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1. Human-wildlife cooperation is a type of mutualism in which a human and a wild, free-living, animal actively coordinate their behaviour to achieve a common beneficial outcome. 2. While other cooperative human-animal interactions involving captive coercion or artificial selection (including domestication) have received extensive attention, we lack integrated insights into the ecology and evolution of human-wildlife cooperative interactions. 3. Here, we review and synthesise the function, mechanism, development, and evolution of human-wildlife cooperation. 4. Active cases involve people cooperating with greater honeyguide birds and with two dolphin species, while historical cases involve wolves and orcas. 5. In all cases, a food source located by the animal is made available to both species by a tool-using human, coordinated with cues or signals. 6. The mechanisms mediating the animal behaviours involved are unclear, but they may resemble those underlying intraspecific cooperation and reduced neophobia. 7. The skills required appear to develop at least partially by social learning in both humans and the animal partners. As a result, distinct behavioural variants have emerged in each type of human-wildlife cooperative interaction in both species, and human-wildlife cooperation is embedded within local human cultures. 8. We propose multiple potential origins for these unique cooperative interactions, and highlight how shifts to other interaction types threaten their persistence. 9. Finally, we identify key questions for future research. We advocate an approach that integrates ecological, evolutionary, and anthropological perspectives to advance our understanding of human-wildlife cooperation. In doing so, we will gain new insights into the diversity of our ancestral, current, and future interactions with the natural world., Natalie Uomini was supported by the Max Planck Society and grant #0271 from the Templeton World Charity Foundation. The opinions expressed in this publication are those of the authors and do not necessarily reflect the views of Templeton World Charity Foundation. Mauricio Cantor was supported by the Department for the Ecology of Animal Societies, Max Planck Institute of Animal Behavior. Fábio Daura-Jorge was supported by CAPES (#88887.374128/2019-00), CNPq (#308867/2019-0).

Purpose of Review: We summarise the current development of autologous haematopoietic stem cell transplantation (AHSCT) in treating multiple sclerosis (MS) and discuss future directions for the general neurologist, transplant haematologist and oncologist. Recent Findings: AHSCT was initially performed to treat MS over 20 years ago. Over recent years, the evidence base has grown, especially in relapsing-remitting MS (RRMS), with significant improvements in safety and efficacy through better patient selection, choice of transplant technique and increase in centre experience. Summary: AHSCT is now a treatment option in very carefully selected patients with severe, treatment-resistant RRMS. However, it is important for transplant haematologists and oncologists to work closely with specialist MS neurologists in patient selection, during transplant and in long-term follow-up of patients. Data should be registered into international transplant registries and, ideally, patients should be enrolled on prospective clinical trials in order to build the evidence base and refine transplant techniques.

This paper is a study on Corona virus and its effects on human beings in particular and how it has become a global pandemic. The reason for the world’s pandemic, Corona virus is an RNA virus found extensively in mammals including humans. It is found that the most human corona virus infections cause from mild symptoms to severe respiratory problems and lead to death. In the recent past the world has faced two great epidemics caused by two different beta-corona viruses and they were named as SARS-CoV (Severe Acute Respiratory Syndrome Corona Virus) and (MERS-CoV Middle East Respiratory Syndrome Coronavirus). Despite these viruses had high infectivity, had less mortality rate. As it is known, these types of viruses, in general, cause a mild illness and considerably affect children and young adults. As the whole world is facing a pandemic situation today, carrying out research on finding vaccine to kill the virus is a need of the time. It is obvious that to understand the fighting measurements, in other words readiness of the nation in handling the situation, the local risk assessments are considered to be one of the key factors in comprehending COVID-19. It is pathetic to know that this virus spreads rapidly everywhere and considering this fast outbreak, the global wide readiness, building capacity and mutual collaborations among countries are the most important needs in order to control the outbreak.

We examined whether a general processing factor emerges when using response times for cognitive processing tasks and whether such a factor is valid across three different cultural groups (Chinese, Canadian, and Greek). Three hundred twenty university students from Canada (n = 115), China (n = 110), and Cyprus (n = 95) were assessed on an adaptation of the Das-Naglieri Cognitive Assessment System (D-N CAS; Naglieri & Das, 1997). Three alternative models were contrasted: a distinct abilities processing speed model (Model 1) that is dictated by the latent four cognitive factors of planning, attention, simultaneous and successive (PASS) processing, a unitary ability processing speed model (Model 2) that is dictated by the response time nature of all measures, and a bifactor model (Model 3) which included the latent scores of Models 1 and 2 and served as the full model. Results of structural equation modeling showed that (a) the model representing processing speed as a collection of four cognitive processes rather than a unitary processing speed factor was the most parsimonious, and (b) the loadings of the obtained factors were invariant across the three cultural groups. These findings enhance our understanding of the nature of speed of processing across diverse cultures and suggest that even when cognitive processes (i.e., PASS) are operationalized with response time measures, the processing component dominates speed.

Introduction: Displaced distal radius fractures are very common injuries and present regularly to all orthopaedic surgeons. Several documented treatment modalities for these fractures have been described with a recent trend for internal fixation with volar plating. However, the literature suggests that there is still no consensus as to the best treatment of these injuries. Distal radius fractures are among the most common bone fractures all over the world. Close reduction and fixation by percutaneous pinning is a less invasive method comparing with other open surgeries. There is still a dearth of prospective randomized trials in this area. Before the advent of volar locking plates the randomized trials for surgical interventions for distal radius fractures show some evidence to support the use of external fixation or percutaneous pinning however their precise role and methods are not established and whether this will produce consistently better long-term outcome is also not clear. Aim & Objective: To compare percutaneous pinning versus volar locking plate in treatment of distal radius fractures in adults in term of: fracture union, post operative pain, functunal outcome, post operative complication (stiffness, CRPS). Materials and Methods: It is Randomised Controlled Trial Study. All Adults Patients aged 16 and above with displaced distal radius fractures fpresented to the Emergency department and out Patient Department of Orthopaedics at BPKIHS from August 2010 to September 2012 were included in the study. Results: 60 patients with fracture distal end of radius who met the inclusion criteria were included in the study, out of which 30 were randamized into group A, treated by closed reduction and percutaneous fixation supplemented by cast and 30 in group B, treated by volar locking plate. The study showed mean age of incidence to be 39.22+- 14.49 years in age group ranging from 16-65 years. In our study we found that the injuries were result of high energy trauma with RTA constituting the commonest mode of injury (75%) followed by fall from height (15%) and play ground injuries (10%). Males constituted the majority of the study population(67%). Age, sex, mode of injury, type of fracture, interval to surgery duration and associated co-morbidities were equally distributed between the two groups showing success of randamization. There was a highly significant diference in the operative ime and blood loss between two groups, illustating that percutaneous fixation is much shorter procedure with mean operative time of 30 mins compared to 60mins of ORIF with volar locking plate and has less blood loss being 5-10ml to 145ml of ORIF with volar plating. Conclusion: ORIF with volar locking plating provide better radilogical outcomes with more stable fixation thus lesser degree of loss of reduction in comparation to percutaneous pinning. It also had better ROM at wrist initially however this difference is not significant in later months. Volar locking plate is more expensive with more operative time and blood loss as compared to pinning.

Dogs (Canis lupus familiaris) are the first species to have been domesticated, and unlike other domesticated species, they have developed a special bonding with their owners. The ability to respond to human gestures and language is a key factor in the socio-cognitive abilities of dogs that have made them our best friend. Free-ranging dogs provide an excellent model system for understanding the dog domestication process. In India, free-ranging dogs occupy every possible human habitation, and interact with humans regularly. They scavenge among garbage, beg for food from humans, give birth in dens close to human habitations, and establish social bonds with people. However, there is ample dog-human conflict on the streets, leading to morbidity and mortality. Hence the ability to assess an unfamiliar human before establishing physical contact could be adaptive for dogs especially in the urban environment. We tested a total of 103 adult free-ranging dogs to investigate their response to immediate and long-term food and social rewards. The dogs were provided a choice of obtaining a food reward either from the hand or the ground. The dogs avoided making physical contact with the unfamiliar human. While immediate rewards were not effective in changing this response, the long-term test showed a strong effect of the social reward on the response of dogs. Our results revealed that dogs tend to build trust based on affection, and not food rewards. This study provides significant insights into nuances of the dynamics that could have paved the path to dog domestication.

© 2017 The Authors. Natural killer (NK) cells perform immunosurveillance of virally infected and transformed cells, and their activation depends on the balance between signaling by inhibitory and activating receptors. Cytokine receptor signaling can synergize with activating receptor signaling to induce NK cell activation. We investigated the interplay between the signaling pathways stimulated by the cytokine interleukin-2 (IL-2) and the activating receptor NKG2D in immature (CD56bright) and mature (CD56dim) subsets of human primary NK cells using mass cytometry experiments and in silico modeling. Our analysis revealed that IL-2 changed the abundances of several key proteins, including NKG2D and the phosphatase CD45. Furthermore, we found differences in correlations between protein abundances, which were associated with the maturation state of the NK cells. The mass cytometry measurements also revealed that the signaling kinetics of key protein abundances induced by NKG2D stimulation depended on the maturation state and the pretreatment condition of the NK cells. Our in silico model, which described the multidimensional data with coupled first-order reactions, predicted that the increase in CD45 abundance was a major enhancer of NKG2Dmediated activation in IL-2-treated CD56brightNK cells but not in IL-2-treated CD56dim NK cells. This dependence on CD45 was verified by measurement of CD107a mobilization to the NK cell surface (a marker of activation). Our mathematical framework can be used to glean mechanisms underlying synergistic signaling pathways in other activated immune cells.

Background: Middle-lobe predominant bronchiectasis affecting the right middle-lobe and/or lingula (RMLP) is classically described in asthenic, elderly females with skeletal abnormalities or associated nontuberculous mycobacterial (NTM) infection. Objectives: We aimed to evaluate the frequency and clinical characteristics of patients with an RMLP phenotype in a cohort of newly diagnosed bronchiectasis patients and determine associations with disease severity. Methods: A retrospective observational cross-sectional cohort study of consecutive bronchiectasis patients in our institution was performed. Data were collected on baseline variables, microbiology status, lung function, and radiology according to the modified Bhalla score. Disease severity was assessed using bronchiectasis severity index (BSI) and FACED severity scores. Results: Of 81 patients (mean age [SD] 62.6 [12.4], females 55 [67.9%], BMI 26.9 [5.7%]), 20 (24.7%) had RMLP disease. These patients were significantly younger, female, and with lower BMIs than patients with the classical bronchiectasis phenotype (p = 0.03, 0.01, and p p = 0.01 and p = 0.03), and higher baseline forced expiratory volume (p = 0.04) were noted. A higher incidence of NTM at diagnosis was demonstrated (p = 0.01). BSI and FACED severity scores in RMLP patients were significantly lower than their counterparts (both p < 0.001). Conclusions: The RMLP phenotype is associated with younger patients than classically described in the literature. An increased rate of NTM infection in this phenotype was noted, particularly in females, but much lower than previously described. Lung function and disease severity scores in this patient group are relatively normal, suggesting a milder phenotype in patients with this form of the disease.

Illegal migration into Assam from Bangladesh has been posing a serious security threat to the identity of Assamese people. It adversely affects the social, economic and political environment of Assam, creating law and order problems where immigrants are present in large number. The flow of immigrants started during the rule of British and continued tills today due to the pull and push factors. The deportation of illegal migrants become difficult due to the lack of strong law and political will, as illegal migrants are used as a vote bank by different political parties. The data provided in the study indicates that if necessary steps are not taken immediately, Assam, the elder sister of North-East India would lose its identity from the map of India very soon. The illegal migration is one of the major reasons for social and ethnic violence in Assam. Therefore it is high time that India takes stringent measures against the illegal migrants who have become a real threat to the security of the country. To meet the problem, a few suggestions are forwarded in this paper.

The paper provides (1) a teacher-administered rating instrument for inattention without confounding the rating with hyperactivity and conduct disorder, and (2) evidence that the ratings correlate with the scores obtained from cognitive tests of attention. In Study I, the first objective was to investigate the construct validity and the inter-rater reliability of the Attention Checklist (ACL) by factor analysing the teacher ratings of 110 Grade 4 children, obtained by using the ACL. The second objective was to investigate the predictive validity of the ACL by examining the relationship between the scores obtained for the participants from teachers' ratings using the ACL and the scores obtained by participants in the lab-type attention tests. The results of factor analysis showed that a single factor labelled ‘inattention’ underlies the 12 items in the ACL. Examining the differences in performance on attention tests, the ‘low attention’ children as rated by the teachers on the ACL scored lower than the ‘high attention’ children on the objective tests of attention. These findings were replicated in Study II, which was conducted to test further the construct validity and predictive validity of the ACL. This time, only those two tests (Auditory Attention and Visual Attention) that had shown relatively poor discrimination between the high and low attention groups in Study I were, again, administered to another cohort of 97 Grade 4 children, as it was our intention to further challenge the reliability of the ACL. Overall, the results of both studies suggest that comprehensive assessment of attention skills should include both ACL and objective measures of selective attention. 17 1 15 32 Cited By :3

A 17 years old boy presented clinically with typical lesions of pustular posriasis. Although his pus culture from the pocket of pus did not reveal any organism, his blood culture reports showed growth of Diplococci pneumoniae, which was sensitive to gentamycin. The patient was completely cured of the lesion after gentamycin therapy.

The half-life of 7Be implanted in a C60 pellet and gold foil has been measured to be about the same within about 0.2%. Using a radiochemical technique, we also measured that the probability of formation of endohedral 7Be@C60 by nuclear implantation technique was (5.6+-0.45)%. It is known from earlier works that the half-life of endohedral 7Be@C60 is about 1.2% shorter than that of 7Be implanted in gold. An analysis of these results using linear muffin-tin orbital method calculations indicates that most of the implanted 7Be ions in fullerene C60 stay at a distance of about 5.3 Angstrom from the centers of nearest C60 molecules forming exohedral compounds and those who enter the fullerene cages go to the centers of the cages forming endohedral 7Be@C60 compounds., Comment: 5 pages, 1 figure, to be submitted to Physical Review C

Angular distribution measurements of $^2$H($^7$Be,$^7$Be)$^2$H and $^2$H($^7$Be,$^8$B)$n$ reactions at $E_{c.m.}\sim$~4.5 MeV were performed to extract the astrophysical $S_{17}(0)$ factor using the asymptotic normalization coefficient (ANC) method. For this purpose a pure, low emittance $^7$Be beam was separated from the primary $^7$Li beam by a recoil mass spectrometer operated in a novel mode. A beam stopper at 0$^{\circ}$ allowed the use of a higher $^7$Be beam intensity. Measurement of the elastic scattering in the entrance channel using kinematic coincidence, facilitated the determination of the optical model parameters needed for the analysis of the transfer data. The present measurement significantly reduces errors in the extracted $^7$Be(p,$\gamma$) cross section using the ANC method. We get $S_{17}$~(0)~=~20.7~$\pm$~2.4 eV~b., Comment: 15 pages including 3 eps figures, one figure removed and discussions updated. Version to appear in Physical Review C

Attention disorders in the school population include attention deficit, hyperactivity and conduct disorders. A key concept for distinguishing hyperactive from attention disorders is behavioural inhibition as advocated by Barkley, a prominent American researcher. However, the concept itself needs to be understood because, as argued in this paper, there are two kinds of inhibition: Pavlov's original concept and the American one. These should be differentiated if the abnormal conditions associated with attention and hyperactivity are to be rationally connected to cognitive characteristics, rather than to be solely based on clinical symptoms and behavioural ratings. We suggest a consensus on the concept of inhibition and a unified view of attention disorders integrating cognitive and behavioural manifestations. Finally, the importance of basing remediation on a theoretically supported and rationally derived set of cognitive training tasks for the amelioration of inattention and hyperactivity is offered. 18 2 183 195 Cited By :2

We present the effect of Zn (S=0) and Cu (S=1/2) substitution at the Ni site of S=1 Haldane chain compound $Y_{2}BaNiO_{5}$. $^{89}$Y NMR allows us to measure the local magnetic susceptibility at different distances from the defects. The $^{89}$Y NMR spectrum consists of one central peak and several less intense satellite peaks. The shift of the central peak measures the uniform susceptibility, which displays a Haldane gap $Delta$$equiv$100 K and it corresponds to an AF coupling J$equiv$260 K between the near-neighbor Ni spins. Zn or Cu substitution does not affect the Haldane gap. The satellites, which are evenly distributed on the two sides of the central peak, probe the antiferromagnetic staggered magnetization near the substituted site, which decays exponentially. Its extension is found identical for both impurities and corresponds accurately to the correlation length $xi$(T) determined by Monte Carlo (QMC) simulations for the pure compound. In the case of non-magnetic Zn, the temperature dependence of the induced magnetization is consistent with a Curie law with an "effective" spin S=0.4 on each side of Zn, which is well accounted by Quantum Monte Carlo computations of the spinless-defect-induced magnetism. In the case of magnetic Cu, the similarity of the induced magnetism to the Zn case implies a weak coupling of the Cu spin to the nearest- neighbor Ni spins. The slight reductionin the induced polarization with respect to Zn is reproduced by QMC computations by considering an antiferromagnetic coupling of strength J'=0.1-0.2 J between the S=1/2 Cu-spin and nearest-neighbor Ni-spin., Comment: 15 pages, 18 figures, submitted to Physical Review B

This article reports two different experiments as part of a longitudinal study. The first experiment examines the long-term efficacy of two brief remedial procedures (a Meaning-Based procedure versus a cognitive remediation program, the PASS Reading Enhancement Program [PREP]) focusing on the differences in phonological and cognitive test performance of 40 children who needed remediation for poor word decoding in Grade 1. The second study reports the outcomes of an intensified version of the PREP program that emphasizes strengthening the cognitive processes underlying reading in a remaining group of 24 difficult-to-remediate Grade 2 students. Follow-up data are also reported for this group. The results of the first study indicated that the PREP group improved significantly more in pseudo-word reading compared to the meaning-based group right after remediation in Grade 1. These differences, however, were somewhat reduced when re-testing occurred in Grade 2 and may be due to the influence of classroom instruction. Indeed, when both groups were compared to the norming sample, they appeared to continue to develop at an accelerated rate. As for the results of the second study, which focused on the longitudinal development of those 24 children who exhibited a history of chronic low reading performance, it was shown that PREP remediation kept producing significant gains, especially in word-decoding, a finding consistent with the theoretical framework of PREP. 24 3 340 366 Cited By :19

This study examined between-group differences in planning of 9 grade 6 children with attention deficit hyperactivity disorder (ADHD) who were on stimulant medication and a matched comparison group of 9 without ADHD on a complex problem solving task. Both computer and verbal protocol data was analyzed to obtain information both about the participants' global performance indicators (accuracy and speed of performance) and their planning process. Consistent with existing literature on medication effects, no between-group differences in performance accuracy and speed were observed. Protocol analyses, however, indicated that planning processes were not identical for the two groups. More particularly, children with ADHD favoured a planning-in-action approach whereas the comparison group favoured a local advance planning approach. Implications of these findings for the current discussion about the medication effects are discussed. (PsycINFO Database Record (c) 2016 APA, all rights reserved) 11 1 51 72 ID: 2001-17295-003; Accession Number: 2001-17295-003. Other Journal Title: The International Journal of Creativity & Problem Solving. Partial author list: First Author & Affiliation: Papadopoulos, Timothy C.; U Cyprus, Dept of Education, Cyprus. Release Date: 20010502. Correction Date: 20150518. Publication Type: Journal (0100), Peer Reviewed Journal (0110). Format Covered: Print. Document Type: Journal Article. Language: English. Major Descriptor: Attention Deficit Disorder with Hyperactivity; Drug Therapy; Group Differences; Methylphenidate; Problem Solving. Minor Descriptor: Cognitive Processes. Classification: Clinical Psychopharmacology (3340). Population: Human (10); Male (30); Female (40). Location: Canada. Age Group: Childhood (birth-12 yrs) (100); School Age (6-12 yrs) (180). Methodology: Empirical Study. References Available: Y. Page Count: 22. Issue Publication Date: Apr, 2001.

Fifty-eight Grade 1 children experiencing reading difficulties were divided into two matched remediation groups: PREP (PASS Reading Enhancement Program) (see Das & Kendrick, 1997) and Meaning-Based Reading intervention. Both groups received remediation twice a week for 20 min over a 9-week period. Participants' reading level was assessed pre- and post-intervention using Word Identification (WI) and Word Attack (WA) tests. Repeated measures ANOVAs showed a significant main effect of Testing Time for both WI and WA. For WA, the Testing Time by Remediation Group interaction was also significant; the PREP group gained more than the meaning-based group in terms of decoding skills. Next, the performance of High-Gainers and No-Gainers in both groups was compared on several cognitive processing tasks. Results indicated that High-Gainers in the PREP group were characterized by a somewhat higher level of successive processing, phonological processing, and word recognition skills at the beginning of the program. In contrast, High-Gainers in the meaning-based program were characterized by a higher level of planning, phonological processing, and visual memory. Implications for education and future directions for research on remediation are also presented. 27 1 31

We present secondary-electron spectra arising from collisions of N7+ ions with a Ni(110) target for kinetic energies ranging between 150 eV and 20 keV and also for different observation angles. The filling of the two K-shell holes in N7+ requires two consecutive KLL Auger processes, giving rise to a double structure in the KLL peak. The ratio of the intensities of the two KLL peaks depends on the collision energy as well as on the angle of observation. We show that this dependence can be explained by assuming that the KLL electrons are emitted after the projectile has penetrated the surface.

Plasma activity and excretion of pancreatic (P) amylase in the rat was found to be negligible. In contrast, the excretion rate of salivary (S) amylase was substantial and variable, depending on diuresis. P-amylase had a higher isoelectric point, a greater sieving coefficient, and a shorter half-life than S-amylase. A bolus injection of 125I-labelled enzymes was followed by the appearance of 125I-labelled enzyme- as well as protein-free 125I activity in the urine. The enzyme loss was smaller and the fraction of protein-free 125I activity higher following injection of P-amylase. The affinity of P-amylase to paraffin oil exceeded that of S-amylase in partition experiments with water and paraffin oil in vitro. It is concluded that both renal filtration and reabsorption of P-amylase exceed those of S-amylase. This might be due to the higher lipophility of P-amylase in comparison to the salivary type.

Different microbial guilds of three rice fields (aerobic (dry or wet) laterite and red sandy, and anaerobic (flooded), clay-loam), a botanical garden (wet, aerobic, humus) and a sorghum (dry, aerobic, sandy) soil were investigated. Population (x106 cfu/g dr. soil) of the aerobic (3.8 - 26.2) and anaerobic (0.91 - 13.6) heterotrophic, aerobic (1.1 - 3.7) and anaerobic (0.8 - 1.3) spore forming, Gram (-)ve (0.3 - 0.7), phosphate solubilizing (0.01 - 0.06), asymbiotic N2-fixing (0.26 - 0.88), sulfur oxidizing (0.13 - 0.75), sulfate reducing (0.01 - 0.1), nitrifying (0.1 - 0.23) and denitrifying (0.04 - 0.25) bacteria; actinomycetes (0.01x104 cfu/g dr. soil), fungi (0.01 - 0.05x105 cfu/g dr. soils) and Bacillus thuringiensis (Bt) (0.13- 0.25x106 cfu/g dr. soil) population were variable in different soils. Nevertheless, proportions of Bt in relation to spore forming bacteria were comparable (index (5-9) x10-4) and they produced either monotypic (bipyramidal or spherical) or heterotypic (polymorphic-bipyramidal or bipyramidalrhomboidal) crystals although the bipyramidal crystal producing Bt were predominant in the soils. The bipyramidal crystal producing Bt were diverse in different ecologies, resistant to penicillin group of antibiotics and tolerated 5 - 6% NaCl. Phenotypic characters allowed to group the Bt isolates of botanic garden as B. thuringiensis subsp. coreanensis and as B. thuringiensis subsp. thompsoni/coreanensis, sorghum fields as B. thuringiensis subsp. finitimus and but those of rice fields as B. thuringiensis subsp. thuringiensis/ shandongiensis, finitimus and thompsoni/coreanensis. The isolates produced 25.78, 25.78, 86.26, 24.73, 68.0, 26.8 and 26.8 kDa proteins and equivalent to Cyt, Cry5 and Cry2 toxins effective against the insects of Diptera and Lepidoptera/Coleoptera.

The crystallographic structures of the ternary complexes of human alpha-thrombin with hirugen (a sulfated hirudin fragment) and the small-molecule active site thrombin inhibitors BMS-186282 and BMS-189090 have been determined at 2.6 and 2.8 A. In both cases, the inhibitors, which adopt very similar bound conformations, bind in an antiparallel beta-strand arrangement relative to the thrombin main chain in a manner like that reported for PPACK, D-Phe-Pro-Arg-CH2Cl. They do, however, exhibit differences in the binding of the alkyl guanidine moiety in the specificity pocket. Numerous hydrophilic and hydrophobic interactions serve to stabilize the inhibitors in the binding pocket. Although PPACK forms covalent bonds to both serine and the histidine of the catalytic triad of thrombin, neither BMS-186282 nor BMS-189090 bind covalently and only BMS-186282 forms a hydrogen bond to the serine of the catalytic triad. Both inhibitors bind with high affinity (Ki = 79 nM and 3.6 nM, respectively) and are highly selective for thrombin over trypsin and other serine proteases.