Miracle-dz/UniFAR-FTUs huggingface dataset:
DEFINING A PHENOTYPE FOR RED CELL VOLUME REGULATION AND POTASSIUM CHLORIDE COTRANSPORT

The potassium chloride co-transporter (KCC) is a member of the electroneutral cation chloride family of cotransporters found in multiple tissues that are involved in transepithelial ion transport and regulation of intracellular ion content and cell volume. We have shown previously that three of the four KCC genes -- KCC1, KCC3, and KCC4 -- are expressed in red blood cells (RBC) (Exp.Hem. 33:624, 2005). Functionally, the KCC mediates volume reduction of reticulocytes that establishes the higher cellular hemoglobin concentration (CHC) of mature RBC. KCC activity is higher in reticulocytes and diminishes with age. KCC activity in RBC containing sickle hemoglobin (SS RBC) is elevated compared to normal (AA RBC) in part due to reticulocytosis in SS blood. However, we have demonstrated that SS reticulocytes have abnormal regulation of KCC activity leading to increased CHC upon activation of KCC compared to AA reticulocytes (Blood 104:2954, 2004; Blood 109:1734, 2007). These findings implicate KCC as a factor in the dehydration of SS RBC, which leads to elevated Hb S concentration and enhances Hb S polymerization and hemolysis. Because KCC activity correlates with cell age, standard flux measurements on blood samples with different numbers of reticulocytes or young non-reticulocytes are not comparable. The Advia automated cell counter measures cell volume (MCV) and cellular hemoglobin concentration (CHC) in reticulocytes, an age-defined population of cells, and thus circumvents the problem of variable reticulocyte counts among SS and AA blood samples. In this study, reticulocyte CHC measurements on fresh blood demonstrated a clear difference between AA and SS cells, reflecting AA reticulocytes, reflecting abnormal regulation in SS cells. These results were reproducible in the same individual over time. KCC flux derived from CHC ranged from 5-10.3 mmolK/kgHb/ min in SS reticulocytes, compared to 2.9-7.2 mmolK/kgHb/min in AA reticulocytes. Such measures of KCC activity in red cell populations controlled for cell age will facilitate further studies correlating KCC activity with phenotypic or genetic variability in sickle cell disease.
Defective Replication in Human Immunodeﬁciency Virus Type 1 When Non-tRNA 3Lys Primers Are Used for Reverse Transcription

tRNA 3Lys , the primer for reverse transcriptase in human immunodeﬁciency virus type 1 (HIV-1), anneals to the primer binding site (PBS) in HIV-1 RNA. It has been shown that altering the PBS and U5 regions upstream of the PBS in HIV-1 so as to be complementary to sequences in tRNA Met or tRNA His will allow these tRNA species to be stably used as primers for reverse transcription. We have examined the replication of these mutant viruses in Sup-T1 cells. When Sup-T1 cells are infected by cocultivation with HIV-1-transfected 293T cells, viruses using tRNA His or tRNA Met are produced at rates that are approximately 1/10 or 1/100, respectively, of rates for wild-type virions that use tRNA 3Lys . When Sup-T1 cells are directly infected with equal amounts of these different viruses isolated from the culture supernatant of transfected 293T cells, virions using tRNA Met are produced at 1/100 the rate of wild-type viruses, and production of virions using tRNA His is not detected. Both wild-type and mutant virions selectively package tRNA Lys only, and examination of the ability of total viral RNA to prime reverse transcription in vitro indicates a >80% reduction in
Conantokins Derived from the Asprella Clade Impart Con Rl -B, an NMDA Receptor Antagonist with a Unique Selectivity Profile for NR2B Subunits

Using molecular phylogeny has accelerated the discovery of peptidic ligands targeted to ion channels and receptors. One clade of venomous cone snails, Asprella , appears to be significantly enriched in conantokins, antagonists of N-Methyl D-Asparate receptors (NMDARs). Here, we describe the characterization of two novel conantokins from Conus rolani , including conantokin con Rl -B that has shown an unprecedented selectivity for blocking NMDARs that contain NR2B subunits. Con Rl -B shares only some sequence similarity to the most studied NR2B-selective conantokin, con G . The divergence between con Rl -B and con G in the second inter-Gla loop was used to design analogs for structure-activity studies; the presence of Pro10 was found to be key to the high potency of con Rl -B for NR2B, whereas the ε -amino group of Lys8 contributed to discrimination in blocking NR2B- and NR2A-containing NMDARs. In contrast to previous findings from Tyr5 substitutions in other conantokins, con Rl -B [L5Y] showed potencies on the four NR2 NMDA receptor subtypes that were similar to those of the native con Rl NMDA receptor subtypes in the nervous system. This work shows the effectiveness of coupling molecular phylogeny, chemical synthesis and pharmacology for discovering new bioactive natural products.
A Line-integral Fuzzy Lyapunov Functional Approach to Sampled-data Tracking Control of Takagi-Sugeno Fuzzy Systems

– This paper deals with a sampled-data tracking control problem for the Takagi–Sugeno fuzzy system with external disturbances. We derive a stability condition guaranteeing both asymptotic stability and H-infinity tracking performance by employing a newly proposed time-dependent line-integral fuzzy Lyapunov–Krasovskii functional. A new integral inequality is also introduced, by which the proposed stability condition is formulated in terms of linear matrix inequalities. Finally, the effectiveness of the proposed method is demonstrated through a simulation example.
Identifying Depression in a National Sample of Caregivers Involved with Child Welfare

Objectives— Identifying depression is the first step in provision of treatment across service settings but can be challenging for non-mental health providers. This study examines how caseworker identification of depression among parents and other caregivers during the child welfare investigation or assessment process varies as a function of different agency, caseworker, and case characteristics. Methods— Data were drawn from the second National Survey of Child and Adolescent Well-Being (NSCAW II), a national probability sample of children referred to U.S. child welfare agencies between February 2008 and April 2009. The study sample was comprised of 889 parents and other caregivers whose children initially remained at home and whose confidential responses on the World Health Organization Composite International Diagnostic Interview Short-Form indicated a major depressive episode within the last 12 months. Weighted logistic regression examined predictors of caseworker identification of caregiver depression at the agency, caseworker, and case level. Results— Investigative caseworkers identified mental health needs in only 38% of caregivers. Caseworkers were more likely to identify caregiver mental health needs when child welfare agency policy specified use of a standardized mental health assessment and when the maltreatment report came from a health or mental health provider relative to other sources, such as teachers or family members. Investigative caseloads were negatively associated with identifying depression. Conclusions— Structured mental health assessments may help non-mental health professionals identify mental health needs among vulnerable populations.
SCIENCE OF MEDICINE

Contact: ycho9@slu.edu; abaldan1@slu.edu The Cho and Baldan labs focus their efforts on novel pathways that control atherogenesis. MIF (Macrophage migration inhibitory factor) recruits macrophages to atherosclerotic lesions and activates the production of matrix proteinases, which in turn destabilize atherosclerotic plaques. On the other hand, miR33 coordinates the expression of several sterol transporters essential for high-density lipoprotein metabolism and bile secretion. Thus, both MIF and miR-33 are promising therapeutic targets to manage patients at risk of developing atherosclerosis.
Conjugated Conduction-Free Convection Heat Transfer in an Annulus Heated at Either Constant Wall Temperature or Constant Heat Flux

In this paper, we investigate numerically the effect of thermal boundary conditions on conjugated conduction-free convection heat transfer in an annulus between two concentric cylinders using Fourier Spectral method. The inner wall of the annulus is heated and maintained at either CWT (Constant Wall Temperature) or CHF (Constant Heat Flux), while the outer wall is maintained at constant temperature. CHF case is relatively more significant for high pressure industrial applications, but it has not received much attention. This study particularly focuses the latter case (CHF). The main influencing parameters on flow and thermal fields within the annulus are: Rayleigh number Ra; thickness of inner wall Rs; radius ratio Rr and inner wall-fluid thermal conductivity ratio Kr. The study has shown that the increase in Kr increases the heat transfer rate through the annulus for heating at CWT and decreases the inner wall dimensionless temperature for heating at CHF and vice versa. It has also been proved that as the Rs increases at fixed Ra and Rr, the heat transfer rate decreases for heating at CWT and the inner wall dimensionless temperature increases for heating at CHF at Kr <1. The study has also discussed that the effect of increase in Rs for both cases of heating at Kr>1 depends on Rr. It has been shown that for certain combinations of controlling parameters there will be a value of Rr at which heat transfer rate will be minimum in the annulus in case of heating at CWT, while there will be a value of Rr at which inner wall dimensionless temperature will be maximum in case of heating at CHF.
Post-Radiation Metabolic Tumor Volume Predicts Outcome in Head-and-Neck Cancer

Purpose— To explore the prognostic value of metabolic tumor volume measured on post-radiation 18 F-fluorodeoxyglucose positron emission tomography (PET) imaging in head-and-neck cancer patients. Methods and Materials— Forty-seven head-and-neck cancer patients who received pre- and post-treatment PET/CT imaging along with definitive chemoradiotherapy were included in this study. PET/CT parameters evaluated include the maximum standardized uptake value, metabolic tumor volume (MTV 2.0 -MTV 4.0 ; where MTV 2.0 refers to the volume above an SUV threshold of 2.0), and integrated tumor volume. Kaplan-Meier and Cox-regression models were used to test for association between PET endpoints and disease-free survival (DFS) and overall survival (OS). Results— Multiple post-radiation PET endpoints correlated significantly with outcome, however the most robust predictor of disease progression and death was MTV 2.0 . An increase in MTV 2.0 of 21cm 3 (difference between 75 th and 25 th percentile) was associated with an increased risk of disease progression (hazard ratio [HR]=2.5, p =0.0001) and death (HR=2.0, p =0.003). In patients with non-nasopharyngeal carcinoma (non-NPC) histology (n=34), MTV 2.0 <18cm 3 and MTV 2.0 ≥ 18cm 3 yielded 2-year DFS rates of 100% and 63%, respectively ( p =0.006) and 2-year OS rates of 100% and 81%, respectively ( p =0.009). There was no correlation between MTV 2.0 and DFS or OS with NPC histology (n=13). On multivariate analysis only post-radiation MTV 2.0 was predictive of DFS (HR=2.47, p =0.0001) and OS (HR=1.98, p =0.003). Conclusions— Post-radiation metabolic tumor volume is an adverse prognostic factor in head-and-neck cancer. Biomarkers such as MTV are important for risk stratification, and will be valuable in the future with risk-adapted therapies.
Formation of Sub-Nuclear Foci is a Novel Spatial Behavior of Mating MAPKs during Hyper-Osmotic Stress

SUMMARY The assembly of signaling components and transcription factors in ordered subcellular structures is increasingly implicated as an important regulatory strategy to modulate the activity of cellular pathways. Here, we document the inducible formation of sub-nuclear foci formed by two mitogen-activated protein kinases (MAPKs) in Saccharomyces cerevisiae upon hyper-osmotic stress. Specifically, we demonstrate that activation of the hyper-osmotic stress response pathway induces the mating pathway MAPK Fus3 and the filamentation pathway MAPK Kss1 to form foci in the nucleus that are organized by their shared downstream transcription factor Ste12. Foci formation of co-localized Ste12, Fus3, and Kss1 requires the kinase activity of the hyper-osmotic response MAPK Hog1 and correlates with attenuated signaling in the mating pathway. Conversely, activation of the mating pathway prevents foci formation upon subsequent hyper-osmotic stress. These results suggest that Hog1-mediated spatial localization of Fus3 and Ste12 into sub-nuclear foci could contribute to uncoupling the pheromone and osmolarity pathways, which share signaling components, under high osmolarity conditions. These data indicate that pre-activation of Ste12 by pheromone signaling inhibits the formation of Fus3/Kss1/Ste12 foci upon subsequent hyper-osmotic stress and abrogates the hyper-osmotic stress inhibition of the pheromone pathway output. These results are consistent with the hypothesis that spatial localization of Fus3, Kss1 and Ste12 into foci
Systematic Review: The Association and Impact of Financial Conflicts of Interest in Basic Science Research

Background— No prior study has evaluated financial relationships of investigators with pharmaceutical manufacturers for basic science. An example of the importance and impact of such relationships is in the evaluation of erythropoietin receptors’(EpoRs) effects on cancer cell lines, since studies have reported increased mortality when cancer patients receive erythropoiesis stimulating agents (ESAs). Purpose— To assess the disclosed association that exist between pharmaceutical industry support and EpoRs effects on solid cancer cell lines. Data Sources— MEDLINE and EMBASE (1988- July 2008) and two EpoR conferences sponsored by the National Institutes of Health. Study Selection— All publications investigating EpoRs that met inclusion criteria were identified and included. Data Extraction— Data were extracted on detection of EpoRs, presence of erythropoietin-induced signaling events, presence of erythropoietin-induced changes in cellular function, nature of qualitative conclusions, and sources of funding for all 74 studies. Data Synthesis— In comparison to studies of academic investigators with no disclosed funding support from ESA manufacturers (n=64), the studies from academic investigators with funding support from ESA manufacturers (n= 7) and the laboratories directed by investigators employed by ESA manufacturers (n=3) were both less likely to identify: EpoR presence on solid tumor cells; erythropoietin-induced signaling events; erythropoietin-induced changes in cellular function; and less likely to conclude that their research had identified potentially harmful effects of erythropoietin on cancer cells. Additionally, presentations from industry-based investigator teams at NIH conferences were less likely to report EpoRs on cancer cell lines, downstream effects of erythropoietin, and cell proliferation and migration effects following EpoR administration. Conclusion— Financial conflicts of interest impact the outcomes and presentation of basic science research data as well as publications. METHODS articles investigating EpoRs in solid tumors (Keywords: (Erythropoietin (Epo), erythropoietin receptor (EpoR)) AND (cancer, tumor, malignancy, carcinoma)). detection of EpoRs, presence of erythropoietin-induced signaling in apoptosis, hypoxia-inducible EpoR angiogenesis,
Model for predicting the success of public–private partnership infrastructure projects in developing countries: a case of Ghana

ABSTRACT This paper develops a practical tool for predicting public–private partnership (PPP) project success in developing countries using Ghana as example. The predictive model examines the causal relationship between CSFs and success criteria for PPP projects. First, a conceptual model for PPP projects success was proposed. Second, the theoretical model was tested by means of a questionnaire survey with experienced PPP experts. Using the regression analysis technique, a predictive model for PPP project success was developed. The regression model shows three best predictors of PPP project success in Ghana, these include; appropriate risk allocation and sharing, sound economic policy and right project identification. Various statistical tests including ANOVA, tolerance and variance inflation factor (VIF), homoscedasticity and Durbin–Watson tests confirmed the validity and goodness of fit for the model. The substantive model will enable PPP practitioners including designers, public clients and engineers in Ghana and other neighbouring developing countries particularly sub-Saharan Africa to predict the likely success of their PPP projects prior to their implementations.
Distribution and phenotypes of unipolar brush cells in relation to the granule cell system of the rat cochlear nuclear nucleus

In most mammals the cochlear nuclear complex (CN) contains a distributed system of granule cells (GCS), whose parallel fiber axons innervate the dorsal cochlear nucleus (DCN). Like their counterpart in cerebellum, CN granules are innervated by mossy fibers of various origins. The GCS is complemented by unipolar brush (UBCs) and Golgi cells, and by stellate and cartwheel cells of the DCN. This cerebellum-like microcircuit modulates the activity of the DCN’s main projection neurons, the pyramidal, giant and tuberculoventral neurons, and is thought to improve auditory performance by integrating acoustic and proprioceptive information. In this paper, we focus on the UBCs, a chemically heterogeneous neuronal population, using antibodies to calretinin, mGluR1 α epidermal growth factor substrate 8 (Eps8) and the transcription factor Tbr2. Eps8 and Tbr2 labeled most of the CN’s UBCs, if not the entire population, while calretinin and mGluR1 α distinguished two largely separate subsets with overlapping distributions. By double labeling with antibodies to Tbr2 and the α 6 GABA A -receptor subunit, we found that UBCs populate all regions of the GCS and occur at remarkably high densities in the DCN and subpeduncular corner, but rarely in the lamina. Although GCS subregions likely share the same microcircuitry, their dissimilar UBC densities suggest they may be functionally distinct. UBCs and granules are also present in regions previously not included in the GCS, namely the rostrodorsal magnocellular portions of VCN, vestibular nerve root, trapezoid body, spinal tract and sensory and principal nuclei of the trigeminal nerve, and cerebellar peduncles. The UBC’s dendritic brush receives AMPA- and NMDA-mediated input from an individual mossy fiber, favoring singularity of input, and its axon most likely forms several mossy fiber-like endings that target numerous granule cells and other UBCs, as in the cerebellum. The UBCs therefore, may amplify afferent signals temporally and spatially, synchronizing pools of target neurons.
Acute ethanol effects on local cerebral glucose utilization in select CNS regions of adolescent alcohol-preferring (P) and alcohol-nonpreferring (NP) rats

Background— Alcohol abuse among adolescents is a major health and developmental problem. The 2-[14C]deoxyglucose (2-DG) technique allows for the in vivo quantification of local cerebral glucose utilization (LCGU) as a measure of functional neuronal activity. Methods— LCGU rates were examined after acute ethanol administration within selected brain regions of adolescent alcohol-preferring (P) and -nonpreferring (NP) rats. Postnatal day 45 male P and NP rats were injected with saline or 1.0 g/kg ethanol, i.p. , 10 min prior to an intravenous bolus of [ 14 C]-2-Deoxyglucose (125 μ Ci/kg). Image densities were determined using quantitative autoradiography and LCGU values calculated. Results— Acute ethanol injection significantly decreased LCGU rates in select brain regions including the olfactory tubercles (OTU), the frontal cortex (Fr) and subregions of the posterior hippocampus (pCA1 and pCA3). Acute ethanol had no significant effects on LCGU rates in any region of the adolescent NP rats. Significant basal LCGU rate differences were apparent between the rat lines in a nearly global fashion with adolescent P rats having much higher basal LCGU rates compared to adolescent NP rats. Conclusions— the adolescent P and NP rats are sensitive to the effects of acute ethanol than their adult counterparts. The adolescent P rat is relatively more sensitive to the initial effects of acute ethanol in select brain regions as compared to the adolescent NP rat. Additionally, the innate hyper-excited state of the adolescent P CNS is a likely factor in the development of their high alcohol drinking behaviors.
Are instrumented knee forces representative of a larger population of cruciate-retaining total knee replacements?

, Abstract Background— It is not known if the loads and motions reported for instrumented knees are generalizable to a larger population of total knee replacement (TKR) patients. The purpose of this study is to: 1) report axial implant force data for chair and stair activities for a population of cruciate-retaining TKR patients and 2) compare the population forces to those measured with instrumented TKRs. Methods— Twenty-three subjects with a cruciate-retaining TKR underwent motion analysis during stair ascending, stair descending, chair sitting, and chair rising activities after informed consent in this IRB approved study. Axial TKR forces were calculated using a previously validated computational model. Differences between the mean and variability of population instrumented TKR peak forces and force impulses were tested using t-tests and Levene’s test. Results— Peak axial forces were 3.06, 2.74, 2.65, and 2.60 kN for stair ascent, stair descent, chair rising, and chair sitting, respectively. Force impulses were 123.3, 123.4, 153.5, and 154.0 kN*% activity cycle for stair ascent, stair descent, chair sitting, and chair rising, respectively. Population TKR and instrumented TKR peak forces were different for stair ascent (p=0.03) and stair descent (p=0.03) in the second half of the activity cycles. The variability of the peak forces and impulses were not different (p=0.106 to p=0.99) Conclusion— The forces and motions presented in this study represent cruciate-retaining TKR patients and could be used for displacement-driven knee wear testing. population of TKR patients, or what effect using inputs that are not population specific for testing of a particular TKR design will have on wear testing. The purpose of this study is to: 1) to report axial implant force data for chair and stair activities for a population of TKR patients implanted with a modern cruciate-retaining implant design and 2) compare the population forces to patient-specific forces measured with instrumented total knee replacements. This study will help determine if force waveform recommendations are representative of a larger population of TKR patients providing insight into considerations for wear simulation, numerical modeling, and implant design.