Thomas W. Sadler, Ph.D.
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However menstruation in space buy fertomid 50 mg lowest price, significant controversy still exists with regard to the interpretation of where the accumulation of the molecules of organic eluent modifier actually occurs. Horvats and further development by Dill [30, 31] stated that organic molecules penetrate between the bonded ligands of the stationary phase, and thus this monomolecular layer of bonded ligands can be considered as a stationary phase. The C1type bonded phase is a limiting case: It is definitely a reversed-phase adsorbent, but there is no possible penetration between bonded trimethylsilane ligands (these ligands do not have conformational freedom), and the accumulation on the surface of this stationary phase should be considered as adsorption. This suggests that there is no actual penetration of the eluent and also the analyte molecules between the bonded ligands, but rather the accumulation (adsorption) of them on the surface. This was also confirmed by the study of the viscosity of bonded chains [32], which shows that the viscosity of bonded C18-type alkyl chains is at least two orders of magnitude higher than the viscosity of corresponding free alkanes (note that free octadecane is solid at room temperature, and it is almost insoluble in acetonitrile). The concept of the void volume and mobile-phase volume was briefly discussed in Chapter 1, Section 1. This model requires the selection of the standard state of given chromatographic system and relation of all parameters to that state. In the majority of recent analytical publications, either thiourea or uracil were used as the void volume markers. As a disclaimer, we have to say here that for the purposes of analytical method development, qualitative or quantitative separation of complex mixtures which involves the use of a "nonretained" component as a void volume marker is acceptable insofar as there are no physicochemical generalization, thermodynamic development, or futher theoretical development performed upon the basis of these "pseudo" void volume determinations. As a simple illustration of the inconsistency of the use of any nonretained components for the void volume determination, we remind the reader that in the basic assumptions and in the derivation of expressions (2-43) and (2-46), void volume of the column was considered to be constant in any eluent type and composition. Acetonitrile/water (solid lines) and methanol/water (dashed lines) were used as the mobilephase components. Note that the retention of both markers for most used eluent compositions is lower than the volume of the liquid phase. This indicates the exclusion of the marker molecules from the adsorbent surface and preferential adsorption of the organic eluent components. The use of the true volume of the liquid phase in the column as the void volume can lead to the principal difficulties in the interpretation of the retention of polar analytes that are also excluded from the contact with the adsorbent surface. The retention volume of these analytes will be lower than the column void volume, and thus their retention factors will be negative. A logarithm of negative retention factors does not exist that shows the applicability limit of the approximate theory described above. In a general sense the void volume should not change as a function of the type and organic composition. Table 2-1 demonstrates the compatibility of the void volume measured using different thermodynamically consistent methods. Integral average of the minor disturbance peak retention dependence on the eluent concentration.
Two of these ate significant amounts of tuna sushi menstrual medication purchase 50 mg fertomid with visa, while one had mercury arising from old dental fillings. One substituted salmon for tuna sushi and within 2 months his mercury level had dropped by half-and the other two had similar experiences in dealing with their mercury sources. For example, two of the Pioneers were homozygous for the variant that causes hemochromatosis (C282Y). In a small proportion of such individuals, this disorder can lead to high iron and ferritin levels in the blood. High blood iron levels can attack the joints, pancreas, the liver, and/or the heart-potentially leading to arthritis, diabetes, liver cirrhosis/cancer, and/or cardiac decompensation in various combinations. Since this disease often presents with the cardiac complications, individuals may be already chronically ill with diabetes or liver disease before they are diagnosed. Send the individuals with the C282Y mutations to their physician for a work-up for the diagnosis; if indicated, the individual can have regular blood draws until normal iron levels are reached. We identified the two individuals with homozygous C282Y genotypes only with the earliest changes, before any serious tissue damage had been done, thus over time Importance of data accessibility from the longitudinal 100K Wellness Project Our view of data accessibility is quite simple. It is essential that all of the patient de-identified data be available to qualified investigators who will mine it for the predictive and preventive medicine of the future. If consumer and patient data are to be made widely available to qualified investigators, two important concerns must be considered. Appropriate methods such as encryption are available for protecting the data and must be employed. Scaling up One of our primary goals was to understand how to scale the wellness program to 100,000 well individuals. Our initial thought was to scale in four tranches-going from 100 to 1000 to 10,000 and finally to 100,000-each over a period of a year or so. A vision for twenty-first century healthcare 1907 saving the healthcare system significant dollars-by avoiding what could have been chronic hemochromatosis. Further, the children of these individuals are being genetically tested-stopping the progression of an undiagnosed and treatable disease to the next generations. Using standard cutoff values for fasting serum glucose, we identified 53 of the 108 participants who had fasting glucose in the prediabetic range at baseline. When the bacterial populations in the gut microbiome were compared against these genetic propensities-two strains of more "pathogenic" bacteria increased as the genetic risk for each group of individuals increased. It is not yet clear what the causal association might be or whether there is a strong actionable possibility here. What is clear is that every one of the 107 Pioneers had multiple actionable possibilities.
Carcinoid heart disease results from prolonged release of biologically active mediators from the tumor that stimulate the formation of a distinctive fibromuscular plaque that destroys the integrity of the cardiac valves menstruation 3 days late purchase 50 mg fertomid amex. Rarely, it occurs in patients with bronchial or ovarian carcinoid tumors, and, if outside the confines of the portal venous system, carcinoid heart disease may develop in the absence of hepatic metastases. The exact mechanism of plaque formation and cardiac injury remains elusive, but a number of possible mediators, including kinins, serotonin, 5-hydroxytryptophan, histamine, and prostaglandins, have been suggested; another as yet unidentified compound or combination of compounds may also contribute. Because these mediators are eliminated by the lungs, the left heart is spared unless a right-to-left shunt is present. The lesions generally appear along the intima of the great veins, the right atrium, and the coronary sinus. The margins and distal (ventricular or downstream) aspect of the tricuspid leaflets are often thickened, and the chordae tendineae may also be involved. The damage appears to be aggravated by turbulent blood flow, which explains the characteristic location of the lesions. When the primary tumor or metastasis is in the lung, the mediators are released directly into the pulmonary venous bed and bypass the inactivating properties of lung tissue; left-sided valvular lesions are seen in such cases. A review of surgically excised valves noted considerable variation in the histological appearance of the material. Tricuspid regurgitation and pulmonic stenosis are typically seen, but in the case of progressive destruction, a rigid tricuspid valve with hemodynamic abnormalities reflecting both stenotic and regurgitant characteristics may be encountered. Stiffening of the right atrium may be noted and contributes to the neck-vein distention commonly seen in patients with the carcinoid syndrome. Some patients are able to tolerate the hemodynamic consequences of their valvular lesions well, whereas others develop symptoms early; this is especially so in the elderly or those with predisposing cardiac abnormalities. Later, symptoms of right-sided congestive heart failure, including edema, hepatomegaly, and ascites, predominate. Cardiac murmurs often predate symptoms, and the murmur of tricuspid regurgitation may be an early finding. Most frequently, the murmur is appreciated as a loud, holosystolic, blowing sound heard along the left lower sternal border. The murmur of pulmonic stenosis cannot always be distinguished from that of the often coexisting tricuspid regurgitation; when heard, the pulmonic murmur is usually harsher and is appreciated most prominently in the second left intercostal space. Unlike congenital pulmonic stenosis, which often includes poststenotic dilatation of the pulmonary trunk, this finding is usually not seen with carcinoid heart disease. Electrocardiographic findings include changes suggestive of right ventricular volume or pressure overload with or without right atrial abnormalities, right ventricular hypertrophy, right bundle-branch block, and/or right axis deviation; low voltage in the standard (limb) leads may also be seen. It not only identifies the valvular abnormality, but, when coupled with Doppler ultrasonography studies, also provides hemodynamic data for estimating the degree of valvular involvement.
The label 2 indicates rough endoplasmic reticulum in the cytoplasm menopause hot flashes purchase fertomid 50 mg line, discussed in the next chapter. During the G1 phase, the cell assesses its environment and will divide if conditions are optimal. If the conditions are right, the cell will enter the S phase, at which time it will be committed to progress through the remainder of the cell cycle back to the G1 phase. The oval structure is the nucleus, and the nuclear envelope is at the tips of the blue arrows. Note the nuclear material in interphase in this cell is largely euchromatin, so individual chromosomes are not seen. Structures called centrioles that assemble the mitotic spindle that guides the chromosomes during mitosis move to opposite poles of the cell (in this image, top and bottom), but these are not visible in this image. The blue arrows in (a) indicate the nuclear envelope, which breaks down in prophase. Helpful Hint Mitosis is a continuum, so many cells seen in tissue specimens are somewhere between the four phases outlined above. Here, the nuclear envelope breaks down, and the chromatin condenses to form visible chromosomes (purple speckles in the center of the cell). The cage-shaped structure is the mitotic spindle (black arrows), which is made up of microtubules and is responsible for movement of the chromosomes. Eventually, the nuclear envelope will reappear, and the chromatin will decondense. To study the phases of mitosis, it is useful to select a specimen containing many rapidly dividing cells, such as embryonic tissue; the following figures show sections from whitefish embryos. Recall that, even in rapidly dividing tissues, many cells will be in interphase, not mitosis. One cell in this image is outlined; the nucleus is the large, basophilic structure in the center of the cell. Note the distinct nuclear envelope; the chromatin is a mixture of euchromatin and heterochromatin (no visible chromosomes). Helpful Hint It might be tempting to think that many of the cells in this image that do not show nuclei are in some phase of mitosis. However, this is not the case because, as the next set of images will demonstrate, mitotic cells have distinct chromosomes. The reason those cells lack a visible nucleus in this image is that the plane of section passed through a portion of the cell that did not include the nucleus. However, in most other tissues, cells in mitosis are not as common, even in proliferative tissues such as the epidermis of the skin. Outlined in yellow is a cell in mitosis, characterized because it lacks a nuclear envelope and has visible dense chromosomes. It is likely that this cell is in late telophase or has just finished cytokinesis and the chromosomes of the progeny cells have yet to decondense. Because it is often difficult to determine a specific stage of mitosis for cells in tissues, they are often referred to as mitotic figures.
Costbenefit of reflectance confocal microscopy in the diagnostic perfor mance of melanoma women's health clinic grenada ms cheap fertomid 50mg online. It allows a horizontal scanning (en face) of the imaged tissue, with the advantage of exploring a larger field of view compared with vertical sectioning. This version is a smaller, flexible device, which is useful in areas that are difficult to access. Unlike the 1,500 version, it has an oninstrument control for laser power, imaging depth, and capture, but it does not allow scanning of a large field of view, which is needed, for example, in some tumors to obtain an overview of the architecture. However, it is a promising tool, which can be used for surgical premap ping or when multiple site imaging is requested. They include the presence of elongated monomorphic nuclei, the polarization of these nuclei along the same axis, a prominent inflammatory infiltrate, increased number of vessels, and the pleomor phism of the overlying epidermis. A confocal microscope consists of a point source of light, a condenser, objective lenses, and a point detector. In gray scale confocal images, structures that appear bright (white) have com ponents with high refractive index compared with their surroundings and are similar in size to the wavelength of light. Backscattering is primarily governed by the refrac tive index of the structure compared with the surrounding medium. The confocal scanning pro duces highresolution blackandwhite horizontal images (0. It consists of single highresolution images acquired from the top skin surface up to 200 mm, corresponding to the papillary dermis, to obtain an optic biopsy. Reflectance confocal microscopy features were correlated with pathology diagnosis to develop diagnostic algorithms. Positive features were polarized elongated features, telangiectasia, and convoluted vessels, basaloid nodules, and epidermal shadowing correspon ding to horizontal clefting. Negative features were nonvisi ble papillae, disarrangement of the epidermal layer, and cerebriform nests. Peritumoral clefting in basal cell carcinoma: correlation of in vivo reflec tance confocal microscopy and routine histology. Classifying distinct basal cell carcinoma subtype by means of dermatoscopy and reflectance confocal microscopy. In vivo confocal microscopy for diagnosis of melanoma and basal cell car cinoma using a twostep method: analysis of 710 consecu tive clinically equivocal cases. It derives from the epithelial squamous cells, and affects more commonly fair skinned individuals in areas of chronic sun exposure. Clinical diagnosis of the tumor is usually readily, even if initial forms may be difficult to distinguish from actinic keratoses that are often numerous in the background of severely sundamaged skin.
Syndromes
Bonded phases of the same type differ in their ability to suppress (or shield) other types of interactions (ionic; dipole) exerted by the base material pregnancy 0 negative blood type cheap fertomid 50 mg visa. Energy of these unwanted interactions is about 10 times greater than the energy of dispersive interactions [2]. Due to the exponential nature of the relationship between retention and interaction energy even the presence of 1% or less of these active centers in the packing material surface can significantly affect the analyte retention. Bonding density is the primary parameter in evaluation of the quality of the bonded material. Usually the higher the bonding density, the better the shielding effect, although care should be taken in cross-evaluation of similar columns on the basis of their bonding density. Base material with smaller pores has higher surface area; however, bonding density is usually lower due to the smaller pores. All parameters of the packing material are interrelated in their influence on the chromatographic performance of the column. Long-term column stability (pH and temperature) and batch-to-batch reproducibility are probably the most important quality characteristics to be considered in column selection in the pharmaceutical industry. Long-term stability of retention and efficiency characteristics are usually different, depending on the testing conditions (mobile phase, temperature, and analyte probes). Efficiency is usually fairly stable at low mobile-phase pH, while retention of the probe analytes may show a drift in retention. However, the retention is generally stable at high pH while efficiency could be deteriorated. Porosity provides the surface area necessary for the analyte retention (usually between 100 and 400 m2/g). Introduction of small nonporous spherical particles in the mid-1990s [3, 4] was an attempt to increase efficiency by eliminating dual column porosity. In the column packed with porous particles, interparticle space is about 100-fold larger than pores inside the particles, and liquid flow around the particles is also faster; this leads to the significant band broadening. Unfortunately, elimination of particle porosity dramatically decreases adsorbent surface area, thereby decreasing the column loading capacity. The introduction of monolithic columns in the 1990s was another and more successful attempt to increase column permeability while decreasing the gap in column dual porosity.
Multiple fraction collectors were daisy-chained in order to provide a sufficient footprint for fraction collection menstrual queening cheap fertomid 50mg mastercard. The exact number of chromatographic peaks for a given sample will be hard to predict, and therefore the footprint for fraction collection will be difficult to predict. When purifying only a small number of samples (<10), it is neither particularly challenging to collect the fractions nor challenging to perform postpurification analysis so as to identify the fraction(s) containing the desired product. His approach was to perform a scouting analytical run prior to purification so as to optimize chromatographic method and fraction collection parameters. The added mass spectrometric information greatly facilitated deconvoluting of collected fractions and streamlined their purification process. Only those compounds found to be 10% pure based on the analytical run are candidates for final product purification. All components of the system are under computer control and are hence truly automated. Typical systems are configured in an automated analytical/preparative mode of operation. In this configuration, the chemist is able to select between a variety of column sizes for either analytical, semipreparative, or preparative separations. In some instances, a solvent pump is added to deliver a methanol make-up flow to the mass spectrometer. The flow splitter and extra solvent pump serve the primary purpose of reducing the potential for overloading of sample into the ion source. The component of interest shows a prominent single chromatographic peak when monitoring specifically for its corresponding mass. Postpurification analysis of this singly isolated fraction (based on mass-directed fractionation) demonstrates that the compound of interest was purified to greater than 90%. This not only would be a time-consuming reanalysis process but also would require significant time to transfer the appropriate fractions to a screening plate for biological assessment. Independent of the debate, it is widely agreed that mass spectrometry serves as a highly sensitive and selective detector for analysis and purification of compound libraries. Mass-triggered fraction collection enables compound libraries to be purified based solely on their expected product mass. Libraries can be purified maintaining a "one compound-one fraction" model, which facilitates sample tracking, registration, and biological testing and enables screening results to be readily correlated with synthetic structure. Conventional split-mix technology was replaced by a number of parallel synthesis strategies that did not require the de-mixing or de-coding step.
This contrasts with cartilage women's health issues in thrombosis and haemostasis 2013 generic fertomid 50 mg on line, which typically has a less intensely stained matrix. This matrix is called osteoid, which will be discussed in greater detail in Chapter 12. These processes extend toward, and make contact with, processes of adjacent osteoblasts before the cells begin secreting matrix. However, the cell-cell connections made by these cells are maintained and are housed in tunnels called canaliculi, which connect adjacent lacunae. Canaliculi are too small to be seen in routine H & Estained slides, but they will be examined later in this chapter. The connections between adjacent bone cells via these canaliculi are crucial because they provide a mechanism for transport of nutrients and waste products between adjacent bone cells. In fact, since the matrix is solidified, these cells are unable to secrete much additional matrix. At the top and bottom of the image, the osteoblasts have separated from the osseous tissue during tissue preparation. However, calcification of bone matrix prevents diffusion (as well as cell movement). Therefore, these cell-cell contacts that enable nutrient exchange must be made before the matrix surrounding these cells calcifies. The plasma membrane adjacent to the bone is extremely undulated, which increases the surface area for proton pumps and release of the secretory lysosomes. As they degrade the bone, the depression created is a Howship lacuna (black arrows), which may not be readily visible in this image, but note its location. Helpful Hint Identification summary: - Osteoblasts are cuboidal, typical-sized cells with single nuclei and basophilic cytoplasm. The balance toward bone deposition is enhanced by several hormones, including estrogen and testosterone. Estrogen, in particular, has an effect that inhibits osteoclast activity and favors bone deposition. This results partially from less activity, but also from changes in hormones, especially the loss of estrogen at menopause. This results in osteoporosis, which is a decrease in bone density that can lead to bone fractures. Hormone replacement therapy, which contains estrogens, may be a viable treatment for osteoporosis but carries other risks, such as an increased risk for breast cancer.
In cutaneous primary melanomas breast cancer zumbathon purchase fertomid 50mg amex, clinical classifica tion does not exactly correlate with dermoscopic observa tion, as this technique permits the observation of colors and structures not visible with the naked eye. The dermoscopic classification of amelanotic mela nomas is different since some of them present pigmen tation traces and it is preferable to call them amelanotic/ hypomelanotic. They are a signifi cant feature in thin melanomas (> 1 mm Breslow thickness) compared to benign melanocytic lesi ons, with 19% sensitivity and 199% specificity in melanoma diagnosis. The milkyred globules and milkyred areas (larger in size) have a 78% prognostic predictive value in the melanoma diagnosis. Recently, a diagnostic algorithms have been devel oped based on conclusions from the study of amelanotic and hypomelanotic melanoma to help detect this type of melanomas. In highly pigmen ted areas of the partially pigmented melanoma, it is possible to find other classical pigmented der moscopic features of melanoma. Melanoma with regression: When the amelanosis in a melanoma is the result of regression, it is possible to visualize the classical dermoscopic features of scar like depigmentation [white areas (fibrosis) and blue areas (melanosis)]. Irregular lineal vessels (white arrow); pink areas (milky-red areas) (black arrow). On occasion we see patients who are deeply concerned about their N, but under exam ination are found to have almost none. But the case that most concerns dermatologists is that of patients with a high M risk. In preder moscopic era this ratio was 18/1 and it has decreased to 4/1 in dermoscopic era. In the formula of specificity are the false positives, which are mostly atypical N and may be confused with M, even under dermoscopic examination. And finally, just dermoscopy is not enough because many benign lesions in patients with multiple N present irregular dermoscopic patterns, which means that many unnecessary excisions are still performed. In fact, any of them could be it since nevi with severe dysplasia are almost indistinguishable from melanoma in situ. Conclusion: It has been proved that with the compara tive approach about 30% fewer N are excised than with just the morphologic approach. Total body skin examination for skin cancer screening in patients with focused symptoms. Addition of dermoscopy to conventional nakedeye examination in melanoma screen ing: a randomized study. Improvement of malignant/ benign ratio in excised melanocytic lesions in the "dermos copy era": a retrospective study 19972001. Analysis of the benign to malignant ratio of lesions biopsied by a general dermatolo gist before and after the adoption of dermoscopy.
Because the fibers are oriented in a cranial-caudal fashion menopause yoga 50 mg fertomid mastercard, they are seen in cross section in sections of the spinal cord cut in cross section. The dotted outline in a indicates the border between gray matter (inside) and white matter (outside). Like most neurons, the motor neuron is a huge cell; the Nissl substance occupies the cytoplasm and extends to the outer boundary of these cells (green arrows). The pale central structure is the nucleus, which is very large and euchromatic, with a prominent nucleolus (yellow arrow). Note that the nuclei of glial cells are about the same size as nucleoli of motor neurons. A neuronal cell body with a process extending to the right is indicated (red arrow). Neuronal cell processes contain abundant proteins, mostly cytoskeletal elements such as microtubules and intermediate filaments. Most of the threadlike structures throughout this slide are dendrites and axons from this or neighboring cells, which were not readily visible in the Nissl-stained images. Axons (yellow arrows) stain darkly with silver, surrounded by pale regions representing myelin. For example, multiple sclerosis is thought to be caused by immune destruction of myelin. The resulting decreased speed of action potentials causes sensory and motor dysfunction. Brain and spinal cord tissues from these patients at autopsy show decreased myelin staining. Although white matter does not stain well with Nissl, special stains can be used to visualize the components of white matter. The axons are surrounded by pale regions representing myelin, which was dissolved away during tissue preparation. From a histologic standpoint, all these structures are bundles of axons with supporting glial cells and connective tissue, so they are indistinguishable. Specific tissue preparation methods and special stains can be used to visualize myelin. Recall that myelin is composed of glial cell membranes wrapped many times around neuronal axons. The axons do not stain well with this preparation, so they are represented by the pale centers in the middle of the dark myelin rings. Myelin (between yellow arrows) stains darkly, while the axons surrounded by myelin are pale. During embryogenesis, a Schwann cell initially surrounds several axons with portions of its cytoplasm and plasma membrane. After the cytoplasm of the Schwann cell is squeezed out, the remaining layers of cell membrane are called myelin. Regularly spaced regions of bare axon not surrounded by myelin, called nodes of Ranvier, are important for propagation of the action potential.
Ronar, 33 years: In addition, the images were oriented so that most of the muscle fibers were cut longitudinally. Although the density of their nuclei varies somewhat, they often lack an easily recognizable nucleolus and do not have "clumpy" chromatin as primary spermatocytes do. Signs or symptoms suggestive of heart failure, dysrhythmia, ischemia, or pericardial disease-all of which are common in the cancer patient-trigger a more rigorous cardiovascular assessment.
Rufus, 51 years: Additionally, yellowish tears and a whitish starbust-like pattern that correspond, respectively, to follicular plugs and parakeratosis were also described. There are several types of glial cells, including microglia, ependymal cells, and astrocytes. On the other hand, analyte retention or selectivity is mainly dependent on the competitive intermolecular interactions and are influenced by eluent type, composition, temperature, and other variables which allow functional variation.
Altus, 53 years: In biological separations, the choice of mobile phase is critical and must consider both column performance and the maintenance of biological function of the sample and the aim of separation. The base peak at m/z 305 might arise from the neutral loss of a 2-vinylamino-ethanol. Liposarcomas are malignant tumors of adipose tissue and contain early and mature adipocytes as well as abnormal fibrous tissue.
Finley, 65 years: This section includes the testis, efferent ductules (black outline), and epididymis (blue outline). Basic Science Correlate: Cell Biology Paneth cells secrete their product apically, into the lumen of the intestine. Because of their narrow spectrum of inhibition, these agents were thought initially to cause minimal end-organ toxicity, unlike conventional chemotherapeutic agents.
Faesul, 43 years: We only assume the existence of specific interactions of positively charged basic analyte and liophilic ions. The cytoplasm (black arrows) and nucleus (yellow arrows) of a single secretory cell, called a goblet cell, is shown. Main equilibria governing the analyte retention is the adsorption of the analyte molecule on the surface of packing material.
Akascha, 28 years: Because the fibers are oriented in a cranial-caudal fashion, they are seen in cross section in sections of the spinal cord cut in cross section. The stronger the analytestationary phase interaction, the longer the analyte retention. However, bridges of connective tissue persist between the capillaries in the central areas not covered by podocytes.
Umul, 27 years: Patients may present with respiratory distress, tachypnea, tachycardia, cyanosis, diaphoresis, and agitation. Clostridium difficile-associated diarrhea If diarrhea is not directly the result of chemotherapy or radiation and particularly if it occurs in a hospital setting, Clostridium difficile infection should be considered as this is the most common cause of infectious diarrhea in hospitalized patients. Cardiac muscle cells supplied by the obstructed vessel become ischemic (myocardial ischemia, experienced as angina pectoris) and may die (myocardial infarction, or heart attack).
Shakyor, 46 years: Surfactant produced by these cells is stored in large vesicles usually demonstrating a lamellar structure (red arrows); these structures are often called lamellar bodies. The response factor is calculated by peak area divided by concentration at each concentration level. This also increases the number of membrane proteins that can act as enzymes or transport channels.
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