The importance of a high spatial resolution in the Mike 3fm model

The importance of a high spatial resolution in the Mike 3fm model is not so pronounced, since this model is used only to analyse the dynamics of T, S, σt and their vertical distribution, not for modelling effluent spreading in the near or far field. Therefore, the results of Mike 3fm simulations, for the domain shown in Figure 2, were used only as ‘input’ for the near-field model. The near-field effluent transport model is defined using set of differential equations for motion on steady control volume (Featherstone 1984). The core of the model assumes an initial effluent inflow through a

check details circular nozzle and a single buoyant jet or plume propagation not interacting with any other buoyant jets or plumes from adjacent nozzles. Volume flux ϕ, mass flux Ψ, specific momentum

flux M, buoyancy flux B and specific buoyant force per unit length of a plume T are expressed by integral (1a,b,c) and (1d,e), where A represents the cross-sectional area of a plume orthogonal to the central trajectory, u is the velocity in PARP inhibitor drugs the plume cross-section, ρ the density in the plume cross-section, Δρ the density deficit (Δρ = ρm – ρ), ρm the sea water density and ρm0 the sea water density at the positions of the diffuser nozzles. equation(1a,b,c) ϕ=∫AudA,ψ=∫AρudA,M=∫Au2dA, equation(1d,e) B=g∫A(Δρρm0)udA,T=g∫A(Δρρm0)dA. The core of the model is contained in the definition of the rate of change for fields ϕ, Ψ, M and B along the central trajectory path s of the stationary plume. Neglecting the influence of the ambient current on the overall plume dynamic, the specific momentum rate of change becomes zero in the horizontal direction ( eq. (2a)). The change in the specific momentum in the vertical direction is caused by buoyancy ( eq. (2b)). As a result of ambient fluid entrainment through the outer contour of the plume, volume flux and mass flux change

Sclareol along path s are defined by equation (3) (Turner 1986). Henceforth, the specific momentum and volume flux follow: equation(2a,b) dds(Mcosθ)=0,dds(Msinθ)=T, equation(3) dϕds=E=2πb αu(s),where u(s) = u(s, r = 0) is the velocity along the central trajectory of the plume, b is the radial distance from the central trajectory to the position where the velocity takes the value of u(s, r = b) = u(s, r = 0)/e, α = 0.083 is the entrainment constant ( Featherstone 1984), and θ is the angle of inclination of the tangent of the plume trajectory to the horizontal axis. One assumes a Gaussian distribution of the velocity u(s, r) and density deficit Δρ(s, r) in the plume cross-section, where the constant λ = 1.16 in the case of scalar transport. equation(4a,b) u(s,r)=u(s)e−r2/b2,Δρ(s,r)=Δρ(s)e−r2/(λb2). Integration of equation (1) (eq. (5)) and definition of the proportionality between dB/ds and ϕ ( eq.

The pattern of higher FA and lower RD observed here in absence of

The pattern of higher FA and lower RD observed here in absence of differences in AD in the genu of the CC could be interpreted either in terms of a higher axonal density or a higher degree of myelination (cf. Beaulieu, 2002 and Jones et al., 2013). Higher axonal density, lower axonal caliber, as well as the higher Ixazomib degree of myelination should be reflected in lower RD and therefore higher FA (cf. Jones et al., 2013). Indeed, it has been demonstrated in eight different fiber tracts in mice that myelin loss

alone (without axonal injury) can cause an increase in RD, while the AD remains unchanged (Song et al., 2002). Additionally, Song et al. (2005) evaluated the sensitivity of DTI parameters to detect the progression of myelin by testing demyelination and remyelination of corpus callosum in the mouse brain. Afatinib supplier Results demonstrated that radial diffusivity offers a specific assessment of demyelination and remyelination, as distinct from acute axonal damage. Thus,

a more specific disruption of myelin is implied when an increase in RD occurs without an accompanying increase in AD (cf., Madden et al., 2012). However, the interpretation of RD as indicator of myelination is not straightforward and should be avoided especially in regions of complex tissue architecture (Sasson et al., 2010 and Wheeler-Kingshott and Cercignani, 2009). We hence assume that the higher directionality of diffusion (as indicated by FA) is either due to differences in the

number of axons and/or in the degree of myelination in more intelligent men. Myelination of axons is known to increase the signal transmission speed (Waxman, 1977) and decrease the refractory time (time needed for repolarization before a new action potential can be supported by Bumetanide the axon; Felts et al., 1997 and Sinha et al., 2006). Accordingly, the degree of myelination improves the integration of information across spatially distributed neural networks supporting cognitive and motor functions (Bartzokis et al., 2010, Fuster, 1999, Lu et al., 2011, Lu et al., 2013, Lutz et al., 2005, Mesulam, 2000 and Srinivasan, 1999). The higher degree of myelination in more intelligent men thus might account for more efficient brain functioning (cf., Miller, 1994). The relationship of intelligence with the efficiency of brain functioning has been studied intensely throughout the past 20 years. It led to the postulation of the neural efficiency hypothesis assuming negative IQ-brain activation relationship, cf. Neubauer and Fink, 2009a, Neubauer and Fink, 2009b and Dunst et al., 2014). This relationship, however, can be moderated by other factors such as sex and task content (Dunst et al., 2013, Jaušovec and Jaušovec, 2008, Lipp et al., 2012, Neubauer et al., 2010, Neubauer et al., 2002 and Neubauer et al., 2005).

Before the surgical procedure, we used the 18F flexible cystoscop

Before the surgical procedure, we used the 18F flexible cystoscope working channel (CYF-2, Olympus Keymed, UK) to examine the location and number of tumors. Patients with larger tumors were examined by cystography. A preprocedural dual-source CT system (Somatom Definition, Siemens Medical Systems, Forchheim, Germany) was employed to assist in the planning of the CT-guided cryoablation treatment

and to serve as the baseline with which postablation CT could be compared. An oral contrast agent in CT imaging was administrated for all patients with bladder cancer, and a three-cavity indwelling catheter was inserted in patients before surgery. Intraoperatively, an intravenous contrast agent for bladder was administered, and the bladder was irrigated with warm water. A catheter MDV3100 research buy was inserted in patients 2–4 weeks after cryoablation. Percutaneous cryotherapy was performed using a cryoablation system (Cryo-hit, Galil Medical, Israel; employing argon/helium gases using 1.47 mm needles), including as many as 25 cryoprobes (Fig 1). Interventional guidance and monitoring for cryotherapy were performed using a CT system scanner. All 32 patients underwent argon–helium cryoablation during a single procedure, expect for two who were re-treated. Procedures were performed after induction of local anesthesia in the patients. All 34 tumors were treated by an argon/helium gases-based Cryo-hit system and cryoprobes.

According to the size and position of the tumor, a single or multiple 1.47 mm cryoprobes were used to freeze the target Vincristine datasheet bladder tumor with a dual freeze–thaw cycle (10-min freeze, 5-min thaw) under CT guidance. In general, one cryoprobe generates 3-mercaptopyruvate sulfurtransferase an ice ball that is 3 cm in diameter and 5 cm in length along the probe shaft [3].The iceball’s dimensions were monitored via intraoperative CT. The rapid expansion of argon gas in a sealed cryoprobe with a distal uninsulated portion resulted in rapid freezing of tumor tissue, and cryoprobe tip temperatures reached a nadir of approximately −140 °C within seconds. Thawing was

accomplished by replacing the argon gas with helium gas. Tumor freezing was monitored; if the ice ball did not encompass the tumor entirely, additional cryoprobes were placed. CT imaging was performed 24 h after cryoablation to document technical success, assessment of complications, such as bleeding or urinary fistula formation, and provide a baseline for future follow-up imaging and pretreatment CT. Follow-up images with CT were obtained at 3, 6, 12, 18, 24, 36 and 48 months after cryoablation. Tumors were considered completely ablated if there was no evidence to suggest tumor enhancement by intravenous contrast material [3]. Data for 32 patients are shown in Table 1. All patients were from China. The images from CT and cystoscopic views revealed that all 32 patients suffered from muscle-invasive bladder cancer (clinical staging T2-T4aN0M0).

Lack of water and periodic hurricanes such as Donna in 1960 and B

Lack of water and periodic hurricanes such as Donna in 1960 and Betsy in 1965 kept development and immigration from the mainland in check. The granddaddy of all hurricanes, of course, was the Labor Day Storm of 1935. It wiped out Flagler’s railroad,

killed more than 400 people, and was a nagging memory for many Keys residents. In the late 1950s, Dr. Gill Voss (one of my professors at the University of Miami) became concerned that increasing numbers of shell and coral collectors were taking excessive amounts of coral. Few knew how fast corals grew back, although researchers at the Carnegie Institute Research Laboratory click here at Loggerhead Key, Dry Tortugas, had determined growth rates in the 1920s and 1930s. Voss teamed up with John Pennekamp, who lobbied, and published articles that paved the way for creation of what became John Pennekamp State Park. The park was dedicated in 1959 at Harry Harris Park. I attended and displayed black-and-white underwater photographs on a poster board. The new marine park was named after Pennekamp because, as Editor of the Miami Herald newspaper, he had played a major role in creating Everglades National Park (ENP) in 1947. National Park rules prevented National Parks from being named after people. As originally proposed, ENP was to include Key Largo and

the offshore coral reefs. That did not happen due to resistance from Key Largo landowners. Ironically, it was the outlawing of spear fishing that drove support for the State Park. Corals really were not yet considered as important as was stopping Ibrutinib spear fishing. There had long been an ongoing war between charter-boat captains/lobstermen PARP phosphorylation and young spear fishermen from Miami. These young divers, including me, brought little money to the Keys, competed for the local fish, and often brought in more fish than people who had paid considerable money for the sports fishing charter-boat experience. It made the charter-boat captains look bad. Also, the local “Conchs” were socially very different and tough minded. In fact, lobster fishermen murdered one diver many of us knew. He was

shot when they caught him robbing traps. A young teenager with him in the boat was spared. No one was indicted and his death added fuel to the feud. Interestingly, very few Keys charter-boat operators or lobster fishermen could swim very well or cared to learn. Fellow fishermen teased any one who accidentally fell in the water. They literally looked down on those who donned masks (we called them face plates) and flippers. Hardcore spear fishermen scorned snorkels. They were for sissy tourists. They usually had Ping-Pong balls or flaps on the top and those who used them we nicknamed “lids.” So, when did the major changes in the Keys begin and why? Major changes began in the mid-1970s. First came the 36-inch water pipe to Key West. Motels and other businesses at last had sufficient water.

, 2011, Sohel et al , 2009 and Wade et al , 2009), or as in the N

, 2011, Sohel et al., 2009 and Wade et al., 2009), or as in the NE Taiwan studies of atherosclerosis

reported significantly increased magnitudes of association in evaluations of very broad, and therefore uninformative, exposure categories including arsenic water concentrations greatly above 100 μg/L (e.g., >50–499 μg/L and possibly higher for some individuals selleck kinase inhibitor in SW Taiwan for which the exposure concentration was the village median μg/L) (Wang et al., 2005) (Table 1). Results for urinary arsenic were similar to those for water arsenic, with some evidence indicating that subjects with a higher proportion of monomethylarsonic acid (MMA, an intermediate methylated metabolite of iAs) in urine and thereby less dimethylarsinic acid (DMA, the end-product of complete iAs methylation in BYL719 concentration humans) formation had a greater risk of atherosclerosis (in combination

with higher plasma homocysteine levels1) (Wu et al., 2006) and heart disease (Chen et al., 2013a). One prospective cohort study and eight population-based cross-sectional or ecologic studies from various regions in the United States were identified and included in the systematic review (Table 1). Outcomes included incident CVD, CVD-related mortality, ischemic stroke admissions, hypertension, coronary heart disease (CHD), and biomarkers of CVD risk (e.g., blood pressure, prolongation of heart rate-corrected QT intervals). Most cross-sectional or ecologic studies reported mixed findings

(Engel and Smith, 1994, Gong and O’Bryant, 2012, Lisabeth et al., 2010, Meliker et al., 2007 and Zierold et al., 2004), with only one study population of elderly men exposed to very low arsenic in drinking water (<1.0 μg/L), but having positive associations between toenail arsenic concentration and QT interval, heart rate-corrected QT duration, and blood pressure (systolic and pulse pressure more than diastolic) (Mordukhovich et al., 2009 and Mordukhovich et al., 2012) (Table 1). Toenail concentrations tended to be higher in summer than in winter (Mordukhovich et al., 2012), indicating that external adherence of arsenic in soil or dust to toenails may be an issue (Tsuji et al., 2005). A nationally representative cross-sectional study of data from heptaminol the National Health and Nutrition Examination Survey (NHANES) (Jones et al., 2011) reported no statistically significant associations between hypertension or systolic or diastolic blood pressures and total urinary arsenic concentration, total urinary arsenic minus arsenobetaine (from seafood), and urinary DMA (arises in urine from metabolism of iAs as well as from its presence in the pentavalent form in some foods, or from other organic precursor compounds in food; Aylward et al., 2014). The U.S. prospective cohort study included 3575 Native American men and women aged 45 years and older from Arizona, Oklahoma, and the Dakotas who had participated in the Strong Heart Study since 1989–1991 (Moon et al., 2013).

, 2003 and Yaraee et al , 2003), which is crucial to the developm

, 2003 and Yaraee et al., 2003), which is crucial to the development of the inflammatory and febrile responses and enhances the release of pro-inflammatory cytokines

in response to LPS ( Berman et al., 1996). Moreover, LPS itself can increase the NK1R expression in some of these cells ( Bost, 2004). In view of such considerations, the present study aimed to investigate, using a selective non-peptide NK1R antagonist SR140333B, whether substance P, released in the periphery or the CNS, participates in the febrile response induced by LPS and two endogenous pyrogens: IL-1β, which induces a prostaglandin-dependent fever, and CCL3/MIP-1α, which induces a prostaglandin-independent fever in conscious PS-341 purchase rats. In addition, we assessed the effects of centrally administered substance P on body temperature in this species. Control animals treated only with vehicle or SR140333B showed a small increase in body temperature over baseline values, returning to pre-injection temperature after 1 h and remaining at this level up to 6 h after administration. In sharp contrast, those given LPS (30 μg/kg, i.p.) displayed an increase in body temperature that peaked after around 2.5 h and continued elevated for the remainder of the observation period. Prior injection of the NK1R antagonist SR140333B (0.3 mg/kg, data not shown or 1 mg/kg, i.p.) failed to impede the development of LPS-induced fever

(Fig. 1A and B). A higher dose of SR140333B (3 mg/kg, i.p.) was tested TSA HDAC cell line but, in combination with LPS, this dose induced a significant decrease in body temperature between 0 and 1.5 h (around 0.7 °C) after injection, which made the interpretation of the results difficult (data not shown). SR140333B (1 mg/kg, i.p.) alone did not alter body temperature from baseline (Fig. 1C). To verify if this dose of SR140333B blocked the peripheral actions of SP we examined

the effect of this treatment on protein extravasation. Intradermal injection of SP induced a significant increase in Evans blue extravasation when compared Thiamet G to saline in vehicle-treated animals (Fig. 1D). As expected, the treatment of the animals with SR140333B, at the same dose that did not affect the febrile response, significantly reduced the protein extravasation by 81% (Fig. 1D). In the next set of experiments we injected SR140333B or the vehicle into the lateral ventricle of the animals. Control animals treated only with the vehicle or SR140333B showed much smaller changes in body temperature than in the previous set of experiments. The pre-treatment of the animals with SR140333B effectively reduced the febrile response induced by LPS (Fig. 2). Fig. 2A shows the time-course of the reduction in the febrile response induced by the higher dose of SR140333B (3 μg, i.c.v.). This dose of SR140333B reduced the fever index by 85% (Fig. 2B). A lower dose of SR140333B (1 μg, i.c.v.

The Schiffer–Edmundson helical wheel showed that the amphipathic

The Schiffer–Edmundson helical wheel showed that the amphipathic α-helical structure (containing hydrophobic residues

on one face of the helix and hydrophilic residues on the opposite face) present in the pleurocidin selleck screening library is also present in the Plc-2 (Fig. 3). Pleurocidin is one of the most noteworthy antimicrobial peptides studied in the past few years. It displays a broad spectrum of activity against bacteria, fungus and some leukemical and eukaryotic cells [17]. In general, the activity of AMP depends on the composition of the membranes with which it interacts together with its structural features; primary structure, conformation, net charge, net hydrophobicity, hydrophobic moment, amphipathicity, size, and polar angle [43]. Therefore, to find the minimal active fragment, Plc was further truncated and assayed against a representative set of Gram-positive (S. aureus and E. faecalis) and Gram negative (P. aeruginosa and E. coli) bacteria and fungi. The bacterium S. aureus has acquired a number of genes that provide antibiotic resistance against

all penicillins, including methicillin and other narrow-spectrum β-lactamase-resistant penicillin antibiotics. Recently, it has become the major cause of hospital-acquired infections [33]. The strain P. aeruginosa typically infects the pulmonary tract, urinary tract, burns, and wounds and also causes other blood infections. It has been reported to be responsible for one in ten hospital-acquired infections are from Pseudomonas [30] and [39]. An important distinction for Gram-positive bacteria is that they possess thicker cell wall than Gram-negative organisms. screening assay This peptidoglycan layer of Gram-positive bacteria remains a relatively porous structure [38]. The essential function of the cell wall is to serve as a selective permeability barrier, protecting bacteria from harmful agents, such as detergents, drugstoxins and degradative enzymes, yet allow the penetration of nutrients to sustain bacterial growth. Evidence from genetic

and chemical experiments have proven that the cell wall plays an essential role in providing a selective permeability barrier for S. aureus and other Gram-positive bacteria. The peptide fragments used here caused cell wall effects such as breaks, thinning, and disintegration Casein kinase 1 as well as abnormal septation. Our experimental results using Plc-1–5, which represent the N-terminal, middle, and C-terminal segments of pleurocidin suggested that only the amino acids present in Plc-2 enhanced the permeability of membrane with a similar potency of the parent molecule, which requires passage through the cell wall. Examining the data in Table 1, the hydrophobicity of the peptides was determined not to be a possible element of influence on the observed activities. Therefore, it was assumed that the structure would be a primary contributing aspect to the mechanism of action.

1) Seven small villages with a total population of about 10,000

1). Seven small villages with a total population of about 10,000 people are situated along the coastline (URT, 2002) (Fig. 1). Fishing is the most important economic activity in the bay (de la Torre-Castro

and Lyimo, 2012). SSF dynamics E7080 ic50 are complex due to the high heterogeneity of the fisher groups involved, the existence of multiple gears and fishing practices linked to a multifaceted combination of regulations and socio-cultural aspects (de la Torre-Castro and Lindstrom, 2010 and de la Torre-Castro, 2012a). SSF take place in a topographically complex sea bed with a tidal regime characterized by large fluctuations and seasonalities caused by the monsoon circulation in the Western Indian Ocean (WIO) (McClanahan, 1996 and Tobisson et al., 1998). The diversity of seagrass species is very high with eleven reported species. The most common species found are Thalassia hemprichii, Cymodocea serrulata, Nutlin-3a molecular weight C. rotundata, Halodule uninervis, H. wrightii, Thalassodendron ciliatum, Syringodium isoetifolium, Enhalus acoroides, and different Halophila spp. Seagrasses are spread throughout the whole bay substrate, but are particularly abundant in the West coast in front of Marumbi village (about 5 km north of Chwaka village, Fig. 1). Seagrasses are found in mixed meadows (primarily

dominated by T. hemprichii, Enhalus acoroides and Cymodocea spp.) as well Thymidylate synthase as mono-specific in shallow, deep and channel areas. Due to these facts, Chwaka Bay has been considered a hot-spot of seagrass diversity ( de la Torre-Castro and Lyimo, 2012). Fishing takes place daily over the entire area of the bay (about 50 km2) following seasonal (northeast monsoon, dry season and southeast monsoon) and tidal cycles (semidiurnal; range 1–4.5 m). Due to the heavy burden of fishing activities

and tidal constraints, fishers make only one trip per day usually spending about 6 h at sea. On the boat, the fish are threaded with a string to form what is colloquially known as a “batch” (mtungo). The “batch” is a collection of fish normally arranged by species which facilitates transportation and selling at the auction. Arriving to the shoreline, the batches are taken directly to the local markets where the fish is auctioned ( Appendix I, Supplementary Information). There are only three fish markets in the bay (Uroa – medium size, Marumbi – very small and Chwaka – biggest), fish coming from other villages along the bay’s coastline are normally sold in the Chwaka market due to the high number of buyers. The Chwaka village fish market besides being the largest, is the most visited and has a good quality paved road linking straight to the “capital” Zanzibar Town, the number of fish traders found in the Chwaka market is very high as well. Due to the above, all data for this research was compiled there ( Fig. 1).

These values imply that plastic meso- and microparticles in the o

These values imply that plastic meso- and microparticles in the ocean will at equilibrium yield a highly concentrated source of POPs. A recent study by Rios and Moore (2007) on plastic mesooparticles on four Hawaiian, one Mexican and five California beaches showed very significant levels of pollutants in the particles. The ranges of values reported were: ∑ PAH = 39–1200 ng/g: ∑ PCB = 27–980 ng/g: ∑ DDT = 22–7100 ng/g. These are cumulative values for 13 PCB congeners and 15 PAHs.The cumulative levels found in plastic pellets collected from locations near industrial sites were understandably much higher. Highest values reported were ∑ PAH = 12,000 ng/g and DDT = 7100 ng/g. A 2009 study reported

LGK-974 order data for 8 US beaches (of which 6 were in CA) as follows (Ogata et al., 2009): ∑ PCB = 32–605 ng/g; ∑ DDT = 2–106 ng/g; and ∑ HCH(4 isomers) = 0–0.94 ng/g. The levels of pollutants in plastic pellets floating in surface layers are comparable to the range observed for sediment concentration

of the same compounds. Recent work has suggested that micro- and mesoplastic debris may also concentrate metals (Ashton et al., 2010) in addition to the POPs. This is an unexpected finding as the plastics are hydrophobic but the oxidised surface could carry functionalities that can bind metals. The situation is reversed in the case of residual monomer and additives compounded into plastics as well as partially degraded plastics carrying degradation products. These plastics

debris will slowly leach out a small fraction of buy Vincristine the POPs (additives, monomer or products) into the sea water until the appropriate KP/W [L/kg] value is reached. The equilibrium is a dynamic one and the POPs are never irreversibly bound to the polymer but diffuse in an out of the plastic fragment depending this website on changes in the concentration of the POP in sea water. In contrast to ‘cleaning’ of sea water by virgin plastics these tend to leach a small amount of the POPs into seawater However, while no good estimates or models are available for the process, the total plastics debris-mediated pollutant load introduced into seawater is likely to be at least several orders of magnitude smaller than that introduced from air and waste water influx into oceans. The critical ecological risk is not due to low-levels of POPs in water but from the bioavailability of highly concentrated pools of POPs in microplastics that can potentially enter the food web via ingestion by marine biota. Microparticles and nanoparticles fall well within the size range of the staple phytoplankton diet of zooplanktons such as the Pacific Krill. There is little doubt that these can be ingested. Plastic microbeads have been commonly used in zooplankton feeding research. There are numerous references in the literature (Berk et al.

1C and D) evidenced by 31%, 13% and 44% of all structures being o

1C and D) evidenced by 31%, 13% and 44% of all structures being obtained with each additive, respectively. Another common component of successful conditions were various salts, with concentrations ranging from 0–1 M, the absence of salt (38%) and 0.2 M (31%) being most popular ( Fig. 1E). Based on these findings we developed a crystallization screen for TCR/pMHC complexes (Tables 1A and 1B). Our screen consisted of two 48 well PEG/pH screens. Each PEG/pH screen consisted of four buffer systems (C2H6AsO2Na, MES, HEPES and TRIS) at a concentration of 0.1 M in combination with PEG 4000, or PEG 8000 at 15, 20 and 25%. These buffers allowed scanning the pH range from 6.0–8.5. 15% glycerol

was added to the first subscreen (Table 1A), whereas 0.2 M ammonium sulfate was added to the second subscreen (Table 1B). In some cases, TOPS generated several crystal Crizotinib mouse selleck chemicals llc hits that were of lower quality, i.e. the crystals were very small, contained cracks or impurities, or did not diffract to high resolution. In these cases, we extended the conditions that yielded crystals to generate a number of other fine screens that proved useful for specific TCR/pMHC complexes. TOPS1 (Supplementary Table 1) was designed by extending the lower range

of pH with C2H6AsO2Na pH 5.0 and 5.5 of the A07 condition of the TOPS screen. In addition, PEG 3350 was compared versus PEG 4000 in this screen. TOPS2 (Supplementary Table 2) was designed by extending the lower range of PEG concentration (10, 12.5, 15, 17.5, 20 and 22.5%) of the

second subscreen of the TOPS screen. In addition, one of the buffer systems (C2H6AsO2Na pH 6.0) was replaced by a non-buffered condition and supplemented by another precipitant (0.2 M sodium sulfate) as some good hits were obtained using a commercially available screen (PACTPremier, condition E08; 0.2 M sodium sulfate and 20% PEG 4000). TOPS3 (Supplementary Table 3) was designed by reducing the range of pH (from 6.5–7.5) and increasing the number of buffer system (MES pH 6.5, BIS TRIS propane pH 7.0 and TRIS pH 7.0) as well as the range of glycerol concentrations (0, 4.4, 8.7 and 17.4%). PEG 4000 was the PEG of choice in this screen. The only difference between TOPS3 and TOPS4 (Supplementary Table 4) was that TOPS4 contained 0.2 M ammonium sulfate. These screens generated Atorvastatin 5 TCR/pMHC complexes as detailed in Table 2. High-throughput crystallization trials were performed using 3 commercially available screens (PACT Premier, JBScreen and JCSG-plus (Molecular Dimensions Ltd, Suffolk, U.K.)) and/or 5 different “homemade” screens (TOPS, TOPS1, TOPS2, TOPS3 and TOPS4) (Tables 1A and 1B, Supplementary Tables 1–4), the last four screens being derivatives of the TOPS screen. Crystallization conditions were successfully identified for 25 TCR/pMHC complexes, 14 of which were derivatives from a common parent complex.