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This is Animal and human studies have used both the abdomen and characterized by macrophage activation and fibroblast pro vagina to arteria transversa colli purchase avalide 162.5mg with mastercard evaluate tissue response to arteria bologna 8 marzo 2014 purchase avalide 162.5 mg free shipping graft materials arrhythmia drugs discount avalide 162.5mg visa. The liferation arrhythmia beta blockers cheap avalide 162.5mg with amex, the activity of which is mediated by cytokines and abdominal wall and pelvic floor clearly represent two dis growth factors [14]. The response also varies depending on tinct anatomic regions, and so whether the foreign-body the particular surface characteristics. They nounced, whereas hydrophilic surfaces caused lower levels found that implantation of the same material in two different of cytokine production and leukocyte adhesion independent anatomic locations—abdomen and vagina—resulted in differ of one another. Tissues surrounding vaginal grafts 672 Int Urogynecol J (2012) 23:669–679 had significantly higher scores for inflammation and neovas cularization and lower scores for fibroplastic proliferation than tissues surrounding abdominal grafts. Clearly, anatomical fac tors need to be considered when interpreting and applying study findings to any particular clinical situation. Bacterial colonization Acontaminatedorinfectedsurgicalsiteisconsidereda contraindication for placement of permanent synthetic ma terial. Release may cause dissemination and acute infection and the use of antibiotic irrigation. Furthermore, out penetration of the antimicrobial agent and altered growth side of preoperative antibiotics, there exist no clear rate of biofilm microorganisms. Antibiotic therapy to Differences in host responses exist given that bacterial treat biofilm-associated infections can restrain bacteria but contamination of the surgical field during vaginal surgery not completely eradicate them [36]. Furthermore, aside from infection of the mycin than were cells in intact biofilms [37]. In that study, altered growth rate of biofilm microorganisms also confers 83% of patients with urge symptoms had bacteria identified antimicrobial resistance [38]. Biofilms Composite meshes A key determinant in the postimplantation infectious pro Per the Amid classification, composite meshes are designat cess may be the formation of a biofilm. It is thought that by adding a partially aggregate of microorganisms existing within a self absorbable monomer to the mesh weave, the graft can be produced matrix surrounding the implanted foreign body. Bio foreign-body load leading to favorable host response with films can make it difficult for host immune responses to good tissue ingrowth, and fewer postoperative complica counter the microbial invasion and proliferation (Fig. Despite a tinucleated giant cells were seen in close apposition to the higher initial macrophage index on day 7, indices for the individual filaments of the multifilamentous tape [46]. After day 56, both groups had with a high degree of biocompatibility, as suggested by the similar inflammatory responses. They looked at material absorption, inflammatory tis inflammatory cell infiltration or proliferation. The tissues were statistically significant, implantation of Monocryl-supple assessed at 56, 84, and 182 days postimplantation. No mented mesh resulted in a lower host inflammatory and significant differences were found 56 days after implanta fibrotic response. There was no difference induce a greater inflammatory response, leading to dis in cell proliferation between groups at any time point. Based organized scar and greater adhesion formation when on these findings, titanium coatings do not necessarily en placed in direct contact with visceral peritoneum [45]. Titanium may up and down regulate various lation of four inflammatory cytokines in the collagen-coated genes associated with functional activities, including apo group compared with the uncoated group. Part Whether such changes are present after implantation of of the manufacturing process involves collage cross-linking. This is performed using chemicals such as hexamethylene Collagen-based biomaterials have been available for sev diisocyanate or glutaraldehyde. Washing may remove most eral decades and are becoming increasingly popular due to but not all the remnants of cross-linking agents [58]. It can be argued that the intense tation, mesh implant sites were harvested and examined for inflammatory response early in the postimplantation period histologic changes. Both meshes induced a chronic mild may, in fact, cause greater local complications, such as pain inflammatory response and received similar scores for in or erosion. Overall, low numbers of apoptotic cells were noted surrounding all implants (<1%), but there was higher apo ptotic activity in the collagen-coated group (0. It is important to note that although this study had a relatively small sample size (five in each group), Morphologic and mechanical properties of various two meshes of similar density and pore size were used. The host response was assessed at 1 and itself, as variations may be due in part to different host 12 weeks. They noted a delayed and poorer tissue integra inflammatory responses to the implanted material. There were no differ Components of this architecture include mesh weight, ences in inflammatory response at 12 weeks. For the most part, com the early inflammatory response associated with parative studies investigating the impact of these indi collagen-coated meshes may be even greater. A more recent vidual characteristics do not always control for other study using the same types of meshes evaluated and com potential confounding characteristics. At day 7 meshes with different pore sizes but that also have Int Urogynecol J (2012) 23:669–679 675 different weights or weaves. This may ultimately affect inflammatory changes at 4 months and 1 year postimplan the results of that study. Heavyweight the enhanced inflammatory response may have more to do meshes have an increased material surface area, whereas with total mesh surface area than mesh weight itself. They found that in vitro bacterial adher However, surface area also depends on the weave, which ence to multifilament mesh was significantly greater when may result in more or less actual surface area. The persistence of bac that by reducing weight, meshes may provide adequate teria did not lead to a clinically higher infection rate, although support with fewer associated side effects. In a recent bacterial contamination of a surgical wound that contains a international expert roundtable discussion, the panelists foreign body may be responsible for late infections months could not concur on the specifications for the respective and years from the initial operation. They did agree that use of a lightweight mesh with a laparoscopic approach to repair hernias is associated with the lowest rates of chronic pain, stiff abdomen, Pore size and foreign-body sensation. Comparative studies of heavy weight and lightweight mesh use in inguinal hernia repair Pore size is an important factor in achieving a favorable host show equally low recurrence rates with less pain and discom response. The use of heavyweight meshes for abdominal tration and collagen deposition with materials of larger pore hernia repair has been associated with adhesions and fistula size [71, 72]. Porosity In vitro animal studies have shown a significantly greater may affect both the degree of mechanical interlock and the and prolonged inflammatory response with heavyweight intrinsic quality and subsequent strength of such ingrown compared with lightweight meshes [68, 69]. Observations were carried out on days 3, 7, 14, 21, and pore surface achieved higher attachment strength. Over that time period, the heavyweight mesh induced a histologically, tissue-surface configuration at the interface of significant amount of collagen production, enclosing the mesh the more porous implant was more irregular. Conversely, the scar tissue the initial postimplantation response involves interaction surrounding the lightweight mesh was limited to the perifila between macrophages, neutrophils, and bacteria. The average mentary region, with pores filled with fat forming only a loose size of bacteria is about 1 fim. At 90 days, apoptotic cells were almost absent in the are unable to enter the interstices or pores <10 fim. Bacteria lightweight group but still significantly elevated in the heavy can enter and proliferate in pores <10 fim in size, rendering weight group, indicating increased cell turnover. Hence, ysis revealed that the incorporated lightweight mesh exhibited pore size may contribute to the initiation and persistence of sufficient maximum tensile strength with double the elasticity mesh-related infections. It is important to note that the geometries of the two meshes differed considerably. The Mpathy mesh also had a significant ly higher incorporation of mature type I collagen. Ideal pore size is one that results in the incorporation of mature collagen while maintaining tissue appropriate tensile strength and minimizing bacterial colonization. The presence of oxygen in addition to Table 3 Nonmesh factors influencing cellular response Fig. From [79], with Individual patient characteristics permission Persistence of dormant bacteria Presence of bacterial biofilms Combinations with other materials mesh. Despite the Prolene mesh having significantly higher Coatings burst strength prior to implantation, at 30 days postimplant, Release of cytotoxic chemicals the T mesh showed similar tensile strength to the Prolene Int Urogynecol J (2012) 23:669–679 677 extreme temperature can also give rise to thermal oxidation. Degra the human eye and compared it to a pristine suture of the dation products may adversely affect exposed humans. There was significantly more degradation in areas found significantly lower concentrations of glutathione in where the suture was in contact with tissue. Despite these findings in light in contributing to or enhancing the host response.

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On the basis of molecules arrhythmia natural cures discount 162.5 mg avalide overnight delivery, which had been the subject of controversy until my experience with diffraction from coiled coils blood pressure medication that does not cause weight gain avalide 162.5mg discount, I was able that time (25) arrhythmia 24 buy avalide 162.5mg mastercard. In fact hypertension medscape order avalide 162.5mg visa, it in 1965, “Principles of Biomolecular Organization,” was an took until 1991 for the atomic details of an -helical coiled exciting reunion of many of the key workers in the major coil to be established with the crystal structure of the fields that were then under study. I should add that Ken (I trust arranged the meeting, and Francis Crick was the chair because of our work together) switched his focus from man. In the Preface to the proceedings of the meeting, the virus structure to the muscle proteins, a field in which he Foundation praised Crick for his “vigorous” leadership of has become a renowned expert. I can certainly attest to how vigorously he Another general point we made, based on the coiled tried to bully me in my presentation about fibrous proteins coil structure, was that the -helix in any protein in aque (30), but I held my own and managed, I believe, to teach ous solution acquires increased stabilization by intramo him something. In all proteins, hydrophobic three levels of organization in fibrous proteins: the mono bonding is a primary driving force for tertiary fold forma mer, the aggregate, and the covalently cross-linked poly tion in aqueous solution. In the case of structural proteins, such as collagen and in globular proteins are complex: they do not display a fibrinogen, assembly proceeds to the covalently bonded simple, systematic scheme, as is found in coiled coils. By contrast, proteins involved in motility ertheless, isolated regions of secondary structure, what lack cross-linking, a feature that allows them to be ever their conformation, simply are not stable. He and Aaron Klug had been trying to Meanwhile, Don and I persisted in our efforts on tropo explain the construction of icosahedral viruses to each myosin. The next morning, (produced by the cross-connections) into a coiled-coil coil we found that the protein had precipitated. In the light is related to the bending of tropomyosin as it winds around microscope, we saw birefringent needles and, by electron the actin filament in muscle. It pleased me, of course, to imagine and paracrystalline forms of tropomyosin was that the that the atmosphere in our laboratory was truly a bit mag molecules have a conserved and invariant head-to-tail ical, but what had really occurredfi It turned out that my connection, whereas other linkages in the lattice, such as generous assistant had added 1000 times the concentra crossover points, are variable. A similar concept applies to 2 many other molecular machines in which the stability of tion of Ca ions that I had suggested. By this happy acci dent, we discovered what others have called “Cohen-Lon the structure is provided by conserved linkages, within or gley paracrystals” (31). This is the only scientific discovery between molecules, while its functions (in different states) to bear my name. Don and I were dismayed to find that the crystallo More About Self-assembly graphic patterns of tropomyosin still did not speak to us. In the late 1960s, Andrew crystals displayed a kite-shaped mesh of cross-connected Szent-Gyofirgyi and I began to focus on a similar compari filaments (32). One day, I was discussing the x-ray patterns son of paramyosin found in the cores of the thick filaments with Don, and I said to him with some frustration, “Look, of molluscan “catch” muscles and its in vitro assembly. We stared at it, and the nicest discoveries we made was that we could repro then, the photograph spoke (in Don’s voice) at last! It told duce, in vitro, this native packing of the paramyosin mol us that we were looking at the same view of the crystal as in ecules. Using optical diffraction, could easily account for this checkerboard array by a spe we could show how the two sets of strands in the mesh, cific shifting of polar subfilaments. The x-ray patterns overlaps in the assembly (37); these gaps were seen as the also told us that the tropomyosin molecules are polar, i. Galvanized by these results, we wrote a series of papers Some years later, after collagen had been sequenced, the on the subject, which we subsequently presented at a vari physical basis for its assembly was shown to be due to both ety of meetings (33–36). The opening sentence of one of long-range repeats of complementary charge interactions those papers was typical of our playfulness: “There are few and apolar interactions (39). Later, still, with the sequenc protein crystals, seriously studied, which give poorer x-ray ing of myosin and paramyosin, long-range repeats of com diffraction patterns than tropomyosin” (35). I believe that plementary charge interactions were found to be the basis it was through this work that David Parry, then a postdoc for intermolecular recognition and to account, as well, for toral fellow in our laboratory, was first introduced to tro the remarkable periodicities seen in the native protein fil pomyosin and actin, fields in which he has since made aments (see, for example, Ref. In fact, analysis of these in vitro forms essential, albeit distant, collaborator and good friend. He Physics Department; Susan, the Biochemistry Depart suggested that “biological specificity results from the ment; and I joined Biology (Fig. We brought with us our interaction of complementary molecular structures,” held ingenious machinist, Charles Ingersoll, who, like his father together by weak forces (42). This molecular matching, he before him, fashioned the innumerable models on which believed, is the real secret of life. Within a year, we were joined by David the Jimmy Fund Laboratory, Revisited DeRosier, who, with Aaron Klug, had developed three There were many other gifted young scientists in the dimensional reconstruction for electron micrographs and laboratory. Lubert Stryer was soon working with me on who was initially appointed to the Physics Department. We were able to show, by a simple both together and with colleagues, for some 30–35 years. Even When we moved our laboratory from the Jimmy Fund tually, Lubert went on to greater glory (both in science and to Brandeis University in 1972, we also began to move, in in textbook writing), while the fibrinogen-fibrin conver effect, from fibers to crystals (see Ref. Perhaps it was fitting sahedral virus structure, first by constructing a novel that the motto of Brandeis is the Hebrew injunction (from focusing x-ray camera suitable for such giant molecule Psalm 51) to pursue “Truth, even unto its innermost crystallography and then by using patient visual inspection parts. A decade after he completed his thesis on the low resolution virus structure, Steve succeeded in determining Now, 58 years after my first summer at Woods Hole, I the first atomic structure of a crystalline virus, which was find myself once again in the library of the Marine Biology followed by many other notable achievements. Laboratory, remembering all the faces, the papers, the I must mention that Don Wiley, whose memory I will amazement, and the joy of these first 2 decades of my life in always cherish, was also a graduate student of Don Caspar science. Eventually, he and Steve Harrison set up learned from our work and the people who were essential their own Structural Biology Laboratory at Harvard Col to the happiness of our enterprise. Young as he was, Don Wiley nevertheless became a want to make some general remarks about structural kind of adviser to me about the sometimes bewildering biology. Many of us have always believed that an understanding of structure leads to an understanding of function, but this A New Beginning path is not always straightforward. As it turns out, general We were active on a number of fronts in our laboratory ideas about function are often derived from relatively low at the Jimmy Fund during that time, but it eventually resolution information, such as that obtained from certain became clear, with Dr. Farber’s failing health, that we forms of light microscopy, electron microscopy, and low should seek to move the group, as a group, to another resolution x-ray diffraction. Of course, it was not easy then, just as it is not sliding-filament theory of muscle contraction, as well as easy now, to secure three tenured appointments, including for the solution of the packing in icosahedral virus parti two for women, in any research university setting. Atomic structures of the proteins were not necessary considering a few possibilities, we found that Brandeis for either proposal. Higher resolution data about finer University, in nearby Waltham, was building the Rosen aspects of structure, however, can provide a far more com stiel Basic Medical Sciences Research Center. For example, only in recent years has infor for us, Andrew Szent-Gyofirgyi was on the faculty in the mation about detailed conformational changes in myosin Department of Biology there, and Sidney Farber was a cross-bridges been obtained from crystals of subfragment University Trustee. Science, these results can be coordinated with such advances as despite some famous aberrations and popular misconcep the visualization of individual motor molecules. Collaborators ical basis underlying general theories can emerge, then, become friends of a special kind. Susan Almost the entire human genome had been sequenced by Lowey has achieved great distinction as a scientist (and 2001, bringing us to the so-called “post-genomic” era. She moved her laboratory to the University speed with which relatively simple structures are now of Vermont in 1998, and we remain good friends. Of course, there was cipline of “proteomics,” or “structural genomics,” will be Don Caspar. There was also Vittorio Luzzati, whose wit key to revealing how individual proteins interact with one and delight in debate I have treasured since we first met at another and function in the cell (47). There were Anne and David Sayre, an We certainly are speeding up structure determination, immensely intelligent and civilized couple whom I met at and we are hoping to encompass a far broader range of Cold Spring Harbor in 1971. A number of scientists have tackled the riddle of Cold Spring Harbor meeting to their nearby home to talk “Whither Structural Biologyfi Harrison foresees a about Rosalind for the book that Anne was writing to chal fusion of “structural molecular biology” and “structural lenge Jim Watson’s best-selling conceit. Anne’s excellent cell biology” into a unified discipline within the decade, book was published in 1975; she died in 1998. Here, I must also mention my But Abad-Zapatero thinks that this goal is insufficient admiration for Aaron Klug, Rosalind’s collaborator and because it is too static. We must also take into account the friend, who has never stopped seeking justice for her concept of “dissipative structures. I salute him for his scholarly articles in Nature, tions, after all, take place far from equilibrium. He dreams following Watson’s book, and for his Nobel address and of mapping, “in space and time,” the dissipative structures Presidential address for the Royal Society (see also Ref. I think I also treasure the memory of the late John Kendrew, a that both predictions imagine achieving an understanding dear friend who was a great scientist, a great leader of of cellular processes and, perhaps, whole organisms by a scientists, and the first Director of the European Molecu reductionist, bottom-up approach.

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Ward should record information on Y Provincial Toxicology Center dosage & time of last dose blood pressure medication fluid retention buy discount avalide 162.5 mg on line. Transport on cold pack arrhythmia general anesthesia purchase avalide 162.5 mg online, by overnight courier pulse pressure genetics buy 162.5 mg avalide mastercard, to hypertension knowledge questionnaire cheap 162.5 mg avalide have specimen arrive at C&W lab by 12:00 hrs (noon) the day after collection. Send at room temperature on Sunquest transport ordered by Add Thalassemia investigation, batch. Yenson Division of Pre and Post Examination, Page 112 of 249 Providence Health Care, Vancouver B. Must Richardson Laboratory, Room 201 provide Hemophilia A and B genotype testing requisition (see Queen’s University, Kingston, forms/reqs) must send on same day collection. If sample is Ontario, K7L 3N6 collected on Friday, freeze whole sample and send frozen on Tel: 613-533-3187 Monday. Division of Pre and Post Examination, Page 113 of 249 Providence Health Care, Vancouver B. Spin and aliquot again and remove the top three quarters of the plasma to a polypropylene plastic tube suitable for freezing. Referring Labs must complete the “4Ts probability score” form and send with sample. Refdiagid=145 Division of Pre and Post Examination, Page 116 of 249 Providence Health Care, Vancouver B. Patient’s doctor must have completed the SickKids physician Molecular Genetics Requisition link below: required. Attach one copy to copy Western Blot of requisition for Sendout, second copy with original requisition. If Tay Sachs carrier testing requested, have patient fill Children’s Hospital Supplemental information form for Ashkenazi Jewish Carrier and Tay Sachs (Non-Pregnant) Tay Sachs enzyme screening: Hexosaminidase,Serum. Collect Sandhoff’s or Carrier Status and hand deliver to Sendout person before 08:30 Monday – if Pregnant, Total Friday or consult Supervisor before collection. Division of Pre and Post Examination, Page 118 of 249 Providence Health Care, Vancouver B. After Hours**Aseptically separate plasma within 4 hrs of collection into sterile plastic cryovial. Division of Pre and Post Examination, Page 120 of 249 Providence Health Care, Vancouver B. Attach one via Local Lifelab copy to copy of requisition for Sendout, second copy with original requisition. Division of Pre and Post Examination, Page 125 of 249 Providence Health Care, Vancouver B. Division of Pre and Post Examination, Page 126 of 249 Providence Health Care, Vancouver B. Copy of Y Provincial Toxicology Center (Motrin Or Advil) requisition for send out. Division of Pre and Post Examination, Page 127 of 249 Providence Health Care, Vancouver B. Division of Pre and Post Examination, Page 128 of 249 Providence Health Care, Vancouver B. Tumor marker useful for diagnosis/screening for aluminium cell tumor in females and for monitoring sex cord stromal tumors in males. Specimens that arrive at 2-8C are acceptable if they were shipped frozen that day. Division of Pre and Post Examination, Page 132 of 249 Providence Health Care, Vancouver B. Division of Pre and Post Examination, Page 133 of 249 Providence Health Care, Vancouver B. Steve Holland, Consent Neutrophil Monitoring Lab gamma Abs) branch chief, sholland@niaid. Store and send whole blood at room temperature on day of collection or next day with priority next day delivery service. Division of Pre and Post Examination, Page 134 of 249 Providence Health Care, Vancouver B. Patient must sign Out of Country 1-800-533-1710 from consent form form and copy of requisition for Sendout bench. Division of Pre and Post Examination, Page 135 of 249 Providence Health Care, Vancouver B. Division of Pre and Post Examination, Page 136 of 249 Providence Health Care, Vancouver B. Division of Pre and Post Examination, Page 137 of 249 Providence Health Care, Vancouver B. Send Specimen Y Specimen Process Center Polymorphism in original tube on Ambient temperature. Phone ward and request they contact on-call Specimen Is Being Sent Quantitation) (Serum is Medical Biochemist for approval. See instructions in 875 411 L Local 68203 acceptable) methanol/ethylene glycol section Tightly Stoppered. Division of Pre and Post Examination, Page 139 of 249 Providence Health Care, Vancouver B. Division of Pre and Post Examination, Page 141 of 249 Providence Health Care, Vancouver B. Ward should record information on Y Provincial Toxicology Center (Lamictal) dosage, time of last dose, and other meds. Division of Pre and Post Examination, Page 142 of 249 Providence Health Care, Vancouver B. Keep at Y Specimen Process Center room temp, stability: 7 days at ambient, 48 hours refrigerated. Indicate on requisition: total urine volume, date and times of collection, and if collected on Acid washed container. 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Copy of Y Provincial Toxicology Center (tetracyclic Antidepressant) requisition for send out. Division of Pre and Post Examination, Page 151 of 249 Providence Health Care, Vancouver B. Division of Pre and Post Examination, Page 153 of 249 Providence Health Care, Vancouver B. Phone ward and request they contact on-Call Specimen Is Being Sent (Serum is Medical Biochemist for approval. See instructions in Stat Test – Process 875 4111 Local 68203 acceptable) methanol/ethylene glycol section Immediately Tightly Stoppered. Division of Pre and Post Examination, Page 155 of 249 Providence Health Care, Vancouver B. Minimum four hour fast or just Y Alberta Children’s Hospital – (Methylpropanedioic Acid; Heparin prior to next feed for newborns. Biochemical Genetics Lab Form Letter Isocuccinic Acid) Write “Na heparin” or “red top” on aliquot tube. Division of Pre and Post Examination, Page 157 of 249 Providence Health Care, Vancouver B. 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In subsequent work blood pressure medication starts with t cheap 162.5 mg avalide with visa, Glazer focused on phycobilisomes from open ocean unicellular cyanobacteria specialized for the absorbance of green light arteria iliaca interna generic 162.5 mg avalide free shipping. His research has also led to heart attack keychain buy 162.5mg avalide mastercard the use of phycobil iproteins as fluorescence tags for cell surface markers arrhythmia 2014 ascoms buy discount avalide 162.5 mg line. In recognition of his contributions to science, Glazer has received many honors and awards including the British Association for the Advancement of Science’s Endeavour Prize (1955), two Guggenheim fellowships (1970–1971 and 1982–1983), the Botanical Society of America’s Darbaker Prize (1980), and the National Academy of Sciences Award for Excellence in Scientific Reviewing (1991). After graduating from high school, he enrolled in a premed program at Boise Junior College, but his interests quickly turned to chemistry after he dissected a poorly embalmed cat in a comparative anatomy course. After 2 years at Boise, Ballou pursued a degree in chemistry at Oregon State College in Corvallis where he became involved in two research projects: the first during his junior year synthe sizing new antimalarial drugs with Bert Chris tensen, and the second during his senior year studying the guinea pig “antistiffness factor” with Willem van Wagtendonk. The military draft was in effect as Ballou en tered his last year of college so he decided to join the U. He was discharged 2 years later and decided to apply for graduate study in biochemistry with Karl Paul Link at the University of Wisconsin-Madison. Ballou arrived in his laboratory in 1946, the primary focus was the structure-function relationship of coumarin anticoagulants. Ballou was imme diately intrigued when he learned of a failed attempt to synthesize the glucoside of dicumarol because the acetylated intermediate was degraded in the alkali conditions used for deacety lation. Because glycosides are acetals, which are typically acid-labile and alkali-stable, Ballou decided to study a variety of synthetic compounds to try to understand the structural basis for alkali sensitivity. This research formed the core of his doctoral dissertation, and his exposure to carbohydrate chemistry influenced the direction of his career. Fischer (the son of Nobel laureate Hermann Emil Fischer) at the University of California, Berkeley. Ballou explained his choice: “I was attracted to Fischer in this paper is available on line at. I guess the idea of being associated with the son of Emil Fischer just seemed ‘real cool’ to me” (2). The 1950s was a time of active research on biosynthetic pathways involving short chain phosphorylated sugars, and collaborating with Fischer and Donald MacDonald, Ballou under took the syntheses of several such metabolic intermediates, including D-glyceric acid 2-phos phate, D-glyceraldehyde 3-phosphate, dihydroxyacetone phosphate, hydroxypyruvic acid 3-phosphate, and D-erythrose 4-phosphate. He also became interested in inositol chemistry as a result of studies on the cyclitols in sugar pine heartwood. In 1955, Ballou was appointed to the biochemistry faculty at Berkeley and went about setting up an independent research program. He decided to work on inositol-containing phospholipids and was able to synthesize and characterize D-myoinositol 1-phosphate. He also spent several years isolating and characterizing myoinositol polyphosphates from beef brain phosphoinositide. There he collaborated with Erna Vilkas on experiments to establish the linkages of both the phosphatidyl and the mannosyl groups to the myoinositol ring (3). Upon his return to Berkeley, Ballou and Yuan Chuan Lee determined the structures of the family of mannosyl phosphoinositides in Mycobacterium smegmatis (4–6). On the basis of their results, they proposed that guanosine diphosphate mannose acts as the sugar donor in the conversion of phosphatidylmyoinositol to phosphatidylmyoinositol dimannoside (dimannophosphoinositide C), which is then acylated in a two-step process to first yield dimannophosphoinositide B and then dimannophosphoinositide A. They showed that label from [ C]palmityl-CoA is incorporated into dimannophosphoinositide C to yield dimannophosphoinositide B. After a short incubation period, this molecule is converted to dimannophosphoinositide A, but with longer incubation periods the product is deacylated to isomeric forms of dimannophosphoi nositides B and C. More recent research has defined the biochemistry and genetics of synthesis of these molecules. Brennan is currently University Distinguished Professor in the Department of Microbiology, Immunology, and Pathology at Colorado State University. He served on the editorial board of the Journal of Biological Chemistry for several years and was also named Colorado State University Researcher of the Year in 1992. In 1991, Ballou became Professor Emeritus of Biochemistry at the University of California, Berkeley, although he continued research and teaching for a few years. In recognition of his contributions to science, Ballou has received many awards and honors including election to the National Academy of Sciences (1975), the American Chemical Society’s Claude Hudson Award in Carbohydrate Chemistry (1981), the Welch Foundation Lectureship (1972), the University of Notre Dame Reilly Lectureship (1976), the Duke University Belfort Lectureship (1977), a National Science Foundation Senior Fellowship (1961), and a University of California Berke ley Citation (1992). Ballou also served as an editorial board member for the Journal of Biological Chemistry. Richards the Preparation of Subtilisin-modified Ribonuclease and the Separation of the Peptide and Protein Components (Richards, F. Interpretation of an Electron Density Map at a Nominal Resolution of 2 A (Wyckoff, H. He attended the Massachusetts Institute of Technology and, after a brief stint in the military, received his B. Richards then enrolled in graduate school at Harvard Medical School, where he worked with Barbara Low and received his Ph. Richards then moved to the Carlsberg Laboratory in Denmark where, with Kaj Linderstrom-Lang and others, he began working on ribonuclease. After a short stint as a postdoctoral fellow at Cambridge University, Richards joined the fac ulty of the Department of Biochemistry at Yale University in 1955 as an assistant professor. That year, Richards was also ap pointed chairman of the Department of Molecular Frederic M. Richards Biology and Biophysics at Yale, which entailed a move from the Medical School to the Yale College campus. Richards remained at Yale for his entire research career, eventually becoming Sterling Professor of Molecular Biophysics and Biochemistry. This structure tied with three others for the third protein structure ever solved to atomic resolution. Richards received many honors and awards for his scientific achievements, including the Pfizer-Paul Lewis Award in Enzyme Chemistry (1965), election as Fellow of the American Academy of Arts and Sciences (1968), election to the National Academy of Sciences (1971), the Kai Linderstrom-Lang Prize in Protein Chemistry (1978), the American Society for Biochem istry and Molecular Biology Merck Award (1988), the Stein and Moore Award of the Protein Society (1988), and the State of Connecticut Medal of Science (1995). Gibson Oxygen Binding and Subunit Interaction of Hemoglobin in Relation to the Two-state Model (Gibson, Q. After graduating, he became a lecturer in the Department of Physiology at the University of Sheffield and worked his way up to become Professor and Head of the Department of Bio chemistry by 1955. He remained at Penn until 1965 when he became the Greater Philadelphia Professor of Biochemistry, Mo lecular and Cell Biology at Cornell University. In 1996, Gibson joined the Department of Biochemistry and Cell Biology at Rice University. Gibson is probably best known for his research on the structure and function of hemoglobin. The hemo globin molecule consists of four globular protein sub units, each of which contains a heme group that can bind to one molecule of oxygen. The binding of oxygen to hemoglobin is cooperative, the first bound oxygen Quentin H. Gibson alters the shape of the molecule to increase the binding affinity of the additional subunits. Conversely, hemo globin’s oxygen binding capacity is decreased in the presence of carbon monoxide because both gases compete for the same binding sites on hemoglobin, carbon monoxide binding preferen tially in place of oxygen. Gibson started his hemoglobin studies in graduate school, submitting a thesis titled “Meth aemoglobin,” in which he studied the form of hemoglobin where the iron in the heme group is 3 2 in the Fe state rather than the Fe state and is thus unable to carry oxygen. He followed this up with research on familial idiopathic methemoglobinemia, a hereditary hematological disease in which hemoglobin is unable to bind to oxygen, causing dyspnea and fatigue after physical exertion. He was able to identify the pathway involved in the reduction of methemo globin (1), thereby describing the first hereditary disorder involving an enzyme deficiency. In 1965, Jacques Monod, Jeffries Wyman, and Jean-Pierre Chan geux proposed a model which stated that proteins that exhibit cooperativity can exist in only two conformational states, and the equilibrium between these two states is modified by binding of a ligand, oxygen in the case of hemoglobin (2). Ackers reported that the subunit interactions of hemoglobin decreased on binding of the fourth molecule of oxygen to hemoglobin (4). In the first Classic, Gibson and Edelstein measured the free energy of binding of the fourth oxygen molecule and compared their result of 8. Gibson’s smaller value was consistent with other values found in the literature, and it also allowed reasonable representation of the equilibrium curve using the two-state model without invok ing quaternary enhancement. This paper was an extension of an analysis Gibson had done the previous year on ligand rebinding to sperm whale myoglobin (5). From these experiments the researchers were able to determine the differences between the overall rate constants of the two hemoglobin subunits as well as the differences in binding of the various ligands. In recognition of his contributions to science, Gibson has earned many honors including memberships in the Royal Society of London, the National Academy of Sciences, and the American Association for the Advancement of Science.

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