A 24 kb Single-Well Mixed 3T Gain-Cell eDRAM with Body-Bias in 28 nm FD-SOI for Refresh-Free DSP Applications

Logic-compatible gain-cell embedded DRAM (GC-eDRAM) is an emerging alternative to conventional SRAM for memory-dominated system-on-chip (SoC) designs due to its high-density, low-power, and two-ported operation. Although GCs have a limited data retention time (DRT) at deeply scaled technology nodes, there are many DSP applications which only require short-term data storage and can therefore avoid refresh. In this paper, we present a novel single-well mixed 3T GC implementation in 28 nm FD-SOI technology. The proposed GC is supplied with body-bias control to improve the DRT by suppressing the leakage through the write port, and extend the maximum operating frequency by forward body-biasing the read port. A 24 kbit GC-eDRAM macro implementing the proposed 3T GC was fabricated in 28 nm FD-SOI technology, resulting in the highest density logic-compatible embedded memory fabricated in any 28 nm process with over 2x higher density compared to a 6T SRAM cell, over 4x higher DRT compared to a conventional 3T GC, and 38 x 47 x lower static power compared to conventional single-ported and two-ported SRAMs

The Hydrogen-Bond Switch Reaction of the Blrb Bluf Domain of <i>Rhodobacter sphaeroides</i>

The BlrB protein from Rhodobacter sphaeroides is a small 136 amino acid photoreceptor belonging to the BLUF family of blue light receptors. It contains merely the conserved BLUF fold responsible for binding the flavin pigment and a short C-terminal extension of unknown function. We investigated the primary photoreactions of BlrB by picosecond fluorescence and transient absorption spectroscopy. After excitation of the flavin the fluorescence decays in an H/D isotope independent manner with time constants of 21 and 390 ps, indicating a BLUF characteristic heterogeneous excited state quenched by electron transfer. By transient absorption spectroscopy, we observed a rapid relaxation of a vibrationally hot excited state within 6 ps upon excitation at 400 nm. The relaxed excited state evolves biexponentially with 18 ps (27%) and 216 ps (73%) into the signaling state spectrum indicated by a growing absorptive feature at 492 nm. Additionally, a broad triplet feature is observed as residual absorbance at a delay of 5 ns, which we attribute to derive from a significant fraction of free flavin in the sample. The photochemistry of BlrB is similar to other small BLUF proteins in respect to the fast formation of the photoproduct but does not resolve any further intermediates. We compare the photoreaction with other BLUF proteins on the basis of available spectroscopic data and crystal structures. An arginine close to the C2O carbonyl of the flavin is likely to be a key determinant for the fast electron transfer in BlrB. Additionally, the orientation of the electron-donating tyrosine in respect to the flavin might play a role in the so far unique kinetic separation of the semiquinonic intermediates in Slr1694

Primary Reactions of the LOV2 Domain of Phototropin Studied with Ultrafast Mid-Infrared Spectroscopy and Quantum Chemistry

AbstractPhototropins, major blue-light receptors in plants, are sensitive to blue light through a pair of flavin mononucleotide (FMN)-binding light oxygen and voltage (LOV) domains, LOV1 and LOV2. LOV2 undergoes a photocycle involving light-driven covalent adduct formation between a conserved cysteine and the FMN C(4a) atom. Here, the primary reactions of Avena sativa phototropin 1 LOV2 (AsLOV2) were studied using ultrafast mid-infrared spectroscopy and quantum chemistry. The singlet excited state (S1) evolves into the triplet state (T1) with a lifetime of 1.5 ns at a yield of ∼50%. The infrared signature of S1 is characterized by absorption bands at 1657 cm−1, 1495–1415 cm−1, and 1375 cm−1. The T1 state shows infrared bands at 1657 cm−1, 1645 cm−1, 1491–1438 cm−1, and 1390 cm−1. For both electronic states, these bands are assigned principally to C=O, C=N, C-C, and C-N stretch modes. The overall downshifting of C=O and C=N bond stretch modes is consistent with an overall bond-order decrease of the conjugated isoalloxazine system upon a π-π∗ transition. The configuration interaction singles (CIS) method was used to calculate the vibrational spectra of the S1 and T1 excited ππ∗ states, as well as respective electronic energies, structural parameters, electronic dipole moments, and intrinsic force constants. The harmonic frequencies of S1 and T1, as calculated by the CIS method, are in satisfactory agreement with the evident band positions and intensities. On the other hand, CIS calculations of a T1 cation that was protonated at the N(5) site did not reproduce the experimental FMN T1 spectrum. We conclude that the FMN T1 state remains nonprotonated on a nanosecond timescale, which rules out an ionic mechanism for covalent adduct formation involving cysteine-N(5) proton transfer on this timescale. Finally, we observed a heterogeneous population of singly and doubly H-bonded FMN C(4)=O conformers in the dark state, with stretch frequencies at 1714 cm−1 and 1694 cm−1, respectively

Hydrogen Bond Switching among Flavin and Amino Acid Side Chains in the BLUF Photoreceptor Observed by Ultrafast Infrared Spectroscopy

AbstractBLUF domains constitute a recently discovered class of photoreceptor proteins found in bacteria and eukaryotic algae. BLUF domains are blue-light sensitive through a FAD cofactor that is involved in an extensive hydrogen-bond network with nearby amino acid side chains, including a highly conserved tyrosine and glutamine. The participation of particular amino acid side chains in the ultrafast hydrogen-bond switching reaction with FAD that underlies photoactivation of BLUF domains is assessed by means of ultrafast infrared spectroscopy. Blue-light absorption by FAD results in formation of FAD•− and a bleach of the tyrosine ring vibrational mode on a picosecond timescale, showing that electron transfer from tyrosine to FAD constitutes the primary photochemistry. This interpretation is supported by the absence of a kinetic isotope effect on the fluorescence decay on H/D exchange. Subsequent protonation of FAD•− to result in FADH• on a picosecond timescale is evidenced by the appearance of a N-H bending mode at the FAD N5 protonation site and of a FADH• C=N stretch marker mode, with tyrosine as the likely proton donor. FADH• is reoxidized in 67ps (180ps in D2O) to result in a long-lived hydrogen-bond switched network around FAD. This hydrogen-bond switch shows infrared signatures from the C-OH stretch of tyrosine and the FAD C4=O and C=N stretches, which indicate increased hydrogen-bond strength at all these sites. The results support a previously hypothesized rotation of glutamine by ∼180° through a light-driven radical-pair mechanism as the determinant of the hydrogen-bond switch

The role of key amino acids in the photoactivation pathway of the Synechocystis Slr1694 BLUF domain

BLUF (blue light sensing using FAD) domains belong to a novel group of blue light sensing receptor proteins found in microorganisms. We have assessed the role of specific aromatic and polar residues in the Synechocystis Slr1694 BLUF protein by investigating site-directed mutants with substitutions Y8W, W91F, and S28A. The W91F and S28A mutants formed the red-shifted signaling state upon blue light illumination, whereas in the Y8W mutant, signaling state formation was abolished. The W91F mutant shows photoactivation dynamics that involve the successive formation of FAD anionic and neutral semiquinone radicals on a picosecond time scale, followed by radical pair recombination to result in the long-lived signaling state in less than 100 ps. The photoactivation dynamics and quantum yield of signaling state formation were essentially identical to those of wild type, which indicates that only one significant light-driven electron transfer pathway is available in Slr1694, involving electron transfer from Y8 to FAD without notable contribution of W91. In the S28A mutant, the photoactivation dynamics and quantum yield of signaling state formation as well as dark recovery were essentially the same as in wild type. Thus, S28 does not play an essential role in the initial hydrogen bond switching reaction in Slr1694 beyond an influence on the absorption spectrum. In the Y8W mutant, two deactivation branches upon excitation were identified: the first involves a neutral semiquinone FADH(*) that was formed in approximately 1 ps and recombines in 10 ps and is tentatively assigned to a FADH(*)-W8(*) radical pair. The second deactivation branch forms FADH(*) in 8 ps and evolves to FAD(*-) in 200 ps, which recombines to the ground state in about 4 ns. In the latter branch, W8 is tentatively assigned as the FAD redox partner as well. Overall, the results are consistent with a photoactivation mechanism for BLUF domains where signaling state formation proceeds via light-driven electron and proton transfer from Y8 to FAD, followed by a hydrogen bond rearrangement and radical pair recombination

pTNM Stage Distribution in Breast Cancer: A Population-Based Survey in Northern Italy

Aims and background The role of distribution by stage at diagnosis in breast cancer has been considered in many studies, with particular regard to evaluation of prognosis, impact of screening programs and quality of care. Nevertheless, international comparisons of descriptive data can be hampered by lack of homogeneity in staging methods. The TNM is presently the most common staging system used all over the world, although some criticism have been raised recently against its pragmatic value. The present study reports a population-based survey of pathologic TNM distribution in incident cases of female breast cancer in the Verona province, a geographical area of northern Italy covered by cancer registration. Methods All histologically proven incident cases of breast cancer were identified in the study period 1988-1990 and classified as for tumor size and nodal involvement according to the pathological TNM criteria. The type of surgical treatment was also registered for all cases diagnosed in 1990. Results one thousand two hundreds and fifty-four invasive and in situ breast cancers were observed and pT1 cases accounted for 44.4%. Nodal involvement was present in 41.5% of invasive cancers. A surgical treatment was performed in 1213 patients (96.7%). Axillary dissection was reported in 1080 cases, 820 of them (76.6%) having 10 or more lymph nodes examined. Radical mastectomy accounted for 74% of the 458 breast cancers diagnosed in 1990 and 31.6% of the eligible cases were conservatively treated. Conclusions Cancer registries should be encouraged to report data on stage distribution in breast cancer (and in other malignancies). This practice could improve international comparisons and give an essential contribution to studies on survival, screening programs and quality of care. </jats:sec