cssi/SciSciGPT-SciSciNet huggingface dataset:
Spinale Kontrolle der Motorik

Das motorische System umfasst alle Muskeln und die Neuronen, die sie steuern. Der wegbereitende englische Neurophysiologe Charles Sherrington hat die Bedeutung des motorischen Systems folgendermasen zusammengefasst: „Bewegungen sind alles, was die Menschheit vollbringen kann. ... Ausgefuhrt werden die Bewegungen alleine durch die Muskeln, ob es um das Flustern eines Wortes oder das Fallen von Baumen geht.“ Schon bei kurzem Nachdenken wird sofort klar, dass das motorische System unglaublich komplex ist. Verhalten erfordert das koordinierte Agieren von fast 700 Muskeln in unterschiedlichen Kombinationen in einer veranderlichen, oft unvorhersehbaren Umwelt. Dieses Kapitel befasst sich mit dem peripheren somatomotorischen System: mit Gelenken, Skelettmuskeln sowie den spinalen Motoneuronen und Interneuronen und ihrer Kommunikation untereinander.
RNAi-Based Functional Genomics Screening of the Human Kinome Identifies Major Growth Regulating Kinases in Acute Myeloid Leukemia Cells

In order to improve treatment strategies for Acute Myeloid Leukemia (AML), we adapted a functional genomics approach using RNAi screening to identify molecular targets that are vital to the growth of AML. Herein we report the first large-scale kinome gene silencing screen in AML. A high throughput RNAi screen was developed for the efficient siRNA transfection of AML cell lines. Eight commercially available cationic lipid-based transfection reagents were tested for their ability to transfect several AML cell lines with siRNA. These extensive transfection optimization experiments identified two AML cells lines TF-1 and ML4 with up to 95–100 and 70–75% transfection efficiency respectively. Two independent replicate kinome screens were performed on both cell lines using a siRNA library targeting 572 kinase genes with 2 siRNA/gene. At 96 hours post transfection, cell proliferation was assessed and the B-score method was used to background correct and analyze the screening data. Several siRNA to specific kinases were identified that significantly inhibit cell proliferation of up to ~40–88%. Hits were defined at two thresholds: siRNA having a B-score of 95%) and a cutoff B-score of <−1.5 providing greater than 87% confidence for each siRNA hit. Two different kinases (2 siRNA/gene/screen) were identified as major growth regulating kinases in TF1 cells with all 4 siRNA/gene having a B-score <−2. For two additional kinases, 3/4 siRNA for each gene had a Bscore <−2. Expanding the cutoff to a B-score <−1.5 three further kinases were targeted by at least 3/4 siRNA/gene. Similar analysis using the same criteria for ML4 cells identified one kinase targeted by 3/4 siRNA at a B-score <−2, seven kinases with 2/4 siRNA <−2 and two kinases with 3/4 siRNA/gene at a B-score of <−1.5. Common hits for both cell lines with at least 6/8 siRNA per gene from 4 screens performing at a B-score <−2 identified two kinases, one of them PLK1. Applying a B-score threshold of <−1.5, we identified five kinases for which at least 5/8 siRNA/gene from 4 screens met these criteria. Kinases/genes will be presented at the meeting.Confirmation of gene silencing and validation of growth response is currently underway for a subset of genes. Among the strongest hits are siRNA targeting PLK1, as well as siRNA targeting three other kinase-genes involved in regulating cell cycle progression and checkpoints and gene ontology (GO) analysis showed enrichment in cell cycle and cell cycle-checkpoint processes. Inhibitors against PLK1 and other kinase hits identified in the screen are in (pre)-clinical development and if confirmed, our experiments provide a strong rational to test these in AML. The application of RNAi based screening is useful in the identification of genes important in AML proliferation, which could serve as targets for therapeutic intervention and guide AML drug development. Furthermore, results from these types of functional genomics approaches hold promise to be rapidly translated into clinical application.
Treatment with a recombinant human IgM that recognizes PSA-NCAM preserves brain pathology in MOG-induced experimental autoimmune encephalomyelitis

A single peripheral dose of CNS-binding IgMs promote remyelination and preserve axons in a number of animal models of neurologic disease. A myelin-binding recombinant human IgM (rHIgM22) is presently in a safety trial in MS patients following an acute MS exacerbation. rHIgM22 (directed against oligodendrocytes) or rHIgM12 (directed against neurons) were administered to mice with MOG-induced experimental autoimmune encephalomyelitis (EAE) with study endpoints: clinical deficits and brain and spinal cord pathology. IgMs were administered at a therapeutic dose of 100 μ g intra peritoneal at the time of immunization (day -1, 0, +$1), disease onset (15 days) or peak of the disease (28 days). Disease course was not worsened by either human IgM regardless of the time of treatment. Of note, the human IgM that recognizes a carbohydrate epitope on gangliosides and NCAM, rHIgM12, reduced brain pathology when given at time of immunization or at onset of disease, but did not reduce clinical deficits or spinal cord disease burden. Hence, treatment with rHIgM12 resulted in marked reduction in meningeal inflammation. Data consistent with the hypothesis that in the EAE model this molecule has an immune-modulatory effect. Treatment with an anti-CD4 blocking IgG prevented both clinical course and CNS pathology. This pre-clinical study further supports the safety of therapeutic CNS-binding human IgMs in the presence of autoimmunity and clearly differentiates them from IgGs directed against MOG or aquaporin-4 that worsen neurologic disease.
Glomangiomatosis of the sciatic nerve: a case report and review of the literature

Glomus tumors are hamartomas, which tend to occur in sites rich in glomus bodies, such as the subungual regions of digits or the deep dermis of the palm, wrist, forearm, and foot. Very rarely, they may involve peripheral nerves. We describe a patient, who, following surgical resection of a solitary glomus tumor of the left distal sciatic nerve in his teens, had recurrence with development of multiple tumors in the course of the nerve over several years. To our knowledge, this is the only known case of glomangiomatosis involving a major peripheral nerve.
Retrospective, correlative study of BRAF mutation V600E in testicular cancer patients.

e15584 Background: Presence of BRAF V600E mutation forms the basis of a successful targeted therapy against malignant melanoma. While this mutation is also demonstrated in various other tumor types, its presence in germ cell tumor (GCT) is inconsistent across various studies. In one study, 9 out of 35 (26%) platinum-refractory GCTs were positive for BRAF V600E mutation (Honecker et al, JCO 2009 May 1; 27(13):2129-36). In the current study we tested tumor tissue of patients for BRAF V600E mutation in order to correlate it with known tumor subtypes and treatment outcomes. Methods: We obtained tumor specimen of 59 patients with GCT that were treated at either Indiana University or University of Pennsylvania from 2000 to 2011 and tested them for presence of BRAF V600E mutation by Sanger sequencing with exon 15 specific primers. Out of 59 tumors, 12 (20%) were seminomas and 47 (80%) were non-seminomas. 26 (44%) patients had no recurrence after first line cisplatin-based chemotherapy whereas 33 (56%) patients h...
Fabrication of non-fluorinated hydrophilic-oleophobic stainless steel mesh for oil-water separation

Abstract Oil-water separation is a worldwide concern due to the increasing emissions of oil-contaminated industrial water, frequent oil spills and the general shortage of clean drinking water. In this study, hydrophilic/underwater superoleophobic stainless steel (SS) meshes were fabricated via a one-step solution-based coating method using methyltrimethoxysilane (MTMS). The dimensions of the meshes were varied to study their effect on wettability and separation efficiency. Coated meshes were then used for gravity-driven oil/water separation with oil-water mixtures and oil-water emulsions in which water passed through the meshes while oil was retained. Contact angles, fluid flux and separation efficiency were evaluated to determine the optimum mesh dimensions. XPS and ATR-FTIR were performed on the coated stainless steel surface to confirm the presence of silanol groups that are accountable for the resultant unique wetting properties. After sand impact durability testing, the treated meshes were still able to separate oil-water mixtures with high separation efficiency and water recovery rates, despite the presence of residual sand particles.
Tetradehydrobenzenes: Singlet−Triplet Energy Separations and Vibrational Frequencies

The energies and structures of the three tetradehydrobenzene (C6H2) isomers (“ortho”, “meta”, and “para”) were studied employing density functional theory (BLYP and B3LYP), complete active space SCF (CASSCF), and the coupled-cluster method with single, double (CCSD), and perturbative triple excitations [CCSD(T)] in conjunction with basis sets of up to triple-ζ plus double polarization quality. The meta isomer, 1,2,3,5-tetradehydrobenzene, is the most favorable cyclic isomer, but is 38 kcal mol-1 less stable than the hexatriyne C6H2 global minimum. All of the cyclic isomers have singlet ground states, but these are less stable for the ortho and para isomers; hence, the singlet−triplet energy splittings for 1,2,4,5- and 1,2,3,4-tetradehydrobenzene are smaller than for ortho-benzyne. Harmonic vibrational frequency analyses [up to CCSD(T)/TZ2P] suggest that the νas(C⋮C) vibration should be observable in the IR spectra of 1,2,4,5-tetradehydrobenzene at ca. 1675 cm-1 but that this vibration might be too weak to...
Cell Adhesion During Drosophila Eye Development

Over a brief few days, thousands of cells in the Drosophila eye are organized to generate a precisely patterned functional organ. Eye morphogenesis requires coordinated cell fate specification and differentiation, local cell movements, niche acquisition, and apoptosis to remove surplus cells. The eye has provided a superb model tissue for studies of the molecular bases of these events and the past decade has been punctuated with studies on the adhesion molecules at play as the fly eye develops. Because of its structure—a neuroepithelium composed of several discrete and easily discernable cell types—the eye provides unique opportunities to examine the roles of adhesion between cells as a complex organ is generated. Indeed, dynamic adhesion plays a significant role in orchestrating, regulating, and driving eye morphogenesis.
VLSI circuit analysis and test generation

A new analysis technique for testing complex VLSI circuits has been developed. Using this technique, the system functions and their interrelationships are visible in the test pattern documentation. This technique required only one fault simulation and yielded in excess of 95% fault detection.
Spin-wave analysis of the low-temperature thermal Hall effect in the candidate Kitaev spin liquid α -RuCl 3

Proposed effective Hamiltonians from the literature for the material $\ensuremath{\alpha}\ensuremath{-}\mathrm{RuCl}{}_{3}$ are used to compute the magnon thermal Hall conductivity ${\ensuremath{\kappa}}_{xy}$ using linear spin-wave theory for the magnetically ordered state. No model previously proposed that was tested explains the published experimental data. Models with Kitaev interaction $Kg0$ are seen to predict ${\ensuremath{\kappa}}_{xy}\ensuremath{\gtrsim}0$, which is inconsistent with the data. Fluctuations toward a Kitaev-type spin liquid would have the wrong sign to explain the data. However, a slight variant of a previously proposed model predicts a large ${\ensuremath{\kappa}}_{xy}$, demonstrating that the low-temperature thermal Hall effect could be generated exclusively by the Berry curvature of the magnon bands. The experimental data of ${\ensuremath{\kappa}}_{xy}$ can therefore serve as another method to constrain a proposed effective Hamiltonian.
Classical strongly coupled quark-gluon plasma. II. Screening and equation of state

We analyze the screening and bulk energy of a classical and strongly interacting plasma of color charges, a model we recently introduced for the description of a quark-gluon plasma at $T=(1\ensuremath{-}3){T}_{c}$. The partition function is organized around the Debye-H\"uckel limit. The linear Debye-H\"uckel limit is corrected by a virial expansion. For the pressure, the expansion is badly convergent even in the dilute limit. The nonlinear Debye-H\"uckel theory is studied numerically as an alternative for moderately strong plasmas. We use the Debye theory of solid to extend the analysis to the crystal phase at very strong coupling. The analytical results for the bulk energy per particle compare well with the numerical results from molecular dynamics simulations for all couplings.
Thermodynamics and the elastic moduli of Pu

Pu exhibits at least five structures below its melting point of 914 K. The lower-temperature phases have unusually low symmetry for an elemental metal, but at higher temperatures, Pu behaves like many other metals, going from fcc (face-centered cubic) to bcc (body-centered cubic) before melting. Electronic structure calculations appear to explain the lowest temperature monoclinic phase and the changes it undergoes with pressure (O. Eriksson, J. D. Baker, A. V. Balatsky, and J. M. Wills, J. Alloys Comp.287, 1 (1999)), but the much simpler fcc phase of Pu remains difficult to understand ab initio. We show how the unusually small values of elastic moduli require that the effects of temperature and phonon entropy be included in any theory of fcc Pu, and we present new high-accuracy data for elastic moduli, that show that the elastic moduli of Ga-stabilized fcc Pu do not depend on Ga at 300 K, and that polycrystal and monocrystal elastic modulus data for Pu are in agreement.
A Controlled Clinical Trial Including Folinic Acid at Two Distinct Dose Levels in Combination with 5-Fluorouracil (5FU) for the Treatment of Advanced Colorectal Cancer: Experience of the Mayo Clinic and North Central Cancer Treatment Group

A prospectively randomized clinical trial was conducted to determine the therapeutic effect of five individual combination chemotherapy regimens compared to single agent FUra for the treatment of advanced colorectal cancer. For the purposes of this symposium, the detailed results of therapy will be presented only for PTS treated with FUra alone or FUra + LV* in a high dose (200 mg/m2) or a low dose (20 mg/m2) daily for five days. Two hundred twelve PTS were randomized to one these three regimens, and 208 PTS (98%) were available for analysis. Median time from randomization is 18 months and anproximately 70% of PTS have died. Both LV* + FUra regimens are associated with significantly improved survival compared to single agent FUra (p ≤ 0.03). In addition, interval-to-tumor-progression, measurable tumor response rates, and measures of quality of life (performance status, weight gain, symptomatic relief) were also significantly improved with the addition of LV*. The most favorable regimen in the trial is low dose LV* + FUra based on considerations of both therapeutic results and cost. A national intergroup trial will examine the efficacy of the low dose LV* + FUra regimen in the surgical adjuvant setting.
Deep feature learning using target priors with applications in ECoG signal decoding for BCI

Recent years have seen a great interest in using deep architectures for feature learning from data. One drawback of the commonly used unsupervised deep feature learning methods is that for supervised or semi-supervised learning tasks, the information in the target variables are not used until the final stage when the classifier or regressor is trained on the learned features. This could lead to over-generalized features that are not competitive on the specific supervised or semi-supervised learning tasks. In this work, we describe a new learning method that combines deep feature learning on mixed labeled and unlabeled data sets. Specifically, we describe a weakly supervised learning method of a prior supervised convolutional stacked auto-encoders (PCSA), of which information in the target variables is represented probabilistically using a Gaussian Bernoulli restricted Boltzmann machine (RBM). We apply this method to the decoding problem of an ECoG based Brain Computer Interface (BCI) system. Our experimental results show that PCSA achieves significant improvement in decoding performance on benchmark data sets compared to the unsupervised feature learning as well as to the current state-of-the-art algorithms that are based on manually crafted features.
Optimal treatment of MSSA bacteraemias: a meta-analysis of cefazolin versus antistaphylococcal penicillins

Background Bacteraemias caused by MSSA are associated with significant morbidity and mortality. Controversy exists over the optimal treatment of severe infections caused by MSSA. This systematic review and meta-analysis aims to identify whether differences in clinical outcomes exist between cefazolin and antistaphylococcal penicillins (ASPs). Methods PubMed, Cochrane Library and Embase were systematically searched for publications reporting clinical outcomes of cefazolin and ASPs for adult patients with MSSA bacteraemias throughout November 2017. Comparative studies reporting 90 day mortality associated with each treatment were included. Random effects models were used to evaluate the impact of directed treatment agent on the odds of 30 and 90 day mortality, clinical failure, discontinuation due to adverse effects and infection recurrence. Results Five hundred and ninety-nine articles were evaluated for inclusion, of which seven met all inclusion criteria. Across all studies, 1589 patients received cefazolin and 2802 received an ASP. All-cause 90 day mortality was lower in patients who received cefazolin (OR 0.63, 95% CI 0.41-0.99; I2 = 58%). Odds of discontinuation due to adverse events was significantly lower in patients receiving cefazolin (OR 0.25, 95% CI 0.11-0.56; I2 = 13%). No differences in clinical failure were observed (OR 0.85, 95% CI 0.41-1.76; I2 = 74%). Conclusions This meta-analysis identified a significant decrease in mortality associated with cefazolin therapy for MSSA bacteraemia compared with ASPs, though no differences in clinical failure were observed. Additionally, cefazolin appeared to be better tolerated. These results should be interpreted with caution given the uncontrolled and retrospective nature of the included studies.
Test Frequency Compaction for Fault Detection in Analog Circuits Using Sensitivity Analysis

In this paper, we present a methodology to test faults induced by large deviations in components in analog circuits through multi-frequency test based on sensitivity analysis. Final compaction of the test frequencies is done using a covering table optimization method. Test Frequency compaction and choice of observation points are based on a novel notation of fault equivalence and sensitivity curves. Our case study shows this method can effectively minimize the sinusoid test frequencies to separate the fault-free and faulty operations of the circuit under test for all faulty components.
Understanding as an Ethical Aspiration in an Era of Digital Technology-Based Communication: An Analysis of Informed Consent Functions.

In their target article, Beskow and Weinfurt (2019) propose that achieving prospective research participants’ understanding of the information presented during the informed consent process is an et...
Evolving Losses for Unlabeled Video Representation Learning

We present a new method to learn video representations from unlabeled data. Given large-scale unlabeled video data, the objective is to benefit from such data by learning a generic and transferable representation space that can be directly used for a new task such as zero/few-shot learning. We formulate our unsupervised representation learning as a multi-modal, multi-task learning problem, where the representations are also shared across different modalities via distillation. Further, we also introduce the concept of finding a better loss function to train such multi-task multi-modal representation space using an evolutionary algorithm; our method automatically searches over different combinations of loss functions capturing multiple (self-supervised) tasks and modalities. Our formulation allows for the distillation of audio, optical flow and temporal information into a single, RGB-based convolutional neural network. We also compare the effects of using additional unlabeled video data and evaluate our representation learning on standard public video datasets.
On enhancing the mechanical behavior of ultra-high performance concrete through multi-scale fiber reinforcement

Abstract Steel fibers are typically used in ultra-high performance concretes (UHPC) to impart flexural ductility and increase fracture toughness. However, the mechanical properties of the steel fibers are underutilized in UHPC, as evidenced by the fact that most of the steel fibers pull out of a UHPC matrix largely undamaged during tensile or flexural tests. This research aims to improve the bond between steel fibers and a UHPC matrix by using steel wool. The underlying mechanism for fiber-matrix bond improvement is the reinforcement of the matrix tunnel, surrounding the steel fibers, by steel wool. Single fiber pullout tests were performed to quantify the effect of steel wool content in UHPC on the fiber-matrix bond. Microscopic observations of pulled-out fibers were used to investigate the fiber-matrix interface. Compared to the control UHPC mixture with no steel wool, significant improvement in the flexural behavior was observed in the UHPC mixtures with steel wool. Thus, the addition of steel wool in steel fiber-reinforced UHPC provides multi-scale reinforcement that leads to significant improvement in fiber-matrix bond and mechanical properties of UHPC.
The Effect of Parathyroid Hormone Analogues When Added to Mineralized Bone Xenografts

Implants can be a treatment option when there is sufficient quantity and quality of bone to provide support for long-term success. In the reconstruction of defects, autogenous bone remains the gold standard for its osteogenic and compatibility properties. However, the disadvantage of secondary surgery and the associated donor site morbidity prompts researchers to develop the ideal bone substitute for optimum bone reconstruction. Parathyroid hormone (PTH1-34) has provided a new option for improvement in bone regeneration. This study used a pig model to evaluate the effectiveness of parathyroid hormone when added to a xenograft, Bio-Oss, in reconstructing mandible defects. Six domestic pigs were used to create 3 posterior mandibular defects measuring 2 × 1-cm bilaterally with a total of 36 defects to simulate tooth extraction sites in humans. The defects were grafted in random order and divided into 3 groups as follows: control (no graft), Bio-Oss without PTH, and Bio-Oss with PTH. Defects were assessed with cone beam computerized tomography (CBCT), micro computerized tomography (microCT), nanoindentation, and histology. Results showed that adding PTH1-34 significantly enhanced the graft construct. CBCT showed a significant increase in the degree of bone mineralization. Nanoindentation showed increased hardness of regenerated bone and accelerated bone mineralization with PTH. MicroCT analysis revealed a trend toward higher bone regeneration and mineralization. The histological analysis showed a positive trend of the increase in cortical bone thickness and mineral apposition rate. In conclusion, the local addition of PTH1-34 to a xenograft has shown promising results to enhance bone regeneration in the reconstruction of mandibular defects.
Chimpanzee normativity: evidence and objections

This paper considers the question of whether chimpanzees possess at least a primitive sense of normativity: i.e., some ability to internalize and enforce social norms—rules governing appropriate and inappropriate behaviour—within their social groups, and to make evaluations of others’ behaviour in light of such norms. A number of scientists and philosophers have argued that such a sense of normativity does exist in chimpanzees and in several other non-human primate and mammalian species. However, the dominant view in the scientific and philosophical literature is that psychological capacities for social norms evolved uniquely in the human lineage, after our last common ancestor with chimpanzees and bonobos. After reviewing some of the existing evidence for normative capacity in chimpanzees, I defend the thesis of chimpanzee normativity against three key theoretical objections that have been presented in the literature, each of which have played a part in motivating the dominant sceptical position. I argue that, while we still have much to learn about the nature and extent of the normative capacities of other animals, there is strong prima facie evidence for social norms and normative evaluation in chimpanzees and the main theoretical objections to chimpanzee normativity are not at all compelling.
Prehospital end-tidal CO2 as an early marker for transfusion requirement in trauma patients.

Abstract Objective: Below normal end-tidal carbon dioxide measurement (ETCO2) is associated with worse outcomes in sepsis and trauma patients as compared to patients with normal ETCO2. We sought to determine if ETCO2 can be used in the prehospital setting to predict transfusion requirement, operative hemorrhage control, or mortality in the first 24 h after admission for trauma. Methods: This is a retrospective cohort study at a suburban, academic Level 1 Trauma Center. Patients were sequentially identified as prehospital trauma alerts from a single EMS system which requires, per policy, ETCO2 for all traumas. One year of prehospital data was collected and paired with hospital trauma registry data. Comparisons were made between ETCO2 values for patients who required transfusion, operative blood loss control, or who died, and those who did not. Results: Two hundred thirty-five trauma patients were transported via the study EMS system, of which 105 (44.7%) had documented ETCO2 values. Patient mean age was 60 (SD24) years with 59 (56.2%) male. Three patients were intubated prehospital and seven were intubated in the trauma bay. Mean prehospital ETCO2 for those who needed transfusion, surgery, or died (n = 11) was 25.7 (9.1) compared to 30.6 (7.8) for those who did not (p = 0.049). Optimal cutoff for our population was EtCO2 ≤ 27 with a sensitivity of 72.7% (95% CI 32–93) and specificity of 72.2% (62–81). Conclusion: Below normal ETCO2 values were associated with increase need for transfusion, operative intervention, and death. Further study is warranted to determine if ETCO2 outperforms other predictors of severe trauma.
A nanoscale vacuum field emission gated diode with an umbrella cathode

A nanoscale field emission vacuum channel gated diode structure is proposed and a tungsten cathode with an umbrella-like geometry and sharp vertical edge is fabricated. The edge of the suspended cathode becomes the field emission surface. Unlike in the traditional transistor with the gate typically located between the source and the drain, the bottom silicon plate becomes the gate here and the anode terminal is located between the umbrella cathode and the gate. The fabricated devices show excellent diode characteristics and the gated diode structure is attractive for extremely low gate leakage.
Adolescent Blount's Disease: Reconstructive Considerations and Approach

Adolescent Blount's disease, also known as late-onset tibia vara, is a multi-factorial developmental disorder of the proximal tibia resulting in three-dimensional deformity of the lower extremity. Surgical correction requires detailed surgical planning to identify and address each contributing aspect of the deformity. The goal of treatment should be to correct the deformity (restore the joint line and mechanical axis), improve function, and decrease the risk of premature joint degeneration. In this paper, the authors discuss pre-operative considerations and planning for this patient population, review treatment options and present their surgical technique with a representative case.
Mejoras cognitivas y el problema de la inequidad: entre bioconservadurismo y bioliberalismo

The notion of cognitive enhancement refers to a group of procedures and technologies aiming at amplifying any capacity of an organism by increasing its internal systems of information processing. After clarifying the term, this article discusses an argument raised in the context of the worries about the potential social consequences of promotion and use of such technologies in society. For some, this process would exacerbate current social inequalities, open the possibility of considering their total prohibition. I call this the argument from inequality against cognitive enhancement. After explaining the dimensions of the debate, I reply to Veit’s1 liberal proposal that claims that cognitive enhancements would not increase social inequality, and that they should be fully embraced and promoted. Finally, I conclude by briefly sketching a moderate alternative that focuses on strict regulation rather than in prohibition.
Improved pharmacokinetic and pharmacodynamic profile of a novel PEGylated native Erwinia chrysanthemi L-Asparaginase

Introduction. Erwinase® (native Erwinia chrysanthemi L-Asparaginase (nErA)) is an approved second-line treatment for acute lymphoblastic leukaemia (ALL) in children and adolescents, who develop hypersensitivity or neutralising antibodies to E.coli derived L-Asparaginases (ASNases). However, nErA has a short in vivo half-life requiring frequent dosing schedules in patients. In this study, nErA was covalently conjugated to PEG molecules with the aim of extending its half-life in vivo. Methods. Firstly, efficacy of this novel product PEG-nErA was investigated on human ALL cell lines (Jurkat, CCRF-CEM and CCRF-HSB2), in vitro. Secondly, its pharmacokinetic (PK) and pharmacodynamic (PD) characteristics were determined, in vivo (12 rats in each group). Results. It was found that the specific activity (U/mg of enzyme) and the kinetic constant (KM) of nErA remained unaltered post PEGylation. PEG-nErA was shown to have similar cytotoxicity to nErA (IC50: 0.06–0.17 U/mL) on human ALL cell lines, in vitro. Further, when compared to nErA, PEG-nErA showed a significantly improved half-life in vivo, which meant that L-Asparagine (Asn) levels in plasma remained depleted for up to 25 days with a four-fold lower dose (100 U/kg) compared with 72 h for nErA at 400 U/kg dose. Conclusion. Overall, this next generation product PEG-nErA (with improved PK and PD characteristics compared to nErA) would bring a significant advantage to the therapeutic needs of ALL patients and should be further explored in clinical trials.
Comparison of pinhole collimation and focusing optics for SANS

Abstract We examine quantitatively the instrumental factors that affect the theoretical performance and practical application of conventional pinhole collimation and focusing optics for small-angle neutron scattering (SANS) measurements. We calculate the relative performance of pinhole collimation vis-a-vis focusing by grazing incidence elliptical mirrors and compare the results with a recent ray-tracing simulation to show that the performance gains due to focusing found in the simulation arise largely from assuming a much larger sample size. We also compare measurements of the parasitic scattering from pinhole collimation with that from focusing cylindrical quartz mirrors, and a focusing refractive optic, to stress the importance of signal-to-noise as the true measure of performance for SANS instruments.
Cloud-radiation feedback and atmosphere-ocean coupling in a stochastic multicloud model

Abstract Despite recent advances in supercomputing, current general circulation models (GCMs) have significant problems in representing the variability associated with organized tropical convection. Furthermore, due to high sensitivity of the simulations to the cloud radiation feedback, the tropical convection remains a major source of uncertainty in long-term weather and climate forecasts. In a series of recent studies, it has been shown, in paradigm two-baroclinic-mode systems and in aquaplanet GCMs, that a stochastic multicloud convective parameterization based on three cloud types (congestus, deep and stratiform) can be used to improve the variability and the dynamical structure of tropical convection, including intermittent coherent structures such as synoptic and mesoscale convective systems. Here, the stochastic multicloud model is modified with a parameterized cloud radiation feedback mechanism and atmosphere-ocean coupling. The radiative convective feedback mechanism is shown to increase the mean and variability of the Walker circulation. The corresponding intensification of the circulation is associated with propagating synoptic scale systems originating inside of the enhanced sea surface temperature area. In column simulations, the atmosphere ocean coupling introduces pronounced low frequency convective features on the time scale associated with the depth of the mixed ocean layer. However, in the presence of the gravity wave mixing of spatially extended simulations, these features are not as prominent. This highlights the deficiency of the column model approach at predicting the behavior of multiscale spatially extended systems. Overall, the study develops a systematic framework for incorporating parameterized radiative cloud feedback and ocean coupling which may be used to improve representation of intraseasonal and seasonal variability in GCMs.
Testing the Tester: Specification and Validation Approaches

It’s a given that ATE test platforms are complex systems. Many HW and SW elements need to be integrated and work together for successful testing solutions. Too often we define a properly working platform within the context of the tools used to test and validate its behavior. Diagnostics, calibration, and special-purpose validation tools are used to prove a platform’s adherence to specifications. However, these tools and usage conditions are usually far removed from the end-use applications environment. They ignore or bypass many of the interactions encountered by a user’s actual test conditions. In an effort to manage the complexity of these interactions, some approaches try to limit the definition of a properly working tester to one that passes a particular validation standard (instead of meeting specifications in any legal usage).
Beyond the Genome

Beyond the genome lies the phenome, which term denotes the global – partly impressionistic – set of traits according to which biologists categorize an organism as a member of one particular taxonomic entity rather than of another. Although there does exist a causal ontogenetic relation between genome and phenome, it is not the case that an organism's genome can be usefully considered as a one-dimensional representation of its multidimensional phenome. Keywords: genetic information; meaning; epigenetic landscape; nervous system; Siamese cat
Automatic identification of causal relations in text and their use for improving precision in information retrieval

This study represents one attempt to make use of relations expressed in text to improve information retrieval effectiveness. In particular, the study investigated whether the information obtained by matching causal relations expressed in documents with the causal relations expressed in users' queries could be used to improve document retrieval results in comparison to using just term matching without considering relations. An automatic method for identifying and extracting cause-effect information in Wall Street Journal text was developed. The method uses linguistic clues to identify causal relations without recourse to knowledge-based inferencing. The method was successful in identifying and extracting about 68% of the causal relations that were clearly expressed within a sentence or between adjacent sentences in Wall Street Journal text. Of the instances that the computer program identified as causal relations, 72% can be considered to be correct. The automatic method was used in an experimental information retrieval system to identify causal relations in a database of full-text Wall Street Journal documents. Causal relation matching was found to yield a small but significant improvement in retrieval results when the weights used for combining the scores from different types of matching were customized for each query--as in an SDI or routing queries situation. The best results were obtained when causal relation matching was combined with word proximity matching (matching pairs of causally related words in the query with pairs of words that co-occur within document sentences). An analysis using manually identified causal relations indicate that bigger retrieval improvements can be expected with more accurate identification of causal relations. The best kind of causal relation matching was found to be one in which one member of the causal relation (either the cause or the effect) was represented as a wildcard that could match with any term. The study also investigated whether using Roget's International Thesaurus (3rd ed.) to expand query terms with synonymous and related terms would improve retrieval effectiveness. Using Roget category codes in addition to keywords did give better retrieval results. However, the Roget codes were better at identifying the nonrelevant documents than the relevant ones.
Screening long-range forces through local symmetry restoration.

We present a screening mechanism that allows a scalar field to mediate a long-range ($\ensuremath{\sim}\mathrm{Mpc}$) force of gravitational strength in the cosmos while satisfying local tests of gravity. The mechanism hinges on local symmetry restoration in the presence of matter. In regions of sufficiently high matter density, the field is drawn towards $\ensuremath{\phi}=0$ where its coupling to matter vanishes and the $\ensuremath{\phi}\ensuremath{\rightarrow}\ensuremath{-}\ensuremath{\phi}$ symmetry is restored. In regions of low density, however, the symmetry is spontaneously broken, and the field couples to matter with gravitational strength. We predict deviations from general relativity in the solar system that are within reach of next-generation experiments, as well as astrophysically observable violations of the equivalence principle. The model can be distinguished experimentally from Brans-Dicke gravity, chameleon theories and brane-world modifications of gravity.
the Meth Project and Teen Meth Use: New Estimates from the National and State Youth Risk Behavior Surveys

In this note, we use data from the national and state Youth Risk Behavior Surveys for the period 1999 through 2011 to estimate the relationship between the Meth Project, an anti-methamphetamine advertising campaign, and meth use among high school students. During this period, a total of eight states adopted anti-meth advertising campaigns. After accounting for pre-existing downward trends in meth use, we find little evidence that the campaign curbed meth use in the full sample. We do find, however, some evidence that the Meth Project may have decreased meth use among White high school students. Copyright © 2014 John Wiley & Sons, Ltd. Language: en
An active transcoding proxy to support mobile web access

In this paper, we present a proxy based system (MOWSER) to support web browsing from mobile clients over wireless networks. Mowser is a proxy agent between the mobile host and the web server, which performs active transcoding of data on both upstream and downstream traffic to present web information to the mobile user according to the QoS parameters set by the user. Active transcoding is defined as modifying the HTTP stream in situ, and it is entirely transparent to the user. Further, our system does not pose any additional requirements on the mobile user. This is an improvement over other proxy based systems, which only transcode images on the downstream and are mostly not configurable. While developed for mobile users, such a system can actually be useful in any low bandwidth scenario.
The Acrodermatitis Enteropathica Mutation Affects Protein Expression in Human Fibroblasts: Analysis by Two-Dimensional Gel Electrophoresis

The acrodermatitis enteropathica (AE) mutation affects zinc uptake in human fibroblasts. However, the specific biochemical lesion has not been identified. We have used the technique of two-dimensional gel electrophoresis to identify protein differences in total cell lysate isolated from normal and AE fibroblasts. Two proteins with estimated molecular weights of 49.6 and 49.9 kDa and an isoelectric point of 5.1 were identified in normal fibroblasts but absent from AE fibroblasts. The proteins were purified, subjected to in-gel trypsin digest and the resulting peptides separated by HPLC. Sequences from three peptide fragments (8, 15 and 18 amino acids) were obtained after Edman degradation. None of the fragments exhibited homology to any amino acid sequences in the nonredundant Genbank database. The 15 and 18 amino acid fragments each exhibited 100% homology to a 136 amino acid expressed sequence tag that was homologous (43%) to adipophilin. However, the 15 and 18 amino acid fragments were only 30 and 44% homologous, respectively, to corresponding regions within the expressed sequence tag. Therefore, the 49.6/49.9 kDa protein absent from AE fibroblasts was not related to adipophilin. The 8 amino acid fragment did not exhibit homology to any expressed sequence tag. Therefore, the 49.6/49.9 kDa proteins are novel and may be the cause of the reduced zinc uptake and abnormal zinc metabolism characteristic of fibroblasts carrying the AE mutation.
Diet and blood cholesterol in population surveys--lessons from analysis of the data from a major survey in Israel

A careful survey of the diet and serum cholesterol of civil servants in Israel covered 8829 men, aged 40-60 y born in six different areas. The authors were disappointed in their failure to find relationships between the diets and serum cholesterol of the individual men. Their report gives mean values for calories, diet fatty acids, and serum cholesterol for the men grouped by areas of birth. Regression analysis shows highly significant relations of serum cholesterol means to means of diet fatty acids for areas of birth. The relations found conform closely to expectations from dietary experiments in metabolic wards. Failure to consider intraindividual relations in the variables explains the disappointment of the authors of the report on the Israelis. Similar lack of attention to intraindividual variability is frequent in surveys and epidemiological studies and leads to error, controversy, and waste of time and money.
Testosterone propionate and arginase activity in diabetic rats.

Abstract The extra endogenous protein metabolism occurring in phlorizin and alloxan diabetes did not significantly change the liver arginase activities of normal or castrated adult male rats. Moreover, no correlation between the degree or duration of the diabetes and the enzyme activities of the liver could be detected. Tremendous increases, 400–600%, in protein ingestion, however, stimulated identical increases in the arginase activities of the livers of diabetic and nondiabetic rats. Smaller increases, 100–200%, produced increases in arginase activity concomitantly with the increase in liver weight. Testosterone propionate did not affect these enzymic changes. The arginase activity of the kidney was not changed except in those rats that had considerable sclerosis of the tubules after prolonged and severe alloxan diabetes. The ability of testosterone propionate to increase the arginase activity of the kidney was not impaired by the diabetes.
Adult Respiratory Distress Syndrome as a Cause of Death in Pneumococcal Pneumonia: Report of Ten Cases

The Pneumococcus continues to be a common cause of infectious pneumonia; however, the cause of death in pneumococcal disease remains obscure. Ten patients are described who developed the adult respiratory distress syndrome (ARDS) secondary to pneumococcal pneumonia. The patients are young (median age, 33 years) and leukopenic (median white blood cell count, 2.1 cells/cu mm) and have a mortality of 50 percent (five patients). It is postulated that pulmonary sequestration of leukocytes may play a role in the pathogenesis of ARDS secondary to pneumococcal disease. Four different pneumococcal capsular subtypes (9V [68]; 9A [33]; 4; 3) were found capable of causing ARDS. The currently available pneumococcal vaccine does not contain two of the capsular subtypes associated with ARDS.
Useful Additional Evaluation Measures

ABSTRACT: Performance evaluation with multiple tasks and multiple measures has been explored in a variety of settings. Yet, the efficient design of a portfolio of performance measures remains opaque, largely because of the multidimensional nature of the exercise. Here we focus on the value of adding measures to an existing portfolio of measures in a multi‐task LEN style agency model. We offer an algebraic decomposition that projects the gain from a set of additional performance measures into “distance” and “risk” components. The distance component comports with task balance and intensity issues and the risk component with the inevitable risk sharing or compensating wage differential issue.
The sensitivity of identified modal parameters to sensor placement errors and construction tolerances

This paper examines the sensitivity of experimentally measured modal frequencies and mode shapes to structural reassembly and sensor placement errors on a suspended three-bay truss. The statistical variations of identified mode shapes and frequencies are measured by repeated experiments. Both parameters are shown to vary measurably more with reassembly than sensor placement errors. Also, a directional stiffness in the truss joints was found to cause a parameter dependence on member orientation during reconstruction.
Irish Pilgrimage: The Different Tradition

Abstract The geographer's contribution to the study of religious phenomena is of special importance under circumstances in which scholars representing various disciplines tend to make generalizations based on a few, possibly nonrepresentative examples. The understanding of contemporary Western European pilgrimage is currently clouded by lack of generally available data on continental shrines and a tendency toward overreliance on Irish cases without adequate consideration of the highly atypical nature of the Irish pilgrimage tradition. This paper, grounded in data on 5,130 currently active Roman Catholic shrines in Western Europe, provides a cultural-historical explanation for the uniqueness of Irish pilgrimage and analyzes the major structural differences between Irish pilgrimage traditions and those found elsewhere in Europe.
Local government fraud: the Roslyn School District case

Purpose – The purpose of this paper is to provide an in‐depth analysis of a major fraud case in a local government setting, specifically a public school district, as a guide to managers and overseers of such organizations and as an instructional resource. Fraud cases outside the corporate arena have not been well represented in the literature.Design/methodology/approach – The paper describes the multi‐faceted fraud that occurred, identifies the control, oversight and auditing deficiencies that permitted it to happen, and suggests how adherence to good practices contributes to fraud prevention. What happened, why it happened, and how it might have been prevented are discussed. An extensive state audit provides richness of detail for this case study.Findings – The absence of, or non‐adherence to, internal controls, failures of oversight by the supervisory board, collusion among top executives, and substandard auditing all contributed to a multi‐million dollar public fraud extending over several years. The c...