Miracle-dz/UniFAR-FTUs huggingface dataset:
Is C2 Monitoring or Another Limited Sampling Strategy Superior to C0 Monitoring in Improving Clinical Outcomes in Adult Liver Transplant Recipients?

Cyclosporine (CsA) has had a major impact on the process and success of solid organ transplantation. Early in the use of CsA, therapeutic monitoring using the predose (trough, or C0) concentration became the standard of care. However, there are complications with the use of C0 monitoring that have only partly been mitigated with the advent of the micro-emulsion formulation (CsA-ME). More recently, limited sampling strategies (LSSs) for measuring the area under the CsA concentration-time curve (AUC) have been investigated to improve the monitoring of CsA post-transplantation. Many centres now routinely monitor CsA therapy using the concentration at 2 hours postdose (C2). In this paper the strength of the evidence for C2 (or other LSSs) relative to C0 monitoring of CsA-ME for improving clinically important outcomes in liver transplant patients is critically examined. Additionally, gaps in the literature are identified and recommendations are made for clinical research that could be done to provide more definitive evidence for the use of C2 or other LSSs in monitoring liver transplant patients.
Systems Genetics Analysis of Mouse Chondrocyte Differentiation

One of the goals of systems genetics is the reconstruction of gene networks that underlie key processes in development and disease. To identify cartilage gene networks that play an important role in bone development, we used a systems genetics approach that integrated microarray gene expression profiles from cartilage and bone phenotypic data from two sets of recombinant inbred strains. Microarray profiles generated from isolated chondrocytes were used to generate weighted gene coexpression networks. This analysis resulted in the identification of subnetworks (modules) of coexpressed genes that then were examined for relationships with bone geometry and density. One module exhibited significant correlation with femur length (r = 0.416), anteroposterior diameter (r = 0.418), mediolateral diameter (r = 0.576), and bone mineral density (r = 0.475). Highly connected genes (n = 28) from this and other modules were tested in vitro using prechondrocyte ATDC5 cells and RNA interference. Five of the 28 genes were found to play a role in chondrocyte differentiation. Two of these, Hspd1 and Cdkn1a, were known previously to function in chondrocyte development, whereas the other three, Bhlhb9, Cugbp1, and Spcs3, are novel genes. Our integrative analysis provided a systems‐level view of cartilage development and identified genes that may be involved in bone development. © 2011 American Society for Bone and Mineral Research.
Increased intraneuronal resting [Ca2+] in adult Alzheimer’s disease mice

Neurodegeneration in Alzheimer’s disease (AD) has been linked to intracellular accumulation of misfolded proteins and dysregulation of intracellular Ca2+. In the current work, we determined the contribution of specific Ca2+ pathways to an alteration in Ca2+ homeostasis in primary cortical neurons from an adult triple transgenic (3xTg‐AD) mouse model of AD that exhibits intraneuronal accumulation of β‐amyloid proteins. Resting free Ca2+ concentration ([Ca2+]i), as measured with Ca2+‐selective microelectrodes, was greatly elevated in neurons from 3xTg‐AD and APPSWE mouse strains when compared with their respective non‐transgenic neurons, while there was no alteration in the resting membrane potential. In the absence of the extracellular Ca2+, the [Ca2+]i returned to near normal levels in 3xTg‐AD neurons, demonstrating that extracellular Ca2+contributed to elevated [Ca2+]i. Application of nifedipine, or a non‐L‐type channel blocker, SKF‐96365, partially reduced [Ca2+]i. Blocking the ryanodine receptors, with ryanodine or FLA‐365 had no effect, suggesting that these channels do not contribute to the elevated [Ca2+]i. Conversely, inhibition of inositol trisphosphate receptors with xestospongin C produced a partial reduction in [Ca2+]i. These results demonstrate that an elevation in resting [Ca2+]i, contributed by aberrant Ca2+entry and release pathways, should be considered a major component of the abnormal Ca2+ homeostasis associated with AD.
Mitochondrial DNA deletions associated with aging and possibly presbycusis: a human archival temporal bone study.

HYPOTHESIS We attempted to determine if the common mitochondrial DNA aging deletion is also associated with presbycusis. BACKGROUND Presbycusis is the most common cause of deafness in adults in the United States, affecting approximately 40% of the population older than 75 years of age. The ability to identify a gene(s) or a specific genetic deficit(s) associated with presbycusis has significant clinical importance. METHODS The current study examined mitochondrial DNA (mtDNA) from cochlear sections of 34 human temporal bones: 17 with normal hearing and 17 with presbycusis. DNA was extracted from celloidin-embedded temporal bone sections; and specific oligonucleotide primers were designed to amplify the cytochrome b gene and a 4,977 base pair (bp) deletion of the mtDNA. Polymerase chain reaction (PCR) was used to amplify the base pair products that correspond to targeted gene regions, and sequencing was used to verify the products. RESULTS Fourteen of the 17 patients with hearing loss showed the 4,977 bp deletion and this deletion was present in only eight of the 17 human specimens with normal audiograms. The cytochrome b gene was amplified from all specimens. CONCLUSIONS The current study demonstrates the presence of a 4,977 bp deletion in human mitochondrial DNA genome that is associated with aging and with some forms of presbycusis. These results, coupled with previous animal studies, suggest that this 4,977 deletion may be associated with presbycusis.
COX‐2 and iNOS are critical in advanced glycation end product‐activated chondrocytes in vitro

Background The advanced glycation end products (AGEs) accumulate in joints of osteoarthritis patients. This study aimed to investigate the roles of cyclooxygenase‐2 (COX‐2) and inducible nitric oxide synthase (iNOS) pathways in AGE‐mediated cartilage damage.
Four ARF GAPs in Saccharomyces cerevisiae have both overlapping and distinct functions

Previous studies in yeast have revealed the presence of four proteins with a conserved, cysteine‐rich, ARF GAP domain that share the ability to suppress the conditional growth defect of the arf1‐3 mutant. Three of these proteins have been shown previously to be ADP‐ribosylation factor (ARF) GTPase‐activating proteins (GAPs). We now demonstrate that the fourth also exhibits in vitro ARF GAP activity and correlates the suppressor and ARF GAP activities for all four. Because the four ARF GAP proteins are quite diverse outside the ARF GAP domain, a genetic analysis was undertaken to define the level of functional cross‐talk between them. A large number of synthetic defects were observed that point to a high degree of functional overlap among the four ARF GAPs. However, several differences were also noted in the ability of each gene to suppress the synthetic defects of others and in the impact of single or combined deletions on assays of membrane traffic. We interpret these results as supportive evidence for roles of ARF GAPs in a number of distinct, essential cellular processes that include cell growth, protein secretion, endocytosis and cell cycling. The description of the specificities of the ARF GAPs for the different responses is viewed as a necessary first step in dissecting biologically relevant pathways through a functionally overlapping family of signalling proteins. Copyright © 2003 John Wiley & Sons, Ltd.
T2 hyperintensities in bipolar disorder: magnetic resonance imaging comparison and literature meta-analysis.

OBJECTIVE Accumulating evidence suggests a greater number of T2 abnormalities in the brains of patients with bipolar I disorder. The authors sought to evaluate the presence of signal "hyperintensities" in both bipolar I and II subjects and systematically review the existing literature. METHOD Magnetic resonance images of the brain were obtained prospectively for 29 patients with bipolar I disorder, 26 patients with bipolar II disorder, and 20 normal comparison subjects. The presence and location of signal hyperintensities in three brain regions (periventricular white matter, subcortical gray matter, and deep white matter) were evaluated. RESULTS No significant differences were found between groups for the presence of subcortical gray or deep white matter hyperintensities. Periventricular hyperintensities were more common in bipolar I patients (62%) than in bipolar II patients (38%) and normal comparison subjects (30%). Within patient groups, medication use was not significantly different for those with or without the presence of white matter hyperintensities. The literature on bipolar disorder and signal hyperintensities is reviewed. A meta-analysis of the pooled data in the literature on bipolar illness and signal hyperintensities revealed that the odds of having a T2 hyperintensity are significantly greater for bipolar I than for normal comparison subjects. CONCLUSIONS Having bipolar I disorder significantly increases the chance of having white matter changes in the brain. This study suggests that bipolar II patients may be more similar than bipolar I patients to comparison subjects on T2 measures. The possible pathophysiological significance of hyperintensities is discussed.
Effect of chemotherapy-induced DNA repair on oncolytic herpes simplex viral replication.

BACKGROUND Gliomas treated with the alkylating agent temozolomide have incomplete responses in part because of tumoral repair of chemotherapy-induced DNA damage. Data from phase I trials suggest that G207, an oncolytic herpes simplex virus (HSV) with mutated ribonucleotide reductase (RR) and gamma34.5 genes, is safe but needs greater viral oncolysis to be effective. We hypothesized that temozolomide and G207 treatment limitations could be jointly addressed using temozolomide-induced tumor-protective DNA repair pathways to enhance viral replication. METHODS Human glioblastoma cells (U87, T98, and U373) and U87 cells transfected with the gene for the DNA repair enzyme O6-methylguanine DNA methyltransferase (MGMT) were treated with G207 and/or temozolomide. Drug interactions, expression of the growth arrest DNA damage 34 (GADD34) and RR transcripts before and after their knockdown with short interfering RNAs, DNA strand breaks, and apoptosis were measured using Chou-Talalay analysis, real-time reverse transcription-polymerase chain reaction, the comet assay, and flow cytometry, respectively. Survival of mice (groups of ten) with intracranial U87 xenograft tumors treated with temozolomide and/or G207 was analyzed using Kaplan-Meier analysis. RESULTS Temozolomide exhibited strong synergy with G207 in both MGMT-negative and the MGMT inhibitor O6-benzylguanine-treated MGMT-expressing gliomas (Chou-Talalay combination indices = 0.005 to 0.39) and induced GADD34 expression primarily in nonapoptotic MGMT-negative U87 glioma cells (fold difference = 16, 95% confidence interval [CI] = 12.6 to 20.4, compared with untreated cells). MGMT-expressing T98 and U87/MGMT cells treated with temozolomide plus O6-benzylguanine had higher RR expression than untreated cells (fold difference =14.9, 95% CI = 10.1 to 22.0 [T98]; 9.9, 95% CI = 7.0 to 13.8 [U87/MGMT]). GADD34 and RR knockdown increased temozolomide-induced DNA damage and inhibited the synergy of G207 and temozolomide in U87 and O6-benzylguanine-treated U87/MGMT cells. Mice bearing intracranial U87 tumors survived longer after combination therapy (100% survival at 90 days) than after single-agent therapy (median survival = 46 and 48 days with G207 and temozolomide treatment, respectively). CONCLUSIONS Temozolomide-induced DNA repair pathways vary with MGMT expression and enhance HSV-mediated oncolysis in glioma cells. These findings unveil the potential of HSV to target cells surviving temozolomide treatment.
Conference Call Tone and Stock Returns: Evidence from the Stock Exchange of Hong Kong†

We investigate market reactions to manager and analyst tones during earnings conference calls using company transcripts from the Stock Exchange of Hong Kong (SEHK). This is the first study to examine the role of conference call tones outside of a US setting. Consistent with previous US-based results, we find that positive tones lead to higher stock returns. In contrast to US-based results, we show that investors place more emphasis on managerial tones than on analyst tones. We also find that stock market reactions to conference call tones are stronger for firms with a sophisticated investor base.
EMPIRICAL EVIDENCE ON DYNAMICS OF CREDIT GROWTH AND FOREIGN RESERVE

The paper presents a model for looking into the nature of change in foreign reserve from movements in domestic credit. This model is relevant to foreign reserve targeting, small and open economies. The model denotes that measures undertaken by central banks to constraint domestic credit growth with the view of controlling capital outflows will also be detrimental to foreign reserves level. The empirical studies with application of Fourier Transformation technique have been used to build a model, which shows that growth in domestic credit is more biased towards positive swings in foreign reserves, rather than being unfavorable. The small and open economies, particularly, the Pacific Island nations, have the right set up for application of this model to safeguard foreign reserves level.
Postnatal development of the cerebellar cortex in the rat. III. Maturation of the components of the granular layer

The migration of granule cells and the maturation of the various elements of the granular layer were studied in the cerebellar cortex of rats aged 0, 3, 5, 7, 10, 12, 15, 21 and 30 days with histological, histochemical, autoradiographic and electron microscopic techniques. The bulk of the granule cells are formed during the second week, but due to the time required for their migration and the lag in the formation of dendrites, few glomerular synapses are formed with mossy fibers before the beginning of the third week and the process is still in progress at 30 days, long after the dissolution of the external germinal layer. The maturation of Golgi cells is a protracted process. Their axons synapse with granule cell dendrites as soon as the glomeruli begin to mature. Evidence was obtained that mossy fibers synapse with the dendrites of Golgi cells. Towards the end of the second week the Lugaro cells are formed and synapses appear on their somata during the third week. Among these synapses the recurrent collaterals of Purkinje cell axons were identified. The Lugaro cells may be the primary targets of the infra and supraganglionic plexuses formed by these collaterals. In conclusion it was suggested that there are three major, successive stages in the neurogenesis of the cerebellar cortex, the morphogenic, synaptogenic and gliogenic. However, in the large Purkinje cell the synaptic maturation of one region (the soma) may begin before the morphogenic and synaptogenic maturation of the entire cell (the dendrites) is completed.
Measuring Latent Risk Preferences: Minimizing Measurement Biases

The results of eliciting risk preferences are highly dependent on the elicitation method used. This raises the question of how risk preferences can be reliably elicited. Using item response theory (IRT), the results of four elicitation methods describing common latent variables identified as risk preferences are combined into a composite score. The responses of 9235 individuals to a dedicated survey indicate that the composite score is a more accurate estimation of latent risk preferences than the results of individual methods, substantially reducing measurement noise and method-specific biases. IRT improves accuracy by allowing variable weighting to be dependent on the most relevant range of each method in estimating latent risk preferences. Therefore, the composite score contains more information about latent risk preferences than the results of either factor-weighted or unweighted methods. Manipulating the specific amounts, order and starting point of the multiple price list method shows that the accuracy of this method is not impervious to framing effects. Combining simpler methods with more advanced methods, which are all framed closely to the relevant situation, yields a more accurate and more robust estimation of latent risk preferences.
Leukocyte CD18 monoclonal antibody worsens endotoxemia and cardiovascular injury in canines with septic shock.

We investigated the effects of a murine monoclonal antibody directed against the canine leukocyte CD11/18 adhesion complex (MAb R15.7) in a canine model of septic shock. Awake 2-yr-old purpose-bred beagles were studied 7 days before and 1, 2, 4, and 10 days after intraperitoneal placement of an Escherichia coli-infected fibrin clot. Starting 12 h before clot placement, animals received 0.5-1 mg/kg iv every 12 h (4 doses total) of either MAb R15.7 (MAb group, n = 8) or, as controls, murine serum protein (n = 8). After infected clot placement, all animals received antibiotic (ceftriaxne, 100 mg.kg-1.day-1 for 4 days). Two of eight control animals and four of eight MAb animals died (P = 0.4). During the first 8 h after clot placement, MAb animals, compared with control animals, had greater (P < 0.06) increases in serum endotoxin levels and higher (P < 0.05) neutrophil counts. Day 1 after clot placement, MAb animals, compared with control animals, had decreased (P < 0.05) central venous pressure and arterial pH and increased (P < 0.05) arterial lactate. Day 2 after clot placement, MAb animals, compared with control animals, had decreased (P < 0.05) cardiac index and mean arterial pressure. In summary, MAb R15.7, although associated with increased neutrophil counts, worsened serum endotoxemia, acidosis, and cardiovascular function in this canine model of septic shock. These data suggest that in septic shock, antibody directed against this leukocyte membrane protein complex may be harmful, possibly via impairment of normal leukocyte function.
Expression of surface lymphotoxin and tumor necrosis factor on activated T, B, and natural killer cells.

The expression of membrane-associated forms of lymphotoxin (LT) and TNF were examined on cell lines of T, B, and myeloid origin, IL-2 dependent T cell clones, and peripheral blood lymphocytes. Inducible and constitutive patterns of surface LT expression were found on T cells as exemplified by the II-23.D7, a CD4+T cell hybridoma, and HUT-78, a T cell lymphoma. Phorbol ester induced surface LT expression on Ramos, an EBV transformed B cell line, but at a slower rate of appearance when compared to the II-23.D7. Secretion of LT was rapidly inducible by phorbol ester in II-23.D7 and also in HUT-78 but with slower kinetics; surface LT expression continued in both lines after secretion had ceased. Low levels of membrane TNF were transiently induced on II-23.D7 and HUT-78, but none was observed on Ramos. Peripheral blood monocytes and some myeloid tumor lines did not express surface LT. Several T cell clones expressed surface LT after Ag-specific stimulation, and expression persisted several days. Stimulation through the TCR or by IL-2 rapidly induced surface LT on resting peripheral T cells and CD56+ NK cells; pokeweed mitogen activation induced expression on CD20+ B cells. Consistent with previous results, immunoprecipitation with anti-LT mAb showed that LT was complexed with a distinct 33 kDa glycoprotein (p33) on cells that expressed surface LT, whereas secreted LT was not associated with p33. Surface and secreted modes of LT expression by activated T, B, and NK cells suggests that LT can be utilized as either a localized or diffusible mediator in immune responses.
Complementary factors contributing to the rapid spread of HIV-I in sub-Saharan Africa: a review.

OBJECTIVE To examine and establish complementary factors that contribute to the alarmingly high prevalence of HIV-1 in sub-Saharan Africa (SSA) in order to create awareness and suggest possible measures to avert the spread of the pandemic. DATA SOURCES Review of literature via Medline, the Internet, articles in refereed journals, and un-refereed features from the East Africa media houses and personal communications. DATA SELECTION Most published data from 1981 to September 2004 found to have revealed an impact on the spread of HIV-1 in SSA were included in the review. Therefore, all selected articles were read and critically evaluated. Where possible the number of citations articles which had been received were sought to established the degree of impact. DATA EXTRACTION Abstracts of all articles identified were accessed, read and analysed to determined possible relevance to the spread of HIV-1. When relevance was established from the abstract the entire paper was read and important points were included in the review. DATA SYNTHESIS A matrix was drawn to include all subtitles (e.g. polygamy, circumcision, poverty, etc). Below each subtitle all published works were included and prioritised. Published works that were found to have impact were included in the review. Finally a percent composite picture of all factors was drawn in an attempt to prioritise the factors, not withstanding the fact that most factors are interrelated and complementary. CONCLUSIONS There are many reasons why the spread of HIV-1 in SSA has not been declining over the years. Main risk factors for HIV-1 infection and AIDS disease in SSA were found to include poverty, famine, low status of women in society, corruption, naive risk taking perception, resistance to sexual behaviour change, high prevalence of sexually transmitted infections (STI), internal conflicts and refugee status, antiquated beliefs, lack of recreational facilities, ignorance of individual's HIV status, child and adult prostitution, uncertainty of safety of blood intended for transfusion, widow inheritance, circumcision, illiteracy and female genital cutting and polygamy. It is suggested that control programmes both local and donor-driven seeking to mitigate the spread of HIV-1 in SSA should take into account the apparent multiplicity of sub-Saharan African cultures and beliefs, some of which augment the spread of HIV-1.
The interfacial thermo-mechanical reliability of 3D memory-chip stacking with through silicon via array

Thermal stress in through silicon vias (TSVs) caused by the mismatch of coefficient of thermal expansion (CTE) between the filling material and silicon is a key challenge for three-dimensional electronic packaging due to the sophisticated inner structures. In most of the previous studies, the thermomechanical properties of TSV structured chips were analyzed in a unit cell so as to simplify the problem. In this simulation study, a seven-layered memory-chip stacking model is constructed, and finite element method is used to evaluate the influence of the inner structure on thermo-mechanical stresses and the interfacial reliability of the TSV structure package. The simulation results show that, due to the large CTE and low yield strength of copper compared to silicon, the stress concentrated zone locates at the chip and PCB interface on the copper side. The placement of TSVs is one of the main considerations in IC design because it has a significant influence on the thermal stress. Use of Pb-free solder such as SAC305 has almost no influence on the maximum stress in TSV interconnects. The radius of keep-away-zone, where transistors should not be arranged, is two times of that of TSVs. TSV parameters have some influence on the interfacial stress. The maximum interfacial stress increases with decreasing diameters of TSVs when the diameter ratio of TSV to Cu nail (i.e., DTSV/DCu) keeps unchanged.