Controlling electronic and magnetic properties of ultra narrow multilayered nanowires

Interest in the study of magnetic/non-magnetic multilayered structures took a giant leap since Grünberg and his group established that the interlayer exchange coupling (IEC) is a function of the non-magnetic spacer width. This interest was further fuelled by the discovery of the phenomenal Giant Magnetoresistance (GMR) effect. In fact, in 2007 Albert Fert and Peter Grünberg were awarded the Nobel Prize in Physics for their contribution to the discovery of GMR. GMR is the key property that is being used in the read-head of the present day computer hard drive as it requires a high sensitivity in the detection of magnetic field. The recent increase in demand for device miniaturization encouraged researchers to look for GMR in nanoscale multilayered structures. In this context, one dimensional(1-D) multilayerd nanowire structure has shown tremendous promise as a viable candidate for ultra sensitive read head sensors. In fact, the phenomenal giant magnetoresistance(GMR) effect, which is the novel feature of the currently used multilayered thin film, has already been observed in multilayered nanowire systems at ambient temperature. Geometrical confinement of the supper lattice along the 2-dimensions (2-D) to construct the 1-D multilayered nanowire prohibits the minimization of magnetic interaction- offering a rich variety of magnetic properties in nanowire that can be exploited for novel functionality. In addition, introduction of non-magnetic spacer between the magnetic layers presents additional advantage in controlling magnetic properties via tuning the interlayer magnetic interaction. Despite of a large volume of theoretical works devoted towards the understanding of GMR and IEC in super lattice structures, limited theoretical calculations are reported in 1-D multilayered systems. Thus to gauge their potential application in new generation magneto-electronic devices, in this thesis, I have discussed the usage of first principles density functional theory (DFT) in predicting the equilibrium structure, stability as well as electronic and magnetic properties of one dimensional multilayered nanowires. Particularly, I have focused on the electronic and magnetic properties of Fe/Pt multilayered nanowire structures and the role of non-magnetic Pt spacer in modulating the magnetic properties of the wire. It is found that the average magnetic moment per atom in the nanowire increases monotonically with an ~1/(N(Fe)) dependance, where N(Fe) is the number of iron layers in the nanowire. A simple model based upon the interfacial structure is given to explain the 1/(N(Fe)) trend in magnetic moment obtained from the first principle calculations. A new mechanism, based upon spin flip with in the layer and multistep electron transfer between the layers, is proposed to elucidate the enhancement of magnetic moment of Iron atom at the Platinum interface. The calculated IEC in the Fe/Pt multilayered nanowire is found to switch sign as the width of the non-magnetic spacer varies. The competition among short and long range direct exchange and the super exchange has been found to play a key role for the non-monotonous sign in IEC depending upon the width of the Platinum spacer layer. The calculated magnetoresistance from Julliere's model also exhibit similar switching behavior as that of IEC. The universality of the behavior of exchange coupling has also been looked into by introducing different non-magnetic spacers like Palladium, Copper, Silver, and Gold in between magnetic Iron layers. The nature of hybridization between Fe and other non-magnetic spacer is found to dictate the inter layer magnetic interaction. For example, in Fe/Pd nanowire the d-p hybridization in two spacer layer case favors anti-ferromagnetic (AFM) configuration over ferromagnetic (FM) configuration. However, the hybridization between half-filled Fe(d) and filled Cu(p) state in Fe/Cu nanowire favors FM coupling in the 2-spacer system.

Cartilage damage in femoroacetabular impingement (FAI): preliminary results on comparison of standard diagnostic vs delayed gadolinium-enhanced magnetic resonance imaging of cartilage (dGEMRIC)

OBJECTIVES: To study the three-dimensional (3D) T1 patterns in different types of femoroacetabular impingement (FAI) by utilizing delayed gadolinium-enhanced magnetic resonance imaging (MRI) of cartilage (dGEMRIC) and subsequent 3D T1 mapping. We used standard grading of OA by Tonnis grade on standard radiographs and morphological grading of cartilage in MRI for comparative analysis. METHODS: dGEMRIC was obtained from ten asymptomatic young-adult volunteers and 26 symptomatic FAI patients. MRI included the routine hip protocol and a dual-flip angle (FA) 3D gradient echo (GRE) sequence utilizing inline T1 measurement. Cartilage was morphologically classified from the radial images based on the extent of degeneration as: no degeneration, degeneration zone measuring <0.75 cm from the rim, >0.75 cm, or total loss. T1 findings were evaluated and correlated. RESULTS: All FAI types revealed remarkably lower T1 mean values in comparison to asymptomatic volunteers in all regions of interest. Distribution of the T1 dGEMRIC values was in accordance with the specific FAI damage pattern. In cam-types (n=6) there was a significant drop (P<0.05) of T1 in the anterior to superior location. In pincer-types (n=7), there was a generalized circumferential decrease noted. High inter-observer (intra-observer) reliability was noted for T1 assessment using intra-class correlation (ICC):intra-class coefficient=0.89 (0.95). CONCLUSIONS: We conclude that a pattern of zonal T1 variation does seem to exist that is unique for different sub-groups of FAI. The FA GRE approach to perform 3D T1 mapping has a promising role for further studies of standard MRI and dGEMRIC in the hip joint.

Feasibility of T2* mapping for the evaluation of hip joint cartilage at 1.5T using a three-dimensional (3D), gradient-echo (GRE) sequence: a prospective study

This study defines the feasibility of utilizing three-dimensional (3D) gradient-echo (GRE) MRI at 1.5T for T(2)* mapping to assess hip joint cartilage degenerative changes using standard morphological MR grading while comparing it to delayed gadolinium-enhanced MRI of cartilage (dGEMRIC). MRI was obtained from 10 asymptomatic young adult volunteers and 33 patients with symptomatic femoroacetabular impingement (FAI). The protocol included T(2)* mapping without gadolinium-enhancement utilizing a 3D-GRE sequence with six echoes, and after gadolinium injection, routine hip sequences, and a dual-flip-angle 3D-GRE sequence for dGEMRIC T(1) mapping. Cartilage was classified as normal, with mild changes, or with severe degenerative changes based on morphological MRI. T(1) and T(2)* findings were subsequently correlated. There were significant differences between volunteers and patients in normally-rated cartilage only for T(1) values. Both T(1) and T(2)* values decreased significantly with the various grades of cartilage damage. There was a statistically significant correlation between standard MRI and T(2)* (T(1)) (P < 0.05). High intraclass correlation was noted for both T(1) and T(2)*. Correlation factor was 0.860 to 0.954 (T(2)*-T(1) intraobserver) and 0.826 to 0.867 (T(2)*-T(1) interobserver). It is feasible to gather further information about cartilage status within the hip joint using GRE T(2)* mapping at 1.5T.

Rapid estimation of cartilage T2 based on double echo at steady state (DESS) with 3 Tesla

The double-echo-steady-state (DESS) sequence generates two signal echoes that are characterized by a different contrast behavior. Based on these two contrasts, the underlying T2 can be calculated. For a flip-angle of 90 degrees , the calculated T2 becomes independent of T1, but with very low signal-to-noise ratio. In the present study, the estimation of cartilage T2, based on DESS with a reduced flip-angle, was investigated, with the goal of optimizing SNR, and simultaneously minimizing the error in T2. This approach was validated in phantoms and on volunteers. T2 estimations based on DESS at different flip-angles were compared with standard multiecho, spin-echo T2. Furthermore, DESS-T2 estimations were used in a volunteer and in an initial study on patients after cartilage repair of the knee. A flip-angle of 33 degrees was the best compromise for the combination of DESS-T2 mapping and morphological imaging. For this flip angle, the Pearson correlation was 0.993 in the phantom study (approximately 20% relative difference between SE-T2 and DESS-T2); and varied between 0.429 and 0.514 in the volunteer study. Measurements in patients showed comparable results for both techniques with regard to zonal assessment. This DESS-T2 approach represents an opportunity to combine morphological and quantitative cartilage MRI in a rapid one-step examination.

T1(Gd) gives comparable information as Delta T1 relaxation rate in dGEMRIC evaluation of cartilage repair tissue

OBJECTIVES: To evaluate the relationship between T1 after intravenous contrast administration (T1Gd) and Delta relaxation rate (DeltaR1) = (1/T1(Gd) - 1/T1o) in the delayed Gadolinium-Enhanced MRI of cartilage (dGEMRIC) evaluation of cartilage repair tissue. MATERIALS AND METHODS: Thirty single MR examinations from 30 patients after matrix-associated autologous chondrocyte transplantations of the knee joint with different postoperative intervals were examined using an 8-channel knee-coil at 3T. T1 mapping using a 3D GRE sequence with a 35/10 degrees flip angle excitation pulse combination was performed before and after contrast administration (dGEMRIC technique). T1 postcontrast (T1(Gd)) and the DeltaR1 (relative index of pre- and postcontrast R1 value) were calculated for repair tissue and the weight-bearing normal appearing control cartilage. For evaluation of the different postoperative intervals, MR exams were subdivided into 3 groups (up to 12 months, 12-24 months, more than 24 months). For statistical analysis Spearman correlation coefficients were calculated. RESULTS: The mean value for T1 postcontrast was 427 +/- 159 ms, for DeltaR1 1.85 +/- 1.0; in reference cartilage 636 +/- 181 ms for T1 postcontrast and 0.83 +/- 0.5 for DeltaR1.The correlation coefficients were highly significant between T1 (Gd) and DeltaR1 for repair tissue (0.969) as well as normal reference cartilage (0.928) in total, and for the reparative cartilage in the early, middle postoperative, and late postoperative interval after surgery (R values: -0.986, -0.970, and -0.978, respectively). Using either T1(Gd) or DeltaR1, the 2 metrics resulted in similar conclusions regarding the time course of change of repair tissue and control tissue, namely that highly significant (P > 0.01) differences between cartilage repair tissue and reference cartilage were found for all follow-up groups. Additionally, for both metrics highly significant differences (P < 0.01) between early follow up and the 2 later postoperative groups for cartilage repair tissue were found. No statistical differences were found between the 2 later follow-up groups of reparative cartilage either for T1 (Gd) or DeltaR1. CONCLUSION: The high correlation between T1 (Gd) and DeltaR1 and the comparable conclusions reached utilizing metric implies that T1 mapping before intravenous administration of MR contrast agent is not necessary for the evaluation of repair tissue. This will help to reduce costs, inconvenience for the patients, simplifies the examination procedure, and makes dGEMRIC more attractive for follow-up of patients after cartilage repair surgeries.

Operative treatment of congenital hip osteoarthritis with high hip luxation (Crowe type IV)

OBJECTIVE The aim of the therapy is mechanical and functional stabilization of high dislocated hips with dysplasia coxarthrosis using total hip arthroplasty (THA). INDICATIONS Developmental dysplasia of the hip (DDH) in adults, symptomatic dysplasia coxarthrosis, high hip dislocation according to Crowe type III/IV, and symptomatic leg length inequality. CONTRAINDICATIONS Cerebrospinal dysfunction, muscular dystrophy, apparent disturbance of bone metabolism, acute or chronic infections, and immunocompromised patients. SURGICAL TECHNIQUE With the patient in a lateral decubitus position an incision is made between the anterior border of the gluteus maximus muscle and the posterior border of the gluteus medius muscle (Gibson interval). Identification of the sciatic nerve to protect the nerve from traction disorders by visual control. After performing trochanter flip osteotomy, preparation of the true actetabulum if possible. Implantation of the reinforcement ring, preparation of the femur and if necessary for mobilization, resection until the trochanter minor. Test repositioning under control of the sciatic nerve. Finally, refixation of the trochanteric crest. POSTOPERATIVE MANAGEMENT During hospital stay, intensive mobilization of the hip joint using a continuous passive motion machine with maximum flexion of 70°. No active abduction and passive adduction over the body midline. Maximum weight bearing 10-15 kg for 8 weeks, subsequently, first clinical and radiographic follow-up and deep venous thrombosis prophylaxis until full weight bearing. RESULTS From 1995 to 2012, 28 THAs of a Crow type IV high hip-dislocation were performed in our institute. Until now 14 patients have been analyzed during a follow-up of 8 years in 2012. Mid-term results showed an improvement of the postoperative clinical score (Merle d'Aubigné score) in 86 % of patients. Good to excellent results were obtained in 79 % of cases. Long-term results are not yet available. In one case an iatrogenic neuropraxia of the sciatic nerve was observed and after trauma a redislocation of the arthroplasty appeared in another case. In 2 cases an infection of the THA appeared 8 and 15 months after index surgery. No pseudoarthrosis of the trochanter or aseptic loosening was noticed.

Privacy Panel: Usable and Quantifiable Mobile Privacy

The ever increasing popularity of apps stems from their ability to provide highly customized services to the user. The flip side is that in order to provide such services, apps need access to very sensitive private information about the user. This leads to malicious apps that collect personal user information in the background and exploit it in various ways. Studies have shown that current app vetting processes which are mainly restricted to install time verification mechanisms are incapable of detecting and preventing such attacks. We argue that the missing fundamental aspect here is a comprehensive and usable mobile privacy solution, one that not only protects the user's location information, but also other equally sensitive user data such as the user's contacts and documents. A solution that is usable by the average user who does not understand or care about the low level technical details. To bridge this gap, we propose privacy metrics that quantify low-level app accesses in terms of privacy impact and transforms them to high-level user understandable ratings. We also provide the design and architecture of our Privacy Panel app that represents the computed ratings in a graphical user-friendly format and allows the user to define policies based on them. Finally, experimental results are given to validate the scalability of the proposed solution.

Resistance prediction in AML: analysis of 4601 patients from MRC/NCRI, HOVON/SAKK, SWOG and MD Anderson Cancer Center

Therapeutic resistance remains the principal problem in acute myeloid leukemia (AML). We used area under receiver-operating characteristic curves (AUCs) to quantify our ability to predict therapeutic resistance in individual patients, where AUC=1.0 denotes perfect prediction and AUC=0.5 denotes a coin flip, using data from 4601 patients with newly diagnosed AML given induction therapy with 3+7 or more intense standard regimens in UK Medical Research Council/National Cancer Research Institute, Dutch–Belgian Cooperative Trial Group for Hematology/Oncology/Swiss Group for Clinical Cancer Research, US cooperative group SWOG and MD Anderson Cancer Center studies. Age, performance status, white blood cell count, secondary disease, cytogenetic risk and FLT3-ITD/NPM1 mutation status were each independently associated with failure to achieve complete remission despite no early death (‘primary refractoriness’). However, the AUC of a bootstrap-corrected multivariable model predicting this outcome was only 0.78, indicating only fair predictive ability. Removal of FLT3-ITD and NPM1 information only slightly decreased the AUC (0.76). Prediction of resistance, defined as primary refractoriness or short relapse-free survival, was even more difficult. Our limited ability to forecast resistance based on routinely available pretreatment covariates provides a rationale for continued randomization between standard and new therapies and supports further examination of genetic and posttreatment data to optimize resistance prediction in AML.

Induction of synthetic lethality in mutant KRAS cells for non-small cell lung cancers chemoprevention and therapy

Lung cancer is the leading cause of cancer death in both men and women in the United States and worldwide. Despite improvement in treatment strategies, the 5-year survival rate of lung cancer patients remains low. Thus, effective chemoprevention and treatment approaches are sorely needed. Mutations and activation of KRAS occur frequently in tobacco users and the early stage of development of non-small cell lung cancers (NSCLC). So they are thought to be the primary driver for lung carcinogenesis. My work showed that KRAS mutations and activations modulated the expression of TNF-related apoptosis-inducing ligand (TRAIL) receptors by up-regulating death receptors and down-regulating decoy receptors. In addition, we showed that KRAS suppresses cellular FADD-like IL-1β-converting enzyme (FLICE)-like inhibitory protein (c-FLIP) expression through activation of ERK/MAPK-mediated activation of c-MYC which means the mutant KRAS cells could be specifically targeted via TRAIL induced apoptosis. The expression level of Inhibitors of Apoptosis Proteins (IAPs) in mutant KRAS cells is usually high which could be overcome by the second mitochondria-derived activator of caspases (Smac) mimetic. So the combination of TRAIL and Smac mimetic induced the synthetic lethal reaction specifically in the mutant-KRAS cells but not in normal lung cells and wild-type KRAS lung cancer cells. Therefore, a synthetic lethal interaction among TRAIL, Smac mimetic and KRAS mutations could be used as an approach for chemoprevention and treatment of NSCLC with KRAS mutations. Further data in animal experiments showed that short-term, intermittent treatment with TRAIL and Smac mimetic induced apoptosis in mutant KRAS cells and reduced tumor burden in a KRAS-induced pre-malignancy model and mutant KRAS NSCLC xenograft models. These results show the great potential benefit of a selective therapeutic approach for the chemoprevention and treatment of NSCLC with KRAS mutations.

PML tumor suppressor potentiates cell death through inhibition of the NF -kappa B survival pathway

The promyelocytic leukemia protein PML is a growth suppressor essential for induction of apoptosis by diverse apoptotic stimuli. The mechanism by which PML regulates cell death remains unclear. In this study we found that ectopic expression of PML potentiates cell death in the TNFα-resistant tumor line U2OS and significantly sensitized these cells to apoptosis induced by TNFα in a p53-independent manner. Our study demonstrated that both PML and PML/TNFα-induced cell death are associated with DNA fragmentation, activation of caspase-3, -7, -8, and degradation of DFF/ICAD. Furthermore, we found that PML-induced and PML/TNFα-induced cell death could be blocked by the caspase-8 inhibitors crmA and c-FLIP, but not by Bcl-2, the inhibitor of mitochondria-mediated apoptotic pathway. These findings indicate that this cell death event is initiated through the death receptor-dependent apoptosis pathway. Our study further showed that PML recruits NF-kappa B (NF-κB) to the PML nuclear body, blocks NF-κB binding to its cognate enhancer, and represses its transactivation function with the C-terminal region. Therefore PML inhibits the NF-κB survival pathway. Overexpression of NF-κB rescued cell death induced by PML and PML/TNFκ. These results imply that PML is a functional repressor of NF-κB. This notion was further supported by the finding that the PML−/− mouse embryo fibroblasts (MEFs) are more resistant than the wild-type MEFs to TNFκ-induced apoptosis. In conclusion, our studies convincingly demonstrated that PML potentiates cell death through inhibition of the NF-κB survival pathway. Activation of NF-κB frequently occurs during oncogenesis. Our study here suggests that a loss of PML function enhances the NF-κB survival pathway and this event may contribute to tumorigenesis. ^

Survey of living conditions of Arctic indigenous peoples

Major findings of the Survey of Living Conditions in the Arctic (SLiCA) are: (1) A combination of traditional activities and cash employment is the prevailing lifestyle of Arctic indigenous peoples; (2) family ties, social support of each other, and traditional activities have a lot to do with why indigenous people choose to remain in Arctic communities; (3) well-being is closely related to job opportunities, locally available fish and game, and a sense of local control. Well-being and depression (and related problems like suicide) are flip sides of the same coin. Improving well-being may reduce social problems; and, (4) health conditions vary widely in the Arctic: three-in-four Greenlandic Inuit self-rate their health as at least very good compared with one-in-two Canadian and Alaska Inuit and one-in-five Chukotka indigenous people. Findings are based on 7,200 interviews in a probability sample of Inupiat settlement regions of Alaska, the four Inuit settlement regions of Canada, all of Greenland, and the Anadyrskij, Anadyr, Shmidtovs, Beringovskij, Chukotskij, Iujl'tinskij, Bilibinskij, Chaunskij, Providenskij, Uel'Kal' districts of Chukotka. Indigenous people and researchers from Greenland, Russia, Canada, the United States, Denmark, Norway, Sweden, and Finland collaborated on all phases of the study.

Combining a Similar Coefficient Identification Algorithm with the Boundary Element Method

The boundary element method (BEM) has been applied successfully to many engineering problems during the last decades. Compared with domain type methods like the finite element method (FEM) or the finite difference method (FDM) the BEM can handle problems where the medium extends to infinity much easier than domain type methods as there is no need to develop special boundary conditions (quiet or absorbing boundaries) or infinite elements at the boundaries introduced to limit the domain studied. The determination of the dynamic stiffness of arbitrarily shaped footings is just one of these fields where the BEM has been the method of choice, especially in the 1980s. With the continuous development of computer technology and the available hardware equipment the size of the problems under study grew and, as the flop count for solving the resulting linear system of equations grows with the third power of the number of equations, there was a need for the development of iterative methods with better performance. In [1] the GMRES algorithm was presented which is now widely used for implementations of the collocation BEM. While the FEM results in sparsely populated coefficient matrices, the BEM leads, in general, to fully or densely populated ones, depending on the number of subregions, posing a serious memory problem even for todays computers. If the geometry of the problem permits the surface of the domain to be meshed with equally shaped elements a lot of the resulting coefficients will be calculated and stored repeatedly. The present paper shows how these unnecessary operations can be avoided reducing the calculation time as well as the storage requirement. To this end a similar coefficient identification algorithm (SCIA), has been developed and implemented in a program written in Fortran 90. The vertical dynamic stiffness of a single pile in layered soil has been chosen to test the performance of the implementation. The results obtained with the 3-d model may be compared with those obtained with an axisymmetric formulation which are considered to be the reference values as the mesh quality is much better. The entire 3D model comprises more than 35000 dofs being a soil region with 21168 dofs the biggest single region. Note that the memory necessary to store all coefficients of this single region is about 6.8 GB, an amount which is usually not available with personal computers. In the problem under study the interface zone between the two adjacent soil regions as well as the surface of the top layer may be meshed with equally sized elements. In this case the application of the SCIA leads to an important reduction in memory requirements. The maximum memory used during the calculation has been reduced to 1.2 GB. The application of the SCIA thus permits problems to be solved on personal computers which otherwise would require much more powerful hardware.

Antibody C219 recognizes an α-helical epitope on P-glycoprotein

The ABC transporter, P-glycoprotein, is an integral membrane protein that mediates the ATP-driven efflux of drugs from multidrug-resistant cancer and HIV-infected cells. Anti-P-glycoprotein antibody C219 binds to both of the ATP-binding regions of P-glycoprotein and has been shown to inhibit its ATPase activity and drug binding capacity. C219 has been widely used in a clinical setting as a tumor marker, but recent observations of cross-reactivity with other proteins, including the c-erbB2 protein in breast cancer cells, impose potential limitations in detecting P-glycoprotein. We have determined the crystal structure at a resolution of 2.4 Å of the variable fragment of C219 in complex with an epitope peptide derived from the nucleotide binding domain of P-glycoprotein. The 14-residue peptide adopts an amphipathic α-helical conformation, a secondary structure not previously observed in structures of antibody–peptide complexes. Together with available biochemical data, the crystal structure of the C219-peptide complex indicates the molecular basis of the cross-reactivity of C219 with non-multidrug resistance-associated proteins. Alignment of the C219 epitope with the recent crystal structure of the ATP-binding subunit of histidine permease suggests a structural basis for the inhibition of the ATP and drug binding capacity of P-glycoprotein by C219. The results provide a rationale for the development of C219 mutants with improved specificity and affinity that could be useful in antibody-based P-glycoprotein detection and therapy in multidrug resistant cancers.

The crystal structure of the Rev binding element of HIV-1 reveals novel base pairing and conformational variability

The crystal and molecular structure of an RNA duplex corresponding to the high affinity Rev protein binding element (RBE) has been determined at 2.1-Å resolution. Four unique duplexes are present in the crystal, comprising two structural variants. In each duplex, the RNA double helix consists of an annealed 12-mer and 14-mer that form an asymmetric internal loop consisting of G-G and G-A noncanonical base pairs and a flipped-out uridine. The 12-mer strand has an A-form conformation, whereas the 14-mer strand is distorted to accommodate the bulges and noncanonical base pairing. In contrast to the NMR model of the unbound RBE, an asymmetric G-G pair with N2-N7 and N1-O6 hydrogen bonding, is formed in each helix. The G-A base pairing agrees with the NMR structure in one structural variant, but forms a novel water-mediated pair in the other. A backbone flip and reorientation of the G-G base pair is required to assume the RBE conformation present in the NMR model of the complex between the RBE and the Rev peptide.

Design of polyzinc finger peptides with structured linkers

Zinc finger domains are perhaps the most versatile of all known DNA binding domains. By fusing up to six zinc finger modules, which normally recognize up to 18 bp of DNA, designer transcription factors can be produced to target unique sequences within large genomes. However, not all continuous DNA sequences make good zinc finger binding sites. To avoid having to target unfavorable DNA sequences, we designed multizinc finger peptides with linkers capable of spanning long stretches of nonbound DNA. Two three-finger domains were fused by using either transcription factor IIIA for the Xenopus 5S RNA gene (TFIIIA) finger 4 or a non-sequence-specific zinc finger as a “structured” linker. Our gel-shift results demonstrate that these peptides are able to bind with picomolar affinities to target sequences containing 0–10 bp of nonbound DNA. Furthermore, these peptides display greater sequence selectivity and bind with higher affinity than similar six-finger peptides containing long, flexible linkers. These peptides are likely to be of use in understanding the behavior of polydactyl proteins in nature and in the targeting of human, animal, or plant genomes for numerous applications. We also suggest that in certain polydactyl peptides an individual finger can “flip” out of the major groove to allow its neighbors to bind shorter, nontarget DNA sequences.