Miracle-dz/UniFAR-FTUs huggingface dataset:
Isologous IgG‐Induced Immunologic Tolerance to Haptens: A Model of Self Versus Non‐Self Recognition

An important function of the immune system is to tolerate self. A sideline of this central role is the defense against foreign antigens. How the body discriminates self from non-self is perhaps one of the most significant biological mechanisms in the life cycle, since if it did not exist, we would be destroyed in utero by an immune response to our own antigens. Whatever this mechanism, it is intimately related to the phenomenon of immunologic tolerance. In this review, the problem of self versus non-self discrimination to simple haptens using the model of carrier-determined tolerance will be reviewed. The system is unique for two reasons: the hapten by itself is neither immunogenic nor tolerogenic; the carrier protein to which the hapten is covalently bound, as tolerance-inducing carrier, is a physiologic protein naturally tolerated by the host. Discussion will be limited to work from the author's laboratory or that done in direct collaboration with others. The main theme of this review is to show how the induction of tolerance to haptens is a simple but powerful tool to examine two fundamental problems: the cellular basis of tolerance and the potential clinical application of tolerance to the treatment of immune disease.
Coenzyme B12 Controls Transcription of the Streptomyces Class Ia Ribonucleotide Reductase nrdABS Operon via a Riboswitch Mechanism

ABSTRACT Ribonucleotide reductases (RNRs) catalyze the conversion of ribonucleotides to deoxyribonucleotides and are essential for de novo DNA synthesis and repair. Streptomycetes contain genes coding for two RNRs. The class Ia RNR is oxygen dependent, and the class II RNR is oxygen independent and requires coenzyme B12. Either RNR is sufficient for vegetative growth. We show here that the Streptomyces coelicolor M145 nrdABS genes encoding the class Ia RNR are regulated by coenzyme B12. The 5′-untranslated region of nrdABS contains a 123-nucleotide B12 riboswitch. Similar B12 riboswitches are present in the corresponding regions of eight other S. coelicolor genes. The effect of B12 on growth and nrdABS transcription was examined in a mutant in which the nrdJ gene, encoding the class II RNR, was deleted. B12 concentrations of just 1 μg/liter completely inhibited growth of the NrdJ mutant strain. Likewise, B12 significantly reduced nrdABS transcription. To further explore the mechanism of B12 repression, we isolated in the nrdJ deletion strain mutants that are insensitive to B12 inhibition of growth. Two classes of mutations were found to map to the B12 riboswitch. Both conferred resistance to B12 inhibition of nrdABS transcription and are likely to affect B12 binding. These results establish that B12 regulates overall RNR expression in reciprocal ways, by riboswitch regulation of the class Ia RNR nrdABS genes and by serving as a cofactor for the class II RNR.
Prenatal Phenol and Phthalate Exposures and Birth Outcomes

BACKGROUND Many phthalates and phenols are hormonally active and are suspected to alter the course of development. OBJECTIVE We investigated prenatal exposures to phthalate and phenol metabolites and their associations with body size measures of the infants at birth. METHODS We measured 5 phenol and 10 phthalate urinary metabolites in a multiethnic cohort of 404 women in New York City during their third trimester of pregnancy and recorded size of infants at birth. RESULTS Median urinary concentrations were > 10 microg/L for 2 of 5 phenols and 6 of 10 phthalate monoester metabolites. Concentrations of low-molecular-weight phthalate monoesters (low-MWP) were approximately 5-fold greater than those of high-molecular-weight metabolites. Low-MWP metabolites had a positive association with gestational age [0.97 day gestational age per ln-biomarker; 95% confidence interval (CI), 0.07-1.9 days, multivariate adjusted] and with head circumference. Higher prenatal exposures to 2,5-dichlorophenol (2,5-DCP) predicted lower birth weight in boys (-210 g average birth weight difference between the third tertile and first tertile of 2,5-DCP; 95% CI, 71-348 g). Higher maternal benzophenone-3 (BP3) concentrations were associated with a similar decrease in birth weight among girls but with greater birth weight in boys. CONCLUSIONS We observed a range of phthalate and phenol exposures during pregnancy in our population, but few were associated with birth size. The association of 2,5-DCP and BP3 with reduced or increased birth weight could be important in very early or small-size births. In addition, positive associations of urinary metabolites with some outcomes may be attributable partly to unresolved confounding with maternal anthropometric factors.
Pseudo-Orthogonal Space-Time Block Codes for MIMO-OFDM Systems over Frequency-Selective Channels

This paper proposes a new class of space-time block code, which is manipulated from the existing transmit diversity schemes. We analyze the performance and the receiver complexity of the proposed scheme and confirm that the new diversity scheme can yield performance gain over other existing four-transmit antenna cases. By relaxing the diversity criterion on code designs, the proposed space-time code provides a full transmission rate for four-transmit antennas and makes it possible to approach the open-loop Shannon channel capacity. Outage capacity and simulation results are used to show that substantial improvements in performance while maintaining a simple linear processing receiver structure are obtained in frequency selective channels
Pubertal delay in male nonhuman primates (Macaca mulatta) treated with methylphenidate

Juvenile male rhesus monkeys treated with methylphenidate hydrochloride (MPH) to evaluate genetic and behavioral toxicity were observed after 14 mo of treatment to have delayed pubertal progression with impaired testicular descent and reduced testicular volume. Further evaluation of animals dosed orally twice a day with (i) 0.5 mL/kg of vehicle (n = 10), (ii) 0.15 mg/kg of MPH increased to 2.5 mg/kg (low dose, n = 10), or (iii) 1.5 mg/kg of MPH increased to 12.5 mg/kg (high dose, n = 10) for a total of 40 mo revealed that testicular volume was significantly reduced (P < 0.05) at months 15 to 19 and month 27. Testicular descent was significantly delayed (P < 0.05) in the high-dose group. Significantly lower serum testosterone levels were detected in both the low- (P = 0.0017) and high-dose (P = 0.0011) animals through month 33 of treatment. Although serum inhibin B levels were increased overall in low-dose animals (P = 0.0328), differences between groups disappeared by the end of the study. Our findings indicate that MPH administration, beginning before puberty, and which produced clinically relevant blood levels of the drug, impaired pubertal testicular development until ∼5 y of age. It was not possible to resolve whether MPH delayed the initiation of the onset of puberty or reduced the early tempo of the developmental process. Regardless, deficits in testicular volume and hormone secretion disappeared over the 40-mo observation period, suggesting that the impact of MPH on puberty is not permanent.
Panic and Agoraphobia: Gender as a Factor

Anxiety is a common experience, particularly as a response to life stressors. However, severe and uncontrollable anxiety can become a mental disorder. Community studies indicate that 19% of men and 31% of women will develop some type of anxiety disorder during their lifetime. In one such study, the National Comorbidity Survey (NCS), risk factors associated with a lifetime of anxiety disorder included lower income, less education, living in the northeast, and being female. The impact of patient sex is profound in that it increases the likelihood of developing an anxiety disorder by 85% in women compared to men. Panic disorder is characterized by brief but intense recurrent episodes of fear or discomfort. Diagnostic criteria require recurrent panic attacks in 1 month or one panic attack with continuous fear of other attacks. Symptoms associated with the panic attack include palpitations; sweating; feeling short of breath or a choking sensation; nausea or abdominal discomfort; feeling dizzy; having a sense of unreality; numbness or tingling; chills or hot flushes; and a fear of dying or losing control.
Active hypertext for distributed Web applications

The prevailing architecture for Web-based applications relies on HTML, HTTP and loosely integrated functional elements, propagating a strong distinction between client and server. The proposed approach for active hypertext documents however realizes applications through hypertext documents with embedded application logic. Furthermore, the need for separating the approach into a model, a development method and supporting tools is identified. The core model is based on open standards such as XML and CSS. It is extended by idioms which describe important concepts and reusable constructs. Examples for the application of the model are given.
Folding of the yeast prion protein Ure2: kinetic evidence for folding and unfolding intermediates.

The Saccharomyces cerevisiae non-Mendelian factor [URE3] propagates by a prion-like mechanism, involving aggregation of the chromosomally encoded protein Ure2. The N-terminal prion domain (PrD) of Ure2 is required for prion activity in vivo and amyloid formation in vitro. However, the molecular mechanism of the prion-like activity remains obscure. Here we measure the kinetics of folding of Ure2 and two N-terminal variants that lack all or part of the PrD. The kinetic folding behaviour of the three proteins is identical, indicating that the PrD does not change the stability, rates of folding or folding pathway of Ure2. Both unfolding and refolding kinetics are multiphasic. An intermediate is populated during unfolding at high denaturant concentrations resulting in the appearance of an unfolding burst phase and "roll-over" in the denaturant dependence of the unfolding rate constants. During refolding the appearance of a burst phase indicates formation of an intermediate during the dead-time of stopped-flow mixing. A further fast phase shows second-order kinetics, indicating formation of a dimeric intermediate. Regain of native-like fluorescence displays a distinct lag due to population of this on-pathway dimeric intermediate. Double-jump experiments indicate that isomerisation of Pro166, which is cis in the native state, occurs late in refolding after regain of native-like fluorescence. During protein refolding there is kinetic partitioning between productive folding via the dimeric intermediate and a non-productive side reaction via an aggregation prone monomeric intermediate. In the light of this and other studies, schemes for folding, aggregation and prion formation are proposed.
Mutual coupling reduction using defected ground structure (DGS) for array applications

In this paper, a compact dumbbell shaped defected ground structure (DGS) is applied to reduce the mutual coupling between array elements with 0.47 λ0 elements spacing. The dumbbell DGS is inserted in the E-plane between the adjacent array coupled elements to suppress the pronounced surface waves. A four-element array with dumbbell shaped DGS is designed, fabricated on a substrate with dielectric constant of 10.2 and thickness of 1.27mm and measured. The results show that a reduction in mutual coupling of 35.6 dB is obtained between elements at the operation frequency of the array. The microstrip arrays with and without DGS are studied by the waveguide simulator method and fabricated by photolithographic technique. The analysis indicates that increasing number of dumbbells reduces the mutual coupling between elements. However, the gain and bandwidth are reduced. The results agree with those obtained by the waveguide simulator method.
HIV Infection Risk among Injection Drug Users in a Methadone Maintenance Treatment Program, Taipei, Taiwan 2007–2010

Background: Taiwan has a growing HIV/AIDS epidemic that has recently shifted to an increase among injection drug users (IDUs). This study aimed to measure the prevalence and incidence and identify the correlates of HIV infection among IDUs in a large methadone maintenance treatment program (MMTP) in Taipei, Taiwan. Methods: Data from intake interviews and HIV testing completed by IDUs upon admission to the Taipei City Hospital MMTP in 2007–2010 were included in this analysis. HIV testing was repeated semi-annually among maintained clients who were HIV-negative during MMTP admission. Results: Of 1444 IDUs admitted, 85.9% were male, median age was 40 years, and mean years of injecting was 14.3 (range: 1–64). The prevalence of HIV, HCV, and HIV/HCV co-infection was 13.4%, 91.1%, and 13.2%, respectively. In multivariable analysis, HIV infection was associated with sharing syringes during the 6 months prior to admission (OR = 14.76, 95% CI 10.31–21.13), homelessness (OR = 6.46, 95% CI 1.49–28.00), and lifetime number of MMTP admissions (OR = 1.76, 95% CI 1.30–2.38) and times incarcerated (OR = 1.10, 95% CI 1.03–1.18). HIV seroincidence was 1.15/100 person-years at risk (95% CI .62–8.77/100 PY) among IDUs who were HIV-negative at first admission. Conclusions: Taiwanese IDUs in MMTP have a high HIV prevalence, which was associated with syringe sharing and other factors related to social marginalization. Our findings highlight the importance of harm reduction programs, including syringe exchange, along with HIV-prevention education.
Toward a Deterministic Model of Planetary Formation v. Accumulation near the Ice Line and Emergence of Short-period Earths

We address two outstanding issues in the sequential accretion scenario for gas giant planet formation, the retention of dust grains in the presence of gas drag and that of cores despite type I migration. Theoretical models suggest that planets form in proto-stellar disk regions with an inactive neutral " dead zone " near the mid plane, sandwiched together by partially ionized surface layers where magnetorotational instability is active. Due to a transition in the abundance of dust grains, the active layer's thickness decreases abruptly near the ice line, which leads to local surface density and pressure distribution maxima near the ice line. This barrier locally retains protoplanetary cores and enhances the heavy element surface density to the critical value needed to initiate efficient gas accretion. We simulate and reproduce the observed frequency and mass-period distribution of gas giants around solar type stars without having to greatly reduce the type I migration strength. We also predict slightly smaller populations of Earth-mass planets in the habitable zone and close to their host stars.
Pegylated IFNs for chronic hepatitis C: an update

For over a decade, IFN-α2 has been the standard treatment for chronic hepatitis C. However, the drug’s rapid clearance and short half-life have led to low rates of sustained virological response. Pegylation is a well-established method of modifying the pharmacological properties of IFNs, causing significant improvements in pharmacokinetics, which in turn lead to improved efficacy. Two pegylated forms of IFN-α2 have been developed: PEG-IFN-α2b and PEG-IFN-α2a, and their efficacy has been established in randomised, -controlled trials. However, the two differ significantly in structure, invitro activity and pharmacological properties, and this may translate into -differences in clinical efficacy. Comparative trials have been initiated that will provide insight into relative importance of pharmacokinetics, bioactivity and dosing regimen.
Have Biologics Changed the Natural History of Crohn's Disease?

Crohn's disease (CD) is a progressive condition, with most patients developing a penetrating or stricturing phenotype over time. The introduction of anti-tumor necrosis factor (TNF) therapies over the past 10-15 years, which was supported by accumulating evidence both from trials and clinical practice, has led to a significant change in patient management, monitoring, and treatment algorithms. Anti-TNF therapy was demonstrated to be effective for both luminal and fistulizing disease. Regular therapy with both infliximab and adalimumab was shown to increase the likelihood of clinical remission and mucosal healing, as well as to reduce the need for surgery and hospitalization in both clinical trials and clinical practice, especially in patients with pediatric-onset CD, shorter disease duration, and when used in combination with immunosuppressives. This has led to new treatment goals and to the use of early aggressive medical therapy in a selected group of patients with a worse prognosis. Exploratory clinical trials are underway to determine if further optimization of therapies and treatment beyond clinical remission leads to superior disease outcomes. However, more long-term clinical data are needed to assess whether an early, aggressive therapeutic strategy employing anti-TNF, alone or in combination with biologicals, can further improve long-term disease outcomes in both pediatric patients and young adults.
Stalled replication fork repair and misrepair during thymineless death in Escherichia coli

Starvation for DNA precursor dTTP, known as ‘thymineless death’ (TLD), kills bacterial and eukaryotic cells alike. Despite numerous investigations, toxic mechanisms behind TLD remain unknown, although wrong nucleotide incorporation with subsequent excision dominates the explanations. We show that kinetics of TLD in Escherichia coli is not affected by mutations in DNA repair, ruling out excision after massive misincorporation as the cause of TLD. We found that the rate of DNA synthesis in thymine‐starved cells decreases exponentially, indicating replication fork stalling. Processing of stalled replication forks by recombinational repair is known to fragment the chromosome, and we detect significant chromosomal fragmentation during TLD. Moreover, we report that, out of major recombinational repair functions, only inactivation of recF and recO relieves TLD, identifying the poisoning mechanism. Inactivation of recJ and rep has slight effect, while the recA, recBC, ruvABC, recG and uvrD mutations all accelerate TLD, identifying the protection mechanisms. Our epistatic analysis argues for two distinct pathways protecting against TLD: RecABCD/Ruv repairs the double‐strand breaks, whereas UvrD counteracts RecAFO‐catalyzed toxic single‐strand gap processing.
Numerical Studies of Unsteady Friction in Transient Pipe Flow

In this thesis, unsteady friction in transient pipe flow is given a closer look. The common quasi-steady friction model and two one-dimensional convolution-based models, developed by Zarzycki and Vardy & Brown, are considered. A quasi-two-dimensional approach to the water hammer problem is also derived, where the pipe friction is related to the near-wall behavior of the velocity profile. The models are implemented using Method of Characteristics as a foundation for the one-dimensional water hammer equations and MacCormack’s method for modeling the velocity profile. The computational results are evaluated and verified with respect to experimental data for both laminar and turbulent flow conditions. For laminar flow it is found that the quasi-steady model gives very poor results while the other friction models considered yield results that are near identical to the experimental data. For turbulent flow the quasisteady model yields better conformance than in the laminar simulations in terms of amplitude, while an unsatisfactory prediction of the shape of the pressure waves is still obtained. The Zarzycki and Vardy & Brown models both underestimate the amplitude while providing a good approximation of the wave shape. The quasi-two-dimensional model yields good conformance with the experimental data, and when assuming a dampened eddy viscosity distribution, the results are near identical to the experimental data.
Lack of cooperation in pediatric dentistry--the role of child personality characteristics.

PURPOSE This study aimed to investigate fear, temperament, behavioral symptoms and verbal intelligence in a study group of uncooperative child dental patients, partly in comparison with a reference group of ordinary child dental patients. A second aim was to explore a hypothesis of heterogeneity by searching for subgroups within the study group. METHODS Parents of 86 study group children (36 aged 4-to 7- years and 50 aged 8- to 12-years) and 117 reference group children (8- to 12-years) answered a questionnaire concerning dental and general fear, temperament and general behavior. Study group children performed a vocabulary test to measure verbal intelligence. Data were analyzed with a variable-based and a person-based approach. RESULTS In addition to dental fear, a higher level of impulsivity most clearly discriminated study group from reference group children. Cluster analyses revealed four different fear and personality subgroups within the study group. CONCLUSIONS Uncooperative child dental patients constitute a heterogeneous group. Subgroups with different fear, temperament and behavior problem profiles can be identified. These subgroups could be presumed to benefit from different treatment regimens, which should be further investigated.
The Relationship between the Firing Rate of a Single Neuron and the Level of Activity in a Population of Neurons

A quantitative comparison is made between experiment and the theoretically predicted dynamics of a neuron population. The experiment confirms the theoretical prediction that under appropriate conditions an enlarged resonant response should appear in the activity of the neuron population, near the frequency at which there is minimum modulation in the instantaneous rate of a single neuron. These findings bear on the relationship between the firing rate of a single neuron and the firing rate of a population of neurons.
Prediction of Hydrophobic Core Residues Based on Network Analysis

In recent years, Protein folding kinetics studies performed the hydrophobic core residues play a key role not only in stabilizing the native state, but also in driving the folding reaction itself. In this work, the protein structure is modeled as an undirected network with the amino acids the vertexes and the contacts between them the edges. We find that the core residues have mainly high degree and low clustering coefficient compared with the surface residues. The four different centrality measurements have been proposed to predict hydrophobic core residues from four well-characterized proteins. We show that the four network-based centrality measurements (degree, clustering coefficient, closeness centrality, betweenness) accurately detect the hydrophobic core residues and there is strong functional relationship between any two different network-based centrality measurements. Additionally, we plot four network centrality measurements versus the Conseq value, the results show that all hydrophobic core residues have high conseq values and this means that the hydrophobic core residues are conserved in proteins.