1. |
- Safavi, Setareh, et al.
(author)
-
HSP90 inhibition blocks ERBB3 and RET phosphorylation in myxoid/round cell liposarcoma and causes massive cell death in vitro and in vivo
- 2016
-
In: OncoTarget. - : Impact Journals, LLC. - 1949-2553. ; 7:1, s. 433-445
-
Journal article (peer-reviewed)abstract
- Myxoid sarcoma (MLS) is one of the most common types of malignant soft tissue tumors. MLS is characterized by the FUS-DDIT3 or EWSR1-DDIT3 fusion oncogenes that encode abnormal transcription factors. The receptor tyrosine kinase (RTK) encoding RET was previously identified as a putative downstream target gene to FUS-DDIT3 and here we show that cultured MLS cells expressed phosphorylated RET together with its ligand Persephin. Treatment with RET specific kinase inhibitor Vandetanib failed to reduce RET phosphorylation and inhibit cell growth, suggesting that other RTKs may phosphorylate RET. A screening pointed out EGFR and ERBB3 as the strongest expressed phosphorylated RTKs in MLS cells. We show that ERBB3 formed nuclear and cytoplasmic complexes with RET and both RTKs were previously reported to form complexes with EGFR. The formation of RTK hetero complexes could explain the observed Vandetanib resistence in MLS. EGFR and ERBB3 are clients of HSP90 that help complex formation and RTK activation. Treatment of cultured MLS cells with HSP90 inhibitor 17-DMAG, caused loss of RET and ERBB3 phosphorylation and lead to rapid cell death. Treatment of MLS xenograft carrying Nude mice resulted in massive necrosis, rupture of capillaries and hemorrhages in tumor tissues. We conclude that complex formation between RET and other RTKs may cause RTK inhibitor resistance. HSP90 inhibitors can overcome this resistance and are thus promising drugs for treatment of MLS/RCLS.
|
|
2. |
- Abdallah, Nancy, et al.
(author)
-
Topology of posets with special partial matchings
- 2019
-
In: Advances in Mathematics. - : Academic Press. - 0001-8708 .- 1090-2082. ; 348, s. 255-276
-
Journal article (peer-reviewed)abstract
- Special partial matchings (SPMs) are a generalisation of Brentis special matchings. Let a pircon be a poset in which every non-trivial principal order ideal is finite and admits an SPM. Thus pircons generalise Mariettis zircons. We prove that every open interval in a pircon is a PL ball or a PL sphere. It is then demonstrated that Bruhat orders on certain twisted identities and quasiparabolic W-sets constitute pircons. Together, these results extend a result of Can, Cherniaysky, and Twelbeck, prove a conjecture of Hultman, and confirm a claim of Rains and Vazirani.
|
|
3. |
- Andersson, Ronnie, 1975, et al.
(author)
-
Druckbehälter
- 2018
-
Patent (other academic/artistic)
|
|
4. |
- Bridel, Claire, et al.
(author)
-
Diagnostic Value of Cerebrospinal Fluid Neurofilament Light Protein in Neurology : A Systematic Review and Meta-analysis
- 2019
-
In: JAMA Neurology. - : American Medical Association (AMA). - 2168-6149 .- 2168-6157. ; 76:9, s. 1035-1048
-
Research review (peer-reviewed)abstract
- Importance Neurofilament light protein (NfL) is elevated in cerebrospinal fluid (CSF) of a number of neurological conditions compared with healthy controls (HC) and is a candidate biomarker for neuroaxonal damage. The influence of age and sex is largely unknown, and levels across neurological disorders have not been compared systematically to date.Objectives To assess the associations of age, sex, and diagnosis with NfL in CSF (cNfL) and to evaluate its potential in discriminating clinically similar conditions.Data Sources PubMed was searched for studies published between January 1, 2006, and January 1, 2016, reporting cNfL levels (using the search terms neurofilament light and cerebrospinal fluid) in neurological or psychiatric conditions and/or in HC.Study Selection Studies reporting NfL levels measured in lumbar CSF using a commercially available immunoassay, as well as age and sex.Data Extraction and Synthesis Individual-level data were requested from study authors. Generalized linear mixed-effects models were used to estimate the fixed effects of age, sex, and diagnosis on log-transformed NfL levels, with cohort of origin modeled as a random intercept.Main Outcome and Measure The cNfL levels adjusted for age and sex across diagnoses.Results Data were collected for 10 059 individuals (mean [SD] age, 59.7 [18.8] years; 54.1% female). Thirty-five diagnoses were identified, including inflammatory diseases of the central nervous system (n = 2795), dementias and predementia stages (n = 4284), parkinsonian disorders (n = 984), and HC (n = 1332). The cNfL was elevated compared with HC in a majority of neurological conditions studied. Highest levels were observed in cognitively impaired HIV-positive individuals (iHIV), amyotrophic lateral sclerosis, frontotemporal dementia (FTD), and Huntington disease. In 33.3% of diagnoses, including HC, multiple sclerosis, Alzheimer disease (AD), and Parkinson disease (PD), cNfL was higher in men than women. The cNfL increased with age in HC and a majority of neurological conditions, although the association was strongest in HC. The cNfL overlapped in most clinically similar diagnoses except for FTD and iHIV, which segregated from other dementias, and PD, which segregated from atypical parkinsonian syndromes.Conclusions and Relevance These data support the use of cNfL as a biomarker of neuroaxonal damage and indicate that age-specific and sex-specific (and in some cases disease-specific) reference values may be needed. The cNfL has potential to assist the differentiation of FTD from AD and PD from atypical parkinsonian syndromes.
|
|
5. |
- Glavå, Mats, et al.
(author)
-
Arbetsrätt
- 2016. - 3
-
Book (other academic/artistic)abstract
- Arbetsrättslagstiftningens närmast explosionsartade utveckling under 1900-talets tre sista decennier kom att förskjuta, men inte på något avgörande sätt förändra, de utgångspunkter som slogs fast genom Decemberkompromissen mellan LO och SAF år 1906. Då fastslogs att arbetsgivaren, i kraft av de s.k. § 32-rättigheterna, har makten över anställningars ingående och upphörande samt rätten att fritt leda och fördela arbetet. När det i början av 2000-talet sluts ett nytt kollektivavtal för en ny bransch är formuleringarna av utgångspunkten för relationen mellan parterna i allt väsentligt desamma som i 1906 års avtal. Med utgångspunkt i dessa s.k. arbetsgivarprerogativ framställs i denna bok arbetsrätten som begränsningar i arbetsgivarens friheter. Ett sådant funktionellt arbetsgivarperspektiv har visat sig göra arbetsrätten mer överskådlig och överbryggar dessutom den stundom konstlade uppdelningen mellan enskild och kollektiv arbetsrätt.Boken spänner över större delen av den civilrättsliga arbetsrättsliga regleringen, även om vissa delar behandlas mer översiktligt. Tonvikten ligger på begränsningar i antagnings- och uppsägningsrätten samt på arbetsmarknadens kollektiva spelregler. Uttryckt i lagstiftningstermer är det MBL, LAS och diskrimineringslagen som ges störst utrymme.Arbetsrätt är i första hand avsedd för utbildningar på högskolenivå men har ett upplägg som gör att den lämpar sig även för andra utbildningar samt för praktiker. Boken innehåller utförliga referat av och hänvisningar till centrala arbetsrättsliga källor.
|
|
6. |
- Glavå, Mats, 1957, et al.
(author)
-
Arbetsrätt, 3:e upplaga
- 2015
-
Book (other academic/artistic)abstract
- Boken spänner över större delen av den civilrättsliga arbetsrättsliga regleringen, även om vissa delar behandlas mer översiktligt. Tonvikten ligger på begränsningar i antagnings- och uppsägningsrätten samt på arbetsmarknadens kollektiva spelregler. Uttryckt i lagstiftningstermer är det MBL, LAS och diskrimi neringslagen som ges störst utrymme. Arbetsrätt är i första hand avsedd för utbildningar på högskolenivå men har ett upplägg som gör att den lämpar sig även för andra utbildningar samt för praktiker. Boken innehåller utförliga referat av och hänvisningar till centrala arbetsrättsliga käll
|
|
7. |
- Hansson, Caroline, 1981, et al.
(author)
-
Risk factors for suicide in bipolar disorder: a cohort study of 12 850 patients
- 2018
-
In: Acta Psychiatrica Scandinavica. - : Wiley. - 0001-690X .- 1600-0447. ; 138:5, s. 456-463
-
Journal article (peer-reviewed)abstract
- ObjectiveMethodBipolar disorder carries a high risk of suicide. Identification of risk factors is important. The aim of this study was to study risk factors for suicide in a large cohort of men and women with bipolar disorder. A prospective cohort study using clinical data from the Swedish National Quality Register for Bipolar Affective Disorder (BipolaR). The outcome variable was suicide captured in the Cause of Death Register between 2004 and 2014. Hazard ratios (HR) were calculated using Cox proportional hazards models. ResultsConclusionsOf 12 850 persons (4844 men and 8006 women) with bipolar disorder, 90 (55 men and 35 women) died by suicide during the follow-up period (between 1 and 10 years). Male sex (HR 2.56), living alone (HR 2.45), previous suicide attempts (HR 4.10), comorbid psychiatric disorder (HR 2.64), recent affective episodes (HR 2.39), criminal conviction (HR 4.43), psychiatric inpatient care (HR 2.79), and involuntary commitment (HR 3.50) were significant risk factors for suicide. Several of the statistically significant risk factors for suicide in bipolar disorder differed between men and women. Risk factors for suicide in bipolar disorder include factors associated with suicide in general, but also diagnosis-specific factors.
|
|
8. |
|
|
9. |
|
|
10. |
- Hansson, Mikael, 1986-
(author)
-
Combinatorics and topology related to involutions in Coxeter groups
- 2018
-
Doctoral thesis (other academic/artistic)abstract
- This dissertation consists of three papers in combinatorial Coxeter group theory.A Coxeter group is a group W generated by a set S, where all relations can be derived from the relations s2 = e for all s ? S, and (ss′)m(s,s′) = e for some pairs of generators s ≠ s′ in S, where e ? W is the identity element and m(s, s′) is an integer satisfying that m(s, s′) = m(s′, s) ≥ 2. Two prominent examples of Coxeter groups are provided by the symmetric group Sn (i.e., the set of permutations of {1, 2, . . . , n}) and finite reflection groups (i.e., finite groups generated by reflections in some real euclidean space). There are also important infinite Coxeter groups, e.g., affine reflection groups.Every Coxeter group can be equipped with various natural partial orders, the most important of which is the Bruhat order. Any subset of a Coxeter group can then be viewed as an induced subposet.In Paper A, we study certain posets of this kind, namely, unions of conjugacy classes of involutions in the symmetric group. We obtain a complete classification of the posets that are pure (i.e., all maximal chains have the same length). In particular, we prove that the set of involutions with exactly one fixed point is pure, which settles a conjecture of Hultman in the affirmative. When the posets are pure, we give their rank functions. We also give a short, new proof of the EL-shellability of the set of fixed-point-free involutions, established by Can, Cherniavsky, and Twelbeck.Paper B also deals with involutions in Coxeter groups. Given an involutive automorphism θ of a Coxeter system (W, S), letℑ(θ) = {w ? W | θ(w) = w−1}be the set of twisted involutions. In particular, ℑ(id) is the set of ordinary involutions in W. It is known that twisted involutions can be represented by words in the alphabet = { | s ? S}, called -expressions. If ss′ has finite order m(s, s′), let a braid move be the replacement of ′ ⋯ by ′ ′ ⋯, both consisting of m(s, s′) letters. We prove a word property for ℑ(θ), for any Coxeter system (W, S) with any θ. More precisely, we provide a minimal set of moves, easily determined from the Coxeter graph of (W, S), that can be added to the braid moves in order to connect all reduced -expressions for any given w ? ℑ(θ). This improves upon a result of Hamaker, Marberg, and Pawlowski, and generalises similar statements valid in certain types due to Hu, Zhang, Wu, and Marberg.In Paper C, we investigate the topology of (the order complexes of) certain posets, called pircons. A special partial matching (SPM) on a poset is a matching of the Hasse diagram satisfying certain extra conditions. An SPM without fixed points is precisely a special matching as defined by Brenti. Let a pircon be a poset in which every non-trivial principal order ideal is finite and admits an SPM. Thus pircons generalise Marietti’s zircons. Our main result is that every open interval in a pircon is a PL ball or a PL sphere.An important subset of ℑ(θ) is the set ?(θ) = {θ(w−1)w | w ? W} of twisted identities. We prove that if θ does not flip any edges with odd labels in the Coxeter graph, then ?(θ), with the order induced by the Bruhat order on W, is a pircon. Hence, its open intervals are PL balls or spheres, which confirms a conjecture of Hultman. It is also demonstrated that Bruhat orders on Rains and Vazirani’s quasiparabolic W-sets (under a boundedness assumption) form pircons. In particular, this applies to all parabolic quotients of Coxeter groups.
|
|