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Friday, July 25, 2008

Hurricanes & Global Connectedness

Many tropical cyclones that threaten the Atlantic coast of the U.S. originate off West Africa near the Cape Verde Islands. This year's Hurricane Bertha was a storm of this type. Once the initiating conditions are met, surface winds begins to circulate counterclockwise around a low pressure center while the system travels westward across the Atlantic. When the surface water temperature is high and the vertical sheer is low, the system develops a core with an eye, an inner wall and an outer wall. Moist hot air rises spiraling ever faster in the inner wall. The circulating winds wrap progressively tighter around the eye and intensify in strength. A hurricane is born. The hurricane's direction and the speed of its forward motion depend on large-scale steering air currents that do not affect the anatomy of the storm directly. Hence, the intrinsic properties of the water molecules suspended in the air determine the storm's anatomy and force lending it the power of self-organization, whereas extrinsic factors govern its path. This deterministic combination of intrinsic, self-organizing properties and extrinsic factors is not unique to cyclones. The networks of nerve cells in the brain are shaped similarly by a combination of the intrinsic properties of the nerve cells and experience-dependent input. I have written about the similarities in my post dated April 29, 2008.

Intriguingly, the precise conditions that trigger the formation of the Cape Verde storms are not yet understood. We only know the seed is somewhere in Africa. Hence, these storms constitute befitting examples of distant events of which we are ignorant that eventually affect us in great ways. The connectedness of seemingly unrelated happenings half a world apart can be found in numerous incidents natural and man-made. The universality of global relationships led to this poem. The poem is written in magic ink. It takes time to fully develop. Start the animation and bear with the ink.


Addendum
  • National Public Radio's All Things Considered covered research examining African climate factors crucial to the evolution of Atlantic cyclones today. Listen to the podcast by Jon Hamilton entitled "African Dust Linked To Hurricane Strength" (09/05/08).

Wednesday, July 16, 2008

The Body Surface Area

Today I deployed my first Google application developed with the Google app engine (GAE). You have to be connected to the internet and establish an account with Google to use it. BSA Calculator is a body surface area (BSA) calculator with a simple layout in font that the visually challenged like me can read without squinting. The large font may also be helpful to the busy physician using an iPhone.

Physicians regularly use body surface area to calculate drug doses for their patients. Notably, the dosing of chemotherapeutic drugs like Cisplatin is determined according to BSA. I use it to control my diet. When my BSA climbs over 2.1 m2, it is high time for me to act.

Estimating human body surface is not trivial. It is difficult to develop one formula that fits all, simply because we come in a wide range of shapes and sizes and the relationship between body height and body weight changes considerably while we grow up. Medcalc provides a handful of methods and references. The suggested formulas have been empirically derived from measurements of height and weight. J.D. Current, 1998, and Than Vu, 1999, critically review the methods in use. Boyd, 1935, published one method that is still widely employed. In recent years the method of Mosteller, 1987, has gained popularity. Both are available in BSAcalc.



References:
  • Boyd E (1935) The growth of the surface area of the human body. University of Minnesota Press, Minneapolis.
  • Mosteller RD (1987) Simplified Calculation of Body Surface Area. New England Journal of Medicine 317: 1098.
The BSA calculator accepts only metric dimensions (Système International). You may use the converter below to convert body height and weight from inches and pounds to centimeters and kilograms, respectively. Enter the body height in inches in the inches box and click on the centimeter box. In analogy, enter the body weight in lbs into the pound box and click on the metric weight box:




[in] :
[cm]:
[lbs]:
[kg] :

Converter © Donate to the effort through PayPalhere.

Proceed to the BSA calculator.


Addendum
  • A authoritative study by Sacks and others (2009) in the New England Journal of Medicine (360:859-873) demonstrates that we can diminish our weight on reduced-calorie diets (02/26/09).

Friday, July 11, 2008

Autism & Genes, Revisited

In a post earlier this year, I summarized the findings of a comprehensive study published in the magazine Science in which the authors screened for faulty genes in people with schizophrenia. Numerous genes with small defects were identified. Some are known to play a role in the growth and stabilization of connections between nerve cells during brain development. The genes were damaged around birth. Schizophrenia's symptoms are narrowly defined compared with autism. Autism is a spectrum disorder with a wide range of behaviors. That is why, the illness is known as Autism Spectrum Disorder, or ASD for short. I suggested that the genes involved in autism may even be more numerous than those implicated in schizophrenia and that the underlying molecular mechanisms may be more diverse.

In a research study published in this week's issue of Science (Vol. 321:218-223), Morrow and others screened for inherited faulty genes in 104 families comprising 115 males and 24 females with ASD. The families were recruited from an ethnic group that allows cousin-to-cousin marriages. Family trees could be reconstructed for 393 members. Maggie Fox reported on the study in an article published on Reuters on July 10, 2008. The researchers concentrated their effort on damaged homozygous autosomal recessive genes. That is, these genes were unrelated to sex and their defects came to bear only when they were inherited in identical pairs. The identified genes differed considerably, involving 1-2 specific chromosomal loci per family. Notably, several families showed large genetic deletions. In one autistic boy suffering from seizures, the largest deletion was situated on chromosome 3q and comprised gene c3orf58 and the beginning of gene NHE9. Smaller deletions were found on chromosome 4q near genes PCDH10 and on chromosome 2q near genes CNTN3, RNF8 and SCN7A. The authors could provide evidence with studies in animal tissue cultures that this type of damage affects the expression of genes that are commonly activated by the electrical activity of nerve cells and are instrumental in the development of nerve cell networks. The products of these genes play crucial roles in the establishment and maintenance of the contacts that nerve cells use to transmit information, i.e. the synapses.

The number of synapses in our cerebral cortex continues to increase after birth and reaches a peak at about 3 years of age. Then, their number gradually declines. Synapses that are used to transmit information between nerve cells are known to stabilize. Synapses that remain underutilized are pruned. The brain is particularly plastic and sensitive to environmental stimuli during this critical period of synaptic exuberance and elimination. Experience-dependent nerve cell activity determines which synapses stay and which go. The behavioral symptoms of autism manifest themselves at that time and experts in special education strive to develop methods for their early detection and intervention.

Fifty years ago, Nicholas Hobbs and Susan Gray pioneered the early detection of behavioral abnormalities with non-interfering observational methods at Peabody College. The assessors examined the social interactions of the children and their care givers unnoticed through one-way mirrors. This type of research continues at the Susan Gray School to the day. My son was a student there. The Director at the time was convinced that an environment rich in sensory experience benefits the mental development of any child and is of special importance to children with learning differences. The curriculum was structured accordingly. In harmony with this concept, the findings of the genetic study discussed above suggest that exposure to enriched environments may be instrumental in the effort to compensate for the deficits caused by inherited genetic deletions in children with ASD.

Addenda

  • On Mar. 16, 2009, Donald G. McNeil Jr. reports in The New York Times on an unusually high occurrence of ASD among Somali children in Minnesota. Somali culture permits marriages among cousins. Taking the findings of the study discussed above into consideration, the most likely cause for this cluster is a genetic predisposition (03/17/09).
  • Today, National Public Radio's Morning Edition broadcast a segment about the utility of a nation-wide register for families affected by ASD. You may wish to check out the interactive autism network site here (04/08/09). 
  • Two recent studies using genome-wide analysis across large numbers of participants identified more variants of genes associated with ASD. The studies were published online back-to-back in the journal Nature on Apr. 29, 2009. In the first study, Wang and others (2009) compared the DNA of children diagnosed with ASD and their families (3101 participants from 780 families) with that of 1204 adults with ASD and that of 6491 unaffected volunteers. The authors found 6 single nucleotide polymorphisms in genes CDH9 and CDH10 to be most tightly associated with ASD. Genes of this type encode nerve cell adhesion molecules that guide the growth of connections between nerve cells during brain development. In the second study, Glessner and others (2009) compared variations in the copy number (CNVs) of DNA segments in DNA from 859 children with ASD and 1409 children without ASD. The authors affirmed the identified gene candidates using DNA from 1336 other cases with ASD and 1110 volunteers without ASD. The authors detected CNVs associated with ASD in cell adhesion-related genes NRXN1, CNTN4, NLGN1 and ASTN2. In addition, CNVs were detected in and near genes, whose products are involved in the metabolism of ubiquitin. It is important to note that the methods used in both studies permit us to identify genetic modifications only for the whole sample. They may not be present in each case of ASD. Furthermore, the candidate genes were implicated only by association. Causalities between the genetic modifications and autistic behavior remain to be established (05/15/09).
  • A genome-wide association study enrolling more than one thousand families with children diagnosed with ASD uncovered a single nucleotide polymorphism (SNP) statistically significantly associated with ASD on chromosome 5p15 between genes SEMA5A, involved in the growth of nerve cell connections, and TAS2R1, playing a role in gustation (Weiss and others, 2009). The expression of the former proved reduced in ASD (11/30/09).
  • Researchers at the University of Washington recently published evidence in support of the contention that early behavioral intervention may ameliorate autism (Dawson and others, 2009). A novel play-at-home therapy called Early Start Denver Model, or ESDM for short, showed promising results after only 24 months. The 20 hour/week program is designed for toddlers diagnosed with autism as young as 18 months of age. Participants scored ten points higher in IQ tests than peers in conventional programs with enhanced scores in listening and understanding as well as motor and self-care skills (11/30/09).
  • In a genome-wide analysis of rare genetic copy number variants (CNVs) in 996 people of European descent with ASD compared to 1,287 controls, Pinto and others (2010) identified genes SHANK2, SYNGAP1 and DLGAP2, in addition to previously implicated genes NRXN1, NLGN3, NLGN4X and SHANK3, as high-probability candidates playing a role in autism. The results of the study were published online yesterday in the journal Nature. The products of these genes are involved in the establishment and maintenance of nerve cell connections. Genes influencing the formation of excitatory nerve cell connections using the neurotransmitter glutamate are of particular interest because of their fundamental role in brain plasticity. Notably, SHANK2 regulates metabotropic glutamate receptors, and SYNGAP1 is engaged in AMPA receptor trafficking (06/10/10).
  • Oller and others (2010) developed a method that allows us to record and analyze the utterances of children as young as ten months of age for speech modifications related to ASD. The LENA Foundation supports the method. Emma Ashburn summarizes the research in her post entitled "Screening speech may aid autism diagnosis: study" on Reuters yesterday. The method may help behavioral intervention experts in their assessment. Modified speech evident early during development suggests that nerve cell connections in Wernicke's area of the cerebral cortex may be the first to be affected in ASD (07/20/10).
  • O'Roak and other (2012) sequenced the exomes, that is the DNA regions that code for the protein product of genes, of children with sporadic autism as well as of their parents and unaffected siblings. Sixhundredseventyseven exomes of 209 families were examined. Eighty percent of the discovered gene mutations were of paternal origin, increasing with age. Roughly 40 percent of the new protein-altering mutations were associated with a molecular signaling pathway regulating gene transcription through beta-catenin/chromatin remodeling. Recurrent mutations were found in genes CHD8 and NTNG1. The product of CHD8 is a protein involved in chromatin remodeling. This finding points at a specific molecular mechanism that may explain impaired transcription of the genetic code, representing the most disruptive genetic modification identified in this study according to the authors. NTNG1's product Netrin-G1 is a protein that serves as cue in nerve cell axon guidance and has been associated with schizophrenia. In addition, mutation screening identified genes GRIN2B, LAMC3 and SCN1A. GRIN2B encodes a subunit protein of N-methyl-D-aspartate (NMDA) receptors for the excitatory neurotransmitter glutamate. NMDA receptors are voltage-gated calcium channels playing an instrumental role in the plasticity of nerve cell connections, memory and learning and have been implicated in schizophrenia. LAMC3's product represents a laminin in the extracellular protein matrix of brain tissue that affects cell adhesion and may guide nerve cell connections. SCN1A codes for a subunit protein of voltage-gated nerve cell sodium channels the malfunction of which is instrumental in migraine and epilepsy. In a companion study, Neale and others (2012) using genetic models identified mutations of genes CHD8 and KATNAL2 as the greatest risk for autism. The latter encodes a protein involved in the organization of microtubule arrays in cells. As interesting as these candidates for a genetic basis of the disorder may seem, it remains difficult to conceive how proteins with such fundamental and ubiquitous influences on brain development that have also been associated with other developmental mental disorders like schizophrenia can cause a spectrum disorder with the diverse behavioral symptoms of autism (04/09/2012).
References
Related Posts:

Thursday, July 10, 2008

Who Owns Your Site?

Recently, a friend of mine was pondering some existential questions about websites. She had started an own business selling customized arts and crafts over the internet. She found an appealing name for her site. She tells us on the site, how her real business grew from an unreal idea. The site offers to customers options to create the product they like to purchase. Sales have been taking off. The business shows all signs of success.

My friend is not a web expert and outsourced site development and administration.  Now, questions arise about the ownership of the site. The details of site registration have fundamental implications for ownership, particularly when the site name is synonymous with the brand and the businesses vitally depends on brand recognition. The person who registers the domain name of the site with the registrar may actually own that name. This person may also own the administrative privileges to add and delete data and permit other parties access to site administration. The administrator can potentially read the e-mails on the site.

For those who are not savvy in the use of the terminal command line, I found an easy way to obtain information about your site. Go to Broadband Report's whois browser application, type in your domain name, that is the site name without "www.",  and hit return. Check carefully that the entries match your expectations.

Small Business Tip #1. Click here.



Wednesday, July 2, 2008

How to Build a Silent PC: Episode II

In episode I, I narrated my first experience with building a personal desktop computer, describing important discoveries I made in the process. Earlier this year I build my second PC. Below I shall summarize the essential lessons I learned.

The purpose of this project was to provide my son with a powerful computer to use for his graphics and arts work as well as his games. My son is learning animation with Maya and chess with Chessmaster.This computer would be stationed in his room. The first machine I built boasts 7 fans. The noise these fans collectively produce is considerable. You would not want to have them in your bedroom. Therefore, I was looking for a very quiet design.

On my search for the noiseless machine, I happened on cases for home theater personal computers (HTPC). Computers for the control of high fidelity entertainment centers must be designed noiseless. Compared with standard cases, the fans in these cases commonly run very quietly. As a drawback, I did not find a case with a small form factor. Even the cases, that can house micro-sized (mATX) motherboards, are not much smaller than mid-size towers. At the high end of the price range I are the impressive cases by Zalman. I opted for Antec's Fusion V2, which is comparatively low in price.

Owing to my good experience with Micro-Star International and Advanced Micro Devices, I chose the K9MM-V motherboard and an Athlon 64 3500+ Socket AM2 central processing unit (SKU:CP2-AM2-3500 AV). I purchased both in a bundle for a bargain price from TigerDirect. The "V"s are important. They indicate that board and processor are designed to fully support virtualization. Microsoft's Hyper-V virtualization software is under development and can be tested with a compatibility check utility that AMD provides for download. I opted for Microsoft's Windows XP Professional x64 as operating system to let my son run his applications smoothly and perhaps will use Xen for virtualization.

In my first assembly, I had the CPU pre-installed. This time, I mounted it myself, before placing the board in the case. It was straight forward. A close check of the instructions in the MSI manual sufficed. You must ground yourself, before you start! The designated corner of the CPU and has to match up with that of socket on the board. When the chip is properly aligned, the pins slip smoothly into the holes of the socket. No force is needed. The chip is fastened by pushing down a lever. Then, I applied an even layer of thermal grease and mounted Ultraproduct's Ultra X-Wind CPU cooler on top. The fan has a diameter of 92 mm and provides air flow at 53.5 CFM. The motherboard was ready to be placed in the case. Next, I filled the the board's memory slots with a pair of 1-GB PC2-5300 DDR2 modules from PNY. Before you order the memory modules, validate the specifications with the recommendations on the manufacturer's site.

The case came with a 430-W power supply with all necessary connectors attached and provided two internal and one external drive bay. I loaded one internal bay with a Seagate SATA hard drive. The SATA cable came with the motherboard. The board features a second SATA input. I may install another SATA drive in the empty bay. The external drive bay was reserved for the DVD/CD drive. I installed Mad Dog's TF-DVDRW TSH652G IDE drive and connected it to the motherboard with the round cable included in the MSI kit.

Micro-ATX motherboards are about 2" shorter than the regular ATX boards, but still accommodate standard PCI and AGP cards. This was important to me, because I had PCI cards in stock and wanted to be able to use AGP graphics cards. I swapped out the ATI Radeon 9600 Pro card used in my first project for a 9800 series card and installed the old card in this computer. The reason was an important discovery. If you use a mATX motherboard, ensure that the graphics card you intend to use matches the shorter length of this board. The ATI Radeon 9600 card was sufficiently short.

The motherboard accommodated all connections from the case, except the firewire port. Therefore, one of the three PCI slots had to be reserved for a USB/firewire card that I purchased from CompUSA. Another slot was taken by a wireless network adapter card. I chose Cisco's Linksys WMP54G v41. The Linksys software does not function properly with Windows XP x64. A compatible driver for the card can found at Ralink support. The driver that matched my card can be downloaded at PCI/mPCI/CB(RT256x/RT266x). After insertion of the PCI card, restart the computer and the hardware wizard will announce that new hardware was detected and prompt you for a driver. At this juncture, the wizard has to be manually pointed to the RT61 file in the Ralink folder under program files (x64). If the wizard does not prompt you, the driver can be loaded manually for the network adapter in the device manager. Should Ralink terminate its support for XP, the driver I used is available for download at BMI under downloads.

As useful amenities, I added Gyration's gyrotools. The compact keyboard is light-weight and short. The buttons have a good feel. The optical air mouse doubles as remote control.

Addendum


For Pros! Beginners try the teaching edition available at Autodesk (use link in the above text).
If you need more advice, check out this book. I own several books in this series and found them helpful.