Participants passively listened to recordings of single adjective

Participants passively listened to recordings of single adjectives spoken in their own and another

person’s voice (alien) preceded by their own or another person’s (alien) face and made self/non self judgments about the source. The patients showed increased error rates comparing to controls, when listening to the distorted self spoken words, misidentifying their own speech as produced by others. Importantly, patients made significantly more errors across all the invalid cue conditions. This suggests not only the presence of pathological misattribution bias, but also an inadequate balance between top-down and bottom-up attentional processes in the patients, which could be responsible for misattribution of the ambiguous sensory material. (C) 2011 Elsevier Ltd. All rights reserved.”
“Delay eyeblink conditioning is established by paired presentations

of a conditioned stimulus (CS) such as a tone or light, and an unconditioned stimulus (US) that elicits the blink reflex. Conditioned stimulus information is projected from the basilar selleck compound pontine nuclei to the cerebellar interpositus nucleus and cortex. The cerebellar cortex, particularly the molecular layer, contains a high density of cannabinoid receptors (CB1R). The CB1Rs are located on the axon terminals of parallel fibers, stellate cells, and basket cells where they inhibit neurotransmitter release. The present study examined the effects of a CB1R agonist WIN55,212-2 and antagonist SR141716A on the acquisition of delay eyeblink conditioning in rats. Rats were given subcutaneous administration of 1, 2, or 3 mg/kg of WIN55,212-2

or 1, 3, or 5 mg/kg of SR141716A before each day of acquisition training (10 sessions). Dose-dependent impairments in acquisition were found for PAK5 WIN55,212-2 and SR141716A, with no effects on spontaneous or nonassociative blinking. However, the magnitude of impairment was greater for WIN55,212-2 than SR141716A. Dose-dependent impairments in conditioned blink response (CR) amplitude and timing were found with WIN55,212-2 but not with SR141716A. The findings support the hypothesis that CB1Rs in the cerebellar cortex play an important role in plasticity mechanisms underlying eyeblink conditioning.”
“To highlight relevant information in dialogues, both wh-question context and pitch accent in answers can be used, such that focused information gains more attention and is processed more elaborately. To evaluate the relative influence of context and pitch accent on the depth of semantic processing, we measured event-related potentials (ERPs) to auditorily presented wh-question-answer pairs. A semantically incongruent word in the answer occurred either in focus or in non-focus position as determined by the context, and this word was either accented or unaccented.

Semantic incongruency elicited different N400 effects in different conditions. The largest N400 effect was found when the question-marked focus was accented, while the other three conditions elicited smaller N400 effects.

The stability data were corroborated by dye binding experiments p

The stability data were corroborated by dye binding experiments performed to probe the solvent-accessible hydrophobic surface of the protein. Our results strongly suggest that the myristoyl moiety is permanently solvent-exposed in Ca2+-free GCAP-2,

whereas it interacts with a hydrophobic part of the protein’s structure in TPCA-1 the Ca2+-bound state.”
“The lateral dynamic flight stability of a model bumblebee in hovering and forward flight is studied, using the method of computational fluid dynamics to compute the stability derivatives and the techniques of eigenvalue and eigenvector analysis for solving the equations of motion. The lateral motion of the model bumblebee is unstable at hovering and low flight speed (advance ratio J=0, 0.13), and becomes neutral or weakly stable at medium and high flight speeds (J=0.31-0.57). The instability at hovering and low speed is mainly caused by a positive roll-moment derivative with respect to the side-slip velocity, which is due to the effect of changing the axial velocity of the leading-edge-vortex (LEV) (i.e. the ‘lateral wind’ due to the side motion of the insect increases the axial velocity of the LEV on one wing and decreases that on the other wing). As flight speed increases, because the mean position of the wings moves more and more backward, the effect of ‘changing-LEV-axial-velocity’ becomes weaker and weaker and the roll-moment derivative decreases first and then changes its

sign to become negative, resulting in the neutrally or weakly stable motion at medium and high flight speeds. (C) 2012 Elsevier Ltd. All rights reserved.”
“The pioneering work of Ramachandran and colleagues check details emphasized the dominance of steric constraints in specifying the structure of polypeptides. The ubiquitous Ramachandran plot of backbone dihedral angles (phi and psi) defined the allowed regions of

conformational space. These predictions were subsequently confirmed in proteins of known structure. Ramachandran and colleagues also investigated the influence of the backbone angle tau on the distribution of allowed phi/psi combinations. The “”bridge region” Tau-protein kinase (phi <= 0 degrees and -20 degrees <= psi <= 40 degrees) was predicted to be particularly sensitive to the value of tau. Here we present an analysis of the distribution of phi/psi angles in 850 nonhomologous proteins whose structures are known to a resolution of 1.7 angstrom or less and sidechain B-factor less than 30 angstrom(2). We show that the distribution of phi/psi angles for all 87,000 residues in these proteins shows the same dependence on tau as predicted by Ramachandran and colleagues. Our results are important because they make clear that steric constraints alone are sufficient to explain the backbone dihedral angle distributions observed in proteins. Contrary to recent suggestions, no additional energetic contributions, such as hydrogen bonding, need be invoked.

Further studies of flow gain obtained

Further studies of flow gain obtained BAY 1895344 datasheet from channel Pz showed two distinct peaks centered at about 12 Hz low frequency and 20 Hz medium frequency respectively.

The low frequency region had a larger value of flow gain. The present study introduced functional connectivity into SSVEP. Furthermore, we put forward the concept of flow gain for the first time to explore the exchange and processing of brain information during SSVEP. (C) 2011 Elsevier Ireland Ltd. All rights reserved.”
“Effluent from oil production activities contains chemicals that are suspected of inducing endocrine disruption in fish. In this study, Atlantic cod (Gadus morhua L.) were exposed to mixtures of low- and medium-molecular-weight alkylphenols (AP) (methyl- to heptylphenol), polycyclic aromatic hydrocarbons

(PAH), diluted produced water, and dispersed oil for 15 d in a flow-through Erastin in vivo exposure system. Condition index (CI), hepatosomatic index (HSI), gonadosomatic index (GSI), concentration of the estrogenic biomarker vitellogenin (Vtg), and modulation of the total sex steroid-binding capacity in plasma were determined to assess whether these mixtures were capable of interfering with endocrine-regulated physiological processes in Atlantic cod. No marked differences in plasma Vtg levels were found between control and exposed groups of either males or females, possibly due to high intergroup variances and low sample numbers. An apparent numerical increase in the number of male and female fish with high plasma Vtg levels was, however, observed in some exposure groups compared to control. This purported weak estrogenic effect was several orders of magnitude

lower than that observed for potent estrogens and suggested that the levels of estrogen receptor (ER) Olopatadine agonists were low. Exposure of female fish to a mixture of dispersed oil and a mixture of AP, PAH, and dispersed oil led to upregulation of the plasma total sex steroid-binding capacity, indicating interference with the normal blood steroid transport. No significant effects were seen for CI, HSI, and GSI, suggesting that the endocrine-disrupting potential was not sufficient to elicit effects on general physiological conditions and gonad development during this short exposure period.”
“We aimed to evaluate the effect of arousal level in healthy subjects on P50 potential, as the variation in the level of arousal may be a source of variance in the recordings as well as it may provide additional information about the pathology under study. Eleven healthy volunteers participated in the study. A standard auditory P50 potential paradigm was applied. Two stimulation conditions were selected: eyes-open, i.e., high arousal level condition and eyes-closed, i.e., low arousal level condition.

24, 95% CI 1 75-2 84) and cardiovascular mortality (HR 2 53, 95%

24, 95% CI 1.75-2.84) and cardiovascular mortality (HR 2.53, 95% CI 1.51-4.23).

Conclusions: Radical nephrectomy is associated with worse overall and cardiovascular survival compared to partial nephrectomy in patients with localized renal cell carcinoma 2 cm or less. These findings justify the widespread application of nephron sparing techniques to treat localized kidney cancer.”
“Rationale The concern that adjuvant cancer chemotherapy agents cause cognitive

impairment in a significant number of patients has been expressed by patients and healthcare providers, but clinical studies have yielded conflicting results to date.

Objective We directly tested two commonly used chemotherapeutic agents in a mouse model of learning and memory.

Materials Selleckchem MK-0518 and methods In the present study, mice were conditioned to respond for a liquid reinforcer (Ensure

solution) in the presence of an audible tone on day 1 as a measure JPH203 of acquisition and were then required to perform the same response on day 2 as a measure of retrieval and retention. Methotrexate and 5-fluorouracil were administered prior to the day 1 session.

Results Methotrexate (1.0-32 mg/kg) alone failed to alter mean latency acquisition, retrieval, or reinforced response rates. Similar to scopolamine, a known amnesic in this assay, 5-fluorouracil (3-75 mg/kg) failed to alter response rates or acquisition latency on day 1 but significantly altered latency to retrieve a previously learned response on day 2. In combination, 3.2 mg/kg methotrexate plus 75 mg/kg 5-fluorouracil significantly increased day 1 and day 2 acquisition and retrieval latencies without altering response rates or motivation to respond as measured by progressive ratio responding.

Conclusion Taken together, these data demonstrate that 5-fluorouracil causes increased latencies for retrieval of previously learned behavioral responses and that combination of chemotherapeutic agents

may produce greater delays than Rebamipide either agent alone, including when neither agent alone does so.”
“How cell envelope constituents are spatially organised and how they interact with the environment are key questions in microbiology. Unlike other bioimaging tools, atomic force microscopy (AFM) provides information about the nanoscale surface architecture of living cells and about the localization and interactions of their individual constituents. These past years have witnessed remarkable advances in our use of the AFM molecular toolbox to observe and force probe microbial cells. Recent milestones include the real-time imaging of the nanoscale organization of cell walls, the quantification of subcellular chemical heterogeneities, the mapping and functional analysis of individual cell wall constituents and the analysis of the mechanical properties of single receptors and sensors.

Interestingly, the latter base changes are probably responsible f

Interestingly, the latter base changes are probably responsible for the increased pyruvate kinase activity of the Htg(+) strain. The possible mechanism leading to this increased activity and to the Htg(+) phenotype, which may lead to the activation of energy metabolism to maintain cellular homeostasis, is discussed.”
“The surrogate light chain (SLC) is a key regulator of B cell development in the bone marrow, resulting in mature

B cells that produce antibodies that are capable of interacting with antigens. The SLC comprises SIS3 research buy two noncovalently interacting proteins: VpreB and 14.1. We engineered a construct to represent the complete immunoglobulin-like domain of the SLC variable domain in a single protein chain that could be bacterially expressed. Bortezomib molecular weight In this construct, the incomplete immunoglobulin domain of VpreB ( residues 1-102) was linked to the J-segment of 14.1 ( residues 40-53), which provided one beta-strand to complete the V-like domain (VpreBJ). Because

VpreBJ has the interface to VH chains, but lacks the unique region of 14.1, which is important for SLC signaling, we predict that a properly folded VpreBJ would have the potential to act as a dominant negative mutant of the surrogate light chain. X-ray crystallography of VpreBJ at 2.0 angstrom resolution showed that the engineering was successful. With its two beta-pleated sheets, packed face-to-face, the single chain VpreBJ resembles a mature light chain immunoglobulin V-domain (VL). The surface that would normally interact with the VH chain interacts with a crystallographically

related VpreBJ molecule. The presence of dimeric species in solution was verified by analytical ultracentrifugation. VpreBJ is easily overexpressed in bacteria, while retaining the native conformation of an immunoglobulin domain, and thus may serve as an important reagent for future studies Chlormezanone in B-cell development.”
“We identified genomic and network properties of similar to 600 genes mutated in different cancer types. These genes tend not to duplicate but, unlike most human singletons, they encode central hubs of highly interconnected modules within the protein-protein interaction network (PIN). We find that cancer genes are fragile components of the human gene repertoire, sensitive to dosage modification. Furthermore, other nodes of the human PIN with similar properties are rare and probably enriched in candidate cancer genes.”
“The present paper reviews oxidases catalyzing conversion of glycolaldehyde into glyoxal. The enzymatic oxidation of glycolaldehyde into glyoxal was first reported in alcohol oxidases (AODs) from methylotrophic yeasts such as Candida and Pichia, and glycerol oxidase (GLOD) from Aspergillus japonicus, although it had been reported that these enzymes are specific to short-chain linear aliphatic alcohols and glycerol, respectively. These enzymes continuously oxidized ethylene glycol into glyoxal via glycolaldehyde.

7 x 10(-9)) In addition, there was a significant association at

7 x 10(-9)). In addition, there was a significant association at the 11p15.4 locus (rs451041: P = 0.02). Thus, associations identified in the GoKinD collections on chromosomes 11p15.4 (near the CARS gene) and 13q33.3 (within an intergenic region between MYO16 and IRS2) are susceptibility loci of kidney disease common to both type 1 and 2 diabetes.”
“Ovulation is the unique biological process by which a mature oocyte (egg) and surrounding somatic

cells, the cumulus cell-oocyte complex (COC), are released from the surface of the ovary into the oviduct for transport and fertilization. Ovulation is similar to an inflammatory response: the follicles become hyperemic, produce prostaglandins and synthesize a hyaluronan-rich extracellular matrix. However, this view of ovulation might be too restrictive and Adavosertib clinical trial needs to be broadened to encompass the innate immune cell surveillance-response

system. selleck kinase inhibitor This hypothesis is being proposed because ovarian granulosa cells and cumulus cells express and respond to innate immune cell-related surveillance proteins (Toll-like receptors 2 and 4) and cytokines, such as interleukin 6 (IL-6), during ovulation.”
“The kidney glomerulus is the site of plasma filtration and production of primary urine in the kidney. The structure not only plays a pivotal role in ultrafiltration of plasma into urine but also is the locus of kidney diseases progressing to chronic renal failure. Patients afflicted with these glomerular diseases frequently progress to irreversible loss of renal function and inevitably require replacement therapies. The diagnosis and treatment of glomerular Non-specific serine/threonine protein kinase diseases are now based on clinical manifestations, urinary protein excretion level,

and renal pathology of needle biopsy specimens. The molecular mechanisms underlying the progression of glomerular diseases are still obscure despite a great number of clinical and experimental studies. Proteomics is a particularly promising approach for the discovery of proteins relevant to physiological and pathophysiological processes, and has been recently employed in nephrology. Although until now most efforts of proteomic analysis have been conducted with urine, the biological fluid that is easily collected without invasive procedures, proteomic analysis of the glomerulus, the tissue most proximal to the disease loci, is the most straightforward approach. In this review, we attempt to outline the current status of clinical proteomics of the glomerulus and provide a perspective of protein biomarker discovery of glomerular diseases.”
“The bile steroids (BS) cholic acid and chenodeoxycholic acid are produced in hepatocytes and in the brain. Nothing is known about neuronal actions of BS.

The use of 8 M urea or thiourea/urea solutions in the electrode w

The use of 8 M urea or thiourea/urea solutions in the electrode wick enables overnight focusing without the appearance of gaps.”
“Objective: This study reviews the results of en bloc resection of the inferior vena cava (IVC) for malignant tumor excision and reconstruction.

Methods: A prospective database was reviewed. IVC resection was categorized as suprarenal, perirenal, infrarenal, or extensive (>one segment resected). Repairs were divided into primary, patch, or circumferential. Tumor type, perioperative morbidity, mortality, and graft patency were recorded.

Results: Between 1990 and 2011, 47 patients (21 women;

mean age, 56; range, 35-89 years) underwent IVC resection for en bloc tumor CHIR98014 molecular weight excision. Sarcomas were most common (36 [77%]: 30 primary IVC). Eleven patients had primary Selleck ACY-1215 IVC repair, nine patch repair (two autogenous), and 27 had circumferential replacement with a polytetrafluoroethylene ringed graft. Extensive IVC reconstruction in 18 patients included the entire IVC, with renal (RV) and hepatic vein reimplantation in eight; suprarenal and perirenal in six (seven RVs reimplanted); and infrarenal and perirenal in four (four RVs

reimplanted). Nine single-segment IVC replacements were infrarenal. Morbidity was 10.6%: one each with bowel obstruction, chyle leak, renal failure with complete recovery (left RV reimplant, right nephrectomy), reoperation for bleeding, and IVC graft thrombosis. Morbidity did not differ by type of reconstruction. There was no mortality. Follow-up ranged from 1.5 to 216 months (18 years) with a mean of 3.5 years. Computed

tomography or duplex scans were available in 28 of 47 patients and in 15 of 27 patients in group 3 at a mean follow-up of 36 and 20 months, respectively. One IVC graft thrombosis was documented at 10 months after chemotherapy/sepsis. Tumor recurrence caused three graft stenoses. Cumulative 5-year patency in group 3 was 80% (imaging) and 92% (clinical). Lower extremity edema was universally avoided. Cumulative 5-year survival for the series was 45% +/- 8.5%. Mean long-term survival was 5.8 +/- 0.56 years (range, 4 months-17 years), with a significant difference between primary or patch (mean, 6.5 years) and circumferential or extensive repair (mean, 4.2 years; P < .005). Cumulative (47% vs 52%) and mean (3.1 vs 3.6 years; buy ZD1839 P > .12) survival was similar between patients with single-segment and extensive IVC resection and replacement.

Conclusions: IVC resection and reconstruction for en bloc tumor excision is safe, even when extensive repairs are necessary. Replacement of the IVC with prosthetic graft avoids extremity venous complications and likely contributes to quality of survival. Survival depends on tumor behavior and degree of IVC involvement, where primary and patch repair has a better prognosis than circumferential resection. (J Vasc Surg 2012;55:1386-93.

0, 40 degrees C, and the major hydrolysis product from the celloo

0, 40 degrees C, and the major hydrolysis product from the cellooligosaccharides was cellobiose. EngZ’s specific activity toward crystalline cellulose (Avicel and acid-swollen cellulose) Metabolism inhibitor was 10-20-fold higher than other

cellulosomal cellulase activities. A large percentage of the reducing ends that were produced by this enzyme from acid-swollen cellulose were released as soluble sugar. EngZ has the capability of reducing the viscosity of Avicel at an intermediate-level between exo- and endo-typing cellulases, suggesting that it is a processive endoglucanase. In conclusion, EngZ was highly expressed in cellulolytic systems and demonstrated processive endoglucanase activity, suggesting that it plays a major role in the hydrolysis of crystalline cellulose and acts as a cellulosomal enzyme in C. cellulovorans.”
“There is renewed interest in the functional role of oscillatory brain activity in specific frequency bands, investigated in humans through electroencephalography (EEG) and magnetoencephalography (MEG) recordings.

In parallel, there is a growing body of research on noninvasive direct stimulation of the human brain via repetitive (rhythmic) transcranial magnetic stimulation (TMS), and on those frequencies that Acalabrutinib nmr have the strongest behavioural impact. There is, therefore, great potential in combining these two lines of research to foster knowledge on brain rhythms, in addition to potential therapeutic applications of rhythmic brain stimulation. Here, we review findings from this rapidly evolving field linking intrinsic brain oscillations to distinct sensory, motor and cognitive operations. The findings emphasize that brain rhythms are causally implicated in cognitive functions.”
“Objective: Aortic valve replacement remains the standard treatment for symptomatic severe aortic stenosis. However, catheter-based approaches have recently emerged as therapeutic options for high-risk surgical candidates. The objective of this study is to use propensity scoring to compare early clinical outcomes after transapical aortic valve implantation and conventional aortic valve replacement.

Method: Propensity scoring based on logistic regression modeling of 16 preoperative patient

characteristics was used to identify a group of very high-risk patients undergoing isolated conventional aortic valve replacement comparable to those patients undergoing transapical aortic valve implantation. Histone demethylase McNemar’s test was used to compare early clinical outcomes between the 2 treatment groups, including 30-day mortality and in-hospital postoperative complications.

Results: Ninety-two patients receiving transapical aortic valve implantation between October 2005 and April 2010 met inclusion criteria for this study. Half of these patients were successfully matched 1:1 to a patient receiving conventional aortic valve replacement. Baseline characteristics were similar between the 2 treatment groups after propensity matching. There were 4 perioperative deaths (8.

Under acute open chest conditions, 4-dimensional

marker c

Under acute open chest conditions, 4-dimensional

marker coordinates were measured using biplane video fluoroscopy with the annuloplasty ring inserted and after annuloplasty ring release. Septal-lateral and commissure-commissure dimensions were calculated from opposing marker pairs on the septal-lateral and commissure-commissure aspect of the anterior mitral leaflet at end diastole and end systole. To assess changes in anterior mitral leaflet shape, a “”planarity index” was assessed by calculating the root mean square values as distances of the 16 anterior mitral leaflet markers to a best fit anterior mitral leaflet plane at end systole.

Results: At end diastole, anterior mitral selleck inhibitor leaflet septal-lateral and commissure-commissure dimensions did not change with the Cosgrove ring compared with control, whereas the rigid saddle-shaped annuloplasty ring and Physio, IMR-ETlogix, and GeoForm rings reduced anterior mitral leaflet commissure-commissure but not septal-lateral anterior mitral leaflet dimensions.

At end systole, the septal-lateral anterior mitral leaflet dimension was smaller with the IMR-ETlogix and GeoForm rings, but did not change with the Cosgrove ring, rigid saddle-shaped annuloplasty ring, and Physio ring. Anterior mitral leaflet shape was unchanged in all 5 groups.

Conclusion: With no changes in anterior mitral leaflet planarity, the 4 complete, rigid rings (rigid saddle-shaped annuloplasty ring, Physio, IMR-ETlogix, and GeoForm) reduced the anterior mitral leaflet commissure-commissure dimension at end diastole. The IMR-ETlogix and GeoForm rings decreased the septal-lateral Pazopanib chemical structure anterior mitral leaflet dimension at end systole, probably as the result of inherent disproportionate downsizing. These changes in anterior mitral leaflet geometry could perturb the stress patterns, which in theory may affect

repair durability. (J Thorac Cardiovasc Surg 2010; 139: 1114-22)”
“Nerve guide implants approved for human application in the peripheral nervous system generally fail to bridge lesion gaps longer than 2 cm and cannot match the clinical performance of autologous nerve transplants. Since current synthetic implants are simply hollow tubes, we aim to recreate the native microarchitecture of nerves inside the tubular implants. Most importantly, in the regenerating nerve, dedifferentiated Schwann cells align to form thousands of long glial strands, which act as guiding structures for the regrowing axons. In order to artificially induce the formation of Schwann cell strands, 28 mu m thick, endless poly-p-dioxanone filaments (PDO) were synthesized with longitudinal grooves. A polycationic coating on the PDO filaments rendered the polymer surface cell-permissive and induced the growth of highly oriented Schwann cells with polarized expression of N-cadherin at cell-cell contact sites.

“The focus of this study was on production, purification a

“The focus of this study was on production, purification and characterization of dehairing protease from Pseudomonas aeruginosa MCM B-327, isolated from vermicompost pit soil. Optimum protease activity, 395 U mL(-1), was observed in the medium containing soybean meal and tryptone, at pH 7 and 30 degrees C. The crude enzyme exhibited dehairing activity. As compared to QNZ chemical method, enzymatic method of dehairing showed reduction in COD, TDS and TSS by 34.28%, 37.32% and 51.58%, respectively. Zymogram of crude

enzyme on native-PAGE presented two bands with protease activity of molecular weights of 56 and 67 kDa. Both proteases showed dehairing activity. Out of these, 56 kDa protease (PA02) was purified 3.05-folds with 2.71% recovery. The enzyme was active in pH range 7-9 and temperature 20-50 degrees C with optimum pH of 8 and temperature 35 degrees C. Moreover, the enzyme activity of PA02 protease was not strongly inhibited by specific inhibitor showing the novel nature of enzyme compared to serine, cysteine, aspartyl and metalloproteases. Kinetic studies indicated that substrate specificity

of PA02 protease was towards various natural and synthetic proteolytic substrates click here but inactive against collagen and keratin. These findings suggest protease secreted by P. aeruginosa MCM B-327 may have application in dehairing for environment-friendly leather processing.”
“An alkaline-fibrinolytic protease-producing bacterial strain (AS-S20-I) isolated from a soil sample in Assam was a Gram-negative rod and grown at temperatures ranging from 25 to 55 degrees C, and pH 6.5 to 11.0. Taxonomic identification of isolated strain by polyphasic Inositol monophosphatase 1 approach (phenotypic characterization, chemotaxonomic properties, and ribotyping data of the strain) suggested that it belongs to

the genus Bacillus, for which the name Bacillus sp. strain AS-S20-I (MTCC 8961) was proposed. The initial screening by using Plackett-Burman’s design demonstrated that among the tested factors, casein, ammonium sulphate and pH of the medium significantly (p < 0.05) enhanced the protease (fibrinolytic enzyme) yield in submerged fermentation. Further optimization of fibrinolytic protease production by Bacillus. sp. strain AS-S20-I in SmF by applying RSM was achieved as 749.0 x 10(3) U L-1 in the presence of 3.0% (w/v) casein and 0.12% (w/v) ammonium sulphate at pH 10.9 and 45 degrees C. This was a 4.0-fold increase in yield compared with that obtained before applying the Plackett-Burman and RSM experimental design. The protease preparation preferentially degraded the fibrin (specific activity 2408.0 +/- 70.0 U mg(-1); mean +/- S.D.) suggesting that its future application in pharmaceutical industry as thrombolytic and anticancer drugs is highly promising.