32 research outputs found
Electronic sculpting of ligand-GPCR subtype selectivity:the case of angiotensin II
GPCR subtypes possess distinct functional
and pharmacological profiles,
and thus development of subtype-selective ligands has immense therapeutic
potential. This is especially the case for the angiotensin receptor
subtypes AT1R and AT2R, where a functional negative control has been
described and AT2R activation highlighted as an important cancer drug
target. We describe a strategy to fine-tune ligand selectivity for
the AT2R/AT1R subtypes through electronic control of ligand aromatic-prolyl
interactions. Through this strategy an AT2R high affinity (<i>K</i><sub>i</sub> = 3 nM) agonist analogue that exerted 18,000-fold
higher selectivity for AT2R versus AT1R was obtained. We show that
this compound is a negative regulator of AT1R signaling since it is
able to inhibit MCF-7 breast carcinoma cellular proliferation in the
low nanomolar range
Application of infrared thermography in computer aided diagnosis
The invention of thermography, in the 1950s, posed a formidable problem to the research community: What is the relationship between disease and heat radiation captured with Infrared (IR) cameras? The research community responded with a continuous effort to find this crucial relationship. This effort was aided by advances in processing techniques, improved sensitivity and spatial resolution of thermal sensors. However, despite this progress fundamental issues with this imaging modality still remain. The main problem is that the link between disease and heat radiation is complex and in many cases even non-linear. Furthermore, the change in heat radiation as well as the change in radiation pattern, which indicate disease, is minute. On a technical level, this poses high requirements on image capturing and processing. On a more abstract level, these problems lead to inter-observer variability and on an even more abstract level they lead to a lack of trust in this imaging modality. In this review, we adopt the position that these problems can only be solved through a strict application of scientific principles and objective performance assessment. Computing machinery is inherently objective; this helps us to apply scientific principles in a transparent way and to assess the performance results. As a consequence, we aim to promote thermography based Computer-Aided Diagnosis (CAD) systems. Another benefit of CAD systems comes from the fact that the diagnostic accuracy is linked to the capability of the computing machinery and, in general, computers become ever more potent. We predict that a pervasive application of computers and networking technology in medicine will help us to overcome the shortcomings of any single imaging modality and this will pave the way for integrated health care systems which maximize the quality of patient care
Correlation of aluminum doping and lithiation temperature with electrochemical performance of LiNi₁-ₓAlₓO₂ cathode material
Abstract
This article presents a process for producing LiNi₁-ₓAlₓO₂ (0 < × < 0.05) cathode material with high capacity and enhanced cycle properties of 145 mAh/g after 600 cycles. The LiNi₁-ₓAlₓO₂ (0 < × < 0.05) cathode material is prepared by mixing coprecipitated Ni(OH)₂ with LiOH and Al(OH)₃, followed by lithiation at temperature range of 650–710 °C, after which any residual lithium from lithiation is washed from the particle surfaces. Electrochemical performance was studied within full-cell and half-cell application; in addition, different material characterization methods were carried out to explain structure changes when certain amount of aluminum is introduced in the LiNi₁-ₓAlₓO₂ structure. Surface analyses were carried out to demonstrate how washing process changes the chemical environment of the LiNi₁-ₓAlₓO₂ secondary particle surface. The results demonstrate how Al doping, lithiation temperature, and the washing process affect the performance of the LiNi₁-ₓAlₓO₂ cathode material
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Factors associated with inpatient mortality in a field hospital following the Haiti earthquake, January-May 2010
To describe factors associated with inpatient mortality in a field hospital established following the 2010 Haiti earthquake.
Data were abstracted from medical records of patients admitted to the University of Miami Global Institute/Project Medishare hospital. Decedents were compared to survivors in terms of age, sex, length of stay, admission ward, diagnosis, and where relevant, injury mechanism and surgical procedure. Three multivariate logistic regression models were constructed to determine predictors of death among all patients, injured patients, and noninjured patients.
During the study period, 1,339 patients were admitted to the hospital with 100 inpatient deaths (7.5 percent). The highest proportion of deaths occurred among patients aged < or = 15 years. Among all patients, adult intensive care unit (ICU) admission (adjusted odds ratio [AOR] = 7.6 and 95% confidence interval [CI] = 3.4-16.8), neonatal ICU/pediatric ICU (NICU/PICU) admission (AOR = 7.8 and 95% CI = 2.7-22.9), and cardiac/respiratory diagnoses (AOR = 8.5 and 95% CI = 4.9-14.8) were significantly associated with death. Among injured patients, adult ICU admission (AOR = 7.4 and 95% CI = 1.7-33.3) and penetrating injury (AOR = 3.3 and 95% CI = 1.004-11.1) were significantly associated with death. Among noninjured patients, adult ICU admission (AOR = 6.6 and 95% CI = 2.7-16.4), NICU/PICU admission (AOR = 8.2 and 95% CI = 2.1-31.8), and cardiac/ respiratory diagnoses (AOR = 6.5 and 95% CI = 3.6-12.0) were significantly associated with death.
Following earthquakes in resource-limited settings, survivors may require care in field hospitals for injuries or exacerbation of chronic medical conditions. Planning for sustained post-earthquake response should address these needs and include pediatric-specific preparation and long-term critical care requirements
Encapsulation of xenon by bridged resorcinarene cages with high 129Xe NMR chemical shift and efficient exchange dynamics
Functionalized cages encapsulating xenon atoms enable highly sensitive, background-free molecular imaging through a technique known as HyperCEST 129Xe MRI. Here, we introduce a class of potential biosensor cage structures based on two resorcinarene macrocycles bridged either by aliphatic carbon chains or piperazines. First-principles-based modeling predicts a high chemical shift (about 345 ppm) outside the typical experimental observation window for 129Xe encapsulated by the aliphatically bridged cage and two 129Xe resonances for the piperazine-bridged cages corresponding to single and double loading. Based on the computational predictions as well as 129Xe chemical exchange saturation transfer (CEST) and T2 relaxation nuclear magnetic resonance experiments, we confirm Xe encapsulation in the aliphatically bridged and double encapsulation in the piperazine-bridged resorcinarene in methanol. The cages show fast Xe exchange rates (12,000–49,000 s−1), resulting in a high CEST response regardless of the relatively low binding constant (0.09–3 M−1).peerReviewe
Encapsulation of xenon by bridged resorcinarene cages with high ¹²⁹Xe NMR chemical shift and efficient exchange dynamics
Abstract
Functionalized cages encapsulating xenon atoms enable highly sensitive, background-free molecular imaging through a technique known as HyperCEST ¹²⁹Xe MRI. Here, we introduce a class of potential biosensor cage structures based on two resorcinarene macrocycles bridged either by aliphatic carbon chains or piperazines. First-principles-based modeling predicts a high chemical shift (about 345 ppm) outside the typical experimental observation window for ¹²⁹Xe encapsulated by the aliphatically bridged cage and two ¹²⁹Xe resonances for the piperazine-bridged cages corresponding to single and double loading. Based on the computational predictions as well as ¹²⁹Xe chemical exchange saturation transfer (CEST) and T₂ relaxation nuclear magnetic resonance experiments, we confirm Xe encapsulation in the aliphatically bridged and double encapsulation in the piperazine-bridged resorcinarene in methanol. The cages show fast Xe exchange rates (12,000–49,000 s⁻¹), resulting in a high CEST response regardless of the relatively low binding constant (0.09–3 M⁻¹)
Travel Health Alert Notices and Haiti Cholera Outbreak, Florida, USA, 2011
To enhance the timeliness of medical evaluation for cholera-like illness during the 2011 cholera outbreak in Hispaniola, printed Travel Health Alert Notices (T-HANs) were distributed to travelers from Haiti to the United States. Evaluation of the T-HANs’ influence on travelers’ health care–seeking behavior suggested T-HANs might positively influence health care–seeking behavior