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The group of AGC kinases consists of 63 evolutionarily related serine/threonine protein kinases comprising PDK1, PKB/Akt, SGK, PKC, PRK/PKN, MSK, RSK, S6K, PKA, PKG, DMPK, MRCK, ROCK, NDR, LATS, CRIK, MAST, GRK, Sgk494, and YANK, while two other families, Aurora and PLK, are the most closely related to the group. Eight of these families are physiologically activated downstream of growth factor signalling, while other AGC kinases are downstream effectors of a wide range of signals. The different AGC kinase families share aspects of their mechanisms of inhibition and activation. In the present review, we update the knowledge of the mechanisms of regulation of different AGC kinases. The conformation of the catalytic domain of many AGC kinases is regulated allosterically through the modulation of the conformation of a regulatory site on the small lobe of the kinase domain, the PIF-pocket. The PIF-pocket acts like an ON-OFF switch in AGC kinases with different modes of regulation, i.e. PDK1, PKB/Akt, LATS and Aurora kinases. In this review, we make emphasis on how the knowledge of the molecular mechanisms of regulation can guide the discovery and development of small allosteric modulators. Molecular probes stabilizing the PIF-pocket in the active conformation are activators, while compounds stabilizing the disrupted site are allosteric inhibitors. One challenge for the rational development of allosteric modulators is the lack of complete structural information of the inhibited forms of full-length AGC kinases. On the other hand, we suggest that the available information derived from molecular biology and biochemical studies can already guide screening strategies for the identification of innovative mode of action molecular probes and the development of selective allosteric drugs for the treatment of human diseases. [ABSTRACT FROM AUTHOR]

Summary Allostery is a phenomenon observed in many proteins where binding of a macromolecular partner or a small-molecule ligand at one location leads to specific perturbations at a site not in direct contact with the region where the binding occurs. The list of proteins under allosteric regulation includes AGC protein kinases. AGC kinases have a conserved allosteric site, the phosphoinositide-dependent protein kinase 1 (PDK1)-interacting fragment (PIF) pocket, which regulates protein ATP-binding, activity, and interaction with substrates. In this study, we identify small molecules that bind to the ATP-binding site and affect the PIF pocket of AGC kinase family members, PDK1 and Aurora kinase. We describe the mechanistic details and show that although PDK1 and Aurora kinase inhibitors bind to the conserved ATP-binding site, they differentially modulate physiological interactions at the PIF-pocket site. Our work outlines a strategy for developing bidirectional small-molecule allosteric modulators of protein kinases and other signaling proteins. [ABSTRACT FROM AUTHOR]

Pkh is the yeast ortholog of the mammalian 3-phosphoinositide-dependent protein kinase 1 (PDK1). Pkh phosphorylates the activation loop of Ypks, Tpks, Sch9 and also phosphorylates the eisosome components Lsp1 and Pil1, which play fundamental roles upstream of diverse signaling pathways, including the cell wall integrity and sphingosine/long-chain base (LCB) signaling pathways. In S. cerevisiae , two isoforms, ScPkh1 and ScPkh2, are required for cell viability, while only one ortholog exists in C. albicans , CaPkh2. In spite of the extensive information gathered on the role of Pkh in the LCB signaling, the yeast Pkh kinases are not known to bind lipids and previous studies did not identify PH domains in Pkh sequences. We now describe that the C-terminal region of CaPkh2 is required for its intrinsic kinase activity. In addition, we found that the C-terminal region of CaPkh2 enables its interaction with structural and signaling lipids. Our results further show that phosphatidylserine, phosphatidic acid, phosphatidylinositol (3,4 and 4,5)-biphosphates, and phosphatidylinositol (3,4,5)-trisphosphate inhibit Pkh activity, whereas sulfatide binds with high affinity but does not affect the intrinsic activity of CaPkh2. Interestingly, we identified that its human ortholog PDK1 also binds to sulfatide. We propose a mechanism by which lipids and dihydrosphingosine regulate CaPkh2 kinase activity by modulating the interaction of the C-terminal region with the kinase domain, while sulfatide-like lipids support localization CaPkh2 mediated by a C-terminal PH domain, without affecting kinase intrinsic activity. [ABSTRACT FROM AUTHOR]

The rational design of allosteric kinase modulators is challenging but rewarding. The protein kinase PDK1, which lies at the center of the growth-factor signaling pathway, possesses an allosteric regulatory site previously validated both in vitro and in cells. ANCHOR.QUERY software was used to discover a potent allosteric PDK1 kinase modulator. Using a recently published PDK1 compound as a template, several new scaffolds that bind to the allosteric target site were generated and one example was validated. The inhibitor can be synthesized in one step by multicomponent reaction (MCR) chemistry when using the ANCHOR.QUERY approach. Our results are significant because the outlined approach allows rapid and efficient scaffold hopping from known molecules into new easily accessible and biologically active ones. Based on increasing interest in allosteric-site drug discovery, we foresee many potential applications for this approach. [ABSTRACT FROM AUTHOR]

The rational design of allosteric kinase modulators is challenging but rewarding. The protein kinase PDK1, which lies at the center of the growth-factor signaling pathway, possesses an allosteric regulatory site previously validated both in vitro and in cells. ANCHOR.QUERY software was used to discover a potent allosteric PDK1 kinase modulator. Using a recently published PDK1 compound as a template, several new scaffolds that bind to the allosteric target site were generated and one example was validated. The inhibitor can be synthesized in one step by multicomponent reaction (MCR) chemistry when using the ANCHOR.QUERY approach. Our results are significant because the outlined approach allows rapid and efficient scaffold hopping from known molecules into new easily accessible and biologically active ones. Based on increasing interest in allosteric-site drug discovery, we foresee many potential applications for this approach. [ABSTRACT FROM AUTHOR]

We present experimental results on the fabrication and characterization of vertical Ge and GeSn heterojunction Tunneling Field Effect Transistors (TFETs). A gate-all-around process with mesa diameters down to 70 nm is used to reduce leakage currents and improve electrostatic control of the gate over the transistor channel. An I ON = 88.4 μA/μm at V DS = V G = −2 V is obtained for a TFET with a 10 nm Ge 0.92 Sn 0.08 layer at the source/channel junction. We discuss further possibilities for device improvements. [ABSTRACT FROM AUTHOR]

Summary: Protein kinases are key mediators of cellular signaling, and therefore, their activities are tightly controlled. AGC kinases are regulated by phosphorylation and by N- and C-terminal regions. Here, we studied the molecular mechanism of inhibition of atypical PKCζ and found that the inhibition by the N-terminal region cannot be explained by a simple pseudosubstrate inhibitory mechanism. Notably, we found that the C1 domain allosterically inhibits PKCζ activity and verified an allosteric communication between the PIF-pocket of atypical PKCs and the binding site of the C1 domain. Finally, we developed low-molecular-weight compounds that bind to the PIF-pocket and allosterically inhibit PKCζ activity. This work establishes a central role for the PIF-pocket on the regulation of PKCζ and allows us to envisage development of drugs targeting the PIF-pocket that can either activate or inhibit AGC kinases. [Copyright &y& Elsevier]

Iba2 is a homolog of ionized calcium-binding adapter molecule 1 (Iba1), a 17-kDa protein that binds and cross-links filamentous actin (F-actin) and localizes to membrane ruffles and phagocytic cups. Here, we present the crystal structure of human Iba2 and its homodimerization properties, F-actin cross-linking activity, cellular localization and recruitment upon bacterial invasion in comparison with Iba1. The Iba2 structure comprises two central EF-hand motifs lacking bound Ca2+. Iba2 crystallized as a homodimer stabilized by a disulfide bridge and zinc ions. Analytical ultracentrifugation revealed a different mode of dimerization under reducing conditions that was independent of Ca2+. Furthermore, no binding of Ca2+ up to 0.1 mm was detected by equilibrium dialysis. Correspondingly, Iba EF-hand motifs lack residues essential for strong Ca2+ coordination. Sedimentation experiments and microscopy detected pronounced, indistinguishable F-actin binding and cross-linking activity of Iba1 and Iba2 with induction of F-actin bundles. Fluorescent Iba fusion proteins were expressed in HeLa cells and co-localized with F-actin. Iba1 was recruited into cellular projections to a larger extent than Iba2. Additionally, we studied Iba recruitment in a Shigella invasion model that induces cytoskeletal rearrangements. Both proteins were recruited into the bacterial invasion zone and Iba1 was again concentrated slightly higher in the cellular extensions. [ABSTRACT FROM AUTHOR]

Abstract: Error-free protein biosynthesis is dependent on the reliable charging of each tRNA with its cognate amino acid. Many bacteria, however, lack a glutaminyl-tRNA synthetase. In these organisms, tRNAGln is initially mischarged with glutamate by a non-discriminating glutamyl-tRNA synthetase (ND-GluRS). This enzyme thus charges both tRNAGlu and tRNAGln with glutamate. Discriminating GluRS (D-GluRS), found in some bacteria and all eukaryotes, exclusively generates Glu-tRNAGlu. Here we present the first crystal structure of a non-discriminating GluRS from Thermosynechococcus elongatus (ND-GluRS Tel ) in complex with glutamate at a resolution of 2.45 Å. Structurally, the enzyme shares the overall architecture of the discriminating GluRS from Thermus thermophilus (D-GluRS Tth ). We confirm experimentally that GluRS Tel is non-discriminating and present kinetic parameters for synthesis of Glu-tRNAGlu and of Glu-tRNAGln. Anticodons of tRNAGlu (34C/UUC36) and tRNAGln (34C/UUG36) differ only in base 36. The pyrimidine base of C36 is specifically recognized in D-GluRS Tth by the residue Arg358. In ND-GluRS Tel this arginine residue is replaced by glycine (Gly366) presumably allowing both cytosine and the bulkier purine base G36 of tRNAGln to be tolerated. Most other ND-GluRS share this structural feature, leading to relaxed substrate specificity. [Copyright &y& Elsevier]

Glutamate-1-semialdehyde 2,1-aminomutase (GSAM) is the second enzyme in the C5 pathway of tetrapyrrole biosynthesis found in most bacteria, in archaea and in plants. It catalyzes the transamination of glutamate-1-semialdehyde to 5-aminolevulinic acid (ALA) in a pyridoxal 5′-phosphate (PLP)-dependent manner. We present the crystal structure of GSAM from the thermophilic cyanobacterium Thermosynechococcus elongatus (GSAM Tel ) in its PLP-bound form at 2.85Å resolution. GSAM Tel is a symmetric homodimer, whereas GSAM from Synechococcus (GSAM Syn ) has been described as asymmetric. The symmetry of GSAM Tel thus challenges the previously proposed negative cooperativity between monomers of this enzyme. Furthermore, GSAM Tel reveals an extensive flexible region at the interface of the proposed complex of GSAM with glutamyl-tRNA reductase (GluTR), the preceding enzyme in tetrapyrrole biosynthesis. Compared to GSAM Syn , the monomers of GSAM Tel are rotated away from each other along the dimerization interface by 10°. The associated flexibility of GSAM may be essential for complex formation with GluTR to occur. Unexpectedly, we find that GSAM is structurally related to 5-aminolevulinate synthase (ALAS), the ALA-producing enzyme in the Shemin pathway of α-proteobacteria and non-plant eukaryotes. This structural relationship applies also to the corresponding subfamilies of PLP-dependent enzymes. We thus propose that the CoA-subfamily (including ALAS) and the aminotransferase subfamily II (including GSAM) are evolutionarily closely related and that ALAS may thus have evolved from GSAM. [Copyright &y& Elsevier]

5-Aminolevulinate synthase (ALAS) is the first and rate-limiting enzyme of heme biosynthesis in humans, animals, other non-plant eukaryotes, and α-proteobacteria. It catalyzes the synthesis of 5-aminolevulinic acid, the first common precursor of all tetrapyrroles, from glycine and succinyl-coenzyme A (sCoA) in a pyridoxal 5′-phosphate (PLP)-dependent manner. X-linked sideroblastic anemias (XLSAs), a group of severe disorders in humans characterized by inadequate formation of heme in erythroblast mitochondria, are caused by mutations in the gene for erythroid eALAS, one of two human genes for ALAS. We present the first crystal structure of homodimeric ALAS from Rhodobacter capsulatus (ALASRc) binding its cofactor PLP. We, furthermore, present structures of ALASRc in complex with the substrates glycine or sCoA. The sequence identity of ALAS from R. capsulatus and human eALAS is 49%. XLSA-causing mutations may thus be mapped, revealing the molecular basis of XLSA in humans. Mutations are found to obstruct substrate binding, disrupt the dimer interface, or hamper the correct folding. The structure of ALAS completes the structural analysis of enzymes in heme biosynthesis. [ABSTRACT FROM AUTHOR]

The PKC-related kinases (PRKs, also termed PKNs) are important in cell migration, cancer, hepatitis C infection, and nutrient sensing. They belong to a group of protein kinases called AGC kinases that share common features like a C-terminal extension to the catalytic domain comprising a hydrophobic motif. PRKs are regulated by N-terminal domains, a pseudosubstrate sequence, Rho-binding domains, and a C2 domain involved in inhibition and dimerization, while Rho and lipids are activators. We investigated the allosteric regulation of PRK2 and its interaction with its upstream kinase PDK1 using a chemical biology approach. We confirmed the phosphoinositide-dependent protein kinase 1 (PDK1)-interacting fragment (PIF)-mediated docking interaction of PRK2 with PDK1 and showed that this interaction can be modulated allosterically. We showed that the polypeptide PIFtide and a small compound binding to the PIF-pocket of PRK2 were allosteric activators, by displacing the pseudosubstrate PKL region from the active site. In addition, a small compound binding to the PIF-pocket allosterically inhibited the catalytic activity of PRK2. Together, we confirmed the docking interaction and allostery between PRK2 and PDK1 and described an allosteric communication between the PIF-pocket and the active site of PRK2, both modulating the conformation of the ATP-binding site and the pseudosubstrate PKL-binding site. Our study highlights the allosteric modulation of the activity and the conformation of PRK2 in addition to the existence of at least two different complexes between PRK2 and its upstream kinase PDK1. Finally, the study highlights the potential for developing allosteric drugs to modulate PRK2 kinase conformations and catalytic activity. [ABSTRACT FROM AUTHOR]

We report a change in the structural and magnetic properties of epitaxial Mn5Ge3 on a Ge-on-Si (111) substrate by applying strain engineering through ms-range flash lamp annealing (FLA). X-ray diffraction results demonstrate that during FLA for 20 ms, the formation of nonmagnetic MnxGey secondary phases is suppressed, while the in-plane expansion of the lattice increases with increasing annealing temperature. Temperature-dependent magnetization results indicate that the Curie temperature of Mn5Ge3 rises from 287 K in the as-prepared sample to above 400 K after FLA, making Mn5Ge3 an attractive material for spintronics. Experimental results together with theoretical Monte Carlo simulations allow us to conclude that the expansion of the in-plane lattice causes the increase of the Curie temperature due to enhancement of the ferromagnetic interaction between Mn atoms. [ABSTRACT FROM AUTHOR]

Plasmonic and nanophotonic structures have been used to enhance the performance of photonic devices through the control and manipulation of photonic energy. Characterization of such devices typically requires the fabrication of contacting structures followed by stepwise spectral illumination and data recording. The acquisition of reflectance and transmittance spectra with Fourier transform infrared spectroscopy (FTIR) is—in contrast—a contactless and faster process. Since FTIR measurements take into account substrate absorption, which does not contribute to photocurrent, the two measurement approaches cannot be compared without further data processing. Here, we present a strategy to separate substrate absorption from absorption processes within the device layers in order to predict device performance from FTIR measurements. We apply our strategy to Ge-on-Si planar photodetectors with and without plasmonic structures. [ABSTRACT FROM AUTHOR]

Modulation-doped field-effect transistors (MODFET) that are typically based on either a two-dimensional electron gas or a two-dimensional hole gas (2DHG) are highly suitable for low-temperature applications due to the high mobilities attained by the charge carriers in the device channel. The Ge 2DHG is particularly interesting, since Ge exhibits the highest hole mobility among all semiconductors. In this paper, we report on the temperature-dependent direct current-characteristics of normally-on MODFETs based on a high mobility Ge 2DHG. Here, we specifically investigate device characteristics down to cryogenic temperatures and analyze the impact of different MOD-doping on device performance. We find that the largest On-Off ratio of I On / I Off = 3.2 × 10 6 and lowest sub-threshold swing (SS) of SS = 64 mV de c − 1 at a temperature of T = 7.5 K are attained for a MOD-doping of N A = 5 × 10 17 c m − 3 , while the highest effective mobility μ eff = 864 c m 2 V − 1 s − 1 is obtained from a device with a MOD-doping of N A = 1.1 × 10 18 c m − 3 . Furthermore, while effective mobilities in the devices are strongly reduced compared to Hall mobilities measured in the unstructured Ge 2DHGs, both quantities can be seen to follow a similar trend. Our results motivate further investigations of Ge 2DHG MODFETs for applications in cryogenic low-noise amplifiers, besides their well-established potential for spintronic applications. [ABSTRACT FROM AUTHOR]

Avalanche photodiodes utilizing GeSn as an absorbing material can be used for low-light detection of telecommunication wavelengths, such as 1550 nm. We present the performance of GeSn-on-Si avalanche photodiodes at low-temperatures down to 110 K. It was found, that at temperatures above 190 K the dark current is dominated by generation-recombination due to trap states at the SiO 2 -semiconductor interface with an activation energy of ∼0.2 eV. At lower temperatures and high reverse voltages the leakage mechanism shifts to trap-assisted-tunneling. Responsivity measurements show the shift of the absorption edge toward shorter wavelengths. For 1550 nm and at 140 K a responsivity of 0.097 A/W is achieved, which is five times higher than a Ge reference-APD. When biased in the Geiger-mode, measurements of the dark count rates were performed, marking the first step towards GeSn-on-Si single-photon detectors for 1550 nm radiation. [ABSTRACT FROM AUTHOR]

We examine the Raman shift in silicon–germanium–tin alloys with high silicon content grown on a germanium virtual substrate by molecular beam epitaxy. The Raman shifts of the three most prominent modes, Si–Si, Si–Ge, and Ge–Ge, are measured and compared with results in previous literature. We analyze and fit the dependence of the three modes on the composition and strain of the semiconductor alloys. We also demonstrate the calculation of the composition and strain of SixGe1 − x − ySny from the Raman shifts alone, based on the fitted relationships. Our analysis extends previous results to samples lattice matched on Ge and with higher Si content than in prior comprehensive Raman analyses, thus making Raman measurements as a local, fast, and nondestructive characterization technique accessible for a wider compositional range of these ternary alloys for silicon‐based photonic and microelectronic devices. [ABSTRACT FROM AUTHOR]

Incorporating group IV photonic nanostructures within active top-illuminated photonic devices often requires light-transmissive contact schemes. In this context, plasmonic nanoapertures in metallic films can not only be realized using CMOS compatible metals and processes, they can also serve to influence the wavelength-dependent device responsivities. Here, we investigate crescent-shaped nanoapertures in close proximity to Ge-on-Si PIN nanopillar photodetectors both in simulation and experiment. In our geometries, the absorption within the devices is mainly shaped by the absorption characteristics of the vertical semiconductor nanopillar structures (leaky waveguide modes). The plasmonic resonances can be used to influence how incident light couples into the leaky modes within the nanopillars. Our results can serve as a starting point to selectively tune our device geometries for applications in spectroscopy or refractive index sensing. [ABSTRACT FROM AUTHOR]

Hybrid materials consisting of organic semiconductors and molecular quantum bits promise to provide a novel platform for quantum spintronic applications. However, investigations of such materials, elucidating both the electrical and quantum dynamical properties of the same material have never been reported. Here the preparation of hybrid materials consisting of conducting polymers and molecular quantum bits is reported. Organic field‐effect transistor measurements demonstrate that the favorable electrical properties are preserved in the presence of the qubits. Chemical doping introduces charge carriers into the material, and variable‐temperature charge transport measurements reveal the existence of mobile charge carriers at temperatures as low as 15 K. Importantly, quantum coherence of the qubit is shown to be preserved up to temperatures of at least 30 K, that is, in the presence of mobile charge carriers. These results pave the way for employing such hybrid materials in novel molecular quantum spintronic architectures. [ABSTRACT FROM AUTHOR]

We report on photodetection in deep subwavelength Ge(Sn) nano-islands on Si nano-pillar substrates, in which self-aligned nano-antennas in the Al contact metal are used to enhance light absorption by means of local surface plasmon resonances. The impact of parameters such as substrate doping and device geometry on the measured responsivities are investigated and our experimental results are supported by simulations of the three-dimensional distribution of the electromagnetic fields. Comparatively high optical responsivities of about 0.1 A W−1 are observed as a consequence of the excitation of localized surface plasmons, making our nano-island photodetectors interesting for applications in which size reduction is essential. [ABSTRACT FROM AUTHOR]

The temperature-dependent electroluminescent properties of Ge-Diodes, especially the Ge-Zener-Emitter, with tunnel transitions are investigated. The direct band-gap behavior of Germanium below a temperature of 140 K is demonstrated, facilitated by Zener tunneling. Pulsed excitation of the Ge-Zener-Emitter results in an optical output power density of 6 μW, which is sufficient to excite quantum dots for single-photon emission. The peak energy of 0.86 eV suits the non-resonant excitation of InGaAs quantum dots at cryogenic temperatures. This paper presents a potential optical pump source for a quantum photonic integrated circuit. [ABSTRACT FROM AUTHOR]

The transcriptional regulator FUSE Binding Protein 1 (FUBP1) is overexpressed in more than 80% of all human hepatocellular carcinomas (HCCs) and other solid tumor entities including prostate and colorectal carcinoma. FUBP1 expression is required for HCC tumor cell expansion, and it functions as an important pro-proliferative and anti-apoptotic oncoprotein that binds to the single-stranded DNA sequence FUSE to regulate the transcription of a variety of target genes. In this study, we screened an FDA-approved drug library and discovered that the Topoisomerase I (TOP1) inhibitor camptothecin (CPT) and its derivative 7-ethyl-10-hydroxycamptothecin (SN-38), the active irinotecan metabolite that is used in the clinics in combination with other chemotherapeutics to treat carcinoma, inhibit FUBP1 activity. Both molecules prevent in vitro the binding of FUBP1 to its single-stranded target DNA FUSE , and they induce deregulation of FUBP1 target genes in HCC cells. Our results suggest the interference with the FUBP1/ FUSE interaction as a further molecular mechanism that, in addition to the inactivation of TOP1, may contribute to the therapeutic potential of CPT/SN-38. Targeting of FUBP1 in HCC therapy with SN-38/irinotecan could be a particularly interesting option because of the high FUBP1 levels in HCC cells and their dependency on FUBP1 expression. [ABSTRACT FROM AUTHOR]

The group-IV semiconductor alloy Ge1-x-ySixSny has recently attracted great interest due to its prospective potential for use in optoelectronics, electronics, and photovoltaics. Here, we investigate molecular beam epitaxy grown Ge1-x-ySixSny alloys lattice-matched to Ge with large Si and Sn concentrations of up to 42% and 10%, respectively. The samples were characterized in detail by Rutherford backscattering/channeling spectroscopy for composition and crystal quality, x-ray diffraction for strain determination, and photoluminescence spectroscopy for the assessment of band-gap energies. Moreover, the experimentally extracted material parameters were used to determine the SiSn bowing and to make predictions about the optical transition energy. [ABSTRACT FROM AUTHOR]

Metallic nanoantennas can be used to enhance the efficiency of optical device operation by redistributing electromagnetic energy. Here, we investigate the effect of a random distribution of disc-shaped Al nanoantennas of different diameters deposited on Ge-on-Si PIN-photodetectors on the wavelength-dependent responsivity. We compare our experimental results to simulations and find that the largest responsivity enhancement is obtained for wavelengths that correspond to energies at or below the bandgap energy of Ge. We argue that this is the result of antenna-mediated scattering of light into waveguide modes within the Ge-on-Si PIN-photodetectors, which is effectively influenced by nanoantenna size, and we discuss a possible application of the concept for integrated biosensing. [ABSTRACT FROM AUTHOR]

In this paper the optical absorption of the GeSn PIN photodetector was investigated. The vertical GeSn PIN photodetectors were fabricated by molecular beam epitaxy (MBE) and dry etching. By means of current density–voltage ( J – V ) and capacity–voltage ( C – V ) measurements the photodetector device was characterized. The absorption coefficients of GeSn material were finally extracted from the optical response of PIN structure. With further direct bandgap analysis the influences of device structure was proved negligible. [ABSTRACT FROM AUTHOR]

We report electrical spin injection and detection in degenerately doped n-type Ge channels using Mn5Ge3C0.8/Al2O3/n+-Ge tunneling contacts for spin injection and detection. The whole structure is integrated on a Si wafer for complementary metal-oxide-semiconductor compatibility. From three-terminal Hanle-effect measurements, we observe a spin accumulation up to 10 K. The spin lifetime is extracted to be 38 ps at T = 4 K using Lorentzian fitting, and the spin diffusion length is estimated to be 367 nm due to the high diffusion coefficient of the highly doped Ge channel. [ABSTRACT FROM AUTHOR]

Antimony-doped Ge-LEDs were subjected to electroluminescence studies at temperatures about 300 K and 80 K. The LEDs were grown on Si substrates by MBE. The thickness of the active layer was 300 nm. For the p+nn+-LEDs the Sb concentrations were 1 × 1018, 1 × 1019, 3 × 1019, 4 × 1019, 7 × 1019 or 1 × 1020 cm-3, respectively. As reference a p+in+-LED without intentional doping in the active layer was used. The investigated specimen exhibited dominance of the direct transition line at about 0.8 eV. Moreover, luminescence indirect transition was observed. In general, the spectra reveal higher EL intensities at room temperature as compared to 80 K. With decreasing temperature the direct peak was blue shifted. The highest EL intensity was found for the LED with Sb concentration of 3 × 1019 cm-3. With increasing Sb doping a red-shift of the direct peak was observed, caused by band gap narrowing. In addition, a simulated curve of the direct transition was compared with our samples and fits well with the measured spectra. (© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim) [ABSTRACT FROM AUTHOR]

Highlights: [•] Pulsed Laser Induced Epitaxy provides controlled intermixing of Si/Ge/Sn in m scale. [•] This techniques guaranties Si/Ge/Sn epitaxial alloying. [•] Controlled depth and lateral concentration gradients of the three elements (Si, Ge and Sn) is observed. [•] Mask Projection assisted PLIE offers simple routes for up and down scaling. [ABSTRACT FROM AUTHOR]

Summary: Protein kinases play important regulatory roles in cells and organisms. Therefore, they are subject to specific and tight mechanisms of regulation that ultimately converge on the catalytic domain and allow the kinases to be activated or inhibited only upon the appropriate stimuli. AGC protein kinases have a pocket in the catalytic domain, the PDK1-interacting fragment (PIF)-pocket, which is a key mediator of the activation. We show here that helix αC within the PIF-pocket of atypical protein kinase C (aPKC) is the target of the interaction with its inhibitory N-terminal domains. We also provide structural evidence that the small compound PS315 is an allosteric inhibitor that binds to the PIF-pocket of aPKC. PS315 exploits the physiological dynamics of helix αC for its binding and allosteric inhibition. The results will support research on allosteric mechanisms and selective drug development efforts against PKC isoforms. [ABSTRACT FROM AUTHOR]

Abstract: Strained and unstrained GeSn layers on Si substrates were grown with Sn contents up to 20% and 25%, respectively. All metastable layer structures were fabricated by means of an ultra-low temperature molecular beam epitaxy process. The useful thickness of the metastable layers for a range of Sn contents, growth temperatures and two different strain values (unstrained, compressive strained) is explored. The epitaxial breakdown thickness which limits the useful thickness range decreases exponentially with increasing growth temperature and Sn concentration. [Copyright &y& Elsevier]

The myotendinous junction (MTJ) is the major site of force transfer in skeletal muscle, and defects in its structure correlate with a subset of muscular dystrophies. Col22a1 encodes the MTJ component collagen XXII, the function of which remains unknown. Here, we have cloned and characterized the zebrafish col22a1 gene and conducted morpholino-based loss-of-function studies in developing embryos. We showed that col22a1 transcripts localize at muscle ends when the MTJ forms and that COLXXII protein integrates the junctional extracellular matrix. Knockdown of COLXXII expression resulted in muscular dystrophy-like phenotype, including swimming impairment, curvature of embryo trunk/tail, strong reduction of twitch-contraction amplitude and contraction-induced muscle fiber detachment, and provoked significant activation of the survival factor Akt. Electron microscopy and immunofluorescence studies revealed that absence of COLXXII caused a strong reduction of MTJ folds and defects in myoseptal structure. These defects resulted in reduced contractile force and susceptibility of junctional extracellular matrix to rupture when subjected to repeated mechanical stress. Co-injection of subphenotypic doses of morpholinos against col22a1 and genes of the major muscle linkage systems showed a synergistic gene interaction between col22a1 and itga7 (α7β1 integrin) that was not observed with dag1 (dystroglycan). Finally, pertinent to a conserved role in humans, the dystrophic phenotype was rescued by microinjection of recombinant human COLXXII. Our findings indicate that COLXXII contributes to the stabilization of myotendinous junctions and strengthens skeletal muscle attachments during contractile activity. [ABSTRACT FROM AUTHOR]

Abstract: The group of AGC protein kinases includes more than 60 protein kinases in the human genome, classified into 14 families: PDK1, AKT/PKB, SGK, PKA, PKG, PKC, PKN/PRK, RSK, NDR, MAST, YANK, DMPK, GRK and SGK494. This group is also widely represented in other eukaryotes, including causative organisms of human infectious diseases. AGC kinases are involved in diverse cellular functions and are potential targets for the treatment of human diseases such as cancer, diabetes, obesity, neurological disorders, inflammation and viral infections. Small molecule inhibitors of AGC kinases may also have potential as novel therapeutic approaches against infectious organisms. Fundamental in the regulation of many AGC kinases is a regulatory site termed the “PIF-pocket” that serves as a docking site for substrates of PDK1. This site is also essential to the mechanism of activation of AGC kinases by phosphorylation and is involved in the allosteric regulation of N-terminal domains of several AGC kinases, such as PKN/PRKs and atypical PKCs. In addition, the C-terminal tail and its interaction with the PIF-pocket are involved in the dimerization of the DMPK family of kinases and may explain the molecular mechanism of allosteric activation of GRKs by GPCR substrates. In this review, we briefly introduce the AGC kinases and their known roles in physiology and disease and the discovery of the PIF-pocket as a regulatory site in AGC kinases. Finally, we summarize the current status and future therapeutic potential of small molecules directed to the PIF-pocket; these molecules can allosterically activate or inhibit the kinase as well as act as substrate-selective inhibitors. This article is part of a Special Issue entitled: Inhibitors of Protein Kinases (2012). [Copyright &y& Elsevier]

Abstract: In this work, electroluminescence from the intrinsic Germanium layer of tensile strained Germanium LEDs is observed at room temperature. The pin LEDs are fabricated by low temperature molecular beam epitaxy with a double-heterojunction process on Silicon substrates. The tensile strain is adjusted at 0.24% with an annealing step at 700°C leading to a lowering of the direct band gap. Electroluminescence spectra show a value of 0.781eV for the direct band gap or an infrared shift of 19meV. Increasing of the intrinsic layer thickness leads to higher electroluminescence intensity. [Copyright &y& Elsevier]

Dislocation related electroluminescence was detected in germanium p-i-n diodes grown on silicon using a virtual substrate. It appears at room temperature and above a certain threshold of the excitation current. The spectral feature characterizing dislocation related radiation consists of three peaks at around 0.45 eV. The appearance of the dislocation related peaks in the spectrum goes along with a change in the growth rate of the direct band-to-band luminescence upon increasing of the current through the structure. The observation is consistent with an injection of minority carriers in the p+ and n+ regions of the diode. As the p+ region contains the misfit dislocation rich virtual substrate it becomes a source of dislocation luminescence. (© 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim) [ABSTRACT FROM AUTHOR]

The protein kinase C-related kinase 2 (PRK2)-interactingfragment(PIF) pocket of phosphoinositide-dependent kinase-1 (PDK1) was proposedas a novel target site for allosteric modulators. In the present work,we describe the design, synthesis, and structure–activity relationshipof a series of 2-(3-oxo-1,3-diphenylpropyl)malonic acids as potentallosteric activators binding to the PIF pocket. Some congeners displayedAC50values for PDK1 activation in the submicromolar range.The potency of the best compounds to stabilize PDK1 in a thermal stabilityshift assay was in the same order of magnitude as that of the PIFpocket binding peptide PIFtide, suggesting comparable binding affinitiesto the PIF pocket. The crystal structure of PDK1 in complex with compound 4hrevealed that additional ionic interactions are mainlyresponsible for the increased potency compared to the monocarboxylateanalogues. Notably, several compounds displayed high selectivity forPDK1. Employing a prodrug strategy, we were able to corroborate thenovel mechanism of action in cells. [ABSTRACT FROM AUTHOR]

Summary: The PIF-pocket of AGC protein kinases participates in the physiologic mechanism of regulation by acting as a docking site for substrates and as a switch for the transduction of the conformational changes needed for activation or inhibition. We describe the effects of compounds that bind to the PIF-pocket of PDK1. In vitro, PS210 is a potent activator of PDK1, and the crystal structure of the PDK1-ATP-PS210 complex shows that PS210 stimulates the closure of the kinase domain. However, in cells, the prodrug of PS210 (PS423) acts as a substrate-selective inhibitor of PDK1, inhibiting the phosphorylation and activation of S6K, which requires docking to the PIF-pocket, but not affecting PKB/Akt. This work describes a tool to study the dynamics of PDK1 activity and a potential approach for drug discovery. [ABSTRACT FROM AUTHOR]

Ge-based p-channel Field-Effect Transistors (FETs) are regarded as the most promising devices to replace Si-based p-channel FETs with emphasis on reducing device power-consumption. Planar-Doped Barrier FETs (PDBFETs) are considered good candidates for tuning Ge-based FETs performance: with channels almost undoped except for a very thin region, creating necessary barrier for operation. PDBFETs enables inspection of behaviour with carriers away from surface, experiencing bulk properties. The aim of this work is to show the capability of the PDBFET concept to improve the performance of Ge-based devices even on large scaled device. Applying the concept of channel doping modulation to Ge-based FETs is demonstrated through fabrication and electrical characterization of Ge-based p-PDBFETs with optimistic results achieving off-state currents of sub-nA/μm even with relatively large sized devices, which are competitive in electrostatic performance to scaled, more complicated design devices. Sources of leakage current are considered through improving surface treatment. Applying low temperature measurements elaborated the possibility of higher performance with dimension scaling availability. [ABSTRACT FROM AUTHOR]

• Preparation of ferromagnetic samples by interdiffusion of Mn with Si x Ge 1-x-y Sn y. • Study of the magnetic properties of Mn-Si x Ge 1-x-y Sn y. • Study of the phase-formation during the diffusion process. • Proposal of a two-layer model to explain the observed magnetic properties. We report on the structure and magnetic properties of Mn based ferromagnetic layers on the semiconductor Si x Ge 1-x-y Sn y with Sn content up to y = 0.15 in comparison with layers on Ge and Si 0.75 Ge 0.25. The ferromagnetic layers grow by interdiffusion between an evaporated Mn layer and molecular-beam-epitaxy grown semiconductor layers. This approach enables the preparation of Mn based layers, e.g., as a ferromagnetic contact material for Si x Ge 1-x-y Sn y using a self-aligned interdiffusion process, opening up the opportunity for large-scale manufacturing. The samples show a clear phase separation into Si-rich and Ge-rich Mn compounds. All samples are ferromagnetic and exhibit a decrease in saturation magnetization and an increase in coercive field with increasing Si content x. The Curie temperature shows no decisive trend with increasing Si content with values around room temperature. Based on the composition, structure and magnetic properties, we propose a two-layer model to correlate the structure and composition with the observed magnetic properties. We show that the changes in magnetic behavior can be explained solely by considering the Si content of the Si x Ge 1-x-y Sn y substrates with the Sn being largely passive. [ABSTRACT FROM AUTHOR]

Examines the structure of the pyramidal germanium islands grown on boron-terminated silicon (111). Description of the magnetic order of the substrate; Assessment of the island shape and size distribution; Effectiveness of small-angle x-ray scattering in determining the complete symmetry of arbitrary-shaped objects.

Here, we report comprehensive investigations of aluminum oxide (Al 2 O 3) high-κ gate oxides deposited via remote plasma enhanced atomic layer deposition (Re-PEALD) with mesh configuration in a commercial 100 mm ALD reactor. Trimethylaluminum (Al(CH 3) 3), dioxygen (O 2) plasma, and Argon (Ar) are used as the metal precursor, oxidant, and carrier/purge, respectively. The growth rate per cycle and non-uniformity of Al 2 O 3 thin films is analyzed with the variation in duration of (Al(CH 3) 3) pulse, O 2 plasma, post-precursor purge, post-oxidant purge, RF power, and substrate temperature. High-quality monolayer type Al 2 O 3 thin films with a growth rate of ~ 1.1 Å/cycle are achieved for a wide temperature range from ~ 100 °C to ~ 300 °C suitable for various nanoelectronics applications ranging from flexible substrates to low thermal budget and high mobility alternate semiconductor substrates. Further, the Al/Re-PEALD-Al 2 O 3 /p-Si, metal-oxide-semiconductor (MOS) structures are investigated for capacitance-voltage, capacitance-frequency, and leakage current-voltage characteristics to demonstrate the quality of Re-PEALD-Al 2 O 3 thin films. The Al/Re-PEALD-Al 2 O 3 /p-Si, MOS structures revealed excellent electrical characteristics with ultralow minimum interface trap density (D it) ~ 9.9 × 109 eV−1cm−2, negative effective oxide charges (N eff) ~ 5.52 × 1012 cm−2, low leakage current density of ~ 4.1 nA/cm2 at −1 V, hysteresis-free, insignificant V th shift, and trivial frequency dispersion. Moreover, the chemical analysis using XPS depth profiling disclosed that Re-PEALD deposited Al 2 O 3 thin films results in a high-quality gradient Al 2 O 3 /SiO x /Si interface rather than an abrupt Al 2 O 3 /Si interface, and the oxygen rich thin films due to the oxygen (O2−) interstitials close to the interface are the sources of negative fixed oxide charges in Re-PEALD-Al 2 O 3 /Si, system. These results intend to boost the investigations of Re-PEALD Al 2 O 3 ultrathin films for low thermal budget high mobility alternate semiconductor substrates for nanoelectronics applications. [ABSTRACT FROM AUTHOR]

• Flexible electronics requires electroless and galvanic Cu plating on Cu. • Advanced flexible substrates have large Cu crystals with cube texture. • Epitaxy during galvanic plating leads to unacceptably rough surfaces. • Recrystallization can be delayed sufficiently by the electroless deposit. • Non-epitaxial electroless Cu seed layers are required. The production of highly flexible printed circuit boards requires copper plating on roll annealed (RA) Cu foils with strong (001) crystallographic orientation, with electroless copper plating followed by galvanic copper plating. Concurrent epitaxial and polycrystalline crystal growth during galvanic plating has to be avoided because it leads to unacceptably rough sample surfaces, with polycrystalline regions protruding. Two electroless plating processes are compared in terms of their interaction with the subsequent galvanic plating step. Plating tests are carried out with RA substrates and (111), (011) and (001) copper single crystals. Crystallite orientation distributions are determined by measuring X-ray diffraction pole figures for the substrates, as well as the substrates with galvanic deposits, electroless deposits and combined electroless and galvanic deposits. One of the electroless processes creates Cu {111} planes parallel to the sample surface, thereby reliably disrupting epitaxy between the substrate surface and the growing galvanic film. Moderate constant stress in the electroless processes enables good mechanical adhesion to the substrate. [ABSTRACT FROM AUTHOR]