Clinical Germline Genome Editing: When Will Good be Good Enough?

Ensuring experimental outcomes are of the highest clinical caliber is crucial prior to the introduction of germline genome editing. However, if we are to police scientific progress using probability or the potential to go wrong, then we must account for the specious standards of human reproduction. With 15% of clinically recognized pregnancies estimated to end in spontaneous miscarriage within the first trimester, and 25% of all pregnancies ending in miscarriage, human reproduction has a high failure rate. These figures, coupled with the percentage of all births with congenital defects and the number of these who will die in the first year of life, paint two scenarios: one, that evolutionary checkpoints are cruel but critical, and two, that for the seemingly inevitable 3%, or 8 million babies born annually with congenital disorders, perhaps more must be done for prevention, when methods exist for prediction. Unifying progress in three coevolving technologies—assisted reproduction, genome editing, and genome sequencing—could produce revolutionary clinical changes in the harsh global statistics of hereditary disease. A historical perspective on the rocky foundations upon which IVF was built suggests that lessons should be learned from the misalignment of research and clinical practice due to funding and research restrictions. At present, it seems likely that history will repeat itself, and that progress in research will be hampered by hypocritical hesitation

Multiscale expansion of the lattice potential KdV equation on functions of infinite slow-varyness order

We present a discrete multiscale expansion of the lattice potential Korteweg-de Vries (lpKdV) equation on functions of infinite order of slow-varyness. To do so we introduce a formal expansion of the shift operator on many lattices holding at all orders. The lowest secularity condition from the expansion of the lpKdV equation gives a nonlinear lattice equation, depending on shifts of all orders, of the form of the nonlinear Schr\"odinger (NLS) equationComment: 9 pages, submitted to Journ. Phys.

Improved self-gain in deep submicrometer strained silicon-germanium pMOSFETs with HfSiOx/TiSiN gate stacks

The self-gain of surface channel compressively strained SiGe pMOSFETs with HfSiOx/TiSiN gate stacks is investigated for a range of gate lengths down to 55 nm. There is 125% and 700% enhancement in the self-gain of SiGe pMOSFETs compared with the Si control at 100 nm and 55 nm lithographic gate lengths, respectively. This improvement in the self-gain of the SiGe devices is due to 80% hole mobility enhancement compared with the Si control and improved electrostatic integrity in the SiGe devices due to less boron diffusion into the channel. At 55 nm gate length, the SiGe pMOSFETs show 50% less drain induced barrier lowering compared with the Si control devices. Electrical measurements show that the SiGe devices have larger effective channel lengths. It is shown that the enhancement in the self-gain of the SiGe devices compared with the Si control increases as the gate length is reduced thereby making SiGe pMOSFETs with HfSiOx/TiSiN gate stacks an excellent candidate for analog/mixed-signal applications

The Energy-Momentum tensor on SpincSpin^c manifolds

On $Spin^c$ manifolds, we study the Energy-Momentum tensor associated with a spinor field. First, we give a spinorial Gauss type formula for oriented hypersurfaces of a $Spin^c$ manifold. Using the notion of generalized cylinders, we derive the variationnal formula for the Dirac operator under metric deformation and point out that the Energy-Momentum tensor appears naturally as the second fundamental form of an isometric immersion. Finally, we show that generalized $Spin^c$ Killing spinors for Codazzi Energy-Momentum tensor are restrictions of parallel spinors.Comment: To appear in IJGMMP (International Journal of Geometric Methods in Modern Physics), 22 page

In-Chain Tunneling Through Charge-Density Wave Nanoconstrictions and Break-Junctions

We have fabricated longitudinal nanoconstrictions in the charge-density wave conductor (CDW) NbSe$_{3}$ using a focused ion beam and using a mechanically controlled break-junction technique. Conductance peaks are observed below the T$_{P1}$$=145$K and T$_{P2}$$=59$K CDW transitions, which correspond closely with previous values of the full CDW gaps $2\Delta_{1}$ and $2\Delta_{2}$ obtained from photo-emission. These results can be explained by assuming CDW-CDW tunneling in the presence of an energy gap corrugation $\epsilon_{2}$ comparable to $\Delta_{2}$, which eliminates expected peak at $\Delta_{1}+\Delta_{2}$. The nanometer length-scales our experiments imply indicate that an alternative explanation based on tunneling through back-to-back CDW-normal junctions is unlikely.Comment: 5 pages, 3 figures, submitted to physical review letter

Demography and disorders of the French Bulldog population under primary veterinary care in the UK in 2013

Abstract Background Despite its Gallic name, the French Bulldog is a breed of both British and French origin that was first recognised by The Kennel Club in 1906. The French Bulldog has demonstrated recent rapid rises in Kennel Club registrations and is now (2017) the second most commonly registered pedigree breed in the UK. However, the breed has been reported to be predisposed to several disorders including ocular, respiratory, neurological and dermatological problems. The VetCompass™ Programme collates de-identified clinical data from primary-care veterinary practices in the UK for epidemiological research. Using VetCompass™ clinical data, this study aimed to characterise the demography and common disorders of the general population of French Bulldogs under veterinary care in the UK. Results French Bulldogs comprised 2228 (0.49%) of 445,557 study dogs under veterinary care during 2013. Annual proportional birth rates showed that the proportional ownership of French Bulldog puppies rose steeply from 0.02% of the annual birth cohort attending VetCompass™ practices in 2003 to 1.46% in 2013. The median age of the French Bulldogs overall was 1.3 years (IQR 0.6–2.5, range 0.0–13.0). The most common colours of French Bulldogs were brindle (solid or main) (32.36%) and fawn (solid or main) (29.9%). Of the 2228 French Bulldogs under veterinary care during 2013, 1612 (72.4%) had at least one disorder recorded. The most prevalent fine-level precision disorders recorded were otitis externa (14.0%, 95% CI: 12.6–15.5), diarrhoea (7.5%, 95% CI: 6.4–8.7), conjunctivitis (3.2%, 95% CI: 2.5–4.0), nails overlong (3.1%, 95% CI% 2.4–3.9) and skin fold dermatitis (3.0%, 95% CI% 2.3–3.8). The most prevalent disorder groups were cutaneous (17.9%, 95% CI: 16.3–19.6), enteropathy (16.7%, 95% CI: 15.2–18.3), aural (16.3%, 95% CI: 14.8–17.9), upper respiratory tract (12.7%, 95% CI: 11.3–14.1) and ophthalmological (10.5%, 95% CI: 9.3–11.9). Conclusions Ownership of French Bulldogs in the UK is rising steeply. This means that the disorder profiles reported in this study reflect a current young UK population and are likely to shift as this cohort ages. Otitis externa, diarrhoea and conjunctivitis were the most common disorders in French Bulldogs. Identification of health priorities based on VetCompass™ data can support evidence–based reforms to improve health and welfare within the breed

The impact of self-heating and SiGe strain-relaxed buffer thickness on the analog performance of strained Si nMOSFETs

The impact of the thickness of the silicon–germanium strain-relaxed buffer (SiGe SRB) on the analog performance of strained Si nMOSFETs is investigated. The negative drain conductance caused by self-heating at high power levels leads to negative self-gain which can cause anomalous circuit behavior like non-linear phase shifts. Using AC and DC measurements, it is shown that reducing the SRB thickness improves the analog design space and performance by minimizing self-heating. The range of terminal voltages that leverage positive self-gain in 0.1 μm strained Si MOSFETs fabricated on 425 nm SiGe SRBs is increased by over 100% compared with strained Si devices fabricated on conventional SiGe SRBs 4 μm thick. Strained Si nMOSFETs fabricated on thin SiGe SRBs also show 45% improvement in the self-gain compared with the Si control as well as 25% enhancement in the on-state performance compared with the strained Si nMOSFETs on the 4 μm SiGe SRB. The extracted thermal resistance is 50% lower in the strained Si device on the thin SiGe SRB corresponding to a 30% reduction in the temperature rise compared with the device fabricated on the 4 μm SiGe SRB. Comparisons between the maximum drain voltages for positive self-gain in the strained Si devices and the ITRS projections of supply-voltage scaling show that reducing the thickness of the SiGe SRB would be necessary for future technology nodes