Miracle-dz/UniFAR-FTUs huggingface dataset:
Genomic cloning and characterization of the human homeobox gene SIX6 reveals a cluster of SIX genes in chromosome 14 and associates SIX6 hemizygosity with bilateral anophthalmia and pituitary anomalies.

The Drosophila gene sine oculis (so), a nuclear homeoprotein that is required for eye development, has several homologues in vertebrates (the SIX gene family). Among them, SIX3 is considered to be the functional orthologue of so because it is strongly expressed in the developing eye. However, embryonic SIX3 expression is not limited to the eye field, and SIX3 has been found to be mutated in some patients with holoprosencephaly type 2 (HPE2), suggesting that SIX3 has wide implications in head development. We report here the cloning and characterization of SIX6, a novel human SIX gene that is the homologue of the chick Six6(Optx2) gene. SIX6 is closely related to SIX3 and is expressed in the developing and adult human retina. Data from chick and mouse suggest that the human SIX6 gene is also expressed in the hypothalamic and the pituitary regions. SIX6 spans 2567 bp of genomic DNA and is split in two exons that are transcribed into a 1393-nucleotide-long mRNA. Chromosomal mapping of SIX6 revealed that it is closely linked to SIX1 and SIX4 in human chromosome 14q22.3-q23, which provides clues about the origin and evolution of the vertebrate SIX family. Recently three independent reports have associated interstitial deletions at 14q22.3-q23 with bilateral anophthalmia and pituitary anomalies. Genomic analyses of one of these cases demonstrated SIX6 hemizygosity, strongly suggesting that SIX6 haploinsufficiency is responsible for these developmental disorders.
Divergence estimation for machine learning and signal processing

Approximating a divergence between two probability distributions from their samples is a fundamental challenge in the statistics, information theory, and machine learning communities, because a divergence estimator can be used for various purposes such as two-sample homogeneity testing, change-point detection, and class-balance estimation. Furthermore, an approximator of a divergence between the joint distribution and the product of marginals can be used for independence testing, which has a wide range of applications including feature selection and extraction, clustering, object matching, independent component analysis, and causality learning. In this talk, we review recent advances in direct divergence approximation that follow the general inference principle advocated by Vladimir Vapnik-one should not solve a more general problem as an intermediate step. More specifically, direct divergence approximation avoids separately estimating two probability distributions when approximating a divergence. We cover direct approximators of the Kullback-Leibler (KL) divergence, the Pearson (PE) divergence, the relative PE (rPE) divergence, and the L2-distance. Despite the overwhelming popularity of the KL divergence, we argue that the latter approximators are more useful in practice due to their computational efficiency, high numerical stability, and superior robustness against outliers.
Identification, Characterization, and Localization of a Novel Kidney Polycystin-1-Polycystin-2 Complex*

The functions of the two proteins defective in autosomal dominant polycystic kidney disease, polycystin-1 and polycystin-2, have not been fully clarified, but it has been hypothesized that they may heterodimerize to form a “polycystin complex” involved in cell adhesion. In this paper, we demonstrate for the first time the existence of a native polycystin complex in mouse kidney tubular cells transgenic for PKD1, non-transgenic kidney cells, and normal adult human kidney. Polycystin-1 is heavilyN-glycosylated, and several glycosylated forms of polycystin-1 differing in their sensitivity to endoglycosidase H (Endo H) were found; in contrast, native polycystin-2 was fully Endo H-sensitive. Using highly specific antibodies to both proteins, we show that polycystin-2 associates selectively with two species of full-length polycystin-1, one Endo H-sensitive and the other Endo H-resistant; importantly, the latter could be further enriched in plasma membrane fractions and co-immunoprecipitated with polycystin-2. Finally, a subpopulation of this complex co-localized to the lateral cell borders of PKD1 transgenic kidney cells. These results demonstrate that polycystin-1 and polycystin-2 interact in vivo to form a stable heterodimeric complex and suggest that disruption of this complex is likely to be of primary relevance to the pathogenesis of cyst formation in autosomal dominant polycystic kidney disease.
Psychiatric comorbidity and functioning in clinically referred preschool children and school-age youths with ADHD.

OBJECTIVE Although the literature documents that attention-deficit/hyperactivity disorder (ADHD) commonly onsets prior to age 6, little is known about the disorder in preschool children. We evaluated the clinical characteristics, psychiatric comorbidity, and functioning of preschool children and school-age youths with ADHD referred to a pediatric psychiatric clinic for evaluation. METHOD Structured psychiatric interviews assessing lifetime psychopathology by DSM-III-R criteria were completed with parents about their children. Family, social, and overall functioning were also assessed at intake. RESULTS We identified 165 children with ADHD aged 4 to 6 years (preschool children) and 381 youths aged 7 to 9 years (school-age) with ADHD. Despite being younger, preschool children had similar rates of comorbid psychopathology compared with school-age youths with ADHD. There was an earlier onset of ADHD and co-occurring psychopathology in the preschool children compared to school-age youths. Both preschool children and school-age youths had substantial impairment in school, social, and overall functioning. CONCLUSIONS The results of this study suggest that despite being significantly younger, clinically referred preschool children with ADHD are reminiscent of school-age youths with ADHD in the quality of ADHD, high rates of comorbid psychopathology, and impaired functioning. Follow-up of these clinically referred preschool children with ADHD to evaluate the stability of their diagnoses, treatment response, and their long-term outcome are necessary.
Exact Output Regulation for Nonlinear Systems Described by Takagi–Sugeno Fuzzy Models

The exact output regulation for Takagi-Sugeno (T-S) fuzzy models depends on two conditions: 1) The local steady-state zero-error manifolds have to be the same for every local subsystem, and 2) the local input matrices have to be the same for every local subsystem included in the T-S fuzzy model. These conditions are difficult to satisfy in general. In this paper, those conditions are relaxed by solving the fuzzy regulation problem directly on the overall T-S fuzzy model, instead of constructing the fuzzy regulator on the basis of linear local controllers. By considering the fuzzy model as a special class of linear time-varying systems, existence conditions are rigorously derived. These new conditions, which can be solved by means of any mathematical software, depend on the solution of a set of symbolic simultaneous linear equations depending on the membership values of the plant and/or the exosystem. Two examples are given to illustrate the construction of the proposed regulator and to validate the improvement that is achieved with the proposed approach.
Multi-Timescale Coordinated Voltage/Var Control of High Renewable-Penetrated Distribution Systems

This paper proposes a multi-timescale coordinated stochastic voltage/var control method for high renewable-penetrated distribution networks. It aims to utilize multiple devices to counteract uncertain voltage fluctuation and deviation. In the hourly timescale (first stage), capacitor banks and transformer tap changers are scheduled before stochastic renewable output and load variations are realized. In the 15-min timescale (second stage), inverters that interface the renewable energy resources provide var support to supplement the first-stage decision after uncertainty is observed. The coordination is model as a two-stage stochastic programming problem with scenario reduction. It is then converted to a deterministic mixed-integer quadratic programming equivalence model and solved by commercial solvers combined. Compared with existing methods, the proposed volt/var control can achieve lower expected energy loss and can sustain a secure voltage level under random load demand and renewable power injection. The proposed method is verified on the IEEE 33-bus distribution network and compared with existing practices.
Jab1/CSN5, a Component of the COP9 Signalosome, Regulates Transforming Growth Factor β Signaling by Binding to Smad7 and Promoting Its Degradation

ABSTRACT Smad7 inhibits responses mediated by transforming growth factor β (TGF-β) and acts in a negative-feedback loop to regulate the intensity or duration of the TGF-β signal. However, the aberrant expression and continued presence of Smad7 may cause TGF-β resistance. Here we report that Jab1/CSN5, which is a component of the COP9 signalosome complex, associates constitutively with Smad7 and that overexpression of Jab1/CSN5 causes the translocation of Smad7 from the nucleus to the cytoplasm, promoting its degradation. Overexpression of Jab1/CSN5 increases Smad2 phosphorylation and enhances TGF-β-induced transcriptional activity. The inhibition of endogenous Jab1/CSN5 expression by small interfering RNA (siRNA) induces Smad7 expression. This study thus defines Jab1/CSN5 as an adapter that targets Smad7 for degradation, thus releasing Smad7-mediated suppression of TGF-β signaling.
Adrenoleukodystrophy: a scoring method for brain MR observations.

PURPOSE To develop a scoring method for brain observations in patients with X-linked adrenoleukodystrophy. METHODS One hundred seventy-five brain MR scans in 83 male subjects less than 20 years of age with proved biochemical defects were reviewed. A severity score (0 to 34), based on a point system derived from location and extent of disease and the presence of focal and/or global atrophy, was calculated for each exam. RESULTS Fifty-five of the 83 patients showed MR findings consistent with adrenoleukodystrophy. Two major patterns were observed. A posterior pattern (mean score, 9; range, 0.5 to 25) was present in 80% of patients, and an anterior pattern (mean score, 10; range, 2 to 18) was present in 15% of patients. Serial MR imaging, positive for adrenoleukodystrophy in 34 patients (mean follow-up, 23 months; range, 2 months to 6 years 11 months), showed progressive disease in 52%, progressive disease with subsequent stabilization in 18%, stable disease in 24%, and minimal improvement in 6%. CONCLUSION The adrenoleukodystrophy MR severity scoring method is a measure that can be used with standard MR images. When used in conjunction with clinical parameters, this scoring method may help define better the natural history of adrenoleukodystrophy and monitor response to developing therapies.
A compact highly selective bandpass filter with wide upper-stopband

In this paper, a compact highly selective bandpass filter with wide upper-stopband using short-circuited microstrip coupled-line hairpin resonator is presented. The equivalent transmission-line circuit model is developed to analyze the performance of the proposed filter. There are two transmission poles existing at each resonance of a single short-circuited microstrip coupled-line hairpin unit. The feeding lines are capacitively coupled to the resonator at the location where the finger of the hairpin is divided into two segments at a ratio of 1∶2. As a result, the first harmonic appears at the frequency which is 5 times of the fundamental frequency and three transmission zeros are also generated to improve the skirt effect. Therefore, a compact bandpass filter with a wide upper-stopband is achieved. Finally, the proposed filter is fabricated to verify the design principles, and the measured results agree well with the predicted ones.
Rho‐kinase 2 is frequently overexpressed in hepatocellular carcinoma and involved in tumor invasion

Deregulation of Rho family small guanosine triphosphatases has been implicated in human carcinogenesis. Rho‐kinases are downstream effectors of Rho guanosine triphosphatases in the regulation of cytoskeletal reorganization and cell motility. However, their functions in human cancers remain elusive. In this study, we aimed to investigate the role of Rho‐kinases in hepatocellular carcinoma (HCC) tumor progression and invasion. We first examined the expression of the two Rho‐kinases (ROCK1 and ROCK2) in human HCC, and found that ROCK2 was frequently overexpressed in primary HCCs (22/41 [53.66%]). Clinico‐pathological analysis revealed that overexpression of ROCK2 was significantly associated with the presence of tumor microsatellite formation (P = 0.005), suggesting that deregulation of ROCK2 may contribute to the intrahepatic metastasis of HCC. Consistently, we demonstrated that stable overexpression of ROCK2 significantly enhanced cell motility and invasiveness in HCC cells. Conversely, stable knockdown of ROCK2 by short hairpin RNA approach remarkably reduced HCC cell migration and invasion. Moreover, orthotopic liver xenograft models provided further support that stable knockdown of ROCK2 suppressed HCC invasion in vivo. Stable knockdown of ROCK2 in HCC cells significantly inhibited Golgi reorientation, myosin phosphatase phosphorylation, and formations of stress fibers, filopodia, and lamellipodia; these molecular and cellular events are crucial for cell motility and cancer invasion. Conclusion: Our results indicate that ROCK2 was overexpressed in human HCCs, and this overexpression was associated with a more aggressive biological behavior. Our findings also demonstrate that ROCK2 played a significant role in regulating cytoskeletal events and contributed to the invasion of HCC. (HEPATOLOGY 2009.)
Sleep Transistor Sizing for Leakage Power Minimization Considering Charge Balancing

One of the effective techniques to reduce leakage power is power gating. Previously, a distributed sleep transistor network was proposed to reduce the sleep transistor area for power gating by connecting all the virtual ground lines together to minimize the maximum instantaneous current flowing through sleep transistors. In this paper, we propose a new methodology for determining the sizes of sleep transistors of the DSTN structure. We present novel algorithms and theorems for efficiently estimating a tight upper bound of the voltage drop and minimizing the sizes of sleep transistors. We also present mathematical proofs of our theorems and lemmas in detail. Our experimental results show 23.36% sleep transistor area reduction compared to the previous work on average.
The rise of infectious syphilis in Victoria and the impact of enhanced clinical testing

Objective: Passive surveillance indicates a clear increase in infectious syphilis cases in Victoria, but trends are likely to be influenced by changes in testing. We therefore used testing data from two Melbourne clinics with a high caseload of men who have sex with men to examine infectious syphilis prevalence, time trends and risk factors for infection.
Transcription of the myogenic regulatory gene Mef2 in cardiac, somatic, and visceral muscle cell lineages is regulated by a Tinman-dependent core enhancer.

The MADS-box transcription factor MEF2 is expressed specifically in developing cardiac, somatic, and visceral muscle cell lineages during Drosophila embryogenesis and is required for myoblast differentiation and muscle morphogenesis. To define the mechanisms that regulate Mef2 transcription, we have analyzed the Mef2 upstream region for sequences sufficient to recapitulate the expression pattern of the gene in Drosophila embryos. Here we describe a complex enhancer located 5.8 kb upstream of the Drosophila Mef2 gene that controls transcription in cardial cells of the dorsal vessel, a subset of somatic muscle founder cells, and the visceral muscle cells. The core of this enhancer contains two evolutionarily conserved binding sites for the homeodomain protein Tinman (Tin), expressed in developing cardiac, somatic, and visceral muscle lineages. Both Tin binding sites are required for enhancer activity in all three muscle cell lineages. Whereas the 285-bp enhancer core alone is sufficient for expression in cardiac cells, expression in somatic founder cells and visceral muscle is dependent on the core enhancer plus unique flanking sequences that include an evolutionarily conserved E box. These results reveal an essential role for Tin in activation of Mef2 transcription in multiple myogenic lineages and demonstrate that transcriptional activity of Tin is dependent on combinatorial interactions with other factors unique to different muscle cell types.
Rash with Both Clopidogrel and Ticlopidine in Two Patients Following Percutaneous Coronary Intervention with Drug-Eluting Stents

Objective: To describe 2 cases of rash that occurred following oral administration of both clopidogrel and ticlopidine and to review previously published case reports. Case Summary: Two patients developed maculopapular pruritic rashes that began on the abdomen and spread to the back, neck, and face following clopidogrel administration after placement of a drug-eluting intracoronary stent. Following recurrence of the rash after ticlopidine was initiated, thienopyridines were discontinued, and the patients were treated for 3–6 months with aspirin, cilostazol, and enoxaparin or warfarin for prevention of stent thrombosis and reinfarction. One patient self-discontinued cilostazol, reinitiated clopidogrel, and redeveloped a rash. Discussion: While there have been several published cases of thienopyridine-associated rash, there have been only 2 reported cases of cross-sensitivity between orally administered clopidogrel and ticlopidine. Preliminary reports suggest that clopidogrel desensitization may be accomplished in selected patients several months to years following thienopyridine rash using an allergy desensitization protocol, with close monitoring for anaphylaxis. An objective causality assessment using the Naranjo probability scale indicated that both ticlopidine and clopidogrel were probable causes of the rash in the first patient; in the second patient, clopidogrel was judged a definite cause and ticlopidine was a probable cause of the rash. Conclusions: In a patient who develops a rash following clopidogrel treatment after intracoronary stent placement, ticlopidine therapy should be attempted, provided the initial reaction did not include life-threatening symptoms. In a patient who experiences rash with both clopidogrel and ticlopidine and does not have a contraindication to cilostazol or anticoagulation, therapy with aspirin, cilostazol, and either enoxaparin or warfarin may be administered for 2–6 months following placement of a drug-eluting stent.
Prevention of Cytomegalovirus Disease in Recipients of Allogeneic Stem Cell Transplants

SUMMARY The main risk factors for cytomegalovirus (CMV) disease in recipients of allogeneic stem cell transplants (SCT) are recipient CMV seropositivity and acute graft-versus-host disease. Currently, two antiviral strategies, prophylactic or preemptive antiviral treatment, are used for prevention of CMV disease. Preemptive treatment is most favorable when short-term (14-day) treatment is applied. Several methods are available for monitoring of CMV reactivation. PCR-based CMV DNA detection assays are the most sensitive methods; however, the clinical benefit of this high sensitivity is unclear. Even more, there is lack of clarity whether PCR tests can better be performed with plasma, whole blood, or peripheral blood leukocyte samples. Recovery of a CMV-specific CD8+ cytotoxic-T-lymphocyte (CTL) response is necessary for preventing CMV reactivation and disease. Reconstitution of absolute CMV-specific CTL counts to values above 10 × 106 to 20 × 106 CTLs/liter is associated with protection from CMV disease. In the near future, preemptive therapy might be withheld in patients with CMV reactivation who are shown to have adequate CMV-specific cytotoxic T-cell levels. Antiviral therapy with (val)acyclovir has been studied only as prophylactic treatment for prevention of CMV infection. High-dose oral valacyclovir is more effective than acyclovir when used in addition to preemptive treatment of CMV reactivation with ganciclovir or foscarnet. Three antiviral drugs have been tested for preemptive therapy of CMV reactivation and/or treatment of CMV disease. Although intravenous ganciclovir is considered the drug of choice, foscarnet has similar efficacy and less toxicity, especially hematologic toxicity. Cidofovir has not been tested extensively, but so far the results are disappointing. Oral valganciclovir for preemptive treatment of SCT recipients is currently being studied. In addition to antiviral therapy, adoptive immunotherapy with CMV-specific cytotoxic T cells as prophylactic or preemptive therapy is a very elegant strategy; however, generation of these cells is expensive and time-consuming, and therefore the therapy is not available at every transplantation center. Magnetic selection of CMV-specific CD8+ T cells from peripheral blood by using HLA class I-peptide tetramers may be very promising, making this strategy more accessible.
A girl with inverted triplication of chromosome 3q25.3 → q29 and multiple congenital anomalies consistent with 3q duplication syndrome

We report a newborn girl with intrachromosomal triplication of 3q25.3 → q29 (mosaicism) who died at the age of 3.5 weeks due to her malformations. She demonstrated disproportionate short stature with short limbs, a prominent and hairy forehead, thick eyebrows, synophrys, small upturned nose, full cheeks, micrognathia, and low set malformed and posteriorly rotated ears, short and webbed neck, hydrocephalus, Dandy–Walker malformation, spina bifida, complex heart defect (ventricular and atrial septal defect, malrotation, and interrupted aortic arch), omphalocele, polycystic kidneys, postaxial polydactyly of left hand, and generalized hirsutism; all signs have been associated with the dup(3q) syndrome previously. The facial appearance (hairy forehead, thick eyebrows, synophrys, small upturned nose, full cheeks, micrognathia, low set malformed and posteriorly rotated ears) showed resemblance to the Brachmann–de Lange syndrome (BDLS), but the patient did not fulfill the diagnostic criteria for BDLS. There has been only one report of a direct triplication of chromosome 3 until now, but in our case the triplicated area is larger, located more proximally, and includes the hypothetical BDLS critical gene region‐CDL1. Our findings lend support to distal chromosome 3q, or chromosome 3q26.3, comprises the critical area for the dup(3q) phenotype resembling the BDLS. © 2005 Wiley‐Liss, Inc.
Hybrid current-controlled VSI-IM drive

Development of the hybrid type of control and the introduction of automation in Voltage Source Inverter switching control creates a basis for the evolution of Switching type Current Control in the direction of good compromise between Switching type Current Control and Pulse-Width Modulation features. The main premises in the design of the proposed hybrid current control are: (i) a stator current error plane in the d-q frame is divided into strip shaped regions for the selection of the controllers design (ii) stability is based on common quadratic Lyapunov function, (iii) the globally stable dynamics should guarantee uniform crossing of boundaries in the d-q frame, and (iv) superimposed automation supervises the non-Zenon VSI switching sequence.