Miracle-dz/UniFAR-FTUs huggingface dataset:
A Distinct Class of Chromoanagenesis Events Characterized by Focal Copy Number Gains

Chromoanagenesis is the process by which a single catastrophic event creates complex rearrangements confined to a single or a few chromosomes. It is usually characterized by the presence of multiple deletions and/or duplications, as well as by copy neutral rearrangements. In contrast, an array CGH screen of patients with developmental anomalies revealed three patients in which a single chromosome carries from 8 to 11 large copy number gains confined to a single chromosome or chromosomal arm, but the absence of deletions. Subsequent fluorescence in situ hybiridization and massive parallel sequencing revealed the duplicons to be clustered together in distinct locations across the altered chromosomes. Breakpoint junction sequences showed both microhomology and non‐templated insertions of up to 40 bp. Hence, these patients each demonstrate a single altered chromosome of clustered insertional duplications, no deletions, and breakpoint junction sequences showing microhomology and/or non‐templated insertions. These observations are difficult to reconcile with current mechanistic descriptions of chromothripsis and chromoanasynthesis. Therefore, we hypothesize those rearrangements to be of a mechanistically different origin. In addition, we suggest that large untemplated insertional sequences observed at breakpoints are driven by a non‐canonical non‐homologous end joining mechanism.
Synthesis and study of a gramicidin B mutant possessing a ditryptophan crosslink

Recent studies of peptide dimers linked by Trp‐Trp (ditryptophan) crosslinks suggest that the crosslinks can reinforce antiparallel β‐structure. Depending on environment, gramicidins A, B and C form either helical ion channels with parallel β‐structure or non‐functional pores with antiparallel β‐structure. In the channel conformation of the gramicidins Trp9 and Trp15 are close in space, but in the pore conformation Trp9 and Trp15 are far apart. We hypothesized that a ditryptophan crosslink between Trp9 and Trp15 could pre‐organize gramicidin in an active conformation. To test the potential for pre‐organization, an intramolecular ditryptophan crosslink was formed between Trp9 and Trp15 in a W13F mutant of gramicidin B. Photooxidative conditions were shown to generate ditryptophan crosslinks in low yields. While not preparatively useful, photooxidative tryptophan crosslinking may have implications for protein aging processes like cataract formation. The ditryptophan crosslink in the gramicidin B mutant substantially lowered the antibiotic activity of the gramicidin B mutant, unlike the ditryptophan crosslink in the antibiotic X‐indolicidin. The biaryl chromophore generated diagnostic Cotton effects in the CD spectrum that revealed the absolute stereochemistry of the biaryl chromophore, but the biaryl chromophore obscured diagnostic features below 220 nm. However, changes in peptide conformation were reflected in changes in the biaryl region of the CD spectrum above 240 nm. Copyright © 2002 European Peptide Society and John Wiley & Sons, Ltd.
Neck Muscle Strength Before and After Cervical Laminoplasty: Relation to Axial Symptoms

Study Design A prospective study to investigate serial changes in neck muscle strength before and after cervical laminoplasty. Objectives To examine the correlation between neck muscle strength and axial symptoms, and to clarify the risk factors for axial symptoms. Summary of Background Data Axial symptoms are common complications after posterior cervical spinal surgery. Although several technical considerations have reduced axial symptoms, the causes of axial symptoms are still largely unknown. Previous studies have indicated that neck muscle strength is reduced in patients with neck pain. Materials and Methods Nineteen consecutive patients underwent cervical expansive laminoplasty for cervical spondylotic myelopathy. Age, sex, operative time, blood loss, clinical results, cervical curvature, range of motion, visual analog scale (VAS) for axial symptoms, and manual muscle strengths were examined before and after surgery. At 3 and 12 months, these factors were compared statistically between the no pain (NP) group (VAS <3) and the pain (P) group (VAS ≥3). The correlation between VAS and neck muscle strength, and the reduction in neck muscle strength in extension were analyzed statistically. Results Six patients (31.5%) complained of axial symptoms at 3 months, and the symptoms continued in 3 patients (15.8%) at 12 months. At 3 months, cervical lordosis was 15.7 degrees in the NP group and 5.0 degrees in the P group, and neck strength in extension was 104.9% and 61.8%, respectively. At 12 months, neck strength in extension was 124.3% and 62.2%, respectively. These differences were statistically significant. The correlation between neck pain VAS and neck muscle strength, and the reduction in neck muscle strength in extension were statistically significant. Conclusions Neck muscle strength recovered to the preoperative value by 3 months and increased to 120% by 12 months in the NP group, whereas in the P group, neck muscle strength remained reduced by 60% and did not recover. Neck muscle strength and axial symptoms were strongly correlated.
EXTRAPULMONARY TRANSLOCATION OF ULTRAFINE CARBON PARTICLES FOLLOWING WHOLE-BODY INHALATION EXPOSURE OF RATS

Studies with intravenously injected ultrafine particles have shown that the liver is the major organ of their uptake from the blood circulation. Measuring translocation of inhaled ultrafine particles to extrapulmonary organs via the blood compartment is hampered by methodological difficulties (i.e., label may come off, partial solubilization) and analytical limitations (measurement of very small amounts). The objective of our pilot study was to determine whether ultrafine elemental carbon particles translocate to the liver and other extrapulmonary organs following inhalation as singlet particles by rats. We generated ultrafine 13 C particles as an aerosol with count median diameters (CMDs) of 20-29 nm (GSD 1.7) using electric spark discharge of 13 C graphite electrodes in argon. Nine Fischer 344 rats were exposed to these particles for 6 h. in whole-body inhalation chambers at concentrations of 180 and 80 w g/m 3 ; 3 animals each were killed at 0.5, 18, and 24 h postexposure. Six unexposed rats served as controls. Lung lobes, liver, heart, brain, olfactory bulb, and kidney were excised, homogenized, and freeze-dried for analysis of the added 13 C by isotope ratio mass spectrometry. Organic 13 C was not detected in the 13 C particles. The 13 C retained in the lung at 0.5 h postexposure was about 70% less than predicted by rat deposition models for ultrafine particles, and did not change significantly during the 24-h postexposure period. Normalized to exposure concentration, the added 13 C per gram of lung on average in the postexposure period was ~9 ng/g organ/ w g/m 3 . Significant amounts of 13 C had accumulated in the liver by 0.5 h postinhalation only at the high exposure concentration, whereas by 18 and 24 h postexposure the 13 C amount of the livers of all exposed rats was about fivefold greater than the 13 C burden retained in the lung. No significant increase in 13 C was detected in the other organs which were examined. These results demonstrate effective translocation of ultrafine elemental carbon particles to the liver by 1 d after inhalation exposure. Translocation pathways include direct input into the blood compartment from ultrafine carbon particles deposited throughout the respiratory tract. However, since predictive particle deposition models indicate that respiratory tract deposits alone may not fully account for the hepatic 13 C burden, input from ultrafine particles present in the GI tract needs to be considered as well. Such translocation to blood and extrapulmonary tissues may well be different between ultrafine carbon and other insoluble (metal) ultrafine particles.
At-Speed Scan Test Method for the Timing Optimization and Calibration

An at-speed scan test methodology is proposed for the purpose of the timing optimization and calibration. The proposed method, called TOC-ATPG, addresses both undertesting and overtesting issues of the traditional at-speed scan-based structural test. A pseudo-random pattern-based circuit analysis is first applied to analyze the potential glitches and transitions due to the functional illegal states. A list of state elements to be constrained during ATPG to prevent the sensitization of the functional illegal transitions and glitches are derived. During ATPG the derived constraints are applied to prevent overtesting, and timing-aware transition fault approach is used simultaneously to detect the fault through the timing critical paths to overcome the undertesting issue. The proposed method demonstrates very high correlation to the purely sequential test in functional mode with bounded run time overhead and can be applied to very large design.
Simultaneous measurement of current and calcium in the ultraviolet‐sensitive cones of zebrafish

In rods and visible cone photoreceptors, multiple measurements cannot be made of intracellular Ca2+ concentration from the same cell using fluorescent dyes, because a single exposure of the measuring light bleaches too large a fraction of the rod or cone photopigment. We have therefore identified and characterized UV‐sensitive cones of the zebrafish, whose wavelength of maximum sensitivity is at 360 nm which is far enough from the wavelength of our measuring light (514.5 nm) so that it has been possible to make multiple determinations of photocurrent and Ca2+ concentration from the same cells. We show that for a limited number of measurements, for which the bleaching of the cone photopigment is too small to affect flash kinetics, the outer segment Ca2+ concentration closely follows the wave form of the flash response convolved with the dominant time constant for Ca2+ removal by Na+–Ca2+–K+ exchange. For a larger number of measurements, significant acceleration of the response kinetics by pigment bleaching inevitably occurs, but the Ca2+ concentration nevertheless rises and falls in approximate agreement with the flash wave form. During exposure to steady background light, the Ca2+ concentration falls in proportion to the steady‐state current for dim backgrounds at all times and for bright backgrounds at steady state. At early times following the onset of bright backgrounds, however, the Ca2+ concentration is markedly higher than expected from the current of the cone. We show this to be the result of light‐dependent Ca2+ release by bright background light, which can be abolished by pre‐exposure of the cone to the membrane‐permeant acetoxymethyl ester of the Ca2+ chelator BAPTA. Our results therefore demonstrate that the cone outer segment Ca2+ concentration is predominantly a function of the rate of influx and efflux of Ca2+ across the plasma membrane, but that a release of Ca2+ in bright light most probably from buffer sites within the cell can transiently elevate the Ca2+ concentration above the level expected from the open probability of the light‐dependent channels.
Resource allocation in a social wasp: effects of breeding system and life cycle on reproductive decisions

Organisms must make important decisions on how to allocate resources to reproduction. We investigated allocation decisions in the social wasp Vespula maculifrons to understand how social insects make reproductive choices. We first determined how annual colonies apportioned resources to growth and reproduction by analysing developing brood. In contrast to expectations, colonies invested in both growth (workers) and reproduction (males) simultaneously. In addition, colonies showed evidence of producing males in pulses and reversing their reproductive choices by decreasing investment in males late in the season. This reversal is consistent with theory suggesting that colonies decrease production in males if fitness of late emerging males is low. To further investigate reproductive decisions within colonies, we determined if the male mates of multiply‐mated queens varied in their reproductive success over time. Sperm use by queens did vary over time suggesting that male success may depend on sperm clumping within the female reproductive tract. Finally, we tested if colony sex ratio conformed to expectations under kin selection theory that nestmate relatedness would positively correlate with investment in new queens if workers controlled sex allocation. Surprisingly, the proportion of queens produced by colonies was negatively correlated with nestmate relatedness, suggesting that allocation may be shaped by advantages arising from increased genetic diversity resulting from multiple mating by queens. Overall, our study suggests that the reproductive decisions of colonies are flexible and may depend both on environmental cues arising from energetic needs of the colony and genetic cues arising from mating behaviours of queens.
An efficient processing element architecture for pairwise sequence alignment

One of the most challenging tasks in sequence alignment is its repetitive and time-consuming alignment matrix computations. Alignment matrix scores are crucial for identifying regions of homology between biological sequences. In this paper, a parametrizable and area efficient processing element (PE) architecture for performing biological sequence alignment task especially for pairwise biological sequence alignment is designed. Its corresponding PE architecture realization was prototyped on Xilinx FPGA platform. FPGA has been chosen as it able to realize an array of systolic array-based PEs. Execution of the proposed parameterizable PE architecture have been conducted and comparison results have shown that the systolic arrays with parameterizable PE has gained at least 15x speed-up as compared to the well-known SSEARCH 35 solution.
Protein Kinase A Associates with Cystic Fibrosis Transmembrane Conductance Regulator via an Interaction with Ezrin*

The cystic fibrosis transmembrane conductance regulator (CFTR) is an epithelial Cl− channel whose activity is controlled by cAMP-dependent protein kinase (PKA)-mediated phosphorylation. We found that CFTR immunoprecipitates from Calu-3 airway cells contain endogenous PKA, which is capable of phosphorylating CFTR. This phosphorylation is stimulated by cAMP and inhibited by the PKA inhibitory peptide. The endogenous PKA that co-precipitates with CFTR could also phosphorylate the PKA substrate peptide, Leu-Arg-Arg-Ala-Ser-Leu-Gly (kemptide). Both the catalytic and type II regulatory subunits of PKA are identified by immunoblotting CFTR immunoprecipitates, demonstrating that the endogenous kinase associated with CFTR is PKA, type II (PKA II). Phosphorylation reactions mediated by CFTR-associated PKA II are inhibited by Ht31 peptide but not by the control peptide Ht31P, indicating that a protein kinase A anchoring protein (AKAP) is responsible for the association between PKA and CFTR. Ezrin may function as this AKAP, since it is expressed in Calu-3 and T84 epithelia, ezrin binds RII in overlay assays, and RII is immunoprecipitated with ezrin from Calu-3 cells. Whole-cell patch clamp of Calu-3 cells shows that Ht31 peptide reduces cAMP-stimulated CFTR Cl− current, but Ht31P does not. Taken together, these data demonstrate that PKA II is linked physically and functionally to CFTR by an AKAP interaction, and they suggest that ezrin serves as an AKAP for PKA-mediated phosphorylation of CFTR.
RESUSCITATION WITH HYDROXYETHYL STARCH SOLUTION PREVENTS CD4+ T-LYMPHOCYTE APOPTOSIS AND MODULATES THE BALANCE OF T HELPER TYPE 1 AND T HELPER TYPE 2 RESPONSES IN THE RAT WITH TRAUMATIC VIRGULE/SHILL HEMORRHAGIC SHOCK

Trauma/hemorrhagic shock (TH/S) has been associated with inflammation and immunodisorders, leading to immunosuppression, multiorgan dysfunction, and death. However, little is known about the effect of resuscitation with different solutions on the immunological function. To address this issue, groups of male Sprague-Dawley rats were induced with TH/S by fracture in the left femur and continual bleeding to keep the MAP of 30 ± 5 mmHg for 30 min, followed by resuscitation with 6% hydroxyethyl starch solution (HES), Ringer's lactate solution (RS), or 5% albumin (ALB), and the impact of resuscitation on the activation, differentiation, and survival of CD4+ T cells was longitudinally examined after TH/S and resuscitation. After resuscitation, the MAP, as expected, gradually increased regardless of the type of fluids transfused. The percentage of CD4+ T cells decreased to 20% to 25%, and the ratio of T helper type 1 (TH1)/TH2 responses was significantly reduced in all TH/S rats, however, resuscitation with HES alone reversed the trends (49.4% ± 9.7% vs. 55.2% ± 2.6% in sham for CD4+ T cells; 0.64 ± 0.23 vs. 0.71 ± 0.16 in sham for the ratio of TH1/TH2, P > 0.05 for both). Treatment with HES or ALB, but not RS, prevented CD4+ T-cell apoptosis (sham, 7.23% ± 3.4%; HES, 10.2% ± 4.1%; RS, 15.2% ± 5.4%; ALB, 10.6% ± 4.3%; 48 h) and nuclear factor-&kgr;B p65 activation (sham, 0.17 ± 0.04; HES, 0.34 ± 0.05; RS, 0.41 ± 0.09; ALB, 0.25 ± 0.09; 48 h) induced by TH/S early after resuscitation. These data demonstrated that HES resuscitation modulated the balance of TH1 and TH2 responses and inhibited TH/S-related nuclear factor-&kgr;B activation and CD4+ T-cell apoptosis in TH/S rats. Our findings provide new insights into understanding the TH/S-related immunodisorders and may aid in the design of new therapy for intervention of TH/S.ABBREVIATIONS: ALB-albumin; ELISA-enzyme-linked immunosorbent assay; HES-hydroxyethyl starch solution; RS-Ringer's lactate solution; TH/S-trauma/hemorrhagic shock; TH1-T helper type 1; TH2-T helper type 2
Initial classification of pediatric hearing impairment using behavioral measures of early prelingual auditory development

Abstract Objective: Determine the sensitivity, specificity, and accuracy of pediatric hearing loss classification using behavioral evidence of early prelingual auditory development (EPLAD). Validate behavioral measures of EPLAD. Design: EPLAD was assessed in a prospective sample of hearing-impaired children using the infant-toddler meaningful auditory integration scale (ITMAIS/MAIS). Hearing losses were classified using tone-burst auditory brainstem response (ABR) and ITMAIS/MAIS scores. This process was repeated in a second retrospective sample. Study sample: The prospective sample was comprised of 139 hearing-impaired children under five years of age. Approximately equal proportions of mild-moderate, severe, and profound losses were included. The second retrospective sample was comprised of case records for 144 hearing-impaired children meeting the same selection criteria. This sample contained more than 80% profound losses. Results: EPLAD trajectories reached different asymptotes after two years of age, depending on the severity of hearing loss, allowing children over this age to be classified. The sensitivity of EPLAD classifications was over 90%; specificity was over 82%; and accuracy was over 88%. Conclusions: Behavioral evidence of EPLAD provides an initial means of classifying pediatric hearing losses which can facilitate initial treatment options prior to diagnostic evaluation with tone-burst ABR.
Endogenous Lipogenic Regulators of Spore Balance in Aspergillus nidulans

ABSTRACT The ability of fungi to produce both meiospores and mitospores has provided adaptive advantages in survival and dispersal of these organisms. Here we provide evidence of an endogenous mechanism that balances meiospore and mitospore production in the model filamentous fungus Aspergillus nidulans. We have discovered a putative dioxygenase, PpoC, that functions in association with a previously characterized dioxygenase, PpoA, to integrate fatty acid derived oxylipin and spore production. In contrast to PpoA, deletion of ppoC significantly increased meiospore production and decreased mitospore development. Examination of the PpoA and PpoC mutants indicate that this ratio control is associated with two apparent feedback loops. The first loop shows ppoC and ppoA expression is dependent upon, and regulates the expression of, nsdD and brlA, genes encoding transcription factors required for meiospore or mitospore production, respectively. The second loop suggests Ppo oxylipin products antagonistically signal the generation of Ppo substrates. These data support a case for a fungal “oxylipin signature-profile” indicative of relative sexual and asexual spore differentiation.
Multi-set factor analysis by means of Parafac2.

We consider multi-set data consisting of Nk observations, k = 1,…, K (e.g., subject scores), on J variables in K different samples. We introduce a factor model for the J × J covariance matrices Σk, k = 1,…, K, where the common part is modelled by Parafac2 and the unique variances Uk, k = 1,…, K, are diagonal. The Parafac2 model implies a common loadings matrix that is rescaled for each k, and a common factor correlation matrix. We estimate the unique variances Uk by minimum rank factor analysis on Σk for each k. The factors can be chosen orthogonal or oblique. We present a novel algorithm to estimate the Parafac2 part and demonstrate its performance in a simulation study. Also, we fit our model to a data set in the literature. Our model is easy to estimate and interpret. The unique variances, the factor correlation matrix and the communalities are guaranteed to be proper, and a percentage of explained common variance can be computed for each k. Also, the Parafac2 part is rotationally unique under mild conditions.
Screening Children for Autism in an Urban Clinic Using an Electronic M-CHAT

Background. The Modified Checklist for Autism in Toddlers (M-CHAT) is a screening tool for autism spectrum disorders in the clinic. However, the follow-up questions in the M-CHAT are difficult to implement on a paper format. Objective. To compare the effectiveness of the M-CHAT on an electronic format versus paper format in an outpatient clinic setting. Methods. A prospective study used electronic M-CHAT on the iPad. A retrospective review of paper M-CHATs 6 months prior to implementation was used as the comparison group. Results. A total of 176 participants completed the electronic M-CHAT format and 197 paper M-CHATs were retrospectively reviewed. The electronic format (3%) resulted in a significant difference in the frequency of children found to be at risk for autism compared with the paper version (11%); 99% of parents rated the experience as “good” or “excellent. ” Conclusion. The electronic format lowered both false at-risk screens and false not-at-risk screens and had higher parental satisfaction.