Miracle-dz/UniFAR-FTUs huggingface dataset:
Seasonal and dose-dependent effects of intracerebroventricular leptin on lh secretion and appetite in sheep.

The role of leptin in neuroendocrine appetite and reproductive regulation remains to be fully resolved. A series of three experiments was conducted using adequately nourished oestradiol-implanted castrated male sheep. In a cross-over design (n=6), responses to a single i.c. v. (third ventricle) injection of leptin (0.5, 1.0 and 1.5 mg ovine leptin (oLEP) and 1.0 mg murine leptin (mLEP)), N-methyl-D-aspartate (NMDA, 20 micro g) or 0.9% saline (control) were measured in terms of LH secretion (4 h post-injection compared with 4 h pre-injection) and appetite (during 2 h post-injection) in autumn (Experiment 1). NMDA and 1.0 mg oLEP treatments were repeated in the same sheep in the following spring (Experiment 2). With an additional 12 sheep (n=18 in cross-over design), responses to low-dose 'physiological' i.c. v. infusion of leptin (8 ng/h for 12 h daily for 4 days), insulin (0.7 ng/h) and artificial cerebrospinal fluid were measured in the next spring (Experiment 3). LH was studied over 8 h and appetite over 1 h on days 1 and 4 of infusion. In Experiment 1 (autumn), oLEP overall increased LH pulse frequency by up to 110% (P<0.05), decreased LH pulse amplitude (P<0.05) and decreased appetite (P<0.05). mLEP reduced LH pulse amplitude (P<0.05) without significant effect on appetite, while NMDA reduced appetite (P<0.05) but had no effect on LH. In Experiment 2 (spring), LH responses were 'surge-like' with highly significant increases in the moving average LH concentration after 1.0 mg oLEP (P<0.001) and after NMDA (P<0.001). Compared with similar analysis of experiment 1 results, the LH response in spring was greater than that in autumn for both 1.0 mg oLEP (P<0.05) and NMDA (P<0.005). Conversely, unlike in autumn (Experiment 1), there was no effect of 1.0 mg oLEP or NMDA on appetite in the spring (Experiment 2). In Experiment 3 (spring), 'physiological' i.c. v. infusion of oLEP or insulin increased LH pulse frequency by up to 100% (P<0.001) compared with the control infusion on both days 1 and 4, but there were no effects on appetite. These results indicate that intracerebral leptin both stimulates reproductive neuroendocrine output and decreases appetite in adequately nourished sheep. However, the responses of these two axes were dose-dependent and differentially affected by the time of year, suggesting dissociation of the neural pathways involved.
Double-blind trial of a polyvalent, shed-antigen, melanoma vaccine.

A polyvalent melanoma vaccine prepared from shed antigens stimulates humoral and cellular immune responses and improves survival compared with historical controls. We conducted a double-blind, prospectively randomized, placebo-controlled trial to assess whether this vaccine could slow the progression of resected melanoma. Thirty-eight patients with resected melanoma metastatic to regional nodes (American Joint Committee on Cancer stage III) who had a particularly poor prognosis on the basis of the nodes being clinically positive or two or more histologically positive nodes were randomly assigned in a 2:1 ratio to treatment with 40 microg of melanoma or placebo (human albumin) vaccine, both of which were bound to alum as an adjuvant. Immunizations were given intradermally into the extremities every 3 weeks x 4, monthly x 3, every 3 months x 2, and then every 6 months for 5 years or until disease progression. Twenty-four patients were treated with the melanoma, and 14 patients were treated with the placebo vaccine. The groups were evenly balanced with respect to prognostic factors. Median length of observation was 2.5 years. There was no local or systemic toxicity. By Kaplan-Meier analysis, median time to disease progression was two and a half times longer in patients treated with melanoma vaccine compared with that in patients treated with placebo vaccine, i.e., 1.6 years (95% confidence interval, 1.0-3.0 years) compared with 0.6 year [95% confidence interval, 0.3-1.9 year(s)]. By Cox proportional hazards analysis, this difference was significant at P = 0.03. Overall survival was 40% longer in the melanoma vaccine-treated group (median overall survival of 3.8 years versus 2.7 years), but this difference was not statistically significant. In a double-blind and placebo-controlled trial, these results suggest that immunization with a melanoma vaccine may be able to slow the progression of melanoma. Although statistically significant, these results must be interpreted with caution because they are based on a small number of patients.
Reply to Cohn's Comments on Cones

In response to Cohn's 1989 remarks, we believe his view that "cautious interpretation" of Grosser and Spafford's 1989 findings is based on an overly hasty reading of our work. We address his issues point by point. Our original study hypothesizes that an unusually high cone density occurs in the periphery of the dyslexic's eye; such a hi h density would account for the high visual acuity noted by Geiger and Lettvin (1987). Even if normal readers' eyes have peripheral cones, these are apparently not arranged densely enough to provide such keen, acute detail vison. Problem I. The pothesis. -The present authors do not declare the peripheral retinas of 2 human eyes to be tot y void of cones. It is a well-known fact that, although the human retina contains approximately 6 million cones (Kalat, 1984, p. 156), these are more commonly located toward the center of the retina (Kalat, 1984, p. 129). Cohn attributes fixation deviations to variations in fixation by the dyslexic reader, particularly along the horizontal meridian. Yes, fixation deviations are relatively large along the horizontal meridian. However, Curcio, Sloan, Packer, Hendrickson, and Kalina (1987) point out that, in their human observers, cones tend to drop more slowly in density along the horizontal meridian than they do along the vertical meridian. If dyslexic eyes tend to lose cone density more slowly in peripheral directions, relatively greater numbers of extra cones should occur along the horizontal than the vertical meridian. Specifically, the sharp decline in cone density from 0" to lo0 indicated in the Osterberg figure (cited by Cohn, 1989) may not (in our view) occur in the dyslexic retina. Perhaps in dyslexics' retinas, the iso-density line runs horizontally across the top of the graph (50,00O/sq. mm.) or perha s the density function decreases slowly from O0 to lo0. rolle em II: Pivial alternative Aypotheses. -These comments do not require response. Problem HI: Reqzriremenk for psychophysical studies of photoreceptors are not met. -If Cohn is correct in assuming the ability of d slexics to identify colored targets is due to reflected energies using their rods, then why was tLs ability not evidenced in the case of proficient readers? Should not their rods [unction also? Concluding remarks. -Cohn, based on his various objections, suggests "further work along this Line is not warranted. " The attempt to shut down further work along the lines indicated by our research seems counter-productive. At the moment, clinical activities aimed at relieving reading difficulties have very little theoretical backing. The building of a sound theoretical understanding can only be helpful. Setting priorities for topics seems preferable to cessation of research efforts. The existence of methodological problems is what makes science interesting and challenging. We must be ingenious to make discoveries in the face of technical difficulties.
Improving Response Time through Multimodal Integration Pattern Modeling

While researchers have focused primarily on accuracy when addressing multimodal input segmentation, response time (or latency) has been rather overlooked in their work, despite its unquestionable importance. We propose a method of the input segmentation through integration pattern modeling that provides a significant improvement in response time over the state-of-the-art approaches, while maintaining remarkably high accuracy (98–99%). To this end, a new Bayesian Belief Network classification model was designed based on the recent empirical evidence about users’ multimodal integration patterns. The model is employed in a procedure to segment related inputs into multimodal units. Using the introduced procedure the response time can be improved to 0.8 seconds for sequential integrators and even dropped bellow 0.5 s for simultaneous, which represents a relative improvement of 20% and 50%, resp. , at the very least. Although demonstrated on a combination of speech and gestures, the suggested approach can be generalized to a broad range of other modality mixtures.
Treatment of Respiratory Syncytial Virus Infection : Past , Present and Future

Respiratory syncytial virus (RSV) has emerged since its isolation from infected children in 1957 as an important respiratory pathogen (Falsey et al, 2005; Hall et al, 2009; Nair et al, 2010; Ruuskanen et al, 2011). Generally, infection is restricted to the upper respiratory tract and not associated with long-term pathology, but progression to a more severe lower respiratory tract infection is frequent.
Patterns of Snow Leopard Site Use in an Increasingly Human-Dominated Landscape

Human population growth and concomitant increases in demand for natural resources pose threats to many wildlife populations. The landscapes used by the endangered snow leopard (Panthera uncia) and their prey is increasingly subject to major changes in land use. We aimed to assess the influence of 1) key human activities, as indicated by the presence of mining and livestock herding, and 2) the presence of a key prey species, the blue sheep (Pseudois nayaur), on probability of snow leopard site use across the landscape. In Gansu Province, China, we conducted sign surveys in 49 grid cells, each of 16 km2 in size, within a larger area of 3392 km2. We analysed the data using likelihood-based habitat occupancy models that explicitly account for imperfect detection and spatial auto-correlation between survey transect segments. The model-averaged estimate of snow leopard occupancy was high [0.75 (SE 0.10)], but only marginally higher than the naïve estimate (0.67). Snow leopard segment-level probability of detection, given occupancy on a 500 m spatial replicate, was also high [0.68 (SE 0.08)]. Prey presence was the main determinant of snow leopard site use, while human disturbances, in the form of mining and herding, had low predictive power. These findings suggest that snow leopards continue to use areas very close to such disturbances, as long as there is sufficient prey. Improved knowledge about the effect of human activity on large carnivores, which require large areas and intact prey populations, is urgently needed for conservation planning at the local and global levels. We highlight a number of methodological considerations that should guide the design of such research.
Clinical aspects of indirect immunofluorescence for autoimmune diseases

Because the most common term used in conversations considering autoimmunity is autoantibodies, it is well-expected that the indirect immunofluorescence assay, which detects antibodies directed against various antigens, is one of our most impressive techniques for investigating autoimmune diseases (AIDs). Roughly speaking, the current literature corroborates that this immunopathologic investigation means that autoantibodies detection makes a considerable contribution to both diagnostic and prognostic aspects of AIDs in the clinical setting. However, it varies between different AIDs, autoantibodies, ethnicities or detection methodologies. Directly focusing on the indirect immunofluorescence assay, we present evidence to support this multidimensional variation regarding the subject via reviewing briefly the best-investigated autoantibodies in the well-documented AIDs, including vasculitis, inflammatory bowel disease, scleroderma, autoimmune hepatitis, primary biliary cirrhosis, systemic lupus erythematosus and Sjögren’s syndrome.
Common Features in Substrates of Multidrug Resistance Transporters

Multidrug resistance (MDR) proteins serve as transporters for chemical compounds, small molecules like antibiotics in almost all species from bacteria to higher eukaryote. They provide the resistance against antibiotics and chemicals for the cells like cancer, fungi and parasite, etc. Therefore, the research on MDR proteins is essential and important in medical, agricultural and scientific fields. Five transporter families are known to contain MDR members as follows. ABC (ATP-binding cassette superfamily), MFS (major-facilitator superfamily), SMR (small multidrug resistance family), RND (resistance-nodulation cell division family), and MATE (multidrug and toxic compound extrusion family). The ABC transporter consists of some subfamilies, such as pgp, mrp and pdr. The ABC transporter is driven by ATP hydrolysis energy, and the other four families are driven by proton/sodium motive force. It was reported that more than 90% of MDR genes are composed of ABC and MFS genes in completely sequenced bacteria genomes [4]. In general, the relationship of the transporter and its substrate is highly specific, but MDRs are known to be transporters that have broad spectrums of drugs and chemical compounds. Thus, MDRs are poly-specific rather than nonspecific transporters [5]. Many substrates have been found and used in experiments for characterizing properties of MDRs. The spectrum of each MDR family is known to be somewhat distinct, but the relationship to the structural and physicochemical properties of substrates has not been well established. Previously, we collected chemical compound structures for substrates of MDR proteins from the published literature and tried to retrieve structural and physicochemical properties [2], They were represented by 67 kinds of the KEGG atom types [1]. In this study, we classified these collected chemical compound substrates and extracted common sub-graphs of them by using Vzyme [3] in order to detect putative recognition sites in chemical compound substrates by the MDR protein.
Intra-articular sodium hyaluronate in osteoarthritis of the knee.

OBJECTIVES Hyaluronan (HA) has recently been approved in the United States for management of pain in osteoarthritis (OA) of the knee and is the first biological available for use in OA. To better understand the therapeutic role of HA, this review focuses on comparative clinical trial data. METHODS Literature reports of clinical trials comparing HA with placebo, nonsteroidal anti-inflammatory drugs, and intra-articular corticosteroids were reviewed. The pivotal US trial evaluating HA efficacy and safety was summarized. RESULTS Over the past decade, 5 of 8 controlled clinical trials demonstrated HA was superior to placebo in relieving the pain of OA. A sixth trial showed improvement in a subset of older patients with more severe disease. Comparison of HA with corticosteroids showed equal pain relief in the first few weeks after therapy, with HA demonstrating more sustained benefit up to 60 days. In the recent US trial, HA was statistically superior to placebo and at least as effective as naproxen in providing analgesia. In all trials reporting adverse effects, the primary adverse effect with HA was pain at the injection site. CONCLUSIONS HA appears effective in relieving the pain of OA of the knee and provides a relatively safe alternative for patients for whom conventional therapy has failed.
Using Probabilistic Model Checking to Evaluate GUI Testing Techniques

Different testing techniques are being proposed in software testing to improve systems quality and increase development productivity. However, it is difficult to determine from a given set of testing techniques, which is the most effective testing technique for a certain domain, particularly if they are random-based. We are proposing a strategy and a framework that can evaluate such testing techniques. Our framework is defined compositionally and parametrically. This allows us to characterize different aspects of systems in an incremental way as well as test specific hypothesis about the system under test. In this paper we focus on GUI-based systems. That is, the specific internal behavior of the system is unknown but it can be approximated by probabilistic behaviors. And the empirical evaluation is based on the probabilistic model checker PRISM.
Deciphering the Transcriptional-Regulatory Network of Flocculation in Schizosaccharomyces pombe

In the fission yeast Schizosaccharomyces pombe, the transcriptional-regulatory network that governs flocculation remains poorly understood. Here, we systematically screened an array of transcription factor deletion and overexpression strains for flocculation and performed microarray expression profiling and ChIP–chip analysis to identify the flocculin target genes. We identified five transcription factors that displayed novel roles in the activation or inhibition of flocculation (Rfl1, Adn2, Adn3, Sre2, and Yox1), in addition to the previously-known Mbx2, Cbf11, and Cbf12 regulators. Overexpression of mbx2+ and deletion of rfl1+ resulted in strong flocculation and transcriptional upregulation of gsf2 +/pfl1+ and several other putative flocculin genes (pfl2+–pfl9+). Overexpression of the pfl+ genes singly was sufficient to trigger flocculation, and enhanced flocculation was observed in several combinations of double pfl+ overexpression. Among the pfl1+ genes, only loss of gsf2+ abrogated the flocculent phenotype of all the transcription factor mutants and prevented flocculation when cells were grown in inducing medium containing glycerol and ethanol as the carbon source, thereby indicating that Gsf2 is the dominant flocculin. In contrast, the mild flocculation of adn2+ or adn3+ overexpression was likely mediated by the transcriptional activation of cell wall–remodeling genes including gas2+, psu1+, and SPAC4H3.03c. We also discovered that Mbx2 and Cbf12 displayed transcriptional autoregulation, and Rfl1 repressed gsf2+ expression in an inhibitory feed-forward loop involving mbx2+. These results reveal that flocculation in S. pombe is regulated by a complex network of multiple transcription factors and target genes encoding flocculins and cell wall–remodeling enzymes. Moreover, comparisons between the flocculation transcriptional-regulatory networks of Saccharomyces cerevisiae and S. pombe indicate substantial rewiring of transcription factors and cis-regulatory sequences.
Development of a Double-Crossover Markerless Gene Deletion System in Bifidobacterium longum: Functional Analysis of the α-Galactosidase Gene for Raffinose Assimilation

ABSTRACT Functional analysis of Bifidobacterium genes is essential for understanding host-Bifidobacterium interactions with beneficial effects on human health; however, the lack of an effective targeted gene inactivation system in bifidobacteria has prevented the development of functional genomics in this bacterium. Here, we report the development of a markerless gene deletion system involving a double crossover in Bifidobacterium longum. Incompatible plasmid vectors were used to facilitate a second crossover step. The conditional replication vector pBS423-ΔrepA, which lacks the plasmid replication gene repA, was integrated into the target gene by a first crossover event. Subsequently, the replicative plasmid pTBR101-CM, which harbors repA, was introduced into this integrant to facilitate the second crossover step and subsequent elimination of the excised conditional replication vector from the cells by plasmid incompatibility. The proposed system was confirmed to work as expected in B. longum 105-A using the chromosomal full-length β-galactosidase gene as a target. Markerless gene deletion was tested using the aga gene, which encodes α-galactosidase, whose substrates include raffinose. Almost all the pTBR101-CM-transformed strains became double-crossover recombinants after subculture, and 4 out of the 270 double-crossover recombinants had lost the ability to assimilate raffinose. Genotype analysis of these strains revealed markerless gene deletion of aga. Carbohydrate assimilation analysis and α-galactosidase activity measurement were conducted using both the representative mutant and a plasmid-based aga-complemented strain. These functional analyses revealed that aga is the only gene encoding a functional α-galactosidase enzyme in B. longum 105-A.
Different cellular backgrounds confer a marked advantage to either mutant or wild-type mitochondrial genomes.

After the introduction of mitochondria with a mixture of mutant and wild-type mitochondrial DNA (mtDNA) into a human rho degree cell line (143B.206), Yoneda et al. [Yoneda, M. , Chomyn, A. , Martinuzzi, A. , Hurko, O. & Attardi, G. (1992) Proc. Natl. Acad. Sci. USA 89, 11164-11168] observed a shift in the proportion of the two mitochondrial genotypes in a number of cybrid clones. In every case where a shift was observed, there was an increase in the proportion of mutant mtDNA. By using the same cell line (143B.206 rho degree), we also generated cybrids that were either stable in their mitochondrial genotype or showed an increase in the proportion of mutant mtDNA. However, temporal analysis of the same mutant mtDNA type in another rho degree cell line revealed a quite distinct outcome. Those clones that showed a change shifted toward higher levels of wild-type rather than mutant mtDNA. These results indicate that the nuclear genetic background of the recipient (rho degree) cell can influence the segregation of mutant and wild-type mitochondrial genomes in cell cybrids.
A tangible user interface using spatial Augmented Reality

In this paper, we describe the novel implementation of a tangible user interface framework, namely the MagicPad, inspired by the concept of Spatial Augmented Reality. By using an Infrared pen with any flat surface, such as a paper pad that receives projected images from a projector, a user is able to perform a variety of interactive visualization and manipulation in the 3D space. Two implementations using the MagicPad framework are presented, which include the magic lenses like interface inside a CAVE-like system and a virtual book in an art installation.
Growth of Thiobacillus ferrooxidans on Elemental Sulfur

Growth kinetics of Thiobacillus ferrooxidans in batch cultures, containing prills of elementary sulfur as the sole energy source, were studied by measuring the incorporation of radioactive phosphorus in free and adsorbed bacteria. The data obtained indicate an initial exponential growth of the attached bacteria until saturation of the susceptible surface was reached, followed by a linear release of free bacteria due to successive replication of a constant number of adsorbed bacteria. These adsorbed bacteria could continue replication provided the colonized prills were transferred to fresh medium each time the stationary phase was reached. The bacteria released from the prills were unable to multiply, and in the medium employed they lost viability with a half-life of 3.5 days. The spreading of the progeny on the surface was followed by staining the bacteria on the prills with crystal violet; this spreading was not uniform but seemed to proceed through distortions present in the surface. The specific growth rate of T. ferrooxidans ATCC 19859 was about 0.5 day−1, both before and after saturation of the sulfur surface. The growth of adsorbed and free bacteria in medium containing both ferrous iron and elementary sulfur indicated that T. ferrooxidans can simultaneously utilize both energy sources.