisphere with the more active dopamine (DA) system. Consistent with the idea of a right-hemispheric hyperdopaminergia in schizophrenia, a leftsided turning bias was described for unmedicated psychotic patients. We investigated the modulating role of DA and schizophrenia-like thought on whole-body turns in a controlled double-blind study. The number of veers to either side when walking blindfolded straight ahead (20 meter) was assessed in 40 healthy righthanded men (20 men received levodopa, the remaining participants placebo). Side preferences were analyzed in terms of individuals' positive (Magical Ideation, MI) and negative (Physical Anhedonia, PhysAn) schizotypal features. In the placebo group, increasing MI scores were related to increasing left-sided veering and increasing PhysAn scores were related to increasing right-sided veering. In the levodopa group, this relationship between preferred veering side and type of schizotypy was reversed. The finding in the placebo group suggests an association between MI and a relative right-hemispheric hyperdopaminergia. Unexpectedly, levodopa did not enhance this veering bias, but reversed it, suggesting that psychosis-protective mechanisms exist in the healthy positive "schizotypic” brain. Also unexpectedly, levodopa made "anhedonics” veer like "magics” after placebo, suggesting that DA agonists suppress negative schizotypal symptom

Subclinical microcrania, subclinical macrocrarnia, and fifth-month fetal markers (of growth retardation or edema) in schizophrenia: a co-twin control study of discordant monozygotic twins.

Summary: We tested the hypothesis that gestational injuries in some patients with schozophrenia would leave their mark as a subtle reduction in head circumference (subclinical microcrania). Conclusions: The head circumferences of all subjects were in the normal range. Decreased head circumference in affected MZ co-twins (relative to unaffected MZ co-twin) characteriazes discordant MZ pairs with larger finger-ridge-count differences (i.e., second-trimester fetal-size differences). This study using ideal genetic controls suggests that, while present only in some patients with schizophrenia, the decrease in head circumference is most likely a consequence of in-utero nonshared environmental deleterious events manifesting as groth retardation or as fetal edema and occurring around the fifth prenatal month

Comparative analysis of the surface exposed proteome of two canine osteosarcoma cell lines and normal canine osteoblasts

BACKGROUND: Osteosarcoma (OSA) is the most common primary bone tumor of dogs and carries a poor prognosis despite aggressive treatment. An improved understanding of the biology of OSA is critically needed to allow for development of novel diagnostic, prognostic, and therapeutic tools. The surface-exposed proteome (SEP) of a cancerous cell includes a multifarious array of proteins critical to cellular processes such as proliferation, migration, adhesion, and inter-cellular communication. The specific aim of this study was to define a SEP profile of two validated canine OSA cell lines and a normal canine osteoblast cell line utilizing a biotinylation/streptavidin system to selectively label, purify, and identify surface-exposed proteins by mass spectrometry (MS) analysis. Additionally, we sought to validate a subset of our MS-based observations via quantitative real-time PCR, Western blot and semi-quantitative immunocytochemistry. Our hypothesis was that MS would detect differences in the SEP composition between the OSA and the normal osteoblast cells. RESULTS: Shotgun MS identified 133 putative surface proteins when output from all samples were combined, with good consistency between biological replicates. Eleven of the MS-detected proteins underwent analysis of gene expression by PCR, all of which were actively transcribed, but varied in expression level. Western blot of whole cell lysates from all three cell lines was effective for Thrombospondin-1, CYR61 and CD44, and indicated that all three proteins were present in each cell line. Semi-quantitative immunofluorescence indicated that CD44 was expressed at much higher levels on the surface of the OSA than the normal osteoblast cell lines. CONCLUSIONS: The results of the present study identified numerous differences, and similarities, in the SEP of canine OSA cell lines and normal canine osteoblasts. The PCR, Western blot, and immunocytochemistry results, for the subset of proteins evaluated, were generally supportive of the mass spectrometry data. These methods may be applied to other cell lines, or other biological materials, to highlight unique and previously unrecognized differences between samples. While this study yielded data that may prove useful for OSA researchers and clinicians, further refinements of the described techniques are expected to yield greater accuracy and produce a more thorough SEP analysis

Model tests of wind turbine with a vertical axis of rotation type Lenz 2

A building design of vertical axis wind turbines (VAWT) was presented in the article. The construction and operating principle of a wind turbine were described therein. Two VAWT turbine models were compared, i.a. Darrieus and Lenz2, taking their strengths and weaknesses into consideration. 3D solid models of turbine components were presented with the use of SolidWorks software. Using CFD methods, the air flow on two aerodynamic fins, symmetrical and asymmetrical, at different angles of attack were tested. On the basis of flow simulation conducted in FlowSimulation, an asymmetrical fin was chosen as the one showing greater load bearing capacities. Due to the uncertainty of trouble-free operation of Darrieus turbine on construction elements creating the basis thereof, a 3D model of Lenz2 turbine was constructed, which is more reliable and makes turbine self-start possible. On the basis of the research, components were designed and technical docu mentation was compiled

A Partial Read Barrier for Efficient Support of Live Object-oriented Programming

International audienceLive programming, originally introduced by Smalltalk and Lisp, and now gaining popularity in contemporary systems such as Swift, requires on-the-fly support for object schema migration, such that the layout of objects may be changed while the program is at one and the same time being run and developed. In Smalltalk schema migration is supported by two primitives, one that answers a collection of all instances of a class, and one that exchanges the identities of pairs of objects, called the become primitive. Existing instances are collected, copies using the new schema created, state copied from old to new, and the two exchanged with become, effecting the schema migration. Historically the implementation of become has either required an extra level of indirection between an object's address and its body, slowing down slot access, or has required a sweep of all objects, a very slow operation on large heaps. Spur, a new object representation and memory manager for Smalltalk-like languages, has neither of these deficiencies. It uses direct pointers but still provides a fast become operation in large heaps, thanks to forwarding objects that when read conceptually answer another object and a partial read barrier that avoids the cost of explicitly checking for forwarding objects on the vast majority of object accesses

Neurodevelopmental risk factors in schizophrenia

The authors review environmental and neurodevelopmental risk factors for schizophrenic disorders, with emphasis on minor physical anomalies, particularly craniofacial anomalies and dermatoglyphic variations. The high prevalence of these anomalies among schizophrenic subjects supports the neurodevelopmental theory of the etiology of schizophrenia, since they suggest either genetically or epigenetically controlled faulty embryonic development of structures of ectodermal origin like brain and skin. This may disturb neurodevelopment that in turn may cause these subjects to be at increased risk for the development of schizophrenia and related disorders. The precise confirmation of this theory, at least in some cases, will provide further understanding of these illnesses, allowing easy and inexpensive identification of subjects at risk and providing guidelines for the development of new pharmacological interventions for early treatment and even for primary prevention of the illness

Antiproliferative effects of masitinib and imatinib against canine oral fibrosarcoma in vitro

Background: Canine oral fibrosarcoma (COF) is one of the most common oral tumors in dogs and carries a guarded prognosis due to a lack of effective systemic therapeutic options. Mastinib and imatinib are two commonly used tyrosine kinase inhibitors (TKIs) in veterinary oncology but their potential efficacy against COF is uncharacterized. To begin investigating the rationale for use of these TKIs against COF, the present study tested for the presence TKI targets PDGFR-α, PDGFR-β, Kit, and VEGFR-2 and examined the in vitro effects on cell viability after TKI treatment alone or with doxorubicin. Immunohistochemistry for PDGFR-α, PDGFR-β, Kit, and VEGFR-2 was performed in 6 COF tumor biopsies. Presence of these same receptors within 2 COF cell lines was probed by reverse transcription-polymerase chain reaction and, for those with mRNA detected, confirmed via western blot. Effects on cell viability were assessed using an MTS assay after masitinib or imatinib treatment alone (0-100 μM), or in combination with doxorubicin (0-3000 nM doxorubicin). Anti-PDGFRB siRNA knockdown was performed and the effect on cell viability quantified. Results: Expression of the TKI targets evaluated was similar between the 2 COF cell lines and the 6 COF tumor biopsies: PDGFR-α and PDGFR-β were detected in neoplastic cells from most COF tumor biopsies (5/6 and 6/6, respectively) and were present in both COF cell lines; KIT and KDR were not detected in any sample. Masitinib and imatinib IC50 values ranged from 7.9–33.4 μM, depending on the specific TKI and cell line tested. The addition of doxorubicin resulted in synergistic cytotoxicity with both TKIs. Anti-PDGFRB siRNA transfection reduced PDGFR-β protein expression by 77 % and 67 % and reduced cell viability by 24 % (p < 0.0001) and 28 % (0 = 0.0003) in the two cell lines, respectively. Conclusions: These results provide rationale for further investigation into the use of TKIs, possibly in combination with doxorubicin, as treatment options for COF.Keywords: Masitinib, Oral fibrosarcoma, Imatinib, Platelet-derived growth factor receptor, Do

Memory consolidation in the cerebellar cortex

Several forms of learning, including classical conditioning of the eyeblink, depend upon the cerebellum. In examining mechanisms of eyeblink conditioning in rabbits, reversible inactivations of the control circuitry have begun to dissociate aspects of cerebellar cortical and nuclear function in memory consolidation. It was previously shown that post-training cerebellar cortical, but not nuclear, inactivations with the GABA(A) agonist muscimol prevented consolidation but these findings left open the question as to how final memory storage was partitioned across cortical and nuclear levels. Memory consolidation might be essentially cortical and directly disturbed by actions of the muscimol, or it might be nuclear, and sensitive to the raised excitability of the nuclear neurons following the loss of cortical inhibition. To resolve this question, we simultaneously inactivated cerebellar cortical lobule HVI and the anterior interpositus nucleus of rabbits during the post-training period, so protecting the nuclei from disinhibitory effects of cortical inactivation. Consolidation was impaired by these simultaneous inactivations. Because direct application of muscimol to the nuclei alone has no impact upon consolidation, we can conclude that post-training, consolidation processes and memory storage for eyeblink conditioning have critical cerebellar cortical components. The findings are consistent with a recent model that suggests the distribution of learning-related plasticity across cortical and nuclear levels is task-dependent. There can be transfer to nuclear or brainstem levels for control of high-frequency responses but learning with lower frequency response components, such as in eyeblink conditioning, remains mainly dependent upon cortical memory storage