Miracle-dz/UniFAR-FTUs huggingface dataset:
Vestibular Role of KCNQ4 and KCNQ5 K+ Channels Revealed by Mouse Models*

Background: KCNQ K+ channels regulate neuronal excitability, and KCNQ4 mutations cause deafness. Results: KCNQ4 and KCNQ5 expression in vestibular organ and the impact on vestibular function are investigated. Conclusion: Both channels reside in postsynaptic calyx membranes of hair cells, and loss of KCNQ4 impairs vestibular function. Significance: KCNQ4 may affect vestibular function because of a novel role in synaptic transmission. The function of sensory hair cells of the cochlea and vestibular organs depends on an influx of K+ through apical mechanosensitive ion channels and its subsequent removal over their basolateral membrane. The KCNQ4 (Kv7.4) K+ channel, which is mutated in DFNA2 human hearing loss, is expressed in the basal membrane of cochlear outer hair cells where it may mediate K+ efflux. Like the related K+ channel KCNQ5 (Kv7.5), KCNQ4 is also found at calyx terminals ensheathing type I vestibular hair cells where it may be localized pre- or postsynaptically. Making use of Kcnq4−/− mice lacking KCNQ4, as well as Kcnq4dn/dn and Kcnq5dn/dn mice expressing dominant negative channel mutants, we now show unambiguously that in adult mice both channels reside in postsynaptic calyx-forming neurons, but cannot be detected in the innervated hair cells. Accordingly, whole cell currents of vestibular hair cells did not differ between genotypes. Neither Kcnq4−/−, Kcnq5dn/dn nor Kcnq4−/−/Kcnq5dn/dn double mutant mice displayed circling behavior found with severe vestibular impairment. However, a milder form of vestibular dysfunction was apparent from altered vestibulo-ocular reflexes in Kcnq4−/−/Kcnq5dn/dn and Kcnq4−/− mice. The larger impact of KCNQ4 may result from its preferential expression in central zones of maculae and cristae, which are innervated by phasic neurons that are more sensitive than the tonic neurons present predominantly in the surrounding peripheral zones where KCNQ5 is found. The impact of postsynaptic KCNQ4 on vestibular function may be related to K+ removal and modulation of synaptic transmission.
Association of mild acetabular dysplasia with an increased risk of incident hip osteoarthritis in elderly white women: the study of osteoporotic fractures.

OBJECTIVE To determine if acetabular dysplasia increases the risk of incident hip osteoarthritis (OA) among elderly white women. METHODS Baseline and followup anteroposterior pelvic radiographs were obtained a mean of 8 years apart, and read for individual radiographic features (IRFs) of hip OA; summary grades (0-4) were then assigned based on the IRFs present. Acetabular dysplasia was defined by the results of measurements of the acetabular depth (<9 mm) or the center-edge angle (<30 degrees). Logistic regression analyses were performed to determine the association between acetabular dysplasia and incident hip OA, and all analyses were adjusted for age, current weight, body mass index, affected side, and investigational site. RESULTS The odds ratios for the association of abnormal center-edge angle and acetabular dysplasia with incident hip OA were 3.3 (95% confidence interval 1.1-10.1) and 2.8 (95% confidence interval 1.0-7.9), respectively. CONCLUSION Acetabular dysplasia, defined by a decrease in the center-edge angle, is associated with a modestly increased risk of incident hip OA in elderly white women.
Pattern of Cortex and White Matter Involvement in Severe Middle Cerebral Artery Ischemia

Background and Purpose. In middle cerebral artery (MCA) stroke, ischemia usually is unevenly distributed within the MCA territory. We sought to investigate which brain structures are critical for the acute neurological deficit in severe MCA stroke. Methods. We used magnetic resonance (MR) imaging and statistical parametric mapping in 64 consecutive stroke patients (64 ±13 years) to study the pattern of the initial perfusion abnormality. Results. Patients with lesion progression had more severe time‐to‐peak (TTP) abnormalities (P < .0001) in the inferior frontal gyrus, superior temporal gyrus, insula, and underlying hemispheric white matter than those with lesion regression. Also, patients with lesion progression had more severe T2 abnormalities on day 8 than those with lesion regression. In contrast, the changes of water diffusion were similar among the two groups resulting in a perfusion–diffusion mismatch in lesion progression. TTP‐lesions were related to the neurological deficit score (rs=−0.563, P < .0001), T2‐lesions (r= 0.686, P < .0001), and cerebral artery abnormalities assessed on MR‐angiography (rs= 0.399, P < .01). Conclusions. In major MCA, stroke ischemia was most severe in the central portion of the MCA territory. It is suggested that involvement of hemispheric white matter accentuated the neurological deficit probably by affecting cortico‐cortical and cortico‐subcortical fibers.
A MEDIAL AXIS TRANSFORMATION BASED PROCESS PLANNING METHOD FOR RAPID TOOLING by Ziyang He A thesis submitted to the graduate faculty in partial fulfillment of the requirements for the degree of MASTER OF SCIENCE Major: Industrial Engineering

This thesis presents an algorithm to automatically select the positions for friction stir spot welding (FSSW) in a laminated rapid tooling process. The work combines a two-dimensional structural analysis with tool path planning to realize the overall process planning for the rapid tooling of a plastic injection mold. The work starts from a two-dimensional cantilever beam model, defining the effective distance of a single spot joint strength, and also considers the effect of a single layer thickness. Secondly, an efficient medial axis transformation algorithm, which is suitable for the general two-dimensional boundary curves, has been proposed to generate the adaptive equidistance offsetting curves. In addition, through different working conditions of the internal and external spot welds, an adaptive discretization method is presented. Then, a selection principle for choosing the initial spot weld location and processing order with optimization to avoid redundancy is presented. Finally, the authors compare the advantages of this novel algorithm and traditional path planning algorithms with respect to strength and processing efficiency while taking into account structural strength. CHAPTER
Use of Distraction Osteogenesis to Change Endocranial Morphology in Unilateral Coronal Craniosynostosis Patients

Background: The endocranial morphology of the skull base is an important factor in determining craniofacial asymmetry. Moreover, although the patency of cranial suture would be the first determining factor, unicoronal, unilambdoid synostosis and deformational plagiocephaly can also be differentiated by means of axis angulation of anterior and posterior cranial fossa. These findings indicate the importance of endocranial morphology in craniofacial asymmetry. The authors hypothesized that distraction of the skull base might cause stress on the skull base that could modify skull base angulation deformities. Methods: This study compared the distraction technique with traditional bone repositioning techniques for remodeling skull base axis deformities in synostotic plagiocephaly patients. The study recruited 19 unicoronal craniosynostotic patients, of whom seven underwent distraction treatment and 12 underwent traditional bone graft treatment. Results: The authors found that both approaches resulted in successful outcomes in terms of exocranial morphology correction, but that the distraction technique may offer advantages over traditional methods. Moreover, the authors found that distraction did modify the skull base angulation. Distraction created more changes in the endocranial morphology. The average correction of skull base angulation with distraction was from 164.6 to 174.3 degrees, whereas the correction for the traditional technique was from 165.2 to 166.2 degrees. The amount of change in skull base axis was statistically significant according to the Mann-Whitney test (p < 0.001), but the change in cranial index of asymmetry was not (p = 0.363). Conclusion: The skull base axis in synostotic plagiocephaly, which is composed of the anterior and posterior cranial fossa, underwent greater correction using the distraction method.
Small animal models of heart failure: development of novel therapies, past and present.

Received June 23, 2008; accepted January 20, 2009. The study of heart failure requires viable animal models whereby chronic changes in myocardial structure and function can evolve and the progression of heart failure and left ventricular (LV) dysfunction can be quantified. During the past 40 years, basic and translational scientists have used small animal models to explore the pathophysiology of heart failure and to develop novel therapies that might slow the progression of this prevalent and fatal disease. The purpose of this review is to describe commonly used heart failure models in rodents and to cite examples of how these models have been used to evaluate novel therapies for the treatment of heart failure. Heart failure models were originally developed in rats because of numerous potential advantages inherent in a small animal model (see Table 1). Housing and maintenance costs for rats are much lower than for large animals, thus reducing costs and increasing the number of animals included in a given study to improve the statistical power. Moreover, more recent technological advances in echocardiography, MRI, and micromanometer conductance catheters have greatly streamlined the assessment of cardiac function in rodents, removing a significant barrier to their use in heart failure research. The development of suitable expertise to perform open-chest surgical procedures and invasive hemodynamic assessments in rats is far easier compared with that required for mice. Additionally, investigators are able to perform a greater number of postmortem histological or molecular biological analyses given the approximately 10-fold greater myocardial mass of rats compared with mice. For these reasons, the rat models detailed below have been the most widely and successfully used heart failure models in basic and translational research. View this table: Table. Commonly Used Rodent Heart Failure Models Myocardial infarctions (MIs) in rats were originally induced by the sequential administration of subcutaneous isoproterenol …
Electron microscopical reconstruction of the anterior sensory anatomy of the nematode caenorhabditis elegans

The complete structure of the anterior sensory nervous system of the small nematode C. elegans has been determined by reconstruction from serial section electronmicrographs. There are 58 neurons in the tip of the head. Fifty‐two of these are arranged in sensilla. These include six inner labial sensilla, six outer labial sensilla, four cephalic sensilla and two amphids. Each sensillum consists of ciliated sensory neurons ending in a channel enclosed by two nonneuronal cells, the sheath and socket cells. The amphidial channel opens to the outside as does that of the inner labial sensilla so that these probably contain chemoreceptive neurons. The endings of the other sensilla are embedded in the cuticle and may be mechanoreceptive. The cell bodies of all the neurons lie near the nerve ring and their axons project into the ring or into ventral ganglia. One of the ciliated sensory neurons in each of the six inner labial sensilla makes direct chemical synapses onto a muscle making these sensory‐motor neurons. The anatomy of four isogenic animals was compared in detail and found to be largely invariant. The anatomy of juveniles is nearly identical to that of the adult, but males have four additional neuron processes.
An Exploration of the Potential Reach of Smartphones in Diabetes

Although smartphones bear potential to improve diabetes self-management, the reach of smartphones in diabetic populations remains uncertain. Using survey data from the Pew Research Center, we compared smartphone use in individuals with and without diabetes, and determined factors associated with smartphone use among those with diabetes. Of the 2989 adults surveyed, 1360 were smartphone users, and 332 individuals had diabetes. Compared to individuals without diabetes, adults with diabetes were less likely to be smartphone users (relative risk of 0.43, 95% CI 0.31 to 0.54) even after adjusting for age, race, ethnicity and socioeconomic status (adjusted RR of 0.78, 95%CI 0.57-0.98). Among individuals with diabetes, high income, younger age and online health information seeking were associated with higher smartphone use. While smartphones can reach subgroups for diabetes care and prevention (racial/ethnic minorities, newly diagnosed individuals), studies are needed to understand this current difference in smartphone use.
Hypofunction of the stress axis in Sjögren's syndrome.

OBJECTIVE To examine the functional integrity of the hypothalamic-pituitary-adrenal (HPA) and thyroid axes in Sjögren's syndrome (SS) via the assessment of basal and stimulated adrenocorticotropin (ACTH), cortisol, thyroid stimulating hormone (TSH), and prolactin levels. METHODS Pituitary function of the HPA axis was assessed by determining the basal plasma levels of ACTH in the late afternoon, as well as the ACTH released to ovine corticotropin releasing hormone (oCRH) stimulation; adrenal function was assessed by measuring plasma cortisol levels in the late afternoon at baseline and after release of the endogenous ACTH during oCRH stimulation. Basal and thyrotropin releasing hormone (TRH) stimulated levels of TSH and prolactin were also assessed. Healthy volunteers were used as controls. RESULTS Patients with SS, compared to controls, were characterized by significantly lower ACTH levels (pg/ml), (5.1 +/- 0.5 vs 11.4 +/- 1.5, respectively; p < 0.05) and cortisol levels (microg/ml), (2.4 +/- 0.6 vs 5.9 +/- 1.2, respectively; p < 0.05). Furthermore, a blunted pituitary and adrenal response to oCRH compared to controls was observed: peak plasma ACTH and cortisol levels for patients with SS were 46.2 +/- 5.4 pg/ml and 15.7 +/- 1.6 microg/ml, respectively, and for controls 61.5 +/- 3.8 and 19.6 +/- 0.7, respectively (p < 0.05). Basal TSH levels were significantly elevated in patients (1.3 +/- 0.3 microIU/ml vs 0.9 +/- 0.05 microIU/ml; p < 0.05). CONCLUSION The above findings indicate hypoactivity of the HPA axis in patients with SS. Further studies are needed to definitively identify the locus of the defects and assess the significance of the pattern of the perturbations to the pathogenesis and expression of SS.
Patterns of joint distribution in hand osteoarthritis: Contribution of age, sex, and handedness

The most frequent site of osteoarthritis (OA) is the hands, but the pattern of hand OA development remains controversial. Understanding these patterns may assist in evaluating biological aging, determining etiology, and proposing ways of preventing hand OA. We investigated the pattern distribution of OA in hands and the influences of age, sex, and handedness on its development. The study population was comprised of Chuvashians (660 males age 18–89 years and 585 females age 18–90 years). OA development was evaluated for 15 joints of each hand according to the Kellgren and Lawrence grading scheme. Statistical analyses included Pearson correlation, cluster analysis, MANCOVA, and linear and polynomial regression. OA changes first appeared in subjects <30 years of age. Metacarpophalangeal (MP) joints underwent the first OA changes until the sixth decade, when the row of distal interphalangeal (DIP) joints became most affected. Cluster analysis showed that symmetry was the most common pattern of interrelationship between rows of joints. The best‐fitting and most parsimonious model of age‐related pattern of hand OA was the polynomial two‐interval linear model. It showed a higher rate of OA development during the relatively young ages, 32–34 years than later on. We found statistically significant differences between sexes only for the DIP (P = 0.019) and PIP (P = 0.011) rows of joints. Handedness had no influence on hand OA development. Am. J. Hum. Biol. 16:125–134, 2004. © 2004 Wiley‐Liss, Inc.
Relationship between Chronic Intermittent Hypoxia and Intraoperative Mean Arterial Pressure in Obstructive Sleep Apnea Patients Having Laparoscopic Bariatric Surgery

Background:Recurrent nocturnal hypoxemia in obstructive sleep apnea enhances sympathetic function, decreases baroreceptor sensitivity, and weakens peripheral vascular responses to adrenergic signals. The authors hypothesized that the percentage of total sleep time spent at oxyhemoglobin saturation (SaO2) less than 90% and minimum nocturnal SaO2 on preoperative polysomnography are associated with decreased intraoperative mean arterial pressure. Methods:The authors examined the records of all patients who had laparoscopic bariatric surgery at Cleveland Clinic between 2005 and 2009 and an available polysomnography study. The authors assessed the relationships between the percentage of total sleep time spent at SaO2 less than 90% and minimum nocturnal SaO2, and the time-weighted average of mean arterial pressure. The authors used multivariable regression models to adjust for prespecified clinical confounders. Results:Two hundred eighty-one patients were included in the analysis. The average change in the time-weighted average of mean arterial pressure was −0.02 (97.5% CI, −0.08, 0.04) mmHg for each 1% absolute increase in the percentage of sleep time spent at SaO2 less than 90% (P = 0.50). The average change was −0.13 (97.5% CI, −0.27, 0.01) mmHg, for each 1% absolute decrease in the minimum SaO2 (P = 0.04 > significance criterion of 0.025, Bonferroni correction). An unplanned analysis estimated 1% absolute decrease in minimum SaO2 was associated with −0.22 (98.75% CI, −0.39, −0.04) mmHg, change in mean arterial pressure (P = 0.002) in the time period between endotracheal intubation and trocar insertion. Conclusion:Recurrent nocturnal hypoxemia in obstructive sleep apnea is not a risk marker for intraoperative hypotension.
Electrophysiological and freeze‐fracture studies of changes following denervation at frog neuromuscular junctions.

1. Changes which occur at frog neuromuscular junctions following denervation have been studied by combining intracellular recording and freeze‐fracture electron microscopy. 2. Shortly after nerve section, both neuromuscular transmission and intramembrane structures of neuromuscular junctions remain normal. 3. Later, neuromuscular transmission fails, beginning with the disappearance of end‐plate potentials (e.p.p.s) and followed by the disappearance of miniature end‐plate potentials (m.e.p.p.s). The frequency of m.e.p.p.s which persist after cessation of e.p.p.s is not increased dramatically in K+‐rich or hypertonic solutions. 4. Concomitant with the changes of transmission are changes in intramembrane structures. The first sign of these changes in disruption of active zones, which become disorganized, fragmented or vanish. Nerve terminals then disintegrate and eventually are engulfed by Schwann cells. 5. When neuromuscular transmission has failed completely, former sites of the neuromuscular junction are occupied by Schwann cells. These cells develop transverse ridges which lie opposed to junctional folds, just like active zones of nerve terminals. However, the ridges on Schwann cells do not contain organized rows of particles or clusters of any synaptic organelles, even at later stages when Schwann cell m.e.p.p.s commence. 6. It is suggested that the failure of e.p.p.s involves at least an impairment of the transmitter release mechanism at the nerve terminal, which is probably associated with the disruption of active zones. The cessation of m.e.p.p.s is thought to be caused by the engulfment of terminals by Schwann cells.
MicroRNA expression profiling of human metastatic cancers identifies cancer gene targets

Small non‐coding microRNAs (miRNAs) contribute to cancer development and progression, and are differentially expressed in normal tissues and cancers. However, the specific role of miRNAs in the metastatic process is still unknown. To seek a specific miRNA expression signature characterizing the metastatic phenotype of solid tumours, we performed a miRNA microarray analysis on 43 paired primary tumours (ten colon, ten bladder, 13 breast, and ten lung cancers) and one of their related metastatic lymph nodes. We identified a metastatic cancer miRNA signature comprising 15 overexpressed and 17 underexpressed miRNAs. Our results were confirmed by qRT‐PCR analysis. Among the miRNAs identified, some have a well‐characterized association with cancer progression, eg miR‐10b, miR‐21, miR‐30a, miR‐30e, miR‐125b, miR‐141, miR‐200b, miR‐200c, and miR‐205. To further support our data, we performed an immunohistochemical analysis for three well‐defined miRNA gene targets (PDCD4, DHFR, and HOXD10 genes) on a small series of paired colon, breast, and bladder cancers, and one of their metastatic lymph nodes. We found that the immunohistochemical expression of these targets significantly follows the corresponding miRNA deregulation. Our results suggest that specific miRNAs may be directly involved in cancer metastasis and that they may represent a novel diagnostic tool in the characterization of metastatic cancer gene targets. Copyright © 2009 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Phosphatidylserine found in intestinal mucus serves as a sole source of carbon and nitrogen for salmonellae and Escherichia coli

Salmonella choleraesuis (a pig pathogen), Salmonella typhimurium (a virulent strain in mice), and three strains of Escherichia coli (including a human enterohemorrhagic strain, a human urinary tract isolate, and a human fecal isolate) grew as well in vitro utilizing the lipids derived from mouse cecal mucus as the sole source of carbon and nitrogen as they did in mouse crude cecal mucus. Further analysis of the total lipid extracts of mucus dialysates showed that the acidic lipid fraction supported growth nearly as well as the total lipid fraction. Interestingly, among the many purified acidic lipids from mucus which were tested and analyzed, including several phospholipids, only phosphatidylserine was found to support the growth of all of these enteric bacteria, including Salmonella milwaukee, a human pathogen. The possible role of growth on pure phosphatidylserine in the pathogenesis of salmonellae is discussed.
Four antennas on smart watch for GPS/UMTS/ WLAN MIMO application

The paper presents a design with four antennas on smart watch for GPS/UMTS/WLAN MIMO application. The overall dimensions of the design are 40 mm × 40 mm × 5.4 mm. The size of the main ground plane is 40 mm × 40 mm × 0.4 mm. These antennas are using the coupled-fed architecture. They are fed by 50-ohm mini coaxial cable lines. The four antennas are placed vertically to the edges of the main ground plane. The GPS and UMTS antennas are designed as open slot antennas; the two WLAN antennas are designed as monopole antennas. The obtained bandwidths can cover the bands of GPS/UMTS/WLAN MIMO; the isolation between these antennas is larger than 15dB. The design covering UMTS (1.92–1.98 GHz, 2.11–2.17 GHz), GPS (1.575 GHz), MIMO WLAN (2.4–2.484 GHz) and with compact and easy to design is good for antennas of smart watch devices.