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United States District Court, N.D. New York
March 24, 2004.
JOHN M. SHUTTS, Plaintiff,
FIRST UNUM LIFE INSURANCE COMPANY OF AMERICA and UNUMPROVIDENT CORPORATION, Defendants
Plaintiff John M. Shutts commenced this declaratory judgment action on
October 30, 2001, seeking a declaration from this Court, pursuant to
28 U.S.C. § 2201-2202, that he is entitled to long-term disability
benefits pursuant to the provisions of the policy that Defendants
Page 2
First UNUM Life Insurance Company of America and Unumprovident
Corporation (hereinafter collectively referred to as "Defendant" or
"First UNUM") issued to him. Presently before the Court are Defendant's
motion for judgment on the administrative record and Plaintiff's
cross-motion for judgment on the administrative record.*fn1
During 1999, Plaintiff was employed as President of the John I. Shutts
Agency, Inc. Defendant issued long-term disability and group health
insurance policies to Plaintiff's employer, the John I. Shutts Agency,
Inc. The policies are governed by the Employee Retirement Income Security
Act of 1974, 29 U.S.C. § 1001, et seq. ("ERISA").*fn2 The
policy's effective date was October 1, 1998.
Plaintiff suffers from organic brain syndrome.*fn3 On July 19, 2000,
he applied for long-term
Page 3
disability benefits, listing April 1, 1999, as his date of disability.
Defendant, relying upon several pieces of written correspondence and
telephone interviews, denied Plaintiff's claim for long-term disability
benefits on the ground that Plaintiff was not in active employment prior
to the effective date of his policy and, as a result, Plaintiff's waiting
period was never satisfied.*fn4
Plaintiff then appealed Defendant's decision on December 5, 2000.
Defendant affirmed its prior determination and upheld its denial. At that
time, Defendant also alleged that Plaintiff failed to provide timely
notice of his alleged disability as the policy required.*fn5
After exhausting his administrative remedies, Plaintiff commenced the
instant action, seeking a declaration from this Court that he is entitled
to long-term disability coverage. Plaintiff bases his claim on various
grounds which the Court will address seriatim.
Page 4
A. Initial Matters
As a preliminary matter, Plaintiff asserts that Defendant waived any
right it may have to dispute the timeliness of Plaintiff's notice of
claim by failing to assert late notice as a ground for denying coverage.
Plaintiff cites Lauder v. First Unum Life Ins. Co.,
284 F.3d 375, 381 (2d Cir. 2002), to support his argument and specifically
asserts that the policy does not require notice within a thirty- or
ninety-day notice period, but, to the contrary, merely encourages
the insured to notify the insurer of a claim within those time periods.
Defendant, on the other hand, argues that Plaintiffs failure to file
proof of loss in a timely manner precludes his claim for benefits under
ERISA. Defendant asserts that under the policy, if Plaintiff was disabled
as of April 1, 1999, he was required to give notice within thirty days of
that date, i.e., May 1, 1999, or, at the latest, December 1999. Plaintiff
did not give notice, however, until July 19, 2000 approximately
seven months later.
The Second Circuit has held that the doctrine of waiver applies to an
ERISA claim. See Lauder, 284 F.3d at 381 (citations omitted).
However, there is no bright-line rule for determining whether waiver
applies in a particular case and a case-specific analysis is required.
See id. First, it is necessary to determine whether timely
notice is a required element of the policy under which the plaintiff
seeks reimbursement, since such an element cannot be waived, and
seemingly, with respect to the first consideration, "a claim of waiver
[can]not be used to expand the policy so that the insured `extend[s] its
coverage to more than it originally bargained.'" Id. (quotation
omitted). However, if waiver would not expand the coverage
Page 5
bargained for, then the court must analyze the particular case
under a different waiver principle, which is as follows: "[A]n insurer is
deemed, as a matter of law, to have intended to waive a defense to
coverage where other defenses are asserted, and where the insurer
possesses sufficient knowledge (actual or constructive) of the
circumstances regarding the unasserted defense.'" Id. at 382
(quotation omitted).
The policy reads:
We encourage you to notify us of your
claim as soon as possible, so that a claim
decision can be made in a timely manner. Written
notice of a claim should be sent within
30 days after the date your disability begins.
However, you must send UNUM written
proof of your claim no later than 90 days after
your eliminations period. If it is not
possible to give proof within 90 days, it must be
given as soon as is reasonably possible.
The policy does not, contrary to Defendant's assertions,
require that notice be given within thirty days but states that
it should be given within that time period. Additionally, although the
policy states that notice must be given within ninety days after the
insured's elimination period, it leaves an exception open to those who
cannot do so. Moreover, failure to timely file proof of loss does not
expand the policy so as to extend its coverage to more than originally
With respect to the second consideration, the Court must look to see if
the record supports Defendant's contention. The administrative record
contains a comment from a UNUM representative, dated March 9, 2001,
stating: "[n]ext steps Uphold denial on reappeal as not actively
employed. (Note N.Y. not a strict time limit state; consequently
will not put in late
Page 6
notice as uphold reason)." See Hall Aff. at Exhibit "B."
Not only did First Unum intend to uphold its denial of benefits on other
grounds and deliberately avoid using failure to timely file as a defense,
but its reason for doing so was based upon its opinion that New York was
not a "strict time limit state." Defendant's statement appears to show
that it indeed intended to waive this defense and uphold its denial on
other grounds to ensure that its decision was not overturned on a
technical ground from an apparently liberal time-limit state.
Accordingly, applying Lauder to the facts of this case, the
Court concludes that Defendant has waived its right to dispute the
timeliness of Plaintiff's filing of his notice of claim.
B. Standard of review
The court reviews an ERISA plan administrator's decision to deny
benefits "`under a de novo standard unless the benefit plan
gives the administrator or fiduciary discretionary authority to determine
eligibility for benefits.'" Henar v. First Unum Life Ins. Co.,
No. 02 Civ. 1570, 2002 WL 31098495, *3 (S.D.N.Y. Sept. 19, 2002) (quoting
Firestone Tire & Rubber Co. v. Bruch, 489 U.S. 101, 115,
109 S.Ct. 948, 103 L.Ed.2d 80 (1989)). When the policy gives the plan
administrator discretionary authority, the court reviews its eligibility
decision under an arbitrary and capricious standard of review except when
there exists a conflict of interest with the plan administrator, in which
case the de novo standard of review applies. See Pagan v.
NYNEX Pension Plan, 52 F.3d 438, 441-42 (2d Cir. 1995) (citations
omitted); Pulvers v. First Unum Life Ins. Co., 210 F.3d 89, 92
(2d Cir. 2000) (citations omitted); Rosenthal v. First Unum Life
Page 7
Co., No. 00 CIV. 3204, 2002 WL 975627, *5 (S.D.N.Y. May 9,
2002) (citation omitted).*fn6,*fn7
There is no question that Defendant had discretionary authority to
determine Plaintiff's eligibility for benefits and to construe the terms
of his policy. The policy states that, "when making a benefit
determination under the policy, UNUM has discretionary authority to
determine your eligibility for benefits and to interpret the terms and
provisions of the policy." See Hall Aff. at Exhibit "B" at CC.
FP-1. Since Defendant clearly has discretionary authority to determine
eligibility and to construe the terms of the policy, the Court must next
determine whether Defendant was operating under a conflict of interest
and, if so, whether Defendant was actually influenced by such a conflict.
Plaintiff argues that Defendant's failure to properly investigate the
claim was intentional
Page 8
and that its subsequent denial of the claim, notwithstanding the
evidence of eligibility, sufficiently shows that Defendant was influenced
by a conflict of interest.
Alternatively, Plaintiff asks the Court to review his claims under a
heightened standard of review, even if it does not find that a conflict
the policy is ambiguous.*fn8 In response, Defendant argues that not only
does Plaintiff fail to identify any conflict of interest it may have but
also alleges that Plaintiff cannot establish that a conflict of interest
impacted Defendant's decision to deny him benefits.
Plaintiff provides no evidentiary support for his assertion that
Defendant's alleged conflict of interest, in fact, affected its decision
to deny him benefits. Plaintiff merely makes conclusory allegations with
regard to this issue. Such allegations are insufficient as a matter of
law to warrant de novo review. See Pulvers, 210 F.3d at
92. Moreover, Plaintiff's proposal to apply a heightened degree of
scrutiny is also without merit. For example, Plaintiff cites Shelden
v. Barre Belt Granite Employer Union Pension Fund, 25 F.3d 74 (2d
Cir. 1994), for the proposition that a heightened degree of scrutiny is
applicable when a defendant is a fiduciary and disregards policy rules.
However, Shelden states that the arbitrary and capricious
standard may be satisfied when a defendant has fiduciary status and
ignores policy requirements. See id. at 80. Thus, Plaintiff's
cases support the application of an arbitrary and capricious standard of
review and not, as Plaintiff claims, a heightened degree of scrutiny. The
Court, therefore, reviews Plaintiff's claims under an arbitrary and
capricious standard of review.
Page 9
In the present case, Plaintiff claims that Defendant acted arbitrarily
and capriciously by failing to properly investigate and conduct a full
and fair review of his claims and by misinterpreting and misapplying
policy provisions. Additionally, he alleges that the policy provisions
upon which Defendant relied are ambiguous.*fn9
C. The policy provisions upon which Defendant relied are not
Plaintiff asserts that the policy's "active employment" provision is
ambiguous. Specifically, he argues that the phrase "at least twenty hours
a week" is not defined. For example, Plaintiff asserts that it is not
clear whether the 20-hour minimum is an average, i.e., work ten hours one
week and thirty hours the following week. As might be expected, Defendant
argues that there is no ambiguity in the twenty-hours-of-work-per-week
requirement. Moreover, Defendant states that, in any event, the alleged
ambiguity has no effect since the rule of contra proferentum
does not apply under an arbitrary and capricious review.*fn10
"The preliminary question of whether a contract is clear or ambiguous
is to be decided by the court as a matter of law." Keiser v. CDC Inv.
Mgmt. Corp., 160 F. Supp.2d 512, 519 (S.D.N.Y. 2001) (citations
omitted). "Contract language is unambiguous if it has a `definite and
precise meaning, unattended by danger of misconception in the purport of
the [contract] itself,
Page 10
and concerning which there is no reasonable basis for a difference
of opinion.'" Id. (quotation and citation omitted). On the other
hand, "[l]anguage `is ambiguous when it is capable of more than one
meaning when viewed objectively by a reasonably intelligent person who
has examined the context of the entire integrated agreement. . . .'"
Id. at 519-20 (quotation and citation omitted).
There can be no other rational interpretation of the phrase "at least
twenty hours a week" aside from its literal meaning, i.e., that the
policyholder must work twenty hours a week. Moreover, Plaintiff's
reliance upon Keiser to support his position that the term "at
least twenty hours a week" is ambiguous is misplaced. In Keiser,
questions of fact existed regarding the ambiguity of the meaning of the
plaintiffs resignation agreement and the meaning of "active employment"
as defined by the policy. Although the ambiguity of the term "active
employment" was in contention, the court found no ambiguity as to the
meaning of "at least thirty hours per week," as was stated in the
plaintiffs policy. Thus, the Court finds that the term "at least twenty
hours a week" is not ambiguous.*fn11
D. Defendant did not misinterpret or misapply policy
Plaintiff asserts that Defendant improperly interpreted the plan and
imposed standards not
Page 11
required under the terms of the policy. Specifically, he alleges
that Defendant's denial letter demonstrates such inappropriate conduct.
Defendant, however, states that Plaintiff has not worked for several
years and, therefore, was not in active employment prior to the policy's
October 1, 1998 effective date. See Plaintiff's Complaint at
Exhibit "E." Thus, Defendant asserts that Plaintiff's waiting period was
never satisfied. See id.
The policy states that the policyholder is eligible for coverage if he
is working for his employer in an eligible group and the date he is
eligible for coverage is the later of his employer's plan effective date;
or the day after he completes his waiting period. See Hall Aff.
at Exhibit "B" at EMPLOYEE-1.
"Waiting Period" means the continuous period of time . . . that you
must be in active employment in an eligible group before you are eligible
for coverage under a plan." See Exhibit "B" at GLOSSARY-4. The
policy defines eligible group(s) as "[a]ll employees of Participating
Agencies in the Professional Insurance Agents of New York State, Inc.
Trust and employees of the Professional Insurance Agents of New York
State, Inc. in active employment." See Exhibit "B" at G-LTD-1.
Active employment means that you are working for earnings that are paid
regularly and that you are performing the material and substantial duties
of your regular occupation for at least twenty hours per week.
See Exhibit "B" at GLOSSARY-1.
Although Defendant's explanation is somewhat convoluted, its reasoning
is apparent and consistent with the policy's provisions.*fn13
Furthermore, Plaintiff did not refer this Court to a specific term that
was misinterpreted or misapplied in the policy or specific standards that
Page 12
Defendant incorrectly imposed on the plan. Defendant asserts that,
in order for Plaintiff to recover under the policy, he had to be in an
eligible group, i.e., in active employment, on either the plan's
effective date, i.e., October 1, 1998, or the day after Plaintiff
completed his waiting period. However, Plaintiff was not in active
employment on the policy's effective date or during the waiting period
since Defendant found that he had not worked in over three years. Thus,
Plaintiff was not in an eligible group and, under the terms of the
policy, unable to obtain benefits. Such reasoning does not contravene the
terms of the policy, but, to the contrary, is consistent with the
definitions set forth in the plan.
E. Whether the Administrator's decision to deny Plaintiff
benefits was arbitrary and capricious*fn14
Plaintiff claims that Defendant acted arbitrarily and capriciously by
failing to properly investigate his claims and conducted an inadequate
and unfair review of his application for benefits. Specifically, he
alleges that Defendant's November 18, 2000 internal memorandum evidences
Defendant's intent to deny Plaintiff's application without conducting an
investigation to answer its remaining questions. Defendant's internal
memorandum states
This is certainly an interesting case. Due to the
late notice of claim, it certainly has made it
difficult to clarify the dol
Page 13
[date of loss], work status and eligibility. The
meds indicate the ee [employee] has been having
difficulty for years. However, the ap is giving a
dol which is within our coverage . . . The late
filing of this claim has prejudiced our ability to
properly adjudicate the claim. At this point, it
appears we are looking to deny eligibility due to
the er stating the ee hasn't worked for years and
the lack of info to support eligibility . . . The
late filing has created this issue . . . Do we
deny based upon info received to date? Do we need
to further investigate payroll, tax, attendance
info? Do we need additional medical involvement?
Should we consult legal?
See Hall Aff. at Exhibit "B."
Moreover, Plaintiff asserts that Defendant failed to inquire about the
material and substantial duties of his employment and the actual number
of hours he engaged in those activities. Plaintiff also alleges that
Defendant's reliance upon his and Ronni Sisson's statements, which were
allegedly inconclusive, at best, was arbitrary and capricious and that
such information was insufficient to adequately determine whether
Plaintiff was in "active employment" as defined by the policy. Plaintiff
also asserts that his Social Security Administration Disability notice
and payroll records show that he received full payment for his services
at the time that the plan became effective.
As might be expected, Defendant has a different view of the sufficiency
of the information it used in arriving at its decision. Defendant
contends that its decision to deny Plaintiff long-term disability
benefits was not arbitrary and capricious but, instead, was reasonable
based upon the information before it. In support of its assertion,
Defendant directs the Court's attention to several steps it took to
evaluate Plaintiff's claim. First, it reviewed the correspondence
provided by Ronni Sisson, Plaintiff's assistant at the John I. Shutts
Agency, Inc. The letter stated that Plaintiff struggled and experienced
difficulties for a long period of time.
Page 14
Defendant also reviewed letters from Plaintiff, in which he wrote that
"in the past year, I doubt that I have worked more than 30% of the time"
and that "[s]everal years ago, maybe three, my assistant, Ronnie brought
a television into the office so I would have something to do" and "[w]hat
I do at work is watch television, play solitaire on my computer, go to
the bank, the post office and take pictures of houses the agency
Second, Defendant interviewed Plaintiff by telephone. In that
conversation, Plaintiff indicated that he had not worked in three years
and that his salary from the John I. Shutts Agency, Inc. was not actual
earnings but was the salary that the family-owned company could afford.
Defendant also interviewed Ronni Sisson by telephone, at which time she
reiterated that Plaintiff had not really worked in over three years.
Defendant determined that, based upon all of the aforementioned
correspondence and phone conversations, Plaintiff was not in active
employment and, thus, not eligible for long-term disability benefits. For
example, Defendant relies on Plaintiffs statement that "if the business
was not family owned, I would be unemployed" and his statement that "[i]n
the past year, I doubt that I worked more than 30% of the time."
See Defendant's Memorandum of Law at 4. Defendant also relied
upon Ronni Sisson's statements that Defendant played solitaire and
watched television while at work. See id. at 5, 8. Furthermore,
Defendant reiterated that, although payroll records revealed that
Plaintiff was being paid at the time the plan became effective, the
information provided to Defendant showed that he was not performing the
substantial and material duties of his occupation for the minimum twenty
hours per week as the policy required.
The court's review under an arbitrary and capricious standard "is
limited to the
Page 15
administrative record," see Miller v. United Welfare Fund,
72 F.3d 1066, 1071 (2d Cir. 1995), and is "highly deferential to a plan
administrator." Martin v. E.I. DuPont de Nemours & Co.,
999 F. Supp. 416, 422 (W.D.N.Y. 1998). Moreover, when applying this standard
a court "may overturn a decision to deny benefits only if it was `without
reason, unsupported by substantial evidence or erroneous as a matter of
law.'" Pagan, 52 F.3d at 442 (quotation and citation omitted);
see also O'Shea v. First Manhattan Co. Thrift Plan & Trust,
55 F.3d 109, 112 (2d Cir. 1995) (quotation omitted). "Substantial
evidence is `such evidence that a reasonable mind might accept as
adequate to support the conclusion reached by the [administrator
and]. . . requires more than a scintilla but less than a preponderance.'"
Short v. Unum Life Ins. Co. of Am., No. Civ. 302CV827, 2003 WL
22937720, *6 (D. Conn. Dec. 3, 2003) (quotation omitted). However,
"`where the administrator imposes "a standard not required by the plan's
provisions, or interpret[s] the plan in a manner inconsistent with its
plain words, or by [his] interpretation render[s] some provisions of the
plan superfluous, [his] actions may well be found to be arbitrary and
capricious.'"" Sullivan v. LTV Aerospace & Defense Co., No.
91-CV-713S, 1993 WL 405495, *5 (W.D.N.Y. Sept. 30, 1993) (quotation
omitted). "Likewise, where there is evidence that the administrator, who
owes a fiduciary duty to plan beneficiaries, breached a duty of good
faith and fair dealing, which is implicit in any ERISA plan, the
administrator's interpretation of plan language may be found to be
arbitrary and capricious." Id. (citation omitted). For example,
the court should look at whether the fiduciary failed to obtain and
develop all relevant information and consider substantial evidence in
rendering its determination to deny benefits. See Toland v.
McCarthy, 499 F. Supp. 1183, 1190 (D. Mass. 1980);
Cutignola, 1984 WL 1324 at *4 (citations omitted).
Page 16
In the present case, there is no doubt that Plaintiff was gradually
deteriorating in his health and, thus, unable to fulfill all of the
duties he once performed as President of the John I. Shutts Agency, Inc.
However, the record is incomplete it fails to detail the duties
of President. Although Ms. Sisson stated that Plaintiff watched televison
and played solitaire, she also stated that Plaintiff went to the bank and
photographed insured properties. These activities, although not
associated with the work that a President of a large company would
perform, could certainly be the every-day, administrative and operational
activities that the President of a small company would perform. The
record, however, is so incomplete with regard to Defendant's
investigation of Plaintiff's "material and substantial duties of his
occupation" that the Court cannot determine what duties Plaintiff was
required to do in his employment capacity and if he did, indeed, perform
such duties. Moreover, the record fails to show whether Plaintiff stopped
doing some of the material and substantial duties of his occupation as
President or all of his duties as President and if the duties he ceased
performing were integral to the execution of his job.
Additionally, the Court is unable to determine if Plaintiff worked "at
least 20 hours a week" as required by the policy. Defendant's reliance
upon Plaintiff's and Ms. Sisson's comments are inadequate for determining
that Plaintiff did not work the required twenty-hour-a-week minimum.
Such comments only evidence Plaintiff's increased difficulty and gradual
deterioration in performing his employment duties.
Based upon the evidence in the administrative record as it is presently
constituted, the Court finds that Defendant failed to investigate and
consider a number of relevant factors in arriving at its determination
that Plaintiff was not in "active employment," as defined by the terms of
the policy. Accordingly, the Court concludes that Defendant's decision to
deny Plaintiff
Page 17
long-term disability benefits was arbitrary and capricious.
This conclusion, however, does not end the Court's inquiry. Having
determined that Defendant is not entitled to summary judgment, the next
question is whether the Court should remand the matter back to Defendant
for further consideration or whether the Court should find, in the first
instance, that Defendant must provide Plaintiff with benefits. The Second
Circuit has stated that
Because district courts are required to limit
their review to the administrative record, it
follows that, if upon review a district court
concludes that the Trustees' decision was
arbitrary and capricious, it must remand
to the Trustees with instructions to consider
additional evidence unless no new
evidence could produce a reasonable conclusion
permitting denial of the claim or remand would
otherwise be a "useless formality."
In the instant case, there is additional, relevant evidence which
Defendant could use to determine whether Plaintiff is eligible for
benefits under the terms of the plan. For example, Defendant could
clarify when and how often Plaintiff worked and at what point, if any, he
stopped working the minimum twenty hours per week. Additionally,
Defendant can inquire what the material and substantial duties of
Plaintiff's job are and when, if ever, he ceased performing those duties
in their entirety. Such inquiries are critical to the determination of
whether Plaintiff was in active employment as defined by the policy, and
a determination as to eligibility cannot adequately be made without such
Accordingly, the Court remands this matter to Defendant for further
investigation of all relevant and necessary information, to consider all
relevant evidence and apply the appropriate
Page 18
standards, and to reach a determination as to whether Plaintiff is
eligible for long-term disability benefits within the meaning of the
F. Attorneys' fees
Plaintiff requests an award of attorneys' fees pursuant to
29 U.S.C. § 1132(g)(1). Although "ERISA grants district courts discretion to
award reasonable attorneys fee," Tholke v. Uninsys Corp., No. 01
Civ. 5495, 2003 WL 22077429, * 2 (S.D.N.Y. Sept. 5, 2003) (citing
29 U.S.C. § 1132(g)(1)) (footnote omitted), it is premature to address
the issue at this juncture since the Court must remand the matter to
Defendant for further consideration.
After carefully considering the file in this matter, the parties'
submissions and the applicable law, and for the reasons stated herein,
the Court hereby
ORDERS that Defendant's motion for judgment on the
administrative record is DENIED; and the Court further
ORDERS that Plaintiff's cross-motion for judgment on the
administrative record is DENIED; and the Court further
ORDERS that this matter is remanded to Defendant for further
investigation of all relevant and necessary information, to consider all
relevant evidence and apply the appropriate standards, and to reach a
determination as to whether Plaintiff is eligible for long-term benefits
within the meaning of the plan; and the Court further
Page 19
ORDERS that Plaintiff is to inform the Court in writing of
the result of Defendant's review process, including any appeals, and the
effect that result has on the continued viability of this action.
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Y.A.B. designed and performed experiments, analyzed data and was the principal author of the paper; A.C.P. performed sequence alignments, statistical receptor footprint analysis and contributed to writing; W.-M.L. performed partial sequencing of clinical isolates, constructed pW10-2R, designed antiviral compound experiments and provided purified HRVs; J.A.R. determined complete genome sequence of HRV-C15; S.P.A. assisted with virus inhibition experiments; X.S. designed and assisted with in situ hybridization experiments; T.R.P. assisted with establishment of the sinus organ culture; N.N.J. and S.B.L. analyzed data and contributed to writing; J.E.G. designed the project, analyzed data and contributed to writing.
A recently recognized human rhinovirus species C (HRV-C) is associated with up to half of HRV infections in young children. We for the first time propagated two HRV-C isolates ex vivo in organ culture of nasal epithelial cells, sequenced a new C15 isolate, and developed the first reverse genetics system for HRV-C. Using contact points for the known HRV receptors, intercellular adhesion molecule 1 (ICAM-1) and low density lipoprotein receptor (LDLR), inter- and intraspecies footprint analysis predicted a unique cell attachment site for HRV-Cs. Antibodies directed to binding sites for HRV-A and -B failed to inhibit HRV-C attachment, consistent with the alternative receptor footprint. HRV-A and -B infected HeLa and WisL cells, but HRV-C did not. However, HRV-C RNA synthesized in vitro and transfected into both cell types resulted in cytopathic effect and recovery of functional virus, indicating that the viral attachment mechanism is a primary distinguishing feature of HRV-C.
Human rhinoviruses (HRV) are positive-strand RNA viruses in the family Picornaviridae. They share a common genome organization, and isolates are typically classified into one of three species (HRV-A, B and C) according to phylogenetic sequence criteria1. HRV is the most frequent cause of the common cold, but recent data have shown that HRV infection has pathogenic potential beyond rhinosinusitis. It is now recognized that 50-85% of asthma exacerbations are due to HRV infections2–4, and that wheezing illnesses in infancy caused by HRV are associated with a high risk of developing childhood asthma5. HRV infections of all types are significant contributors to morbidity associated with exacerbations of other chronic lung diseases such as cystic fibrosis and chronic obstructive pulmonary disease6,7.
Recently, partial or full genome sequencing has been utilized to place clinical isolates within the 99 types of HRV-A and -B. However, cases began to appear, often associated with children hospitalized with lower respiratory tract disease, where the identified HRV sequences were not consistent with those of known HRV types8–14. Full genome sequencing has shown the distinct nature of these HRVs, which are now designated as the HRV-C1,15,16. The pathogenesis and antigenic variability associated with HRV-C, the mechanism of viral attachment to host cells, and potential treatments, have been elusive because unlike HRV-A and B, HRV-C has not been successfully propagated in any cell type in vitro17.
To address these fundamental questions about HRV-C biology, it is first necessary to develop a functional culture system. We now report the characterization and complete genome sequencing of an HRV-C isolate (HRV-C15 type) that can be grown in mucosal organ culture. Bioinformatic comparisons of this new genome and other HRV-C sequences showed unique composition profiles in the putative intercellular adhesion molecule-1 (ICAM-1) and low density lipoprotein receptor (LDLR) footprint locales, inconsistent with all known major and minor group virus-receptor interactions. Full-length HRV-C15 RNA synthesized in vitro from a cDNA clone was shown to be infectious when transfected into cultured cell lines. We have used this methodology to initiate descriptions of the virus biology, tissue tropism, the replication cycle, and response to antiviral and anti-receptor compounds.
We introduced several specimens of nasal lavage fluid (NLF) with high copy number of HRV-C RNA into multiple cell lines (WI-38, WisL, BEAS-2B, A549, HeLa) susceptible to HRV-A and HRV-B infection, and primary cultures of lung fibroblasts and bronchial, sinus and adenoidal epithelial cells from several donors. The latter included cell monolayers, differentiated cells (air-liquid interface method), and primary bronchial epithelial (PBE) cells treated with interleukin 13 to induce goblet cell metaplasia. Assigning an increase in the quantitative (q) RT-PCR signal as an indicator of HRV-C replication, none of these attempts were successful, including those where multiple serial blind passages were undertaken.
Reasoning that organ culture might best mimic natural replication circumstances, surgery-derived byproduct tissues (multiple anonymous donors) from sinus mucosa, adenoids, tonsils and nasal polyps, were cultured. After 1–3 days, viable tissues (continuous ciliary activity) negative for common respiratory viral pathogens were inoculated with representative laboratory HRV-A strains that utilize ICAM-1 (A16) or the LDLR (A1) for cell attachment. Sinus mucosal cultures inoculated with HRV-A16 (109 viral [v] RNA copies ml–1) increased viral RNA by up to 100-fold, even at low (108 vRNA copies ml–1) dose (Fig. 1a). Repeated tests with tonsils and nasal polyps (data not shown) and adenoid tissues (Fig. 1b) exhibited lower (≤ 5-fold) levels of virus replication. Furthermore, a NLF specimen containing 2 × 108 vRNA copies ml–1 of a field HRV-A isolate (A78) responded similar to laboratory strains and was passaged serially into three tissue specimens (Fig. 1c).
Using this approach, a HRV-C15 isolate from a specimen of NLF was inoculated (2.6 × 108 vRNA copies ml-1) into sinus organ culture, and high level viral replication was maintained through seven serial passages (Fig. 1d). During each passage, partial inhibition of ciliary beating was observed at 48–72 h, coinciding with the peak of virus replication, but no other specific cytopathic effects were noted. When similar doses (109 vRNA copies ml-1) of HRV-C15 (Fig. 1e, d11) and HRV-A16 (Fig. 1a, high dose) were used for infection, the growth kinetics were equivalent. Serial passage of a second HRV-C isolate (W23)10 was also accomplished using a similar approach (data not shown). Our attempts to adapt these isolates grown in organ culture to multiple cell lines (listed above) were not successful.
HRV-C15 replication in sinus tissues was analyzed by in situ hybridization using whole mount procedures and a digoxigenin-labeled RNA probe specific for the HRV-C15 plus-strand RNA. Positive hybridization was observed in both of the inoculated sinus organ cultures (Fig. 2a, center and right), but was absent from the mock-infected cultures (Fig. 2a, left). Higher resolution images showed a patchy distribution of HRV-C15-positive cells with the highest signal intensities at the edges of tissues (Fig. 2b, right), suggesting that mechanical injury may increase susceptibility to infection, perhaps by exposing sub-apical epithelial layers expressing virus receptor(s).
The two tissue specimens inoculated with HRV-C15 differed in signal intensity and corresponding virus yield. In the tissue (dn17) with the lower yield (107 vRNA copies ml-1, Fig. 2b, center) the RNA signal was limited to small area at the fragment edge, whereas the higher-yield tissue (dn13, 2 × 109 vRNA copies ml-1), gave many foci, with a greater total density of infected cells (Fig. 2b, right). In tissue cross sections the positive signals originated mainly from middle and upper epithelial layers (Fig. 2c). An outermost sloughing of ciliated cells (Fig. 2c, right) was particularly apparent in the higher titer tissues. There was no evidence for infection of cells deeper than the epithelial layer in either sample.
From the organ culture supernatant fluid (passage 4), we sequenced the complete HRV-C15 genome consisting of 7111 bases. The single open reading frame encodes a polyprotein of 2153 amino acids (the longest among the reported HRV-C strains), flanked by the 5′- and 3′-untranslated regions (UTR) of 607 and 45 nucleotides, respectively. The RNA and deduced polyprotein sequences share characteristic HRV-C features such as a putative internal cis-acting replication element (cre) located within VP2 (1B), Met67/Ser68 cleavage site at the VP4/VP2 junction, species-specific insertions and deletions in the VP1 region, and an isoleucine at the termination of the 3D polymerase15,16,18,19. The full sequence itself shares only 56–62% aligned nucleotide identity with other members of the HRV-C species and less than 41% with HRV-A and B strains.
After our recent complete genome sequencing of the known HRVs, we performed an alignment based on crystal structure superimposition and optimal energy RNA configurations, which we term a structure-based sequence alignment1. This dataset was augmented with the HRV-C15 and other recently published HRV-C sequences13,18,19 in order to infer phylogeny and establish species- or genus-specific motifs to predict cell attachment binding sites of HRV-C. A neighbor-joining tree calculated from the complete genomes (representing 74 HRV-A, 25 HRV-B and 12 HRV-C types) placed HRV-C15 in HRV-C cluster on a branch most closely related to strain n4 (19% p-distance), isolated in China in 2006 (Fig. 3); 5′-UTR analysis revealed HRV-"Ca" type18 clustering (Supplementary Fig. 1 online). The available HRV-C sequences, including HRV-C15, show more collective diversity than the known types of HRV-A and HRV-B, suggesting there is still additional sequence "space" for other strains in this species.
Differences in overall capsid sequence together with the failure of HRV-C15 to replicate in standard cell lines suggest that HRV-C viruses have unique growth requirements, possibly including binding to distinct cellular receptors. Notably, great plasticity and rapid evolution of HRVs have been demonstrated by adaptation of major group HRV (A89) to use another receptor (heparan sulfate) for cell entry20. It was therefore of interest to determine whether the HRV-C have sequence consistency in the same sites as receptor footprints mapped for HRV-A and B21–24.
For each alignment position harboring known contacts for ICAM-1 (HRV-B14, HRV-A16 or human coxsackievirus A21) or LDLR (HRV-A2), the group amino acid populations were recorded and then compared (as groups or internally and pairwise, Supplementary Tables 1 and 2 online). When the ICAM-1 binders were compared among themselves, about 40% of identified footprint positions showed strong (r > 0.6) composition conservation (e.g. HRV-B14-Threonine-VP3-180 (14-T-3-180)). Some of these positions were conserved among all HRVs (e.g. 14-P-1-155 and 16-G-1-148). In contrast, other sites displayed a compositional bias between receptor groups (e.g. 14-P-3-178). Fig. 4a depicts the most abundant residues at each footprint position, when the HRV-A and HRV-B were subdivided by ICAM-1 and LDLR receptor groups, and compared to the HRV-C. There was little commonality between HRV-C and either the ICAM-1 or the LDLR contact points. For example, 6 of 7 LDLR footprint positions, and 47 of 50 ICAM-1 footprint locations were rejected by both statistical methods as compositional matches to the HRV-C (Supplementary Table 2 online, columns "h" or "j"). Overall, the analysis predicts the HRV-C viruses use a different receptor(s), with a distinct compositional footprint.
The distinct HRV-C receptor footprint prediction was then tested in cell culture, using antibodies to block attachment of HRV to ICAM-1 or LDLR. In the absence of these antibodies, binding of HRV-A1 and HRV-A16 to both HeLa and PBE cells were 2–3 logs higher compared to HRV-C15 (Fig. 4b,c). Preincubation of HeLa cells with an ICAM-1-specific antibody reduced binding of major group HRV-A16 but not minor group HRV-A1 (Fig. 4b). In cultures of PBE cells, only HRV-A1 was inhibited by pre-incubation with an LDLR-specific antibody (Fig. 4c).When the experiment was carried out using matched tissue snippets from sinus organ cultures, binding of HRV-C15 was similar to that of the other two viruses. Receptor-specific antibodies inhibited attachment of the respective major (80% inhibition) and minor (58% inhibition) viruses, but there was no effect on HRV-C15 binding (Fig. 4d).
HRVs have been divided into two groups (A and B) based on their sensitivity to different antiviral compounds known as capsid binding agents25. These compounds (e.g., WIN56291, WIN52084) intercalate into a hydrophobic pocket within VP1 protein and prevent viral attachment or uncoating by deforming the receptor binding site or inhibiting a requisite conformational change26,27,28; thus the primary sequence dictating shape and charge of the pocket determine the response to specific antivirals. Preincubation of virus inoculums with WIN56291 inhibited propagation of HRV-A16 (group B) and HRV-C15, but not HRV-B14 (group A), in sinus organ culture (Fig. 4e).
The results of the viral binding studies suggest that HRV-C15 does not replicate in HeLa and PBE cells, which are readily infected with HRV-A and -B, because these cells do not express a cell surface receptor for the virus. Alternatively, these cells could lack an intracellular protein that is required for HRV-C replication. To test this hypothesis, a plasmid (pC15) was developed for cell transfection (as opposed to viral infection) by cloning a full-length cDNA copy of the HRV-C15 genome into the plasmid vector pMJ329 directly downstream of the T7 RNA polymerase promoter (Supplementary Fig. 2 online). The cloned HRV-C15 sequence was identical to the complete genome sequence of passage four HRV-C15 (Fig. 1d, P4) and contained a 3'end poly(A29) tail.
RNA transcripts synthesized in vitro from pC15 induced cytopathic effects when transfected into both HeLa and WisL (fetal lung fibroblast) cell monolayers, and these effects were similar to those induced by parallel transfection of HRV-A16 RNA from pR16.1130 (Fig. 5a). Transfection of about 107 WisL cells (T75 flask) yielded 2–4 × 1010 vRNA copies of virus progeny after purification and concentration steps, and this high output was comparable to that of HRV-A16 transfection. After transfection of lower doses of RNA, only HRV-A16 RNA caused CPE progression over time, confirming that the newly synthesized HRV-C15 virus cannot spread from transfected cells to neighboring (not transfected) cells (Supplementary Fig. 3 online). HRV-C15 virus recovered 24 h after transfection was inoculated (109 vRNA copies ml-1) into mucosal organ cultures, and growth kinetics of progeny virus (Fig. 5b) was similar to those of the parental HRV-C15 (Fig. 1e). Examination of concentrated cell lysates by electron microscopy revealed intact HRV virions (about 30 nm in diameter) as well as the expected empty capsids (Fig. 5c).
HRV-C viruses do not grow in standard cell culture used for virus isolation, and have only been detected using molecular assays. Since 2006, over 60 types of this species have been implicated in both upper and lower respiratory tract infections, particularly in children and in individuals with chronic respiratory diseases31. We employed human organ culture of sinus mucosa to propagate in vitro and study the basic biologic properties of an HRV-C clinical isolate (C15 type). Virus replication was demonstrated by an increase in viral RNA, which localized to focal areas in epithelial cell layers. The high-titer virus obtained after serial passage in sinus organ culture allowed complete genome sequencing and cloning of the full-length cDNA copy of the HRV-C15 genome into a plasmid vector. RNA transcripts synthesized in vitro from this clone were infectious when transfected into cell lines resistant to HRV-C15 infection providing an efficient system for production of recombinant HRV-C. Our experimental findings and bioinformatic predictions indicate unique HRV-C receptor-binding specificity.
Mucosal organ culture is the only model to date that supports HRV-C infection in vitro. We and others have tried to grow these newly discovered rhinoviruses from numerous NLF samples in multiple cell cultures without success, indicating novel growth requirements10,15,16. Moreover, our attempts to adapt high-titer HRV-C15 virus grown in sinus cultures or recombinant virus from transfected cells to a cell line were not successful. HRV-C replication in sinus tissue appears to be limited to the epithelium, and hybridization signals were associated with both non-ciliated and ciliated cells. The degree of virus amplification (high or low virus yields) showed considerable variability, which could be related to the condition of the epithelium (all specimens were from patients with sinusitis), other underlying diagnoses (e.g. allergy or asthma), or perhaps the status of local innate immune elements. Furthermore, the expression of HRV-C-specific receptor(s) on epithelial cells may depend on factors found in vivo such as microbial products or interactions with other types of cells (e.g. dendritic cells or lymphocytes) present in human airways.
Footprints of virus capsid residues that make contact with the cellular receptors have been determined for both major and minor HRV groups21–24. Sequence comparisons within the mapped receptor footprints show variability and a tendency towards a species-specific compositional bias among ICAM-1 binders32. However, amino acid residues corresponding to the documented ICAM-1 footprint have been shown to clearly classify the two receptor groups33. The LDLR binders are harder to define by sequence. They always display a conserved central lysine (e.g. HRV-A2, VP1, Lys224), but this residue is not unique to LDLR binders and predictive modeling instead suggests that the overall binding specificity primarily relies on a favorable combination of charge complementarities and hydrophobic interactions34. Comparisons of the group amino acid populations of the all known ICAM-1 or LDLR contact residues using two correlation metrics (Spearman and Pearson) revealed that the majority of footprint locations were rejected by both methods as compositional matches to the HRV-C suggesting that an alternate receptor is used by these viruses. In agreement with this analysis, very low amounts of HRV-C15 attached to HeLa and PBE cells, and incubation of mucosal organ cultures with blocking antibodies to major and minor HRV receptors showed no effects on HRV-C15 binding.
The development of sinus organ culture and a reverse genetics system have enabled studies of HRV-C15 growth in vitro and provided new insights into its unique replication cycle. HRV-C15 binds to an unknown receptor(s) that is expressed on epithelial cells in differentiated tissues, but is either absent or underexpressed in many cell lines, and is clearly distinct from receptors utilized by other HRV species. It is possible that the lack of knowledge about HRV-C receptor and biology has impeded the development of effective antivirals for HRV, since previous candidate medications were tested only against HRV-A and -B viruses before moving into clinical trials. Even though not all enterovirus species have VP1 motifs that confer susceptibility to capsid binding agents, our results demonstrate that this approach can be used to block HRV-C binding and replication. Thus, these studies provide evidence that there are at least two feasible approaches to the treatment or prevention of HRV infections; refinement of capsid binding agents that target multiple species, and development of competitive antagonists for the HRV receptors. The availability of organ culture and reverse genetics system should greatly facilitate further studies on HRV-C biology and its receptor identification.
We thank Drs. D. Heatley, G. Hartig and J.S. McMurray (University of Wisconsin-Madison) for providing surgical samples; and R. Brockman-Schneider, R. Vrtis, T. Pappas, G. Crisafi, M. Hill, J. Bork, R. Massey, A. Lashua and E. Domyan for technical assistance. This work was supported by NIH grants U19 AI070503, U19 AI070503-04S1, R01 HL080412, R01 HL091490, and the NIAID-funded University of Maryland School of Medicine Genome Sequencing Center for Infectious Disease.
Virus nomenclature follows current recommendations of the ICTV Picornaviridae Study Group, designating the HRV species (A, B, C), followed by the assigned virus type (e.g. HRV-A16, C15 etc.). We propagated laboratory stocks of HRVA1 strain A (minor receptor group), HRV-A16 and HRV-B14 (major receptor group) in H1-HeLa cells (ATCC CRL1958), and purified and titered as previously described29,37. HRV-A78 and HRV-C15 (previously designated W10) are clinical isolates that we identified by partial sequencing of the 5′-UTR as described10.
All protocols for these studies were reviewed and approved by the UW-Madison Health Sciences Institutional Review Board. We obtained residual airway tissue specimens from individuals with chronic sinusitis undergoing endoscopic surgery. We washed, sectioned (4 × 4 mm) and submerged snippets of epithelium along with underlying tissues individually in 24-well plates with 0.3 ml bronchial epithelial growth medium (BEGM, Lonza) and incubated them at 37 °C (5% CO2). Before use, we tested all specimens for preexisting respiratory viruses, including HRV, adenoviruses, influenza, parainfluenza, enteroviruses, respiratory syncytial virus, metapneumovirus, coronaviruses, and bocavirus (Respiratory Multi-Code PLx Assay, EraGen Biosciences)38.
We washed tissue squares (4–5 per well) with PBS (3 × 0.5 ml) before inoculation (2 × 108 vRNA copies ml–1) with a virus suspension. After a period of collective incubation (4–6 h, 34 °C, 5% CO2) we aspirated the media and redistributed the individual tissue samples into separate wells with fresh BEGM (0.3 ml) for further incubation (72–96 h). At harvest, we exposed the combined media and tissue from each well to one freeze-thaw cycle, clarified them by low speed centrifugation (3000 × g, 5 min), then passaged with fresh tissue snippets, or aliquoted and stored (–80 °C).
We evaluated virus concentration by SYBR Green qPCR reagents (Applied Biosystems) using primers (forward, 5′-CCTCCGGCCCCTGAAT-3′; reverse, 5′-AAACACGGACACCCAAAGTAGT-3′) which are complementary to the 5′-UTR of HRV-A1, A16, B14 and C15. We used primers and probe for human actin, beta (ACTB) (#4326315E, Applied Biosystems) to normalize RNA content in cell and tissue lysates. We isolated total RNA from 100 μl of growth medium or mucosal tissue (RNeasy Mini Kit, Qiagen), reverse-transcribed it (TaqMan, Applied Biosystems), and performed PCR in duplicate (ABI 7000 Real-Time PCR System, Applied Biosystems). We derived the standard curve from purified HRVC15 RNA transcripts synthesized in vitro. We performed melting curve analysis of the amplicons after each PCR to confirm reaction specificity.
We cloned a cDNA fragment (867 bases) of HRV-C15, encoding 5'-UTR (partial), VP4 and partial VP2 genes into plasmid pMJ329 after a T7 RNA polymerase promoter in reverse orientation to create plasmid pW10-2R. T7-induced transcription of linearized pW10-2R produced digoxigenin-labeled (Roche) probes that detect the viral genome RNA. We fixed, processed, and hybridized sinus tissue samples according to described protocols39,40. Additional details are provided in the Supplementary Methods online.
We pre-incubated cultured cells or tissue samples (30 min, 37 °C) with monoclonal ICAM-1-specific (# BBA3) or polyclonal LDLR-specific (# AF2148) antibodies (R&D Systems) diluted in growth media (10 μg ml-1) or media alone (control). Next, we added 2 × 108 vRNA copies of virus per well containing either mucosal organ culture or PBE cell monolayers (6-well plate), or per tube containing 1 × 106 HeLa cells in suspension. We incubated cells or tissues with the virus (1 h, 25 °C), washed three times, and analyzed by qPCR. To test the efficacy of the capsid-binding compound WIN56291, we incubated (30 min, 25 °C) virus samples (2 × 108 vRNA copies) in 0.1 ml BEGM containing the compound (0.5 μg ml–1, 0.1% DMSO), followed by inoculation (5 h, 34 °C) into sinus organ cultures. After aspirating unattached virus, we incubated tissues for 72 h and tested by qPCR.
We isolated total RNA (RNeasy Mini Kit, Qiagen) from 100 μl of organ culture supernatant (HRV-C15 passage 4). After reverse-transcription with random primers (TaqMan, Applied Biosystems), we performed PCR with the Platinum PCR SuperMix HF (Invitrogen) and primers (Supplementary Table 3 online). The strategy for cloning full-length cDNA copy of HRV-C15 is described in Supplementary Fig. 2 online. We confirmed each viral cDNA insert by automated sequencing of both strands.
We purified full-length RNA transcripts synthesized from the linearized (BstBI) pC15 DNA (RiboMax large-scale RNA production system T7, Promega) with an RNeasy Mini Kit (Qiagen) and analyzed by agarose gel electrophoresis. We transfected cells with RNA and Lipofectamine 2000 (Invitrogen) mixture (1 to 5 w/v ratio) using manufacturer's recommendations, and incubated for 24–72 h. See the Supplementary Methods online for detailed protocol.
We used Student's t test to analyze viral replication data (SigmaPlot 11.0, Systat Software). Significance was defined at P < 0.05. Statistical evaluation of HRV receptor footprints is described in the Supplementary Methods online.
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A Biography of Jerome David Salinger
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Jerome David Salinger was born in 1919 on New Years Day Growing up in New York City he soon learned all about the bustle of the city His parents were Sol Salinger a wealthy ham importer and Miriam Salinger Salinger attended New York public high school and was considered an average student in most subjects Most of his teachers found him to be a shy polite introverted boy He flunked out of the first private school he attended-- McBurney Later he enrolled in Valley Forge Military Academy and graduated in 1936 Soon he began to write despite his fathers efforts to teach him the business of importing Salinger was drafted by the United States Army in 1942 where he specialized in counter-intelligence In 1944 he stormed Normandy with the other allies during D-Day Soon after returning from the war Salinger began to isolate himself more and more from society He married in 1955 and has two children Salingers continued withdrawal from society has continued and today he is virtually unknown outside of the world of literature Plot The Catcher in the Rye is a story of an emotionally disturbed young sixteen year old boy named Holden Caulfield Holden tells the story himself so you can see first hand what kind of person he is The story begins as he is leaves Pencey Prep his school He was actually thrown out of it because he flunked five of his six courses The way Holden describes his school you kind of understand that he isnt very sad about it He hated this school He also hated the other schools he flunked out of After a fight with his roommate he decides to go to New York before he goes home to his parents who by then should have already received the letter in which the news of his being thrown out would be given When he arrives in New York Holden checks himself in a hotel
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Lilly, the main character of Camilla Gibb's stunning new novel, has anything but a stable childhood. The daughter of English/Irish hippies, she was "born in Yugoslavia, breast-fed in the Ukraine, weaned in Corsica, freed from nappies in Sicily and walking by the time [they] got to the Algarve..." The family's nomadic adventure ends in Tangier when Lilly's parents are killed in a drug deal gone awry. Orphaned at eight, Lilly is left in the care of a Sufi sheikh, who shows her the way of Islam through the Qur'an. When political turmoil erupts, Lilly, now sixteen, is sent to the ancient walled city of Harar, Ethiopia, where she stays in a dirt-floored compound with an impoverished widow named Nouria and her four children. In Harar, Lilly earns her keep by helping with the household chores and teaching local children the Qur'an. Ignoring the cries of "farenji" (foreigner), she slowly begins to put down roots, learning the language and immersing herself in a culture rich in customs and rituals and lush with glittering bright headscarves, the chorus of muezzins and the scent of incense and coffee. She is drawn to an idealistic half-Sudanese doctor named Aziz, and the two begin to meet every Saturday at a social gathering. As they stay behind to talk, Lilly finds her faith tested for the first time in her life: "The desire to remain in his company overwhelmed common sense- I would pick up my good Muslim self on the way home." Just as their love begins to blossom, they are wrenched apart when the aging emperor Haile Selassie is deposed by the brutal Dergue regime. Lilly seeks exile in London, while Aziz stays to pursue his revolutionary passions. In London, Lilly's life as a white Muslim is no less complicated. A hospital staff nurse, she befriends a refugee from Ethiopia named Amina, whose daughter she helped to deliver in a back alley. The two women set up a community association to re-unite refugees with lost family members. Their work, however, isn't entirely altruistic. Both women are looking for someone: Amina, her husband, Yusuf, and Lilly, Aziz, who remains firmly, painfully, implanted in her heart. The first-person narrative alternates seamlessly between England (1981-91) and Ethiopia (1970-74), weaving a rich tapestry of one woman's quest to maintain faith and love through revolution, upheaval and the alienation of life in exile. Sweetness in the Belly" "was universally praised for the tremendous empathy that Gibb brings to an ambitious story. "Kirkus Reviews" writes that the novel "reflect(s) the pain, cultural relocation and uncertainty of tribal, political and religious refugees the world over. Gibb's territory is urgently modern and controversial but she enters it softly, with grace, integrity and a lovely compassionate story. [It is a] poem to belief and to the displaced-humane, resonant, original, impressive." According to the "Literary Review of Canada, "Sweetness in the Belly is ..".a novel that is culturally sensitive, consummately researched and deeply compassionate...richly imagined, full of sensuous detail and arresting imagery...Gibb has smuggled Western readers into the centre of lives they might never otherwise come into contact with, let alone understand."
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|Doubleday Canada
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|29 March 2005
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|415 pages
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Michael Sean Winters is the author of Left At the Altar: How Democrats Lost The Catholics And How Catholics Can Save The Democrats (Basic Books, 2008). His biography of the Rev. Jerry Falwell, God's Right Hand: How Jerry Falwell Made God a Republican and Baptized the American Right was published by Harper One in January 2012 to critical acclaim. He is a Visiting Fellow at Catholic University's Institute for Policy Research and Catholic Studies.
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December 2-15, 2016
- Read select articles from our print issue
- Special Section [Print Only]: Spirituality


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FREE SHIPPING* on orders of $50 or more. Ends at 11:59PM 12/3/16.
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Dance Dance Carabao
Played 11277 times
Dance Dance Carabao game information:
There are four arrows that correspond to your keyboard directional keys. Once the game starts, arrows would start scrolling up. Time the key pressing of the corresponding keyboard directional keys once the scrolling arrows overlap it. You score with every timed arrows.
How to play:
Use arrow keys to interact.
Add this game to your website or blog!
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Hi there! I'm new to this whole wikia community! I don't think I'll be making any games (my friend SerpentKing or SirdentKing or whatshisname told me about everything you can do on this wiki), but I'll submit tributes! Treat me well, please!Read more >


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|By PR Newswire
Article Rating:
|January 11, 2013 02:00 AM EST
NORTH ANDOVER, Mass., Jan. 11, 2013 /PRNewswire/ -- Urban Ag Corp. / (AQUM.PK) (the "Company"), announced today that the Company has executed a letter of intent to acquire all of the outstanding shares of Green Wire Enterprises, Inc. ("GWE"). This acquisition is the first by the Company using the recently announced acquisition model. GWE operates primarily in the Southwestern United States in the Telecom market but has contracts with major telecommunication companies and general contractors in other locations within the United States.
Projected Revenues used to calculate the purchase price for the three operating subsidiaries of Green Wire Enterprises averaged over $6 million per year for the measurement period with projected average Net Income of over $550,000.00. The purchase price will be made up of Equity, Cash and Seller Notes. The final documentation will also include a spin-out provision. GWE will operate as a separate division of the Company.
Billy V. Ray, Jr. CEO of the Company stated," As our first potential acquisition using the Model we have developed to implement our acquisition/incubator strategy, GWE give us the opportunity to see our plans come to fruition. This transaction will expand our services into the Telecom market while allowing us to offer the abatement/remediation services to the overall customer base. We look forward to coming to a quick close of this transaction within the coming weeks. "
GWE's operating subsidiaries serve a wide customer base that includes Telecom customers such as Verizon, Motorola, Alcatel-Lucent, Time Warner and General Contractors serving customers such as Wal-Mart, CVS and Gulf Marine. The subsidiaries also network and design services to a multiple of state and county government agencies, colleges and school in the Texas market.
Contact: Billy V. Ray, Jr
E: [email protected]
Urban Ag Corp. Corporate Office
Email address Investor Relations Department
[email protected]
This news release contains forward-looking statements within the meaning of Section 37A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934. These forward-looking statements involve risks and uncertainties. A number of factors could cause actual results to differ from those indicated in the forward-looking statements, including the Company's ability to continue to successfully market and provide its services, maintain its effectiveness and its customer base and general economic conditions. The Company undertakes no obligation to publicly update or revise forward-looking statements whether as a result of new information, future events or otherwise.
SOURCE Urban Ag Corp.
"Once customers get a year into their IoT deployments, they start to realize that they may have been shortsighted in the ways they built out their deployment and the key thing I see a lot of people looking at is - how can I take equipment data, pull it back in an IoT solution and show it in a dashboard," stated Dave McCarthy, Director of Products at Bsquare Corporation, in this SYS-CON.tv interview at @ThingsExpo, held November 1-3, 2016, at the Santa Clara Convention Center in Santa Clara, CA.
Dec. 2, 2016 11:15 PM EST Reads: 845
20th Cloud Expo, taking place June 6-8, 2017, at the Javits Center in New York City, NY, will feature technical sessions from a rock star conference faculty and the leading industry players in the world. Cloud computing is now being embraced by a majority of enterprises of all sizes. Yesterday's debate about public vs. private has transformed into the reality of hybrid cloud: a recent survey shows that 74% of enterprises have a hybrid cloud strategy.
Dec. 2, 2016 11:15 PM EST Reads: 1,669
IoT is rapidly changing the way enterprises are using data to improve business decision-making. In order to derive business value, organizations must unlock insights from the data gathered and then act on these. In their session at @ThingsExpo, Eric Hoffman, Vice President at EastBanc Technologies, and Peter Shashkin, Head of Development Department at EastBanc Technologies, discussed how one organization leveraged IoT, cloud technology and data analysis to improve customer experiences and effici...
Dec. 2, 2016 08:30 PM EST Reads: 4,965
Fact is, enterprises have significant legacy voice infrastructure that's costly to replace with pure IP solutions. How can we bring this analog infrastructure into our shiny new cloud applications? There are proven methods to bind both legacy voice applications and traditional PSTN audio into cloud-based applications and services at a carrier scale. Some of the most successful implementations leverage WebRTC, WebSockets, SIP and other open source technologies. In his session at @ThingsExpo, Da...
Dec. 2, 2016 08:15 PM EST Reads: 1,551
"IoT is going to be a huge industry with a lot of value for end users, for industries, for consumers, for manufacturers. How can we use cloud to effectively manage IoT applications," stated Ian Khan, Innovation & Marketing Manager at Solgeniakhela, in this SYS-CON.tv interview at @ThingsExpo, held November 3-5, 2015, at the Santa Clara Convention Center in Santa Clara, CA.
Dec. 2, 2016 06:45 PM EST Reads: 3,981
As data explodes in quantity, importance and from new sources, the need for managing and protecting data residing across physical, virtual, and cloud environments grow with it. Managing data includes protecting it, indexing and classifying it for true, long-term management, compliance and E-Discovery. Commvault can ensure this with a single pane of glass solution – whether in a private cloud, a Service Provider delivered public cloud or a hybrid cloud environment – across the heterogeneous enter...
Dec. 2, 2016 06:30 PM EST Reads: 1,474
The cloud promises new levels of agility and cost-savings for Big Data, data warehousing and analytics. But it's challenging to understand all the options – from IaaS and PaaS to newer services like HaaS (Hadoop as a Service) and BDaaS (Big Data as a Service). In her session at @BigDataExpo at @ThingsExpo, Hannah Smalltree, a director at Cazena, provided an educational overview of emerging "as-a-service" options for Big Data in the cloud. This is critical background for IT and data professionals...
Dec. 2, 2016 05:00 PM EST Reads: 4,076
@GonzalezCarmen has been ranked the Number One Influencer and @ThingsExpo has been named the Number One Brand in the "M2M 2016: Top 100 Influencers and Brands" by Onalytica. Onalytica analyzed tweets over the last 6 months mentioning the keywords M2M OR "Machine to Machine." They then identified the top 100 most influential brands and individuals leading the discussion on Twitter.
Dec. 2, 2016 04:45 PM EST Reads: 1,968
Today we can collect lots and lots of performance data. We build beautiful dashboards and even have fancy query languages to access and transform the data. Still performance data is a secret language only a couple of people understand. The more business becomes digital the more stakeholders are interested in this data including how it relates to business. Some of these people have never used a monitoring tool before. They have a question on their mind like "How is my application doing" but no id...
Dec. 2, 2016 04:45 PM EST Reads: 2,102
What happens when the different parts of a vehicle become smarter than the vehicle itself? As we move toward the era of smart everything, hundreds of entities in a vehicle that communicate with each other, the vehicle and external systems create a need for identity orchestration so that all entities work as a conglomerate. Much like an orchestra without a conductor, without the ability to secure, control, and connect the link between a vehicle's head unit, devices, and systems and to manage the ...
Dec. 2, 2016 04:15 PM EST Reads: 363
More and more brands have jumped on the IoT bandwagon. We have an excess of wearables – activity trackers, smartwatches, smart glasses and sneakers, and more that track seemingly endless datapoints. However, most consumers have no idea what "IoT" means. Creating more wearables that track data shouldn't be the aim of brands; delivering meaningful, tangible relevance to their users should be. We're in a period in which the IoT pendulum is still swinging. Initially, it swung toward "smart for smar...
Dec. 2, 2016 04:15 PM EST Reads: 346
In an era of historic innovation fueled by unprecedented access to data and technology, the low cost and risk of entering new markets has leveled the playing field for business. Today, any ambitious innovator can easily introduce a new application or product that can reinvent business models and transform the client experience. In their Day 2 Keynote at 19th Cloud Expo, Mercer Rowe, IBM Vice President of Strategic Alliances, and Raejeanne Skillern, Intel Vice President of Data Center Group and G...
Dec. 2, 2016 04:00 PM EST Reads: 1,865
Information technology is an industry that has always experienced change, and the dramatic change sweeping across the industry today could not be truthfully described as the first time we've seen such widespread change impacting customer investments. However, the rate of the change, and the potential outcomes from today's digital transformation has the distinct potential to separate the industry into two camps: Organizations that see the change coming, embrace it, and successful leverage it; and...
Dec. 2, 2016 03:30 PM EST Reads: 3,192
With major technology companies and startups seriously embracing IoT strategies, now is the perfect time to attend @ThingsExpo 2016 in New York. Learn what is going on, contribute to the discussions, and ensure that your enterprise is as "IoT-Ready" as it can be! Internet of @ThingsExpo, taking place June 6-8, 2017, at the Javits Center in New York City, New York, is co-located with 20th Cloud Expo and will feature technical sessions from a rock star conference faculty and the leading industry p...
Dec. 2, 2016 01:30 PM EST Reads: 1,812
20th Cloud Expo, taking place June 6-8, 2017, at the Javits Center in New York City, NY, will feature technical sessions from a rock star conference faculty and the leading industry players in the world. Cloud computing is now being embraced by a majority of enterprises of all sizes. Yesterday's debate about public vs. private has transformed into the reality of hybrid cloud: a recent survey shows that 74% of enterprises have a hybrid cloud strategy.
Dec. 2, 2016 01:15 PM EST Reads: 2,084
Internet of @ThingsExpo, taking place June 6-8, 2017 at the Javits Center in New York City, New York, is co-located with the 20th International Cloud Expo and will feature technical sessions from a rock star conference faculty and the leading industry players in the world. @ThingsExpo New York Call for Papers is now open.
Dec. 2, 2016 12:00 PM EST Reads: 1,837
"ReadyTalk is an audio and web video conferencing provider. We've really come to embrace WebRTC as the platform for our future of technology," explained Dan Cunningham, CTO of ReadyTalk, in this SYS-CON.tv interview at WebRTC Summit at 19th Cloud Expo, held November 1-3, 2016, at the Santa Clara Convention Center in Santa Clara, CA.
Dec. 2, 2016 12:00 PM EST Reads: 240
Everyone knows that truly innovative companies learn as they go along, pushing boundaries in response to market changes and demands. What's more of a mystery is how to balance innovation on a fresh platform built from scratch with the legacy tech stack, product suite and customers that continue to serve as the business' foundation. In his General Session at 19th Cloud Expo, Michael Chambliss, Head of Engineering at ReadyTalk, discussed why and how ReadyTalk diverted from healthy revenue and mor...
Dec. 2, 2016 11:45 AM EST Reads: 1,472
Extracting business value from Internet of Things (IoT) data doesn't happen overnight. There are several requirements that must be satisfied, including IoT device enablement, data analysis, real-time detection of complex events and automated orchestration of actions. Unfortunately, too many companies fall short in achieving their business goals by implementing incomplete solutions or not focusing on tangible use cases. In his general session at @ThingsExpo, Dave McCarthy, Director of Products...
Dec. 2, 2016 11:00 AM EST Reads: 427
You have great SaaS business app ideas. You want to turn your idea quickly into a functional and engaging proof of concept. You need to be able to modify it to meet customers' needs, and you need to deliver a complete and secure SaaS application. How could you achieve all the above and yet avoid unforeseen IT requirements that add unnecessary cost and complexity? You also want your app to be responsive in any device at any time. In his session at 19th Cloud Expo, Mark Allen, General Manager of...
Dec. 2, 2016 10:45 AM EST Reads: 1,607


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Check in from 14h / Check out prior to 10h
Tladi Lodge Johannesburg: Find photos, reviews, information, amenities and compare prices for 5 stars hotels in Johannesburg, South Africa.
Tladi Lodge Johannesburg is located in Johannesburg and offers outdoor tennis courts. The guest house offers an outdoor pool and a swimming pool, as well as rooms with private terraces.
Hotel description
Every luxury room at Tladi Lodge Johannesburg includes an in-room dining area and a refrigerator, while the bathrooms feature showers and bathrobes. All include a flat-screen TV, a walk-in closet and tea and coffee making facilities.
Tladi offers breakfast each morning that guests can enjoy before heading out to explore the area.
Tladi Lodge features a golf course and is close to the area's well-known attractions. The Civic Theatre is just an easy car ride from the guest house.
Hotel features
Non-Smoking Rooms, Refrigerator, Cable / Satellite TV, Connecting Rooms, Coffee / Tea Maker, Hair Dryer, TV, Shower, En suite, Private Bathroom
Business Center, Conference Room(s), Safe-Deposit Box, Wake-up Service, Meeting Rooms, Laundry service, Desk, Luggage Storage, Express Check-In/Check-Out, Self Laundry
Swimming pool, Tour Desk, Tennis Courts, Golf Course, Garden, Pool Outdoor
High-speed Internet, Internet Connection (wireless)
Parking, Airport shuttle
Bathrobes, Private Toilet, Gay/Lesbian Friendly
Availability and Prices
Booking Site
Room Type
Per room
Per night
Per night
Users who viewed Tladi Lodge Johannesburg also viewed these 5 stars Johannesburg hotels:
Morrells Manor House Johannesburg
Corner of Weltevreden Road & Taaibos Street, Northcliff, Johannesburg
Corner of Weltevreden Road & Taaibos Street, Northcliff, Johannesburg
Monarch Hotel Johannesburg
167 Oxford Road , Johannesburg
167 Oxford Road , Johannesburg
10 2nd Avenue Houghton Estate
10 2nd Avenue , Johannesburg
10 2nd Avenue , Johannesburg
Search hotels
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74 reviews
Nearest hotels
- Moloko Strathavon hotel
371 m
- Ruby Homes - Via Arezzio
531 m
- Marion Lodge Johannesburg
653 m


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Herman Medel
Property Manager LREA
Appreciated for his honesty, sincerity and personable nature, Herman combines an intimate local market knowledge with a keen enthusiasm to the management of his client's most valuable possessions; their homes.
He has been welcomed into the Century 21 Property Management team in Newtown.
Herman has acquired extensive market knowledge through living and working in the popular suburbs for over 40 years and brings passion, efficiency and diplomacy to helping his clients reach all of their property goals.
Herman values the opportunity he is given to meet with a diverse range of people, while bringing out his own virtues through communicating with people and fine-tuning process driven systems.
The competitive real estate industry provides Herman with a great level of satisfaction in continuing to meet the needs of both the landlords and tenants. Throughout recent years, he has proven his commitment to providing an outstanding management service and has consistently secured an impressive list of rental results.
Herman feels an affinity with Century 21 Chris Papas , a highly respected and nationally recognised company for its strength in branding, exceptional results and dynamic team of management specialists who are continually going above and beyond client expectations.
Contact Herman to employ the knowledge, reliability and personable approach needed to guarantee your property is managed as if you could take the time to do it yourself


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To the Editor:
In a ''A War for Oil?'' (column, Jan. 5), Thomas L. Friedman argues that a war to prevent an ''evil, megalomaniacal dictator'' from acquiring control over oil would be morally justified if the United States acted so as to protect world interests in access to oil and other energy sources.
But even if the United States acts as Mr. Friedman wishes, war always imposes enormous costs in lives and welfare.
If the United States supported the International Criminal Court, we might be able to remove megalomaniacal dictators without resorting to war. But the United States, jealous of its sovereignty, would apparently prefer to wage war rather than build civilized international law-giving institutions.
This is a great shame for our country and a tragedy for the planet.
Brooklyn, Jan. 5, 2003Continue reading the main story


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Adriatic Opportunities Fund Form D
The Alabama-based Adriatic Opportunities Fund, Lp had published form D because of $3.75 million offering. The date of first sale was 2014-09-14. The Limited Partnership raised $3.75 million. The offering is still open. The total offering amount amount was $3.75 million. The offering form was filed on 2016-10-11. Adriatic Opportunities Fund, Lp's clarification was: unspecified.
Adriatic Opportunities Fund is based in Alabama. The company's business is Pooled Investment Fund. The form D was filed by Kent Utsey Managing Member of the General Partner. The company was incorporated in 2013. The filler's address is: 11N. 2Nd Avenue, St. Charles, Il, Illinois, 60174. Kent Utsey is the related person in the form and it has address: 11 N. 2Nd Avenue, St. Charles, Il, Illinois, 60174. Link to Adriatic Opportunities Fund Filing: 000160749616000002.
Analysis of Adriatic Opportunities Fund Offering
On average, companies in the Pooled Investment Fund sector, sell 37.80% investment fund interests. Adriatic Opportunities Fund sold 100.00% of the offering. The average offering amount is $24.76 million for companies in the Pooled Investment Fund industry sector. The total amount raised is 84.85% smaller than the average for companies in the Pooled Investment Fund sector.
Receive News & Ratings Via Email - Enter your email address below to receive a concise daily summary of the latest news and analysts' ratings with our FREE daily email newsletter.


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Today's Devotional
Sacrificial LoveWhat does it mean for you to carry your cross?
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The hotel staff was exceptionally friendly. The room was clean, the bed was comfortable, the bathroom very clean. We would stay here again. We stay at Hampton Inn's because they are usually consistently nice.
- Reservation Options:
- TripAdvisor is proud to partner with Hilton Hotels, Booking.com, Hotels.com, Priceline and Odigeo so you can book your Hampton Inn Ft. Lauderdale Plantation reservations with confidence. We help millions of travelers each month to find the perfect hotel for both vacation and business trips, always with the best discounts and special offers.
- Also Known As:
- Hampton Inn Ft. Lauderdale Plantation Hotel Plantation
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