bluuebunny/crossref_metadata_2025 huggingface dataset:
Synthesis of unlabelled and tritium labelled 4‐isothiocyanato‐1‐(1‐phenylcyclohexyl)piperidine (fourphit), tools for the study of the dopamine reuptake complex.
Authors: Linders Joannes T. M. , de Costa Brian R. , Grayson Neile A. , Rice Kenner C.
Published: October 2006

The synthesis of high specific activity tritium labelled 4‐isothiocyanato‐1‐(1‐phenylcyclohexyl)piperidine ([3H]fourphit), a probe for the autoradiographic study of the dopamine reuptake complex, is described. An improved, facile synthesis of unlabelled fourphit in high overall yield is also presented. Detailed study of the interaction of unlabelled and tritium labelled fourphit with the dopamine reuptake complex may lead to a better understanding of the actions of cocaine.
Marquage par 14C de la triethylamine
Authors: Madelmont J. C. , Guerin P. , Domurado D.
Published: October 2006

Triethylamine was labelled by 14C using Na14CN as precursor in a ten steps chemical pathway. The radiochemical yield is 40%. The chemical procedure can be used for tritium labelling.
Practical synthesis of 14C S‐ribosyl‐l‐homocysteine uniformely labelled on the sugar moiety. An enzymatic route from (U‐14C) adenosine
Authors: Guillerm G. , Allart B.
Published: October 2006

[(U‐14C) S‐Ribosyl]‐L‐homocysteine has been prepared enzymatically from (U‐14C) adenosine in two steps using S‐adenosyl homocysteine hydrolase (EC.3.31.1) and bacterial S‐adenosyl homocysteine nucleosidase (EC.3.2.2.9) as catalysts.
Synthesis of tritium labelled 24‐epibrassinolide
Authors: Kolbe A. , Marquardt V. , Adam G.
Published: October 2006

Deuterium and tritium 5,7,7‐tris‐labelled 24‐epibrassinolide were prepared by base catalyzed exchange reaction using 24‐epicastasterone tetraacetate 1 or bis‐isopropylidenedioxy‐24‐epicastasterone 8 and labelled water. Baeyer‐Villiger oxidation of the obtained labelled 6‐ketones 2 and 3 with CF3CO3H gave after alkaline deacetylation of the resulting 4 and 5 the desired tris‐labelled 24‐epibrassinolides 6 and 7, respectively, or starting from 9 under simultaneous oxidation and deprotection in one step the same final products.
Synthesis of carbon‐14 and carbon‐13 labelled (R)‐(−)‐2[[4‐(2,6‐di‐1‐pyrrolidinyl‐4‐pyrimidinyl)‐1‐piperazinyl]methyl]‐3,4‐dihydro‐2,5,7,8‐tetramethyl‐2H‐1‐benzopyran‐6‐ol
Authors: Ackland M. J. , Howard M. R. , Jacobsen E. J. , Secreast S. L. , Dring L. G.
Published: October 2006

This paper describes the synthesis and characterisation of 2[[4‐(2,6‐di‐1‐pyrrolidinyl‐4‐pyrimidinyl)‐1‐piperazinyl]‐[14C]‐ methyl]‐3,4‐dihydro‐2,5,7,8‐tetramethyl‐2H‐1‐benzopyran‐6‐ol and 2[[4‐(2,6‐di‐1‐pyrrolidinyl‐4‐[13C2]‐pyrimidinyl)‐1‐ piperazinyl]‐[13C]‐methyl]‐3,4‐dihydro‐2,5,7,8‐tetramethyl‐2H‐1‐ benzopyran‐6‐ol. Intermediates in the synthesis included R‐(+)‐[13C]‐Trolox®(R‐(+)‐6‐hydroxy‐2,5,7,8‐tetramethylchroman‐[2‐13C]‐carboxylic acid), [2,5‐13C2]‐barbituric acid, 2,4,6‐trichloro‐[2,5‐13C2]‐pyrimidine, 2,6‐di‐pyrrolidinyl‐4‐chloro‐[2,5‐13C2]‐pyrimidine and 4‐(1‐piperazinyl)‐2,6‐di‐1‐pyrrolidinyl‐[2,5‐13C2]‐ pyrimidine.
Synthesis of carrier‐free rhenium‐188(V)DMSA using triphenyl phosphine as a facile reducing agent
Authors: Lisic Edward C. , Mirzadeh Saed , Knapp F. F.
Published: October 2006

Rhenium‐188‐labeled ReOCl3(PPh3)2 is an important reactive complex which can be prepared in > 95% yield by the reaction of perrhenate (188ReO4−) or perrhenic acid with triphenyl phosphine (PPh3) and HCl with subsequent extraction into CH2Cl2 or CHCl3. The yield is dependent upon a high HCl concentration. Because of the potential important use of 188Re(V)DMSA for therapy of tumors of the head and neck, we have used the 188ReOCl3(PPh3)intermediate for the facile synthesis of the ReO(DMSA)2 complex.

Although the Re(V)O(DMSA)2 is a monovalent anion, for simplicity the charge is not included and the species denoted as Re(V)DMSA in this discussion

Reaction of ReOCl3(PPh3)2 with naturally abundant Re or carrier free Re‐188, with DMSA (meso‐1,2‐dimercaptosuccinic acid) yields ReO(DMSA)2 in high yield. The 188Re(V)DMSA can also be prepared by reaction of Re‐188 perrhenate or perrhenic acid with SnCl2 in the presence of DMSA.
Synthesis of tritium labeled (±) 15‐deoxyspergualin trihydrochloride
Authors: Dischino D. D. , Cook D. J. , Saulnier M. G. , Tepper M. A.
Published: October 2006

Tritium labeled (±) 15‐deoxyspergualin, (±)‐7‐[(aminoiminomethyl) amino]‐N‐[2‐[[4‐[(3‐aminopropyl) amino]butyl]amino]‐1‐hydroxy‐2‐oxoethyl][4,5‐3H2]heptanamide trihydrochloride was prepared from the acid catalyzed condensation of 7‐guanidino[4,5‐3H2] heptanamide hydrochloride and glyoxyloylspermidine dihydrochloride in a total yield of 14.5%. The radiochemical purity was determined to be 91.1% and 95.4% on two different HPLC systems.
Tritium studies of catalysis over microporous aluminophosphate surfaces
Authors: Long Mervyn A. , He Simon J. X. , Than Chit
Published: October 2006

Microporous AlPO4‐5 catalysts exhibit catalytic activity for tritium isotope exchange and other reactions but the activity of the catalyst may vary widely from one batch of catalyst to another although all catalyst samples appear to show pure AlPO4‐5 phase. This catalytic activity appears to correlate with the presence of octahedral aluminium in the catalyst samples as revealed by solid sate 27Al NMR spectroscopy and this is attributed to defect sites in the lattice. The exchange patterns may show high regional specificity. These patterns have some of the features of acid catalysis but are assumed to be modified by the constraints imposed by the micropore geometry.
Tritium NMR in the analysis of tritiated compounds
Authors: Kaspersen Frans M. , Funke Carel W. , Vader Jan , Wagenaars Gerard N.
Published: October 2006

An overview is given of the possibilites of 3H NMR in the characterisation of 3H‐labelled compounds. This technique gives information on the identity of the tritiated compounds, the position of the tritium, the distribution of the label and even the radiochemical purity of the labelled products.
Enzymatic and chemical labelling of prostaglandin E1 and 13,14‐dihydro‐15‐keto‐prostaglandin E1
Authors: Tsikas Dimitrios , Bracht Stefan , Stichtenoth Dirk , Frölich Jürgen C.
Published: October 2006

Chemical and enzymatic tools were employed to synthesize [1,1‐18O2]‐prostaglandin (PG) E1, [1,1‐18O2]‐13,14‐dihydro‐15‐keto‐PGE1 and [5,6‐3H2]‐13,14‐dihydro‐15‐keto‐PGE1 starting from the corresponding unlabelled compounds adn [5,6‐3H2]‐PGE1, respectively. Reaction products were purified by high‐performance liquid chromatography and their isotopic purity was determined by gas chromatographymass spectrometry (GC‐MS). The utility of [1,1‐18O2]‐PGE1 and [1,1‐18O2]‐13,14‐dihydro‐15‐keto‐PGE1 as internal standards for GC‐MS analysis of the corresponding endogenous compounds in biological fluids is demonstrated. [5,6‐3H2]‐13,14‐dihydro‐15‐keto‐PGE1 was found to be useful in developing extraction and purification procedures for the quantitation of endogenous 13,14‐dihydro‐15‐keto‐PGE1 in human plasma by GC‐tandem MS.
Synthesis of 14C‐labelled aminoguanidine
Authors: Lo Theodore W. C. , Thornalley Paul J.
Published: October 2006

[14C]Aminoguanidine was synthesized by the reaction of hydrazine sulphate with barium [14C]cyanamide in a one‐step synthesis, and conveniently isolated by crystallization as the bicarbonate salt. The yield was 32%.
Synthesis of 15N labelled isophosphoramide mustard
Authors: Shulman‐Roskes Ellen M. , Gamcsik Michael P. , Colvin O. Michael , Chang Young H. , Koo Kyo I. , Ludeman Susan M.
Published: October 2006

The ifosfamide metabolite isophosphoramide mustard (IPM) was synthesized with isotopic enrichment at each nitrogen site. Glycine‐15N was converted to 2‐chloroethylamine‐15N hydrochloride (4 steps, 21% net yield) which was then reacted with phenyl dichlorophosphate to provide N,N′‐bis(2‐chloroethyl)phosphorodiamidic‐15N2 acid phenyl ester [62%, PhOP(O) (15NHCH2CH2Cl)2]. Catalytic hydrogenation of this phenyl ester followed by the addition of cyclohexylamine (CHA) provided IPM‐15N2 as the CHA salt (63%).
Acid‐catalyzed deuterium exchange of aromatic protons. Part III1: Accelerated exchange by microwave irradiation
Authors: Köves G. J.
Published: October 2006

Conventional acid‐catalyzed 2H/1H exchange in aromatic rings requires long reaction times, high temperatures and pressure. This paper reports that accelerated deuterium exchange can be achieved in a microwave oven. Experiments were carried out on benzodiazepines, tricyclic antidepressants and phenothiazines. The reaction time was decreased from days to minutes, the preparatory work was simpler than with conventional heating and the labelled products were cleaner.
Synthesis of [4,5‐3H‐Leu4]Salmon Calcitonin
Authors: Birtle T. , White A. J. , Woodhouse D. P.
Published: October 2006

The synthesis of salmon calcitonin, a C‐terminal amide dotriacontapeptide, labelled with tritium in the leucine residue at position 4 to a specific activity of 100Ci mmole−1 is described. The peptide was assembled using the Fmoc‐Polyamide solid‐phase synthesis strategy incorporating tritium labelled leucine, in the form of Fmoc‐4,5‐3H‐leucinepentafluorophenylester, at the appropriate stage. The Fmoc‐4,5‐3H‐leucinepentafluorophenylester was prepared via a multistage synthesis from 4,5‐dehydroleucine.
Biotechnological production of high specific activity L‐35 S‐cysteine and L‐35 S‐methionine by using a diploid yeast Saccharomyces cerevisiae
Authors: Gajendiran N. , Jayachandran N. , Rao B. S. , Unny V. K. P. , Thyagarajan S.
Published: October 2006

High specific activity L‐35 S‐cysteine and L‐35 S‐methionine were synthesised by using a wild type diploid strain of baker's yeast—Saccharomyces cerevisiae. Yeast cells were grown in a sulphur depleted synthetic medium in which Na2 35 SO4 (50 mCi/ml) was supplemented as the sole sulphur source. The level of incorporation was 60% on an average. The protein hydrolysate of the cultured cells was subjected to paper and column chromatographic separations to get the individual L‐35 S‐aminoacids. The radiochemical yields of cysteine and methionine were 6–7% and 18–20% respectively. The radiochemical purity of the products was >95%. The highest specific activity for the products obtained by employing this method was 1100 Ci/mmole from the starting material, Na2 35 SO4, with a specific activity of 1350 Ci/mmole.
Synthesis of [D5‐ethyl]‐tamoxifen; a mechanistic probe of tamoxifen induced hepatic DNA adduct formation
Authors: Horton Martin N. , Jarman Michael , Potter Gerard A.
Published: October 2006

Tamoxifen which incorporates a fully deuterated ethyl group, [D5‐ethyl]‐tamoxifen, has been synthesised in order to probe the mechanism of tamoxifen induced hepatic DNA adduct formation. The pentadeuteroethyl group was introduced into the tamoxifen structure by treatment of the ketone precursor 1‐[4‐(2‐chloroethoxy)phenyl]‐2‐phenylethanone, as its sodium enolate, with [D5]‐iodoethane.
The synthesis of d6‐α‐farnesene
Authors: Fielder Simon , Rowan Daryl D.
Published: October 2006

D6‐α‐Farnesene (3,7‐dimethyl‐11‐2H3‐methyl‐12,12,12‐2H3‐dodeca‐1,3E,6E,10‐tetraene) has been synthesised by two routes. Thermolysis of 2‐geranyl‐3‐methylsulpholene (5) yielded unlabelled α‐farnesene (93%) which was epoxidized at Δ10 in 31% yield. Oxidative cleavage of the epoxide (42%) and Wittig elaboration of the resultant trienal with d6‐isopropyl triphenylphosphorane gave d6‐α‐farnesene (73%). Alternatively, selective epoxidation of (5) gave the terminal 6′,7′ mono‐epoxide in 74% yield. Oxidative cleavage (73%) and Wittig elaboration of the resultant aldehyde yielded deuterated 2‐geranyl‐3‐methylsulpholene (46%). Thermal elimination of sulphur dioxide afforded the title compound in 91% yield.
Synthesis of 20‐[18F]fluoroarachidonic acid: A potential phospholipid metabolic agent
Authors: Nagatsugi Fumi , Hokazono Junji , Sasaki Shigeki , Maeda Minoru
Published: October 2006

A fluorine‐18 labelled analog of arachidonic acid, 20‐[18F]fluoroarachidonic acid, was prepared for evaluation as a potential phospholipid metabolic agent.

The radiosynthesis was accomplished by [18F]fluoride ion displacement on the tosylate precursor followed by basic hydrolysis of the ester group, in isolated radiochemical yield (not decay corrected) of 10 % in overall synthesis time (including HPLC purification) of 110 min.
A chemical probe for the estrogen receptor: Synthesis of the 3H‐isotopomer of raloxifene
Authors: Dodge Jeffrey A. , Stocksdale Mark G. , Jones C. David
Published: October 2006

Radiolabelled raloxifene (LY156758) has been prepared by tritium gas hydrogenolysis of a 3‐aroyl‐bis‐brominated precursor. The requisite halogenated intermediate was accessed by regioselective aroylation of benzothiophene 6 with the acid chloride of 3,5‐dibromo‐4‐[2‐(1‐piperdinyl)ethoxy]benzoic acid (5). Selective deprotection of the aryl methyl ethers in the presence of the ethoxy side‐chain followed by palladium catalyzed halogen‐tritium exchange provided the target compound with a specific activity of 30.1 Ci/mmol.
Synthesis of 2‐amino‐3,5‐dihydro‐7‐(3‐thienylmethyl)‐[6‐14C]‐4H‐pyrrolo[3,2‐d]pyrimidin‐4‐one monohydrochloride ([14C]CI‐1000)
Authors: Hicks James L.
Published: October 2006

2‐Amino‐3,5‐dihydro‐7‐(3‐thienylmethyl)‐[6‐14C]‐4H‐pyrrolo [3,2‐d]pyrimidin‐4‐one monohydrochloride ([14C]Cl‐1000), a potent purine nucleoside phosphorylase inhibitor, was made in six steps from potassium [14C]cyanide. A key step was the reduction of a nitro and a nitrile group with sodium hypophosphite and RaNi followed by cyclization of the resulting intermediate to form a pyrrolo[3,2‐d] pyrimidinone.
Synthesis of cyclophosphamide‐4,4,5,5‐d4
Authors: Walsh Shawn P. , Shulman‐Roskes Ellen M. , Anderson Lawrence W. , Chang Young H. , Ludeman Susan M.
Published: October 2006

3‐Hydroxypropionitrile was subjected to a base‐catalyzed exchange reaction in D2O which provided 2,2‐dideuterio‐3‐deuteroxypropionitrile (DOCH2CD2CN) in 70% yield. Reduction of the nitrile with LiAlD4 gave 3‐amino‐2,2,3,3‐tetradeuteriopropan‐1‐o1 (HOCH2CD2CD2NH2) in a crude yield of 71%. Reaction of this intermediate with N,N‐bis(2‐chloroethyl)phosphoramidic dichloride [Cl2P(O)N(CH2CH2Cl)2] followed by the combination of those chromatography fractions which contained only pure material gave cyclophosphamide‐4,4,5,5‐d4 as a white oil in 13% yield. A portion of this oil was converted to the monohydrate by the addition of water (1.1 equivalents) and crystallization from ether/petroleum ether (62% yield). For the hydrate, MS analyses gave an average mole percent enrichment (with average deviation over 5 determinations) of 89.1 ± 0.5% d4.
Synthese des bis‐ (β aminocrotonsaure‐2, 4‐ 14C)‐ thiodiathylenglycol (1,1‐14C) ‐esters
Authors: Figge K. , Voss H. P.
Published: October 2006

Der markierte PVC‐Stabilisator Bis‐(β‐aminocrotonsäure‐2,4‐14C)‐thiodiäthylenglykol(1,1′‐14C)‐ester (I) wird über die folgenden synthesestufen dargestellt:

Thiodiäthylenglykol‐1‐1′‐14C (II) aus 2‐Chloräthanol‐1‐14C (III) und Natriumsulfid; Ausbeute: 88 % d.Th., bzg. auf III.

Acetessigsäure(2,4‐14C)‐äthylester (IV) aus Essigsäure (2‐14C)‐äthyleser (V) in Gegenwart von na‐Äthylat; Ausbeute: 46 % d.Th.

Bis‐(acetessigsäure‐2,4‐14C)‐thiodiäthylenglykol(1,1′‐14C)‐ester (VII) durch Umesterung von IV mit II; Ausbeute: 72 % d.Th., bzg. auf II.

PVC‐Stabilisator I durch Umsetzung von VII mit Flüssigem Ammoniak; Ausbeute; 80 % d.Th., bzg. auf VII.

Die chemische und radiochemische Reinheit der einzelnen Reaktionsprodukte wird radiodünnschichtchromatographisch überprüft.
Purification of tpitiated gentamichin
Authors: Wilson T. W. , Kadar D. , Inaba T. , Jhhnson J. E.
Published: October 2006

A simple, high capacity method for the purification of 3H‐gentamicin is described. Confirmation of radiochemical purity using several thin layer chromatography systems is presented. Based on the weith of biologically active material, the specific activity is 1.02 Ci/mM.
Clinical trials update from the joint European Society and World Congress of Cardiology meeting: PEP‐CHF, ACCLAIM and the HHH study
Authors: Cleland John G.F. , Coletta Alison P. , Clark Andrew L.
Published: October 2006

This article provides information and a commentary on trials relevant to the pathophysiology, prevention and treatment of heart failure, presented at the joint European Society and World Congress of Cardiology meeting held in Barcelona in September 2006. All reports should be considered as preliminary data, as analyses may change in the final publication.

The PEP‐CHF study suggests that perindopril improves symptoms and functional capacity and may reduce heart failure hospitalisations in patients with diastolic heart failure. Although immune modulation therapy failed to reduce the incidence of all‐cause mortality and cardiovascular hospitalisations in the ACCLAIM study, the observed differences in outcome in some heart failure patients warrants further investigation. The HHH study failed to show a beneficial effect of telemonitoring over usual care in patients with heart failure but potentially important country interactions were observed.
Multiple sclerosis and milk: to drink or not to drink?
Authors: RUTTER EMMA R F
Published: October 2006

Multiple sclerosis (MS) is a condition of the central nervous system. It is the most common disabling neurological disease among young adults. The aetiology of this condition, which affects approximately 85 000 people in the UK, is unknown. It has been suggested that environmental factors including nutrition may be involved in its development in susceptible individuals. In the past, it has been suggested that milk and dairy products could exacerbate, cause relapses in, and even progress the symptoms of MS. This paper discusses the role of dairy products and their components in relation to MS, and is based on recently published research.
Effects of antibiotics on fitness of the B biotype and a non‐B biotype of the whitefly Bemisia tabaci
Authors: Ruan Yong‐Ming , Xu Jing , Liu Shu‐Sheng
Published: October 2006

The whitefly, Bemisia tabaci Gennadius (Homoptera: Aleyrodidae), harbors primary and secondary endosymbionts. Previous research showed that the invasive B biotype and an indigenous non‐B biotype (named non‐B ZHJ‐1 population) of B. tabaci from Zhejiang, China, harbored different endosymbionts. To investigate the function of these endosymbionts in the two biotypes of B. tabaci, we fed adult whiteflies with three antibiotics, tetracycline, ampicillin trihydrate, and rifampicin, and evaluated the fitness of their offspring on cotton plants. These three antibiotics did not remove the primary endosymbiont Portiera aleyrodidarum but were capable of eliminating the secondary endosymbionts. In the B biotype, treatments of adults with tetracycline or ampicillin trihydrate accelerated development and increased the survival of their offspring, while treatment of adults with rifampicin significantly retarded the development of their offspring but did not affect their survival. In the non‐B ZHJ‐1 population, treatments of adults with tetracycline or ampicillin trihydrate also accelerated the development of their offspring but did not significantly affect their survival, while treatment of adults with rifampicin significantly retarded development and reduced the survival of their offspring. These results suggest that removal of some secondary endosymbionts and/or reduction of the primary endosymbiont from B. tabaci may produce both favorable and unfavorable effects on the fitness of the host insects.
Postentry Events Are Responsible for Restriction of Productive Varicella-Zoster Virus Infection in Chinese Hamster Ovary Cells
Authors: Finnen Renée L. , Mizokami Kara R. , Banfield Bruce W. , Cai Guang-Yun , Simpson Scott A. , Pizer Lewis I. , Levin Myron J.
Published: October 2006

Productive infection of varicella-zoster virus (VZV) in vitro is restricted almost exclusively to cells derived from humans and other primates. We demonstrate that the restriction of productive VZV infection in CHO-K1 cells occurs downstream of virus entry. Entry of VZV into CHO-K1 cells was characterized by utilizing an ICP4/β-galactosidase reporter gene that has been used previously to study herpes simplex virus type 1 entry. Entry of VZV into CHO-K1 cells involved cell surface interactions with heparan sulfate glycosaminoglycans and a cation-independent mannose-6-phosphate receptor. Lysosomotropic agents inhibited the entry of VZV into CHO-K1 cells, consistent with a low-pH-dependent endocytic mechanism of entry. Infection of CHO-K1 cells by VZV resulted in the production of both immediate early and late gene products, indicating that a block to progeny virus production occurs after the initiation of virus gene expression.
Frequency, prognostic impact, and subtype association of 8p12, 8q24, 11q13, 12p13, 17q12, and 20q13 amplifications in breast cancers
Authors: Letessier Anne , Sircoulomb Fabrice , Ginestier Christophe , Cervera Nathalie , Monville Florence , Gelsi-Boyer Véronique , Esterni Benjamin , Geneix Jeannine , Finetti Pascal , Zemmour Christophe , Viens Patrice , Charafe-Jauffret Emmanuelle , Jacquemier Jocelyne , Birnbaum Daniel , Chaffanet Max
Published: October 2006

Background

Oncogene amplification and overexpression occur in tumor cells. Amplification status may provide diagnostic and prognostic information and may lead to new treatment strategies. Chromosomal regions 8p12, 8q24, 11q13, 17q12 and 20q13 are recurrently amplified in breast cancers.

Methods

To assess the frequencies and clinical impact of amplifications, we analyzed 547 invasive breast tumors organized in a tissue microarray (TMA) by fluorescence in situ hybridization (FISH) and calculated correlations with histoclinical features and prognosis. BAC probes were designed for: (i) two 8p12 subregions centered on RAB11FIP1 and FGFR1 loci, respectively; (ii) 11q13 region centered on CCND1; (iii) 12p13 region spanning NOL1; and (iv) three 20q13 subregions centered on MYBL2, ZNF217 and AURKA, respectively. Regions 8q24 and 17q12 were analyzed with MYC and ERBB2 commercial probes, respectively.

Results

We observed amplification of 8p12 (amplified at RAB11FIP1 and/or FGFR1) in 22.8%, 8q24 in 6.1%, 11q13 in 19.6%, 12p13 in 4.1%, 17q12 in 9.9%, 20q13Z (amplified at ZNF217 only) in 9.9%, and 20q13Co (co-amplification of two or three 20q13 loci) in 8.5% of cases. The 8q24, 12p13, and 17q12 amplifications were correlated with high grade. The most frequent single amplifications were 8p12 (9.8%), 8q24 (3.3%) and 12p13 (3.3%), 20q13Z and 20q13Co (1.6%) regions. The 17q12 and 11q13 regions were never found amplified alone. The most frequent co-amplification was 8p12/11q13. Amplifications of 8p12 and 17q12 were associated with poor outcome. Amplification of 12p13 was associated with basal molecular subtype.

Conclusion

Our results establish the frequencies, prognostic impacts and subtype associations of various amplifications and co-amplifications in breast cancers.
Utilization of Time-Based Techniques in Research and Teaching
Authors: Sanguinetti Paola
Published: October 2006

This article describes how computer animations, combined with cinematic techniques, have served as a teaching and research tool in architecture. Animations were used in the following areas: case studies of precedents in architecture using the animated modeling as a form of tectonic analysis; conceptualization of space through the study of film, specifically three approaches using film in the early stages of design: cinematic structure, film as site, and transcoding transparency; and mapping the urban fabric combining various time-based media.
Physical Modeling: The Convergence of Cutting-Edge Technologies and Miniature Tooling
Authors: Kenzari Bechir
Published: October 2006

When Rapid Prototyping and CAD/CAM technologies (including CNC and Laser Cutting) became affordable, ten years ago or so, their reception within model-making circles turned from positive to disappointing because of their incomplete adaptability to the making of architectural objects. Then it was discovered, just few years later, that many modeling details can only be worked out through the use of specific materials, accessories and miniature tools which neither fall under the CNC, Laser or Rapid Prototyping headings. This new situation has implied, among other things, that the status of the model is to be defined in terms of a convergence of particular technological possibilities. Using two specific models as examples, the present article will debate this convergence, which is now allowing a smooth and fluid interaction between several model-making techniques. The tendency of model-making to move closer to the real act of building will also be highlighted.
Quantitative Assay of Deletion or Duplication Genotype by Capillary Electrophoresis System: Application in Prader–Willi Syndrome and Duchenne Muscular Dystrophy
Authors: Hung Chia-Cheng , Chen Chih-Ping , Lin Shuan-Pei , Chien Shu-Chin , Lee Chien-Nan , Cheng Wen-Fang , Hsieh Wu-Shiun , Liu Ming S , Su Yi-Ning , Lin Win-Li
Published: October 2006

Background: Deletions and duplications involving large DNA segments result in underexpression or overexpression, depending on the changes in allele dose, and are known to cause many common disorders. Detection of allele dose variations in the human genome is increasingly important in medical genetic diagnosis.

Methods: We used multiplex quantitative PCR coupled with capillary electrophoresis for accurate allele dose determination. In cases of Prader–Willi syndrome (PWS), a total of 24 patients with PWS, as well as 205 control individuals from the general population, were analyzed by use of multiplex quantitative PCR to amplify the FGFR2 gene, the KRIT1 gene, and the SNRPN gene simultaneously. In cases of Duchenne muscular dystrophy (DMD), we optimized the multiplex quantitative PCR to amplify 38 exons to analyze the DMD gene for rapid diagnosis of 12 DMD-affected males, 12 obligate carriers from families, and 50 unaffected female controls.

Results: We were able to unambiguously diagnose the deletion genotype in PWS patients and identify all deletion or duplication genotypes and carrier status in DMD-affected cases with 100% sensitivity and specificity.

Conclusions: This report describes a novel single assay that can rapidly quantify allele dose to provide accurate clinical genetic diagnosis. This technique offers a valuable alternative for the rapid detection of genomic deletions or duplications and decreases costs because it does not require expensive fluorescent reagents.
Beating Heart Transplant Procedures Using Organs From Donors With Circulatory Death
Authors: Krishnan Aravind , Ruaengsri Chawannuch , Guenthart Brandon A. , Shudo Yasuhiro , Wang Hanjay , Ma Michael R. , MacArthur John Ward , Hiesinger William , Woo Y. Joseph
Published: March 2024

Importance

The use of ex vivo normothermic organ perfusion has enabled the use of deceased after circulatory death (DCD) donors for heart transplants. However, compared with conventional brain death donation, DCD heart transplantation performed with ex vivo organ perfusion involves an additional period of warm and cold ischemia, exposing the allograft to multiple bouts of ischemia reperfusion injury and may contribute to the high rates of extracorporeal membrane oxygenation usage after DCD heart transplantation.

Objective

To assess whether the beating heart method of DCD heart transplantation is safe and whether it has an acceptable rate of extracorporeal membrane oxygenation use postoperatively.

Design, Setting, and Participants

This case series includes 10 patients with end-stage heart failure undergoing DCD heart transplantation at a single academic medical center from October 1, 2022, to August 3, 2023. Data were analyzed from October 2022 to August 2023.

Interventions

Using a beating heart method of implantation of the donor allograft.

Main Outcomes and Measures

The main outcome was primary graft dysfunction necessitating postoperative initiation of mechanical circulatory support. Survival and initiation of mechanical circulatory support were secondary outcomes.

Results

In this case series, 10 consecutive patients underwent DCD heart transplantation via the beating heart method. Ten of 10 recipients were male (100%), the mean (SD) age was 51.2 (13.8) years, and 7 (70%) had idiopathic dilated cardiomyopathy. Ten patients (100%) survived, and 0 patients had initiation of extracorporeal membrane oxygenation postoperatively. No other mechanical circulatory support, including intra-aortic balloon pump, was initiated postoperatively. Graft survival was 100% (10 of 10 patients), and, at the time of publication, no patients have been listed for retransplantation.

Conclusions and Relevance

In this study of 10 patients undergoing heart transplantation, the beating heart implantation method for DCD heart transplantation was safe and may mitigate ischemia reperfusion injury, which may lead to lower rates of primary graft dysfunction necessitating extracorporeal membrane oxygenation. These results are relevant to institutions using DCD donors for heart transplantation.
Medical Spending Among US Households With Children With a Mental Health Condition Between 2017 and 2021
Authors: Loo Theoren M. , Altman Myra , Bravata Dena M. , Whaley Christopher
Published: March 2024

This cross-sectional study examines US household medical spending for children with a mental health condition between 2017 and 2021.
Development of a Health Equity Framework for the US Preventive Services Task Force
Authors: Lin Jennifer S. , Webber Elizabeth M. , Bean Sarah I. , Evans Corinne V.
Published: March 2024

Importance

Clinical practice guidelines can play an important role in mitigating health inequities. The US Preventive Services Task Force (USPSTF) has prioritized addressing health equity and racism in its recommendations.

Objective

To develop a framework that would allow the USPSTF to incorporate a health equity lens that spans the entirety of its recommendation-making process.

Evidence Review

Key guidance, policy, and explanatory frameworks related to health equity were identified, and their recommendations and findings were mapped to current USPSTF methods. USPSTF members as well as staff from multiple entities supporting the USPSTF portfolio were consulted. Based on all the gathered information, a draft health equity framework and checklist were developed; they were then circulated to the USPSTF’s key partners for input and review.

Findings

An equity framework was developed that could be applied to all phases of the recommendation process: (1) topic nomination, selection, and prioritization; (2) development of the work plan; (3) evidence review; (4) evidence deliberation; (5) development of the recommendation statement; and (6) dissemination of recommendations. For each phase, several considerations and checklist items to address are presented. These items include using health equity as a prioritization criterion and engaging a diverse group of stakeholders at the earliest phases in identifying topics for recommendations; developing necessary equity-relevant questions (eg, beyond effectiveness and harms) to address during the protocol phase; using methods in synthesizing the evidence and contextual issues in the evidence review related to specific populations experiencing a disproportionate burden of disease; and examining the magnitude and certainty of net benefit, implementation considerations, risk assessment, and evidence gaps through an equity lens when developing evidence-based recommendations.

Conclusions and Relevance

Executing this entire framework and checklist as described will be challenging and will take additional time and resources. Nonetheless, whether adopted in its entirety or in parts, this framework offers guidance to the USPSTF, as well as other evidence-based guideline entities, in its mission to develop a more transparent, consistent, and intentional approach to addressing health equity in its recommendations.
Partnering With Parents to Dismantle “Good-Death” Narratives
Authors: Broden Elizabeth G. , McCarthy Sarah , Snaman Jennifer M.
Published: March 2024

This Viewpoint dismantles the notion of a “good death” in pediatrics using quotes from bereaved parents and provides actionable alternatives to improve quality end-of-life care for dying children and their families.
Closing the loop – the role of pathologists in digital and computational pathology research
Authors: Rau Tilman T , Cross William , Lastra Ricardo R , Lo Regina C‐L , Matoso Andres , Herrington C Simon
Published: March 2024

An increasing number of manuscripts related to digital and computational pathology are being submitted to The Journal of Pathology: Clinical Research as part of the continuous evolution from digital imaging and algorithm‐based digital pathology to computational pathology and artificial intelligence. However, despite these technological advances, tissue analysis still relies heavily on pathologists' annotations. There are three crucial elements to the pathologist's role during annotation tasks: granularity, time constraints, and responsibility for the interpretation of computational results. Granularity involves detailed annotations, including case level, regional, and cellular features; and integration of attributions from different sources. Time constraints due to pathologist shortages have led to the development of techniques to expedite annotation tasks from cell‐level attributions up to so‐called unsupervised learning. The impact of pathologists may seem diminished, but their role is crucial in providing ground truth and connecting pathological knowledge generation with computational advancements. Measures to display results back to pathologists and reflections about correctly applied diagnostic criteria are mandatory to maintain fidelity during human–machine interactions. Collaboration and iterative processes, such as human‐in‐the‐loop machine learning are key for continuous improvement, ensuring the pathologist's involvement in evaluating computational results and closing the loop for clinical applicability. The journal is interested particularly in the clinical diagnostic application of computational pathology and invites submissions that address the issues raised in this editorial.
Creating intelligent cyberinfrastructure for democratizing AI
Authors: Panda Dhabaleswar K. , Chaudhary Vipin , Fosler‐Lussier Eric , Machiraju Raghu , Majumdar Amit , Plale Beth , Ramnath Rajiv , Sadayappan Ponnuswamy , Savardekar Neelima , Tomko Karen
Published: March 2024

Artificial intelligence (AI) has the potential for vast societal and economic gain; yet applications are developed in a largely ad hoc manner, lacking coherent, standardized, modular, and reusable infrastructures. The NSF‐funded Intelligent CyberInfrastructure with Computational Learning in the Environment AI Institute (“ICICLE”) aims to fundamentally advance edge‐to‐center, AI‐as‐a‐Service, achieved through intelligent cyberinfrastructure (CI) that spans the edge‐cloud‐HPC computing continuum, plug‐and‐play next‐generation AI and intelligent CI services, and a commitment to design for broad accessibility and widespread benefit. This design is foundational to the institute's commitment to democratizing AI. The institute's CI activities are informed by three high‐impact domains: animal ecology, digital agriculture, and smart foodsheds. The institute's workforce development and broadening participation in computing efforts reinforce the institute's commitment to democratizing AI. ICICLE seeks to serve as the national nexus for AI and intelligent CI, and welcomes engagement across its wide set of programs.
Supervisory adaptive control revisited: Linear‐like convolution bounds and tolerance of slow time‐variations
Authors: Lalumiere Craig J. , Miller Daniel E.
Published: March 2024

Supervisory control has been shown to be a very effective approach to adaptive control which ensures step‐tracking, exponential stability, and a degree of robustness to unmodeled dynamics. Here we apply the technique to the classical ‐step‐ahead adaptive control problem: we not only prove exponential stability and tracking of a general bounded reference signal, but also a never‐before‐seen linear‐like convolution bound on the effect of the noise/disturbance. This latter property is then leveraged to not only prove robustness to a degree of unmodeled dynamics, but also to a never‐before‐seen tolerance to a degree of nonlinearities and to slow (on average) plant parameter variations.
Optical Evidence of Compositional Fractioning between Plasma‐Condensed and Melt Pool Matter
Authors: Hubbard Lance , Hilty Floyd , Roy Ankit , Miley Sarah , Overman Nicole , Muller Scott , Fiedler Kevin R. , Horangic Diana , Olszta Matt
Published: March 2024

Control of multicomponent alloys during welding is challenging because it lacks a real‐time understanding of composition. The optical emissions of plasma formed during laser‐induced metal welding correlate with the composition of particles ejected from the melt pool. Plasma emissions observed in this study contain large iron, manganese, chrome, and copper signatures, which match the composition of emitted particles. Particles recovered closest to the melt pool exhibit a core–shell morphology that is composed of iron‐manganese‐chrome intermetallic cores within copper shells. Particles collected farther from the melt pool, do not share this core–shell morphology, though similar elemental compositions are observed. The correlation between plasma optical emissions and particle composition can be used to predict the composition of the melt pool, allowing for real‐time welding and sintering control.
Tuning the FEC‐Related Electrolyte Solvation Structures in Ether Solvents Enables High‐Performance Lithium Metal Anode
Authors: Zhang Yaru , Li Fan , Cao Yu , Yang Min , Han Xinpeng , Ji Yi , Chen Kuizhi , Liang Lixin , Sun Jie , Hou Guangjin
Published: March 2024

Lithium metal is the most promising high‐energy‐density anode. However, it is incompatible with high‐voltage cathodes in ether solvents due to their narrow electrochemical window. Herein, fluoroethylene carbonate (FEC) co‐solvent is introduced to regulate the Li+ solvation structures in ether solvents, including cyclic ether (1,3‐dioxolane [DOL]) and linear glymes with different chain lengths (1,2‐dimethoxyethane [DME], diglyme [G2] and triglyme [G3]). The apparently different effects of ether solvents on solvation ability and interaction strength with FEC are revealed. FEC plays a diverse role and function in 1 m lithium bis(trifluoromethanesulfonyl)imide (LiTFSI)‐ether/FEC electrolyte, thus relevant batteries perform distinct performances due to various ionic dynamics and solid‐electrolyte interphase. The Li+‐solvation structures are explored by Raman and nuclear magnetic resonance spectroscopies. Specifically, part of FEC molecules are inserted into the first solvation shell in 1 m LiTFSI‐DOL/FEC because of the weak solvation ability of DOL and strong interaction of DOL‐FEC, leading to few coordinated TFSI− and sluggish interfacial kinetics. In sharp contrast, FEC as a weak coordinated solvent almost exclusively occupies the second solvation sheath in 1 m LiTFSI‐glyme/FEC, favoring TFSI− coordination and rapid de‐solvation dynamics. Ultimately, the LiNi0.8Co0.1Mn0.1O2/Li battery in G2/FEC presents the most excellent performance, derived from abundant free‐FEC and rapid ionic kinetics.
2D Is Better: Engineering Polydopamine into Cationic Nanosheets to Enhance Anti‐Inflammatory Capability
Authors: Liu Lulu , Lu Chenxin , Tao Zhenchao , Zha Zhengbao , Wang Hua , Miao Zhaohua
Published: March 2024

Polydopamine nanomaterials have emerged as one of the most popular organic materials for the management of oxidative stress‐mediated inflammatory diseases. However, their current anti‐inflammatory ability is still unsatisfactory because of limited phenolic hydroxyl groups, and oxidation reaction‐medicated reactive oxygen and nitrogen species (RONS) scavenging. Herein, via fusing dimension engineering and surface charge engineering, 2D cationic polydopamine nanosheets (PDA NSs) capable of scavenging multiple danger signals to enhance anti‐inflammatory capability are reported. Compared with conventional spherical polydopamine nanoparticles, 2D PDA NSs exhibit three‐ to fourfold enhancement in RONS scavenging capability, which should be attributed to high specific surface area and abundant phenol groups of 2D ultrathin structure. To further enhance the anti‐inflammatory ability, polylysine molecules are absorbed on the surface of PDA NSs to endow the scavenging capability of cell‐free DNA (cfDNA), another typical inflammatory factor to exacerbate the pathogenesis of inflammation. Molecular mechanisms reveal that cationic PDA NSs can concurrently activate Keap1‐Nrf2 and block TLR9 signaling pathway, achieving synergistical inflammation inhibition. As a proof of concept, cationic PDA NSs with RONS and cfDNA dual‐scavenging capability effectively alleviate the inflammatory bowel disease in both delayed and prophylactic models, much better than the clinical drug 5‐aminosalicylic acid.
Electrically Controlled All‐Antiferromagnetic Tunnel Junctions on Silicon with Large Room‐Temperature Magnetoresistance
Authors: Shi Jiacheng , Arpaci Sevdenur , Lopez‐Dominguez Victor , Sangwan Vinod K. , Mahfouzi Farzad , Kim Jinwoong , Athas Jordan G. , Hamdi Mohammad , Aygen Can , Arava Hanu , Phatak Charudatta , Carpentieri Mario , Jiang Jidong S. , Grayson Matthew A. , Kioussis Nicholas , Finocchio Giovanni , Hersam Mark C. , Khalili Amiri Pedram
Published: March 2024

Antiferromagnetic (AFM) materials are a pathway to spintronic memory and computing devices with unprecedented speed, energy efficiency, and bit density. Realizing this potential requires AFM devices with simultaneous electrical writing and reading of information, which are also compatible with established silicon‐based manufacturing. Recent experiments have shown tunneling magnetoresistance (TMR) readout in epitaxial AFM tunnel junctions. However, these TMR structures are not grown using a silicon‐compatible deposition process, and controlling their AFM order required external magnetic fields. Here are shown three‐terminal AFM tunnel junctions based on the noncollinear antiferromagnet PtMn3, sputter‐deposited on silicon. The devices simultaneously exhibit electrical switching using electric currents, and electrical readout by a large room‐temperature TMR effect. First‐principles calculations explain the TMR in terms of the momentum‐resolved spin‐dependent tunneling conduction in tunnel junctions with noncollinear AFM electrodes.
Binary Solvent Induced Stable Interphase Layer for Ultra‐Long Life Sodium Metal Batteries
Authors: Vaidyula Rinish Reddy , Nguyen Mai H. , Weeks Jason. A. , Wang Yixian , Wang Ziqing , Kawashima Kenta , Paul‐Orecchio Austin G. , Celio Hugo , Dolocan Andrei , Henkelman Graeme , Mullins C. Buddie
Published: March 2024

Sodium foil, promising for high‐energy‐density batteries, faces reversibility challenges due to its inherent reactivity and unstable solid electrolyte interphase (SEI) layer. In this study, a stable sodium metal battery (SMB) is achieved by tuning the electrolyte solvation structure through the addition of co‐solvent 2‐methyl tetrahydrofuran (MTHF) to diglyme (Dig). The introduction of cyclic ether‐based MTHF results in increased anion incorporation in the solvation structure, even at lower salt concentrations. Specifically, the anion stabilization capabilities of the environmentally sustainable MTHF co‐solvent lead to a contact‐ion pair‐based solvation structure. Time‐of‐flight mass spectroscopy analysis reveals that a shift toward an anion‐dominated solvation structure promotes the formation of a thin and uniform SEI layer. Consequently, employing a NaPF6‐based electrolyte with a Dig:MTHF ratio of 50% (v/v) binary solvent yields an average Coulombic efficiency of 99.72% for 300 cycles in Cu||Na cell cycling. Remarkably, at a C/2 cycling rate, Na||Na symmetric cell cycling demonstrates ultra‐long‐term stability exceeding 7000 h, and full cells with Na0.44MnO2 as a cathode retain 80% of their capacity after 500 cycles. This study systematically examines solvation structure, SEI layer composition, and electrochemical cycling, emphasizing the significance of MTHF‐based binary solvent mixtures for high‐performance SMBs.
Impact of Band‐gap Gradient in Semi‐Transparent and Bifacial Ultra‐Thin Cu(In,Ga)Se2 Solar Cells
Authors: Rath Christoph , Gao Yao , Koehler Tristan , Schmid Martina
Published: March 2024

Ultra‐thin Cu(In,Ga)Se2 (CIGSe) solar cells on transparent conductive oxide back contact reduce the material consumption of rare indium and gallium and simultaneously exhibit great potential for semi‐transparent bifacial application. For highly efficient CIGSe solar cells, a steep back Ga grading and Na treatment are expected. However, Na will promote the formation of highly resistive GaOx at the rear interface owing to Ga accumulation. In this work, the three‐stage co‐evaporation process is renewed and the effect of the deposition sequence in the first stage on the Ga distribution as well as the cross‐correlated influence of Na is explored. In particular, the standard deposition sequence of Ga+In is altered to start with In. When a thin In layer is pre‐deposited on the back contact, the fill factor and efficiency increase. The deposition of In+Ga+In in the first stage of CIGSe growth leads to efficiencies 28% (on average) higher than for the standard deposition sequence of Ga+In. Additionally, 2.74% efficiency is reached under rear and 9.32% under simultaneous front and rear illumination. Therefore, adapting the deposition sequence in the first stage of CIGSe growth is identified as a key to improving the device performance on transparent back contact.
Luminescent Properties Variation Caused by Metal Cations Effect on the Deep Energy Levels in Cu(I) and Ag(I) Complexes
Authors: Jia Ji‐Hui , Zhang Deng‐Chao , Liang Dong , Wang Qianting , Wang Zhan‐Qi , Zhang Lei , Lu Can‐Zhong
Published: March 2024

In this work, a donor‐acceptor (D‐A) type ligand is prepared to construct Cu(I) and Ag(I) complexes. These complexes possess similar molecular structures, distributions of molecular orbitals, and distributions of electrons and holes in excited states. However, they exhibit distinct photophysical properties, such as luminescent spectra and transient photo‐luminescent decay spectra. Through analysis of deep‐lying molecular orbitals in a tetrahedral field, it is determined that the variation in d‐p π conjugation between the metal cation's d‐orbitals and the π orbitals of the electron‐acceptor part of the D‐A ligand is the reason for the different photophysical properties. This research contributes to an in‐depth understanding of the role of metal ions in luminescent complexes, providing insights from the perspective of coordination chemistry.
Suppressing Trap‐Assisted Nonradiative Recombination via Interface Modification for Achieving Efficient Organic Solar Cells
Authors: Ge Zhongwei , Qiao Jiawei , Song Jiali , Li Xiaoming , Fu Jiawei , Fu Zhen , Gao Jiaxin , Tang Xian , Jiang Lang , Tang Zheng , Lu Guanghao , Hao Xiaotao , Sun Yanming
Published: March 2024

Trap states in organic solar cells (OSCs) can capture free charges, leading to a reduction in current density and significant energy loss. Since charge collection is primarily dependent on the interface layer, minimizing trap states at interfaces can effectively suppress energy losses, a topic that has been rarely explored. Herein, an interface strategy is proposed by combining Me‐4PACz and PEDOT:PSS to mitigate the trap‐assisted nonradiative recombination at the hole transport layer (HTL). OSCs based on the Me‐4PACz/PEDOT:PSS exhibit reduced trap densities and low energy losses compared to devices fabricated with a single‐layer HTL. This reduction can be attributed to a lower nonradiative recombination rate during hole transport at the interface. Changes in the work function of the two interlayers due to contact result in the existence of a built‐in potential inside the composite interlayer, promoting charge collection and reducing energy loss from charge recombination. Furthermore, the composite HTL interface induces vertical phase separation of active layer, leading to significant improvements of the fill factor for OSCs. As a result, high power conversion efficiencies (PCEs) of 18.70% and 19.02% are achieved for binary all‐polymer solar cells and polymer donor/small molecule acceptor solar cells, respectively.