Miracle-dz/UniFAR-FTUs huggingface dataset:
Pathways Leading from BarA/SirA to Motility andVirulence Gene Expression inSalmonella

ABSTRACT The barA and sirA genes of Salmonellaenterica serovar Typhimurium encode a two-component sensor kinase and a response regulator, respectively. This system increases the expression of virulence genes and decreases the expression of motility genes. In this study, we examined the pathways by which SirA affects these genes. We found that the master regulator of flagellar genes, flhDC, had a positive regulatory effect on the primary regulator of intestinal virulence determinants, hilA, but that hilA had no effect on flhDC. SirA was able to repress flhDC in a hilA mutant and activate hilA in an flhDC mutant. Therefore, although the flhDC and hilA regulatory cascades interact, sirA affects each of them independently. A form of BarA lacking the two N-terminal membrane-spanning domains, BarA198, autophosphorylates in the presence of ATP and transfers the phosphate to purified SirA. Phosphorylated SirA was found to directly bind the hilA and hilC promoters in gel mobility shift assays but not the flhD, fliA, hilD, and invF promoters. Given that the CsrA/csrB system is known to directly affect flagellar gene expression, we tested the hypothesis that SirA affects flagellar gene expression indirectly by regulating csrA or csrB. The sirA gene did not regulate csrA but did activate csrB expression. Consistent with these results, phosphorylated SirA was found to directly bind the csrB promoter but not the csrA promoter. We propose a model in which SirA directly activates virulence expression via hilA and hilC while repressing the flagellar regulon indirectly via csrB.
Retardation of Cochlear Maturation and Impaired Hair Cell Function Caused by Deletion of All Known Thyroid Hormone Receptors

The deafness caused by early onset hypothyroidism indicates that thyroid hormone is essential for the development of hearing. We investigated the underlying roles of the TRα1 and TRβ thyroid hormone receptors in the auditory system using receptor-deficient mice. TRα1 and TRβ, which act as hormone-activated transcription factors, are encoded by the Thra and Thrb genes, respectively, and both are expressed in the developing cochlea. TRβ is required for hearing because TRβ-deficient (Thrbtm1/tm1) mice have a defective auditory-evoked brainstem response and retarded expression of a potassium current (IK,f) in the cochlear inner hair cells. Here, we show that although TRα1 is individually dispensable, TRα1 and TRβ synergistically control an extended array of functions in postnatal cochlear development. Compared with Thrbtm1/tm1 mice, the deletion of all TRs inThratm1/tm1Thrbtm1/tm1mice produces exacerbated and novel phenotypes, including delayed differentiation of the sensory epithelium, malformation of the tectorial membrane, impairment of electromechanical transduction in outer hair cells, and a low endocochlear potential. The induction ofIK,f in inner hair cells was not markedly more retarded than in Thrbtm1/tm1mice, suggesting that this feature of hair cell maturation is primarily TRβ-dependent. These results indicate that distinct pathways mediated by TRβ alone or by TRβ and TRα1 together facilitate control over an extended range of functions during the maturation of the cochlea.
Bridging the Gap between QoE and User Engagement in HTTP Video Streaming

On video streaming platforms, users expect a high Quality of Experience (QoE). In contrast, service and content providers aim at high User Engagement, most notably because their revenue is usually dependent on it. In order to satisfy users, it is critical to know how QoE is related to the User Engagement. However, no model for this relation exists yet. Current approaches to managing QoE are usually based on traffic analysis. However, this will become more difficult in the future since the encryption of Internet traffic progresses. In this paper, we present an approach to bringing QoE and User Engagement together with video streaming as the use case. We do this by fitting existing measurement data of User Engagement to obtain a model. Furthermore, we extend the existing queuing model for QoE and investigate the correlation between QoE and User Engagement in a simulation. Hereby, we model different scenarios where we quantify network bandwidth and video requirements. Our results show that there is a strong correlation between QoE and User Engagement. Additionally, we observe that simple buffer policies, which do not rely on buffer information, can still perform well. These revelations open the way for new approaches to QoE Management in the future Internet.
0 Secular Evolution of Satellites by Tidal Effect

Both the Earth’s Moon and Pluto’s moon, Charon, have an important fraction of the mass of their systems, and therefore they could be classified as double-planets rather than as satellites. The proto-planetary disk is unlikely to produce such systems, and their origin seems to be due to a catastrophic impact of the initial planet with a body of comparable dimensions (e.g. Canup, 2005; Canup & Asphaug, 2001). On the other hand, Neptune’s moon, Triton, and the Martian moon, Phobos, are spiraling down into the planet, clearly indicating that the present orbits are not primordial, and may have undergone a long evolving process from a previous capture (e.g. Goldreich et al., 1989; Mignard, 1981).
The relationship between perception of vocal effort and relative fundamental frequency during voicing offset and onset.

PURPOSE In this study, the authors aimed to determine the relationship between relative fundamental frequency (RFF) and listener perception of vocal effort in individuals with varying degrees of vocal hyperfunction. METHOD Thirty women diagnosed with voice disorders commonly associated with vocal hyperfunction and 10 healthy women provided speech samples that were used to obtain parameters of RFF. Twelve listeners judged the speech samples for overall severity and vocal effort (VE) using rating scales. RESULTS Significant but relatively weak negative correlations were found between perceptual measures and offset RFF parameters. Although offset RFF was increased in healthy participants relative to speakers with voice disorders, no differences were seen in RFF as a function of severity of VE in individuals with voice disorders. CONCLUSIONS Although a statistically significant correlation between offset RFF and VE was found, examination of data as a function of both VE and health status indicated that RFF more accurately classifies the presence of a voice disorder than does severity of voice quality or VE. There is a need for further research to investigate the clinical utility of RFF measures for assessment of rehabilitation progress.
Microscopical Examination of Clarke's Column in Man, the Monkey, and the Dog.

THIS column of cells has lately excited considerable interest on account of the very important and original paper by Dr Gaskell " On the Nerves of the Visceral and Vascular System. " Both Dr Ross and Dr Alexander Hill had previously suggested that the cells of Clarke's -column were connected with the innervation of the viscera; but Dr Gaskell proved the outflow of the fine medullated fibres of the visceral and vascular system to agree in position exactly with the cells of Clarke's column in the spinal cord. No anatomical connection has been proved between these fibres and the cells. The older view of Flechsig is, that they are connected with the innervation of the trunk muscles' One fact in connection with these cells is pretty well established, and was first shown by Lockhart Clarke, namely, that these cells are connected with the fibres of the direct cerebellar tract. The subject is one of great interest, both physiologically and pathologically, and I have examined a great number of sections with a view of ascertaining whether any new light can be thrown upon it. The materials which have been used were as follows:-The spinal cord of a healthy boy, who died from injury; ditto of a healthy bonnet monkey; ditto of a small young dog; also that of a full-termed fetus; added to these a number of pathological specimens bearing on the subject. The tissues were hardened in 2 per cent. solution of bichromate of ammonia, subsequently in alcohol, and then sections were cut of nearly uniform thickness, both transverse and vertical, of each segment of the cord. The sections were made by means of a freezing microtome, and stained by the Weigert method. Each section was examined with a view of determining the situation,
Recurrent Events in Transient Ischemic Attack and Minor Stroke: What Events Are Happening and to Which Patients?

Background and Purpose— The risk of a recurrent stroke after transient ischemic attack (TIA) or minor stroke is high. Clinical trials are needed to assess acute treatment options in these patients. We sought to evaluate the type of recurrent events and to identify which subsets of patients are at risk for recurrent events. Methods— One hundred and eighty patients with TIA or minor stroke were examined within 12 hours and underwent brain MRI within 24 hours. Any neurological deterioration was recorded, and a combination of clinical and MRI factors were used to create a combined event classification. Subgroups of patients analyzed included classical TIA, patients with NIHSS=0, and patients with NIHSS >0 in ED. Results— Overall there were 38 events in 36 patients (20% event rate); 20 were symptomatic and 18 were silent (only evident because of the follow up MRI). 18/20 (90%) symptomatic events were associated with progression of presenting symptoms, compared to 2/20 (10%) with a clear recurrent stroke distinct from the original event. We found a low risk of recurrent stroke among classical definition TIA patients (1.1%). Patients with an NIHSS=0 in the ED, had an intermediate event rate (6.6%) between TIA (classical – 1.1%) and NIHSS >0 (14.4%; &khgr;2 test for trend, P=0.02). All clinical categories of patient (TIA, stroke, NIHSS=0) accumulated silent lesions on MRI. Conclusions— Most events were classified as stroke progression or infarct growth rather than a recurrent stroke. A low risk of recurrence was found in patients with classical TIA and those with no neurological deficits on initial assessment.
Merger Policy in Digital Markets: An Ex-Post Assessment

Production planning on multiple parallel machines is an interesting problem, both from a theoretical and practical point of view. The parallel machine lotsizing problem consists of finding the optimal timing and level of production and the best allocation of products to machines. In this paper we look at how to incorporate parallel machines in a Mixed Integer Programming model when using commercial optimization software. More specifically, we look at the issue of symmetry. When multiple identical machines are available, many alternative optimal solutions can be created by renumbering the machines. These alternative solutions lead to difficulties in the branch-and-bound algorithm. We propose new constraints to break this symmetry. We tested our approach on the parallel machine lotsizing problem with setup costs and times, using a network reformulation for this problem. Computational tests indicate that several of the proposed symmetry breaking constraints substantially improve the solution time, except when used for solving the very easy problems. The results highlight the importance of creative modeling in solving Mixed Integer Programming problems.
Physical Symptoms Distress Index: a sensitive tool to evaluate the impact of pharmacological agents on quality of life.

OBJECTIVES To examine whether the degree of stress associated with adverse physical side effects correlates with overall quality of life (QOL) and compliance rates. To determine if instruments used to assess QOL can detect differences between treatments that have no known central nervous system effects. PATIENTS AND METHODS This randomized, double-blind, parallel group study evaluated 180 to 480 mg of controlled onset, extended release (COER)-verapamil (n = 259) or 30 to 120 mg/d of nifedipine gastrointestinal therapeutic system (GITS) (n = 269) in men and women between 21 and 80 years of age with stages 1 to 3 hypertension. A battery of questions evaluating psychological well-being and a physical symptom distress index was administered after a 4-week placebo washout (baseline) and after 10 weeks of treatment or at dropout. RESULTS Both treatments effectively lowered blood pressure, and there were no significant between-group differences in psychosocial QOL. A difference in the level of physical symptom distress was detected between treatments (P = .002; multivariate analysis of variance), with 7 significant univariate treatment effects, all favoring COER-verapamil, being noted-pedal edema, polyuria, rapid heart beat or palpitations, hives, muscle cramps, abdominal cramps, and headaches. Constipation-related distress increased significantly (P = .001) but to a similar extent with both treatments. The difference in symptom distress tended to predict compliance as there were more withdrawals in the nifedipine GITS group (n = 85) vs COER-verapamil group (n = 64) (P = .08). CONCLUSIONS Patient-assessed physical symptom distress is a sensitive, simple technique to evaluate the effect of antihypertensive medications on QOL and tolerability, as shown by its ability to detect the improvement associated with COER-verapamil. Depending on the agents involved, the Physical Symptom Distress Index may more closely predict dropout rates than the traditional psychosocial instruments, as suggested by the lower dropout rate in the COER-verapamil group. Thus, in studying treatment effects on QOL, both the distress of physical symptoms and the impact of psychosocial factors should be evaluated.
Enhanced Effective Connectivity Between Primary Motor Cortex and Intraparietal Sulcus in Well-Recovered Stroke Patients

Background and Purpose— Ischemic strokes with motor deficits lead to widespread changes in neural activity and interregional coupling between primary and secondary motor areas. Compared with frontal circuits, the knowledge is still limited to what extent parietal cortices and their interactions with frontal motor areas undergo plastic changes and might contribute to residual motor functioning after stroke. Methods— Fifteen well-recovered patients were evaluated 3 months after stroke by means of functional magnetic resonance imaging while performing visually guided hand grips with their paretic hand. Dynamic causal modeling was used to investigate task-related effective connectivity between ipsilesional posterior parietal regions along the intraparietal sulcus and frontal key motor areas, such as the primary motor cortex, the ventral premotor cortex, and the supplementary motor area. Results— Compared with healthy controls of similar age and sex, we observed significantly enhanced reciprocal facilitatory connectivity between the primary motor cortex and the anterior intraparietal sulcus of the ipsilesional hemisphere. Beyond that and as a fingerprint of excellent recovery, the coupling pattern of the parietofrontal network was near-normal. An association between coupling parameters and clinical scores was not detected. Conclusions— The present analysis further adds to the understanding of the parietofrontal network of the ipsilesional hemisphere as a prominent circuit involved in plastic changes after stroke.
Frova introducer for tracheal intubation – our comments and experience

ML. Ultrasound guidance with nerve stimulation reduces the time necessary for resident peripheral nerve blockade. Regional Anesthesia and Pain Medicine 2007; 32: 448–54. 4 Loubert C, Williams SR, Helie F, Arcand G. Complication during ultrasound-guided regional block: accidental intravascular injection of local anesthetic. Anesthesiology 2008; 108: 759–60. 5 Russon K, Blanco R. Accidental intraneural injection into the musculocutaneous nerve visualized with ultrasound. Anesthesia and Analgesia 2007; 105: 1504–5. 6 Schafhalter-Zoppoth I, Zeitz ID, Gray AT. Inadvertent femoral nerve impalement and intraneural injection visualized by ultrasound. Anesthesia and Analgesia 2004; 99: 627–8. 7 Zetlaoui PJ, Labbe JP, Benhamou D. Ultrasound guidance for axillary plexus block does not prevent intravascular injection. Anesthesiology 2008; 108: 761. 8 Perlas A, Niazi A, McCartney C, Chan V, Xu D, Abbas S. The sensitivity of motor to nerve stimulation and paresthesia for nerve localization as evaluated by ultrasound. Regional Anesthesia and Pain Medicine 2006; 31: 445–50. 9 Bigeleisen PE. Nerve puncture and apparent intraneural injection during ultrasound-guided axillary block does not invariably result in neurologic injury. Anesthesiology 2006; 105: 779–83. 10 Tsai TP, Vuckovic I, Dilberovic F, et al. Intensity of the stimulating current may not be a reliable indicator of intraneural needle placement. Regional Anesthesia and Pain Medicine 2008; 33: 207–10. 11 Chan VW. Applying ultrasound imaging to interscalene brachial plexus block. Regional Anesthesia and Pain Medicine 2003; 28: 340–6. 12 Brull SJ. Lipid emulsion for the treatment of local anesthetic toxicity: patient safety implications. Anesthesia and Analgesia 2008; 106: 1337–9. 13 Rowlingson JC. Lipid rescue: a step forward in patient safety? Likely so! Anesthesia and Analgesia 2008; 106: 1333–6. A reply We thank Macfarlane et al for their comments on our survey. We were interested to read of their clinical experience in undertaking peripheral nerve blocks and are pleased that our survey has prompted this sharing of information. We agree that the ideal situation is one in which feedback from a cooperative, relaxed, conscious patient serves as the final clinical check in undertaking regional blocks. We did not specifically explore the reasons why anaesthetists in the Oxford region tend to perform peripheral blocks on anaesthetised patients, as we were simply comparing local clinical practice with that seen 5 years earlier. However, we do believe that further examination of the reasons behind current practice is warranted. It is an essential first step in changing the current clinical culture to one in which the default position is to perform blocks on conscious patients. Our study has shown that practice with regard to central blocks has evolved. With further time and exploration of the issues surrounding the practice of peripheral blocks, we believe that this too will evolve.
Creativity room 5555: evoking creativity in game design amongst CS students

This paper highlights the importance of computer-free meeting places for Computer Science (CS) students participating in game design courses in the sense of learning spaces. Such environments have the potential of countering possible negative attitudes of CS students towards creative processes. During a game design course we offered a unique meeting room that offered playful and creative elements. Furthermore, the room had to be rearranged by the participants of the course. We describe the course and analyze it through observations and three formal surveys. Both the results and the quality of resulting prototypes indicate that CS students strongly benefit in their creative processes from working in individually arranged playful environments.
Defining the Role of Ubiquitin-interacting Motifs in the Polyglutamine Disease Protein, Ataxin-3*

Polyglutamine (polyQ) expansions cause neurodegeneration that is associated with protein misfolding and influenced by functional properties of the host protein. The polyQ disease protein, ataxin-3, has predicted ubiquitin-specific protease and ubiquitin-binding domains, which suggest that ataxin-3 functions in ubiquitin-dependent protein surveillance. Here we investigate direct links between the ubiquitin-proteasome pathway and ataxin-3. In neural cells we show that, through its ubiquitin interaction motifs (UIMs), normal or expanded ataxin-3 binds a broad range of ubiquitinated proteins that accumulate when the proteasome is inhibited. The expression of a catalytically inactive ataxin-3 (normal or expanded) causes ubiquitinated proteins to accumulate in cells, even in the absence of proteasome inhibitor. This accumulation of ubiquitinated proteins occurs primarily in the cell nucleus in transfected cells and requires intact UIMs in ataxin-3. We further show that both normal and expanded ataxin-3 can undergo oligoubiquitination. Although this post-translational modification occurs in a UIM-dependent manner, it becomes independent of UIMs when the catalytic cysteine residue of ataxin-3 is mutated, suggesting that ataxin-3 ubiquitination is itself regulated in trans by its own de-ubiquitinating activity. Finally, pulse-chase labeling reveals that ataxin-3 is degraded by the proteasome, with expanded ataxin-3 being as efficiently degraded as normal ataxin-3. Mutating the UIMs does not alter degradation, suggesting that UIM-mediated oligoubiquitination of ataxin-3 modulates ataxin-3 function rather than stability. The function of ataxin-3 as a de-ubiquitinating enzyme, its post-translational modification by ubiquitin, and its degradation via the proteasome link this polyQ protein to ubiquitin-dependent pathways already implicated in disease pathogenesis.
The genetics of panic disorder

Panic disorder (PD) is one of the most common anxiety disorders, with a prevalence of 3.4–4.7%. Although PD seems to have no known cause, and its underlying aetiology is not well understood, studies have consistently shown that genetic factors explain about half of the variance. It is likely that most cases of PD have a complex genetic basis. Existing data suggest, however, that the genetic architecture underlying PD is heterogeneous and differs between cases. For example, the degree of genetic complexity, and the pattern of genes involved might differ in familial versus non-familial cases, in early- versus late-onset cases, or when different comorbid conditions, gender and potential intermediate or sub-phenotypes are considered. At the molecular genetic level, linkage and association studies—the latter including traditional candidate gene and recent genome-wide studies—have been used to study PD. Although no robust molecular genetic findings have emerged so far, it is conceivable that the first PD susceptibility genes will be identified in the coming years via the application of modern molecular genetic methods and through multicentre collaborations to bring together combined, large datasets. Such findings could have a major impact on our understanding of the pathophysiology of this disorder, and would provide important opportunities to investigate genotype–phenotype correlations, as well as the interaction between genetic and environmental factors involved in the pathogenesis of PD. Here, the authors summarise the latest genetics findings about PD, and give an overview of anticipated future developments.