bluuebunny/crossref_metadata_2025_split huggingface dataset:
Simplified Synthetic TMC‐95A/B Analogues Retain the Potency of Proteasome Inhibitory Activity
Authors: Yang Zhi‐Qiang , Kwok Benjamin H. B. , Lin Songnian , Koldobskiy Michael A. , Crews Craig M. , Danishefsky Samuel J. 
Published: June 2003

AbstractThe proteasome regulates diverse intracellular processes, including cell‐cycle progression, antigen presentation, and inflammatory response. Selective inhibitors of the proteasome have great therapeutic potential for the treatment of cancer and inflammatory disorders. Natural cyclic peptides TMC‐95A and B represent a new class of noncovalent, selective proteasome inhibitors. To explore the structure–activity relationship of this class of proteasome inhibitors, a series of TMC‐95A/B analogues were prepared and analyzed. We found that the unique enamide functionality at the C8 position of TMC‐95s can be replaced with a simple allylamide. The asymmetric center at C36 that distinguishes TMC‐95A from TMC‐95B but which necessitates a complicated separation of the two compounds can be eliminated. Therefore, these findings could lead to the development of more accessible simple analogues as potential therapeutic agents.
Relative Stability of Major Types of β‐Turns as a Function of Amino Acid Composition: A Study Based on Ab Initio Energetic and Natural Abundance Data
Authors: Perczel András , Jákli Imre , McAllister Michael A. , Csizmadia Imre G. 
Published: June 2003

AbstractFolding properties of small globular proteins are determined by their amino acid sequence (primary structure). This holds both for local (secondary structure) and for global conformational features of linear polypeptides and proteins composed from natural amino acid derivatives. It thus provides the rational basis of structure prediction algorithms. The shortest secondary structure element, the β‐turn, most typically adopts either a type I or a type II form, depending on the amino acid composition. Herein we investigate the sequence‐dependent folding stability of both major types of β‐turns using simple dipeptide models (‐Xxx‐Yyy‐). Gas‐phase ab initio properties of 16 carefully selected and suitably protected dipeptide models (for example Val‐Ser, Ala‐Gly, Ser‐Ser) were studied. For each backbone fold most probable side‐chain conformers were considered. Fully optimized 321G RHF molecular structures were employed in medium level [B3LYP/6‐311++G(d,p)//RHF/3‐21G] energy calculations to estimate relative populations of the different backbone conformers. Our results show that the preference for β‐turn forms as calculated by quantum mechanics and observed in Xray determined proteins correlates significantly.
Controlling Short‐ and Long‐Range Electron Transfer Processes in Molecular Dyads and Triads
Authors: Sánchez Luis , Pérez Ignacio , Martín Nazario , Guldi Dirk M. 
Published: June 2003

AbstractNovel π‐extended tetrathiafulvalene (exTTF)‐based donor acceptor hybrids—dyads and triads—have been synthesized following a multistep synthetic procedure. Cyclic voltammetry and absorption spectroscopy, conducted in room temperature solutions, reveal features that are identical to the sum of the separate donor and acceptor moieties. Steady‐state and time‐resolved photolytic techniques confirm that upon photoexcitation of the fullerene chromophore, rapid (1.25×1010 s−1) and efficient (67 %) charge separation leads to long‐lived, charge‐separated radical pairs. Typical lifetimes for the dyad ensembles range between 54 and 460 ns, with the longer values found in more polar solvents. This indicates that the dynamics are located in the 'normal region' of the Marcus curve. In the triads, subsequent charge shifts transform the adjacent radical pair into the distant radical pair, for which we determined lifetimes of up to 111 μs in DMF—values never previously accomplished in molecular triads. In the final charge‐separated state, large donor‐acceptor separation (center‐to‐center distances: ≈30 Å) minimizes the coupling between reduced acceptor and oxidized donor. Analysis of the charge recombination kinetics shows that a stepwise mechanism accounts for the unusually long lifetimes.
Potassium Selective Calix[4]semitubes
Authors: Webber Philip R. A. , Cowley Andrew , Drew Michael G. B. , Beer Paul D. 
Published: June 2003

AbstractA new class of ionophore consisting of two calix[4]arene units linked through the lower rim by two ethylene chains, in combination with propyl ether and phenolic functional groups, has been developed. These calix[4]semitube molecules exhibit remarkable selectivity and fast complexation kinetics for potassium over all Group 1 metal cations. Molecular modelling studies, using structural models derived from crystallographic data, suggest the potassium cation is complexed by a horizontal, side‐on route and not through the calix[4]arene annulus. The length of the bridging alkylene chain between the respective calix[4]arenes of the semitube structure dictates the strength and selectivity of alkali metal cation binding.
Facile Optical Resolution of tert‐Butanethiosulfinate by Molecular Complexation with (R)‐BINOL and Study of Chiral Discrimination of the Diastereomeric Complexes
Authors: Liao Jian , Sun Xiaoxia , Cui Xin , Yu Kaibei , Zhu Jin , Deng Jingen 
Published: June 2003

AbstractAn important synthon, tert‐butanethiosulfinate (2), has been effectively resolved by forming molecular complexes with (R)‐2,2′‐dihydroxy‐1,1′‐binaphthyl (BINOL, 3) in high enantioselectivity (>99 % ee). The present procedure represents the first example of the resolution of thiosulfinate. The mechanism of chiral discrimination is discussed in terms of molecular recognition based on IR and Xray analyses of the diastereomeric complexes during the resolution. In the less‐soluble complex, (R)‐3 and (R)‐2 self‐assembled as a linear supramolecule; however, in the more‐soluble complex, (R)‐3 and (S)‐2 formed a simple bimolecular complex by one stronger hydrogen bond. Hydrogen bonding is the major driving force for effective resolution.
Polymer‐Supported Triazenes as Smart Reagents for the Alkylation of Carboxylic Acids
Authors: Erb Bernhard , Kucma Jean‐Philippe , Mourey Sandrine , Struber Fritz 
Published: June 2003

AbstractStarting from polystyrene, a simple four‐step synthesis of polymer‐supported alkyltriazenes (alkyl=Me, Et, benzyl) is described. With this synthesis, a loading capacity of 2.2 mmol g−1 can be reached. The most prominent application of these polymer‐supported reagents is the rapid, highly selective and high‐yielding esterification of carboxylic acids, which involves a simple “mix and filter off” procedure at room temperature. If stored in a refrigerator, these reagents are stable for many months and they can be recycled several times.
Phospholipase A2 Hydrolysis of Mixed Phospholipid Vesicles Formed on Polyelectrolyte Hollow Capsules
Authors: Ge Liqin , Möhwald Helmuth , Li Junbai 
Published: June 2003

AbstractMixtures of the phospholipids L‐α‐dimyristoylphosphatidic acid (DMPA) and L‐α‐dipalmitoylphosphatidylcholine (DPPC) have been successfully adsorbed onto the charged surface of multilayer polyelectrolyte capsules to form a novel vesicle. Leaving such vesicles in phospholipase A2 solution, we observed the hydrolysis reaction on the surface of the lipid/polymer vesicles and a permeability change before and after the reaction by confocal‐laser scanning microscopy (CLSM). A capsule with adjustable permeability was constructed. This method may provide new features for drug‐release vesicles.
Synthesis and Fluorescence Ion‐Sensory Properties of the First Dehydropyridoannulene‐Type Cyclophane with Enforced Exotopic Metal Ion Binding Sites
Authors: Baxter Paul. N. W. 
Published: June 2003

AbstractThe new twistophane 4 has been synthesised, which comprises a conjugated dehydropyridoannulene‐type macrocyclic scaffold with outwardly projecting nitrogen‐donor sites for the purpose of metal ion coordination. The macrocyclíc structure of 4 was assigned by using spectroscopic methods, and shown to exist in a twisted and chiral ground state conformation by semi‐empirical theoretical calculations. A detailed spectroscopic investigation into the metal ion binding properties of 4 and precursor 11 revealed that they functioned as selective complexants, affording a fluorescence quenching output response characteristic of PdII and HgII ions. Furthermore, 4 also signalled the presence of FeII, CoII, NiII and AgI ions by the precipitation of coordination polymers, and exhibited reversible proton‐triggered fluorescence quenching behaviour. Macrocycle 4 thus represents a unique type of molecular sensory platform, which may find a wealth of potential applications such as the detection of heavy‐metal pollutants, as well as for the fabrication of proton‐switchable materials and coordination polymers with novel electronic and magnetic properties.
CLIP‐170 interacts with dynactin complex and the APC‐binding protein EB1 by different mechanisms
Authors: Goodson Holly V. , Skube Susan B. , Stalder Romaine , Valetti Caterina , Kreis Thomas E. , Morrison Ewan E. , Schroer Trina A. 
Published: June 2003

AbstractCLIP‐170 is a “cytoplasmic linker protein” implicated in endosome‐microtubule interactions and in control of microtubule dynamics. CLIP‐170 localizes dynamically to growing microtubule plus ends, colocalizing with the dynein activator dynactin and the APC‐binding protein EB1. This shared “plus‐end tracking” behavior suggests that CLIP‐170 might interact with dynactin and/or EB1. We have used site‐specific mutagenesis of CLIP‐170 and a transfection/colocalization assay to address this question in mammalian tissue culture cells. Our results indicate that CLIP‐170 interacts, directly or indirectly, with both dynactin and EB1. We find that the CLIP‐170/dynactin interaction is mediated by the second metal binding motif of the CLIP‐170 tail. In contrast, the CLIP‐170/EB1 interaction requires neither metal binding motif. In addition, our experiments suggest that the CLIP‐170 /dynactin interaction occurs via the shoulder/sidearm subcomplex of dynactin and can occur in the cytosol (i.e., it does not require microtubule binding). These results have implications for the targeting of both dynactin and EB1 to microtubule plus ends. Our data suggest that the CLIP‐170/dynactin interaction can target dynactin complex to microtubule plus ends, although dynactin likely also targets MT plus ends directly via the microtubule binding motif of the p150Glued subunit. We find that CLIP‐170 mutants alter p150Glued localization without affecting EB1, indicating that EB1 can target microtubule plus ends independently of dynactin. Cell Motil. Cytoskeleton 55:156–173, 2003. © 2003 Wiley‐Liss, Inc.
Renal cell carcinoma with retroperitoneal lymph nodes
Authors: Pantuck Allan J. , Zisman Amnon , Dorey Frederich , Chao Debby H. , Han Ken‐ryu , Said Jonathan , Gitlitz Barbara , Belldegrun Arie S. , Figlin Robert A. 
Published: May 2003

AbstractBACKGROUNDThe current study was performed to determine the impact of the presence of retroperitoneal lymphadenopathy on the survival and response to immunotherapy of patients with metastatic renal cell carcinoma (RCC).METHODSA retrospective cohort study was performed with outcome assessment based on the chart review of demographic, clinical, and pathologic data from 1087 patients. Patients with RCC who did not present with metastatic disease, who did not undergo nephrectomy as part of their cancer treatment, and those in whom either the lymph node (N) or metastatic (M) status was unknown, were excluded. A total of 322 M1 patients who met these criteria and who underwent nephrectomy for unilateral RCC formed the principal study population.RESULTSTwo hundred thirty‐six patients presented with N0M1 disease and 86 patients presented with N+M1 disease. In M1 patients, the presence of positive regional lymph nodes was associated with larger sized, higher grade, locally advanced primary tumors that were more commonly associated with sarcomatoid features. N0M1 patients were more likely to achieve an objective response to systemic immunotherapy compared with N+M1 patients (P = 0.01). N+M1 patients overall had worse short‐term and long‐term survival compared with N0M1 patients, with a median survival of 10.5 months compared with 20.4 months, respectively. The median survival of N0M1 patients was improved to 28 months in those who received adjunctive immunotherapy (P = 0.0008), whereas the median survival of patients with N+M1 disease was the same in those treated with and those treated without adjunctive immunotherapy (P = 0.18).CONCLUSIONSEven in the modern era of systemic immunotherapy, the presence of regional lymphadenopathy exerts a detrimental effect on the survival of patients with metastatic RCC. Lymph node status is a strong predictor of the failure to achieve either an objective immunotherapy response or an improvement in survival when immunotherapy is given as an adjunctive treatment after cytoreductive nephrectomy. However, in multivariate analysis, including both clinical and pathologic variables, lymph node status was found to have less of an impact on survival than primary tumor stage and grade and patient performance status. Cancer 2003;97:2995–3002. © 2003 American Cancer Society.DOI 10.1002/cncr.11422
Hepatic focal nodular hyperplasia in children previously treated for a solid tumor
Authors: Bouyn Celine Icher‐De , Leclere Jerome , Raimondo Graziella , le Pointe Hubert Ducou , Couanet Dominique , Valteau‐Couanet Dominique , Hartmann Olivier 
Published: May 2003

AbstractBACKGROUNDThe detection of hepatic nodules, particularly in patients treated for a previous malignancy, raises a diagnostic dilemma. Focal nodular hyperplasia (FNH) of the liver is an uncommon, benign tumor in children and must be differentiated from malignant hepatic lesions. The etiology of FNH is obscure, and its pathogenesis is poorly understood. FNH may be a reaction to localized vascular abnormalities and circulatory disturbances. The goal of the current study was to identify risk factors for the occurrence of FNH in children who had received prior treatment for a malignant tumor.METHODSThe current retrospective study examined 14 cases of FNH in pediatric patients who previously had been treated for a malignancy. Diagnosis was based on clinical and radiologic findings and was proven histologically in four cases.RESULTSFNH lesions were discovered by chance during routine examination in 78% of patients. The incidence of FNH was particularly high in the current series (0.45%) compared with the incidence in the general pediatric population. High doses of alkylating agents (e.g., busulfan or melphalan), venoocclusive disease, and liver radiotherapy may be responsible for injury to the vascular endothelium and subsequent localized circulatory disturbances. FNH is characterized by the absence of complications after its detection; therefore, only close follow‐up is recommended.CONCLUSIONSFNH appears to be a late complication of an iatrogenic vascular disease in children with a history of malignancy. Cancer 2003;97:3107–13. © 2003 American Cancer Society.DOI 10.1002/cncr.11452
Invariant measures on G/Γ for split simple Lie groups G
Authors: Einsiedler Manfred , Katok Anatole 
Published: June 2003

AbstractWe study the left action α of a Cartan subgroup on the space X = G/Γ, where Γ is a lattice in a simple split connected Lie group G of rank n > 1. Let μ be an α‐invariant measure on X. We give several conditions using entropy and conditional measures, each of which characterizes the Haar measure on X. Furthermore, we show that the conditional measure on the foliation of unstable manifolds has the structure of a product measure. The main new element compared to the previous work on this subject is the use of noncommutativity of root foliations to establish rigidity of invariant measures. © 2003 Wiley Periodicals, Inc.
What's so different about older people?
Authors: Woods Bob T. 
Published: May 2003

AbstractThis paper introduces the special section on psychological therapy with older adults. It is widely accepted that the provision of health services, including psychological services, to older people is subject to ageism. There is no justification for arbitrary age cut‐offs in making decisions about the appropriateness of psychological treatment, and good practice with younger adults is just as applicable in later life. The specialist aspects of working with older adults, which are highlighted in this paper, include working with people with cognitive impairment, the recognition of the importance and impact of past events and the importance of the social context in which older people find themselves. These aspects are not unique to work with older adults, and indeed should also be considered in work with younger adults. However, they form a constant backdrop to psychological therapy with older adults, which has an increasingly strong evidence‐base to underpin it. Copyright © 2003 John Wiley & Sons, Ltd.
Working with older people: implications for schema theory
Authors: James Ian A. 
Published: May 2003

AbstractWorking with older people requires therapists to examine issues regarding information processing often not dealt with by therapists working with younger patients. It is suggested that these processing issues may be especially salient to therapists working with older people, owing to their greater reliance on their theoretical knowledge of memory (declarative, procedural, working etc.) and neuropsychology. The present paper draws on this more holistic background, and presents a theory designed to facilitate therapy in general: particularly schema focused therapy for both the young and old.Employing knowledge and models routinely used in an older people's setting, this paper redefines schemata in terms of networks of information and memories rather than viewing them solely as self‐referent beliefs (e.g. I am worthless; I am inadequate). This change in perspective allows us to see schemata more validly as elaborate structures, composed of many elements, including behavioural, emotional and visceral features. A rationale in support of this holistic perspective is outlined, together with a review of its implications in terms of schema assessment and change techniques. Copyright © 2003 John Wiley & Sons, Ltd.
Some implications of attachment theory for understanding psychological functioning in old age: an illustration from the long‐term psychological effects of World War Two
Authors: McCarthy Gerard , Davies Stephen 
Published: May 2003

AbstractThis paper aims to outline some of the implications of attachment theory for understanding the way in which older adults deal with the salient developmental tasks of later life. The paper aims to illustrate this theme by exploring the way in which negative childhood attachment‐related experiences brought about by the Second World War may have adversely affected the way in which some of the current generation of older adults function in old age. The paper begins with a brief introduction to attachment theory and research and then moves on to consider some of the ways in which the Second World War may have affected the attachment‐related experiences of the United Kingdom population. Finally, some of the clinical implications of attachment theory are briefly discussed, and the implications for assessing and treating older adults are considered. Copyright © 2003 John Wiley & Sons, Ltd.
When late life brings a diagnosis of Alzheimer's Disease and early life brought trauma. A cognitive‐analytic understanding of loss of mind
Authors: Sutton Laura 
Published: May 2003

AbstractThis paper contrasts the loss of mind from the loss of brain cells in Alzheimer's Disease and other neurodegenerative conditions with the threats to one's mind from the mindlessness of others from a cognitive‐analytic perspective. Case studies are presented that show how the therapeutic framework of Cognitive‐Analytic Therapy (CAT: Ryle 1990, 1995, 1997) can bring containment for both client and therapist for clients facing this dilemma, particularly when past trauma is potentially overwhelming. This is set in a dialogue with the pioneering work of Tom Kitwood (1990, 1995, 1997) in dementia care, in which Kitwood's thesis of the ‘malignant social psychology’ surrounding people with dementia is re‐stated in terms of ‘reciprocal roles’ developed in Cognitive‐Analytic Therapy. Copyright © 2003 John Wiley & Sons, Ltd.
Life review: treating the dyadic family unit with dementia
Authors: Haight Barbara K. , Bachman David L. , Hendrix Shirley , Wagner Mark T. , Meeks Alison , Johnson Jolene 
Published: May 2003

AbstractThe application of reminiscence with people with dementia is reviewed, and promising findings identified. This paper distinguishes life review from other, less specific, forms of reminiscence. It is carried out over several months, on a one‐to‐one basis and covers the person's entire life in a structured way, encouraging evaluation of memories and events. A life story is a tangible outcome of the life review process, and is created by the person with dementia, containing pictures and words and other memorabilia selected by the person him/herself. This paper describes early qualitative and quantitative results from a project evaluating life review work carried out jointly with the person with dementia and his caregiver, compared with life review carried out with the caregiver alone, and an untreated control group. 22 dyads have entered the study. The mood of the person with dementia (as rated by the caregiver) was significantly improved for those people with dementia participating actively in the life review, although their cognitive function decreased slightly. Caregivers participating in the life review, alone or with the person with dementia, reported significantly reduced burden and behaviour problems in the person with dementia. Two case studies illustrate how life review, with its emphasis on active listening, may enable the person to ‘move on’ from being apparently preoccupied with particular memories or concerns. Further evaluative work is required to confirm the usefulness of this promising therapeutic approach with people with dementia. Copyright © 2003 John Wiley & Sons, Ltd.
A series of brief cognitive therapy interventions with people experiencing both dementia and depression: a description of techniques and common themes
Authors: Scholey Keith A , Woods Bob T. 
Published: May 2003

AbstractDepression in the context of dementia is common, but treatment approaches are under‐developed. This paper presents one of the first case series of cognitive therapy interventions with individuals with concurrent dementia and depression. Seven patients diagnosed as having mild/moderate dementia (MMSE range 20–30) each received eight individual cognitive therapy sessions. On average, there was a statistically significant 3.7 point improvement on the Geriatric Depression Scale (30 items). Two of the patients showed a significant Reliable Change Index. It is argued that with some modification a cognitive therapy approach can facilitate a reduction in the level of depression experienced by this particular group. In this sample, impaired cognitive abilities did not prove to be an insurmountable obstacle to the application of cognitive therapy. A number of common themes arose, including attributions about the cause of the cognitive impairment, catastrophic thinking regarding the implications of the diagnosis and the emergence of previous trauma. Whilst a full understanding of the interrelationship between dementia and depression has yet to be developed, a body of literature is developing that describes some of the skills necessary for this type of work. Controlled studies of psychological treatments for depression in dementia are now required. Copyright © 2003 John Wiley & Sons, Ltd.