Miracle-dz/UniFAR-FTUs huggingface dataset:
Migration of brain tumor cells on extracellular matrix proteins in vitro correlates with tumor type and grade and involves alphaV and beta1 integrins.

An important contributor to the malignancy of brain tumors is their ability to infiltrate the brain. Extracellular matrix molecules and cell adhesion molecules on cell surfaces play key roles in cell migration. In the present study, we used reaggregates of dissociated cells from freshly excised human brain tumors to analyze the migration of cells from human brain tumors of different types and grades on many different adhesion proteins adsorbed to glass substrates. Proteins were chosen based on their presence in normal or neoplastic nervous tissue, and included the extra-cellular matrix molecules fibronectin, collagens, fibrinogen, laminin, tenascin-C, thrombospondin, and the neuron-glia cell adhesion molecule, Ng-CAM. Cells from astrocytomas (n = 24) migrated on a variety of substrates, in contrast to cells from primitive neuroectodermal tumors cells (n=6), which only migrated well on laminin, fibronectin, or type IV collagen but not on the other substrates. Typically, migrating cells from astrocytomas of all grades had long, slender processes, were usually bipolar, and their cell bodies did not spread well on any substrate. Although there was variability in the migration of cells from astrocytomas of the same grade, cells from high-grade astrocytomas tended to migrate more extensively (42.3 +/- 4.7 micrometers/16 h: n = 16) than cells from lower grade astrocytomas (28.9 +/- 3.9 micrometers/16 h; P = 0.07; n = 8); the most striking differences were observed for collagen substrates, on which cells from lower grade astrocytomas migrated at very low levels (7.6 +/- 2 .6 micrometers/16 h) and cells from high-grade astrocytomas at higher levels (24.4 +/- 5.2 micrometers;P = 0.01). In contrast to primary cells from glioblastomas (n = 13), glioblastoma cell lines (n = 10) consistently spread on various substrates and migrated at high levels (69.5 +/- 7.6 versus 46.4 +/-5.7 micrometers/16 h; P = 0.03), in particular, on collagens (108.4 +/- 20.2 versus 28.0 +/- 6.1 micrometers/16 h; P= 0.001). Specific monoclonal antibodies to alphaV and beta1 integrin monomers completely inhibited the migration of astrocytoma cells on most substrates, suggesting that alphaV and beta1 integrins play a crucial role in brain tumor infiltration. These studies also suggest that although a large number of extracellular matrix molecules may promote tumor cell migration, disrupting the function of only a few tumor cell receptors may be critical for tumor infiltration in the brain.
O6-methylguanine-DNA methyltransferase gene: epigenetic silencing and prognostic value in head and neck squamous cell carcinoma.

BACKGROUND Alkylating N-nitroso compounds can interact directly with DNA, forming O(6)-alkylguanine, a DNA adduct proved to be mutagenic and carcinogenic if not sufficiently repaired. A specific DNA repair enzyme, O(6)-methylguanine-DNA methyltransferase (MGMT), can remove the alkyl group from the O(6)-position of the guanine, thereby preventing its mutagenic and carcinogenic effects. Inactivation of the MGMT gene in association with promoter hypermethylation results in persistence of O(6)-alkylguanine in DNA, leading to G:C to A:T transition mutation and these G:C to A:T transition mutations can inactivate p53 tumor suppressor gene or activate ras proto-oncogene. METHODS We analyzed MGMT promoter hypermethylation and protein expression patterns in 94 cases of primary head and neck squamous cell carcinoma (HNSCC) by methylation-specific PCR (MSP) and immunohistochemical staining. The results were then correlated with clinical follow-up data. RESULTS MGMT promoter hypermethylation was present in 17 of 94 patients (18.1%) and apparent loss of protein expression was seen in 19 of 93 HNSCC patients (20.4%). The presence of MGMT promoter hypermethylation was significantly correlated with loss of MGMT protein expression in HNSCC. Both MGMT promoter hypermethylation and loss of protein expression were significantly correlated to increased tumor recurrences and decreased patient survival, independent of other risk factors, such as tumor site, tumor size, nodal status, age, and chemoradiation therapy. CONCLUSIONS MGMT promoter hypermethylation and apparent loss of protein expression are reliable and independent prognostic factors in HNSCC. The above study may also provide guideline or basis for applying alkylating antitumor agents to patients with HNSCC that display MGMT promoter hypermethylation and/or loss of MGMT protein expression.
Integrated method for the measurement of trace nitrogenous atmospheric bases

Abstract. Nitrogenous atmospheric bases are thought to play a key role in the global nitrogen cycle, but their sources, transport, and sinks remain poorly understood. Of the many methods available to measure such compounds in ambient air, few meet the current need of being applicable to the complete range of potential analytes and fewer still are convenient to implement using instrumentation that is standard to most laboratories. In this work, an integrated approach to measuring trace, atmospheric, gaseous nitrogenous bases has been developed and validated. The method uses a simple acid scrubbing step to capture and concentrate the bases as their phosphite salts, which then are derivatized and analyzed using GC/MS and/or LC/MS. The advantages of both techniques in the context of the present measurements are discussed. The approach is sensitive, selective, reproducible, as well as convenient to implement and has been validated for different sampling strategies. The limits of detection for the families of tested compounds are suitable for ambient measurement applications (e.g., methylamine, 1 pptv; ethylamine, 2 pptv; morpholine, 1 pptv; aniline, 1 pptv; hydrazine, 0.1 pptv; methylhydrazine, 2 pptv), as supported by field measurements in an urban park and in the exhaust of on-road vehicles.
Rapid genotyping assays for the 4–base pair deletion of canine MDR1/ABCB1 gene and low frequency of the mutant allele in Border Collie dogs

P-glycoprotein, encoded by the MDR1 or ABCB1 gene, is an integral component of the blood–brain barrier as an efflux pump for xenobiotics crucial in limiting drug uptake into the central nervous system. Dogs homozygous for a 4–base pair deletion of the canine MDR1 gene show altered expression or function of P-glycoprotein, resulting in neurotoxicosis after administration of the substrate drugs. In the present study, the usefulness of microchip electrophoresis for genotyping assays detecting this deletion mutation was evaluated. Mutagenically separated polymerase chain reaction (MS-PCR) and real-time PCR assays were newly developed and evaluated. Furthermore, a genotyping survey was carried out in a population of Border Collies dogs in Japan to determine the allele frequency in this breed. Microchip electrophoresis showed advantages in detection sensitivity and time saving over other modes of electrophoresis. The MS-PCR assay clearly discriminated all genotypes. Real-time PCR assay was most suitable for a large-scale survey due to its high throughput and rapidity. The genotyping survey demonstrated that the carrier and mutant allele frequencies were 0.49% and 0.25%, respectively, suggesting that the mutant allele frequency in Border Collies is markedly low compared to that in the susceptible dog breeds such as rough and smooth Collies.
Carawan: a clinical documentation system for use in mobile ad-hoc networks

Clinical documentation systems are commonly used in hospitals to efficiently manage patient data. In areas of crises such as refugee camps, however, physicians are forced to resort to conventional paper-based documentation: The camps lack essential IT infrastructure, computers are regarded unreliable and complicated, and network cabling would restrict the users' mobility. A software aiding physicians in such a scenario must be easy to use, offer a high degree of reliability but yet manage without any infrastructure except energy. In this paper, we present a clinical documentation system allowing technically untrained users to electronically create and edit Healthcards, a basic health documentation form proposed by the WHO. Changes are distributed and received automatically using a wireless mobile ad-hoc network. Each notebook computer functions as a node participating in a pure peer to peer network without the need for a server. Not relying on a distinguished server or network cabling, the system aims to be quickly established, yet deliver a high degree of reliability and mobility to its users. On the other hand, the system has no authoritative instance that helps announce and distribute new datasets, manage versioning conflicts or determine whether a given Healthcard is up-to-date. We propose a request-response-based system for exchanging datasets, utilizing timestamps to resolve versioning conflicts and negotiating per-Healthcard IDs which can be used to determine whether a Healthcard is up-to-date.
Sustained-release methylphenidate in a randomized trial of treatment of methamphetamine use disorder.

BACKGROUND AND AIMS No effective pharmacotherapy for methamphetamine (MA) use disorder has yet been found. This study evaluated sustained-release methylphenidate (MPH-SR) compared with placebo (PLA) for treatment of MA use disorder in people also undergoing behavioral support and motivational incentives. DESIGN This was a randomized, double-blind, placebo-controlled design with MPH-SR or PLA provided for 10 weeks (active phase) followed by 4 weeks of single-blind PLA. Twice-weekly clinic visits, weekly group counseling (CBT) and motivational incentives (MI) for MA-negative urine drug screens (UDS) were included. SETTING Treatment sites were in Los Angeles, California (LA) and Honolulu, Hawaii (HH), USA. PARTICIPANTS A total of 110 MA-dependent (via DSM-IV) participants (LA = 90; HH = 20). MEASUREMENTS The primary outcome measure is self-reported days of MA use during the last 30 days of the active phase. Included in the current analyses are drug use (UDS and self-report), retention, craving, compliance (dosing, CBT, MI), adverse events and treatment satisfaction. FINDINGS No difference was found between treatment groups in self-reported days of MA use during the last 30 days of the active phase (P = 0.22). In planned secondary outcomes analyses, however, the MPH group had fewer self-reported MA use days from baseline through the active phase compared with the PLA group (P = 0.05). The MPH group also had lower craving scores and fewer marijuana-positive UDS than the PLA group in the last 30 days of the active phase. The two groups had similar retention, other drug use, adverse events and treatment satisfaction. CONCLUSIONS Methylphenidate may lead to a reduction in concurrent methamphetamine use when provided as treatment for patients undergoing behavioral support for moderate to severe methamphetamine use disorder, but this requires confirmation.
Multicast MIMO enhancement for V2X over LTE

Motivated by recent interest in vehicle-to-vehicle/ infrastructure/pedestrian (V2X) communication over the fourth generation of the Long-Term Evolution (LTE) cellular standard, we study the efficiency of the Multimedia Broadcast Multicast Services (MBMS), a key enabler for V2X communication, which currently employs only single antenna transmission. We show that by utilizing more transmit antennas at the base station - which are already used for point-to-point communications - and simple space-time coding (STC) techniques, a significant boost in performance can be achieved. To this end, we evaluate the performance of different transmission strategies along with the information theoretic optimal performance. For a fast Rayleigh fading channel, we show that a gain of 1 bit/sec/Hz is achieved for a signal-to-noise ratio of 10dB, and higher gains for higher signalto- noise-ratios for for an outage probability of 0.01. Moreover, we demonstrate that Alamouti STC is near optimum for typical signal-to-noise ratios. However, for more antennas, due to the inherent loss of multiplexing of orthogonal STC schemes, non-orthogonal STC schemes with higher multiplexing need to be considered.
Crisscross CTL Induction by SYT-SSX Junction Peptide and Its HLA-A*2402 Anchor Substitute1

To investigate the effects of anchor substitutions in SYT-SSX junction peptide, an HLA-A24 anchor residue (position 9) of the SYT-SSX B peptide (GYDQIMPKK) was substituted to more favorable residues according to the HLA-A24-binding motif. Among four substitutes constructed, a substitute with isoleucine (termed K9I peptide) most apparently enhanced the affinity for HLA-A24 molecule. Subsequent in vitro CTL induction analysis using PBMCs of 15 HLA-A24+ synovial sarcoma patients revealed that the original B peptide allowed to induce synovial sarcoma-specific CTLs from 7 patients (47%), whereas such CTLs were inducible from 12 patients (80%) with K9I peptide. Moreover, the extent of cytotoxicity against HLA-A24+ synovial sarcoma cell lines was higher in K9I peptide-induced CTLs than B peptide-induced CTLs. Influence of anchor substitution on peptide/TCR interaction was evaluated by cytotoxicity assays against autologous cells and tetramer analysis. CTLs induced from a synovial sarcoma patient using K9I peptide did not lyse autologous PHA blasts or EBV-infected B cells. In vitro stimulations of PBMCs from 5 HLA-A24+ synovial sarcoma patients with K9I peptide increased the frequency of T cells reacting with both HLA-A24/K9I peptide tetramer and HLA-A24/B peptide tetramer. In contrast, the frequency of T cells reacting with HLA/HIV-derived peptide tetramer remained low. These findings support the validity in design of anchor residue substitution in SYT-SSX fusion gene-derived peptide, and provide a potential clue to the current stagnation in vaccination trials of fusion gene-derived natural junction peptides.
Normal reference range of fetal nuchal translucency thickness in pregnant women in the first trimester, one center study

Background: Considering that establishment of reference value of nuchal translucency (NT)-related to the crown rump length (CRL) during the first trimester will be helpful for determining an appropriate cutoff level for screening of increased NT thickness-related abnormalities, we determined the NT thickness and investigated its relation with different chromosomal and nonchromosomal abnormalities among a large sample size of pregnant Iranian women. Materials and Methods: In this analytic cross-sectional study, pregnant women who were in their first trimester were enrolled at their antenatal visit. Using an abdominal ultrasonography, the fetal NT thickness of the studied population was measured. Those with increased NT thickness were determined. The reference value of NT thickness (5th, 25th, 50th, 75th, and 95th percentiles) within each 5-mm range of CRL and during the 11th, 12th, and 13th gestational weeks were determined. The presences of the different chromosomal and nonchromosomal abnormalities were compared in women with different percentiles of NT thickness who underwent amniocentesis and those who did not. Results: 1,614 pregnant women were evaluated. The mean NT thickness was 1.30 ± 0.54 mm. Increased NT thickness >2 mm and >95th percentile according to their gestational age (GA) was detected in 89 (5.5%) and 58 (3.6%) pregnant women. The reference 95th percentile value range for NT was 1.8-2.35 and increased NT thickness according to our obtained values was associated significantly with chromosomal abnormalities. Conclusion: The obtained reference range in our studied population was different from that reported for other ethnic groups and it is suggested that using this values are more favorable for screening of chromosomal abnormalities during the first trimester of pregnancy than the recommended single cutoff value.
Regulation of the G 2 – M cell cycle progression by the ERK 5 – NF κ B signaling pathway

The extracellular signal–regulated kinase (ERK) 5 is a member of the MAPKs (Lee et al., 1995; Zhou et al., 1995). The Nterminal kinase domain of ERK5 is highly homologous to the prototypical MAPKs ERK1/2. However, ERK5 is selectively activated by its upstream kinase MEK5 (English et al., 1995) and ERK5-null mice are embryonic lethal (Hayashi and Lee, 2004), suggesting that ERK5 has unique biological functions that cannot be compensated for by ERK1/2. Stimulation of ERK5 regulates neuronal survival, muscle cell differentiation, and cellular proliferation and transformation (Kato et al., 1998; Pearson et al., 2001; Watson et al., 2001; Liu et al., 2003; Shalizi et al., 2003). Hyperactivity of the ERK5 pathway is associated with highly aggressive forms of breast and prostate cancers (Esparis-Ogando et al., 2002; Mehta et al., 2003). Mechanisms for ERK5 regulation of proliferation are not well understood. However, several targets of ERK5 have been identifi ed, including nuclear factor κB (NFκB), c-myc, and cyclin D, all of which are potential regulators of proliferation (Wang and Tournier, 2006). NFκB is of particular interest because it regulates the G1–S transition of the cell cycle and is required for oncogenic transformation by Ras (Finco et al., 1997; Hinz et al., 1999). Mutations that result in constitutive activation of NFκB are common in epithelial tumors, tumor cell lines, and lymphoid malignancies. These NFκB mutations cause increased proliferation rates and metastatic capacity (Karin et al., 2002). Interestingly, ERK5-mediated activation of NFκB promotes cellular transformation in NIH 3T3 cells (Pearson et al., 2001). To elucidate mechanisms for ERK5 regulation of cellular proliferation, we investigated the importance of ERK5 in cell cycle progression. We examined ERK5 activity at different stages of the cell cycle and discovered that ERK5 is activated in a cell cycle–dependent manner, with maximal activation at G2–M. Evidence is presented supporting a critical role for ERK5 in the G2–M progression. Our data also identify NFκB-mediated transcription as a key downstream mechanism by which ERK5 regulates the G2–M phase transition.
Liquidity shock management: Lessons from Australian banks

Prior to the 2007–2009 financial crisis, international banks had an average share of around 65% of the syndicated loan market in Australia. When the crisis hit, the resulting liquidity shock resulted in globally active international banks exiting the Australian market. With limited global operations, the major Australian banks were able to absorb and manage the liquidity shock. This resulted in domestic banks carrying a significantly greater proportion of revolving credit facilities in their syndicated loan portfolios after 2008. Domestic bank willingness and ability to deal with the market disruption and to hold a greater proportion of high liquidity risk revolvers are directly linked to the level of their transaction deposits. Their increased involvement in revolving facilities cannot be fully explained by the certification effect or flight-to-home effect. It is not demand driven and is robust to endogeneity tests.
A Truncated Form of Nef Selected during Pathogenic Reversion of Simian Immunodeficiency Virus SIVmac239Δnef Increases Viral Replication

ABSTRACT The live, attenuated vaccine simian immunodeficiency virus SIVmac239Δnef efficiently protects rhesus macaques against infection with wild-type SIVmac but occasionally causes CD4+ T-cell depletion and progression to simian AIDS (SAIDS). Virus recovered from a vaccinated macaque (Rh1490) that progressed to SAIDS had acquired an additional deletion in the nef gene, resulting in a frameshift that restored the original nef open reading frame (R. I. Connor, D. C. Montefiori, J. M. Binley, J. P. Moore, S. Bonhoeffer, A. Gettie, E. A. Fenamore, K. E. Sheridan, D. D. Ho, P. J. Dailey, and P. A. Marx, J. Virol. 72:7501-7509, 1998). Intravenous inoculation of the Rh1490 viral isolate into four naive rhesus macaques induced CD4+ T-cell depletion and disease in three out of four animals within 2 years, indicating a restoration of virulence. A DNA fragment encompassing the truncated nef gene amplified from the Rh1490 isolate was inserted into the genetic backbone of SIVmac239. The resulting clone, SIVmac239-Δ2nef, expressed a Nef protein of approximately 23 kDa, while the original SIVmac239Δnef clone expressed a shorter protein of 8 kDa. The revertant form of Nef did not cause downregulation of CD4, CD3, or major histocompatibility complex class I. The infectivity of SIVmac239-Δ2nef was similar to that of SIVmac239Δnef in single-cycle assays using indicator cell lines. In contrast, SIVmac239-Δ2nef replicated more efficiently than SIVmac239Δnef in peripheral blood mononuclear cell (PBMC) cultures infected under unstimulated conditions. The p27 Gag antigen levels in SIVmac239-Δ2nef-infected cultures were still lower than those obtained with wild-type SIVmac239, consistent with a partial recovery of Nef function. The transcriptional activity of long terminal repeat (LTR)-luciferase constructs containing the nef deletions did not differ markedly from that of wild-type LTR. Introduction of a premature stop codon within Nef-Δ2 abolished the replicative advantage in PBMCs, demonstrating that the Nef-Δ2 protein, rather than the structure of the U3 region of the LTR, was responsible for the increase in viral replication. Taken together, these results show that SIV with a deletion in the nef gene can revert to virulence and that expression of a form of nef with multiple deletions may contribute to this process by increasing viral replication.
Impairment of constructive memory in schizophrenia

Episodic memories are characterized by a specific state of awareness, conscious recollection, which allows subjects to mentally relive past events. They are not a literal reproduction of the past but instead depend on constructive processes. Patients with schizophrenia exhibit a specific impairment of conscious recollection. The aim of this study was to investigate the role of constructive processes into defective conscious recollection of patients with schizophrenia. An experiential approach to false recognition and related states of awareness was used. Thirty patients with schizophrenia, who were matched with 30 normal subjects, studied lists of words semantically related to a non-presented theme word (critical lure). On a recognition memory task with both previously presented words and non presented critical lures, they were asked to give Remember, Know or Guess responses to items that were recognized on the basis of conscious recollection, familiarity or guessing, respectively. Patients with schizophrenia recognized fewer studied words and critical lures than normal subjects. This deficit was restricted to memories associated with conscious recollection as indicated by a decrease in Remember responses, but not Know and Guess responses. Our results indicate that patients with schizophrenia exhibit an impaired conscious recollection, whether memories are true or false. They provide evidence that schizophrenia impairs the mere construction of conscious recollection.
Leadership for school improvement

4 LIST OF FIGURES . 13 LIST OF TABLES . 14 CHAPTER 1: INTRODUCTION AND CONTEXT OF THE RESEARCH . 15 1.0 INTRODUCTION . 15 1.1 The Context of the Research Problem . 16 1.1.1 Personal Context . 16 1.1.2 The International Context . 16 1.1.3 The National Context . 17 1.1.4 The Sydney Archdiocesan Context . 19 1.2 The Research Problem Defined . 20 1.3 The Research Purpose . 20 1.4 Overall Research Question . 21 1.5 Significance of the Research . 21 CHAPTER 2: REVIEW OF THE LITERATURE AND MAJOR THEMES . 22 2.0 INTRODUCTION . 22 2.1 Theme 1: LEADERSHIP . 23 2.1.1 General Leadership . 23 2.1.1.1 Subsidiarity . 23 2.1.1.2 Management . 24 2.1.1.3 Transformational leadership . 26 2.1.1.3. 1 Focus of Leadership . 26