Miracle-dz/UniFAR-FTUs huggingface dataset:
Paternal uniparental heterodisomy with partial isodisomy of chromosome 1 in a patient with retinitis pigmentosa without hearing loss and a missense mutation in the Usher syndrome type II gene USH2A.

OBJECTIVE To evaluate a form of nonmendelian inheritance in a patient with retinitis pigmentosa (RP). METHODS Direct DNA sequencing of the USH2A coding region and microsatellite analysis of polymorphic markers from chromosome 1 and other chromosomes. RESULTS A patient with RP without hearing loss caused by the homozygous mutation Cys759Phe in the USH2A gene on chromosome 1q was found to be the daughter of a noncarrier mother and a father who was heterozygous for this change. Further evaluation with microsatellite markers revealed that the patient had inherited 2 copies of chromosome 1 from her father and none from her mother. The paternally derived chromosome 1's were heteroallelic from the centromere of chromosome 1 to the proximal short and long arms. The distal regions of the short and long arms of chromosome 1 were homoallelic, including the region of 1q with the mutant USH2A allele. This genetic pattern is compatible with a phenomenon of uniparental primary heterodisomy with regions of homozygosity arising through a nondisjunction event during paternal meiosis I and subsequent trisomy rescue or gamete complementation. A paternal second cousin of the patient also had RP and also had an identical heterozygous mutation in the USH2A gene in the same codon. However, the analysis of an isocoding polymorphism 20 base pairs away and closely linked microsatellite markers in the patient and family members indicated that the 2 mutant alleles are unlikely to be identical by descent and that the 2 relatives fortuitously had RP and a mutation in the same codon of the USH2A gene. CONCLUSION This family illustrates that recessive RP without hearing loss can rarely be inherited from only 1 unaffected carrier parent in a nonmendelian manner. CLINICAL RELEVANCE The genetic counseling of families with recessively inherited eye diseases must take into consideration the possibility that an unaffected heterozygous carrier can have an affected offspring homozygous for the same mutation, even if the carrier's spouse has wild-type alleles at the disease locus.
Atmospheric Chemistry and Physics Global Indirect Aerosol Effects: a Review

Aerosols affect the climate system by changing cloud characteristics in many ways. They act as cloud condensation and ice nuclei, they may inhibit freezing and they could have an influence on the hydrological cycle. While the cloud albedo enhancement (Twomey effect) of warm clouds received most attention so far and traditionally is the only indirect aerosol forcing considered in transient climate simulations , here we discuss the multitude of effects. Different approaches how the climatic implications of these aerosol effects can be estimated globally as well as improvements that are needed in global climate models in order to better represent indirect aerosol effects are discussed in this paper.
Uncertainty and exploration in a restless bandit task

Decision-making in noisy and changing environments requires a fine balance between exploiting knowledge about good courses of action and exploring the environment in order to improve upon this knowledge. We present an experiment in which participants made repeated choices between options for which the average rewards changed over time. Comparing a number of computational models of participants' behaviour in this task, we find evidence that a substantial number of them balanced exploration and exploitation by considering the probability that an option offers the maximum reward out of all the available options.
Late bloomer or language impaired? Screening the speech of a Spanish-English bilingual toddler for early signs of language impairment

This case study presents corpus data gathered from a Spanish-English bilingual child with expressive language delay. Longitudinal data on the child’s linguistic development was collected from the onset of productive speech at age 1;1 until age 4 over the course of 28 video-taped sessions with the child’s principal caregivers. A literature review focused on the relationship between language delay and persisting disorders—including a discussion of the frequent difficulty in distinguishing between the two at early stages of bilingual development—is followed by an analysis of the child’s productive development in 2 distinct phases. An attempt is made to assess the child’s speech at age 4 for preliminary signs of SLI and to consider techniques for identifying ‘at risk’ bilingual children (that is, those with productive language delay, poor oral fluency, and family history of language problems) based on samples of recorded and transcribed speech.
A constrained latent variable model

Latent variable models provide valuable compact representations for learning and inference in many computer vision tasks. However, most existing models cannot directly encode prior knowledge about the specific problem at hand. In this paper, we introduce a constrained latent variable model whose generated output inherently accounts for such knowledge. To this end, we propose an approach that explicitly imposes equality and inequality constraints on the model's output during learning, thus avoiding the computational burden of having to account for these constraints at inference. Our learning mechanism can exploit non-linear kernels, while only involving sequential closed-form updates of the model parameters. We demonstrate the effectiveness of our constrained latent variable model on the problem of non-rigid 3D reconstruction from monocular images, and show that it yields qualitative and quantitative improvements over several baselines.
STIMULUS GENERALIZATION AS A FUNCTION OF MENTAL AGE.

Using frequency as a measure of stimulus-generalization reactivity, the investigator found that lower-mental-age children gave significantly more responses than average-mental-age children and that these in turn demonstrated significantly more responsivity than high-mental-age children. All three groups had irregular latency gradients. The results were interpreted as supporting the hypothesis that stimulus generalization represents a failure to form effective associations to the stimulus as defined by E. Examination of the proportion of Ss responding on the first test trial failed to support the unit hypothesis.
Treatment of extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) with mitoxantrone, chlorambucil and prednisone (MCP).

BACKGROUND Mucosa-associated lymphoid tissue (MALT) lymphoma is a relatively common type of lymphoma arising in various tissues throughout the human body. Currently, there is no standard chemotherapy for advanced stage MALT lymphoma. This has prompted us to retrospectively analyse our experience with the MCP regimen (mitoxantrone, chlorambucil and prednisone) in patients with MALT lymphoma. PATIENTS AND METHODS Patients with histologically verified MALT lymphoma undergoing chemotherapy with MCP were evaluated retrospectively. The MCP regimen consists of mitoxantrone 8 mg/m(2) intravenously on days 1 and 2, chlorambucil 3 x 3 mg/m(2) per os (p.o.) on days 1-5 and prednisone 25 mg/m(2) p.o. on days 1-5. Information analysed included localisation of the lymphoma, clinical stage, pretreatment, number of chemotherapy cycles administered, toxicity, response to treatment, follow-up time, relapse and survival. RESULTS A total of 15 patients (six females and nine males aged between 34 and 88 years) with histologically ascertained MALT lymphoma undergoing treatment with the MCP regimen were identified from our records. Ten patients had extragastric lymphoma, while five patients suffered from gastric MALT lymphoma. All patients were chemotherapy-naïve, while two had been locally irradiated before application of MCP for recurrent disease. A total of 74 cycles was administered to our patients, with a median number of five cycles per patient. Eight (53%) patients achieved complete remission, six (40%) patients partial response and only one (7%) patient had progressive disease. Subjective tolerance was excellent, and toxicities were mainly haematological, including granulocytopenia World Health Organisation grade 3 and 4 in three patients each. In two patients, this was accompanied by single episodes of uncomplicated herpes simplex infection. At the time of analysis, all patients are still alive. No relapses have occurred after a median follow-up time of 16 (range 12-29) months. CONCLUSIONS Our data suggest that MCP is an effective and well-tolerated regimen for treatment of patients with MALT lymphoma irrespective of localisation. Judging from our data, MCP also appears to be a feasible regimen in elderly patients.
Secondary stability assessment of titanium implants with an alkali-etched surface: a resonance frequency analysis study in beagle dogs.

PURPOSE This study was carried out to quantify the effect of an alkali-modified surface on implant stability during healing using an animal model. MATERIALS AND METHODS A total of 24 screw-shaped, self-tapping, commercially pure titanium dental implants, divided into a test group (implants with an alkali-modified surface or "biosurface") and a control group (implants with a turned, machined surface) were inserted without pretapping in the tibiae of 3 beagle dogs. The resonance frequency analysis method was used to measure the implant stability quotient (ISQ) 0, 1, 3, 9, and 12 weeks after implantation. The animals were sacrificed after 2, 5, and 12 weeks, and the bone-implant contact (BIC%) was evaluated histomorphometrically. RESULTS The difference in the osseointegration rates (deltaISQ/deltahealing time) between the implants with alkali-modified surface (biosurface) and those with a turned, machined surface was evaluated as a mean of 0.843 ISQ/week within the first 9 weeks of healing. The mean increase in the secondary implant stability was found to be proportional to the mean increase in the BIC at healing period earlier than 5 weeks. DISCUSSION The characteristics that differed between the implant surfaces, ie, specific surface area, contact angle, and hydroxylation/hydration, may represent factors that influence the rate of osseointegration and the secondary implant stability. CONCLUSION The alkali-treated surface enhances the secondary stability in the early stages of healing compared to the turned, machined surface, as a consequence of faster BIC formation.
The Biofilm Matrix : A Sticky Framework

The extracellular matrix of structured microbial communities constitutes the framework that holds the component cells together. Although the presence of cell-to-cell interconnecting matrices appears to be a common feature of structured microbial communities, there is a remarkable diversity in the composition of these matrices. Compounds such as polysaccharides, fimbriae, mating pili, and extracellular DNA can all function as extracellular matrix components. In the present chapter we provide examples of the diversity of
A novel mechanism for evoked responses in the human brain

Magnetoencephalographic and electroencephalographic evoked responses are primary real‐time objective measures of cognitive and perceptual processes in the human brain. Two mechanisms (additive activity and phase reset) have been debated and considered as the only possible explanations for evoked responses. Here we present theoretical and empirical evidence of a third mechanism contributing to the generation of evoked responses. Interestingly, this mechanism can be deduced entirely from the characteristics of spontaneous oscillations in the absence of stimuli. We show that the amplitude fluctuations of neuronal α oscillations at rest are associated with changes in the mean value of ongoing activity in magnetoencephalography, a phenomenon that we term baseline shifts associated with α oscillations. When stimuli modulate the amplitude of α oscillations, baseline shifts become the basis of a novel mechanism for the generation of evoked responses; the averaging of several trials leads to a cancellation of the oscillatory component but the baseline shift remains, which gives rise to an evoked response. We propose that the presence of baseline shifts associated with α oscillations can be explained by the asymmetric flow of inward and outward neuronal currents related to the generation of α oscillations. Our findings are relevant to the vast majority of electroencephalographic and magnetoencephalographic studies involving perceptual, cognitive and motor activity.
Utility of MELD and Child-Turcotte-Pugh scores and the Canadian waitlisting algorithm in predicting short-term survival after liver transplant.

BACKGROUND The Model for End-Stage Liver Disease (MELD) and Child-Turcotte-Pugh (CTP) scores are important predictors for survival after liver transplantation (LT). The objective of this study was to compare the utility of MELD and CTP scores with Canadian waitlisting algorithm in transplantation (CanWAIT) status for predicting 90-day survival after LT. METHODS Retrospectively, we analyzed all 228 liver transplants performed in adults by the Atlantic Liver Transplant Program since 1985. These cases included combined transplants, retransplants and those after fulminant liver failure. MELD and CTP scores were calculated, and CanWAIT status and waiting time on the day of LT determined. We used c-statistic for 90-day outcome as the endpoint (survival), comparing areas under the receiver operating characteristic (ROC) curves for MELD and CTP scores and CanWAIT status. RESULTS Mean (and standard deviation [SD]) MELD score was 18 (SD 12); CTP score, 10 (SD 3); and waiting time, 97 (SD 132) days. At the time of LT, 54% were in CanWAIT status 1; 4% in 1T; 14% in 2; 11% in 3; 6% in 3F; 4% in 4; and 7% in status 4F. Overall 90-day survival was 80% (95% confidence interval [CI] 75%-85%), exceeding the predicted survival by MELD scale with transplant of only 51% (CI 47%-55%). By c-statistic, CanWAIT is a clinically relevant predictor of 90-day outcomes in LT. By multivariate regression analysis, only CanWAIT status and age were found to have independent associations for short-term outcomes after LT. INTERPRETATION CanWAIT status stratifies LT patients better and predicts short-term outcome more accurately than MELD or CTP scores, and so should not be replaced by MELD or CTP scores. This observation should be confirmed by a prospective and multicentre study in Canada.
Rescue of Very Virulent and Mosaic Infectious Bursal Disease Virus from Cloned cDNA: VP2 Is Not the Sole Determinant of the Very Virulent Phenotype

ABSTRACT Many recent outbreaks of infectious bursal disease in commercial chicken flocks worldwide are due to the spread of very virulent strains of infectious bursal disease virus (vvIBDV). The molecular determinants for the enhanced virulence of vvIBDV compared to classical IBDV are unknown. The lack of a reverse genetics system to rescue vvIBDV from its cloned cDNA hampers the identification and study of these determinants. In this report we describe, for the first time, the rescue of vvIBDV from its cloned cDNA. Two plasmids containing a T7 promoter and either the full-length A- or B-segment cDNA of vvIBDV (D6948) were cotransfected into QM5 cells expressing T7 polymerase. The presence of vvIBDV could be detected after passage of the transfection supernatant in either primary bursa cells (in vitro) or embryonated eggs (in vivo), but not QM5 cells. Rescued vvIBDV (rD6948) appeared to have the same virulence as the parental isolate, D6948. Segment-reassorted IBDV, in which one of the two genomic segments originated from cDNA of classical attenuated IBDV CEF94 and the other from D6948, could also be rescued by using this system. Segment-reassorted virus containing the A segment of the classical attenuated isolate (CEF94) and the B segment of the very virulent isolate (D6948) is not released until 15 h after an in vitro infection. This indicates a slightly retarded replication, as the first release of CEF94 is already found at 10 h after infection. Next to segment reassortants, we generated and analyzed mosaic IBDVs (mIBDVs). In these mIBDVs we replaced the region of CEF94 encoding one of the viral proteins (pVP2, VP3, or VP4) by the corresponding region of D6948. Analysis of these mIBDV isolates showed that tropism for non-B-lymphoid cells was exclusively determined by the viral capsid protein VP2. However, the very virulent phenotype was not solely determined by this protein, since mosaic virus containing VP2 of vvIBDV induced neither morbidity nor mortality in young chickens.
Protective Effects of Acyl-coA Thioesterase 1 on Diabetic Heart via PPARα/PGC1α Signaling

Background Using fatty acids (FAs) exclusively for ATP generation was reported to contribute to the development of diabetic cardiomyopathy. We studied the role of substrate metabolism related genes in the heart of the diabetes to find out a novel therapeutic target for diabetic cardiomyopathy. Methods and Results By microarray analysis of metabolic gene expression, acyl-CoA thioesterase 1 (acot1) was clearly upregulated in the myocardia of db/db mice, compared with normal control C57BL/Ks. Therefore, gain-of-function and loss-of-function approaches were employed in db/db mice to investigate the functions of ACOT1 in oxidative stress, mitochondrial dysfunction and heart function. We found that in the hearts of db/db mice which overexpressed ACOT1, H2O2 and malondialdehyde (MDA) were reduced, the activities of ATPases in mitochondria associated with mitochondrial function were promoted, the expression of uncoupling protein 3 (UCP3) contributing to oxygen wastage for noncontractile purposes was decreased, and cardiac dysfunction was attenuated, as determined by both hemodynamic and echocardiographic detections. Consistently, ACOT1 deficiency had opposite effects, which accelerated the cardiac damage induced by diabetes. Notably, by real-time PCR, we found that overexpression of ACOT1 in diabetic heart repressed the peroxisome proliferator-activated receptor alpha/PPARγ coactivator 1α (PPARα/PGC1α) signaling, as shown by decreased expression of PGC1α and the downstream genes involved in FAs use. Conclusion Our results demonstrated that ACOT1 played a crucial protective role in diabetic heart via PPARα/PGC1α signaling.
Integration of Fault Diagnosis and Fault-Tolerant Control for Health Monitoring of a Class of MIMO Intelligent Autonomous Vehicles

This paper deals with the integration of robust bondgraph-model-based fault diagnosis (FD) with structural recoverability analysis and fault-tolerant control (FTC) of an intelligent heavy-size and autonomous vehicle, used for loading and routing 20- and 40-ft containers inside port terminals. The overactuated vehicle is an omnidirectional mobile platform with redundant actuators such as four independent driven wheels, four independent braking wheels, and four-wheel steering systems. The supervision system is able to monitor the health condition of the vehicle and to study the fault recoverability possibilities to reconfigure the control input when a fault occurs. For FD, analytical redundancy relations (ARRs) are derived from the bond graph model. The latter is constraint relations describing the nominal system behavior and is written in terms of the measured system variables. To perform robust FD, adaptive thresholds are generated. They consider modeling and measurement uncertainties. Once a fault is detected, the structural recoverability algorithm analyzes the redundancy presented on the system, and an appropriate control strategy is applied. The designed procedure of FD and FTC is validated by considering a multiple-fault scenario on the vehicle and comparing its results with the nominal case.
In Vitro Characterization of Enzymatic Properties and Inhibition of the p53R2 Subunit of Human Ribonucleotide Reductase

p53R2 is a newly identified subunit of ribonucleotide reductase (RR) and plays a crucial role in supplying precursors for DNA repair in a p53-dependent manner. In our current work, all three human RR subunit proteins (p53R2, hRRM2, and hRRM1) were prokaryotically expressed and highly purified. Using an in vitro [3H]CDP reduction assay, the activity of RR reconstituted with either p53R2 or hRRM2 was found to be time, concentration, and hRRM1 dependent. The kinetic activity of p53R2-containing RR was about 20–50% lower than that of hRRM2-containing RR. Using a synthetic heptapeptide to inhibit RR activity, it was shown that p53R2 bound to hRRM1 through the same COOH-terminal heptapeptide as hRRM2. However, hRRM2 had a 4.76-fold higher binding affinity for hRRM1 than p53R2, which may explain the reduced RR activity of p53R2 relative to hRRM2. Of interest, p53R2 was 158-fold more susceptible to the iron chelator deferoxamine mesylate than hRRM2, although the iron content of the two proteins determined by atomic absorption spectrometer was almost the same. To the contrary, p53R2 was 2.50-fold less sensitive than hRRM2 to the radical scavenger hydroxyurea, whereas EPR showed similar spectra of the tyrosyl radical in two proteins. Triapine, a new RR inhibitor, was equally potent for p53R2 and hRRM2. These inhibition studies showed that the iron center and tyrosyl radical are involved in RR activity for both p53R2 and hRRM2. The susceptibility differences to RR inhibitors between p53R2 and hRRM2 may lead to a new direction in drug design for human cancer treatment.
Personal skills development and first year undergraduate accounting education: a teaching note

There is a growing awareness of the need to develop a broad range of competencies in accounting undergraduates. In recognition of this, Thames Valley University developed an accounting biased Personal Skills Development (PSD) module to run alongside the first year introductory module in accounting. This note summarises the characteristics of the PSD module and some of the students views on its effectiveness. It also briefly looks at the possible impact of taking the PSD module on students performance in the introductory module in accounting.
The Tsimane Health and Life History Project: Integrating anthropology and biomedicine

The Tsimane Health and Life History Project, an integrated bio‐behavioral study of the human life course, is designed to test competing hypotheses of human life‐history evolution. One aim is to understand the bidirectional connections between life history and social behavior in a high‐fertility, kin‐based context lacking amenities of modern urban life (e.g. sanitation, banks, electricity). Another aim is to understand how a high pathogen burden influences health and well‐being during development and adulthood. A third aim addresses how modernization shapes human life histories and sociality. Here we outline the project's goals, history, and main findings since its inception in 2002. We reflect on the implications of current findings and highlight the need for more coordinated ethnographic and biomedical study of contemporary nonindustrial populations to address broad questions that can situate evolutionary anthropology in a key position within the social and life sciences.