Proof Of Principle Studies Research Articles

Splaying hyperthin polyelectrolyte multilayers to increase their gas permeability.

The concept of splayed, hyperthin polyelectrolyte multilayers (PEMs) is introduced in which a bulky, hydrophilic and charged pendant group is used to increase the gas permeability of a PEM without reducing its permeation selectivity. Proof of principle studies are reported using nm-thick PEMs made from poly(sodium 4-styrene sulfonate) () and poly(allylamine hydrochloride) () bearing bulky cobaltocenium ions.

No evidence that embryo selection by near-infrared spectroscopy in addition to morphology is able to improve live birth rates: results from an individual patient data meta-analysis

What is the value of embryo selection by metabolomic profiling of culture medium with near-infrared (NIR) spectroscopy as an adjunct to morphology, compared with embryo selection by morphology alone, based on an individual patient data meta-analysis (IPD MA)? The IPD MA indicates that the live birth rate after embryo selection by NIR spectroscopy and morphology is not significantly different compared with the live birth rate after embryo selection by morphology alone. Retrospective proof of principle studies has consistently shown that high NIR viability scores are correlated with a high implantation potential of embryos. However, randomized controlled trials (RCTs) have generally shown no benefit of the NIR technology over embryo morphology, although there have been some conflicting results between pregnancy outcomes on different days of embryo transfer. This IPD MA included all existing RCTs (n = 4) in which embryo selection by morphology was compared with embryo selection by morphology and the use of NIR spectroscopy of spent embryo culture medium by the Viametrics-E(™). Searches of PubMed, the Cochrane Library and the WHO International Clinical Trials Registry were conducted and the sole manufacturer of the Viametrics-E(™) was consulted to identify clinics where an RCT comparing embryo selection by morphology to embryo selection by morphology and the use of the Viametrics-E(™) (NIR viability score) was performed. A total of 20 citations were potentially eligible for inclusion, two of which met the inclusion criteria. The manufacturer of the Viametrics-E(™) provided two additional clinical sites of use. In total, four RCTs were identified as eligible for inclusion. The IPD MA was based on a fixed effect model due to the lack of heterogeneity between included studies. Differences between study groups were tested and reported using logistic regression models adjusted for significant confounders. The pooled analysis of the primary outcome led to a total sample size of 924 patients: 484 patients in the control group (embryo selection by morphology alone) and 440 patients in the treatment group (embryo selection by morphology plus NIR spectroscopy). The live birth rates in the control group and the NIR group were 34.7% (168 of 484) and 33.2% (146 of 440), respectively. The pooled odds ratio (OR) was 0.98 [95% confidence interval (CI) 0.74-1.29], indicating no difference in live birth rates between the two study groups. The data of the four studies showed no significant heterogeneity (I(2) = 26.2% P = 0.26). The multivariate regression analysis including all confounders show that maternal age (OR 0.90, 95% CI 0.87-0.94) and the number of previous IVF cycles (OR 0.83, 95% CI 0.71-0.96) were significantly related to live birth. The study group (i.e. embryo selection by morphology or embryo selection by morphology plus NIR) was not related to live birth (OR 0.97, 95% CI 0.73-1.29). The availability of at least two similar best quality embryos as an inclusion criterion prior to transfer in the two largest RCTs might have caused a selection bias towards a better prognosis patient group. There is at present no evidence that NIR spectroscopy of spent embryo culture media in its current form can be used in daily practice to improve live birth rates.

What got us here will not get us there

This is an exciting yet trying time for people living with neuromuscular diseases and those who care for them. The exciting aspect is that at last the advances in genetics and translational research have resulted in clinical trials testing novel compounds. Examples include the exon-skipping approaches in Duchenne Muscular Dystrophy (DMD). Resulting from a sophisticated understanding of the consequences of dystrophin gene mutations, ASOs were developed to help transform the “garbled” message resulting from a disrupted reading frame into a “translatable”, in-frame, message. This rational and targeted approach worked in pre-clinical studies, but it yet has to confirm its efficacy in patients. The trying aspect illustrated by this example is that it has taken over 10 years to get from pre-clinical proofof principle studies to clinical trials. Some of this is the inevitable development time needed for candidate selection, lead optimization, pre-clinical toxicology, and manufacturing issues. However, an additional source of delay may be the limited tools and data available for trial planning: The available methodology to measure dystrophin in muscle biopsies may not be sensitive enough, and may show too much variation due to sampling or differences in laboratory measurements. Similarly, existing clinical outcome measures have limitations in terms of floor and ceiling effects, in terms of their applicability to

Progress and prospects in stem cell therapy

In the past few years, progress being made in stem cell studies has incontestably led to the hope of developing cell replacement based therapy for diseases deficient in effective treatment by conventional ways. The induced pluripotent stem cells (iPSCs) are of great interest of cell therapy research because of their unrestricted self-renewal and differentiation potentials. Proof of principle studies have successfully demonstrated that iPSCs technology would substantially benefit clinical studies in various areas, including neurological disorders, hematologic diseases, cardiac diseases, liver diseases and etc. On top of this, latest advances of gene editing technologies have vigorously endorsed the possibility of obtaining disease-free autologous cells from patient specific iPSCs. Here in this review, we summarize current progress of stem cell therapy research with special enthusiasm in iPSCs studies. In addition, we compare current gene editing technologies and discuss their potential implications in clinic application in the future.

Rapid screening of membrane protein expression in transiently transfected insect cells

Membrane proteins play critical roles in many biological processes and are the focus of intense biomedical research. One bottleneck for studying membrane proteins is the difficulty in expressing correctly folded and stable proteins, which often requires extensive protein engineering and multiple rounds of optimization, a time and resource intensive process. Here, we describe a method for rapidly screening membrane protein expression in insect cells. The method uses a green fluorescent protein (GFP) covalently fused to target membrane proteins and the resulting fusion proteins are then transiently expressed in insect cells. This approach enables us to dramatically reduce the time and resources required for expression screening by eliminating the need to create recombinant baculovirus. We show that transiently expressed membrane proteins can be directly monitored for their subcellular localizations by fluorescence microscopy. Moreover, their expression levels, approximate molecular mass, and stability can be evaluated with nanogram levels of unpurified proteins by ultrasensitive fluorescence-detection size exclusion chromatography (FSEC). We present our proof of principle studies using a homotrimeric ion channel (ASIC3) and a heterodimeric transporter (SLC7A5/SLC3A2) as examples, and demonstrate the utility of transient expression coupled with FSEC in optimizing membrane protein expression.

Abstract P5-04-04: Significance of PELP1/HDAC2/microRNA-200 regulatory network in EMT and metastasis of breast cancer

Abstract Tumor metastasis remains a significant clinical problem and is the leading cause of death among breast cancer patients. Estrogen receptor (ER)-coregulators play an essential role in cancer progression and metastatic tumors express increased levels of coregulators. Proline glutamic acid rich protein (PELP1) is an ER coregulator, its expression is upregulated during breast cancer progression to metastasis and is an independent prognostic predictor of shorter survival of breast cancer patients. MicroRNA (miR) mediated regulation of tumorigenesis is emerging as a new paradigm in cancer biology and widespread misexpression of miRs has been reported in breast cancer. The objective of this study is to examine the mechanism and therapeutic significance of PELP1 regulation of miRs leading to breast cancer metastasis. We have used both ER+ve (ZR75, MCF7) and ER-ve (MDAMB231, MDAMB468) models that either stably overexpress PELP1 or PELP1shRNA. Boyden chamber, and invasion assays demonstrated that PELP1 down regulation significantly affect migration of both ER+ve and ER-ve cells. Epithelial to Mesenchymal Transition (EMT) real time qPCR Array studies identified PELP1 modulate expression of EMT genes Snail, Twist, ZEB1, ZEB2, Vimentin and MMPs. Importantly, whole genome microRNA array analysis using PELP1 model cells revealed that miR200a and miR141 were significantly upregulated in cells expressing PELP1-shRNA compared to control cells. Accordingly, over expression of PELP1 in low metastatic model cells decreased expression of miR200a and miR141. PELP1 regulation of miRs was further confirmed by ZEB1 and ZEB2 3′ UTR luciferase reporter assays. ChIP analysis revealed recruitment of PELP1 to the proximal promoter region of miR-200a and miR141 and promoter reporter assays further confirmed PELP1 regulation of miRs. Interestingly, PELP1 down regulated expression of miR200a and miR141 by promoting repressive chromatin modifications via HDAC2. Supporting this, HDAC inhibitors reversed PELP1 driven repressive effects. Further, ectopic expression of miR200a and miR141 mimetic decreased PELP1 mediated invasion/metastatic functions. Prognostic significance of PELP1-miRNA axis was determined using Tissue micro-array (TMA) and in situ hybridization (ISH assays) of Locked Nucleic Acid (LNA™)-based microarray approach in 102 human breast tumors. To test therapeutic potential in vivo, we have generated ZR-PELP1- and MCF7-PELP1-shMIMIC of miR200a and miR141 stable cells. In vitro gene expression and Boyden chamber assays using these model cells revealed that shMIMIC of miR200a and miR141 reversed PELP1 mediated alterations in gene expression and reduced PELP1 driven migration/invasion. Proof of principle studies using IVIS imaging of nude mice based assays of GFP-Luc labeled cells demonstrated therapeutic efficacy of miRIDIAN shMIMIC of miR200a and miR141 on PELP1 driven in vivo metastasis. Collectively, these novel findings demonstrate for the first time a previously unknown role for PELP1 in epigenetically controlling the functions of tumor metastasis suppressor miR-200a and miR141. These results suggest that PELP1-miR axis may be crucial stimulus for promoting EMT and breast cancer metastasis. This study is funded by NIH T32CA148724 Postdoc Fellowship Grant. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P5-04-04.

Non-invasive brain stimulation and language processing in the healthy brain

Background: Non-invasive brain stimulation (NIBS) has been used as a probe to modulate cognitive functions in humans for the last 20 years. The two most commonly reported techniques are transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS), which have both been used with different stimulation parameters to increase or decrease excitability in target cortical regions. Aims: In the present review, we highlight recent developments in TMS and tDCS in language research in healthy individuals. Main Contribution: We will first describe how tDCS and TMS have been employed to improve either performance of language tasks, or learning in the language domain (facilitatory brain stimulation). Then, we will show how these techniques were used as interference techniques (inhibitory brain stimulation) for understanding brain–behaviour interactions and to explore possible cause–effect links between altered activity in specific brain areas and particular behaviours. We will only review studies in healthy individuals, and first pilot trials in patient population with more general cognitive impairments (idiopathic Parkinson's Disease, Alzheimer's Disease). For tDCS studies in aphasia, see Holland and Crinion (2012); for TMS studies in aphasia, see Medina et al. (2012). Conclusions: In the healthy brain, NIBS can be used to delineate the functional significance of a particular brain region for the respective language task under study. Here, new possibilities of combining TMS or tDCS with functional imaging techniques offer unique opportunities to not only address the functional significance of a brain area underlying the coil or electrode, but in addition allow testing NIBS effects on an entire network. In this setting, TMS, both in its single-pulse and its repetitive form, allows the modulation of a specific function within milliseconds (single-pulse) or the order of seconds (particularly high-frequency rTMS trains), while tDCS has the disadvantage of requiring longer stimulation times. On the other hand, the relatively easy use of tDCS in the magnetic resonance scanner environment will render simultaneous recording of brain function and activation much more accessible, thus offering novel avenues in the study of network effects of NIBS. For proof-of principle studies to improve language learning in the healthy brain, tDCS may be the most fruitful approach due to its easy applicability and excellent safety profile. Subsequent use of this technique in parallel to training protocols to improve re-acquisition of language functions aphasic patients offers exciting possibilities in the realm of neurorehabilitation.

PET imaging with radiolabeled antibodies and tyrosine kinase inhibitors: immuno-PET and TKI-PET

During the last decade, the discovery of critical tumor targets has boosted the design of targeted therapeutic agents with monoclonal antibodies (mAbs) and tyrosine kinase inhibitors (TKIs) receiving most of the attention. Immuno-positron emission tomography (immuno-PET) and TKI-PET, the in vivo tracking and quantification of mAbs and TKIs biodistribution with PET, are exciting novel options for better understanding of the in vivo behavior and efficacy of these targeted drugs in individual patients and for more efficient drug development. Very recently, current good manufacturing practice compliant procedures for labeling of mAbs with positron emitters have been described, as well as the preparation of some radiolabeled TKIs, while the first proof of principle studies has been performed in patients. In this review, technical developments in immuno-PET and TKI-PET are described, and their clinical potential is discussed. An overview is provided for the most appealing preclinical immuno-PET and TKI-PET studies, as well as the first clinical achievements with these emerging technologies.

The road to biological pacing

The field of biological pacing is entering its second decade of active investigation. The inception of this area of study was serendipitous, deriving largely from observations made by several teams of investigators, whose common interest was to understand the mechanisms governing cardiac impulse initiation. Research directions taken have fallen under the broad headings of gene therapy and cell therapy, and biomaterials research has also begun to enter the field. In this Review, we revisit certain milestones achieved through the construction of a 'roadmap' in biological pacing. Whether the end result will be a clinically applicable biological pacemaker is still uncertain. However, promising constructs that achieve physiologically relevant heart rates and good autonomic responsiveness are now available, and proof of principle studies are giving way to translation to large-animal models in long-term studies. Provided that interest in the field continues, the next decade should see either biological pacemakers become a clinical reality or the improvement of electronic pacemakers to a point where the biological approach is no longer a viable alternative.

SL24 Cortical recording and stimulation using subdural electrodes

that excessive beta synchrony is delayed in its development in toxininduced animal models of parkinsonism. Thus it may not contribute to the earliest deficits. Second, the proof of principle studies showing worsening of bradykinesia with stimulation of the basal ganglia at beta band frequencies in patients have only produced mild, albeit significant, worsening. The latter brings in to question the quantitive importance of beta synchrony in bradykinesia and rigidity. Still, its value as a biomarker in parkinsonism seems strong, and as such it could be used as a surrogate measure of efficacy in animal models of parkinsonism and as a feedback signal in closed-loop deep bran stimulation systems.

Generation, Isolation, and Maintenance of Human Mast Cells and Mast Cell Lines Derived from Peripheral Blood or Cord Blood

Antigen-mediated mast cell activation is a pivotal step in the initiation of allergic disorders including anaphylaxis and atopy. To date, studies aimed at investigating the mechanisms regulating these responses, and studies designed to identify potential ways to prevent them, have primarily been conducted in rodent mast cells. However, to understand how these responses pertain to human disease, and to investigate and develop novel therapies for the treatment of human mast cell-driven disease, human mast cell models may have greater relevance. Recently, a number of systems have been developed to allow investigators to readily obtain sufficient quantities of human mast cells to conduct these studies. These mast cells release the appropriate suite of inflammatory mediators in response to known mast cell activators including antigen. These systems have also been employed to examine the signaling events regulating these responses. Proof of principle studies has also demonstrated utility of these systems for the identification of potential inhibitors of mast cell activation and growth. In this unit, techniques for the development and culture of human mast cells from their progenitors and the culture of human mast cell lines are described. The relative merits and drawbacks of each model are also described.

Abstract 1506: Prodrug targeted gene therapy for colorectal cancer

Abstract In the US colorectal cancer is the second and third most common cause of cancer death in men and women, respectively. The drawback of conventional therapy is its non-specificity and a median survival of only 10-15 months with the present combinations. Our studies with human colorectal cancer cell lines demonstrate a relationship between human nicotinamide mononucleotide adenylyltransferase-2 (hNMNAT-2) expression and cell kill with tiazofurin (TR) and benzamide riboside (BR). Thus, the purpose of the present study is to examine whether over-expressing hNMNAT-2 selectively confers sensitivity to TR and BR in human colorectal cancer cells that show resistance to TR and BR therapy. TR and BR are pro-drugs that are metabolized by the action of NMNAT to its active form, TAD (thiazole-4-carboxamide adenine dinucleotide) and BAD (Benzamide adenine dinucleotide), respectively. TAD/BAD potently inhibit inosine-5’-monophosphate dehydrogenase (IMPDH) causing reduced guanylate synthesis resulting in cancer cell death. We achieved 2- to 5-fold increase in expression of hNMNAT-2 by transfecting colorectal cancer cells (Caco-2 and HT-29) with pTracerNMNAT-2 as demonstrated by Western blot and FACS. hNMNAT-2 transfected colorectal cancer cells exhibited a 3- to 7-fold increase in tumor-cell kill with TR and BR. hNMNAT-2 transfected cells did not exhibit modulation of either NAD levels or IMPDH expression. Folate receptor alpha (FR-α) is overexpressed on the colorectal cancer cell surface to sequester available folate to promote cancer cell proliferation. Primary colorectal carcinomas which exhibit high FR-α overexpression also correlated with decreased 5-year survival. We demonstrated an upregulation of FR-α expression in human colorectal cancer cells (up to 10-fold) by adaptation to growth in physiological low folate medium resulting in 2- to 5-fold increase in colorectal cancer cell-kill with TR or BR encapsulated in folate-tethered liposomes. To translate in vitro studies to in vivo applicability, we are utilizing adeno-associated virus (AAV-2) to transduce hNMNAT-2 gene into colorectal cancers implanted in athymic mice. To achieve this goal, we engineered hNMNAT-2 gene into AAV-2 vector to increase efficiency of gene transfer, and encapsulated in folate-tethered liposomes to target colorectal cancer cells. The potential significance of these new proof-of principle studies is that they will set the stage for the next level of studies that could culminate in a new form of pro-drug targeted gene therapy for colorectal cancer with enhanced tumor cell-kill with little toxicity. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1506.

Nanoparticles for Local Drug Delivery to the Oral Mucosa: Proof of Principle Studies

PurposeTo determine if solid lipid nanoparticles represent a viable strategy for local delivery of poorly water soluble and unstable chemopreventive compounds to human oral tissues.MethodsNanoparticle uptake and compound retention evaluations employed monolayer-cultured human oral squamous cell carcinoma (OSCC) cell lines and normal human oral mucosal explants. Feasibility of nanoparticle delivery was also evaluated with respect to the presence of phase-III efflux transporters in normal oral mucosal tissue and OSCC tissues.ResultsFunctional uptake assays confirmed significantly greater internalization of nanoparticle-delivered fluorescent probe relative to free-fluorescent probe delivery, while concurrently demonstrating nanoparticle uptake rate differences among the OSCC cell lines and the phagocytic control human monocyte cell line. Mucosal explants exhibited nanoparticle penetration and internalization in the spinous and basal epithelial layers (7/10 specimens), and also exhibited the presence of the phase-III efflux transporters multidrug resistance-associated protein 1 (MRP1) and breast cancer resistance protein (BCRP).ConclusionsThese data confirm nanoparticle internalization by OSCC cells and support the premise that nanoparticle-based delivery provides higher final intracellular levels relative to bolus administration. Furthermore, the penetration and subsequent internalization of nanoparticles within the proliferating basal layer cells demonstrates the feasibility of nanoparticle formulations for local delivery and stabilization of oral chemopreventive compounds.

A single step multiplex immunofluorometric assay for differential diagnosis of BSE and scrapie

Although there is no evidence that the European sheep population has been infected with bovine spongiform encephalopathy (BSE), distinguishing this from scrapie is paramount, given the association between BSE exposure and the human transmissible spongiform encephalopathy (TSE), variant Creutzfeldt-Jakob disease. The capability to differentially diagnose TSEs in sheep is thus essential in order to safeguard the food chain and human health. Biochemical methods for differentiating BSE and scrapie are largely reliant on assessment by Western blot (WB) analysis of the abnormal disease associated prion protein PrP(D) following partial proteolytic digestion. WB banding patterns obtained using a panel of antibodies enable different strain specific conformations of PrP(D) to be distinguished. This approach provides a robust confirmatory test but one which is not appropriate for high throughput screening. A simple, one step, bead array flow cytometry based multiplex immunofluorometric assay has been developed which is suitable for simultaneous screening and confirmation. Using a combination of antibodies directed towards three PrP epitopes enabled differential diagnosis of scrapie and BSE. Proof of principle studies indicated a high predictive value (100%) when applied to brain samples from control animals, BSE infected cattle and sheep naturally infected with scrapie or experimentally infected with BSE.

Nanoparticles for Local Drug Delivery to the Oral Mucosa: Proof of Principle Studies

Nanoparticles for Local Drug Delivery to the Oral Mucosa: Proof of Principle Studies

Stimulated smooth muscle neosphincter in male intrinsic sphincter deficiency: Proof of principle studies in a rabbit model

Intrinsic sphincter deficiency (ISD) causes significant disability and impairment of quality of life despite a range of treatment options. We investigated a novel method to improve sphincter function that does not appear to have been previously attempted, that is, transplantation to create a smooth muscle cuff, that subsequently becomes innervated, around the urethra. Bladder pressure and passage of urine were measured in conscious, sedated rabbits of three groups: 6 control (unoperated) rabbits, 8 rabbits rendered incontinent by incision of their urethral wall, and 12 lesioned rabbits treated by transplantation of a circumferential strip of autologous dartos muscle whose innervation was later stimulated electrically. Effects of stimulation were tested up to 6 months after surgery. Lesions of the proximal urethra caused the bladder to leak at filling volumes that previously caused no leak. The volume added to cause first leak was less than half the volume added to cause a voiding reflex in unoperated rabbits. Transplantation of dartos to the lesioned bladder neck did not affect urodynamic parameters. However, electrical stimulation of the innervation of the transplant increased the bladder volume necessary to cause voiding and restored voiding pressures and filling volumes towards normal. These effects were maintained for 6 months and were not related to spontaneous healing. Free transplants of smooth muscle that become innervated offer promise as a treatment for ISD that is unlikely to cause urethral erosion and will not require a pump to restore continence.

Electrophoretic exclusion for the selective transport of small molecules

A novel method capable of differentiating and concentrating small molecules in bulk solution termed "electrophoretic exclusion" is described and experimentally investigated. In this technique, the hydrodynamic flow of the system is countered by the electrophoretic velocity to prevent a species from entering into the channel. The separation can be controlled by changing the flow rate or applied electric field in order to exclude certain species selectively while allowing others to pass through the capillary. Proof of principle studies employed a flow injection regime of the method and examined the exclusion of Methyl Violet dye in the presence of a neutral species. Methyl Violet was concentrated almost 40 times the background concentration in 30 s using 6 kV. Additionally, a threshold voltage necessary for exclusion was determined. The establishment of a threshold voltage enabled the differentiation of two similar cationic species: Methyl Green and Neutral Red.

The hepoxilins and some analogues: a review of their biology

The hepoxilin pathway was discovered over two decades ago. Products in this pathway are derived through the 12S-lipoxygenase/hepoxilin synthase enzyme system and contain intrinsic biological activity. This activity relates to the reorganization of calcium and potassium ions within the cell, and in inflammation and insulin secretion. Although the natural hepoxilins are chemically unstable, chemical analogues (PBTs) have been synthesized with chemical and biological stability. The PBTs antagonize the natural hepoxilins. The PBTs showed bioavailability, excellent tolerance and stability in vivo. In proof of principle studies in vivo in animal models, the PBTs have shown actions as anti-inflammatory agents, anti-thrombotic agents, anti-cancer agents and anti-diabetic agents. These studies demonstrate the effectiveness of the base structure of the hepoxilin (and PBT) molecule and serve as an excellent framework for the design and preparation of second-generation compounds with improved pharmaceutical properties as therapeutics for the above-mentioned diseases.

Mid-IR Contact Probe for Examination of Live Cell Cultures

Continuous monitoring of live cell cultures and in-vitro tissues is a major challenge in the study of model systems for cancer research. Specifically, monitoring chemical changes often requires the cells to be stained with specific fluorophores (limited chemical content) or harvested from culture (precluding longitudinal study). Recently, mid-infrared spectroscopy is being increasingly applied to measure chemical content of cells and tissues. There are no reports, however, of in-vitro monitoring of cell cultures. The major reason is the high absorption of water in this spectral region and lack of instrumentation to address this need. This project seeks to apply mid-IR in a non-destructive manner to live cell cultures and tissues while maintaining rich information content. We accomplish this by the design of a contact-method probe. We have designed a fiber optic-base beam guidance geometry and coupled it to a total internal reflection sensing element. The entire sensor is coupled to a commercial spectrometer, thus allowing for rapid translation to other laboratories. It is believed it can be a cost effective solution using current technologies with adequate SNR for down-stream chemometric analysis. One of the major design challenges was to optimally guide and utilize light from the spectrometer within the constraints of leveraging as many commercially available components, processes, and methods to most quickly translate this idea into a working device. Our major task was optical modeling and subsequent fabrication of the device. The optical models show 6 percent throughput is possible using currently available parts; 1 percent is required. The design was implemented with the optical system placed wholly within a single chassis. While a single chassis design allows for miniaturization, it presents substantial alignment challenges due to the lack of degrees of freedom for movement. These challenges are the current work focus. Proof of principle studies are on-going. We anticipate that the goal of continuous cell monitoring and in-vitro cell spectroscopy will be attained upon final integration of the device with our experimental setup.

Interhemispheric inhibition between primary motor cortices: what have we learned?

Interhemispheric inhibition between primary motor cortices: what have we learned?