Miracle-dz/UniFAR-FTUs huggingface dataset:
Piwil 2 Expression Is Correlated with Disease-Specific and Progression-Free Survival of Chemotherapy-Treated Bladder Cancer Patients

Piwi-like 2 (Piwil 2) belongs to the family of Argonaute genes/proteins. The expression of Piwil 2 is associated with stem cells. A role in tumorigenesis and/or tumor progression is proposed for different cancers but not yet for bladder cancer (BCa). We investigated Piwil 2 expression by immunohistochemistry in a cohort of 202 BCa patients treated by cystectomy and adjuvant chemotherapy. The association between Piwil 2 expression and disease-specific (DSS) or progression-free survival (PFS) was calculated using Kaplan-Meier analyses and univariate/multivariate Cox regression hazard models. In a multivariate Cox regression analysis, Piwil 2 expression, either in the cytoplasm or the nucleus, was significantly associated with DSS and PFS. A weak cytoplasmic staining pattern was associated with poor DSS and tumor progression (relative risk [RR] = 2.7, P = 0.004, and RR = 2.4, P = 0.027). Likewise, absent nuclear Piwil 2 immunoreactivity was associated with poor DSS and tumor progression (RR = 2.3, P = 0.023, and RR = 2.2, P = 0.022). BCa patients whose tumors exhibited a combination of weak cytoplasmic and absent nuclear immunoreactivity had a 6-fold increased risk of tumor-related death (P = 0.005) compared with patients with strong expression. Considering only patients with high-grade G3 tumors, a 7.8-fold risk of tumor-associated death and a 3.6-fold risk of tumor progression were detected independently of the histologic tumor subtype or the chemotherapy regimen. In summary, a combination of weak cytoplasmic and absent nuclear expression of Piwil 2 is significantly associated with an increased risk of DSS and tumor progression. This indicates that Piwil 2 could be a valuable prognostic marker for high-risk BCa patients.
FORCE‐‐TIME CURVE CHARACTERISTICS OF DYNAMIC AND ISOMETRIC MUSCLE ACTIONS OF ELITE WOMEN OLYMPIC WEIGHTLIFTERS

Six elite women weightlifters were tested to evaluate force–time curve characteristics and intercorrelations of isometric and dynamic muscle actions. Subjects performed isometric and dynamic mid-thigh clean pulls at 30% of maximal isometric peak force and 100 kg from a standardized position on a 61.0 X 121.9 cm AMTI forceplate. Isometric peak force showed strong correlations to the athletes' competitive snatch, clean and jerk, and combined total (r = 0.93, 0.64, and 0.80 respectively). Isometric rate of force development showed moderate to strong relationships to the athletes' competitive snatch, clean and jerk, and combined total (r = 0.79, 0.69, and 0.80 respectively). The results of this study suggest that the ability to perform maximal snatch and clean and jerks shows some structural and functional foundation with the ability to generate high forces rapidly in elite women weightlifters.
The vaccinia virus I1 protein is essential for the assembly of mature virions

The product of the vaccinia virus I1 gene was characterized biochemically and genetically. This 35-kDa protein is conserved in diverse members of the poxvirus family but shows no homology to nonviral proteins. We show that recombinant I1 binds to both single-stranded and double-stranded DNA in a sequence-nonspecific manner in an electrophoretic mobility shift assay. The protein is expressed at late times during infection, and approximately 700 copies are encapsidated within the virion core. To determine the role of the I1 protein during the viral life cycle, a inducible viral recombinant in which the I1 gene was placed under the regulation of the Escherichia coli lac operator/repressor was constructed. In the absence of isopropyl-beta-D-thiogalactopyranoside, plaque formation was abolished and yields of infectious, intracellular virus were dramatically reduced. Although all phases of gene expression and DNA replication proceeded normally during nonpermissive infections, no mature virions were produced. Electron microscopic analysis confirmed the absence of mature virion assembly but revealed that apparently normal immature virions accumulated. Thus, I1 is an encapsidated DNA-binding protein required for the latest stages of vaccinia virion morphogenesis.
Controlling Specific Locomotor Behaviors through Multidimensional Monoaminergic Modulation of Spinal Circuitries

Descending monoaminergic inputs markedly influence spinal locomotor circuits, but the functional relationships between specific receptors and the control of walking behavior remain poorly understood. To identify these interactions, we manipulated serotonergic, dopaminergic, and noradrenergic neural pathways pharmacologically during locomotion enabled by electrical spinal cord stimulation in adult spinal rats in vivo. Using advanced neurobiomechanical recordings and multidimensional statistical procedures, we reveal that each monoaminergic receptor modulates a broad but distinct spectrum of kinematic, kinetic, and EMG characteristics, which we expressed into receptor-specific functional maps. We then exploited this catalog of monoaminergic tuning functions to devise optimal pharmacological combinations to encourage locomotion in paralyzed rats. We found that, in most cases, receptor-specific modulatory influences summed near algebraically when stimulating multiple pathways concurrently. Capitalizing on these predictive interactions, we elaborated a multidimensional monoaminergic intervention that restored coordinated hindlimb locomotion with normal levels of weight bearing and partial equilibrium maintenance in spinal rats. These findings provide new perspectives on the functions of and interactions between spinal monoaminergic receptor systems in producing stepping, and define a framework to tailor pharmacotherapies for improving neurological functions after CNS disorders.
The molecular basis of thalassaemia major and thalassaemia intermedia in Asian Indians: application to prenatal diagnosis

A study of the molecular pathology of β thalassaemia in the Asian Indian immigrant population in the U.K. included 37 patients with thalassaemia major and 14 with thalassaemia intermedia. Using a combination of oligonucleotide probe hybridization and restriction endonuclease analysis the mutations in 100/102 (98%) of the β thalassaemia genes were characterized. Nine different types were found, of which six are associated with β, one with severe β+ and two with mild β+ thalassaemia. Comparison of the β‐globin gene cluster haplotypes, α globin genotypes and β gene mutations of the thalassaemia major group with the thalassaemia intermedia group suggests that the co‐inheritance of a high Hb F determinant associated with the ‐ + ‐ ++ 5’β haplotype and the inheritance of a mild β‐thalassaemia mutation are the major ameliorating factors of disease severity in Asian Indians. In comparison with other population groups, β thalassaemia in Asian Indians is not associated with one or two predominant mutations. Despite this, prenatal diagnosis by direct detection is possible in the majority of families by restriction analysis and a limited number of oligonucleotide probes since the majority of severely affected individuals are homozygous for a single mutation. The characterization of these mutations should be useful for the planning of prenatal diagnosis programmes for β thalassaemia in other Asian Indian communities.
Optimization of Bacteriocin Production by Batch Fermentation of Lactobacillus plantarum LPCO10

ABSTRACT Optimization of bacteriocin production by Lactobacillus plantarum LPCO10 was explored by an integral statistical approach. In a prospective series of experiments, glucose and NaCl concentrations in the culture medium, inoculum size, aeration of the culture, and growth temperature were statistically combined using an experimental 235-2 fractional factorial two-level design and tested for their influence on maximal bacteriocin production by L. plantarum LPCO10. After the values for the less-influential variables were fixed, NaCl concentration, inoculum size, and temperature were selected to study their optimal relationship for maximal bacteriocin production. This was achieved by a new experimental 323-1 fractional factorial three-level design which was subsequently used to build response surfaces and analyzed for both linear and quadratic effects. Results obtained indicated that the best conditions for bacteriocin production were shown with temperatures ranging from 22 to 27°C, salt concentration from 2.3 to 2.5%, and L. plantarum LPCO10 inoculum size ranging from 107.3 to 107.4 CFU/ml, fixing the initial glucose concentration at 2%, with no aeration of the culture. Under these optimal conditions, about 3.2 × 104 times more bacteriocin per liter of culture medium was obtained than that used to initially purify plantaricin S from L. plantarum LPCO10 to homogeneity. These results indicated the importance of this study in obtaining maximal production of bacteriocins from L. plantarum LPCO10 so that bacteriocins can be used as preservatives in canned foods.
A reversible encryption technique for storing weld piece related information during digital archiving of industrial radiographs

Archival of digital radiographs is the growing need in weld industries. However in addition to radiographs, the information about the weld piece must also be stored for future documentation. However the information about the radiographs may be confidential and should not be stored as such. Also matching the radiographs with the corresponding radiographs is also a major area of concern. Hence it necessitates an effective encryption technique that hides the information about the weld piece in the radiograph itself. The proposed technique involves hiding the nature of the weld defect in the radiographs. The paper also proposes an extraction technique to effectively extract the signature image.
In vitro regeneration of Salvia nemorosa L. from shoot tips and leaf explants

SummaryShoot tips and leaves excised from in vitro shoot cultures of Salvia nemorosa were evaluated for their organogenic capacity under in vitro conditions. The best shoot proliferation from shoot tips was obtained on Murashige and Skoog (MS) medium supplemented with 8.9 μM 6-benzylaminopurine (BA) and 2.9 μM indole-3-acetic acid (IAA). Leaf lamina and petiole explants formed shoots through organogenesis via callus stage and/or directly from explant tissue. The highest values for shoot regeneration were obtained with 0.9 μM BA and 2.9 μM IAA for lamina explants. No shoot organogenesis was obtained on leaf explants cultured on MS medium supplemented with α-naphthaleneacetic acid (NAA). The regenerated shoots rooted the best on MS medium containing 0.6 μM IAA or 0.5 μM NAA. In vitro-propagated plants were transferred to soil with a survival rate of 85% after 3 mo.
Successful PBSC mobilization with high-dose G-CSF for patients failing a first round of mobilization.

PBSC are the preferred source of stem cells for autologous transplantation. However, regardless of the mobilization procedure used, 10%-20% of patients fail to collect an adequate number to ensure prompt engraftment. There is as yet no standard mobilization procedure for patients who fail a first mobilization attempt. Here, we describe a highly efficient strategy to obtain an adequate number of stem cells for patients who failed a first mobilization attempt. Seventy-four patients with various hematologic malignancies underwent initial mobilization with various regimens including hematopoietic growth factors with or without chemotherapy. In 72% of patients, > or =2 x 10(6) CD34+ stem cells/kg were collected in the initial mobilization attempt, and patients engrafted in a median of 10 days for neutrophils and 12 days for platelets. Eighteen patients failed to mobilize adequate numbers of stem cells, defined as the inability to collect 0.2 x 10(6) CD34+ stem cells/kg/day in the first 2-3 days. These patients had their apheresis halted. Patients were immediately given G-CSF (32 microg/kg/day) for 4 days as a second attempt at mobilization. Eighty-eight percent of these patients achieved the target of > or =2 x 10(6) CD34+ cells/kg, with a median duration of apheresis of 5 days (including the first and second mobilizations). The mean CD34+ cells/kg/day increased after administration of high-dose G-CSF from 0.16 after the first mobilization attempt to 0.61 (p = 0.0002) after the second mobilization. All patients engrafted in a median of 11 and 13 days for neutrophils and platelets, respectively. We conclude that patients whose apheresis yield is <0.4 x 10(6) CD34+ cells/kg after the first two apheresis collections can be successfully mobilized if high-dose G-CSF is administered immediately and continued until achieving > or =2 x 10(6) CD34+ stem cells/kg.
Inhibition of Thymidine Transport in dnaA Mutants of Escherichia coli *

DnaA protein is the initiator of chromosomal DNA replication in Escherichia coli. We report here our evidence that thymidine transport across cytoplasmic membranes in temperature-sensitive dnaA mutants is greatly decreased at a permissive temperature for growth of the mutants. Complementation analysis with a plasmid containing the wild type dnaA gene and P1 phage-mediated transduction confirmed that mutations in thednaA gene were responsible for the phenotype. A low level of nucleoside transport in the dnaA mutant was specific for thymidine; transport activities for other nucleosides were much the same as those in wild type cells. Membrane vesicles prepared from thednaA mutant showed much the same activity of thymidine transport as did those from the wild type cells. No significant difference in the activity of thymidine kinase, which is known to facilitate thymidine transport, was seen between the mutant and the wild type cells. An increase in the pool of dTTP, a negative regulator for thymidine kinase, was observed in the dnaA mutant. Based on these observations, we suggest that inhibition of thymidine transport in dnaA mutants is caused by increases in the dTTP pool.
Sustained Endothelial Nitric-oxide Synthase Activation Requires Capacitative Ca2+ Entry*

Endothelial nitric-oxide synthase (eNOS), a Ca2+/calmodulin-dependent enzyme, is critical for vascular homeostasis. While eNOS is membrane-associated through itsN-myristoylation, the significance of membrane association in locating eNOS near sources of Ca2+ entry is uncertain. To assess the Ca2+ source required for eNOS activation, chimera containing the full-length eNOS cDNA and HA-tagged aequorin sequence (EHA), and MHA (myristoylation-deficient EHA) were generated and transfected into COS-7 cells. The EHA chimera was primarily targeted to the plasma membrane while MHA was located intracellularly. Both constructs retained enzymatic eNOS activity and aequorin-mediated Ca2+ sensitivity. The plasma membrane-associated EHA and intracellular MHA were compared in their ability to sense changes in local Ca2+ concentration, demonstrating preferential sensitivity to Ca2+ originating from intracellular pools (MHA) or from capacitative Ca2+ entry (EHA). Measurements of eNOS activation in intact cells revealed that the eNOS enzymatic activity of EHA was more sensitive to Ca2+ influx via capacitative Ca2+ entry than intracellular release, whereas MHA eNOS activity was more responsive to intracellular Ca2+release. When eNOS activation by CCE was compared with that generated by an equal rise in [Ca2+] i due to the Ca2+ ionophore ionomycin, a 10-fold greater increase in NO production was found in the former condition. These results demonstrate that EHA and MHA chimera are properly targeted and retain full functions of eNOS and aequorin, and that capacitative Ca2+influx is the principle stimulus for sustained activation of eNOS on the plasma membrane in intact cells.
Concurrent validity of digital inclinometer and universal goniometer in assessing passive hip mobility in healthy subjects.

BACKGROUND Hip range of motion is an important component in assessing clinical orthopedic conditions of the hip, low back and lower extremities. However it remains unclear as to what constitutes the best tool for clinical measurement. The purpose of this study was to investigate the concurrent validity of passive range of motion (ROM) measurements of hip extension and hip internal and external rotation using a digital inclinometer and goniometer. DESIGN Criterion Standard. SETTING Clinical research laboratory. PARTICIPANTS 30 healthy subjects without pain, radicular symptoms or history of surgery in the low back or hip regions. MAIN OUTCOME MEASURES Passive hip range of motion for extension, hip internal rotation and hip external rotation. A digital inclinometer and universal goniometer were utilized as the tools for comparisons between measurements. RESULTS There was a statistically significant difference (p < 0.05) between the goniometer and digital inclinometer in measured hip ROM except for measurements of right hip external rotation (p > 0.05). The mean difference between the goniometer and digital inclinometer in left hip extension, internal rotation and external rotation were 3.5°, 4.5° and 5.0° respectively. The mean difference between the two devices in right hip extension, internal rotation and external rotation were 2.8°, 4.2° and 2.6° respectively. On average, the difference between the goniometer and digital inclinometer in extension was 3.2°, internal rotation was 4.5° and external rotation was 3.8°. The digital inclinometer had greater measurement during EXT and ER. Furthermore, there was no statistically significant difference (p > 0.05) in hip ROM between the left and right side for either goniometric or digital inclinometer measurements. CONCLUSIONS This results of this study indicate that a significant difference exists between the two devices in all measurements with exception of right hip extension. The differences were noted to be between 3-5 degrees for all planes measured. These findings suggest that caution should be used if these two devices are to be used interchangeably to quantify passive hip range of motion in either clinical practice or when comparing studies that utilize different instruments. LEVEL OF EVIDENCE 2b.
CENTERING VULNERABLE INTERESTS: THE CONSTRUCTION OF WOMEN’S PROTECTION MODEL FROM FIELD LESSONS

The position of women in Indonesian society is progressing. The progress trend is supported by several legal instruments and policies that guarantee women's rights. Although adequate legal instruments began, many implementations in the field are distorted. Implementation of the protection schemes for women does not address to the changing of the poor women’s living condition, instead it remains vulnerable. This action research was addressed to analyze and discuss the practices of state social protection for the poor communities, as well as the testimony of beneficiaries. Based on the field learning from both parties, activists from universities and non-governmental organizations, attempt was made to knit some state schemes and policies into a model of protection; it also aimed to facilitate access and accelerate changes.
An analysis of adaptive design variations on the sequential parallel comparison design for clinical trials

Background Currently, a growing placebo response rate has been observed in clinical trials for antidepressant drugs, a phenomenon that has made it increasingly difficult to demonstrate efficacy. The sequential parallel comparison design (SPCD) is a clinical trial design that was proposed to address this issue. The SPCD theoretically has the potential to reduce the sample-size requirement for a clinical trial and to simultaneously enrich the study population to be less responsive to the placebo. Purpose Because the basic SPCD already reduces the placebo response by removing placebo responders between the first and second phases of a trial, the purpose of this study was to examine whether we can further improve the efficiency of the basic SPCD and whether we can do so when the projected underlying drug and placebo response rates differ considerably from the actual ones. Methods Three adaptive designs that used interim analyses to readjust the length of study duration for individual patients were tested to reduce the sample-size requirement or increase the statistical power of the SPCD. Various simulations of clinical trials using the SPCD with interim analyses were conducted to test these designs through calculations of empirical power. Results From the simulations, we found that the adaptive designs can recover unnecessary resources spent in the traditional SPCD trial format with overestimated initial sample sizes and provide moderate gains in power. Under the first design, results showed up to a 25% reduction in person-days, with most power losses below 5%. In the second design, results showed up to a 8% reduction in person-days with negligible loss of power. In the third design using sample-size re-estimation, up to 25% power was recovered from underestimated sample-size scenarios. Limitations Given the numerous possible test parameters that could have been chosen for the simulations, the study’s results are limited to situations described by the parameters that were used and may not generalize to all possible scenarios. Furthermore, dropout of patients is not considered in this study. Conclusions It is possible to make an already complex design such as the SPCD adaptive, and thus more efficient, potentially overcoming the problem of placebo response at lower cost. Ultimately, such a design may expedite the approval of future effective treatments.
GABAB receptors play an essential role in maintaining sleep during the second half of the night in Drosophila melanogaster

SUMMARY GABAergic signalling is important for normal sleep in humans and flies. Here we advance the current understanding of GABAergic modulation of daily sleep patterns by focusing on the role of slow metabotropic GABAB receptors in the fruit fly Drosophila melanogaster. We asked whether GABAB-R2 receptors are regulatory elements in sleep regulation in addition to the already identified fast ionotropic Rdl GABAA receptors. By immunocytochemical and reporter-based techniques we show that the pigment dispersing factor (PDF)-positive ventrolateral clock neurons (LNv) express GABAB-R2 receptors. Downregulation of GABAB-R2 receptors in the large PDF neurons (l-LNv) by RNAi reduced sleep maintenance in the second half of the night, whereas sleep latency at the beginning of the night that was previously shown to depend on ionotropic Rdl GABAA receptors remained unaltered. Our results confirm the role of the l-LNv neurons as an important part of the sleep circuit in D. melanogaster and also identify the GABAB-R2 receptors as the thus far missing component in GABA-signalling that is essential for sleep maintenance. Despite the significant effects on sleep, we did not observe any changes in circadian behaviour in flies with downregulated GABAB-R2 receptors, indicating that the regulation of sleep maintenance via l-LNv neurons is independent of their function in the circadian clock circuit.