String Unification, Higher-Level Gauge Symmetries, and Exotic Hypercharge Normalizations

We explore the extent to which string theories with higher-level gauge symmetries and non-standard hypercharge normalizations can reconcile the discrepancy between the string unification scale and the GUT scale extrapolated from the Minimal Supersymmetric Standard Model (MSSM). We determine the phenomenologically allowed regions of (k_Y,k_2,k_3) parameter space, and investigate the proposal that there might exist string models with exotic hypercharge normalizations k_Y which are less than their usual value k_Y=5/3. For a broad class of heterotic string models (encompassing most realistic string models which have been constructed), we prove that k_Y >= 5/3. Beyond this class, however, we show that there exist consistent MSSM embeddings which lead to k_Y < 5/3. We also consider the constraints imposed on k_Y by demanding charge integrality of all unconfined string states, and show that only a limited set of hypercolor confining groups and corresponding values of k_Y are possible.Comment: 59 pages, standard LaTeX, 4 figures (Encapsulated PostScript). Expanded reference

Realizing Higher-Level Gauge Symmetries in String Theory: New Embeddings for String GUTs

We consider the methods by which higher-level and non-simply laced gauge symmetries can be realized in free-field heterotic string theory. We show that all such realizations have a common underlying feature, namely a dimensional truncation of the charge lattice, and we identify such dimensional truncations with certain irregular embeddings of higher-level and non-simply laced gauge groups within level-one simply-laced gauge groups. This identification allows us to formulate a direct mapping between a given subgroup embedding, and the sorts of GSO constraints that are necessary in order to realize the embedding in string theory. This also allows us to determine a number of useful constraints that generally affect string GUT model-building. For example, most string GUT realizations of higher-level gauge symmetries G_k employ the so-called diagonal embeddings G_k\subset G\times G \times...\times G. We find that there exist interesting alternative embeddings by which such groups can be realized at higher levels, and we derive a complete list of all possibilities for the GUT groups SU(5), SU(6), SO(10), and E_6 at levels k=2,3,4 (and in some cases up to k=7). We find that these new embeddings are always more efficient and require less central charge than the diagonal embeddings which have traditionally been employed. As a byproduct, we also prove that it is impossible to realize SO(10) at levels k>4. This implies, in particular, that free-field heterotic string models can never give a massless 126 representation of SO(10).Comment: 69 pages, LaTeX, 5 figures (Encapsulated PostScript). Revised to match published versio

Glycogen Storage Disease Type Ia in Canines: A Model for Human Metabolic and Genetic Liver Disease

A canine model of Glycogen storage disease type Ia (GSDIa) is described. Affected dogs are homozygous for a previously described M121I mutation resulting in a deficiency of glucose-6-phosphatase-α. Metabolic, clinicopathologic, pathologic, and clinical manifestations of GSDIa observed in this model are described and compared to those observed in humans. The canine model shows more complete recapitulation of the clinical manifestations seen in humans including “lactic acidosis”, larger size, and longer lifespan compared to other animal models. Use of this model in preclinical trials of gene therapy is described and briefly compared to the murine model. Although the canine model offers a number of advantages for evaluating potential therapies for GSDIa, there are also some significant challenges involved in its use. Despite these challenges, the canine model of GSDIa should continue to provide valuable information about the potential for generating curative therapies for GSDIa as well as other genetic hepatic diseases

Utilisation of sperm‐binding assay combined with computer‐assisted sperm analysis to evaluate frozen‐thawed bull semen

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/110567/1/and12225.pd

A Molecular Census of Arcuate Hypothalamus and Median Eminence Cell Types

The hypothalamic arcuate-median eminence complex (Arc-ME) controls energy balance, fertility, and growth through molecularly distinct cell types, many of which remain unknown. To catalog cell types in an unbiased way, we profiled gene expression in 20,921 individual cells in and around the adult mouse Arc-ME using Drop-seq. We identify 50 transcriptionally distinct Arc-ME cell populations, including a rare tanycyte population at the Arc-ME diffusion barrier, a novel leptin-sensing neuronal population, multiple AgRP and POMC subtypes, and an orexigenic somatostatin neuronal population. We extended Drop-seq to detect dynamic expression changes across relevant physiological perturbations, revealing cell type-specific responses to energy status, including distinctly responsive subtypes of AgRP and POMC neurons. Finally, integrating our data with human GWAS data implicates two previously unknown neuronal subtypes in the genetic control of obesity. This resource will accelerate biological discovery by providing insights into molecular and cell type diversity from which function can be inferred

Criteria for preclinical models of cholangiocarcinoma:scientific and medical relevance

Cholangiocarcinoma (CCA) is a rare malignancy that develops at any point along the biliary tree. CCA has a poor prognosis, its clinical management remains challenging, and effective treatments are lacking. Therefore, preclinical research is of pivotal importance and necessary to acquire a deeper understanding of CCA and improve therapeutic outcomes. Preclinical research involves developing and managing complementary experimental models, from in vitro assays using primary cells or cell lines cultured in 2D or 3D to in vivo models with engrafted material, chemically induced CCA or genetically engineered models. All are valuable tools with well-defined advantages and limitations. The choice of a preclinical model is guided by the question(s) to be addressed; ideally, results should be recapitulated in independent approaches. In this Consensus Statement, a task force of 45 experts in CCA molecular and cellular biology and clinicians, including pathologists, from ten countries provides recommendations on the minimal criteria for preclinical models to provide a uniform approach. These recommendations are based on two rounds of questionnaires completed by 35 (first round) and 45 (second round) experts to reach a consensus with 13 statements. An agreement was defined when at least 90% of the participants voting anonymously agreed with a statement. The ultimate goal was to transfer basic laboratory research to the clinics through increased disease understanding and to develop clinical biomarkers and innovative therapies for patients with CCA

Use of midlatency auditory-evoked potentials as indicator of unconsciousness in the dog: characterisation of the effects of acepromazine-thiopentone, medetomidine-thiopentone and medetomidine-butorphanol-midazolam combinations

info:eu-repo/semantics/publishe

L’incompétence du sphincter urétral chez la chienne. Revue de la littérature

Urethral sphincter mechanism incompetence is characterized by unvoluntary urine leakage, worsening when the animal is recumbent or asleep, or during excitement. It mainly affects large breed dogs, and mostly middle-aged spayed bitches. The aetiology of this condition is multifactorial and predisposing factors include a decrease urethral tone, an intrapelvic bladder neck position, a short urethra, sterilisation, obesity, and age. Diagnostic workup should include a vaginourethrography to identify possible vaginal abnormalities and to visualize the urethra and the position of the bladder neck, and urethral profilometry to demonstrate a decrease in maximal urethral pressure and functional profile length. Medical treatment with oestriol is an option. This short-acting oestrogen does not exhibit oestrogenic side effects. Unfortunately, its success rate is only of 65 % of complete continence. The a- adrenergic agents ( phenylpropanolamine and ephedrine) are more efficacious, with a success rate reaching 75 to 90 %, with very few side effects. In absence of response to the treatment, or if the animal becomes refractory, a colposuspension can be recommended, with a fairly good prognosis

Bovine placental alphamelanotropine

The immunocytochemical study of the bovine placenta has demonstrated the presence of cells containing alphamelanotropic hormones, in the decidual epithelium, since the 4th month of pregnancy. The number and the staining intensity of those cells grow up with the placental development. Since the 6th month, we observed the immunoreactional presence of cells in the foetal chorionic epithelium.L'étude immunocytochimique du placenta bovin a permis de démontrer la présence dans l'épithelium décidual, dès le 4e mois de la gestation, de celluls contenant de l'hormone alphamélanotrope. Les nombre et intensité de marquage de ces cellules augmentent ave l'avancement de la gestation. A parti du 6e mois, nous observons d eplus la présence de cellules réactionnelles dans l'épithélium chorionique foetal