text:
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1058 Current Topics in Medicinal Chemistry, 2011, 11, 1058-1067
1568-0266/11 $58.00+.00 © 2011 Bentham Science Publishers Ltd.
Uridine Function in the Central Nervous System
Arpád Dobolyi1,*, Gábor Juhász2, Zsolt Kovács3 and Julianna Kardos4
1Neuromorphological and Neuroendocrine Research Laboratory, Department of Anatomy, Histology and Embryology,
Semmelweis University and the Hungarian Academy of Sciences, H-1094 Budapest, Hungary; 2Laboratory of Pro-
teomics, Institute of Biology, Eötvös Loránd University, H-1117 Budapest, Hungary; 3Department of Zoology, Univer-
sity of West Hungary, Savaria Campus, Szombathely, Hungary; 4Department of Neurochemistry, Institute of Biomolecu-
lar Chemistry, Chemical Research Center, Hungarian Academy of Sciences, H-1025 Budapest, Hungary
Abstract: In the adult nervous system, the major source of nucleotide synthesis is the salvage pathway. Uridine is the ma-
jor form of pyrimidine nucleosides taken up by the brain. Uridine is phosphorylated to nucleotides, which are used for
DNA and RNA synthesis as well as for the synthesis of membrane constituents and glycosylation. Uridine nucleotides and
UDP-sugars may be released from neuronal and glial cells. Plasmamembrane receptors of 7 transmembrane domains have
been identified that recognize UTP, UDP, and UDP-sugar conjugates. These receptors are called P2Y2 and P2Y4, P2Y6,
and P2Y14 receptors, respectively. In addition, binding sites for uridine itself have also been suggested. Furthermore,
uridine administration had sleep-promoting and anti-epileptic actions, improved memory function and affected neuronal
plasticity. Information only starts to be accumulating on potential mechanisms of these uridine actions. Some data are
available on the topographical distribution of pyrimidine receptors and binding sites in the brain, however, their exact role
in neuronal functions is not established yet. There is also a scarcity of data regarding the brain distribution of other com-
ponents of the pyrimidine metabolism although site specific functions exerted by their receptors might require different
metabolic support. Despite the gaps in our knowledge on the neuronal functions of pyrimidine nucleosides, their therapeu-
tic utilization is appealing. They have been suggested for the treatment of epileptic and neurodegenerative diseases as neu-
roprotective agents. In addition, the development of traditional drugs acting specifically on pyrimidine receptor subtypes
is also promising as a new direction to treat neurological disorders.
Keywords: Epilepsy, neural function, neuronal plasticity, nucleoside transport, nucleotide receptor, pyrimidine salvage, sleep,
therapeutic application.
the brain. It supplies nervous tissue with the pyrimidine ring,
and in turn, participates in a number of important metabolic
pathways. Uridine and its nucleotide derivatives may also
have an additional role in the function of the central nervous
system as signaling molecules. There are established signal-
ing molecules in the brain, such as amino acids, and adeno-
sine, which are also available in large pools as metabolites.
Adenosine is not a typical neuronal signaling molecule since
it is not released from synapses on an action potential trig-
ger. Rather, it is produced with the extracellular degradation
of ATP or is released via nucleoside transporters [1, 2],
which are not highly specific to any particular nucleoside [3].
In contrast to adenosine, the neuromodulator role of uridine
is not established yet with certainty. However, an increasing
body of evidence suggests that uridine participates in the
control of physiological and pathophysiological brain func-
tions. This review is an attempt to summarize the available
data supporting that uridine plays a role in neuronal func-
tions by collecting information from the literature about the
potential mechanisms behind its putative neuromodulator
Uridine has crucial role in the pyrimidine metabolism of
*Address correspondence to this author at the Laboratory of Neuromorphol-
ogy, Department of Anatomy, Histology and Embryology, Semmelweis
University, Tüzolto u. 58, Budapest, H-1094, Hungary;
Tel: +36-1-215-6920 / 53634; Fax: +36-1-218-1612;
E-mail: firstname.lastname@example.com
function. Transport of uridine as well as its metabolism in
brain cells is summarized and we also refer to excellent re-
cent reviews on this topic [4, 5]. Finally, the potential thera-
peutic applications of uridine are discussed.
from the intestine in the form of nucleosides after degrada-
tion from nucleic acids and nucleotides [6]. As opposed to
purines that are further degraded in intestinal epithelial cells
to uric acid and pentose moiety, a portion of uridine is trans-
ported in the plasma [4, 7]. The liver plays a pivotal role in
purine and pyrimidine metabolism because virtually all of
the nucleosides in the blood stream derive from their secre-
tion from the liver following de novo nucleoside synthesis to
keep a steady level of nucleosides in the plasma [8, 9]. There
are species differences in the plasma levels of pyrimidines.
In human and gerbil, uridine is the predominant form due to
cytidine deaminase activity in plasma, while in rats the
plasma concentration of cytidine is higher [4]. Although a
low level of do novo pyrimidine synthesis has been demon-
strated in the brain [10], most of the pyrimidine content of
the brain is supplied by the uptake of pyrimidine nucleo-
sides, particularly uridine from the plasma [11], which is
required for the maintenance of electrophysiological activity
in the brain [12]. There are 4 genes encoding the equilibra-
The purine and pyrimidine bases are mostly absorbed
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Brain Function of Uridine Current Topics in Medicinal Chemistry, 2011, Vol. 11, No. 8 1059
tive (ENT1-4) and 3 genes encoding the Na+-dependent con-
centrative (CNT1-3) nucleoside transporters [3, 5]. Brain
endothelial cells contain ENT1, ENT2 and CNT2 while
choroid plexus epithelial cells also express CNT3 [13]. In the
human choroid plexus, ENT2 and CNT3 are dominant [14].
In brain endothelial cells, CNT2 and ENT2 are present on
the cell surface facing the interstitial fluid. In the choroid
plexus, CNTs are present on the surface facing the cerebro-
spinal fluid. The opposite cell surfaces contain only equili-
brative transporters [13]. These transporters can all transport
uridine (as well as purines) and are responsible for the trans-
port of uridine in and out of the brain [4]. Since the affinity
of CNT2 is higher for uridine than cytidine [15, 16], the main
form of pyrimidine uptake into the brain is uridine even in
species like rat where plasma cytidine level is relatively high
Neurons and glial cells also take up uridine from the ex-
tracellular space via equilibrative and concentrative nucleo-
side transporters. Investigation of the topographical and cel-
lular distribution of the nucleoside transporters has started
recently and initial results suggest differences in the localiza-
tion of different types of transporters within the brain [18-
21]. Spatial differences in the uptake process may result in
differences in the local extracellular concentration of uridine,
which has been reported to be lower in the thalamic extracel-
lular space than in the cerebrospinal fluid [22, 23]. Uridine
tissue levels also show uneven spatial distributions in the
brain [24, 25] and depend on gender and age as well [26].
Uridine transport may also be affected by the activity of a
particular brain region as extracellular uridine levels in-
creased following pharmacological depolarization [27, 28]
and experimentally induced epilepsy [29, 30].
synthesis Fig. (1). This enzyme as well as subsequent
uridine-phosphorylating enzymes are of low affinity, and
therefore unsaturated with their substrates. Consequently,
providing the brain with uridine increases its formation and
levels of UTP [4]. On the other hand, uridine kinase is inhib-
ited by UTP and CTP, the final products of the pyrimidine
salvage pathway. Thus, at relatively low UTP and CTP level,
uridine is mainly anabolized to uridine nucleotides. In con-
trast, at relatively high UTP and CTP levels the inhibition of
uridine kinase channels uridine towards phosphorolysis. The
ribose-1-phosphate is then transformed into phosphoribo-
sylpyrophosphate (PRPP), which is used for purine salvage
synthesis [31].
UTP can be aminated to CTP by CTP synthetase. This
metabolic sequence explains how the brain gets CTP – to use
in the Kennedy Cycle – even in species like humans, in
which cytidine level is low in the circulation. UTP and CTP
are both required for the formation of RNA Fig. (1). CTP
also provides CDP-choline and CDP-ethanolamine for mem-
brane formation [32, 33]. Uridine nucleotides can also be
used for the synthesis of dUTP, which is further processed to
dTTP for DNA synthesis. dUTP pyrophosphatase is a key
enzyme of dTTP formation and also serves to prevent the
incorporation of dUTP into DNA [34]. Another important
metabolic function of UTP is to serve as an intermediate for
Uridine kinase catalyzes the first step of UTP salvage
sugar conjugates such as UDP-glucose and UDP-galactose
(UDP-sugars), which are in turn further metabolized for gly-
cogen synthesis [35] or enter the endoplasmic reticulum (ER)
for protein and lipid glycosylation [36]. Relatively recently,
an additional function of UTP, UDP, and UDP-sugars was
revealed. These uridine derivatives are released into the ex-
tracellular space where they act on specific plasmamembrane
receptors [37-40]. Considering these important roles of
uridine in the neuronal metabolism, it is not surprising that
deficiencies in uridine metabolism or its pharmacological
alterations can lead to neurological symptomes [41].
Fig. (1). Schematic diagram of the metabolic pathways of uridine in
the brain.
Abbreviations: CDP - cytidine-5'-diphosphate; CTP - cytidine-5'-
triphosphate; dCTP - deoxycytidine-5'-triphosphate; dTTP - de-
triphosphate; ER, endoplasmic reticulum; UDP - uridine-5'-
diphosphate; UMP - uridine-5'-monophosphate; Ura - uracil; Urd -
uridine; UTP - uridine-5'-triphosphate. Key enzymes are shown by
numbers: 1 - Uridine kinase; 2 – UMP kinase; 3 – ribonucleotide
reductase; 4 - dUTP pyrophosphatase; 5 - CTP synthetase.
dUTP - deoxyuridine-5'-
have been suggested. In this chapter, we summarize the find-
ings that support the neural actions of uridine.
Several different effects of uridine on the nervous system
The Effect of Uridine on Sleep
promoting substance purified from the brainstem of sleep-
deprived rats [42, 43]. A 10-h intracerebroventricular infu-
sion of 10 pmol of uridine increased slow wave sleep as well
as paradoxical sleep due to increases in the frequencies of
sleep episodes but not to their durations [44]. Intraperito-
neally injected uridine resulted in a dose-dependent transient
excess of slow-wave sleep if administered shortly before
onset of the dark period. The sleep latency was remarkably
shortened [45]. A brain area in the preoptic region of the hy-
pothalamus, the so-called ventrolateral preoptic nucleus was
described as a sleep center [46]. Interestingly, localized elec-
trolytic lesions made bilaterally in the lateral preoptic area in
rats eliminated the slow wave sleep-promoting effect of
uridine [47] suggesting that the integrity of preoptic sleep
Uridine was identified as an active component of sleep-
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1060 Current Topics in Medicinal Chemistry, 2011, Vol. 11, No. 8
Dobolyi et al.
centers is crucial for slow wave sleep-promoting action of
Uridine in Epilepsy Models
some decades ago as uridine reduced penicillin- [48, 49],
pentylenetetrazole- [50], and electroconvulsion-induced [51]
seizures in experimental rodent models of epilepsy. In more
recent experiments, uridine was found to be antiepilepto-
genic in hippocampal kindling models [52, 53]. Uridine de-
creased kindling rates and afterdischarge durations in rats
[53]. On the other hand, uridine did not protect against elec-
troshock-induced convulsions [50]. The inconsistent anticon-
vulsant effect of uridine in different seizure models from
different laboratories may reflect the different amount and
dosing applied. For example, three-times-daily intraperito-
neal injections of 200 mg / kg uridine reduced kindling rates
in rats but once-daily administration was without effect [53].
An anti-convulsant effect of uridine has been suggested
Thermoregulatory Effects of Uridine
hypothermia of 6-10 degrees C in mice and rats [54]. In con-
trast, low dose of uridine resulted in a slight increase in tem-
perature in rodents [54]. The hypothermia might be related to
breakdown products of uridine, since inhibition of uridine
breakdown partially prevented hypothermia and since in
brain uracil nucleotide levels were only slightly increased
after uridine administration, while those of uracil were more
markedly increased than in other tissues. [54]. Interestingly,
in human and rabbit, high dose of uridine induced fever [55].
The change in body temperature associated with uridine ad-
ministration was not due to bacterial pyrogens but that one of
the degradation products might be involved in thermoregula-
tion [55].
Administration of high-dose uridine resulted in severe
Evidence for Mood Altering Effects of Uridine
avoidance responding in rats. While uridine itself does not
affect animals' performance in this model, uridine signifi-
cantly potentiated the disruption of avoidance and avoidance
latency induced by the neuroleptic haloperidol, a known do-
pamin receptor antagonist when coadministered with it [56].
Chronic uridine adminstration also increased in the stereo-
typy scores and the catalepsy induced by acute haloperidol
injection [57]. Haloperidol-induced [57] and potassium-
induced striatal dopamine release was potentiated [58]. The
effect of uridine on haloperidol-evoked neural changes may
be related to the dopaminerg actions of haloperidol because
uridine itself was shown to affect brain dopaminerg systems.
In activity tests, uridine-treated rats exhibited a significant
increase in the sensitivity to amphetamine [59]. Uridine also
potentiated the amphetamine and cocaine-induced rotation in
rats with unilateral dopaminergic lesions [59]. Furthermore,
chronic uridine treatment reduced the level of dopamine re-
ceptors and enhanced their turnover rate in the striatum [60]
and might affect the dopamine-dependent prolactin release
[61]. In addition to potentiating the action of anti-psychotic
drugs, uridine was also suggested to have anxyolitic activity
as well [62, 63].
Neuroleptic drugs induce disruption of conditioned
The Effect of Uridine on Memory
to increased uridine improves certain types of memory func-
tion. Rats were assessed for learning and memory skills us-
ing 2 versions of the Morris water maze, the hidden platform
version that assesses hippocampal-dependent cognitive
memory processing, and the visible platform version that
assesses striatal-dependent habit memory [64-66]. Chronic,
but not acute, dietary supplementation with CDP-choline
prevented hippocampal-dependent, memory deficits in aged
rats and by younger rats reared under impoverished envi-
ronmental conditions but did not affect striatal-dependent
learning and memory [64, 65]. In rats, dietary CDP-choline is
rapidly metabolized into cytidine and choline, the cytidine is
then readily converted to uridine, which enters the brain [67].
To confirm that uridine is the compound to affect memory
function, a diet supplemented with the uridine source
uridine-5'-monophosphate (UMP) was tested similar to the
CDP-choline administration. Indeed, UMP was similarly
effective to alleviate memory dysfunction tested by Morris
water maze as CDP-choline [66]. Increasing uridine levels by
dietary UMP administration also improved the performance
in gerbils in memory tests using the four-arm radial maze, T-
maze, and Y-maze tests [68]. Similar to animal studies, in-
creased uridine formation may have been the mediator of the
positive effects of CDP-choline on verbal memory in aging
human individuals with relatively inefficient memories [69].
Accumulating evidence suggest that long-term exposure
The Effect of Uridine on Neuronal Plasticity
tion of neuronal plasticity came from experiments demon-
strating that it enhances neurite outgrowth in PC12 rat pheo-
chromocytoma cells. PC12 cells were differentiated by nerve
growth factor and exposed to various concentrations of
uridine. After 4 but not 2 days uridine significantly and dose-
dependently increased the number of neurites per cell. This
increase was accompanied by increases in neurite branching
and in levels of the neurite proteins neurofilament M and
neurofilament 70 [70]. In subsequent experiments, gerbils
received a diet containing UMP as uridine source daily for 4
weeks. This treatment significantly increased the amount of
presynaptic protein synapsin-1, postsynaptic protein PSD-95
and neurite neurofibrillar proteins NF-70 and NF-M [71-73].
In contrast, elevated uridine level had no effect on the cy-
toskeletal protein beta-tubulin [71]. In addition, dietary ad-
ministration of UMP together with the omega-3 fatty acid
docosahexaenoic acid substantially increased the number of
dendritic spines in adult gerbil hippocampus. This increase
in dendritic spines was accompanied by parallel increases in
membrane phosphatides and in pre- and post-synaptic pro-
teins within the adult hippocampus [74]. These actions of
elevated uridine levels in the brain on the level of synaptic
proteins and the number of dendritic spines were also de-
scribed during development. When dams consumed UMP for
10 days before parturition and 20 days while nursing, the
brains of weanlings exhibited significant increases in mem-
brane phosphatides, various pre- and postsynaptic proteins
and in hippocampal dendritic spine densities [75, 76]. These
data suggest that chronic uridine treatment promotes synap-
togenesis at least in certain parts of the developing as well as
the adult rodent brain [72, 77, 78]. To demonstrate the rele-
The first clue that uridine may be involved in the regula-
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Brain Function of Uridine Current Topics in Medicinal Chemistry, 2011, Vol. 11, No. 8 1061
vance of uridine in the regulation of synaptic function, the
effect of oral administration of the uridine source uridine-5'-
monophosphate (UMP) was investigated on the release of
the neurotransmitters dopamine and acetyl-choline (ACh).
Potassium-evoked dopamine release measured by in vivo
brain microdialysis in the striatum was significantly greater
among chronically UMP-treated rats [58]. For ACh, baseline
levels in striatum and striatal extracellular fluid were signifi-
cantly elevated after the rats consumed UMP-containing diet
for at least a week [79]. Furthermore, atropine-induced ACh
release was also enhanced by chronic elevation of uridine
levels [79].
thesis of different molecules, which could potentially ac-
count for its neural actions. Thus, it has been hypothesized
that elevated uridine level can increase the rate of RNA syn-
thesis under pathological conditions, e.g. following epileptic
seizures [48], which might contribute to its anticonvulsant
properties. There is more evidence available that uridine
exerts some of its actions via elevated synthesis of mem-
brane constituents and of transmitter uridine nucleotides,
which could affect neuronal signal transmission. Experimen-
tal support of these suggestions is summarized in this chap-
ter. In addition, the existence of a uridine receptor has been
proposed, and a potential direct action of uridine will also be
Uridine, as a precursor metabolite, can support the syn-
Neuronal Membrane Formation
CDP-choline from UTP in the brain seem to depend on the
availability of uridine rather than on the activity of the par-
ticipating enzymes. A similar feature of brain metabolism,
the dependence of synthesis on local concentrations of sub-
strates, which are nutrients that cross the blood-brain barrier,
has been recognized for other important reactions, including
the neuronal production of serotonin, dopamine, or acetyl-
choline from tryptophan, tyrosine, or choline, respectively
[80]. Stimulation of UTP and CDP-choline synthesis by
uridine was first demonstrated in PC12 cells. Adding uridine
to the incubation medium caused significant elevations in
UTP and CDP-choline levels [81]. In a subsequent study, in
which adult gerbils received UMP by gavage, plasma and
brain uridine levels were markedly elevated but cytidine lev-
els were only slightly increased [82]. At the same time, brain
UTP, CTP, and CDP-choline were all elevated 15 min after
UMP administration [82]. Since uridine did not affect the
synthesis of diacylglycerol or the activity of the phos-
photransferase, which catalyzes the synthesis of phosphati-
dylcholine from diacylglycerol and CDP-choline, it is un-
likely that uridine treatment inhibits the conversion of en-
dogenous CDP-choline to phosphatidylcholine [81]. As
CDP-choline is an immediate and rate-limiting precursor of
phosphatidylcholine synthesis, these results suggest that
uridine may also enhance phosphatidylcholine synthesis and
membrane formation [81, 82]. This mechanism is likely to
play a role in the effects of uridine on memory and neuronal
plasticity [73, 77].
The rates of the formation of UTP from uridine and
Uridine Action Via Released Uridine Nucleotides
been proposed [83] after the discovery of receptors recogniz-
ing uridine nucleotides based on analogy with the release of
adenine nucleotides [84, 85]. Cellular release of uridine nu-
cleotides was first reported from bovine vascular endothelial
cells loaded with radiolabeled uridine [86]. Following the
development of a sensitive enzymatic assay [87, 88] quanti-
fication of physiologically relevant concentrations of UTP
became possible. Caspase-dependent release was found in
thymocytes [89]. A calcium-dependent release of UTP has
been demonstrated from lung cells [90, 91]. The release of
UTP from astrocytoma cells in response to mechanical
stimulation was also demonstrated [87, 92]. It was verified
that the increases in UTP levels were not the result of cell
lysis [87]. In addition to UTP, UDP-sugars were also re-
leased from a variety of cell types including glioma cells [93-
95]. Although these findings suggest that uridine nucleotides
are present in synaptic vesicles, direct evidence of such stor-
age has not been reported. However, a strong argument for
the release of uridine nucleotides is the existence of uridine
nucleotide receptors on plasmamembranes [39]. These recep-
tors belong to the P2Y family of 7 transmembrane domain
G-protein coupled receptors as reviewed extensively [2, 36,
40, 96]. The members of the P2Y receptors family that are
activated by pyrimidines are shown in Table 1. Other mem-
bers of the P2Y receptor family are G-protein coupled recep-
tors that are activated by purine and not pyrimidine nucleo-
tides [2, 96].
Information on the localization of pyrimidine receptors
mostly derives from RT-PCR [98, 100], western blotting
[101], and cell culture studies [102], which did not allow the
determination of the precise distribution of pyrimidine recep-
tors. Therefore, these receptors are to be investigated by in
situ hybridization, immunocytochemical, electronmicro-
scopical as well as functional approaches in the future. Initial
functional studies suggest the involvement of pyrimidine
receptors in the proliferation, differentiation, survival of
cells, as well as the removal of damaged cells. UTP induces
proliferation and neuronal differentiation of olfactory epithe-
lium [103] and augments the proliferation of adult neural
progenitor cells via P2Y2 receptors [104]. UTP was also neu-
roprotective against cerebral ischemia reperfusion injury
[105]. Microglia expressing P2Y6 receptors show phagocy-
tosis by the stimulation of UDP [106] while UTP was shown
to promote the removal of apoptotic cells by phagocytes via
P2Y2 receptors [89].
The experimental data are scarce as to whether the effects
of uridine are exerted via pyrimidine receptors. While
uridine is known to increase the level of intracellular UTP
[81, 82], there is no information whether it also increases the
level of the releasable pool of pyrimidine nucleotides. Nev-
ertheless, available evidence suggests that uridine nucleo-
tides and pyrimidine receptors contribute to the neurite out-
growth enhancing effect of uridine in PC12 cells. The in-
crease in neurite outgrowth produced by uridine administra-
tion was mimicked by exposing the cells to UTP, and could
be blocked by various drugs known to antagonize P2Y re-
ceptors, such as suramin, reactive blue 2, and pyridoxal-
phosphate-6-azophenyl-2',4' disulfonic acid [70]. Moreover,
The release of uridine nucleotides from brain cells has
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1062 Current Topics in Medicinal Chemistry, 2011, Vol. 11, No. 8
Dobolyi et al.
degradation of nucleotides by apyrase blocked the stimula-
tory effect of uridine on neuritogenesis [70].
Evidence for a Uridine Receptor in the Brain
in the extracellular space by nucleotide-converting ectoen-
zymes [1, 37, 107, 108]. Indeed, depolarization leads to ele-
vated extracellular uridine levels. Labeled uridine taken up
by synaptosomes in a dipyridamole-sensitive process was
shown to be released by 4-aminopyridine-induced depolari-
zation [109]. In vivo depolarization of neuronal cells by oua-
bain, high-potassium ion concentration, and glutamate recep-
tor agonists lead to increased concentrations of uridine in the
extracellular space measured by brain microdialysis [27, 28].
Elevated level of uridine was also found during seizures in
the extracellular space of the hippocampus in an aminopyri-
dine-induced rat model of epilepsy and the levels of uridine
correlated with seizure activity [29]. Furthermore, local ad-
ministration of uridine inhibited hippocampal unit activity in
anaesthetized rats without any change in the local extracellu-
lar adenosine levels [28]. In analogy with the adenosine sys-
tem where ATP as well as its extracellular degradation prod-
uct adenosine have their own receptors [96], the existence of
uridine receptors has also been suggested. Although uridine
receptors have not been cloned yet, evidence keeps accumu-
lating on the direct binding and action of uridine in the cen-
tral nervous system.
Released uridine nucleotides can be degraded to uridine
brain extracellular space was first provided by the demon-
stration that uridine and GABA interacted competitively
with GABA binding sites in rat cerebellar buffer-washed
membranes. Both high and low affinities of GABA for its
receptors were affected by 1 mM uridine administration,
whereas the apparent number of binding sites remained un-
charged [110]. Subsequently, it was also shown that the
GABA binding to membrane preparations from frontal cor-
tex, hippocampus, and thalamus were all competitively in-
hibited by the in vitro addition of uridine [111]. Since intrap-
eritoneal injection of uridine produced a dose-related de-
crease in the cerebellar content of cyclic GMP and antago-
nized its increase elicited by bicuculline as well as reduced
bicuculline-induced seizures, the anti-convulsant actions of
Evidence that uridine itself may have an active role in the
uridine were suggested to be the result of the modulation of
GABA-mediated inhibitory neurotransmission [111].
Another line of research based on the sleep-promoting
activity of uridine also lead to the suggestion that uridine
exerts some of its actions through its own receptors. Intrac-
erebroventricular injection of uridine derivatives including
N3-benzyluridine [112, 113], N3-benzyl-6-azauridine [114,
115] and N3-phenacyluridine Fig. (2). [116] resulted in hyp-
notic activity and prolonged the duration of pentobarbital-
induced sleep. In contrast, a number of structurally related
compounds were without effects [114, 115]. Furthermore, an
uridine analogue, N3-alpha-hydroxy-beta-phenethyluridine
Fig. (2). was identified whose N3-(S)-(+)- but not N3-(R)-(-)-
alpha-hydroxy-beta-phenethyluridine isomer had potent
hypnotic activity and inhibited N3-phenacyluridine binding
[117]. In additional experiments, specific uridine binding
was demonstrated in synaptic membranes from bovine
thalamus and N3-Phenacyl derivatives of uridine inhibited
specific uridine binding [118]. In contrast, N3-phenacyl-2',3'-
O-isopropylideneuridine, whose sugar moiety is different
from uridine, and N3-benzyluracil and N3-phenacyluracil that
have no ribose moiety, did not have hypnotic activity and
exhibited no binding affinity [118]. The affinities of N3-
phenacyluridine to benzodiazepine, GABA, 5-HT, and
adenosine receptors were quite low [119]. Therefore, the
binding site of uridine and N3-phenacyluridine was proposed
to represent a uridine receptor, which may play a role in the
induction of sleep mediated by uridine [119].
Fig. (2). Chemical structure of uridine and uridine analogues with
hypnotic activity. The asymmetric center of N3-?-Hydroxy-?-
phenylethyluridine is indicated by *.
Table 1. Pyrimidine Receptors and Their Localization in the Central Nervous System
Endogenous Agonists Receptor Localization
P2Y2 UTP=ATP Neurons and glial cells in several brain regions [96]
P2Y4 UTP>ATP Neurons and glial cells in several brain regions [96]
P2Y6 UDP Neurons and glial cells in several brain regions [96]
P2Y14 UDP-sugars Mostly astrocytes, microglia [97]
GPR17 UDP, UDP-sugars, cysteinyl-leukotrienes
Neurons in several brain regions but not in astrocytes
There are five currently known receptors that recognize uridine derivatives. These are listed in the first column. The recently deorphanized G-protein-coupled receptor 17 (GPR17)
has not yet been renamed. The second column indicates the endogenous agonists and also their relative affinities. The third column of the table describes the localization of the
receptors and the corresponding references.
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Brain Function of Uridine Current Topics in Medicinal Chemistry, 2011, Vol. 11, No. 8 1063
in rat synaptosomal membranes [109]. Pyrimidine and purine
analogues displayed different rank order of potency in dis-
placement of specifically bound uridine (uridine > 5-F-
uridine > 5-Br-uridine similar to adenosine >> 5-ethyl-
uridine similar to suramin > theophylline) and in the inhibi-
tion of uridine uptake (adenosine > uridine > 5-Br-uridine
similar to 5-F-uridine similar to 5-ethyl-uridine) into purified
cerebrocortical synaptosomes [120]. Furthermore, dipyrida-
mole did not affect uridine binding and the effective ligand
concentration for the inhibition of uridine uptake was about
two orders of magnitude higher than that for the displace-
ment of specifically bound uridine supporting that the bind-
ing site is not a nucleoside transporter. Actions of uridine,
UDP, UTP, ATP, and adenosine were studied by fluorescent
labeling of ion fluxes into cortical synaptosomes. Uridine
evoked the largest transmembrane Ca2+ ion influx, whereas
adenosine evoked K+ ion influx [109, 120]. Also, uridine was
shown to increase free intracellular Ca2+ ion levels in hippo-
campal slices [120]. Uridine analogues were found to be in-
effective in displacing radioligands that were bound to vari-
ous glutamate and adenosine-recognition and modulatory-
binding sites, which is important because [S]-willardiine, a
specific agonist of the AMPA receptor [121] is an uridine
derivative [122]. Moreover, the GTP binding site on
AMPA/kainate receptor may show affinity for uridine [123,
124]. In additional characterization of the uridine binding
site, it was shown that [35S]GTPgammaS binding to mem-
branes isolated from the rat cerebral cortex was enhanced by
uridine arguing for the involvement of a G-protein-coupled
receptor [120]. Altogether, these findings provide evidence
for a rather specific, G-protein-coupled binding site of exci-
tatory action for uridine in the brain. However, the direct
evidence for the existence of a uridine receptor is still miss-
ing. The protein(s) responsible for binding uridine and mak-
ing alterations in brain functions are not identified yet. The
existence of a putative uridine receptor has probability but
the final validation of the receptor requires molecular bio-
logical and additional pharmacological studies. Thus, identi-
fication and characterization of uridine receptor would be the
next essential step for understanding the role of uridine in the
nervous system.
In another approach, uridine binding sites were identified
for therapeutic use because of its low toxicity. Uridine ad-
ministration was tested in human in order to alleviate the
side-effects of anti-cancer drugs [125]. It was established that
the major limiting factors in increasing the dose of uridine in
human are fever and diarrhea [126, 127]. Since orally admin-
istered formulas can increase uridine levels in the plasma as
well as in the brain [82], it is relatively straightforward to
address the central actions of uridine for therapeutic pur-
poses. Based on the actions of uridine, its potential antiepi-
leptic effects as well as its potential effects on memory in
Alzheimer disease have been tested.
Uridine, as a natural endogenous molecule, is attractive
developmental delay, seizures, ataxia, severe language defi-
cit, and an unusual behavioral phenotype were investigated.
Examination of the cultured fibroblasts of these patients re-
Four unrelated patients with a syndrome that included
vealed that the activity of cytosolic 5'-nucleotidase was
markedly elevated, which resulted in a decreased incorpora-
tion of uridine into nucleotides with normal utilization of
purine bases [128]. In response to oral uridine administration,
the patients experienced fewer seizures, decreased ataxia,
improved speech and behavior, and improved cognitive per-
formance in a double-blind placebo trial. On replacement of
the supplements with placebo, the patients rapidly regressed
to their pretreatment states. These observations suggest that
increased nucleotide catabolism causes the symptoms of
these patients, which can be reversed by administration of
uridine [128].
In another human study, the effect of CDP-choline (citi-
coline) was tested on the verbal memory of older volunteers.
Dietary CDP-choline is known to increase the levels of
uridine in the brain [67]. In a randomized, double-blind, pla-
cebo-controlled, parallel group design study, the subjects
took either placebo or citicoline (1000 mg/d) for 3 months.
Citicoline therapy improved delayed recall on logical mem-
ory only for the subjects with relatively inefficient memories
[69]. These subjects with relatively inefficient memories
were recruited for a second study that used a crossover de-
sign where subjects took both placebo and citicoline (2000
mg/d), each for 2 months. In this study, citicoline was clearly
associated with improved immediate and delayed logical
memory [69]. Consequently, citicoline may prove effective
in treating age-related cognitive decline that may be the pre-
cursor of dementia. Therefore, CDP-choline and other nutri-
tional components that increase brain uridine levels may be
important in the treatment of Alzheimer's disease [129]. Alz-
heimer's disease is a progressive memory impairment char-
acterized by neurodegeneration and the dense deposition of
misfolded proteins in the brain. There is no cure for Alz-
heimer's disease and current treatments usually only provide
a temporary reduction of symptoms. An Alzheimer's dis-
eased brain contains fewer synapses and reduced levels of
synaptic proteins and membrane phosphatides [130]. The
ability of nutritional compositions to stimulate synapse for-
mation and effectively reduce Alzheimer's disease neuropa-
thology in these preclinical models provides a solid basis to
predict potential to modify the disease process, especially
during the early phases of Alzheimer's disease [73, 129].
Whether these potential therapeutic effects of a nutrient ap-
proach observed in animal models can also be replicated in a
clinical study needs further investigation [72, 131].
Uridine might also be effective in the treatment of other
neurodegenerative disorders than Alzheimer's disease. In a
recent study, co-administration of UMP and docosahex-
aenoic acid known to increase synapse formation alleviated
the behavioral consequences of 6-hydroxydopamine injec-
tion in a rat model of Parkinson's disease [132]. In addition,
the levels of striatal dopamine, synapsin-1, and the activity
of tyrosine hydroxylase were increased by the treatment at
the lesioned side [132]. The finding that uridine and docosa-
hexaenoic acid partially restored dopaminergic neurotrans-
mission in this model of Parkinson's disease suggest that
they may also be effective in the human disorder. The poten-
tiation of haloperidol effects by uridine suggests that uridine
coadministration might enhance the antipsychotic action of
traditional neuroleptics. This would allow for a reduction in
the therapeutic dose of the antipsychotic, thereby making it
Page 7
1064 Current Topics in Medicinal Chemistry, 2011, Vol. 11, No. 8
Dobolyi et al.
possible to relieve some of the side effects of neuroleptic
therapy [56, 57].
Uridine might also be useful as a nutrition supplement
during development. Uridine (as uridine monophosphate) is
found in mother's milk and has been proposed to play a role
in regulatory mechanism through which plasma composition
influences brain development [76]. UMP and docosahex-
aenoic acid administered orally to rat dams during gestation
and nursing increased synaptic elements in brains of wean-
ling pups suggesting that the administration of these phos-
phatide precursors to lactating mothers or infants could be
useful for treating developmental disorders characterized by
deficient synapses [75].
molecule, which is involved in the regulation of certain neu-
ral functions apart from its role in pyrimidine metabolism.
Uridine has sleep-promoting and anti-epileptic effects, might
affect mood, improves memory function and influences neu-
ronal plasticity. Evidence for the existence of uridine-
sensitive neurons is also convincing. These actions are likely
to be exerted via its actions on membrane formation, by the
known uridine nucleotide receptors, or even on its own puta-
tive receptor predicted in plasmamembranes or intracellular
binding sites in the central nervous system. Since uridine, as
a dietary component, is not toxic and has access to the brain
from the plasma through transporters, it is an appealing lead
molecule for the development of drugs with central site of
action. Based on its actions, the therapeutic application of
uridine and its derivatives are being explored.
Emerging evidence suggests that uridine is a neuroactive
Grant of the Hungarian Academy of Sciences, and the Hun-
garian Scientific Research Fund Research Grants NFM-
OTKA NNF2 85612, and NKTH-OTKA K67646 for AD,
and the Scientific Foundation of NYME SEK (2009-2010)
Hungary for ZsK and NKTH TECH_09_A1 for AD and JK,
and TAMOP 4.2.1./B-09/1KMR-2010-0003 to GJ.
Support was provided by the Bolyai János Fellowship
CNT = Concentrative nucleoside transporter
dTTP = Deoxythymidine-5'-triphosphate
Endoplasmic reticulum
GPR17 = G-protein-coupled receptor 17
PRPP = Phosphoribosylpyrophosphate
UDP = Uridine-5'-diphosphate
Uridine kinase
Ura = Uracil
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Received: June 10, 2010 Revised: September 07, 2010 Accepted: September 10, 2010


text:
With which app?
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when we can install 2 roms and choose which one we want to boot,f.e. you use your daily rom and can test a new a new rom at the same time on the same device
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I would appreciate if someone could help me out with this issue. What I want to know is how to add show_count function of wp_list_categories in WordPress custom menu navigation under Appearances > Menu? Is it even possible to include number of posts inside of a category if added that category is added in the menu?
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You'd have to override the
Some reading:


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text:
A transfer arrangement (10) for gripping articles (at 60) comprises a central wheel body with a multiplicity of arms (20), which can be pivoted about a first axis (23) in each case, articulated along its periphery. The arms (20) have a gripper (60) for receiving in each case one or more articles (15). Each gripper (60) can be rotated about a second axis (33) for predetermined positioning of the articles, while the connecting body (30) can be rotated about the first axis (23). The rotary movement of the gripper (60), then, can be transferred to the gripper (60), rotating about the second axis (33), via a shaft (28) arranged along the first axis (23), with the aid of a transfer element (25, 26, 27). Finally, a third axis (43) is arranged on the connecting body (30), between the first and second axes (23, 33). This allows rotation of the connecting body (30) to be transferred in a controlled manner to the connecting body (30), at the location of the first axis (33), via a shaft (49) arranged along the third axis (43), with the aid of a transfer element (45, 46, 47). This means that articles (15) can be tracked.
1. A transfer device (10) for gripping articles (15) from a first feed conveyor, which points in a first direction, and for subsequently placing the articles (15) on a second, removing conveyor that points in a second direction and is composed of a central wheel body (11), which rotates in a plane of rotation, on the periphery (12) of which a large number of arms (20) is hingedly connected such that the arms (20) are capable of being swiveled (21) around a first axis (23), which is perpendicular to the plane of rotation, each of the arms (20) including at least one gripping device (60, 70), with which at least one article (15) may be received; each arm (20) also has a second axis (33), which is parallel to the first axis, with a sleeve (31) on which the gripping device (60, 70) is mounted being located on the second axis (33), the sleeve (31) being rotatable for a specified orientation of the articles (15),
each movable arm (20) is designed as a connecting body (30), which is rotatable about the first axis (23); the rotational motion of the gripper device (60, 70) is transferrable from a shaft (28) located in the first (23) with the aid of a transfer element (25, 26, 27) to a sleeve (31), which rotates around a third axis (43) between the first and second axes (23, 33); and a controlled rotational motion of the connecting body (30) is transferrable via a shaft (49, 77) located in the third axis (43) with the aid of a second transfer element (45, 46, 47; 76, 77, 80) and via a shaft (49, 77) located in the third axis (43) to an element (21; 47, 80) that is attachable to the central wheel body (11) and is positioned such that it may rotate coaxially around the first axis (23).
2. The device as recited in
the wheel body (11) is driveable with a constant rotational speed.
3. The device as recited in
the gripping device (60, 70) is displaceable on the second axis (33) in a translatory manner along the second axis (33), the gripping device (60) being connected with the second axis (33) in a non-positive or form-fit manner.
4. The device as recited in
the gripping device (60, 70) is movable in a translatory manner using a lever (32) controlled via a pivoted link guide, in particular a drum-type cam.
5. The device as recited in
the gripping device (60, 70) is a suction device (70).
6. The device as recited in
the connecting body (30) includes a cavity (53), and the gripping device (60) is a sleeve (31) that is connected with the cavity (53), thereby making it possible to connect an element (61) close to the wheel with the suction device in order to create a vacuum.
7. The device as recited in
a valve (62) is provided at the transition from the cavity (53) in the connecting body (30) to the element (61) close to the wheel; the valve (62) may be switched by an actuating element (64) provided on the connecting body (30).
8. The device as recited in
the third axis (43) is located between the first (23) and second (33) axis, in a position between ⅓ and ⅔ the distance between the two, and preferably in the center.
9. The device as recited in
the third axis (43) is rotatable using a lever (44) controlled via a face cam.
10. The device as recited in
the position of the third axis (43) is changeable depending on the rotation of the element (21; 47, 80).
11. The device as recited in
the transfer elements (25, 26, 27 and 45, 46, 47) are deflection rollers or toothed rings, which are interconnected via drive belts or toothed belts.
12. The device as recited in
the deflection rollers or toothed rings are designed to be identical to each other.
13. The device as recited in
the belt tension of the first transfer element (25, 26, 27) is adjustable using an eccentric bush (41, 42) located on the second axis (33).
14. The device as recited in
the conveyors are conveyor belts or conveyor chains with drivers located at intervals thereon.
15. The device as recited in
the supply conveyor and the removing conveyor form an angle of 90 degrees.
16. The device as recited in
the positive control of the first transfer element (25, 26, 27) via a lever (24) is designed to maintain the orientation of the longitudinal articles while they are being transferred from the supply conveyor to the removing conveyor.
17. The device as recited in
the positive control of the second transfer element (45, 46, 47; 76, 77, 80) via a lever (76) is designed to maintain the orientation of the longitudinal articles while they are being transferred from the supply conveyor to the removing conveyor.
The present invention relates to a transfer device for gripping articles from a first supply conveyor, which points in a first direction, and then placing the articles on a second, removing conveyor, which points in a second direction, it being possible, in particular, for the first and second directions to be at right angles to each other.
A number of devices of this type have been known from the related art for a long time. For example, publication DE 25 51 538 disclosed a device of this type, as described in the preamble of Claim 1. The transfer device described therein is designed to lift easily deformable packaging articles from a first conveyor, and to deposit them, with the same orientation, onto a second conveyor. A revolving system of suction carriages is used for this purpose, with which the suction devices that grip the packaging articles are rotatable by 90 degrees, so that the orientation of the packaging articles remains the same. The related art is designed to convey soap pieces. These pieces have relatively similar dimensions in terms of width and length in the plane of the conveyors.
The device in the related art is less suitable for transporting longitudinal or extremely long articles. �Longitudinal articles� are understood to be elements to be transported that have a ratio of longitudinal dimension to transverse dimension of at least 4:1 or more, and, in particular, of 10:1 and more.
Based on the related art, the object of the present invention is to provide a transfer device for gripping longitudinal articles that may easily compensate for the great difference in speed between a slow supply conveyor and the subsequent removing conveyor.
When supplying longitudinal articles that are essentially transported transversely and that have a width of, e.g., 19 millimeters and a length of 152 millimeters, and which are transported 19 millimeters apart on the supply conveyor and 38 millimeters apart on the removing conveyor, the speed ratio between the two conveyors is 38 to 190, i.e., 1:5.
This object is achieved via a device with the features of Claim 1.
The inventive transfer device includes a wheel with movable arms that perform a tracking swivel motion of the connecting body to pick up, rotate, and deposit the products in a positioned manner.
A transfer device for gripping articles is preferably composed of a central wheel body, on the periphery of which a large number of arms is hingedly connected, the arms being swivelable around a first axis. The arms includes a gripper for picking up one article or several articles. Each gripper is rotatable around a second axis for a specified orientation of the articles, while the connecting body is rotatable around the first axis. The rotational motion of the gripper is transferrable via a shaft located in the first axis with the aid of a transfer element to a gripper that rotates around the second axis.
In a first embodiment, a third axis is located between the first and second axis on the connecting body. This makes it possible for the connecting body to perform a controlled rotation via a shaft located in the third axis with the aid of a transfer element on the connecting body at the location of the first axis. This makes it possible to track articles.
Longitudinal articles that are supplied in a transverse position may therefore be reoriented into a longitudinal orientation, e.g., for loading a horizontal tubular-bag machine. A high rate of throughput is attainable, e.g., 600 products per minute, and a removal speed of 100 meters per minute is possible, because the great change in speed�which results from reorienting the longitudinal articles from �transverse� to �longitudinal� for an �in-line positioning� for a horizontal tubular-bag machine�is bridged by the tracking arms.
A device of this type is excellently suited for transferring longitudinal articles of this type.
Rotating by 90 degrees and depositing is often selected for practical reasons, but it is not absolutely necessary. Angles of, e.g., 60 or 120 degrees may also be selected, or angles between these values may be selected.
Further advantageous embodiments of the inventive device and variants result from the dependent Claims.
Exemplary embodiments of the present invention are shown in the figures.
Articles 15 shown in
This is explained with reference to
The illustration presented in
A first toothed ring 25 is fastened to inner shaft 28. A rotary motion of lever 24 is therefore transferred via first toothed ring 25 to first, internally toothed drive belt 26, which drives a second toothed ring 27. Toothed rings 25 and 27 have the same diameter. A rotational motion of lever 24 about a certain angle therefore results in an identical rotation of outer shaft 29. Outer shaft 29, which is located coaxially around outer axis 33, is supported in a rod-shaped arm sleeve 30, which extends essentially horizontally and transversely to first and second axes 23 and 33.
Outer shaft 29 or outer axis 33 are located far from the wheel, that is, they are located on the side of the hub of wheel 11 opposite to inner axis 23. Outer shaft 29 and second toothed ring 27 may be designed as one piece, or they may be composed of two separate yet interconnected elements. Elements 25, 26, and 27 represent a first transfer element.
An inner lift shaft 31 is guided in outer shaft 29. Due to the passage 53 described below, the arm sleeve or connecting body 30 is a sleeve, although it may also be a connecting body made of essentially solid material. Lift shaft 31 is fixedly connected with an articulated carrier 34 via a fixing screw 35. Two diametrically opposed pins 36, which are positioned vertically with a minimum of play, are provided in articulated carrier 34. Pins 36 are inserted in upper flange 37 of outer shaft 29, and they are preferably secured in a press fit or with screws.
As a result of this connection, the rotation of outer shaft 29 is transferred directly to lift shaft 31. Lift shaft 31 is simultaneously positioned such that it may be moved up and so down along outer rotation axis 33 given that a non-rotatable form-fit connection is provided between lift shaft 31 and outer shaft 29 in one region.
This translational reciprocating motion is brought about via articulated carrier 34, to which a forked pivoting lever 38 is hingedly connected. Pivoting lever 38 is attached to connecting body 30 with segments 39, on both sides in this case. An actuating lever 32 extends past pivoting lever 38 along the rigid transverse axis defined by segments 39, thereby enabling actuating lever 32 to perform the reciprocating motion.
By way of brief reference to
A central shaft 49 is mounted on arm sleeve 30 in the center. A third toothed ring 45 is mounted on central shaft 49, in a central position. Third toothed ring 45 is rotatable around central shaft 49 and, therefore, central axis 43.
In this context, �central� refers to a location between axes 23 and 33 on the free ends of connecting body 30. The location of third axis 43 between first and second axes 23 and 33 does not necessarily mean a location on the direct line between axes 23 and 33, but rather a third axis 43, which may not be stationary, and which is located essentially in the region between axes 23 and 33.
Third toothed ring 45 is connected via a second belt 46 with a fourth toothed ring 47, which is located coaxially around inner axis 23. Third toothed ring 45 may be rotated using a lever 44, which is controllable using a face cam. Since third toothed ring 45 is located on arm sleeve 30 at a fixed distance from inner axis 23 in such a manner that it is rotatable around its main axis, but fourth toothed ring 47 is fixedly connected with fastening sleeve 21 and not with arm sleeve 30, when lever 44 rotates, this induces a direct pivoting motion of arm sleeve 30 and, therefore, entire arm 20 around the attachment point on central wheel 11. Elements 45, 46 and 47 represent a second transfer element.
Lift shaft 31 is hollow in its lower to central part. It includes a cavity 51, which is open at the bottom and is enclosed coaxially by a jacket. A flange 60 is provided on the lower section of lift shaft 31, on which a suction device or a gripper may be located, in a known manner. For simplicity, gripping device 60 will be discussed here. Reference is is made to
The jacket of lift shaft 31 is also open on the side in the central part of lift shaft 31. Cavity 51 is therefore open on the side, as indicated with reference numeral 52. Cavity 51 is therefore in direct contact with passage 53, which is positioned horizontally and is enclosed in arm sleeve 30. Passage 53 transitions into tube connection 61, which, in this case, is guided in the shape of an �L� to a not-shown vacuum pump or related connections.
The transition between passage 53 and tube connection 61 is created by vacuum control sleeve 62, which includes a jacket that is open at the bottom but is closed everywhere else, and which includes at least one vacuum control opening 63. Vacuum control sleeve 62 is rotatably supported in arm sleeve 30 and may be rotated upwardly via an actuating bolt 64. Vacuum control sleeve 62 is closed in the position shown in
Instead of the devices shown here for controlling a suction device 70, and instead of a preferred suction device 70, it is also possible to provide another known type of gripping device.
In summary, the following motions may be carried out by each arm 20 of a transfer device 10: When lever 24 on inner axis 23 is driven, this ultimately results in a rotational motion of flange 60 with gripping device or suction device 70. In contrast, when lever 44 is pivoted�since the four toothed rings 25, 27 and 45, 47 all have the same diameter�the arm sleeve rotates back around the same angle, thereby making it possible to easily adjust the orientation of outer axis 33 and, therefore, suction device 70 (viewed at the position of flange 60) in three dimensions relative to the axis of wheel 11. Articles 15 to be picked up may therefore be tracked very easily.
Further details of arms 20 are described in conjunction with
This is explained in greater detail with reference to
The illustration presented in
A holding insert 73 is non-rotatably inserted in an opening in fastening sleeve 30. Holding insert 73 is fixedly connected with an arm 75 oriented in the direction of outer axis 33. Holding insert 73 and arm 75 may also be designed as one piece, of course. A slot 72 oriented between two axes 23 and 33 is provided in arm 75. A pin 84 is inserted and guided in slot 72, and it engages in an arm of knee joint 76, which therefore may pivot. Slot 72 could also be integrated in fastening sleeve 30, or it could be realized in an overhanging projection at this point.
Knee joint 76 is connected with transfer lever 80 via a bolt 77. Transfer lever 80 is therefore rotatable using an actuating bolt 74, which is provided on the other arm end of knee joint 76 and is controllable via a face cam. Since actuating bolt 74 is located such that it may pivot relative to arm sleeve 30 using the coupling via arm 75 and knee joint 76, but transfer lever 80 is fixedly connected with fastening sleeve 21 in the region of axis 23, when actuating bolt 74 rotates, the direct result is that arm sleeve 30 and, therefore, entire arm 20, pivot. Third central axis 43 is therefore realized at the point where bolt 77 is located. In contrast to the first exemplary embodiment, this bolt is not stationary. Instead, it changes its position when lever 80 pivots and, in fact, in accordance with its angular position.
Lift shaft 31 is hollow in its lower to central part. It is therefore designed the same as in the first exemplary embodiment, up to tube connection 61. In this case, vacuum control sleeve 62 is opened with its vacuum control opening 63 in the position shown in
In summary, the following motions may be carried out by each arm 20 of a transfer device 10 as shown in
As essential feature of all exemplary embodiments, which one skilled in the art may expand upon based on the present invention, is that a wheel 11 with a large number (twelve, in this case) arms 20 may quickly reorient longitudinal articles that are conveyed at a high rate of speed, thereby enabling them to be conveyed with a relatively much higher rate of speed. There do not necessarily have to be twelve arms, of course. A different number of arms, e.g., eight arms 20 or sixteen arms 20 may also be used.
As evidenced by the descriptions above, the device is independent of the further means used in the packaging system. This applies to the type of supply conveyor belt and the actual picking device or the downstream conveyor belt.
Instead of toothed rings 25, 27, 45 and 47, it is also possible to use deflection rollers, with which belts 26, 46 must be under tension in order to be driven. Instead of belts 26, 46, it is also possible to use chains or other driving elements with a form-fit or non-positive connection.
10 Transfer device
11 Central wheel
12 Receptacle for an arm
15 Longitudinal article
20 Arm
21 Fastening sleeve
22 Fastening screw
23 Inner axis
24 Lever
25 First toothed ring
26 First drive belt
27 Second toothed ring
28 Inner shaft
29 Outer shaft
30 Arm sleeve, connecting body
31 Lift shaft
32 Actuating lever
33 Outer axis
34 Articulated carrier
35 Fixing screw
36 Pin
37 Flange
38 Pivoting lever
39 Segment
41 Eccentric bush
42 Adjustment screw
43 Central axis
44 Lever
45 Third toothed ring
46 Second belt
47 Fourth toothed ring
49 Central shaft
51 Cavity
52 Side opening
53 Passage
60 Flange
61 Tube connection
62 Vacuum control sleeve
63 Vacuum control opening
64 Actuating bolt
70 Suction device
72 Slot
73 Holding insert
74 Actuating bolt
75 Arm
76 Knee joint
77 Bolt
80 Transfer lever
84 Pin
Referenced by
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text:
Sensitive Skin Triple Action Pads are advertised as being alcohol-free, and that's great. However, although these pads do not contain alcohol, they are still terrible for sensitive skin because they contain menthol and an essentially ineffective amount of salicylic acid.
Sensitive Skin Pad's formula contains skin soothers, including aloe, to clean your skin gently. The pads are recommended for cases of mild to moderate acne on skin that is dry or easily irritated. Work's to treat and help prevent pimples. Alcohol Free!
Active: Salicylic Acid (0.5%), Other: Aloe Barbadensis Gel, Ammonium Lauryl Sulfate, Ammonium Xylenesulfonate, Citric Acid, DMDM Hydantoin, Fragrance, Witch Hazel Extract, Menthol, PPG-5-Ceteth-20, Purified Water, Simethicone, Sodium Borate, Tetrasodium EDTA,
Stridex At-A-Glance
Strengths: A couple of benzoyl peroxide options that are fragrance- and irritant-free.
Weaknesses: All the pads with salicylic acid contain irritants such as menthol, alcohol, or witch hazel; poor cleansers; no oil-absorbing products; no effective AHA or BHA products.
Long a drugstore staple in the anti-acne section of skin-care products, Stridex, like so many lines aimed at blemish-prone skin, has yet to offer an effective range of products. None of the options with salicylic acid are advisable due to the presence of needless irritants, and the cleansers share the same problem. The only bright spot is that Stridex offers two benzoyl peroxide products. They both include 2.5% as an active ingredient, an amount many will find successful, and these are effective, irritant-free, and affordable. Otherwise, this line is seemingly convinced that the path to clear skin involves lots of menthol. If menthol were an anti-acne ally, this line would be a slam-dunk—but it isn't. There isn't a shred of research showing menthol has any benefit for skin, for blemishes or for any skin type. Using these products with their injurious irritants will only hinder skin's healing process and worsen the inflammation seen in most cases of acne.
For more information about Stri-Dex, call (888) 784-2472 or visit www.stridex.com.
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Since its humble beginnings in 1986, Fishs Eddy has become a New York institution. Its quirky and classic housewares can be found in kitchen cupboards from Williamsburg to Washington Heights. Made of high-fired ceramic, the Tunnel Vision Mug refers to the Holland Tunnel, and how it spans what Manhattanites might consider the Great Divide.
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What to Watch on Saturday: Lifetime remakes 'The Trip to Bountiful'
The Trip to Bountiful (8pm, Lifetime) - Lifetime remakes Horton Foote's classic "The Trip to Bountiful" with Cicely Tyson, Vanessa Williams, Blair Underwood and Keke Palmer. It's the story of an elderly woman who lives with her overprotective son and yearns for a little freedom. When he refuses to take her to visit her hometown of Bountiful, she escapes to the bus station to make the trip on her own. The story was originally written by Foote for TV (and was also on Broadway), and Geraldine Page won an Oscar for her role in the 1985 film version.
Also on tonight . . .
A Ring by Spring (7pm, Hallmark) - A woman visits a fortuneteller and is told she will never get marred if she doesn't receive a proposal by spring. As the soothsayer's other predictions come true, the woman starts to believe the prophecy.
Too Cute! (8pm, Animal Planet) - Still a sucker for this show. Tonight, tabby kittens befriend a bearded dragon; Burmese kittens explore their new home; and Siberian kittens vie for their mother's attention.
Saturday Night Live (11:30, NBC) - Lena Dunham ("Girls") hosts with musical guest National.
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White God
Imagine an "R" rated "Lassie" by way of "Spartacus." That's Kornél Mundruczó's "White God," a brutal but stirring fantasy about street dogs rising up against…
Imagine an "R" rated "Lassie" by way of "Spartacus." That's Kornél Mundruczó's "White God," a brutal but stirring fantasy about street dogs rising up against…
In this exuberant but ultimately simpleminded comedy, a car wash owner (Kevin Hart) helps a wimpy hedge fund manager (Will Ferrell) get ready for prison…
"The Ballad of Narayama" is a Japanese film of great beauty and elegant artifice, telling a story of startling cruelty. What a space it opens…
Patrice Leconte's "Monsieur Hire" is a tragedy about loneliness and erotomania, told about two solitary people who have nothing else in common. It involves a…
A gallery of photos, videos and links illustrating Chaz's journey relating to Roger's legacy in the two years since his death.
A Kickstarter for a fascinating new documentary is almost there. You can help.
A gallery of photos, videos and links illustrating Chaz's journey relating to Roger's legacy in the two years since his death.
A Kickstarter for a fascinating new documentary is almost there. You can help.
An FFC reviews Jodoroswky's The Dance of Reality.
Our Far-Flung Correspondent Brings Explosive Polish 1980s Sci-Fi to NYC
The video of 2014's memorable "Remembering Roger" panel at Ebertfest.
An interview with "Woman in Gold" director Simon Curtis.
"Voyager" starts in mystery, and intrigues us. It continues with intelligence, and absorbs us. And then it ends in melodrama, and disappoints us - not least because characters as smart as these should be able to solve the movie's central question long before they do.
The film, set in the 1950s, stars Sam Shepard, very dry and analytical, as an engineer who stands aside from everything, as if detached from life itself. Once it was not so with him. Once he was in love. That was long ago. Now, on board an airplane, he is faced with a situation many of us have fantasized: The plane is going to crash, and he has plenty of time to think about it. He does. He does not panic, and indeed seems absorbed in all of the mechanics of the approaching disaster.
When he is spared, he seems detached from that, too. But through a coincidence he has met a man on the plane who can give him news about a friend from his past, and the news sets him off on an odyssey through strange places to find a woman he did not know was still alive, the woman he once loved. Along the way on this journey, aboard a ship, he meets a young woman (Julie Delpy), and feels an instinctive closeness to her. The feeling is returned, up to a point.
They decide to travel together through southern Europe, sharing a car, he playing the mentor role as they visit the ruins and remnants of earlier civilizations. Eventually he learns something we have been half-expecting all along, the name of the young woman's mother. She is the woman who was once his lover. Does that make the girl . . .
Don't be in a hurry to ask. The movie isn't. And in a way the possibility of incest is the least interesting thing about this movie, even though the screenplay treats it as the most important.
That wise critic Stanley Kauffmann, of the New Republic, observes about incest that it makes an unsatisfactory topic for fiction, because we do not know how to feel about it. Of course we are against forced incest - child abuse and so on. But what about accidental incest, in which the parties discover too late what their real relationship is? Does that fascinate us? Not much, because almost by definition it's of interest only to the involved parties. They can be expected to have strong feelings, but we don't share them because, when you get right down to it, we're not related to them.
"Voyager," based on the novel Homo Faber by Max Frisch, has been directed by Volker Schlondorff ("The Tin Drum") as if he, too, is more interested in what the characters say than in how they're related. He makes the Shepard character into a kind of man not often seen in the movies, a literate engineer, given to dispassionate analysis. The daughter is pretty and smart and, like many young women, too quick to believe romantic love is an answer to anything.
Her mother, played by the gifted Polish actress Barbara Sukowa, has great reason to be angry with Shepard because of what happened long ago, but (as we can see in flashback) she should also be angry at the conventions of the Idiot Plot syndrome, which prevented both her and Shepard from saying absolutely obvious things that would have greatly lessened their pain.
The end of "Voyager" does not leave us with very much. The film follows its melodramatic compulsion right into oblivion, like a lemming.
Thinking back, we realize we've met some interesting people and heard some good talk, and that it's shame all those contrived plot points about incest got in the way of what was otherwise a perfectly stimulating relationship. This is a movie that is good in spite of what it thinks it's about.
A film teacher looks back on "The Breakfast Club," partly through the eyes of her students.
As we mourn Abrams' macho Star Trek obliteration, it's a good time to revisit that most Star Trek-ian of accomplishme...
A piece on the use of animals in film in light of "White God".
The conversation about Woody Allen's personal and professional lives intertwining continues, but to what end?


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