Ultrasonography of the hand, wrist, and elbow.

PubMed

Bodor, Marko; Fullerton, Brad

2010-08-01

High-frequency diagnostic ultrasonography of the hand, wrist and elbow has significant potential to improve the quality of diagnosis and care provided by neuromuscular and musculoskeletal specialists. In patients referred for weakness, pain and numbness of the hand, wrist or elbow, diagnostic ultrasonography can be an adjunct to electrodiagnosis and help in identifying ruptured tendons and treating conditions such as carpal tunnel syndrome or trigger finger. Use of a small high-frequency (>10-15 MHz) transducer, an instrument with a blunt pointed tip to enhance sonopalpation and a model of the hand, wrist and elbow is advised to enhance visualization of small anatomical structures and complex bony contours. A range of conditions, including tendon and ligament ruptures, trigger finger, de Quervain tenosynovitis, intersection syndrome, lateral epicondylitis, and osteoarthritis, is described along with detailed ultrasonography-guided injection techniques for carpal tunnel syndrome and trigger finger. Copyright 2010 Elsevier Inc. All rights reserved.

One Digit Interruption: The Altered Force Patterns during Functionally Cylindrical Grasping Tasks in Patients with Trigger Digits

PubMed Central

Chen, Po-Tsun; Lin, Chien-Ju; Jou, I-Ming; Chieh, Hsiao-Feng; Su, Fong-Chin; Kuo, Li-Chieh

2013-01-01

Most trigger digit (TD) patients complain that they have problems using their hand in daily or occupational tasks due to single or multiple digits being affected. Unfortunately, clinicians do not know much about how this disease affects the subtle force coordination among digits during manipulation. Thus, this study examined the differences in force patterns during cylindrical grasp between TD and healthy subjects. Forty-two TD patients with single digit involvement were included and sorted into four groups based on the involved digits, including thumb, index, middle and ring fingers. Twelve healthy subjects volunteered as healthy controls. Two testing tasks, holding and drinking, were performed by natural grasping with minimal forces. The relations between the force of the thumb and each finger were examined by Pearson correlation coefficients. The force amount and contribution of each digit were compared between healthy controls and each TD group by the independent t test. The results showed all TD groups demonstrated altered correlation patterns of the thumb relative to each finger. Larger forces and higher contributions of the index finger were found during holding by patients with index finger involved, and also during drinking by patients with affected thumb and with affected middle finger. Although no triggering symptom occurred during grasping, the patients showed altered force patterns which may be related to the role of the affected digit in natural grasping function. In conclusion, even if only one digit was affected, the subtle force coordination of all the digits was altered during simple tasks among the TD patients. This study provides the information for the future studies to further comprehend the possible injuries secondary to the altered finger coordination and also to adopt suitable treatment strategies. PMID:24391799

One digit interruption: the altered force patterns during functionally cylindrical grasping tasks in patients with trigger digits.

PubMed

Chen, Po-Tsun; Lin, Chien-Ju; Jou, I-Ming; Chieh, Hsiao-Feng; Su, Fong-Chin; Kuo, Li-Chieh

2013-01-01

Most trigger digit (TD) patients complain that they have problems using their hand in daily or occupational tasks due to single or multiple digits being affected. Unfortunately, clinicians do not know much about how this disease affects the subtle force coordination among digits during manipulation. Thus, this study examined the differences in force patterns during cylindrical grasp between TD and healthy subjects. Forty-two TD patients with single digit involvement were included and sorted into four groups based on the involved digits, including thumb, index, middle and ring fingers. Twelve healthy subjects volunteered as healthy controls. Two testing tasks, holding and drinking, were performed by natural grasping with minimal forces. The relations between the force of the thumb and each finger were examined by Pearson correlation coefficients. The force amount and contribution of each digit were compared between healthy controls and each TD group by the independent t test. The results showed all TD groups demonstrated altered correlation patterns of the thumb relative to each finger. Larger forces and higher contributions of the index finger were found during holding by patients with index finger involved, and also during drinking by patients with affected thumb and with affected middle finger. Although no triggering symptom occurred during grasping, the patients showed altered force patterns which may be related to the role of the affected digit in natural grasping function. In conclusion, even if only one digit was affected, the subtle force coordination of all the digits was altered during simple tasks among the TD patients. This study provides the information for the future studies to further comprehend the possible injuries secondary to the altered finger coordination and also to adopt suitable treatment strategies.

The effect of night extension orthoses following surgical release of Dupuytren contracture: a single-center, randomized, controlled trial.

PubMed

Collis, Julie; Collocott, Shirley; Hing, Wayne; Kelly, Edel

2013-07-01

To clarify the efficacy and detrimental effects of orthoses used to maintain finger extension following surgical release of Dupuytren contracture. We conducted a single-center, randomized, controlled trial to investigate the effect of night extension orthoses on finger range of motion and hand function for 3 months following surgical release of Dupuytren contracture. We also wanted to determine how well finger extension was maintained in the total sample. We randomized 56 patients to receive a night extension orthosis plus hand therapy (n = 26) or hand therapy alone (n = 30). The primary outcome was total active extension of the operated fingers (°). Secondary outcomes were total active flexion of the operated fingers (°), active distal palmar crease (cm), grip strength (kg), and self-reported hand function using the Disabilities of the Arm, Shoulder, and Hand questionnaire (0-100 scale). There were no statistically significant differences between the no-orthosis and orthosis groups for total active extension or for any of the secondary outcomes. Between the first postoperative measure and 3 months after surgery, 62% of little fingers had maintained or improved total active extension. The use of a night extension orthosis in combination with standard hand therapy has no greater effect on maintaining finger extension than hand therapy alone in the 3 months following surgical release of Dupuytren contracture. Our results indicate that the practice of providing every patient with a night extension orthosis following surgical release of Dupuytren contracture may not be justified except for cases in which extension loss occurs after surgery. Our results also challenge clinicians to research ways of maintaining finger extension in a greater number of patients. Copyright © 2013 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.

Trigger finger

MedlinePlus

... by: C. Benjamin Ma, MD, Assistant Professor, Chief, Sports Medicine and Shoulder Service, UCSF Department of Orthopaedic Surgery. Also reviewed by David Zieve, MD, MHA, Isla Ogilvie, PhD, and the A.D.A.M. Editorial team. Related MedlinePlus Health Topics Finger Injuries and Disorders ...

A medical imaging analysis system for trigger finger using an adaptive texture-based active shape model (ATASM) in ultrasound images

PubMed Central

Chuang, Bo-I; Kuo, Li-Chieh; Yang, Tai-Hua; Su, Fong-Chin; Jou, I-Ming; Lin, Wei-Jr; Sun, Yung-Nien

2017-01-01

Trigger finger has become a prevalent disease that greatly affects occupational activity and daily life. Ultrasound imaging is commonly used for the clinical diagnosis of trigger finger severity. Due to image property variations, traditional methods cannot effectively segment the finger joint’s tendon structure. In this study, an adaptive texture-based active shape model method is used for segmenting the tendon and synovial sheath. Adapted weights are applied in the segmentation process to adjust the contribution of energy terms depending on image characteristics at different positions. The pathology is then determined according to the wavelet and co-occurrence texture features of the segmented tendon area. In the experiments, the segmentation results have fewer errors, with respect to the ground truth, than contours drawn by regular users. The mean values of the absolute segmentation difference of the tendon and synovial sheath are 3.14 and 4.54 pixels, respectively. The average accuracy of pathological determination is 87.14%. The segmentation results are all acceptable in data of both clear and fuzzy boundary cases in 74 images. And the symptom classifications of 42 cases are also a good reference for diagnosis according to the expert clinicians’ opinions. PMID:29077737

Using the international classification of functioning to examine the impact of trigger finger.

PubMed

Langer, Danit; Maeir, Adina; Michailevich, Michael; Applebaum, Yael; Luria, Shai

2016-12-01

To evaluate the impact of trigger finger (TF) on hand motor function, activity and participation (A&P) and quality of life (QOL), and to evaluate the association between personal factors (age and gender, disease severity) and body functions (dexterity and strength) with A&P and QOL in patients with TF. Sixty-six patients with TF (study group) and 66 healthy volunteers (control group) participated in the study. TF symptoms were graded using the Quinnell classification. A&P was evaluated using the Disabilities of Arm Shoulder and Hand questionnaire and the QOL using the World Health Organization Quality of Life questionnaire. Dexterity was evaluated using the Functional Dexterity Test and the Purdue Pegboard Test; hand strength was evaluated using the Jamar Dynamometer and Pinch Gauge. The comparisons between the study and control groups revealed significant differences in all measures. The study group reported lower perceived QOL, A&P and reduced hand strength and dexterity. Hierarchical regression analyses revealed that (a) the severity of TF contributed significantly to the explained variance of QOL, while demographics and hand functioning did not; (b) demographics, TF severity and hand function all contributed significantly to the explained variance of A&P. The findings of the study point to the importance of addressing the functional implications and QOL of individuals with TF. Implications for Rehabilitation Although trigger finger is considered to be a mild hand pathology, it has a wide-ranging impact on hand functioning, daily activities and quality of life. Clinicians should include assessments of these outcomes in the treatment of individuals with trigger finger. Treatment efficacy should be evaluated with International Classification of Functioning outcomes, and not limited to symptomatology.

[10 congenital trigger fingers. Apropos of a case report].

PubMed

Moutet, F; Lebrun, C; Sartorius, C

1987-01-01

Ten congenital triggers fingers have been treated on a 3 years old girl after correction of congenital bilateral club feet. Such a case, without any other congenital malformation seems to be unique in the French literature and only found twice in the English one. This child in spite of a normal growth and good psychomotor development, presents an unusual face, with a mouth a little bit too small, but her karyotype is normal. No trismus and no microstomia were found to enable this case to be classified in a specific syndrome. The right diagnosis may be a non evolutive arthrogryposis of the extremities. Dividing the ten proximal pulleys (A1) let 10 voluminous nodules pass through and allowed full range of motion in nine out of ten fingers. A remaining flexion deformity of the proximal interphalangeal joint needed an anterior arthrolysis, the final result was good.

Clinical Assessment and Diagnostics of Patients With Hand Disorders: A Case Study Approach.

PubMed

Leow, Mabel Qi He; Lim, Rebecca Qian Ru; Tay, Shian Chao

Clinical assessment of the hand is important for diagnosing underlying hand disorders. Using a case study approach, the clinical assessment for three disorders of the hands is presented: trigger finger (stenosing tenosynovitis), carpal tunnel syndrome, and ulnar-sided wrist injury (styloid impingement). We assess the annular one pulley and finger range of motion for patients with trigger finger. To diagnose for carpal tunnel syndrome, assessment for Tinel's sign, Phalen's sign, abductor pollicis brevis muscle bulk, two-point discrimination, and obtaining a nerve conduction study are performed. Assessment for ulnar-sided wrist injury includes wrist range of motion, assessment of distal radial ulnar joint stability, provocation tests, grip strength, x-ray, and magnetic resonance imaging. This article begins with a description of the hand and wrist anatomy. For each case study, the clinical history is described, followed by a discussion of the pathophysiology, clinical assessments, and diagnostic tests.

Mechanisms of inhibition of zinc-finger transcription factors by selenium compounds ebselen and selenite.

PubMed

Larabee, Jason L; Hocker, James R; Hanas, Jay S

2009-03-01

The anti-inflammatory selenium compounds, ebselen (2-phenyl-1,2-benzisoselenazol-3[2H]-one) and selenite, were found to alter the DNA binding mechanisms and structures of cysteine-rich zinc-finger transcription factors. As assayed by DNase I protection, DNA binding by TFIIIA (transcription factor IIIA, prototypical Cys(2)His(2) zinc finger protein), was inhibited by micromolar amounts of ebselen. In a gel shift assay, ebselen inhibited the Cys(2)His(2) zinc finger-containing DNA binding domain (DBD) of the NF-kappaB mediated transcription factor Sp1. Ebselen also inhibited DNA binding by the p50 subunit of the pro-inflammatory Cys-containing NF-kappaB transcription factor. Electrospray ionization mass spectrometry (ESI-MS) was utilized to elucidate mechanisms of chemical interaction between ebselen and a zinc-bound Cys(2)His(2) zinc finger polypeptide modeled after the third finger of Sp1 (Sp1-3). Exposing Sp1-3 to micromolar amounts of ebselen resulted in Zn(2+) release from this peptide and the formation of a disulfide bond by oxidation of zinc finger SH groups, the likely mechanism for DNA binding inhibition. Selenite was shown by ESI-MS to also eject zinc from Sp1-3 as well as induce disulfide bond formation through SH oxidation. The selenite-dependent inhibition/oxidation mechanism differed from that of ebselen by inducing the formation of a stable selenotrisulfide bond. Selenite-induced selenotrisulfide formation was dependent upon the structure of the Cys(2)His(2) zinc finger as alteration in the finger structure enhanced this reaction as well as selenite-dependent zinc release. Ebselen and selenite-dependent inhibition/oxidation of Cys-rich zinc finger proteins, with concomitant release of zinc and finger structural changes, points to mechanisms at the atomic and protein level for selenium-induced alterations in Cys-rich proteins, and possible amelioration of certain inflammatory, neurodegenerative, and oncogenic responses.

In vivo electrode implanting system

NASA Technical Reports Server (NTRS)

Collins, Jr., Earl R. (Inventor)

1989-01-01

A cylindrical intramuscular implantable electrode is provided with a strip of fabric secured around it. The fabric is woven from a polyester fiber having loops of the fiber protruding. The end of the main cylindrical body is provided with a blunt conductive nose, and the opposite end is provided with a smaller diameter rear section with an annular groove to receive tips of fingers extending from a release tube. The fingers are formed to spring outwardly and move the fingertips out of the annular groove in order to release the electrode from the release tube when a sheath over the electrode is drawn back sufficiently. The sheath compresses the fingers of the release tube and the fabric loops until it is drawn back. Muscle tissue grows into the loops to secure the electrode in place after the sheath is drawn back. The entire assembly of electrode, release tube and sheath can be inserted into the patient's muscle to the desired position through a hypodermic needle. The release tube may be used to manipulate the electrode in the patient's muscle to an optimum position before the electrode is released.

Management of the Stiff Finger: Evidence and Outcomes

PubMed Central

Yang, Guang; McGlinn, Evan P.; Chung, Kevin C.

2014-01-01

SYNOPSIS The term “stiff finger” refers to a reduction in the range of motion in the finger, and it is a condition that has many different causes and involves a number of different structures. Almost all injuries of the fingers and some diseases can cause finger stiffness. Hand surgeons often face difficulty treating stiff fingers that are affected by irreversible soft tissues fibrosis. Stiff fingers can be divided into flexion and extension deformities. They can also be sub-classified into four categories according to the involved tissues extending from the skin to the joint capsule. Prevention of stiff fingers by judicious mobilization of the joints is prudent to avoid more complicated treatment after established stiffness occurs. Static progressive and dynamic splints have been considered as effective non-operative interventions to treat stiff fingers. Most authors believe force of joint distraction and time duration of stretching are two important factors to consider while applying a splint or cast. We also introduce the concepts of capsulotomy and collateral ligament release and other soft tissue release of the MCP and PIP joint in this article. Future outcomes research is vital to assessing the effectiveness of these surgical procedures and guiding postoperative treatment recommendations. PMID:24996467

Generation of dense plume fingers in saturated-unsaturated homogeneous porous media

NASA Astrophysics Data System (ADS)

Cremer, Clemens J. M.; Graf, Thomas

2015-02-01

Flow under variable-density conditions is widespread, occurring in geothermal reservoirs, at waste disposal sites or due to saltwater intrusion. The migration of dense plumes typically results in the formation of vertical plume fingers which are known to be triggered by material heterogeneity or by variations in source concentration that causes the density variation. Using a numerical groundwater model, six perturbation methods are tested under saturated and unsaturated flow conditions to mimic heterogeneity and concentration variations on the pore scale in order to realistically generate dense fingers. A laboratory-scale sand tank experiment is numerically simulated, and the perturbation methods are evaluated by comparing plume fingers obtained from the laboratory experiment with numerically simulated fingers. Dense plume fingering for saturated flow can best be reproduced with a spatially random, time-constant perturbation of the solute source. For unsaturated flow, a spatially and temporally random noise of solute concentration or a random conductivity field adequately simulate plume fingering.

Upper limb congenital muscular hypertrophy and aberrant muscle syndrome in children.

PubMed

Dahan, Emmanuel; Chaves, Camilo; Bachy, Manon; Fitoussi, Frank

2018-01-01

Congenital muscle hypertrophy of the upper limb is a very rare condition with unknown aetiology. This descriptive observational and retrospective series included eight children followed by a multidisciplinary team from 2005 to 2017. The diagnosis was based on a cluster of clinical and radiological characteristics after elimination of differential diagnoses. Patients were categorized according to: anomalies of the wrist, anomalies of long fingers of intrinsic or extrinsic origin; and anomalies of the thumb with or without first web space contracture. Treatment begins in young children with hand orthoses to limit muscle contraction and joint malposition. The purpose of surgical treatment was to release contractures and to restore muscle balance through, in the main, finger intrinsic releases and first web releases. At the 2-year follow-up, we found that limited surgical procedures improved finger, thumb and wrist positions. We conclude that muscle hypertrophy is the main cause of deformity and that selective releases of contracted musculo-tendinous units and skin lengthening are effective. IV.

Experimental viscous fingering in a tapered radial Hele-Shaw cell

NASA Astrophysics Data System (ADS)

Bongrand, Gregoire; Tsai, Peichun Amy; Complex Fludis Group Team

2017-11-01

The fluid-fluid displacement in porous media is a common process that finds direct applications in various fields, such as enhanced oil recovery and geological CO2 sequestration. In this work, we experimentally investigate the influence of converging cells on viscous fingering instabilities using a radially-tapered cell. For air displacing oil, in contrast to the classical Saffman-Taylor fingering, our results show that a converging gradient in a radial propagation can provide a stabilizing effect and hinder fingering. For a fixed gap gradient and thickness, with increasing injection rates we find a stable displacement under small flow rates, whereas unstable fingering occurs above a certain threshold. We further investigate this critical flow rate delineating the stable and unstable regimes for different gap gradients. These results reveal that the displacement efficiency not only depends on the fluid properties but also on the interfacial velocity and channel structure. The latter factors provide a useful and convenient control to either trigger or inhibit fingering instability. NSERC Discovery, Accelerator, and CRC programs.

Brain activity during bilateral rapid alternate finger tapping measured with magnetoencephalography

NASA Astrophysics Data System (ADS)

Fukuda, Hiroshi; Odagaki, Masato; Hiwaki, Osamu; Kodabashi, Atsushi; Fujimoto, Toshiro

2009-04-01

Using magnetoencephalography (MEG), brain regions involved in an alternate bimanual tapping task by index fingers triggered with spontaneous timing were investigated. The tapping mode in which both index fingers moved simultaneously was interlaced during the task. The groups of the alternate tapping (AL mode) and the simultaneous tapping (SI mode) were extracted from the successive alternating taps with a histogram of intervals between the right and left index fingers. MEG signals in each mode were averaged separately before and after the tapping initiation of the dominant index finger. The activities of the contralateral sensorimotor cortex before and after the tapping initiation in the AL mode were larger than that in the SI mode. The result indicates that the activity of the contralateral sensorimotor cortex depends on the degree of achievement in the difficult motor task such as the voluntary alternate tapping movements.

Radial extracorporeal shockwave therapy for the treatment of finger tenosynovitis (trigger digit)

PubMed Central

Malliaropoulos, Nikos; Jury, Rosanna; Pyne, Debasish; Padhiar, Nat; Turner, Jennifer; Korakakis, Vasileios; Meke, Maria; Lohrer, Heinz

2016-01-01

Introduction Stenosing tenosynovitis that is characterized by the inability to flex the digit smoothly, usually leads to prolonged rehabilitation or surgery. Study design This case series is a retrospective cohort study. Purpose The aim of this case series was to evaluate the effectiveness of radial extracorporeal shockwave therapy (rESWT) for the treatment of stenosing tenosynovitis of the digital flexor tendon (trigger digit). Methods A retrospective analysis of 44 patients (49 fingers) treated with an individually adapted rESWT protocol was conducted. Trigger digit pain and function were evaluated at baseline and 1-, 3-, and 12-months posttreatment. Recurrence and pretreatment symptom duration were analyzed. Results Significant reductions in pain scores and functional improvement were found between baseline and all follow-up assessments (P<0.001). Pretreatment symptom duration was significantly correlated with the number of rESWT sessions required (r=0.776, P<0.001) and 1-year posttreatment pain score (r=0.335, P=0.019). Conclusion This study provides initial evidence that rESWT is an effective treatment for trigger digit, but randomised controlled trials are required to provide further evidence of this effect. PMID:27843364

Viscous Fingering on an Immiscible Reactive Interface with Variation of Interfacial Tension

NASA Astrophysics Data System (ADS)

Tsuzuki, Reiko; Nagatsu, Yuichiro; Li, Qian; Chen, Ching-Yao

2017-11-01

The effects of chemical reaction, in which surfactants are produced on the interface of two immiscible fluids, on viscous fingering in a radial Hele-Shaw flow are numerically investigated. The presence of surfactants reduces interfacial tension, which is an important factor to the fingering pattern formation. In the present study, influences of reaction rate and dispersion of produced surfactants, represented respectively by dimensionless parameters of Damkohler number and Peclet number, are evaluated systematically. Secondary fingering instability, e.g., tip-splitting and side-branching, is triggered by chemical reactions. Weaker surface tension generally induces tip-splitting. For the case of high Damkohler number, because of the vortex pairs generated within each finger, surfactant tends to accumulate significantly on the side of finger, so that side-branching is preferred. Nevertheless, side-branching is suppressed in the cases associated with low Peclet number, in which strong dispersion reduces the local variation of surfactant concentration. Considering the coupled effects by Damkohler number and Peclet number, the patterns obtained by the simulations qualitatively agree with the observations in the experiments.

Genome Editing in Neuroepithelial Stem Cells to Generate Human Neurons with High Adenosine-Releasing Capacity.

PubMed

Poppe, Daniel; Doerr, Jonas; Schneider, Marion; Wilkens, Ruven; Steinbeck, Julius A; Ladewig, Julia; Tam, Allison; Paschon, David E; Gregory, Philip D; Reik, Andreas; Müller, Christa E; Koch, Philipp; Brüstle, Oliver

2018-06-01

As a powerful regulator of cellular homeostasis and metabolism, adenosine is involved in diverse neurological processes including pain, cognition, and memory. Altered adenosine homeostasis has also been associated with several diseases such as depression, schizophrenia, or epilepsy. Based on its protective properties, adenosine has been considered as a potential therapeutic agent for various brain disorders. Since systemic application of adenosine is hampered by serious side effects such as vasodilatation and cardiac suppression, recent studies aim at improving local delivery by depots, pumps, or cell-based applications. Here, we report on the characterization of adenosine-releasing human embryonic stem cell-derived neuroepithelial stem cells (long-term self-renewing neuroepithelial stem [lt-NES] cells) generated by zinc finger nuclease (ZFN)-mediated knockout of the adenosine kinase (ADK) gene. ADK-deficient lt-NES cells and their differentiated neuronal and astroglial progeny exhibit substantially elevated release of adenosine compared to control cells. Importantly, extensive adenosine release could be triggered by excitation of differentiated neuronal cultures, suggesting a potential activity-dependent regulation of adenosine supply. Thus, ZFN-modified neural stem cells might serve as a useful vehicle for the activity-dependent local therapeutic delivery of adenosine into the central nervous system. Stem Cells Translational Medicine 2018;7:477-486. © 2018 The Authors Stem Cells Translational Medicine published by Wiley Periodicals, Inc. on behalf of AlphaMed Press.

Development of an externally powered prosthetic hook for amputees

NASA Technical Reports Server (NTRS)

Karchak, A., Jr.; Allen, J. R.; Bontrager, E. L.

1973-01-01

The powered hook with trigger finger appears to be a useful adaptation of a terminal device for an amputee when performing vocational activities involving the use of a powered tool requiring a trigger control. The proportional control system includes transducers and amplifiers and appears to have widespread application for control of any external power, whether it be in the orthotic or prosthetic field.

Finger forces in fastball baseball pitching.

PubMed

Kinoshita, Hiroshi; Obata, Satoshi; Nasu, Daiki; Kadota, Koji; Matsuo, Tomoyuki; Fleisig, Glenn S

2017-08-01

Forces imparted by the fingers onto a baseball are the final, critical aspects for pitching, however these forces have not been quantified previously as no biomechanical technology was available. In this study, an instrumented baseball was developed for direct measurement of ball reaction force by individual fingers and used to provide fundamental information on the forces during a fastball pitch. A tri-axial force transducer with a cable having an easily-detachable connector were installed in an official baseball. Data were collected from 11 pitchers who placed the fingertip of their index, middle, ring, or thumb on the transducer, and threw four-seam fastballs to a target cage from a flat mound. For the index and middle fingers, resultant ball reaction force exhibited a bimodal pattern with initial and second peaks at 38-39ms and 6-7ms before ball release, and their amplitudes were around 97N each. The ring finger and thumb produced single-peak forces of approximately 50 and 83N, respectively. Shear forces for the index and middle fingers formed distinct peak at 4-5ms before release, and the peaks summed to 102N; a kinetic source for backspin on the ball. An additional experiment with submaximal pitching effort showed a linear relationship of peak forces with ball velocity. The peak ball reaction force for fastballs exceeded 80% of maximum finger strength measured, suggesting that strengthening of the distal muscles is important both for enhancing performance and for avoiding injuries. Copyright © 2017 Elsevier B.V. All rights reserved.

Quick-connect fasteners for assembling devices in space

NASA Technical Reports Server (NTRS)

Evenson, Erik E. (Inventor); Wesselski, Clarence J. (Inventor); Ruiz, Steve C. (Inventor)

1993-01-01

A quick-connect fastener of a relatively-simple straightforward design is arranged with a tubular body adapted to be engaged against an attachment fitting in coincidental alignment with an opening in that fitting. A tubular collet having flexible fingers projecting from its forward end is arranged in the fastener body to be shifted forwardly by an elongated expander member coaxially arranged within the tubular collet for advancing the collet fingers into the opening in the attachment fitting. Biasing means are arranged between the elongated expander member and a rotatable actuator which is threadedly mounted within the tubular collet so as to be rotated for urging the expander member into engagement with the collet fingers. A first coupling member is arranged on the rotatable actuator to be accessible from outside of the fastener so that a second coupling member on the distal end of a flexible shaft can be introduced into the fastener body and coupled to the first coupling member to enable a typical actuating tool coupled to the shaft outside of the fastener body to be operated for advancing the outwardly-enlarged ends of the collet fingers into the opening in the attachment fitting and thereafter rotating the actuator member to expand the fingers within the opening for releasably latching the fastener to that attachment fitting. Upon expansion of the collet fingers, the biasing means impose a biasing force on the expander to releasably retain the fingers in their latching positions.

Prosthetic Hand For Holding Rods, Tools, And Handles

NASA Technical Reports Server (NTRS)

Belcher, Jewell G., Jr.; Vest, Thomas W.

1995-01-01

Prosthetic hand with quick-grip/quick-release lever broadens range of specialized functions available to lower-arm amputee by providing improved capabilities for gripping rods, tools, handles, and like. Includes two stationary lower fingers opposed by one pivoting upper finger. Lever operates in conjunction with attached bracket.

The relation between attention and tic generation in Tourette syndrome.

PubMed

Misirlisoy, Erman; Brandt, Valerie; Ganos, Christos; Tübing, Jennifer; Münchau, Alexander; Haggard, Patrick

2015-07-01

Many neuropsychiatric disorders involve abnormal attentional processing. Systematic investigations of how attention may affect tic frequency in Tourette syndrome are lacking. Patients performed rhythmic finger movements, approximately once every 2 s. Each movement triggered a unique visual color stimulus. Patients were asked to monitor and remember their finger actions, the external colors caused by their actions, or their tics. Sixteen adult Tourette syndrome patients performed each task twice: once while inhibiting tics, and once without inhibiting tics. During the "freely tic" condition, patients had significantly fewer tics when attending to finger movements, or to the ensuing colors, compared with when attending to their tics. Attention to fingers produced the fewest tics overall. During tic suppression, tic frequency was reduced to an equal level in all conditions. Focusing attention away from tics significantly reduces tic frequency. This attentional process may operate by regulating motor noise. (c) 2015 APA, all rights reserved).

The Relation Between Attention and Tic Generation in Tourette Syndrome

PubMed Central

2014-01-01

Objective: Many neuropsychiatric disorders involve abnormal attentional processing. Systematic investigations of how attention may affect tic frequency in Tourette syndrome are lacking. Method: Patients performed rhythmic finger movements, approximately once every 2 s. Each movement triggered a unique visual color stimulus. Patients were asked to monitor and remember their finger actions, the external colors caused by their actions, or their tics. Sixteen adult Tourette syndrome patients performed each task twice: once while inhibiting tics, and once without inhibiting tics. Results: During the “freely tic” condition, patients had significantly fewer tics when attending to finger movements, or to the ensuing colors, compared with when attending to their tics. Attention to fingers produced the fewest tics overall. During tic suppression, tic frequency was reduced to an equal level in all conditions. Conclusions: Focusing attention away from tics significantly reduces tic frequency. This attentional process may operate by regulating motor noise. PMID:25486384

[Symbrachydactyly].

PubMed

Samson, P; Mevio, G

2008-12-01

Symbrachydactyly is literally defined as a combination of short fingers with syndactyly. Blauth and Gekeler described four types of symbrachydactyly, ranging from simple shortness of middle phalanges to complete absence of digital rays. In type I (short finger) function is quite normal and syndactyly release is usually the only procedure needed. In type II (cleft hand), presence of a thumb and at least one ulnar finger allows pinch function. Surgical treatment, when needed, consists in separation of webbed fingers, resection of nonfunctional digital stumps, or finger translocation. In type III (monodactyly) all long fingers are absent. Pinch function can be created between the thumb and a toe transfer in ulnar location. Bone lengthening is an alternative procedure to create a pincer. Surgery is not always indicated in type IV (peromely) as function can only be restored if active motion is already present at wrist or carpometacarpal levels.

PHF20 regulates NF-κB signalling by disrupting recruitment of PP2A to p65

PubMed Central

Zhang, Tiejun; Park, Kyeong Ah; Li, Yuwen; Byun, Hee Sun; Jeon, Juhee; Lee, Yoonjung; Hong, Jang Hee; Kim, Jin Man; Huang, Song-Mei; Choi, Seung-Won; Kim, Sun-Hwan; Sohn, Kyung-Cheol; Ro, Hyunju; Lee, Ji Hoon; Lu, Tao; Stark, George R.; Shen, Han-Ming; Liu, Zheng-gang; Park, Jongsun; Hur, Gang Min

2014-01-01

Constitutive NF-κB activation in cancer cells is caused by defects in the signalling network responsible for terminating the NF-κB response. Here we report that plant homeodomain finger protein 20 maintains NF-κB in an active state in the nucleus by inhibiting the interaction between PP2A and p65. We show that plant homeodomain finger protein 20 induces canonical NF-κB signalling by increasing the DNA-binding activity of NF-κB subunit p65. In plant homeodomain finger protein 20-overexpressing cells, the termination of tumour necrosis factor-induced p65 phosphorylation is impaired whereas upstream signalling events triggered by tumour necrosis factor are unaffected. This effect strictly depends on the interaction between plant homeodomain finger protein 20 and methylated lysine residues of p65, which hinders recruitment of PP2A to p65, thereby maintaining p65 in a phosphorylated state. We further show that plant homeodomain finger protein 20 levels correlate with p65 phosphorylation levels in human glioma specimens. Our work identifies plant homeodomain finger protein 20 as a novel regulator of NF-κB activation and suggests that elevated expression of plant homeodomain finger protein 20 may drive constitutive NF-κB activation in some cancers. PMID:23797602

Surgery for trigger finger.

PubMed

Fiorini, Haroldo Junior; Tamaoki, Marcel Jun; Lenza, Mário; Gomes Dos Santos, Joao Baptista; Faloppa, Flávio; Belloti, Joao Carlos

2018-02-20

Trigger finger is a common clinical disorder, characterised by pain and catching as the patient flexes and extends digits because of disproportion between the diameter of flexor tendons and the A1 pulley. The treatment approach may include non-surgical or surgical treatments. Currently there is no consensus about the best surgical treatment approach (open, percutaneous or endoscopic approaches). To evaluate the effectiveness and safety of different methods of surgical treatment for trigger finger (open, percutaneous or endoscopic approaches) in adults at any stage of the disease. We searched CENTRAL, MEDLINE, Embase and LILACS up to August 2017. We included randomised or quasi-randomised controlled trials that assessed adults with trigger finger and compared any type of surgical treatment with each other or with any other non-surgical intervention. The major outcomes were the resolution of trigger finger, pain, hand function, participant-reported treatment success or satisfaction, recurrence of triggering, adverse events and neurovascular injury. Two review authors independently selected the trial reports, extracted the data and assessed the risk of bias. Measures of treatment effect for dichotomous outcomes calculated risk ratios (RRs), and mean differences (MDs) or standardised mean differences (SMD) for continuous outcomes, with 95% confidence intervals (CIs). When possible, the data were pooled into meta-analysis using the random-effects model. GRADE was used to assess the quality of evidence for each outcome. Fourteen trials were included, totalling 1260 participants, with 1361 trigger fingers. The age of participants included in the studies ranged from 16 to 88 years; and the majority of participants were women (approximately 70%). The average duration of symptoms ranged from three to 15 months, and the follow-up after the procedure ranged from eight weeks to 23 months.The studies reported nine types of comparisons: open surgery versus steroid injections (two studies); percutaneous surgery versus steroid injection (five studies); open surgery versus steroid injection plus ultrasound-guided hyaluronic acid injection (one study); percutaneous surgery plus steroid injection versus steroid injection (one study); percutaneous surgery versus open surgery (five studies); endoscopic surgery versus open surgery (one study); and three comparisons of types of incision for open surgery (transverse incision of the skin in the distal palmar crease, transverse incision of the skin about 2-3 mm distally from distal palmar crease, and longitudinal incision of the skin) (one study).Most studies had significant methodological flaws and were considered at high or unclear risk of selection bias, performance bias, detection bias and reporting bias. The primary comparison was open surgery versus steroid injections, because open surgery is the oldest and the most widely used treatment method and considered as standard surgery, whereas steroid injection is the least invasive control treatment method as reported in the studies in this review and is often used as first-line treatment in clinical practice.Compared with steroid injection, there was low-quality evidence that open surgery provides benefits with respect to less triggering recurrence, although it has the disadvantage of being more painful. Evidence was downgraded due to study design flaws and imprecision.Based on two trials (270 participants) from six up to 12 months, 50/130 (or 385 per 1000) individuals had recurrence of trigger finger in the steroid injection group compared with 8/140 (or 65 per 1000; range 35 to 127) in the open surgery group, RR 0.17 (95% CI 0.09 to 0.33), for an absolute risk difference that 29% fewer people had recurrence of symptoms with open surgery (60% fewer to 3% more individuals); relative change translates to improvement of 83% in the open surgery group (67% to 91% better).At one week, 9/49 (184 per 1000) people had pain on the palm of the hand in the steroid injection group compared with 38/56 (or 678 per 1000; ranging from 366 to 1000) in the open surgery group, RR 3.69 (95% CI 1.99 to 6.85), for an absolute risk difference that 49% more had pain with open surgery (33% to 66% more); relative change translates to worsening of 269% (585% to 99% worse) (one trial, 105 participants).Because of very low quality evidence from two trials we are uncertain whether open surgery improve resolution of trigger finger in the follow-up at six to 12 months, when compared with steroid injection (131/140 observed in the open surgery group compared with 80/130 in the control group; RR 1.48, 95% CI 0.79 to 2.76); evidence was downgraded due to study design flaws, inconsistency and imprecision. Low-quality evidence from two trials and few event rates (270 participants) from six up to 12 months of follow-up, we are uncertain whether open surgery increased the risk of adverse events (incidence of infection, tendon injury, flare, cutaneous discomfort and fat necrosis) (18/140 observed in the open surgery group compared with 17/130 in the control group; RR 1.02, 95% CI 0.57 to 1.84) and neurovascular injury (9/140 observed in the open surgery group compared with 4/130 in the control group; RR 2.17, 95% CI 0.7 to 6.77). Twelve participants (8 versus 4) did not complete the follow-up, and it was considered that they did not have a positive outcome in the data analysis. We are uncertain whether open surgery was more effective than steroid injection in improving hand function or participant satisfaction as studies did not report these outcomes. Low-quality evidence indicates that, compared with steroid injection, open surgical treatment in people with trigger finger, may result in a less recurrence rate from six up to 12 months following the treatment, although it increases the incidence of pain during the first follow-up week. We are uncertain about the effect of open surgery with regard to the resolution rate in follow-up at six to 12 months, compared with steroid injections, due high heterogeneity and few events occurred in the trials; we are uncertain too about the risk of adverse events and neurovascular injury because of a few events occurred in the studies. Hand function or participant satisfaction were not reported.

Optimization for Guitar Fingering on Single Notes

NASA Astrophysics Data System (ADS)

Itoh, Masaru; Hayashida, Takumi

This paper presents an optimization method for guitar fingering. The fingering is to determine a unique combination of string, fret and finger corresponding to the note. The method aims to generate the best fingering pattern for guitar robots rather than beginners. Furthermore, it can be applied to any musical score on single notes. A fingering action can be decomposed into three motions, that is, a motion of press string, release string and move fretting hand. The cost for moving the hand is estimated on the basis of Manhattan distance which is the sum of distances along fret and string directions. The objective is to minimize the total fingering costs, subject to fret, string and finger constraints. As a sequence of notes on the score forms a line on time series, the optimization for guitar fingering can be resolved into a multistage decision problem. Dynamic programming is exceedingly effective to solve such a problem. A level concept is introduced into rendering states so as to make multiple DP solutions lead a unique one among the DP backward processes. For example, if two fingerings have the same value of cost at different states on a stage, then the low position would be taken precedence over the high position, and the index finger would be over the middle finger.

A method to locate the radial digital nerve of the index finger.

PubMed

Lourie, G M; Rudolph, H P; Lundy, D W

1998-08-01

The radial digital nerve of the index finger is susceptible to injury during penetrating trauma or elective release of the A1 pulley. The intersection of a line drawn down the midline of the index finger and the proximal palmar crease identifies the location of the radial digital nerve. This method of identifying the topography of the nerve should assist the surgeon in determining the likelihood of injury after penetrating trauma, and preventing injury during elective procedures.

Competition of wormholes during the evolution of cave passages

NASA Astrophysics Data System (ADS)

Gabrovsek, Franci; Dreybrodt, Wolfgang

2017-04-01

Reactive fronts in two-dimensional plane parallel fractures, with constant head difference between input and output and with diffusion controlled first order reaction rates R = keff ṡ (Ceq - C), where keff = k ṡ (1 + ka/6D)-1, are instable to infinitesimal perturbations in fracture aperture width (1), causing spontaneous fingering of the reactive front resulting in the formation of wormholes. C is the actual concentration and Ceq the equilibrium concentration, a, is the actual aperture width of the fracture , and D the constant of molecular diffusion. Fingering happens also in plane-parallel rough fractures where it is triggered by the existence of statistically more favorable pathways. The same behavior is observed in rectangular two-dimensional networks of "one-dimensional" smooth fractures used in modeling the evolution of caves in soluble rock (2). Here the formation of caves can be regarded as the evolution of wormholes along the two-dimensional network. Once fingering has been triggered, either by instability or by roughness, many small fingers compete with each other and only a few survive. Here we investigate the competition between two seeded fingers in initially homogeneous fracture networks with identical aperture width of all fractures and also in inhomogeneous ones where the aperture widths are distributed log normally. In both cases our modeling reveals the rules of competition: By instability one of the fingers grows faster than its competitor therefore penetrating somewhat deeper. As a consequence the hydraulic head at its tip is higher than that close to the tip of the shorter finger. Therefore the fractures connecting the tip regions of both fingers carry flow from the deep finger to the tip region of its competitor. This cross-flow is replaced by increasing inflow of aggressive solution into the input of the winner, enhancing further dissolution and growth. On the other hand the cross-flow increases the head at the tip of the losing finger, and consequently decreases inflow of aggressive solution into it, thus inhibiting its further evolution. This mechanism supports further growth of the winner (wormhole) and stops the growth of its competitor. Similar competition happens in the case of several fingers competing. In any case we observe flow from the winning fingers to the loosing ones. The communication between the competitors is always established by cross flow between its tip regions. We will present various scenarios of wormhole formation, which demonstrate details of the competition of fingers arising from either the reactive instability or from the statistical distribution of fracture aperture widths. In conclusion we find that the initiation of wormholes results either from instability or from the statistical distribution of favorable pathways. Once growth of fingers has been initiated the evolution of the wormhole patterns becomes deterministic. (1) Szymczak, P., and A.J.C. Ladd (2011), The initial stages of cave formation: Beyond the one-dimensional paradigm, Earth Planet. Sci. Lett. 301, 424-432 (2) Dreybrodt, W., Gabrovšek, F., Romanov, D.(2005) Processes of Speleogenesis: A Modeling Approach. ZRC Publishing, Karst Research Institute at ZRC SAZU, Ljubljana

Salt-Finger Convection in a Stratified Fluid Layer Induced by Thermal and Solutal Capillary Motion

NASA Technical Reports Server (NTRS)

Chen, Chuan F.; Chan, Cho Lik

1996-01-01

Salt-finger convection in a double-diffusive system is a motion driven by the release of gravitational potential due to different diffusion rates. Normally, when the gravitational field is reduced, salt-finger convection together with other convective motions driven by buoyancy forces will be rapidly suppressed. However, because the destabilizing effect of the concentration gradient is amplified by the Lewis number, with values varying from 10(exp 2) for aqueous salt solutions to 10 (exp 4) for liquid metals, salt-finger convection may be generated at much reduced gravity levels. In the microgravity environment, the surface tension gradient assumes a dominant role in causing fluid motion. In this paper, we report on some experimental results showing the generation of salt-finger convection due to capillary motio on the surface of a stratified fluid layer. A numerical simulation is presented to show the cause of salt-finger convection.

Erosion waves: Transverse instabilities and fingering

NASA Astrophysics Data System (ADS)

Malloggi, F.; Lanuza, J.; Andreotti, B.; Clément, E.

2006-09-01

Two laboratory scale experiments of dry and underwater avalanches of non-cohesive granular materials are investigated. We trigger solitary waves and study the conditions under which the front is transversally stable. We show the existence of a linear instability followed by a coarsening dynamics and finally the onset of a fingering pattern. Due to the different operating conditions, both experiments strongly differ by the spatial and time scales involved. Nevertheless, the quantitative agreement between the stability diagram, the wavelengths selected and the avalanche morphology suggest a common scenario for an erosion/deposition process.

Compact Dexterous Robotic Hand

NASA Technical Reports Server (NTRS)

Lovchik, Christopher Scott (Inventor); Diftler, Myron A. (Inventor)

2001-01-01

A compact robotic hand includes a palm housing, a wrist section, and a forearm section. The palm housing supports a plurality of fingers and one or more movable palm members that cooperate with the fingers to grasp and/or release an object. Each flexible finger comprises a plurality of hingedly connected segments, including a proximal segment pivotally connected to the palm housing. The proximal finger segment includes at least one groove defining first and second cam surfaces for engagement with a cable. A plurality of lead screw assemblies each carried by the palm housing are supplied with power from a flexible shaft rotated by an actuator and output linear motion to a cable move a finger. The cable is secured within a respective groove and enables each finger to move between an opened and closed position. A decoupling assembly pivotally connected to a proximal finger segment enables a cable connected thereto to control movement of an intermediate and distal finger segment independent of movement of the proximal finger segment. The dexterous robotic hand closely resembles the function of a human hand yet is light weight and capable of grasping both heavy and light objects with a high degree of precision.

Splint therapy for trigger finger in children.

PubMed

Tsuyuguchi, Y; Tada, K; Kawaii, H

1983-02-01

During the last 9 years, 83 trigger digits in 65 children were treated using a modified coil spring splint which maintains the interphalangeal (IP) joint in neutral extension or hyperextension. Sixty-two digits (75%) were completely healed following splint therapy alone, after an average period of splinting for 9.4 months. Eight digits which did not improve with splinting were surgically treated. Splint therapy to maintain the IP joint in neutral extension or hyperextension proved markedly effective in our series.

Electromechanical hand incorporates touch sensors and trigger function

NASA Technical Reports Server (NTRS)

Dane, D. H.

1970-01-01

Electromechanical hand incorporates touch sensors, concealed fingers, and a structure that allows the hand to hold a tool on a flat surface. The hands can be mounted on most types of existing manipulators either directly or by means of modified mounting brackets.

Numerical Generation of Dense Plume Fingers in Unsaturated Homogeneous Porous Media

NASA Astrophysics Data System (ADS)

Cremer, C.; Graf, T.

2012-04-01

In nature, the migration of dense plumes typically results in the formation of vertical plume fingers. Flow direction in fingers is downwards, which is counterbalanced by upwards flow of less dense fluid between fingers. In heterogeneous media, heterogeneity itself is known to trigger the formation of fingers. In homogeneous media, however, fingers are also created even if all grains had the same diameter. The reason is that pore-scale heterogeneity leading to different flow velocities also exists in homogeneous media due to two effects: (i) Grains of identical size may randomly arrange differently, e.g. forming tetrahedrons, hexahedrons or octahedrons. Each arrangement creates pores of varying diameter, thus resulting in different average flow velocities. (ii) Random variations of solute concentration lead to varying buoyancy effects, thus also resulting in different velocities. As a continuation of previously made efforts to incorporate pore-scale heterogeneity into fully saturated soil such that dense fingers are realistically generated (Cremer and Graf, EGU Assembly, 2011), the current paper extends the research scope from saturated to unsaturated soil. Perturbation methods are evaluated by numerically re-simulating a laboratory-scale experiment of plume transport in homogeneous unsaturated sand (Simmons et al., Transp. Porous Media, 2002). The following 5 methods are being discussed: (i) homogeneous sand, (ii) initial perturbation of solute concentration, (iii) spatially random, time-constant perturbation of solute source, (iv) spatially and temporally random noise of simulated solute concentration, and (v) random K-field that introduces physically insignificant but numerically significant heterogeneity. Results demonstrate that, as opposed to saturated flow, perturbing the solute source will not result in plume fingering. This is because the location of the perturbed source (domain top) and the location of finger generation (groundwater surface) do not coincide. Alternatively, similar to saturated flow, applying either a random concentration noise (iv) or a random K-field (v) generates realistic plume fingering. Future work will focus on the generation mechanisms of plume finger splitting.

Deformation of interface in a partially miscible system during favorable displacement

NASA Astrophysics Data System (ADS)

Suzuki, Ryuta; Nagatsu, Yuichiro; Mishra, Manoranjan; Ban, Takahiko

2017-11-01

The Saffman-Taylor instability triggers a well-known viscous fingering (VF, called unfavorable displacement), occurring when a less viscous fluid displaces a more viscous one in porous media or in a Hele-Shaw cell because the boundary of the two fluids becomes hydrodynamically unstable. In the reverse situation (called favorable displacement) in which a more viscous fluid displaces a less viscous one, no instabilities occur due to hydrodynamically stable system. It has been reported that the favorable displacements become unstable by several physicochemical effects. So far, studies of both displacements have focused on fluids that are either fully miscible or immiscible. However, little attention has been paid to displacements in partially miscible system. Here, we have discovered that a partial miscibility triggers fingering instability in a favorable displacement without any chemical reactions. The occurrence of this new instability is induced by not hydrodynamic effects but a thermodynamic effect that is so-called Korteweg effect in which convection is induced during phase separation process in a partially miscible system.

Application of the IFSSH(3)-classification for congenital anomalies of the hand; results and problems.

PubMed

De Smet, L; Matton, G; Monstrey, S; Cambier, E; Fabry, G

1997-09-01

The extended classification proposed by the IFSSH was used to classify 1013 hand anomalies in 925 hands of 650 patients. We found associated anomalies in 26.7%. The classification was straightforward in 86%, difficult in 6.6% and not possible in 7.8%. In group I the radial and ulnar deficiencies, limited to the hand and without forearm deficiencies should be included. Group II was the most important group including 513 anomalies. We propose to include in this group the Madelung deformity, the Kirner deformity and congenital trigger fingers and trigger thumbs. Triphalangeal thumbs are a problem, we suggest to list this anomaly in group III and to consider it as a duplication in length. It is not always possible to evaluate the (transverse) absence of the fingers or hand. Longitudinal deficiencies (group IIB), symbrachydactyly group (V) and amniotic bands (group VI) occasionally develop a phenotype similar to the genuine transverse deficiency (group IA).

PRDM9 variation strongly influences recombination hot-spot activity and meiotic instability in humans.

PubMed

Berg, Ingrid L; Neumann, Rita; Lam, Kwan-Wood G; Sarbajna, Shriparna; Odenthal-Hesse, Linda; May, Celia A; Jeffreys, Alec J

2010-10-01

PRDM9 has recently been identified as a likely trans regulator of meiotic recombination hot spots in humans and mice. PRDM9 contains a zinc finger array that, in humans, can recognize a short sequence motif associated with hot spots, with binding to this motif possibly triggering hot-spot activity via chromatin remodeling. We now report that human genetic variation at the PRDM9 locus has a strong effect on sperm hot-spot activity, even at hot spots lacking the sequence motif. Subtle changes within the zinc finger array can create hot-spot nonactivating or enhancing variants and can even trigger the appearance of a new hot spot, suggesting that PRDM9 is a major global regulator of hot spots in humans. Variation at the PRDM9 locus also influences aspects of genome instability-specifically, a megabase-scale rearrangement underlying two genomic disorders as well as minisatellite instability-implicating PRDM9 as a risk factor for some pathological genome rearrangements.

PRDM9 variation strongly influences recombination hot-spot activity and meiotic instability in humans

PubMed Central

Berg, Ingrid L.; Neumann, Rita; Lam, Kwan-Wood G.; Sarbajna, Shriparna; Odenthal-Hesse, Linda; May, Celia A.; Jeffreys, Alec J.

2011-01-01

PRDM9 has recently been identified as a likely trans-regulator of meiotic recombination hot spots in humans and mice1-3. The protein contains a zinc finger array that in humans can recognise a short sequence motif associated with hot spots4, with binding to this motif possibly triggering hot-spot activity via chromatin remodelling5. We now show that variation in the zinc finger array in humans has a profound effect on sperm hot-spot activity, even at hot spots lacking the sequence motif. Very subtle changes within the array can create hot-spot non-activating and enhancing alleles, and even trigger the appearance of a new hot spot. PRDM9 thus appears to be the preeminent global regulator of hot spots in humans. Variation at this locus also influences aspects of genome instability, specifically a megabase-scale rearrangement underlying two genomic disorders6 as well as minisatellite instability7, implicating PRDM9 as a risk factor for some pathological genome rearrangements. PMID:20818382

NbCZF1, a Novel C2H2-Type Zinc Finger Protein, as a New Regulator of SsCut-Induced Plant Immunity in Nicotiana benthamiana.

PubMed

Zhang, Huajian; Zhao, Tongyao; Zhuang, Peitong; Song, Zhiqiang; Du, Hui; Tang, Zhaozhao; Gao, Zhimou

2016-12-01

SsCut, which functions as an elicitor, can induce plant immunity. In this study, we utilized Nicotiana benthamiana and virus-induced gene silencing to decrease the expression of > 2,500 genes individually. Using this forward genetics approach, several genes were identified that, when silenced, compromised SsCut-triggered cell death based on a cell death assay. A C 2 H 2 -type zinc finger gene was isolated from N. benthamiana Sequence analysis indicated that the gene encodes a 27 kDa protein with 253 amino acids containing two typical C 2 H 2 -type zinc finger domains; this gene was named NbCZF1 We found that SsCut-induced cell death could be inhibited by virus-induced gene silencing of NbCZF1 in N. benthamiana In addition, SsCut induces stomatal closure, accompanied by reactive oxygen species (ROS) production by NADPH oxidases and nitric oxide (NO) production. NbCZF1-silenced plants showed impaired SsCut-induced stomatal closure, decreased SsCut-induced production of ROS and NO in guard cells and reduced SsCut-induced resistance against Phytophthora nicotianae Taken together, these results demonstrate that the NbCZF1-ROS-NO pathway mediates multiple SsCut-triggered responses, including stomatal closure, hypersensitive responses and defense-related gene expression. This is the first report describing the function of a C 2 H 2 -type zinc finger protein in N. benthamiana. © The Author 2016. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists. All rights reserved. For permissions, please email: journals.permissions@oup.com.

L-Menthol attenuates the magnitude of cold-induced vasodilation on the extremities of young females.

PubMed

Kim, Siyeon; Lee, Joo-Young

2018-05-09

Menthol chemically triggers cold-sensitive receptors in the skin without conductive skin cooling. We investigated the effects of menthol-induced activation of cutaneous cold receptors on the cold-induced vasodilation (CIVD) of the finger. We hypothesized that the menthol application would attenuate typical CIVD responses. 1.5% L-menthol was fully applied over the left hand and forearm, and then, the middle finger of the left hand was immersed into 4 °C water for 30 min. A trial consisted of 10-min rest followed by 30-min immersion and 20-min recovery in 28 °C air temperature with 20% relative humidity. Another trial without the menthol application was carried out as a control. Seventeen females (24.2 ± 2.6 years in age, 160.5 ± 5.1 cm in height, and 51.2 ± 5.7 kg in body weight) participated in the two trials. The results showed that the maximum and average temperatures of the finger during the water immersion were lower in the menthol application when compared to control (P < 0.05), whereas no significant differences appeared in the onset time of CIVD, the frequency of CIVD, and minimum finger temperature. These results imply that stronger stimulation of cold receptors without additional conductive skin cooling did not attenuate the triggering of CIVD responses but intensified vasoconstriction after the first occurrence of CIVD. It is suggested that substantial and conductive heat loss through the skin along with activation of cold receptors may be required to retain rewarming at a certain level.

State-based decoding of hand and finger kinematics using neuronal ensemble and LFP activity during dexterous reach-to-grasp movements

PubMed Central

Mollazadeh, Mohsen; Davidson, Adam G.; Schieber, Marc H.; Thakor, Nitish V.

2013-01-01

The performance of brain-machine interfaces (BMIs) that continuously control upper limb neuroprostheses may benefit from distinguishing periods of posture and movement so as to prevent inappropriate movement of the prosthesis. Few studies, however, have investigated how decoding behavioral states and detecting the transitions between posture and movement could be used autonomously to trigger a kinematic decoder. We recorded simultaneous neuronal ensemble and local field potential (LFP) activity from microelectrode arrays in primary motor cortex (M1) and dorsal (PMd) and ventral (PMv) premotor areas of two male rhesus monkeys performing a center-out reach-and-grasp task, while upper limb kinematics were tracked with a motion capture system with markers on the dorsal aspect of the forearm, hand, and fingers. A state decoder was trained to distinguish four behavioral states (baseline, reaction, movement, hold), while a kinematic decoder was trained to continuously decode hand end point position and 18 joint angles of the wrist and fingers. LFP amplitude most accurately predicted transition into the reaction (62%) and movement (73%) states, while spikes most accurately decoded arm, hand, and finger kinematics during movement. Using an LFP-based state decoder to trigger a spike-based kinematic decoder [r = 0.72, root mean squared error (RMSE) = 0.15] significantly improved decoding of reach-to-grasp movements from baseline to final hold, compared with either a spike-based state decoder combined with a spike-based kinematic decoder (r = 0.70, RMSE = 0.17) or a spike-based kinematic decoder alone (r = 0.67, RMSE = 0.17). Combining LFP-based state decoding with spike-based kinematic decoding may be a valuable step toward the realization of BMI control of a multifingered neuroprosthesis performing dexterous manipulation. PMID:23536714

Finger-tapping motion analysis in cervical myelopathy by magnetic-sensor tapping device.

PubMed

Miwa, Toshitada; Hosono, Noboru; Mukai, Yoshihiro; Makino, Takahiro; Kandori, Akihiko; Fuji, Takeshi

2013-08-01

Case-control study. The purpose of this study is to determine finger motion of patients with cervical myelopathy during finger-tapping cycles. A major symptom of patients with compressive cervical myelopathy is finger clumsiness. Therefore, understanding finger motion is prerequisite in assessing the severity of myelopathy. The popular grip-and-release test evaluates only the number of motion cycles, which is insufficient to fully describe complex finger motion. Forty-three patients with cervical myelopathy and 41 healthy controls tapped their index fingers against their thumbs as rapidly as possible for 30 seconds and the motion was recorded by a magnetic-sensor coil attached to the nail surface. Output signals were stored in a computer, which automatically calculated tapping frequency, distance moved, ratio of opening/closing velocity and the SD of the tapping interval. The SD of the tapping interval was significantly greater and all other measures were significantly smaller in patients with cervical myelopathy, than in healthy controls. All indices significantly improved after surgical decompression of the cervical spine. Distance moved (Pearson correlation coefficient: r=0.590, P<0.001) and the SD of the tapping interval (r=-0.451; P=0.002) were significantly correlated with the Japanese Orthopedic Association score (neurological scale). The quantitative evaluation of finger paralysis was performed by this tapping device. Speed and regularity in repetitive motion of fingers were correlated with the severity of cervical myelopathy.

Project Aims to Bridge Neuroscience and Schools

ERIC Educational Resources Information Center

Samuels, Christina A.

2008-01-01

Using imaging technology that can probe the deepest workings of the brain, researchers have found that children with attention deficit hyperactivity disorder are using less of a certain part of their brains to hold back their itchy trigger fingers, compared with typically developing children performing the same task. This information was shared…

Red in Tooth, Claw, and Trigger Finger

ERIC Educational Resources Information Center

Barash, David P.

2005-01-01

Quoting literary and scientific works, the duality of good and evil in human nature is analyzed. Article discusses mankind's detrimental behavior towards the environment and extreme acts of violence among human beings while examining similar violent behavior in animals. It is concluded that humanity's deeds stem from shared cultural traits,…

Pregabalin

MedlinePlus

Pregabalin capsules, oral solution (liquid), and extended-release (long-acting) tablets are used to relieve neuropathic pain (pain from damaged nerves) that can occur in your arms, hands, fingers, ...

Grasping and fingering (active or haptic touch) in healthy newborns.

PubMed

Adamson-Macedo, Elvidina Nabuco; Barnes, Christopher R

2004-12-01

The traditional view that the activity of the baby's hands are triggered by a stimulus in an automatic, compulsory, stereotyped way and persisting view that fingering does not occur prior to 4 months of age, have led perception researchers to the assumption that the processing, encoding, and retainment of sensory information could not take place through the manual mode. This study aims to investigate whether fingering and different types of grasping occur before 3 months of age and can be modulated by surface texture of three objects. Using naturalistic observations, this small sample developmental study applied the AB experimental design to achieve aims above. Babies were video taped every week for 12 weeks. Three special manual stimuli were developed for this study. Focal sampling method with either zero-sampling or instantaneous sampling recording rules were used to analyse data with the Observer Video Pro. Each session comprising baseline and 3 experimental conditions lasted for four minutes. Fingering or 'proto fingering' as it is suggested in this article emerges as early as the first week of postnatal life; texture of a handled object modulates both 'proto-palm' and hand-grasp behaviour of healthy newborns. Results suggest that texture also modulates 'proto-fingering' and challenge persisting current assumption that fingering does not occur before four months of age, and further validates the phrase 'neo-haptic' touch to describe hands-on exploration of the newborn. The author suggests that some 'mental representation' of the stimulus is present during 'neo-haptic' recognition of the objects which is in accordance to a constructivist approach to (touch) perception.

Catastrophic Thinking Is Associated With Finger Stiffness After Distal Radius Fracture Surgery.

PubMed

Teunis, Teun; Bot, Arjan G J; Thornton, Emily R; Ring, David

2015-10-01

To identify demographic, injury-related, or psychologic factors associated with finger stiffness at suture removal and 6 weeks after distal radius fracture surgery. We hypothesize that there are no factors associated with distance to palmar crease at suture removal. Prospective cohort study. Level I Academic Urban Trauma Center. One hundred sixteen adult patients underwent open reduction and internal fixation of their distal radius fractures; 96 of whom were also available 6 weeks after surgery. None. At suture removal, we recorded patients' demographics, AO fracture type, carpal tunnel release at the time of surgery, pain catastrophizing scale, Whiteley Index, Patient Health Questionnaire-9, and disabilities of the arm, shoulder, and hand questionnaire, 11-point ordinal measure of pain intensity, distance to palmar crease, and active flexion of the thumb through the small finger. At 6 weeks after surgery, we measured motion, disabilities of the arm, shoulder, and hand, and pain intensity. Prereduction and postsurgery radiographic fracture characteristics were assessed. Female sex, being married, specific surgeons, carpal tunnel release, AO type C fractures, and greater catastrophic thinking were associated with increased distance to palmar crease at suture removal. At 6 weeks, greater catastrophic thinking was the only factor associated with increased distance to palmar crease. Catastrophic thinking was a consistent and major determinant of finger stiffness at suture removal and 6 weeks after injury. Future research should assess if treatments that ameliorate catastrophic thinking can facilitate recovery of finger motion after operative treatment of a distal radius fracture. Prognostic Level I. See Instructions for Authors for a complete description of levels of evidence.

Light-Triggered Release of DNA from Plasmon-Resonant Nanoparticles

NASA Astrophysics Data System (ADS)

Huschka, Ryan

Plasmon-resonant nanoparticle complexes show promising potential for lighttriggered, controllable delivery of deoxyribonucleic acids (DNA) for research and therapeutic purposes. For example, the approach of RNA interference (RNAi) . using antisense DNA or RNA oligonucleotides to silence activity of a specific pathogenic gene transcript and reduce expression of the encoded protein . is very useful in dissecting genetic function and holds promise as a molecular therapeutic. Herein, we investigate the mechanism and probe the in vitro therapeutic potential of DNA light-triggered release from plasmonic nanoparticles. First, we investigate the mechanism of light-triggered release by dehybridizing double-stranded (dsDNA) via laser illumination from two types of nanoparticle substrates: gold (Au) nanoshells and Au nanorods. Both light-triggered and thermally induced releases are distinctly observable from nanoshell-based complexes. Surprisingly, no analogous measurable light-triggered release was observable from nanorod-based complexes below the DNA melting temperature. These results suggest that a nonthermal mechanism may play a role in light-triggered DNA release. Second, we demonstrate the in vitro light-triggered release of molecules noncovalently attached within dsDNA bound to the Au nanoshell surface. DAPI (4',6- diamidino-2-phenylindole), a bright blue fluorescent molecule that binds reversibly to double-stranded DNA, was chosen to visualize this intracellular light-induced release process. Illumination through the cell membrane of the nanoshell-dsDNA-DAPI complexes dehybridizes the DNA and releases the DAPI molecules within living cells. The DAPI molecules diffuse to the nucleus and associate with the cell's endogenous DNA. This work could have future applications towards drug delivery of molecules that associate with dsDNA. Finally, we demonstrate an engineered Au nanoshell (AuNS)-based therapeutic oligonucleotide delivery vehicle, designed to release its cargo on demand upon illumination with a near-infrared (NIR) laser. A poly(L)lysine peptide (PLL) epilayer coated onto the AuNS surface (AuNS-PLL) is used to capture intact, single-stranded antisense DNA oligonucleotide, or alternatively, double-stranded short-interfering RNA (siRNA) molecules. A green fluorescent protein (GFP)-expressing human lung cancer H1299 cell line was used to determine cellular uptake and GFP gene silencing mediated by AuNS-PLL delivery vector. The light-triggered release of oligonucleotides could have broad applications in the study of cellular processes and in the development of intracellular targeted therapies.

Reduced surround inhibition in musicians.

PubMed

Shin, Hae-Won; Kang, Suk Y; Hallett, Mark; Sohn, Young H

2012-06-01

To investigate whether surround inhibition (SI) in the motor system is altered in professional musicians, we performed a transcranial magnetic stimulation (TMS) study in 10 professional musicians and 15 age-matched healthy non-musicians. TMS was set to be triggered by self-initiated flexion of the index finger at different intervals ranging from 3 to 1,000 ms. Average motor evoked potential (MEP) amplitudes obtained from self-triggered TMS were normalized to average MEPs of the control TMS at rest and expressed as a percentage. Normalized MEP amplitudes of the abductor digiti minimi (ADM) muscles were compared between the musicians and non-musicians with the primary analysis being the intervals between 3 and 80 ms (during the movement). A mixed-design ANOVA revealed a significant difference in normalized ADM MEPs during the index finger flexion between groups, with less SI in the musicians. This study demonstrated that the functional operation of SI is less strong in musicians than non-musicians, perhaps due to practice of movement synergies involving both muscles. Reduced SI, however, could lead susceptible musicians to be prone to develop task-specific dystonia.

Three-Dimensional Numerical Modeling of Crustal Growth at Active Continental Margins

NASA Astrophysics Data System (ADS)

Zhu, G.; Gerya, T.; Tackley, P. J.

2011-12-01

Active margins are important sites of new continental crust formation by magmatic processes related to the subduction of oceanic plates. We investigate these phenomena using a three-dimensional coupled petrological-geochemical-thermomechanical numerical model, which combines a finite-difference flow solver with a non-diffusive marker-in-cell technique for advection (I3ELVIS code, Gerya and Yuen, PEPI,2007). The model includes mantle flow associated with the subducting plate, water release from the slab, fluid propagation that triggers partial melting at the slab surface, melt extraction and the resulting volcanic crustal growth at the surface. The model also accounts for variations in physical properties (mainly density and viscosity) of both fluids and rocks as a function of local conditions in temperature, pressure, deformation, nature of the rocks, and chemical exchanges. Our results show different patterns of crustal growth and surface topography, which are comparable to nature, during subduction at active continental margins. Often, two trench-parallel lines of magmatic activity, which reflect two maxima of melt production atop the slab, are formed on the surface. The melt extraction rate controls the patterns of new crust at different ages. Moving free water reflects the path of fluids, and the velocity of free water shows the trend of two parallel lines of magmatic activity. The formation of new crust in particular time intervals is distributed in finger-like shapes, corresponding to finger-like and ridge-like cold plumes developed atop the subducting slabs (Zhu et al., G-cubed,2009; PEPI,2011). Most of the new crust is basaltic, formed from peridotitic mantle. Granitic crust extracted from melted sediment and upper crust forms in a line closer to the trench, and its distribution reflects the finger-like cold plumes. Dacitic crust extracted from the melted lower crust forms in a line farther away from the trench, and its distribution is anticorrelated with the finger-like plumes. We demonstrate the potential applicability of our model to clustering of arc magmatism in several subduction zones, such as Baja California (Ramos-Velázquez et al., Revista Mexicana de Ciencias Geológicas,2008), North Island of New Zealand (Booden et al., J. Volcanol. Geotherm. Res., 2010), Northeast Japan (Kimura and Yoshida,Journal of Petrology, 2006); Ecuador (Schütte et al., Tectonophysics,2010) and Lesser Antilles (Labanieh et al., EPSL,2010).

The potential complications of open carpal tunnel release surgery to the ulnar neurovascular bundle and its branches: A cadaveric study.

PubMed

Boughton, O; Adds, P J; Jayasinghe, J A P

2010-07-01

This study investigated the ulnar artery and the ulnar nerve and its branches in the palm to assess how frequently they may be at risk of damage during open carpal tunnel release surgery. Twenty-one formalin-embalmed cadaveric hands were dissected, and the proximity of the ulnar neurovascular bundle to two different lines of incision, the 3rd and 4th interdigital web space axis and the ring finger axis, was assessed and compared. It was found that an incision in the latter (ring finger) axis put the ulnar artery at risk in 12 of 21 specimens, whereas an incision in the former axis (3rd/4th interdigital web space) put the ulnar artery at risk in only two specimens. In 15 hands at least one structure (the ulnar artery or a branch of the ulnar nerve) was at risk in the ring finger axis compared to only seven hands in the axis of the 3rd/4th interdigital web space. We conclude that the ulnar artery and branches of the ulnar nerve are at increased risk of damage with an incision in the axis of the ring finger. The importance of using a blunt dissection technique under direct vision during surgery to identify and preserve these structures and median nerve branches is emphasized. (c) 2010 Wiley-Liss, Inc.

The Effective Connectivity Between the Two Primary Motor Areas in the Brain during Bilateral Tapping of Hand Fingers

NASA Astrophysics Data System (ADS)

Yusoff, A. N.; Hamid, K. A.

Dynamic causal modeling (DCM) was implemented on datasets obtained from an externally-triggered finger tapping functional MRI experiment performed by 5 male and female subjects. The objective was to model the effective connectivity between two significantly activated primary motor regions (M1). The left and right hemisphere M1s are found to be effectively and bidirectionally connected to each other. Both connections are modulated by the stimulus-free contextual input. These connectivities are however not gated (influenced) by any of the two M1s, ruling out the possibility of the non-linear behavior of connections between both M1s. A dynamic causal model was finally suggested.

Sensing and Force-Feedback Exoskeleton (SAFE) Robotic Glove.

PubMed

Ben-Tzvi, Pinhas; Ma, Zhou

2015-11-01

This paper presents the design, implementation and experimental validation of a novel robotic haptic exoskeleton device to measure the user's hand motion and assist hand motion while remaining portable and lightweight. The device consists of a five-finger mechanism actuated with miniature DC motors through antagonistically routed cables at each finger, which act as both active and passive force actuators. The SAFE Glove is a wireless and self-contained mechatronic system that mounts over the dorsum of a bare hand and provides haptic force feedback to each finger. The glove is adaptable to a wide variety of finger sizes without constraining the range of motion. This makes it possible to accurately and comfortably track the complex motion of the finger and thumb joints associated with common movements of hand functions, including grip and release patterns. The glove can be wirelessly linked to a computer for displaying and recording the hand status through 3D Graphical User Interface (GUI) in real-time. The experimental results demonstrate that the SAFE Glove is capable of reliably modeling hand kinematics, measuring finger motion and assisting hand grasping motion. Simulation and experimental results show the potential of the proposed system in rehabilitation therapy and virtual reality applications.

Remotely Triggered Cisplatin Release from Carbon Nanocapsules by Radiofrequency Fields

PubMed Central

Raoof, Mustafa; Cisneros, Brandon T.; Guven, Adem; Corr, Stuart J.; Wilson, Lon J.; Curley, Steven A.

2013-01-01

The efficacy of nanoparticle-mediated drug delivery is limited by its peri-vascular sequestration, thus necessitating a strategy to trigger drug release from such intra-tumoral nanocarrier-drug depots. In our efforts to explore remotely-activated nanocarriers, we have developed carbon nanocapsules comprised of an ultrashort carbon nanotube shell (US-tubes) loaded with cisplatin (CDDP@US-tubes) and covered with a Pluronic surfactant wrapping to minimize passive release. We demonstrate here that non-invasive radiofrequency (RF) field activation of the CDDP@US-tubes produces heat that causes Pluronic disruption which triggers cisplatin release in an RF-dependent manner. Furthermore, release-dependent cytotoxicity is demonstrated in human hepatocellular carcinoma cell lines. PMID:23228421

Fastener starter tool

NASA Technical Reports Server (NTRS)

Chandler, Faith T. (Inventor); Arnett, Michael C. (Inventor); Garton, Harry L. (Inventor); Valentino, William D. (Inventor)

2003-01-01

A fastener starter tool includes a number of spring retention fingers for retaining a small part, or combination of parts. The tool has an inner housing, which holds the spring retention fingers, a hand grip, and an outer housing configured to slide over the inner housing and the spring retention fingers toward and away from the hand grip, exposing and opening, or respectively, covering and closing, the spring retention fingers. By sliding the outer housing toward (away from) the hand grip, a part can be released from (retained by) the tool. The tool may include replaceable inserts, for retaining parts, such as screws, and configured to limit the torque applied to the part, to prevent cross threading. The inner housing has means to transfer torque from the hand grip to the insert. The tool may include replaceable bits, the inner housing having means for transferring torque to the replaceable bit.

Comparative analysis of solid-state bioprocessing and enzymatic treatment of finger millet for mobilization of bound phenolics.

PubMed

Yadav, Geetanjali; Singh, Anshu; Bhattacharya, Patrali; Yuvraj, Jude; Banerjee, Rintu

2013-11-01

The present work investigates the probable bioprocessing technique to mobilize the bound phenolics naturally found in finger millet cell wall for enriching it with dietary antioxidants. Comparative study was performed between the exogenous enzymatic treatment and solid-state fermentation of grain (SSF) with a food grade organism Rhizopus oryzae. SSF results indicated that at the 6th day of incubation, total phenolic content (18.64 mg gallic acid equivalent/gds) and antioxidant property (DPPH radical scavenging activity of 39.03 %, metal chelating ability of 54 % and better reducing power) of finger millet were drastically enhanced when fermented with GRAS filamentous fungi. During the enzymatic bioprocessing, most of the phenolics released during the hydrolysis, leached out into the liquid portion rather than retaining them within the millet grain, resulting in overall loss of dietary antioxidant. The present study establishes the most effective strategy to enrich the finger millet with phenolic antioxidants.

Smart material joint band

NASA Astrophysics Data System (ADS)

Tucchio, Michael A.; Stoodt, Robert A.; Livsey, Robert A.

1994-11-01

The present invention relates to an improved connector for joining two tubular members together. The connector is formed by a plurality of longitudinally extending fingers extending from an end of one of tubular members and at least one locking groove in the other of the tubular members for receiving the fingers. The connector further includes a circumferentially extending wire member which is received in a notch in a head portion of each of the plurality of fingers. The wire member is preferably formed from a shape memory alloy and has an original circumference less than the circumference of a circle formed by the notches in a head portions of the fingers. The connector includes apertures through which electric wires may be connected to the shape memory alloy ring member so as to cause the shape memory alloy ring member to return to its original shape and allow release of the joint connection.

Smart material joint band

NASA Astrophysics Data System (ADS)

Tucchio, Michael A.; Stoodt, Robert A.; Livsey, Robert A.

1993-12-01

The present invention relates to an improved connector for joining two tubular members together. The connector is formed by a plurality of longitudinally extending fingers extending from an end of one of the tubular members and at least one locking groove in the other of the tubular members for receiving the fingers. The connector further includes a circumferentially extending wire member which is received in a notch in a head portion of each of the plurality of fingers. The wire member is preferably formed from a shape memory alloy and has an original circumference less than the circumference of a circle formed by the notches in the head portions of the fingers. The connector includes apertures through which electric wires may be connected to the shape memory alloy ring member so as to cause the shape memory alloy ring member to return to its original shape and allow release of the joint connection.

Debris of carbon-fibers originated from a CFRP (pEEK) wrist-plate triggered a destruent synovitis in human.

PubMed

Merolli, Antonio; Rocchi, Lorenzo; De Spirito, Marco; Federico, Francesco; Morini, Alessandro; Mingarelli, Luigi; Fanfani, Francesco

2016-03-01

Application of carbon-fiber-reinforced-polymer (CFRP) artifacts in humans has been promoted in Orthopedic and Trauma Surgery. Literature documents the biocompatibility of materials used, namely carbon fibers (CF) and poly-ether thermoplastics, like poly-ether-ether-ketone (PEEK). A properly designed and accurately implanted composite artifact should not expose its fibers during or after surgery: however this may happen. A white Caucasian woman came to our attention 11 months after surgery for a wrist fracture. She had a severe impairment, being unable to flex the thumb; index finger and distal phalanx of third finger. We retrieved a correctly positioned plate and documented an aggressive erosive flexor tendons synovitis with eroded stumps of flexor tendons. The plate and soft tissues were analyzed by Visible Light and Scanning Electron Microscopy. Histopathology showed granulomatous fibrogenic process with CF engulfed inside multinucleated giant cells. Fibers were unmasked and disrupted inside the holes where screws were tightened and corrugation of the polymer coating led to further unmasking. The mechanism of foreign-body reaction to CF has not been studied in depth yet, particularly at the ultrastructural level and in Humans. This case documents a damage occurred in a clinical application and which was theoretically possible. Our opinion is that a proper way to promote the use of CRFP in the Clinic in the short term is to direct Research towards finding a better way to prevent CF debris to be exposed and released. In the longer term, the biological response to CF deserves a deeper understanding.

Low-visibility light-intensity laser-triggered release of entrapped calcein from 1,2-bis (tricosa-10,12-diynoyl)-sn-glycero-3-phosphocholine liposomes is mediated through a type I photoactivation pathway

PubMed Central

Yavlovich, Amichai; Viard, Mathias; Gupta, Kshitij; Sine, Jessica; Vu, Mylinh; Blumenthal, Robert; Tata, Darrell B; Puri, Anu

2013-01-01

We recently reported on the physical characteristics of photo-triggerable liposomes containing dipalmitoylphosphatidylcholine (DPPC), and 1,2-bis (tricosa-10,12-diynoyl)-sn-glycero-3-phosphocholine (DC8,9PC) carrying a photo agent as their payload. When exposed to a low-intensity 514 nm wavelength (continuous-wave) laser light, these liposomes were observed to release entrapped calcein green (Cal-G; Ex/Em 490/517 nm) but not calcein blue (Cal-B; Ex/Em 360/460 nm). In this study, we have investigated the mechanism for the 514 nm laser-triggered release of the Cal-G payload using several scavengers that are known specifically to inhibit either type I or type II photoreaction pathways. Liposomes containing DPPC:DC8,9PC: distearoylphosphatidylethanolamine (DSPE)-polyethylene glycol (PEG)-2000 (86:10:04 mole ratio) were loaded either with fluorescent (calcein) or nonfluorescent (3H-inulin) aqueous markers. In addition, a non-photo-triggerable formulation (1-palmitoyl-2-oleoyl phosphatidylcholine [POPC]:DC8,9PC:DSPE-PEG2000) was also studied with the same payloads. The 514 nm wavelength laser exposure on photo-triggerable liposomes resulted in the release of Cal-G but not that of Cal-B or 3H-inulin, suggesting an involvement of a photoactivated state of Cal-G due to the 514 nm laser exposure. Upon 514 nm laser exposures, substantial hydrogen peroxide (H2O2, ≈100 μM) levels were detected from only the Cal-G loaded photo-triggerable liposomes but not from Cal-B-loaded liposomes (≤10 μM H2O2). The Cal-G release from photo-triggerable liposomes was found to be significantly inhibited by ascorbic acid (AA), resulting in a 70%–80% reduction in Cal-G release. The extent of AA-mediated inhibition of Cal-G release from the liposomes also correlated with the consumption of AA. No AA consumption was detected in the 514 nm laserexposed Cal B-loaded liposomes, thus confirming a role of photoactivation of Cal-G in liposome destabilization. Inclusion of 100 mM K3Fe(CN)6 (a blocker of electron transfer) in the liposomes substantially inhibited Cal-G release, whereas inclusion of 10 mM sodium azide (a blocker of singlet oxygen of type II photoreaction) in the liposomes failed to block 514 nm laser-triggered Cal-G release. Taken together, we conclude that low-intensity 514 nm laser-triggered release of Cal-G from photo-triggerable liposomes involves the type I photoreaction pathway. PMID:23901274

Viscous and gravitational fingering in multiphase compositional and compressible flow

NASA Astrophysics Data System (ADS)

Moortgat, Joachim

2016-03-01

Viscous and gravitational fingering refer to flow instabilities in porous media that are triggered by adverse mobility or density ratios, respectively. These instabilities have been studied extensively in the past for (1) single-phase flow (e.g., contaminant transport in groundwater, first-contact-miscible displacement of oil by gas in hydrocarbon production), and (2) multi-phase immiscible and incompressible flow (e.g., water-alternating-gas (WAG) injection in oil reservoirs). Fingering in multiphase compositional and compressible flow has received much less attention, perhaps due to its high computational complexity. However, many important subsurface processes involve multiple phases that exchange species. Examples are carbon sequestration in saline aquifers and enhanced oil recovery (EOR) by gas or WAG injection below the minimum miscibility pressure. In multiphase flow, relative permeabilities affect the mobility contrast for a given viscosity ratio. Phase behavior can also change local fluid properties, which can either enhance or mitigate viscous and gravitational instabilities. This work presents a detailed study of fingering behavior in compositional multiphase flow in two and three dimensions and considers the effects of (1) Fickian diffusion, (2) mechanical dispersion, (3) flow rates, (4) domain size and geometry, (5) formation heterogeneities, (6) gravity, and (7) relative permeabilities. Results show that fingering in compositional multiphase flow is profoundly different from miscible conditions and upscaling techniques used for the latter case are unlikely to be generalizable to the former.

Light induced cytosolic drug delivery from liposomes with gold nanoparticles.

PubMed

Lajunen, Tatu; Viitala, Lauri; Kontturi, Leena-Stiina; Laaksonen, Timo; Liang, Huamin; Vuorimaa-Laukkanen, Elina; Viitala, Tapani; Le Guével, Xavier; Yliperttula, Marjo; Murtomäki, Lasse; Urtti, Arto

2015-04-10

Externally triggered drug release at defined targets allows site- and time-controlled drug treatment regimens. We have developed liposomal drug carriers with encapsulated gold nanoparticles for triggered drug release. Light energy is converted to heat in the gold nanoparticles and released to the lipid bilayers. Localized temperature increase renders liposomal bilayers to be leaky and triggers drug release. The aim of this study was to develop a drug releasing system capable of releasing its cargo to cell cytosol upon triggering with visible and near infrared light signals. The liposomes were formulated using either heat-sensitive or heat- and pH-sensitive lipid compositions with star or rod shaped gold nanoparticles. Encapsulated fluorescent probe, calcein, was released from the liposomes after exposure to the light. In addition, the pH-sensitive formulations showed a faster drug release in acidic conditions than in neutral conditions. The liposomes were internalized into human retinal pigment epithelial cells (ARPE-19) and human umbilical vein endothelial cells (HUVECs) and did not show any cellular toxicity. The light induced cytosolic delivery of calcein from the gold nanoparticle containing liposomes was shown, whereas no cytosolic release was seen without light induction or without gold nanoparticles in the liposomes. The light activated liposome formulations showed a controlled content release to the cellular cytosol at a specific location and time. Triggering with visual and near infrared light allows good tissue penetration and safety, and the pH-sensitive liposomes may enable selective drug release in the intracellular acidic compartments (endosomes, lysosomes). Thus, light activated liposomes with gold nanoparticles are an attractive option for time- and site-specific drug delivery into the target cells. Copyright © 2015 Elsevier B.V. All rights reserved.

Indocyanine Green-Loaded Liposomes for Light-Triggered Drug Release.

PubMed

Lajunen, Tatu; Kontturi, Leena-Stiina; Viitala, Lauri; Manna, Moutusi; Cramariuc, Oana; Róg, Tomasz; Bunker, Alex; Laaksonen, Timo; Viitala, Tapani; Murtomäki, Lasse; Urtti, Arto

2016-06-06

Light-triggered drug delivery systems enable site-specific and time-controlled drug release. In previous work, we have achieved this with liposomes containing gold nanoparticles in the aqueous core. Gold nanoparticles absorb near-infrared light and release the energy as heat that increases the permeability of the liposomal bilayer, thus releasing the contents of the liposome. In this work, we replaced the gold nanoparticles with the clinically approved imaging agent indocyanine green (ICG). The ICG liposomes were stable at storage conditions (4-22 °C) and at body temperature, and fast near-infrared (IR) light-triggered drug release was achieved with optimized phospholipid composition and a 1:50 ICG-to-lipid molar ratio. Encapsulated small molecular calcein and FITC-dextran (up to 20 kDa) were completely released from the liposomes after light exposure for 15 s. Location of ICG in the PEG layer of the liposomes was simulated with molecular dynamics. ICG has important benefits as a light-triggering agent in liposomes: fast content release, improved stability, improved possibility of liposomal size control, regulatory approval to use in humans, and the possibility of imaging the in vivo location of the liposomes based on the fluorescence of ICG. Near-infrared light used as a triggering mechanism has good tissue penetration and safety. Thus, ICG liposomes are an attractive option for light-controlled and efficient delivery of small and large drug molecules.

Hydrodynamic fingering instability induced by a precipitation reaction

NASA Astrophysics Data System (ADS)

De Wit, Anne; Nagatsu, Yuichiro

2014-05-01

We experimentally demonstrate that a precipitation reaction at the miscible interface between two reactive solutions can trigger a hydrodynamic instability due to the build-up of a locally adverse mobility gradient related to a decrease in permeability. The precipitate results from an A+B → C type of reaction when a solution containing one of the reactant is injected into a solution of the other reactant in a porous medium or a Hele-Shaw cell. Finger-like precipitation patterns are observed upon displacement, the properties of which depend on whether A displaces B or vice-versa. A mathematical modeling of the underlying mobility profile in the cell reconstructed on the basis of one-dimensional reaction-diffusion concentration profiles confirms that the instability originates from a local decrease in mobility driven by the precipitation. Nonlinear simulations of the related reaction-diffusion-convection model reproduce the properties of the instability observed experimentally. In particular, the simulations suggest that differences in diffusivity between A and B may contribute to the asymmetric characteristics of the fingering precipitation patterns.

The Use of Opioid Analgesics following Common Upper Extremity Surgical Procedures: A National, Population-Based Study.

PubMed

Waljee, Jennifer F; Zhong, Lin; Hou, Hechuan; Sears, Erika; Brummett, Chad; Chung, Kevin C

2016-02-01

The misuse of opioid analgesics is a major public health concern, and guidelines regarding postoperative opioid use are sparse. The authors examined the use of opioids following outpatient upper extremity procedures to discern the variation by procedure type and patient factors. The authors studied opioid prescriptions among 296,452 adults older than 18 years who underwent carpal tunnel release, trigger finger release, cubital tunnel release, or thumb carpometacarpal arthroplasty from 2009 to 2013 using insurance claims drawn from the Truven Health MarketScan Commercial Claims and Encounters, which encompasses over 100 health plans in the United States. Using multivariable regression, the authors compared the receipt of opioids, number of days supplied, indicators of inappropriate prescriptions, and number of refills by patient factors. In this cohort, 59 percent filled a postoperative prescription for opioid medication, and 8.8 percent of patients had an indicator of inappropriate prescribing. The probability of filling an opioid prescription declined linearly with advancing age. On multivariate analysis, patients who had previously received opioids were more likely to fill a postoperative opioid prescription (66 percent versus 59 percent), receive longer prescriptions (24 versus 5 days), receive refills following surgery (24 percent versus 5 percent), and have at least one indicator of potentially inappropriate prescribing (19 percent versus 6 percent). Current opioid users are more likely to require postoperative opioid analgesics for routine procedures and more likely to receive inappropriate prescriptions. More evidence is needed to identify patients who derive the greatest benefit from opioids to curb opioid prescriptions when alternative analgesics may be equally effective and available. Risk, III.

The Utilization of Opioid Analgesics Following Common Upper Extremity Surgical Procedures: A National, Population-Based Study

PubMed Central

Waljee, Jennifer F.; Zhong, Lin; Hou, Hechuan; Sears, Erika; Brummet, Chad; Chung, Kevin C.

2016-01-01

Background The misuse of opioid analgesics is a major public health concern, and guidelines regarding postoperative opioid use are sparse. We examined the use of opioids following outpatient upper extremity procedures. We hypothesized that opioid use varies widely by procedure and patient factors. Methods We studied opioid prescriptions among 296,452 adults ages ≥ 18 years who underwent carpal tunnel release, trigger finger release, cubital tunnel release, and thumb carpometacarpal (CMC) arthroplasty from 2009 to 2013. We analyzed insurance claims drawn using Truven Health MarketScan Commercial Claims and Encounters, which encompasses over 100 health plans in the United States. Using multivariable regression, we compared the receipt of opioids, number of days supplied, indicators of inappropriate prescriptions, and number of refills by patient factors. Results In this cohort, 59% filled a postoperative prescription for opioid medication, and 8.8% patients had an indicator of inappropriate prescribing. The probability of filling an opioid prescription declined linearly with advancing age. In multivariate analysis, patients who had previously received opioids were more likely to fill a postoperative opioid prescription (66% vs. 59%), receive longer prescriptions (24 vs. 5 days), receive refills following surgery (24% vs. 5%), and have at least one indicator of potentially inappropriate prescribing (19% vs 6%). Conclusions Current opioid users are more likely to require postoperative opioid analgesics for routine procedures, and more likely to receive inappropriate prescriptions. More evidence is needed to identify patients who derive the greatest benefit from opioids in order to curb opioids prescriptions when alternative analgesics may be equally effective and available. PMID:26818326

Quick-connect fasteners for assembling devices in space

NASA Technical Reports Server (NTRS)

Wesselski, Clarence J. (Inventor); Evenson, Erik E. (Inventor); Ruiz, Steve L. (Inventor)

1992-01-01

A quick-connect fastener of a relatively-simple straightforward design is arranged with a tubular body adapted to be engaged against an attachment fitting in coincidental alignment with an opening in that fitting. A tubular collet having flexible finger projecting from its forward end is arranged in the fastener body to be shifted forwardly by an elongated expander member coaxially arranged within the tubular collet for advancing the collet fingers into the opening in the attachment fitting. Biasing means are arranged between the elongated expander member and a rotatable actuator which is threadedly mounted within the tubular collet so as to be rotated for urging the expander member into engagement with the collet fingers. A first coupling member is arranged on the rotatable actuator to be accessible from outside of the fastener so that a second coupling member on the distal end of a flexible shaft can be introduced into the fastener body and coupled to the first coupling member to enable a typical actuating tool coupled to the shaft outside of the fastener body to be operated for advancing the outwardly-enlarged ends of the collet fingers into the opening in the attachment fitting and thereafter rotating the actuator member to expand the fingers to that attachment fitting. Upon expansion of the collet fingers, the biasing means impose a biasing force on the expander to releasably retain the fingers in their latching positions.

Photolysis of Caged Ca2+ But Not Receptor-Mediated Ca2+ Signaling Triggers Astrocytic Glutamate Release

PubMed Central

Smith, Nathan A.; Xu, Qiwu; Goldman, Siri; Peng, Weiguo; Huang, Jason H.; Takano, Takahiro; Nedergaard, Maiken

2013-01-01

Astrocytes in hippocampal slices can dynamically regulate synaptic transmission in a process mediated by increases in intracellular Ca2+. However, it is debated whether astrocytic Ca2+ signals result in release of glutamate. We here compared astrocytic Ca2+ signaling triggered by agonist exposure versus photolysis side by side. Using transgenic mice in which astrocytes selectively express the MrgA1 receptor, we found that receptor-mediated astrocytic Ca2+ signaling consistently triggered neuronal hyperpolarization and decreased the frequency of miniature excitatory postsynaptic currents (EPSCs). In contrast, photolysis of caged Ca2+ (o-nitrophenyl–EGTA) in astrocytes led to neuronal depolarization and increased the frequency of mEPSCs through a metabotropic glutamate receptor-mediated pathway. Analysis of transgenic mice in which astrocytic vesicular release is suppressed (dominant-negative SNARE mice) and pharmacological manipulations suggested that glutamate is primarily released by opening of anion channels rather than exocytosis. Combined, these studies show that photolysis but not by agonists induced astrocytic Ca2+ signaling triggers glutamate release. PMID:24174673

Tension - Type - Headache treated by Positional Release Therapy: a case report.

PubMed

Mohamadi, Marzieh; Ghanbari, Ali; Rahimi Jaberi, Abbas

2012-10-01

Tension Type Headache (T.T.H) is the most prevalent headache. Myofascial abnormalities & trigger points are important in this type of headache which can be managed by Positional Release Therapy (PRT). This is a report of a 47 years old female patient with Tension Type Headache treated by Positional Release Therapy for her trigger points. She had a constant dull headache, which continued all the day for 9 months. A physiotherapist evaluated the patient and found active trigger points in her cervical muscles. Then, she received Positional Release Therapy for her trigger points. After 3 treatment sessions, the patient's headache stopped completely. During the 8 months following the treatment she was without pain, and did not use any medication. Positional Release Therapy was effective in treating Tension Type Headache. This suggests that PRT could be an alternative treatment to medication in patients with T.T.H if the effectiveness of that can be confirmed by further studies. Copyright © 2012 Elsevier Ltd. All rights reserved.

EEG controlled neuromuscular electrical stimulation of the upper limb for stroke patients

NASA Astrophysics Data System (ADS)

Tan, Hock Guan; Shee, Cheng Yap; Kong, Keng He; Guan, Cuntai; Ang, Wei Tech

2011-03-01

This paper describes the Brain Computer Interface (BCI) system and the experiments to allow post-acute (<3 months) stroke patients to use electroencephalogram (EEG) to trigger neuromuscular electrical stimulation (NMES)-assisted extension of the wrist/fingers, which are essential pre-requisites for useful hand function. EEG was recorded while subjects performed motor imagery of their paretic limb, and then analyzed to determine the optimal frequency range within the mu-rhythm, with the greatest attenuation. Aided by visual feedback, subjects then trained to regulate their mu-rhythm EEG to operate the BCI to trigger NMES of the wrist/finger. 6 post-acute stroke patients successfully completed the training, with 4 able to learn to control and use the BCI to initiate NMES. This result is consistent with the reported BCI literacy rate of healthy subjects. Thereafter, without the loss of generality, the controller of the NMES is developed and is based on a model of the upper limb muscle (biceps/triceps) groups to determine the intensity of NMES required to flex or extend the forearm by a specific angle. The muscle model is based on a phenomenological approach, with parameters that are easily measured and conveniently implemented.

Congruency sequence effect without feature integration and contingency learning.

PubMed

Kim, Sanga; Cho, Yang Seok

2014-06-01

The magnitude of congruency effects, such as the flanker-compatibility effects, has been found to vary as a function of the congruency of the previous trial. Some studies have suggested that this congruency sequence effect is attributable to stimulus and/or response priming, and/or contingency learning, whereas other studies have suggested that the control process triggered by conflict modulates the congruency effect. The present study examined whether sequential modulation can occur without stimulus and response repetitions and contingency learning. Participants were asked to perform two color flanker-compatibility tasks alternately in a trial-by-trial manner, with four fingers of one hand in Experiment 1 and with the index and middle fingers of two hands in Experiment 2, to avoid stimulus and response repetitions and contingency learning. A significant congruency sequence effect was obtained between the congruencies of the two tasks in Experiment 1 but not in Experiment 2. These results provide evidence for the idea that the sequential modulation is, at least in part, an outcome of the top-down control process triggered by conflict, which is specific to response mode. Copyright © 2014 Elsevier B.V. All rights reserved.

Near-IR-induced dissociation of thermally-sensitive star polymers.

PubMed

Dai, Yuqiong; Sun, Hao; Pal, Sunirmal; Zhang, Yunlu; Park, Sangwoo; Kabb, Christopher P; Wei, Wei David; Sumerlin, Brent S

2017-03-01

Responsive systems sensitive to near-infrared (NIR) light are promising for triggered release due to efficient deep tissue penetration of NIR irradiation relative to higher energy sources ( e.g. , UV), allowing for spatiotemporal control over triggering events with minimal potential for tissue damage. Herein, we report star polymers containing thermally-labile azo linkages that dissociate during conventional heating or during localized heating via the photothermal effect upon NIR irradiation. Controlled release during conventional heating was investigated for the star polymers loaded with a model dye, with negligible release being observed at 25 °C and >80% release at 90 °C. Star polymers co-loaded with NIR-responsive indocyanine green showed rapid dye release upon NIR irradiation ( λ ≥ 715 nm) due to the photothermally-induced degradation of azo linkages within the cores of the star polymers. This approach provides access to a new class of delivery and release systems that can be triggered by noninvasive external stimulation.

Influence of finger and mouth action observation on random number generation: an instance of embodied cognition for abstract concepts.

PubMed

Grade, Stéphane; Badets, Arnaud; Pesenti, Mauro

2017-05-01

Numerical magnitude and specific grasping action processing have been shown to interfere with each other because some aspects of numerical meaning may be grounded in sensorimotor transformation mechanisms linked to finger grip control. However, how specific these interactions are to grasping actions is still unknown. The present study tested the specificity of the number-grip relationship by investigating how the observation of different closing-opening stimuli that might or not refer to prehension-releasing actions was able to influence a random number generation task. Participants had to randomly produce numbers after they observed action stimuli representing either closure or aperture of the fingers, the hand or the mouth, or a colour change used as a control condition. Random number generation was influenced by the prior presentation of finger grip actions, whereby observing a closing finger grip led participants to produce small rather than large numbers, whereas observing an opening finger grip led them to produce large rather than small numbers. Hand actions had reduced or no influence on number production; mouth action influence was restricted to opening, with an overproduction of large numbers. Finally, colour changes did not influence number generation. These results show that some characteristics of observed finger, hand and mouth grip actions automatically prime number magnitude, with the strongest effect for finger grasping. The findings are discussed in terms of the functional and neural mechanisms shared between hand actions and number processing, but also between hand and mouth actions. The present study provides converging evidence that part of number semantics is grounded in sensory-motor mechanisms.

Rapid Light-Triggered Drug Release in Liposomes Containing Small Amounts of Unsaturated and Porphyrin-Phospholipids.

PubMed

Luo, Dandan; Li, Nasi; Carter, Kevin A; Lin, Cuiyan; Geng, Jumin; Shao, Shuai; Huang, Wei-Chiao; Qin, Yueling; Atilla-Gokcumen, G Ekin; Lovell, Jonathan F

2016-06-01

Prompt membrane permeabilization is a requisite for liposomes designed for local stimuli-induced intravascular release of therapeutic payloads. Incorporation of a small amount (i.e., 5 molar percent) of an unsaturated phospholipid, such as dioleoylphosphatidylcholine (DOPC), accelerates near infrared (NIR) light-triggered doxorubicin release in porphyrin-phospholipid (PoP) liposomes by an order of magnitude. In physiological conditions in vitro, the loaded drug can be released in a minute under NIR irradiation, while liposomes maintain serum stability otherwise. This enables rapid laser-induced drug release using remarkably low amounts of PoP (i.e., 0.3 molar percent). Light-triggered drug release occurs concomitantly with DOPC and cholesterol oxidation, as detected by mass spectrometry. In the presence of an oxygen scavenger or an antioxidant, light-triggered drug release is inhibited, suggesting that the mechanism is related to singlet oxygen mediated oxidization of unsaturated lipids. Despite the irreversible modification of lipid composition, DOPC-containing PoP liposome permeabilization is transient. Human pancreatic xenograft growth in mice is significantly delayed with a single chemophototherapy treatment following intravenous administration of 6 mg kg(-1) doxorubicin, loaded in liposomes containing small amounts of DOPC and PoP. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Apparatus and method of capturing an orbiting spacecraft

NASA Technical Reports Server (NTRS)

Harwell, William D. (Inventor); Gardner, Dale A. (Inventor)

1987-01-01

Apparatus and a method of capturing an orbiting spacecraft by attaching a grapple fixture are discussed. A probe is inserted into an opening, such as a rocket nozzle, in the spacecraft until a stop on the prove mechanism contacts the spacecraft. A lever is actuated releasing a spring loaded rod which moves axially along the probe removing a covering sleeve to expose spring loaded toffle fingers which pivot open engaging the side of the opening. The probe is shortened and tensioned by turning a screw thread, pressing the fingers inside of the opening to compress the spacecraft between the toggle fingers and the stop. A grapple fixture attached to the probe, which is thus secured to the spacecraft, is engaged by appropriate retrieval means such as a remote manipulator arm.

Signal transduction at fertilization: the Ca2+ release pathway in echinoderms and other invertebrate deuterostomes.

PubMed

Townley, Ian K; Roux, Michelle M; Foltz, Kathy R

2006-04-01

Gamete interaction and fusion triggers a number of events that lead to egg activation and development of a new organism. A key event at fertilization is the rise in intracellular calcium. In deuterostomes, this calcium is released from the egg's endoplasmic reticulum and is necessary for proper activation. This article reviews recent data regarding how gamete interaction triggers the initial calcium release, focusing on the echinoderms (invertebrate deuterostomes) as model systems. In eggs of these animals, Src-type kinases and phospholipase C-gamma are required components of the initial calcium trigger pathway in eggs.

Calcium-dependent transferrin receptor recycling in bovine chromaffin cells.

PubMed

Knight, Derek E

2002-04-01

The release of regulated secretory granules is known to be calcium dependent. To examine the Ca2+-dependence of other exocytic fusion events, transferrin recycling in bovine chromaffin cells was examined. Internalised 125I-transferrin was released constitutively from cells with a half-time of about 7 min. Secretagogues that triggered catecholamine secretion doubled the rate of 125I-transferrin release, the time courses of the two triggered secretory responses being similar. The triggered 125I-transferrin release came from recycling endosomes rather than from sorting endosomes or a triggered secretory vesicle pool. Triggered 125I-transferrin release, like catecholamine secretion from the same cells, was calcium dependent but the affinities for calcium were very different. The extracellular calcium concentrations that gave rise to half-maximal evoked secretion were 0.1 mm for 125I-transferrin and 1.0 mm for catecholamine, and the intracellular concentrations were 0.1 microm and 1 microm, respectively. There was significant 125I-transferrin recycling in the virtual absence of intracellular Ca2+, but the rate increased when Ca2+ was raised above 1 nm, and peaked at 1 microm when the rate had doubled. Botulinum toxin type D blocked both transferrin recycling and catecholamine secretion. These results indicate that a major component of the vesicular transport required for the constitutive recycling of transferrin in quiescent cells is calcium dependent and thus under physiological control, and also that some of the molecular machinery involved in transferrin recycling/fusion processes is shared with that for triggered neurosecretion.

A new therapeutic application of brain-machine interface (BMI) training followed by hybrid assistive neuromuscular dynamic stimulation (HANDS) therapy for patients with severe hemiparetic stroke: A proof of concept study.

PubMed

Kawakami, Michiyuki; Fujiwara, Toshiyuki; Ushiba, Junichi; Nishimoto, Atsuko; Abe, Kaoru; Honaga, Kaoru; Nishimura, Atsuko; Mizuno, Katsuhiro; Kodama, Mitsuhiko; Masakado, Yoshihisa; Liu, Meigen

2016-09-21

Hybrid assistive neuromuscular dynamic stimulation (HANDS) therapy improved paretic upper extremity motor function in patients with severe to moderate hemiparesis. We hypothesized that brain machine interface (BMI) training would be able to increase paretic finger muscle activity enough to apply HANDS therapy in patients with severe hemiparesis, whose finger extensor was absent. The aim of this study was to assess the efficacy of BMI training followed by HANDS therapy in patients with severe hemiparesis. Twenty-nine patients with chronic stroke who could not extend their paretic fingers were participated this study. We applied BMI training for 10 days at 40 min per day. The BMI detected the patients' motor imagery of paretic finger extension with event-related desynchronization (ERD) over the affected primary sensorimotor cortex, recorded with electroencephalography. Patients wore a motor-driven orthosis, which extended their paretic fingers and was triggered with ERD. When muscle activity in their paretic fingers was detected with surface electrodes after 10 days of BMI training, we applied HANDS therapy for the following 3 weeks. In HANDS therapy, participants received closed-loop, electromyogram-controlled, neuromuscular electrical stimulation (NMES) combined with a wrist-hand splint for 3 weeks at 8 hours a day. Before BMI training, after BMI training, after HANDS therapy and 3month after HANDS therapy, we assessed Fugl-Meyer Assessment upper extremity motor score (FMA) and the Motor Activity Log14-Amount of Use (MAL-AOU) score. After 10 days of BMI training, finger extensor activity had appeared in 21 patients. Eighteen of 21 patients then participated in 3 weeks of HANDS therapy. We found a statistically significant improvement in the FMA and the MAL-AOU scores after the BMI training, and further improvement was seen after the HANDS therapy. Combining BMI training with HANDS therapy could be an effective therapeutic strategy for severe UE paralysis after stroke.

Fingering convection induced by atomic diffusion in stars: 3D numerical computations and applications to stellar models

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zemskova, Varvara; Garaud, Pascale; Deal, Morgan

2014-11-10

Iron-rich layers are known to form in the stellar subsurface through a combination of gravitational settling and radiative levitation. Their presence, nature, and detailed structure can affect the excitation process of various stellar pulsation modes and must therefore be modeled carefully in order to better interpret Kepler asteroseismic data. In this paper, we study the interplay between atomic diffusion and fingering convection in A-type stars, as well as its role in the establishment and evolution of iron accumulation layers. To do so, we use a combination of three-dimensional idealized numerical simulations of fingering convection (which neglect radiative transfer and complexmore » opacity effects) and one-dimensional realistic stellar models. Using the three-dimensional simulations, we first validate the mixing prescription for fingering convection recently proposed by Brown et al. (within the scope of the aforementioned approximation) and identify what system parameters (total mass of iron, iron diffusivity, thermal diffusivity, etc.) play a role in the overall evolution of the layer. We then implement the Brown et al. prescription in the Toulouse-Geneva Evolution Code to study the evolution of the iron abundance profile beneath the stellar surface. We find, as first discussed by Théado et al., that when the concurrent settling of helium is ignored, this accumulation rapidly causes an inversion in the mean molecular weight profile, which then drives fingering convection. The latter mixes iron with the surrounding material very efficiently, and the resulting iron layer is very weak. However, taking helium settling into account partially stabilizes the iron profile against fingering convection, and a large iron overabundance can accumulate. The opacity also increases significantly as a result, and in some cases it ultimately triggers dynamical convection. The direct effects of radiative acceleration on the dynamics of fingering convection (especially in the nonlinear regime) remain to be added in the future to improve the quantitative predictions of the model.« less

State-of-the-Art Materials for Ultrasound-Triggered Drug Delivery

PubMed Central

Sirsi, Shashank; Borden, Mark

2014-01-01

Ultrasound is a unique and exciting theranostic modality that can be used to track drug carriers, trigger drug release and improve drug deposition with high spatial precision. In this review, we briefly describe the mechanisms of interaction between drug carriers and ultrasound waves, including cavitation, streaming and hyperthermia, and how those interactions can promote drug release and tissue uptake. We then discuss the rational design of some state-of-the-art materials for ultrasound-triggered drug delivery and review recent progress for each drug carrier, focusing on the delivery of chemotherapeutic agents such as doxorubicin. These materials include nanocarrier formulations, such as liposomes and micelles, designed specifically for ultrasound-triggered drug release, as well as microbubbles, microbubble-nanocarrier hybrids, microbubble-seeded hydrogels and phase-change agents. PMID:24389162

Self-defensive antibiotic-loaded layer-by-layer coatings: Imaging of localized bacterial acidification and pH-triggering of antibiotic release.

PubMed

Albright, Victoria; Zhuk, Iryna; Wang, Yuhao; Selin, Victor; van de Belt-Gritter, Betsy; Busscher, Henk J; van der Mei, Henny C; Sukhishvili, Svetlana A

2017-10-01

Self-defensive antibiotic-loaded coatings have shown promise in inhibiting growth of pathogenic bacteria adhering to biomaterial implants and devices, but direct proof that their antibacterial release is triggered by bacterially-induced acidification of the immediate environment under buffered conditions remained elusive. Here, we demonstrate that Staphylococcus aureus and Escherichia coli adhering to such coatings generate highly localized acidification, even in buffered conditions, to activate pH-triggered, self-defensive antibiotic release. To this end, we utilized chemically crosslinked layer-by-layer hydrogel coatings of poly(methacrylic acid) with a covalently attached pH-sensitive SNARF-1 fluorescent label for imaging, and unlabeled-antibiotic (gentamicin or polymyxin B) loaded coatings for antibacterial studies. Local acidification of the coatings induced by S. aureus and E. coli adhering to the coatings was demonstrated by confocal-laser-scanning-microscopy via wavelength-resolved imaging. pH-triggered antibiotic release under static, small volume conditions yielded high bacterial killing efficiencies for S. aureus and E. coli. Gentamicin-loaded films retained their antibacterial activity against S. aureus under fluid flow in buffered conditions. Antibacterial activity increased with the number of polymer layers in the films. Altogether, pH-triggered, self-defensive antibiotic-loaded coatings become activated by highly localized acidification in the immediate environment of an adhering bacterium, offering potential for clinical application with minimized side-effects. Polymeric coatings were created that are able to uptake and selectively release antibiotics upon stimulus by adhering bacteria in order to understand the fundamental mechanisms behind pH-triggered antibiotic release as a potential way to prevent biomaterial-associated infections. Through fluorescent imaging studies, this work importantly shows that adhering bacteria produce highly localized pH changes even in buffer. Accordingly such coatings only demonstrate antibacterial activity by antibiotic release in the presence of adhering bacteria. This is clinically important, because ad libitum releasing antibiotic coatings usually show a burst release and have often lost their antibiotic content when bacteria adhere. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Inertial cavitation to non-invasively trigger and monitor intratumoral release of drug from intravenously delivered liposomes.

PubMed

Graham, Susan M; Carlisle, Robert; Choi, James J; Stevenson, Mark; Shah, Apurva R; Myers, Rachel S; Fisher, Kerry; Peregrino, Miriam-Bazan; Seymour, Len; Coussios, Constantin C

2014-03-28

The encapsulation of cytotoxic drugs within liposomes enhances pharmacokinetics and allows passive accumulation within tumors. However, liposomes designed to achieve good stability during the delivery phase often have compromised activity at the target site. This problem of inefficient and unpredictable drug release is compounded by the present lack of low-cost, non-invasive methods to measure such release. Here we show that focused ultrasound, used at pressures similar to those applied during diagnostic ultrasound scanning, can be utilised to both trigger and monitor release of payload from liposomes. Notably, drug release was influenced by liposome composition and the presence of SonoVue® microbubbles, which provided the nuclei for the initiation of an event known as inertial cavitation. In vitro studies demonstrated that liposomes formulated with a high proportion of 1,2 distearoyl-sn-glycero-3-phosphoethanolamine (DSPE) released up to 30% of payload following ultrasound exposure in the presence of SonoVue®, provided that the exposure created sufficient inertial cavitation events, as characterised by violent bubble collapse and the generation of broadband acoustic emissions. In contrast a 'Doxil'-like liposome formulation gave no such triggered release. In pre-clinical studies, ultrasound was used as a non-invasive, targeted stimulus to trigger a 16-fold increase in the level of payload release within tumors following intravenous delivery. The inertial cavitation events driving this release could be measured remotely in real-time and were a reliable predictor of drug release. Copyright © 2013 The Authors. Published by Elsevier B.V. All rights reserved.

Linear Hand Burn Contracture Release under Local Anesthesia without Tourniquet.

PubMed

Prasetyono, Theddeus O H; Koswara, Astrid F

2015-10-01

The objective of this report is to present a case of hand burn linear contracture release performed under local anesthesia. It also introduces the one-per-mil tumescent solution consisted of 0.2% lidocaine and 1:1.000.000 epinephrine as a local anesthesia formula, which has the potential of providing adequate anesthesia as well as hemostatic effect during surgery of the hand without tourniquet. The surgery was performed on a 19 year-old male patient with multiple thumb and fingers flexion linear contracture for 105 minutes without any obstacle. The patient did not complain any pain and discomfort during the procedure; while bloodless operative field was successfully achieved. At four-month follow up, the patient could fully extend his thumb, middle and ring finger, while the index was limited by 10° at the DIP joint. Overall, the patient was satisfied with the outcome.

WATER LEVEL DRAWDOWN TRIGGERS SYSTEM-WIDE BUBBLE RELEASE FROM RESERVOIR SEDIMENTS

EPA Science Inventory

Reservoirs are an important anthropogenic source of methane and ebullition is a key pathway by which methane stored in reservoir sediments can be released to the atmosphere. Changes in hydrostatic pressure during periods of falling water levels can trigger bubbling events, sugge...

Industrial accidents triggered by lightning.

PubMed

Renni, Elisabetta; Krausmann, Elisabeth; Cozzani, Valerio

2010-12-15

Natural disasters can cause major accidents in chemical facilities where they can lead to the release of hazardous materials which in turn can result in fires, explosions or toxic dispersion. Lightning strikes are the most frequent cause of major accidents triggered by natural events. In order to contribute towards the development of a quantitative approach for assessing lightning risk at industrial facilities, lightning-triggered accident case histories were retrieved from the major industrial accident databases and analysed to extract information on types of vulnerable equipment, failure dynamics and damage states, as well as on the final consequences of the event. The most vulnerable category of equipment is storage tanks. Lightning damage is incurred by immediate ignition, electrical and electronic systems failure or structural damage with subsequent release. Toxic releases and tank fires tend to be the most common scenarios associated with lightning strikes. Oil, diesel and gasoline are the substances most frequently released during lightning-triggered Natech accidents. Copyright © 2010 Elsevier B.V. All rights reserved.

External wire-frame fixation of digital skin grafts: a non-invasive alternative to the K-wire insertion method.

PubMed

Huang, Chenyu; Ogawa, Rei; Hyakusoku, Hiko

2014-08-01

The current skin graft fixation methods for digits, including the Kirschner wire insertion technique, can be limited by inadequate or excessive fixation and complications such as infection or secondary injuries. Therefore, the external wire-frame fixation method was invented and used for skin grafting of digits. This study aimed to investigate external wire-frame fixation of digital skin grafts as a non-invasive alternative to the K-wire insertion method. In 2005-2012, 15 patients with burn scar contractures on the hand digits received a skin graft that was then fixed with an external wire frame. The intra-operative time needed to make the wire frame, the postoperative time to frame and suture removal, the graft survival rate, the effect of contracture release and the complications were recorded. In all cases, the contracture release was 100%. The complete graft survival rate was 98.6%. Four patients had epithelial necrosis in <5% of the total area. There were no other complications such as pressure ulcer or hypoxia of fingers. External wire-frame fixation is simple, minimally invasive and a custom-made technique for skin grafting of the fingers. It was designed for its potential benefits and the decreased risk it poses to patients with scar contractures on their fingers. It can be implemented in three phases of grafting, does not affect the epiphyseal line or subsequent finger growth and is suitable for children with multi-digit involvement. Copyright © 2013 Elsevier Ltd and ISBI. All rights reserved.

Photo-triggered release from liposomes without membrane solubilization, based on binding to poly(vinyl alcohol) carrying a malachite green moiety.

PubMed

Uda, Ryoko M; Kato, Yutaka; Takei, Michiko

2016-10-01

When working with liposomes analogous to cell membranes, it is important to develop substrates that can regulate interactions with the liposome surface in response to light. We achieved a photo-triggered release from liposomes by using a copolymer of poly(vinyl alcohol) carrying a malachite green moiety (PVAMG). Although PVAMG is a neutral polymer under dark conditions, it is photoionized upon exposure to UV light, resulting in the formation of a cationic site for binding to liposomes with a negatively charged surface. Under UV irradiation, PVAMG showed effective interaction with liposomes, releasing the encapsulated compound; however, this release was negligible under dark conditions. The poly(vinyl alcohol) moiety of PVAMG played an important role in the photo-triggered release. This release was caused by membrane destabilization without lipid solubilization. We also investigated different aspects of liposome/PVAMG interactions, including PVAMG-induced fusion between the liposomes and the change in the liposome morphologies. Copyright © 2016 Elsevier B.V. All rights reserved.

Can Pulsed Electromagnetic Fields Trigger On-Demand Drug Release from High-Tm Magnetoliposomes?

PubMed Central

Nardoni, Martina; della Valle, Elena; Relucenti, Michela; Casadei, Maria Antonietta; Paolicelli, Patrizia; Apollonio, Francesca; Petralito, Stefania

2018-01-01

Recently, magnetic nanoparticles (MNPs) have been used to trigger drug release from magnetoliposomes through a magneto-nanomechanical approach, where the mechanical actuation of the MNPs is used to enhance the membrane permeability. This result can be effectively achieved with low intensity non-thermal alternating magnetic field (AMF), which, however, found rare clinic application. Therefore, a different modality of generating non-thermal magnetic fields has now been investigated. Specifically, the ability of the intermittent signals generated by non-thermal pulsed electromagnetic fields (PEMFS) were used to verify if, once applied to high-transition temperature magnetoliposomes (high-Tm MLs), they could be able to efficiently trigger the release of a hydrophilic model drug. To this end, hydrophilic MNPs were combined with hydrogenated soybean phosphatidylcholine and cholesterol to design high-Tm MLs. The release of a dye was evaluated under the effect of PEMFs for different times. The MNPs motions produced by PEMF could effectively increase the bilayer permeability, without affecting the liposomes integrity and resulted in nearly 20% of release after 3 h exposure. Therefore, the current contribution provides an exciting proof-of-concept for the ability of PEMFS to trigger drug release, considering that PEMFS find already application in therapy due to their anti-inflammatory effects. PMID:29584700

Can Pulsed Electromagnetic Fields Trigger On-Demand Drug Release from High-Tm Magnetoliposomes?

PubMed

Nardoni, Martina; Della Valle, Elena; Liberti, Micaela; Relucenti, Michela; Casadei, Maria Antonietta; Paolicelli, Patrizia; Apollonio, Francesca; Petralito, Stefania

2018-03-27

Recently, magnetic nanoparticles (MNPs) have been used to trigger drug release from magnetoliposomes through a magneto-nanomechanical approach, where the mechanical actuation of the MNPs is used to enhance the membrane permeability. This result can be effectively achieved with low intensity non-thermal alternating magnetic field (AMF), which, however, found rare clinic application. Therefore, a different modality of generating non-thermal magnetic fields has now been investigated. Specifically, the ability of the intermittent signals generated by non-thermal pulsed electromagnetic fields (PEMFS) were used to verify if, once applied to high-transition temperature magnetoliposomes (high-Tm MLs), they could be able to efficiently trigger the release of a hydrophilic model drug. To this end, hydrophilic MNPs were combined with hydrogenated soybean phosphatidylcholine and cholesterol to design high-Tm MLs. The release of a dye was evaluated under the effect of PEMFs for different times. The MNPs motions produced by PEMF could effectively increase the bilayer permeability, without affecting the liposomes integrity and resulted in nearly 20% of release after 3 h exposure. Therefore, the current contribution provides an exciting proof-of-concept for the ability of PEMFS to trigger drug release, considering that PEMFS find already application in therapy due to their anti-inflammatory effects.

A multifunctional magnetic nanocarrier bearing fluorescent dye for targeted drug delivery by enhanced two-photon triggered release

NASA Astrophysics Data System (ADS)

Banerjee, Shashwat S.; Chen, Dong-Hwang

2009-05-01

We report a novel nanoformulation for targeted drug delivery which utilizes nanophotonics through the fusion of nanotechnology with biomedical application. The approach involves an energy-transferring magnetic nanoscopic co-assembly fabricated of rhodamine B (RDB) fluorescent dye grafted gum arabic modified Fe3O4 magnetic nanoparticle and photosensitive linker by which dexamethasone drug is conjugated to the magnetic nano-assembly. The advantage offered by this nanoformulation is the indirect photo-triggered-on-demand drug release by efficient up-converting energy of the near-IR (NIR) light to higher energy and intraparticle energy transfer from the dye grafted magnetic nanoparticle to the linker for drug release by cleavage. The synthesized nanoparticles were found to be of ultra-small size (13.33 nm) and are monodispersed in an aqueous suspension. Dexamethasone (Dexa) drug conjugated to RDB-GAMNP by photosensitive linker showed appreciable release of Dexa by photo-triggered response on exposure to radiation having a wavelength in the NIR region whereas no detectable release was observed in the dark. Photo-triggered response for the nanoformulation not bearing the rhodamine B dye was drastically less as less Dexa was released on exposure to NIR radiation which suggest that the photo-cleavage of linker and release of Dexa mainly originated from the indirect excitation through the uphill energy conversions based on donor-acceptor model FRET. The promising pathway of nanophotonics for the on-demand release of the drug makes this nanocarrier very promising for applications in nanomedicine.

Drug Release from Phase-Changeable Nanodroplets Triggered by Low-Intensity Focused Ultrasound

PubMed Central

Cao, Yang; Chen, Yuli; Yu, Tao; Guo, Yuan; Liu, Fengqiu; Yao, Yuanzhi; Li, Pan; Wang, Dong; Wang, Zhigang; Chen, Yu; Ran, Haitao

2018-01-01

Background: As one of the most effective triggers with high tissue-penetrating capability and non-invasive feature, ultrasound shows great potential for controlling the drug release and enhancing the chemotherapeutic efficacy. In this study, we report, for the first time, construction of a phase-changeable drug-delivery nanosystem with programmable low-intensity focused ultrasound (LIFU) that could trigger drug-release and significantly enhance anticancer drug delivery. Methods: Liquid-gas phase-changeable perfluorocarbon (perfluoropentane) and an anticancer drug (doxorubicin) were simultaneously encapsulated in two kinds of nanodroplets. By triggering LIFU, the nanodroplets could be converted into microbubbles locally in tumor tissues for acoustic imaging and the loaded anticancer drug (doxorubicin) was released after the microbubble collapse. Based on the acoustic property of shell materials, such as shell stiffness, two types of nanodroplets (lipid-based nanodroplets and PLGA-based nanodroplets) were activated by different acoustic pressure levels. Ultrasound irradiation duration and power of LIFU were tested and selected to monitor and control the drug release from nanodroplets. Various ultrasound energies were introduced to induce the phase transition and microbubble collapse of nanodroplets in vitro (3 W/3 min for lipid nanodroplets; 8 W/3 min for PLGA nanodroplets). Results: We detected three steps in the drug-releasing profiles exhibiting the programmable patterns. Importantly, the intratumoral accumulation and distribution of the drug with LIFU exposure were significantly enhanced, and tumor proliferation was substantially inhibited. Co-delivery of two drug-loaded nanodroplets could overcome the physical barriers of tumor tissues during chemotherapy. Conclusion: Our study provides a new strategy for the efficient ultrasound-triggered chemotherapy by nanocarriers with programmable LIFU capable of achieving the on-demand drug release. PMID:29507623

The effectiveness of manual versus algometer pressure release techniques for treating active myofascial trigger points of the upper trapezius.

PubMed

Abu Taleb, Walaa; Rehan Youssef, Aliaa; Saleh, Amir

2016-10-01

Manual pressure release (MPR) is a popular treatment of trigger points. Yet, treatment response may be influenced by inconsistent application of pressure. Further, it may contribute to increased risk of work-related musculoskeletal disorders of the wrist and hand in therapists. Therefore, this study aimed at introducing a novel method to apply pressure using the algometer and to compare its effectiveness to MPR. Forty-five volunteers with active trigger points of the upper trapezius received algometer pressure release (APR), MPR, or sham ultrasound (US). Pain pressure threshold (PPT) and contralateral active and passive neck side-bending ranges were assessed at baseline and immediately after a single session. Results showed no significant differences in post-treatment PPT between the study groups (p > 0.05). The APR group showed a significant increase in passive side-bending range compared with the two other groups, whereas active range improved in the APR compared with the US group (p < 0.05). Our results show that using algometer to apply pressure release to upper trapezius trigger points is more effective compared with manual release and sham US. Copyright © 2016 Elsevier Ltd. All rights reserved.

A novel zinc finger protein 219-like (ZNF219L) is involved in the regulation of collagen type 2 alpha 1a (col2a1a) gene expression in zebrafish notochord.

PubMed

Lien, Huang-Wei; Yang, Chung-Hsiang; Cheng, Chia-Hsiung; Hung, Chin-Chun; Liao, Wei-Hao; Hwang, Pung-Pung; Han, Yu-San; Huang, Chang-Jen

2013-01-01

The notochord is required for body plan patterning in vertebrates, and defects in notochord development during embryogenesis can lead to diseases affecting the adult. It is therefore important to elucidate the gene regulatory mechanism underlying notochord formation. In this study, we cloned the zebrafish zinc finger 219-like (ZNF219L) based on mammalian ZNF219, which contains nine C2H2-type zinc finger domains. Through whole-mount in situ hybridization, we found that znf219L mRNA is mainly expressed in the zebrafish midbrain-hindbrain boundary, hindbrain, and notochord during development. The znf219L morpholino knockdown caused partial abnormal notochord phenotype and reduced expression of endogenous col2a1a in the notochord specifically. In addition, ZNF219L could recognize binding sites with GGGGG motifs and trigger augmented activity of the col2a1a promoter in a luciferase assay. Furthermore, in vitro binding experiments revealed that ZNF219L recognizes the GGGGG motifs in the promoter region of the zebrafish col2a1a gene through its sixth and ninth zinc finger domains. Taken together, our results reveal that ZNF219L is involved in regulating the expression of col2a1a in zebrafish notochord specifically.

A Novel Zinc Finger Protein 219-like (ZNF219L) is Involved in the Regulation of Collagen Type 2 Alpha 1a (col2a1a) Gene Expression in Zebrafish Notochord

PubMed Central

Lien, Huang-Wei; Yang, Chung-Hsiang; Cheng, Chia-Hsiung; Hung, Chin-Chun; Liao, Wei-Hao; Hwang, Pung-Pung; Han, Yu-San; Huang, Chang-Jen

2013-01-01

The notochord is required for body plan patterning in vertebrates, and defects in notochord development during embryogenesis can lead to diseases affecting the adult. It is therefore important to elucidate the gene regulatory mechanism underlying notochord formation. In this study, we cloned the zebrafish zinc finger 219-like (ZNF219L) based on mammalian ZNF219, which contains nine C2H2-type zinc finger domains. Through whole-mount in situ hybridization, we found that znf219L mRNA is mainly expressed in the zebrafish midbrain-hindbrain boundary, hindbrain, and notochord during development. The znf219L morpholino knockdown caused partial abnormal notochord phenotype and reduced expression of endogenous col2a1a in the notochord specifically. In addition, ZNF219L could recognize binding sites with GGGGG motifs and trigger augmented activity of the col2a1a promoter in a luciferase assay. Furthermore, in vitro binding experiments revealed that ZNF219L recognizes the GGGGG motifs in the promoter region of the zebrafish col2a1a gene through its sixth and ninth zinc finger domains. Taken together, our results reveal that ZNF219L is involved in regulating the expression of col2a1a in zebrafish notochord specifically. PMID:24155663

Kriging modeling and SPSA adjusting PID with KPWF compensator control of IPMC gripper for mm-sized objects

NASA Astrophysics Data System (ADS)

Chen, Yang; Hao, Lina; Yang, Hui; Gao, Jinhai

2017-12-01

Ionic polymer metal composite (IPMC) as a new smart material has been widely concerned in the micromanipulation field. In this paper, a novel two-finger gripper which contains an IPMC actuator and an ultrasensitive force sensor is proposed and fabricated. The IPMC as one finger of the gripper for mm-sized objects can achieve gripping and releasing motion, and the other finger works not only as a support finger but also as a force sensor. Because of the feedback signal of the force sensor, this integrated actuating and sensing gripper can complete gripping miniature objects in millimeter scale. The Kriging model is used to describe nonlinear characteristics of the IPMC for the first time, and then the control scheme called simultaneous perturbation stochastic approximation adjusting a proportion integration differentiation parameter controller with a Kriging predictor wavelet filter compensator is applied to track the gripping force of the gripper. The high precision force tracking in the foam ball manipulation process is obtained on a semi-physical experimental platform, which demonstrates that this gripper for mm-sized objects can work well in manipulation applications.

Simultaneous Force Regression and Movement Classification of Fingers via Surface EMG within a Unified Bayesian Framework.

PubMed

Baldacchino, Tara; Jacobs, William R; Anderson, Sean R; Worden, Keith; Rowson, Jennifer

2018-01-01

This contribution presents a novel methodology for myolectric-based control using surface electromyographic (sEMG) signals recorded during finger movements. A multivariate Bayesian mixture of experts (MoE) model is introduced which provides a powerful method for modeling force regression at the fingertips, while also performing finger movement classification as a by-product of the modeling algorithm. Bayesian inference of the model allows uncertainties to be naturally incorporated into the model structure. This method is tested using data from the publicly released NinaPro database which consists of sEMG recordings for 6 degree-of-freedom force activations for 40 intact subjects. The results demonstrate that the MoE model achieves similar performance compared to the benchmark set by the authors of NinaPro for finger force regression. Additionally, inherent to the Bayesian framework is the inclusion of uncertainty in the model parameters, naturally providing confidence bounds on the force regression predictions. Furthermore, the integrated clustering step allows a detailed investigation into classification of the finger movements, without incurring any extra computational effort. Subsequently, a systematic approach to assessing the importance of the number of electrodes needed for accurate control is performed via sensitivity analysis techniques. A slight degradation in regression performance is observed for a reduced number of electrodes, while classification performance is unaffected.

The unique N-terminal zinc finger of synaptotagmin-like protein 4 reveals FYVE structure.

PubMed

Miyamoto, Kazuhide; Nakatani, Arisa; Saito, Kazuki

2017-12-01

Synaptotagmin-like protein 4 (Slp4), expressed in human platelets, is associated with dense granule release. Slp4 is comprised of the N-terminal zinc finger, Slp homology domain, and C2 domains. We synthesized a compact construct (the Slp4N peptide) corresponding to the Slp4 N-terminal zinc finger. Herein, we have determined the solution structure of the Slp4N peptide by nuclear magnetic resonance (NMR). Furthermore, experimental, chemical modification of Cys residues revealed that the Slp4N peptide binds two zinc atoms to mediate proper folding. NMR data showed that eight Cys residues coordinate zinc atoms in a cross-brace fashion. The Simple Modular Architecture Research Tool database predicted the structure of Slp4N as a RING finger. However, the actual structure of the Slp4N peptide adopts a unique C 4 C 4 -type FYVE fold and is distinct from a RING fold. To create an artificial RING finger (ARF) with specific ubiquitin-conjugating enzyme (E2)-binding capability, cross-brace structures with eight zinc-ligating residues are needed as the scaffold. The cross-brace structure of the Slp4N peptide could be utilized as the scaffold for the design of ARFs. © 2017 The Protein Society.

Risk factors for operated carpal tunnel syndrome: a multicenter population-based case-control study

PubMed Central

Mattioli, Stefano; Baldasseroni, Alberto; Bovenzi, Massimo; Curti, Stefania; Cooke, Robin MT; Campo, Giuseppe; Barbieri, Pietro G; Ghersi, Rinaldo; Broccoli, Marco; Cancellieri, Maria Pia; Colao, Anna Maria; dell'Omo, Marco; Fateh-Moghadam, Pirous; Franceschini, Flavia; Fucksia, Serenella; Galli, Paolo; Gobba, Fabriziomaria; Lucchini, Roberto; Mandes, Anna; Marras, Teresa; Sgarrella, Carla; Borghesi, Stefano; Fierro, Mauro; Zanardi, Francesca; Mancini, Gianpiero; Violante, Francesco S

2009-01-01

Background Carpal tunnel syndrome (CTS) is a socially and economically relevant disease caused by compression or entrapment of the median nerve within the carpal tunnel. This population-based case-control study aims to investigate occupational/non-occupational risk factors for surgically treated CTS. Methods Cases (n = 220) aged 18-65 years were randomly drawn from 13 administrative databases of citizens who were surgically treated with carpal tunnel release during 2001. Controls (n = 356) were randomly sampled from National Health Service registry records and were frequency matched by age-gender-specific CTS hospitalization rates. Results At multivariate analysis, risk factors were blue-collar/housewife status, BMI ≥ 30 kg/m2, sibling history of CTS and coexistence of trigger finger. Being relatively tall (cut-offs based on tertiles: women ≥165 cm; men ≥175 cm) was associated with lower risk. Blue-collar work was a moderate/strong risk factor in both sexes. Raised risks were apparent for combinations of biomechanical risk factors that included frequent repetitivity and sustained force. Conclusion This study strongly underlines the relevance of biomechanical exposures in both non-industrial and industrial work as risk factors for surgically treated CTS. PMID:19758429

Ibuprofen timing for hand surgery in ambulatory care

PubMed Central

Giuliani, Enrico; Bianchi, Anna; Marcuzzi, Augusto; Landi, Antonio; Barbieri, Alberto

2015-01-01

OBJECTIVE: To evaluate the effect of pre-operative administration of ibuprofen on post-operative pain control vs. early post-operative administration for hand surgery procedures performed under local anaesthesia in ambulatory care. METHODS: Candidates to trigger finger release by De Quervain tenosynovitis and carpal tunnel operation under local anesthesia were enrolled in the study. Group A received 400 mg ibuprofen before the operation and placebo after the procedure; group B received placebo before the operation and ibuprofen 400 mg at the end of the procedure; both groups received ibuprofen 400 mg every 6h thereafter. Visual analogue scale (VAS) was measured at fixed times before and every 6h after surgery, for a total follow-up of 18h. RESULTS: Groups were similar according to age, gender and type of surgery. Median VAS values did not produce any statistical significance, while there was a statistically significant difference on pre-operative and early post-operative VAS values between groups (A -8.53 mm vs. B 3.36 mm, p=0.0085). CONCLUSION: Average pain levels were well controlled by local anesthesia and post-operative ibuprofen analgesia. Pre-operative ibuprofen administration can contribute to improve early pain management. Level of Evidence II, Therapeutic Studies. PMID:26327799

Trigger chemistries for better industrial formulations.

PubMed

Wang, Hsuan-Chin; Zhang, Yanfeng; Possanza, Catherine M; Zimmerman, Steven C; Cheng, Jianjun; Moore, Jeffrey S; Harris, Keith; Katz, Joshua S

2015-04-01

In recent years, innovations and consumer demands have led to increasingly complex liquid formulations. These growing complexities have provided industrial players and their customers access to new markets through product differentiation, improved performance, and compatibility/stability with other products. One strategy for enabling more complex formulations is the use of active encapsulation. When encapsulation is employed, strategies are required to effect the release of the active at the desired location and time of action. One particular route that has received significant academic research effort is the employment of triggers to induce active release upon a specific stimulus, though little has translated for industrial use to date. To address emerging industrial formulation needs, in this review, we discuss areas of trigger release chemistries and their applications specifically as relevant to industrial use. We focus the discussion on the use of heat, light, shear, and pH triggers as applied in several model polymeric systems for inducing active release. The goal is that through this review trends will emerge for how technologies can be better developed to maximize their value through industrial adaptation.

Enzymatic triggered release of an HIV-1 entry inhibitor from prostate specific antigen degradable microparticles.

PubMed

Clark, Meredith R; Aliyar, Hyder A; Lee, Chang-won; Jay, Julie I; Gupta, Kavita M; Watson, Karen M; Stewart, Russell J; Buckheit, Robert W; Kiser, Patrick F

2011-07-15

This paper describes the design, construction and characterization of the first anti-HIV drug delivery system that is triggered to release its contents in the presence of human semen. Microgel particles were synthesized with a crosslinker containing a peptide substrate for the seminal serine protease prostate specific antigen (PSA) and were loaded with the HIV-1 entry inhibitor sodium poly(styrene-4-sulfonate) (pSS). The particles were composed of N-2-hydroxyproplymethacrylamide and bis-methacrylamide functionalized peptides based on the PSA substrates GISSFYSSK and GISSQYSSK. Exposure to human seminal plasma (HSP) degraded the microgel network and triggered the release of the entrapped antiviral polymer. Particles with the crosslinker composed of the substrate GISSFYSSK showed 17 times faster degradation in seminal plasma than that of the crosslinker composed of GISSQYSSK. The microgel particles containing 1 mol% GISSFYSSK peptide crosslinker showed complete degradation in 30 h in the presence of HSP at 37°C and pSS released from the microgels within 30 min reached a concentration of 10 μg/mL, equivalent to the published IC(90) for pSS. The released pSS inactivated HIV-1 in the presence of HSP. The solid phase synthesis of the crosslinkers, preparation of the particles by inverse microemulsion polymerization, HSP-triggered release of pSS and inactivation of HIV-1 studies are described. Copyright © 2011 Elsevier B.V. All rights reserved.

MLKL activation triggers NLRP3-mediated processing and release of IL-1β independent of gasdermin-D

PubMed Central

Gutierrez, Kimberley D.; Davis, Michael A.; Daniels, Brian P.; Olsen, Tayla M.; Ralli-Jain, Pooja; Tait, Stephen W.G.; Gale, Michael; Oberst, Andrew

2017-01-01

Necroptosis is a form of programmed cell death defined by activation of the kinase RIPK3 and its downstream effector, the pseudokinase MLKL. Activated MLKL translocates to the cell membrane and disrupts it, leading to loss of cellular ion homeostasis. Here, we use a system in which this event can be specifically triggered by a small-molecule ligand to show that MLKL activation is sufficient to induce the processing and release of bioactive IL-1β. MLKL activation triggers potassium efflux and assembly of the NLRP3 inflammasome, which is required for the processing and activity of IL-1β released during necroptosis. Notably, MLKL activation also causes cell membrane disruption, which allows efficient release of IL-1β independent of the recently described pyroptotic effector gasdermin-D. Together, our findings indicate that MLKL is an endogenous activator of the NLRP3 inflammasome, and that MLKL activation provides a mechanism for concurrent processing and release of IL-1β independent of gasdermin-D. PMID:28130493

A three-fingered, touch-sensitive, metrological micro-robotic assembly tool

NASA Astrophysics Data System (ADS)

Torralba, Marta; Hastings, D. J.; Thousand, Jeffery D.; Nowakowski, Bartosz K.; Smith, Stuart T.

2015-12-01

This article describes a metrological, robotic hand to manipulate and measure micrometer size objects. The presented work demonstrates not only assembly operations, but also positioning control and metrology capability. Sample motion is achieved by a commercial positioning stage, which provides XYZ-displacements for assembly of components. A designed and manufactured gripper tool that incorporates 21 degrees-of-freedom for independent alignment of actuators, sensors, and the three fingers of this hand is presented. These fingers can be opened and closed by piezoelectric actuators through levered flexures providing an 80 μm displacement range measured with calibrated opto-interrupter based, knife-edge sensors. The operational ends of the fingers comprise of a quartz tuning fork with a 7 μm diameter 3.2 mm long carbon fiber extending from the end of one tuning fork tine. Finger-tip force-sensing is achieved by the monitoring of individual finger resonances typically at around 32 kHz. Experimental results included are focused on probe performance analysis. Pick and place operation using the three fingers is demonstrated with all fingers being continuously oscillated, a capability not possible with the previous single or two finger tweezer type designs. By monitoring electrical feedback during pick and place operations, changes in the response of the three probes demonstrate the ability to identify both grab and release operations. Component metrology has been assessed by contacting different micro-spheres of diameters 50(±7.5) μm, 135(±20) μm, and 140(±20) μm. These were measured by the micro robot to have diameters of 67, 133, and 126 μm respectively with corresponding deviations of 4.2, 4.9, and 4.3 μm. This deviation in the measured results was primarily due to the manual, joystick-based, contacting of the fingers, difficulties associated with centering the components to the axis of the hand, and lower contact sensitivity for the smallest sphere. Finally, assemblies of spheres onto the edge of a razor blade plus assembly of spherical contact probes for micro-meter scale coordinate measurement applications are presented.

The sympathetic release test: a test used to assess thermoregulation and autonomic control of blood flow.

PubMed

Tansey, E A; Roe, S M; Johnson, C J

2014-03-01

When a subject is heated, the stimulation of temperature-sensitive nerve endings in the skin, and the raising of the central body temperature, results in the reflex release of sympathetic vasoconstrictor tone in the skin of the extremities, causing a measurable temperature increase at the site of release. In the sympathetic release test, the subject is gently heated by placing the feet and calves in a commercially available foot warming pouch or immersing the feet and calves in warm water and wrapping the subject in blankets. Skin blood flow is estimated from measurements of skin temperature in the fingers. Normally skin temperature of the fingers is 65-75°F in cool conditions (environmental temperature: 59-68°F) and rises to 85-95°F during body heating. Deviations in this pattern may mean that there is abnormal sympathetic vasoconstrictor control of skin blood flow. Abnormal skin blood flow can substantially impair an individual's ability to thermoregulate and has important clinical implications. During whole body heating, the skin temperature from three different skin sites is monitored and oral temperature is monitored as an index of core temperature. Students determine the fingertip temperature at which the reflex release of sympathetic activity occurs and its maximal attainment, which reflects the vasodilating capacity of this cutaneous vascular bed. Students should interpret typical sample data for certain clinical conditions (Raynaud's disease, peripheral vascular disease, and postsympathectomy) and explain why there may be altered skin blood flow in these disorders.

Ultrasound Enhanced Matrix Metalloproteinase-9 Triggered Release of Contents from Echogenic Liposomes

PubMed Central

Nahire, Rahul; Paul, Shirshendu; Scott, Michael D.; Singh, Raushan K.; Muhonen, Wallace W.; Shabb, John; Gange, Kara N.; Srivastava, D. K.; Sarkar, Kausik; Mallik, Sanku

2012-01-01

The extracellular enzyme matrix metalloproteinase-9 (MMP-9) is overexpressed in atherosclerotic plaques and in metastatic cancers. The enzyme is responsible for rupture of the plaques and for the invasion and metastasis of a large number of cancers. The ability of ultrasonic excitation to induce thermal and mechanical effects has been used to release drugs from different carriers. However, majority of these studies were performed with low frequency ultrasound (LFUS) at kHz frequencies. Clinical usage of LFUS excitations will be limited due to harmful biological effects. Herein, we report our results on the release of encapsulated contents from substrate lipopeptide incorporated echogenic liposomes triggered by recombinant human MMP-9. The contents release was further enhanced by the application of diagnostic frequency (3 MHz) ultrasound. The echogenic liposomes were successfully imaged employing a medical ultrasound transducer (4 – 15 MHz). The conditioned cell culture media from cancer cells (secreting MMP-9) released the encapsulated dye from the liposomes (30 – 50%) and this release is also increased (50 – 80%) by applying diagnostic frequency ultrasound (3 MHz) for 3 minutes. With further developments, these liposomes have the potential to serve as multimodal carriers for triggered release and simultaneous ultrasound imaging. PMID:22849291

Laser-triggered release of encapsulated molecules from polylactic-co-glycolic acid microcapsules

NASA Astrophysics Data System (ADS)

Ariyasu, Kazumasa; Ishii, Atsuhiro; Umemoto, Taiga; Terakawa, Mitsuhiro

2016-08-01

The controlled release of encapsulated molecules from a microcapsule is a promising method of targeted drug delivery. Laser-triggered methods for the release of encapsulated molecules have the advantage of spatial and temporal controllability. In this study, we demonstrated the release of encapsulated molecules from biodegradable polymer-based microcapsules using near-infrared femtosecond laser pulses. The polylactic-co-glycolic acid microcapsules encapsulating fluorescein isothiocyanate-dextran molecules were fabricated using a dual-coaxial nozzle system. Irradiation of femtosecond laser pulses enhanced the release of the molecules from the microcapsules, which was accompanied by a decrease in the residual ratio of the microcapsules. The laser-induced modification of the surface of the shell of the microcapsules indicated the potential for sustained release as well as burst release.

UV-crosslinkable and thermo-responsive chitosan hybrid hydrogel for NIR-triggered localized on-demand drug delivery.

PubMed

Wang, Lei; Li, Baoqiang; Xu, Feng; Xu, Zheheng; Wei, Daqing; Feng, Yujie; Wang, Yaming; Jia, Dechang; Zhou, Yu

2017-10-15

Innovative drug delivery technologies based on smart hydrogels for localized on-demand drug delivery had aroused great interest. To acquire smart UV-crosslinkable chitosan hydrogel for NIR-triggered localized on-demanded drug release, a novel UV-crosslinkable and thermo-responsive chitosan was first designed and synthesized by grafting with poly N-isopropylacrylamide, acetylation of methacryloyl groups and embedding with photothermal carbon. The UV-crosslinkable unit (methacryloyl groups) endowed chitosan with gelation via UV irradiation. The thermo-responsive unit (poly N-isopropylacrylamide) endowed chitosan hydrogel with temperature-triggered volume shrinkage and reversible swelling/de-swelling behavior. The chitosan hybrid hydrogel embedded with photothermal carbon exhibited distinct NIR-triggered volume shrinkage (∼42% shrinkage) in response to temperature elevation as induced by NIR laser irradiation. As a demonstration, doxorubicin release rate was accelerated and approximately 40 times higher than that from non-irradiated hydrogels. The UV-crosslinkable and thermal-responsive hybrid hydrogel served as in situ forming hydrogel-based drug depot is developed for NIR-triggered localized on-demand release. Copyright © 2017 Elsevier Ltd. All rights reserved.

Electrochemically triggered release of acetylcholine from scCO2 impregnated conductive polymer films evokes intracellular Ca2+ signaling in neurotypic SH-SY5Y cells.

PubMed

Löffler, Susanne; Seyock, Silke; Nybom, Rolf; Jacobson, Gunilla B; Richter-Dahlfors, Agneta

2016-12-10

Implantable devices for electronically triggered drug release are attractive to achieve spatial and temporal control over drug concentrations in patients. Realization of such devices is, however, associated with technical and biological challenges. Among these are containment of drug reservoirs, lack of precise control cues, as well as the charge and size of the drug. Here, we present a method for electronically triggered release of the quaternary ammonium cation acetylcholine (ACh) from an impregnated conductive polymer film. Using supercritical carbon dioxide (scCO 2 ), a film of PEDOT/PSS (poly(3,4)-ethylenedioxythiophene doped with poly(styrenesulfonate)) is impregnated with the neurotransmitter acetylcholine. The gentle scCO 2 process generated a dry, drug-impregnated surface, well suited for interaction with biological material, while maintaining normal electrochemical properties of the polymer. Electrochemical switching of impregnated PEDOT/PSS films stimulated release of ACh from the polymer matrix, likely due to swelling mediated by the influx and efflux of charged and solvated ions. Triggered release of ACh did not affect the biological activity of the drug. This was shown by real-time monitoring of intracellular Ca 2+ signaling in neurotypic cells growing on the impregnated polymer surface. Collectively, scCO 2 impregnation of conducting polymers offers the first one-step, dopant-independent drug impregnation process, potentially facilitating loading of both anionic and cationic drugs that can be dissolved in scCO2 on its own or by using a co-solvent. We foresee that scCO 2 -loaded devices for electronically triggered drug release will create novel opportunities when generating active bio-coatings, tunable for specific needs, in a variety of medical settings. Copyright © 2016 Elsevier B.V. All rights reserved.

DNA Microcapsule for Photo-Triggered Drug Release Systems.

PubMed

Kamiya, Yukiko; Yamada, Yoshinobu; Muro, Takahiro; Matsuura, Kazunori; Asanuma, Hiroyuki

2017-12-19

In this study we constructed spherical photo-responsive microcapsules composed of three photo-switchable DNA strands. These strands first formed a three-way junction (TWJ) motif that further self-assembled to form microspheres through hybridization of the sticky-end regions of each branch. To serve as the photo-switch, multiple unmodified azobenzene (Azo) or 2,6-dimethyl-4-(methylthio)azobenzene (SDM-Azo) were introduced into the sticky-end regions via a d-threoninol linker. The DNA capsule structure deformed upon trans-to-cis isomerization of Azo or SDM-Azo induced by specific light irradiation. In addition, photo-triggered release of encapsulated small molecules from the DNA microcapsule was successfully achieved. Moreover, we demonstrated that photo-triggered release of doxorubicin caused cytotoxicity to cultured cells. This biocompatible photo-responsive microcapsule has potential application as a photo-controlled drug-release system. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Firearm trigger assembly

DOEpatents

Crandall, David L.; Watson, Richard W.

2010-02-16

A firearm trigger assembly for use with a firearm includes a trigger mounted to a forestock of the firearm so that the trigger is movable between a rest position and a triggering position by a forwardly placed support hand of a user. An elongated trigger member operatively associated with the trigger operates a sear assembly of the firearm when the trigger is moved to the triggering position. An action release assembly operatively associated with the firearm trigger assembly and a movable assembly of the firearm prevents the trigger from being moved to the triggering position when the movable assembly is not in the locked position.

Repeated bubble breakup and coalescence in perturbed Hele-Shaw channels

NASA Astrophysics Data System (ADS)

Thompson, Alice; Franco-Gomez, Andres; Hazel, Andrew; Juel, Anne

2017-11-01

The introduction of an axially-uniform, centred constriction in a Hele-Shaw channel leads to multiple propagation modes for both air fingers and bubbles, including symmetric and asymmetric steadily propagating modes along with oscillations. These multiple modes correspond to a non-trivial bifurcation structure, and relate to the plethora of steadily propagating bubbles and fingers which exist in the Saffman-Taylor system. In both experiments and depth-averaged computations, a very small centred occlusion can be enough to trigger bubble breakup, with a single large centred bubble splitting into two smaller bubbles which propagate along each side of the channel. We present numerical simulations for the depth-averaged model, implementing geometric criteria for pinchoff and coalescence in order to track the bubble before and beyond breakup. We find that the two-bubble state is itself unstable, with finger competition causing one bubble to move ahead; the trailing bubble then moves across the channel to merge with the leading bubble. However, the story is not always so simple, enabling complicated cascades of splitting and merging bubbles. We compare the general dynamical behaviour, basins of attraction, and the details of merging and splitting, to experimental observations.

External triggering and triggered targeting strategies for drug delivery

NASA Astrophysics Data System (ADS)

Wang, Yanfei; Kohane, Daniel S.

2017-06-01

Drug delivery systems that are externally triggered to release drugs and/or target tissues hold considerable promise for improving the treatment of many diseases by minimizing nonspecific toxicity and enhancing the efficacy of therapy. These drug delivery systems are constructed from materials that are sensitive to a wide range of external stimuli, including light, ultrasound, electrical and magnetic fields, and specific molecules. The responsiveness conferred by these materials allows the release of therapeutics to be triggered on demand and remotely by a physician or patient. In this Review, we describe the rationales for such systems and the types of stimuli that can be deployed, and provide an outlook for the field.

Risk analysis for dry snow slab avalanche release by skier triggering

NASA Astrophysics Data System (ADS)

McClung, David

2013-04-01

Risk analysis is of primary importance for skier triggering of avalanches since human triggering is responsible for about 90% of deaths from slab avalanches in Europe and North America. Two key measureable quantities about dry slab avalanche release prior to initiation are the depth to the weak layer and the slope angle. Both are important in risk analysis. As the slope angle increases, the probability of avalanche release increases dramatically. As the slab depth increases, the consequences increase if an avalanche releases. Among the simplest risk definitions is (Vick, 2002): Risk = (Probability of failure) x (Consequences of failure). Here, these two components of risk are the probability or chance of avalanche release and the consequences given avalanche release. In this paper, for the first time, skier triggered avalanches were analyzed from probability theory and its relation to risk for both the D and . The data consisted of two quantities : (,D) taken from avalanche fracture line profiles after an avalanche has taken place. Two data sets from accidentally skier triggered avalanches were considered: (1) 718 for and (2) a set of 1242 values of D which represent average values along the fracture line. The values of D were both estimated (about 2/3) and measured (about 1/3) by ski guides from Canadian Mountain Holidays CMH). I also analyzed 1231 accidentally skier triggered avalanches reported by CMH ski guides for avalanche size (representing destructive potential) on the Canadian scale. The size analysis provided a second analysis of consequences to verify that using D. The results showed that there is an intermediate range of both D and with highest risk. ForD, the risk (product of consequences and probability of occurrence) is highest for D in the approximate range 0.6 m - 1.0 m. The consequences are low for lower values of D and the chance of release is low for higher values of D. Thus, the highest product is in the intermediate range. For slope angles, the risk analysis showed there are two ranges: ˜ 320; × 460for which risk is lowest. In this case, both the range of and the consequences vary by about a factor of two so the probability of release dominates the risk analysis to yield low risk at the tails of the distribution of with highest risk in the middle (330 - 450) of the expected range (250 - 550).

Presynaptic strontium dynamics and synaptic transmission.

PubMed Central

Xu-Friedman, M A; Regehr, W G

1999-01-01

Strontium can replace calcium in triggering neurotransmitter release, although peak release is reduced and the duration of release is prolonged. Strontium has therefore become useful in probing release, but its mechanism of action is not well understood. Here we study the action of strontium at the granule cell to Purkinje cell synapse in mouse cerebellar slices. Presynaptic residual strontium levels were monitored with fluorescent indicators, which all responded to strontium (fura-2, calcium orange, fura-2FF, magnesium green, and mag-fura-5). When calcium was replaced by equimolar concentrations of strontium in the external bath, strontium and calcium both entered presynaptic terminals. Contaminating calcium was eliminated by including EGTA in the extracellular bath, or by loading parallel fibers with EGTA, enabling the actions of strontium to be studied in isolation. After a single stimulus, strontium reached higher peak free levels than did calcium (approximately 1.7 times greater), and decayed more slowly (half-decay time 189 ms for strontium and 32 ms for calcium). These differences in calcium and strontium dynamics are likely a consequence of greater strontium permeability through calcium channels, lower affinity of the endogenous buffer for strontium, and less efficient extrusion of strontium. Measurements of presynaptic divalent levels help to explain properties of release evoked by strontium. Parallel fiber synaptic currents triggered by strontium are smaller in amplitude and longer in duration than those triggered by calcium. In both calcium and strontium, release consists of two components, one more steeply dependent on divalent levels than the other. Strontium drives both components less effectively than does calcium, suggesting that the affinities of the sensors involved in both phases of release are lower for strontium than for calcium. Thus, the larger and slower strontium transients account for the prominent slow component of release triggered by strontium. PMID:10096899

Complete annular and partial oblique pulley release for pediatric locked trigger thumb

PubMed Central

Kuo, Meiying

2010-01-01

Purpose To report the surgical treatment outcome of pediatric locked trigger thumb by sequential release of the annular pulley and partial release of the oblique pulley. Materials and Methods A retrospective review was undertaken on 28 operative thumbs in 24 patients with an average follow-up of 79 months. Intraoperative observations focused on the pathology of the pulley system. Surgical technique involved complete release of the annular pulley, which alone was insufficient in relieving the deformity, along with release of the proximal 50% of the oblique pulley in all patients. Postoperative parameters of bowstringing, resolution of Notta's node, thumb interphalangeal motion, and patient/parent satisfaction were assessed. Results The oblique pulley appeared stenotic, whereas the annular pulley was observed to be membranous and nearly indistinguishable from the tendon sheath. No patients had recurrence of thumb locking or triggering. No bowstringing was detected, and Notta’s node resolved fully in 19 of 20 thumbs. Five thumbs had an average of 12o less active IP joint motion without flexion contracture (i.e., less flexion). All patients or families expressed overall satisfaction with the procedure. Conclusion The annular pulley was attenuated in the majority of cases and the proximal half of the oblique pulley was stenotic in all patients. Releasing 50% of the oblique pulley after complete annular pulley release was necessary in all thumbs to achieve full FPL excursion. Mistaking the constricted proximal oblique pulley for an annular pulley may encourage releasing the entire oblique pulley, leading to an adverse result. Satisfactory outcome was achieved after surgical treatment of pediatric locked trigger thumbs. Type of Study/Level of Evidence Therapeutic IV. PMID:22131924

78 FR 38074 - Announcement Regarding a Change in Eligibility for Unemployment Insurance (UI) Claimants in...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-06-25

...Announcement regarding a change in eligibility for Unemployment Insurance (UI) claimants in Alabama, Alaska, Delaware, Illinois, Louisiana, Michigan, Mississippi, Ohio, the Virgin Islands and Wisconsin in the Emergency Unemployment Compensation (EUC08) program, and the Federal-State Extended Benefits (EB) program. The U.S. Department of Labor (Department) produces trigger notices indicating which states qualify for both EB and EUC08 benefits, and provides the beginning and ending dates of payable periods for each qualifying state. The trigger notices covering state eligibility for these programs can be found at: http://ows.doleta.gov/unemploy/claims-- arch.asp. The following changes have occurred since the publication of the last notice regarding states EUC08 and EB trigger status: Alabama's trigger value had fallen below the 7.0% threshold and has triggered ``off'' Tier 3 of EUC08. Based on data released by the Bureau of Labor Statistics on March 18, 2013, the three month average, seasonally adjusted total unemployment rate (TUR) in Alabama was 6.9%, falling below the 7.0% trigger threshold necessary to remain ``on'' Tier 3 of EUC08. The week ending April 13, 2013, was the last week in which EUC08 claimants in Alabama could exhaust Tier 2 and establish Tier 3 eligibility. Under the phase-out provisions, claimants could receive any remaining entitlement they had for Tier 3 after April 13, 2013. Alaska's insured unemployment rate (IUR) has fallen below the 6.0% trigger threshold and has triggered ``off'' of EB. Based on data from Alaska for the week ending April 13, 2013, the 13 week IUR in Alaska fell below the 6.0% trigger threshold necessary to remain ``on'' EB. The payable period in EB for Alaska ended May 4, 2013. Alaska's IUR has fallen below the 6.0% trigger threshold and has triggered ``off'' Tier 4 of EUC08. Based on data from Alaska for the week ending April 13, 2013, the 13 week IUR in Alaska fell below the 6.0% trigger rate threshold to remain ``on'' Tier 4 of EUC08. The week ending May 4, 2013, was the last week in which EUC08 claimants in Alaska could exhaust Tier 3, and establish Tier 4 eligibility. Under the phase-out provisions, claimants could receive any remaining entitlement they had for Tier 4 after May 4, 2013. Delaware's trigger value exceeds the 7.0% trigger threshold and has triggered ``on'' Tier 3 of EUC08. Based on data released by the Bureau of Labor Statistics on March 18, 2013, the three month average, seasonally adjusted TUR in Delaware was 7.1%, exceeding the 7.0% threshold necessary to trigger ``on'' Tier 3 of EUC08. The week beginning April 7, 2013, was the first week in which EUC08 claimants in Delaware who had exhausted Tier 2, and are otherwise eligible, could establish Tier 3 eligibility. Illinois' trigger value met the 9.0% trigger threshold and has triggered ``on'' Tier 4 of EUC08. Based on data released by the Bureau of Labor Statistics on March 29, 2013, the three month average, seasonally adjusted TUR in Illinois met the 9.0% trigger threshold to trigger ``on'' Tier 4 of EUC08. The week beginning April 14, 2013, was the first week in which EUC08 claimants in Illinois who had exhausted Tier 3, and were otherwise eligible, could establish Tier 4 eligibility. Louisiana's trigger value has fallen below the 6.0% trigger threshold and has triggered ``off'' Tier 2 of EUC08. Based on data released by the Bureau of Labor Statistics on March 18, 2013, the three month average, seasonally adjusted TUR in Louisiana was 5.8%, falling below the 6.0% trigger threshold to remain ``on'' Tier 2 of EUC08. The week ending April 13, 2013, was the last week in which EUC08 claimants in Louisiana could exhaust Tier 1, and establish Tier 2 eligibility. Under the phase-out provisions, claimants could receive any remaining entitlement they had in Tier 2 after April 13, 2013. Michigan's trigger value has fallen below the 9.0% trigger threshold and has triggered ``off'' Tier 4 of EUC08. Based on data released by the Bureau of Labor Statistics on March 18, 2013, the three month average, seasonally adjusted TUR for Michigan was 8.9%, falling below the 9.0% trigger threshold to remain ``on'' Tier 4 of EUC08. The week ending April 13, 2013, was the last week in which EUC08 claimants in Michigan could exhaust Tier 3, and establish Tier 4 eligibility. Under the phase-out provisions, claimants could receive any remaining entitlement they had in Tier 4 after April 13, 2013. Mississippi's trigger value exceeds the 9.0% trigger threshold and has triggered ``on'' Tier 4 of EUC08. Based on data released by the Bureau of Labor Statistics on March 29, 2013, the three month average, seasonally adjusted TUR in Mississippi was 9.3%, exceeding the 9.0% trigger threshold to trigger ``on'' Tier 4 of EUC08. The week beginning April 14, 2013, was the first week in which EUC08 claimants in Mississippi who had exhausted Tier 3, and are otherwise eligible, could establish Tier 4 eligibility. Ohio's trigger value met the 7.0% trigger threshold and has triggered ``on'' Tier 3 of EUC08. Based on data released by the Bureau of Labor Statistics on April 19, 2013, the three month average, seasonally adjusted total unemployment rate in Ohio had met 7.0% trigger threshold to trigger ``on'' in Tier 3 of EUC08. The week beginning May 5, 2013, was the first week in which EUC08 claimants in Ohio who had exhausted Tier 2, and were otherwise eligible, could establish Tier 3 eligibility. The Virgin Islands' estimated trigger rate fell below the 6.0% threshold and has triggered ``off'' both Tier 2 and Tier 3 of EUC08. Based on data released by the Bureau of Labor Statistics on March 8, 2013, the estimated three month average, seasonally adjusted TUR in the Virgin Islands fell below the 6.0% trigger threshold rate to remain ``on'' both Tier 2 and Tier 3 of EUC08. That triggered the Virgin Islands off both Tier 2 and Tier 3 of EUC08. The week ending March, 30 2013, was the last week in which EUC08 claimants in the Virgin Islands could exhaust Tier 1 and establish Tier 2 eligibility, or exhaust Tier 2 and establish Tier 3 eligibility. Wisconsin's trigger value met the 7.0% threshold and has triggered ``on'' Tier 3 of EUC08, however mandatory 13 week ``off'' period delayed effective date. Based on data released by the Bureau of Labor Statistics on April 19, 2013, the three month average, seasonally adjusted TUR for Wisconsin has met the 7.0% trigger rate threshold to trigger ``on'' Tier 3 of EUC08. However, Wisconsin was in a 13 week mandatory ``off'' period that started February 9, 2013, and did not conclude until May 11, 2013. As a result, Wisconsin remained in an ``off'' period for Tier 3 of EUC08 through May 11, 2013, and triggered ``on'' Tier 3 of EUC08 effective May 12, 2013. The week beginning May 12, 2013, was the first week in which EUC08 claimants in Wisconsin who have exhausted Tier 2, and are otherwise eligible, can establish Tier 3 eligibility.

A novel fluoride anion modified gelatin nanogel system for ultrasound-triggered drug release.

PubMed

Wu, Daocheng; Wan, Mingxi

2008-01-01

Controlled drug release, especially tumor-targeted drug release, remains a great challenge. Here, we prepare a novel fluoride anion-modified gelatin nanogel system and investigate its characteristics of ultrasound-triggered drug release. Adriamycin gelatin nanogel modified with fluoride anion (ADM-GNMF) was prepared by a modified co-precipitation method with fluoride anion and sodium sulfate. The loading and encapsulation efficiency of the anti-neoplastic agent adriamycin (ADM) were measured by high performance liquid chromatography (HPLC). The size and shape of ADM-GNMF were determined by electron microscopy and photo-correlation spectroscopy. The size distribution and drug release efficiency of ADM-GNMF, before and after sonication, were measured by two designed measuring devices that consisted of either a submicron particle size analyzer and an ultrasound generator as well as an ultrasound generator, automatic sampler, and HPLC. The ADM-GNMF was stable in solution with an average diameter of 46+/-12 nm; the encapsulation and loading efficiency of adriamycin were 87.2% and 6.38%, respectively. The ultrasound-triggered drug release and size change were most efficient at a frequency of 20 kHz, power density of 0.4w/cm2, and a 1~2 min duration. Under this ultrasound-triggered condition, 51.5% of drug in ADM-GNMF was released within 1~2 min, while the size of ADM-GNMF changed from 46 +/- 12 nm to 1212 +/- 35 nm within 1~2 min of sonication and restored to its previous size in 2~3 min after the ultrasound stopped. In contrast, 8.2% of drug in ADM-GNMF was released within 2~3 min without sonication, and only negligible size changes were found. The ADM-GNMF system efficiently released the encompassed drug in response to ultrasound, offering a novel and promising controlled drug release system for targeted therapy for cancer or other diseases.

Flow of viscoplastic suspensions in a hydraulic fracture: implications to overflush

NASA Astrophysics Data System (ADS)

Boronin, S. A.; Osiptsov, A. A.; Desroches, J.

2017-10-01

The study is devoted to modeling of multiphase flows of immiscible viscoplastic fluids in a hydraulic fracture. In the framework of the lubrication approximation, three-dimensional Navier-Stokes equations are reduced to hyperbolic transport equations for the fluid tracers and a quasi-linear elliptic equation in terms of the fluid pressure. The governing equations are solved numerically using the finite-difference approach. A parametric study of the displacement of Bingham fluids in a Hele-Shaw cell is carried out. It is found that fingers developed through the pillar of a yield-stress suspension trigger the development of unyielded zones. An increase in the Bingham number leads to an increase in the so-called finger shielding effect, which manifests itself via an increase in the overall finger penetration zone and a decrease in the total number of fingers. The effect of flow parameters on the displacement of hydraulic fracturing proppant-laden suspension by a clean fluid in the vicinity of the perforation zone is carried out. This particular case is considered in application to overflush at the end of a stimulation treatment, when a small portion of a thin clean fluid is injected to wash out the particles from the wellbore into the fracture. It is found that an increase in the yield stress and the viscosity contrast between the fracturing and the overflush fluids typically reduces the area of the cavity thus mitigating the risk of loosing the conductive path between the wellbore and the fracture after the fracture closure.

Site-Specific Editing of the Plasmodium falciparum Genome Using Engineered Zinc-Finger Nucleases

PubMed Central

Straimer, Judith; Lee, Marcus CS; Lee, Andrew H; Zeitler, Bryan; Williams, April E; Pearl, Jocelynn R; Zhang, Lei; Rebar, Edward J; Gregory, Philip D; Llinás, Manuel; Urnov, Fyodor D; Fidock, David A

2013-01-01

Malaria afflicts over 200 million people worldwide and its most lethal etiologic agent, Plasmodium falciparum, is evolving to resist even the latest-generation therapeutics. Efficient tools for genome-directed investigations of P. falciparum pathogenesis, including drug resistance mechanisms, are clearly required. Here we report rapid and targeted genetic engineering of this parasite, using zinc-finger nucleases (ZFNs) that produce a double-strand break in a user-defined locus and trigger homology-directed repair. Targeting an integrated egfp locus, we obtained gene deletion parasites with unprecedented speed (two weeks), both with and without direct selection. ZFNs engineered against the endogenous parasite gene pfcrt, responsible for chloroquine treatment escape, rapidly produced parasites that carried either an allelic replacement or a panel of specified point mutations. The efficiency, versatility and precision of this method will enable a diverse array of genome editing approaches to interrogate this human pathogen. PMID:22922501

Hydrodynamic Fingering Instability Induced by a Precipitation Reaction

NASA Astrophysics Data System (ADS)

Nagatsu, Y.; Ishii, Y.; Tada, Y.; De Wit, A.

2014-07-01

We experimentally demonstrate that a precipitation reaction at the miscible interface between two reactive solutions can trigger a hydrodynamic instability due to the buildup of a locally adverse mobility gradient related to a decrease in permeability. The precipitate results from an A +B→C type of reaction when a solution containing one of the reactants is injected into a solution of the other reactant in a porous medium or a Hele-Shaw cell. Fingerlike precipitation patterns are observed upon displacement, the properties of which depend on whether A displaces B or vice versa. A mathematical modeling of the underlying mobility profile confirms that the instability originates from a local decrease in mobility driven by the localized precipitation. Nonlinear simulations of the related reaction-diffusion-convection model reproduce the properties of the instability observed experimentally. In particular, the simulations suggest that differences in diffusivity between A and B may contribute to the asymmetric characteristics of the fingering precipitation patterns.

Design and Fabrication of a Universal Soft Gripper

NASA Astrophysics Data System (ADS)

Sabzehzar, Amin

Inspired from nature, soft robots capable of actively tuning their mechanical rigidity can rapidly transition between a broad range of motor tasks, from lifting heavy loads to dexterous manipulation of delicate objects. Reversible rigidity tuning also enables soft robotic actuators to reroute their internal loading and alter their mode of deformation in response to intrinsic activation. In this study, we demonstrate this principle with a three-fingered pneumatic gripper that contains programmable ligaments that change stiness when activated with electrical current. The ligaments are composed of a conductive thermoplastic elastomer composite that reversibly softens under resistive heating. Depending on which ligaments are activated, the gripper will bend inward to pick up an object, bend laterally to twist it, or bend outward to release it. Each finger consists of three PDMS phalanges that are attached with two Ecoflex joints. Three ligaments (strips of a cPBE-PDMS composite layer) are attached along the finger and are stimulated with electricity individually. When the high pressure air is injected in the hollow middle part of the finger, the finger will be bent in the opposite direction of the stimulated cPBE-PDMS element (softer wall). This enables the gripper's fingers to grab and twist objects with dierent sizes and shapes. All of the gripper motions are generated with a single pneumatic source of pressure and are controlled with an electrical board. The ability to incorporate electrically programmable ligaments in pneumatic or hydraulic actuators has the potential to enhance versatility and reduce dependency on tubing and valves. In this study, an activation/deactivation cycle can be completed within 15 s.

Frostbite in an adolescent football player: a case report.

PubMed

Rivlin, Michael; King, Marnie; Kruse, Richard; Ilyas, Asif M

2014-01-01

To present the case of vascular compromise of a finger from a confluent circumferential blister due to an inappropriately applied commercial cold pack in a high school athlete and to describe the mechanism of iatrogenic injury, acute surgical management, rehabilitation, and pathophysiology of frostbite and constriction injuries. A 17-year-old male football player presented with a frostbite and constriction injury to the index finger secondary to prolonged use of a cooling pack after a mild traumatic injury to the digit. He developed a prolonged sensory deficit from thermal injury, as well as acute vascular compromise requiring urgent operative intervention. Frostbite and constriction injury to the index finger. Emergency surgical decompression and occupational therapy. Frostbite injuries can occur iatrogenically because of inappropriate use of cooling devices or gel packs. Fingers are commonly injured extremities that are particularly susceptible to frostbite and compression injuries. To our knowledge, no case of vascular compromise from the blister constriction of digits has been reported. Patients and their caregivers must be educated about how to properly use cooling devices. Clinicians need to fully evaluate patients with iatrogenic frostbite injuries, giving particular attention to neurovascular status, and must recognize the need for surgical release of constriction syndrome to prevent substantial morbidity.

Mechanistic Studies on the Triggered Release of Liposomal Contents by Matrix Metalloproteinase-9

PubMed Central

Elegbede, Adekunle I.; Banerjee, Jayati; Hanson, Andrea J.; Tobwala, Shakila; Ganguli, Bratati; Wang, Rongying; Lu, Xiaoning; Srivastava, D. K.; Mallik, Sanku

2009-01-01

Matrix metalloproteinases (MMPs) are a class of extracellular matrix degrading enzymes over-expressed in many cancers and contribute to the metastatic ability of the cancer cells. We have recently demonstrated that liposomal contents can be released when triggered by the enzyme MMP-9. Herein, we report our results on the mechanistic studies of the MMP-9 triggered release of the liposomal contents. We synthesized peptides containing the cleavage site for MMP-9 and conjugated them with fatty acids to prepare the corresponding lipopeptides. By employing Circular Dichroism spectroscopy, we demonstrate that the lipopeptides, when incorporated in liposomes, are de-mixed in the lipid bilayers and generate triple helical structures. MMP-9 cleaves the triple helical peptides, leading to the release of the liposomal contents. Other MMPs, which cannot hydrolyze triple helical peptides, failed to release the contents from the liposomes. We also observed that the rate and the extent of release of the liposomal contents depend on the mismatch between acyl chains of the synthesized lipopeptide and phospholipid components of the liposomes. Circular Dichroism spectroscopic studies imply that the observed differences in the release reflect the ability of the liposomal membrane to anneal the defects following the enzymatic cleavage of the liposome-incorporated lipopeptides. PMID:18642903

Nickel (II) nitrate hexahydrate triggered canine neutrophil extracellular traps release in vitro.

PubMed

Wei, Zhengkai; Zhang, Xu; Wang, Yanan; Wang, Jingjing; Fu, Yunhe; Yang, Zhengtao

2018-05-30

Nickel (II) nitrate hexahydrate (Ni) is a common heavy metal material in battery manufacturing, electroplating alloy parts and ceramic staining, therefore we frequently contact with Ni-related products in daily life. In this study, we aimed to investigate the effects of Ni on neutrophils extracellular traps (NETs) release by canine polymorphonuclear neutrophils (PMNs). The structure of Ni-induced NETs was observed by fluorescence confocal microscopy. Ni-triggered NETs release was quantified by Pico Green ® and fluorescence microplate reader. In addition, the inhibitors of NADPH oxidase, ERK1/2-, p38 - signaling pathways were used for preliminary inquiry into the potential mechanism of this process. The results showed that Ni markedly triggered the formation of NETs-like structures, and these structures were mainly consisted of DNA decorated with NE and MPO. Furthermore, quantification experiments showed that Ni significantly increased NETs formation compared to control groups. These results forcefully confirmed that nickel nitrate possesses the ability to induce NETs formation. However, inhibiting the NADPH oxidase, ERK1/2- and p38 MAPK-signaling pathways did not significantly change the quantitation of Ni-induced NETs release. To our knowledge, this study is the first report of Ni-triggered NETs release in vitro, which might provide an entirely new mechanism of several diseases and health issues induced by nickel overexposure. Copyright © 2018. Published by Elsevier Ltd.

In vitro selection of shape-changing DNA nanostructures capable of binding-induced cargo release.

PubMed

Oh, Seung Soo; Plakos, Kory; Xiao, Yi; Eisenstein, Michael; Soh, H Tom

2013-11-26

Many biological systems employ allosteric regulatory mechanisms, which offer a powerful means of directly linking a specific binding event to a wide spectrum of molecular functionalities. There is considerable interest in generating synthetic allosteric regulators that can perform useful molecular functions for applications in diagnostics, imaging and targeted therapies, but generating such molecules through either rational design or directed evolution has proven exceptionally challenging. To address this need, we present an in vitro selection strategy for generating conformation-switching DNA nanostructures that selectively release a small-molecule payload in response to binding of a specific trigger molecule. As an exemplar, we have generated a DNA nanostructure that hybridizes with a separate 'cargo strand' containing an abasic site. This abasic site stably sequesters a fluorescent cargo molecule in an inactive state until the DNA nanostructure encounters an ATP trigger molecule. This ATP trigger causes the nanostructure to release the cargo strand, thereby liberating the fluorescent payload and generating a detectable fluorescent readout. Our DNA nanostructure is highly sensitive, with an EC50 of 30 μM, and highly specific, releasing its payload in response to ATP but not to other chemically similar nucleotide triphosphates. We believe that this selection approach could be generalized to generate synthetic nanostructures capable of selective and controlled release of other small-molecule cargos in response to a variety of triggers, for both research and clinical applications.

Development of Active Control Method for Supercooling Releasing of Water

NASA Astrophysics Data System (ADS)

Mito, Daisuke; Kozawa, Yoshiyuki; Tanino, Masayuki; Inada, Takaaki

We have tested the prototype ice-slurry generator that enables both production of supercooled water (-2°C) and releasing of its supercooling simultaneously and continuously in a closed piping system. In the experiment, we adopted the irradiation of ultrasonic wave as an active control method of triggering for supercooling releasing, and evaluated the reliability for a practical use compared with the seed ice-crystal trigger. As the results, it has been confirmed that the ultrasonic wave trigger acts assuredly at the same level of degree of supercooling as that by using the seed ice-crystal Trigger. Moreover, it can be found that the ultrasonic wave trigger has the advantage of removing the growing ice-crystals on the pipe wall at the same time. Finally, we have specified the bombardment condition of ultrasonic wave enough to make continuously the ice-slurry in a closed system as the output surface power density > 31.4kW/m2 and the superficial bombardment time > 4.1sec. We have also demonstrated the continuous ice-slurry making for more than 6hours by using the refrigerator system with the practical scale of 88kW.

Spontaneous Release Regulates Synaptic Scaling in the Embryonic Spinal Network In Vivo

PubMed Central

Garcia-Bereguiain, Miguel Angel; Gonzalez-Islas, Carlos; Lindsly, Casie

2016-01-01

Homeostatic plasticity mechanisms maintain cellular or network spiking activity within a physiologically functional range through compensatory changes in synaptic strength or intrinsic cellular excitability. Synaptic scaling is one form of homeostatic plasticity that is triggered after blockade of spiking or neurotransmission in which the strengths of all synaptic inputs to a cell are multiplicatively scaled upward or downward in a compensatory fashion. We have shown previously that synaptic upscaling could be triggered in chick embryo spinal motoneurons by complete blockade of spiking or GABAA receptor (GABAAR) activation for 2 d in vivo. Here, we alter GABAAR activation in a more physiologically relevant manner by chronically adjusting presynaptic GABA release in vivo using nicotinic modulators or an mGluR2 agonist. Manipulating GABAAR activation in this way triggered scaling in a mechanistically similar manner to scaling induced by complete blockade of GABAARs. Remarkably, we find that altering action-potential (AP)-independent spontaneous release was able to fully account for the observed bidirectional scaling, whereas dramatic changes in spiking activity associated with spontaneous network activity had little effect on quantal amplitude. The reliance of scaling on an AP-independent process challenges the plasticity's relatedness to spiking in the living embryonic spinal network. Our findings have implications for the trigger and function of synaptic scaling and suggest that spontaneous release functions to regulate synaptic strength homeostatically in vivo. SIGNIFICANCE STATEMENT Homeostatic synaptic scaling is thought to prevent inappropriate levels of spiking activity through compensatory adjustments in the strength of synaptic inputs. Therefore, it is thought that perturbations in spike rate trigger scaling. Here, we find that dramatic changes in spiking activity in the embryonic spinal cord have little effect on synaptic scaling; conversely, alterations in GABAA receptor activation due to action-potential-independent GABA vesicle release can trigger scaling. The findings suggest that scaling in the living embryonic spinal cord functions to maintain synaptic strength and challenge the view that scaling acts to regulate spiking activity homeostatically. Finally, the results indicate that fetal exposure to drugs that influence GABA spontaneous release, such as nicotine, could profoundly affect synaptic maturation. PMID:27383600

Remote modulation of neural activities via near-infrared triggered release of biomolecules.

PubMed

Li, Wei; Luo, Rongcong; Lin, Xudong; Jadhav, Amol D; Zhang, Zicong; Yan, Li; Chan, Chung-Yuan; Chen, Xianfeng; He, Jufang; Chen, Chia-Hung; Shi, Peng

2015-10-01

The capability to remotely control the release of biomolecules provides an unique opportunity to monitor and regulate neural signaling, which spans extraordinary spatial and temporal scales. While various strategies, including local perfusion, molecular "uncaging", or photosensitive polymeric materials, have been applied to achieve controlled releasing of neuro-active substances, it is still challenging to adopt these technologies in many experimental contexts that require a straightforward but versatile loading-releasing mechanism. Here, we develop a synthetic strategy for remotely controllable releasing of neuro-modulating molecules. This platform is based on microscale composite hydrogels that incorporate polypyrrole (PPy) nanoparticles as photo-thermal transducers and is triggered by near-infrared-light (NIR) irradiation. Specifically, we first demonstrate the utility of our technology by recapitulating the "turning assay" and "collapse assay", which involve localized treatment of chemotactic factors (e.g. Netrin or Semaphorin 3A) to subcellular neural elements and have been extensively used in studying axonal pathfinding. On a network scale, the photo-sensitive microgels are also validated for light-controlled releasing of neurotransmitters (e.g. glutamate). A single NIR-triggered release is sufficient to change the dynamics of a cultured hippocampal neuron network. Taking the advantage of NIR's capability to penetrate deep into live tissue, this technology is further shown to work similarly well in vivo, which is evidenced by synchronized spiking activity in response to NIR-triggered delivery of glutamate in rat auditory cortex, demonstrating remote control of brain activity without any genetic modifications. Notably, our nano-composite microgels are capable of delivering various molecules, ranging from small chemicals to large proteins, without involving any crosslinking chemistry. Such great versatility and ease-of-use will likely make our optically-controlled delivery technology a general and important tool in cell biology research. Copyright © 2015 Elsevier Ltd. All rights reserved.

Programmable hydrogels for controlled cell catch and release using hybridized aptamers and complementary sequences.

PubMed

Zhang, Zhaoyang; Chen, Niancao; Li, Shihui; Battig, Mark R; Wang, Yong

2012-09-26

The ability to regulate cell-material interactions is important in various applications such as regenerative medicine and cell separation. This study successfully demonstrates that the binding states of cells on a hydrogel surface can be programmed by using hybridized aptamers and triggering complementary sequences (CSs). In the absence of the triggering CSs, the aptamers exhibit a stable, hybridized state in the hydrogel for cell-type-specific catch. In the presence of the triggering CSs, the aptamers are transformed into a new hybridized state that leads to the rapid dissociation of the aptamers from the hydrogel. As a result, the cells are released from the hydrogel. The entire procedure of cell catch and release during the transformation of the aptamers is biocompatible and does not involve any factor destructive to either the cells or the hydrogel. Thus, the programmable hydrogel is regenerable and can be applied to a new round of cell catch and release when needed.

Thermosensitive liposomes for localized delivery and triggered release of chemotherapy

PubMed Central

Ta, Terence; Porter, Tyrone M.

2016-01-01

Liposomes are a promising class of nanomedicine with the potential to provide site-specific chemotherapy, thus improving the quality of cancer patient care. First-generation liposomes have emerged as one of the first nanomedicines used clinically for localized delivery of chemotherapy. Second-generation liposomes, i.e. stimuli-responsive liposomes, have the potential to not only provide site-specific chemotherapy, but also triggered drug release and thus greater spatial and temporal control of therapy. Temperature-sensitive liposomes are an especially attractive option, as tumors can be heated in a controlled and predictable manner with external energy sources. Traditional thermosensitive liposomes are composed of lipids that undergo a gel-to-liquid phase transition at several degrees above physiological temperature. More recently, temperature-sensitization of liposomes has been demonstrated with the use of lysolipids and synthetic temperature-sensitive polymers. The design, drug release behavior, and clinical potential of various temperature-sensitive liposomes, as well as the various heating modalities used to trigger release, are discussed in this review. PMID:23583706

Slip triggered on southern California faults by the 1992 Joshua Tree, Landers, and big bear earthquakes

USGS Publications Warehouse

Bodin, Paul; Bilham, Roger; Behr, Jeff; Gomberg, Joan; Hudnut, Kenneth W.

1994-01-01

Five out of six functioning creepmeters on southern California faults recorded slip triggered at the time of some or all of the three largest events of the 1992 Landers earthquake sequence. Digital creep data indicate that dextral slip was triggered within 1 min of each mainshock and that maximum slip velocities occurred 2 to 3 min later. The duration of triggered slip events ranged from a few hours to several weeks. We note that triggered slip occurs commonly on faults that exhibit fault creep. To account for the observation that slip can be triggered repeatedly on a fault, we propose that the amplitude of triggered slip may be proportional to the depth of slip in the creep event and to the available near-surface tectonic strain that would otherwise eventually be released as fault creep. We advance the notion that seismic surface waves, perhaps amplified by sediments, generate transient local conditions that favor the release of tectonic strain to varying depths. Synthetic strain seismograms are presented that suggest increased pore pressure during periods of fault-normal contraction may be responsible for triggered slip, since maximum dextral shear strain transients correspond to times of maximum fault-normal contraction.

Zn(2+)-Triggered Drug Release from Biocompatible Zirconium MOFs Equipped with Supramolecular Gates.

PubMed

Tan, Li-Li; Li, Haiwei; Zhou, Yue; Zhang, Yuanyuan; Feng, Xiao; Wang, Bo; Yang, Ying-Wei

2015-08-01

A new theranostic nanoplatform, comprising of monodisperse zirconium metal-organic frameworks (MOFs) as drug carriers and carboxylatopillar[5]arene-based supramolecular switches as gating entities, is constructed, and controlled drug release triggered by bio-friendly Zn(2+) ions (abundant in synaptic vesicles) and auxiliary thermal stimulus is realized. This on-command drug delivery system exhibits large pore sizes for drug encapsulation, excellent biodegradability and biocompatibility, extremely low cytotoxicity and premature drug release, and superior dual-stimuli responsiveness, opening a new avenue in targeted drug delivery and controlled release of therapeutic agents, especially in the treatment of central nervous system diseases. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Collagenase Treatment in Dupuytren Contractures: A Review of the Current State Versus Future Needs.

PubMed

Degreef, Ilse

2016-06-01

Dupuytren disease is highly prevalent and the finger contractures can be very extensile, compromising the patients' hand function. To restore full function, contractures have been addressed by cutting the causative strands for nearly 200 years, ever since Baron Guillaume Dupuytren demonstrated his technique at the beginning of the nineteenth century. Surgery can be minimal (fasciotomy) or quite invasive (fasciectomy and even skin replacement). However, in the last decade translational research has introduced the non-surgical technique of enzymatic fasciotomy with collagenase injections. Now, finger contractures can be released with single injections on monthly intervals, to address one joint contracture at a time. However, in hands affected with Dupuytren contractures to the extent that the patient calls for treatment, most often more than one joint is involved. In surgical treatment options all contracted joints are addressed in a single procedure. Nevertheless, extensile surgery withholds inherent risks of complications and intense rehabilitation. Today, the minimally-invasive method with enzymatic fasciotomy by collagenase injection has demonstrated reliable outcomes with few morbidities and early recovery. However, single-site injection is todays' standard procedure and multiple joints are addressed in several sessions with monthly intervals. This triggers a longer recovery and treatment burden in severely affected hands even though surgery is avoided. Therefore, further treatment modalities of collagenase use are explored. Adjustments in the treatment regimes' flexibility and collagenase injections addressing more than one joint contracture simultaneously will improve the burden of multiple sessions and, therefore, enzymatic fasciotomy may become the preferred method in more extensile Dupuytren contractures. In this independent review, the challenge of Dupuytren disease affecting a single versus multiple joints is presented. The pros and cons of collagenase use are weighed, founded by the available scientific background. The demands and options for collagenase in future treatment regimens for extensile Dupuytren contractures are discussed.

Mixing and Transport in the Solar Nebula

NASA Technical Reports Server (NTRS)

Boss, Alan P.

2003-01-01

Boss & Vanhala (2000, 2001) prepared reviews of triggered collapse and injection models, using Prudence Foster's finite differences code at very high spatial resolution (440 x 1440 cells) to demonstrate the convergence of the R-T fingers in triggered injection models. A two dimensional hydrodynamical calculation with unprecedentedly high spatial resolution (960 x 2880 zones, or almost 3 million grid points) demonstrated that it suitable shock front can both trigger the collapse of an otherwise stable presolar cloud, and inject shock front particles into the collapsing cloud through the formation of what become Rayleigh-Taylor fingers of compressed fluid layers falling into the gravitational potential well of the growing protostar. These calculations suggest that heterogeneity derived from these R-T fingers will persist down to the scale of their injection onto the surface of the solar nebula. Haghighipour developed a numerical code capable of calculating the orbital evolution of dust grains of varied sizes in a gaseous nebula, subject to Epstein and Stokes drag as well as the self-gravity of the disk. In collaboration with the PI and George W. Wetherill, Haghighipour has been involved in development of a new idea on the possibility of rapid formation of ice giant planets via the disk instability mechanism. Haghighipour studied the stability of a five-body system consisting of the Sun and four protoplanets by numerically integrating their equations of motions. Using Levison and Duncan s SWIFT integrator, Haghighipour showed that, depending on the orbital parameters of the bodies, such a system can be stable for 0.1-10 Myr. Time periods of 1 Myr or more are long enough to be consistent with the time scale proposed for the formation of giant planets by the disk instability mechanism and the photoevaporation of the gaseous envelopes of the outermost protoplanets by a nearby OB star, resulting in the formation of ice giant planets. The PI has used his three dimensional models of marginally gravitationally unstable disks to study the preservation of isotopic heterogeneity in evolving protoplanetary disks. Such heterogeneity might arise from the infall onto the disk s surface of solids processed in the X-wind region of the disk, or derived from stellar nucleosynthesis and injected by R-T fingers. The technique used consists of solving a color equation, identical to the gas continuity equation, which follows the time evolution in three space dimensions of an arbitrarily placed initial color field, i.e., a dye inserted the disk. The models show that significant concentrations of color could persist for time periods of about a thousand years or more, even in the most dynamically active region of such a disk. Such a time period might be long enough for solids to coagulate and grow to significant sizes while retaining the isotopic signature of their birth region in the nebula.

Assessment of the Short-Term Effectiveness of Kinesiotaping and Trigger Points Release Used in Functional Disorders of the Masticatory Muscles

PubMed Central

Lietz-Kijak, Danuta; Kopacz, Łukasz; Grzegocka, Marta

2018-01-01

Chronic face pain syndrome is a diagnostic and therapeutic problem for many specialists, and this proves the interdisciplinary and complex nature of this ailment. Physiotherapy is of particular importance in the treatment of pain syndrome in the course of temporomandibular joint functional disorders. In patients with long-term dysfunction of masticatory muscles, the palpation examination can localize trigger points, that is, thickening in the form of nodules in the size of rice grains or peas. Latent trigger points located in the muscles can interfere with muscular movement patterns, cause cramps, and reduce muscle strength. Because hidden trigger points can spontaneously activate, they should be found and released to prevent further escalation of the discomfort. Kinesiotaping (KT) is considered as an intervention that can be used to release latent myofascial trigger points. It is a method that involves applying specific tapes to the patient's skin in order to take advantage of the natural self-healing processes of the body. The aim of the study was to evaluate the effect of the kinesiotaping method and trigger points inactivation on the nonpharmacological elimination of pain in patients with temporomandibular disorders. The study was conducted in 60 patients (18 to 35 years old). The subjects were randomly divided into two subgroups of 30 people each. Group KT (15 women and 15 men) were subjected to active kinesiotaping application. Group TrP, composed of 16 women and 14 men, was subjected to physiotherapy with the release of trigger points by the ischemic compression method. The results show that the KT method and TrP inactivation brought significant therapeutic analgesic effects in the course of pain-related functional disorders of the muscles of mastication. The more beneficial outcomes of the therapy were observed after using the KT method, which increased the analgesic effect in dysfunctional patients. PMID:29861804

Reduction-Responsive Polymeric Micelles and Vesicles for Triggered Intracellular Drug Release

PubMed Central

Sun, Huanli; Cheng, Ru; Deng, Chao

2014-01-01

Abstract Significance: The therapeutic effects of current micellar and vesicular drug formulations are restricted by slow and inefficient drug release at the pathological site. The development of smart polymeric nanocarriers that release drugs upon arriving at the target site has received a tremendous amount of attention for cancer therapy. Recent Advances: Taking advantage of a high reducing potential in the tumor tissues and in particular inside the tumor cells, various reduction-sensitive polymeric micelles and vesicles have been designed and explored for triggered anticancer drug release. These reduction-responsive nanosystems have demonstrated several unique features, such as good stability under physiological conditions, fast response to intracellular reducing environment, triggering drug release right in the cytosol and cell nucleus, and significantly improved antitumor activity, compared to traditional reduction-insensitive counterparts. Critical Issues: Although reduction-sensitive micelles and polymersomes have accomplished rapid intracellular drug release and enhanced in vitro antitumor effect, their fate inside the cells including the mechanism, site, and rate of reduction reaction remains unclear. Moreover, the systemic fate and performance of reduction-sensitive polymeric drug formulations have to be investigated. Future Directions: Biophysical studies should be carried out to gain insight into the degradation and drug release behaviors of reduction-responsive nanocarriers inside the tumor cells. Furthermore, novel ligand-decorated reduction-sensitive nanoparticulate drug formulations should be designed and explored for targeted cancer therapy in vivo. Antioxid. Redox Signal. 21, 755–767. PMID:24279980

MLKL Activation Triggers NLRP3-Mediated Processing and Release of IL-1β Independently of Gasdermin-D.

PubMed

Gutierrez, Kimberley D; Davis, Michael A; Daniels, Brian P; Olsen, Tayla M; Ralli-Jain, Pooja; Tait, Stephen W G; Gale, Michael; Oberst, Andrew

2017-03-01

Necroptosis is a form of programmed cell death defined by activation of the kinase receptor interacting protein kinase 3 and its downstream effector, the pseudokinase mixed lineage kinase domain-like (MLKL). Activated MLKL translocates to the cell membrane and disrupts it, leading to loss of cellular ion homeostasis. In this study, we use a system in which this event can be specifically triggered by a small-molecule ligand to show that MLKL activation is sufficient to induce the processing and release of bioactive IL-1β. MLKL activation triggers potassium efflux and assembly of the NLRP3 inflammasome, which is required for the processing and activity of IL-1β released during necroptosis. Notably, MLKL activation also causes cell membrane disruption, which allows efficient release of IL-1β independently of the recently described pyroptotic effector gasdermin-D. Taken together, our findings indicate that MLKL is an endogenous activator of the NLRP3 inflammasome, and that MLKL activation provides a mechanism for concurrent processing and release of IL-1β independently of gasdermin-D. Copyright © 2017 by The American Association of Immunologists, Inc.

Polymer Coated Echogenic Lipid Nanoparticles with Dual Release Triggers

PubMed Central

Nahire, Rahul; Haldar, Manas K.; Paul, Shirshendu; Mergoum, Anaas; Ambre, Avinash H.; Katti, Kalpana S.; Gange, Kara N.; Srivastava, D. K.; Sarkar, Kausik; Mallik, Sanku

2013-01-01

Although lipid nanoparticles are promising drug delivery vehicles, passive release of encapsulated contents at the target site is often slow. Herein, we report contents release from targeted, polymer coated, echogenic lipid nanoparticles in the cell cytoplasm by redox trigger and simultaneously enhanced by diagnostic frequency ultrasound. The lipid nanoparticles were polymerized on the external leaflet using a disulfide cross-linker. In the presence of cytosolic concentrations of glutathione, the lipid nanoparticles released 76% of encapsulated contents. Plasma concentrations of glutathione failed to release the encapsulated contents. Application of 3 MHz ultrasound for 2 minutes simultaneously with the reducing agent enhanced the release to 96%. Folic acid conjugated, doxorubicin loaded nanoparticles showed enhanced uptake and higher cytotoxicity in cancer cells overexpressing the folate receptor (compared to the control). With further developments, these lipid nanoparticles have the potential to be used as multimodal nanocarriers for simultaneous targeted drug delivery and ultrasound imaging. PMID:23394107

Adjuvant gonadotrophin-releasing hormone agonist trigger with human chorionic gonadotrophin to enhance ooplasmic maturity.

PubMed

Pereira, Nigel; Elias, Rony T; Neri, Queenie V; Gerber, Rachel S; Lekovich, Jovana P; Palermo, Gianpiero D; Rosenwaks, Zev

2016-11-01

This study investigates whether an adjuvant gonadotrophin-releasing hormone agonist (GnRHa) trigger with human chorionic gonadotrophin (HCG) improves fresh intracytoplasmic sperm injection (ICSI) cycle outcomes in patients with poor fertilization history after standard HCG trigger alone. This study compared 156 patients with <40% fertilization rate in a prior ICSI cycle with standard HCG trigger who underwent another ICSI cycle with a combined 2 mg GnRHa and 1500 IU HCG ovulatory trigger. There was no difference in the baseline demographics, ovarian stimulation outcomes or sperm parameters of the groups. More mature oocytes were retrieved in the combined trigger group compared with the HCG trigger group: 12 (9-14) versus 10 (7-12); P = 0.01. The fertilization rate in the combined trigger group (59.2%) was higher than the HCG group (35.3%); P = 0.01. The odds of clinical pregnancy and live birth were 1.8 and 1.7 times higher, respectively, when comparing the former group to the latter; P = 0.03. The results suggest that combined GnRHa and HCG trigger in ICSI cycles is a reasonable approach to increase oocyte maturity, specifically ooplasmic maturity, thereby increasing fertilization and improving ICSI cycle outcomes in patients with a history of poor fertilization after standard HCG trigger alone. Copyright © 2016 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

Risk of Prolonged Opioid Use Among Opioid-Naïve Patients Following Common Hand Surgery Procedures.

PubMed

Johnson, Shepard P; Chung, Kevin C; Zhong, Lin; Shauver, Melissa J; Engelsbe, Michael J; Brummett, Chad; Waljee, Jennifer F

2016-10-01

To evaluate prolonged opioid use in opioid-naïve patients after common hand surgery procedures in the United States. We studied insurance claims from the Truven MarketScan databases to identify opioid-naïve adult patients (no opioid exposure 11 months before the perioperative period) who underwent an elective (carpal tunnel release, carpometacarpal arthroplasty/arthrodesis, cubital tunnel release, or trigger finger release) or trauma-related (closed distal radius fracture fixation, flexor tendon repair, metacarpal fracture fixation, or phalangeal fracture fixation) hand surgery procedure between 2010 and 2012 (N = 77,573 patients). Patients were observed for 6 months to determine the number, timing, duration, and oral morphine equivalent dosage of postoperative opioid prescriptions. We assessed prolonged postoperative opioid use, defined as patients who filled a perioperative opioid prescription followed by a prescription between 90 and 180 days after surgery, and evaluated associated risk factors using multivariable logistic regression. In this cohort, 59,725 opioid-naïve patients (77%) filled a perioperative opioid prescription. Of these, 13% of patients continued to fill prescriptions between 90 and 180 days after surgery. Elective surgery patients were more likely to continue to fill opioid prescriptions after 90 days compared with trauma patients (13.5% vs 10.5%). Younger age, female gender, lower income, comprehensive insurance, higher Elixhauser comorbidity index, mental health disorders, and tobacco dependence or abuse were associated with prolonged opioid use. Approximately 13% of opioid-naïve patients continue to fill opioid prescriptions after hand surgery procedures 90 days after surgery. Preoperative interventions centered on opioid alternatives and early cessation, particularly among patients at risk for long-term use, is critical to addressing the prescription opioid crisis in the United States. The current national opioid use epidemic requires an assessment of the prevalence of hand surgery patients who receive and fill opioid prescriptions after common hand surgery procedures. Copyright © 2016 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.

Proportional estimation of finger movements from high-density surface electromyography.

PubMed

Celadon, Nicolò; Došen, Strahinja; Binder, Iris; Ariano, Paolo; Farina, Dario

2016-08-04

The importance to restore the hand function following an injury/disease of the nervous system led to the development of novel rehabilitation interventions. Surface electromyography can be used to create a user-driven control of a rehabilitation robot, in which the subject needs to engage actively, by using spared voluntary activation to trigger the assistance of the robot. The study investigated methods for the selective estimation of individual finger movements from high-density surface electromyographic signals (HD-sEMG) with minimal interference between movements of other fingers. Regression was evaluated in online and offline control tests with nine healthy subjects (per test) using a linear discriminant analysis classifier (LDA), a common spatial patterns proportional estimator (CSP-PE), and a thresholding (THR) algorithm. In all tests, the subjects performed an isometric force tracking task guided by a moving visual marker indicating the contraction type (flexion/extension), desired activation level and the finger that should be moved. The outcome measures were mean square error (nMSE) between the reference and generated trajectories normalized to the peak-to-peak value of the reference, the classification accuracy (CA), the mean amplitude of the false activations (MAFA) and, in the offline tests only, the Pearson correlation coefficient (PCORR). The offline tests demonstrated that, for the reduced number of electrodes (≤24), the CSP-PE outperformed the LDA with higher precision of proportional estimation and less crosstalk between the movement classes (e.g., 8 electrodes, median MAFA ~ 0.6 vs. 1.1 %, median nMSE ~ 4.3 vs. 5.5 %). The LDA and the CSP-PE performed similarly in the online tests (median nMSE < 3.6 %, median MAFA < 0.7 %), but the CSP-PE provided a more stable performance across the tested conditions (less improvement between different sessions). Furthermore, THR, exploiting topographical information about the single finger activity from HD-sEMG, provided in many cases a regression accuracy similar to that of the pattern recognition techniques, but the performance was not consistent across subjects and fingers. The CSP-PE is a method of choice for selective individual finger control with the limited number of electrodes (<24), whereas for the higher resolution of the recording, either method (CPS-PA or LDA) can be used with a similar performance. Despite the abundance of detection points, the simple THR showed to be significantly worse compared to both pattern recognition/regression methods. Nevertheless, THR is a simple method to apply (no training), and it could still give satisfactory performance in some subjects and/or simpler scenarios (e.g., control of selected fingers). These conclusions are important for guiding future developments towards the clinical application of the methods for individual finger control in rehabilitation robotics.

Controlled drug-release system based on pH-sensitive chloride-triggerable liposomes.

PubMed

Wehunt, Mark P; Winschel, Christine A; Khan, Ali K; Guo, Tai L; Abdrakhmanova, Galya R; Sidorov, Vladimir

2013-03-01

New pH-sensitive lipids were synthesized and utilized in formulations of liposomes suitable for controlled drug release. These liposomes contain various amounts of NaCl in the internal aqueous compartments. The release of the drug model is triggered by an application of HCl cotransporter and exogenous physiologically relevant NaCl solution. HCl cotransporter allows an uptake of HCl by liposomes to the extent of their being proportional to the transmembrane Cl(-) gradient. Therefore, each set of liposomes undergoes internal acidification, which, ultimately, leads to the hydrolysis of the pH-sensitive lipids and content release at the desired time. The developed system releases the drug model in a stepwise fashion, with the release stages separated by periods of low activity. These liposomes were found to be insensitive to physiological concentrations of human serum albumin and to be nontoxic to cells at concentrations exceeding pharmacological relevance. These results render this new drug-release model potentially suitable for in vivo applications.

40 CFR 355.33 - What release quantities of EHSs and CERCLA hazardous substances trigger the emergency release...

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 27 2010-07-01 2010-07-01 false What release quantities of EHSs and..., EMERGENCY PLANNING, AND COMMUNITY RIGHT-TO-KNOW PROGRAMS EMERGENCY PLANNING AND NOTIFICATION Emergency Release Notification Who Must Comply § 355.33 What release quantities of EHSs and CERCLA hazardous...

Evaluation of thermo-triggered drug release in intramuscular-transplanted tumors using thermosensitive polymer-modified liposomes and MRI.

PubMed

Kokuryo, Daisuke; Nakashima, Seiji; Ozaki, Fuminori; Yuba, Eiji; Chuang, Kai-Hsiang; Aoshima, Sadahito; Ishizaka, Yukihito; Saga, Tsuneo; Kono, Kenji; Aoki, Ichio

2015-01-01

Multi-modal thermo-sensitive polymer-modified liposomes (MTPLs) containing an anticancer drug, MR contrast agent, and fluorescent dye have been investigated as "theranostic" nanodevices that can be used to monitor drug delivery in cancer therapy. Here, we measured the physical characteristics of MTPLs, observed the dynamics of MTPLs in vivo, visualized heat-triggered drug release using MRI, and evaluated the treatment effects of the MTPLs with and without heating. In vitro experiments demonstrated that the MTPLs released drugs at temperatures above 41°C. In vivo MTPLs accumulated in tumor tissue, with the accumulation maximized for 4-12hours. MR signal in the tumor was significantly elevated after mild heating for 15 minutes, indicating release of the contrast agent from the MTPLs was facilitated by heat-triggering. Tumor size after treatment with MTPLs and heating was significantly smaller than those of the control groups. In conclusion, MTPLs with MRI are useful for low-invasive cancer theranostics. Crown Copyright © 2015. Published by Elsevier Inc. All rights reserved.

Zinc finger-inspired nanohydrogels with glutathione/pH triggered degradation based on coordination substitution for highly efficient delivery of anti-cancer drugs.

PubMed

Zhang, Zihao; Wan, Jiaxun; Sun, Luyan; Li, Yongjing; Guo, Jia; Wang, Changchun

2016-03-10

Biodegradable materials used for drug delivery are of great demand due to their ability to degrade into low molecular weight species and further excrete from the body by metabolism. Herein, we report a new kind of zinc(II) crosslinked poly(methacrylic acid) nanohydrogels (ZCLNs) inspired by zinc finger proteins with dual stimuli-triggered degradation (glutathione and pH) for the first time. Compared with the disulfide bond crosslinked nanohydrogels, this new kind of ZCLNs is beneficial to the degradation of a wide range of cells, including normal cells. Ex vivo fluorescence images showed that the DOX-loaded folate-PEG conjugated zinc(II)-crosslinked polymeric nanohydrogels (FPZCLNs-15) preferentially accumulated in tumor tissue and the accumulation in normal tissues was much less compared with DOX-loaded PZCLNs-15 (non-targeted nanohydrogels) and free DOX, the FPZCLNs-15 (targeting system) delivered DOX to the tumor site with approximately 3.6- and 1.6-fold higher than free DOX and PZCLNs-15, respectively. Meanwhile, the PZCLNs-15 and FPZCLNs-15 reduced the concentration of DOX in the heart by 3.2- and 5.0-fold respectively, as compared to the free DOX. Moreover, a superior tumor growth inhibition and negligible damage to normal organs like the heart and kidney, which is reported to be vulnerable to DOX-associated side effects, are further demonstrated. Copyright © 2016 Elsevier B.V. All rights reserved.

Comparison of dominant hand range of motion among throwing types in baseball pitchers.

PubMed

Wang, Lin-Hwa; Kuo, Li-Chieh; Shih, Sheng-Wen; Lo, Kuo-Cheng; Su, Fong-Chin

2013-08-01

Previous research on baseball pitchers' wrists, elbows, and should joints contributes to our understanding of pitchers' control over delicate joint motion and ball release. However, limited research on forearm, wrist, and hand joints prevents full comprehension of the throwing mechanism. The present descriptive laboratory study quantifies angular performances of hand and wrist joints while pitching breaking balls, including fastballs, curveballs and sliders, among pitchers with different skill levels. Nineteen baseball pitchers performed required pitching tasks (10 from university and 9 from high school). A three-dimensional motion analysis system collected pitching motion data. The range of joint motion in the wrist and proximal interphalangeal (PIP) and metacarpophalangeal (MP) joints of the index and middle fingers were compared among fastballs, curveballs and sliders. Thirteen reflective markers were placed on selected anatomic landmarks of the wrist, middle and index fingers of the hand. Wrist flexion angle in the pitching acceleration phase was larger in fastballs (20.58±4.07°) and sliders (22.48±5.45°) than in curveballs (9.08±3.03°) (p = .001). The flexion angle of the PIP joint was significantly larger in curveballs (38.5±3.8°) than in fastballs (30.3±4.8°) and sliders (30.2±4.5°) (p=.004) of the middle finger. Abduction angle of MP joint on the middle finger was significantly larger in curveballs (15.4 ±3.6°) than in fastballs (8.9±1.2°) and sliders (6.9±2.9°) (p=.001) of the middle finger, and the abduction angle of index finger was significantly larger in sliders (13.5±15.0°) than in fastballs (7.2 ±2.8°) (p=.007). Hand and wrist motion and grip types affect the relative position between fingers and ball, which produces different types of baseball pitches. A larger extension angle of the wrist joint and the coordination of middle and index fingers are crucial when pitching a fastball. Abduction and flexion movement on the MP joint of the middle finger are important for a curveball. MP joint abduction and flexion movement of the index finger produce sliders. Understanding the control mechanism in a throwing hand can help improve training protocols in either injury prevention or performance improvement for baseball pitchers. Copyright © 2013 Elsevier B.V. All rights reserved.

Trigger wrist caused by avascular necrosis of the capitate: a case report.

PubMed

Matsui, Yuichiro; Kawamura, Daisuke; Kida, Hiroaki; Hatanaka, Kanako C; Iwasaki, Norimasa

2018-03-27

Trigger wrist is a rare condition first described by Marti in 1960, and various causes have been reported. The condition mostly occurs with finger flexion and extension, and rarely with flexion and extension of the wrist itself. Avascular necrosis of the capitate is also a rare condition, first described by Jönsson in 1942. While some reports of this condition have been published, little is known about its etiology. Therefore, no established treatment exists. We report a case of trigger wrist caused by avascular necrosis of the capitate. A 16-year-old right-handed male who was a high school handball player was referred to our department from a nearby hospital 5 months after the onset of pain in the dorsal aspect of the right wrist, with an unknown cause. At the previous hospital, imaging findings led to a diagnosis of avascular necrosis of the capitate, and conservative treatment with a wrist brace did not improve the pain. At the initial visit to our department, the patient was noted to have a painful trigger wrist that was brought on by wrist flexion and extension. Preoperative imaging findings led to a diagnosis of trigger wrist caused by capitolunate instability secondary to avascular necrosis of the capitate. We performed a partial excision of the proximal capitate with tendon ball interposition. Two years after surgery, the patient's clinical outcome was favorable, with no recurrence of wrist pain or triggering. Both trigger wrist and avascular necrosis of the capitate are rare disorders. When a patient presents with painful triggering at the wrist, surgeons must bear in mind that avascular necrosis of the capitate may result in this phenomenon. We recommend partial excision of the proximal capitate with tendon ball interposition for the treatment of this lesion.

Ultrasound stimulated release of mimosa medicine from cellulose hydrogel matrix.

PubMed

Jiang, Huixin; Tovar-Carrillo, Karla; Kobayashi, Takaomi

2016-09-01

Ultrasound (US) drug release system using cellulose based hydrogel films was developed as triggered to mimosa. Here, the mimosa, a fascinating drug to cure injured skin, was employed as the loading drug in cellulose hydrogel films prepared with phase inversion method. The mimosa hydrogels were fabricated from dimethylacetamide (DMAc)/LiCl solution in the presence of mimosa, when the solution was exposed to ethanol vapor. The US triggered release of the mimosa from the hydrogel matrix was carried out under following conditions of US powers (0-30W) and frequencies (23, 43 and 96kHz) for different mimosa hydrogel matrix from 0.5wt% to 2wt% cellulose solution. To release the drug by US trigger from the matrix, the better medicine release was observed in the matrix prepared from the 0.5wt% cellulose solution when the 43kHz US was exposed to the aqueous solution with the hydrogel matrix. The release efficiency increased with the increase of the US power from 5 to 30W at 43kHz. Viscoelasticity of the hydrogel matrix showed that the hydrogel became somewhat rigid after the US exposure. FT-IR analysis of the mimosa hydrogel matrixes showed that during the US exposure, hydrogen bonds in the structure of mimosa-water and mimosa-cellulose were broken. This suggested that the enhancement of the mimosa release was caused by the US exposure. Copyright © 2016 Elsevier B.V. All rights reserved.

Tumor-triggered drug release from calcium carbonate-encapsulated gold nanostars for near-infrared photodynamic/photothermal combination antitumor therapy.

PubMed

Liu, Yanlei; Zhi, Xiao; Yang, Meng; Zhang, Jingpu; Lin, Lingnan; Zhao, Xin; Hou, Wenxiu; Zhang, Chunlei; Zhang, Qian; Pan, Fei; Alfranca, Gabriel; Yang, Yuming; de la Fuente, Jesús M; Ni, Jian; Cui, Daxiang

2017-01-01

Different stimulus including pH, light and temperature have been used for controlled drug release to prevent drug inactivation and minimize side-effects. Herein a novel nano-platform (GNS@CaCO 3 /ICG) consisting of calcium carbonate-encapsulated gold nanostars loaded with ICG was established to couple the photothermal properties of gold nanostars (GNSs) and the photodynamic properties of indocyanine green (ICG) in the photodynamic/photothermal combination therapy (PDT/PTT). In this study, the calcium carbonate worked not only a drug keeper to entrap ICG on the surface of GNSs in the form of a stable aggregate which was protected from blood clearance, but also as the a pH-responder to achieve highly effective tumor-triggered drug release locally. The application of GNS@CaCO 3 /ICG for in vitro and in vivo therapy achieved the combined antitumor effects upon the NIR irradiation, which was superior to the single PDT or PTT. Meanwhile, the distinct pH-triggered drug release performance of GNS@CaCO 3 /ICG implemented the tumor-targeted NIR fluorescence imaging. In addition, we monitored the bio-distribution and excretion pathway of GNS@CaCO 3 /ICG based on the NIR fluorescence from ICG and two-photon fluorescence and photoacoustic signal from GNSs, and the results proved that GNS@CaCO 3 /ICG had a great ability for tumor-specific and tumor-triggered drug release. We therefore conclude that the GNS@CaCO 3 /ICG holds great promise for clinical applications in anti-tumor therapy with tumor imaging or drug tracing.

pH-Triggered Echogenicity and Contents Release from Liposomes

PubMed Central

2015-01-01

Liposomes are representative lipid nanoparticles widely used for delivering anticancer drugs, DNA fragments, or siRNA to cancer cells. Upon targeting, various internal and external triggers have been used to increase the rate for contents release from the liposomes. Among the internal triggers, decreased pH within the cellular lysosomes has been successfully used to enhance the rate for releasing contents. However, imparting pH sensitivity to liposomes requires the synthesis of specialized lipids with structures that are substantially modified at a reduced pH. Herein, we report an alternative strategy to render liposomes pH sensitive by encapsulating a precursor which generates gas bubbles in situ in response to acidic pH. The disturbance created by the escaping gas bubbles leads to the rapid release of the encapsulated contents from the liposomes. Atomic force microscopic studies indicate that the liposomal structure is destroyed at a reduced pH. The gas bubbles also render the liposomes echogenic, allowing ultrasound imaging. To demonstrate the applicability of this strategy, we have successfully targeted doxorubicin-encapsulated liposomes to the pancreatic ductal carcinoma cells that overexpress the folate receptor on the surface. In response to the decreased pH in the lysosomes, the encapsulated anticancer drug is efficiently released. Contents released from these liposomes are further enhanced by the application of continuous wave ultrasound (1 MHz), resulting in substantially reduced viability for the pancreatic cancer cells (14%). PMID:25271780

pH-triggered echogenicity and contents release from liposomes.

PubMed

Nahire, Rahul; Hossain, Rayat; Patel, Rupa; Paul, Shirshendu; Meghnani, Varsha; Ambre, Avinash H; Gange, Kara N; Katti, Kalpana S; Leclerc, Estelle; Srivastava, D K; Sarkar, Kausik; Mallik, Sanku

2014-11-03

Liposomes are representative lipid nanoparticles widely used for delivering anticancer drugs, DNA fragments, or siRNA to cancer cells. Upon targeting, various internal and external triggers have been used to increase the rate for contents release from the liposomes. Among the internal triggers, decreased pH within the cellular lysosomes has been successfully used to enhance the rate for releasing contents. However, imparting pH sensitivity to liposomes requires the synthesis of specialized lipids with structures that are substantially modified at a reduced pH. Herein, we report an alternative strategy to render liposomes pH sensitive by encapsulating a precursor which generates gas bubbles in situ in response to acidic pH. The disturbance created by the escaping gas bubbles leads to the rapid release of the encapsulated contents from the liposomes. Atomic force microscopic studies indicate that the liposomal structure is destroyed at a reduced pH. The gas bubbles also render the liposomes echogenic, allowing ultrasound imaging. To demonstrate the applicability of this strategy, we have successfully targeted doxorubicin-encapsulated liposomes to the pancreatic ductal carcinoma cells that overexpress the folate receptor on the surface. In response to the decreased pH in the lysosomes, the encapsulated anticancer drug is efficiently released. Contents released from these liposomes are further enhanced by the application of continuous wave ultrasound (1 MHz), resulting in substantially reduced viability for the pancreatic cancer cells (14%).

SGR9, a RING type E3 ligase, modulates amyloplast dynamics important for gravity sensing.

NASA Astrophysics Data System (ADS)

Morita, Miyo T.; Nakamura, Moritaka; Tasaka, Masao

Gravitropism is triggered when the directional change of gravity is sensed in the specific cells, called statocytes. In higher plants, statocytes contain sinking heavier amyloplasts which are particular plastids accumulating starch granules. The displacement of amyloplasts within the statocytes is thought to be the initial event of gravity perception. We have demonstrated that endodermal cells are most likely to be the statocytes in Arabidop-sis shoots. Live cell imaging of the endodermal cell of stem has shown that most amyloplasts are sediment to the direction of gravity but they are not static. Several amyloplasts move dynamically in an actin filament (F-actin) dependent manner. In the presence of actin poly-merization inhibitor, all amyloplasts become static and sediment to the direction of gravity. In addition, stems treated with the inhibitor can exhibit gravitropism. These results suggest that F-actin-dependent dynamic movement of amyloplasts is not essential for gravity sensing. sgr (shoot gravitropism) 9 mutant exhibits greatly reduced shoot gravitropism. In endodermal cells of sgr9, dynamic amyloplast movement was predominantly observed and amyloplasts did not sediment to the direction of gravity. Interestingly, inhibition of actin polymerization re-stored both gravitropism and amyloplast sedimentation in sgr9. The SGR9 encodes a novel RING finger protein, which is localized to amyloplasts in endodermal cells. SGR9 showed ubiq-uitin E3 ligase activity in vitro. Together with live cell imaging of amyloplasts and F-actin, our data suggest that SGR9 modulate interaction between amyloplasts and F-actin on amylo-plasts. SGR9 positively act on amyloplasts sedimentation, probably by releasing amyloplasts from F-actin. SGR9 that is localized to amyloplast, possibly degrades unknown substrates by its E3 ligase activity, and this might promote release of amyloplasts from F-actin.

Management of an unusual extreme extension contracture of the wrist: role of a custom-designed exercise program in achieving a good range of movement and prevention of recontraction.

PubMed

Saraiya, Hemant

2003-01-01

An extreme extension contracture of wrist with dorsal contracture of fingers 15 years after burn injury is described. Shortening of extensor tendons, secondary lengthening of flexor tendons, contracted wrist joint capsule, unusual dislocation of carpals, dorsal dislocation of metacarpophalangeal joints of fingers, and provision of sufficient amount of good-quality skin were some of the issues that had to be addressed in treatment. The contracture was released, the carpals and metacarpophalangeal joint dislocations were corrected and fixed with K wires, and the resulting defect was covered with a sheet split-thickness skin graft. An exercise program was designed that consisted of isotonic, isokinetic, and isometric resistance exercises and passive, active, and active-assistive range of motion exercises. These exercises were pursued with the intention of increasing dynamic strength, endurance, and overall functional recovery of the flexor muscles by exploiting the immature nature of early scar tissue. The resultant enhanced flexor muscle power from exercises along with the dynamic splint helped in lengthening of extensor tendons, wrist joint capsule, and split-thickness skin graft. It also helped in resisting the recontracting tendency, with further recovery of good range of wrist and fingers movements, obviating the need of tendon-lengthening surgery and flap coverage. One and half years of follow up didn't show any sign of recontracture, and the patient was able to perform his routine activities. Postburn wrist contractures of such magnitude have been seldom described. Emphasis is put on simple contracture release and a postoperative exercise program.

Assessing the influence of antivibration glove on digital vascular responses to acute hand-arm vibration.

PubMed

Mahbub, Md H; Yokoyama, Kenjiro; Laskar, Md S; Inoue, Masaiwa; Takahashi, Yukio; Yamamoto, Shinji; Harada, Noriaki

2007-05-01

This study was designed to assess the influence of an antivibration glove on digital vascular responses in healthy subjects exposed to short-term grasping of a vibrating handle. To measure finger blood flow (FBF) and finger skin temperature (FST) once at the end of every min, a blood flowmeter sensor was attached to the dorsum and a thermistor sensor was attached to the medial surface of the subject's middle phalanx of the third finger of the right hand. After 5 min of baseline measurements without or with an antivibration glove meeting ISO standard 10819, worn on the right hand, subjects gripped a vibrating handle with the same hand for a period of 5 min. Vibration was generated at two frequencies of 31.5 Hz and 250 Hz with a frequency weighted rms acceleration of 5.5 m/s(2). FBF and FST continued to be recorded for a further 5 min after release of the vibrating handle. Statistical analysis showed no significant change after vibration exposure in either FST or FBF at 250 Hz, compared to baseline (control) measurements while using the antivibration glove. At 31.5 Hz, FBF data exhibited a significant difference between before and after grasping of vibrating handle, which was less under the condition of wearing the antivibration glove than under the condition of bare hand. The results provide evidence that the antivibration glove considerably influenced finger vascular changes in healthy subjects induced by vibration exposure, especially against high frequency vibration. Further studies are required to assess finger vascular responses to hand-transmitted vibration with antivibration gloves of different manufacturers.

A SERS protocol as a potential tool to access 6-mercaptopurine release accelerated by glutathione-S-transferase.

PubMed

Wang, Ying; Sun, Jie; Yang, Qingran; Lu, Wenbo; Li, Yan; Dong, Jian; Qian, Weiping

2015-11-21

The developed method for monitoring GST, an important drug metabolic enzyme, could greatly facilitate researches on relative biological fields. In this work, we have developed a SERS technique to monitor the absorbance behaviour of 6-mercaptopurine (6-MP) and its glutathione-S-transferase (GST)-accelerated glutathione (GSH)-triggered release behaviour on the surface of gold nanoflowers (GNFs), using the GNFs as excellent SERS substrates. The SERS signal was used as an indicator of absorbance or release of 6-MP on the gold surface. We found that GST can accelerate GSH-triggered release behaviour of 6-MP from the gold surface. We speculated that GST catalyzes nucleophilic GSH to competitively bind with the electrophilic substance 6-MP. Experimental results have proved that the presented SERS protocol can be utilized as an effective tool for accessing the release of anticancer drugs.

Detonation control

DOEpatents

Mace, Jonathan L.; Seitz, Gerald J.; Bronisz, Lawrence E.

2016-10-25

Detonation control modules and detonation control circuits are provided herein. A trigger input signal can cause a detonation control module to trigger a detonator. A detonation control module can include a timing circuit, a light-producing diode such as a laser diode, an optically triggered diode, and a high-voltage capacitor. The trigger input signal can activate the timing circuit. The timing circuit can control activation of the light-producing diode. Activation of the light-producing diode illuminates and activates the optically triggered diode. The optically triggered diode can be coupled between the high-voltage capacitor and the detonator. Activation of the optically triggered diode causes a power pulse to be released from the high-voltage capacitor that triggers the detonator.

An implantable smart magnetic nanofiber device for endoscopic hyperthermia treatment and tumor-triggered controlled drug release.

PubMed

Sasikala, Arathyram Ramachandra Kurup; Unnithan, Afeesh Rajan; Yun, Yeo-Heung; Park, Chan Hee; Kim, Cheol Sang

2016-02-01

The study describes the design and synthesis of an implantable smart magnetic nanofiber device for endoscopic hyperthermia treatment and tumor-triggered controlled drug release. This device is achieved using a two-component smart nanofiber matrix from monodisperse iron oxide nanoparticles (IONPs) as well as bortezomib (BTZ), a chemotherapeutic drug. The IONP-incorporated nanofiber matrix was developed by electrospinning a biocompatible and bioresorbable polymer, poly (d,l-lactide-co-glycolide) (PLGA), and tumor-triggered anticancer drug delivery is realized by exploiting mussel-inspired surface functionalization using 2-(3,4-dihydroxyphenyl)ethylamine (dopamine) to conjugate the borate-containing BTZ anticancer drug through a catechol metal binding in a pH-sensitive manner. Thus, an implantable smart magnetic nanofiber device can be exploited to both apply hyperthermia with an alternating magnetic field (AMF) and to achieve cancer cell-specific drug release to enable synergistic cancer therapy. These results confirm that the BTZ-loaded mussel-inspired magnetic nanofiber matrix (BTZ-MMNF) is highly beneficial not only due to the higher therapeutic efficacy and low toxicity towards normal cells but also, as a result of the availability of magnetic nanoparticles for repeated hyperthermia application and tumor-triggered controlled drug release. The current work report on the design and development of a smart nanoplatform responsive to a magnetic field to administer both hyperthermia and pH-dependent anticancer drug release for the synergistic anticancer treatment. The iron oxide nanoparticles (IONPs) incorporated nanofiber matrix was developed by electrospinning a biocompatible polymer, poly (d,l-lactide-co-glycolide) (PLGA), and tumor-triggered anticancer drug delivery is realized by surface functionalization using 2-(3,4-dihydroxyphenyl)ethylamine (dopamine) to conjugate the boratecontaining anticancer drug bortezomib through a catechol metal binding in a pH-sensitive manner. This implantable magnetic nanofiber device can be exploited to apply hyperthermia with an alternating magnetic field and to achieve cancer cell-specific drug release to enable synergistic cancer therapy, which results in an improvement in both quality of life and patient compliance. Copyright © 2015 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Mucin-mediated nanocarrier disassembly for triggered uptake of oligonucleotides as a delivery strategy for the potential treatment of mucosal tumours

NASA Astrophysics Data System (ADS)

Martirosyan, A.; Olesen, M. J.; Fenton, R. A.; Kjems, J.; Howard, K. A.

2016-06-01

This work demonstrates gastric mucin-triggered nanocarrier disassembly for release of antisense oligonucleotides and consequent unassisted cellular entry as a novel oral delivery strategy. A fluorescence activation-based reporter system was used to investigate the interaction and mucin-mediated disassembly of chitosan-based nanocarriers containing a 13-mer DNA oligonucleotide with a flanked locked RNA nucleic acid gapmer design. Gastric mucins were shown to trigger gapmer release from nanocarriers that was dependent on the interaction time, mucin concentration and N : P ratio with a maximal release at N : P 10. In contrast to siRNA, naked gapmers exhibited uptake into mucus producing HT-MTX mono-cultures and HT-MTX co-cultured with the carcinoma epithelial cell line Caco-2. Importantly, in vivo gapmer uptake was observed in epithelial tissue 30 min post-injection in murine intestinal loops. The findings present a mucosal design-based system tailored for local delivery of oligonucleotides that may maximize the effectiveness of gene silencing therapeutics within tumours at mucosal sites.This work demonstrates gastric mucin-triggered nanocarrier disassembly for release of antisense oligonucleotides and consequent unassisted cellular entry as a novel oral delivery strategy. A fluorescence activation-based reporter system was used to investigate the interaction and mucin-mediated disassembly of chitosan-based nanocarriers containing a 13-mer DNA oligonucleotide with a flanked locked RNA nucleic acid gapmer design. Gastric mucins were shown to trigger gapmer release from nanocarriers that was dependent on the interaction time, mucin concentration and N : P ratio with a maximal release at N : P 10. In contrast to siRNA, naked gapmers exhibited uptake into mucus producing HT-MTX mono-cultures and HT-MTX co-cultured with the carcinoma epithelial cell line Caco-2. Importantly, in vivo gapmer uptake was observed in epithelial tissue 30 min post-injection in murine intestinal loops. The findings present a mucosal design-based system tailored for local delivery of oligonucleotides that may maximize the effectiveness of gene silencing therapeutics within tumours at mucosal sites. Electronic supplementary information (ESI) available. See DOI: 10.1039/c5nr07206a

Light-triggered methylcellulose gold nanoparticle hydrogels for leptin release to inhibit fat stores in adipocytes.

PubMed

Liao, Zi-Xian; Liu, Meng-Chia; Kempson, Ivan M; Fa, Yu-Chen; Huang, Kuo-Yen

2017-01-01

Leptin is released in response to increased triglyceride storage in adipocytes and impacts body weight, but has drawbacks such as poor therapeutic effect and side effects when delivered systemically. Leptin also modifies adipocyte sensitivity to insulin to inhibit lipid accumulation. Here, light-triggered degradation of hydrogels was used to improve accuracy and effectiveness for sustained and controllable release. In our approach, leptin was entrapped within methylcellulose (MC)-based hydrogels, with incorporation of gold nanoparticles (NP). The incorporation of gold NP into MC hydrogels led to a tunable light irradiation response that dictated the hydrogel release rate of leptin. This manuscript demonstrates feasibility in designing tunable thermosensitive hydrogels for loading multimodality therapeutic agents to enhance the bioactivity of leptin for obesity therapy.

Highly efficient drug delivery nanosystem via L-phenylalanine triggering based on supramolecular polymer micelles.

PubMed

Dong, Haiqing; Li, Yongyong; Wen, Huiyun; Xu, Meng; Liu, Lijian; Li, Zhuoquan; Guo, Fangfang; Shi, Donglu

2011-03-16

An intelligent drug delivery nanosystem has been developed based on biodegradable supramolecular polymer micelles (SMPMs). The drug release can be triggered from SMPMs responsively by a bioactive agent, L-phenylalanine in a controlled fashion. The SMPMs are constructed from ethylcellulose-graft-poly(ε-caprolactone) (EC-g-PCL) and α-cyclodextrin (α-CD) derivate via host-guest and hydrophobic interactions. It has been found that these SMPMs have disassembled rapidly in response to an additional L-phenylalanine, due to great affinity discrepancy to α-CD between L-phenylalanine and PCL. Experiments have been carried out on trigger-controlled in vitro drug release of the SMPMs loaded with a model porphyrin based photosensitizer THPP. The result shows that the SMPMs released over 85% THPP in 6 h, which is two orders magnitudes faster than that of control. Also investigated is the photodynamic therapy (PDT) of THPP-loaded SMPMs with and without L-phenylalanine on MCF-7 carcinoma cell line. An effective trigger-concentration dependent lethal effect has been found showing promise in clinical photodynamic therapy. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Multifunctional Surface-Enhanced Raman Spectroscopy-Detectable Silver Nanoparticles Combined Photodynamic Therapy and pH-Triggered Chemotherapy.

PubMed

Srinivasan, Supriya; Bhardwaj, Vinay; Nagasetti, Abhignyan; Fernandez-Fernandez, Alicia; McGoron, Anthony J

2016-12-01

This research paper reports the development of a multifunctional anti-cancer prodrug system based on silver nanoparticles. This prodrug system is composed of 70-nm sized nanoparticles and features photodynamic therapeutic properties and active, pH-triggered drug release. The silver nanoparticles are decorated with a folic acid (FA) targeting ligand via an amide bond, and also conjugated to the chemotherapeutic drug doxorubicin (DOX) via an acid-cleavable hydrazone bond. Both FA and DOX are attached to the silver nanoparticles through a polyethylene glycol (PEG) spacer. This prodrug system can preferentially enter cells that over-express folic acid receptors, with subsequent intracellular drug release triggered by reduced intracellular pH. Moreover, the silver nanoparticle carrier system exhibits photodynamic therapeutic (PDT) activity, so that the cell viability of cancer cells that overexpress folate receptors can be further reduced upon light irradiation. The dual effects of pH-triggered drug release and PDT increase the therapeutic efficacy of this system. The multifunctional nanoparticles can be probed intracellularly through Surface-Enhanced Raman Spectroscopy (SERS) and fluorescence spectroscopy. The current report explores the applicability of this multifunctional silver nanoparticle-based system for cancer theranostics.

Human cortical activity related to unilateral movements. A high resolution EEG study.

PubMed

Urbano, A; Babiloni, C; Onorati, P; Babiloni, F

1996-12-20

In the present study a modern high resolution electroencephalography (EEG) technique was used to investigate the dynamic functional topography of human cortical activity related to simple unilateral internally triggered finger movements. The sensorimotor area (M1-S1) contralateral to the movement as well as the supplementary motor area (SMA) and to a lesser extent the ipsilateral M1-S1 were active during the preparation and execution of these movements. These findings suggest that both hemispheres may cooperate in both planning and production of simple unilateral volitional acts.

Temperature responsive porous silicon nanoparticles for cancer therapy - spatiotemporal triggering through infrared and radiofrequency electromagnetic heating.

PubMed

Tamarov, Konstantin; Xu, Wujun; Osminkina, Liubov; Zinovyev, Sergey; Soininen, Pasi; Kudryavtsev, Andrey; Gongalsky, Maxim; Gaydarova, Azha; Närvänen, Ale; Timoshenko, Victor; Lehto, Vesa-Pekka

2016-11-10

One critical functionality of the carrier system utilized in targeted drug delivery is its ability to trigger the release of the therapeutic cargo once the carrier has reached its target. External triggering is an alluring approach as it can be applied in a precise spatiotemporal manner. In the present study, we achieved external triggering through the porous silicon (PSi) nanoparticles (NPs) by providing a pulse of infrared or radiofrequency radiation. The NPs were grafted with a temperature responsive polymer whose critical temperature was tailored to be slightly above 37°C. The polymer coating improved the biocompatibility of the NPs significantly in comparison with their uncoated counterparts. Radiation induced a rapid temperature rise, which resulted in the collapse of the polymer chains facilitating the cargo release. Both infrared and radiofrequency radiation were able to efficiently trigger the release of the encapsulated drug in vitro and induce significant cell death in comparison to the control groups. Radiofrequency radiation was found to be more efficient in vitro, and the treatment efficacy was verified in vivo in a lung carcinoma (3LL) mice model. After a single intratumoral administration of the carrier system combined with radiofrequency radiation, there was clear suppression of the growth of the carcinoma and a prolongation of the survival time of the animals. The temperature responsive (TR) polymer grafted on the surface of porous silicon nanoparticles (PSi NPs) changes its conformation in response to the heating induced by infrared or radiofrequency radiation. The conformation change allows the loaded doxorubicin to escape from the pores, achieving controlled drug release from TR PSi NPs, which displayed efficacy against malignant cells both in vitro and in vivo. Copyright © 2016 Elsevier B.V. All rights reserved.

The effect of trigger point management by positional release therapy on tension type headache.

PubMed

Ghanbari, Ali; Rahimijaberi, Abbas; Mohamadi, Marzieh; Abbasi, Leila; Sarvestani, Fahimeh Kamali

2012-01-01

The aim of this study was to compare the effectiveness of trigger points' management by Positional Release Therapy (PRT) and routine medical therapy in treatment of Tension Type Headache. Tension Type Headache is the most frequent headache with the basis of myofascial and trigger point disorders. PRT is an indirect technique that treats trigger points. 30 Patients with active trigger points in cervical muscles entered to the study. They were randomly assigned to PRT or medical therapy group. Headache frequency, intensity and duration and tablet count were recorded by use of a daily headache diary. Sensitivity of trigger points was assessed by numeric pain intensity and by use of a digital force gauge (FG 5020). Both groups showed significant reduction in headache frequency and duration and tablet count after treatment phase. However, the reduction of study variables was persisted only in PRT group after follow up phase. There was no significant reduction in headache intensity, neither in PRT and nor in medication group. Sensitivity of trigger points was significantly reduced. In comparison of the two study groups, there was no significant difference in headache frequency, intensity, duration and tablet count (p> 0.05). Both procedures were equally effective according to the study. Thus, PRT can be a treatment choice for patients with T.T.H.

PML-RARα stabilized by zinc in human acute promyelocytic leukemia NB4 cells.

PubMed

Zhu, Bo; Wang, Jia-Yu; Zhou, Jun-Jie; Zhou, Feng; Cheng, Wei; Liu, Ying-Ting; Wang, Jie; Chen, Xiao; Chen, Dian-Hua; Luo, Lan; Hua, Zi-Chun

2017-10-01

Acute promyelocytic leukemia (APL) is characterized and driven by the promyelocytic leukemia protein-retinoic acid receptor alpha (PML-RARα) fusion gene. Previous studies have highlighted the importance of PML-RARα degradation in the treatment against APL. Considering the presence of two zinc fingers in the PML-RARα fusion protein, we explored the function of zinc homeostasis in maintaining PML-RARα stability. We demonstrated for the first time that zinc depletion by its chelator N,N,N',N'-tetrakis(2-pyridylmethyl)ethylenediamine (TPEN) triggered PML-RARα degradation in NB4 APL cells via the proteasome pathway rather than the autophagy-lysosomal pathway. In contrast, autophagy protected TPEN-mediated PML-RARα degradation in NB4 APL cells. We further demonstrated that crosstalk between zinc homeostasis and nitric oxide pathway played a key role in maintaining PML-RARα stability in NB4 APL cells. These results demonstrate that zinc homeostasis is vital for maintaining PML-RARα stability, and zinc depletion by TPEN may be useful as a potential strategy to trigger PML-RARα degradation in APL cells. We also found that TPEN triggered apoptosis of NB4 APL cells in a time-dependent manner. The relationship between PML-RARα degradation and apoptosis triggered by TPEN deserves further study. Copyright © 2017 Elsevier Inc. All rights reserved.

Inflammatory Flt3L is essential to mobilize dendritic cells and for T cell responses during Plasmodium infection

PubMed Central

Guermonprez, Pierre; Helft, Julie; Claser, Carla; Deroubaix, Stephanie; Karanje, Henry; Gazumyan, Anna; Darrasse-Jeze, Guillaume; Telerman, Stephanie B.; Breton, Gaëlle; Schreiber, Heidi A.; Frias-Staheli, Natalia; Billerbeck, Eva; Dorner, Marcus; Rice, Charles M.; Ploss, Alexander; Klein, Florian; Swiecki, Melissa; Colonna, Marco; Kamphorst, Alice O.; Meredith, Matthew; Niec, Rachel; Takacs, Constantin; Mikhail, Fadi; Hari, Aswin; Bosque, David; Eisenreich, Tom; Merad, Miriam; Shi, Yan; Ginhoux, Florent; Rénia, Laurent; Urban, Britta C.; Nussenzweig, Michel C.

2014-01-01

Summary Innate sensing mechanisms trigger a variety of humoral and cellular events that are essential to adaptive immune responses. Here we describe an innate sensing pathway triggered by Plasmodium infection that regulates dendritic cell (DC) homeostasis and adaptive immunity via Flt3L release. Plasmodium-induced Flt3L release requires toll-like receptor activation and type I interferon production. We find that type I interferon supports the up-regulation of xanthine dehydrogenase, which metabolizes the xanthine accumulating in infected erythrocytes to uric acid. Uric acid crystals trigger mast cells to release soluble Flt3L from a pre-synthesized membrane-associated precursor. During infection Flt3L preferentially stimulates expansion of the CD8α+/CD103+ DC subset or its BDCA3+ human DC equivalent and has a significant impact on the magnitude of T cell activation, mostly in the CD8+ compartment. Our findings highlight a new mechanism that regulates DC homeostasis and T cell responses to infection. PMID:23685841

The Initial Inflammatory Response to Bioactive Implants Is Characterized by NETosis

PubMed Central

Stoiber, Walter; Hannig, Matthias; Klappacher, Michaela; Hartl, Dominik

2015-01-01

Implants trigger an inflammatory response, which is important for osseointegration. Here we studied neutrophil extracellular trap (NET) release of human neutrophils in response to sandblasted large-grit acid etched (SLA) implants using fluorescent, confocal laser scanning and scanning electron microscopy. Our studies demonstrate that human neutrophils rapidly adhered to SLA surfaces, which triggered histone citrullination and NET release. Further studies showed that albumin or acetylsalicylic acid had no significant effects on the inflammatory response to SLA surfaces. In contrast to bioinert materials, which do not osseointegrate, the bioactivity of SLA surfaces is coupled with the ability to release NETs. Further investigations are necessary for clarifying the role of NETosis for osseointegration. PMID:25798949

RIM-BPs Mediate Tight Coupling of Action Potentials to Ca(2+)-Triggered Neurotransmitter Release.

PubMed

Acuna, Claudio; Liu, Xinran; Gonzalez, Aneysis; Südhof, Thomas C

2015-09-23

Ultrafast neurotransmitter release requires tight colocalization of voltage-gated Ca(2+) channels with primed, release-ready synaptic vesicles at the presynaptic active zone. RIM-binding proteins (RIM-BPs) are multidomain active zone proteins that bind to RIMs and to Ca(2+) channels. In Drosophila, deletion of RIM-BPs dramatically reduces neurotransmitter release, but little is known about RIM-BP function in mammalian synapses. Here, we generated double conditional knockout mice for RIM-BP1 and RIM-BP2, and analyzed RIM-BP-deficient synapses in cultured hippocampal neurons and the calyx of Held. Surprisingly, we find that in murine synapses, RIM-BPs are not essential for neurotransmitter release as such, but are selectively required for high-fidelity coupling of action potential-induced Ca(2+) influx to Ca(2+)-stimulated synaptic vesicle exocytosis. Deletion of RIM-BPs decelerated action-potential-triggered neurotransmitter release and rendered it unreliable, thereby impairing the fidelity of synaptic transmission. Thus, RIM-BPs ensure optimal organization of the machinery for fast release in mammalian synapses without being a central component of the machinery itself. Copyright © 2015 Elsevier Inc. All rights reserved.

Cysteine Depletion Causes Oxidative Stress and Triggers Outer Membrane Vesicle Release by Neisseria meningitidis; Implications for Vaccine Development

PubMed Central

van de Waterbeemd, Bas; Zomer, Gijsbert; van den IJssel, Jan; van Keulen, Lonneke; Eppink, Michel H.; van der Ley, Peter; van der Pol, Leo A.

2013-01-01

Outer membrane vesicles (OMV) contain immunogenic proteins and contribute to in vivo survival and virulence of bacterial pathogens. The first OMV vaccines successfully stopped Neisseria meningitidis serogroup B outbreaks but required detergent-extraction for endotoxin removal. Current vaccines use attenuated endotoxin, to preserve immunological properties and allow a detergent-free process. The preferred process is based on spontaneously released OMV (sOMV), which are most similar to in vivo vesicles and easier to purify. The release mechanism however is poorly understood resulting in low yield. This study with N. meningitidis demonstrates that an external stimulus, cysteine depletion, can trigger growth arrest and sOMV release in sufficient quantities for vaccine production (±1500 human doses per liter cultivation). Transcriptome analysis suggests that cysteine depletion impairs iron-sulfur protein assembly and causes oxidative stress. Involvement of oxidative stress is confirmed by showing that addition of reactive oxygen species during cysteine-rich growth also triggers vesiculation. The sOMV in this study are similar to vesicles from natural infection, therefore cysteine-dependent vesiculation is likely to be relevant for the in vivo pathogenesis of N. meningitidis. PMID:23372704

Dynamic microvesicle release and clearance within the cardiovascular system: triggers and mechanisms.

PubMed

Ayers, Lisa; Nieuwland, Rienk; Kohler, Malcolm; Kraenkel, Nicolle; Ferry, Berne; Leeson, Paul

2015-12-01

Interest in cell-derived microvesicles (or microparticles) within cardiovascular diagnostics and therapeutics is rapidly growing. Microvesicles are often measured in the circulation at a single time point. However, it is becoming clear that microvesicle levels both increase and decrease rapidly in response to certain stimuli such as hypoxia, acute cardiac stress, shear stress, hypertriglyceridaemia and inflammation. Consequently, the levels of circulating microvesicles will reflect the balance between dynamic mechanisms for release and clearance. The present review describes the range of triggers currently known to lead to microvesicle release from different cellular origins into the circulation. Specifically, the published data are used to summarize the dynamic impact of these triggers on the degree and rate of microvesicle release. Secondly, a summary of the current understanding of microvesicle clearance via different cellular systems, including the endothelial cell and macrophage, is presented, based on reported studies of clearance in experimental models and clinical scenarios, such as transfusion or cardiac stress. Together, this information can be used to provide insights into potential underlying biological mechanisms that might explain the increases or decreases in circulating microvesicle levels that have been reported and help to design future clinical studies. © 2015 Authors; published by Portland Press Limited.

Near-infrared remotely triggered drug-release strategies for cancer treatment

NASA Astrophysics Data System (ADS)

Goodman, Amanda M.; Neumann, Oara; Nørregaard, Kamilla; Henderson, Luke; Choi, Mi-Ran; Clare, Susan E.; Halas, Naomi J.

2017-11-01

Remotely controlled, localized drug delivery is highly desirable for potentially minimizing the systemic toxicity induced by the administration of typically hydrophobic chemotherapy drugs by conventional means. Nanoparticle-based drug delivery systems provide a highly promising approach for localized drug delivery, and are an emerging field of interest in cancer treatment. Here, we demonstrate near-IR light-triggered release of two drug molecules from both DNA-based and protein-based hosts that have been conjugated to near-infrared-absorbing Au nanoshells (SiO2 core, Au shell), each forming a light-responsive drug delivery complex. We show that, depending upon the drug molecule, the type of host molecule, and the laser illumination method (continuous wave or pulsed laser), in vitro light-triggered release can be achieved with both types of nanoparticle-based complexes. Two breast cancer drugs, docetaxel and HER2-targeted lapatinib, were delivered to MDA-MB-231 and SKBR3 (overexpressing HER2) breast cancer cells and compared with release in noncancerous RAW 264.7 macrophage cells. Continuous wave laser-induced release of docetaxel from a nanoshell-based DNA host complex showed increased cell death, which also coincided with nonspecific cell death from photothermal heating. Using a femtosecond pulsed laser, lapatinib release from a nanoshell-based human serum albumin protein host complex resulted in increased cancerous cell death while noncancerous control cells were unaffected. Both methods provide spatially and temporally localized drug-release strategies that can facilitate high local concentrations of chemotherapy drugs deliverable at a specific treatment site over a specific time window, with the potential for greatly minimized side effects.

Protease-sensitive, polymer-caged liposomes: a method for making highly targeted liposomes using triggered release.

PubMed

Basel, Matthew T; Shrestha, Tej B; Troyer, Deryl L; Bossmann, Stefan H

2011-03-22

Liposomes have become useful and well-known drug delivery vehicles because of their ability to entrap drugs without chemically modifying them and to deliver them somewhat selectively to tumorous tissue via the enhanced permeation and retention (EPR) effect. Although useful, liposome preparations are still less than ideal because of imperfect specificity, slow release kinetics in the tumor, and leakiness prior to reaching the tumor site. Cancer-associated proteases (CAPs), which are differentially expressed in tumors, have also gained traction recently as a method for tumor targeting and drug delivery. By combining the EPR effect with CAPs sensitivity, a much more specific liposome can be produced. The method described here creates an improved liposome system that can target more specifically, with faster release kinetics and lower general leaking, by deliberately producing a very unstable liposome (loaded with hyperosmotic vehicle) that is subsequently stabilized by a cross-linked polymer shell containing consensus sequences for cancer-associated proteases (protease-triggered, caged liposomes). A cholesterol-anchored, graft copolymer, composed of a short peptide sequence for urokinase plasminogen activator (uPA) and poly(acrylic acid), was synthesized and incorporated into liposomes prepared at high osmolarities. Upon cross-linking of the polymers, the protease-triggered, caged liposomes showed significant resistance to osmotic swelling and leaking of contents. Protease-triggered, caged liposomes also showed significant and substantial differential release of contents in the presence of uPA, while bare liposomes showed no differential effect in the presence of uPA. Thus a protease-sensitive liposome system with fast release kinetics was developed that could be used for more specific targeting to tumors.

Geologic fracturing method and resulting fractured geologic structure

DOEpatents

Mace, Jonathan L.; Bradley, Christopher R.; Greening, Doran R.; Steedman, David W.

2016-11-08

Detonation control modules and detonation control circuits are provided herein. A trigger input signal can cause a detonation control module to trigger a detonator. A detonation control module can include a timing circuit, a light-producing diode such as a laser diode, an optically triggered diode, and a high-voltage capacitor. The trigger input signal can activate the timing circuit. The timing circuit can control activation of the light-producing diode. Activation of the light-producing diode illuminates and activates the optically triggered diode. The optically triggered diode can be coupled between the high-voltage capacitor and the detonator. Activation of the optically triggered diode causes a power pulse to be released from the high-voltage capacitor that triggers the detonator.

Magnetically triggered release of molecular cargo from iron oxide nanoparticle loaded microcapsules

NASA Astrophysics Data System (ADS)

Carregal-Romero, Susana; Guardia, Pablo; Yu, Xiang; Hartmann, Raimo; Pellegrino, Teresa; Parak, Wolfgang J.

2014-12-01

Photothermal release of cargo molecules has been extensively studied for bioapplications. For instance, microcapsules decorated with plasmonic nanoparticles have been widely used in in vitro assays. However, some concerns about their suitability for some in vivo applications cannot be easily overcome, in particular the limited penetration depth of light (even infrared). Magnetic nanoparticles are alternative heat-mediators for local heating, which can be triggered by applying an alternating magnetic field (AMF). AMFs are much less absorbed by tissue than light and thus can penetrate deeper overcoming the above mentioned limitations. Here we present iron oxide nanocube-modified microcapsules as a platform for magnetically triggered molecular release. Layer-by-layer assembled polyelectrolyte microcapsules with 4.6 μm diameter, which had 18 nm diameter iron oxide nanocubes integrated in their walls, were synthesized. The microcapsules were further loaded with an organic fluorescent polymer (Cascade Blue-labelled dextran), which was used as a model of molecular cargo. Through an AMF the magnetic nanoparticles were able to heat their surroundings and destroy the microcapsule walls, leading to a final release of the embedded cargo to the surrounding solution. The cargo release was monitored in solution by measuring the increase in both absorbance and fluorescence signal after the exposure to an AMF. Our results demonstrate that magnetothermal release of the encapsulated material is possible using magnetic nanoparticles with a high heating performance.Photothermal release of cargo molecules has been extensively studied for bioapplications. For instance, microcapsules decorated with plasmonic nanoparticles have been widely used in in vitro assays. However, some concerns about their suitability for some in vivo applications cannot be easily overcome, in particular the limited penetration depth of light (even infrared). Magnetic nanoparticles are alternative heat-mediators for local heating, which can be triggered by applying an alternating magnetic field (AMF). AMFs are much less absorbed by tissue than light and thus can penetrate deeper overcoming the above mentioned limitations. Here we present iron oxide nanocube-modified microcapsules as a platform for magnetically triggered molecular release. Layer-by-layer assembled polyelectrolyte microcapsules with 4.6 μm diameter, which had 18 nm diameter iron oxide nanocubes integrated in their walls, were synthesized. The microcapsules were further loaded with an organic fluorescent polymer (Cascade Blue-labelled dextran), which was used as a model of molecular cargo. Through an AMF the magnetic nanoparticles were able to heat their surroundings and destroy the microcapsule walls, leading to a final release of the embedded cargo to the surrounding solution. The cargo release was monitored in solution by measuring the increase in both absorbance and fluorescence signal after the exposure to an AMF. Our results demonstrate that magnetothermal release of the encapsulated material is possible using magnetic nanoparticles with a high heating performance. Electronic supplementary information (ESI) available. See DOI: 10.1039/c4nr04055d

A DNS study of the physical mechanisms associated with density ratio influence on turbulent burning velocity in premixed flames

NASA Astrophysics Data System (ADS)

Lipatnikov, Andrei N.; Chomiak, Jerzy; Sabelnikov, Vladimir A.; Nishiki, Shinnosuke; Hasegawa, Tatsuya

2018-01-01

Data obtained in 3D direct numerical simulations of statistically planar, 1D weakly turbulent flames characterised by different density ratios σ are analysed to study the influence of thermal expansion on flame surface area and burning rate. Results show that, on the one hand, the pressure gradient induced within a flame brush owing to heat release in flamelets significantly accelerates the unburned gas that deeply intrudes into the combustion products in the form of an unburned mixture finger, thus causing large-scale oscillations of the burning rate and flame brush thickness. Under the conditions of the present simulations, the contribution of this mechanism to the creation of the flame surface area is substantial and is increased by σ, thus implying an increase in the burning rate by σ. On the other hand, the total flame surface areas simulated at σ = 7.53 and 2.5 are approximately equal. The apparent inconsistency between these results implies the existence of another thermal expansion effect that reduces the influence of σ on the flame surface area and burning rate. Investigation of the issue shows that the flow acceleration by the combustion-induced pressure gradient not only creates the flame surface area by pushing the finger tip into the products, but also mitigates wrinkling of the flame surface (the side surface of the finger) by turbulent eddies. The latter effect is attributed to the high-speed (at σ = 7.53) axial flow of the unburned gas, which is induced by the axial pressure gradient within the flame brush (and the finger). This axial flow acceleration reduces the residence time of a turbulent eddy in an unburned zone of the flame brush (e.g. within the finger). Therefore, the capability of the eddy for wrinkling the flamelet surface (e.g. the side finger surface) is weakened owing to a shorter residence time.

Secure RFID tag or sensor with self-destruction mechanism upon tampering

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nekoogar, Faranak; Dowla, Farid; Twogood, Richard

A circuit board anti-tamper mechanism comprises a circuit board having a frangible portion, a trigger having a trigger spring, a trigger arming mechanism actuated by the trigger wherein the trigger arming mechanism is initially non-actuated, a force producing mechanism, a latch providing mechanical communication between the trigger arming mechanism and the force producing mechanism, wherein the latch initially retains the force producing mechanism in a refracted position. Arming pressure applied to the trigger sufficient to overcome the trigger spring force will actuate the trigger arming mechanism, causing the anti-tamper mechanism to be armed. Subsequent tampering with the anti-tamper mechanism resultsmore » in a decrease of pressure on the trigger below the trigger spring force, thereby causing the trigger arming mechanism to actuate the latch, thereby releasing the force producing mechanism to apply force to the frangible portion of the circuit board, thereby breaking the circuit board.« less

A model system for targeted drug release triggered by biomolecular signals logically processed through enzyme logic networks.

PubMed

Mailloux, Shay; Halámek, Jan; Katz, Evgeny

2014-03-07

A new Sense-and-Act system was realized by the integration of a biocomputing system, performing analytical processes, with a signal-responsive electrode. A drug-mimicking release process was triggered by biomolecular signals processed by different logic networks, including three concatenated AND logic gates or a 3-input OR logic gate. Biocatalytically produced NADH, controlled by various combinations of input signals, was used to activate the electrochemical system. A biocatalytic electrode associated with signal-processing "biocomputing" systems was electrically connected to another electrode coated with a polymer film, which was dissolved upon the formation of negative potential releasing entrapped drug-mimicking species, an enzyme-antibody conjugate, operating as a model for targeted immune-delivery and consequent "prodrug" activation. The system offers great versatility for future applications in controlled drug release and personalized medicine.

Encapsulation of NF-κ B Decoy Oligonucleotides within Echogenic Liposomes and Ultrasound-Triggered Release

PubMed Central

Buchanan, Kyle D.; Huang, Shao-Ling; Kim, Hyunggun; McPherson, David D.; MacDonald, Robert C.

2011-01-01

Echogenic liposomes (ELIP) have additional promise, beyond diagnostic agents, as vehicles for delivering oligonucleotides (ODN), especially if the release of the agent can be triggered and its uptake can be enhanced by ultrasound application at a specific site. The purpose of this study was to co-encapsulate air and NF-κB decoy ODN within ELIP allowing ultrasound to release encapsulated ODN from ELIP, and to accurately quantify release of encapsulated ODN from ELIP upon ultrasound application. FITC-labeled sense ODN (2 mM) was incorporated within ELIP using freeze/thaw method. Encapsulation efficiency of FITC-ODN was spectrofluorometrically analyzed by quenching fluorescence of unencapsulated FITC-ODN using a complementary strand tagged with Iowa Black FQ-ODN. Quenching of FITC-ODN (0.05 μM) with Iowa Black FQ-ODN (0.1 μM) was found to be efficient (92.4 ± 0.2 %), allowing accurate determination of encapsulated ODN. Encapsulation efficiency of ODN was 14.2 ± 2.5 % in DPPC/DOPC/DPPG/CH liposomes and 29.6 ± 1.5 % in DPPC/DOPE/DPPG/CH liposomes. Application of ultrasound (1 MHz continuous wave, 0.26 MPa peak-to-peak pressure amplitude, 60 seconds.) to the latter formulation triggered 41.6 ± 4.3 % release of ODN from ODN-containing ELIP. We have thus demonstrated that ODN can be encapsulated into ELIP and released efficiently upon ultrasound application. These findings suggest potential applications for gene therapy in atherosclerosis treatment. PMID:19804805

Coordination responsive tellurium-containing multilayer film for controlled delivery.

PubMed

Cao, Wei; Wang, Lu; Xu, Huaping

2015-03-28

A coordination-responsive tellurium containing film was fabricated for controlled release. The coordination chemistry between telluride molecules and cisplatin was utilized for the loading of cisplatin, while competitive ligands were used for triggered release. This work could enrich the coordination responsive system and further tune the release kinetics of cisplatin.

A model of cardiac ryanodine receptor gating predicts experimental Ca2+-dynamics and Ca2+-triggered arrhythmia in the long QT syndrome

NASA Astrophysics Data System (ADS)

Wilson, Dan; Ermentrout, Bard; Němec, Jan; Salama, Guy

2017-09-01

Abnormal Ca2+ handling is well-established as the trigger of cardiac arrhythmia in catecholaminergic polymorphic ventricular tachycardia and digoxin toxicity, but its role remains controversial in Torsade de Pointes (TdP), the arrhythmia associated with the long QT syndrome (LQTS). Recent experimental results show that early afterdepolarizations (EADs) that initiate TdP are caused by spontaneous (non-voltage-triggered) Ca2+ release from Ca2+-overloaded sarcoplasmic reticulum (SR) rather than the activation of the L-type Ca2+-channel window current. In bradycardia and long QT type 2 (LQT2), a second, non-voltage triggered cytosolic Ca2+ elevation increases gradually in amplitude, occurs before overt voltage instability, and then precedes the rise of EADs. Here, we used a modified Shannon-Puglisi-Bers model of rabbit ventricular myocytes to reproduce experimental Ca2+ dynamics in bradycardia and LQT2. Abnormal systolic Ca2+-oscillations and EADs caused by SR Ca2+-release are reproduced in a modified 0-dimensional model, where 3 gates in series control the ryanodine receptor (RyR2) conductance. Two gates control RyR2 activation and inactivation and sense cytosolic Ca2+ while a third gate senses luminal junctional SR Ca2+. The model predicts EADs in bradycardia and low extracellular [K+] and cessation of SR Ca2+-release terminate salvos of EADs. Ca2+-waves, systolic cell-synchronous Ca2+-release, and multifocal diastolic Ca2+ release seen in subcellular Ca2+-mapping experiments are observed in the 2-dimensional version of the model. These results support the role of SR Ca2+-overload, abnormal SR Ca2+-release, and the subsequent activation of the electrogenic Na+/Ca2+-exchanger as the mechanism of TdP. The model offers new insights into the genesis of cardiac arrhythmia and new therapeutic strategies.

Cyclosporine Induces Endothelial Cell Release of Complement-Activating Microparticles

PubMed Central

Renner, Brandon; Klawitter, Jelena; Goldberg, Ryan; McCullough, James W.; Ferreira, Viviana P.; Cooper, James E.; Christians, Uwe

2013-01-01

Defective control of the alternative pathway of complement is an important risk factor for several renal diseases, including atypical hemolytic uremic syndrome. Infections, drugs, pregnancy, and hemodynamic insults can trigger episodes of atypical hemolytic uremic syndrome in susceptible patients. Although the mechanisms linking these clinical events with disease flares are unknown, recent work has revealed that each of these clinical conditions causes cells to release microparticles. We hypothesized that microparticles released from injured endothelial cells promote intrarenal complement activation. Calcineurin inhibitors cause vascular and renal injury and can trigger hemolytic uremic syndrome. Here, we show that endothelial cells exposed to cyclosporine in vitro and in vivo release microparticles that activate the alternative pathway of complement. Cyclosporine-induced microparticles caused injury to bystander endothelial cells and are associated with complement-mediated injury of the kidneys and vasculature in cyclosporine-treated mice. Cyclosporine-induced microparticles did not bind factor H, an alternative pathway regulatory protein present in plasma, explaining their complement-activating phenotype. Finally, we found that in renal transplant patients, the number of endothelial microparticles in plasma increases 2 weeks after starting tacrolimus, and treatment with tacrolimus associated with increased C3 deposition on endothelial microparticles in the plasma of some patients. These results suggest that injury-associated release of endothelial microparticles is an important mechanism by which systemic insults trigger intravascular complement activation and complement-dependent renal diseases. PMID:24092930

A photosensitive liposome with NIR light triggered doxorubicin release as a combined photodynamic-chemo therapy system.

PubMed

Li, Qingpo; Li, Wei; Di, Haixiao; Luo, Lihua; Zhu, Chunqi; Yang, Jie; Yin, Xiaoyi; Yin, Hang; Gao, Jianqing; Du, Yongzhong; You, Jian

2018-05-10

The targeted drug delivery with the help of nanocarriers and the controlled drug release at the lesion sites are the most effective ways to enhance therapeutic efficacy and reduce side effects. Here, we built a light sensitive liposome (Her2-I&D-LSL) which was formed by a special phospholipid (PLsPC) and a hydrophobically modified photosensitizer (ICG-ODA). DOX was employed as the therapeutic drug, encapsulating in the internal phase of the liposome whose surface was modified by Her2 antibodies for recognizing tumor cells with high Her2 receptor expression. Mediated by NIR light, Her2-I&D-LSL was proved to generate sufficient ROS to realize PDT, which then triggered the release of DOX for combined chemotherapy. The ROS generation and DOX release were verified to be strictly controlled by NIR light and the proportion of ICG-ODA. Thanks to the mediation of Her2 receptor, the specific DOX release and the combination of PDT-chemotherapy triggered by NIR light, Her2-I&D-LSL showed a significant accumulation in MCF7 and SKOV3 tumors, thus leading to the strongest tumor growth inhibition effect compared to PDT alone (I-LSL) or chemotherapy alone (D-LSL). Her2-I&D-LSL also possessed a great biocompatibility due to the targeted treatment, holding promise for future cancer therapy in clinic. Copyright © 2018 Elsevier B.V. All rights reserved.

Cardiopathogenic mediators generated by GATA4 signaling upon co-activation with endothelin-1 and Trypanosoma cruzi infection.

PubMed

Rigazio, Cristina S; Hernández, Matías; Corral, Ricardo S

2014-08-01

Trypanosoma cruzi (Tc), the etiological agent of Chagas disease, triggers multiple responses in the myocardium, a central organ of infection and pathology in the host. Parasite-driven induction of diverse regulators of cardiovascular function, including the vasoconstrictor endothelin-1 (ET-1), the inducible form of nitric oxide synthase (iNOS) and the B-type natriuretic peptide (BNP), has been linked to the development of severe chagasic cardiomyopathy. Our current goal was to analyze the participation of the zinc finger transcription factor GATA4, critically implicated in pathological cardiac hypertrophic response, in the generation of key mediators involved in the pathogenesis of Tc-elicited heart dysfunction. In this study, we found that the combined effects of Tc and ET-1 on atrial myocytes promoted the protein expression, phosphorylation and DNA-binding activity of GATA4, leading to augmented protein levels of iNOS and increased nitric oxide release. Moreover, Tc- and ET-1-co-activation of cardiomyocytes resulted in enhanced GATA4-dependent secretion of BNP. Accordingly, mice with chronic chagasic cardiomyopathy showed increased expression of GATA4, iNOS and BNP at inflammatory lesions in cardiac muscle. Our findings support a role for the GATA4 signaling pathway in the myocardial production of pathogenic mediators associated with Chagas heart disease, and may help define novel therapeutic targets. Copyright © 2014 Elsevier Ltd. All rights reserved.

A Photo-triggered and photo-calibrated nitric oxide donor: Rational design, spectral characterizations, and biological applications.

PubMed

He, Haihong; Liu, Yuxin; Zhou, Zhongneng; Guo, Chunlei; Wang, Hong-Yin; Wang, Zhuang; Wang, Xueli; Zhang, Ziqian; Wu, Fu-Gen; Wang, Haolu; Chen, Daijie; Yang, Dahai; Liang, Xiaowen; Chen, Jinquan; Zhou, Shengmin; Liang, Xin; Qian, Xuhong; Yang, Youjun

2018-04-27

Nitric oxide (NO) donors are valuable tools to probe the profound implications of NO in health and disease. The elusive nature of NO bio-relevance has largely limited the use of spontaneous NO donors and promoted the development of next generation NO donors, whose NO release is not only stimulated by a trigger, but also readily monitored via a judiciously built-in self-calibration mechanism. Light is without a doubt the most sensitive, versatile and biocompatible method of choice for both triggering and monitoring, for applications in complex biological matrices. Herein, we designed and synthesized an N-nitroso rhodamine derivative (NOD560) as a photo-triggered and photo-calibrated NO donor to address this need. NOD560 is essentially non-fluorescent. Upon irradiation by green light (532 nm), it efficiently release NO and a rhodamine dye, the dramatic fluorescence turn-on from which could be harnessed to conveniently monitor the localization, flux, and dose of NO release. The potentials of NOD560 for in vitro biological applications were also exemplified in in vitro biological models, i.e. mesenchymal stem cell (MSC) migration suppression. NOD560 is expected to complement the existing NO donors and find widespread applications in chemical biological studies. Copyright © 2018 Elsevier Inc. All rights reserved.

Materials to clinical devices: technologies for remotely triggered drug delivery.

PubMed

Timko, Brian P; Kohane, Daniel S

2012-11-01

Technologies in which a remote trigger is used to release drug from an implanted or injected device could enable on-demand release profiles that enhance therapeutic effectiveness or reduce systemic toxicity. A number of new materials have been developed that exhibit sensitivity to light, ultrasound, or electrical or magnetic fields. Delivery systems that incorporate these materials might be triggered externally by the patient, parent or physician to provide flexible control of dose magnitude and timing. To review injectable or implantable systems that are candidates for translation to the clinic, or ones that have already undergone clinical trials. Also considered are applicability in pediatrics and prospects for the future of drug delivery systems. We performed literature searches of the PubMed and Science Citation Index databases for articles in English that reported triggerable drug delivery devices, and for articles reporting related materials and concepts. Approaches to remotely-triggered systems that have clinical potential were identified. Ideally, these systems have been engineered to exhibit controlled on-state release kinetics, low baseline leak rates, and reproducible dosing across multiple cycles. Advances in remotely-triggered drug delivery have been brought about by the convergence of numerous scientific and engineering disciplines, and this convergence is likely to play an important part in the current trend to develop systems that provide more than one therapeutic modality. Preclinical systems must be carefully assessed for biocompatibility, and engineered to ensure pharmacokinetics within the therapeutic window. Future drug delivery systems may incorporate additional modalities, such as closed-loop sensing or onboard power generation, enabling more sophisticated drug delivery regimens. Copyright © 2012 Elsevier HS Journals, Inc. All rights reserved.

Preferential flow systems amended with biogeochemical components: imaging of a two-dimensional study

NASA Astrophysics Data System (ADS)

Pales, Ashley R.; Li, Biting; Clifford, Heather M.; Kupis, Shyla; Edayilam, Nimisha; Montgomery, Dawn; Liang, Wei-zhen; Dogan, Mine; Tharayil, Nishanth; Martinez, Nicole; Moysey, Stephen; Powell, Brian; Darnault, Christophe J. G.

2018-04-01

The vadose zone is a highly interactive heterogeneous system through which water enters the subsurface system by infiltration. This paper details the effects of simulated plant exudate and soil component solutions upon unstable flow patterns in a porous medium (ASTM silica sand; US Silica, Ottawa, IL, USA) through the use of two-dimensional tank light transmission method (LTM). The contact angle (θ) and surface tension (γ) of two simulated plant exudate solutions (i.e., oxalate and citrate) and two soil component solutions (i.e., tannic acid and Suwannee River natural organic matter, SRNOM) were analyzed to determine the liquid-gas and liquid-solid interface characteristics of each. To determine if the unstable flow formations were dependent on the type and concentration of the simulated plant exudates and soil components, the analysis of the effects of the simulated plant exudate and soil component solutions were compared to a control solution (Hoagland nutrient solution with 0.01 M NaCl). Fingering flow patterns, vertical and horizontal water saturation profiles, water saturation at the fingertips, finger dimensions and velocity, and number of fingers were obtained using the light transmission method. Significant differences in the interface properties indicated a decrease between the control and the plant exudate and soil component solutions tested; specifically, the control (θ = 64.5° and γ = 75.75 mN m-1) samples exhibited a higher contact angle and surface tension than the low concentration of citrate (θ = 52.6° and γ = 70.8 mN m-1). Wetting front instability and fingering flow phenomena were reported in all infiltration experiments. The results showed that the plant exudates and soil components influenced the soil infiltration as differences in finger geometries, velocities, and water saturation profiles were detected when compared to the control. Among the tested solutions and concentrations of soil components, the largest finger width (10.19 cm) was generated by the lowest tannic acid solution concentration (0.1 mg L-1), and the lowest finger width (6.00 cm) was induced by the highest SRNOM concentration (10 mg L-1). Similarly, for the plant exudate solutions, the largest finger width (8.36 cm) was generated by the lowest oxalate solution concentration (0.1 mg L-1), and the lowest finger width (6.63 cm) was induced by the lowest citrate concentration (0.1 mg L-1). The control solution produced fingers with average width of 8.30 cm. Additionally, the wettability of the medium for the citrate, oxalate, and SRNOM solutions increased with an increase in concentration. Our research demonstrates that the plant exudates and soil components which are biochemical compounds produced and released in soil are capable of influencing the process of infiltration in soils. The results of this research also indicate that soil wettability, expressed as cosθ1/2, should be included in the scaling of the finger dimension, i.e., finger width, when using the Miller and Miller (1956) scaling theory for the scaling of flow in porous media.

Antimicrobial and water-triggered release characteristics of a copper sulfate-polyvinyl acetate adhesive composite

NASA Astrophysics Data System (ADS)

De Jesus, A. P. O.; Roxas-Villanueva, R. M. L.; Herrera, M. U.

2017-05-01

Water-triggered release of antimicrobial solutions is advantageous in inhibiting the growth of bacteria and fungi in moist and wet environments. In this study, we fabricated a composite, by mixing polyvinyl acetate adhesive with copper sulfate solution, which exhibits antimicrobial activities against bacteria. Polyvinyl acetate adhesive serves as the binder and water soluble substance while copper sulfate serves as the antimicrobial agent. The composite was coated in an acetate film and air-dried. To monitor the rate of release of copper ions, the composite was submerged in water and the conductivity was measured. The conductivity saturation time was determined. The composite showed antimicrobial activity against Escherichia coli (Gram-negative) and Staphylococcus aureus (Gram-positive).

Leaky synapses: Regulation of spontaneous neurotransmission in central synapses

PubMed Central

Wasser, Catherine R.; Kavalali, Ege T.

2009-01-01

The mechanisms underlying spontaneous neurotransmitter release are not well understood. Under physiological as well as pathophysiological circumstances, spontaneous fusion events can set the concentration of ambient levels of neurotransmitter within the synaptic cleft and in the extracellular milieu. In the brain, unregulated release of excitatory neurotransmitters, exacerbated during pathological conditions such as stroke, can lead to neuronal damage and death. In addition, recent findings suggest that under physiological circumstances spontaneous release events can trigger postsynaptic signaling events independent of evoked neurotransmitter release. Therefore, elucidation of mechanisms underlying spontaneous neurotransmission may help us better understand the functional significance of this form of release and provide tools for its selective manipulation. For instance, our recent investigations indicate that the level of cholesterol in the synapse plays a critical role in limiting spontaneous synaptic vesicle fusion. Therefore, alterations in synaptic cholesterol metabolism can be a critical determinant of glutamatergic neurotransmission at rest. This article aims to provide a closer look into our current understanding of the mechanisms underlying spontaneous neurotransmission and the signaling triggered by these unitary release events. PMID:18434032

Multicompartmental Microcapsules with Orthogonal Programmable Two-Way Sequencing of Hydrophobic and Hydrophilic Cargo Release.

PubMed

Xu, Weinan; Ledin, Petr A; Iatridi, Zacharoula; Tsitsilianis, Constantinos; Tsukruk, Vladimir V

2016-04-11

Multicompartmental responsive microstructures with the capability for the pre-programmed sequential release of multiple target molecules of opposite solubility (hydrophobic and hydrophilic) in a controlled manner have been fabricated. Star block copolymers with dual-responsive blocks (temperature for poly(N-isopropylacrylamide) chains and pH for poly(acrylic acid) and poly(2-vinylpyridine) arms) and unimolecular micellar structures serve as nanocarriers for hydrophobic molecules in the microcapsule shell. The interior of the microcapsule can be loaded with water-soluble hydrophilic macromolecules. For these dual-loaded microcapsules, a programmable and sequential release of hydrophobic and hydrophilic molecules from the shell and core, respectively, can be triggered independently by temperature and pH variations. These stimuli affect the hydrophobicity and chain conformation of the star block copolymers to initiate out-of-shell release (elevated temperature), or change the overall star conformation and interlayer interactions to trigger increased permeability of the shell and out-of-core release (pH). Reversing stimulus order completely alters the release process. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

A multifunctional β-CD-modified Fe3O4@ZnO:Er(3+),Yb(3+) nanocarrier for antitumor drug delivery and microwave-triggered drug release.

PubMed

Peng, Hongxia; Cui, Bin; Li, Guangming; Wang, Yingsai; Li, Nini; Chang, Zhuguo; Wang, Yaoyu

2015-01-01

We constructed a novel core-shell structured Fe3O4@ZnO:Er(3+),Yb(3+)@(β-CD) nanoparticles used as drug carrier to investigate the loading and controllable release properties of the chemotherapeutic drug etoposide (VP-16). The cavity of β-cyclodextrin is chemically inert, it can store etoposide molecules by means of hydrophobic interactions. The Fe3O4 core and ZnO:Er(3+),Yb(3+) shell functioned successfully for magnetic targeting and up-conversion fluorescence imaging, respectively. In addition, the ZnO:Er(3+),Yb(3+) shell acts as a good microwave absorber with excellent microwave thermal response property for microwave triggered drug release (the VP-16 release of 18% under microwave irradiation for 15 min outclass the 2% within 6h without microwave irradiation release). The release profile could be controlled by the duration and number of cycles of microwave application. This material therefore promises to be a useful noninvasive, externally controlled drug-delivery system in cancer therapy. Copyright © 2014 Elsevier B.V. All rights reserved.

Near-Infrared-Induced Heating of Confined Water in Polymeric Particles for Efficient Payload Release

PubMed Central

2015-01-01

Near-infrared (NIR) light-triggered release from polymeric capsules could make a major impact on biological research by enabling remote and spatiotemporal control over the release of encapsulated cargo. The few existing mechanisms for NIR-triggered release have not been widely applied because they require custom synthesis of designer polymers, high-powered lasers to drive inefficient two-photon processes, and/or coencapsulation of bulky inorganic particles. In search of a simpler mechanism, we found that exposure to laser light resonant with the vibrational absorption of water (980 nm) in the NIR region can induce release of payloads encapsulated in particles made from inherently non-photo-responsive polymers. We hypothesize that confined water pockets present in hydrated polymer particles absorb electromagnetic energy and transfer it to the polymer matrix, inducing a thermal phase change. In this study, we show that this simple and highly universal strategy enables instantaneous and controlled release of payloads in aqueous environments as well as in living cells using both pulsed and continuous wavelength lasers without significant heating of the surrounding aqueous solution. PMID:24717072

Near-infrared-induced heating of confined water in polymeric particles for efficient payload release.

PubMed

Viger, Mathieu L; Sheng, Wangzhong; Doré, Kim; Alhasan, Ali H; Carling, Carl-Johan; Lux, Jacques; de Gracia Lux, Caroline; Grossman, Madeleine; Malinow, Roberto; Almutairi, Adah

2014-05-27

Near-infrared (NIR) light-triggered release from polymeric capsules could make a major impact on biological research by enabling remote and spatiotemporal control over the release of encapsulated cargo. The few existing mechanisms for NIR-triggered release have not been widely applied because they require custom synthesis of designer polymers, high-powered lasers to drive inefficient two-photon processes, and/or coencapsulation of bulky inorganic particles. In search of a simpler mechanism, we found that exposure to laser light resonant with the vibrational absorption of water (980 nm) in the NIR region can induce release of payloads encapsulated in particles made from inherently non-photo-responsive polymers. We hypothesize that confined water pockets present in hydrated polymer particles absorb electromagnetic energy and transfer it to the polymer matrix, inducing a thermal phase change. In this study, we show that this simple and highly universal strategy enables instantaneous and controlled release of payloads in aqueous environments as well as in living cells using both pulsed and continuous wavelength lasers without significant heating of the surrounding aqueous solution.

Architecture of the Synaptotagmin-SNARE Machinery for Neuronal Exocytosis

PubMed Central

Zhou, Qiangjun; Lai, Ying; Bacaj, Taulant; Zhao, Minglei; Lyubimov, Artem Y.; Uervirojnangkoorn, Monarin; Zeldin, Oliver B.; Brewster, Aaron S.; Sauter, Nicholas K.; Cohen, Aina E.; Soltis, S. Michael; Alonso-Mori, Roberto; Chollet, Matthieu; Lemke, Henrik T.; Pfuetzner, Richard A.; Choi, Ucheor B.; Weis, William I.; Diao, Jiajie; Südhof, Thomas C.; Brunger, Axel T.

2015-01-01

Summary Synaptotagmin-1 and neuronal SNARE proteins play key roles in evoked synchronous neurotransmitter release. However, it is unknown how they cooperate to trigger synaptic vesicle fusion. Here we report atomic-resolution crystal structures of Ca2+- and Mg2+-bound complexes between synaptotagmin-1 and the neuronal SNARE complex, one of which was determined with diffraction data from an X-ray free electron laser, leading to an atomic-resolution structure with accurate rotamer assignments for many sidechains. The structures revealed several interfaces, including a large, specific, Ca2+-independent, and conserved interface. Tests of this interface by mutagenesis suggest that it is essential for Ca2+-triggered neurotransmitter release in neuronal synapses and for Ca2+-triggered vesicle fusion in a reconstituted system. We propose that this interface forms prior to Ca2+-triggering, and moves en bloc as Ca2+ influx promotes the interactions between synaptotagmin-1 and the plasma membrane, and consequently remodels the membrane to promote fusion, possibly in conjunction with other interfaces. PMID:26280336

Development of a non-explosive release actuator using shape memory alloy wire.

PubMed

Yoo, Young Ik; Jeong, Ju Won; Lim, Jae Hyuk; Kim, Kyung-Won; Hwang, Do-Soon; Lee, Jung Ju

2013-01-01

We have developed a newly designed non-explosive release actuator that can replace currently used release devices. The release mechanism is based on a separation mechanism, which relies on segmented nuts and a shape memory alloy (SMA) wire trigger. A quite fast and simple trigger operation is made possible through the use of SMA wire. This actuator is designed to allow a high preload with low levels of shock for the solar arrays of medium-size satellites. After actuation, the proposed device can be easily and instantly reset. Neither replacement, nor refurbishment of any components is necessary. According to the results of a performance test, the release time, preload capacity, and maximum shock level are 50 ms, 15 kN, and 350 G, respectively. In order to increase the reliability of the actuator, more than ten sets of performance tests are conducted. In addition, the proposed release actuator is tested under thermal vacuum and extreme vibration environments. No degradation or damage was observed during the two environment tests, and the release actuator was able to operate successfully. Considering the test results as a whole, we conclude that the proposed non-explosive release actuator can be applied reliably to intermediate-size satellites to replace existing release systems.

Tailorable drug capacity of dexamethasone-loaded conducting polymer matrix

NASA Astrophysics Data System (ADS)

Krukiewicz, K.

2018-05-01

The unique properties of conducting polymers, which are in the same time biocompatible and electrically responsive materials, make them perfect candidates for controlled drug release systems. In this study, the electrically-triggered controlled release system based on dexamethasone-loaded poly (3, 4-ethylenedioxypyrrole) (PEDOP) matrix is described. It is shown that the electropolymerization conditions can facilitate or suppress the formation of PEDOP/Dex matrix, as well as they can have the effect on its electrochemical performance. The release experiments performed in three different modes show that the drug capacity of PEDOP matrix increases with the increase in Dex concentration in the step of matrix synthesis, and higher Dex concentrations make it easier to control the amount of Dex released in an electrically-triggered mode. These results confirm the importance of the careful optimization of immobilization conditions to maximize drug capacity of matrix and maintain its electrochemical properties.

Ultrasound triggered drug delivery with liposomal nested microbubbles.

PubMed

Wallace, N; Wrenn, S P

2015-12-01

When ultrasound contrast agent microbubbles are nested within a liposome, damage to the liposome membrane caused by both stable and inertial cavitation of the microbubble allows for release of the aqueous core of the liposome. Triggered release was not accomplished unless microbubbles were present within the liposome. Leakage was tested using fluorescence assays developed specifically for this drug delivery vehicle and qualitative measurements using an optical microscope. These studies were done using a 1 MHz focused ultrasound transducer while varying parameters including peak negative ultrasound pressure, average liposome diameter, and microbubble concentration. Two regimes exist for membrane disruption caused by cavitating microbubbles. A faster release rate, as well as permanent membrane damage are seen for samples exposed to high pressure (2.1-3.7 MPa). A slower release rate and dilation/temporary poration are characteristic of stable cavitation for low pressure studies (0.54-1.7 MPa). Copyright © 2015 Elsevier B.V. All rights reserved.

Triggered metal ion release and oxidation: Ferrocene as new mechanophore in polymers.

PubMed

Di Giannantonio, Michela; Ayer, Mathieu A; Verde-Sesto, Ester; Lattuada, Marco; Weder, Christoph; Fromm, Katharina M

2018-06-13

The introduction of mechanophores into polymers allows transducing mechanical forces into chemical reactions for e.g. self-healing, catalytic activity, or mechanochromic response. Here, the first example of mechanically induced metal ion release from a polymer is reported. Ferrocene (Fc) was incorporated as an Fe-ion releasing mechanophore into poly(methyl acrylate)s (PMAs) and polyurethanes (PUs). Sonication triggered the preferential cleavage of the polymers at the Fc units over other bonds, as shown by a kinetic study of the molar mass distribution of the cleaved Fc-containing and Fc-free reference polymers. The released and oxidized Fe2+ ions can be detected with KSCN to generate the red-colored [Fe(SCN)n(H2O)6-n)](3-n)+ or reacted with K4[Fe(CN)6] to afford Prussian blue. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

3D DNS of Turbulent Premixed Flame with over 50 Species and 300 Elementary Reactions

NASA Astrophysics Data System (ADS)

Shimura, Masayasu; Yenerdag, Basmil; Naka, Yoshitsugu; Nada, Yuzuru; Tanahashi, Mamoru

2014-11-01

Three-dimensional direct numerical simulation of methane-air premixed planar flame propagating in homogenous isotropic turbulence is conducted to investigate local flame structure in thin reaction zones. Detailed kinetic mechanism, GRI-Mech 3.0 which includes 53 species and 325 elementary reactions, is used to represent methane-air reaction, and temperature dependences of transport and thermal properties are considered. For a better understanding of the local flame structure in thin reaction zones regime, distributions of mass fractions of major species, heat release rate, temperature and turbulent structures are investigated. Characteristic flame structures, such as radical fingering and multi-layered-like flame structures, are observed. The most expected maximum heat release rate in flame elements is lower than that of laminar flame with same mixture. To clarify mechanism of the decrease in local heat release rate, effects of strain rates tangential to flame front on local heat release rate are investigated.

To bind or not to bind? Different temporal binding effects from voluntary pressing and releasing actions.

PubMed

Zhao, Ke; Chen, Yu-Hsin; Yan, Wen-Jing; Fu, Xiaolan

2013-01-01

Binding effect refers to the perceptual attraction between an action and an outcome leading to a subjective compression of time. Most studies investigating binding effects exclusively employ the "pressing" action without exploring other types of actions. The present study addresses this issue by introducing another action, releasing action or the voluntary lifting of the finger/wrist, to investigate the differences between voluntary pressing and releasing actions. Results reveal that releasing actions led to robust yet short-lived temporal binding effects, whereas pressing condition had steady temporal binding effects up to super-seconds. The two actions also differ in sensitivity to changes in temporal contiguity and contingency, which could be attributed to the difference in awareness of action. Extending upon current models of "willed action," our results provide insights from a temporal point of view and support the concept of a dual system consisting of predictive motor control and top-down mechanisms.

hCG Triggering in ART: An Evolutionary Concept.

PubMed

Hershko Klement, Anat; Shulman, Adrian

2017-05-17

Human chorionic gonadotropin (hCG) is no longer a single, omnipotent ovulation triggering option. Gonadotropin releasing hormone (GnRH) agonist, initially presented as a substitute for hCG, has led to a new era of administering GnRH agonist followed by hCG triggering. According to this new concept, GnRH agonist enables successful ovum maturation, while hCG supports the luteal phase and pregnancy until placental shift.

Antitumor triptycene analogs directly interact with isolated mitochondria to rapidly trigger markers of permeability transition.

PubMed

Perchellet, Elisabeth M; Wang, Yang; Lou, Kaiyan; Zhao, Huiping; Battina, Srinivas K; Hua, Duy H; Perchellet, Jean-Pierre H

2007-01-01

Substituted triptycenes (TT code number), which block nucleoside transport, macromolecule syntheses and DNA topoisomerase activities, induce cytochrome c release and apoptotic DNA fragmentation, inhibit the proliferation of drug-sensitive and -resistant tumor cells in the nM range in vitro and rapidly trigger the collapse of mitochondrial transmembrane potential in cell and cell-free systems. Because mitochondrial permeability transition (MPT) requires more than depolarization, antitumor TTs were tested for their ability to directly trigger specific markers of MPT in isolated mitochondria. Large amplitude swelling and Ca2+ release were assayed in isolated mitochondria to demonstrate TT-induced MPT. Antitumor TTs interact with isolated mitochondria in a concentration- and time-dependent manner to rapidly cause large amplitude swelling and Ca2+ release in relation with their antiproliferative activities in L1210, HL-60 and LL/2 tumor cells in vitro. The ability of 4-10 uM TT15, TT16 and TT24 to maximally induce mitochondrial swelling and Ca2+ release within 20 min is similar to that of classic MPT inducers, such as 5 microg/ml alamethicin, 200 microM atractyloside, 5 microM phenylarsine oxide, 100 microM arsenic trioxide and a 100 microM Ca2+ overload. TT15 requires a priming concentration of 20 microM Ca2+ to trigger mitochondrial swelling and Ca2+ release and these 0.1 microM ruthenium red-sensitive MPT events are abolished by 1 microM cyclosporin A, 2 mM ADP and 20 microM bongkrekic acid, which block components of the permeability transition pore (PTP), and by 50-100 microM of various ubiquinones, which interact with the quinone binding site of the PTP and raise the Ca2+ load required for PTP opening. Antitumor TTs that trigger MPT in isolated mitochondria might interact with components of the PTP to boost its Ca2+-sensitive transition from the closed to the open state and might be valuable to develop mitochondriotoxic drugs that directly activate early components of apoptosis.

Light-stimulated cargo release from a core–shell structured nanocomposite for site-specific delivery

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cai, Yun; Ling, Li; Li, Xiaofang

This paper reported a core–shell structured site-specific delivery system with a light switch triggered by low energy light (λ=510 nm). Its core was composed of supermagnetic Fe{sub 3}O{sub 4} nanoparticles for magnetic guiding and targeting. Its outer shell consisted of mesoporous silica molecular sieve MCM-41 which offered highly ordered hexagonal tunnels for cargo capacity. A light switch N1-(4aH-cyclopenta[1,2-b:5,4-b′]dipyridin-5(5aH)-ylidene)benzene-1, 4-diamine (CBD) was covalently grafted into these hexagonal tunnels, serving as light stimuli acceptor with loading content of 1.1 μM/g. This composite was fully characterized and confirmed by SEM, TEM, XRD patterns, N{sub 2} adsorption/desorption, thermogravimetric analysis, IR, UV–vis absorption and emissionmore » spectra. Experimental data suggested that this composite had a core as wide as 150 nm and could be magnetically guided to specific sites. Its hexagonal tunnels were as long as 180 nm. Upon light stimuli of “on” and “off” states, controllable release was observed with short release time of ~900 s (90% capacity). - Graphical abstract: A core–shell structured site-specific delivery system with a light switch triggered by yellow light was constructed. Controllable release was observed with short release time of ~900 s (90% capacity). - Highlights: • A core–shell structured site-specific delivery system was constructed. • It consisted of Fe{sub 3}O{sub 4} core and MCM-41 shell grafted with light switch. • This delivery system was triggered by low energy light. • Controllable release was observed with short release time of ~900 s.« less

Production of interleukin-1alpha by human endometrial stromal cells is triggered during menses and dysfunctional bleeding and is induced in culture by epithelial interleukin-1alpha released upon ovarian steroids withdrawal.

PubMed

Pretto, Chrystel M; Gaide Chevronnay, Héloïse P; Cornet, Patricia B; Galant, Christine; Delvaux, Denis; Courtoy, Pierre J; Marbaix, Etienne; Henriet, Patrick

2008-10-01

Endometrial breakdown during menstruation and dysfunctional bleeding is triggered by the abrupt expression of matrix metalloproteinases (MMPs), including interstitial collagenase (MMP-1). The paracrine induction of MMP-1 in stromal cells via epithelium-derived IL-1alpha is repressed by ovarian steroids. However, the control by estradiol (E) and progesterone (P) of endometrial IL-1alpha expression and bioactivity remains unknown. Variations of endometrial IL-1alpha mRNA and protein along the menstrual cycle and during dysfunctional bleeding were determined using RT-PCR, in situ hybridization, and immunolabeling. The mechanism of EP control was analyzed using culture of explants, laser capture microdissection, and purified cells. Data were compared with expression changes of IL-1beta and IL-1 receptor antagonist. IL-1alpha is synthesized by epithelial cells throughout the cycle but E and/or P prevents its release. In contrast, endometrial stromal cells produce IL-1alpha only at menses and during irregular bleeding in areas of tissue breakdown. Stromal expression of IL-1alpha, like that of MMP-1, is repressed by P (alone or with E) but triggered by epithelium-derived IL-1alpha released upon EP withdrawal. Our experiments in cultured endometrium suggest that IL-1alpha released by epithelial cells triggers the production of IL-1alpha by stromal cells in a paracrine amplification loop to induce MMP-1 expression during menstruation and dysfunctional bleeding. All three steps of this amplification cascade are repressed by EP.

Further investigation into the mechanism of tachykinin NK(2) receptor-triggered serotonin release from guinea-pig proximal colon.

PubMed

Kojima, Shu-Ichi; Ikeda, Masashi; Kamikawa, Yuichiro

2009-05-01

The effects of the monoamine oxidase A (MAO-A) inhibitor clorgyline, the L-type calcium-channel blocker nicardipine, the syntaxin inhibitor botulinum toxin type C, and the potent thiol-oxidant phenylarsine oxide (PAO) on the selective tachykinin NK(2)-receptor agonist [beta-Ala(8)]-neurokinin A(4-10) [betaAla-NKA-(4-10)]-evoked 5-hydroxytryptamine (5-HT) outflow from colonic enterochromaffin (EC) cells was investigated in vitro using isolated guinea-pig proximal colon. The betaAla-NKA-(4-10)-evoked outflow of 5-HT from clorgyline-treated colonic strips was markedly higher than that from clorgyline-untreated colonic strips. The betaAla-NKA-(4-10)-evoked 5-HT outflow from the clorgyline-treated colonic strips was sensitive to nicardipine or botulinum toxin type C. Moreover, PAO concentration-dependently suppressed the betaAla-NKA-(4-10)-evoked 5-HT outflow from the clorgyline-treated colonic strips. The suppressant action of PAO was reversed by the reducing agent dithiothrietol, but was not blocked by the protein tyrosine kinase inhibitor genistein. These results suggest that the tachykinin NK(2) receptor-triggered 5-HT release from guinea-pig colonic EC cells is mediated by syntaxin-related exocytosis mechanisms and that colonic mucosa MAO-A activity has the important function of modulating the tachykinin NK(2) receptor-triggered 5-HT release. It also appears that PAO-mediated sulfhydryl oxidation plays a role in modulating the tachykinin NK(2) receptor-triggered 5-HT release through a mechanism independent of inhibition of protein tyrosine phosphatase activity.

Superoxide anion radical-triggered Ca2+ release from cardiac sarcoplasmic reticulum through ryanodine receptor Ca2+ channel.

PubMed

Kawakami, M; Okabe, E

1998-03-01

The ryanodine receptor Ca2+ channel (RyRC) constitutes the Ca2+-release pathway in sarcoplasmic reticulum (SR) of cardiac muscle. A direct mechanical and a Ca2+-triggered mechanism (Ca2+-induced Ca2+ release) have been proposed to explain the in situ activation of Ca2+ release in cardiac muscle. A variety of chemical oxidants have been shown to activate RyRC; however, the role of modification induced by oxygen-derived free radicals in pathological states of the muscle remains to be elucidated. It has been hypothesized that oxygen-derived free radicals initiate Ca2+-mediated functional changes in or damage to cardiac muscle by acting on the SR and promoting an increase in Ca2+ release. We confirmed that superoxide anion radical (O2-) generated from hypoxanthine-xanthine oxidase reaction decreases calmodulin content and increases 45Ca2+ efflux from the heavy fraction of canine cardiac SR vesicles; hypoxanthine-xanthine oxidase also decreases Ca2+ free within the intravesicular space of the SR with no effect on Ca2+-ATPase activity. Current fluctuations through single Ca2+-release channels have been monitored after incorporation into planar phospholipid bilayers. We demonstrate that activation of the channel by O2- is dependent of the presence of calmodulin and identified calmodulin as a functional mediator of O2--triggered Ca2+ release through the RyRC. For the first time, we show that O2- stimulates Ca2+ release from heavy SR vesicles and suggest the importance of accessory proteins such as calmodulin in modulating the effect of O2-. The decreased calmodulin content induced by oxygen-derived free radicals, especially O2-, is a likely mechanism of accumulation of cytosolic Ca2+ (due to increased Ca2+ release from SR) after reperfusion of the ischemic heart.

Activation of M1 muscarinic receptors triggers transmitter release from rat sympathetic neurons through an inhibition of M-type K+ channels.

PubMed

Lechner, Stefan G; Mayer, Martina; Boehm, Stefan

2003-12-15

Acetylcholine has long been known to excite sympathetic neurons via M1 muscarinic receptors through an inhibition of M-currents. Nevertheless, it remained controversial whether activation of muscarinic receptors is also sufficient to trigger noradrenaline release from sympathetic neurons. In primary cultures of rat superior cervical ganglia, the muscarinic agonist oxotremorine M inhibited M-currents with half-maximal effects at 1 microM and induced the release of previously incorporated [3H]noradrenaline with half-maximal effects at 10 microM. This latter action was not affected by the nicotinic antagonist mecamylamine which, however, abolished currents through nicotinic receptors elicited by high oxotremorine M concentrations. Ablation of the signalling cascades linked to inhibitory G proteins by pertussis toxin potentiated the release stimulating effect of oxotremorine M, and the half-maximal concentration required to stimulate noradrenaline release was decreased to 3 microM. Pirenzepine antagonized the inhibition of M-currents and the induction of release by oxotremorine M with identical apparent affinity, and both effects were abolished by the muscarinic toxin 7. These results indicate that one muscarinic receptor subtype, namely M1, mediates these two effects. Retigabine, which enhances M-currents, abolished the release induced by oxotremorine M, but left electrically induced release unaltered. Moreover, retigabine shifted the voltage-dependent activation of M-currents by about 20 mV to more negative potentials and caused 20 mV hyperpolarisations of the membrane potential. In the absence of retigabine, oxotremorine M depolarised the neurons and elicited action potential discharges in 8 of 23 neurons; in its presence, oxotremorine M still caused equal depolarisations, but always failed to trigger action potentials. Action potential waveforms caused by current injection were not affected by retigabine. These results indicate that the inhibition of M-currents is the basis for the stimulation of transmitter release from sympathetic neurons via M1 muscarinic receptors.

Evaluating the Mechanisms of Light-Triggered siRNA Release from Nanoshells for Temporal Control Over Gene Regulation.

PubMed

Riley, Rachel S; Dang, Megan N; Billingsley, Margaret M; Abraham, Baxter; Gundlach, Lars; Day, Emily S

2018-06-13

The ability to regulate intracellular gene expression with exogenous nucleic acids such as small interfering RNAs (siRNAs) has substantial potential to improve the study and treatment of disease. However, most transfection agents and nanoparticle-based carriers that are used for the intracellular delivery of nucleic acids cannot distinguish between diseased and healthy cells, which may cause them to yield unintended widespread gene regulation. An ideal delivery system would only silence targeted proteins in diseased tissue in response to an external stimulus. To enable spatiotemporal control over gene silencing, researchers have begun to develop nucleic acid-nanoparticle conjugates that keep their nucleic acid cargo inactive until it is released from the nanoparticle on-demand by externally applied near-infrared laser light. This strategy can overcome several limitations of other nucleic acid delivery systems, but the mechanisms by which these platforms operate remain ill understood. Here, we perform a detailed investigation of the mechanisms by which silica core/gold shell nanoshells (NSs) release conjugated siRNA upon excitation with either pulsed or continuous wave (CW) near-infrared (NIR) light, with the goal of providing insight into how these nanoconjugates can enable on-demand gene regulation. We demonstrate that siRNA release from NSs upon pulsed laser irradiation is a temperature-independent process that is substantially more efficient than siRNA release triggered by CW irradiation. Contrary to literature, which suggests that only pulsed irradiation releases siRNA duplexes, we found that both modes of irradiation release a mixture of siRNA duplexes and single-stranded oligonucleotides, but that pulsed irradiation results in a higher percentage of released duplexes. To demonstrate that the siRNA released from NSs upon pulsed irradiation remains functional, we evaluated the use of NSs coated with green fluorescent protein (GFP)-targeted siRNA (siGFP-NS) for on-demand knockdown of GFP in cells. We found that GFP-expressing cells treated with siGFP-NS and irradiated with a pulsed laser experienced a 33% decrease in GFP expression compared to cells treated with no laser. Further, we observed that light-triggered gene silencing mediated by siGFP-NS is more potent than using commercial transfection agents to deliver siRNA into cells. This work provides unprecedented insight into the mechanisms by which plasmonic NSs release siRNA upon light irradiation and demonstrates the importance of thoroughly characterizing photoresponsive nanosystems for applications in triggered gene regulation.

How a RING finger protein and a steroid hormone control autophagy.

PubMed

Lindmo, Karine; Stenmark, Harald

2006-01-01

Previous work in our laboratory has indicated that the steroid hormone ecdysone triggers programmed autophagy in the fat body of Drosophila larvae by downregulating the class I phosphoinositide 3-kinase (PI3K) pathway. We recently found evidence that Deep orange (Dor), a Drosophila RING finger protein implicated in late-endosomal trafficking, controls ecdysone signaling as well as autolysosome fusion, thus exerting a dual regulation of autophagy. We found that dor mutants are defective in programmed autophagy. The mutant larvae showed impaired upregulation of ecdysone signaling during development, accompanied by a failure to downregulate the PI3K pathway. Downregulation of the PI3K pathway could be restored by feeding the dor mutants with ecdysone. Even though ecdysone signaling and autophagy were impaired in the dor mutants, we detected an accumulation of autophagosomes in dor mutant fat bodies. This could probably be attributed to the failure of autophagosomes to fuse with lysosomes. In this Addendum we review these findings and provide some speculations about how Dor may control both ecdysone signalling and autolysosomal fusion.

Mitochondrial damage elicits a TCDD-inducible poly(ADP-ribose) polymerase-mediated antiviral response

PubMed Central

Kozaki, Tatsuya; Komano, Jun; Kanbayashi, Daiki; Takahama, Michihiro; Misawa, Takuma; Satoh, Takashi; Takeuchi, Osamu; Kawai, Taro; Shimizu, Shigeomi; Matsuura, Yoshiharu; Akira, Shizuo; Saitoh, Tatsuya

2017-01-01

The innate immune system senses RNA viruses by pattern recognition receptors (PRRs) and protects the host from virus infection. PRRs mediate the production of immune modulatory factors and direct the elimination of RNA viruses. Here, we show a unique PRR that mediates antiviral response. Tetrachlorodibenzo-p-dioxin (TCDD)-inducible poly(ADP ribose) polymerase (TIPARP), a Cysteine3 Histidine (CCCH)-type zinc finger-containing protein, binds to Sindbis virus (SINV) RNA via its zinc finger domain and recruits an exosome to induce viral RNA degradation. TIPARP typically localizes in the nucleus, but it accumulates in the cytoplasm after SINV infection, allowing targeting of cytoplasmic SINV RNA. Redistribution of TIPARP is induced by reactive oxygen species (ROS)-dependent oxidization of the nuclear pore that affects cytoplasmic-nuclear transport. BCL2-associated X protein (BAX) and BCL2 antagonist/killer 1 (BAK1), B-cell leukemia/lymphoma 2 (BCL2) family members, mediate mitochondrial damage to generate ROS after SINV infection. Thus, TIPARP is a viral RNA-sensing PRR that mediates antiviral responses triggered by BAX- and BAK1-dependent mitochondrial damage. PMID:28213497

Arsenic trioxide controls the fate of the PML-RARalpha oncoprotein by directly binding PML.

PubMed

Zhang, Xiao-Wei; Yan, Xiao-Jing; Zhou, Zi-Ren; Yang, Fei-Fei; Wu, Zi-Yu; Sun, Hong-Bin; Liang, Wen-Xue; Song, Ai-Xin; Lallemand-Breitenbach, Valérie; Jeanne, Marion; Zhang, Qun-Ye; Yang, Huai-Yu; Huang, Qiu-Hua; Zhou, Guang-Biao; Tong, Jian-Hua; Zhang, Yan; Wu, Ji-Hui; Hu, Hong-Yu; de Thé, Hugues; Chen, Sai-Juan; Chen, Zhu

2010-04-09

Arsenic, an ancient drug used in traditional Chinese medicine, has attracted worldwide interest because it shows substantial anticancer activity in patients with acute promyelocytic leukemia (APL). Arsenic trioxide (As2O3) exerts its therapeutic effect by promoting degradation of an oncogenic protein that drives the growth of APL cells, PML-RARalpha (a fusion protein containing sequences from the PML zinc finger protein and retinoic acid receptor alpha). PML and PML-RARalpha degradation is triggered by their SUMOylation, but the mechanism by which As2O3 induces this posttranslational modification is unclear. Here we show that arsenic binds directly to cysteine residues in zinc fingers located within the RBCC domain of PML-RARalpha and PML. Arsenic binding induces PML oligomerization, which increases its interaction with the small ubiquitin-like protein modifier (SUMO)-conjugating enzyme UBC9, resulting in enhanced SUMOylation and degradation. The identification of PML as a direct target of As2O3 provides new insights into the drug's mechanism of action and its specificity for APL.

Conservative management of partial extensor tendon lacerations greater than half the width of the tendon in manual workers.

PubMed

Al-Qattan, Mohammad M

2015-04-01

Conservative management (without suturing or splints) of partial extensor tendon lacerations greater than half the width of the tendon has not been previously investigated. In this prospective study, a total of 45 injured tendons (with lacerations involving 55%-90% of the width of the tendon) in 39 patients were treated conservatively. Injury zones I, III, and V of the fingers; and zones I and III of the thumb were excluded. Immediate non-resistive active mobilization was initiated and continued for 4 weeks, followed by resistive exercises. Patients were allowed to go back to work after 6 weeks. There were no cases of ruptures, triggering, infection, or complex regional pain syndrome. At final follow-up (8-9 months after injury), all patients obtained full range of motion with no extension lags. All patients were able to go back to normal duties. We conclude that early active motion without the use of splints or sutures in major extensor tendon lacerations in zones II, IV, VI-VIII of the fingers; and zones II, IV, and V of the thumb is safe.

Common Soft Tissue Musculoskeletal Pain Disorders.

PubMed

Hubbard, Matthew J; Hildebrand, Bernard A; Battafarano, Monica M; Battafarano, Daniel F

2018-06-01

Soft tissue musculoskeletal pain disorders are common in the primary care setting. Early recognition and diagnosis of these syndromes minimizes patient pain and disability. This article gives a brief overview of the most common soft tissue musculoskeletal pain syndromes. The authors used a regional approach to organize the material, as providers will encounter these syndromes with complaints of pain referring to an anatomic location. The covered disorders include myofascial pain syndrome, rotator cuff tendinopathy, bicipital tendinopathy, subacromial bursitis, olecranon bursitis, epicondylitis, De Quervain disease, trigger finger, trochanteric bursitis, knee bursitis, pes anserine bursitis, Baker cyst, plantar fasciitis, and Achilles tendinopathy. Published by Elsevier Inc.

Multi-functional liposomes showing radiofrequency-triggered release and magnetic resonance imaging for tumor multi-mechanism therapy.

PubMed

Du, Bin; Han, Shuping; Li, Hongyan; Zhao, Feifei; Su, Xiangjie; Cao, Xiaohui; Zhang, Zhenzhong

2015-03-12

Recently, nanoplatforms with multiple functions, such as tumor-targeting drug carriers, MRI, optical imaging, thermal therapy etc., have become popular in the field of cancer research. The present study reports a novel multi-functional liposome for cancer theranostics. A dual targeted drug delivery with radiofrequency-triggered drug release and imaging based on the magnetic field influence was used advantageously for tumor multi-mechanism therapy. In this system, the surface of fullerene (C60) was decorated with iron oxide nanoparticles, and PEGylation formed a hybrid nanosystem (C60-Fe3O4-PEG2000). Thermosensitive liposomes (dipalmitoylphosphatidylcholine, DPPC) with DSPE-PEG2000-folate wrapped up the hybrid nanosystem and docetaxel (DTX), which were designed to combine features of biological and physical (magnetic) drug targeting for fullerene radiofrequency-triggered drug release. The magnetic liposomes not only served as powerful tumor diagnostic magnetic resonance imaging (MRI) contrast agents, but also as powerful agents for photothermal ablation of tumors. Furthermore, a remarkable thermal therapy combined chemotherapy multi-functional liposome nanoplatform converted radiofrequency energy into thermal energy to release drugs from thermosensitive liposomes, which was also observed during both in vitro and in vivo treatment. The multi-functional liposomes also could selectively kill cancer cells in highly localized regions via their excellent active tumor targeting and magnetic targeted abilities.

Distinct neuronal coding schemes in memory revealed by selective erasure of fast synchronous synaptic transmission.

PubMed

Xu, Wei; Morishita, Wade; Buckmaster, Paul S; Pang, Zhiping P; Malenka, Robert C; Südhof, Thomas C

2012-03-08

Neurons encode information by firing spikes in isolation or bursts and propagate information by spike-triggered neurotransmitter release that initiates synaptic transmission. Isolated spikes trigger neurotransmitter release unreliably but with high temporal precision. In contrast, bursts of spikes trigger neurotransmission reliably (i.e., boost transmission fidelity), but the resulting synaptic responses are temporally imprecise. However, the relative physiological importance of different spike-firing modes remains unclear. Here, we show that knockdown of synaptotagmin-1, the major Ca(2+) sensor for neurotransmitter release, abrogated neurotransmission evoked by isolated spikes but only delayed, without abolishing, neurotransmission evoked by bursts of spikes. Nevertheless, knockdown of synaptotagmin-1 in the hippocampal CA1 region did not impede acquisition of recent contextual fear memories, although it did impair the precision of such memories. In contrast, knockdown of synaptotagmin-1 in the prefrontal cortex impaired all remote fear memories. These results indicate that different brain circuits and types of memory employ distinct spike-coding schemes to encode and transmit information. Copyright © 2012 Elsevier Inc. All rights reserved.

Photo-triggered release of 5-fluorouracil from a MOF drug delivery vehicle.

PubMed

Roth Stefaniak, Kristina; Epley, Charity C; Novak, Joshua J; McAndrew, Margaret L; Cornell, Hannah D; Zhu, Jie; McDaniel, Dylan K; Davis, Jennifer L; Allen, Irving C; Morris, Amanda J; Grove, Tijana Z

2018-06-21

A nano metal-organic-framework (nanoMOF) was employed as a first-of-its kind drug delivery vehicle (DDV) for the photo-controlled release of therapeutics with simultaneous breakdown of the carrier into small molecules.

Activation of a promyelocytic leukemia-tumor protein 53 axis underlies acute promyelocytic leukemia cure.

PubMed

Ablain, Julien; Rice, Kim; Soilihi, Hassane; de Reynies, Aurélien; Minucci, Saverio; de Thé, Hugues

2014-02-01

Acute promyelocytic leukemia (APL) is driven by the promyelocytic leukemia (PML)-retinoic acid receptor-α (PML-RARA) fusion protein, which interferes with nuclear receptor signaling and PML nuclear body (NB) assembly. APL is the only malignancy definitively cured by targeted therapies: retinoic acid (RA) and/or arsenic trioxide, which both trigger PML-RARA degradation through nonoverlapping pathways. Yet, the cellular and molecular determinants of treatment efficacy remain disputed. We demonstrate that a functional Pml-transformation-related protein 53 (Trp53) axis is required to eradicate leukemia-initiating cells in a mouse model of APL. Upon RA-induced PML-RARA degradation, normal Pml elicits NB reformation and induces a Trp53 response exhibiting features of senescence but not apoptosis, ultimately abrogating APL-initiating activity. Apart from triggering PML-RARA degradation, arsenic trioxide also targets normal PML to enhance NB reformation, which may explain its clinical potency, alone or with RA. This Pml-Trp53 checkpoint initiated by therapy-triggered NB restoration is specific for PML-RARA-driven APL, but not the RA-resistant promyelocytic leukemia zinc finger (PLZF)-RARA variant. Yet, as NB biogenesis is druggable, it could be therapeutically exploited in non-APL malignancies.

Kisspeptin as a promising oocyte maturation trigger for in vitro fertilisation in humans.

PubMed

Kasum, Miro; Franulić, Daniela; Čehić, Ermin; Orešković, Slavko; Lila, Albert; Ejubović, Emina

2017-08-01

The aim of this review is to analyse the effectiveness of exogenous kisspeptin administration as a novel alternative of triggering oocyte maturation, instead of currently used triggers such as human chorionic gonadotropin (hCG) or gonadotropin releasing hormone (GnRH) agonist, in women undergoing in vitro fertilisation (IVF) treatment. Kisspeptin has been considered a master regulator of two modes of GnRH and hence gonadotropin secretion, pulses and surges. Administration of kisspeptin-10 and kisspeptin-54 induces the luteinising hormone (LH) surge required for egg maturation and ovulation in animal investigations and LH release during the preovulatory phase of the menstrual cycle and hypothalamic amenorrhoea in humans. Exogenous kisspeptin-54 has been successfully administered as a promising method of triggering oocyte maturation, following ovarian stimulation with gonadotropins and GnRH antagonists in women undergoing IVF, due to its efficacy considering achieved pregnancy rates compared to hCG and GnRH agonists. Also, its safety in patients at high risk of developing ovarian hyperstimulation syndrome is noteworthy. Nevertheless, further studies would be desirable to establish the optimal trigger of egg maturation and to improve the reproductive outcome for women undergoing IVF treatment.

Development of Overflow-Prevention Valve with Trigger Mechanism.

NASA Astrophysics Data System (ADS)

Ishino, Yuji; Mizuno, Takeshi; Takasaki, Masaya

2016-09-01

A new overflow-prevention valve for combustible fluid is developed which uses a trigger mechanism. Loading arms for combustible fluid are used for transferring oil from a tanker to tanks and vice versa. The loading arm has a valve for preventing overflow. Overflow- prevention valves cannot use any electric component to avoid combustion. Therefore, the valve must be constructed only by mechanical parts. The conventional overflow-prevention valve uses fluid and pneumatic forces. It consists of a sensor probe, a cylinder, a main valve for shutting off the fluid and a locking mechanism for holding an open state of the main valve. The proposed overflow-prevention valve uses the pressure due to the height difference between the fluid level of the tank and the sensor probe. However, the force of the cylinder produced by the pressure is too small to release the locking mechanism. Therefore, a trigger mechanism is introduced between the cylinder and the locking mechanism. The trigger mechanism produces sufficient force to release the locking mechanism and close the main valve when the height of fluid exceeds a threshold value. A trigger mechanism is designed and fabricated. The operation necessary for closing the main valve is conformed experimentally.

Photoresponsive lipid-polymer hybrid nanoparticles for controlled doxorubicin release

NASA Astrophysics Data System (ADS)

Yao, Cuiping; Wu, Ming; Zhang, Cecheng; Lin, Xinyi; Wei, Zuwu; Zheng, Youshi; Zhang, Da; Zhang, Zhenxi; Liu, Xiaolong

2017-06-01

Currently, photoresponsive nanomaterials are particularly attractive due to their spatial and temporal controlled drug release abilities. In this work, we report a photoresponsive lipid-polymer hybrid nanoparticle for remote controlled delivery of anticancer drugs. This hybrid nanoparticle comprises three distinct functional components: (i) a poly(D,L-lactide-co-glycolide) (PLGA) core to encapsulate doxorubicin; (ii) a soybean lecithin monolayer at the interface of the core and shell to act as a molecular fence to prevent drug leakage; (iii) a photoresponsive polymeric shell with anti-biofouling properties to enhance nanoparticle stability, which could be detached from the nanoparticle to trigger the drug release via a decrease in the nanoparticle’s stability under light irradiation. In vitro results revealed that this core-shell nanoparticle had excellent light-controlled drug release behavior (76% release with light irradiation versus 10% release without light irradiation). The confocal microscopy and flow cytometry results also further demonstrated the light-controlled drug release behavior inside the cancer cells. Furthermore, a CCK8 assay demonstrated that light irradiation could significantly improve the efficiency of killing cancer cells. Meanwhile, whole-animal fluorescence imaging of a tumor-bearing mouse also confirmed that light irradiation could trigger drug release in vivo. Taken together, our data suggested that a hybrid nanoparticle could be a novel light controlled drug delivery system for cancer therapy.

Programming temporal shapeshifting

NASA Astrophysics Data System (ADS)

Hu, Xiaobo; Zhou, Jing; Vatankhah-Varnosfaderani, Mohammad; Daniel, William F. M.; Li, Qiaoxi; Zhushma, Aleksandr P.; Dobrynin, Andrey V.; Sheiko, Sergei S.

2016-09-01

Shapeshifting enables a wide range of engineering and biomedical applications, but until now transformations have required external triggers. This prerequisite limits viability in closed or inert systems and puts forward the challenge of developing materials with intrinsically encoded shape evolution. Herein we demonstrate programmable shape-memory materials that perform a sequence of encoded actuations under constant environment conditions without using an external trigger. We employ dual network hydrogels: in the first network, covalent crosslinks are introduced for elastic energy storage, and in the second one, temporary hydrogen-bonds regulate the energy release rate. Through strain-induced and time-dependent reorganization of the reversible hydrogen-bonds, this dual network allows for encoding both the rate and pathway of shape transformations on timescales from seconds to hours. This generic mechanism for programming trigger-free shapeshifting opens new ways to design autonomous actuators, drug-release systems and active implants.

Inner layer-embedded contact lenses for pH-triggered controlled ocular drug delivery.

PubMed

Zhu, Qiang; Liu, Chang; Sun, Zheng; Zhang, Xiaofei; Liang, Ning; Mao, Shirui

2018-07-01

Contact lenses (CLs) are ideally suited for controlled ocular drug delivery, but are limited by short release duration, poor storage stability and low drug loading. In this study, we present a novel inner layer-embedded contact lens capable of pH-triggered extended ocular drug delivery with good storage stability. Blend film of ethyl cellulose and Eudragit S100 was used as the inner layer, while pHEMA hydrogel was used as outer layer to fabricate inner layer-embedded contact lens. Using diclofenac sodium(DS) as a drug model, influence of polymer ratio in the blend film, EC viscosity, drug/polymer ratio, inner layer thickness and outlayer thickness of pHEMA hydrogel on drug release behavior was studied and optimized for daily use. The pH-triggered drug eluting pattern enables the inner layer-embedded contact lens being stored in phosphate buffer solution pH 6.8 with ignorable drug loss and negligible changes in drug release pattern. In vivo pharmacokinetic study in rabbits showed sustained drug release for over 24 h in tear fluid, indicating significant improvement in drug corneal residence time. A level A IVIVC was established between in vitro drug release and in vivo drug concentration in tear fluid. In conclusion, this inner layer embedded contact lens design could be used as a platform for extended ocular drug delivery with translational potential for both anterior and posterior ocular diseases therapy. Copyright © 2018 Elsevier B.V. All rights reserved.

An effective trigger for energy release of vinylheptafulvene-based solar heat batteries.

PubMed

Cacciarini, Martina; Vlasceanu, Alexandru; Jevric, Martyn; Nielsen, Mogens Brøndsted

2017-05-30

Stoichiometric copper(i) tetrakis(acetonitrile) is found to activate the thermal ring-closure reaction of a series of high-energy vinylheptafulvene isomers to the corresponding low-energy and photoactive dihydroazulenes, allowing the release of energy upon request.

Porcine reproductive and respiratory syndrome virus infection triggers HMGB1 release to promote inflammatory cytokine production

DOE Office of Scientific and Technical Information (OSTI.GOV)

Duan, Erzhen; Wang, Dang; Luo, Rui

The high mobility group box 1 (HMGB1) protein is an endogenous damage-associated molecular pattern (DAMP) molecule involved in the pathogenesis of various infectious agents. Based on meta-analysis of all publicly available microarray datasets, HMGB1 has recently been proposed as the most significant immune modulator during the porcine response to porcine reproductive and respiratory syndrome virus (PRRSV) infection. However, the function of HMGB1 in PRRSV pathogenesis is unclear. In this study, we found that PRRSV infection triggers the translocation of HMGB1 from the nucleus to the extracellular milieu in MARC-145 cells and porcine alveolar macrophages. Although HMGB1 has no effect onmore » PRRSV replication, HMGB1 promotes PRRSV-induced NF-κB activation and subsequent expression of inflammatory cytokines through receptors RAGE, TLR2 and TLR4. Our findings show that HMGB1 release, triggered by PRRSV infection, enhances the efficiency of virus-induced inflammatory responses, thereby providing new insights into the pathogenesis of PRRSV infection. - Highlights: • PRRSV infection triggers HMGB1 release from MARC-145 cells and PAMs. • HMGB1 does not significantly affect PRRSV proliferation. • HMGB1 is involved in PRRSV-induced NF-κB activation and inflammatory responses. • HMGB1 promotes PRRSV-induced inflammatory responses through TLR2/4 and RAGE.« less

Kirschner-wire fixation for postburn flexion contracture deformity and consequences on articular surface.

PubMed

Sungur, Nezih; Ulusoy, Mustafa Gürhan; Boyacgil, Süreyya; Ortaparmak, Hülya; Akyüz, Mihriban; Ortak, Turgut; Koçer, Uğur; Sensöz, Omer

2006-02-01

Kirschner-wire (K-wire) fixation for 3-6 weeks is an approved method for stabilization of the fingers after the release of flexion contracture deformity. On the other hand, articular surface damage in small joints due to pin fixation is still a topic of debate. Reports claiming permanent joint destruction due to this procedure exist in the literature. To clarify this doubt, a prospective study was carried out in 72 patients with flexion contracture of the hand fingers. After the surgical release of the deformity, immobilization of the interphalangeal (IP) and metacarpophalangeal (MCP) joints was carried out with K-wire fixation for 3 weeks. Clinical evaluation of the patients was accomplished with total active motion (TAM), grip, and pinch force measurements, whereas magnetic resonance (MR) and radionuclide imaging were used as radiodiagnostic tools. Mean follow-up period of the patients was 32 months. Satisfactory results were obtained in terms of functional and esthetic aspects. Evaluation of the data derived from the clinical and radiologic measurements revealed no permanent articular surface damage. K-wire fixation was documented to be an invaluable therapeutic approach not only to prevent recurrence of the contracture deformity but also to stabilize the skin graft effectively. This technique was concluded to provide effective immobilization without permanent articular damage.

Gonadotropin-releasing hormone agonist trigger increases the number of oocytes and embryos available for cryopreservation in cancer patients undergoing ovarian stimulation for fertility preservation.

PubMed

Pereira, Nigel; Kelly, Amelia G; Stone, Logan D; Witzke, Justine D; Lekovich, Jovana P; Elias, Rony T; Schattman, Glenn L; Rosenwaks, Zev

2017-09-01

To compare the oocyte and embryo yield associated with GnRH-agonist triggers vs. hCG triggers in cancer patients undergoing controlled ovarian stimulation (COS) for fertilization preservation. Retrospective cohort study. Academic center. Cancer patients undergoing COS with letrozole and gonadotropins or gonadotropin-only protocols for oocyte or embryo cryopreservation. Gonadotropin-releasing hormone agonist or hCG trigger. Number of metaphase II (MII) oocytes or two-pronuclei (2PN) embryos available for cryopreservation were primary outcomes. Separate multivariate linear regression models were used to assess the effect of trigger type on the primary outcomes, after controlling for confounders of interest. A total of 341 patients were included, 99 (29.0%) in the GnRH-agonist group and 242 (71%) in the hCG group. There was no difference in the baseline demographics of patients receiving GnRH-agonist or hCG triggers. Within the letrozole and gonadotropins group (n = 269), the number (mean ± SD, 11.8 ± 5.8 vs. 9.9 ± 6.0) and percentage of MII oocytes (89.6% vs. 73.0%) available for cryopreservation was higher with GnRH-agonist triggers compared with hCG triggers. Similar results were noted with GnRH-agonist triggers in the gonadotropin-only group (n = 72) (i.e., a higher number [13.3 ± 7.9 vs. 9.3 ± 6.0] and percentage of MII oocytes [85.7% vs. 72.8%] available for cryopreservation). Multivariate linear regression demonstrated approximately three more MII oocytes and 2PN embryos available for cryopreservation in the GnRH-agonist trigger group, irrespective of cancer and COS protocol type. Utilization of a GnRH-agonist trigger increases the number of MII oocytes and 2PN embryos available for cryopreservation in cancer patients undergoing COS for fertility preservation. Copyright © 2017 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Comorbidities in rotator cuff disease: a case-control study.

PubMed

Titchener, Andrew G; White, Jonathan J E; Hinchliffe, Sally R; Tambe, Amol A; Hubbard, Richard B; Clark, David I

2014-09-01

Rotator cuff disease is a common condition in the general population, but relatively little is known about its associated risk factors. We have undertaken a large case-control study using The Health Improvement Network database to assess and to quantify the relative contributions of some constitutional and environmental risk factors for rotator cuff disease in the community. Our data set included 5000 patients with rotator cuff disease who were individually matched with a single control by age, sex, and general practice (primary care practice). The median age at diagnosis was 55 years (interquartile range, 44-65 years). Multivariate analysis showed that the risk factors associated with rotator cuff disease were Achilles tendinitis (odds ratio [OR] = 1.78), trigger finger (OR = 1.99), lateral epicondylitis (OR = 1.71), and carpal tunnel syndrome (OR = 1.55). Oral corticosteroid therapy (OR = 2.03), oral antidiabetic use (OR = 1.66), insulin use (OR = 1.77), and "overweight" body mass index of 25.1 to 30 (OR = 1.15) were also significantly associated. Current or previous smoking history, body mass index of greater than 30, any alcohol intake, medial epicondylitis, de Quervain syndrome, cubital tunnel syndrome, and rheumatoid arthritis were not found to be associated with rotator cuff disease. We have identified a number of comorbidities and risk factors for rotator cuff disease. These include lateral epicondylitis, carpal tunnel syndrome, trigger finger, Achilles tendinitis, oral corticosteroid use, and diabetes mellitus. The findings should alert the clinician to comorbid pathologic processes and guide future research into the etiology of this condition. Copyright © 2014 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Mosby, Inc. All rights reserved.

Light-triggered 5-fluorouracil release via UiO-66 coated optical fiber

NASA Astrophysics Data System (ADS)

Nazari, Marziyeh; Rubio-Martinez, Marta; Nazari, Fatemeh; Younis, Adel Ayad; Collins, Stephen F.; Duke, Mikel C.; Hill, Matthew R.

2017-07-01

UiO-66 thin film coated optical fiber end-face is fabricated and was utilized for 5-Fluorouracil (5-FU) anti-cancer medicine encapsulation and the drug was released by applying the appropriate light delivered via the optical fiber.

Augmentation of blood circulation to the fingers by warming distant body areas

NASA Technical Reports Server (NTRS)

Koscheyev, V. S.; Leon, G. R.; Paul, S.; Tranchida, D.; Linder, I. V.

2000-01-01

Future activities in space will require greater periods of time in extreme environments in which the body periphery will be vulnerable to chilling. Maintaining the hands and fingers in comfortable conditions enhances finger flexibility and dexterity, and thus effects better work performance. We have evaluated the efficacy of promoting heat transfer and release by the extremities by increasing the blood flow to the periphery from more distant parts of the body. The experimental garment paradigm developed by the investigators was used to manipulate the temperature of different body areas. Six subjects, two females and four males, were evaluated in a stage-1 baseline condition, with the inlet temperature of the circulating water in the liquid cooling/warming garment (LCWG) at 33 degrees C. At stage 2 the total LCWG water inlet temperature was cooled to 8 degrees C, and at stage 3 the inlet water temperature in specific segments of the LCWG was warmed (according to protocol) to 45 degrees C, while the inlet temperature in the rest of the LCWG was maintained at 8 degrees C. The following four body-area-warming conditions were studied in separate sessions: (1) head, (2) upper torso/arm, (3) upper torso/arm/head, and (4) legs/feet. Skin temperature, heat flux and blood perfusion of the fingers, and subjective perception of thermal sensations and overall physical comfort were assessed. Finger temperature (T(fing)) analyses showed a statistically significant condition x stage interaction. Post-hoc comparisons (T(fing)) indicated that at stage 3, the upper torso/arm/head warming condition was significantly different from the head, upper torso/arm and legs/feet conditions, showing an increase in T(fing). There was a significant increase in blood perfusion in the fingers at stage 3 in all conditions. Subjective perception of hand warmth, and overall physical comfort level significantly increased in the stage 3 upper torso/arm/head condition. The findings indicate that physiological methods to enhance heat transfer by the blood to the periphery within protective clothing provide an additional tool for increasing total and local human comfort in extreme environments.

Electrodeposition to construct free-standing chitosan/layered double hydroxides hydro-membrane for electrically triggered protein release.

PubMed

Zhao, Pengkun; Zhao, Yanan; Xiao, Ling; Deng, Hongbing; Du, Yumin; Chen, Yun; Shi, Xiaowen

2017-10-01

In this study, we report the electrodeposition of a chitosan/layered double hydroxides (LDHs) hydro-membrane for protein release triggered by an electrical signal. The electrodeposition was performed in a chitosan and insulin loaded LDHs suspension in the absence of salt. A free-standing chitosan/LDHs hydro-membrane was generated on the electrode with improved mechanical properties, which is dramatically different from the weak hydrogel deposited in the presence of salt. The amount of LDHs in the hydro-membrane affects the optical transmittance and multilayered structure of the hybrid membrane. Compared to the weak chitosan/LDHs hydrogel, the hydro-membrane has a higher insulin loading capacity and the release of insulin is relatively slow. By biasing electrical potentials to the hydro-membrane, the release behavior of insulin can be adjusted accordingly. In addition, the chitosan/LDHs hydro-membrane showed no toxicity to cells. Our results provide a facile method to construct a chitosan/LDHs hybrid multilayered hydro-membrane and suggest the great potential of the hydro-membrane in controlled protein release. Copyright © 2017 Elsevier B.V. All rights reserved.

Polymeric micelle for tumor pH and folate-mediated targeting.

PubMed

Lee, Eun Seong; Na, Kun; Bae, You Han

2003-08-28

Novel pH-sensitive polymeric mixed micelles composed of poly(L-histidine) (polyHis; M(w) 5000)/PEG (M(n) 2000) and poly(L-lactic acid) (PLLA) (M(n) 3000)/PEG (M(n) 2000) block copolymers with or without folate conjugation were prepared by diafiltration. The micelles were investigated for pH-dependent drug release, folate receptor-mediated internalization and cytotoxicity using MCF-7 cells in vitro. The polyHis/PEG micelles showed accelerated adriamycin release as the pH decreased from 8.0. When the cumulative release for 24 h was plotted as a function of pH, the gradual transition in release rate appeared in a pH range from 8.0 to 6.8. In order to tailor the triggering pH of the polymeric micelles to the more acidic extracellular pH of tumors, while improving the micelle stability at pH 7.4, the PLLA/PEG block copolymer was blended with polyHis/PEG to form mixed micelles. Blending shifted the triggering pH to a lower value. Depending on the amount of PLLA/PEG, the mixed micelles were destabilized in the pH range of 7.2-6.6 (triggering pH for adriamycin release). When the mixed micelles were conjugated with folic acid, the in vitro results demonstrated that the micelles were more effective in tumor cell kill due to accelerated drug release and folate receptor-mediated tumor uptake. In addition, after internalization polyHis was found to be effective for cytosolic ADR delivery by virtue of fusogenic activity. This approach is expected to be useful for treatment of solid tumors in vivo.

Extracellular ATP induces the rapid release of HIV-1 from virus containing compartments of human macrophages

PubMed Central

Graziano, Francesca; Desdouits, Marion; Garzetti, Livia; Podini, Paola; Alfano, Massimo; Rubartelli, Anna; Furlan, Roberto; Benaroch, Philippe; Poli, Guido

2015-01-01

HIV type 1 (HIV-1) infects CD4+ T lymphocytes and tissue macrophages. Infected macrophages differ from T cells in terms of decreased to absent cytopathicity and for active accumulation of new progeny HIV-1 virions in virus-containing compartments (VCC). For these reasons, infected macrophages are believed to act as “Trojan horses” carrying infectious particles to be released on cell necrosis or functional stimulation. Here we explored the hypothesis that extracellular ATP (eATP) could represent a microenvironmental signal potentially affecting virion release from VCC of infected macrophages. Indeed, eATP triggered the rapid release of infectious HIV-1 from primary human monocyte-derived macrophages (MDM) acutely infected with the CCR5-dependent HIV-1 strain. A similar phenomenon was observed in chronically infected promonocytic U1 cells differentiated to macrophage-like cells (D-U1) by costimulation with phorbol esters and urokinase-type plasminogen activator. Worthy of note, eATP did not cause necrotic, apoptotic, or pyroptotic cell death, and its effect on HIV-1 release was suppressed by Imipramine (an antidepressant agent known to inhibit microvesicle formation by interfering with membrane-associated acid sphingomyelinase). Virion release was not triggered by oxidized ATP, whereas the effect of eATP was inhibited by a specific inhibitor of the P2X7 receptor (P2X7R). Thus, eATP triggered the discharge of virions actively accumulating in VCC of infected macrophages via interaction with the P2X7R in the absence of significant cytopathicity. These findings suggest that the microvesicle pathway and P2X7R could represent exploitable targets for interfering with the VCC-associated reservoir of infectious HIV-1 virions in tissue macrophages. PMID:26056317

Extracellular ATP induces the rapid release of HIV-1 from virus containing compartments of human macrophages.

PubMed

Graziano, Francesca; Desdouits, Marion; Garzetti, Livia; Podini, Paola; Alfano, Massimo; Rubartelli, Anna; Furlan, Roberto; Benaroch, Philippe; Poli, Guido

2015-06-23

HIV type 1 (HIV-1) infects CD4(+) T lymphocytes and tissue macrophages. Infected macrophages differ from T cells in terms of decreased to absent cytopathicity and for active accumulation of new progeny HIV-1 virions in virus-containing compartments (VCC). For these reasons, infected macrophages are believed to act as "Trojan horses" carrying infectious particles to be released on cell necrosis or functional stimulation. Here we explored the hypothesis that extracellular ATP (eATP) could represent a microenvironmental signal potentially affecting virion release from VCC of infected macrophages. Indeed, eATP triggered the rapid release of infectious HIV-1 from primary human monocyte-derived macrophages (MDM) acutely infected with the CCR5-dependent HIV-1 strain. A similar phenomenon was observed in chronically infected promonocytic U1 cells differentiated to macrophage-like cells (D-U1) by costimulation with phorbol esters and urokinase-type plasminogen activator. Worthy of note, eATP did not cause necrotic, apoptotic, or pyroptotic cell death, and its effect on HIV-1 release was suppressed by Imipramine (an antidepressant agent known to inhibit microvesicle formation by interfering with membrane-associated acid sphingomyelinase). Virion release was not triggered by oxidized ATP, whereas the effect of eATP was inhibited by a specific inhibitor of the P2X7 receptor (P2X7R). Thus, eATP triggered the discharge of virions actively accumulating in VCC of infected macrophages via interaction with the P2X7R in the absence of significant cytopathicity. These findings suggest that the microvesicle pathway and P2X7R could represent exploitable targets for interfering with the VCC-associated reservoir of infectious HIV-1 virions in tissue macrophages.

An alkaline follicular fluid fraction induces capacitation and limited release of oviduct epithelium-bound stallion sperm.

PubMed

Leemans, Bart; Gadella, Bart M; Stout, Tom A E; Nelis, Hilde; Hoogewijs, Maarten; Van Soom, Ann

2015-09-01

Induction of hyperactivated motility is considered essential for triggering the release of oviduct-bound mammalian spermatozoa in preparation for fertilization. In this study, oviduct-bound stallion spermatozoa were exposed for 2 h to: i) pre-ovulatory and ii) post-ovulatory oviductal fluid; iii) 100% and iv) 10% follicular fluid (FF); v) cumulus cells, vi) mature equine oocytes, vii) capacitating and viii) non-capacitating medium. None of these triggered sperm release or hyperactivated motility. Interestingly, native FF was detrimental to sperm viability, an effect that was negated by heat inactivation, charcoal treatment and 30 kDa filtration alone or in combination. Moreover, sperm suspensions exposed to treated FF at pH 7.9 but not pH 7.4 showed Ca(2+)-dependent hypermotility. Fluo-4 AM staining of sperm showed elevated cytoplasmic Ca(2+) in hyperactivated stallion spermatozoa exposed to treated FF at pH 7.9 compared to a modest response in defined capacitating conditions at pH 7.9 and no response in treated FF at pH 7.4. Moreover, 1 h incubation in alkaline, treated FF induced protein tyrosine phosphorylation in 20% of spermatozoa. None of the conditions tested induced widespread release of sperm pre-bound to oviduct epithelium. However, the hyperactivating conditions did induce release of 70-120 spermatozoa per oviduct explant, of which 48% showed protein tyrosine phosphorylation and all were acrosome-intact, but capable of acrosomal exocytosis in response to calcium ionophore. We conclude that, in the presence of elevated pH and extracellular Ca(2+), a heat-resistant, hydrophilic, <30 kDa component of FF can trigger protein tyrosine phosphorylation, elevated cytoplasmic Ca(2+) and hyperactivated motility in stallion sperm, but infrequent release of sperm pre-bound to oviduct epithelium. © 2015 Society for Reproduction and Fertility.

Raynaud's phenomenon: peripheral catecholamine concentration and effect of sympathectomy.

PubMed

Nielsen, S L; Christensen, N J; Olsen, N; Lassen, N A

1980-01-01

The reaction to body and finger cooling was recorded in seven patients with relapse of primary Raynaud's phenomenon after sufficiently performed bilateral upper thoracic sympathectomy and for comparison in eight young women with primary Raynaud's phenomenon as well as in seven normal women. The forearm venous concentration of noradrenaline was lower and adrenaline concentration higher in the sympathectomized patients than in the other groups (p less than 0,05). Noradrenaline showed a significant increase during body cooling in normals and primary Raynaud's (p less than 0,05). There was no significant correlation between the vasoconstrictor response to cooling of a finger and the noradrenaline concentration probably due to the fact that skin vasoconstriction impeded release of noradrenaline from the skin. The relapse of Raynaud's phenomenon after surgically sufficient sympathectomy could not be treated by reserpine or alfa-adrenergic receptor blockers in two patients in whom this was tried.

Release of Bacterial Spores from the Inner Walls of a Stainless Steel Cup Subjected to Thermal Stresses and Mechanical Shock

NASA Technical Reports Server (NTRS)

Wolochow, H.; Chatigny, M.; Hebert, J.

1973-01-01

The release and fallout of particulates from surfaces afforded thermal or impact stress is of concern for control of contamination of Mars from planetary landing vehicles. A metal vessel contaminated by aerosols of spores was used as a model system and the fallout of spores as affected by various mechanisms was examined. Thermal stresses simulating those expected on the Mars lander dislodged approximately .01% of the aerosol deposited surface burden as did a landing shock of 8 to 10G deceleration. Spores imprinted by finger or swab contact yielded similar results. In all cases where repeated cycling of temperature, motion, or shock were employed the majority of fallout occurred in the first cycle. Particles released from the surface were predominantly in the size range 1 to 5 microns.

The novel asymmetric entry intermediate of a picornavirus captured with nanodiscs

PubMed Central

Lee, Hyunwook; Shingler, Kristin L.; Organtini, Lindsey J.; Ashley, Robert E.; Makhov, Alexander M.; Conway, James F.; Hafenstein, Susan

2016-01-01

Many nonenveloped viruses engage host receptors that initiate capsid conformational changes necessary for genome release. Structural studies on the mechanisms of picornavirus entry have relied on in vitro approaches of virus incubated at high temperatures or with excess receptor molecules to trigger the entry intermediate or A-particle. We have induced the coxsackievirus B3 entry intermediate by triggering the virus with full-length receptors embedded in lipid bilayer nanodiscs. These asymmetrically formed A-particles were reconstructed using cryo-electron microscopy and a direct electron detector. These first high-resolution structures of a picornavirus entry intermediate captured at a membrane with and without imposing icosahedral symmetry (3.9 and 7.8 Å, respectively) revealed a novel A-particle that is markedly different from the classical A-particles. The asymmetric receptor binding triggers minimal global capsid expansion but marked local conformational changes at the site of receptor interaction. In addition, viral proteins extrude from the capsid only at the site of extensive protein remodeling adjacent to the nanodisc. Thus, the binding of the receptor triggers formation of a unique site in preparation for genome release. PMID:27574701

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hu, Xiaobo; Zhou, Jing; Vatankhah-Varnosfaderani, Mohammad

Shapeshifting enables a wide range of engineering and biomedical applications, but until now transformations have required external triggers. This prerequisite limits viability in closed or inert systems and puts forward the challenge of developing materials with intrinsically encoded shape evolution. Herein we demonstrate programmable shape-memory materials that perform a sequence of encoded actuations under constant environment conditions without using an external trigger. We employ dual network hydrogels: in the first network, covalent crosslinks are introduced for elastic energy storage, and in the second one, temporary hydrogen-bonds regulate the energy release rate. Through strain-induced and time-dependent reorganization of the reversible hydrogen-bonds,more » this dual network allows for encoding both the rate and pathway of shape transformations on timescales from seconds to hours. In conclusion, this generic mechanism for programming trigger-free shapeshifting opens new ways to design autonomous actuators, drug-release systems and active implants.« less

Programming temporal shapeshifting

DOE PAGES

Hu, Xiaobo; Zhou, Jing; Vatankhah-Varnosfaderani, Mohammad; ...

2016-09-27

Shapeshifting enables a wide range of engineering and biomedical applications, but until now transformations have required external triggers. This prerequisite limits viability in closed or inert systems and puts forward the challenge of developing materials with intrinsically encoded shape evolution. Herein we demonstrate programmable shape-memory materials that perform a sequence of encoded actuations under constant environment conditions without using an external trigger. We employ dual network hydrogels: in the first network, covalent crosslinks are introduced for elastic energy storage, and in the second one, temporary hydrogen-bonds regulate the energy release rate. Through strain-induced and time-dependent reorganization of the reversible hydrogen-bonds,more » this dual network allows for encoding both the rate and pathway of shape transformations on timescales from seconds to hours. In conclusion, this generic mechanism for programming trigger-free shapeshifting opens new ways to design autonomous actuators, drug-release systems and active implants.« less

The Plasma Membrane as a Reservoir, Protective Shield, and Light-Triggered Launch Pad for Peptide Therapeutics.

PubMed

O'Banion, Colin P; Nguyen, Luong T; Wang, Qunzhao; Priestman, Melanie A; Holly, Stephen P; Parise, Leslie V; Lawrence, David S

2016-01-18

Although peptide-based therapeutics are finding increasing application in the clinic, extensive structural modification is typically required to prevent their rapid degradation by proteases in the blood. We have evaluated the ability of erythrocytes to serve as reservoirs, protective shields (against proteases), and light-triggered launch pads for peptides. We designed lipidated peptides that are anchored to the surface of red blood cells, which furnishes a protease-resistant environment. A photocleavable moiety is inserted between the lipid anchor and the peptide backbone, thereby enabling light-triggered peptide release from erythrocytes. We have shown that a cell-permeable peptide, a hormone (melanocyte stimulating hormone), and a blood-clotting agent can be anchored to erythrocytes, protected from proteases, and photolytically released to create the desired biological effect. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

A FRET-guided, NIR-responsive bubble-generating liposomal system for in vivo targeted therapy with spatially and temporally precise controlled release.

PubMed

Chuang, Er-Yuan; Lin, Chia-Chen; Chen, Ko-Jie; Wan, De-Hui; Lin, Kun-Ju; Ho, Yi-Cheng; Lin, Po-Yen; Sung, Hsing-Wen

2016-07-01

The nonspecific distribution of therapeutic agents and nontargeted heating commonly produce undesirable side effects during cancer treatment since the optimal timing of triggering the carrier systems is unknown. This work proposes a multifunctional liposomal system that can intracellularly and simultaneously deliver the therapeutic drug doxorubicin (DOX), heat, and a bubble-generating agent (ammonium bicarbonate, ABC) into targeted tumor cells to have a cytotoxic effect. Gold nanocages that are encapsulated in liposomes effectively convert near-infrared light irradiation into localized heat, which causes the decomposition of ABC and generates CO2 bubbles, rapidly triggering the release of DOX. Additionally, a hybridized Mucin-1 aptamer is conjugated on the surface of the test liposomes, which then function as a recognition probe to enhance the uptake of those liposomes by cells, and as a molecular beacon to signal when the internalized particles have been maximized, which is the optimal time for photothermally triggering the release of the drug following the systemic administration of the liposomes. Empirical results reveal that this combined treatment effectively controls targeted drug release in a spatially and temporally precise fashion and so significantly increases the potency of the drug while minimizing unwanted side effects, making it a promising treatment for cancer. Copyright © 2016 Elsevier Ltd. All rights reserved.

Enhanced hydrogen peroxide release from macrophages stimulated with streptococcal preparation OK-432.

PubMed Central

Saito, H; Tomioka, H

1979-01-01

Wheat germ lectin was found to be a potent triggering agent for hydrogen peroxide release from mouse peritoneal macrophages. Macrophages stimulated by intraperitoneal injection of OK-432, a lyophilized attenuated streptococcal preparation, were highly responsive to wheat germ lectin. PMID:546795

Activity-Dependent Exocytosis of Lysosomes Regulates the Structural Plasticity of Dendritic Spines.

PubMed

Padamsey, Zahid; McGuinness, Lindsay; Bardo, Scott J; Reinhart, Marcia; Tong, Rudi; Hedegaard, Anne; Hart, Michael L; Emptage, Nigel J

2017-01-04

Lysosomes have traditionally been viewed as degradative organelles, although a growing body of evidence suggests that they can function as Ca 2+ stores. Here we examined the function of these stores in hippocampal pyramidal neurons. We found that back-propagating action potentials (bpAPs) could elicit Ca 2+ release from lysosomes in the dendrites. This Ca 2+ release triggered the fusion of lysosomes with the plasma membrane, resulting in the release of Cathepsin B. Cathepsin B increased the activity of matrix metalloproteinase 9 (MMP-9), an enzyme involved in extracellular matrix (ECM) remodelling and synaptic plasticity. Inhibition of either lysosomal Ca 2+ signaling or Cathepsin B release prevented the maintenance of dendritic spine growth induced by Hebbian activity. This impairment could be rescued by exogenous application of active MMP-9. Our findings suggest that activity-dependent exocytosis of Cathepsin B from lysosomes regulates the long-term structural plasticity of dendritic spines by triggering MMP-9 activation and ECM remodelling. Crown Copyright © 2017. Published by Elsevier Inc. All rights reserved.

pH-Responsive mineralized nanoparticles as stable nanocarriers for intracellular nitric oxide delivery.

PubMed

Lee, Hong Jae; Kim, Da Eun; Park, Dong Jin; Choi, Gi Hyun; Yang, Dal-Nim; Heo, Jung Sun; Lee, Sang Cheon

2016-10-01

We describe a calcium carbonate (CaCO3) mineralization approach to generate pH-responsive nanocarriers that can stably load S-nitrosoglutathione (GSNO) and dissolve at acidic endosomes to trigger intracellular release of nitric oxide (NO). GSNO-loaded CaCO3-mineralized nanoparticles (GSNO-MNPs) were prepared by an anionic block copolymer (PEG-Poly(l-aspartic acid))-templated mineralization. Ionic GSNO could be loaded in situ inside the CaCO3 core during the mineralization process. The stability of GSNO shielded within the crystalline CaCO3 core was greatly enhanced. The GSNO-MNPs triggered NO release at endosomal pH and an intracellular ascorbic acid level. Confocal microscopy demonstrated that the GSNO-MNPs could be dissolved at endosomal environments to release GSNO and sequentially generate NO through the GSNO reduction in the cytosol. In vitro cell experiments demonstrated that NO release by the GSNO-MNPs efficiently improved therapeutic activity of doxorubicin (DOX). Copyright © 2016 Elsevier B.V. All rights reserved.

Multifunctional polymer-capped mesoporous silica nanoparticles for pH-responsive targeted drug delivery.

PubMed

Niedermayer, Stefan; Weiss, Veronika; Herrmann, Annika; Schmidt, Alexandra; Datz, Stefan; Müller, Katharina; Wagner, Ernst; Bein, Thomas; Bräuchle, Christoph

2015-05-07

A highly stable modular platform, based on the sequential covalent attachment of different functionalities to the surface of core-shell mesoporous silica nanoparticles (MSNs) for targeted drug delivery is presented. A reversible pH-responsive cap system based on covalently attached poly(2-vinylpyridine) (PVP) was developed as drug release mechanism. Our platform offers (i) tuneable interactions and release kinetics with the cargo drug in the mesopores based on chemically orthogonal core-shell design, (ii) an extremely robust and reversible closure and release mechanism based on endosomal acidification of the covalently attached PVP polymer block, (iii) high colloidal stability due to a covalently coupled PEG shell, and (iv) the ability to covalently attach a wide variety of dyes, targeting ligands and other functionalities at the outer periphery of the PEG shell. The functionality of the system was demonstrated in several cell studies, showing pH-triggered release in the endosome, light-triggered endosomal escape with an on-board photosensitizer, and efficient folic acid-based cell targeting.

BH3-only proteins trigger cytochrome c release, but how?

PubMed

Häcker, Georg; Weber, Arnim

2007-06-15

The mitochondrial apoptosis pathway has been neatly ordered. Mitochondrial apoptosis is governed by Bcl-2 family proteins, and their respective contributions determine the release of cytochrome c. It is clear that, among the Bcl-2 family, BH3-only proteins are the triggers: activation of BH3-only proteins by apoptotic stimuli initiates the process. BH3-only proteins cause cytochrome c release by activating Bax and/or Bak, and the anti-apoptotic group of Bcl-2-like proteins prevents this. However, it is curiously uncertain how BH3-only proteins activate Bax/Bak. Current models suggest that this is either through direct interaction--although this interaction is not detectable experimentally--or by the neutralisation of Bcl-2-like proteins. Here we discuss the context in which these models are placed and attempt to weigh the evidence.

GPR30: a seven-transmembrane-spanning estrogen receptor that triggers EGF release.

PubMed

Filardo, Edward J; Thomas, Peter

2005-10-01

Heterotrimeric G proteins and seven-transmembrane-spanning (7TM) receptors are implicated in rapid estrogen signaling. The orphan 7TM receptor GPR30 is linked to estrogen-mediated activation of adenylyl cyclase, release of epidermal growth factor (EGF)-related ligands, and specific estrogen binding. GPR30 acts independently of estrogen receptors, ERalpha and ERbeta, and probably functions as a heptahelical ER. 7TM receptors elicit signals that stimulate second messengers, and convey intracellular signals via EGF receptors. Identification of GPR30 as a Gs-coupled 7TM receptor that triggers release of heparin-binding EGF establishes its role in cell signaling cascades initiated by estrogens, and explains their capacity to activate second messengers and promote EGF-like effects. Thus, estrogen can signal by the same mechanism as various other hormones, through a specific 7TM receptor.

Preparation of a mesoporous silica-based nano-vehicle for dual DOX/CPT pH-triggered delivery.

PubMed

Llinàs, Maria C; Martínez-Edo, Gabriel; Cascante, Anna; Porcar, Irene; Borrós, Salvador; Sánchez-García, David

2018-11-01

A dual doxorubicin/camptothecin (DOX/CPT) pH-triggered drug delivery mesoporous silica nanoparticle (MSN)-based nano-vehicle has been prepared. In this drug-delivery system (DDS), CPT is loaded inside the pores of the MSNs, while DOX is covalently attached to the surface of an aldehyde-functionalized MSN through a dihydrazide-polyethylene glycol chain. Thus, DOX and the linker act as pH-sensitive gatekeeper. The system is versatile and easy to assemble, not requiring the chemical modification of the drugs. While at physiological conditions the release of the drugs is negligible, at acidic pH a burst release of DOX and a gradual release of CPT take place. In vitro cytotoxicity tests have demonstrated that this DDS can deliver efficiently DOX and CPT for combination therapy.

Classification for congenital anomalies of the hand: the IFSSH classification and the JSSH modification.

PubMed

De Smet, L

2002-01-01

The purpose of a classification for clinical problems which, except for a few specialized centers, occur only sporadically is to provide a system where these cases can be stored. This should allow all involved investigators to speak the same language; so-doing syndromes can be delinated, frequencies of occurence established and results of--different--treatments compared. A classification system should be simple to use, reliable and uniformly accepted. It should allow space for adaptations and/or extensions. The IFSSH proposed a 7 categories classification based on the proposed classification of Swanson et al. in 1976. This classification, was based on, which was thought in the seventies, etiopathogenic pathways. These 7 groups are: I. Failure of formation; transverse (A), or longitudinal (B) II. Failure of differentiation III. Polydactyly IV. Overgrowth V. Undergrowth VI. Amniotic band syndrome VII. Generalized skeletal syndromes. The extended classification proposed by IFSSH was used to classify 1013 hand differences in 925 hands of 650 patients. We found associated anomalies in 26.7%. The classification was straightforward in 86%, difficult in 6.6% and not possible in 7.8%. Group II was the most numerous group including 513 anomalies. We propose to include in this group the Madelung deformity, the Kirner deformity and congenital trigger fingers and trigger thumbs. In group I the radial and ulnar deficiencies, limited to the hand without forearm deficlencies should be Included. Triphalangeal thumbs are a problem, we suggest it to be listed in group III and consider it as a duplication in length. It is not always possible to evaluate the (transverse) absence of the fingers or hand. Longitudinal deficiencies (group IIB), symbrachydactyly (group V), and amniotic bands (group IV) occasionally develop a phenotype similar to the genuine transverse deficiency (group IA). Recently, the Japanese Society for Surgery of the Hand (JSSH) (16) proposed an extension/modification of the IFSSH classification. Based on newer knowledge on teratology, symbrachydactyly in all stages were transfered to group I. Two new groups were introduced. A group "failure of finger ray induction" including typical cleft hand (IC), central polydactyly (III) and (bony) syndactyly (II)--was included. Also a group of "unclassifiable" cases was added. This Japanese proposed classification is a real improvement and most clinicians and surgeons tend to use it in the future.

Triggers and Manifestations of Flare Energy Release in the Low Atmosphere

NASA Astrophysics Data System (ADS)

Kosovichev, A. G.; Sharykin, I. N.; Sadykov, V. M.; Vargas, S.; Zimovets, I. V.

2016-12-01

The main goal is to understand triggers and manifestations of the flare energy release in the lower layers of the solar atmosphere (the photosphere and chromosphere) using high-resolution optical observations and magnetic field measurements. As a case study we present results for an M-class flare. We analyze optical images, HMI Dopplergrams and vector magnetograms, and use Non-Linear Force-Free Field (NLFFF) extrapolation for reconstruction of the magnetic topology. The NLFFF modelling reveals interaction of oppositely directed magnetic flux-tubes in the Polarity Inversion Line (PIL). These two interacting magnetic flux tubes are observed as a compact sheared arcade along the PIL in the high-resolution broad-band continuum images from New Solar Telescope (NST). In the vicinity of the PIL, the NST H-alpha observations reveal formation of a thin three-ribbon structure corresponding to the small-scale photospheric magnetic arcade. Magnetic reconnection is triggered by two interacting magnetic flux tubes with forming current sheet extended along the PIL. Presented observational results evidence in favor of location of the primary energy release site in the dense chromosphere where plasma is partially ionized in the region of strong electric currents concentrated near the polarity inversion line.

Nanocomposite thin films for triggerable drug delivery.

PubMed

Vannozzi, Lorenzo; Iacovacci, Veronica; Menciassi, Arianna; Ricotti, Leonardo

2018-05-01

Traditional drug release systems normally rely on a passive delivery of therapeutic compounds, which can be partially programmed, prior to injection or implantation, through variations in the material composition. With this strategy, the drug release kinetics cannot be remotely modified and thus adapted to changing therapeutic needs. To overcome this issue, drug delivery systems able to respond to external stimuli are highly desirable, as they allow a high level of temporal and spatial control over drug release kinetics, in an operator-dependent fashion. Areas covered: On-demand drug delivery systems actually represent a frontier in this field and are attracting an increasing interest at both research and industrial level. Stimuli-responsive thin films, enabled by nanofillers, hold a tremendous potential in the field of triggerable drug delivery systems. The inclusion of responsive elements in homogeneous or heterogeneous thin film-shaped polymeric matrices strengthens and/or adds intriguing properties to conventional (bare) materials in film shape. Expert opinion: This Expert Opinion review aims to discuss the approaches currently pursued to achieve an effective on-demand drug delivery, through nanocomposite thin films. Different triggering mechanisms allowing a fine control on drug delivery are described, together with current challenges and possible future applications in therapy and surgery.

Novel substituted 1,4-anthracenediones with antitumor activity directly induce permeability transition in isolated mitochondria.

PubMed

Perchellet, Elisabeth M; Wang, Yang; Lou, Kaiyan; Zhao, Huiping; Battina, Srinivas K; Hua, Duy H; Perchellet, Jean-Pierre H

2007-11-01

Synthetic analogs of 1,4-anthraquinone (AQ code number), which block nucleoside transport, decrease DNA, RNA and protein syntheses, trigger cytochrome c release without caspase activation, induce apoptotic DNA fragmentation and inhibit the proliferation of wild-type and multidrug resistant tumor cells in the nM range in vitro, rapidly cause the collapse of mitochondrial transmembrane potential in cell and cell-free systems. Because mitochondrial permeability transition (MPT) requires more than depolarization to occur, antitumor AQs were tested for their ability to directly trigger specific markers of MPT in isolated mitochondria. In contrast to a spectrum of conventional anticancer drugs that are inactive, various AQs interact with isolated mitochondria in a concentration- and time-dependent manner to rapidly cause large amplitude swelling and Ca2+ release in relation with their effectiveness against L1210, HL-60 and LL/2 tumor cells in vitro. Indeed, the lead antitumor AQ8, AQ9 and AQ17 are also the most effective inducers of MPT in isolated mitochondria, whereas all AQ derivatives devoid of anti-proliferative activity also fail to trigger mitochondrial swelling and Ca2+ release. Moreover, the ability of 4 microM AQ17 to maximally induce mitochondrial swelling and Ca2+ release within 15 min is similar to that of classic MPT-inducing agents, such as 5 microg/ml alamethicin, 200 microM atractyloside, 5 microM phenylarsine oxide, 100 microM arsenic trioxide and a 100 microM Ca2+ overload. Interestingly, AQ17 requires a priming concentration of 20 microM Ca2+ to trigger mitochondrial swelling and Ca2+ release and these 0.1 microM ruthenium red-sensitive MPT events are abolished by 1 microM cyclosporin A, 2 mM ADP and 20 microM bongkrekic acid, which block components of the permeability transition pore (PTP), and also inhibited by 50-100 microM of various ubiquinones, which interact with the quinone binding site of the PTP and raise the Ca2+ load required for PTP opening. Hence, antitumor AQs that target isolated mitochondria and trigger MPT might directly interact with components of the PTP to induce conformational changes that increase its Ca2+ sensitivity and transition from the closed to the open state.

Dynamics of shear-induced ATP release from red blood cells.

PubMed

Wan, Jiandi; Ristenpart, William D; Stone, Howard A

2008-10-28

Adenosine triphosphate (ATP) is a regulatory molecule for many cell functions, both for intracellular and, perhaps less well known, extracellular functions. An important example of the latter involves red blood cells (RBCs), which help regulate blood pressure by releasing ATP as a vasodilatory signaling molecule in response to the increased shear stress inside arterial constrictions. Although shear-induced ATP release has been observed widely and is believed to be triggered by deformation of the cell membrane, the underlying mechanosensing mechanism inside RBCs is still controversial. Here, we use an in vitro microfluidic approach to investigate the dynamics of shear-induced ATP release from human RBCs with millisecond resolution. We demonstrate that there is a sizable delay time between the onset of increased shear stress and the release of ATP. This response time decreases with shear stress, but surprisingly does not depend significantly on membrane rigidity. Furthermore, we show that even though the RBCs deform significantly in short constrictions (duration of increased stress <3 ms), no measurable ATP is released. This critical timescale is commensurate with a characteristic membrane relaxation time determined from observations of the cell deformation by using high-speed video. Taken together our results suggest a model wherein the retraction of the spectrin-actin cytoskeleton network triggers the mechanosensitive ATP release and a shear-dependent membrane viscosity controls the rate of release.

Enzyme-triggered compound release using functionalized antimicrobial peptide derivatives† †Electronic supplementary information (ESI) available. See DOI: 10.1039/c6sc04435b Click here for additional data file.

PubMed Central

Kashibe, Masayoshi; Matsumoto, Kengo; Hori, Yuichiro

2017-01-01

Controlled release is one of the key technologies for medical innovation, and many stimulus-responsive nanocarriers have been developed to utilize this technology. Enzyme activity is one of the most useful stimuli, because many enzymes are specifically activated in diseased tissues. However, controlled release stimulated by enzyme activity has not been frequently reported. One of the reasons for this is the lack of versatility of carriers. Most of the reported stimulus-responsive systems involve a sophisticated design and a complicated process for the synthesis of stimulus-responsive nanocarrier components. The purpose of this study was to develop versatile controlled release systems triggered by various stimuli, including enzyme activity, without modifying the nanocarrier components. We developed two controlled release systems, both of which comprised a liposome as the nanocarrier and a membrane-damaging peptide, temporin L (TL), and its derivatives as the release-controllers. One system utilized branched peptides for proteases, and the other utilized phosphopeptides for phosphatases. In our systems, the target enzymes converted the non-membrane-damaging TL derivatives into membrane-damaging peptides and released the liposome inclusion. We demonstrated the use of our antimicrobial peptide-based controlled release systems for different enzymes and showed the promise of this technology as a novel theranostic tool. PMID:28451373

Soft Sensors and Actuators based on Nanomaterials

NASA Astrophysics Data System (ADS)

Yao, Shanshan

The focus of this research is using novel bottom-up synthesized nanomaterials and structures to build up devices for wearable sensors and soft actuators. The applications of the wearable sensors towards motion detection and health monitoring are investigated. In addition, flexible heaters for bimorph actuators and stretchable patches made of microgel depots containing drug-loaded nanoparticles (NPs) for stretch-triggered wearable drug delivery are studied. Considerable efforts have been made to achieve highly sensitive and wearable sensors that can simultaneously detect multiple stimuli such as stretch, pressure, temperature or touch. Highly stretchable multifunctional sensors that can detect strain (up to 50%), pressure (up to 1 MPa) and finger touch with good sensitivity, fast response time ( 40 ms) and good pressure mapping function were developed. The sensors were demonstrated for several wearable applications including monitoring thumb movements and knee motions, illustrating the potential utilities of such sensors in robotic systems, prosthetics, healthcare and flexible touch panels. In addition to mechanical sensors, a wearable skin hydration sensor made of silver nanowires (AgNWs) in a polydimethylsiloxane (PDMS) matrix was demonstrated based on skin impedance measurement. The hydration sensors were packaged into a flexible wristband for skin hydration monitoring and a chest patch consisting of a strain sensor, three electrocardiogram (ECG) electrodes and a skin hydration sensor for multimodal sensing. The wearable wristband and chest patch may be used for low-cost, wireless and continuous sensing of skin hydration and other health parameters. Two representative applications of the nanomaterials for soft actuators were investigated. In the first application on bimorph actuation, low-voltage and extremely flexible electrothermal bimorph actuators were fabricated in a simple, efficient and scalable process. The bimorph actuators were made of flexible AgNW based heaters, which exhibited a fast heating rate of 18°C/s and stable heating performance under large bending. The actuators offered the largest bending angle (720°) or curvature (2.6 cm-1) at a very low actuation voltage (0.2 V sq-1 or 4.5 V) among all types of bimorph actuators that have been reported. The actuators can be designed and fabricated in different configurations that can achieve complex patterns and shapes upon actuation. Two applications of this type of soft actuators were demonstrated towards biomimetic robotics - a crawling robot that can walk spontaneously on ratchet surfaces and a soft gripper that is capable of manipulating lightweight and delicate objects. In another application towards wearable drug delivery, a wearable, tensile strain-triggered drug delivery device consisting of a stretchable elastomer and microgel depots containing drug loaded nanoparticles is described. By applying a tensile strain to the elastomer film, the release of drug from the micro-depot is promoted. Correspondingly, both sustained drug release by daily body motions and pulsatile release by intentional administration can be conveniently achieved. The work demonstrated that the tensile strain, applied to the stretchable device, facilitated release of therapeutics from micro-depots for anticancer and antibacterial treatments, respectively. Moreover, polymeric microneedles were further integrated with the stretch-responsive device for transcutaneous delivery of insulin and regulation of blood glucose levels of chemically-induced type 1 diabetic mice.

Comparison of Transverse Intraosseous Loop Technique and Pull Out Suture for Reinsertion of the Flexor Digitorum Profundus tendon. A Retrospective Study.

PubMed

Rigó, István Zoltán; Røkkum, Magne

2013-12-01

We compared the results of two methods for reinsertion of flexor digitorum profundus tendons retrospectively. In 35 fingers of 29 patients pull-out suture and in 13 fingers of 11 patients transverse intraosseous loop technique was performed with a mean follow-up of 8 and 6 months, respectively. Eleven and nine fingers achieved "excellent" or "good" function according to Strickland and Glogovac at 8 weeks; 20 and ten at the last control in the pull-out and transverse intraosseous loop groups, respectively. The difference at 8 weeks was statistically significant in favour of the transverse intraosseous loop group. Ten patients underwent 12 complications in the pull-out group (four superficial infections; one rerupture, one PIP and one DIP joint contracture, one adhesion, two granulomas, one nail deformity and one carpal tunnel syndrome) and four of them were reoperated (one carpal tunnel release, one teno-arthrolysis and two resections of granuloma). There was no complication and no reoperation in the transverse intraosseous loop group, the difference being statistically significant for the former. In our study the transverse intraosseous loop technique seemed to be a safe alternative with possibly better functional results compared to the pull-out suture.

[A case of mixed connective tissue disease positive for proteinase 3 antineutrophil cytoplasmic antibody in a patient with slowly progressive type 1 diabetes mellitus and chronic thyroiditis].

PubMed

Michitsuji, Tohru; Horai, Yoshiro; Sako, Ayaka; Asano, Taro; Iwanaga, Nozomi; Izumi, Yasumori; Kawakami, Atsushi

2017-01-01

  A female in her sixties with slowly progressive type 1 diabetes mellitus (SPT1DM) and chronic thyroiditis was referred to our rheumatology department with swelling in her fingers. A prominent atherosclerotic lesion was revealed upon brain magnetic resonance imaging, and she was found to have mixed connective tissue disease (MCTD) positive for proteinase 3 (PR3)-antineutrophil cytoplasmic antibody (ANCA). This rare case of MCTD accompanying SPT1DM and PR3-ANCA suggested that a synergy between MCTD and PR3-ANCA triggers atherosclerosis.

Hand pain other than carpal tunnel syndrome (CTS): the role of occupational factors.

PubMed

Andréu, José-Luis; Otón, Teresa; Silva-Fernández, Lucía; Sanz, Jesús

2011-02-01

Some occupational factors have been implicated in the development of disorders manifested as hand pain. The associations seem to be well documented in processes such as hand-arm vibration syndrome (HAVS) or writer's cramp. There are contradictory data in the literature about the relationships of trigger finger, De Quervain's tenosynovitis (DQT) and tenosynovitis of the wrist with occupational factors. In this article, we review current knowledge about clinical manifestations, case definition, implicated occupational factors, diagnosis and treatment of the most relevant hand pain disorders that have been associated with occupational factors, excluding carpal tunnel syndrome (CTS). Copyright © 2010 Elsevier Ltd. All rights reserved.

TRIGGER MECHANISM OF SOLAR SUBFLARES IN A BRAIDED CORONAL MAGNETIC STRUCTURE

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tiwari, Sanjiv K.; Alexander, Caroline E.; Winebarger, Amy R.

Fine-scale braiding of coronal magnetic loops by continuous footpoint motions may power coronal heating via nanoflares, which are spontaneous fine-scale bursts of internal reconnection. An initial nanoflare may trigger an avalanche of reconnection of the braids, making a microflare or larger subflare. In contrast to this internal triggering of subflares, we observe external triggering of subflares in a braided coronal magnetic field observed by the High-resolution Coronal Imager (Hi-C). We track the development of these subflares using 12 s cadence images acquired by SDO/AIA in 1600, 193, 94 Å, and registered magnetograms of SDO/HMI, over four hours centered on the Hi-Cmore » observing time. These data show numerous recurring small-scale brightenings in transition-region emission happening on polarity inversion lines where flux cancellation is occurring. We present in detail an example of an apparent burst of reconnection of two loops in the transition region under the braided coronal field which is appropriate for releasing a short reconnected loop downward and a longer reconnected loop upward. The short loop presumably submerges into the photosphere, participating in observed flux cancellation. A subflare in the overlying braided magnetic field is apparently triggered by the disturbance of the braided field by the reconnection-released upward loop. At least 10 subflares observed in this braided structure appear to be triggered this way. How common this external trigger mechanism for coronal subflares is in other active regions, and how important it is for coronal heating in general, remain to be seen.« less

Development of a liposomal delivery system for temperature-triggered release of a tumor targeting agent, Ln(III)-DOTA-phenylboronate.

PubMed

Djanashvili, Kristina; ten Hagen, Timo L M; Blangé, Roy; Schipper, Debby; Peters, Joop A; Koning, Gerben A

2011-02-01

Liposomes, capable of temperature-triggered content release at the site of interest, can be of great importance for imaging and therapy of tumors. The delivery of imaging agents or therapeutics can be improved by application of liposomes with a gel-to-liquid phase-transition temperature suitable for mild hyperthermia (41-43°C), and by prolonging their circulation time by incorporation of lipids containing polyethyleneglycol moieties. Still, the rapid wash out of the delivered material from the tumor tissue is a major obstacle for both imaging and therapy. In this study, we developed an optimized temperature sensitive liposomal system to be used with mild hyperthermia: highly stable at physiological temperature and with a sharp transition of the bilayer at 41.5°C, with subsequent rapid release of entrapped compounds such as calcein or tumor cell-targeting contrast agents. Intravital microscopy on calcein/rhodamine containing liposomes was applied to demonstrate the applicability of this system in vivo. The calcein loaded liposomes were injected iv into nude mice with a human BLM melanoma tumor implanted in a dorsal skin-fold window chamber. Arrival of the liposomes at the tumor site and content release after temperature increase were monitored. The results demonstrated not only accumulation of the liposomes at the tumor site, but also a massive release of calcein after increase of the temperature to 41°C. The versatility of the thermosensitive liposomes was further demonstrated by encapsulation of a tumor cell-targeting DOTA-phenylboronate conjugate and its release at elevated temperatures. The DOTA ligand in this system is able to chelate a variety of metals suitable for both diagnostic and therapeutic applications, whereas the phenylboronate function is able to target specifically to tumor cells through a covalent binding with sialic acid moieties over-expressed on their surface upon heat-triggered release from the liposomal carrier. Copyright © 2010 Elsevier Ltd. All rights reserved.

Zinc triggers microglial activation.

PubMed

Kauppinen, Tiina M; Higashi, Youichirou; Suh, Sang Won; Escartin, Carole; Nagasawa, Kazuki; Swanson, Raymond A

2008-05-28

Microglia are resident immune cells of the CNS. When stimulated by infection, tissue injury, or other signals, microglia assume an activated, "ameboid" morphology and release matrix metalloproteinases, reactive oxygen species, and other proinflammatory factors. This innate immune response augments host defenses, but it can also contribute to neuronal death. Zinc is released by neurons under several conditions in which microglial activation occurs, and zinc chelators can reduce neuronal death in animal models of cerebral ischemia and neurodegenerative disorders. Here, we show that zinc directly triggers microglial activation. Microglia transfected with a nuclear factor-kappaB (NF-kappaB) reporter gene showed a severalfold increase in NF-kappaB activity in response to 30 microm zinc. Cultured mouse microglia exposed to 15-30 microm zinc increased nitric oxide production, increased F4/80 expression, altered cytokine expression, and assumed the activated morphology. Zinc-induced microglial activation was blocked by inhibiting NADPH oxidase, poly(ADP-ribose) polymerase-1 (PARP-1), or NF-kappaB activation. Zinc injected directly into mouse brain induced microglial activation in wild-type mice, but not in mice genetically lacking PARP-1 or NADPH oxidase activity. Endogenous zinc release, induced by cerebral ischemia-reperfusion, likewise induced a robust microglial reaction, and this reaction was suppressed by the zinc chelator CaEDTA. Together, these results suggest that extracellular zinc triggers microglial activation through the sequential activation of NADPH oxidase, PARP-1, and NF-kappaB. These findings identify a novel trigger for microglial activation and a previously unrecognized mechanism by which zinc may contribute to neurological disorders.

Risk factors for Raynaud's phenomenon among workers in poultry slaughterhouses and canning factories.

PubMed

Kaminski, M; Bourgine, M; Zins, M; Touranchet, A; Verger, C

1997-04-01

Apart from the use of vibrating tools, little is known about risk factors for Raynaud's phenomenon. However, it has been hypothesized that this disorder may have a multifactorial aetiology, involving potential causal or triggering factors which can be found in the workplace. The objective of the study is to identify individual and occupational risk factors of Raynaud's phenomenon in a population of workers not exposed to vibration, but exposed to cold. The survey was carried out in 1987-1988 in 17 poultry slaughterhouses and six canning factories and included 1474 employees. Data were collected at the annual visit to the occupational health physician. Finger sensitivity to cold and Raynaud's phenomenon were identified from a list of symptoms occurring from exposure to cold. The role of potential risk factors was assessed using multiple logistic regression. A high prevalence of symptoms of finger sensitivity to cold was observed. Raynaud's phenomenon was more common in women than in men, was related to family history of the disease but not to smoking or alcohol consumption. After controlling for non-occupational factors, the following working conditions appeared as risk factors for Raynaud's phenomenon: use of plastic gloves, less than four rest breaks, breaks in an unheated place, continual repetition of the same series of operations, exertion of the arm or hand and being able to think of something else while working. The study showed that a number of working conditions were associated with an increased risk of Raynaud's phenomenon and finger sensitivity to cold. Changes in working conditions might reduce the risk of this disorder in the food processing industry.

Ring finger protein 145 (RNF145) is a ubiquitin ligase for sterol-induced degradation of HMG-CoA reductase.

PubMed

Jiang, Lu-Yi; Jiang, Wei; Tian, Na; Xiong, Yan-Ni; Liu, Jie; Wei, Jian; Wu, Kai-Yue; Luo, Jie; Shi, Xiong-Jie; Song, Bao-Liang

2018-03-16

Cholesterol biosynthesis is tightly regulated in the cell. For example, high sterol concentrations can stimulate degradation of the rate-limiting cholesterol biosynthetic enzyme 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMG-CoA reductase, HMGCR). HMGCR is broken down by the endoplasmic reticulum membrane-associated protein complexes consisting of insulin-induced genes (Insigs) and the E3 ubiquitin ligase gp78. Here we found that HMGCR degradation is partially blunted in Chinese hamster ovary (CHO) cells lacking gp78 ( gp78 -KO). To identify other ubiquitin ligase(s) that may function together with gp78 in triggering HMGCR degradation, we performed a small-scale short hairpin RNA-based screening targeting endoplasmic reticulum-localized E3s. We found that knockdown of both ring finger protein 145 ( Rnf145 ) and gp78 genes abrogates sterol-induced degradation of HMGCR in CHO cells. We also observed that RNF145 interacts with Insig-1 and -2 proteins and ubiquitinates HMGCR. Moreover, the tetrapeptide sequence YLYF in the sterol-sensing domain and the Cys-537 residue in the RING finger domain were essential for RNF145 binding to Insigs and RNF145 E3 activity, respectively. Of note, amino acid substitutions in the YLYF or of Cys-537 completely abolished RNF145-mediated HMGCR degradation. In summary, our study reveals that RNF145, along with gp78, promotes HMGCR degradation in response to elevated sterol levels and identifies residues essential for RNF145 function. © 2018 by The American Society for Biochemistry and Molecular Biology, Inc.

Ca2+ release triggered by nicotinate adenine dinucleotide phosphate in intact sea urchin eggs.

PubMed Central

Perez-Terzic, C M; Chini, E N; Shen, S S; Dousa, T P; Clapham, D E

1995-01-01

Nicotinate adenine dinucleotide phosphate (NAADP) was recently identified [Lee and Aarhus (1995) J. Biol. Chem. 270, 2152-2157; Chini, Beers and Dousa (1995) J. Biol. Chem. 270, 3116-3223] as a potent Ca(2+)-releasing agent in sea urchin egg homogenates. NAADP triggered Ca2+ release by a mechanism that was distinct from inositol 1,4,5-trisphosphate (InsP3)- and cyclic ADP-ribose (cADPR)-induced Ca2+ release. When NAADP was microinjected into intact sea urchin eggs it induced a dose-dependent increase in cytoplasmic free Ca2+ which was independent of the extracellular [Ca2+]. The Ca2+ waves elicited by microinjections of NAADP originated at the site of injection and swept across the cytosol. As previously found in sea urchin egg homogenates, NAADP-induced Ca2+ release in intact eggs was not blocked by heparin or by prior desensitization to InsP3 or cADPR. Thio-NADP, a specific inhibitor of the NAADP-induced Ca2+ release in sea urchin homogenates [Chini, Beers and Dousa (1995) J. Biol. Chem. 270, 3116-3223] blocked NAADP (but not InsP3 or cADPR) injection-induced Ca2+ release in intact sea urchin eggs. Finally, fertilization of sea urchin eggs abrogated subsequent NAADP-induced Ca2+ release, suggesting that the NAADP-sensitive Ca2+ pool may participate in the fertilization response. This study demonstrates that NAADP acts as a selective Ca(2+)-releasing agonist in intact cells. Images Figure 2 PMID:8554544

Reversible chemoselective tagging and functionalization of methionine containing peptides.

PubMed

Kramer, Jessica R; Deming, Timothy J

2013-06-07

Reagents were developed to allow chemoselective tagging of methionine residues in peptides and polypeptides, subsequent bioorthogonal functionalization of the tags, and cleavage of the tags when desired. This methodology can be used for triggered release of therapeutic peptides, or release of tagged protein digests from affinity columns.

Innovative application of metal-organic frameworks for encapsulation and controlled release of allyl isothiocyanate

USDA-ARS?s Scientific Manuscript database

This research investigated the technical feasibility of metal-organic frameworks (MOFs) as novel delivery systems for encapsulation and controlled release of volatile allyl isothiocyanate (AITC) molecules. We hypothesized that water vapor molecules could act as an external stimulus to trigger the re...

Variable and Asymmetric Range of Enslaving: Fingers Can Act Independently over Small Range of Flexion

PubMed Central

van den Noort, Josien C.; van Beek, Nathalie; van der Kraan, Thomas; Veeger, DirkJan H. E. J.; Stegeman, Dick F.; Veltink, Peter H.; Maas, Huub

2016-01-01

The variability in the numerous tasks in which we use our hands is very large. However, independent movement control of individual fingers is limited. To assess the extent of finger independency during full-range finger flexion including all finger joints, we studied enslaving (movement in non-instructed fingers) and range of independent finger movement through the whole finger flexion trajectory in single and multi-finger movement tasks. Thirteen young healthy subjects performed single- and multi-finger movement tasks under two conditions: active flexion through the full range of movement with all fingers free to move and active flexion while the non-instructed finger(s) were restrained. Finger kinematics were measured using inertial sensors (PowerGlove), to assess enslaving and range of independent finger movement. Although all fingers showed enslaving movement to some extent, highest enslaving was found in adjacent fingers. Enslaving effects in ring and little finger were increased with movement of additional, non-adjacent fingers. The middle finger was the only finger affected by restriction in movement of non-instructed fingers. Each finger showed a range of independent movement before the non-instructed fingers started to move, which was largest for the index finger. The start of enslaving was asymmetrical for adjacent fingers. Little finger enslaving movement was affected by multi-finger movement. We conclude that no finger can move independently through the full range of finger flexion, although some degree of full independence is present for smaller movements. This range of independent movement is asymmetric and variable between fingers and between subjects. The presented results provide insight into the role of finger independency for different types of tasks and populations. PMID:27992598

Identification of memory reactivation during sleep by EEG classification.

PubMed

Belal, Suliman; Cousins, James; El-Deredy, Wael; Parkes, Laura; Schneider, Jules; Tsujimura, Hikaru; Zoumpoulaki, Alexia; Perapoch, Marta; Santamaria, Lorena; Lewis, Penelope

2018-04-17

Memory reactivation during sleep is critical for consolidation, but also extremely difficult to measure as it is subtle, distributed and temporally unpredictable. This article reports a novel method for detecting such reactivation in standard sleep recordings. During learning, participants produced a complex sequence of finger presses, with each finger cued by a distinct audio-visual stimulus. Auditory cues were then re-played during subsequent sleep to trigger neural reactivation through a method known as targeted memory reactivation (TMR). Next, we used electroencephalography data from the learning session to train a machine learning classifier, and then applied this classifier to sleep data to determine how successfully each tone had elicited memory reactivation. Neural reactivation was classified above chance in all participants when TMR was applied in SWS, and in 5 of the 14 participants to whom TMR was applied in N2. Classification success reduced across numerous repetitions of the tone cue, suggesting either a gradually reducing responsiveness to such cues or a plasticity-related change in the neural signature as a result of cueing. We believe this method will be valuable for future investigations of memory consolidation. Copyright © 2018 Elsevier Inc. All rights reserved.

Psychophysiological patterns during cell phone text messaging: a preliminary study.

PubMed

Lin, I-Mei; Peper, Erik

2009-03-01

This study investigated the psychophysiological patterns associated with cell phone text messaging (texting). Twelve college students who were very familiar with texting were monitored with surface electromyography (SEMG) from the shoulder (upper trapezius) and thumb (abductor pollicis brevis/opponens pollicis); blood volume pulse (BVP) from the middle finger, temperature from the index finger, and skin conductance (SC) from the palm of the non-texting hand; and respiration from the thorax and abdomen. The counter-balanced procedure consisted of a 2 min pre-baseline, 1 min receiving text messages, 2 min middle baseline, 1 min sending text messages and 2 min post-baseline. The results indicated that all subjects showed significant increases in respiration rate, heart rate, SC, and shoulder and thumb SEMG as compared to baseline measures. Eighty-three percentage of the participants reported hand and neck pain during texting, and held their breath and experienced arousal when receiving text messages. Subjectively, most subjects were unaware of their physiological changes. The study suggests that frequent triggering of these physiological patterns (freezing for stability and shallow breathing) may increase muscle discomfort symptoms. Thus, participants should be trained to inhibit these responses to prevent illness and discomfort.

The Combined Effects of Adaptive Control and Virtual Reality on Robot-Assisted Fine Hand Motion Rehabilitation in Chronic Stroke Patients: A Case Study.

PubMed

Huang, Xianwei; Naghdy, Fazel; Naghdy, Golshah; Du, Haiping; Todd, Catherine

2018-01-01

Robot-assisted therapy is regarded as an effective and reliable method for the delivery of highly repetitive training that is needed to trigger neuroplasticity following a stroke. However, the lack of fully adaptive assist-as-needed control of the robotic devices and an inadequate immersive virtual environment that can promote active participation during training are obstacles hindering the achievement of better training results with fewer training sessions required. This study thus focuses on these research gaps by combining these 2 key components into a rehabilitation system, with special attention on the rehabilitation of fine hand motion skills. The effectiveness of the proposed system is tested by conducting clinical trials on a chronic stroke patient and verified through clinical evaluation methods by measuring the key kinematic features such as active range of motion (ROM), finger strength, and velocity. By comparing the pretraining and post-training results, the study demonstrates that the proposed method can further enhance the effectiveness of fine hand motion rehabilitation training by improving finger ROM, strength, and coordination. Copyright © 2018 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Effectiveness of finger-equipped electrode (FEE)-triggered electrical stimulation improving chronic stroke patients with severe hemiplegia.

PubMed

Inobe, Jun-ichi; Kato, Takashi

2013-01-01

Electric stimulation (ES) has been recognized as an effective method to improve motor function to paralysed patients with stroke. It is important for ES to synchronize with voluntary movement. To enhance this co-ordination, the finger-equipped electrode (FEE) was developed. The purpose of this study was to evaluate FEE in improving motor function of upper extremities (UEs) in patients with chronic stroke. The study participants included four patients with chronic stroke who received FEE electronic stimulation (FEE-ES) plus passive and active training and three control patients who underwent training without FEE-ES. The patients were treated five times weekly for 4 weeks. UE motor function was evaluated before and after treatment using Fugl-Meyer Assessment (FMA) and Brunnstrom recovery staging. The mean age of patients in each group was 60-years and there was a mean of 49 months since the onset of symptoms. All patients had severe UE weakness. The patients receiving FEE-ES had greater improvement in UE function than control patients (total, proximal and distal FMA, p < 0.05; Brunnstrom staging of UE, p < 0.05). The results indicate that FEE-ES may be an effective treatment for patients with chronic stroke.

Biocompatible Collagen Paramagnetic Scaffold for Controlled Drug Release.

PubMed

Bettini, Simona; Bonfrate, Valentina; Syrgiannis, Zois; Sannino, Alessandro; Salvatore, Luca; Madaghiele, Marta; Valli, Ludovico; Giancane, Gabriele

2015-09-14

A porous collagen-based hydrogel scaffold was prepared in the presence of iron oxide nanoparticles (NPs) and was characterized by means of infrared spectroscopy and scanning electron microscopy. The hybrid scaffold was then loaded with fluorescein sodium salt as a model compound. The release of the hydrosoluble species was triggered and accurately controlled by the application of an external magnetic field, as monitored by fluorescence spectroscopy. The biocompatibility of the proposed matrix was also tested by the MTT assay performed on 3T3 cells. Cell viability was only slightly reduced when the cells were incubated in the presence of the collagen-NP hydrogel, compared to controls. The economicity of the chemical protocol used to obtain the paramagnetic scaffolds as well as their biocompatibility and the safety of the external trigger needed to induce the drug release suggest the proposed collagen paramagnetic matrices for a number of applications including tissue engeneering and drug delivery.

Chronic stress triggers social aversion via glucocorticoid receptor in dopaminoceptive neurons.

PubMed

Barik, Jacques; Marti, Fabio; Morel, Carole; Fernandez, Sebastian P; Lanteri, Christophe; Godeheu, Gérard; Tassin, Jean-Pol; Mombereau, Cédric; Faure, Philippe; Tronche, François

2013-01-18

Repeated traumatic events induce long-lasting behavioral changes that are key to organism adaptation and that affect cognitive, emotional, and social behaviors. Rodents subjected to repeated instances of aggression develop enduring social aversion and increased anxiety. Such repeated aggressions trigger a stress response, resulting in glucocorticoid release and activation of the ascending dopamine (DA) system. We bred mice with selective inactivation of the gene encoding the glucocorticoid receptor (GR) along the DA pathway, and exposed them to repeated aggressions. GR in dopaminoceptive but not DA-releasing neurons specifically promoted social aversion as well as dopaminergic neurochemical and electrophysiological neuroadaptations. Anxiety and fear memories remained unaffected. Acute inhibition of the activity of DA-releasing neurons fully restored social interaction in socially defeated wild-type mice. Our data suggest a GR-dependent neuronal dichotomy for the regulation of emotional and social behaviors, and clearly implicate GR as a link between stress resiliency and dopaminergic tone.

Neuronal somatic ATP release triggers neuron–satellite glial cell communication in dorsal root ganglia

PubMed Central

Zhang, X.; Chen, Y.; Wang, C.; Huang, L.-Y. M.

2007-01-01

It has been generally assumed that the cell body (soma) of a neuron, which contains the nucleus, is mainly responsible for synthesis of macromolecules and has a limited role in cell-to-cell communication. Using sniffer patch recordings, we show here that electrical stimulation of dorsal root ganglion (DRG) neurons elicits robust vesicular ATP release from their somata. The rate of release events increases with the frequency of nerve stimulation; external Ca2+ entry is required for the release. FM1–43 photoconversion analysis further reveals that small clear vesicles participate in exocytosis. In addition, the released ATP activates P2X7 receptors in satellite cells that enwrap each DRG neuron and triggers the communication between neuronal somata and glial cells. Blocking L-type Ca2+ channels completely eliminates the neuron–glia communication. We further show that activation of P2X7 receptors can lead to the release of tumor necrosis factor-α (TNFα) from satellite cells. TNFα in turn potentiates the P2X3 receptor-mediated responses and increases the excitability of DRG neurons. This study provides strong evidence that somata of DRG neurons actively release transmitters and play a crucial role in bidirectional communication between neurons and surrounding satellite glial cells. These results also suggest that, contrary to the conventional view, neuronal somata have a significant role in cell–cell signaling. PMID:17525149

Artificial grasping system for the paralyzed hand.

PubMed

Ferrari de Castro, M C; Cliquet, A

2000-03-01

Neuromuscular electrical stimulation has been used in upper limb rehabilitation towards restoring motor hand function. In this work, an 8 channel microcomputer controlled stimulator with monophasic square voltage output was used. Muscle activation sequences were defined to perform palmar and lateral prehension and power grip (index finger extension type). The sequences used allowed subjects to demonstrate their ability to hold and release objects that are encountered in daily living, permitting activities such as drinking, eating, writing, and typing.

Regulation of Epidermal Growth Factor Receptor Expression by PML in Human Breast Cancer.

DTIC Science & Technology

1996-08-01

Characterization of a zinc finger gene disrupted by the t(15; 17) in acute promyelocytic leukemia. Science, 254:1371-1374. (32) Fagioli , M., Alcalay, M...DISTRIBUTION CODE Approved for public release; distribution unlimited 13. ABSTRACT (Maximum 200 We have determined that PML is a novel growth suppressor that...was found to be translocated from chromosome 15 and fused with the retinoic acid receptor- a gene on chromosome 17 (t(15; 17) in acute promyelogenous

Triggering collapse of the presolar dense cloud core and injecting short-lived radioisotopes with a shock wave. III. Rotating three-dimensional cloud cores

DOE Office of Scientific and Technical Information (OSTI.GOV)

Boss, Alan P.; Keiser, Sandra A., E-mail: boss@dtm.ciw.edu

2014-06-10

A key test of the supernova triggering and injection hypothesis for the origin of the solar system's short-lived radioisotopes is to reproduce the inferred initial abundances of these isotopes. We present here the most detailed models to date of the shock wave triggering and injection process, where shock waves with varied properties strike fully three-dimensional, rotating, dense cloud cores. The models are calculated with the FLASH adaptive mesh hydrodynamics code. Three different outcomes can result: triggered collapse leading to fragmentation into a multiple protostar system; triggered collapse leading to a single protostar embedded in a protostellar disk; or failure tomore » undergo dynamic collapse. Shock wave material is injected into the collapsing clouds through Rayleigh-Taylor fingers, resulting in initially inhomogeneous distributions in the protostars and protostellar disks. Cloud rotation about an axis aligned with the shock propagation direction does not increase the injection efficiency appreciably, as the shock parameters were chosen to be optimal for injection even in the absence of rotation. For a shock wave from a core-collapse supernova, the dilution factors for supernova material are in the range of ∼10{sup –4} to ∼3 × 10{sup –4}, in agreement with recent laboratory estimates of the required amount of dilution for {sup 60}Fe and {sup 26}Al. We conclude that a type II supernova remains as a promising candidate for synthesizing the solar system's short-lived radioisotopes shortly before their injection into the presolar cloud core by the supernova's remnant shock wave.« less

Improving the Efficacy of Anticancer Drugs via Encapsulation and Acoustic Release.

PubMed

Ahmed, Salma E; Awad, Nahid; Paul, Vinod; Moussa, Hesham G; Husseini, Ghaleb A

2018-06-08

Conventional chemotherapeutics lack the specificity and controllability, thus may poison healthy cells while attempting to kill cancerous ones. Newly developed nano-drug delivery systems have shown promise in delivering anti-tumor agents with enhanced stability, durability and overall performance; especially when used along with targeting and triggering techniques. This work traces back the history of chemotherapy, addressing the main challenges that have encouraged the medical researchers to seek a sanctuary in nanotechnological-based drug delivery systems that are grafted with appropriate targeting techniques and drug release mechanisms. A special focus will be paid towards acoustically triggered liposomes encapsulating doxorubicin. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Recognizing Myofascial Pelvic Pain in the Female Patient with Chronic Pelvic Pain

PubMed Central

Pastore, Elizabeth Anne; Katzman, Wendy B.

2012-01-01

Myofascial pelvic pain (MFPP) is a major component of chronic pelvic pain (CPP) and often is not properly identified by healthcare providers. The hallmark diagnostic indicator of MFPP is myofascial trigger points in the pelvic floor musculature that refer pain to adjacent sites. Effective treatments are available to reduce MFPP, including myofascial trigger point release, PMID:22862153

Preparation of Porous γ-Fe2O3@mWO3 Multifunctional Nanoparticles for Drug Loading and Controlled Release.

PubMed

Peng, Hongxia; Huang, Qin; Wu, Tengyan; Wen, Jin; He, Hengping

2018-02-14

The use of chemotherapy drug is hindered by relatively low selectivity toward cancer cells and severe side effects from uptake by noncancerous cells and tissue. Thus, targeted drug delivery systems are preferred to increase the efficiency of drug delivery to specific tissues as well as to decrease its side effects. The aims of this paper are develop microwave-triggered controlled-release drug delivery systems using porous γ-Fe2O3@mWO3 multifunctional core-shell nanoparticles. We also studied its magnetic- microwave to heat responsive properties and large specific surface area. We chose ibuprofen (IBU) as a model drug to evaluate the loading and release function of the γ- Fe2O3@mWO3 nanoparticles. We used a direct precipitation method and thermal decomposition of CTAB template method to synthesize core-shell structured γ-Fe2O3@mWO3 nanoparticles. The specific surface areas were calculated by the Brunauer-Emmett-Teller (BET) method. The load drug and controlled release of the γ-Fe2O3@mWO3 triggered by microwave was determined with ultraviolet-visible spectroscopic analysis. The γ-Fe2O3@mWO3 nanoparticles possesses high surface area of 100.09 m2/g, provides large accessible pore diameter of 6.0 nm for adsorption of drug molecules, high magnetization saturation value of 43.6 emu/g for drug targeting under foreign magnetic fields, quickly convert electromagnetic energy into thermal energy for controlled release by microwave-triggered which was caused by mWO3 shell. The IBU release of over 78% under microwave discontinuous irradiation out classes the 0.15% within 20s only stirring release. This multifunctional material shows good performance for targeting delivery and mWO3 microwave controlled release of anticancer drugs based on all the properties they possess. The porous shell and the introduction of absorbing material not only increased the drug loading efficiency of the nanoparticles but also realized the microwave-stimulated anticancer drug controlled release. The nanoparticles would be very promising for microwave-induced controlled drug release, targeted drug delivery and hyperthermia therapy using microwave. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Gene Silencing by Gold Nanoshell-Mediated Delivery and Laser-Triggered Release of Antisense Oligonucleotide and siRNA

PubMed Central

Huschka, Ryan; Barhoumi, Aoune; Liu, Qing; Roth, Jack A.; Ji, Lin; Halas, Naomi J.

2013-01-01

The approach of RNA interference (RNAi)- using antisense DNA or RNA oligonucleotides to silence activity of a specific pathogenic gene transcript and reduce expression of the encoded protein- is very useful in dissecting genetic function and holds significant promise as a molecular therapeutic. A major obstacle in achieving gene silencing with RNAi technology is the systemic delivery of therapeutic oligonucleotides. Here we demonstrate an engineered gold nanoshell (NS)-based therapeutic oligonucleotide delivery vehicle, designed to release its cargo on demand upon illumination with a near-infrared (NIR) laser. A poly(L)lysine peptide (PLL) epilayer covalently attached to the NS surface (NS-PLL) is used to capture intact, single-stranded antisense DNA oligonucleotides, or alternatively, double-stranded short-interfering RNA (siRNA) molecules. Controlled release of the captured therapeutic oligonucleotides in each case is accomplished by continuous wave NIR laser irradiation at 800 nm, near the resonance wavelength of the nanoshell. Fluorescently tagged oligonucleotides were used to monitor the time-dependent release process and light-triggered endosomal release. A green fluorescent protein (GFP)-expressing human lung cancer H1299 cell line was used to determine cellular uptake and gene silencing mediated by the NS-PLL carrying GFP gene-specific single-stranded DNA antisense oligonucleotide (AON-GFP), or a double-stranded siRNA (siRNA-GFP), in vitro. Light-triggered delivery resulted in ∼ 47% and ∼49% downregulation of the targeted GFP expression by AON-GFP and siRNA-GFP, respectively. Cytotoxicity induced by both the NS-PLL delivery vector and by laser irradiation is minimal, as demonstrated by a XTT cell proliferation assay. PMID:22862291

Dancing girl flap: a new flap suitable for web release.

PubMed

Shinya, K

1999-12-01

To create a deep web, a flap must be designed to have a high elongation effect in one direction along the mid-lateral line of the finger and also to have a shortening effect in the other direction, crossing at a right angle to the mid-lateral line. The dancing girl flap is a modification of a four-flap Z-plasty with two additional Z-plasties. It has a high elongation effect in one direction (>550%) and a shortening effect in the other direction at a right angle (<33%), creating a deep, U-shaped surface. This new flap can be used to release severe scar contracture with a web, and is most suitable for incomplete syndactyly with webs as high as the proximal interphalangeal joint.

Triggered seismicity and deformation between the Landers, California, and Little Skull Mountain, Nevada, earthquakes

USGS Publications Warehouse

Bodin, Paul; Gomberg, Joan

1994-01-01

This article presents evidence for the channeling of strain energy released by the Ms = 7.4 Landers, California, earthquake within the eastern California shear zone (ECSZ). We document an increase in seismicity levels during the 22-hr period starting with the Landers earthquake and culminating 22 hr later with the Ms = 5.4 Little Skull Mountain (LSM), Nevada, earthquake. We evaluate the completeness of regional seismicity catalogs during this period and find that the continuity of post-Landers strain release within the ECSZ is even more pronounced than is evident from the catalog data. We hypothesize that regional-scale connectivity of faults within the ECSZ and LSM region is a critical ingredient in the unprecedented scale and distribution of remotely triggered earthquakes and geodetically manifest strain changes that followed the Landers earthquake. The viability of static strain changes as triggering agents is tested using numerical models. Modeling results illustrate that regional-scale fault connectivity can increase the static strain changes by approximately an order of magnitude at distances of at least 280 km, the distance between the Landers and LSM epicenters. This is possible for models that include both a network of connected faults that slip “sympathetically” and realistic levels of tectonic prestrain. Alternatively, if dynamic strains are a more significant triggering agent than static strains, ECSZ structure may still be important in determining the distribution of triggered seismic and aseismic deformation.

Programmable release of multiple protein drugs from aptamer-functionalized hydrogels via nucleic acid hybridization.

PubMed

Battig, Mark R; Soontornworajit, Boonchoy; Wang, Yong

2012-08-01

Polymeric delivery systems have been extensively studied to achieve localized and controlled release of protein drugs. However, it is still challenging to control the release of multiple protein drugs in distinct stages according to the progress of disease or treatment. This study successfully demonstrates that multiple protein drugs can be released from aptamer-functionalized hydrogels with adjustable release rates at predetermined time points using complementary sequences (CSs) as biomolecular triggers. Because both aptamer-protein interactions and aptamer-CS hybridization are sequence-specific, aptamer-functionalized hydrogels constitute a promising polymeric delivery system for the programmable release of multiple protein drugs to treat complex human diseases.

Smart pH- and reduction-dual-responsive folate-PEG-coated polymeric lipid vesicles for tumor-triggered targeted drug delivery

NASA Astrophysics Data System (ADS)

Wang, Sheng; Wang, Hanjie; Liu, Zhongyun; Wang, Liangliang; Wang, Xiaomin; Su, Lin; Chang, Jin

2014-06-01

To improve their therapeutic index, designed nanocarriers should preferentially accumulate in tumor tissues and then rapidly enter tumor cells to release the encapsulated drugs in a triggered manner. In this article, a new kind of a smart pH- and reduction-dual-responsive drug delivery system based on folate-PEG-coated polymeric lipid vesicles (FPPLVs) formed from amphiphilic dextran derivatives was designed and prepared successfully. PEG chains with pH-sensitive hydrazone bonds, stearyl alcohol (SA) chains with reduction-sensitive disulfide bonds and folate were connected to a dextran main chain. The newly developed FPPLVs had a nano-sized structure (~50 nm) with a PEG coating. The in vitro DOX release profiles showed that the FPPLVs achieved a triggered drug release in response to acidic pH and reducing environments due to the cleavage of hydrazone bonds and disulfide bonds. It has also been demonstrated by an in vitro cellular uptake study that the FPPLVs lose their PEG coating as well as expose the folate in acidic conditions, which allows them to efficiently enter tumor cells through ligand-receptor interactions. In vitro cytotoxicity measurements also confirmed that FPPLVs exhibited pronounced antitumor activity against HeLa cells. These results suggest that FPPLVs are promising carriers for smart antitumor drug delivery applications.To improve their therapeutic index, designed nanocarriers should preferentially accumulate in tumor tissues and then rapidly enter tumor cells to release the encapsulated drugs in a triggered manner. In this article, a new kind of a smart pH- and reduction-dual-responsive drug delivery system based on folate-PEG-coated polymeric lipid vesicles (FPPLVs) formed from amphiphilic dextran derivatives was designed and prepared successfully. PEG chains with pH-sensitive hydrazone bonds, stearyl alcohol (SA) chains with reduction-sensitive disulfide bonds and folate were connected to a dextran main chain. The newly developed FPPLVs had a nano-sized structure (~50 nm) with a PEG coating. The in vitro DOX release profiles showed that the FPPLVs achieved a triggered drug release in response to acidic pH and reducing environments due to the cleavage of hydrazone bonds and disulfide bonds. It has also been demonstrated by an in vitro cellular uptake study that the FPPLVs lose their PEG coating as well as expose the folate in acidic conditions, which allows them to efficiently enter tumor cells through ligand-receptor interactions. In vitro cytotoxicity measurements also confirmed that FPPLVs exhibited pronounced antitumor activity against HeLa cells. These results suggest that FPPLVs are promising carriers for smart antitumor drug delivery applications. Electronic supplementary information (ESI) available. See DOI: 10.1039/c4nr00843j

Integrated nanotechnology platform for tumor-targeted multimodal imaging and therapeutic cargo release

PubMed Central

Hosoya, Hitomi; Dobroff, Andrey S.; Driessen, Wouter H. P.; Cristini, Vittorio; Brinker, Lina M.; Staquicini, Fernanda I.; Cardó-Vila, Marina; D’Angelo, Sara; Ferrara, Fortunato; Proneth, Bettina; Lin, Yu-Shen; Dunphy, Darren R.; Dogra, Prashant; Melancon, Marites P.; Stafford, R. Jason; Miyazono, Kohei; Gelovani, Juri G.; Kataoka, Kazunori; Brinker, C. Jeffrey; Sidman, Richard L.; Arap, Wadih; Pasqualini, Renata

2016-01-01

A major challenge of targeted molecular imaging and drug delivery in cancer is establishing a functional combination of ligand-directed cargo with a triggered release system. Here we develop a hydrogel-based nanotechnology platform that integrates tumor targeting, photon-to-heat conversion, and triggered drug delivery within a single nanostructure to enable multimodal imaging and controlled release of therapeutic cargo. In proof-of-concept experiments, we show a broad range of ligand peptide-based applications with phage particles, heat-sensitive liposomes, or mesoporous silica nanoparticles that self-assemble into a hydrogel for tumor-targeted drug delivery. Because nanoparticles pack densely within the nanocarrier, their surface plasmon resonance shifts to near-infrared, thereby enabling a laser-mediated photothermal mechanism of cargo release. We demonstrate both noninvasive imaging and targeted drug delivery in preclinical mouse models of breast and prostate cancer. Finally, we applied mathematical modeling to predict and confirm tumor targeting and drug delivery. These results are meaningful steps toward the design and initial translation of an enabling nanotechnology platform with potential for broad clinical applications. PMID:26839407

Degradable cationic nanohydrogel particles for stimuli-responsive release of siRNA.

PubMed

Nuhn, Lutz; Braun, Lydia; Overhoff, Iris; Kelsch, Annette; Schaeffel, David; Koynov, Kaloian; Zentel, Rudolf

2014-12-01

Well-defined nanogels have become quite attractive as safe and stable carriers for siRNA delivery. However, to avoid nanoparticle accumulation, they need to provide a stimuli-responsive degradation mechanism that can be activated at the payload's site of action. In this work, the synthetic concept for generating well-defined nanohydrogel particles is extended to incorporate disulfide cross-linkers into a cationic nanonetwork for redox-triggered release of oligonucleotide payload as well as nanoparticle degradation under reductive conditions of the cytoplasm. Therefore, a novel disulfide-modified spermine cross-linker is designed that both allows disassembly of the nanogel as well as removal of cationic charge from residual polymer fragments. The degradation process is monitored by scanning electron microscopy (SEM) and fluorescence correlation spectroscopy (FCS). Moreover, siRNA release is analyzed by agarose gel electrophoresis and a fluorescent RNA detection assay. The results exemplify the versatility of the applied nanogel manufacturing process, which allows alternative stimuli-responsive core cross-linkers to be integrated for triggered oligonucleotide release as well as effective biodegradation for reduced nanotoxicity. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Integrated nanotechnology platform for tumor-targeted multimodal imaging and therapeutic cargo release.

PubMed

Hosoya, Hitomi; Dobroff, Andrey S; Driessen, Wouter H P; Cristini, Vittorio; Brinker, Lina M; Staquicini, Fernanda I; Cardó-Vila, Marina; D'Angelo, Sara; Ferrara, Fortunato; Proneth, Bettina; Lin, Yu-Shen; Dunphy, Darren R; Dogra, Prashant; Melancon, Marites P; Stafford, R Jason; Miyazono, Kohei; Gelovani, Juri G; Kataoka, Kazunori; Brinker, C Jeffrey; Sidman, Richard L; Arap, Wadih; Pasqualini, Renata

2016-02-16

A major challenge of targeted molecular imaging and drug delivery in cancer is establishing a functional combination of ligand-directed cargo with a triggered release system. Here we develop a hydrogel-based nanotechnology platform that integrates tumor targeting, photon-to-heat conversion, and triggered drug delivery within a single nanostructure to enable multimodal imaging and controlled release of therapeutic cargo. In proof-of-concept experiments, we show a broad range of ligand peptide-based applications with phage particles, heat-sensitive liposomes, or mesoporous silica nanoparticles that self-assemble into a hydrogel for tumor-targeted drug delivery. Because nanoparticles pack densely within the nanocarrier, their surface plasmon resonance shifts to near-infrared, thereby enabling a laser-mediated photothermal mechanism of cargo release. We demonstrate both noninvasive imaging and targeted drug delivery in preclinical mouse models of breast and prostate cancer. Finally, we applied mathematical modeling to predict and confirm tumor targeting and drug delivery. These results are meaningful steps toward the design and initial translation of an enabling nanotechnology platform with potential for broad clinical applications.

Integrated nanotechnology platform for tumor-targeted multimodal imaging and therapeutic cargo release

DOE PAGES

Hosoya, Hitomi; Dobroff, Andrey S.; Driessen, Wouter H. P.; ...

2016-02-02

A major challenge of targeted molecular imaging and drug delivery in cancer is establishing a functional combination of ligand-directed cargo with a triggered release system. Here we develop a hydrogel-based nanotechnology platform that integrates tumor targeting, photon-to-heat conversion, and triggered drug delivery within a single nanostructure to enable multimodal imaging and controlled release of therapeutic cargo. In proof-of-concept experiments, we show a broad range of ligand peptide-based applications with phage particles, heat-sensitive liposomes, or mesoporous silica nanoparticles that self-assemble into a hydrogel for tumor-targeted drug delivery. Because nanoparticles pack densely within the nanocarrier, their surface plasmon resonance shifts to near-infrared,more » thereby enabling a laser-mediated photothermal mechanism of cargo release. We demonstrate both noninvasive imaging and targeted drug delivery in preclinical mouse models of breast and prostate cancer. Finally, we applied mathematical modeling to predict and confirm tumor targeting and drug delivery. We conclude that these results are meaningful steps toward the design and initial translation of an enabling nanotechnology platform with potential for broad clinical applications.« less

Integrated nanotechnology platform for tumor-targeted multimodal imaging and therapeutic cargo release

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hosoya, Hitomi; Dobroff, Andrey S.; Driessen, Wouter H. P.

A major challenge of targeted molecular imaging and drug delivery in cancer is establishing a functional combination of ligand-directed cargo with a triggered release system. Here we develop a hydrogel-based nanotechnology platform that integrates tumor targeting, photon-to-heat conversion, and triggered drug delivery within a single nanostructure to enable multimodal imaging and controlled release of therapeutic cargo. In proof-of-concept experiments, we show a broad range of ligand peptide-based applications with phage particles, heat-sensitive liposomes, or mesoporous silica nanoparticles that self-assemble into a hydrogel for tumor-targeted drug delivery. Because nanoparticles pack densely within the nanocarrier, their surface plasmon resonance shifts to near-infrared,more » thereby enabling a laser-mediated photothermal mechanism of cargo release. We demonstrate both noninvasive imaging and targeted drug delivery in preclinical mouse models of breast and prostate cancer. Finally, we applied mathematical modeling to predict and confirm tumor targeting and drug delivery. We conclude that these results are meaningful steps toward the design and initial translation of an enabling nanotechnology platform with potential for broad clinical applications.« less

Spatial focalization of pheromone/MAPK signaling triggers commitment to cell–cell fusion

PubMed Central

Merlini, Laura

2016-01-01

Cell fusion is universal in eukaryotes for fertilization and development, but what signals this process is unknown. Here, we show in Schizosaccharomyces pombe that fusion does not require a dedicated signal but is triggered by spatial focalization of the same pheromone–GPCR (G-protein-coupled receptor)–MAPK signaling cascade that drives earlier mating events. Autocrine cells expressing the receptor for their own pheromone trigger fusion attempts independently of cell–cell contact by concentrating pheromone release at the fusion focus, a dynamic actin aster underlying the secretion of cell wall hydrolases. Pheromone receptor and MAPK cascade are similarly enriched at the fusion focus, concomitant with fusion commitment in wild-type mating pairs. This focalization promotes cell fusion by immobilizing the fusion focus, thus driving local cell wall dissolution. We propose that fusion commitment is imposed by a local increase in MAPK concentration at the fusion focus, driven by a positive feedback between fusion focus formation and focalization of pheromone release and perception. PMID:27798845

Engineered modular biomaterial logic gates for environmentally triggered therapeutic delivery

NASA Astrophysics Data System (ADS)

Badeau, Barry A.; Comerford, Michael P.; Arakawa, Christopher K.; Shadish, Jared A.; Deforest, Cole A.

2018-03-01

The successful transport of drug- and cell-based therapeutics to diseased sites represents a major barrier in the development of clinical therapies. Targeted delivery can be mediated through degradable biomaterial vehicles that utilize disease biomarkers to trigger payload release. Here, we report a modular chemical framework for imparting hydrogels with precise degradative responsiveness by using multiple environmental cues to trigger reactions that operate user-programmable Boolean logic. By specifying the molecular architecture and connectivity of orthogonal stimuli-labile moieties within material cross-linkers, we show selective control over gel dissolution and therapeutic delivery. To illustrate the versatility of this methodology, we synthesized 17 distinct stimuli-responsive materials that collectively yielded all possible YES/OR/AND logic outputs from input combinations involving enzyme, reductant and light. Using these hydrogels we demonstrate the first sequential and environmentally stimulated release of multiple cell lines in well-defined combinations from a material. We expect these platforms will find utility in several diverse fields including drug delivery, diagnostics and regenerative medicine.

Drug-sensing hydrogels for the inducible release of biopharmaceuticals

NASA Astrophysics Data System (ADS)

Ehrbar, Martin; Schoenmakers, Ronald; Christen, Erik H.; Fussenegger, Martin; Weber, Wilfried

2008-10-01

Drug-dependent dissociation or association of cellular receptors represents a potent pharmacologic mode of action for regulating cell fate and function. Transferring the knowledge of pharmacologically triggered protein-protein interactions to materials science will enable novel design concepts for stimuli-sensing smart hydrogels. Here, we show the design and validation of an antibiotic-sensing hydrogel for the trigger-inducible release of human vascular endothelial growth factor. Genetically engineered bacterial gyrase subunit B (GyrB) (ref. 4) coupled to polyacrylamide was dimerized by the addition of the aminocoumarin antibiotic coumermycin, resulting in hydrogel formation. Addition of increasing concentrations of clinically validated novobiocin (Albamycin) dissociated the GyrB subunits, thereby resulting in dissociation of the hydrogel and dose- and time-dependent liberation of the entrapped protein pharmaceutical VEGF121 for triggering proliferation of human umbilical vein endothelial cells. Pharmacologically controlled hydrogels have the potential to fulfil the promises of stimuli-sensing materials as smart devices for spatiotemporally controlled delivery of drugs within the patient.

Engineered modular biomaterial logic gates for environmentally triggered therapeutic delivery.

PubMed

Badeau, Barry A; Comerford, Michael P; Arakawa, Christopher K; Shadish, Jared A; DeForest, Cole A

2018-03-01

The successful transport of drug- and cell-based therapeutics to diseased sites represents a major barrier in the development of clinical therapies. Targeted delivery can be mediated through degradable biomaterial vehicles that utilize disease biomarkers to trigger payload release. Here, we report a modular chemical framework for imparting hydrogels with precise degradative responsiveness by using multiple environmental cues to trigger reactions that operate user-programmable Boolean logic. By specifying the molecular architecture and connectivity of orthogonal stimuli-labile moieties within material cross-linkers, we show selective control over gel dissolution and therapeutic delivery. To illustrate the versatility of this methodology, we synthesized 17 distinct stimuli-responsive materials that collectively yielded all possible YES/OR/AND logic outputs from input combinations involving enzyme, reductant and light. Using these hydrogels we demonstrate the first sequential and environmentally stimulated release of multiple cell lines in well-defined combinations from a material. We expect these platforms will find utility in several diverse fields including drug delivery, diagnostics and regenerative medicine.

A new Scheme for ATLAS Trigger Simulation using Legacy Code

NASA Astrophysics Data System (ADS)

Galster, Gorm; Stelzer, Joerg; Wiedenmann, Werner

2014-06-01

Analyses at the LHC which search for rare physics processes or determine with high precision Standard Model parameters require accurate simulations of the detector response and the event selection processes. The accurate determination of the trigger response is crucial for the determination of overall selection efficiencies and signal sensitivities. For the generation and the reconstruction of simulated event data, the most recent software releases are usually used to ensure the best agreement between simulated data and real data. For the simulation of the trigger selection process, however, ideally the same software release that was deployed when the real data were taken should be used. This potentially requires running software dating many years back. Having a strategy for running old software in a modern environment thus becomes essential when data simulated for past years start to present a sizable fraction of the total. We examined the requirements and possibilities for such a simulation scheme within the ATLAS software framework and successfully implemented a proof-of-concept simulation chain. One of the greatest challenges was the choice of a data format which promises long term compatibility with old and new software releases. Over the time periods envisaged, data format incompatibilities are also likely to emerge in databases and other external support services. Software availability may become an issue, when e.g. the support for the underlying operating system might stop. In this paper we present the encountered problems and developed solutions, and discuss proposals for future development. Some ideas reach beyond the retrospective trigger simulation scheme in ATLAS as they also touch more generally aspects of data preservation.

Multifunctional Micelles Dually Responsive to Hypoxia and Singlet Oxygen: Enhanced Photodynamic Therapy via Interactively Triggered Photosensitizer Delivery.

PubMed

Li, Juanjuan; Meng, Xuan; Deng, Jian; Lu, Di; Zhang, Xin; Chen, Yanrui; Zhu, Jundong; Fan, Aiping; Ding, Dan; Kong, Deling; Wang, Zheng; Zhao, Yanjun

2018-05-23

Nanoparticulate antitumor photodynamic therapy (PDT) has been suffering from the limited dose accumulation in tumor. Herein, we report dually hypoxia- and singlet oxygen-responsive polymeric micelles to efficiently utilize the photosensitizer deposited in the disease site and hence facilely improve PDT's antitumor efficacy. Tailored methoxy poly(ethylene glycol)-azobenzene-poly(aspartic acid) copolymer conjugate with imidazole as the side chains was synthesized. The conjugate micelles (189 ± 19 nm) obtained by self-assembly could efficiently load a model photosensitizer, chlorin e6 (Ce6) with a loading of 4.1 ± 0.5% (w/w). The facilitated cellular uptake of micelles was achieved by the triggered azobenzene collapse that provoked poly(ethylene glycol) shedding; rapid Ce6 release was enabled by imidazole oxidation that induced micelle disassembly. In addition, the singlet oxygen-mediated cargo release not only addressed the limited diffusion range and short half-life of singlet oxygen but also decreased the oxygen level, which could in turn enhance internalization and increase the intracellular Ce6 concentration. The hypoxia-induced dePEGylation and singlet oxygen-triggered Ce6 release was demonstrated both in aqueous buffer and in Lewis lung carcinoma (LLC) cells. The cellular uptake study demonstrated that the dually responsive micelles could deliver significantly more Ce6 to the cells, which resulted in a substantially improved cytotoxicity. This concurred well with the superior in vivo antitumor ability of micelles in a LLC tumor-bearing mouse model. This study presented an intriguing nanoplatform to realize interactively triggered photosensitizer delivery and improved antitumor PDT efficacy.

Zinc triggers microglial activation

PubMed Central

Kauppinen, Tiina M.; Higashi, Youichirou; Suh, Sang Won; Escartin, Carole; Nagasawa, Kazuki; Swanson, Raymond A.

2009-01-01

Microglia are resident immune cells of the central nervous system. When stimulated by infection, tissue injury, or other signals, microglia assume an activated, “amoeboid” morphology and release matrix metalloproteinases, reactive oxygen species, and other pro-inflammatory factors. This innate immune response augments host defenses, but it can also contribute to neuronal death. Zinc is released by neurons under several conditions in which microglial activation occurs, and zinc chelators can reduce neuronal death in animal models of cerebral ischemia and neurodegenerative disorders. Here we show that zinc directly triggers microglial activation. Microglia transfected with an NF-kB reporter gene showed a several-fold increase in NF-kB activity in response to 30 μM zinc. Cultured mouse microglia exposed to 15 – 30 μM zinc increased nitric oxide production, increased F4/80 expression, altered cytokine expression, and assumed the activated morphology. Zinc-induced microglial activation was blocked by inhibiting NADPH oxidase, poly(ADP-ribose) polymerase-1 (PARP-1), or NF-κB activation. Zinc injected directly into mouse brain induced microglial activation in wild-type mice, but not in mice genetically lacking PARP-1 or NADPH oxidase activity. Endogenous zinc release, induced by cerebral ischemia-reperfusion, likewise induced a robust microglial reaction, and this reaction was suppressed by the zinc chelator CaEDTA. Together, these results suggest that extracellular zinc triggers microglial activation through the sequential activation of NADPH oxidase, PARP-1, and NF-κB. These findings identify a novel trigger for microglial activation and a previously unrecognized mechanism by which zinc may contribute to neurological disorders. PMID:18509044

Long-term impacts of boreal wildfire on carbon cycling dynamics in Interior Alaska

NASA Astrophysics Data System (ADS)

Gaglioti, B.; Mann, D. H.; Finney, B.; Pohlman, J.; Jones, B. M.; Arp, C. D.; Wooller, M. J.

2013-12-01

Wildland fire is a major disturbance in the boreal forest, and warming climate will likely increase the frequency and severity of burning. Fires trigger thermokarst, the thawing of permafrost (perennially frozen ground), which can release large amounts of ancient carbon to the atmosphere. But how vulnerable is the organic carbon stored in permafrost in the boreal forest to a changing fire regime? Paleolimnological records can tell us how the landscape actually responded during prehistoric fires and provide a valuable perspective on future events. Here we present a whole-watershed summary of terrestrial and aquatic carbon dynamics during multiple fire and thermokarst disturbances over the last millennia. We use laminated lake sediments laid down in a permanently stratified, thermokarst lake basin in Interior Alaska to decipher the impacts of wildfires on permafrost carbon release from the surrounding watershed. Sediment chronologies based on layer counts, lead and cesium dating, and radiocarbon dating of plant macrofossils, provide a near-annual resolution of environmental changes over the last 1100 years. Charcoal accumulation rates quantified from sediment thin-sections and fire-scarred spruce trees constrain the timing of fires. The variability of permafrost carbon release before and after fires was investigated by analyzing several geochemical indices including radiocarbon dating on the sediment organic matter directly above and below charcoal layers in the sediment stack. The difference between a sediment layers 'true' age of deposition based on layer counts and the apparent radiocarbon age on the same bulk sediment material (radiocarbon age offset) is then used as a proxy for permafrost carbon release. The relative age of permafrost-derived organic carbon entering the lake before and after past fires was determined by radiocarbon age offsets before and after wildfire events. Fires are not the only triggers of permafrost-C release. Thermokarst caused by shoreline erosion triggered by some combination of fires, beaver dams that raise lake levels, and chance events complicate the larger watershed signal of C release.

Changes in blood flow and cellular metabolism at a myofascial trigger point with trigger point release (ischemic compression): a proof-of-principle pilot study

PubMed Central

Moraska, Albert F.; Hickner, Robert C.; Kohrt, Wendy M.; Brewer, Alan

2012-01-01

Objective To demonstrate proof-of-principle measurement for physiological change within an active myofascial trigger point (MTrP) undergoing trigger point release (ischemic compression). Design Interstitial fluid was sampled continuously at a trigger point before and after intervention. Setting A biomedical research clinic at a university hospital. Participants Two subjects from a pain clinic presenting with chronic headache pain. Interventions A single microdialysis catheter was inserted into an active MTrP of the upper trapezius to allow for continuous sampling of interstitial fluid before and after application of trigger point therapy by a massage therapist. Main Outcome Measures Procedural success, pain tolerance, feasibility of intervention during sample collection, determination of physiologically relevant values for local blood flow, as well as glucose and lactate concentrations. Results Both patients tolerated the microdialysis probe insertion into the MTrP and treatment intervention without complication. Glucose and lactate concentrations were measured in the physiological range. Following intervention, a sustained increase in lactate was noted for both subjects. Conclusions Identifying physiological constituents of MTrP’s following intervention is an important step toward understanding pathophysiology and resolution of myofascial pain. The present study forwards that aim by showing proof-of-concept for collection of interstitial fluid from an MTrP before and after intervention can be accomplished using microdialysis, thus providing methodological insight toward treatment mechanism and pain resolution. Of the biomarkers measured in this study, lactate may be the most relevant for detection and treatment of abnormalities in the MTrP. PMID:22975226

One Single Graphene Oxide Film for Responsive Actuation.

PubMed

Cheng, Huhu; Zhao, Fei; Xue, Jiangli; Shi, Gaoquan; Jiang, Lan; Qu, Liangti

2016-09-22

Graphene, because of its superior electrical/thermal conductivity, high surface area, excellent mechanical flexibility, and stability, is currently receiving significant attention and benefit to fabricate actuator devices. Here, a sole graphene oxide (GO) film responsive actuator with an integrated self-detecting sensor has been developed. The film exhibits an asymmetric surface structure on its two sides, creating a promising actuation ability triggered by multistimuli, such as moisture, thermals, and infrared light. Meanwhile, the built-in laser-writing reduced graphene oxide (rGO) sensor in the film can detect its own deformation in real time. Smart perceptual fingers in addition to rectangular-shaped and even four-legged walking robots have been developed based on the responsive GO film.

Epigenetic regulation of puberty via Zinc finger protein-mediated transcriptional repression.

PubMed

Lomniczi, Alejandro; Wright, Hollis; Castellano, Juan Manuel; Matagne, Valerie; Toro, Carlos A; Ramaswamy, Suresh; Plant, Tony M; Ojeda, Sergio R

2015-12-16

In primates, puberty is unleashed by increased GnRH release from the hypothalamus following an interval of juvenile quiescence. GWAS implicates Zinc finger (ZNF) genes in timing human puberty. Here we show that hypothalamic expression of several ZNFs decreased in agonadal male monkeys in association with the pubertal reactivation of gonadotropin secretion. Expression of two of these ZNFs, GATAD1 and ZNF573, also decreases in peripubertal female monkeys. However, only GATAD1 abundance increases when gonadotropin secretion is suppressed during late infancy. Targeted delivery of GATAD1 or ZNF573 to the rat hypothalamus delays puberty by impairing the transition of a transcriptional network from an immature repressive epigenetic configuration to one of activation. GATAD1 represses transcription of two key puberty-related genes, KISS1 and TAC3, directly, and reduces the activating histone mark H3K4me2 at each promoter via recruitment of histone demethylase KDM1A. We conclude that GATAD1 epitomizes a subset of ZNFs involved in epigenetic repression of primate puberty.

Connector systems for structures

NASA Technical Reports Server (NTRS)

Lupo, Christian (Inventor); Evenson, Erik (Inventor); Wesselski, Clarence (Inventor)

1993-01-01

A releasable coupling device for connecting two members to one another where a collet type fastener has normally retracted latching fingers insertable into a latching recess and a longitudinally movable expander for activating the fastener is described. The longitudinal movement is retained with a paraffin actuated system which can reset. The longitudinal movement of the expander in one direction is through a one way threaded ratchet system which provides an automatic locking action and the expander is movable in either direction by an independently operated threaded action.

Britle failure of non-Newtonian, floating, extensional flows

NASA Astrophysics Data System (ADS)

Sayag, Roiy; Worster, Michael

2011-11-01

Glacier ice is driven by gravity to flow from the land, where it is under shear, into the ocean, where it floats and extends. Owing to its non-Newtonian rheology, the ice can flow axisymmetrically over the bed but undergo brittle failure once it is floating on the ocean, as observed for example in crevassing of ice shelves. We model this coupled flow as an intrusion of a viscous gravity current into a denser ocean and study it both theoretically and experimentally. We have conducted laboratory experiments using a shear-thinning suspension that represents ice, and a denser inviscid fluid that represents an ocean. The non-Newtonian fluid was released at a constant flux through a cylindrical nozzle over a horizontal plane. The grounded, shear-dominated region of the flow was axisymmetric throughout the experiment, while past the transition line axisymmetry broke down into a seemingly ordered set of finger-like extensions (floating shelves) that demonstrated brittle behaviour. We have found that the width of the fingers as well as their radial extent increase with the flux. We attempt to explain these observations through a fingering instability that is driven by the dynamical differences between the two flow domains and by the material rheology, and we project that analysis to formulate a linkage between the material properties of ice and an upper bound on the width of ice shelves. NERC

The joint Simon effect depends on perceived agency, but not intentionality, of the alternative action

PubMed Central

Stenzel, Anna; Dolk, Thomas; Colzato, Lorenza S.; Sellaro, Roberta; Hommel, Bernhard; Liepelt, Roman

2014-01-01

A co-actor's intentionality has been suggested to be a key modulating factor for joint action effects like the joint Simon effect (JSE). However, in previous studies intentionality has often been confounded with agency defined as perceiving the initiator of an action as being the causal source of the action. The aim of the present study was to disentangle the role of agency and intentionality as modulating factors of the JSE. In Experiment 1, participants performed a joint go/nogo Simon task next to a co-actor who either intentionally controlled a response button with own finger movements (agency+/intentionality+) or who passively placed the hand on a response button that moved up and down on its own as triggered by computer signals (agency−/intentionality−). In Experiment 2, we included a condition in which participants believed that the co-actor intentionally controlled the response button with a Brain-Computer Interface (BCI) while placing the response finger clearly besides the response button, so that the causal relationship between agent and action effect was perceptually disrupted (agency−/intentionality+). As a control condition, the response button was computer controlled while the co-actor placed the response finger besides the response button (agency−/intentionality−). Experiment 1 showed that the JSE is present with an intentional co-actor and causality between co-actor and action effect, but absent with an unintentional co-actor and a lack of causality between co-actor and action effect. Experiment 2 showed that the JSE is absent with an intentional co-actor, but no causality between co-actor and action effect. Our findings indicate an important role of the co-actor's agency for the JSE. They also suggest that the attribution of agency has a strong perceptual basis. PMID:25140144

The joint Simon effect depends on perceived agency, but not intentionality, of the alternative action.

PubMed

Stenzel, Anna; Dolk, Thomas; Colzato, Lorenza S; Sellaro, Roberta; Hommel, Bernhard; Liepelt, Roman

2014-01-01

A co-actor's intentionality has been suggested to be a key modulating factor for joint action effects like the joint Simon effect (JSE). However, in previous studies intentionality has often been confounded with agency defined as perceiving the initiator of an action as being the causal source of the action. The aim of the present study was to disentangle the role of agency and intentionality as modulating factors of the JSE. In Experiment 1, participants performed a joint go/nogo Simon task next to a co-actor who either intentionally controlled a response button with own finger movements (agency+/intentionality+) or who passively placed the hand on a response button that moved up and down on its own as triggered by computer signals (agency-/intentionality-). In Experiment 2, we included a condition in which participants believed that the co-actor intentionally controlled the response button with a Brain-Computer Interface (BCI) while placing the response finger clearly besides the response button, so that the causal relationship between agent and action effect was perceptually disrupted (agency-/intentionality+). As a control condition, the response button was computer controlled while the co-actor placed the response finger besides the response button (agency-/intentionality-). Experiment 1 showed that the JSE is present with an intentional co-actor and causality between co-actor and action effect, but absent with an unintentional co-actor and a lack of causality between co-actor and action effect. Experiment 2 showed that the JSE is absent with an intentional co-actor, but no causality between co-actor and action effect. Our findings indicate an important role of the co-actor's agency for the JSE. They also suggest that the attribution of agency has a strong perceptual basis.

Monitoring crater-wall collapse at active volcanoes: a study of the 12 January 2013 event at Stromboli

NASA Astrophysics Data System (ADS)

Calvari, Sonia; Intrieri, Emanuele; Di Traglia, Federico; Bonaccorso, Alessandro; Casagli, Nicola; Cristaldi, Antonio

2016-05-01

Crater-wall collapses are fairly frequent at active volcanoes and they are normally studied through the analysis of their deposits. In this paper, we present an analysis of the 12 January 2013 crater-wall collapse occurring at Stromboli volcano, investigated by means of a monitoring network comprising visible and infrared webcams and a Ground-Based Interferometric Synthetic Aperture Radar. The network revealed the triggering mechanisms of the collapse, which are comparable to the events that heralded the previous effusive eruptions in 1985, 2002, 2007 and 2014. The collapse occurred during a period of inflation of the summit cone and was preceded by increasing explosive activity and the enlargement of the crater. Weakness of the crater wall, increasing magmastatic pressure within the upper conduit induced by ascending magma and mechanical erosion caused by vent opening at the base of the crater wall and by lava fingering, are considered responsible for triggering the collapse on 12 January 2013 at Stromboli. We suggest that the combination of these factors might be a general mechanism to generate crater-wall collapse at active volcanoes.

Silk-elastin-like protein biomaterials for the controlled delivery of therapeutics.

PubMed

Huang, Wenwen; Rollett, Alexandra; Kaplan, David L

2015-05-01

Genetically engineered biomaterials are useful for controlled delivery owing to their rational design, tunable structure-function, biocompatibility, degradability and target specificity. Silk-elastin-like proteins (SELPs), a family of genetically engineered recombinant protein polymers, possess these properties. Additionally, given the benefits of combining semi-crystalline silk-blocks and elastomeric elastin-blocks, SELPs possess multi-stimuli-responsive properties and tunability, thereby becoming promising candidates for targeted cancer therapeutics delivery and controlled gene release. An overview of SELP biomaterials for drug delivery and gene release is provided. Biosynthetic strategies used for SELP production, fundamental physicochemical properties and self-assembly mechanisms are discussed. The review focuses on sequence-structure-function relationships, stimuli-responsive features and current and potential drug delivery applications. The tunable material properties allow SELPs to be pursued as promising biomaterials for nanocarriers and injectable drug release systems. Current applications of SELPs have focused on thermally-triggered biomaterial formats for the delivery of therapeutics, based on local hyperthermia in tumors or infections. Other prominent controlled release applications of SELPs as injectable hydrogels for gene release have also been pursued. Further biomedical applications that utilize other stimuli to trigger the reversible material responses of SELPs for targeted delivery, including pH, ionic strength, redox, enzymatic stimuli and electric field, are in progress. Exploiting these additional stimuli-responsive features will provide a broader range of functional biomaterials for controlled therapeutics release and tissue regeneration.

DsbA-L prevents obesity-induced inflammation and insulin resistance by suppressing the mtDNA release-activated cGAS-cGAMP-STING pathway

USDA-ARS?s Scientific Manuscript database

Chronic inflammation in adipose tissue plays a key role in obesity-induced insulin resistance. However, the mechanisms underlying obesity-induced inflammation remain elusive. Here we show that obesity promotes mtDNA release into the cytosol, where it triggers inflammatory responses by activating the...

Light-triggerable formulations for the intracellular controlled release of biomolecules.

PubMed

Lino, Miguel M; Ferreira, Lino

2018-05-01

New therapies based on the use of biomolecules [e.g., proteins, peptides, and non-coding (nc)RNAs] have emerged during the past few years. Given their instability, adverse effects, and limited ability to cross cell membranes, delivery systems are required to fully reveal their biological potential. Sophisticated nanoformulations responsive to light offer an excellent opportunity for the controlled release of these biomolecules, enabling the control of timing, duration, location, and dosage. In this review, we discuss the design principles for the delivery of biomolecules, in particular proteins and RNA-based therapeutics, by light-triggerable formulations. We further discuss the opportunities offered by these formulations in terms of endosomal escape, as well as their limitations. Copyright © 2018 Elsevier Ltd. All rights reserved.

Signal transduction and amplification through enzyme-triggered ligand release and accelerated catalysis.

PubMed

Goggins, Sean; Marsh, Barrie J; Lubben, Anneke T; Frost, Christopher G

2015-08-01

Signal transduction and signal amplification are both important mechanisms used within biological signalling pathways. Inspired by this process, we have developed a signal amplification methodology that utilises the selectivity and high activity of enzymes in combination with the robustness and generality of an organometallic catalyst, achieving a hybrid biological and synthetic catalyst cascade. A proligand enzyme substrate was designed to selectively self-immolate in the presence of the enzyme to release a ligand that can bind to a metal pre-catalyst and accelerate the rate of a transfer hydrogenation reaction. Enzyme-triggered catalytic signal amplification was then applied to a range of catalyst substrates demonstrating that signal amplification and signal transduction can both be achieved through this methodology.

Enzyme-activated intracellular drug delivery with tubule clay nanoformulation

PubMed Central

Dzamukova, Maria R.; Naumenko, Ekaterina A.; Lvov, Yuri M.; Fakhrullin, Rawil F.

2015-01-01

Fabrication of stimuli-triggered drug delivery vehicle s is an important milestone in treating cancer. Here we demonstrate the selective anticancer drug delivery into human cells with biocompatible 50-nm diameter halloysite nanotube carriers. Physically-adsorbed dextrin end stoppers secure the intercellular release of brilliant green. Drug-loaded nanotubes penetrate through the cellular membranes and their uptake efficiency depends on the cells growth rate. Intercellular glycosyl hydrolases-mediated decomposition of the dextrin tube-end stoppers triggers the release of the lumen-loaded brilliant green, which allowed for preferable elimination of human lung carcinoma cells (А549) as compared with hepatoma cells (Hep3b). The enzyme-activated intracellular delivery of brilliant green using dextrin-coated halloysite nanotubes is a promising platform for anticancer treatment. PMID:25976444

Finger tapping ability in healthy elderly and young adults.

PubMed

Aoki, Tomoko; Fukuoka, Yoshiyuki

2010-03-01

The maximum isometric force production capacity of the fingers decreases with age. However, little information is available on age-related changes in dynamic motor capacity of individual fingers. The purpose of this study was to compare the dynamic motor function of individual fingers between elderly and young adults using rapid single-finger and double-finger tapping. Fourteen elderly and 14 young adults performed maximum frequency tapping by the index, middle, ring, or little finger (single-finger tapping) and with alternate movements of the index-middle, middle-ring, or ring-little finger-pair (double-finger tapping). The maximum pinch force between the thumb and each finger, tactile sensitivity of each fingertip, and time taken to complete a pegboard test were also measured. Compared with young subjects, the older subjects had significantly slower tapping rates in all fingers and finger-pairs in the tapping tasks. The age-related decline was also observed in the tactile sensitivities of all fingers and in the pegboard test. However, there was no group difference in the pinch force of any finger. The tapping rate of each finger did not correlate with the pinch force or tactile sensitivity for the corresponding finger in the elderly subjects. Maximum rate of finger tapping was lower in the elderly adults compared with the young adults. The decline of finger tapping ability in elderly adults seems to be less affected by their maximum force production capacities of the fingers as well as tactile sensitivities at the tips of the fingers.

Hand digit control in children: motor overflow in multi-finger pressing force vector space during maximum voluntary force production.

PubMed

Shim, Jae Kun; Karol, Sohit; Hsu, Jeffrey; de Oliveira, Marcio Alves

2008-04-01

The aim of this study was to investigate the contralateral motor overflow in children during single-finger and multi-finger maximum force production tasks. Forty-five right handed children, 5-11 years of age produced maximum isometric pressing force in flexion or extension with single fingers or all four fingers of their right hand. The forces produced by individual fingers of the right and left hands were recorded and analyzed in four-dimensional finger force vector space. The results showed that increases in task (right) hand finger forces were linearly associated with non-task (left) hand finger forces. The ratio of the non-task hand finger force magnitude to the corresponding task hand finger force magnitude, termed motor overflow magnitude (MOM), was greater in extension than flexion. The index finger flexion task showed the smallest MOM values. The similarity between the directions of task hand and non-task hand finger force vectors in four-dimensional finger force vector space, termed motor overflow direction (MOD), was the greatest for index and smallest for little finger tasks. MOM of a four-finger task was greater than the sum of MOMs of single-finger tasks, and this phenomenon was termed motor overflow surplus. Contrary to previous studies, no single-finger or four-finger tasks showed significant changes of MOM or MOD with the age of children. We conclude that the contralateral motor overflow in children during finger maximum force production tasks is dependent upon the task fingers and the magnitude and direction of task finger forces.

Release of nickel and chromium in common foods during cooking in 18/10 (grade 316) stainless steel pots.

PubMed

Guarneri, Fabrizio; Costa, Chiara; Cannavò, Serafinella P; Catania, Stefania; Bua, Giuseppe D; Fenga, Concettina; Dugo, Giacomo

2017-01-01

Literature data on the release of nickel and chromium from stainless steel cookware during food preparation are contrasting, have often been obtained with uncommon foods and/or procedures, and are thus not widely applicable. To assess the release of nickel and chromium from 18/10 (grade 316) stainless steel pots in cooking conditions that are common in an urban lifestyle. Tomato sauce and lemon marmalade were cooked for 1 h, alone or with added EDTA, in used or unused stainless steel pots from different manufacturers. Additionally, aqueous solutions at pH 2.3, 7.7 and 9 were boiled for 1 h in the same pots. Metal release was assessed with inductively coupled plasma mass spectrometry. The release of nickel and chromium increased with cooking/boiling time, was higher with unused pots, at low pH or with EDTA, and was sometimes remarkably different between manufacturers. In all experiments, the amounts released were below known allergy-triggering thresholds. Under common conditions, the use of 18/10 stainless steel pots is considered to be safe for the majority of nickel-allergic and/or chromium-allergic subjects. However, the total amount of nickel contained in foods and released from pots may exceed the individual threshold for triggering allergy, potentially causing problems for highly sensitive patients, or, conversely, contribute to induction of immunotolerance by oral low-dose exposure. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Breeding system and bumblebee drone pollination of an explosively pollen-releasing plant, Meliosma tenuis (Sabiaceae).

PubMed

Wong Sato, A A; Kato, M

2018-05-01

Explosive pollen release is a mechanism used by some angiosperms that serves to attach pollen to a pollinator's body. It is usually adopted by species with zygomorphic tubular flowers and pollinated by birds and bees. The tree genus Meliosma (Sabiaceae, Proteales) has unique disc-like flowers that are externally actinomorphic, but internally zygomorphic, and release pollen explosively. To elucidate the adaptive significance of explosive pollen release, we observed flowering behaviour, the breeding system and pollinator visits to flowers of the Japanese species Meliosma tenuis in a temperate forest. Flowers bloomed in June and were nectariferous and protandrous. Explosive pollen release was triggered by slight tactile stimuli to anther filaments or staminodes in male-stage flowers. Because pollen cannot come into contact with the pistils enclosed by staminodes, M. tenuis is functionally protandrous. Artificial pollination treatments revealed that M. tenuis is allogamous. The dominant flower visitors were nectar-seeking drones of the bumblebee species Bombus ardens (Apidae). The drones' behaviour, pollen attachment on their bodies and fruit set of visit-restricted flowers suggest that they are the only agent triggering the explosive pollen release mechanism, and are the main pollinator of M. tenuis. The finding that bumblebee workers rarely visit these flowers suggests that the explosive pollen release has another function, namely to discourage pollen-harvesting bumblebee workers. © 2018 German Society for Plant Sciences and The Royal Botanical Society of the Netherlands.

Viscoelastic Fracturing As a Migration and Expulsion Mechanism for Hydrocarbons in Shales: Analog Experiments

NASA Astrophysics Data System (ADS)

Van Damme, H.

2014-12-01

We report the results of simple laboratory experiments aimed at mimicking the generation, migration, and expulsion process of oil or gas from soft clayey sediments, triggered by thermal decomposition of organic matter. In previously published work, we showed that the injection of fluids into a soft sediment layer confined within a quasi-2D Hele-Shaw cell led to the transition from a viscous fingering invasion regime to a viscoelastic fracturing regime. The transition is controlled by the ratio of the characteristic times for the invasion process and for the structural relaxation in the sediment, respectively (Deborah number). Here we show that expulsion is a discontinuous quasi-periodic process, driven by the elastic energy stored in the embedding layers. We report also about two sets of experiments aimed at understanding the conditions in which fluid generation from multiple sources can generate a highly connected network of fractures for expulsion. In a first set of experiments, a Hele-Shaw cell with multiple injection points and multiple outlets was used. It is shown that, due to attractive elastic interactions between cracks, a network spontaneously forms as soon as invasion proceeds in the viscoelastic regime. On the contrary, no network of migration paths is forming in the viscous fingering regime, due to the effective repulsion of the fluid channels. In the second set of analog experiments, we used a thermostated mini-Hele-Shaw cell, the gap of which was filled with a strong clay mud in which microcrystals of reactive organic matter (azoisobutyronitrile, AIBN) are dispersed, or with a mud prepared with clay particles on which the organic matter was pre-impregnated. AIBN decomposes around 70°C, releasing nitrogen gas. It was again observed that, depending on the viscoelastic properties of the clay matrix, gas evolution occurs either by formation and coalescence of bubbles, or by formation of a percolating network of fractures. The length of the fracture network is initially linearly related to the Total (reactive) Organic Matter content. The expulsion process is remarkably effective in the fracturing regime (close to 100 percent), even at vey low TOC (below 0.5 percent). The relevance of these experiments for oil and gas migration in natural conditions will be discussed.

Simulation of stimuli-triggered release of molecular species from halloysite nanotubes

NASA Astrophysics Data System (ADS)

Elumalai, Divya Narayan; Tully, Joshua; Lvov, Yuri; Derosa, Pedro A.

2016-10-01

A Monte Carlo model is used to study the effect of environmental variables (pH and temperature) on the transport and release of dexamethasone molecules from Halloysite Nanotubes (HNTs) in a dielectric fluid medium. The model used for this study was introduced elsewhere and it is based on basic physics interactions without experimental parameters for these interactions. An intermediate phase between the burst and saturation phase is found and explained. Molecules experience a 1-D diffusion process that is different from the diffusion in the burst phase or the surface diffusion experienced by molecules attached to the wall. It is predicted that this phase exists when the molecule-wall interaction is attractive but not always noticeable in the release profile. In this work, it is shown that an agreement with the experiment better than previously reported is obtained when simulated delivery curves are produced by the weighted average of the release profiles from a collection of HNTs with diameters and lengths distributed according to the experimental sample, highlighting the relevance of HNTs' morphology in the release. HNTs are suitable for environment-triggered release and thus the effect of temperature, molecule zeta potential, and pH is studied. It is observed that for temperatures that significantly differ from room temperature (by 100's of degrees), the release profile changes significantly, increasing the delivery speed at high temperature and reducing that speed at low temperature. Finally, it is observed that as the pH becomes more acidic, both the molecule and inner wall surface become more positive (or less negative) with both eventually becoming positive leading to a repulsive interaction; thus, molecules are pushed out by electrostatic repulsion. On the contrary, as the pH becomes more basic, positive molecules become more positive while the wall becomes less negative, but even at pH 12, the wall remains negative and the interaction is attractive. Changes in pH between different regions may act as a trigger for delivery or as a control in the delivery rate.

Smart IR780 Theranostic Nanocarrier for Tumor-Specific Therapy: Hyperthermia-Mediated Bubble-Generating and Folate-Targeted Liposomes.

PubMed

Guo, Fang; Yu, Meng; Wang, Jinping; Tan, Fengping; Li, Nan

2015-09-23

The therapeutic effectiveness of chemotherapy was hampered by dose-limiting toxicity and was optimal only when tumor cells were subjected to a maximum drug exposure. The purpose of this work was to design a dual-functional thermosensitive bubble-generating liposome (BTSL) combined with conjugated targeted ligand (folate, FA) and photothermal agent (IR780), to realize enhanced therapeutic and diagnostic functions. This drug carrier was proposed to target tumor cells owing to FA-specific binding, followed by triggering drug release due to the decomposition of encapsulated ammonium bicarbonate (NH4HCO3) (generated CO2 bubbles) by being subjected to near-infrared (near-IR) laser irradiation, creating permeable defects in the lipid bilayer that rapidly release drug. In vitro temperature-triggered release study indicated the BTSL system was sensitive to heat triggering, resulting in rapid drug release under hyperthermia. For in vitro cellular uptake experiments, different results were observed on human epidermoid carcinoma cells (KB cells) and human lung cancer cells (A549 cells) due to their different (positive or negative) response to FA receptor. Furthermore, in vivo biodistribution analysis and antitumor study indicated IR780-BTSL-FA could specifically target KB tumor cells, exhibiting longer circulation time than free drug. In the pharmacodynamics experiments, IR780-BTSL-FA efficiently inhibited tumor growth in nude mice with no evident side effect to normal tissues and organs. Results of this study demonstrated that the constructed smart theranostic nanocarrier IR780-BTSL-FA might contribute to establishment of tumor-selective and effective chemotherapy.

The release of Doxorubicin from liposomes monitored by MRI and triggered by a combination of US stimuli led to a complete tumor regression in a breast cancer mouse model.

PubMed

Rizzitelli, S; Giustetto, P; Faletto, D; Delli Castelli, D; Aime, S; Terreno, E

2016-05-28

The work aimed at developing a novel MRI-based theranostic protocol for improving the anticancer efficacy of a Doxil-like liposomal formulation. The goal was achieved stimulating the intratumor release of the drug from the nanocarrier and favoring its diffusion in the lesion by the sequential application of low-intensity pulsed ultrasound. The protocol was tested on mice bearing a syngeneic breast cancer model. The combination of acoustic waves with different characteristics allowed for: i) the release of the drug and the co-encapsulated MRI agent (Gadoteridol) from the liposomes in the vessels of the tumor region, and ii) the extravasation of the released material, as well as intact liposomes, in the tumor stroma. The MR-T1 contrast enhancement measured in the tumor reported on the delivery and US-triggered release of Doxorubicin. The developed protocol resulted in a marked increase in the intratumor drug concentration that, in turn, led to the complete regression of the lesion. The protocol has a good clinical translatability because all the components of the theranostic agent (Doxorubicin, liposomes, Gadoteridol) are approved for human use. Copyright © 2016 Elsevier B.V. All rights reserved.

Finger Interdependence: Linking the Kinetic and Kinematic Variables

PubMed Central

Kim, Sun Wook; Shim, Jae Kun; Zatsiorsky, Vladimir M.; Latash, Mark L.

2008-01-01

We studied the dependence between voluntary motion of a finger and pressing forces produced by the tips of other fingers of the hand. Subjects moved one of the fingers (task finger) of the right hand trying to follow a cyclic, ramp-like flexion-extension template at different frequencies. The other fingers (slave fingers) were restricted from moving; their flexion forces were recorded and analyzed. Index finger motion caused the smallest force production by the slave fingers. Larger forces were produced by the neighbors of the task finger; these forces showed strong modulation over the range of motion of the task finger. The enslaved forces were higher during the flexion phase of the movement cycle as compared to the extension phase. The index of enslaving expressed in N/rad was higher when the task finger moved through the more flexed postures. The dependence of enslaving on both range and direction of task finger motion poses problems for methods of analysis of finger coordination based on an assumption of universal matrices of finger inter-dependence. PMID:18255182

Design and preliminary evaluation of the FINGER rehabilitation robot: controlling challenge and quantifying finger individuation during musical computer game play.

PubMed

Taheri, Hossein; Rowe, Justin B; Gardner, David; Chan, Vicki; Gray, Kyle; Bower, Curtis; Reinkensmeyer, David J; Wolbrecht, Eric T

2014-02-04

This paper describes the design and preliminary testing of FINGER (Finger Individuating Grasp Exercise Robot), a device for assisting in finger rehabilitation after neurologic injury. We developed FINGER to assist stroke patients in moving their fingers individually in a naturalistic curling motion while playing a game similar to Guitar Hero. The goal was to make FINGER capable of assisting with motions where precise timing is important. FINGER consists of a pair of stacked single degree-of-freedom 8-bar mechanisms, one for the index and one for the middle finger. Each 8-bar mechanism was designed to control the angle and position of the proximal phalanx and the position of the middle phalanx. Target positions for the mechanism optimization were determined from trajectory data collected from 7 healthy subjects using color-based motion capture. The resulting robotic device was built to accommodate multiple finger sizes and finger-to-finger widths. For initial evaluation, we asked individuals with a stroke (n = 16) and without impairment (n = 4) to play a game similar to Guitar Hero while connected to FINGER. Precision design, low friction bearings, and separate high speed linear actuators allowed FINGER to individually actuate the fingers with a high bandwidth of control (-3 dB at approximately 8 Hz). During the tests, we were able to modulate the subject's success rate at the game by automatically adjusting the controller gains of FINGER. We also used FINGER to measure subjects' effort and finger individuation while playing the game. Test results demonstrate the ability of FINGER to motivate subjects with an engaging game environment that challenges individuated control of the fingers, automatically control assistance levels, and quantify finger individuation after stroke.

Nanocomplexes of Photolabile Polyelectrolyte and Upconversion Nanoparticles for Near-Infrared Light-Triggered Payload Release.

PubMed

Xiang, Jun; Ge, Feijie; Yu, Bing; Yan, Qiang; Shi, Feng; Zhao, Yue

2018-06-07

A new approach to encapsulating charged cargo molecules into a nanovector and subsequently using near-infrared (NIR) light to trigger the release is demonstrated. NIR light-responsive nanovector was prepared through electrostatic interaction-driven complexation between negatively charged silica-coated upconversion nanoparticles (UCNP@silica, 87 nm hydrodynamic diameter, polydispersity index ∼0.05) and a positively charged UV-labile polyelectrolyte bearing pendants of poly(ethylene glycol) and o-nitrobenzyl side groups; whereas charged fluorescein (FLU) was loaded through a co-complexation process. By controlling the amount of polyelectrolyte, UCNP@silica can be covered by the polymer, whereas remaining dispersed in aqueous solution. Under 980 nm laser excitation, UV light emitted by UCNP is absorbed by photolytic side groups within polyelectrolyte, which results in cleavage of o-nitrobenzyl groups and formation of carboxylic acid groups. Such NIR light-induced partial reversal of positive charge to negative charge on the polyelectrolyte layer disrupts the equilibrium among UCNP@silica, polyelectrolyte, and FLU and, consequently, leads to release of FLU molecules.

A gonad-expressed opsin mediates light-induced spawning in the jellyfish Clytia

PubMed Central

Quiroga Artigas, Gonzalo; Lapébie, Pascal; Leclère, Lucas; Takeda, Noriyo; Deguchi, Ryusaku; Jékely, Gáspár

2018-01-01

Across the animal kingdom, environmental light cues are widely involved in regulating gamete release, but the molecular and cellular bases of the photoresponsive mechanisms are poorly understood. In hydrozoan jellyfish, spawning is triggered by dark-light or light-dark transitions acting on the gonad, and is mediated by oocyte maturation-inducing neuropeptide hormones (MIHs) released from the ectoderm. We determined in Clytia hemisphaerica that blue-cyan light triggers spawning in isolated gonads. A candidate opsin (Opsin9) was found co-expressed with MIH within specialised ectodermal cells. Opsin9 knockout jellyfish generated by CRISPR/Cas9 failed to undergo oocyte maturation and spawning, a phenotype reversible by synthetic MIH. Gamete maturation and release in Clytia is thus regulated by gonadal photosensory-neurosecretory cells that secrete MIH in response to light via Opsin9. Similar cells in ancestral eumetazoans may have allowed tissue-level photo-regulation of diverse behaviours, a feature elaborated in cnidarians in parallel with expansion of the opsin gene family. PMID:29303477

Spontaneous activity of cochlear hair cells triggered by fluid secretion mechanism in adjacent support cells

PubMed Central

Wang, Han Chin; Lin, Chun-Chieh; Cheung, Rocky; Zhang-Hooks, YingXin; Agarwal, Amit; Ellis-Davies, Graham; Rock, Jason; Bergles, Dwight E.

2015-01-01

Summary Spontaneous electrical activity of neurons in developing sensory systems promotes their maturation and proper connectivity. In the auditory system, spontaneous activity of cochlear inner hair cells (IHCs) is initiated by the release of ATP from glia-like inner supporting cells (ISCs), facilitating maturation of central pathways before hearing onset. Here, we find that ATP stimulates purinergic autoreceptors in ISCs, triggering Cl− efflux and osmotic cell shrinkage by opening TMEM16A Ca2+-activated Cl− channels. Release of Cl− from ISCs also forces K+ efflux, causing transient depolarization of IHCs near ATP release sites. Genetic deletion of TMEM16A markedly reduces the spontaneous activity of IHCs and spiral ganglion neurons in the developing cochlea, and prevents ATP-dependent shrinkage of supporting cells. These results indicate that support cells in the developing cochlea have adapted a pathway used for fluid secretion in other organs to induce periodic excitation of hair cells. PMID:26627734

Magnetically triggered dual functional nanoparticles for resistance-free apoptotic hyperthermia.

PubMed

Yoo, Dongwon; Jeong, Heeyeong; Noh, Seung-Hyun; Lee, Jae-Hyun; Cheon, Jinwoo

2013-12-02

Overcoming resistance: Heat-treated cancer cells possess a protective mechanism for resistance and survival. Resistance-free apoptosis-inducing magnetic nanoparticles (RAINs) successfully promote hyperthermic apoptosis, obstructing cell survival by triggering two functional units of heat generation and the release of geldanamycin (GM) for heat shock protein (Hsp) inhibition under an alternating magnetic field (AMF). Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Fish in hot water: hypoxaemia does not trigger catecholamine mobilization during heat shock in rainbow trout (Oncorhynchus mykiss).

PubMed

Currie, S; Ahmady, E; Watters, M A; Perry, S F; Gilmour, K M

2013-06-01

Rainbow trout (Oncorhynchus mykiss) exposed to an acute heat shock (1 h at 25 °C after raising water temperature from 13 °C to 25 °C over 4 h) mount a significant catecholamine response. The present study investigated the proximate mechanisms underlying catecholamine mobilization. Trout exposed to heat shock in vivo exhibited a significant reduction in arterial O(2) tension, but arterial O(2) concentration was not affected by heat shock, nor was catecholamine release during heat shock prevented by prior and concomitant exposure to hyperoxia (to prevent the fall in arterial O(2) tension). Thus, catecholamine mobilization probably was not triggered by impaired blood O(2) transport. Heat-shocked trout also exhibited an elevation of arterial CO(2) tension coupled with a fall in arterial pH, but these factors are not expected to trigger catecholamine release. The changes in blood O(2) and CO(2) tension occurred despite a significant hyperventilatory response to heat shock. Future studies should investigate whether catecholamine mobilization during heat shock in rainbow trout is triggered by a specific effect of high temperature activating the sympathetic nervous system via a thermosensitive transient receptor potential channel. Copyright © 2013 Elsevier Inc. All rights reserved.

Internal and External Triggering Mechanism of "Smart" Nanoparticle-Based DDSs in Targeted Tumor Therapy.

PubMed

Qiana, Xian-Ling; Li, Jun; Wei, Ran; Lin, Hui; Xiong, Li-Xia

2018-05-09

Anticancer chemotherapeutics have a lot of problems via conventional drug delivery systems (DDSs), including non-specificity, burst release, severe side-effects, and damage to normal cells. Owing to its potential to circumventing these problems, nanotechnology has gained increasing attention in targeted tumor therapy. Chemotherapeutic drugs or genes encapsulated in nanoparticles could be used to target therapies to the tumor site in three ways: "passive", "active", and "smart" targeting. To summarize the mechanisms of various internal and external "smart" stimulating factors on the basis of findings from in vivo and in vitro studies. A thorough search of PubMed was conducted in order to identify the majority of trials, studies and novel articles related to the subject. Activated by internal triggering factors (pH, redox, enzyme, hypoxia, etc.) or external triggering factors (temperature, light of different wavelengths, ultrasound, magnetic fields, etc.), "smart" DDSs exhibit targeted delivery to the tumor site, and controlled release of chemotherapeutic drugs or genes. In this review article, we summarize and classify the internal and external triggering mechanism of "smart" nanoparticle-based DDSs in targeted tumor therapy, and the most recent research advances are illustrated for better understanding. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Target-triggering multiple-cycle signal amplification strategy for ultrasensitive detection of DNA based on QCM and SPR.

PubMed

Song, Weiling; Yin, Wenshuo; Sun, Wenbo; Guo, Xiaoyan; He, Peng; Yang, Xiaoyan; Zhang, Xiaoru

2018-04-24

Detection of ultralow concentrations of nucleic acid sequences is a central challenge in the early diagnosis of genetic diseases. Herein, we developed a target-triggering cascade multiple cycle amplification for ultrasensitive DNA detection using quartz crystal microbalance (QCM) and surface plasmon resonance (SPR). It was based on the exonuclease Ⅲ (Exo Ⅲ)-assisted signal amplification and the hybridization chain reaction (HCR). The streptavidin-coated Au-NPs (Au-NPs-SA) were assembled on the HCR products as recognition element. Upon sensing of target DNA, the duplex DNA probe triggered the Exo Ⅲ cleavage process, accompanied by generating a new secondary target DNA and releasing target DNA. The released target DNA and the secondary target DNA were recycled. Simultaneously, numerous single strands were liberated and acted as the trigger of HCR to generate further signal amplification, resulting in the immobilization of abundant Au-NPs-SA on the gold substrate. The QCM sensor results were found to be comparable to that achieved using a SPR sensor platform. This method exhibited a high sensitivity toward target DNA with a detection limit of 0.70 fM. The high sensitivity and specificity make this method a great potential for detecting DNA with trace amounts in bioanalysis and clinical biomedicine. Copyright © 2018 Elsevier Inc. All rights reserved.

Butyric acid released during milk lipolysis triggers biofilm formation of Bacillus species.

PubMed

Pasvolsky, Ronit; Zakin, Varda; Ostrova, Ievgeniia; Shemesh, Moshe

2014-07-02

Bacillus species form biofilms within milking pipelines and on surfaces of equipment in the dairy industry which represent a continuous hygiene problem and can lead to serious economic losses due to food spoilage and equipment impairment. Although much is known about the mechanism by which the model organism Bacillus subtilis forms biofilms in laboratory mediums in vitro, little is known of how these biofilms are formed in natural environments such as milk. Besides, little is known of the signaling pathways leading to biofilm formation in other Bacillus species, such as Bacillus cereus and Bacillus licheniformis, both of which are known to contaminate milk. In this study, we report that milk triggers the formation of biofilm-related structures, termed bundles. We show this to be a conserved phenomenon among all Bacillus members tested. Moreover, we demonstrate that the tasA gene, which encodes a major portion of the matrix which holds the biofilm together, is vital for this process. Furthermore, we show that the free fatty acid (FFA) - butyric acid (BA), which is released during lipolysis of milk fat and demonstrates antimicrobial activity, is the potent trigger for biofilm bundle formation. We finally show that BA-triggered biofilm bundle formation is mediated by the histidine kinase, KinD. Taken together, these observations indicate that BA, which is a major FFA within milk triggers biofilm formation in a conserved mechanism among members of the Bacillus genus. Copyright © 2014 Elsevier B.V. All rights reserved.

Integration of tactile input across fingers in a patient with finger agnosia.

PubMed

Anema, Helen A; Overvliet, Krista E; Smeets, Jeroen B J; Brenner, Eli; Dijkerman, H Chris

2011-01-01

Finger agnosia has been described as an inability to explicitly individuate between the fingers, which is possibly due to fused neural representations of these fingers. Hence, are patients with finger agnosia unable to keep tactile information perceived over several fingers separate? Here, we tested a finger agnosic patient (GO) on two tasks that measured the ability to keep tactile information simultaneously perceived by individual fingers separate. In experiment 1 GO performed a haptic search task, in which a target (the absence of a protruded line) needed to be identified among distracters (protruded lines). The lines were presented simultaneously to the fingertips of both hands. Similarly to the controls, her reaction time decreased when her fingers were aligned as compared to when her fingers were stretched and in an unaligned position. This suggests that she can keep tactile input from different fingers separate. In experiment two, GO was required to judge the position of a target tactile stimulus to the index finger, relatively to a reference tactile stimulus to the middle finger, both in fingers uncrossed and crossed position. GO was able to indicate the relative position of the target stimulus as well as healthy controls, which indicates that she was able to keep tactile information perceived by two neighbouring fingers separate. Interestingly, GO performed better as compared to the healthy controls in the finger crossed condition. Together, these results suggest the GO is able to implicitly distinguish between tactile information perceived by multiple fingers. We therefore conclude that finger agnosia is not caused by minor disruptions of low-level somatosensory processing. These findings further underpin the idea of a selective impaired higher order body representation restricted to the fingers as underlying cause of finger agnosia. Copyright © 2010 Elsevier Ltd. All rights reserved.

Repetition priming of motor activity mediated by a central pattern generator: the importance of extrinsic vs. intrinsic program initiators

PubMed Central

Siniscalchi, Michael J.; Jing, Jian; Weiss, Klaudiusz R.

2016-01-01

Repetition priming is characterized by increased performance as a behavior is repeated. Although this phenomenon is ubiquitous, mediating mechanisms are poorly understood. We address this issue in a model system, the feeding network of Aplysia. This network generates both ingestive and egestive motor programs. Previous data suggest a chemical coding model: ingestive and egestive inputs to the feeding central pattern generator (CPG) release different modulators, which act via different second messengers to prime motor activity in different ways. The ingestive input to the CPG (neuron CBI-2) releases the peptides feeding circuit activating peptide and cerebral peptide 2, which produce an ingestive pattern of activity. The egestive input to the CPG (the esophageal nerve) releases the peptide small cardioactive peptide. This model is based on research that focused on a single aspect of motor control (radula opening). Here we ask whether repetition priming is observed if activity is triggered with a neuron within the core CPG itself and demonstrate that it is not. Moreover, previous studies demonstrated that effects of modulatory neurotransmitters that induce repetition priming persist. This suggests that it should be possible to “prime” motor programs triggered from within the CPG by first stimulating extrinsic modulatory inputs. We demonstrate that programs triggered after ingestive input activation are ingestive and programs triggered after egestive input activation are egestive. We ask where this priming occurs and demonstrate modifications within the CPG itself. This arrangement is likely to have important consequences for “task” switching, i.e., the cessation of one type of motor activity and the initiation of another. PMID:27466134

Limaprost alfadex improves myelopathy symptoms in patients with cervical spinal canal stenosis.

PubMed

Sugawara, Taku; Hirano, Yoshitaka; Higashiyama, Naoki; Mizoi, Kazuo

2009-03-15

Myelopathy symptoms were prospectively studied in patients with cervical spinal canal stenosis (CSCS), using objective grading systems and stabilometry, to examine the effect of administration of prostaglandin E1 derivative limaprost alfadex (limaprost). Myelopathy scores/grades and stabilometry parameters were evaluated before, and 1 and 3 months after starting the limaprost treatment. Limaprost is a potent vasodilator and antiplatelet agent and has been used to treat the symptoms of lumbar spinal canal stenosis. The action presumably involves increased blood flow in the compressed cauda equina. Limaprost can also increase blood flow in the compressed spinal cord, but effects on myelopathy symptoms in patients with CSCS have not been established. This study examined 21 patients with mild spondylotic CSCS based on neurologic findings and compression of the cervical spinal cord on magnetic resonance imaging. Japanese Orthopedic Association score, grip and release test, and finger escape sign were measured, and stabilometry was performed by independent examiners, before, and 1 and 3 months after starting the oral limaprost treatment. Most patients experienced amelioration of the symptoms at 1 month after starting the treatment. Mean Japanese Orthopedic Association score and grip and release count were significantly improved and finger escape sign grade was higher in some patients. Stabilometry area with eyes closed and Romberg rate were also significantly improved. These improvements were maintained at 3 months. The efficacy of oral limaprost administration for patients with CSCS was confirmed by objective scoring and quantitative data.

The outer mitochondrial membrane protein mitoNEET contains a novel redox-active 2Fe-2S cluster.

PubMed

Wiley, Sandra E; Paddock, Mark L; Abresch, Edward C; Gross, Larry; van der Geer, Peter; Nechushtai, Rachel; Murphy, Anne N; Jennings, Patricia A; Dixon, Jack E

2007-08-17

The outer mitochondrial membrane protein mitoNEET was discovered as a binding target of pioglitazone, an insulin-sensitizing drug of the thiazolidinedione class used to treat type 2 diabetes (Colca, J. R., McDonald, W. G., Waldon, D. J., Leone, J. W., Lull, J. M., Bannow, C. A., Lund, E. T., and Mathews, W. R. (2004) Am. J. Physiol. 286, E252-E260). We have shown that mitoNEET is a member of a small family of proteins containing a 39-amino-acid CDGSH domain. Although the CDGSH domain is annotated as a zinc finger motif, mitoNEET was shown to contain iron (Wiley, S. E., Murphy, A. N., Ross, S. A., van der Geer, P., and Dixon, J. E. (2007) Proc. Natl. Acad. Sci. U. S. A. 104, 5318-5323). Optical and electron paramagnetic resonance spectroscopy showed that it contained a redox-active pH-labile Fe-S cluster. Mass spectrometry showed the loss of 2Fe and 2S upon cofactor extrusion. Spectroscopic studies of recombinant proteins showed that the 2Fe-2S cluster was coordinated by Cys-3 and His-1. The His ligand was shown to be involved in the observed pH lability of the cluster, indicating that loss of this ligand via protonation triggered release of the cluster. mitoNEET is the first identified 2Fe-2S-containing protein located in the outer mitochondrial membrane. Based on the biophysical data and domain fusion analysis, mitoNEET may function in Fe-S cluster shuttling and/or in redox reactions.

SNT-1 functions as the Ca2+ sensor for tonic and evoked neurotransmitter release in C. elegans.

PubMed

Li, Lei; Liu, Haowen; Wang, Wei; Chandra, Mintu; Collins, Brett M; Hu, Zhitao

2018-05-14

Synaptotagmin-1 (Syt1) binds Ca 2+ through its tandem C2 domains (C2A and C2B) and triggers Ca 2+ -dependent neurotransmitter release. Here we show that snt-1 , the homolog of mammalian Syt1, functions as the Ca 2+ sensor for both tonic and evoked neurotransmitter release at the C. elegans neuromuscular junction. Mutations that disrupt Ca 2+ binding in double C2 domains of SNT-1 significantly impaired tonic release, whereas disrupting Ca 2+ binding in a single C2 domain had no effect, indicating that the Ca 2+ binding of the two C2 domains is functionally redundant for tonic release. Stimulus-evoked release was significantly reduced in snt-1 mutants, with prolonged release latency as well as faster rise and decay kinetics. Unlike tonic release, evoked release was triggered by Ca 2+ binding solely to the C2B domain. Moreover, we showed that SNT-1 plays an essential role in the priming process in different subpopulations of synaptic vesicles with tight or loose coupling to Ca 2+ entry. SIGNIFICANCE STATEMENT We showed that SNT-1 in C. elegans regulates evoked neurotransmitter release through Ca 2+ binding to its C2B domain, a similar way to Syt1 in the mouse CNS and the fly NMJ. However, the largely decreased tonic release in snt-1 mutants argues SNT-1 has a clamping function. Indeed, Ca 2+ -binding mutations in the C2 domains in SNT-1 significantly reduced the frequency of the miniature excitatory postsynaptic current (mEPSC), indicating that SNT-1 also acts as a Ca 2+ sensor for tonic release. Therefore, revealing the differential mechanisms between invertebrates and vertebrates will provide significant insights into our understanding how synaptic vesicle fusion is regulated. Copyright © 2018 the authors.

Status-Relevant Experiences and Conspicuous Consumption - the Moderating Role of Prenatal Androgen Exposure.

PubMed

Cornelissen, Gert; Palacios-Fenech, Javier

2016-09-20

In this paper we study consumers' interest in acquiring and displaying expensive luxury products. Based on recent insights in consumer psychology, which build on developments in evolutionary biology, we consider luxury products as "costly signals": wasteful and costly goods, whose purpose is to communicate one's biological fitness, and social status, to others. In line with previous research, we show that experiences that trigger mate attraction goals (Study 1: Exposure to others in bathing outfit) or status display goals (Study 2: Experiencing a vicarious victory of one's favorite sports team) can increase people's interest in luxury products. However, we demonstrate that some individuals are predictably more responsive to those experiences than others. We used a physiological measure (the proportion of the length of the index finger and ring finger of the right hand, 2D:4D) as a proxy for individual differences in exposure to prenatal androgens (i.e., testosterone). This measure has been related to dominant and competitive behavior later in life. We predict and find that individuals with a low 2D:4D (i.e., high exposure to prenatal androgens) were more responsive to the status-relevant experiences: they became more interested in luxury goods after these experiences. This was not the case for high 2D:4D individuals.

Psychomotor Impairment Detection via Finger Interactions with a Computer Keyboard During Natural Typing

NASA Astrophysics Data System (ADS)

Giancardo, L.; Sánchez-Ferro, A.; Butterworth, I.; Mendoza, C. S.; Hooker, J. M.

2015-04-01

Modern digital devices and appliances are capable of monitoring the timing of button presses, or finger interactions in general, with a sub-millisecond accuracy. However, the massive amount of high resolution temporal information that these devices could collect is currently being discarded. Multiple studies have shown that the act of pressing a button triggers well defined brain areas which are known to be affected by motor-compromised conditions. In this study, we demonstrate that the daily interaction with a computer keyboard can be employed as means to observe and potentially quantify psychomotor impairment. We induced a psychomotor impairment via a sleep inertia paradigm in 14 healthy subjects, which is detected by our classifier with an Area Under the ROC Curve (AUC) of 0.93/0.91. The detection relies on novel features derived from key-hold times acquired on standard computer keyboards during an uncontrolled typing task. These features correlate with the progression to psychomotor impairment (p < 0.001) regardless of the content and language of the text typed, and perform consistently with different keyboards. The ability to acquire longitudinal measurements of subtle motor changes from a digital device without altering its functionality may allow for early screening and follow-up of motor-compromised neurodegenerative conditions, psychological disorders or intoxication at a negligible cost in the general population.

Fliposomes: pH-triggered conformational flip of new trans-2-aminocyclohexanol-based amphiphiles causes instant cargo release in liposomes.

PubMed

Liu, Xin; Zheng, Yu; Samoshina, Nataliya M; Franz, Andreas H; Guo, Xin; Samoshin, Vyacheslav V

2012-12-01

A new type of pH-sensitive liposomes (fliposomes) was designed based on the amphiphiles that are able to perform a pH-triggered conformational flip (flipids). This flip disrupts the liposome membrane and causes rapid release of the liposome cargo, specifically in response to lowered pH. The flipids (1) and (2) are equipped with a trans-2-aminocyclohexanol conformational switch. pH-sensitive fliposomes containing one or both of these flipids, as well as POPC and PEG ceramide, were constructed and characterized. These compositions were stable at 4°C and pH 7.4 for several months. Fliposomes loaded with ANTS/DPX performed an unusually quick content release within a few seconds at pH below 8.5 (in case of 2) and 6.0 (in case of 1). This difference in pH sensitivity demonstrates a potential for the custom design of flipids by variation of the amino group to target areas with specific pH values. The pH titration curves for the fliposome leakage parallel the curves for the acid-induced conformational flip of 1 and 2 studied by ¹H NMR. A plausible mechanism of pH sensitivity starts with an acid-triggered conformational flip of 1 or 2, which changes the molecular size and shape, shortens the lipid tails, and perturbs the liposome membrane, resulting in the content leakage.

Synaptically released zinc triggers metabotropic signaling via a zinc-sensing receptor in the hippocampus.

PubMed

Besser, Limor; Chorin, Ehud; Sekler, Israel; Silverman, William F; Atkin, Stan; Russell, James T; Hershfinkel, Michal

2009-03-04

Zn(2+) is coreleased with glutamate from mossy fiber terminals and can influence synaptic function. Here, we demonstrate that synaptically released Zn(2+) activates a selective postsynaptic Zn(2+)-sensing receptor (ZnR) in the CA3 region of the hippocampus. ZnR activation induced intracellular release of Ca(2+), as well as phosphorylation of extracellular-regulated kinase and Ca(2+)/calmodulin kinase II. Blockade of synaptic transmission by tetrodotoxin or CdCl inhibited the ZnR-mediated Ca(2+) rises. The responses mediated by ZnR were largely attenuated by the extracellular Zn(2+) chelator, CaEDTA, and in slices from mice lacking vesicular Zn(2+), suggesting that synaptically released Zn(2+) triggers the metabotropic activity. Knockdown of the expression of the orphan G-protein-coupled receptor 39 (GPR39) attenuated ZnR activity in a neuronal cell line. Importantly, we observed widespread GPR39 labeling in CA3 neurons, suggesting a role for this receptor in mediating ZnR signaling in the hippocampus. Our results describe a unique role for synaptic Zn(2+) acting as the physiological ligand of a metabotropic receptor and provide a novel pathway by which synaptic Zn(2+) can regulate neuronal function.

Caprine Monocytes Release Extracellular Traps against Neospora caninum In Vitro

PubMed Central

Yang, Zhengtao; Wei, Zhengkai; Hermosilla, Carlos; Taubert, Anja; He, Xuexiu; Wang, Xiaocen; Gong, Pengtao; Li, Jianhua; Zhang, Xichen

2018-01-01

Neospora caninum is an obligate intracellular apicomplexan parasite that causes reproductive loss and severe economic losses in dairy and goat industry. In the present study, we aim to investigate the effects of N. caninum tachyzoites on the release of extracellular traps (ETs) in caprine monocytes and furthermore elucidated parts of its molecular mechanisms. N. caninum tachyzoite-induced monocytes-derived ETs formation was detected by scanning electron microscopy. H3 and myeloperoxidase (MPO) within monocyte-ETs structures were examined using laser scanning confocal microscopy analyses. The results showed that N. caninum tachyzoites were not only able to trigger ETs formation in caprine monocytes, but also that monocyte-released ETs were capable of entrapping viable tachyzoites. Histones and MPO were found to be decorating the DNA within the monocytes derived-ETs structures thus proving the classical components of ETs. Furthermore, inhibitors of NADPH oxidase-, MPO-, ERK 1/2-, or p38 MAPK-signaling pathway significantly decreased N. caninum tachyzoite-triggered caprine monocyte-derived ETosis. This is the first report of ETs release extruded from caprine monocytes after N. caninum exposure and thus showing that this early innate immune effector mechanism might be relevant during the acute phase of caprine neosporosis. PMID:29403487

Minocycline attenuates both OGD-induced HMGB1 release and HMGB1-induced cell death in ischemic neuronal injury in PC12 cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kikuchi, Kiyoshi; Department of Neurosurgery, Omuta City General Hospital, 2-19-1 Takarazaka, Omuta-City, Fukuoka 836-8567; Kawahara, Ko-ichi

2009-07-24

High mobility group box-1 (HMGB1), a non-histone DNA-binding protein, is massively released into the extracellular space from neuronal cells after ischemic insult and exacerbates brain tissue damage in rats. Minocycline is a semisynthetic second-generation tetracycline antibiotic which has recently been shown to be a promising neuroprotective agent. In this study, we found that minocycline inhibited HMGB1 release in oxygen-glucose deprivation (OGD)-treated PC12 cells and triggered the activation of p38mitogen-activated protein kinase (MAPK) and extracellular signal-regulated kinases (ERK1/2). The ERK kinase (MEK)1/2 inhibitor U-0126 and p38MAPK inhibitor SB203580 blocked HMGB1 release in response to OGD. Furthermore, HMGB1 triggered cell death inmore » a dose-dependent fashion. Minocycline significantly rescued HMGB1-induced cell death in a dose-dependent manner. In light of recent observations as well as the good safety profile of minocycline in humans, we propose that minocycline might play a potent neuroprotective role through the inhibition of HMGB1-induced neuronal cell death in cerebral infarction.« less

Design and preliminary evaluation of the FINGER rehabilitation robot: controlling challenge and quantifying finger individuation during musical computer game play

PubMed Central

2014-01-01

Background This paper describes the design and preliminary testing of FINGER (Finger Individuating Grasp Exercise Robot), a device for assisting in finger rehabilitation after neurologic injury. We developed FINGER to assist stroke patients in moving their fingers individually in a naturalistic curling motion while playing a game similar to Guitar Hero®a. The goal was to make FINGER capable of assisting with motions where precise timing is important. Methods FINGER consists of a pair of stacked single degree-of-freedom 8-bar mechanisms, one for the index and one for the middle finger. Each 8-bar mechanism was designed to control the angle and position of the proximal phalanx and the position of the middle phalanx. Target positions for the mechanism optimization were determined from trajectory data collected from 7 healthy subjects using color-based motion capture. The resulting robotic device was built to accommodate multiple finger sizes and finger-to-finger widths. For initial evaluation, we asked individuals with a stroke (n = 16) and without impairment (n = 4) to play a game similar to Guitar Hero® while connected to FINGER. Results Precision design, low friction bearings, and separate high speed linear actuators allowed FINGER to individually actuate the fingers with a high bandwidth of control (−3 dB at approximately 8 Hz). During the tests, we were able to modulate the subject’s success rate at the game by automatically adjusting the controller gains of FINGER. We also used FINGER to measure subjects’ effort and finger individuation while playing the game. Conclusions Test results demonstrate the ability of FINGER to motivate subjects with an engaging game environment that challenges individuated control of the fingers, automatically control assistance levels, and quantify finger individuation after stroke. PMID:24495432

Development of cylindrical-type finger force measuring system using force sensors and its characteristics evaluation

NASA Astrophysics Data System (ADS)

Kim, Hyeon-Min; Yoon, Joungwon; Shin, Hee-Suk; Kim, Gab-Soon

2012-02-01

Some patients cannot use their hands because of the paralysis of their fingers. Their fingers can recover with rehabilitative training, and the extent of rehabilitation can be judged by grasping a cylindrical-object with their fingers. At present, the cylindrical-object used in hospitals is only a plastic cylinder, which cannot measure grasping force of the fingers. Therefore, doctors must judge the extent of rehabilitation by watching patients' fingers as they grasp the plastic cylinder. In this paper, the development of two cylindrical-type finger force measuring systems with four force sensors for left hand and right hand were developed. The developed finger force measuring system can measure the grasping force of patients' each finger (forefinger, middle finger, ring finger and little finger), and the measured results could be used to judge the rehabilitation extent of a finger patient. The grasping force tests of men and women were performed using the developed cylindrical-type finger force measuring systems. The tests confirm that the average finger forces of right hand and left hand for men were about 194 N and 179 N, and for women, 108 N and 95 N.

Intracellular energy depletion triggers programmed cell death during petal senescence in tulip.

PubMed

Azad, A K; Ishikawa, Takayuki; Ishikawa, Takahiro; Sawa, Y; Shibata, H

2008-01-01

Programmed cell death (PCD) in petals provides a model system to study the molecular aspects of organ senescence. In this study, the very early triggering signal for PCD during the senescence process from young green buds to 14-d-old petals of Tulipa gesneriana was determined. The opening and closing movement of petals of intact plants increased for the first 3 d and then gradually decreased. DNA degradation and cytochrome c (Cyt c) release were clearly observed in 6-d-old flowers. Oxidative stress or ethylene production can be excluded as the early signal for petal PCD. In contrast, ATP was dramatically depleted after the first day of flower opening. Sucrose supplementation to cut flowers maintained their ATP levels and the movement ability for a longer time than in those kept in water. The onset of DNA degradation, Cyt c release, and petal senescence was also delayed by sucrose supplementation to cut flowers. These results suggest that intracellular energy depletion, rather than oxidative stress or ethylene production, may be the very early signal to trigger PCD in tulip petals.

Intracellular energy depletion triggers programmed cell death during petal senescence in tulip

PubMed Central

Azad, A. K.; Ishikawa, Takayuki; Ishikawa, Takahiro; Shibata, H.

2008-01-01

Programmed cell death (PCD) in petals provides a model system to study the molecular aspects of organ senescence. In this study, the very early triggering signal for PCD during the senescence process from young green buds to 14-d-old petals of Tulipa gesneriana was determined. The opening and closing movement of petals of intact plants increased for the first 3 d and then gradually decreased. DNA degradation and cytochrome c (Cyt c) release were clearly observed in 6-d-old flowers. Oxidative stress or ethylene production can be excluded as the early signal for petal PCD. In contrast, ATP was dramatically depleted after the first day of flower opening. Sucrose supplementation to cut flowers maintained their ATP levels and the movement ability for a longer time than in those kept in water. The onset of DNA degradation, Cyt c release, and petal senescence was also delayed by sucrose supplementation to cut flowers. These results suggest that intracellular energy depletion, rather than oxidative stress or ethylene production, may be the very early signal to trigger PCD in tulip petals. PMID:18515833

Smart nanoparticles as targeting platforms for HIV infections

NASA Astrophysics Data System (ADS)

Adhikary, Rishi Rajat; More, Prachi; Banerjee, Rinti

2015-04-01

While Human Immunodeficiency Virus (HIV) infections are reducing in incidence with the advent of Highly Active Anti-retroviral Therapy (HAART), there remain a number of challenges including the existence of reservoirs, drug resistance and anatomical barriers to antiretroviral therapy. To overcome these, smart nanoparticles with stimuli responsive release are proposed for delivery of anti-retroviral agents. The paper highlights the strategic similarities between the design of smart antiretroviral nanocarriers and those optimized for cancer chemotherapy. This includes the development of nanoparticles capable of passive and active targeting as well as those that are responsive to various internal and external triggers. For antiretroviral therapy, the relevant triggers for stimuli responsive release of drugs include semen, enzymes, endosomal escape, temperature and magnetic field. Deriving from the experience of cancer chemotherapy, additional potential triggers are light and ultrasound which remain hitherto unexplored in HIV therapy. In addition, the roles of nanomicrobicides (nanogels) and virus mimetic nanoparticles are discussed from the point of view of prevention of HIV transmission. The challenges associated with translation of smart nanoparticles for HIV infections to realize the Millennium Development Goal of combating HIV infections are discussed.

Smart nanoparticles as targeting platforms for HIV infections.

PubMed

Adhikary, Rishi Rajat; More, Prachi; Banerjee, Rinti

2015-05-07

While Human Immunodeficiency Virus (HIV) infections are reducing in incidence with the advent of Highly Active Anti-retroviral Therapy (HAART), there remain a number of challenges including the existence of reservoirs, drug resistance and anatomical barriers to antiretroviral therapy. To overcome these, smart nanoparticles with stimuli responsive release are proposed for delivery of anti-retroviral agents. The paper highlights the strategic similarities between the design of smart antiretroviral nanocarriers and those optimized for cancer chemotherapy. This includes the development of nanoparticles capable of passive and active targeting as well as those that are responsive to various internal and external triggers. For antiretroviral therapy, the relevant triggers for stimuli responsive release of drugs include semen, enzymes, endosomal escape, temperature and magnetic field. Deriving from the experience of cancer chemotherapy, additional potential triggers are light and ultrasound which remain hitherto unexplored in HIV therapy. In addition, the roles of nanomicrobicides (nanogels) and virus mimetic nanoparticles are discussed from the point of view of prevention of HIV transmission. The challenges associated with translation of smart nanoparticles for HIV infections to realize the Millennium Development Goal of combating HIV infections are discussed.

Ultrasound-enhanced localized chemotherapy of drug-sensitive and multidrug resistant tumors

NASA Astrophysics Data System (ADS)

Rapoport, Natalya Y.; Gao, Zhonggao; Kamaev, Pavel; Christensen, Douglas A.

2006-05-01

A new modality of targeted tumor chemotherapy is based on the drug encapsulation in polymeric nanoparticles followed by a localized release at the tumor site triggered by focused ultrasound. Effect of 1 MHz and 3 MHz unfocused ultrasound applied locally to the tumor on the Doxorubicin (DOX) biodistribution and tumor growth rates was measured for ovarian carcinoma tumors in nu/nu mice. The bioeffects of ultrasound were investigated on the systemic and cellular levels. Growth rates of A2780 ovarian carcinoma tumors were substantially reduced by combining micellar drug delivery with tumor irradiation. Ultrasound effect was not thermal as manifested by intratumoral temperature measurements during sonication. Biodistribution studies showed that ultrasound did not enhance micelle extravasation. Main mechanisms of the ultrasound-enhanced chemotherapy included (i) passive targeting of drug-loaded micelles to the tumor interstitium; (ii) ultrasound-triggered localized drug release from micelles in the tumor volume; (iii) enhanced micelle and drug diffusion through the tumor interstitium; and (iv) ultrasound-triggered cell membrane damage resulting in the enhanced micelle and drug uptake by tumor cells.

Polymeric micelles with stimuli-triggering systems for advanced cancer drug targeting.

PubMed

Nakayama, Masamichi; Akimoto, Jun; Okano, Teruo

2014-08-01

Since the 1990s, nanoscale drug carriers have played a pivotal role in cancer chemotherapy, acting through passive drug delivery mechanisms and subsequent pharmaceutical action at tumor tissues with reduction of adverse effects. Polymeric micelles, as supramolecular assemblies of amphiphilic polymers, have been considerably developed as promising drug carrier candidates, and a number of clinical studies of anticancer drug-loaded polymeric micelle carriers for cancer chemotherapy applications are now in progress. However, these systems still face several issues; at present, the simultaneous control of target-selective delivery and release of incorporated drugs remains difficult. To resolve these points, the introduction of stimuli-responsive mechanisms to drug carrier systems is believed to be a promising approach to provide better solutions for future tumor drug targeting strategies. As possible trigger signals, biological acidic pH, light, heating/cooling and ultrasound actively play significant roles in signal-triggering drug release and carrier interaction with target cells. This review article summarizes several molecular designs for stimuli-responsive polymeric micelles in response to variation of pH, light and temperature and discusses their potentials as next-generation tumor drug targeting systems.

Modification of Silicone Elastomer Surfaces with Zwitterionic Polymers: Short-Term Fouling Resistance and Triggered Biofouling Release.

PubMed

Shivapooja, Phanindhar; Yu, Qian; Orihuela, Beatriz; Mays, Robin; Rittschof, Daniel; Genzer, Jan; López, Gabriel P

2015-11-25

We present a method for dual-mode-management of biofouling by modifying surface of silicone elastomers with zwitterionic polymeric grafts. Poly(sulfobetaine methacrylate) was grafted from poly(vinylmethylsiloxane) elastomer substrates using thiol-ene click chemistry and surface-initiated, controlled radical polymerization. These surfaces exhibited both fouling resistance and triggered fouling-release functionality. The zwitterionic polymers exhibited fouling resistance over short-term (∼hours) exposure to bacteria and barnacle cyprids. The biofilms that eventually accumulated over prolonged-exposure (∼days) were easily detached by applying mechanical strain to the elastomer substrate. Such dual-functional surfaces may be useful in developing environmentally and biologically friendly coatings for biofouling management on marine, industrial, and biomedical equipment because they can obviate the use of toxic compounds.

Enzyme-activated intracellular drug delivery with tubule clay nanoformulation

DOE PAGES

Dzamukova, Maria R.; Naumenko, Ekaterina A.; Lvov, Yuri M.; ...

2015-05-15

Fabrication of stimuli-triggered drug delivery vehicle is is an important milestone in treating cancer. Here we demonstrate the selective anticancer drug delivery into human cells with biocompatible 50-nm diameter halloysite nanotube carriers. Physically-adsorbed dextrin end stoppers secure the intercellular release of brilliant green. Drug-loaded nanotubes penetrate through the cellular membranes and their uptake efficiency depends on the cells growth rate. Intercellular glycosyl hydrolases-mediated decomposition of the dextrin tube-end stoppers triggers the release of the lumen-loaded brilliant green, which allowed for preferable elimination of human lung carcinoma cells (А549) as compared with hepatoma cells (Hep3b). In conclusion, the enzyme-activated intracellular deliverymore » of brilliant green using dextrin-coated halloysite nanotubes is a promising platform for anticancer treatment.« less

An estimation of finger-tapping rates and load capacities and the effects of various factors.

PubMed

Ekşioğlu, Mahmut; İşeri, Ali

2015-06-01

The aim of this study was to estimate the finger-tapping rates and finger load capacities of eight fingers (excluding thumbs) for a healthy adult population and investigate the effects of various factors on tapping rate. Finger-tapping rate, the total number of finger taps per unit of time, can be used as a design parameter of various products and also as a psychomotor test for evaluating patients with neurologic problems. A 1-min tapping task was performed by 148 participants with maximum volitional tempo for each of eight fingers. For each of the tapping tasks, the participant with the corresponding finger tapped the associated key in the standard position on the home row of a conventional keyboard for touch typing. The index and middle fingers were the fastest fingers for both hands, and little fingers the slowest. All dominant-hand fingers, except little finger, had higher tapping rates than the fastest finger of the nondominant hand. Tapping rate decreased with age and smokers tapped faster than nonsmokers. Tapping duration and exercise had also significant effect on tapping rate. Normative data of tapping rates and load capacities of eight fingers were estimated for the adult population. In designs of psychomotor tests that require the use of tapping rate or finger load capacity data, the effects of finger, age, smoking, and tapping duration need to be taken into account. The findings can be used for ergonomic designs requiring finger-tapping capacity and also as a reference in psychomotor tests. © 2015, Human Factors and Ergonomics Society.

Gravity-Driven Hydraulic Fractures

NASA Astrophysics Data System (ADS)

Germanovich, L. N.; Garagash, D.; Murdoch, L. C.; Robinowitz, M.

2014-12-01

This study is motived by a new method for disposing of nuclear waste by injecting it as a dense slurry into a hydraulic fracture that grows downward to great enough depth to permanently isolate the waste. Disposing of nuclear waste using gravity-driven hydraulic fractures is mechanically similar to the upward growth of dikes filled with low density magma. A fundamental question in both applications is how the injected fluid controls the propagation dynamics and fracture geometry (depth and breadth) in three dimensions. Analog experiments in gelatin [e.g., Heimpel and Olson, 1994; Taisne and Tait, 2009] show that fracture breadth (the short horizontal dimension) remains nearly stationary when the process in the fracture "head" (where breadth is controlled) is dominated by solid toughness, whereas viscous fluid dissipation is dominant in the fracture tail. We model propagation of the resulting gravity-driven (buoyant or sinking), finger-like fracture of stationary breadth with slowly varying opening along the crack length. The elastic response to fluid loading in a horizontal cross-section is local and can be treated similar to the classical Perkins-Kern-Nordgren (PKN) model of hydraulic fracturing. The propagation condition for a finger-like crack is based on balancing the global energy release rate due to a unit crack extension with the rock fracture toughness. It allows us to relate the net fluid pressure at the tip to the fracture breadth and rock toughness. Unlike the PKN fracture, where breadth is known a priori, the final breadth of a finger-like fracture is a result of processes in the fracture head. Because the head is much more open than the tail, viscous pressure drop in the head can be neglected leading to a 3D analog of Weertman's hydrostatic pulse. This requires relaxing the local elasticity assumption of the PKN model in the fracture head. As a result, we resolve the breadth, and then match the viscosity-dominated tail with the 3-D, toughness-dominated head to obtain a complete closed-form solution. We then analyze the gravity fracture propagation in conditions of either continuous injection or finite volume release for sets of parameters representative of dense waste injection technique and low viscosity magma diking.

Image guided drug release from pH-sensitive Ion channel-functionalized stealth liposomes into an in vivo glioblastoma model.

PubMed

Pacheco-Torres, Jesus; Mukherjee, Nobina; Walko, Martin; López-Larrubia, Pilar; Ballesteros, Paloma; Cerdan, Sebastian; Kocer, Armagan

2015-08-01

Liposomal drug delivery vehicles are promising nanomedicine tools for bringing cytotoxic drugs to cancerous tissues selectively. However, the triggered cargo release from liposomes in response to a target-specific stimulus has remained elusive. We report on functionalizing stealth-liposomes with an engineered ion channel and using these liposomes in vivo for releasing an imaging agent into a cerebral glioma rodent model. If the ambient pH drops below a threshold value, the channel generates temporary pores on the liposomes, thus allowing leakage of the intraluminal medicines. By using magnetic resonance spectroscopy and imaging, we show that engineered liposomes can detect the mildly acidic pH of the tumor microenvironment with 0.2 pH unit precision and they release their content into C6 glioma tumors selectively, in vivo. A drug delivery system with this level of sensitivity and selectivity to environmental stimuli may well serve as an optimal tool for environmentally-triggered and image-guided drug release. Cancer remains a leading cause of mortality worldwide. With advances in science, delivery systems of anti-cancer drugs have also become sophisticated. In this article, the authors designed and characterized functionalized liposomal vehicles, which would release the drug payload in a highly sensitive manner in response to a change in pH environment in an animal glioma model. The novel data would enable better future designs of drug delivery systems. Copyright © 2015 Elsevier Inc. All rights reserved.

Lecithin/chitosan controlled release nanopreparations of tamoxifen citrate: loading, enzyme-trigger release and cell uptake.

PubMed

Barbieri, Stefano; Sonvico, Fabio; Como, Caterina; Colombo, Gaia; Zani, Franca; Buttini, Francesca; Bettini, Ruggero; Rossi, Alessandra; Colombo, Paolo

2013-05-10

Tamoxifen citrate (TAM), an anticancer drug with amphiphilic properties, was loaded in lecithin/chitosan nanoparticles (LCN) with a view to oral administration. The influence of tamoxifen loading on the physico-chemical properties of nanoparticles was studied. Size, surface charge and morphological properties of tamoxifen-loaded nanoparticles (LCN-TAM) were assessed. The increase in the tamoxifen amount in the LCN-TAM preparation up to 60 mg/100 ml maintained the positive zeta potential value of about +45 mV. A statistically significant decrease in particle size was observed for TAM amounts between 5 and 20mg. A strong influence of loaded tamoxifen on the structure of lecithin/chitosan nanoparticles was observed, supported by the quantification of free chitosan and morphological analysis. A loading of tamoxifen in nanoparticles of around 19% was obtained. The release of the drug from the LCN-TAM colloidal dispersion was measured, showing that tamoxifen citrate was released very slowly in simulated gastro-intestinal fluids without enzymes. When enzymes able to dismantle the nanoparticle structure were added to the dissolution medium, drug release was triggered and continued in a prolonged manner. Tamoxifen-loaded nanoparticles showed cytotoxicity towards MCF-7 cells comparable to that obtained with tamoxifen citrate solution, but the rate of this toxic effect was dependent on drug release. Caco-2 cells, used as a model of the intestinal epithelium, were shown to take up the TAM loaded nanoparticles extensively. Copyright © 2013 Elsevier B.V. All rights reserved.

Design and Fabrication of Multifunctional Sericin Nanoparticles for Tumor Targeting and pH-Responsive Subcellular Delivery of Cancer Chemotherapy Drugs.

PubMed

Huang, Lei; Tao, Kaixiong; Liu, Jia; Qi, Chao; Xu, Luming; Chang, Panpan; Gao, Jinbo; Shuai, Xiaoming; Wang, Guobin; Wang, Zheng; Wang, Lin

2016-03-01

The severe cytotoxicity of cancer chemotherapy drugs limits their clinical applications. Various protein-based nanoparticles with good biocompatibility have been developed for chemotherapy drug delivery in hope of reducing drugs' side effects. Sericin, a natural protein from silk, has no immunogenicity and possesses diverse bioactivities that have prompted sericin's application studies. However, the potential of sericin as a multifunctional nanoscale vehicle for cancer therapy have not been fully explored. Here we report the successful fabrication and characterization of folate-conjugated sericin nanoparticles with cancer-targeting capability for pH-responsive release of doxorubicin (these nanoparticles are termed "FA-SND"). DOX is covalently linked to sericin through pH-sensitive hydrazone bonds that render a pH-triggered release property. The hydrophobicity of DOX and the hydrophilicity of sericin promote the self-assembly of sericin-DOX (SND) nanoconjugates. Folate (FA) is then covalently grafted to SND nanoconjugates as a binding unit for actively targeting cancer cells that overexpress folate receptors. Our characterization study shows that FA-SND nanoparticles exhibit negative surface charges that would reduce nonspecific clearance by circulation. These nanoparticles possess good cytotoxicity and hemocompatibiliy. Acidic environment (pH 5.0) triggers effective DOX release from FA-SND, 5-fold higher than does a neutral condition (pH 7.4). Further, FA-SND nanoparticles specifically target folate-receptor-rich KB cells, and endocytosed into lysosomes, an acidic organelle. The acidic microenvironment of lysosomes promotes a rapid release of DOX to nuclei, producing cancer specific chemo-cytotoxicity. Thus, FA-mediated cancer targeting and lysosomal-acidity promoting DOX release, two sequentially-occurring cellular events triggered by the designed components of FA-SND, form the basis for FA-SND to achieve its localized and intracellular chemo-cytotoxicity. Together, this study suggests that these FA-SND nanoparticles may be a potentially effective carrier particularly useful for delivering hydrophobic chemotherapeutic agents for treating cancers with high-level expression of folate receptors.

Calcium-Induced Calcium Release during Action Potential Firing in Developing Inner Hair Cells

PubMed Central

Iosub, Radu; Avitabile, Daniele; Grant, Lisa; Tsaneva-Atanasova, Krasimira; Kennedy, Helen J.

2015-01-01

In the mature auditory system, inner hair cells (IHCs) convert sound-induced vibrations into electrical signals that are relayed to the central nervous system via auditory afferents. Before the cochlea can respond to normal sound levels, developing IHCs fire calcium-based action potentials that disappear close to the onset of hearing. Action potential firing triggers transmitter release from the immature IHC that in turn generates experience-independent firing in auditory neurons. These early signaling events are thought to be essential for the organization and development of the auditory system and hair cells. A critical component of the action potential is the rise in intracellular calcium that activates both small conductance potassium channels essential during membrane repolarization, and triggers transmitter release from the cell. Whether this calcium signal is generated by calcium influx or requires calcium-induced calcium release (CICR) is not yet known. IHCs can generate CICR, but to date its physiological role has remained unclear. Here, we used high and low concentrations of ryanodine to block or enhance CICR to determine whether calcium release from intracellular stores affected action potential waveform, interspike interval, or changes in membrane capacitance during development of mouse IHCs. Blocking CICR resulted in mixed action potential waveforms with both brief and prolonged oscillations in membrane potential and intracellular calcium. This mixed behavior is captured well by our mathematical model of IHC electrical activity. We perform two-parameter bifurcation analysis of the model that predicts the dependence of IHCs firing patterns on the level of activation of two parameters, the SK2 channels activation and CICR rate. Our data show that CICR forms an important component of the calcium signal that shapes action potentials and regulates firing patterns, but is not involved directly in triggering exocytosis. These data provide important insights into the calcium signaling mechanisms involved in early developmental processes. PMID:25762313

Calcium-Induced calcium release during action potential firing in developing inner hair cells.

PubMed

Iosub, Radu; Avitabile, Daniele; Grant, Lisa; Tsaneva-Atanasova, Krasimira; Kennedy, Helen J

2015-03-10

In the mature auditory system, inner hair cells (IHCs) convert sound-induced vibrations into electrical signals that are relayed to the central nervous system via auditory afferents. Before the cochlea can respond to normal sound levels, developing IHCs fire calcium-based action potentials that disappear close to the onset of hearing. Action potential firing triggers transmitter release from the immature IHC that in turn generates experience-independent firing in auditory neurons. These early signaling events are thought to be essential for the organization and development of the auditory system and hair cells. A critical component of the action potential is the rise in intracellular calcium that activates both small conductance potassium channels essential during membrane repolarization, and triggers transmitter release from the cell. Whether this calcium signal is generated by calcium influx or requires calcium-induced calcium release (CICR) is not yet known. IHCs can generate CICR, but to date its physiological role has remained unclear. Here, we used high and low concentrations of ryanodine to block or enhance CICR to determine whether calcium release from intracellular stores affected action potential waveform, interspike interval, or changes in membrane capacitance during development of mouse IHCs. Blocking CICR resulted in mixed action potential waveforms with both brief and prolonged oscillations in membrane potential and intracellular calcium. This mixed behavior is captured well by our mathematical model of IHC electrical activity. We perform two-parameter bifurcation analysis of the model that predicts the dependence of IHCs firing patterns on the level of activation of two parameters, the SK2 channels activation and CICR rate. Our data show that CICR forms an important component of the calcium signal that shapes action potentials and regulates firing patterns, but is not involved directly in triggering exocytosis. These data provide important insights into the calcium signaling mechanisms involved in early developmental processes. Copyright © 2015 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Microbubble-mediated ultrasound therapy: a review of its potential in cancer treatment

PubMed Central

Ibsen, Stuart; Schutt, Carolyn E; Esener, Sadik

2013-01-01

The inherently toxic nature of chemotherapy drugs is essential for them to kill cancer cells but is also the source of the detrimental side effects experienced by patients. One strategy to reduce these side effects is to limit the healthy tissue exposure by encapsulating the drugs in a vehicle that demonstrates a very low leak rate in circulation while simultaneously having the potential for rapid release once inside the tumor. Designing a vehicle with these two opposing properties is the major challenge in the field of drug delivery. A triggering event is required to change the vehicle from its stable circulating state to its unstable release state. A unique mechanical actuation type trigger is possible by harnessing the size changes that occur when microbubbles interact with ultrasound. These mechanical actuations can burst liposomes and cell membranes alike allowing for rapid drug release and facilitating delivery into nearby cells. The tight focusing ability of the ultrasound to just a few cubic millimeters allows for precise control over the tissue location where the microbubbles destabilize the vehicles. This allows the ultrasound to highlight the tumor tissue and cause rapid drug release from any carrier present. Different vehicle designs have been demonstrated from carrying drug on just the surface of the microbubble itself to encapsulating the microbubble along with the drug within a liposome. In the future, nanoparticles may extend the circulation half-life of these ultrasound triggerable drug-delivery vehicles by acting as nucleation sites of ultrasound-induced mechanical actuation. In addition to the drug delivery capability, the microbubble size changes can also be used to create imaging contrast agents that could allow the internal chemical environment of a tumor to be studied to help improve the diagnosis and detection of cancer. The ability to attain truly tumor-specific release from circulating drug-delivery vehicles is an exciting future prospect to reduce chemotherapy side effects while increasing drug effectiveness. PMID:23667309

Vasoactive intestinal peptide test

MedlinePlus

... found in cells in the nervous system and gut. VIP has many functions, including relaxing certain muscles, triggering release of hormones from the pancreas, gut, and hypothalamus, and increasing the amount of water ...

Triggering vacuum capillaries for pneumatic pumping and metering liquids in point-of-care immunoassays.

PubMed

Weng, Kuo-Yao; Chou, Nien-Jen; Cheng, Jya-Wei

2008-07-01

An innovative vacuum capillary pneumatic actuation concept that can be used for point-of-care testing has been investigated. The vacuum glass capillaries are encapsulated within a laminated pouch and incorporated into the fluidic card. Vacuum glass capillaries broken by external force such as finger pressure, generate the pneumatic forces to induce liquid flow in the fluidic system. The sizes of vacuum capillary play a vital role in the pumping and metering functions of the system. The luteinizing hormone (LH) chromatographic immunoassay performances in the fluidic cards show consistency comparable to that obtained by manual micropipetting. The vacuum capillary pneumatic actuation will be applied in other complex handling step bioassays and lab-on-a-chip devices.

Trigger Menu-aware Monitoring for the ATLAS experiment

NASA Astrophysics Data System (ADS)

Hoad, Xanthe; ATLAS Collaboration

2017-10-01

We present a“trigger menu-aware” monitoring system designed for the Run-2 data-taking of the ATLAS experiment at the LHC. Unlike Run-1, where a change in the trigger menu had to be matched by the installation of a new software release at Tier-0, the new monitoring system aims to simplify the ATLAS operational workflows. This is achieved by integrating monitoring updates in a quick and flexible manner via an Oracle DB interface. We present the design and the implementation of the menu-aware monitoring, along with lessons from the operational experience of the new system with the 2016 collision data.

Activation of PPARδ attenuates neurotoxicity by inhibiting lipopolysaccharide-triggered glutamate release in BV-2 microglial cells.

PubMed

Lee, Won Jin; Ham, Sun Ah; Yoo, Hyunjin; Hwang, Jung Seok; Yoo, Taesik; Paek, Kyung Shin; Lim, Dae-Seog; Han, Sung Gu; Lee, Chi-Ho; Hong, Kwonho; Seo, Han Geuk

2018-02-01

Neuroinflammation-associated release of glutamate from activated microglia has been implicated in the progression of neurodegenerative diseases. However, the regulatory mechanisms underlying this glutamate release are poorly understood. Here, we show that peroxisome proliferator-activated receptor delta (PPARδ) modulates neurotoxicity by inhibiting glutamate release in lipopolysaccharide (LPS)-activated BV-2 microglial cells. Activation of PPARδ by GW501516, a specific PPARδ agonist, inhibited glutamate release in BV-2 cells. This effect of GW501516 was significantly blocked by shRNA-mediated knockdown of PPARδ and by treatment with GSK0660, a specific PPARδ antagonist, indicating that PPARδ is associated with blockade of glutamate release. Additionally, GW501516-activated PPARδ suppressed generation of reactive oxygen species and expression of gp91phox, a functional subunit of NADPH oxidase 2, in BV-2 cells stimulated with LPS. The inhibitory effect of GW501516 on gp91phox expression and glutamate release was further potentiated in the presence of AG490, a specific inhibitor of janus kinase 2 (JAK2), leading to the inhibition of signal transducer and activator of transcription 1 (STAT1). By contrast, GW501516 upregulated the expression of suppressor of cytokine signaling 1 (SOCS1), an endogenous inhibitor of JAK2. Furthermore, neurotoxicity induced by conditioned media from LPS-stimulated BV-2 cells was significantly reduced when conditioned media from BV-2 cells treated with both LPS and GW501516 were used. These results indicate that PPARδ attenuates LPS-triggered neuroinflammation by enhancing SOCS1-mediated inhibition of JAK2/STAT1 signaling, thereby inhibiting neurotoxicity associated with glutamate release. © 2018 Wiley Periodicals, Inc.

Exocytosis of ATP From Astrocytes Modulates Phasic and Tonic Inhibition in the Neocortex

PubMed Central

Rasooli-Nejad, Seyed; Andrew, Jemma; Haydon, Philip G.; Pankratov, Yuriy

2014-01-01

Communication between neuronal and glial cells is important for many brain functions. Astrocytes can modulate synaptic strength via Ca2+-stimulated release of various gliotransmitters, including glutamate and ATP. A physiological role of ATP release from astrocytes was suggested by its contribution to glial Ca2+-waves and purinergic modulation of neuronal activity and sleep homeostasis. The mechanisms underlying release of gliotransmitters remain uncertain, and exocytosis is the most intriguing and debated pathway. We investigated release of ATP from acutely dissociated cortical astrocytes using “sniff-cell” approach and demonstrated that release is vesicular in nature and can be triggered by elevation of intracellular Ca2+ via metabotropic and ionotropic receptors or direct UV-uncaging. The exocytosis of ATP from neocortical astrocytes occurred in the millisecond time scale contrasting with much slower nonvesicular release of gliotransmitters via Best1 and TREK-1 channels, reported recently in hippocampus. Furthermore, we discovered that elevation of cytosolic Ca2+ in cortical astrocytes triggered the release of ATP that directly activated quantal purinergic currents in the pyramidal neurons. The glia-driven burst of purinergic currents in neurons was followed by significant attenuation of both synaptic and tonic inhibition. The Ca2+-entry through the neuronal P2X purinoreceptors led to phosphorylation-dependent down-regulation of GABAA receptors. The negative purinergic modulation of postsynaptic GABA receptors was accompanied by small presynaptic enhancement of GABA release. Glia-driven purinergic modulation of inhibitory transmission was not observed in neurons when astrocytes expressed dn-SNARE to impair exocytosis. The astrocyte-driven purinergic currents and glia-driven modulation of GABA receptors were significantly reduced in the P2X4 KO mice. Our data provide a key evidence to support the physiological importance of exocytosis of ATP from astrocytes in the neocortex. PMID:24409095

The luteal phase after GnRH-agonist triggering of ovulation: present and future perspectives.

PubMed

Humaidan, Peter; Papanikolaou, E G; Kyrou, D; Alsbjerg, B; Polyzos, N P; Devroey, P; Fatemi, Human M

2012-02-01

In stimulated IVF/intracytoplasmic sperm injection cycles, the luteal phase is disrupted, necessitating luteal-phase supplementation. The most plausible reason behind this is the ovarian multifollicular development obtained after ovarian stimulation, resulting in supraphysiological steroid concentrations and consecutive inhibition of LH secretion by the pituitary via negative feedback at the level of the hypothalamic-pituitary axis. With the introduction of the gonadotrophin-releasing hormone-(GnRH) antagonist, an alternative to human chorionic gonadotrophin triggering of final oocyte maturation is the use of GnRH agonist (GnRHa) which reduces or even prevents ovarian hyperstimulation syndrome (OHSS). Interestingly, the current regimens of luteal support after HCG triggering are not sufficient to secure the early implanting embryo after GnRHa triggering. This review discusses the luteal-phase insufficiency seen after GnRHa triggering and the various trials that have been performed to assess the most optimal luteal support in relation to GnRHa triggering. Although more research is needed, GnRHa triggering is now an alternative to HCG triggering, combining a significant reduction in OHSS with high ongoing pregnancy rates. Copyright © 2011 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

Development and characterization of multifunctional nanoparticles for drug delivery to cancer cells

NASA Astrophysics Data System (ADS)

Nahire, Rahul Rajaram

Lipid and polymeric nanoparticles, although proven to be effective drug delivery systems compared to free drugs, have shown considerable limitations pertaining to their uptake and release at tumor sites. Spatial and temporal control over the delivery of anticancer drugs has always been challenge to drug delivery scientists. Here, we have developed and characterized multifunctional nanoparticles (liposomes and polymersomes) which are targeted specifically to cancer cells, and release their contents with tumor specific internal triggers. To enable these nanoparticles to be tracked in blood circulation, we have imparted them with echogenic characteristic. Echogenicity of nanoparticles is evaluated using ultrasound scattering and imaging experiments. Nanoparticles demonstrated effective release with internal triggers such as elevated levels of MMP-9 enzyme found in the extracellular matrix of tumor cells, decreased pH of lysosome, and differential concentration of reducing agents in cytosol of cancer cells. We have also successfully demonstrated the sensitivity of these particles towards ultrasound to further enhance the release with internal triggers. To ensure the selective uptake by folate receptor- overexpressing cancer cells, we decorated these nanoparticles with folic acid on their surface. Fluorescence microscopic images showed significantly higher uptake of folate-targeted nanoparticles by MCF-7 (breast cancer) and PANC-1 (pancreatic cancer) cells compared to particles without any targeting ligand on their surface. To demonstrate the effectiveness of these nanoparticles to carry the drugs inside and kill cancer cells, we encapsulated doxorubicin and/or gemcitabine employing the pH gradient method. Drug loaded nanoparticles showed significantly higher killing of the cancer cells compared to their non-targeted counterparts and free drugs. With further development, these nanoparticles certainly have potential to be used as a multifunctional nanocarriers for image guided, targeted delivery of anticancer drugs.

Perceiving fingers in single-digit arithmetic problems.

PubMed

Berteletti, Ilaria; Booth, James R

2015-01-01

In this study, we investigate in children the neural underpinnings of finger representation and finger movement involved in single-digit arithmetic problems. Evidence suggests that finger representation and finger-based strategies play an important role in learning and understanding arithmetic. Because different operations rely on different networks, we compared activation for subtraction and multiplication problems in independently localized finger somatosensory and motor areas and tested whether activation was related to skill. Brain activations from children between 8 and 13 years of age revealed that only subtraction problems significantly activated finger motor areas, suggesting reliance on finger-based strategies. In addition, larger subtraction problems yielded greater somatosensory activation than smaller problems, suggesting a greater reliance on finger representation for larger numerical values. Interestingly, better performance in subtraction problems was associated with lower activation in the finger somatosensory area. Our results support the importance of fine-grained finger representation in arithmetical skill and are the first neurological evidence for a functional role of the somatosensory finger area in proficient arithmetical problem solving, in particular for those problems requiring quantity manipulation. From an educational perspective, these results encourage investigating whether different finger-based strategies facilitate arithmetical understanding and encourage educational practices aiming at integrating finger representation and finger-based strategies as a tool for instilling stronger numerical sense.

Perceiving fingers in single-digit arithmetic problems

PubMed Central

Berteletti, Ilaria; Booth, James R.

2015-01-01

In this study, we investigate in children the neural underpinnings of finger representation and finger movement involved in single-digit arithmetic problems. Evidence suggests that finger representation and finger-based strategies play an important role in learning and understanding arithmetic. Because different operations rely on different networks, we compared activation for subtraction and multiplication problems in independently localized finger somatosensory and motor areas and tested whether activation was related to skill. Brain activations from children between 8 and 13 years of age revealed that only subtraction problems significantly activated finger motor areas, suggesting reliance on finger-based strategies. In addition, larger subtraction problems yielded greater somatosensory activation than smaller problems, suggesting a greater reliance on finger representation for larger numerical values. Interestingly, better performance in subtraction problems was associated with lower activation in the finger somatosensory area. Our results support the importance of fine-grained finger representation in arithmetical skill and are the first neurological evidence for a functional role of the somatosensory finger area in proficient arithmetical problem solving, in particular for those problems requiring quantity manipulation. From an educational perspective, these results encourage investigating whether different finger-based strategies facilitate arithmetical understanding and encourage educational practices aiming at integrating finger representation and finger-based strategies as a tool for instilling stronger numerical sense. PMID:25852582

Activity patterns of extrinsic finger flexors and extensors during movements of instructed and non-instructed fingers.

PubMed

van Beek, Nathalie; Stegeman, Dick F; van den Noort, Josien C; H E J Veeger, DirkJan; Maas, Huub

2018-02-01

The fingers of the human hand cannot be controlled fully independently. This phenomenon may have a neurological as well as a mechanical basis. Despite previous studies, the neuromechanics of finger movements are not fully understood. The aims of this study were (1) to assess the activation and coactivation patterns of finger specific flexor and extensor muscle regions during instructed single finger flexion and (2) to determine the relationship between enslaved finger movements and respective finger muscle activation. In 9 healthy subjects (age 22-29), muscle activation was assessed during single finger flexion using a 90 surface electromyography electrode grid placed over the flexor digitorum superficialis (FDS) and the extensor digitorum (ED). We found (1) no significant differences in muscle activation timing between fingers, (2) considerable muscle activity in flexor and extensor regions associated with the non-instructed fingers and (3) no correlation between the muscle activations and corresponding movement of non-instructed fingers. A clear disparity was found between the movement pattern of the non-instructed fingers and the activity pattern of the corresponding muscle regions. This suggests that mechanical factors, such as intertendinous and myofascial connections, may also affect finger movement independency and need to be taken into consideration when studying finger movement. Copyright © 2017 Elsevier Ltd. All rights reserved.

Stabilization of the total force in multi-finger pressing tasks studied with the ‘inverse piano’ technique

PubMed Central

Martin, J.R.; Budgeon, M.K.; Zatsiorsky, V.M.; Latash, M.L.

2010-01-01

When one finger changes its force, other fingers of the hand can show unintended force changes in the same direction (enslaving) and in the opposite direction (error compensation). We tested a hypothesis that externally imposed changes in finger force predominantly lead to error compensation effects in other fingers thus stabilizing the total force. A novel device, the “inverse piano”, was used to impose controlled displacements to one of the fingers over different magnitudes and at different rates. Subjects (n =10) pressed with four fingers at a constant force level and then one of the fingers was unexpectedly raised. The subjects were instructed not to interfere with possible changes in the finger forces. Raising a finger caused an increase in its force and a drop in the force of the other three fingers. Overall, total force showed a small increase. Larger force drops were seen in neighbors of the raised finger (proximity effect). The results show that multi-finger force stabilizing synergies dominate during involuntary reactions to externally imposed finger force changes. Within the referent configuration hypothesis, the data suggest that the instruction “not to interfere” leads to adjustments of the referent coordinates of all the individual fingers. PMID:21450360

Stabilizing Alginate Confinement and Polymer Coating of CO-Releasing Molecules Supported on Iron Oxide Nanoparticles To Trigger the CO Release by Magnetic Heating.

PubMed

Meyer, Hajo; Winkler, Felix; Kunz, Peter; Schmidt, Annette M; Hamacher, Alexandra; Kassack, Matthias U; Janiak, Christoph

2015-12-07

Maghemite (Fe2O3) iron oxide nanoparticles (IONPs) were synthesized, modified with covalent surface-bound CO-releasing molecules of a tri(carbonyl)-chlorido-phenylalaninato-ruthenium(II) complex (CORM), and coated with a dextran polymer. The time- and temperature-dependent CO release from this CORM-3 analogue was followed by a myoglobin assay. A new measurement method for the myoglobin assay was developed, based on confining "water-soluble" polymer-coated Dextran500k@CORM@IONP particles in hollow spheres of nontoxic and easily prepared calcium alginate. Dropping a mixture of Dextran500k@CORM@IONP and sodium alginate into a CaCl2 solution leads to stable hollow spheres of Ca(2+) cross-linked alginate which contain the Dextran500k@CORM@IONP particles. This "alginate-method" (i) protects CORM-3 analogues from rapid CO-displacement reactions with a protein, (ii) enables a spatial separation of the CORM from its surrounding myoglobin assay with the alginate acting as a CO-permeable membrane, and (iii) allows the use of substances with high absorptivity (such as iron oxide nanoparticles) in the myoglobin assay without interference in the optical path of the UV cell. Embedding the CORM@IONP nanoparticles in the alginate vessel represents a compartmentation of the reactive component and allows for close contact with, yet facile separation from, the surrounding myoglobin assay. The half-life of the CO release from Dextran500k@CORM@IONP particles surrounded by alginate was determined to be 890 ± 70 min at 20 °C. An acceleration of the CO release occurs at higher temperature with a half-life of 172 ± 27 min at 37 °C and 45 ± 7 min at 50 °C. The CO release can be triggered in an alternating current magnetic field (31.7 kA m(-1), 247 kHz, 39.9 mT) through local magnetic heating of the susceptible iron oxide nanoparticles. With magnetic heating at 20 °C in the bulk solution, the half-life of CO release from Dextran500k@CORM@IONP particles decreased to 155 ± 18 min without a noticeable temperature increase in the dispersion. At 37 and 50 °C, the half-life for the CO release triggered by local magnetic heating was 65 ± 5 min and 30 ± 3 min, respectively. Thus, at a physiological temperature of 37 °C, magnetic heating accelerates the CO release of the IONP-bound CORM by a factor of ∼ 2.6. The activation energy for CO release from a CORM-3 analogue was determined to be EA = 78 kJ/mol.

Congenital symbrachydactyly: outcomes of surgical treatment in 120 webs.

PubMed

Li, Wen-jun; Zhao, Jun-hui; Tian, Wen; Tian, Guang-lei

2013-01-01

Symbrachydactyly is defined as a combination of short fingers with syndactyly. There are few published reports estimating the incidence of symbrachydactyly. The aim of this study was to investigate the clinical features and the outcome of surgical treatment for congenital symbrachydactyly. One hundred and twenty webs of thirty-four patients of symbrachydactyly were involved in the study. The sex ratio was 21 males/13 females. The age ranged from 1 year to 8 years, average 2.6 years. Four cases had both hands involved and 30 patients had one hand involvement. Release of the syndactylous digits webs were completed by one surgical procedure in 14 cases and more than one surgical procedure in 20 cases; 3 to 6 months between the procedures. In the meantime, some of the associated hand deformities were treated. Postoperative follow-up time was 10 to 18 months, average 12 months. All the fingers involved in this study were separated successfully. However, 6 fingers had scar tissue contracture and 8 had web scar adhesion. All complications needed further surgical treatment. Parents of 94.1% of the patients were satisfied with the overall function of the hand, and 76.5% were satisfied with the cosmetic appearance of hand. The combination of syndactyly and brachydactyly is the main clinical feature in symbrachydactyly. Separation of the digital webs can greatly improve the function of the hand. However, more work needs to be done to improve the cosmetic appearance of the hand.

Mallet finger - aftercare

MedlinePlus

Baseball finger - aftercare; Drop finger - aftercare; Avulsion fracture - mallet finger - aftercare ... away from the rest of the bone (avulsion fracture) Mallet finger most often occurs when something hits ...

Smart Coating for Corrosion Indication and Prevention: Recent Progress

NASA Technical Reports Server (NTRS)

Li, Wenyan; Hintze, Paul; Calle, Luz M.; Buhrow, Jerry; Curran, Jerry; Muehlberg, A. J.; Gelling, V. J.; Webster, D. C.; Croll, S. G.; Contu, F.;

Bioactive films of zein/magnetite magnetically stimuli-responsive for controlled drug release

NASA Astrophysics Data System (ADS)

Marín, Tíffany; Montoya, Paula; Arnache, Oscar; Pinal, Rodolfo; Calderón, Jorge

2018-07-01

The Zein films in two configurations with magnetite nanoparticles (zein/NPs) and magnetite-acetaminophen (zein/NPs/Drug) were used as magnetically stimuli-responsive systems to propose a model of controlled release by dissolution and diffusion mechanism. Composite material films of zein/NPs and zein/NPs/Drug were made by dispersion of magnetite nanoparticles into zein solution then solvent casting of the solution on a flat Teflon substrate. The properties of composite films were analyzed by magnetization curves of (MvsH) and measurements of magnetic force microscopy (MFM). Drug release from the zein/NPs/Drug composite films was determined using a type II dissolution apparatus for a period of 2 h under applied magnetic field conditions. In addition, the diffusion mechanism was tested with zein/NPs films into diffusion cell containing acetaminophen solution for 24 h and using a permanent magnet as a remote trigger device. The results showed that the magnetite nanoparticles contained in the zein/NPs and zein/NPs/Drug composite films are stable, i.e., they do not undergo sufficiently high levels of oxidation as to alter their magnetic properties. Furthermore, the dissolution and diffusion results lead us to conclude that zein composite films effectively behave as stimuli-responsive systems triggered by an external magnetic field applied. The result is a model controlled release system whereby drug release can be controlled by adjusting the magnitude of the applied magnetic field.

Programmable display of DNA-protein chimeras for controlling cell-hydrogel interactions via reversible intermolecular hybridization.

PubMed

Zhang, Zhaoyang; Li, Shihui; Chen, Niancao; Yang, Cheng; Wang, Yong

2013-04-08

Extensive studies have been recently carried out to achieve dynamic control of cell-material interactions primarily through physicochemical stimulation. The purpose of this study was to apply reversible intermolecular hybridization to program cell-hydrogel interactions in physiological conditions based on DNA-antibody chimeras and complementary oligonucleotides. The results showed that DNA oligonucleotides could be captured to and released from the immobilizing DNA-functionalized hydrogels with high specificity via DNA hybridization. Accordingly, DNA-antibody chimeras were captured to the hydrogels, successfully inducing specific cell attachment. The cell attachment to the hydrogels reached the plateau at approximately half an hour after the functionalized hydrogels and the cells were incubated together. The attached cells were rapidly released from the bound hydrogels when triggering complementary oligonucleotides were introduced to the system. However, the capability of the triggering complementary oligonucleotides in releasing cells was affected by the length of intermolecular hybridization. The length needed to be at least more than 20 base pairs in the current experimental setting. Notably, because the procedure of intermolecular hybridization did not involve any harsh condition, the released cells maintained the same viability as that of the cultured cells. The functionalized hydrogels also exhibited the potential to catch and release cells repeatedly. Therefore, this study demonstrates that it is promising to regulate cell-material interactions dynamically through the DNA-programmed display of DNA-protein chimeras.

Triggered intracellular calcium waves in dog and human left atrial myocytes from normal and failing hearts.

PubMed

Aistrup, Gary L; Arora, Rishi; Grubb, Søren; Yoo, Shin; Toren, Benjamin; Kumar, Manvinder; Kunamalla, Aaron; Marszalec, William; Motiwala, Tej; Tai, Shannon; Yamakawa, Sean; Yerrabolu, Satya; Alvarado, Francisco J; Valdivia, Hector H; Cordeiro, Jonathan M; Shiferaw, Yohannes; Wasserstrom, John Andrew

2017-11-01

Abnormal intracellular Ca2+ cycling contributes to triggered activity and arrhythmias in the heart. We investigated the properties and underlying mechanisms for systolic triggered Ca2+ waves in left atria from normal and failing dog hearts. Intracellular Ca2+ cycling was studied using confocal microscopy during rapid pacing of atrial myocytes (36 °C) isolated from normal and failing canine hearts (ventricular tachypacing model). In normal atrial myocytes (NAMs), Ca2+ waves developed during rapid pacing at rates ≥ 3.3 Hz and immediately disappeared upon cessation of pacing despite high sarcoplasmic reticulum (SR) load. In heart failure atrial myocytes (HFAMs), triggered Ca2+ waves (TCWs) developed at a higher incidence at slower rates. Because of their timing, TCW development relies upon action potential (AP)-evoked Ca2+ entry. The distribution of Ca2+ wave latencies indicated two populations of waves, with early events representing TCWs and late events representing conventional spontaneous Ca2+ waves. Latency analysis also demonstrated that TCWs arise after junctional Ca2+ release has occurred and spread to non-junctional (cell core) SR. TCWs also occurred in intact dog atrium and in myocytes from humans and pigs. β-adrenergic stimulation increased Ca2+ release and abolished TCWs in NAMs but was ineffective in HFAMs making this a potentially effective adaptive mechanism in normals but potentially arrhythmogenic in HF. Block of Ca-calmodulin kinase II also abolished TCWs, suggesting a role in TCW formation. Pharmacological manoeuvres that increased Ca2+ release suppressed TCWs as did interventions that decreased Ca2+ release but these also severely reduced excitation-contraction coupling. TCWs develop during the atrial AP and thus could affect AP duration, producing repolarization gradients and creating a substrate for reentry, particularly in HF where they develop at slower rates and a higher incidence. TCWs may represent a mechanism for the initiation of atrial fibrillation particularly in HF. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions please email: journals.permissions@oup.com.

Patterns of Dupuytren disease in fingers: studying correlations with a multivariate ordinal logit model.

PubMed

Lanting, Rosanne; Nooraee, Nazanin; Werker, Paul M N; van den Heuvel, Edwin R

2014-09-01

Dupuytren disease affects fingers in a variable fashion. Knowledge about specific disease patterns (phenotype) based on location and severity of the disease is lacking. In this cross-sectional study, 344 primary affected hands with Dupuytren disease were physically examined. The Pearson correlation coefficient between the coexistence of Dupuytren disease in pairs of fingers was calculated, and agglomerative hierarchical clustering was applied to identify possible clusters of affected fingers. With a multivariate ordinal logit model, the authors studied the correlation on severity, taking into account age and sex, and tested hypotheses on independence between groups of fingers. The ring finger was most frequently affected by Dupuytren disease, and contractures were seen in 15.1 percent of affected rays. The severity of thumb and index finger, middle and ring fingers, and middle and little fingers was significantly correlated. Occurrences in pairs of fingers were highest in the middle and ring fingers and lowest in the thumb and index finger. Correlation between the ring and little fingers and a correlation between fingers from the ulnar and radial sides could not be demonstrated. Rays on the ulnar side of the hand are predominantly affected. The middle finger is substantially correlated with other fingers on the ulnar side, and the thumb and index finger are correlated; however, there was no evidence that the ulnar side and the radial side were correlated in any way, which suggests that occurrence on one side of the hand does not predict Dupuytren disease on the other side of the hand. Risk, III.

Adaptive flexibility of the within-hand attentional gradient in touch: An MEG study.

PubMed

Kida, Tetsuo; Tanaka, Emi; Kakigi, Ryusuke

2018-06-21

Previous studies have demonstrated the cortical mechanisms for the gradient of spatial attention in vision and audition, whereas those for touch have yet to be elucidated in detail. In order to examine the within-hand gradient of tactile spatial attention in the cerebral cortex, we used magnetoencephalography (MEG) to record cortical responses to an electrocutaneous stimulation presented randomly to any of the five fingers of the right hand at a random interstimulus interval (750-1250 ms). Participants attended to the index finger, ring finger, or both to detect a rare target stimulus in a sequence of frequent standard stimuli presented to the attended finger(s) by silent counting. Neuromagnetic responses around the contralateral primary and secondary somatosensory cortices (SIc and SIIc) at 50-70 ms and 80-100 ms, respectively, for the stimulation of the index or ring finger were stronger when that finger was attended than when the distant finger was attended or at rest. The amplitude of the SIIc response was also intermediate when the index and ring fingers were simultaneously attended. The SIIc response to the task-irrelevant stimulation of the thumb or little finger increased when the index or ring finger was attended, respectively, suggesting an across-finger gradient of tactile attention. Simultaneous attention to the index and ring fingers decreased the SIIc response to the task-irrelevant stimulation of the intervening middle finger more than that with attention to either one of the two fingers. The earliest attentional sign was observed for the SI M40c response, with the amplitude increasing with the stimulation of the unattended finger. Furthermore, late responses in the temporo-parietal junction (TPJ) and prefrontal cortex (PFC) were stronger with the stimulation of the unattended finger than with that of the attended finger. Thus, the present study provides cortical evidence for the adaptive control of the within-hand, across-finger gradient of tactile attention that depends on whether attention is focused on a single finger or divided into non-adjacent different fingers. Copyright © 2018. Published by Elsevier Inc.

Finger wear detection for production line battery tester

DOEpatents

Depiante, Eduardo V.

1997-01-01

A method for detecting wear in a battery tester probe. The method includes providing a battery tester unit having at least one tester finger, generating a tester signal using the tester fingers and battery tester unit with the signal characteristic of the electrochemical condition of the battery and the tester finger, applying wavelet transformation to the tester signal including computing a mother wavelet to produce finger wear indicator signals, analyzing the signals to create a finger wear index, comparing the wear index for the tester finger with the index for a new tester finger and generating a tester finger signal change signal to indicate achieving a threshold wear change.

Factor XII full and partial null in rat confers robust antithrombotic efficacy with no bleeding.

PubMed

Cai, Tian-Quan; Wu, Weizhen; Shin, Myung K; Xu, Yiming; Jochnowitz, Nina; Zhou, Yuchen; Hoos, Lizbeth; Bentley, Ross; Strapps, Walter; Thankappan, Anil; Metzger, Joseph M; Ogletree, Martin L; Tadin-Strapps, Marija; Seiffert, Dietmar A; Chen, Zhu

2015-12-01

This report aims at exploring quantitatively the relationship between FXII inhibition and thromboprotection. FXII full and partial null in rats were established via zinc finger nuclease-mediated knockout and siRNA-mediated knockdown, respectively. The rats were subsequently characterized in thrombosis and hemostasis models. Knockout rats exhibited complete thromboprotection in both the arteriovenous shunt model (∼100% clot weight reduction) and the FeCl3-induced arterial thrombosis model (no reduction in blood flow), without any increase in cuticle bleeding time compared with wild-type control rats. Ex-vivo aPTT and the ellagic acid-triggered thrombin generation assay (TGA) exhibited anticoagulant changes. In contrast, ex-vivo PT or high tissue factor-triggered TGA was indistinguishable from control. Rats receiving single doses (0, 0.01, 0.03, 0.1, 0.3, 1 mg/kg) of FXII siRNA exhibited dose-dependent knockdown in liver FXII mRNA and plasma FXII protein (95 and 99%, respectively, at 1 mg/kg) at day 7 post dosing. FXII knockdown was associated with dose-dependent thromboprotection (maximal efficacy achieved with 1 mg/kg in both models) and negligible change in cuticle bleeding times. Ex-vivo TGA triggered with low-level (0.5 μmol/l) ellagic acid tracked best with the knockdown levels and efficacy. Our findings confirm and extend literature reports of an attractive benefit-to-risk profile of targeting FXII for antithrombotic therapies. Titrating of FXII is instructive for its pharmacological inhibition. The knockout rat is valuable for evaluating both mechanism-based safety concerns and off-target effects of FXII(a) inhibitors. Detailed TGA analyses will inform on optimal trigger conditions in studying pharmacodynamic effects of FXII(a) inhibition.

Scattering Removal for Finger-Vein Image Restoration

PubMed Central

Yang, Jinfeng; Zhang, Ben; Shi, Yihua

2012-01-01

Finger-vein recognition has received increased attention recently. However, the finger-vein images are always captured in poor quality. This certainly makes finger-vein feature representation unreliable, and further impairs the accuracy of finger-vein recognition. In this paper, we first give an analysis of the intrinsic factors causing finger-vein image degradation, and then propose a simple but effective image restoration method based on scattering removal. To give a proper description of finger-vein image degradation, a biological optical model (BOM) specific to finger-vein imaging is proposed according to the principle of light propagation in biological tissues. Based on BOM, the light scattering component is sensibly estimated and properly removed for finger-vein image restoration. Finally, experimental results demonstrate that the proposed method is powerful in enhancing the finger-vein image contrast and in improving the finger-vein image matching accuracy. PMID:22737028

Development of Bioorthogonally Degradable Linkers and Polymers Using alpha-Azidoethers

NASA Astrophysics Data System (ADS)

Rajagopalan, Chandrasekhar Ramasubramanian

Degradable polymers have gained a lot of attention in recent years for applications in biotechnology and medicine. External control over polymer degradation can be obtained by incorporating functional groups that cleave in the presence of triggers that would normally be absent in biological environments, i.e. are bioorthogonal. This thesis explores the use of chemically cleavable alpha-azidoethers as a new method to obtain external control over the degradation behavior of polymers. My first goal is to illustrate the potential of alpha-azidoethers toward developing cleavable linkers. We have studied the relationship between alpha-azidoether structure and hydrolytic stability, to prepare linkers that withstand background hydrolytic cleavage until they are exposed to the cleaving trigger. The cleavage kinetics of the alpha-azidoether functional group was quantified. In addition to the conventionally used tris(2-carboxyethyl)phosphine (TCEP), dihydrolipoic acid (DHLA), a previously unexplored, biocompatible reducing agent, was also evaluated as a cleaving trigger. Based on these results, we have proposed design rules for utilizing alpha-azidoethers as cleavable linkers in applications that require bioorthogonal control over linker cleavage. Secondly, the alpha-azidoether cleavable linker chemistry was implemented into the development of polymeric materials. Two different types of polymers were developed. Polyamides incorporating alpha-azidoethers along the backbone were synthesized, and their physical properties and chemically triggered degradation behavior were characterized. The degradation timescale of these polymers can be tuned simply by manipulating the concentration of the externally applied chemical trigger. The alpha-azidoether functional group was then utilized to develop a unique triggered-release polymeric adhesive for potential applications in dental adhesive formulations. A methacrylamide-phosphonate adhesive monomer incorporating an alpha-azidoether group was designed and synthesized. The monomer was polymerized to adhere polymer-composite substrates. Adhesion strength was quantified, and on-demand release of bonded substrates was demonstrated using DHLA as a trigger. The results presented here shed some light on the scope, advantages and drawbacks of utilizing alpha-azidoethers to develop new types of cleavable linkers and degradable polymers. In principle, the triggered degradation method described here could be incorporated into polymers with different chemical structures, to develop a variety of materials that offer an external control over degradation.

NIR-triggered high-efficient photodynamic and chemo-cascade therapy using caspase-3 responsive functionalized upconversion nanoparticles.

PubMed

Zhao, Na; Wu, Baoyan; Hu, Xianglong; Xing, Da

2017-10-01

Stimuli-responsive nanoparticles with multiple therapeutic/diagnostic functions are highly desirable for effective tumor treatment. Herein novel caspase-3 responsive functionalized upconversion nanoparticles (CFUNs) were fabricated with three-in-one functional integration: near-infrared (NIR) triggered photodynamic damage along with caspase-3 activation, subsequent caspase-3 responsive drug release, and cascade chemotherapeutic activation. CFUNs were formulated from the self-assembly of caspase-3 responsive doxorubicin (DOX) prodrug tethered with DEVD peptide (DEVD-DOX), upconversion nanoparticles (UCNP), a photosensitizer (pyropheophorbide-a methyl ester, MPPa), and tumor-targeting cRGD-PEG-DSPE to afford multifunctional CFUNs, MPPa/UCNP-DEVD-DOX/cRGD. Upon cellular uptake and NIR irradiation, the visible light emission of UCNP could excite MPPa to produce reactive oxygen species for photodynamic therapy (PDT) along with the activation of caspase-3, which further cleaved DEVD peptide to release DOX within tumor cells, thus accomplishing NIR-triggered PDT and cascade chemotherapy. CFUNs presented silent therapeutic potency and negligible cytotoxicity in the dark, whereas in vitro and in vivo experiments demonstrated the NIR-triggered cascade therapeutic activation and tumor inhibition due to consecutive PDT and chemotherapy. Current NIR-activated cascade tumor therapy with two distinct mechanisms is significantly favorable to overcome multidrug resistance and tumor heterogeneity for persistent tumor treatment. Copyright © 2017 Elsevier Ltd. All rights reserved.

Paired-pulse facilitation and depression at unitary synapses in rat hippocampus: quantal fluctuation affects subsequent release.

PubMed Central

Debanne, D; Guérineau, N C; Gähwiler, B H; Thompson, S M

1996-01-01

1. Excitatory synaptic transmission between pairs of monosynaptically coupled pyramidal cells was examined in rat hippocampal slice cultures. Action potentials were elicited in single CA3 pyramidal cells impaled with microelectrodes and unitary excitatory postsynaptic currents (EPSCs) were recorded in whole-cell voltage-clamped CA1 or CA3 cells. 2. The amplitude of successive unitary EPSCs in response to single action potentials varied. The amplitude of EPSCs was altered by adenosine or changes in the [Mg2+]/[CA2+] ratio. We conclude that single action potentials triggered the release of multiple quanta of glutamate. 3. When two action potentials were elicited in the presynaptic cell, the amplitude of the second EPSC was inversely related to the amplitude of the first. Paired-pulse facilitation (PPF) was observed when the first EPSC was small, i.e. the second EPSC was larger than the first, whereas paired-pulse depression (PPD) was observed when the first EPSC was large. 4. The number of trials displaying PPD was greater when release probability was increased, and smaller when release probability was decreased. 5. PPD was not postsynaptically mediated because it was unaffected by decreasing ionic flux with 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) or receptor desensitization with aniracetam. 6. PPF was maximal at an interstimulus interval of 70 ms and recovered within 500 ms. Recovery from PPD occurred within 5 s. 7. We propose that multiple release sites are formed by the axon of a CA3 pyramidal cell and a single postsynaptic CA1 or CA3 cell. PPF is observed if the first action potential fails to release transmitter at most release sites. PPD is observed if the first action potential successfully triggers release at most release sites. 8. Our observations of PPF are consistent with the residual calcium hypothesis. We conclude that PPD results from a decrease in quantal content, perhaps due to short-term depletion of readily releasable vesicles. PMID:9011608

pH dependent silver nanoparticles releasing titanium implant: A novel therapeutic approach to control peri-implant infection.

PubMed

Dong, Yiwen; Ye, Hui; Liu, Yi; Xu, Lihua; Wu, Zuosu; Hu, Xiaohui; Ma, Jianfeng; Pathak, Janak L; Liu, Jinsong; Wu, Gang

2017-10-01

Peri-implant infection control is crucial for implant fixation and durability. Antimicrobial administration approaches to control peri-implant infection are far from satisfactory. During bacterial infection, pH level around the peri-implant surface decreases as low as pH 5.5. This change of pH can be used as a switch to control antimicrobial drug release from the implant surface. Silver nanoparticles (AgNPs) have broad-spectrum antimicrobial properties. In this study, we aimed to design a pH-dependent AgNPs releasing titania nanotube arrays (TNT) implant for peri-implant infection control. The nanotube arrays were fabricated on the surface of titanium implant as containers; AgNPs were grafted on TNT implant surface via a low pH-sensitive acetal linker (TNT-AL-AgNPs). SEM, TEM, AFM, FTIR as well as XPS data showed that AgNPs have been successfully linked to TNT via acetal linker without affecting the physicochemical characteristics of TNT. The pH 5.5 enhanced AgNPs release from TNT-AL-AgNPs implant compared with pH 7.4. AgNPs released at pH 5.5 robustly increased antimicrobial activities against gram-positive and gram-negative bacteria compared with AgNPs released at pH 7.4. TNT-AL-AgNPs implant enhanced osteoblast proliferation, differentiation, and did not affect osteoblast morphology in vitro. In conclusion, incorporation of AgNPs in TNT via acetal linker maintained the surface characteristics of TNT. TNT-AL-AgNPs implant was biocompatible to osteoblasts and showed osteoinductive properties. AgNPs were released from TNT-AL-AgNPs implant in high dose at pH 5.5, and this release showed strong antimicrobial properties in vitro. Therefore, this novel design of low pH-triggered AgNPs releasing TNT-AL-AgNPs could be an infection-triggered antimicrobial releasing implant model to control peri-implant infection. Copyright © 2017 Elsevier B.V. All rights reserved.

Photoresponsive cross-linked polymeric particles for phototriggered burst release.

PubMed

Wang, Zhen; Yu, Lili; Lv, Cong; Wang, Peng; Chen, Yedong; Tang, Xinjing

2013-01-01

We synthesized a series of cross-linked photoresponsive polymeric particles with photolabile monomers and cross-linkers through miniemulsion polymerization. These particles are quite stable in dark, while light irradiation caused the breakage of particles and the efficient release of encapsulated contents up to 95% based on Nile red fluorescence. Photoswitches of particle systems were confirmed by fluorescence spectroscopy, SEM and colorimetry. Particle uptake and triggered release in RAW264.7 cells were confirmed by fluorescein diacetate loaded particles. © 2013 The Authors. Photochemistry and Photobiology © 2013 The American Society of Photobiology.

[Effectiveness of dorsal metacarpal island flap for treating scar contracture of finger web].

PubMed

Qian, Jun; Rui, Yongjun; Zhang, Quanrong; Xue, Mingyu; Zhang, Zhihai

2011-11-01

To investigate the effectiveness of dorsal metacarpal island flap for treating scar contracture of the finger web. Between June 2009 and December 2010, 10 patients with scar contracture of the finger web were treated. There were 6 males and 4 females with an average age of 30 years (range, 14-57 years). Scar contracture was caused by injury in 8 cases, by burn in 1 case, and by operation in 1 case. The locations were the 1st web space in 1 case, the 2nd web space in 3 cases, the 3rd web space in 5 cases, and the 4th web space in 1 case. The disease duration was 3 to 9 months with an average of 5 months. The maximum abduction was 10-20 degrees. After web space scar release, the dorsal metacarpal island flap (3.5 cm x 1.2 cm-4.0 cm x 2.0 cm in size) was used to reconstruct web space (2.0 cm x 1.0 cm-3.0 cm x 1.8 cm in size). The donor site was directly sutured or repaired with local flaps. At 2 days after operation, necrosis occurred in 1 flap, which healed by extractive treatment. The other flaps survived and wound healed by first intention; all the flaps at donor sites survived and incision healed by first intention. Ten patients were followed up 6 to 15 months (mean, 9 months). The reconstructed web space had good appearance, the maximum abduction was 80 degrees in 1 case of the 1st web space scars contracture, and the maximum abduction was 35-45 degrees (mean, 40 degrees) in the other 9 cases. In 8 scar patients causing by injury, no scar contracture recurred during follow-up. It can achieve good results in appearance and function to use dorsal metacarpal island flap for treating scar contracture of the finger web.

Selective recruitment of single motor units in human flexor digitorum superficialis muscle during flexion of individual fingers.

PubMed

Butler, T J; Kilbreath, S L; Gorman, R B; Gandevia, S C

2005-08-15

Flexor digitorum superficialis (FDS) is an extrinsic multi-tendoned muscle which flexes the proximal interphalangeal joints of the four fingers. It comprises four digital components, each with a tendon that inserts onto its corresponding finger. To determine the degree to which these digital components can be selectively recruited by volition, we recorded the activity of a single motor unit in one component via an intramuscular electrode while the subject isometrically flexed each of the remaining fingers, one at a time. The finger on which the unit principally acted was defined as the 'test finger' and that which flexed isometrically was the 'active' finger. Activity in 79 units was recorded. Isometric finger flexion forces of 50% maximum voluntary contraction (MVC) activated less than 50% of single units in components of FDS acting on fingers that were not voluntarily flexed. With two exceptions, the median recruitment threshold for all active-test finger combinations involving the index, middle, ring and little finger test units was between 49 and 60% MVC (60% MVC being the value assigned to those not recruited). The exceptions were flexion of the little finger while recording from ring finger units (median: 40% MVC), and vice versa (median: 2% MVC). For all active-test finger combinations, only 35/181 units were activated when the active finger flexed at less than 20% MVC, and the fingers were adjacent for 28 of these. Functionally, to recruit FDS units during grasping and lifting, relatively heavy objects were required, although systematic variation occurred with the width of the object. In conclusion, FDS components can be selectively activated by volition and this may be especially important for grasping at high forces with one or more fingers.

Ca2+-induced Ca2+ Release Phenomena in Mammalian Sympathetic Neurons Are Critically Dependent on the Rate of Rise of Trigger Ca2+

PubMed Central

Hernández-Cruz, Arturo; Escobar, Ariel L.; Jiménez, Nicolás

1997-01-01

The role of ryanodine-sensitive intracellular Ca2+ stores present in nonmuscular cells is not yet completely understood. Here we examine the physiological parameters determining the dynamics of caffeine-induced Ca2+ release in individual fura-2–loaded sympathetic neurons. Two ryanodine-sensitive release components were distinguished: an early, transient release (TR) and a delayed, persistent release (PR). The TR component shows refractoriness, depends on the filling status of the store, and requires caffeine concentrations ≥10 mM. Furthermore, it is selectively suppressed by tetracaine and intracellular BAPTA, which interfere with Ca2+-mediated feedback loops, suggesting that it constitutes a Ca2+-induced Ca2+-release phenomenon. The dynamics of release is markedly affected when Sr2+ substitutes for Ca2+, indicating that Sr2+ release may operate with lower feedback gain than Ca2+ release. Our data indicate that when the initial release occurs at an adequately fast rate, Ca2+ triggers further release, producing a regenerative response, which is interrupted by depletion of releasable Ca2+ and Ca2+-dependent inactivation. A compartmentalized linear diffusion model can reproduce caffeine responses: When the Ca2+ reservoir is full, the rapid initial Ca2+ rise determines a faster occupation of the ryanodine receptor Ca2+ activation site giving rise to a regenerative release. With the store only partially loaded, the slower initial Ca2+ rise allows the inactivating site of the release channel to become occupied nearly as quickly as the activating site, thereby suppressing the initial fast release. The PR component is less dependent on the store's Ca2+ content. This study suggests that transmembrane Ca2+ influx in rat sympathetic neurons does not evoke widespread amplification by CICR because of its inability to raise [Ca2+] near the Ca2+ release channels sufficiently fast to overcome their Ca2+-dependent inactivation. Conversely, caffeine-induced Ca2+ release can undergo considerable amplification especially when Ca2+ stores are full. We propose that the primary function of ryanodine-sensitive stores in neurons and perhaps in other nonmuscular cells, is to emphasize subcellular Ca2+ gradients resulting from agonist-induced intracellular release. The amplification gain is dependent both on the agonist concentration and on the filling status of intracellular Ca2+ stores. PMID:9041445

Finger posture modulates structural body representations

PubMed Central

Tamè, Luigi; Dransfield, Elanah; Quettier, Thomas; Longo, Matthew R.

2017-01-01

Patients with lesions of the left posterior parietal cortex commonly fail in identifying their fingers, a condition known as finger agnosia, yet are relatively unimpaired in sensation and skilled action. Such dissociations have traditionally been interpreted as evidence that structural body representations (BSR), such as the body structural description, are distinct from sensorimotor representations, such as the body schema. We investigated whether performance on tasks commonly used to assess finger agnosia is modulated by changes in hand posture. We used the ‘in between’ test in which participants estimate the number of unstimulated fingers between two touched fingers or a localization task in which participants judge which two fingers were stimulated. Across blocks, the fingers were placed in three levels of splay. Judged finger numerosity was analysed, in Exp. 1 by direct report and in Exp. 2 as the actual number of fingers between the fingers named. In both experiments, judgments were greater when non-adjacent stimulated fingers were positioned far apart compared to when they were close together or touching, whereas judgements were unaltered when adjacent fingers were stimulated. This demonstrates that BSRs are not fixed, but are modulated by the real-time physical distances between body parts. PMID:28223685

Epigenetic regulation of puberty via Zinc finger protein-mediated transcriptional repression

PubMed Central

Lomniczi, Alejandro; Wright, Hollis; Castellano, Juan Manuel; Matagne, Valerie; Toro, Carlos A.; Ramaswamy, Suresh; Plant, Tony M.; Ojeda, Sergio R.

2015-01-01

In primates, puberty is unleashed by increased GnRH release from the hypothalamus following an interval of juvenile quiescence. GWAS implicates Zinc finger (ZNF) genes in timing human puberty. Here we show that hypothalamic expression of several ZNFs decreased in agonadal male monkeys in association with the pubertal reactivation of gonadotropin secretion. Expression of two of these ZNFs, GATAD1 and ZNF573, also decreases in peripubertal female monkeys. However, only GATAD1 abundance increases when gonadotropin secretion is suppressed during late infancy. Targeted delivery of GATAD1 or ZNF573 to the rat hypothalamus delays puberty by impairing the transition of a transcriptional network from an immature repressive epigenetic configuration to one of activation. GATAD1 represses transcription of two key puberty-related genes, KISS1 and TAC3, directly, and reduces the activating histone mark H3K4me2 at each promoter via recruitment of histone demethylase KDM1A. We conclude that GATAD1 epitomizes a subset of ZNFs involved in epigenetic repression of primate puberty. PMID:26671628

Development of a press and drag method for hyperlink selection on smartphones.

PubMed

Chang, Joonho; Jung, Kihyo

2017-11-01

The present study developed a novel touch method for hyperlink selection on smartphones consisting of two sequential finger interactions: press and drag motions. The novel method requires a user to press a target hyperlink, and if a touch error occurs he/she can immediately correct the touch error by dragging the finger without releasing it in the middle. The method was compared with two existing methods in terms of completion time, error rate, and subjective rating. Forty college students participated in the experiments with different hyperlink sizes (4-pt, 6-pt, 8-pt, and 10-pt) on a touch-screen device. When hyperlink size was small (4-pt and 6-pt), the novel method (time: 826 msec; error: 0.6%) demonstrated better completion time and error rate than the current method (time: 1194 msec; error: 22%). In addition, the novel method (1.15, slightly satisfied, in 7-pt bipolar scale) had significantly higher satisfaction scores than the two existing methods (0.06, neutral). Copyright © 2017 Elsevier Ltd. All rights reserved.

Integration of a Micro-Chip Amino Acid Chirality Detector into the MOD Instrument Concept

NASA Technical Reports Server (NTRS)

Bada, Jeffrey L.; Grunthaner, Frank; Mathies, Richard

2004-01-01

The MOD (Mars Organic Detector) instrument concept consists of a sublimation apparatus for organic compound isolation connected to a microfabricated microfluidic analyzer containing a sipper, pumps and a separation channel for organic compound characterization. The target organic compounds are amino acids and polycyclic aromatic hydrocarbons (PAHs). Solid samples are placed within the sublimation apparatus and heated to release organic compounds which sublime onto a cold finger. Half of the cold finger is coated with fluorescamine. which reacts with amino acids and other primary amines to generate an intense fluorescent derivative while the other half is uncoated and is used to directly detect PAH fluorescence, A capillary sipper is then used to dissolve and sample the labeled amino acids and integrated microfabricated pumps transport the labeled amino acids to the chip for analysis. The sample is separated using capillary zone electrophoresis (CZE) together with chiral dextrins to determine amino acid composition and chirality. During the grant period, the following steps have been completed toward the development of a robust instrument and chemistry.

Biointerfacing polymeric microcapsules for in vivo near-infrared light-triggered drug release

NASA Astrophysics Data System (ADS)

Shao, Jingxin; Xuan, Mingjun; Si, Tieyan; Dai, Luru; He, Qiang

2015-11-01

Seeking safe and effective water-soluble drug carriers is of great significance in nanomedicine. To achieve this goal, we present a novel drug delivery system based on biointerfacing hollow polymeric microcapsules for effectively encapsulating water-soluble antitumor drug and gold nanorod (GNR) functionalization for triggered release of therapeutic drugs on-demand using low power near-infrared (NIR) radiation. The surface of polymeric microcapsules is covered with fluidic lipid bilayers to decrease the permeability of the wall of polymeric capsules. The temperature increase upon NIR illumination deconstructs the structure of the lipid membrane and polyelectrolyte multilayers, which in turn results in the rapid release of encapsulated water-soluble drug. In vivo antitumor tests demonstrate that this microcapsule has the effective ability of inhibiting tumor growth and preventing metastases. Real time in vivo fluorescence imaging results confirm that capsules can be excreted gradually from the animal body which in turn demonstrates the biocompatibility and biodegradation of these biointerfacing GNR-microcapsules. This intelligent system provides a novel anticancer platform with the advantages of controlled release, biological friendliness and credible biosafety.Seeking safe and effective water-soluble drug carriers is of great significance in nanomedicine. To achieve this goal, we present a novel drug delivery system based on biointerfacing hollow polymeric microcapsules for effectively encapsulating water-soluble antitumor drug and gold nanorod (GNR) functionalization for triggered release of therapeutic drugs on-demand using low power near-infrared (NIR) radiation. The surface of polymeric microcapsules is covered with fluidic lipid bilayers to decrease the permeability of the wall of polymeric capsules. The temperature increase upon NIR illumination deconstructs the structure of the lipid membrane and polyelectrolyte multilayers, which in turn results in the rapid release of encapsulated water-soluble drug. In vivo antitumor tests demonstrate that this microcapsule has the effective ability of inhibiting tumor growth and preventing metastases. Real time in vivo fluorescence imaging results confirm that capsules can be excreted gradually from the animal body which in turn demonstrates the biocompatibility and biodegradation of these biointerfacing GNR-microcapsules. This intelligent system provides a novel anticancer platform with the advantages of controlled release, biological friendliness and credible biosafety. Electronic supplementary information (ESI) available. See DOI: 10.1039/c5nr06350g

Design and analysis of an underactuated anthropomorphic finger for upper limb prosthetics.

PubMed

Omarkulov, Nurdos; Telegenov, Kuat; Zeinullin, Maralbek; Begalinova, Ainur; Shintemirov, Almas

2015-01-01

This paper presents the design of a linkage based finger mechanism ensuring extended range of anthropomorphic gripping motions. The finger design is done using a path-point generation method based on geometrical dimensions and motion of a typical index human finger. Following the design description, and its kinematics analysis, the experimental evaluation of the finger gripping performance is presented using the finger 3D printed prototype. The finger underactuation is achieved by utilizing mechanical linkage system, consisting of two crossed four-bar linkage mechanisms. It is shown that the proposed finger design can be used to design a five-fingered anthropomorphic hand and has the potential for upper limb prostheses development.

Finger wear detection for production line battery tester

DOEpatents

Depiante, E.V.

1997-11-18

A method is described for detecting wear in a battery tester probe. The method includes providing a battery tester unit having at least one tester finger, generating a tester signal using the tester fingers and battery tester unit with the signal characteristic of the electrochemical condition of the battery and the tester finger, applying wavelet transformation to the tester signal including computing a mother wavelet to produce finger wear indicator signals, analyzing the signals to create a finger wear index, comparing the wear index for the tester finger with the index for a new tester finger and generating a tester finger signal change signal to indicate achieving a threshold wear change. 9 figs.

Magnetic/NIR-thermally responsive hybrid nanogels for optical temperature sensing, tumor cell imaging and triggered drug release

NASA Astrophysics Data System (ADS)

Wang, Hui; Yi, Jinhui; Mukherjee, Sumit; Banerjee, Probal; Zhou, Shuiqin

2014-10-01

The paper demonstrates a class of multifunctional core-shell hybrid nanogels with fluorescent and magnetic properties, which have been successfully developed for simultaneous optical temperature sensing, tumor cell imaging and magnetic/NIR-thermally responsive drug carriers. The as-synthesized hybrid nanogels were designed by coating bifunctional nanoparticles (BFNPs, fluorescent carbon dots embedded in the porous carbon shell and superparamagnetic iron oxide nanocrystals clustered in the core) with a thermo-responsive poly(N-isopropylacrylamide-co-acrylamide) [poly(NIPAM-AAm)]-based hydrogel as the shell. The BFNPs in hybrid nanogels not only demonstrate excellent photoluminescence (PL) and photostability due to the fluorescent carbon dots embedded in the porous carbon shell, but also has targeted drug accumulation potential and a magnetic-thermal conversion ability due to the superparamagnetic iron oxide nanocrystals clustered in the core. The thermo-responsive poly(NIPAM-AAm)-based gel shell can not only modify the physicochemical environment of the BFNPs core to manipulate the fluorescence intensity for sensing the variation of the environmental temperature, but also regulate the release rate of the loaded anticancer drug (curcumin) by varying the local temperature of environmental media. In addition, the carbon layer of BFNPs can adsorb and convert the NIR light to heat, leading to a promoted drug release under NIR irradiation and improving the therapeutic efficacy of drug-loaded hybrid nanogels. Furthermore, the superparamagnetic iron oxide nanocrystals in the core of BFNPs can trigger localized heating using an alternating magnetic field, leading to a phase change in the polymer gel to trigger the release of loaded drugs. Finally, the multifunctional hybrid nanogels can overcome cellular barriers to enter the intracellular region and light up the mouse melanoma B16F10 cells. The demonstrated hybrid nanogels would be an ideal system for the biomedical applications due to their excellent optical properties, magnetic properties, high drug loading capacity and responsive drug release behavior.The paper demonstrates a class of multifunctional core-shell hybrid nanogels with fluorescent and magnetic properties, which have been successfully developed for simultaneous optical temperature sensing, tumor cell imaging and magnetic/NIR-thermally responsive drug carriers. The as-synthesized hybrid nanogels were designed by coating bifunctional nanoparticles (BFNPs, fluorescent carbon dots embedded in the porous carbon shell and superparamagnetic iron oxide nanocrystals clustered in the core) with a thermo-responsive poly(N-isopropylacrylamide-co-acrylamide) [poly(NIPAM-AAm)]-based hydrogel as the shell. The BFNPs in hybrid nanogels not only demonstrate excellent photoluminescence (PL) and photostability due to the fluorescent carbon dots embedded in the porous carbon shell, but also has targeted drug accumulation potential and a magnetic-thermal conversion ability due to the superparamagnetic iron oxide nanocrystals clustered in the core. The thermo-responsive poly(NIPAM-AAm)-based gel shell can not only modify the physicochemical environment of the BFNPs core to manipulate the fluorescence intensity for sensing the variation of the environmental temperature, but also regulate the release rate of the loaded anticancer drug (curcumin) by varying the local temperature of environmental media. In addition, the carbon layer of BFNPs can adsorb and convert the NIR light to heat, leading to a promoted drug release under NIR irradiation and improving the therapeutic efficacy of drug-loaded hybrid nanogels. Furthermore, the superparamagnetic iron oxide nanocrystals in the core of BFNPs can trigger localized heating using an alternating magnetic field, leading to a phase change in the polymer gel to trigger the release of loaded drugs. Finally, the multifunctional hybrid nanogels can overcome cellular barriers to enter the intracellular region and light up the mouse melanoma B16F10 cells. The demonstrated hybrid nanogels would be an ideal system for the biomedical applications due to their excellent optical properties, magnetic properties, high drug loading capacity and responsive drug release behavior. Electronic supplementary information (ESI) available: Fig. S1-S12. See DOI: 10.1039/c4nr03748k

Differing Dynamics of Intrapersonal and Interpersonal Coordination: Two-finger and Four-Finger Tapping Experiments

PubMed Central

Kodama, Kentaro; Furuyama, Nobuhiro; Inamura, Tetsunari

2015-01-01

Finger-tapping experiments were conducted to examine whether the dynamics of intrapersonal and interpersonal coordination systems can be described equally by the Haken—Kelso—Bunz model, which describes inter-limb coordination dynamics. This article reports the results of finger-tapping experiments conducted in both systems. Two within-subject factors were investigated: the phase mode and the number of fingers. In the intrapersonal experiment (Experiment 1), the participants were asked to tap, paced by a gradually hastening auditory metronome, looking at their fingers moving, using the index finger in the two finger condition, or the index and middle finger in the four-finger condition. In the interpersonal experiment (Experiment 2), pairs of participants performed the task while each participant used the outside hand, tapping with the index finger in the two finger condition, or the index and middle finger in the four-finger condition. Some results did not agree with the HKB model predictions. First, from Experiment 1, no significant difference was observed in the movement stability between the in-phase and anti-phase modes in the two finger condition. Second, from Experiment 2, no significant difference was found in the movement stability between the in-phase and anti-phase mode in the four-finger condition. From these findings, different coordination dynamics were inferred between intrapersonal and interpersonal coordination systems against prediction from the previous studies. Results were discussed according to differences between intrapersonal and interpersonal coordination systems in the availability of perceptual information and the complexity in the interaction between limbs derived from a nested structure. PMID:26070119

Transfer of tactile perceptual learning to untrained neighboring fingers reflects natural use relationships

PubMed Central

Harrar, Vanessa; Oliver, Jonathan; Johansen-Berg, Heidi; Spence, Charles

2015-01-01

Tactile learning transfers from trained to untrained fingers in a pattern that reflects overlap between the representations of fingers in the somatosensory system (e.g., neurons with multifinger receptive fields). While physical proximity on the body is known to determine the topography of somatosensory representations, tactile coactivation is also an established organizing principle of somatosensory topography. In this study we investigated whether tactile coactivation, induced by habitual inter-finger cooperative use (use pattern), shapes inter-finger overlap. To this end, we used psychophysics to compare the transfer of tactile learning from the middle finger to its adjacent fingers. This allowed us to compare transfer to two fingers that are both physically and cortically adjacent to the middle finger but have differing use patterns. Specifically, the middle finger is used more frequently with the ring than with the index finger. We predicted this should lead to greater representational overlap between the former than the latter pair. Furthermore, this difference in overlap should be reflected in differential learning transfer from the middle to index vs. ring fingers. Subsequently, we predicted temporary learning-related changes in the middle finger's representation (e.g., cortical magnification) would cause transient interference in perceptual thresholds of the ring, but not the index, finger. Supporting this, longitudinal analysis revealed a divergence where learning transfer was fast to the index finger but relatively delayed to the ring finger. Our results support the theory that tactile coactivation patterns between digits affect their topographic relationships. Our findings emphasize how action shapes perception and somatosensory organization. PMID:26631145

Transfer of tactile perceptual learning to untrained neighboring fingers reflects natural use relationships.

PubMed

Dempsey-Jones, Harriet; Harrar, Vanessa; Oliver, Jonathan; Johansen-Berg, Heidi; Spence, Charles; Makin, Tamar R

2016-03-01

Tactile learning transfers from trained to untrained fingers in a pattern that reflects overlap between the representations of fingers in the somatosensory system (e.g., neurons with multifinger receptive fields). While physical proximity on the body is known to determine the topography of somatosensory representations, tactile coactivation is also an established organizing principle of somatosensory topography. In this study we investigated whether tactile coactivation, induced by habitual inter-finger cooperative use (use pattern), shapes inter-finger overlap. To this end, we used psychophysics to compare the transfer of tactile learning from the middle finger to its adjacent fingers. This allowed us to compare transfer to two fingers that are both physically and cortically adjacent to the middle finger but have differing use patterns. Specifically, the middle finger is used more frequently with the ring than with the index finger. We predicted this should lead to greater representational overlap between the former than the latter pair. Furthermore, this difference in overlap should be reflected in differential learning transfer from the middle to index vs. ring fingers. Subsequently, we predicted temporary learning-related changes in the middle finger's representation (e.g., cortical magnification) would cause transient interference in perceptual thresholds of the ring, but not the index, finger. Supporting this, longitudinal analysis revealed a divergence where learning transfer was fast to the index finger but relatively delayed to the ring finger. Our results support the theory that tactile coactivation patterns between digits affect their topographic relationships. Our findings emphasize how action shapes perception and somatosensory organization. Copyright © 2016 the American Physiological Society.

Impact of Finger Type in Fingerprint Authentication

NASA Astrophysics Data System (ADS)

Gafurov, Davrondzhon; Bours, Patrick; Yang, Bian; Busch, Christoph

Nowadays fingerprint verification system is the most widespread and accepted biometric technology that explores various features of the human fingers for this purpose. In general, every normal person has 10 fingers with different size. Although it is claimed that recognition performance with little fingers can be less accurate compared to other finger types, to our best knowledge, this has not been investigated yet. This paper presents our study on the topic of influence of the finger type into fingerprint recognition performance. For analysis we employ two fingerprint verification software packages (one public and one commercial). We conduct test on GUC100 multi sensor fingerprint database which contains fingerprint images of all 10 fingers from 100 subjects. Our analysis indeed confirms that performance with small fingers is less accurate than performance with the others fingers of the hand. It also appears that best performance is being obtained with thumb or index fingers. For example, performance deterioration from the best finger (i.e. index or thumb) to the worst fingers (i.e. small ones) can be in the range of 184%-1352%.

Metal coated colloidosomes as carriers for an antibiotic

NASA Astrophysics Data System (ADS)

Sun, Qian; Zhao, Ziyan; Hall, Elizabeth A. H.; Routh, Alexander F.

2018-06-01

Colloidosomes are polymer shell microcapsules. They are stable and easy to prepare and have been used to encapsulate drugs for release at specific areas in the body. Traditional polymer shell capsules cannot totally seal drugs, since they are porous and small molecules diffuse through the polymer shell. In this paper, we report a method for encapsulating an antibiotic kanamycin using gold or silver coated colloidosomes. The colloidosomes are impermeable and can be triggered using ultrasound. To investigate the application of the capsules in a biological system, Escherichia Coli (E.coli) was chosen as a model organism. After triggering, the released antibiotic, as well as the metal shell fragments, kill E.coli. Both the silver and gold shells colloidosomes are toxic to this bacterial system and the gold coated colloidosomes can load a higher concentration of kanamycin.

Halloysite Nanotubes: Controlled Access and Release by Smart Gates.

PubMed

Cavallaro, Giuseppe; Danilushkina, Anna A; Evtugyn, Vladimir G; Lazzara, Giuseppe; Milioto, Stefana; Parisi, Filippo; Rozhina, Elvira V; Fakhrullin, Rawil F

2017-07-28

Hollow halloysite nanotubes have been used as nanocontainers for loading and for the triggered release of calcium hydroxide for paper preservation. A strategy for placing end-stoppers into the tubular nanocontainer is proposed and the sustained release from the cavity is reported. The incorporation of Ca(OH)₂ into the nanotube lumen, as demonstrated using transmission electron microscopy (TEM) imaging and Energy Dispersive X-ray (EDX) mapping, retards the carbonatation, delaying the reaction with CO₂ gas. This effect can be further controlled by placing the end-stoppers. The obtained material is tested for paper deacidification. We prove that adding halloysite filled with Ca(OH)₂ to paper can reduce the impact of acid exposure on both the mechanical performance and pH alteration. The end-stoppers have a double effect: they preserve the calcium hydroxide from carbonation, and they prevent from the formation of highly basic pH and trigger the response to acid exposure minimizing the pH drop-down. These features are promising for a composite nanoadditive in the smart protection of cellulose-based materials.

Targeted intracellular delivery of proteins with spatial and temporal control.

PubMed

Morales, Demosthenes P; Braun, Gary B; Pallaoro, Alessia; Chen, Renwei; Huang, Xiao; Zasadzinski, Joseph A; Reich, Norbert O

2015-02-02

While a host of methods exist to deliver genetic materials or small molecules to cells, very few are available for protein delivery to the cytosol. We describe a modular, light-activated nanocarrier that transports proteins into cells by receptor-mediated endocytosis and delivers the cargo to the cytosol by light triggered endosomal escape. The platform is based on hollow gold nanoshells (HGN) with polyhistidine tagged proteins attached through an avidity-enhanced, nickel chelation linking layer; here, we used green fluorescent protein (GFP) as a model deliverable cargo. Endosomal uptake of the GFP loaded nanocarrier was mediated by a C-end Rule (CendR) internalizing peptide fused to the GFP. Focused femtosecond pulsed-laser excitation triggered protein release from the nanocarrier and endosome disruption, and the released protein was capable of targeting the nucleoli, a model intracellular organelle. We further demonstrate the generality of the approach by loading and releasing Sox2 and p53. This method for targeting of individual cells, with resolution similar to microinjection, provides spatial and temporal control over protein delivery.

The primed SNARE–complexin–synaptotagmin complex for neuronal exocytosis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhou, Qiangjun; Zhou, Peng; Wang, Austin L.

Synaptotagmin, complexin, and neuronal SNARE (soluble N-ethylmaleimide sensitive factor attachment protein receptor) proteins mediate evoked synchronous neurotransmitter release, but the molecular mechanisms mediating the cooperation between these molecules remain unclear. Here we determine crystal structures of the primed pre-fusion SNARE–complexin–synaptotagmin-1 complex. These structures reveal an unexpected tripartite interface between synaptotagmin-1 and both the SNARE complex and complexin. Simultaneously, a second synaptotagmin-1 molecule interacts with the other side of the SNARE complex via the previously identified primary interface. Mutations that disrupt either interface in solution also severely impair evoked synchronous release in neurons, suggesting that both interfaces are essential for themore » primed pre-fusion state. Ca 2+ binding to the synaptotagmin-1 molecules unlocks the complex, allows full zippering of the SNARE complex, and triggers membrane fusion. In conclusion, the tripartite SNARE–complexin–synaptotagmin-1 complex at a synaptic vesicle docking site has to be unlocked for triggered fusion to start, explaining the cooperation between complexin and synaptotagmin-1 in synchronizing evoked release on the sub-millisecond timescale.« less

The primed SNARE–complexin–synaptotagmin complex for neuronal exocytosis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhou, Qiangjun; Zhou, Peng; Wang, Austin L.

Synaptotagmin, complexin, and neuronal SNARE (soluble N-ethylmaleimide sensitive factor attachment protein receptor) proteins mediate evoked synchronous neurotransmitter release, but the molecular mechanisms mediating the cooperation between these molecules remain unclear. Here we determine crystal structures of the primed pre-fusion SNARE–complexin–synaptotagmin-1 complex. These structures reveal an unexpected tripartite interface between synaptotagmin-1 and both the SNARE complex and complexin. Simultaneously, a second synaptotagmin-1 molecule interacts with the other side of the SNARE complex via the previously identified primary interface. Mutations that disrupt either interface in solution also severely impair evoked synchronous release in neurons, suggesting that both interfaces are essential for themore » primed pre-fusion state. Ca2+ binding to the synaptotagmin-1 molecules unlocks the complex, allows full zippering of the SNARE complex, and triggers membrane fusion. The tripartite SNARE–complexin–synaptotagmin-1 complex at a synaptic vesicle docking site has to be unlocked for triggered fusion to start, explaining the cooperation between complexin and synaptotagmin-1 in synchronizing evoked release on the sub-millisecond timescale.« less

The primed SNARE–complexin–synaptotagmin complex for neuronal exocytosis

DOE PAGES

Zhou, Qiangjun; Zhou, Peng; Wang, Austin L.; ...

2017-08-16

Synaptotagmin, complexin, and neuronal SNARE (soluble N-ethylmaleimide sensitive factor attachment protein receptor) proteins mediate evoked synchronous neurotransmitter release, but the molecular mechanisms mediating the cooperation between these molecules remain unclear. Here we determine crystal structures of the primed pre-fusion SNARE–complexin–synaptotagmin-1 complex. These structures reveal an unexpected tripartite interface between synaptotagmin-1 and both the SNARE complex and complexin. Simultaneously, a second synaptotagmin-1 molecule interacts with the other side of the SNARE complex via the previously identified primary interface. Mutations that disrupt either interface in solution also severely impair evoked synchronous release in neurons, suggesting that both interfaces are essential for themore » primed pre-fusion state. Ca 2+ binding to the synaptotagmin-1 molecules unlocks the complex, allows full zippering of the SNARE complex, and triggers membrane fusion. In conclusion, the tripartite SNARE–complexin–synaptotagmin-1 complex at a synaptic vesicle docking site has to be unlocked for triggered fusion to start, explaining the cooperation between complexin and synaptotagmin-1 in synchronizing evoked release on the sub-millisecond timescale.« less

Self-assembled nanofiber hydrogels for mechanoresponsive therapeutic anti-TNFα antibody delivery.

PubMed

Kaplan, J A; Barthélémy, P; Grinstaff, M W

2016-04-30

Low molecular weight hydrogels, prepared from glycosyl-nucleoside-lipid amphiphiles, exhibit shear-thinning behaviour and reversible thermally- and mechanically-triggered sol-gel transitions. Using mechanical shear stimulation, the release of entrapped anti-TNFα increases and the released anti-TNFα demonstrates efficacy in in vitro neutralization bioassays. Delivery of anti-TNFα is of general interest and broad medicinal utility for treating autoimmune diseases such as rheumatoid arthritis.

Synthesis and characterization of a multifunctional gold-doxorubicin nanoparticle system for pH triggered intracellular anticancer drug release.

PubMed

Khutale, Ganesh V; Casey, Alan

2017-10-01

A nanoparticle drug carrier system has been developed to alter the cellular uptake and chemotherapeutic performance of an available chemotherapeutic drug. The system comprises of a multifunctional gold nanoparticle based drug delivery system (Au-PEG-PAMAM-DOX) as a novel platform for intracellular delivery of doxorubicin (DOX). Spherical gold nanoparticles were synthesized by a gold chloride reduction, stabilized with thiolated polyethylene glycol (PEG) and then covalently coupled with a polyamidoamine (PAMAM) G4 dendrimer. Further, conjugation of an anti-cancer drug doxorubicin to the dendrimer via amide bond resulted in Au-PEG-PAMAM-DOX drug delivery system. Acellular drug release studies proved that DOX released from Au-PEG-PAMAM-DOX at physiological pH was negligible but it was significantly increased at a weak acidic milieu. The intracellular drug release was monitored with confocal laser scanning microscopy analysis. In vitro viability studies showed an increase in the associated doxorubicin cytotoxicity not attributed to carrier components indicating the efficiency of the doxorubicin was improved, upon conjugation to the nano system. As such it is postulated that the developed pH triggered multifunctional doxorubicin-gold nanoparticle system, could lead to a promising platform for intracellular delivery of variety of anticancer drugs. Copyright © 2017 Elsevier B.V. All rights reserved.

Return to drug use and overdose after release from prison: a qualitative study of risk and protective factors.

PubMed

Binswanger, Ingrid A; Nowels, Carolyn; Corsi, Karen F; Glanz, Jason; Long, Jeremy; Booth, Robert E; Steiner, John F

2012-01-01

Former inmates are at high risk for death from drug overdose, especially in the immediate post-release period. The purpose of the study is to understand the drug use experiences, perceptions of overdose risk, and experiences with overdose among former prisoners. This qualitative study included former prison inmates (N=29) who were recruited within two months after their release. Interviewers conducted in-person, semi-structured interviews which explored participants' experiences and perceptions. Transcripts were analyzed utilizing a team-based method of inductive analysis. The following themes emerged: 1) Relapse to drugs and alcohol occurred in a context of poor social support, medical co-morbidity and inadequate economic resources; 2) former inmates experienced ubiquitous exposure to drugs in their living environments; 3) intentional overdose was considered "a way out" given situational stressors, and accidental overdose was perceived as related to decreased tolerance; and 4) protective factors included structured drug treatment programs, spirituality/religion, community-based resources (including self-help groups), and family. Former inmates return to environments that strongly trigger relapse to drug use and put them at risk for overdose. Interventions to prevent overdose after release from prison may benefit from including structured treatment with gradual transition to the community, enhanced protective factors, and reductions of environmental triggers to use drugs.

Intensity Variation Normalization for Finger Vein Recognition Using Guided Filter Based Singe Scale Retinex

PubMed Central

Xie, Shan Juan; Lu, Yu; Yoon, Sook; Yang, Jucheng; Park, Dong Sun

2015-01-01

Finger vein recognition has been considered one of the most promising biometrics for personal authentication. However, the capacities and percentages of finger tissues (e.g., bone, muscle, ligament, water, fat, etc.) vary person by person. This usually causes poor quality of finger vein images, therefore degrading the performance of finger vein recognition systems (FVRSs). In this paper, the intrinsic factors of finger tissue causing poor quality of finger vein images are analyzed, and an intensity variation (IV) normalization method using guided filter based single scale retinex (GFSSR) is proposed for finger vein image enhancement. The experimental results on two public datasets demonstrate the effectiveness of the proposed method in enhancing the image quality and finger vein recognition accuracy. PMID:26184226

Intensity Variation Normalization for Finger Vein Recognition Using Guided Filter Based Singe Scale Retinex.

PubMed

Xie, Shan Juan; Lu, Yu; Yoon, Sook; Yang, Jucheng; Park, Dong Sun

2015-07-14

Finger vein recognition has been considered one of the most promising biometrics for personal authentication. However, the capacities and percentages of finger tissues (e.g., bone, muscle, ligament, water, fat, etc.) vary person by person. This usually causes poor quality of finger vein images, therefore degrading the performance of finger vein recognition systems (FVRSs). In this paper, the intrinsic factors of finger tissue causing poor quality of finger vein images are analyzed, and an intensity variation (IV) normalization method using guided filter based single scale retinex (GFSSR) is proposed for finger vein image enhancement. The experimental results on two public datasets demonstrate the effectiveness of the proposed method in enhancing the image quality and finger vein recognition accuracy.

Zinc finger proteins in cancer progression.

PubMed

Jen, Jayu; Wang, Yi-Ching

2016-07-13

Zinc finger proteins are the largest transcription factor family in human genome. The diverse combinations and functions of zinc finger motifs make zinc finger proteins versatile in biological processes, including development, differentiation, metabolism and autophagy. Over the last few decades, increasing evidence reveals the potential roles of zinc finger proteins in cancer progression. However, the underlying mechanisms of zinc finger proteins in cancer progression vary in different cancer types and even in the same cancer type under different types of stress. Here, we discuss general mechanisms of zinc finger proteins in transcription regulation and summarize recent studies on zinc finger proteins in cancer progression. In this review, we also emphasize the importance of further investigations in elucidating the underlying mechanisms of zinc finger proteins in cancer progression.

EMG finger movement classification based on ANFIS

NASA Astrophysics Data System (ADS)

Caesarendra, W.; Tjahjowidodo, T.; Nico, Y.; Wahyudati, S.; Nurhasanah, L.

2018-04-01

An increase number of people suffering from stroke has impact to the rapid development of finger hand exoskeleton to enable an automatic physical therapy. Prior to the development of finger exoskeleton, a research topic yet important i.e. machine learning of finger gestures classification is conducted. This paper presents a study on EMG signal classification of 5 finger gestures as a preliminary study toward the finger exoskeleton design and development in Indonesia. The EMG signals of 5 finger gestures were acquired using Myo EMG sensor. The EMG signal features were extracted and reduced using PCA. The ANFIS based learning is used to classify reduced features of 5 finger gestures. The result shows that the classification of finger gestures is less than the classification of 7 hand gestures.

Cortical effect and functional recovery by the electromyography-triggered neuromuscular stimulation in chronic stroke patients.

PubMed

Shin, Hwa Kyung; Cho, Sang Hyun; Jeon, Hye-seon; Lee, Young-Hee; Song, Jun Chan; Jang, Sung Ho; Lee, Chu-Hee; Kwon, Yong Hyun

2008-09-19

We investigated the effect of electromyography (EMG)-triggered neuromuscular electrical stimulation (NMES; EMG-stim) on functional recovery of the hemiparetic hand and the related cortical activation pattern in chronic stroke patients. We enrolled 14 stroke patients, who were randomly assigned to the EMG-stim (n=7) or the control groups (n=7). The EMG-stim was applied to the wrist extensor of the EMG-stim group for two sessions (30 min/session) a day, five times per week for 10 weeks. Four functional tests (box and block, strength, the accuracy index, and the on/offset time of muscle contraction) and functional MRI (fMRI) were performed before and after treatment. fMRI was measured at 1.5 T in parallel with timed finger flexion-extension movements at a fixed rate. Following treatment, the EMG-stim group showed a significant improvement in all functional tests. The main cortical activation change with such functional improvement was shifted from the ipsilateral sensorimotor cortex (SMC) to the contralateral SMC. We demonstrated that 10-week EMG-stim can induce functional recovery and change of cortical activation pattern in the hemiparetic hand of chronic stroke patients.

The E3 ubiquitin ligase and RNA-binding protein ZNF598 orchestrates ribosome quality control of premature polyadenylated mRNAs

PubMed Central

Garzia, Aitor; Jafarnejad, Seyed Mehdi; Meyer, Cindy; Chapat, Clément; Gogakos, Tasos; Morozov, Pavel; Amiri, Mehdi; Shapiro, Maayan; Molina, Henrik; Tuschl, Thomas; Sonenberg, Nahum

2017-01-01

Cryptic polyadenylation within coding sequences (CDS) triggers ribosome-associated quality control (RQC), followed by degradation of the aberrant mRNA and polypeptide, ribosome disassembly and recycling. Although ribosomal subunit dissociation and nascent peptide degradation are well-understood, the molecular sensors of aberrant mRNAs and their mechanism of action remain unknown. We studied the Zinc Finger Protein 598 (ZNF598) using PAR-CLIP and revealed that it cross-links to tRNAs, mRNAs and rRNAs, thereby placing the protein on translating ribosomes. Cross-linked reads originating from AAA-decoding tRNALys(UUU) were 10-fold enriched over its cellular abundance, and poly-lysine encoded by poly(AAA) induced RQC in a ZNF598-dependent manner. Encounter with translated polyA segments by ZNF598 triggered ubiquitination of several ribosomal proteins, requiring the E2 ubiquitin ligase UBE2D3 to initiate RQC. Considering that human CDS are devoid of >4 consecutive AAA codons, sensing of prematurely placed polyA tails by a specialized RNA-binding protein is a novel nucleic-acid-based surveillance mechanism of RQC. PMID:28685749

The E3 ubiquitin ligase and RNA-binding protein ZNF598 orchestrates ribosome quality control of premature polyadenylated mRNAs.

PubMed

Garzia, Aitor; Jafarnejad, Seyed Mehdi; Meyer, Cindy; Chapat, Clément; Gogakos, Tasos; Morozov, Pavel; Amiri, Mehdi; Shapiro, Maayan; Molina, Henrik; Tuschl, Thomas; Sonenberg, Nahum

2017-07-07

Cryptic polyadenylation within coding sequences (CDS) triggers ribosome-associated quality control (RQC), followed by degradation of the aberrant mRNA and polypeptide, ribosome disassembly and recycling. Although ribosomal subunit dissociation and nascent peptide degradation are well-understood, the molecular sensors of aberrant mRNAs and their mechanism of action remain unknown. We studied the Zinc Finger Protein 598 (ZNF598) using PAR-CLIP and revealed that it cross-links to tRNAs, mRNAs and rRNAs, thereby placing the protein on translating ribosomes. Cross-linked reads originating from AAA-decoding tRNA Lys (UUU) were 10-fold enriched over its cellular abundance, and poly-lysine encoded by poly(AAA) induced RQC in a ZNF598-dependent manner. Encounter with translated polyA segments by ZNF598 triggered ubiquitination of several ribosomal proteins, requiring the E2 ubiquitin ligase UBE2D3 to initiate RQC. Considering that human CDS are devoid of >4 consecutive AAA codons, sensing of prematurely placed polyA tails by a specialized RNA-binding protein is a novel nucleic-acid-based surveillance mechanism of RQC.

Landslide susceptibility in the Tully Valley area, Finger Lakes region, New York

USGS Publications Warehouse

Jager, Stefan; Wieczorek, Gerald E.

1994-01-01

As a consequence of a large landslide in the Tully Valley, Onondaga County, New York, an investigation was undertaken to determine the factors responsible for the landslide in order to develop a model for regional landslide susceptibility. The April 27, 1993 Tully Valley landslide occurred within glacial lake clays overlain by till and colluvium on gentle slopes of 9-12 degrees. The landslide was triggered by extreme climatic events of prolonged heavy rainfall combined with rapid melting of a winter snowpack. A photoinventory and field checking of landslides within a 415 km2 study area, including the Tully Valley, revealed small recently-active landslides and other large dormant prehistoric landslides, probably Pleistocene in age. Similar to the larger Tully Valley landslide, the smaller recently-active landslides occurred in red, glacial lake clays very likely triggered by seasonal rainfall. The large dormant landslides have been stable for long periods as evidenced by slope denudational processes that have modified the landslides. These old and ancient landslides correspond with proglacial lake levels during the Pleistocene, suggesting that either inundation or rapid drainage was responsible for triggering these landslides. A logistic regression analysis was performed within a Geographic Information System (GIS) environment to develop a model of landslide susceptibility for the Tully Valley study area. Presence of glacial clays, slope angle, and glacial lake levels were used as explanatory variables for landslide incidence. The spatial probability of landsliding, categorized as low, moderate and high, is portrayed within 90-m square cells on the susceptibility map.

Central mechanisms of stress-induced headache.

PubMed

Cathcart, S; Petkov, J; Winefield, A H; Lushington, K; Rolan, P

2010-03-01

Stress is the most commonly reported trigger of an episode of chronic tension-type headache (CTTH); however, the causal significance has not been experimentally demonstrated to date. Stress may trigger CTTH through hyperalgesic effects on already sensitized pain pathways in CTTH sufferers. This hypothesis could be partially tested by examining pain sensitivity in an experimental model of stress-induced headache in CTTH sufferers. Such examinations have not been reported to date. We measured pericranial muscle tenderness and pain thresholds at the finger, head and shoulder in 23 CTTH sufferers (CTH-S) and 25 healthy control subjects (CNT) exposed to an hour-long stressful mental task, and in 23 CTTH sufferers exposed to an hour-long neutral condition (CTH-N). Headache developed in 91% of CTH-S, 4% of CNT, and 17% of CTH-N subjects. Headache sufferers had increased muscle tenderness and reduced pain thresholds compared with healthy controls. During the task, muscle tenderness increased and pain thresholds decreased in the CTH-S group compared with CTH-N and CNT groups. Pre-task muscle tenderness and reduction in pain threshold during task were predictive of the development and intensity of headache following task. The main findings are that stress induced a headache in CTTH sufferers, and this was associated with pre-task muscle tenderness and stress-induced reduction in pain thresholds. The results support the hypothesis that stress triggers CTTH through hyperalgesic effects on already increased pain sensitivity in CTTH sufferers, reducing the threshold to noxious input from pericranial structures.

Real time relationship between individual finger force and grip exertion on distal phalanges in linear force following tasks.

PubMed

Luo, Shi-Jian; Shu, Ge; Gong, Yan

2018-05-01

Individual finger force (FF) in a grip task is a vital concern in rehabilitation engineering and precise control of manipulators because disorders in any of the fingers will affect the stability or accuracy of the grip force (GF). To understand the functions of each finger in a dynamic grip exertion task, a GF following experiment with four individual fingers without thumb was designed. This study obtained four individual FFs from the distal phalanges with a cylindrical handle in dynamic GF following tasks. Ten healthy male subjects with similar hand sizes participated in the four-finger linear GF following tasks at different submaximal voluntary contraction (SMVC) levels. The total GF, individual FF, finger force contribution, and following error were subsequently calculated and analyzed. The statistics indicated the following: 1) the accuracy and stability of GF at low %MVC were significantly higher than those at high SMVC; 2) at low SMVC, the ability of the fingers to increase the GF was better than the ability to reduce it, but it was contrary at high SMVC; 3) when the target wave (TW) was changing, all four fingers strongly participated in the force exertion, but the participation of the little finger decreased significantly when TW remained stable; 4) the index finger and ring finger had a complementary relationship and played a vital role in the adjustment and control of GF. The middle finger and little finger had a minor influence on the force control and adjustment. In conclusion, each of the fingers had different functions in a GF following task. These findings can be used in the assessment of finger injury rehabilitation and for algorithms of precise control. Copyright © 2017 Elsevier Ltd. All rights reserved.

Preliminary Test Results of a Non-Contacting Finger Seal on a Herringbone-Grooved Rotor

NASA Technical Reports Server (NTRS)

Proctor, Margaret P.; Delgado, Irebert R.

2009-01-01

The baseline non-contacting finger seal is a NASA patented design. The primary difference between it and Gul Aroras design patented by AlliedSignal is that there are no lift pads on the high pressure fingers. The baseline non-contacting finger seal is comprised of a back plate, aft spacer, aft (or low pressure) finger element, forward (or high pressure) finger element, forward spacer, and front plate. The components are held together with 20 flat head screws. A typical seal would have a back plate of approximately the same thickness as the front plate and would be riveted together. The thicker back plate allows use of threaded fasteners so that different finger elements can be tested without having to replace all the individual seal components. The finger elements are essentially washers made of thin sheet stock with multiple curved slots machined around the inner diameter to form the fingers. They are clocked so that the fingers of one cover the slots of the other. The aft finger element fingers have axial extensions or "lift pads" at the seal id that are concentric to the rotor. The fingers act as cantilever beams and flex in response to rotor dynamic motion and radial growth of the rotor due to centrifugal or thermal forces.

Weak endogenous Ca2+ buffering supports sustained synaptic transmission by distinct mechanisms in rod and cone photoreceptors in salamander retina

PubMed Central

Van Hook, Matthew J; Thoreson, Wallace B

2015-01-01

Differences in synaptic transmission between rod and cone photoreceptors contribute to different response kinetics in rod- versus cone-dominated visual pathways. We examined Ca2+ dynamics in synaptic terminals of tiger salamander photoreceptors under conditions that mimicked endogenous buffering to determine the influence on kinetically and mechanistically distinct components of synaptic transmission. Measurements of ICl(Ca) confirmed that endogenous Ca2+ buffering is equivalent to ˜0.05 mmol/L EGTA in rod and cone terminals. Confocal imaging showed that with such buffering, depolarization stimulated large, spatially unconstrained [Ca2+] increases that spread throughout photoreceptor terminals. We calculated immediately releasable pool (IRP) size and release efficiency in rods by deconvolving excitatory postsynaptic currents and presynaptic Ca2+ currents. Peak efficiency of ˜0.2 vesicles/channel was similar to that of cones (˜0.3 vesicles/channel). Efficiency in both cell types was not significantly affected by using weak endogenous Ca2+ buffering. However, weak Ca2+ buffering speeded Ca2+/calmodulin (CaM)-dependent replenishment of vesicles to ribbons in both rods and cones, thereby enhancing sustained release. In rods, weak Ca2+ buffering also amplified sustained release by enhancing CICR and CICR-stimulated release of vesicles at nonribbon sites. By contrast, elevating [Ca2+] at nonribbon sites in cones with weak Ca2+ buffering and by inhibiting Ca2+ extrusion did not trigger additional release, consistent with the notion that exocytosis from cones occurs exclusively at ribbons. The presence of weak endogenous Ca2+ buffering in rods and cones facilitates slow, sustained exocytosis by enhancing Ca2+/CaM-dependent replenishment of ribbons in both rods and cones and by stimulating nonribbon release triggered by CICR in rods. PMID:26416977

Distinct neural control of intrinsic and extrinsic muscles of the hand during single finger pressing.

PubMed

Dupan, Sigrid S G; Stegeman, Dick F; Maas, Huub

2018-06-01

Single finger force tasks lead to unintended activation of the non-instructed fingers, commonly referred to as enslaving. Both neural and mechanical factors have been associated with this absence of finger individuality. This study investigates the amplitude modulation of both intrinsic and extrinsic finger muscles during single finger isometric force tasks. Twelve participants performed single finger flexion presses at 20% of maximum voluntary contraction, while simultaneously the electromyographic activity of several intrinsic and extrinsic muscles associated with all four fingers was recorded using 8 electrode pairs in the hand and two 30-electrode grids on the lower arm. The forces exerted by each of the fingers, in both flexion and extension direction, were recorded with individual force sensors. This study shows distinct activation patterns in intrinsic and extrinsic hand muscles. Intrinsic muscles exhibited individuation, where the agonistic and antagonistic muscles associated with the instructed fingers showed the highest activation. This activation in both agonistic and antagonistic muscles appears to facilitate finger stabilisation during the isometric force task. Extrinsic muscles show an activation independent from instructed finger in both agonistic and antagonistic muscles, which appears to be associated with stabilisation of the wrist, with an additional finger-dependent modulation only present in the agonistic extrinsic muscles. These results indicate distinct muscle patterns in intrinsic and extrinsic hand muscles during single finger isometric force pressing. We conclude that the finger specific activation of intrinsic muscles is not sufficient to fully counteract enslaving caused by the broad activation of the extrinsic muscles. Copyright © 2018 Elsevier B.V. All rights reserved.

Dual drug delivery using "smart" liposomes for triggered release of anticancer agents

NASA Astrophysics Data System (ADS)

Jain, Ankit; Gulbake, Arvind; Jain, Ashish; Shilpi, Satish; Hurkat, Pooja; Jain, Sanjay K.

2013-07-01

Ovarian cancer is one of the most fatal gynecologic cancers. In this debut study, dual approach using synergistically active combination of paclitaxel-topotecan (Pac-Top; 20:1, w/w) is investigated with utilization of characteristic features of tumor micro-environment and additionally overexpressed folate receptors (FR-α) to achieve targeting to tumor site. Various liposomes namely liposomes, PEGylated liposomes, and FR-targeted PEGylated liposomes with lipid compositions viz. DPPC:DMPG (85.5:9.5), DPPC:DMPG:mPEG2000-DSPE (85.5:9.5:5), and DPPC:DMPG:mPEG2000-DSPE:DSPE-PEG-folate (85.5:9.5:4.5:0.5), respectively, were developed using thin film casting method. These were nanometric in size around 200 nm. In vitro drug release study showed initial burst release followed by sustained release for more than 72 h at physiological milieu (37 ± 0.5 °C, pH 7.4) while burst release (i.e., more than 90 %) within 5 min at simulated tumor milieu (41 ± 1 °C, pH 4). SRB cytotoxicity assay in OVCAR-3 cell line revealed Pac-Top free (20:1, w/w) to be more toxic (GI50 = 6.5 μg/ml) than positive control (Adriamycin, GI50 = 9.1 μg/ml) and FR-targeted PEGylated liposomes GI50 (14.7 μg/ml). Moreover, florescence microscopy showed the highest cell uptake of FR-targeted PEGylated liposomes so called "smart liposomes" which has not only mediated effective targeting to FR-α but also triggered release of drugs upon hyperthermia.

New Finger Biometric Method Using Near Infrared Imaging

PubMed Central

Lee, Eui Chul; Jung, Hyunwoo; Kim, Daeyeoul

2011-01-01

In this paper, we propose a new finger biometric method. Infrared finger images are first captured, and then feature extraction is performed using a modified Gaussian high-pass filter through binarization, local binary pattern (LBP), and local derivative pattern (LDP) methods. Infrared finger images include the multimodal features of finger veins and finger geometries. Instead of extracting each feature using different methods, the modified Gaussian high-pass filter is fully convolved. Therefore, the extracted binary patterns of finger images include the multimodal features of veins and finger geometries. Experimental results show that the proposed method has an error rate of 0.13%. PMID:22163741

Beyond Hangovers: Understanding Alcohol's Impact on Your Health

MedlinePlus

... a wide range of abilities, including motor coordination; temperature regulation; sleep; mood; and various cognitive functions, including ... vessels stiffen, making them less flexible. Heavy alcohol consumption triggers the release of certain stress hormones that ...

Dual trigger of triptorelin and HCG optimizes clinical outcome for high ovarian responder in GnRH-antagonist protocols.

PubMed

Li, Saijiao; Zhou, Danni; Yin, Tailang; Xu, Wangming; Xie, Qingzhen; Cheng, Dan; Yang, Jing

2018-01-12

In this paper, a retrospective cohort study was conducted to the high ovarian responders in GnRH-antagonist protocols of IVF/ICSI cycles. The purpose of the study is to investigate whether dual triggering of final oocyte maturation with a combination of gonadotropin-releasing hormone (GnRH) agonist and human chorionic gonadotropin (HCG) can improve the clinical outcome compared with traditional dose (10000IU) HCG trigger and low-dose (8000IU) HCG trigger for high ovarian responders in GnRH-antagonist in vitro fertilization/intracytoplasmic sperm injection (IVF-ICSI) cycles. Our study included 226 couples with high ovarian responders in GnRH-antagonist protocols of IVF/ICSI cycles. Standard dosage of HCG trigger (10000 IU of recombinant HCG) versus dual trigger (0.2 mg of triptorelin and 2000 IU of recombinant HCG) and low-dose HCG trigger (8000IU of recombinant HCG) were used for final oocyte maturation. Our main outcome measures were high quality embryo rate, the number of usable embryos, the risk of OHSS, duration of hospitalization and incidence rate of complications. Our evidence demonstrated that dual trigger is capable of preventing severe OHSS while still maintaining excellent high quality embryo rate in in high ovarian responders of GnRH-antagonist protocols.

Real-time noble gas release signaling rock deformation

NASA Astrophysics Data System (ADS)

Bauer, S. J.; Gardner, W. P.; Lee, H.

2016-12-01

We present empirical results/relationships of rock strain, microfracture density, acoustic emissions, and noble gas release from laboratory triaxial experiments for a granite and basalt. Noble gases are contained in most crustal rock at inter/intra granular sites, their release during natural and manmade stress and strain changes represents a signal of brittle/semi brittle deformation. The gas composition depends on lithology, geologic history and age, fluids present, and uranium, thorium and potassium-40 concentrations in the rocks that affect radiogenic noble gases (helium, argon) production. Noble gas emission and its relationship to crustal processes have been studied, including correlations to tectonic velocities and qualitative estimates of deep permeability from surface measurements, finger prints of nuclear weapon detonation, and as potential precursory signals to earthquakes attributed to gas release due to pre-seismic stress, dilatancy and/or rock fracturing. Helium emission has been shown as a precursor of volcanic activity. Real-time noble gas release is observed using an experimental system utilizing mass spectrometers to measure gases released during triaxial rock deformation. Noble gas release is shown to represent a sensitive precursor signal of rock deformation by relating real-time noble gas release to stress-strain state changes and acoustic emissions. We propose using noble gas release to also signal rock deformation in boreholes, mines and nuclear waste repositories. We postulate each rock exhibits a gas release signature which is microstructure, stress/strain state, and or permanent deformation dependent. Such relationships, when calibrated, may be used to sense rock deformation and then develop predictive models. Sandia National Laboratories is a multi-program laboratory managed and operated by Sandia Corporation, a wholly owned subsidiary of Lockheed Martin Corp., for the US Dept. of Energy's National Nuclear Security Administration under contract DE-AC04-94AL85000. SAND2016-7468 A

HSA/PSS coated gold nanorods as thermo-triggered drug delivery vehicles for combined cancer photothermal therapy and chemotherapy

NASA Astrophysics Data System (ADS)

Tu, Ting-Yu; Yang, Shu-Jyuan; Wang, Chung-Hao; Lee, Shin-Yu; Shieh, Ming-Jium

2018-02-01

Drug delivery systems combined multimodal therapy strategies are very promising in cancer theranostic applications. In this work, a new drug-delivery vehicles based on human serum albumin (HSA)-coated gold nanorods (GNR/PSS/HSA NPs) was developed. The success of coating was verified by transmission electron microscopy (TEM), zeta potential and fourier transform infrared spectroscopy (FTIR). Furthermore, it is demonstrated that doxorubicin (DOX) is successfully loaded among multilayered gold nanorods by the electrostatic and hydrophobic force, and DOX@GNR/PSS/HSA NPs were highly biocompatible and stable in various physiological solutions. The NPs possess strong absorbance in nearinfrared (NIR) region, and high photothermal conversion efficiency for outstanding photothermal therapy applications. A bimodal drug release triggered by proteinase or NIR irradiation has been revealed, resulting in a significant chemotherapeutic effect in tumor sites because of the preferential drug accumulation and triggered release. Importantly, the in vitro and in vivo experiments demonstrated that DOX@GNR/PSS/HSA NPs, which combined photothermal and chemotherapy for cancer therapy, revealing a remarkably superior synergistic anticancer effect over either monotherapy. All these results suggested a considerable potential of DOX@GNR/PSS/HSA NPs nano-platform for antitumor therapy.

The role of inflammation in preterm birth--focus on periodontitis.

PubMed

Klebanoff, M; Searle, K

2006-12-01

It is universally accepted that acute inflammation is responsible for a substantial fraction of preterm births, particularly early cases. Much of this inflammation is caused by intrauterine infection. There is also evidence that infection and perhaps inflammation remote from the genitourinary tract can trigger preterm labour. Several studies have suggested that periodontitis during pregnancy increases the risk of preterm birth. Periodontitis may cause preterm birth by causing low-grade bacteraemia, which lodges in the decidua, chorion and amnion or by releasing endotoxin into the maternal circulation, which triggers intrauterine inflammation and preterm birth. Alternatively, it may release cytokines and other inflammatory products, which then trigger preterm labour. It is also conceivable that periodontitis might serve as a marker for other unhealthy behaviours, or immune hyperresponsiveness and that hyperresponsiveness to low-grade intrauterine infection itself might cause preterm birth. Currently, there are few data available to distinguish these possibilities. Such distinctions are important since they have clear implications for whether treatment of periodontitis might reduce the incidence of preterm birth. Several clinical trials of treatment of periodontitis are continuing, but until their results are known there is currently little evidence that treatment of periodontitis during pregnancy reduces the incidence of preterm birth.

Introduction: Management of the luteal phase in assisted reproductive technology.

PubMed

Griesinger, Georg; Meldrum, David

2018-05-01

The increasing utilization of a gonadotropin-releasing hormone agonist ovulation trigger and the widespread use of artificial cycles for the transfer of frozen-thawed or donated embryos has renewed interest in the luteal phase in assisted reproductive technology. The "luteal phase defect" phenomenon is now understood as a continuum: there is less impairment with milder stimulation than with more intense ovarian stimulation, and less impairment after controlled ovarian stimulation and human chorionic gonadotropin ovulation triggering than after gonadotropin-releasing hormone agonist ovulation triggering, the latter being associated with rapid luteolysis. The intensity of the support of luteal phase necessary to achieve optimal outcomes therefore depends on the degree of luteal phase defect encountered in different treatment protocols. Ultimately, the luteal phase of an artificial cycle in which ovulation is suppressed, a corpus luteum is therefore absent, and the establishment of endometrial receptivity completely relies on the orchestrated exogenous administration of sex steroids, is the litmus test situation for the study of the efficacy of different luteal phase support preparations, doses, regimens, and routes of administration. Copyright © 2018 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Absence of luteal phase defect and spontaneous pregnancy in IVF patients despite GnRH-agonist trigger and "freeze all policy" without luteal phase support: a report of four cases.

PubMed

Gurbuz, Ali Sami; Deveer, Ruya; Ozcimen, Necati; Ozcimen, Emel Ebru; Lawrenz, Barbara; Banker, Manish; Garcia-Velasco, Juan Antonio; Fatemi, Human Mousavi

2016-01-01

Human chorionic gonadotropin (hCG) is commonly used for final oocyte maturation in "in vitro fertilization" (IVF)-treatment cycles, however, the main important risk is development of severe ovarian hyperstimulation syndrome (OHSS). OHSS can almost be avoided by using gonadotrophin-releasing-hormone agonist for final oocyte maturation in an antagonist protocol. However, primarily this approach lead to a very poor reproductive outcome, despite the use of a standard luteal phase support. The reason seems to be severe luteolysis. Obviously, luteolysis post-gonadotropin-releasing-hormone-agonist (post-GnRH-a) trigger is individual specific, and not all patients will develop a complete luteolysis, as expected previously. Luteolysis can been reverted by the administration of hCG. Unprotected intercourse around the time of ovulation induction and oocyte retrieval can lead to a spontaneous conception in IVF treatment and, endogenous hCG, produced by the trophoblast, will rescue the corpora lutea. Therefore, one should not rely on complete luteolysis after GnRH-a triggering and, especially patients for egg donation and pre-implantation-genetic diagnosis for single gene disorder, have to be counselled to avoid unprotected intercourse.

Development of pressure-sensitive dosage forms with a core liquefying at body temperature.

PubMed

Wilde, Lisa; Bock, Mona; Wolf, Marieke; Glöckl, Gunnar; Garbacz, Grzegorz; Weitschies, Werner

2014-04-01

Pressure-sensitive dosage forms have been developed that are intended for pulsatile delivery of drugs to the proximal small intestine. The novel dosage forms are composed of insoluble shell and either a hard fat W32 or polyethylene glycol (PEG) 1000 core that are both liquidizing at body temperature. The release is triggered by predominant pressure waves such as contractions of the pylorus causing rupture of the shell and an immediate emptying of the liquefied filling containing the active ingredient. In consequence immediately after the trigger has been effective the total amount of the drug is intended to be available for absorption in the upper small intestine. Both core types were coated with a cellulose acetate film that creates a pressure-sensitive shell in which mechanical resistance is depending on the coating thickness. Results of the texture analysis confirmed a correlation between the polymer load of the coating and the mechanical resistance. The dissolution test performed under conditions of physiological meaningful mechanical stress showed that the drug release is triggered by pressure waves of ⩾300 mbar which are representing the maximal pressure occurring during the gastric emptying. Copyright © 2013 Elsevier B.V. All rights reserved.

Sliding Window-Based Region of Interest Extraction for Finger Vein Images

PubMed Central

Yang, Lu; Yang, Gongping; Yin, Yilong; Xiao, Rongyang

2013-01-01

Region of Interest (ROI) extraction is a crucial step in an automatic finger vein recognition system. The aim of ROI extraction is to decide which part of the image is suitable for finger vein feature extraction. This paper proposes a finger vein ROI extraction method which is robust to finger displacement and rotation. First, we determine the middle line of the finger, which will be used to correct the image skew. Then, a sliding window is used to detect the phalangeal joints and further to ascertain the height of ROI. Last, for the corrective image with certain height, we will obtain the ROI by using the internal tangents of finger edges as the left and right boundary. The experimental results show that the proposed method can extract ROI more accurately and effectively compared with other methods, and thus improve the performance of finger vein identification system. Besides, to acquire the high quality finger vein image during the capture process, we propose eight criteria for finger vein capture from different aspects and these criteria should be helpful to some extent for finger vein capture. PMID:23507824

Personalized keystroke dynamics for self-powered human--machine interfacing.

PubMed

Chen, Jun; Zhu, Guang; Yang, Jin; Jing, Qingshen; Bai, Peng; Yang, Weiqing; Qi, Xuewei; Su, Yuanjie; Wang, Zhong Lin

2015-01-27

The computer keyboard is one of the most common, reliable, accessible, and effective tools used for human--machine interfacing and information exchange. Although keyboards have been used for hundreds of years for advancing human civilization, studying human behavior by keystroke dynamics using smart keyboards remains a great challenge. Here we report a self-powered, non-mechanical-punching keyboard enabled by contact electrification between human fingers and keys, which converts mechanical stimuli applied to the keyboard into local electronic signals without applying an external power. The intelligent keyboard (IKB) can not only sensitively trigger a wireless alarm system once gentle finger tapping occurs but also trace and record typed content by detecting both the dynamic time intervals between and during the inputting of letters and the force used for each typing action. Such features hold promise for its use as a smart security system that can realize detection, alert, recording, and identification. Moreover, the IKB is able to identify personal characteristics from different individuals, assisted by the behavioral biometric of keystroke dynamics. Furthermore, the IKB can effectively harness typing motions for electricity to charge commercial electronics at arbitrary typing speeds greater than 100 characters per min. Given the above features, the IKB can be potentially applied not only to self-powered electronics but also to artificial intelligence, cyber security, and computer or network access control.

The Effects of Age, Gender, and Hand on Force Control Capabilities of Healthy Adults.

PubMed

Lee, Baekhee; Lee, Mina; Yoh, Myeung Sook; You, Heecheon; Park, Hyunji; Jung, Kihyo; Lee, Byung Hwa; Na, Duk L; Kim, Geon Ha

2015-12-01

The present study examined the effects of age (20s to 70s), gender (male and female), and hand (dominant and nondominant) on force control capabilities (FCCs) in four force control phases (initiation, development, maintenance, and termination). Normative data of FCCs by force control phase are needed for various populations in age and gender to identify a type of motor performance reduction and its severity. FCCs of 360 participants (30 for each combination of age group and gender) were measured using a finger dynamometer and quantified in terms of initiation time (IT), development time (DT), maintenance error (ME), and termination time (TT). Although gradual increases (1%~28%) by age were shown in IT, DT, and TT, a dramatic increase in ME was observed among participants in their 50s (26%), 60s (68%), and 70s (160%) compared to those in their 20s~40s. The most distinctive interaction effect of age and gender was found in ME out of the four FCC measures. Lastly, hand and its related interactions were not found significant. Normative FCC data were established for four age groups (20s~40s, 50s, 60s, and 70s) and gender. The normative FCC data can be used for evaluating an individual's motor performance, screening patients with brain disorders, and designing input devices triggered and/or operated by the finger. © 2015, Human Factors and Ergonomics Society.

Why Compositional Convection Cannot Explain Substellar Objects’ Sharp Spectral-type Transitions

NASA Astrophysics Data System (ADS)

Leconte, Jérémy

2018-02-01

As brown dwarfs and young giant planets cool down, they are known to experience various chemical transitions—for example, from {CO} rich L-dwarfs to methane rich T-dwarfs. Those chemical transitions are accompanied by spectral transitions with sharpness that cannot be explained by chemistry alone. In a series of articles, Tremblin et al. proposed that some of the yet-unexplained features associated with these transitions could be explained by a reduction of the thermal gradient near the photosphere. To explain, in turn, this more isothermal profile, they invoke the presence of an instability analogous to fingering convection—compositional convection—triggered by the change in mean molecular weight of the gas due to the chemical transitions mentioned above. In this Letter, we use existing arguments to demonstrate that any turbulent transport, if present, would in fact increase the thermal gradient. This misinterpretation comes from the fact that turbulence mixes/homogenizes entropy (potential temperature) instead of temperature. So, while increasing transport, turbulence in an initially stratified atmosphere actually carries energy downward, whether it is due to fingering or any other type of compositional convection. These processes therefore cannot explain the features observed along the aforementioned transitions by reducing the thermal gradient in the atmosphere of substellar objects. Understanding the microphysical and dynamical properties of clouds at these transitions thus probably remains our best way forward.

Robot-Assisted Guitar Hero for Finger Rehabilitation after Stroke

PubMed Central

Taheri, Hossein; Rowe, Justin B.; Gardner, David; Chan, Vicky; Reinkensmeyer, David J.; Wolbrecht, Eric T.

2014-01-01

This paper describes the design and testing of a robotic device for finger therapy after stroke: FINGER (Finger Individuating Grasp Exercise Robot). FINGER makes use of stacked single degree-of-freedom mechanisms to assist subjects in moving individual fingers in a naturalistic grasping pattern through much of their full range of motion. The device has a high bandwidth of control (−3dB at approximately 8 Hz) and is backdriveable. These characteristics make it capable of assisting in grasping tasks that require precise timing. We therefore used FINGER to assist individuals with a stroke (n = 8) and without impairment (n = 4) in playing a game similar to Guitar Hero©. The subjects attempted to move their fingers to target positions at times specified by notes that were graphically streamed to popular music. We show here that by automatically adjusting the robot gains, it is possible to use FINGER to modulate the subject’s success rate at the game, across a range of impairment levels. Modulating success rates did not alter the stroke subject’s effort, although the unimpaired subjects exerted more force when they were made less successful. We also present a novel measure of finger individuation that can be assessed as individuals play Guitar Hero with FINGER. The results demonstrate the ability of FINGER to provide controlled levels of assistance during an engaging computer game, and to quantify finger individuation after stroke. PMID:23366783

GnRH agonist trigger for the induction of oocyte maturation in GnRH antagonist IVF cycles: a SWOT analysis.

PubMed

Engmann, Lawrence; Benadiva, Claudio; Humaidan, Peter

2016-03-01

Gonadotrophin releasing hormone agonist (GnRHa) trigger is effective in the induction of oocyte maturation and prevention of ovarian hyperstimulation syndrome during IVF treatment. This trigger concept, however, results in early corpora lutea demise and consequently luteal phase dysfunction and impaired endometrial receptivity. The aim of this strenghths, weaknesses, opportunities and threats analysis was to summarize the progress made over the past 15 years to optimize ongoing pregnancy rates after GnRHa trigger. The advantages and potential drawbacks of this type of triggering are reviewed. The current approach to the management of GnRHa trigger in autologous cycles is based on the peak serum oestradiol level or follicle number and aims at a fresh embryo transfer or a segmentation approach with elective cryopreservation policy. We recommend intensive luteal support with transdermal oestradiol and intramuscular progesterone alone if peak serum oestradiol is 4000 or more pg/ml after GnRHa trigger or dual trigger with GnRHa and HCG 1000 IU if peak serum oestradiol is less than 4000 pg/mL. On the contrary, we recommend HCG 1500 IU 35 h after GnRHa trigger if there are less than 25 follicles, or freeze all oocytes or embryos if there are over 25 follicles. Copyright © 2015. Published by Elsevier Ltd.

Rainfall-triggered shallow landslides at catchment scale: Threshold mechanics-based modeling for abruptness and localization

NASA Astrophysics Data System (ADS)

von Ruette, J.; Lehmann, P.; Or, D.

2013-10-01

Rainfall-induced shallow landslides may occur abruptly without distinct precursors and could span a wide range of soil mass released during a triggering event. We present a rainfall-induced landslide-triggering model for steep catchments with surfaces represented as an assembly of hydrologically and mechanically interconnected soil columns. The abruptness of failure was captured by defining local strength thresholds for mechanical bonds linking soil and bedrock and adjacent columns, whereby a failure of a single bond may initiate a chain reaction of subsequent failures, culminating in local mass release (a landslide). The catchment-scale hydromechanical landslide-triggering model (CHLT) was applied to results from two event-based landslide inventories triggered by two rainfall events in 2002 and 2005 in two nearby catchments located in the Prealps in Switzerland. Rainfall radar data, surface elevation and vegetation maps, and a soil production model for soil depth distribution were used for hydromechanical modeling of failure patterns for the two rainfall events at spatial and temporal resolutions of 2.5 m and 0.02 h, respectively. The CHLT model enabled systematic evaluation of the effects of soil type, mechanical reinforcement (soil cohesion and lateral root strength), and initial soil water content on landslide characteristics. We compared various landslide metrics and spatial distribution of simulated landslides in subcatchments with observed inventory data. Model parameters were optimized for the short but intense rainfall event in 2002, and the calibrated model was then applied for the 2005 rainfall, yielding reasonable predictions of landslide events and volumes and statistically reproducing localized landslide patterns similar to inventory data. The model provides a means for identifying local hot spots and offers insights into the dynamics of locally resolved landslide hazards in mountainous regions.

Two-pore channels: Regulation by NAADP and customized roles in triggering calcium signals

PubMed Central

Patel, Sandip; Marchant, Jonathan; Brailoiu, Eugen

2010-01-01

NAADP is a potent regulator of cytosolic calcium levels. Much evidence suggests that NAADP activates a novel channel located on an acidic (lysosomal-like) calcium store, the mobilisation of which results in further calcium release from the endoplasmic reticulum. Here, we discuss the recent identification of a family of poorly characterized ion channels (the two-pore channels) as endo-lysosomal NAADP receptors. The generation of calcium signals by these channels is likened to those evoked by depolarisation during excitation-contraction coupling in muscle. We discuss the idea that two pore-channels can mediate a trigger release of calcium which is then amplified by calcium-induced calcium release from the endoplasmic reticulum. This is similar to the activation of voltage-sensitive calcium channels and subsequent mobilisation of sarcoplasmic reticulum calcium stores in cardiac tissue. We suggest that two-pore channels may physically interact with ryanodine receptors to account for more direct release of calcium from the endoplasmic reticulum in analogy with the conformational coupling of voltage-sensitive calcium channels and ryanodine receptors in skeletal muscle. Interaction of two-pore channels with other calcium release channels likely occurs between stores “trans-chatter” and possibly within the same store “cis-chatter”. We also speculate that trafficking of two-pore channels through the endolysosomal system facilitates interactions with calcium entry channels. Strategic placing of two-pore channels thus provides a versatile means of generating spatiotemporally complex cellular calcium signals. PMID:20621760

Near-infrared light-triggered thermochemotherapy of cancer using a polymer-gold nanorod conjugate

NASA Astrophysics Data System (ADS)

Ko, Hyewon; Son, Soyoung; Bae, Seonghwan; Kim, Joo-Hyung; Yi, Gi-Ra; Park, Jae Hyung

2016-04-01

A biocompatible polymer-gold nanorod (P-AuNR) conjugate was developed as a thermo-chemotherapeutic nano-sized drug carrier for cancer therapy using near-infrared (NIR) light as an external trigger. The amphiphilic polymer, poly(ethylene glycol)-block-poly(caprolactone) (PEG-b-PCL) bearing a disulfide bond, was prepared using a facile synthetic route via copper(I)-free click chemistry and covalently linked to AuNR. The chemical structures and successful conjugation of PEG-b-PCL were analyzed using 1H NMR and FT-IR. Doxorubicin (DOX), a hydrophobic anticancer drug, was effectively loaded into the hydrophobic PCL domain of P-AuNR through a simple dialysis method. P-AuNR showed longitudinal plasmon resonance absorption at the NIR region, thus generating heat under irradiation at 808 nm. Interestingly, exposure of P-AuNRs to NIR induced a structural change in the PCL block from a crystalline to an amorphous state, leading to the temporally controlled release of DOX. No significant release of DOX was observed from P-AuNRs under physiological conditions (pH 7.4), whereas the release rate of DOX was remarkably enhanced in response to NIR irradiation. In vitro cellular experiments to assess cytotoxicity and intracellular drug release behavior of DOX-P-AuNRs demonstrated that the release of DOX could be selectively regulated by NIR irradiation. Overall, DOX-P-AuNRs might have the potential to overcome the indiscriminate toxicity of free DOX.

Oral gold compound auranofin triggers arachidonate release and cyclooxygenase metabolism in the alveolar macrophage

DOE Office of Scientific and Technical Information (OSTI.GOV)

Peters-Golden, M.; Shelly, C.

1988-12-01

We examined the effect of in vitro incubation with the oral gold compound auranofin (AF) on arachidonic acid (AA) release and metabolism by rat alveolar macrophages (AMs). AF stimulated dose- and time-dependent release of /sup 14/C-AA from prelabeled AMs, which reached 4.7 +/- 0.3% (mean +/- SEM) of incorporated radioactivity at 10 micrograms/ml for 90 min, as compared to 0.5 +/- 0.1% release following control incubation for 90 min (p less than 0.001). Similar dose- and time-dependent synthesis of thromboxane (Tx) A2 (measured as TxB2) and prostaglandin (PG) E2 was demonstrated by radioimmunoassay of medium from unlabeled cultures, reaching 18-foldmore » and 9-fold, respectively, of the control values at 10 micrograms/ml AF for 90 min (p less than 0.001 for both). AF-induced TxB2 and PGE2 synthesis was inhibited by indomethacin as well as by pretreatment with methylprednisolone. No increase in the synthesis of immunoreactive leukotrienes (LT) B4 or C4 was noted at any dose or time of AF. High performance liquid chromatographic separation of /sup 14/C-eicosanoids synthesized by prelabeled AMs confirmed that AF induced the release of free AA and its metabolism to cyclooxygenase, but not 5-lipoxygenase, metabolites. The ability of AF to trigger macrophage AA metabolism may be relevant to the exacerbation of certain inflammatory processes which sometimes accompany gold therapy.« less

Enzymatic degradation of poly(L-lactide) nanoparticles followed by the release of octenidine and their bactericidal effects.

PubMed

Baier, Grit; Cavallaro, Alex; Friedemann, Kathrin; Müller, Beate; Glasser, Gunnar; Vasilev, Krasimir; Landfester, Katharina

2014-01-01

The enzyme-triggered release of the antimicrobial agent octenidine out of poly(l-lactide)-based nanoparticles (PLLA-NPs) and their in vitro antibacterial activities in the presence of gram-positive and gram-negative bacteria are presented. The formation of the nanoparticles was achieved using a combination of the solvent evaporation and the miniemulsion approach. For the stabilization of the polymeric nanoparticles, non-ionic polymers (polyvinylalcohol [PVA], hydroxyethyl starch [HES], human serum albumin [HSA]) were successfully used for enzymatic degradation; ionic surfactants such as sodium dodecyl sulfate and cetyltrimethylammonium chloride inhibited the enzymatic degradation. The change in pH, size, size distribution and morphology during the degradation process of PLLA-NPs and the release of the antimicrobial agent was studied. The influence of the different amounts of octenidine and of the different stabilizers on the NPs' stability, size, size distribution, morphology, zeta potential and on the surface group's density is discussed. Fluorescently labeled HES-stabilized PLLA-NPs are immobilized by colloidal electrospinning. The observed data from HPLC measurements show that octenidine is released out of PLLA-NPs which are stabilized with PVA, HES or HSA. In bacteria tests the PLLA nanoparticles showed a greater ability to inhibit the growth of Staphylococcus aureus compared to Escherichia coli. This article discusses the enzyme-triggered release and antibacterial effects of octenidine from poly(l-lactide)-based nanoparticles demonstrating the viability of this approach for potential future antibacterial therapy. © 2013.

Neuropeptide Secreted from a Pacemaker Activates Neurons to Control a Rhythmic Behavior

PubMed Central

Wang, Han; Girskis, Kelly; Janssen, Tom; Chan, Jason P.; Dasgupta, Krishnakali; Knowles, James A.; Schoofs, Liliane; Sieburth, Derek

2013-01-01

Summary Background Rhythmic behaviors are driven by endogenous biological clocks in pacemakers, which must reliably transmit timing information to target tissues that execute rhythmic outputs. During the defecation motor program in C. elegans, calcium oscillations in the pacemaker (intestine), which occur about every 50 seconds, trigger rhythmic enteric muscle contractions through downstream GABAergic neurons that innervate enteric muscles. However, the identity of the timing signal released by the pacemaker and the mechanism underlying the delivery of timing information to the GABAergic neurons are unknown. Results Here we show that a neuropeptide-like protein (NLP-40) released by the pacemaker triggers a single rapid calcium transient in the GABAergic neurons during each defecation cycle. We find that mutants lacking nlp-40 have normal pacemaker function, but lack enteric muscle contractions. NLP-40 undergoes calcium-dependent release that is mediated by the calcium sensor, SNT-2/synaptotagmin. We identify AEX-2, the G protein-coupled receptor on the GABAergic neurons, as the receptor of NLP-40. Functional calcium imaging reveals that NLP-40 and AEX-2/GPCR are both necessary for rhythmic activation of these neurons. Furthermore, acute application of synthetic NLP-40-derived peptide depolarizes the GABAergic neurons in vivo. Conclusions Our results show that NLP-40 carries the timing information from the pacemaker via calcium-dependent release and delivers it to the GABAergic neurons by instructing their activation. Thus, we propose that rhythmic release of neuropeptides can deliver temporal information from pacemakers to downstream neurons to execute rhythmic behaviors. PMID:23583549

Radiation safety education reduces the incidence of adult fingers on neonatal chest radiographs.

PubMed

Sahota, N; Burbridge, B E; Duncan, M D

2014-06-01

A previous audit revealed a high frequency of adult fingers visualised on neonatal intensive care unit (NICU) chest radiographs-representing an example of inappropriate occupational radiation exposure. Radiation safety education was provided to staff and we hypothesised that the education would reduce the frequency of adult fingers visualised on NICU chest radiographs. Two cross-sectional samples taken before and after the administration of the education were compared. We examined fingers visualised directly in the beam, fingers in the direct beam but eliminated by technologists editing the image, and fingers under the cones of the portable x-ray machine. There was a 46.2% reduction in fingers directly in the beam, 50.0% reduction in fingers directly in the beam but cropped out, and 68.4% reduction in fingers in the coned area. There was a 57.1% overall reduction in adult fingers visualised, which was statistically significant (Z value - 7.48, P < 0.0001). This study supports radiation safety education in minimising inappropriate occupational radiation exposure.

Photocontrol of Drug Release from Supramolecular Hydrogels with Green Light.

PubMed

Karcher, Johannes; Pianowski, Zbigniew

2018-06-26

Photoresponsive smart materials transform light energy into sophisticated functions. They find increasing biomedical applications in light-induced drug release and photopharmacology, as they can locally provide the desired therapeutic effect due to precise spatiotemporal dosage control. However, the majority of reported studies rely on cytotoxic UV light that poorly penetrates tissues. Here we report the first drug-releasing system based on photochromic low molecular weight supramolecular hydrogels that is triggered with visible light. We demonstrated green-light-induced release of structurally unmodified antibiotic, anticancer, and anti-inflammatory drugs under physiological conditions. Using the antibiotic-loaded gel, we selectively inhibited bacterial growth with green light. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Novel self-assembled sandwich nanomedicine for NIR-responsive release of NO

PubMed Central

Fan, Jing; He, Qianjun; Liu, Yi; Ma, Ying; Fu, Xiao; Liu, Yijing; Huang, Peng; He, Nongyue; Chen, Xiaoyuan

2015-01-01

A novel sandwich nanomedicine (GO-BNN6) for near-infrared (NIR) light responsive release of nitric oxide (NO) has been constructed by self-assembling of graphene oxide (GO) nanosheets and a NO donor BNN6 through the π-π stacking interaction. GO-BNN6 nanomedicine has an extraordinarily high drug loading capacity (1.2 mg BNN6 per mg GO), good thermal stability, and high NIR responsiveness. The NO release from GO-BNN6 can be easily triggered and effectively controlled by adjusting the switching, irradiation time and power density of NIR laser. The intracellular NIR-responsive release of NO from GO-BNN6 nanomedicine causes a remarkable anti-cancer effect. PMID:26568270

1H NMR investigation of thermally triggered insulin release from poly(N-isopropylacrylamide) microgels.

PubMed

Nolan, Christine M; Gelbaum, Leslie T; Lyon, L Andrew

2006-10-01

We describe investigations of insulin release from thermoresponsive microgels using variable temperature (1)H NMR. Microgel particles composed of poly(N-isopropylacrylamide) were loaded with the peptide via a swelling technique, and this method was compared to simple equilibrium partitioning. Variable temperature (1)H NMR studies suggest that the swelling loading method results in enhanced entrapment of the peptide versus equilibrium partitioning. A centrifugation-loading assay supports this finding. Pseudo-temperature jump (1)H NMR measurements suggest that the insulin release rate is partially decoupled from microgel collapse. These types of direct release investigations could prove to be useful methods in the future design of controlled macromolecule drug delivery devices.

Tendon Driven Finger Actuation System

NASA Technical Reports Server (NTRS)

Ihrke, Chris A. (Inventor); Reich, David M. (Inventor); Bridgwater, Lyndon (Inventor); Linn, Douglas Martin (Inventor); Askew, Scott R. (Inventor); Diftler, Myron A. (Inventor); Platt, Robert (Inventor); Hargrave, Brian (Inventor); Valvo, Michael C. (Inventor); Abdallah, Muhammad E. (Inventor);

Gonadotropin-releasing hormone agonist triggering with concomitant administration of low doses of human chorionic gonadotropin or a freeze-all strategy in high responders.

PubMed

Karacan, Meric; Erdem, Erkan; Usta, Akin; Arvas, Ayse; Cebi, Ziya; Camlibel, Teksen

2017-06-01

To compare the live birth rates and moderate/severe ovarian hyperstimulation syndrome (OHSS) rates of 2 different approaches using gonadotropin-releasing hormone (GnRH) agonist triggering in high responder women. Methods: A retrospective cohort study was performed to evaluate intracytoplasmic sperm injection (ICSI) and embryo transfer (ET) outcomes in high responder women who underwent ovulation induction with a GnRH antagonist protocol between April 2011 and March 2015. In group 1 (n=74), GnRH agonist was used for ovulation triggering with the concomitant use of 1500 IU of urinary human chorionic gonadotropin (hCG) immediately after oocyte retrieval followed by fresh ET and standard luteal support. In group 2 (n=48), GnRH agonist was used for triggering after freezing all embryos and subsequent frozen/thawed embryo transfer (FET); this approach is considered the "freeze-all" approach. Results: Baseline characteristics were similar between the groups. The clinical pregnancy rates for group 1 was 45.9% and group 2 was 43.8% (p=0.812, chi-squared test) and live birth rates for group 1 was 40.5% and for group 2 41.7% (p=0.902, chi-squared test) were comparable between groups. In group 1, late-onset OHSS was observed (one severe case and one moderate case) in 2 patients (2.7%). In group 2, none of the patients experienced moderate/severe OHSS. Conclusion: The live birth rate with GnRH agonist triggering and concomitant use of 1500 IU of hCG immediately after oocyte retrieval was similar to that obtained with the freeze-all approach and FET in a subsequent cycle. The administration of a low dose of hCG in GnRH agonist trigger cycles caused moderate/severe OHSS in 2.7% of the patients.

pH-triggered chitosan nanogels via an ortho ester-based linkage for efficient chemotherapy.

PubMed

Yang, Guanqing; Wang, Xin; Fu, Shengxiang; Tang, Rupei; Wang, Jun

2017-09-15

We report on new types of chitosan-based nanogels via an ortho ester-based linkage, used as drug carriers for efficient chemotherapy. First, we synthesized a novel diacrylamide containing ortho ester (OEAM) as an acid-labile cross-linker. Subsequently, methacrylated succinyl-chitosan (MASCS) was prepared and polymerized with OEAM at different molar ratios to give a series of pH-triggered MASCS nanogels. Doxorubicin (DOX) as a model anticancer drug was loaded into MASCS nanogels with a loading content of 16.5%. As expected, with the incorporation of ortho ester linkages, these nanogels showed pH-triggered degradation and drug release at acidic pH values. In vitro cellular uptake shows that the DOX-loaded nanogels could be preferentially internalized by two-dimensional (2D) cells and three-dimensional (3D) multicellular spheroids (MCs), resulting in higher inhibition of the proliferation of tumor cells. In vivo biodistribution and anti-tumor effect were determined in H22 tumor-bearing mice, and the results demonstrate that the acid-labile MASCS nanogels can significantly prolong the blood circulation time of DOX and improve the accumulation in tumor areas, leading to higher therapeutic efficacy. We designed new pH-triggered chitosan nanogels via an ortho ester-based cross-linker for efficient drug-loading and chemotherapy. These drug-loaded nanogels exhibit excellent pH-triggered drug release behavior due to the degradation of ortho ester linkages in mildly acidic environments. In vitro and in vivo results demonstrate that the nanogels could be efficiently internalized by 2D cells and 3D-MCs, improve drug concentration in solid tumors, and lead to higher therapeutic efficacy. To the best of our knowledge, this is the first report on using an ortho ester-based cross-linker to prepare pH-triggered chitosan nanogels as tumor carriers, which may provide a potential route for improved safety and to increase the therapeutic efficacy of anticancer therapy. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

The GAP arginine finger movement into the catalytic site of Ras increases the activation entropy

PubMed Central

Kötting, Carsten; Kallenbach, Angela; Suveyzdis, Yan; Wittinghofer, Alfred; Gerwert, Klaus

2008-01-01

Members of the Ras superfamily of small G proteins play key roles in signal transduction pathways, which they control by GTP hydrolysis. They are regulated by GTPase activating proteins (GAPs). Mutations that prevent hydrolysis cause severe diseases including cancer. A highly conserved “arginine finger” of GAP is a key residue. Here, we monitor the GTPase reaction of the Ras·RasGAP complex at high temporal and spatial resolution by time-resolved FTIR spectroscopy at 260 K. After triggering the reaction, we observe as the first step a movement of the switch-I region of Ras from the nonsignaling “off” to the signaling “on” state with a rate of 3 s−1. The next step is the movement of the “arginine finger” into the active site of Ras with a rate of k2 = 0.8 s−1. Once the arginine points into the binding pocket, cleavage of GTP is fast and the protein-bound Pi intermediate forms. The switch-I reversal to the “off” state, the release of Pi, and the movement of arginine back into an aqueous environment is observed simultaneously with k3 = 0.1 s−1, the rate-limiting step. Arrhenius plots for the partial reactions show that the activation energy for the cleavage reaction is lowered by favorable positive activation entropy. This seems to indicate that protein-bound structured water molecules are pushed by the “arginine finger” movement out of the binding pocket into the bulk water. The proposed mechanism shows how the high activation barrier for phosphoryl transfer can be reduced by splitting into partial reactions separated by a Pi-intermediate. PMID:18434546

Does finger training increase young children's numerical performance?

PubMed

Gracia-Bafalluy, Maria; Noël, Marie-Pascale

2008-04-01

Butterworth (1999) suggested that fingers are important in representing numerosities. Furthermore, scores on a finger gnosis test are a better predictor of numerical performance up to 3 years later than intellectual measures (Marinthe et al., 2001; Noël, 2005). We hypothesised that training in finger differentiation would increase finger gnosis and might also improve numerical performance. Accordingly, 47 first-grade children were selected and divided into 3 groups: children with poor finger gnosis who followed the finger-differentiation training programme (G1), a control-intervention who were trained in story comprehension (G2), and a group with high finger gnosis scores who just continued with normal school lessons (G3). The finger training consisted of 2 weekly sessions of half an hour each, for 8 weeks. Before the training period, children in G3 performed better in finger gnosis and enumeration than children in the two other groups. After the training period this pattern remained for the children in G2 and G3, but the children in G1 were significantly better than those in G2 at finger gnosis, representation of numerosities with fingers, and quantification tasks; they also tended to be better at the processing of Arabic digits. These results indicate that improving finger gnosis in young children is possible and that it can provide a useful support to learning mathematics. Such an approach could be particularly appropriate for children with a developmental Gerstmann syndrome. Theoretically, these results are important because they suggest a functional link between finger gnosis and number skills.

Darwin's bee-trap: The kinetics of Catasetum, a new world orchid.

PubMed

Nicholson, Charles C; Bales, James W; Palmer-Fortune, Joyce E; Nicholson, Robert G

2008-01-01

The orchid genera Catasetum employs a hair-trigger activated, pollen release mechanism, which forcibly attaches pollen sacs onto foraging insects in the New World tropics. This remarkable adaptation was studied extensively by Charles Darwin and he termed this rapid response "sensitiveness." Using high speed video cameras with a frame speed of 1000 fps, this rapid release was filmed and from the subsequent footage, velocity, speed, acceleration, force and kinetic energy were computed.

ZifBASE: a database of zinc finger proteins and associated resources.

PubMed

Jayakanthan, Mannu; Muthukumaran, Jayaraman; Chandrasekar, Sanniyasi; Chawla, Konika; Punetha, Ankita; Sundar, Durai

2009-09-09

Information on the occurrence of zinc finger protein motifs in genomes is crucial to the developing field of molecular genome engineering. The knowledge of their target DNA-binding sequences is vital to develop chimeric proteins for targeted genome engineering and site-specific gene correction. There is a need to develop a computational resource of zinc finger proteins (ZFP) to identify the potential binding sites and its location, which reduce the time of in vivo task, and overcome the difficulties in selecting the specific type of zinc finger protein and the target site in the DNA sequence. ZifBASE provides an extensive collection of various natural and engineered ZFP. It uses standard names and a genetic and structural classification scheme to present data retrieved from UniProtKB, GenBank, Protein Data Bank, ModBase, Protein Model Portal and the literature. It also incorporates specialized features of ZFP including finger sequences and positions, number of fingers, physiochemical properties, classes, framework, PubMed citations with links to experimental structures (PDB, if available) and modeled structures of natural zinc finger proteins. ZifBASE provides information on zinc finger proteins (both natural and engineered ones), the number of finger units in each of the zinc finger proteins (with multiple fingers), the synergy between the adjacent fingers and their positions. Additionally, it gives the individual finger sequence and their target DNA site to which it binds for better and clear understanding on the interactions of adjacent fingers. The current version of ZifBASE contains 139 entries of which 89 are engineered ZFPs, containing 3-7F totaling to 296 fingers. There are 50 natural zinc finger protein entries ranging from 2-13F, totaling to 307 fingers. It has sequences and structures from literature, Protein Data Bank, ModBase and Protein Model Portal. The interface is cross linked to other public databases like UniprotKB, PDB, ModBase and Protein Model Portal and PubMed for making it more informative. A database is established to maintain the information of the sequence features, including the class, framework, number of fingers, residues, position, recognition site and physio-chemical properties (molecular weight, isoelectric point) of both natural and engineered zinc finger proteins and dissociation constant of few. ZifBASE can provide more effective and efficient way of accessing the zinc finger protein sequences and their target binding sites with the links to their three-dimensional structures. All the data and functions are available at the advanced web-based search interface http://web.iitd.ac.in/~sundar/zifbase.

Headaches: Reduce Stress to Prevent the Pain

MedlinePlus

... your ability to cope with stress. Lack of sleep puts your body under stress and may trigger the release of stress hormones, such as adrenaline and cortisol. Seek support. Talking things out with family or friends or allowing ...

A SPION-eicosane protective coating for water soluble capsules: Evidence for on-demand drug release triggered by magnetic hyperthermia.

PubMed

Che Rose, Laili; Bear, Joseph C; McNaughter, Paul D; Southern, Paul; Piggott, R Ben; Parkin, Ivan P; Qi, Sheng; Mayes, Andrew G

2016-02-04

An orally-administered system for targeted, on-demand drug delivery to the gastrointestinal (GI) tract is highly desirable due to the high instances of diseases of that organ system and harsh mechanical and physical conditions any such system has to endure. To that end, we present an iron oxide nanoparticle/wax composite capsule coating using magnetic hyperthermia as a release trigger. The coating is synthesised using a simple dip-coating process from pharmaceutically approved materials using a gelatin drug capsule as a template. We show that the coating is impervious to chemical conditions within the GI tract and is completely melted within two minutes when exposed to an RF magnetic field under biologically-relevant conditions. The overall simplicity of action, durability and non-toxic and inexpensive nature of our system demonstrated herein are key for successful drug delivery systems.

Magnetic nanobubbles with potential for targeted drug delivery and trimodal imaging in breast cancer: an in vitro study.

PubMed

Song, Weixiang; Luo, Yindeng; Zhao, Yajing; Liu, Xinjie; Zhao, Jiannong; Luo, Jie; Zhang, Qunxia; Ran, Haitao; Wang, Zhigang; Guo, Dajing

2017-05-01

The aim of this study was to improve tumor-targeted therapy for breast cancer by designing magnetic nanobubbles with the potential for targeted drug delivery and multimodal imaging. Herceptin-decorated and ultrasmall superparamagnetic iron oxide (USPIO)/paclitaxel (PTX)-embedded nanobubbles (PTX-USPIO-HER-NBs) were manufactured by combining a modified double-emulsion evaporation process with carbodiimide technique. PTX-USPIO-HER-NBs were examined for characterization, specific cell-targeting ability and multimodal imaging. PTX-USPIO-HER-NBs exhibited excellent entrapment efficiency of Herceptin/PTX/USPIO and showed greater cytotoxic effects than other delivery platforms. Low-frequency ultrasound triggered accelerated PTX release. Moreover, the magnetic nanobubbles were able to enhance ultrasound, magnetic resonance and photoacoustics trimodal imaging. These results suggest that PTX-USPIO-HER-NBs have potential as a multimodal contrast agent and as a system for ultrasound-triggered drug release in breast cancer.

Polymeric Micelles in Anticancer Therapy: Targeting, Imaging and Triggered Release

PubMed Central

Bult, Wouter; Bos, Mariska; Storm, Gert; Nijsen, J. Frank W.; Hennink, Wim E.

2010-01-01

ABSTRACT Micelles are colloidal particles with a size around 5–100 nm which are currently under investigation as carriers for hydrophobic drugs in anticancer therapy. Currently, five micellar formulations for anticancer therapy are under clinical evaluation, of which Genexol-PM has been FDA approved for use in patients with breast cancer. Micelle-based drug delivery, however, can be improved in different ways. Targeting ligands can be attached to the micelles which specifically recognize and bind to receptors overexpressed in tumor cells, and chelation or incorporation of imaging moieties enables tracking micelles in vivo for biodistribution studies. Moreover, pH-, thermo-, ultrasound-, or light-sensitive block copolymers allow for controlled micelle dissociation and triggered drug release. The combination of these approaches will further improve specificity and efficacy of micelle-based drug delivery and brings the development of a ‘magic bullet’ a major step forward. PMID:20725771

Morphological changes in vesicles and release of an encapsulated compound triggered by a photoresponsive Malachite Green leuconitrile derivative.

PubMed

Uda, Ryoko M; Hiraishi, Eri; Ohnishi, Ryo; Nakahara, Yoshio; Kimura, Keiichi

2010-04-20

Photoinduced morphological changes in phosphatidylcholine vesicles are triggered by a Malachite Green leuconitrile derivative dissolved in the lipidic membrane, and are observed at Malachite Green derivative/lipid ratios <5 mol %. This Malachite Green derivative is a photoresponsive compound that undergoes ionization to afford a positive charge on the molecule by UV irradiation. The Malachite Green derivative exhibits amphiphilicity when ionized photochemically, whereas it behaves as a lipophilic compound under dark conditions. Cryo-transmission electron microscopy was used to determine vesicle morphology. The effects of the Malachite Green derivative on vesicles were studied by dynamic light scattering and fluorescence resonance energy transfer. Irradiation of vesicles containing the Malachite Green derivative induces nonspherical vesicle morphology, fusion of vesicles, and membrane solubilization, depending on conditions. Furthermore, irradiation of the Malachite Green derivative induces the release of a vesicle-encapsulated compound.

Recent Developments on Autonomous Corrosion Protection Through Encapsulation

NASA Technical Reports Server (NTRS)

Li, W.; Buhrow, J. W.; Calle, L. M.; Gillis, M.; Blanton, M.; Hanna, J.; Rawlins, J.

2015-01-01

This paper concerns recent progress in the development of a multifunctional smart coating, based on microencapsulation, for the autonomous detection and control of corrosion. Microencapsulation has been validated and optimized to incorporate desired corrosion control functionalities, such as early corrosion detection and inhibition, through corrosion-initiated release of corrosion indicators and inhibitors, as well as self-healing agent release triggered by mechanical damage. While proof-of-concept results have been previously reported, more recent research and development efforts have concentrated on improving coating compatibility and synthesis procedure scalability, with a targeted goal of obtaining easily dispersible pigment-grade type microencapsulated materials. The recent progress has resulted in the development of pH-sensitive microparticles as a corrosion-triggered delivery system for corrosion indicators and inhibitors. The synthesis and early corrosion indication results obtained with coating formulations that incorporate these microparticles are reported. The early corrosion indicating results were obtained with color changing and with fluorescent indicators.

Amphiphilic Imbalance and Stabilization of Block Copolymer Micelles on-Demand through Combinational Photo-Cleavage and Photo-Crosslinking.

PubMed

Zhang, Xuan; Wang, Youpeng; Li, Guo; Liu, Zhaotie; Liu, Zhongwen; Jiang, Jinqiang

2017-01-01

An amphiphilic block copolymer of poly(ethylene oxide)-b-poly((N-methacryloxy phthalimide)-co-(7-(4-vinyl-benzyloxyl)-4-methylcoumarin)) (PEO 45 -b-P(MAPI 36 -co-VBC 4 )) is designed to improve the micellar stability during the photo-triggered release of hydrophobic cargoes. Analysis of absorption and emission spectra, solution transmittance, dynamic light scattering, and transmission electron microscopy supports that polymer micelles of PEO 45 -b-P(MAPI 36 -co-VBC 4 ) upon the combinational irradiation of 365 and 254 nm light can be solubilized through the photolysis of phthalimide esters and simultaneously crosslinked via the partially reversible photo-dimerization of coumarins. The photo-triggered release experiment shows that the leakage of doxorubicin molecules from crosslinked micelles can be predictably regulated by controlling the irradiation time of 365 and 254 nm light. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Earthquake Simulator Finds Tremor Triggers

ScienceCinema

Johnson, Paul

2018-01-16

Using a novel device that simulates earthquakes in a laboratory setting, a Los Alamos researcher has found that seismic waves-the sounds radiated from earthquakes-can induce earthquake aftershocks, often long after a quake has subsided. The research provides insight into how earthquakes may be triggered and how they recur. Los Alamos researcher Paul Johnson and colleague Chris Marone at Penn State have discovered how wave energy can be stored in certain types of granular materials-like the type found along certain fault lines across the globe-and how this stored energy can suddenly be released as an earthquake when hit by relatively small seismic waves far beyond the traditional “aftershock zone” of a main quake. Perhaps most surprising, researchers have found that the release of energy can occur minutes, hours, or even days after the sound waves pass; the cause of the delay remains a tantalizing mystery.

Three-Dimensional Spatiotemporal Modeling of Colon Cancer Organoids Reveals that Multimodal Control of Stem Cell Self-Renewal is a Critical Determinant of Size and Shape in Early Stages of Tumor Growth.

PubMed

Yan, Huaming; Konstorum, Anna; Lowengrub, John S

2018-05-01

We develop a three-dimensional multispecies mathematical model to simulate the growth of colon cancer organoids containing stem, progenitor and terminally differentiated cells, as a model of early (prevascular) tumor growth. Stem cells (SCs) secrete short-range self-renewal promoters (e.g., Wnt) and their long-range inhibitors (e.g., Dkk) and proliferate slowly. Committed progenitor (CP) cells proliferate more rapidly and differentiate to produce post-mitotic terminally differentiated cells that release differentiation promoters, forming negative feedback loops on SC and CP self-renewal. We demonstrate that SCs play a central role in normal and cancer colon organoids. Spatial patterning of the SC self-renewal promoter gives rise to SC clusters, which mimic stem cell niches, around the organoid surface, and drive the development of invasive fingers. We also study the effects of externally applied signaling factors. Applying bone morphogenic proteins, which inhibit SC and CP self-renewal, reduces invasiveness and organoid size. Applying hepatocyte growth factor, which enhances SC self-renewal, produces larger sizes and enhances finger development at low concentrations but suppresses fingers at high concentrations. These results are consistent with recent experiments on colon organoids. Because many cancers are hierarchically organized and are subject to feedback regulation similar to that in normal tissues, our results suggest that in cancer, control of cancer stem cell self-renewal should influence the size and shape in similar ways, thereby opening the door to novel therapies.

A plant EPF-type zinc-finger protein, CaPIF1, involved in defence against pathogens.

PubMed

Oh, Sang-Keun; Park, Jeong Mee; Joung, Young Hee; Lee, Sanghyeob; Chung, Eunsook; Kim, Soo-Yong; Yu, Seung Hun; Choi, Doil

2005-05-01

SUMMARY To understand better the defence responses of plants to pathogen attack, we challenged hot pepper plants with bacterial pathogens and identified transcription factor-encoding genes whose expression patterns were altered during the subsequent hypersensitive response. One of these genes, CaPIF1 (Capsicum annuum Pathogen-Induced Factor 1), was characterized further. This gene encodes a plant-specific EPF-type protein that contains two Cys(2)/His(2) zinc fingers. CaPIF1 expression was rapidly and specifically induced when pepper plants were challenged with bacterial pathogens to which they are resistant. In contrast, challenge with a pathogen to which the plants are susceptible only generated weak CaPIF1 expression. CaPIF1 expression was also strongly induced in pepper leaves by the exogenous application of ethephon, an ethylene-releasing compound, and salicylic acid, whereas methyl jasmonate had only moderate effects. CaPIF1 localized to the nuclei of onion epidermis when expressed as a CaPIF1-smGFP fusion protein. Transgenic tobacco plants over-expressing CaPIF1 driven by the CaMV 35S promoter showed increased resistance to challenge with a tobacco-specific pathogen or non-host bacterial pathogens. These plants also showed constitutive up-regulation of multiple defence-related genes. Moreover, virus-induced silencing of the CaPIF1 orthologue in Nicotiana benthamiana enhanced susceptibility to the same host or non-host bacterial pathogens. These observations provide evidence that an EPF-type Cys(2)/His(2) zinc-finger protein plays a crucial role in the activation of the pathogen defence response in plants.

Biofortification in Millets: A Sustainable Approach for Nutritional Security.

PubMed

Vinoth, A; Ravindhran, R

2017-01-01

Nutritional insecurity is a major threat to the world's population that is highly dependent on cereals-based diet, deficient in micronutrients. Next to cereals, millets are the primary sources of energy in the semi-arid tropics and drought-prone regions of Asia and Africa. Millets are nutritionally superior as their grains contain high amount of proteins, essential amino acids, minerals, and vitamins. Biofortification of staple crops is proved to be an economically feasible approach to combat micronutrient malnutrition. HarvestPlus group realized the importance of millet biofortification and released conventionally bred high iron pearl millet in India to tackle iron deficiency. Molecular basis of waxy starch has been identified in foxtail millet, proso millet, and barnyard millet to facilitate their use in infant foods. With close genetic-relatedness to cereals, comparative genomics has helped in deciphering quantitative trait loci and genes linked to protein quality in finger millet. Recently, transgenic expression of zinc transporters resulted in the development of high grain zinc while transcriptomics revealed various calcium sensor genes involved in uptake, translocation, and accumulation of calcium in finger millet. Biofortification in millets is still limited by the presence of antinutrients like phytic acid, polyphenols, and tannins. RNA interference and genome editing tools [zinc finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs), and clustered regularly interspaced short palindromic repeats (CRISPR)] needs to be employed to reduce these antinutrients. In this review paper, we discuss the strategies to accelerate biofortification in millets by summarizing the opportunities and challenges to increase the bioavailability of macro and micronutrients.

Biofortification in Millets: A Sustainable Approach for Nutritional Security

PubMed Central

Vinoth, A.; Ravindhran, R.

2017-01-01

Nutritional insecurity is a major threat to the world’s population that is highly dependent on cereals-based diet, deficient in micronutrients. Next to cereals, millets are the primary sources of energy in the semi-arid tropics and drought-prone regions of Asia and Africa. Millets are nutritionally superior as their grains contain high amount of proteins, essential amino acids, minerals, and vitamins. Biofortification of staple crops is proved to be an economically feasible approach to combat micronutrient malnutrition. HarvestPlus group realized the importance of millet biofortification and released conventionally bred high iron pearl millet in India to tackle iron deficiency. Molecular basis of waxy starch has been identified in foxtail millet, proso millet, and barnyard millet to facilitate their use in infant foods. With close genetic-relatedness to cereals, comparative genomics has helped in deciphering quantitative trait loci and genes linked to protein quality in finger millet. Recently, transgenic expression of zinc transporters resulted in the development of high grain zinc while transcriptomics revealed various calcium sensor genes involved in uptake, translocation, and accumulation of calcium in finger millet. Biofortification in millets is still limited by the presence of antinutrients like phytic acid, polyphenols, and tannins. RNA interference and genome editing tools [zinc finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs), and clustered regularly interspaced short palindromic repeats (CRISPR)] needs to be employed to reduce these antinutrients. In this review paper, we discuss the strategies to accelerate biofortification in millets by summarizing the opportunities and challenges to increase the bioavailability of macro and micronutrients. PMID:28167953

Three-Dimensional Spatiotemporal Modeling of Colon Cancer Organoids Reveals that Multimodal Control of Stem Cell Self-Renewal is a Critical Determinant of Size and Shape in Early Stages of Tumor Growth

PubMed Central

Yan, Huaming; Konstorum, Anna

2017-01-01

We develop a three-dimensional multispecies mathematical model to simulate the growth of colon cancer organoids containing stem, progenitor and terminally differentiated cells, as a model of early (prevascular) tumor growth. Stem cells (SCs) secrete short-range self-renewal promoters (e.g., Wnt) and their long-range inhibitors (e.g., Dkk) and proliferate slowly. Committed progenitor (CP) cells proliferate more rapidly and differentiate to produce post-mitotic terminally differentiated cells that release differentiation promoters, forming negative feedback loops on SC and CP self-renewal. We demonstrate that SCs play a central role in normal and cancer colon organoids. Spatial patterning of the SC self-renewal promoter gives rise to SC clusters, which mimic stem cell niches, around the organoid surface, and drive the development of invasive fingers. We also study the effects of externally applied signaling factors. Applying bone morphogenic proteins, which inhibit SC and CP self-renewal, reduces invasiveness and organoid size. Applying hepatocyte growth factor, which enhances SC self-renewal, produces larger sizes and enhances finger development at low concentrations but suppresses fingers at high concentrations. These results are consistent with recent experiments on colon organoids. Because many cancers are hierarchically organized and are subject to feedback regulation similar to that in normal tissues, our results suggest that in cancer, control of cancer stem cell self-renewal should influence the size and shape in similar ways, thereby opening the door to novel therapies. PMID:28681151

Development and Applications of Photo-triggered Theranostic Agents

PubMed Central

Rai, Prakash; Mallidi, Srivallesha; Zheng, Xiang; Rahmanzadeh, Ramtin; Mir, Youssef; Elrington, Stefan; Khurshid, Ahmat; Hasan, Tayyaba

2010-01-01

Theranostics, the fusion of therapy and diagnostics for optimizing efficacy and safety of therapeutic regimes, is a growing field that is paving the way towards the goal of personalized medicine for the benefit of patients. The use of light as a remote-activation mechanism for drug delivery has received increased attention due to its advantages in highly specific spatial and temporal control of compound release. Photo-triggered theranostic constructs could facilitate an entirely new category of clinical solutions which permit early recognition of the disease by enhancing contrast in various imaging modalities followed by the tailored guidance of therapy. Finally, such theranostic agents could aid imaging modalities in monitoring response to therapy. This article reviews recent developments in the use of light-triggered theranostic agents for simultaneous imaging and photoactivation of therapeutic agents. Specifically, we discuss recent developments in the use of theranostic agents for photodynamic-, photothermal- or photo-triggered chemo-therapy for several diseases. PMID:20858520

Antisense knockdown of sphingosine kinase 1 in human macrophages inhibits C5a receptor-dependent signal transduction, Ca2+ signals, enzyme release, cytokine production, and chemotaxis.

PubMed

Melendez, Alirio J; Ibrahim, Farazeela Bte Mohd

2004-08-01

The anaphylatoxin C5a is produced following the activation of the complement system and is associated with a variety of pathologies, including septic shock and adult respiratory distress syndrome, and with immune complex-dependent diseases such as rheumatoid arthritis. C5a has been shown to regulate inflammatory functions by interacting with its receptor, C5aR, which belong to the rhodopsin family of seven-transmembrane GPCRs. However, the intracellular signaling pathways triggered by C5aR on immune-effector cells are not well understood. In this report we present data showing that, in human monocyte-derived macrophages, C5aR uses the intracellular signaling molecule sphingosine kinase (SPHK)1 to trigger various physiological responses. Our data show that C5a rapidly stimulates the generation of sphingosine-1-phosphate, SPHK activity, and membrane translocation of SPHK1. Using an antisense oligonucleotide against SPHK1, we show that knockdown of SPHK1 abolishes the C5a-triggered intracellular Ca(2+) signals, degranulation, cytokine generation, and chemotaxis. Our study shows for the first time that SPHK1 not only plays a key role in the generation and release of proinflammatory mediators triggered by anaphylatoxins from human macrophages but is also involved in the process of immune cell motility, thus pointing out SPHK1 as a potential therapeutic target for the treatment of inflammatory and autoimmune diseases.

Smart nanovehicles based on pH-triggered disassembly of supramolecular peptide-amphiphiles for efficient intracellular drug delivery.

PubMed

Xu, Xianghui; Li, Yunkun; Li, Haiping; Liu, Rong; Sheng, Mingming; He, Bin; Gu, Zhongwei

2014-03-26

A novel type of nanovehicle (NV) based on stimuli-responsive supramolecular peptide-amphiphiles (SPAs, dendritic poly (L-lysine) non-covalently linked poly (L-leucine)) is developed for intracellular drug delivery. To determine the pH-dependent mechanism, the supramolecular peptide-amphiphile system (SPAS) is investigated at different pH conditions using a variety of physical and chemical approaches. The pH-triggered disassembly of SPAS can be attributed to the disappearance of non-covalent interactions within SPAs around the isoelectric point of poly (L-leucine). SPAS is found to encapsulate guest molecules at pH 7.4 but release them at pH 6.2. In this way, SPAS is able to act as a smart NV to deliver its target to tumor cells using intracellular pH as a trigger. The DOX-loaded NVs are approximately 150 nm in size. In vitro release profiles and confocal laser scanning microscopy (CLSM) images of HepG2 cells confirm that lower pH conditions can trigger the disassembly of NVs and so achieve pH-dependent intracellular DOX delivery. In vitro cytotoxicity of the DOX-loaded NVs to HepG2 cells demonstrate that the smart NVs enhance the efficacy of hydrophobic DOX. Fluorescence-activated cell sorting (FACS) and CLSM results show that the NVs can enhance the endocytosis of DOX into HepG2 cells considerably and deliver DOX to the nuclei. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Active accommodation of plate convergence in Southern Iran: Earthquake locations, triggered aseismic slip, and regional strain rates

NASA Astrophysics Data System (ADS)

Barnhart, William D.; Lohman, Rowena B.; Mellors, Robert J.

2013-10-01

We present a catalog of interferometric synthetic aperture radar (InSAR) constraints on deformation that occurred during earthquake sequences in southern Iran between 1992 and 2011, and explore the implications on the accommodation of large-scale continental convergence between Saudi Arabia and Eurasia within the Zagros Mountains. The Zagros Mountains, a salt-laden fold-and-thrust belt involving ~10 km of sedimentary rocks overlying Precambrian basement rocks, have formed as a result of ongoing continental collision since 10-20 Ma that is currently occurring at a rate of ~3 cm/yr. We first demonstrate that there is a biased misfit in earthquake locations in global catalogs that likely results from neglect of 3-D velocity structure. Previous work involving two M ~ 6 earthquakes with well-recorded aftershocks has shown that the deformation observed with InSAR may represent triggered slip on faults much shallower than the primary earthquake, which likely occurred within the basement rocks (>10 km depth). We explore the hypothesis that most of the deformation observed with InSAR spanning earthquake sequences is also due to shallow, triggered slip above a deeper earthquake, effectively doubling the moment release for each event. We quantify the effects that this extra moment release would have on the discrepancy between seismically and geodetically constrained moment rates in the region, finding that even with the extra triggered fault slip, significant aseismic deformation during the interseismic period is necessary to fully explain the convergence between Eurasia and Saudi Arabia.

Insect haptoelectrical stimulation of Venus flytrap triggers exocytosis in gland cells.

PubMed

Scherzer, Sönke; Shabala, Lana; Hedrich, Benjamin; Fromm, Jörg; Bauer, Hubert; Munz, Eberhard; Jakob, Peter; Al-Rascheid, Khaled A S; Kreuzer, Ines; Becker, Dirk; Eiblmeier, Monika; Rennenberg, Heinz; Shabala, Sergey; Bennett, Malcolm; Neher, Erwin; Hedrich, Rainer

2017-05-02

The Venus flytrap Dionaea muscipula captures insects and consumes their flesh. Prey contacting touch-sensitive hairs trigger traveling electrical waves. These action potentials (APs) cause rapid closure of the trap and activate secretory functions of glands, which cover its inner surface. Such prey-induced haptoelectric stimulation activates the touch hormone jasmonate (JA) signaling pathway, which initiates secretion of an acidic hydrolase mixture to decompose the victim and acquire the animal nutrients. Although postulated since Darwin's pioneering studies, these secretory events have not been recorded so far. Using advanced analytical and imaging techniques, such as vibrating ion-selective electrodes, carbon fiber amperometry, and magnetic resonance imaging, we monitored stimulus-coupled glandular secretion into the flytrap. Trigger-hair bending or direct application of JA caused a quantal release of oxidizable material from gland cells monitored as distinct amperometric spikes. Spikes reminiscent of exocytotic events in secretory animal cells progressively increased in frequency, reaching steady state 1 d after stimulation. Our data indicate that trigger-hair mechanical stimulation evokes APs. Gland cells translate APs into touch-inducible JA signaling that promotes the formation of secretory vesicles. Early vesicles loaded with H + and Cl - fuse with the plasma membrane, hyperacidifying the "green stomach"-like digestive organ, whereas subsequent ones carry hydrolases and nutrient transporters, together with a glutathione redox moiety, which is likely to act as the major detected compound in amperometry. Hence, when glands perceive the haptoelectrical stimulation, secretory vesicles are tailored to be released in a sequence that optimizes digestion of the captured animal.

Effects of rainfall spatial variability and intermittency on shallow landslide triggering patterns at a catchment scale

NASA Astrophysics Data System (ADS)

von Ruette, J.; Lehmann, P.; Or, D.

2014-10-01

The occurrence of shallow landslides is often associated with intense and prolonged rainfall events, where infiltrating water reduces soil strength and may lead to abrupt mass release. Despite general understanding of the role of rainfall water in slope stability, the prediction of rainfall-induced landslides remains a challenge due to natural heterogeneity that affect hydrologic loading patterns and the largely unobservable internal progressive failures. An often overlooked and potentially important factor is the role of rainfall variability in space and time on landslide triggering that is often obscured by coarse information (e.g., hourly radar data at spatial resolution of a few kilometers). To quantify potential effects of rainfall variability on failure dynamics, spatial patterns, landslide numbers and volumes, we employed a physically based "Catchment-scale Hydromechanical Landslide Triggering" (CHLT) model for a study area where a summer storm in 2002 triggered 51 shallow landslides. In numerical experiments based on the CHLT model, we applied the measured rainfall amount of 53 mm in different artificial spatiotemporal rainfall patterns, resulting in between 30 and 100 landslides and total released soil volumes between 3000 and 60,000 m3 for the various scenarios. Results indicate that low intensity rainfall below soil's infiltration capacity resulted in the largest mechanical perturbation. This study illustrates how small-scale rainfall variability that is often overlooked by present operational rainfall data may play a key role in shaping landslide patterns.

Let your fingers do the walking: The projects most invaluable tool

NASA Technical Reports Server (NTRS)

Zirk, Deborah A.

1993-01-01

The barrage of information pertaining to the software being developed for a project can be overwhelming. Current status information, as well as the statistics and history of software releases, should be 'at the fingertips' of project management and key technical personnel. This paper discusses the development, configuration, capabilities, and operation of a relational database, the System Engineering Database (SEDB) which was designed to assist management in monitoring of the tasks performed by the Network Control Center (NCC) Project. This database has proven to be an invaluable project tool and is utilized daily to support all project personnel.

Mesofluidic controlled robotic or prosthetic finger

DOEpatents

Lind, Randall F; Jansen, John F; Love, Lonnie J

2013-11-19

A mesofluidic powered robotic and/or prosthetic finger joint includes a first finger section having at least one mesofluidic actuator in fluid communication with a first actuator, a second mesofluidic actuator in fluid communication with a second actuator and a second prosthetic finger section pivotally connected to the first finger section by a joint pivot, wherein the first actuator pivotally cooperates with the second finger to provide a first mechanical advantage relative to the joint point and wherein the second actuator pivotally cooperates with the second finger section to provide a second mechanical advantage relative to the joint point.

Cradle and pressure grippers

DOEpatents

Muniak, John E.

2001-01-01

A gripper that is designed to incorporate the functions of gripping, supporting and pressure tongs into one device. The gripper has two opposing finger sections with interlocking fingers that incline and taper to form a wedge. The interlocking fingers are vertically off-set so that the opposing finger sections may close together allowing the inclined, tapered tips of the fingers to extend beyond the plane defined by the opposing finger section's engagement surface. The range of motion defined by the interlocking relationship of the finger sections allows the gripper to grab, lift and support objects of varying size and shape. The gripper has one stationary and one moveable finger section. Power is provided to the moveable finger section by an actuating device enabling the gripper to close around an object to be lifted. A lifting bail is attached to the gripper and is supported by a crane that provides vertical lift.