Miracle-dz/UniFAR-FTUs huggingface dataset:
Immune Protection Function of Multipotent Mesenchymal Stromal Cells: Role of Transforming Growth Factor-β1

The immunosuppressive functions of multipotent mesenchymal stromal cells (MSCs) may give cancer cells a survival advantage. This study tests the hypothesis that MSCs protect leukemia cells from immune clearance. Our results demonstrate that MSCs are capable of inhibiting peripheral blood mononuclear cells (PBMNCs) proliferation and their migration toward leukemic cells by the reduction of CCL5 and CXCL12. In addition, we find that MSCs can inhibit the cytolytic functions of NK-cells and CTLs. TGF-β1 secreted by MSCs is responsible for impaired CTLs and NK function by down-modulating surface NKG2D expression. These inhibitory functions of MSCs have negative effects on the CTLs or NK-mediated graft-versus-leukemia (GVL), particularly in the allogeneic hematopoietic stem cells transplantation setting.
Use of internally nuclease‐protected single‐strand DNA oligonucleotides and silencing of the mismatch repair protein, MSH2, enhances the replication of corrected cells following gene editing

Gene editing is potentially a powerful technology for introducing genetic changes by using short single‐stranded DNA oligonucleotides (ssODNs). However, their efficiency is reduced by the mismatch repair system, especially MSH2, which may suppress gene editing, although findings vary depending on readout and type of oligonucleotide used. Additionally, successfully edited cells are reported to arrest at the S‐ or G2‐phase. In the present study, we evaluate whether a novel ssODN design and down‐regulation of MSH2 expression allows the isolation of replicating gene‐edited cells.
Chronic Recurrent Subarachnoid Hemorrhage from a Trigeminal Nerve Malignant Peripheral Nerve Sheath Tumor: Case Report

OBJECTIVE:Clinically significant intratumoral or peritumoral bleeding from trigeminal nerve tumors is very rare. CLINICAL PRESENTATION:We report the case of a 59-year-old man who presented with recurrent subarachnoid hemorrhage from a left trigeminal nerve malignant peripheral nerve sheath tumor. He presented with decreased consciousness, left facial hypesthesia, and left facial weakness. Trigeminal neuralgia was present for 18 months. Cranial computed tomographic and magnetic resonance imaging scans revealed a left parapontine mass with cystic changes and intratumoral bleeding. Furthermore, signs of hemosiderosis of the subarachnoid space were noted. Lumbar puncture revealed fresh bleeding. Angiography detected no aneurysm or other causes of bleeding. The patient became fully alert within hours, the facial weakness improved within a few days. There was no evidence of vasospasm or persisting hydrocephalus. He underwent left-sided suboccipital craniotomy for macroscopically total tumor removal. INTERVENTION:The patient underwent total tumor removal via a left suboccipital approach. Intraoperatively, evidence of recurrent intratumoral bleeding was noted. Histological examination revealed a malignant peripheral nerve sheath tumor (World Health Organization Grade III). Postoperatively, the hypesthesia improved significantly. The patient was transferred to radiotherapy for external beam radiation. CONCLUSIONS:This is the first report regarding a malignant peripheral nerve sheath tumor of the trigeminal nerve that caused clinically significant subarachnoid hemorrhage caused by intratumoral bleeding.
Steroid Hormone Actions on the Brain: When Is the Genome Involved?

It has become customary to distinguish between so-called "genomic" actions of steroid hormones involving intracellular receptors and "non-genomic" effects of steroids that involve putative cell surface receptors. Whereas there is no doubt that this distinction has considerable validity, it does not go far enough in addressing the variety of mechanisms that steroid hormones use to produce their effects on cells. This is because cell surface receptors may signal changes in gene expression, while genomic actions sometimes affect neuronal excitability, often doing so quite rapidly. Moreover, steroid hormones and neurotransmitters may operate together to produce effects, and sometimes these effects involve collaborations between groups of neurons. As illustrations, evidence is reviewed in this article that a number of steroid actions in the hippocampus involves the co-participation of excitatory amino acids. These interactions are evident for the regulation of synaptogenesis by estradiol in the CA1 pyramidal neurons of hippocampus and for the induction of dendritic atrophy of CA3 neurons by repeated stress as well as by glucocorticoid injections. In addition, neurogenesis in the adult and developing dentate gyrus is "contained" by adrenal steroids as well as by excitatory amino acids. In each of these three examples, NMDA receptors are involved. These results not only point to a high degree of interdependency between certain neurotransmitters and the actions of steroid hormones but also emphasize the degree to which structural plasticity is an important aspect of steroid hormone action in the adult as well as developing nervous system.
The genetics of uveal melanoma: an emerging framework for targeted therapy

Uveal melanoma is the second most common form of melanoma and the most common primary intraocular malignancy. Until recently, very little was known about the genetics of this aggressive cancer. Mutations in oncogenes and tumor suppressors that are common in other cancers are conspicuously absent in uveal melanoma. In recent years, however, uveal melanoma has begun to yield its secrets, and a fascinating picture is emerging of how it develops and progresses. Mutations in the Gq alpha subunits, encoded by GNAQ and GNA11, appear to be early or perhaps initiating events that require further mutations for malignant transformation. On the other hand, mutations in the BRCA1‐associated protein‐1 (BAP1) appear to occur later and demarcate a molecular brink beyond which metastasis becomes highly likely. BAP1 mutations can also occur in the germline, leading to a distinctive cancer predisposition syndrome. These mutations appear to be key events that provide the potential for targeted therapy. This article will review the genetic findings in uveal melanoma over the past two decades and suggest important areas for future work.
Diversity of Nitrite Reductase (nirK and nirS) Gene Fragments in Forested Upland and Wetland Soils

ABSTRACT The genetic heterogeneity of nitrite reductase gene (nirK and nirS) fragments from denitrifying prokaryotes in forested upland and marsh soil was investigated using molecular methods. nirK gene fragments could be amplified from both soils, whereas nirS gene fragments could be amplified only from the marsh soil. PCR products were cloned and screened by restriction fragment length polymorphism (RFLP), and representative fragments were sequenced. The diversity of nirK clones was lower than the diversity of nirS clones. Among the 54 distinct nirK RFLP patterns identified in the two soils, only one pattern was found in both soils and in each soil two dominant groups comprised >35% of all clones. No dominance and few redundant patterns were seen among the nirS clones. Phylogenetic analysis of deduced amino acids grouped the nirK sequences into five major clusters, with one cluster encompassing most marsh clones and all upland clones. Only a few of the nirK clone sequences branched with those of known denitrifying bacteria. The nirS clones formed two major clusters with several subclusters, but all nirS clones showed less than 80% identity to nirS sequences from known denitrifying bacteria. Overall, the data indicated that the denitrifying communities in the two soils have many members and that the soils have a high richness of different nir genes, especially of the nirS gene, most of which have not yet been found in cultivated denitrifiers.
Standardization of direct susceptibility test for blood cultures

Insufficient data are available to establish the reliability of direct disk diffusion susceptibility tests performed utilizing positive blood culture broth as inoculum. When Staphylococcus aureus ATCC 25923, Escherichia coli ATCC 25922, and Pseudomonas aeruginosa ATCC 27853 were used, 0.03 ml of turbid overnight blood culture broth was found to produce zone diameters closely approximating the size of diameters obtained by a standardized method. Results of direct (0.03 ml of inoculum) and standardized susceptibility tests were then compared for 116 positive blood cultures (1,069 individual disk comparisons). There were 1,011 test agreements (94.6%). There were also 48 (4.5%) minor discrepancies (change between sensitive and intermediate or between intermediate and resistant) and 10 (0.9%) major discrepancies (change between sensitive and resistant). The major discrepancies were randomly distributed among several organisms and antibiotics. Discrepancies occurred most frequently in the more clinically acceptable direction; i.e., in 79.3% the direct test indicted greater resistance than the standardized test. These data establish that 0.03 ml of turbid overnight blood culture broth produces results which compare closely to those obtained with standard methods, and in practice yield direct susceptibility results with a clinically acceptable level of reliability.
Rethinking Speed Theories of Cognitive Development

Researchers have suggested that developmental improvements in immediate recall stem from increases in the speed of mental processes. However, that inference has depended on evidence from correlation, regression, and structural equation modeling. We provide counter-examples in two experiments in which the speed of spoken recall was manipulated. In one experiment, second-grade children and adults recalled lists of digits more quickly than usual when the lists were presented at a rapid rate of two items per second. In a second experiment, children received lists at a rate of one item per second; half the children were trained (successfully) to speak their responses more quickly than usual, at a rate similar to adults' usual rate. Recall accuracy was completely unaffected by either of these response-speed manipulations. Thus, although response rate is a strong marker of an individual's maturational level, it does not appear to determine the accuracy of immediate recall. These results have important methodological and theoretical implications for human development.
Ultrastructural study of the primary olfactory pathway in Macaca fascicularis

Olfactory ensheathing glial cells (OEGs) interact with a wide repertoire of cell types and support extension of olfactory axons (OAs) within the olfactory pathway. OEGs are thought to exclude OAs from contact with all other cells between the olfactory epithelium and the glomerulus of the olfactory bulb. These properties have lead to testing to determine whether OEGs support axonal growth following transplantation. The cellular interactions of transplanted OEGs will probably resemble those that occur within the normal pathway where interactions between OEGs and fibroblasts are prominent. No previous primate studies have focused on these interactions, knowledge of which is important if clinical application is envisioned. We describe the detailed intercellular interactions of OAs with supporting cells throughout the olfactory epithelium, the lamina propria, the fila olfactoria, and the olfactory nerve layer by using transmission electron microscopy in adult Macaca fascicularis. Patterns of OEG ensheathment and variations of the endo‐ and perineurium formed by olfactory nerve fibroblasts are described. OAs mainly interacted with horizontal basal cells, OEGs, and astrocytes. At both transitional ends of the pathway seamless intercellular interactions were observed, and fibroblast processes were absent. Perineurial cells produced surface basal lamina; however, endoneurial, epineurial, and meningeal fibroblasts did not. Perineurial cells contained intermediate filaments and were distinct from other fibroblasts and meningeal cells. OAs had direct contacts with astrocytes near the glia limitans. The properties of OEGs differed depending on whether astrocytic or fibroblastic processes were present. This indicates the importance of the cellular milieu in the structure and function of OEGs in primates. J. Comp. Neurol. 488:427–441, 2005. © 2005 Wiley‐Liss, Inc.
Occurrence of yeasts in faecal samples from Antarctic and South American seabirds

During an expedition to the Southern Argentinean town of Ushuaia, the Antarctic Peninsula, Antarctic Islands and the Falkland Islands, we collected 94 faecal specimens from wild birds to screen for yeast within the different bird species. The yeast species were identified by morphological features and commercial characterisation kits. From 54% of the specimens, we isolated 122 strains representing 29 yeast species. Debaryomyces hansenii, Candida lambica and Candida krusei were the most frequently isolated species. We found a plethora of yeasts in birds living in proximity to humans, whereas birds living in more remote areas were colonised with a lower number of fungal species.
The addition of interleukin-6 soluble receptor and transforming growth factor beta1 improves a preoperative nomogram for predicting biochemical progression in patients with clinically localized prostate cancer.

PURPOSE Several preoperative prostate cancer nomograms have been developed that predict risk of progression using pretreatment prostate-specific antigen (PSA) level, clinical stage, and biopsy Gleason grade. We describe the development and performance of a new nomogram. The nomogram adds new markers to the standard clinical predictors that reflect the biologic behavior of prostate cancer: pretreatment plasma levels of interleukin-6 soluble receptor (IL6SR) and transforming growth factor beta1 (TGF-beta1). PATIENTS AND METHODS Between November 7, 1994 and December 22, 1997, 714 patients with stage cT1c to cT3a prostate cancer and no prior therapy were treated with radical prostatectomy at the Methodist Hospital, Houston TX. Plasma levels of IL6SR and TGF-beta1 were measured in banked preoperative plasma. With these data, a nomogram was developed to predict the probability of PSA progression within 5 years of surgery. The nomogram was validated with bootstrapping to assess its discrimination and calibration performance. RESULTS In the multivariable Cox model, PSA (P =.004), IL6SR (P <.001), TGF-beta1 (P <.001), primary Gleason grade (P <.002), and secondary Gleason grade (P =.029) were associated with PSA progression, whereas clinical stage (P =.696) was not. The nomogram seemed to be well calibrated and had a bootstrap-corrected area under the receiver operating characteristic curve (ie, concordance index) of 0.83. For comparison, a nomogram that omitted IL6SR and TGF-beta1 achieved a concordance index of only 0.75. CONCLUSION We found that pretreatment plasma levels of IL6SR and TGF-beta1 improved the ability to predict biochemical progression by a prognostically substantial margin. A nomogram including the pretreatment levels of these molecular markers, along with standard clinical markers, has been developed and internally validated.
Efficacy and safety of high‐dose pravastatin in hypercholesterolemic patients with well‐compensated chronic liver disease: Results of a prospective, randomized, double‐blind, placebo‐controlled, multicenter trial

The hepatotoxic potential of 3‐hydroxy‐3‐methylglutaryl coenzyme A reductase inhibitors in patients with underlying chronic liver disease remains controversial. We performed a multicenter, randomized, double‐blind, placebo‐controlled, parallel‐group trial that compared pravastatin (80 mg) to a placebo administered once daily to hypercholesterolemic subjects greater than 18 years of age with at least a 6‐month history of compensated chronic liver disease and with a low‐density lipoprotein cholesterol (LDL‐C) level greater than or equal to 100 mg/dL and a triglyceride (TG) level lower than 400 mg/dL. The efficacy was determined by the percentage change in LDL‐C [along with the total cholesterol (TC), high‐density lipoprotein cholesterol, and TG] from the baseline to week 12. The safety was analyzed by the proportion of subjects who developed at least 1 alanine aminotransferase (ALT) value greater than or equal to 2 times the upper limit of normal for those with normal ALT at the baseline or a doubling of the baseline ALT for those with elevated ALT at the baseline during 36 weeks of treatment. A total of 630 subjects were screened, and 326 subjects were randomized; nonalcoholic fatty liver disease was present in 64%, and chronic hepatitis C was present in 23%. In the intent‐to‐treat population, pravastatin (80 mg/day) significantly lowered the mean LDL‐C, TC, and TG values at week 12 and at other times (weeks 4, 8, 24, and 36) in comparison with the placebo. The incidence of subjects who met the primary prespecified ALT event definition was lower in the pravastatin group at all times over the 36 weeks of therapy in comparison with the placebo group, although the difference was not statistically significant. No differences were seen on the basis of the baseline ALT values or among the different liver disease groups. Conclusion: High‐dose pravastatin (80 mg/day) administered to hypercholesterolemic subjects with chronic liver disease significantly lowered LDL‐C, TC, and TGs in comparison with the placebo and was safe and well tolerated. The concern over an increased potential for statin‐induced hepatotoxicity in patients with chronic liver disease appears to be lessened on the basis of these results. (HEPATOLOGY 2007.)
Novel Wavelet Approach to Current Differential Pilot Relay Protection

This paper describes a novel technique for current differential pilot relay protection (CDPR) by using wavelet analysis. PSCAD is used to generate current signals at both ends of a transmission line in a typical system with fault at various locations. Discriminating between internal fault and extemal fault/change, identifying of faulted phase, and classifying fault type are achieved by using wavelet analysis. The simulation results show that this approach provides a high operating sensitivity for internal fault and remains stable for external fault/change.
Modulation of GABAergic transmission by endogenous glutamate in the rat supraoptic nucleus

The presence of group III metabotropic glutamate receptors on GABAergic terminals in the supraoptic nucleus suggests that the level of glutamate in the extracellular space may regulate synaptic strength at inhibitory synapses. To test this hypothesis we examined the consequences of increasing ambient glutamate on GABA‐mediated synaptic activity in supraoptic neurons. The concentration of the excitatory amino acid in the extracellular space was increased pharmacologically by blocking glutamate transporters. Inhibition of the astrocyte‐specific GLT‐1 glutamate transporter led to a reversible decrease in evoked inhibitory postsynaptic current amplitude. This modulation had a presynaptic origin as revealed by analysis of paired‐pulse ratio and miniature inhibitory currents. Furthermore, blocking group III metabotropic glutamate receptors with the specific antagonist MAP4 prevented the depression of GABAergic transmission induced by glutamate transporter blockade. Thus, presynaptic metabotropic glutamate receptors located on inhibitory terminals in the supraoptic nucleus appear to sense changes in ambient glutamate and modify GABA release accordingly. However, it seems that such changes need to reach a certain magnitude because the discrete deficit in glutamate clearance which occurs in the supraoptic nucleus of lactating rats is not sufficient to modulate GABA‐mediated transmission. These results suggest that ambient glutamate contributes to the modulation of synaptic efficacy not only at glutamatergic synapses but also at inhibitory GABAergic synapses.
Thermal Design of an Integrated Motor Drive

A drive based on a matrix power converter for a 30 kW totally enclosed, fan cooled induction motor was developed to be fully integrated within the spatial envelope of the motor, located inside the end cover at the fan end of the machine. This paper describes the thermal design of the motor to dissipate the losses from the drive, which were approximately a third of those from the motor. The power electronic components were mounted on the inside of a new end cover which was equipped with an extensive array of fins cooled by air from the external fan. The electronic components were insulated from the air in the end region of the motor. A heat sink plate was installed within the motor behind the end cover to conduct the heat from the motor that would otherwise have been dissipated through the end cover. Computational fluid dynamics (CFD) was used to model the ventilation and heat transfer from the new end cover and to develop improved fan geometries. It was concluded that CFD can be used effectively to design motor cooling systems. An improved fan geometry was designed to keep the power electronics cool under high ambient temperatures with the motor running at full load
SDC25, a CDC25-like gene which contains a RAS-activating domain and is a dispensable gene of Saccharomyces cerevisiae

In the yeast Saccharomyces cerevisiae, the CDC25 gene product activates adenylate cyclase through RAS1 and RAS2 gene products. We have recently described the cloning of a DNA fragment which suppresses the cdc25 mutation but not ras1, ras2, or cdc35 mutations. This fragment contains a 5'-truncated open reading frame which shares 47% identity with the C-terminal part of the CDC25 gene. We named the entire gene SDC25. In this paper, we report the cloning, sequencing, and characterization of the complete SDC25 gene. The SDC25 gene is located on the chromosome XII close to the centromere. It is transcribed into a 4-kb-long mRNA that contains an open reading frame of 1,251 codons. Homology with the CDC25 gene extends in the N-terminal part, although the degree of similarity is lower than in the C-terminal part. In contrast with the C-terminal part, the complete SDC25 gene was found not to suppress the CDC25 gene defect. A deletion in the N-terminal part restored the suppressing activity, a result which suggests the existence of a regulatory domain. The SDC25 gene was found to be dispensable for cell growth under usual conditions. No noticeable phenotype was found in the deleted strain.
How Does Stigma “Get Under the Skin”?

Stigma is a risk factor for mental health problems, but few studies have considered how stigma leads to psychological distress. The present research examined whether specific emotion-regulation strategies account for the stigma-distress association. In an experience-sampling study, rumination and suppression occurred more on days when stigma-related stressors were reported than on days when these stressors were not reported, and rumination mediated the relationship between stigma-related stress and psychological distress. The effect of social support on distress was moderated by the concealability of the stigma: Lesbian, gay, and bisexual (LGB) respondents reported more isolation and less social support than African American respondents subsequent to experiencing stigma-related stressors, whereas African Americans reported greater social support than LGB participants. Social isolation mediated the stigma-distress association among LGB respondents. In a second experimental study, participants who ruminated following the recall of an autobiographical discrimination event exhibited prolonged distress on both implicit and explicit measures relative to participants who distracted themselves; this finding provides support for a causal role of rumination in the stigma-distress relationship.