BME Friday Student Seminar and Happy Hour

First FSSHH of this year at Homewood!!

2010-08-31T20:22:00.000-07:00

Come enjoy the friendly welcome from Homewood at this upcoming FSSHH!

Jake is presenting with food volunteered by Sravanti.

Who: Jake Simson

When: September 17th

Where: Clark 110 Homewood

See you all there!

Title: The application of a chondroitin sulfate-bone marrow adhesive towards

meniscal repair

Abstract: Meniscal injuries may lead to joint degeneration and the development of post-traumatic osteoarthritis. There are few technologies beyond sutures available for surgeons to repair the meniscus, and sutures inherently cause additional damage to the tissue. Adhesives that work to repair meniscus while fixing the tissue in place offer an appealing alternative solution. Here, we demonstrate the use of a NHS-functionalized chondroitin sulfate (CS-NHS) bioadhesive for use in meniscal repair. 10% CS-NHS was mixed with 10% Polyethylene Glycol (PEG) in a 1:1 ratio, and with BM in ratios of 3:7 (70% BM), 1:1 (50% BM), and 7:3 (30% BM). Meniscus cells were encapsulated in gels to quantify in vitro tissue generation, and bovine meniscus explants were glued to observe meniscus cell migration into the adhesive. Constructs were analyzed at one and three weeks using live/dead, H&E staining, and Hoescht dye DNA assays. Glued tissue explants were sectioned and stained with H&E at two and four weeks. Live/dead and Hoescht DNA assays showed statistically significantly higher viability at both time points in CS-BM gels in comparison to CS-PEG. At one week normalized DNA levels increased with BM concentration, but this effect diminished by week three. However, extensive clustering of cells was observed at three weeks in CS-BM gels, indicating cell proliferation. In the explant study cells were observed proliferating on the surface of 70% BM at week two, and at week four cells were seen within the gel proliferating and depositing matrix. These findings indicate that meniscal cell viability in the CS-BM gel remains high after several weeks in culture, they proliferate within the gel, and that meniscal cells are capable of migrating from meniscal tissue first onto the hydrogel surface, and later into BM gels. These are promising preliminary results for the use of CS-BM adhesive in regenerating meniscus tissue.

FSSHH this Friday!

2010-08-31T20:20:00.000-07:00

Come to the first FSSHH (Friday Student Seminar and Happy Hour) of the year!

Food and drink and fun; plus learn about the cool work of one of your fellow grad students.

WHO: Matt Fifer, a second year student from Dr. Thakor's lab is giving the talk

WHAT: Decoding grasp kinematics from human electrocorticography (ECoG)

WHERE: Traylor 709

WHEN: 5pm Friday August 27th.

Title:

Decoding grasp kinematics from human electrocorticography (ECoG)

Abstract:

Human electrocorticography (ECoG) is a neural recording modality used for seizure localization in epileptic patients prior to resection surgery. We measured ECoG amplitude in 4 subjects and attempted to predict the degree of grasp aperture during a slow grasping motion of the hand. Decoding accuracy was found to be high (mean r > 0.6), to be relatively invariant to wrist rotation angle, and to require relatively few electrodes to achieve maximal performance. This work is promising for the potential future development of a reliable, low-footprint ECoG-driven neuroprosthetic. Future work is targeting the application of similar methods to more natural reach-to-grasp motions.

FSSHH: Friday April 2 5pm Traylor 709 Med Campus

2010-03-24T05:03:00.000-07:00

Presenter: Susan Thompson

Title: Human Embryonic Stem Cell Derived Cardiomyocytes Ameliorate Vulnerability for Arrhythmias in an In Vitro Model of Cardiac Fibrosis

Abstract: Human embryonic stem cells (hESCs) are an attractive candidate for cardiac regeneration because of their potential to supply a large number of differentiated cardiomyocytes that can integrate into the host tissue, thereby replacing the myocytes lost during myocardial aging, disease or damage. Numerous studies have already demonstrated improved myocardial function with grafts of human embryonic stem cell-derived cardiomyocytes (hESC-CMs), alluding to possible roles of paracrine effects and direct myocardial regeneration. However, little attention has been given to the electrophysiological benefit that these cells may have on diseased myocardium, and specifically, on cardiac fibrosis, a pathological condition found in aging, heart failure, and myocardial infarction. We therefore set out to characterize the electrophysiological benefits of adding hESC-CMs to our previously reported, in vitro model of cardiac fibrosis. Following engraftment of hESC-CMs from beating hESC-CMs, LCV and TCV of fibrotic monolayers increased to 39.3±2.7 and 12.5±1.3 cm/s, respectively (n=6). In contrast, addition of hESCs from non-beating EBs suppressed LCV and TCV to 6.5±1.3 and 2.1±1 cm/s, respectively (n=4). We show for the first time that hESC-CMs reverse the loss of conduction velocity and reduce the incidence of spiral waves in an in vitro fibrosis model. This finding is significant in that it suggests that specifically hESC-CMs can directly participate in electrical propagation, perhaps through gap junction coupling, and can ameliorate abnormal conduction in fibrotic myocardium.

Last FSSHH of this year: Jacob Koskimaki

2009-12-04T13:29:00.001-08:00

Last FSSHH of this year!!!!

Come enjoy Jacob's presentation, free food + drinks and awesome company of fellow BMEers!

Dec 11th (Friday) 5pm at Clark 110.

Title & abstract: Peptide optimization strategies: merging experimental data with bioinformatics tools to develop potent inhibitors of angiogenesis in breast cancer

The emergence of genomics, proteomics and new peptidomics has provided several advances in the data available to develop endogenous regulators of angiogenesis. Angiogeneis, or neovascularization, is the process where new vessels form from a preexisting microvasculature, and involves interactions among several cell types. Tumors require a blood supply to grow; similarly, abrogating this blood supply is an emerging paradigm to treat diseases such as breast cancer. Our laboratory recently developed a systematic bioinformatics-based methodology to identify several endogenous regulators of angiogenesis, and experimentally verified their activity in vitro and in vivo breast xenograft models. We now have begun to optimize these sequences to enhance activity, and show different experimental techniques combined with bioinformatics tools to increase activity of endogenous therapeutics.

FSSHH Friday Nov 6

2009-11-02T11:18:00.000-08:00

This Friday Nov 6, 5pm - 6pm, Med school (Traylor 709)

Mohsen Mollazadeh is presenting! Title and abstract coming soon

title: Monitoring of neuronal activity during dexterous hand movements.
abstract: In the first part of the talk, I will present the VLSI circuit we have developed for monitoring neuronal activity in awake behaving studies. In the second part, I will present the study of population neuronal activity in primate's motor cortex during dexterous hand movements. I will present how LFP signals are modulated with various grasp patterns and their relationship to single unit activity.

FSSHH this Friday!!!

2009-09-21T15:09:00.001-07:00

This Friday Sept 25th 5pm - 6pm, Med school (Traylor 709)

Kartik is presenting on 'optical techniques and VLSI systems for structural and functional brain imaging'.

See you all there!

Abstract: optical techniques for investigating the brain offer several key strengths - non-contact, minimally invasive, multi-scale (single cells to populations), functional/structural observation. currently, most small animal imaging is restricted to restrained &/or anesthetized animals. electrophysiology in awake, behaving rodents has led to many interesting behavioral results, but imaging in a similar scenario has not been explored well. i've been working on designing miniaturized optical imaging systems that incorporate illumination, optics and image sensing electronics in a small volume device that can be mounted on a rodent for chronic imaging in awake and behaving animals. i'll talk about the design and characterization of the imaging system and the image sensor and some preliminary experiments in rats.

Next FSSHH Friday Sept 11 2009: Sabyasachi Roy

2009-09-08T15:02:00.001-07:00

FSSHH Returns this fall on Friday Setp 11, 2009. Sabyasachi Roy will be presenting at Talbot Library (Traylor 709)

Abstract:
Application of multi-channel telemetry in auditory neurophysiology & behavior

The neural basis of vocal control and auditory feedback has long interested neuroscientist and biomedical engineers alike. Our lab has focused on studying the cortical neural activity in the common marmoset in understanding this basic sensory-motor system. The marmoset monkeys (Callithrix Jacchus) is an ideal animal model given the fact that they remain highly vocal in captivity. This essential vocal behavior is primarily elicited when the subject is in a natural behavior state i.e. free roaming condition. Typically, neurophysiological experiments on vocal production and feedback have involved either restrained subjects or tethered setups that severely restrict the behavior of the subject. This is where multi-channel neural telemetry can play a vital role of enabling the vocal behavior of primates during auditory experiments and providing the same quality of neural data as tethered setups. We are developing the essential wireless radio link as well as the backend processing capability to make this technology practical and effective. These small, lightweight wireless devices can continuously transmit multiple channels of neural data from the relevant cortical area of the marmoset while it is engaged in an experimental task. I will briefly highlight our progress in developing custom telemetry system and integrating existing devices as well as the experimental opportunities that this technology opens up.

Need volunteers for Fall 2009!

2009-08-15T10:36:00.000-07:00

please email luke ( lukejohnson07 AT gmail.com) and/or Yoonju (cho.yoonju AT jhmi.edu) to volunteer!

What is the Friday Student Seminar and Happy Hour?

FSSHH is a regularly scheduled seminar series for Johns Hopkins BME grad students and other interested students that includes a seminar talk, happy hour refreshments (beer, soda appetizers), and fun social interactions.

Why have it?

It has gives students opportunities to present their work and learn about their peers research in a relaxed environment. It also is a great opportunity for students to socialize and meet students from other labs and years.

When is it?

One or two Fridays a month @ 5pm

Where is it?

Either Homewood Clark 110, or 7th floor Library in Traylor (Talbot) at the Med Campus

What will go on?

Generally, the first 15 - 30 minutes will be spent drinking, eating snacks, etc, and the last 20-30 minutes there will be a talk by a fellow grad student. The nature of the talk is completely up to the presenter, but the hope is that they wont be overly technical, so that anybody from our very diverse department could listen and be interested and at least somewhat understand.

Questions/Comments? email lukejohnson07 AT gmail.com or cho.yoonju AT jhmi.edu

2009-06-04T14:33:00.000-07:00

June 19th, Homewood Clark 110

-- Yi Zhang

We performed on-chip DNA methylation analysis using methylation-specific PCR (MSP) within an arrayed micro droplet-in-oil platform that is designed for more practical application of microfluidic droplet technologies in clinical applications. Unique features of this ready-to-use device include arrayed primers that are pre-deposited into micro-reaction chambers and use of the oil phase as a companion fluid for both sample actuation and compartmentalization. These technical advantages allow for infusion of minute amounts of sample for arrayed MSP analysis, without the added complexities inherent in microfluidic droplet-based studies. Ease of use of this micro device is exemplified by analysis of two tumor suppressor promoters, p15 and TMS1 using an on-chip methylation assay. These results were consistent with standard MSP protocols, yet the simplicity of the droplet-in-oil microfluidic PCR platform provides and easy and efficient tool for DNA methylation analysis in a large-scale arrayed manner.

2009-05-12T08:04:00.000-07:00

May 15, 2009; Homewood, Clark 110
-- Chris Puleo

Title: "Accessible Single Molecule Detection Technologies: Microfluidic Interfaces
for Diagnostic and Single Cell Applications"

Abstract: The long term goal of this proposal is to develop microfluidic technologies that enable the widespread use of confocal fluorescence spectroscopy (CFS) for single molecule detection (SMD) in vital applications including, single molecule diagnostics and single cell analysis. Currently amplification techniques have been used to determine the presence of rare biomolecules in such applications; however, the cost, complexity, and time requirements associated with these tests limit clinical value and general utility. Direct molecule-by-molecule assessment using SMD remains an intriguing replacement for amplification technologies due to high sensitivity, assay simplicity, and low costs; however, technical challenges continue to limit the utility of these single molecule techniques. We use microfluidic interfaces for SMD platforms to expand applicability in the analysis of rare molecules from complex biological fluids. The overall goal of this work is apply microfluidics to SMD assays in order to obtain the lowest possible detection limits from the smallest possible sample volume. Direct implications are clear, high-throughput biomolecular analysis from the most precious and rare biological samples. In theory, single molecule sensitivity confers infinite detection limits in CFS platforms; however, in practice SMD platforms rely on continuous flow formats and bulk probe-target reactions. These design flaws yield significant fundamental pitfalls and result in practical limitations: 1) Analyte delivery to the microscale sensing elements is wasteful, leading to extremely low measurement efficiencies and the need for excessive sample volumes. 2) Passive probe-target interactions result in slow reaction kinetics and prohibitive assay run times. 3) Unoptimized and manual processing of target molecules results in low molecular throughput and incompatibility with arrayed formats. Experiments will be performed using two microfluidic platforms, multilayer soft lithography and water-in-oil droplets. Coupling these discrete volume control technologies with SMD provides direct control over probe hybridization, efficient transfer of target molecules to optical detection volumes, and automated processing of large numbers of sample in relatively short assay times. These improvements serve to open the door to practical use of single molecule assays in areas of vital need, such as, non-invasive diagnostic screening and investigation of cell-to-cell heterogeneity. Our lab stands in a unique position to take advantage of this potential due to practical experience in all three aspects of this challenge, including single molecule probe design, microfluidic device design and fabrication, and optical CFS platform engineering.

FSSHH still in water!

2009-04-12T17:55:00.000-07:00

Need a pregame(?) before the cruise?

This Friday 4/17 Hannah will be presenting at Homewood Clark 110 from 5:00 though 6:00pm (5:00 for food and 5:30 for the talk). We still need a volunteer for food and drinks, so if you are interested in it, please contact me (cho.yoonju@jhmi.edu) or Luke (luke.johnson@jhu.edu).

This is going to be AWESOME so just come and enjoy some 1st light dinner for the day before your 2nd light dinner at the cruise :)

See you all there!

April 17, 2009; Homewood, Clark 110
-- Hannah Carter

In cancer, normal cells are transformed through accumulated genetic alterations that confer a selective advantage. Somatic missense mutations are one form of genetic aberration that contribute to tumor initiation and progression. Each tumor harbors a set of these mutations, but it is unclear which are drivers, causally associated with the tumor's progression, and which are passengers, neutral in the context of selective advantage for the cancer cell. We have applied modern machine learning techniques to develop a high-throughput method for discriminating between driver and passenger somatic missense mutations identified in large scale tumor sequencing studies.

2009-03-29T19:52:00.000-07:00

April 3, 2009; Homewood, Clark 110
-- Raymond Cheong

Title: "How to use bioinformatics and other methods to win sports pools without knowing anything (much) about sports"

Abstract: In sports pools, such as those related to the ongoing men's college basketball tournament, it is often observed that those who know the least about sports end up making more accurate predictions than those who are more "knowledgeable" about sports. As a hobby project over the past ~10 years, I have been putting this idea to the test by investigating the performance of unsupervised algorithms to predict the winner of team sports. In this informal talk, I will highlight a variety of creative algorithms and discuss associated methodology and strategy. These algorithms include simple coin-flipping and Google-based methods, as well as bioinformatics-inspired linear models, network-oriented ratings, and clustering.

First FSSHH of 2009!!!!

2009-01-14T11:04:00.000-08:00

FSSHH is back for 2009!!

The honorable speaker of this year's first FSSHH is Deok-Ho and it will be held on Jan 23rd Friday - of course ;) - at Homewood Clark 110 from 5:00pm through 6:00pm. As usual, the food and drinks at 5pm and the talk will begin at 5:30.

Hope to see you all there!

Jan 23, 2009; Homewood Clark 110
-- Deok-Ho Kim

Title: Analysis and Engineering of Cell Function with Nanoscale Cues

Abstract: In this talk, I will present multidisciplinary efforts directed towards better understanding of how diverse cell functions are controlled by the nano-scale features of cell micro-environment through active mechanosensing. I will particularly focus on three different settings in normal and pathophysiological contexts, in which cellular sensing of local force and geometry can have dramatic consequences: guided cell migration by well organized extracellular matrix, controlled stem cell differentiation via matrix topology, and development of tissue-engineered cardiac grafts. As novel tools to address these questions, I will introduce a series of biomimetic micro-devices combining the advantages of precise definition of both nano-topographic features and chemical ligands on chips, and then discuss how these tools help to gain better understanding of the fundamental aspects of establishment of cell polarity and guidance, and allow us to establish general principles for development of more precise and defined scaffolds for tissues engineering.

2008-12-16T14:38:00.000-08:00

FSSHH will return after the holidays. (January sometime)

Yoonju Cho will now be in charge of organizing FSSHH on the Homewood Campus!!!

Please talk to Yoonju or Luke Johnson if you want to volunteer to present or get food/drink for one of the happy hours.

2008-12-01T13:31:00.000-08:00

NEXT FSSHH: Holiday Extravaganza!

As the final FSSHH of this semester, and given the season, I think it makes sense to make it a holiday extravaganza. If you have ideas for food/drink fitting for such an event, please let me know: luke.johnson AT jhu.edu

Dec 5, 2008
-- Jacob Koskimaki

Location: Med School Talbot Library (Traylor 709)

Title: A Peptidomic approach to curing breast cancer

Abstract: Breast cancer is the most commonly diagnosed female malignancy in the United States, proving fatal to nearly 40,000 people in 2007 with 180,000 additional diagnoses. Angiogenesis or neovascularization, the process of new blood vessel formation from pre-existing microvasculature, involves interactions between several types of cells including endothelial cells (ECs), and stromal cells. We previously introduced a novel systematic methodology to identify putative endogenous antiangiogenic peptides and validated these predictions in vitro in human umbilical vein endothelial cell (HUVEC) proliferation and migration assays [1]. These peptides are derived from several protein families including type IV collagen, thrombospondin domain-containing proteins, and CXC chemokines. Based on the results from the in vitro screening, we have evaluated the ability of several peptides selected from the different families to suppress angiogenesis in breast cancer orthotopic xenograft models in severe combined immunodeficient (SCID) mice using MDA-MB-231 human breast cancer cells. We have demonstrated significant suppression of tumor growth in vivo, indicating the potential of these peptides as novel breast cancer therapeutics.

2008-10-21T10:37:00.000-07:00

October 24, 2008
-- Tao Yu

Location: Homewood Clark 110

Title: An introduction to Synthetic Biology and the iGEM competition

Abstract: Synthetic biology, a new discipline to "make biology easier to be engineered", is an emerging branch of biology in recent years. Though quite some researchers are participating the research in such a field, synthetic biology is still far from familiar to a broad range of investigators in biology, medicine and engineering scopes. iGEM, which is short for the international Genetically Engineered Machines competition, is an annual undergrad competition aiming to recruit more participants in the community of synthetic biology. Here, I would like to introduce you to some key concepts and typical research in synthetic biology, and share with you the great fun I had in the iGEM competition last year.

2008-10-08T16:04:00.000-07:00

October 10, 2008
-- Suneil Hosmane

Location: Med Campus Talbot Library (Traylor 709)

Title: TBA

Abstract: Microfluidics has the potential to uncover mechanisms behind many neurodegenerative diseases by enabling engineers and scientists to recreate the diseased cellular microenvironment. By doing so, a repeatable, efficient, and quantitative approach can be taken to understand the neurobiology of disease in vitro. To this extent, we have developed a novel device platform that merges conventional macro-sized features with microfluidic technology to yield a hybrid device compatible with standard biological protocols. This device allows for numerous experimental modalities through the replication of a single master design using conventional polymethyldisiloxane (PDMS) soft lithography.

Laboratory: Biomedical Instrumentation and Neuroengineering Laboratory
http://www.jhu.edu/nthakor/

2008-09-12T16:47:00.000-07:00

September 26 2008
-- Tri Ngo

A first year has stepped up and volunteered to present. How awesome is that?

Title: Stochastic White Matter Tractography

Abstract: Stochastic Tractography is a Bayesian approach for inferring nerve
fiber tract parameters from DTI (Diffusion Tensor Imaging) data. We
use this framework to calculate the posterior probability of the
existence of tracts given our observations. Additionally, the
Bayesian framework allows the algorithm to infer tracts which pass
through regions with uncertain fiber orientations, previously
unreachable by non-Bayesian methods, thereby revealing more details
about structural connectivity.

We have implemented the algorithm into the ITK medical image analysis
toolkit, an open source NIH supported medical image analysis toolkit.
Additionally we created a user interface which allows the program to
be integrated in the popular 3D Slicer medical image visualization
program. Finally we present some potential clinical studies for the
algorithm.
Location: Clark 110 Homewood

2008-09-08T18:58:00.000-07:00

September 12 2008
-- Robert Jacques

Location: Med Campus Talbot Library (Traylor 709)

Title: Towards Real-Time Radiation Therapy:GPU Accelerated Superposition/Convolution

Abstract: We demonstrate the use of highly parallel graphics processing units (GPUs) to accelerate the Superposition/Convolution (S/C) algorithm to interactive rates while reducing the number of approximations. S/C first transports the incident fluence to compute the total energy released per unit mass (TERMA) grid. Dose is then calculated by superimposing the dose
deposition kernel at each point in the TERMA grid and summing the contributions to the surrounding voxels. The TERMA algorithm was enhanced with physically correct multi-spectral attenuation and a novel inverse formulation for increased performance, accuracy and simplicity. Dose deposition utilized a tilted poly-energetic inverse cumulative-cumulative kernel, with the novel option of using volumetric mip-maps to approximate solid angle ray-casting. Exact radiological path ray-casting decreased discretization errors. We achieved a speed-up of 34x-98x over a highly optimized CPU implementation.

Full Paper:
http://www.cse.buffalo.edu/hpmiccai/pdf/HPMICCAI2008-V1.pdf

Laboratory: The Computer Integrated Interventional Systems Laboratory
New page: http://ciis.lcsr.jhu.edu/Research
Old page: http://www.cisst.org/

2008-08-18T12:08:00.000-07:00

Friday Sept 12 2008 at 5pm, Med Campus Talbot 709

Wow, that was a pretty fantastic FSSHH on Aug 13th. Great turnout -- I'd say 35 people or so, plus tons of first years. It was nice to have a happy hour after so many months off.

Next FSSHH is Friday Sept 12. Robert Jacques is giving the talk. Special thanks to him for volunteering, and thanks to John Issa for getting the refreshments.

STILL NEED VOLUNTEERS!

We are looking for groups of 1-2 students to sign up to get the food
and drinks for each week.
NEED SPEAKERS! (20-30 minute informal talk) -- see schedule at right

Previous FSSHH

2008-08-12T07:18:00.000-07:00

Friday Aug 13 2008 at 5pm, Homewood Clark 110

Super first-year (now second-year, I suppose) Laura Doyle is getting the food/drinks.

This is just a happy hour to get the ball rolling for this year. No seminar, though I may lock people in and not let them out until we get people committed to presenting and getting refreshments for the rest of the dates this semester.

Special invitation to the new incoming first-years! We are excited to meet you.

STILL NEED VOLUNTEERS!

We are looking for one person to help Luke in scheduling FSSHH for the next year.
We are looking for groups of 1-2 students to sign up to get the food
and drinks for that week.
NEED SPEAKERS! (20-30 minute informal talk) -- see schedule at right

The Future of FSSHH

2008-05-06T06:06:00.000-07:00

We are looking for one person to help Luke in scheduling FSSHH for
the next year.

Tentative dates have been set, so responsibilities would include:
-- finding speakers for the scheduled dates
-- finding people to be in charge of getting food/drinks for the scheduled dates
-- reminding those people and the speaker about the happy hour as the
date approaches

We are looking for groups of 1-2 students to sign up to get the food
and drinks for that week.

Each happy hour a DIFFERENT group of 2 would be in charge of food/drinks and setup. This way more people could get involved, and they could get whatever they want (more variety from week to week). This has the added benefit that one person would not have to do everything (scheduling, purchasing, setting up) for the entire year.

Responsibilities include:
-- buying food and drinks
-- setting up the happy hour / cleaning up afterwards
-- make sure presenter has laptop and connector for projector
-- get reimbursed for expenses (simple process; ask Luke about it)
-- people who do the setup get to decide the location (med school / homewood)

Please see the tentative schedule below or at http://fsshh.blogspot.com/ and contact Luke (lukejohnson07@gmail.com) if you are interested in helping out. It is expected that many first-years would contribute by signing up to buy and setup for one of the days, and older year students would contribute by signing up to give a presentation.

However, if a first year wishes to present, that is great. If an older year wants to setup, fantastic.

Tentative Schedule for 2008

August 15
September 12
September 26
October 10
October 24
November 7
November 21

2008-04-06T20:27:00.000-07:00

April 18 2008 -- Molly Maleckar

Location: Clark 110 Homewood Campus

Title: Searching High and Low: Incorporating various levels of structure and function to more realistically model cardiac arrhythmias

Abstract: Myocytes and fibroblasts are the two major cell types in healthy mammalian myocardium. Although myocytes are primarily responsible for the mechanical function and occupy most of the tissue volume, fibroblasts outnumber myocytes by a ratio of approximately 3:2. In canine left ventricle, fibroblasts have been identified in the immediate vicinity of each myocyte. Gap junctional proteins, connexins 43 (Cx43) and 45 (Cx45), are expressed by cardiac fibroblasts, and dye coupling from fibroblasts to atrial and ventricular myocytes has been demonstrated, suggesting that myocytes and fibroblasts are functionally coupled by gap junctions and may interact via two-way electrotonic signaling. Studies involving electrophysiological coupling have shown that when variable numbers of myofibroblasts were cultured over sheets of neonatal myocytes, recordings from myocytes showed that the rate of action potential depolarization and conduction velocity decreased with increasing density of myofibroblasts. Previous work had shown that mechanosensitive atrial or sinoatrial fibroblasts were also coupled electrotonically to adjacent myocytes Thus, electrotonic coupling can occur in vivo as well as in vitro settings. In addition to having potentially significant effects upon the electrophysiological responses of the myocyte and the local conduction environment, the role of fibroblast membrane kinetics and fibroblast-myocyte coupling in the pathophysiological setting of myocardial fibrosis remains poorly understood. This presentation will offer an overview of a pair of studies whose goal is to elucidate the effects of fibroblast-myocyte interactions on conduction and excitation at the tissue and cellular levels, respectively.

Laboratory: Computational Cardiac Electrophysiology Lab -- Dr. Trayanova

2008-04-01T08:50:00.000-07:00

Friday Student Seminar and Happy Hour (FSSHH)

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April 4 2008 -- John Issa

Location: Talbot Library Med Campus

Title: Calcium-dependent facilitation of P/Q-type calcium channels

Abstract: Due to its importance in many cellular processes, intracellular calcium is under tight control, thus allowing cells to be sensitive to small changes in calcium levels. One example of this control is the P/Q-type calcium channel, commonly found in neural synapses. Specifically, while a rise in global calcium causes a decrease in currents through these channels, a rise in local calcium on a short timescale causes an increase in currents, a process known as calcium-dependent facilitation (CDF). In this study, we analyzed the nature of this mechanism by recording currents through single P/Q-type channels and comparing the ability of candidate kinetic models to explain the data. Our findings suggest that CDF occurs by an increase in a channel's open probability and not just by increased kinetics or a reduction of inhibition.

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February 29 2008 -- Marcus Jeschke

Location: Clark 110 Homewood Campus

Title: Gamma oscillations during an auditory target-discrimination task reflect matches with short-term memory –
A parallel study in humans and rodents

Abstract: Gamma-band oscillations have been implicated in a variety of cognitive functions as well as more basic stimulus-related aspects of neuronal activity. In an effort to combine a large body of these findings it has recently been proposed that gamma-band oscillations reflect the interaction of incoming sensory information with information about past stimuli stored in memory. Here we investigated the prediction of this ’match-and-utilization’ model that the strength of gamma oscillations depends on the similarity of present stimuli with stored memory templates. We employed an auditory target-discrimination task in which the subjects had to respond to one out of four frequency-modulated tones that varied with respect to two stimulus dimensions, viz. "spectral content" and "modulation direction". We conducted the study in rodents and in humans to exploit the complementary advantages of both paradigms, viz. easy intracerebral recording from primary sensory cortex and monitoring of learning-effects in the rodent experiment, and whole scalp accessibility of EEG signals and straightforward instruction of subjects in the human experiment. In both species, we found that the early, evoked gamma-band activity did not show task- or learning-related modulations, indicating that it reflects aspects of the physical nature of the stimuli. In contrast, the late, induced gamma-band activity was significantly influenced by the task. In both paradigms the target always elicited the strongest gamma-band response, while partial matches with the target resulted in intermediate response strengths. Assigning the role of the target to different stimuli led to the same result in the human subjects. In the
animal subjects, the dependence of the gamma-band response strength on the similarity with the target developed with learning and was not found in naïve animals. In combination, our results add further support for the general validity of the match-and-utilization model of gamma-band oscillations.

Laboratory: Laboratory of Auditory Neurophysiology -- Dr. Wang -- http://www.jhu.edu/xwang/

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February 15 2008 -- Laura Doyle

Location: Clark 110 Homewood Campus

Title: A virtual environment simulator for cataract surgery

Abstract: Phacoemulsification cataract surgery is one of the most commonly performed surgical procedures in the western world. Conventional training for this procedure involves didactic lectures and practice on pig and human cadaver eyes, none of which allow trainees to form an accurate predictive model of human tissue behavior during surgery. A virtual environment simulator for capsulorrhexis, one of the first steps in cataract surgery, has been developed. The simulator invokes a deformable mass-spring-damper mesh model of the tissue that can be grasped and torn via shearing. The trainee controls tool motion using a 3-degree-of-freedom haptic device, and haptic feedback is provided from the virtual tissue.

Laboratory: Haptics Laboratory -- Dr. Okamura -- http://haptics.lcsr.jhu.edu/Main_Page

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November 30 2007 -- Mike Tadross

Location: Talbot Library Med Campus

Title: Mechanism of Spatial Ca2+ Selectivity within Nanometers of a Ca 2+ Source

Abstract: A prototype for Ca2+ sensors positioned within nanometers of a Ca 2+ source is calmodulin (CaM) in complex with Ca2+ channels. The C-lobe of CaM senses local, large Ca2+ oscillations due to Ca 2+ influx from its home channel, and its N-lobe senses global, albeit diminutive Ca2+ changes arising from distant sources. Though biologically essential, the mechanism of global Ca2+ sensing has defied explanation. Here, we advance a theory of how global selectivity arises, and validate this proposal with new experimental tools enabling millisecond control of Ca 2+ oscillations within nanometers of intact channels. We find that global selectivity arises from rapid Ca2+ release from CaM combined with greater affinity of the channel for Ca2+‑free versus Ca2+-bound CaM. The emergence of complex decoding properties from the combination of common elements, and the techniques developed herein, promise generalization to numerous molecules residing near Ca 2+ sources.

Laboratory: Calcium Signals Laboratory -- Dr. Yue -- http://webhost5.nts.jhu.edu/csl/

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November 16 2007-- Ivy Dick

Location: Talbot Library Med Campus

Title: Modular transformation of spatial Ca2+ selectivity in the calmodulin regulation of Ca2+ channels

Abstract: Ca2+/calmodulin-dependent regulation of voltage-gated CaV1-2 Ca2+ channels exhibits extraordinary modes of spatial Ca2+ decoding and channel modulation1-6, which are vital for many biological functions6-9 . A single calmodulin (CaM) constitutively associates with the channel carboxy tail3,10-13, and Ca2+ binding to the C- and N-terminal lobes of CaM can each initiate distinct channel regulatory processes2,14. As expected from close channel proximity, the C-lobe responds rapidly to the ~100 mM pulses driven by the associated channel15,16, a behavior defined as ‘local Ca2+ selectivity.’ Conversely, all prior observations indicate that the N-lobe somehow senses the far weaker signals from distant Ca2+ sources 2,3,17,18. This ‘global Ca2+ selectivity’ satisfies a general signaling requirement, enabling a resident molecule to remotely sense cellular Ca2+ activity, which would otherwise be overshadowed by Ca2+ entry through the host channel5,6. Here, we report that the spatial Ca2+ selectivity of N-lobe CaM regulation is not invariably global, but can be switched by a novel Ca2+/CaM binding site within the amino terminus of channels (NSCaTE, N-terminal Spatial Ca2+ Transforming Element). Native CaV2.2 channels lack this element, and display N-lobe regulation with a global selectivity. Upon introducing NSCaTE into these channels, spatial Ca2+ selectivity transforms from a global to local profile. Given this effect, we examine CaV1.2/CaV1.3 channels, which naturally contain NSCaTE, and find that their N-lobe selectivity is indeed local. Disruption of this element produces a global selectivity, confirming the native function of NSCaTE. Thus differences in spatial selectivity between advanced CaV1 and CaV 2 channel isoforms are explained by the presence or absence of NSCaTE. Beyond functional effects, the position of NSCaTE on the channel amino terminus indicates that CaM can bridge the amino and carboxy termini of channels. Finally, the modularity of NSC
aTE offers practical means to understand the basis of global Ca2+ selectivity19.

Laboratory: Calcium Signals Laboratory -- Dr. Yue -- http://webhost5.nts.jhu.edu/csl/

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October 12 2007 -- Hermenegild Arevalo

Location: Clark 110 Homewood Campus

Title: Role of intrinsic heterogeneities in organization of ventricular fibrillation

Abstract: Although ventricular fibrillation (VF) is the prevalent cause of sudden cardiac death, the mechanisms that underlie VF remain elusive. Two hypothesis have been presented concerning the organization of electrical activity during VF. One posits that VF is driven by dynamic break-up of wavefronts due to functional heterogeneities, while the other predicts that intrinsic heterogeneity can lead to the formation of a single rotor that drives the fibrillatory activity in the entire heart. To provide insight into this mechanism, we incorporate action potential duration (APD) heterogeneity between the left and right ventricles in a computational model of the rabbit heart. Our simulations show that APD heterogeneity contributes to the initiation and maintenance of VF by providing regions of different refractoriness which serves as sites of wave break and rotor formation. The 3D computer simulations suggest that APD spatial heterogeneity alone can not lead to the formation of a stable
rotor. Although the results of this study support the multiple wavelet hypothesis, I will present new results suggesting that the incorporation of other types of intrinsic heterogeneity can lead to the formation of mother rotor activity.

Laboratory: Computational Cardiac Electrophysiology Lab -- Dr. Trayanova --
http://www.jhu.edu/trayanova/research/lab/lab.html

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September 21 2007 -- Elias Issa

Location: Talbot Library Med Campus

Title: Why you do not hear as well while you sleep

Abstract: Whereas the eyelids block most incoming light, the ears are open to sounds even when you sleep. Somewhere in the brain, activity may be switched off. Surprisingly, though, researchers have found sound-evoked activity as far as primary auditory cortex during sleep. We hypothesized that the switch may lie in the next stage, secondary auditory cortex. Instead, we found that activity is not attenuated even in this higher brain area. An alternative hypothesis is that the switch may not be a simple on/off. Supporting this notion, we find that responses to quiet sounds but not loud sounds are depressed, and inhibitory, not excitatory, processes are selectively turned off. Both phenomena limit the dynamic range available for processing sounds without necessarily switching off responses. The emerging view is that general monitoring of sounds can still occur during sleep but that active, fine-grained listening may only be possible while awake.

Laboratory: Laboratory of Auditory Neurophysiology -- Dr. Wang -- http://www.jhu.edu/xwang/

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September 7 2007 -- Manos Karagiannis

Location: Talbot Library Med Campus

Title: Deciphering the antiangiogenic code: Genome-wide identification of novel endogenous angiogenesis inhibitors

Abstract: Angiogenesis, or neovascularization, is tightly orchestrated by endogenous regulators that promote or inhibit the process. The fine-tuning of these pro- and antiangiogenic elements (the angiogenic balance) helps establishing the homeostasis in tissues, and aberrations lead to pathologic conditions. To date, the quest for the experimental identification of novel angiogenesis inhibitors has been an empirical time-consuming process. In this presentation, we will describe a computational bioinformatics methodology followed by in vitro, ex vivo and in vivo experimental screening to identify and classify 110 novel endogenous putative antiangiogenic peptides. By integrating computational and experimental approaches we introduce a novel systematic methodology to identify endogenous bioactive peptides. The identification of such novel peptides enhances our knowledge of the control of the angiogenic balance and can lead to development of diverse antiangiogenic therapies.

Laboratory: Systems Biology Laboratory -- Dr. Popel -- http://www.jhu.edu/apopel/

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August 24 2007 -- Yasmin Hashambhoy

Location: Clark 110 Homewood Campus

Title: Why CaMKII is important to YOU

Abstract: I will briefly talk about the Winslow lab's cardiac ventricular myocyte models and how such mathematical representations can be used to further drive experiments. For the most part, the presentation will focus on calmodulin kinase II (CaMKII), a protein kinase that is suspected to play a significant role in the generation of arrhythmias. I will describe the approach I am taking to build a mechanistic model of the kinase with its substrates, and the fluorescence reporter I will use to test predictions generated from my model.

Laboratory: Center for Cardiovascular Bioinformatics and Modeling -- Dr. Winslow -- http://www.ccbm.jhu.edu/index.php

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August 3 2007 -- Charles Fisher

Location: Talbot Library Med Campus

Title: Surface-induced organization of Filamentous Actin

Abstract: Crucial for cell motility, actin polymerization generates forces against a surface. However, direct physical characterization has been sparse. Using indirect methods, we first showed anomalous mechanical motions of particles in actin gels correlate with surface binding. Although depletion of actin filaments has been suggested as an explanation, electron microscopy has been inconclusive. Using confocal microscopy, we directly characterize the concentration profile of fluorescently modified actin near a flat surface. Marked with a different fluorescent label, the glass surface is the fiducial reference. As expected, surfaces that bind actin show an enrichment near the surface. Interestingly, a non-actin binding surface shows a monotonic depletion of F-actin concentration, often starting more than three micrometers from the surface. In contrast, monomeric actin has a uniform concentration throughout the depth of the slide. Starting with monomeric actin, depletion proceeds concomitantly with polymerization. With higher actin concentrations, depletion kinetics are faster but the extent is reduced. Because F-actin is semiflexible, we hypothesize depletion is dependent on both persistence length and average length. Consistent with this notion, phalloidin increases while capping protein reduces the depletion zone. This work provides the first direct evidence of mechanically induced rearrangement of F-actin proximal to a surface. The unexpected size of the depletion zone suggests a new role for actin regulatory processes to properly localize F-actin within cells.

Laboratory: Advanced Optics Laboratory -- Dr. Kuo -- http://www.jhu.edu/cmml/index.html

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July 20 2007 -- Eric Tuday

Location: Talbot Library Med Campus

Title: Microgravity Induced Changes in Aortic Stiffness and Their Role in Orthostatic Intolerance

Abstract:

Microgravity (µG) induced orthostatic intolerance (OI) in astronauts, a common consequence of manned spaceflight, is characterized by a marked decrease in cardiac output (CO) in response to an orthostatic stress. Since CO is highly dependent on venous return, alterations in the resistance to venous return (RVR) may be important in contributing to OI. The RVR is directly dependent on arterial compliance (C_A), where aortic compliance (C_a) contributes up to 60% of C_A. We tested the hypothesis that µG induced changes in C_a may represent a protective mechanism against OI. A retrospective analysis on hemodynamic data collected from astronauts after 5-18 day spaceflight missions revealed that orthostatically tolerant (OT) astronauts showed a significant decrease in C_a after spaceflight (1.996±0.09741 ml/mmHg to 1.707±0.08313 ml/mmHg; p=0.0011; N =40) while OI astronauts showed a slight increase in C_a. A ground based animal model simulating µG, hindlimb unweighted rats, was used to explore this phenomenon. Two independent assessments of C_a, in vivo pulse wave velocity (PWV) and in vitro pressure-diameter squared relationships were determined, both showed significant increases in aortic stiffness compared to control (PWV: 7.227±0.1375 m/s vs. 4.074±0.1879 m/s, p<0.0001). id="jccu">a. The difference in C_a in OT and OI astronaut suggests that the µG induced decrease in C_a is a protective adaptation to spaceflight that reduces the RVR and allows for the maintenance of adequate CO in response to an orthostatic stress.

Laboratory: Cardiovascular Systems Laboratory -- Dr. Shoukas -- http://webhost5.nts.jhu.edu/shoukas/

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June 22 2007 -- Tricia Arauz

Location: Talbot Library Med Campus

Title: Characterization of Fibroblast-Derived Extracellular Matrices for Tissue Engineering

Abstract: Cellular functions, such as proliferation and differentiation, are affected by their microenvironment. Cells cultured on typical two dimensional plastic culture dishes do not mimic the natural three dimensional extracellular matrix (ECM) environment found in vivo and thus, the cells respond differently in the two different environments. Synthetic materials have been developed to mimic the regulatory characteristics of natural ECM. However, these simplified models lack the essential spatial and temporal complexity found in vivo. We have developed a technique in which fibroblast-produced ECM can be used as a scaffold to study three dimensional culture of endothelial cells. We have characterized the biochemical, structural, and mechanical properties of the ECM. Finally, we have seeded endothelial cells onto the ECMs to study the cell interaction with the matrices and their potential use as a tissue engineering scaffold.

Laboratory: Cellular and Molecular Medicine -- Dr. Romer -- http://cmm.jhmi.edu/index.php?title=Home

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June 8 2007 -- Brock Tice

Location: Clark 110 Homewood Campus

Title: Using PubMed, HubMed, RSS, and Cite-U-Like to collect and manage references

Abstract: Over the past few years, a number of new reference tools, as well as new methods for accessing older reference tools, have emerged. The tools to be covered in this talk are PubMed, which you are probably familiar with, HubMed, which is a cleaner interface to PubMed with some nice features, how to get RSS feeds that deliver the papers you want on a regular basis automatically, and Cite-U-Like (an online reference manager) to wrangle your findings from the others. I will present a brief overview of how to search PubMed and HubMed, perhaps in ways you're not familiar with, the nature of RSS in case you're not familiar with it, and how to get and use RSS feeds from both. I'll demonstrate the key features of Cite-U-Like, how to post articles to it, how to add your personal PDF copies of articles, and how to set up a Cite-U-Like group for your lab. Finally, I'll demonstrate typical workflows for pulling references from a journal article and posting them to Cite-U-Like, and for processing incoming RSS feeds and adding important items from them to Cite-U-Like.

I'll work hard to keep it concise and useful, and leave plenty of time for questions.

Laboratory: Computational Cardiac Electrophysiology Lab -- Dr. Trayanova --
http://www.jhu.edu/trayanova/research/lab/lab.html
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May 11 2007 -- Chris Long

Location: Talbot Library Med Campus

Title: Molecular Imaging in Tumor Immunology

Abstract: Cancer vaccines have been used in the clinic for two decades obtaining only low objective response rates. The field is in need of adjuvants to aide in vaccine responses. However, to date, most studies have focused on clinical responses without monitoring relevant immune responses. A combination will help us improve the use of adjuvants and extend our ability to monitor the benefits of cancer vaccines. I will describe one such scenario where we monitor dendritic cell trafficking using magnetic resonance imaging in an attempt to develop a better adjuvant-vaccine combination.

Laboratory: Institute for Cellular Engineering, Vascular Biology -- Dr. Bulte --
http://www.hopkins-ice.org/vascular/int/bulte.html

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April 27 2007 -- Brock Tice

Location: Clark 110 Homewood Campus

Title: Development and Study of Models of Endocardial Microstructure

Abstract: Optical Coherence Tomography (OCT) can be used to acquire high-resolution images from relatively thin preparations. In collaboration with the lab of Igor Efimov, we have used OCT data from the rabbit right-ventricular endocardium to develop three small wedge models of the endocardial surface. Experimentally, it has been shown that small to medium structures on the endocardial surface of the atria can precipitate the breakup of electrical conduction at high pacing rate. We are using these small models of the right-ventricular endocardium to find out whether, and under what conditions, this can occur in the endocardial microstructure of the ventricles. Experimental techniques that image activity in the endocardium typically use optical mapping of voltage-sensitive dyes, which results in "blurred" data due to light scattering. Using these small, high-resolution computational models, we are able to determine which structures affect propagation and breakup when rapid stimuli are applied.

Laboratory: Computational Cardiac Electrophysiology Lab -- Dr. Trayanova --
http://www.jhu.edu/trayanova/research/lab/lab.html

http://virtuallyshocking.com/about/

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April 13 2007 -- Dan Bendor

Location: Talbot Library Med Campus

Title: How do monkeys hear sounds?

Abstract: We recognize a musical tune, by identifying the pattern of changing pitches (melody) and temporal rates (rhythm). By studying the brain areas of the marmoset monkey involved in hearing, I have identified neurons that recognize the pitch and temporal rate of sounds. This talk will discuss how we record single neuron activity in awake monkeys, and briefly summarize my findings.

Laboratory: Laboratory of Auditory Neurophysiology -- Dr. Wang -- http://www.jhu.edu/xwang/

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